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Biomarker identifies precancerous pancreatic cysts

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

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

 


Courtesy Dr. Lance Liotta Laboratory
Dr. Majumder presented the results at the annual meeting of the American College of Gastroenterology.

Less than 50% of cysts that are surgically resected turn out to be HGD or cancerous. “Having a cyst fluid marker could identify the patients that would benefit the most from surgery. If you’re going to go through a pancreatic resection, we’d rather give you the best chance of saying that we removed something that either has early cancer in it or will turn into cancer in the near future,” said Dr. Majumder.

The study looked at pancreatic cyst fluid from 83 cysts that had been surgically resected. The DNA samples were taken from the cyst fluid. Dr. Majumder believes that the cells shed from the cyst wall into the fluid. As a result, DNA from the fluid captures heterogeneity in the cyst more effectively than a biopsied sample.

Dr. Shounak Majumder
The researchers performed methylation-specific PCR of the samples, normalizing the levels to beta-actin and age. Fourteen of the cysts were adenocarcinoma or HGD, and these were compared to cysts that had low-grade dysplasia or no dysplasia.

The researchers found five methylated DNA markers that distinguished cancer or HGD from controls with areas under the ROC curve of 0.90 or higher. The top two (BMP3, EMX1) detected 93% of cases (95% CI, 66%-100%) at a specificity of 90% (95% CI, 80%-96%). Applied to eight cysts with intermediate-grade dysplasia, the biomarkers would have identified three at 95% specificity.

By comparison, the Fukuoka guidelines have 56% sensitivity and 73% specificity.

A limitation to the technique is that DNA cannot be extracted from all samples. About 5%-10% of pancreatic fluid samples are unusable, according to Somashekar Krishna, MD, MPH, assistant professor of medicine at the Ohio State University Medical Center, who attended the session. Dr. Krishna is conducting research combining endomicroscopy with molecular markers.

“We should have a foolproof system where if one fails, the other kicks in, and we have an answer for every patient. My opinion is that endomicroscopy has to be combined with molecular studies. I think combined we’ll have an excellent diagnostic yield,” Dr. Krishna said in an interview.

Dr. Majumder and Dr. Krishna have declared no conflicts of interest.
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– In fluid derived from pancreatic cysts, methylated DNA markers predict the presence of high-grade dysplasia (HGD) or cancer, and could help physicians decide whether to surgically remove cysts – a procedure that often has serious complications.

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

 


Courtesy Dr. Lance Liotta Laboratory
Dr. Majumder presented the results at the annual meeting of the American College of Gastroenterology.

Less than 50% of cysts that are surgically resected turn out to be HGD or cancerous. “Having a cyst fluid marker could identify the patients that would benefit the most from surgery. If you’re going to go through a pancreatic resection, we’d rather give you the best chance of saying that we removed something that either has early cancer in it or will turn into cancer in the near future,” said Dr. Majumder.

The study looked at pancreatic cyst fluid from 83 cysts that had been surgically resected. The DNA samples were taken from the cyst fluid. Dr. Majumder believes that the cells shed from the cyst wall into the fluid. As a result, DNA from the fluid captures heterogeneity in the cyst more effectively than a biopsied sample.

Dr. Shounak Majumder
The researchers performed methylation-specific PCR of the samples, normalizing the levels to beta-actin and age. Fourteen of the cysts were adenocarcinoma or HGD, and these were compared to cysts that had low-grade dysplasia or no dysplasia.

The researchers found five methylated DNA markers that distinguished cancer or HGD from controls with areas under the ROC curve of 0.90 or higher. The top two (BMP3, EMX1) detected 93% of cases (95% CI, 66%-100%) at a specificity of 90% (95% CI, 80%-96%). Applied to eight cysts with intermediate-grade dysplasia, the biomarkers would have identified three at 95% specificity.

By comparison, the Fukuoka guidelines have 56% sensitivity and 73% specificity.

A limitation to the technique is that DNA cannot be extracted from all samples. About 5%-10% of pancreatic fluid samples are unusable, according to Somashekar Krishna, MD, MPH, assistant professor of medicine at the Ohio State University Medical Center, who attended the session. Dr. Krishna is conducting research combining endomicroscopy with molecular markers.

“We should have a foolproof system where if one fails, the other kicks in, and we have an answer for every patient. My opinion is that endomicroscopy has to be combined with molecular studies. I think combined we’ll have an excellent diagnostic yield,” Dr. Krishna said in an interview.

Dr. Majumder and Dr. Krishna have declared no conflicts of interest.

 

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

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

 


Courtesy Dr. Lance Liotta Laboratory
Dr. Majumder presented the results at the annual meeting of the American College of Gastroenterology.

Less than 50% of cysts that are surgically resected turn out to be HGD or cancerous. “Having a cyst fluid marker could identify the patients that would benefit the most from surgery. If you’re going to go through a pancreatic resection, we’d rather give you the best chance of saying that we removed something that either has early cancer in it or will turn into cancer in the near future,” said Dr. Majumder.

The study looked at pancreatic cyst fluid from 83 cysts that had been surgically resected. The DNA samples were taken from the cyst fluid. Dr. Majumder believes that the cells shed from the cyst wall into the fluid. As a result, DNA from the fluid captures heterogeneity in the cyst more effectively than a biopsied sample.

Dr. Shounak Majumder
The researchers performed methylation-specific PCR of the samples, normalizing the levels to beta-actin and age. Fourteen of the cysts were adenocarcinoma or HGD, and these were compared to cysts that had low-grade dysplasia or no dysplasia.

The researchers found five methylated DNA markers that distinguished cancer or HGD from controls with areas under the ROC curve of 0.90 or higher. The top two (BMP3, EMX1) detected 93% of cases (95% CI, 66%-100%) at a specificity of 90% (95% CI, 80%-96%). Applied to eight cysts with intermediate-grade dysplasia, the biomarkers would have identified three at 95% specificity.

By comparison, the Fukuoka guidelines have 56% sensitivity and 73% specificity.

A limitation to the technique is that DNA cannot be extracted from all samples. About 5%-10% of pancreatic fluid samples are unusable, according to Somashekar Krishna, MD, MPH, assistant professor of medicine at the Ohio State University Medical Center, who attended the session. Dr. Krishna is conducting research combining endomicroscopy with molecular markers.

“We should have a foolproof system where if one fails, the other kicks in, and we have an answer for every patient. My opinion is that endomicroscopy has to be combined with molecular studies. I think combined we’ll have an excellent diagnostic yield,” Dr. Krishna said in an interview.

Dr. Majumder and Dr. Krishna have declared no conflicts of interest.
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Key clinical point: The method outperforms the Fukuoka method for predicting high-risk cysts, and could improve candidate selection for surgical resection.

Major finding: DNA markers isolated from pancreatic fluid predicted cancer or high-grade dysplasia with 90% specificity and 93% sensitivity.

Data source: Pilot study, retrospective analysis.

Disclosures: Dr. Majumder and Dr. Krishna have declared no conflicts of interest.

VIDEO: Pre–gastric bypass antibiotics alter gut microbiome

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– Antibiotics given in advance of gastric bypass surgery preferentially alter the microbiome, nudging it toward a more “lean” physiologic profile.

Given before a sleeve gastrectomy, vancomycin, which has little gut penetration, barely shifted the high ratio of Firmicutes to Bacteroidetes, a profile typically associated with obesity and insulin resistance. But cefazolin, which has much higher gut penetration, suppressed the presence of Firmicutes, which metabolize fat, and allowed the expansion of carbohydrate-loving Bacteroidetes – a profile generally seen in lean people.

 


Cyrus Jahansouz, MD, of the University of Minnesota, Minneapolis, and his colleagues wanted to examine whether a shift in preoperative antibiotics might affect the way the microbiome re-establishes itself in the wake of vertical sleeve gastrectomy. They enrolled 32 patients who were candidates for the procedure. None had undergone prior gastrointestinal surgery, and none had been exposed to antibiotics in the 3 months prior to bariatric surgery. They were similar in age, weight, body mass index, and fasting glucose. The mean HbA1c was about 6%.

Patients were randomized to three groups: maximal diet therapy (800 calories per day) without surgery; vertical sleeve gastrectomy with the usual preoperative antibiotic cefazolin and the postsurgical diet; and vertical sleeve gastrectomy with preoperative vancomycin and the postsurgical diet. All patients gave a fecal sample immediately before surgery and another one 6 days after surgery.

Preoperative cluster analysis of bacterial DNA showed that all of the samples had a similar composition, predominated by Firmicutes species (60%-70%). Bacteroidetes species made up about 20%-30%, with Proteobacteriae, Actinobacteriae, Verrucomicrobia, and other phyla comprising the remainder of the microbiome.

At the second sampling, the diet-only group showed no microbiome changes at all. The vancomycin group showed a very small but not significant expansion of Bacteroidetes and reduction of Firmicutes.

Patients in the cefazolin group showed a significant shift in the ratio – and it was quite striking, Dr. Jahansouz said. Among these patients, Firmicutes had decreased from 70% to 40% of the community. Bacteroidetes showed a corresponding shift, increasing from 20% of the community to 45%. The findings are quite surprising, he noted, considering that only one dose of antibiotic was associated with the changes and that they were evident within just a few days.

Although “a little hard to interpret” because of its small size and short follow-up, the study suggests that antibiotic choice might contribute to the success of weight-loss surgery, Dr. Jahansouz said at the annual clinical congress of the American College of Surgeons.

“There are still several factors in the perioperative period that we have to study to be able to identify what other things might have also influenced the shift,” he said in an interview. “But I do think that, in the future, these changes can be manipulated to benefit metabolic outcomes.”

Two phyla – Bacteroidetes and Firmicutes – dominate the human gut microbiome in a dynamic ratio that is highly associated with the way energy is extracted from food. Bacteroidetes species specialize in carbohydrate digestion and Firmicutes in fat digestion. “In a lean, insulin-sensitive state, Bacteroidetes dominates the human gut microbiome,” Dr. Jahansouz said. “With the progression of obesity and insulin resistance, there is a subsequent shift in the microbiome phenotype, favoring the growth of Firmicutes at the expense and reduction of Bacteroidetes. This is a significant change, because this obesity-associated phenotype has an increased capacity to harvest energy. It’s not the same for a lean person to consume 1,000 calories as it is for an obese person to consume them.”

Bariatric surgery has been shown to alter the gut microbiome, shifting it toward this more “lean” profile (Cell Metab. 2015 Aug 4;22[2]:228-38). This shift may be an important component of the still not fully elucidated mechanisms by which bariatric surgery causes weight loss and normalizes insulin signaling, Dr. Jahansouz said.

Dr. Jahansouz is following this group of patients to explore whether there are differences in weight loss and insulin signaling. He also will track whether the microbiome stabilizes at its early postsurgical profile, or continues to shift, either toward an even higher Bacteroidetes to Firmicutes ratio, or back to a more “obese” profile.

He and his colleagues are also investigating the effect of antibiotics and gastric bypass surgery in mouse models. “I can say that antibiotics seem to have a remarkable impact on the effect of mouse sleeve gastrectomy. We’re not quite there yet with humans,” but the data are compelling.

Dr. Jahansouz said that he had no financial disclosures.

The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
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– Antibiotics given in advance of gastric bypass surgery preferentially alter the microbiome, nudging it toward a more “lean” physiologic profile.

Given before a sleeve gastrectomy, vancomycin, which has little gut penetration, barely shifted the high ratio of Firmicutes to Bacteroidetes, a profile typically associated with obesity and insulin resistance. But cefazolin, which has much higher gut penetration, suppressed the presence of Firmicutes, which metabolize fat, and allowed the expansion of carbohydrate-loving Bacteroidetes – a profile generally seen in lean people.

 


Cyrus Jahansouz, MD, of the University of Minnesota, Minneapolis, and his colleagues wanted to examine whether a shift in preoperative antibiotics might affect the way the microbiome re-establishes itself in the wake of vertical sleeve gastrectomy. They enrolled 32 patients who were candidates for the procedure. None had undergone prior gastrointestinal surgery, and none had been exposed to antibiotics in the 3 months prior to bariatric surgery. They were similar in age, weight, body mass index, and fasting glucose. The mean HbA1c was about 6%.

Patients were randomized to three groups: maximal diet therapy (800 calories per day) without surgery; vertical sleeve gastrectomy with the usual preoperative antibiotic cefazolin and the postsurgical diet; and vertical sleeve gastrectomy with preoperative vancomycin and the postsurgical diet. All patients gave a fecal sample immediately before surgery and another one 6 days after surgery.

Preoperative cluster analysis of bacterial DNA showed that all of the samples had a similar composition, predominated by Firmicutes species (60%-70%). Bacteroidetes species made up about 20%-30%, with Proteobacteriae, Actinobacteriae, Verrucomicrobia, and other phyla comprising the remainder of the microbiome.

At the second sampling, the diet-only group showed no microbiome changes at all. The vancomycin group showed a very small but not significant expansion of Bacteroidetes and reduction of Firmicutes.

Patients in the cefazolin group showed a significant shift in the ratio – and it was quite striking, Dr. Jahansouz said. Among these patients, Firmicutes had decreased from 70% to 40% of the community. Bacteroidetes showed a corresponding shift, increasing from 20% of the community to 45%. The findings are quite surprising, he noted, considering that only one dose of antibiotic was associated with the changes and that they were evident within just a few days.

Although “a little hard to interpret” because of its small size and short follow-up, the study suggests that antibiotic choice might contribute to the success of weight-loss surgery, Dr. Jahansouz said at the annual clinical congress of the American College of Surgeons.

“There are still several factors in the perioperative period that we have to study to be able to identify what other things might have also influenced the shift,” he said in an interview. “But I do think that, in the future, these changes can be manipulated to benefit metabolic outcomes.”

Two phyla – Bacteroidetes and Firmicutes – dominate the human gut microbiome in a dynamic ratio that is highly associated with the way energy is extracted from food. Bacteroidetes species specialize in carbohydrate digestion and Firmicutes in fat digestion. “In a lean, insulin-sensitive state, Bacteroidetes dominates the human gut microbiome,” Dr. Jahansouz said. “With the progression of obesity and insulin resistance, there is a subsequent shift in the microbiome phenotype, favoring the growth of Firmicutes at the expense and reduction of Bacteroidetes. This is a significant change, because this obesity-associated phenotype has an increased capacity to harvest energy. It’s not the same for a lean person to consume 1,000 calories as it is for an obese person to consume them.”

Bariatric surgery has been shown to alter the gut microbiome, shifting it toward this more “lean” profile (Cell Metab. 2015 Aug 4;22[2]:228-38). This shift may be an important component of the still not fully elucidated mechanisms by which bariatric surgery causes weight loss and normalizes insulin signaling, Dr. Jahansouz said.

Dr. Jahansouz is following this group of patients to explore whether there are differences in weight loss and insulin signaling. He also will track whether the microbiome stabilizes at its early postsurgical profile, or continues to shift, either toward an even higher Bacteroidetes to Firmicutes ratio, or back to a more “obese” profile.

He and his colleagues are also investigating the effect of antibiotics and gastric bypass surgery in mouse models. “I can say that antibiotics seem to have a remarkable impact on the effect of mouse sleeve gastrectomy. We’re not quite there yet with humans,” but the data are compelling.

Dr. Jahansouz said that he had no financial disclosures.

The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel

 

– Antibiotics given in advance of gastric bypass surgery preferentially alter the microbiome, nudging it toward a more “lean” physiologic profile.

Given before a sleeve gastrectomy, vancomycin, which has little gut penetration, barely shifted the high ratio of Firmicutes to Bacteroidetes, a profile typically associated with obesity and insulin resistance. But cefazolin, which has much higher gut penetration, suppressed the presence of Firmicutes, which metabolize fat, and allowed the expansion of carbohydrate-loving Bacteroidetes – a profile generally seen in lean people.

 


Cyrus Jahansouz, MD, of the University of Minnesota, Minneapolis, and his colleagues wanted to examine whether a shift in preoperative antibiotics might affect the way the microbiome re-establishes itself in the wake of vertical sleeve gastrectomy. They enrolled 32 patients who were candidates for the procedure. None had undergone prior gastrointestinal surgery, and none had been exposed to antibiotics in the 3 months prior to bariatric surgery. They were similar in age, weight, body mass index, and fasting glucose. The mean HbA1c was about 6%.

Patients were randomized to three groups: maximal diet therapy (800 calories per day) without surgery; vertical sleeve gastrectomy with the usual preoperative antibiotic cefazolin and the postsurgical diet; and vertical sleeve gastrectomy with preoperative vancomycin and the postsurgical diet. All patients gave a fecal sample immediately before surgery and another one 6 days after surgery.

Preoperative cluster analysis of bacterial DNA showed that all of the samples had a similar composition, predominated by Firmicutes species (60%-70%). Bacteroidetes species made up about 20%-30%, with Proteobacteriae, Actinobacteriae, Verrucomicrobia, and other phyla comprising the remainder of the microbiome.

At the second sampling, the diet-only group showed no microbiome changes at all. The vancomycin group showed a very small but not significant expansion of Bacteroidetes and reduction of Firmicutes.

Patients in the cefazolin group showed a significant shift in the ratio – and it was quite striking, Dr. Jahansouz said. Among these patients, Firmicutes had decreased from 70% to 40% of the community. Bacteroidetes showed a corresponding shift, increasing from 20% of the community to 45%. The findings are quite surprising, he noted, considering that only one dose of antibiotic was associated with the changes and that they were evident within just a few days.

Although “a little hard to interpret” because of its small size and short follow-up, the study suggests that antibiotic choice might contribute to the success of weight-loss surgery, Dr. Jahansouz said at the annual clinical congress of the American College of Surgeons.

“There are still several factors in the perioperative period that we have to study to be able to identify what other things might have also influenced the shift,” he said in an interview. “But I do think that, in the future, these changes can be manipulated to benefit metabolic outcomes.”

Two phyla – Bacteroidetes and Firmicutes – dominate the human gut microbiome in a dynamic ratio that is highly associated with the way energy is extracted from food. Bacteroidetes species specialize in carbohydrate digestion and Firmicutes in fat digestion. “In a lean, insulin-sensitive state, Bacteroidetes dominates the human gut microbiome,” Dr. Jahansouz said. “With the progression of obesity and insulin resistance, there is a subsequent shift in the microbiome phenotype, favoring the growth of Firmicutes at the expense and reduction of Bacteroidetes. This is a significant change, because this obesity-associated phenotype has an increased capacity to harvest energy. It’s not the same for a lean person to consume 1,000 calories as it is for an obese person to consume them.”

Bariatric surgery has been shown to alter the gut microbiome, shifting it toward this more “lean” profile (Cell Metab. 2015 Aug 4;22[2]:228-38). This shift may be an important component of the still not fully elucidated mechanisms by which bariatric surgery causes weight loss and normalizes insulin signaling, Dr. Jahansouz said.

Dr. Jahansouz is following this group of patients to explore whether there are differences in weight loss and insulin signaling. He also will track whether the microbiome stabilizes at its early postsurgical profile, or continues to shift, either toward an even higher Bacteroidetes to Firmicutes ratio, or back to a more “obese” profile.

He and his colleagues are also investigating the effect of antibiotics and gastric bypass surgery in mouse models. “I can say that antibiotics seem to have a remarkable impact on the effect of mouse sleeve gastrectomy. We’re not quite there yet with humans,” but the data are compelling.

Dr. Jahansouz said that he had no financial disclosures.

The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
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EXPERT ANALYSIS FROM THE ACS CLINICAL CONGRESS

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Young patients suffer most from PBC

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

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

 


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

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

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

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

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

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

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

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

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

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

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

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

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

 


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

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

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

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

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

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

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

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

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

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

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

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

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

 


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

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

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

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

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

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

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

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

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

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

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

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FROM ALIMENTARY PHARMACOLOGY AND THERAPEUTICS

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Key clinical point: Youth is no ally when it comes to primary biliary cholangitis.

Major finding: There was a linear relationship between age and quality of life (QoL) in patients with primary biliary cholangitis, with younger presenting patients having the poorest QoL. Each 10-year increase in presentation age was associated with a 14% decrease in the risk of poor QoL.

Data source: Review of 1,990 patients in the United Kingdom–PBC cohort.

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

Pancreaticobiliary potpourri

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

Dr. Todd H. Baron
There were many useful take-home points from the three lectures. Dr. Chari pointed out that, while most incidentally identified pancreatic cysts are clinically innocuous, it is often difficult to provide cost-effective care for patients with this entity. There are myriad pathologies in the differential diagnosis of the incidental cyst. Algorithms are available to differentiate benign cysts from those that are malignant or premalignant. Imaging features on CT and/or MRI can be useful, as can endoscopic ultrasound (EUS). The latter can allow for aspiration of fluid for analysis and provide tissue in some cases.
 

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

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

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

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

Dr. Todd H. Baron
There were many useful take-home points from the three lectures. Dr. Chari pointed out that, while most incidentally identified pancreatic cysts are clinically innocuous, it is often difficult to provide cost-effective care for patients with this entity. There are myriad pathologies in the differential diagnosis of the incidental cyst. Algorithms are available to differentiate benign cysts from those that are malignant or premalignant. Imaging features on CT and/or MRI can be useful, as can endoscopic ultrasound (EUS). The latter can allow for aspiration of fluid for analysis and provide tissue in some cases.
 

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

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

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

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

Dr. Todd H. Baron
There were many useful take-home points from the three lectures. Dr. Chari pointed out that, while most incidentally identified pancreatic cysts are clinically innocuous, it is often difficult to provide cost-effective care for patients with this entity. There are myriad pathologies in the differential diagnosis of the incidental cyst. Algorithms are available to differentiate benign cysts from those that are malignant or premalignant. Imaging features on CT and/or MRI can be useful, as can endoscopic ultrasound (EUS). The latter can allow for aspiration of fluid for analysis and provide tissue in some cases.
 

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

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

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

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Patient-reported outcomes tied to long-term outcomes in bariatric surgery

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Patient-reported outcomes tied to long-term outcomes in bariatric surgery

Clinical outcomes of surgery and patient-reported outcomes of function, disability, and health status are two different measures of surgical success.

A large study of patients who had bariatric surgery showed that patient-reported outcomes were correlated with long-term weight loss but not with short-term complication rates. In addition, obesity-specific patient-reported quality of life scores were associated with a reduction in medications required for the treatment of obesity-related conditions.

 

“Clinical outcomes, such as perioperative morbidity and mortality, are commonly used to benchmark hospital performance,” reported Jennifer F. Waljee, MD, and her associates at the University of Michigan, Ann Arbor (Ann Surg. 2016. doi: 10.1097/SLA.0000000000001852).

“However, for many surgical procedures, such as bariatric surgery ... complications may be rare, and may not entirely reflect treatment effectiveness. Alternatively, patient-reported measures of function, disability, and health status may offer a unique and more reliable assessment of provider quality and performance,” she explained. Yet despite growing interest in using patient-reported measures, many important questions regarding their accuracy, applicability, and clinical utility remain. The purpose of this study was, therefore, to evaluate how patient-reported quality of life measures compared to short-term and long-term clinical outcomes in patients who underwent bariatric surgery.

 

©Vasilis Varsakelis/fotolia.com

The majority of the study’s 11,420 participants were female (79.8%), were white (84.1%), and underwent Roux-en-Y laparoscopic gastric bypass (56.8%). For each study participant, both short-term and long-term clinical outcome measures were obtained from medical board review. Short-term clinical outcomes were defined as the rate of perioperative complications within 30 days of bariatric surgery. Percent excess weight loss at 1 year post surgery was used as a long-term clinical outcome.

In addition, two patient-reported outcomes were collected: an overall health-related quality of life score called the Health and Activities Limitations Index (HALex) and an obesity-specific quality of life score, the Bariatric Quality of Life (BQL) index, which measures well-being, social and physical functioning, and obesity-related symptoms.

Multivariate and linear regression models demonstrated that short-term complication rates were not correlated to the overall patient-reported quality of life score (P = .32) or to the obesity-specific BQL score (P = .74).

However, the long-term measure of excess weight loss at 1 year post surgery was significantly associated with both overall and obesity-specific patient-reported measures of health-related quality of life (P less than .002 and P less than .001 respectively).

Moreover, scores indicating improved quality of life were associated with greater weight loss.

Finally, comorbidity resolution, estimated by the reduction in the use of medications taken to treat conditions related to obesity, was significantly associated with the obesity-specific measure, BQL, but not the overall quality of life measure, HALex.

“In conclusion, [patient-reported outcomes] are distinct from clinical outcomes,” investigators wrote. Patient-reported outcomes “provide an opportunity for improved population-based cost-effectiveness analyses using outcomes germane to procedures performed for symptomatology and improving QOL,” they added.

The Agency for Healthcare Research and Quality supported the research. The investigators reported having no disclosures.

jcraig@frontlinemedcom.com

On Twitter @jessnicolecraig

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Clinical outcomes of surgery and patient-reported outcomes of function, disability, and health status are two different measures of surgical success.

A large study of patients who had bariatric surgery showed that patient-reported outcomes were correlated with long-term weight loss but not with short-term complication rates. In addition, obesity-specific patient-reported quality of life scores were associated with a reduction in medications required for the treatment of obesity-related conditions.

 

“Clinical outcomes, such as perioperative morbidity and mortality, are commonly used to benchmark hospital performance,” reported Jennifer F. Waljee, MD, and her associates at the University of Michigan, Ann Arbor (Ann Surg. 2016. doi: 10.1097/SLA.0000000000001852).

“However, for many surgical procedures, such as bariatric surgery ... complications may be rare, and may not entirely reflect treatment effectiveness. Alternatively, patient-reported measures of function, disability, and health status may offer a unique and more reliable assessment of provider quality and performance,” she explained. Yet despite growing interest in using patient-reported measures, many important questions regarding their accuracy, applicability, and clinical utility remain. The purpose of this study was, therefore, to evaluate how patient-reported quality of life measures compared to short-term and long-term clinical outcomes in patients who underwent bariatric surgery.

 

©Vasilis Varsakelis/fotolia.com

The majority of the study’s 11,420 participants were female (79.8%), were white (84.1%), and underwent Roux-en-Y laparoscopic gastric bypass (56.8%). For each study participant, both short-term and long-term clinical outcome measures were obtained from medical board review. Short-term clinical outcomes were defined as the rate of perioperative complications within 30 days of bariatric surgery. Percent excess weight loss at 1 year post surgery was used as a long-term clinical outcome.

In addition, two patient-reported outcomes were collected: an overall health-related quality of life score called the Health and Activities Limitations Index (HALex) and an obesity-specific quality of life score, the Bariatric Quality of Life (BQL) index, which measures well-being, social and physical functioning, and obesity-related symptoms.

Multivariate and linear regression models demonstrated that short-term complication rates were not correlated to the overall patient-reported quality of life score (P = .32) or to the obesity-specific BQL score (P = .74).

However, the long-term measure of excess weight loss at 1 year post surgery was significantly associated with both overall and obesity-specific patient-reported measures of health-related quality of life (P less than .002 and P less than .001 respectively).

Moreover, scores indicating improved quality of life were associated with greater weight loss.

Finally, comorbidity resolution, estimated by the reduction in the use of medications taken to treat conditions related to obesity, was significantly associated with the obesity-specific measure, BQL, but not the overall quality of life measure, HALex.

“In conclusion, [patient-reported outcomes] are distinct from clinical outcomes,” investigators wrote. Patient-reported outcomes “provide an opportunity for improved population-based cost-effectiveness analyses using outcomes germane to procedures performed for symptomatology and improving QOL,” they added.

The Agency for Healthcare Research and Quality supported the research. The investigators reported having no disclosures.

jcraig@frontlinemedcom.com

On Twitter @jessnicolecraig

Clinical outcomes of surgery and patient-reported outcomes of function, disability, and health status are two different measures of surgical success.

A large study of patients who had bariatric surgery showed that patient-reported outcomes were correlated with long-term weight loss but not with short-term complication rates. In addition, obesity-specific patient-reported quality of life scores were associated with a reduction in medications required for the treatment of obesity-related conditions.

 

“Clinical outcomes, such as perioperative morbidity and mortality, are commonly used to benchmark hospital performance,” reported Jennifer F. Waljee, MD, and her associates at the University of Michigan, Ann Arbor (Ann Surg. 2016. doi: 10.1097/SLA.0000000000001852).

“However, for many surgical procedures, such as bariatric surgery ... complications may be rare, and may not entirely reflect treatment effectiveness. Alternatively, patient-reported measures of function, disability, and health status may offer a unique and more reliable assessment of provider quality and performance,” she explained. Yet despite growing interest in using patient-reported measures, many important questions regarding their accuracy, applicability, and clinical utility remain. The purpose of this study was, therefore, to evaluate how patient-reported quality of life measures compared to short-term and long-term clinical outcomes in patients who underwent bariatric surgery.

 

©Vasilis Varsakelis/fotolia.com

The majority of the study’s 11,420 participants were female (79.8%), were white (84.1%), and underwent Roux-en-Y laparoscopic gastric bypass (56.8%). For each study participant, both short-term and long-term clinical outcome measures were obtained from medical board review. Short-term clinical outcomes were defined as the rate of perioperative complications within 30 days of bariatric surgery. Percent excess weight loss at 1 year post surgery was used as a long-term clinical outcome.

In addition, two patient-reported outcomes were collected: an overall health-related quality of life score called the Health and Activities Limitations Index (HALex) and an obesity-specific quality of life score, the Bariatric Quality of Life (BQL) index, which measures well-being, social and physical functioning, and obesity-related symptoms.

Multivariate and linear regression models demonstrated that short-term complication rates were not correlated to the overall patient-reported quality of life score (P = .32) or to the obesity-specific BQL score (P = .74).

However, the long-term measure of excess weight loss at 1 year post surgery was significantly associated with both overall and obesity-specific patient-reported measures of health-related quality of life (P less than .002 and P less than .001 respectively).

Moreover, scores indicating improved quality of life were associated with greater weight loss.

Finally, comorbidity resolution, estimated by the reduction in the use of medications taken to treat conditions related to obesity, was significantly associated with the obesity-specific measure, BQL, but not the overall quality of life measure, HALex.

“In conclusion, [patient-reported outcomes] are distinct from clinical outcomes,” investigators wrote. Patient-reported outcomes “provide an opportunity for improved population-based cost-effectiveness analyses using outcomes germane to procedures performed for symptomatology and improving QOL,” they added.

The Agency for Healthcare Research and Quality supported the research. The investigators reported having no disclosures.

jcraig@frontlinemedcom.com

On Twitter @jessnicolecraig

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FROM ANNALS OF SURGERY

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Key clinical point: Patient-reported quality of life measures were associated with long-term but not short-term clinical outcomes.

Major finding: Overall and obesity-specific patient-reported quality of life scores were associated with long-term excess weight loss (P less than .002 and P less than .001 respectively).

Data source: A retrospective study of 11,420 patients who underwent bariatric surgery.

Disclosures: The Agency for Healthcare Research and Quality supported the study. The investigators reported having no disclosures.

Data point to optimal window for endoscopy in sicker patients with peptic ulcer bleeding

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Data point to optimal window for endoscopy in sicker patients with peptic ulcer bleeding

 

The timing of endoscopy may make the difference between life and death in sicker patients with peptic ulcer bleeding, according to an analysis of more than 12,000 patients treated in Denmark.

Patients who were hemodynamically stable but had a higher level of comorbidity were about half as likely to die during their hospital stay if they underwent endoscopy within 12-36 hours of presentation as compared with sooner or later, results showed (Gastrointest Endosc. 2016 Sep 10. doi: 10.1016/j.gie.2016.08.049). And hemodynamically unstable patients had a roughly one-fourth reduction in the odds of death if they underwent the procedure within 6-24 hours.
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“Although caution should be applied when interpreting these data, the current recommendation of endoscopy within 0-24 hours may not be optimal for all patients,” wrote the investigators, who were led by Stig B. Laursen, PhD, department of medical gastroenterology, Odense (Denmark) University Hospital.

“Our data may suggest that in patients with major comorbidities, the first few hours of hospital admission might be best used for optimising treatment of comorbidities, which may include correction of severe anaemia, reversal of anticoagulants, and investigation for possible infection that requires rapid treatment with antibiotics,” they elaborate. “Likewise, in patients with hemodynamic instability, endoscopy between 6 and 24 hours from time of admission to hospital allows time for optimal resuscitation and initiating treatment of comorbid diseases before endoscopy. However, these data should not lead to delayed endoscopy in patients with severe hemodynamic instability not responding to intensive resuscitation.”

The investigators analyzed data from 12,601 consecutive patients with peptic ulcer bleeding admitted between January 2005 and September 2013 to Danish hospitals, where all patients had access to 24-hour endoscopy. Time to endoscopy was assessed from hospital admission, defined as arrival in the emergency department, or from symptom onset in patients who developed bleeding when already hospitalized.

For analyses, the patients were stratified by hemodynamic status (a marker for the severity of bleeding) and by American Society of Anesthesiologists score (a marker for the extent of comorbidity).
 

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The timing of endoscopy did not significantly influence in-hospital or 30-day mortality in hemodynamically stable patients with an American Society of Anesthesiologists score of 1-2 as a whole, Dr. Laursen and his colleagues report. Subgroup analyses suggested a reduction of in-hospital mortality when it was done between 0 and 24 hours in those patients whose bleeding began outside the hospital (adjusted odds ratio, 0.48).

In contrast, analyses revealed a U-shaped association between timing and mortality for hemodynamically stable patients with an American Society of Anesthesiologists score of 3-5. For this group, in-hospital mortality was significantly lower when endoscopy was performed within 12-36 hours as compared with times outside this window (adjusted OR, 0.48), and 30-day mortality tended to be lower as well.

Similarly, timing appeared to influence outcome for hemodynamically unstable patients, having both systolic blood pressure below 100 mm Hg and heart rate above 100 beats/min. For this group, performance of endoscopy within 6-24 hours was associated with significantly lower in-hospital mortality (adjusted OR, 0.73) and also 30-day mortality (adjusted OR, 0.66). Patients’ American Society of Anesthesiologists score did not appear to play a role here.

The study’s findings may have been affected by unmeasured and unknown confounders, acknowledge the investigators, who declared that they have no competing interests related to the research.

“Although a well-powered randomized controlled trial represents the best way to account for these problems, randomizing patients with [peptic ulcer bleeding] to early versus late endoscopy will be very difficult, including from an ethical and methodological point of view,” they note.

 

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The timing of endoscopy may make the difference between life and death in sicker patients with peptic ulcer bleeding, according to an analysis of more than 12,000 patients treated in Denmark.

Patients who were hemodynamically stable but had a higher level of comorbidity were about half as likely to die during their hospital stay if they underwent endoscopy within 12-36 hours of presentation as compared with sooner or later, results showed (Gastrointest Endosc. 2016 Sep 10. doi: 10.1016/j.gie.2016.08.049). And hemodynamically unstable patients had a roughly one-fourth reduction in the odds of death if they underwent the procedure within 6-24 hours.
[[{"attributes":{},"fields":{}}]]

 

“Although caution should be applied when interpreting these data, the current recommendation of endoscopy within 0-24 hours may not be optimal for all patients,” wrote the investigators, who were led by Stig B. Laursen, PhD, department of medical gastroenterology, Odense (Denmark) University Hospital.

“Our data may suggest that in patients with major comorbidities, the first few hours of hospital admission might be best used for optimising treatment of comorbidities, which may include correction of severe anaemia, reversal of anticoagulants, and investigation for possible infection that requires rapid treatment with antibiotics,” they elaborate. “Likewise, in patients with hemodynamic instability, endoscopy between 6 and 24 hours from time of admission to hospital allows time for optimal resuscitation and initiating treatment of comorbid diseases before endoscopy. However, these data should not lead to delayed endoscopy in patients with severe hemodynamic instability not responding to intensive resuscitation.”

The investigators analyzed data from 12,601 consecutive patients with peptic ulcer bleeding admitted between January 2005 and September 2013 to Danish hospitals, where all patients had access to 24-hour endoscopy. Time to endoscopy was assessed from hospital admission, defined as arrival in the emergency department, or from symptom onset in patients who developed bleeding when already hospitalized.

For analyses, the patients were stratified by hemodynamic status (a marker for the severity of bleeding) and by American Society of Anesthesiologists score (a marker for the extent of comorbidity).
 

[[{"attributes":{},"fields":{}}]]

The timing of endoscopy did not significantly influence in-hospital or 30-day mortality in hemodynamically stable patients with an American Society of Anesthesiologists score of 1-2 as a whole, Dr. Laursen and his colleagues report. Subgroup analyses suggested a reduction of in-hospital mortality when it was done between 0 and 24 hours in those patients whose bleeding began outside the hospital (adjusted odds ratio, 0.48).

In contrast, analyses revealed a U-shaped association between timing and mortality for hemodynamically stable patients with an American Society of Anesthesiologists score of 3-5. For this group, in-hospital mortality was significantly lower when endoscopy was performed within 12-36 hours as compared with times outside this window (adjusted OR, 0.48), and 30-day mortality tended to be lower as well.

Similarly, timing appeared to influence outcome for hemodynamically unstable patients, having both systolic blood pressure below 100 mm Hg and heart rate above 100 beats/min. For this group, performance of endoscopy within 6-24 hours was associated with significantly lower in-hospital mortality (adjusted OR, 0.73) and also 30-day mortality (adjusted OR, 0.66). Patients’ American Society of Anesthesiologists score did not appear to play a role here.

The study’s findings may have been affected by unmeasured and unknown confounders, acknowledge the investigators, who declared that they have no competing interests related to the research.

“Although a well-powered randomized controlled trial represents the best way to account for these problems, randomizing patients with [peptic ulcer bleeding] to early versus late endoscopy will be very difficult, including from an ethical and methodological point of view,” they note.

 

 

The timing of endoscopy may make the difference between life and death in sicker patients with peptic ulcer bleeding, according to an analysis of more than 12,000 patients treated in Denmark.

Patients who were hemodynamically stable but had a higher level of comorbidity were about half as likely to die during their hospital stay if they underwent endoscopy within 12-36 hours of presentation as compared with sooner or later, results showed (Gastrointest Endosc. 2016 Sep 10. doi: 10.1016/j.gie.2016.08.049). And hemodynamically unstable patients had a roughly one-fourth reduction in the odds of death if they underwent the procedure within 6-24 hours.
[[{"attributes":{},"fields":{}}]]

 

“Although caution should be applied when interpreting these data, the current recommendation of endoscopy within 0-24 hours may not be optimal for all patients,” wrote the investigators, who were led by Stig B. Laursen, PhD, department of medical gastroenterology, Odense (Denmark) University Hospital.

“Our data may suggest that in patients with major comorbidities, the first few hours of hospital admission might be best used for optimising treatment of comorbidities, which may include correction of severe anaemia, reversal of anticoagulants, and investigation for possible infection that requires rapid treatment with antibiotics,” they elaborate. “Likewise, in patients with hemodynamic instability, endoscopy between 6 and 24 hours from time of admission to hospital allows time for optimal resuscitation and initiating treatment of comorbid diseases before endoscopy. However, these data should not lead to delayed endoscopy in patients with severe hemodynamic instability not responding to intensive resuscitation.”

The investigators analyzed data from 12,601 consecutive patients with peptic ulcer bleeding admitted between January 2005 and September 2013 to Danish hospitals, where all patients had access to 24-hour endoscopy. Time to endoscopy was assessed from hospital admission, defined as arrival in the emergency department, or from symptom onset in patients who developed bleeding when already hospitalized.

For analyses, the patients were stratified by hemodynamic status (a marker for the severity of bleeding) and by American Society of Anesthesiologists score (a marker for the extent of comorbidity).
 

[[{"attributes":{},"fields":{}}]]

The timing of endoscopy did not significantly influence in-hospital or 30-day mortality in hemodynamically stable patients with an American Society of Anesthesiologists score of 1-2 as a whole, Dr. Laursen and his colleagues report. Subgroup analyses suggested a reduction of in-hospital mortality when it was done between 0 and 24 hours in those patients whose bleeding began outside the hospital (adjusted odds ratio, 0.48).

In contrast, analyses revealed a U-shaped association between timing and mortality for hemodynamically stable patients with an American Society of Anesthesiologists score of 3-5. For this group, in-hospital mortality was significantly lower when endoscopy was performed within 12-36 hours as compared with times outside this window (adjusted OR, 0.48), and 30-day mortality tended to be lower as well.

Similarly, timing appeared to influence outcome for hemodynamically unstable patients, having both systolic blood pressure below 100 mm Hg and heart rate above 100 beats/min. For this group, performance of endoscopy within 6-24 hours was associated with significantly lower in-hospital mortality (adjusted OR, 0.73) and also 30-day mortality (adjusted OR, 0.66). Patients’ American Society of Anesthesiologists score did not appear to play a role here.

The study’s findings may have been affected by unmeasured and unknown confounders, acknowledge the investigators, who declared that they have no competing interests related to the research.

“Although a well-powered randomized controlled trial represents the best way to account for these problems, randomizing patients with [peptic ulcer bleeding] to early versus late endoscopy will be very difficult, including from an ethical and methodological point of view,” they note.

 

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Key clinical point: There appears to be an optimal window for performing endoscopy in sicker patients with peptic ulcer bleeding, balancing the benefit of prompt therapy with the benefit of stabilizing clinical status.

Major finding: In-hospital mortality was lower when endoscopy was performed within 12-36 hours in hemodynamically stable patients with higher comorbidity (odds ratio, 0.48) and within 6-24 hours in hemodynamically unstable patients (OR, 0.73).

Data source: A nationwide cohort study of 12,601 consecutive patients admitted to Danish hospitals with peptic ulcer bleeding.

Disclosures: The investigators declare that they do not have any competing interests.

Antibiotic susceptibility differs in transplant recipients

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Antibiotic susceptibility differs in transplant recipients

Antibiotic susceptibility in bacteria cultured from transplant recipients at a single hospital differed markedly from that in hospital-wide antibiograms, according to a report published in Diagnostic Microbiology and Infectious Disease.

Understanding the differences in antibiotic susceptibility among these highly immunocompromised patients can help guide treatment when they develop infection, and reduce the delay before they begin receiving appropriate antibiotics, said Rossana Rosa, MD, of Jackson Memorial Hospital, Miami, and her associates.

The investigators examined the antibiotic susceptibility of 1,889 isolates from blood and urine specimens taken from patients who had received solid-organ transplants at a single tertiary-care teaching hospital and then developed bacterial infections during a 2-year period. These patients included both children and adults who had received kidney, pancreas, liver, heart, lung, or intestinal transplants and were treated in numerous, “geographically distributed” units throughout the hospital. Their culture results were compared with those from 10,439 other patients with bacterial infections, which comprised the hospital-wide antibiograms developed every 6 months during the study period.

 

The Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa isolates from the transplant recipients showed markedly less susceptibility to first-line antibiotics than would have been predicted by the hospital-antibiograms. In particular, in the transplant recipients E. coli infections were resistant to trimethoprim-sulfamethoxazole, levofloxacin, and ceftriaxone; K. pneumoniae infections were resistant to every antibiotic except amikacin; and P. aeruginosa infections were resistant to levofloxacin, cefepime, and amikacin (Diag Microbiol Infect Dis. 2016 Aug 25. doi: 10.1016/j.diagmicrobio.2016.08.018).

“We advocate for the development of antibiograms specific to solid-organ transplant recipients. This may allow intrahospital comparisons and intertransplant-center monitoring of trends in antimicrobial resistance over time,” Dr. Rosa and her associates said.

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Antibiotic susceptibility in bacteria cultured from transplant recipients at a single hospital differed markedly from that in hospital-wide antibiograms, according to a report published in Diagnostic Microbiology and Infectious Disease.

Understanding the differences in antibiotic susceptibility among these highly immunocompromised patients can help guide treatment when they develop infection, and reduce the delay before they begin receiving appropriate antibiotics, said Rossana Rosa, MD, of Jackson Memorial Hospital, Miami, and her associates.

The investigators examined the antibiotic susceptibility of 1,889 isolates from blood and urine specimens taken from patients who had received solid-organ transplants at a single tertiary-care teaching hospital and then developed bacterial infections during a 2-year period. These patients included both children and adults who had received kidney, pancreas, liver, heart, lung, or intestinal transplants and were treated in numerous, “geographically distributed” units throughout the hospital. Their culture results were compared with those from 10,439 other patients with bacterial infections, which comprised the hospital-wide antibiograms developed every 6 months during the study period.

 

The Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa isolates from the transplant recipients showed markedly less susceptibility to first-line antibiotics than would have been predicted by the hospital-antibiograms. In particular, in the transplant recipients E. coli infections were resistant to trimethoprim-sulfamethoxazole, levofloxacin, and ceftriaxone; K. pneumoniae infections were resistant to every antibiotic except amikacin; and P. aeruginosa infections were resistant to levofloxacin, cefepime, and amikacin (Diag Microbiol Infect Dis. 2016 Aug 25. doi: 10.1016/j.diagmicrobio.2016.08.018).

“We advocate for the development of antibiograms specific to solid-organ transplant recipients. This may allow intrahospital comparisons and intertransplant-center monitoring of trends in antimicrobial resistance over time,” Dr. Rosa and her associates said.

Antibiotic susceptibility in bacteria cultured from transplant recipients at a single hospital differed markedly from that in hospital-wide antibiograms, according to a report published in Diagnostic Microbiology and Infectious Disease.

Understanding the differences in antibiotic susceptibility among these highly immunocompromised patients can help guide treatment when they develop infection, and reduce the delay before they begin receiving appropriate antibiotics, said Rossana Rosa, MD, of Jackson Memorial Hospital, Miami, and her associates.

The investigators examined the antibiotic susceptibility of 1,889 isolates from blood and urine specimens taken from patients who had received solid-organ transplants at a single tertiary-care teaching hospital and then developed bacterial infections during a 2-year period. These patients included both children and adults who had received kidney, pancreas, liver, heart, lung, or intestinal transplants and were treated in numerous, “geographically distributed” units throughout the hospital. Their culture results were compared with those from 10,439 other patients with bacterial infections, which comprised the hospital-wide antibiograms developed every 6 months during the study period.

 

The Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa isolates from the transplant recipients showed markedly less susceptibility to first-line antibiotics than would have been predicted by the hospital-antibiograms. In particular, in the transplant recipients E. coli infections were resistant to trimethoprim-sulfamethoxazole, levofloxacin, and ceftriaxone; K. pneumoniae infections were resistant to every antibiotic except amikacin; and P. aeruginosa infections were resistant to levofloxacin, cefepime, and amikacin (Diag Microbiol Infect Dis. 2016 Aug 25. doi: 10.1016/j.diagmicrobio.2016.08.018).

“We advocate for the development of antibiograms specific to solid-organ transplant recipients. This may allow intrahospital comparisons and intertransplant-center monitoring of trends in antimicrobial resistance over time,” Dr. Rosa and her associates said.

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Antibiotic susceptibility differs in transplant recipients
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Key clinical point: Antibiotic susceptibility in bacteria cultured from transplant recipients differs markedly from that in hospital-wide antibiograms.

Major finding: In the transplant recipients, E. coli infections were resistant to trimethoprim-sulfamethoxazole, levofloxacin, and ceftriaxone; K. pneumoniae infections were resistant to every antibiotic except amikacin; and P. aeruginosa infections were resistant to levofloxacin, cefepime, and amikacin.

Data source: A single-center study comparing the antibiotic susceptibility of 1,889 bacterial isolates from transplant recipients with 10,439 isolates from other patients.

Disclosures: This study was not supported by funding from any public, commercial, or not-for-profit entities. Dr. Rosa and her associates reported having no relevant financial disclosures.

Roux-en-Y gastric bypass associated with long-term weight loss

Debunking bariatric surgery myths
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Obese patients who underwent Roux-en-Y gastric bypass had higher percentages of weight loss at long-term follow-up, compared with obese patients who underwent other surgical procedures or who did not undergo surgery, according to a large, cohort study published in JAMA Surgery.

While prior research has clearly demonstrated that bariatric surgery is the most effective intervention for inducing weight loss among obese patients, the majority of those studies were short term; therefore, there is little known about the durability of weight loss following bariatric surgery, wrote Matthew Maciejewski, PhD, of Duke University, Durham, N.C., and Durham Veterans Affairs Medical Center and his associates.

 

Dr. Matthew Maciejewski

This study compared the 10-year weight change in patients who underwent Roux-en-Y gastric bypass to patients who did not receive bariatric surgical intervention of any kind. A total of 1,787 patients who had undergone Roux-en-Y gastric bypass surgery were identified and matched by investigators to one or more patients with similar demographic characteristics (age, sex, race, body mass index, diabetes diagnosis). A total of 5,305 nonsurgical matches were selected for analysis. For the Roux-en-Y gastric bypass group, mean age was 52.1 years, and for the nonsurgical matches mean age was 52.2 years. Both groups were predominantly male (73.1% and 73.7%, respectively) and had high 10-year follow-up rates of 81.9% for surgical patients and 67.4% for nonsurgical matches (JAMA Surgery. 2016. doi: 10.1001/jamasurg.2016.2317).

The study’s primary outcome of percentage change in weight at 10-year follow-up, compared with baseline strongly favored Roux-en-Y gastric bypass over no surgical intervention. At the 10-year time point, patients who underwent Roux-en-Y gastric bypass had lost 21.3% more of their baseline weight than nonsurgical matches.

 

Remarkably, only 3.4% of patients who underwent Roux-en-Y gastric bypass were within 5% of their original baseline weight at 10 years while 55.5% of those who did not receive surgical intervention had regained most of their weight.

Additionally, investigators compared percentage change in weight at 4-year follow-up for obese patients who underwent either Roux-en-Y gastric bypass (n = 1,785), sleeve gastrectomy (n = 379), or adjustable gastric banding (n = 246). At this time point, patients who underwent Roux-en-Y gastric bypass had lost an average of 28% of their baseline weight while patients who underwent sleeve gastrectomy or adjustable gastric banding only lost 18% and 11% of their baseline weights, respectively.

“These results provide further evidence for the beneficial association between surgery and long-term weight loss that has been demonstrated in shorter-term studies of younger, predominantly female populations,” the investigators concluded.

This study was funded by the Department of Veterans Affairs. Dr. Maciejewski and four of his associates reported receiving financial compensation from or holding stock in various companies and institutions including the Department of Veterans Affairs.

jcraig@frontlinemedcom.com

On Twitter @jessnicolecraig

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One of the most prevalent perceptions held by many is that most bariatric surgery patients will eventually gain all of their weight back. As illustrated in the article by Maciejewski et al., studies that follow up with a large cohort of bariatric surgery patients for more than a few years are limited and hampered by low rates of long-term follow-up. While the results of these studies generally imply that long-term weight loss is possible in most patients, poor follow-up leaves one to wonder whether this is a generalizable conclusion.

In the article by Maciejewski et al., it is remarkable that such a low number of gastric bypass patients (3%) regained weight back to within 5% of their baseline weight by 10 years. With the publication of the article by Maciejewski et al., the perception that all metabolic and bariatric surgery patients gain their weight back has become less valid.

Jon C. Gould, MD, is the chief of the division of general surgery at the Medical College of Wisconsin in Milwaukee. His comments were taken from his editorial accompanying the report by Dr. Maciejewski and his colleagues (JAMA Surgery. 2016. doi: 10.1001/jamasurg.2016.2301).

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One of the most prevalent perceptions held by many is that most bariatric surgery patients will eventually gain all of their weight back. As illustrated in the article by Maciejewski et al., studies that follow up with a large cohort of bariatric surgery patients for more than a few years are limited and hampered by low rates of long-term follow-up. While the results of these studies generally imply that long-term weight loss is possible in most patients, poor follow-up leaves one to wonder whether this is a generalizable conclusion.

In the article by Maciejewski et al., it is remarkable that such a low number of gastric bypass patients (3%) regained weight back to within 5% of their baseline weight by 10 years. With the publication of the article by Maciejewski et al., the perception that all metabolic and bariatric surgery patients gain their weight back has become less valid.

Jon C. Gould, MD, is the chief of the division of general surgery at the Medical College of Wisconsin in Milwaukee. His comments were taken from his editorial accompanying the report by Dr. Maciejewski and his colleagues (JAMA Surgery. 2016. doi: 10.1001/jamasurg.2016.2301).

Body

One of the most prevalent perceptions held by many is that most bariatric surgery patients will eventually gain all of their weight back. As illustrated in the article by Maciejewski et al., studies that follow up with a large cohort of bariatric surgery patients for more than a few years are limited and hampered by low rates of long-term follow-up. While the results of these studies generally imply that long-term weight loss is possible in most patients, poor follow-up leaves one to wonder whether this is a generalizable conclusion.

In the article by Maciejewski et al., it is remarkable that such a low number of gastric bypass patients (3%) regained weight back to within 5% of their baseline weight by 10 years. With the publication of the article by Maciejewski et al., the perception that all metabolic and bariatric surgery patients gain their weight back has become less valid.

Jon C. Gould, MD, is the chief of the division of general surgery at the Medical College of Wisconsin in Milwaukee. His comments were taken from his editorial accompanying the report by Dr. Maciejewski and his colleagues (JAMA Surgery. 2016. doi: 10.1001/jamasurg.2016.2301).

Title
Debunking bariatric surgery myths
Debunking bariatric surgery myths

Obese patients who underwent Roux-en-Y gastric bypass had higher percentages of weight loss at long-term follow-up, compared with obese patients who underwent other surgical procedures or who did not undergo surgery, according to a large, cohort study published in JAMA Surgery.

While prior research has clearly demonstrated that bariatric surgery is the most effective intervention for inducing weight loss among obese patients, the majority of those studies were short term; therefore, there is little known about the durability of weight loss following bariatric surgery, wrote Matthew Maciejewski, PhD, of Duke University, Durham, N.C., and Durham Veterans Affairs Medical Center and his associates.

 

Dr. Matthew Maciejewski

This study compared the 10-year weight change in patients who underwent Roux-en-Y gastric bypass to patients who did not receive bariatric surgical intervention of any kind. A total of 1,787 patients who had undergone Roux-en-Y gastric bypass surgery were identified and matched by investigators to one or more patients with similar demographic characteristics (age, sex, race, body mass index, diabetes diagnosis). A total of 5,305 nonsurgical matches were selected for analysis. For the Roux-en-Y gastric bypass group, mean age was 52.1 years, and for the nonsurgical matches mean age was 52.2 years. Both groups were predominantly male (73.1% and 73.7%, respectively) and had high 10-year follow-up rates of 81.9% for surgical patients and 67.4% for nonsurgical matches (JAMA Surgery. 2016. doi: 10.1001/jamasurg.2016.2317).

The study’s primary outcome of percentage change in weight at 10-year follow-up, compared with baseline strongly favored Roux-en-Y gastric bypass over no surgical intervention. At the 10-year time point, patients who underwent Roux-en-Y gastric bypass had lost 21.3% more of their baseline weight than nonsurgical matches.

 

Remarkably, only 3.4% of patients who underwent Roux-en-Y gastric bypass were within 5% of their original baseline weight at 10 years while 55.5% of those who did not receive surgical intervention had regained most of their weight.

Additionally, investigators compared percentage change in weight at 4-year follow-up for obese patients who underwent either Roux-en-Y gastric bypass (n = 1,785), sleeve gastrectomy (n = 379), or adjustable gastric banding (n = 246). At this time point, patients who underwent Roux-en-Y gastric bypass had lost an average of 28% of their baseline weight while patients who underwent sleeve gastrectomy or adjustable gastric banding only lost 18% and 11% of their baseline weights, respectively.

“These results provide further evidence for the beneficial association between surgery and long-term weight loss that has been demonstrated in shorter-term studies of younger, predominantly female populations,” the investigators concluded.

This study was funded by the Department of Veterans Affairs. Dr. Maciejewski and four of his associates reported receiving financial compensation from or holding stock in various companies and institutions including the Department of Veterans Affairs.

jcraig@frontlinemedcom.com

On Twitter @jessnicolecraig

Obese patients who underwent Roux-en-Y gastric bypass had higher percentages of weight loss at long-term follow-up, compared with obese patients who underwent other surgical procedures or who did not undergo surgery, according to a large, cohort study published in JAMA Surgery.

While prior research has clearly demonstrated that bariatric surgery is the most effective intervention for inducing weight loss among obese patients, the majority of those studies were short term; therefore, there is little known about the durability of weight loss following bariatric surgery, wrote Matthew Maciejewski, PhD, of Duke University, Durham, N.C., and Durham Veterans Affairs Medical Center and his associates.

 

Dr. Matthew Maciejewski

This study compared the 10-year weight change in patients who underwent Roux-en-Y gastric bypass to patients who did not receive bariatric surgical intervention of any kind. A total of 1,787 patients who had undergone Roux-en-Y gastric bypass surgery were identified and matched by investigators to one or more patients with similar demographic characteristics (age, sex, race, body mass index, diabetes diagnosis). A total of 5,305 nonsurgical matches were selected for analysis. For the Roux-en-Y gastric bypass group, mean age was 52.1 years, and for the nonsurgical matches mean age was 52.2 years. Both groups were predominantly male (73.1% and 73.7%, respectively) and had high 10-year follow-up rates of 81.9% for surgical patients and 67.4% for nonsurgical matches (JAMA Surgery. 2016. doi: 10.1001/jamasurg.2016.2317).

The study’s primary outcome of percentage change in weight at 10-year follow-up, compared with baseline strongly favored Roux-en-Y gastric bypass over no surgical intervention. At the 10-year time point, patients who underwent Roux-en-Y gastric bypass had lost 21.3% more of their baseline weight than nonsurgical matches.

 

Remarkably, only 3.4% of patients who underwent Roux-en-Y gastric bypass were within 5% of their original baseline weight at 10 years while 55.5% of those who did not receive surgical intervention had regained most of their weight.

Additionally, investigators compared percentage change in weight at 4-year follow-up for obese patients who underwent either Roux-en-Y gastric bypass (n = 1,785), sleeve gastrectomy (n = 379), or adjustable gastric banding (n = 246). At this time point, patients who underwent Roux-en-Y gastric bypass had lost an average of 28% of their baseline weight while patients who underwent sleeve gastrectomy or adjustable gastric banding only lost 18% and 11% of their baseline weights, respectively.

“These results provide further evidence for the beneficial association between surgery and long-term weight loss that has been demonstrated in shorter-term studies of younger, predominantly female populations,” the investigators concluded.

This study was funded by the Department of Veterans Affairs. Dr. Maciejewski and four of his associates reported receiving financial compensation from or holding stock in various companies and institutions including the Department of Veterans Affairs.

jcraig@frontlinemedcom.com

On Twitter @jessnicolecraig

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Roux-en-Y gastric bypass associated with long-term weight loss
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Key clinical point: Roux-en-Y gastric bypass led to higher percentages of weight loss at long-term follow-up.

Major finding: Four years post treatment, patients who underwent Roux-en-Y gastric bypass lost an average of 28% of their baseline weight while patients who underwent sleeve gastrectomy or adjustable gastric banding lost only 18% and 11% of their baseline weights, respectively. At 10 years, patients who underwent Roux-en-Y had lost 21% more of their baseline weight than those who did not receive surgery.

Data source: Retrospective cohort study of 1,787 patients who had undergone Roux-en-Y gastric bypass surgery.

Disclosures: This study was funded by the Department of Veterans Affairs. Dr. Maciejewski and four of his associates reported receiving financial compensation from or holding stock in various companies and institutions including the Department of Veterans Affairs.

Two incretin-based drugs linked to increased bile duct disease but not pancreatitis

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Two incretin-based drugs linked to increased bile duct disease but not pancreatitis

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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Two incretin-based drugs linked to increased bile duct disease but not pancreatitis
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Key clinical point: Glucagon-like peptide 1 agonists do not appear to increase the risk of acute pancreatitis in individuals with diabetes but are associated with an increased risk of bile duct and gallbladder disease.

Major finding: GLP-1 agonists are associated with a 79% increase in the risk of bile duct and gallbladder disease, compared with other oral antidiabetic medications, but do not increase the risk of acute pancreatitis.

Data source: Two population-based cohort studies; one involving more than 1.5 million individuals with type 2 diabetes across three countries, and the other involving 71,368 patients with type 2 diabetes.

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

Rectal indomethacin cut odds of post-ERCP pancreatitis in real-world study

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Rectal indomethacin cut odds of post-ERCP pancreatitis in real-world study

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.

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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.

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Key clinical point: A single 100-mg rectal dose of indomethacin given immediately after endoscopic retrograde cholangiopancreatography significantly reduced the odds of postprocedural pancreatitis, including in low-risk patients and those with malignant obstruction.

Major finding: The odds of pancreatitis were 65% lower when patients received rectal indomethacin than otherwise.

Data source: A single-center retrospective cohort study of 4,017 patients undergoing ERCP.

Disclosures: The investigators reported no funding sources and had no disclosures.