Endoscopy, Pancreas, & Biliary Tract

Patients with diabetes who take either sitagliptin or exenatide were twice as likely to experience acute pancreatitis as those who did not take the GLP-1 inhibitors, a large database review has determined.

The authors made no recommendations about using the drugs, instead saying that the findings call for confirmation by more rigorous studies.

"Further studies using new user designs should clarify the exact timing of these risks and determine whether susceptible subgroups, such as those with genetic mutations, or pancreatitis risks, such as obesity, may be at the highest risk," Dr. Sonal Singh and his colleagues wrote in the Feb. 25 online issue of JAMA Internal Medicine (formerly Archives of Internal Medicine) (doi: 10.1001/jamainternmed.2013.2720).

But the American Association of Clinical Endocrinologists (AACE), the American Diabetes Association, and the Endocrine Society are criticizing the study, saying that the risk of pancreatitis over a large population is very low, and that for most patients, the drugs’ benefits far outweigh that risk.

"This story is very simple," said Dr. Yehuda Handelsman, speaking for AACE. "Since day 1, we have been telling physicians there could be a bit of increase in the risk of pancreatitis with the drugs. But the risk is so minimal that we don’t believe anyone should change their practice based on this study."

The review included 1,269 controls and 1,269 patients who used the drugs and were hospitalized for acute pancreatitis during 2005-2008. Study subjects had a mean age of 52 years. Several comorbidities were significantly more common among the case patients than among controls, including elevated triglycerides (13% vs. 8%), alcohol use (3.2% vs. 0.2%), gallstones (9% vs. 1%), tobacco abuse (16% vs. 6%), obesity (20% vs. 10%), biliary and pancreatic cancer (3% vs. 0%), cystic fibrosis (1% vs. 0%), and any neoplasm (30% vs. 18%).

Photo courtesy of Dr. Yehuda Handelsman

Dr. Singh of Johns Hopkins University, Baltimore, and his associates controlled for all of these factors by using a multifactorial analysis, as well as an indicator of general morbidity level developed by the university.

After adjustment for these confounders and for metformin use, patients who had taking either sitagliptin or exenatide in the past 30 days were more than twice as likely to have experienced acute pancreatitis (odds ratio, 2.24). Those who had taken the drugs within the past 30 days to 2 years were twice as likely to have had the illness (OR, 2). Any use of the drugs – which included both 30-day and recent use – was associated with a doubling of the risk (OR, 2.1).

A sensitivity analysis excluded nine case-control pairs who were exposed to a combination of metformin and sitagliptin. After adjustment for the confounders, this subanalysis agreed with the primary findings. Current use of either drug within 30 days was associated with a doubled risk (OR, 2) as was recent use (OR, 1.95), and any use (OR, 2).

The study did not indicate the total number of patients in the database who were taking the drugs and who developed pancreatitis. This skewed the findings, said Dr. Handelsman, because it misrepresented the actual frequency of the illness in this group, which he said was very, very low. In an e-mail, Dr. Singh said, "Those numbers are not available in a case-control study."

And even though the study controlled for the significant baseline differences between the two groups, these also tainted the conclusions, said Dr. Handelsman, who is also the principal investigator at the Metabolic Institute of America in Tarzana, Calif. "Patients who are obese, who drink a lot and smoke a lot, who have gallstones – they are all more likely to get pancreatitis. We tell doctors, if you’re going to give the drugs to these patients, just watch them more carefully."

In a joint statement, AACE and ADA voiced concern that patients could stop taking their prescribed treatments. "We encourage patients to speak with their doctors to assess which treatments are best for them and not to stop therapy on their own without consulting their doctors."

A link between glucagonlike peptide–1(GLP-1) inhibitors and pancreatitis has never been firmly established. But, according to a recent review, questions remain – many centering around safety reviews performed by pharmaceutical companies, which were based on their own prospective studies (Gastroenterology 2011;141:20-3).

Animal studies have suggested a physiological link, wrote Dr. Joachim Spranger of the German Medical Association. "Exocrine pancreatic cells express the GLP-1 receptor [GLP-1R], and administering GLP-1 has biological effects on these cells. In animal experiments (Diabetes 2009;58:2148-61), 1 week of GLP-1R activation with liraglutide or exenatide increased pancreatic weight and changed pancreatitis-associated gene expression, although the DPP-4 [dipeptidyl peptidase–4] inhibitor sitagliptin had no such effects. Theoretically, the increased pancreatic weight may reflect edema or similar changes, although the underlying cause of the weight increase was not further analyzed and histopathology results were not reported."

Any pancreatic effect of the drugs could be directly related to the beneficial physiological changes they induce in the pancreas, Dr. Spranger wrote. GLP-1 agonists increase beta-cell mass in rodents, by enhancing beta-cell proliferation, inhibiting apoptosis, and enhancing stem cell differentiation in the ductal pancreatic epithelium.

"Although beta-cell proliferation may be beneficial with regard to progression of type 2 diabetes, similar trophic mechanisms in other cell types might be detrimental. Thus, the epidermal growth factor receptor system and the Src kinase have been implicated in the pathogenesis and progression of numerous malignant tumors, including pancreatic cancer; mechanisms increasing the activity of these pathways could promote tumor development or progression."

The observations raise safety concerns which should be heeded until proven unfounded, Dr. Spranger wrote.

More detailed data about the link between incretin-based therapies and pancreatitis should be forthcoming, as long-term prospective studies continue to collect a wide range of safety information.

"There are at least nine prospective trials looking at cardiovascular outcomes which are capturing a lot of other outcomes data as well – including pancreatitis," Dr. Handelsman said. "In a few years we might be able to identify the true risk. But a scare based on an observational study from one insurance database, from years ago, is not enough to change practice."

The Endocrine Society’s response to Dr. Singh’s study echoed that of AACE and ADA, and added that "an important but unanswered question is whether or not the morbidity and mortality from incretin-associated pancreatitis is the same as that of other causes of pancreatitis," in particular whether such cases would lead to an increased incidence of pancreatic cancer similar to that seen in some other causes of acute pancreatitis. The statement suggested that some of the ongoing trials "may also help elucidate the conflict between Singh’s finding of increased incidence of acute pancreatitis with these drugs and the four recent retrospective database analyses and 1 meta-analysis cited in Singh’s paper which found no such association."

Dr. Singh’s study was sponsored by Johns Hopkins University and the National Institutes of Health. He had no financial disclosures. Dr. Handelsman has been a consultant to numerous drug companies developing diabetes treatments. Dr. Spranger has lectured for or received consultant honoraria from Eli Lilly and NovoNordisk.

[email protected]

Patients with diabetes who take either sitagliptin or exenatide were twice as likely to experience acute pancreatitis as those who did not take the GLP-1 inhibitors, a large database review has determined.

The authors made no recommendations about using the drugs, instead saying that the findings call for confirmation by more rigorous studies.

"Further studies using new user designs should clarify the exact timing of these risks and determine whether susceptible subgroups, such as those with genetic mutations, or pancreatitis risks, such as obesity, may be at the highest risk," Dr. Sonal Singh and his colleagues wrote in the Feb. 25 online issue of JAMA Internal Medicine (formerly Archives of Internal Medicine) (doi: 10.1001/jamainternmed.2013.2720).

But the American Association of Clinical Endocrinologists (AACE), the American Diabetes Association, and the Endocrine Society are criticizing the study, saying that the risk of pancreatitis over a large population is very low, and that for most patients, the drugs’ benefits far outweigh that risk.

"This story is very simple," said Dr. Yehuda Handelsman, speaking for AACE. "Since day 1, we have been telling physicians there could be a bit of increase in the risk of pancreatitis with the drugs. But the risk is so minimal that we don’t believe anyone should change their practice based on this study."

The review included 1,269 controls and 1,269 patients who used the drugs and were hospitalized for acute pancreatitis during 2005-2008. Study subjects had a mean age of 52 years. Several comorbidities were significantly more common among the case patients than among controls, including elevated triglycerides (13% vs. 8%), alcohol use (3.2% vs. 0.2%), gallstones (9% vs. 1%), tobacco abuse (16% vs. 6%), obesity (20% vs. 10%), biliary and pancreatic cancer (3% vs. 0%), cystic fibrosis (1% vs. 0%), and any neoplasm (30% vs. 18%).

Photo courtesy of Dr. Yehuda Handelsman

Dr. Singh of Johns Hopkins University, Baltimore, and his associates controlled for all of these factors by using a multifactorial analysis, as well as an indicator of general morbidity level developed by the university.

After adjustment for these confounders and for metformin use, patients who had taking either sitagliptin or exenatide in the past 30 days were more than twice as likely to have experienced acute pancreatitis (odds ratio, 2.24). Those who had taken the drugs within the past 30 days to 2 years were twice as likely to have had the illness (OR, 2). Any use of the drugs – which included both 30-day and recent use – was associated with a doubling of the risk (OR, 2.1).

A sensitivity analysis excluded nine case-control pairs who were exposed to a combination of metformin and sitagliptin. After adjustment for the confounders, this subanalysis agreed with the primary findings. Current use of either drug within 30 days was associated with a doubled risk (OR, 2) as was recent use (OR, 1.95), and any use (OR, 2).

The study did not indicate the total number of patients in the database who were taking the drugs and who developed pancreatitis. This skewed the findings, said Dr. Handelsman, because it misrepresented the actual frequency of the illness in this group, which he said was very, very low. In an e-mail, Dr. Singh said, "Those numbers are not available in a case-control study."

And even though the study controlled for the significant baseline differences between the two groups, these also tainted the conclusions, said Dr. Handelsman, who is also the principal investigator at the Metabolic Institute of America in Tarzana, Calif. "Patients who are obese, who drink a lot and smoke a lot, who have gallstones – they are all more likely to get pancreatitis. We tell doctors, if you’re going to give the drugs to these patients, just watch them more carefully."

In a joint statement, AACE and ADA voiced concern that patients could stop taking their prescribed treatments. "We encourage patients to speak with their doctors to assess which treatments are best for them and not to stop therapy on their own without consulting their doctors."

A link between glucagonlike peptide–1(GLP-1) inhibitors and pancreatitis has never been firmly established. But, according to a recent review, questions remain – many centering around safety reviews performed by pharmaceutical companies, which were based on their own prospective studies (Gastroenterology 2011;141:20-3).

Animal studies have suggested a physiological link, wrote Dr. Joachim Spranger of the German Medical Association. "Exocrine pancreatic cells express the GLP-1 receptor [GLP-1R], and administering GLP-1 has biological effects on these cells. In animal experiments (Diabetes 2009;58:2148-61), 1 week of GLP-1R activation with liraglutide or exenatide increased pancreatic weight and changed pancreatitis-associated gene expression, although the DPP-4 [dipeptidyl peptidase–4] inhibitor sitagliptin had no such effects. Theoretically, the increased pancreatic weight may reflect edema or similar changes, although the underlying cause of the weight increase was not further analyzed and histopathology results were not reported."

Any pancreatic effect of the drugs could be directly related to the beneficial physiological changes they induce in the pancreas, Dr. Spranger wrote. GLP-1 agonists increase beta-cell mass in rodents, by enhancing beta-cell proliferation, inhibiting apoptosis, and enhancing stem cell differentiation in the ductal pancreatic epithelium.

"Although beta-cell proliferation may be beneficial with regard to progression of type 2 diabetes, similar trophic mechanisms in other cell types might be detrimental. Thus, the epidermal growth factor receptor system and the Src kinase have been implicated in the pathogenesis and progression of numerous malignant tumors, including pancreatic cancer; mechanisms increasing the activity of these pathways could promote tumor development or progression."

The observations raise safety concerns which should be heeded until proven unfounded, Dr. Spranger wrote.

More detailed data about the link between incretin-based therapies and pancreatitis should be forthcoming, as long-term prospective studies continue to collect a wide range of safety information.

"There are at least nine prospective trials looking at cardiovascular outcomes which are capturing a lot of other outcomes data as well – including pancreatitis," Dr. Handelsman said. "In a few years we might be able to identify the true risk. But a scare based on an observational study from one insurance database, from years ago, is not enough to change practice."

The Endocrine Society’s response to Dr. Singh’s study echoed that of AACE and ADA, and added that "an important but unanswered question is whether or not the morbidity and mortality from incretin-associated pancreatitis is the same as that of other causes of pancreatitis," in particular whether such cases would lead to an increased incidence of pancreatic cancer similar to that seen in some other causes of acute pancreatitis. The statement suggested that some of the ongoing trials "may also help elucidate the conflict between Singh’s finding of increased incidence of acute pancreatitis with these drugs and the four recent retrospective database analyses and 1 meta-analysis cited in Singh’s paper which found no such association."

Dr. Singh’s study was sponsored by Johns Hopkins University and the National Institutes of Health. He had no financial disclosures. Dr. Handelsman has been a consultant to numerous drug companies developing diabetes treatments. Dr. Spranger has lectured for or received consultant honoraria from Eli Lilly and NovoNordisk.

[email protected]

Patients with diabetes who take either sitagliptin or exenatide were twice as likely to experience acute pancreatitis as those who did not take the GLP-1 inhibitors, a large database review has determined.

The authors made no recommendations about using the drugs, instead saying that the findings call for confirmation by more rigorous studies.

"Further studies using new user designs should clarify the exact timing of these risks and determine whether susceptible subgroups, such as those with genetic mutations, or pancreatitis risks, such as obesity, may be at the highest risk," Dr. Sonal Singh and his colleagues wrote in the Feb. 25 online issue of JAMA Internal Medicine (formerly Archives of Internal Medicine) (doi: 10.1001/jamainternmed.2013.2720).

But the American Association of Clinical Endocrinologists (AACE), the American Diabetes Association, and the Endocrine Society are criticizing the study, saying that the risk of pancreatitis over a large population is very low, and that for most patients, the drugs’ benefits far outweigh that risk.

"This story is very simple," said Dr. Yehuda Handelsman, speaking for AACE. "Since day 1, we have been telling physicians there could be a bit of increase in the risk of pancreatitis with the drugs. But the risk is so minimal that we don’t believe anyone should change their practice based on this study."

The review included 1,269 controls and 1,269 patients who used the drugs and were hospitalized for acute pancreatitis during 2005-2008. Study subjects had a mean age of 52 years. Several comorbidities were significantly more common among the case patients than among controls, including elevated triglycerides (13% vs. 8%), alcohol use (3.2% vs. 0.2%), gallstones (9% vs. 1%), tobacco abuse (16% vs. 6%), obesity (20% vs. 10%), biliary and pancreatic cancer (3% vs. 0%), cystic fibrosis (1% vs. 0%), and any neoplasm (30% vs. 18%).

Photo courtesy of Dr. Yehuda Handelsman

Dr. Singh of Johns Hopkins University, Baltimore, and his associates controlled for all of these factors by using a multifactorial analysis, as well as an indicator of general morbidity level developed by the university.

After adjustment for these confounders and for metformin use, patients who had taking either sitagliptin or exenatide in the past 30 days were more than twice as likely to have experienced acute pancreatitis (odds ratio, 2.24). Those who had taken the drugs within the past 30 days to 2 years were twice as likely to have had the illness (OR, 2). Any use of the drugs – which included both 30-day and recent use – was associated with a doubling of the risk (OR, 2.1).

A sensitivity analysis excluded nine case-control pairs who were exposed to a combination of metformin and sitagliptin. After adjustment for the confounders, this subanalysis agreed with the primary findings. Current use of either drug within 30 days was associated with a doubled risk (OR, 2) as was recent use (OR, 1.95), and any use (OR, 2).

The study did not indicate the total number of patients in the database who were taking the drugs and who developed pancreatitis. This skewed the findings, said Dr. Handelsman, because it misrepresented the actual frequency of the illness in this group, which he said was very, very low. In an e-mail, Dr. Singh said, "Those numbers are not available in a case-control study."

And even though the study controlled for the significant baseline differences between the two groups, these also tainted the conclusions, said Dr. Handelsman, who is also the principal investigator at the Metabolic Institute of America in Tarzana, Calif. "Patients who are obese, who drink a lot and smoke a lot, who have gallstones – they are all more likely to get pancreatitis. We tell doctors, if you’re going to give the drugs to these patients, just watch them more carefully."

In a joint statement, AACE and ADA voiced concern that patients could stop taking their prescribed treatments. "We encourage patients to speak with their doctors to assess which treatments are best for them and not to stop therapy on their own without consulting their doctors."

A link between glucagonlike peptide–1(GLP-1) inhibitors and pancreatitis has never been firmly established. But, according to a recent review, questions remain – many centering around safety reviews performed by pharmaceutical companies, which were based on their own prospective studies (Gastroenterology 2011;141:20-3).

Animal studies have suggested a physiological link, wrote Dr. Joachim Spranger of the German Medical Association. "Exocrine pancreatic cells express the GLP-1 receptor [GLP-1R], and administering GLP-1 has biological effects on these cells. In animal experiments (Diabetes 2009;58:2148-61), 1 week of GLP-1R activation with liraglutide or exenatide increased pancreatic weight and changed pancreatitis-associated gene expression, although the DPP-4 [dipeptidyl peptidase–4] inhibitor sitagliptin had no such effects. Theoretically, the increased pancreatic weight may reflect edema or similar changes, although the underlying cause of the weight increase was not further analyzed and histopathology results were not reported."

Any pancreatic effect of the drugs could be directly related to the beneficial physiological changes they induce in the pancreas, Dr. Spranger wrote. GLP-1 agonists increase beta-cell mass in rodents, by enhancing beta-cell proliferation, inhibiting apoptosis, and enhancing stem cell differentiation in the ductal pancreatic epithelium.

"Although beta-cell proliferation may be beneficial with regard to progression of type 2 diabetes, similar trophic mechanisms in other cell types might be detrimental. Thus, the epidermal growth factor receptor system and the Src kinase have been implicated in the pathogenesis and progression of numerous malignant tumors, including pancreatic cancer; mechanisms increasing the activity of these pathways could promote tumor development or progression."

The observations raise safety concerns which should be heeded until proven unfounded, Dr. Spranger wrote.

More detailed data about the link between incretin-based therapies and pancreatitis should be forthcoming, as long-term prospective studies continue to collect a wide range of safety information.

"There are at least nine prospective trials looking at cardiovascular outcomes which are capturing a lot of other outcomes data as well – including pancreatitis," Dr. Handelsman said. "In a few years we might be able to identify the true risk. But a scare based on an observational study from one insurance database, from years ago, is not enough to change practice."

The Endocrine Society’s response to Dr. Singh’s study echoed that of AACE and ADA, and added that "an important but unanswered question is whether or not the morbidity and mortality from incretin-associated pancreatitis is the same as that of other causes of pancreatitis," in particular whether such cases would lead to an increased incidence of pancreatic cancer similar to that seen in some other causes of acute pancreatitis. The statement suggested that some of the ongoing trials "may also help elucidate the conflict between Singh’s finding of increased incidence of acute pancreatitis with these drugs and the four recent retrospective database analyses and 1 meta-analysis cited in Singh’s paper which found no such association."

Dr. Singh’s study was sponsored by Johns Hopkins University and the National Institutes of Health. He had no financial disclosures. Dr. Handelsman has been a consultant to numerous drug companies developing diabetes treatments. Dr. Spranger has lectured for or received consultant honoraria from Eli Lilly and NovoNordisk.

[email protected]

The age and sex of the patient at the onset of primary biliary cirrhosis predict the severity of disease and the likelihood of response to treatment with ursodeoxycholic acid, Dr. Marco Carbone and his associates reported in Gastroenterology.

In what they described as the first study large enough to permit examination of meaningful numbers of patient subgroups, the researchers found that among women, older age at diagnosis correlated with a better chance of responding to UDCA and with a less severe disease phenotype. These findings are reassuring because women with primary biliary cirrhosis outnumber men by approximately 10 to 1, and most are older than 50 years at disease onset.

Source: American Gastroenterological Association

But the other side of the coin is that the minority of patients who do present at an earlier age, or are men, are more likely to have a severe disease phenotype and less likely to respond to therapy.

"Collectively our findings highlight that primary biliary cirrhosis is not a uniform disease with uniform risks and impact, but one with high- and low-risk patients," said Dr. Carbone of the department of hepatology, Cambridge (England) University Hospitals National Health Service Foundation Trust, and his associates (doi:10.1053/j.gastro.2012.12.005).

The researchers analyzed data from the United Kingdom–Primary Biliary Cirrhosis cohort, an ongoing national genetic study of the disease that enrolled patients from every hospital in the country during a recent 3-year period. This patient population represents 25% of all primary biliary cirrhosis patients in the United Kingdom.

Dr. Carbone and his colleagues assessed the records of 2,353 participants in the UK-PBC, including a subgroup of 1,379 who supplied extra detailed clinical information. The cohort included 221 men.

More than 80% of the study subjects were managed outside of specialist liver transplant centers. These patients were just as likely as were those managed at specialty centers to be offered therapy with UDCA.

Women who presented at age 50 or older were significantly more likely than were younger women or men to have less severe disease and to respond to UDCA. In particular, women aged 70 and older at presentation had a greater than 90% chance of responding.

One possible explanation for this finding is that hormones, particularly high estrogen levels, may raise resistance to treatment. "There certainly are plausible biologic mechanisms for such an endocrine effect, as female sex hormones modulate immune regulation and biliary epithelial cell turnover. Furthermore, case reports show that tamoxifen, an antiestrogen, improves liver biochemistry in primary biliary cirrhosis," the investigators said.

This finding suggests that a clinical trial of antiestrogens as adjunctive therapy should be considered for high-risk patients who don’t respond to UDCA, they noted.

Men typically presented at an older age but with more severe disease, as evidenced by their reduced platelet counts and higher frequency of splenomegaly.

"This is likely to represent delayed diagnosis resulting from the misperception that primary biliary cirrhosis is ‘a female disease,’ with the presence of features such as elevated [liver enzymes] being falsely ascribed to conditions or etiologies that are common in the male population, such as increased alcohol consumption," Dr. Carbone and his associates said.

Men were just as likely as were women to be offered UDCA therapy, but were significantly less likely to respond adequately.

Autonomic symptoms were more marked among women than men. In a substudy in which male subjects were matched with female subjects, the difference in autonomic symptoms closely correlated with differences in fatigue severity, "raising the obvious question as to whether reduction in autonomic dysfunction might reduce fatigue," the investigators said.

One possible reason that men have fewer autonomic symptoms may be that they tend to have higher underlying blood pressure than women, they added.

Overall, it appears that most patients with primary biliary cirrhosis present at an older age, have few symptoms, and respond well to UDCA – a "benign picture" that should guide planning and delivery of care.

In contrast, younger patients tend to have a more complex course, with more symptoms that interfere with daily life and a higher risk of treatment failure. "Such patients should be the focus for novel therapy to improve outcomes."

Men have a lower chance of responding to therapy, but fortunately they have a lower symptom burden and their age at disease onset doesn’t affect prognosis.

No financial conflicts were reported.

The age and sex of the patient at the onset of primary biliary cirrhosis predict the severity of disease and the likelihood of response to treatment with ursodeoxycholic acid, Dr. Marco Carbone and his associates reported in Gastroenterology.

In what they described as the first study large enough to permit examination of meaningful numbers of patient subgroups, the researchers found that among women, older age at diagnosis correlated with a better chance of responding to UDCA and with a less severe disease phenotype. These findings are reassuring because women with primary biliary cirrhosis outnumber men by approximately 10 to 1, and most are older than 50 years at disease onset.

Source: American Gastroenterological Association

But the other side of the coin is that the minority of patients who do present at an earlier age, or are men, are more likely to have a severe disease phenotype and less likely to respond to therapy.

"Collectively our findings highlight that primary biliary cirrhosis is not a uniform disease with uniform risks and impact, but one with high- and low-risk patients," said Dr. Carbone of the department of hepatology, Cambridge (England) University Hospitals National Health Service Foundation Trust, and his associates (doi:10.1053/j.gastro.2012.12.005).

The researchers analyzed data from the United Kingdom–Primary Biliary Cirrhosis cohort, an ongoing national genetic study of the disease that enrolled patients from every hospital in the country during a recent 3-year period. This patient population represents 25% of all primary biliary cirrhosis patients in the United Kingdom.

Dr. Carbone and his colleagues assessed the records of 2,353 participants in the UK-PBC, including a subgroup of 1,379 who supplied extra detailed clinical information. The cohort included 221 men.

More than 80% of the study subjects were managed outside of specialist liver transplant centers. These patients were just as likely as were those managed at specialty centers to be offered therapy with UDCA.

Women who presented at age 50 or older were significantly more likely than were younger women or men to have less severe disease and to respond to UDCA. In particular, women aged 70 and older at presentation had a greater than 90% chance of responding.

One possible explanation for this finding is that hormones, particularly high estrogen levels, may raise resistance to treatment. "There certainly are plausible biologic mechanisms for such an endocrine effect, as female sex hormones modulate immune regulation and biliary epithelial cell turnover. Furthermore, case reports show that tamoxifen, an antiestrogen, improves liver biochemistry in primary biliary cirrhosis," the investigators said.

This finding suggests that a clinical trial of antiestrogens as adjunctive therapy should be considered for high-risk patients who don’t respond to UDCA, they noted.

Men typically presented at an older age but with more severe disease, as evidenced by their reduced platelet counts and higher frequency of splenomegaly.

"This is likely to represent delayed diagnosis resulting from the misperception that primary biliary cirrhosis is ‘a female disease,’ with the presence of features such as elevated [liver enzymes] being falsely ascribed to conditions or etiologies that are common in the male population, such as increased alcohol consumption," Dr. Carbone and his associates said.

Men were just as likely as were women to be offered UDCA therapy, but were significantly less likely to respond adequately.

Autonomic symptoms were more marked among women than men. In a substudy in which male subjects were matched with female subjects, the difference in autonomic symptoms closely correlated with differences in fatigue severity, "raising the obvious question as to whether reduction in autonomic dysfunction might reduce fatigue," the investigators said.

One possible reason that men have fewer autonomic symptoms may be that they tend to have higher underlying blood pressure than women, they added.

Overall, it appears that most patients with primary biliary cirrhosis present at an older age, have few symptoms, and respond well to UDCA – a "benign picture" that should guide planning and delivery of care.

In contrast, younger patients tend to have a more complex course, with more symptoms that interfere with daily life and a higher risk of treatment failure. "Such patients should be the focus for novel therapy to improve outcomes."

Men have a lower chance of responding to therapy, but fortunately they have a lower symptom burden and their age at disease onset doesn’t affect prognosis.

No financial conflicts were reported.

The age and sex of the patient at the onset of primary biliary cirrhosis predict the severity of disease and the likelihood of response to treatment with ursodeoxycholic acid, Dr. Marco Carbone and his associates reported in Gastroenterology.

In what they described as the first study large enough to permit examination of meaningful numbers of patient subgroups, the researchers found that among women, older age at diagnosis correlated with a better chance of responding to UDCA and with a less severe disease phenotype. These findings are reassuring because women with primary biliary cirrhosis outnumber men by approximately 10 to 1, and most are older than 50 years at disease onset.

Source: American Gastroenterological Association

But the other side of the coin is that the minority of patients who do present at an earlier age, or are men, are more likely to have a severe disease phenotype and less likely to respond to therapy.

"Collectively our findings highlight that primary biliary cirrhosis is not a uniform disease with uniform risks and impact, but one with high- and low-risk patients," said Dr. Carbone of the department of hepatology, Cambridge (England) University Hospitals National Health Service Foundation Trust, and his associates (doi:10.1053/j.gastro.2012.12.005).

The researchers analyzed data from the United Kingdom–Primary Biliary Cirrhosis cohort, an ongoing national genetic study of the disease that enrolled patients from every hospital in the country during a recent 3-year period. This patient population represents 25% of all primary biliary cirrhosis patients in the United Kingdom.

Dr. Carbone and his colleagues assessed the records of 2,353 participants in the UK-PBC, including a subgroup of 1,379 who supplied extra detailed clinical information. The cohort included 221 men.

More than 80% of the study subjects were managed outside of specialist liver transplant centers. These patients were just as likely as were those managed at specialty centers to be offered therapy with UDCA.

Women who presented at age 50 or older were significantly more likely than were younger women or men to have less severe disease and to respond to UDCA. In particular, women aged 70 and older at presentation had a greater than 90% chance of responding.

One possible explanation for this finding is that hormones, particularly high estrogen levels, may raise resistance to treatment. "There certainly are plausible biologic mechanisms for such an endocrine effect, as female sex hormones modulate immune regulation and biliary epithelial cell turnover. Furthermore, case reports show that tamoxifen, an antiestrogen, improves liver biochemistry in primary biliary cirrhosis," the investigators said.

This finding suggests that a clinical trial of antiestrogens as adjunctive therapy should be considered for high-risk patients who don’t respond to UDCA, they noted.

Men typically presented at an older age but with more severe disease, as evidenced by their reduced platelet counts and higher frequency of splenomegaly.

"This is likely to represent delayed diagnosis resulting from the misperception that primary biliary cirrhosis is ‘a female disease,’ with the presence of features such as elevated [liver enzymes] being falsely ascribed to conditions or etiologies that are common in the male population, such as increased alcohol consumption," Dr. Carbone and his associates said.

Men were just as likely as were women to be offered UDCA therapy, but were significantly less likely to respond adequately.

Autonomic symptoms were more marked among women than men. In a substudy in which male subjects were matched with female subjects, the difference in autonomic symptoms closely correlated with differences in fatigue severity, "raising the obvious question as to whether reduction in autonomic dysfunction might reduce fatigue," the investigators said.

One possible reason that men have fewer autonomic symptoms may be that they tend to have higher underlying blood pressure than women, they added.

Overall, it appears that most patients with primary biliary cirrhosis present at an older age, have few symptoms, and respond well to UDCA – a "benign picture" that should guide planning and delivery of care.

In contrast, younger patients tend to have a more complex course, with more symptoms that interfere with daily life and a higher risk of treatment failure. "Such patients should be the focus for novel therapy to improve outcomes."

Men have a lower chance of responding to therapy, but fortunately they have a lower symptom burden and their age at disease onset doesn’t affect prognosis.

No financial conflicts were reported.

SAN FRANCISCO – Japanese patients who underwent surgery for pancreatic cancer were 44% less likely to die within 2 years if they were treated postoperatively with the chemotherapy drug S-1, compared with those given gemcitabine, an interim analysis of an ongoing phase III clinical trial found.

S-1 is not approved in the United States but is used in Japan to treat pancreatic cancer and several other cancers. A separate phase III clinical trial in the United States is underway to study S-1 in the treatment of stomach cancer, several oncology experts said in a press briefing held by the American Society of Clinical Oncology (ASCO).

The current Japanese study randomized 385 patients with pancreatic cancer to postoperative adjuvant therapy with S-1 or gemcitabine. A preplanned interim analysis conducted after the first 205 deaths found that 70% of the 187 patients on S-1 were alive at 2 years, compared with 53% of the 191 patients on gemcitabine, Dr. Katsuhiko Uesaka and his associates reported at a meeting on gastrointestinal cancers.

Patients in the S-1 group also were less likely to relapse. At 2 years, 49% on S-1 were free of disease progression, compared with 29% on gemcitabine, said Dr. Uesaka, medical deputy director of the Shizuoka (Japan) Cancer Center Hospital. The median time to disease progression was 23 months on S-1 and 11 months on gemcitabine.

The study is ongoing; a final analysis is planned after 240 deaths.

S-1 is an oral fluoropyrimidine that combines tegafur, gimeracil, and oteracil. It is approved in Europe for the treatment of gastric cancer at a lower dose than is used in Japan because the drug causes higher rates of diarrhea in white patients. "If the dose and schedule are optimized or adjusted, I expect that S-1 may be applicable for Caucasian patients with pancreatic cancer," he said. "I also expect that some kind of clinical study with S-1 will be done among Caucasian patients with pancreatic cancer."

Patients in the Japanese study tolerated S-1 relatively well, with rates of grade 3 or 4 adverse events below 5% for all except grade 3 hemoglobin toxicity, which affected 9% in the S-1 group. Rates of hematologic adverse events such as leukocytopenia or thrombocytopenia were lower with S-1, compared with gemcitabine, but the S-1 group had slightly higher rates of GI side effects such as stomatitis or diarrhea, he said.

Twenty-eight percent of patients in the S-1 group and 42% in the gemcitabine discontinued treatment, mainly because of toxicity or cancer recurrence, Dr. Uesaka said.

Dr. Philip A. Philip, who discussed Dr. Uesaka’s study at the meeting, said it’s likely that S-1 will become the standard of care for pancreatic cancer treatment in Japan. "In my opinion, non-Japanese studies must be considered to define the role of S-1" in non-Japanese populations, said Dr. Philip, leader of the gastrointestinal cancer multidisciplinary team and professor of medicine and oncology at Wayne State University, Detroit.

Studies should examine the feasibility of using a lower dose of S-1 in non-Japanese populations, he suggested, and explore S-1 treatment for early- and late-stage pancreatic cancer, use of the drug with other cancer drugs or drug combinations, and potential biomarkers that might identify which patients will respond best to S-1.

In a press briefing before the meeting, Dr. Kenneth H. Yu called the results from Dr. Uesaka’s study "very impressive." The findings "will lead to a lot more discussion about whether or not S-1 can be developed for use in the U.S. population," said Dr. Yu of Memorial Sloan-Kettering Cancer Center, New York.

The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

Taiho Pharmaceutical Company, which makes S-1, funded the study. Dr. Uesaka has received honoraria from Taiho and Eli Lilly and Co. Some of his associates in the study have received honoraria or research funding from Taiho or other pharmaceutical companies. Dr. Philip disclosed financial relationships with multiple pharmaceutical companies, though not with Taiho.

[email protected]

On Twitter @SherryBoschert

SAN FRANCISCO – Japanese patients who underwent surgery for pancreatic cancer were 44% less likely to die within 2 years if they were treated postoperatively with the chemotherapy drug S-1, compared with those given gemcitabine, an interim analysis of an ongoing phase III clinical trial found.

S-1 is not approved in the United States but is used in Japan to treat pancreatic cancer and several other cancers. A separate phase III clinical trial in the United States is underway to study S-1 in the treatment of stomach cancer, several oncology experts said in a press briefing held by the American Society of Clinical Oncology (ASCO).

The current Japanese study randomized 385 patients with pancreatic cancer to postoperative adjuvant therapy with S-1 or gemcitabine. A preplanned interim analysis conducted after the first 205 deaths found that 70% of the 187 patients on S-1 were alive at 2 years, compared with 53% of the 191 patients on gemcitabine, Dr. Katsuhiko Uesaka and his associates reported at a meeting on gastrointestinal cancers.

Patients in the S-1 group also were less likely to relapse. At 2 years, 49% on S-1 were free of disease progression, compared with 29% on gemcitabine, said Dr. Uesaka, medical deputy director of the Shizuoka (Japan) Cancer Center Hospital. The median time to disease progression was 23 months on S-1 and 11 months on gemcitabine.

The study is ongoing; a final analysis is planned after 240 deaths.

S-1 is an oral fluoropyrimidine that combines tegafur, gimeracil, and oteracil. It is approved in Europe for the treatment of gastric cancer at a lower dose than is used in Japan because the drug causes higher rates of diarrhea in white patients. "If the dose and schedule are optimized or adjusted, I expect that S-1 may be applicable for Caucasian patients with pancreatic cancer," he said. "I also expect that some kind of clinical study with S-1 will be done among Caucasian patients with pancreatic cancer."

Patients in the Japanese study tolerated S-1 relatively well, with rates of grade 3 or 4 adverse events below 5% for all except grade 3 hemoglobin toxicity, which affected 9% in the S-1 group. Rates of hematologic adverse events such as leukocytopenia or thrombocytopenia were lower with S-1, compared with gemcitabine, but the S-1 group had slightly higher rates of GI side effects such as stomatitis or diarrhea, he said.

Twenty-eight percent of patients in the S-1 group and 42% in the gemcitabine discontinued treatment, mainly because of toxicity or cancer recurrence, Dr. Uesaka said.

Dr. Philip A. Philip, who discussed Dr. Uesaka’s study at the meeting, said it’s likely that S-1 will become the standard of care for pancreatic cancer treatment in Japan. "In my opinion, non-Japanese studies must be considered to define the role of S-1" in non-Japanese populations, said Dr. Philip, leader of the gastrointestinal cancer multidisciplinary team and professor of medicine and oncology at Wayne State University, Detroit.

Studies should examine the feasibility of using a lower dose of S-1 in non-Japanese populations, he suggested, and explore S-1 treatment for early- and late-stage pancreatic cancer, use of the drug with other cancer drugs or drug combinations, and potential biomarkers that might identify which patients will respond best to S-1.

In a press briefing before the meeting, Dr. Kenneth H. Yu called the results from Dr. Uesaka’s study "very impressive." The findings "will lead to a lot more discussion about whether or not S-1 can be developed for use in the U.S. population," said Dr. Yu of Memorial Sloan-Kettering Cancer Center, New York.

The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

Taiho Pharmaceutical Company, which makes S-1, funded the study. Dr. Uesaka has received honoraria from Taiho and Eli Lilly and Co. Some of his associates in the study have received honoraria or research funding from Taiho or other pharmaceutical companies. Dr. Philip disclosed financial relationships with multiple pharmaceutical companies, though not with Taiho.

[email protected]

On Twitter @SherryBoschert

SAN FRANCISCO – Japanese patients who underwent surgery for pancreatic cancer were 44% less likely to die within 2 years if they were treated postoperatively with the chemotherapy drug S-1, compared with those given gemcitabine, an interim analysis of an ongoing phase III clinical trial found.

S-1 is not approved in the United States but is used in Japan to treat pancreatic cancer and several other cancers. A separate phase III clinical trial in the United States is underway to study S-1 in the treatment of stomach cancer, several oncology experts said in a press briefing held by the American Society of Clinical Oncology (ASCO).

The current Japanese study randomized 385 patients with pancreatic cancer to postoperative adjuvant therapy with S-1 or gemcitabine. A preplanned interim analysis conducted after the first 205 deaths found that 70% of the 187 patients on S-1 were alive at 2 years, compared with 53% of the 191 patients on gemcitabine, Dr. Katsuhiko Uesaka and his associates reported at a meeting on gastrointestinal cancers.

Patients in the S-1 group also were less likely to relapse. At 2 years, 49% on S-1 were free of disease progression, compared with 29% on gemcitabine, said Dr. Uesaka, medical deputy director of the Shizuoka (Japan) Cancer Center Hospital. The median time to disease progression was 23 months on S-1 and 11 months on gemcitabine.

The study is ongoing; a final analysis is planned after 240 deaths.

S-1 is an oral fluoropyrimidine that combines tegafur, gimeracil, and oteracil. It is approved in Europe for the treatment of gastric cancer at a lower dose than is used in Japan because the drug causes higher rates of diarrhea in white patients. "If the dose and schedule are optimized or adjusted, I expect that S-1 may be applicable for Caucasian patients with pancreatic cancer," he said. "I also expect that some kind of clinical study with S-1 will be done among Caucasian patients with pancreatic cancer."

Patients in the Japanese study tolerated S-1 relatively well, with rates of grade 3 or 4 adverse events below 5% for all except grade 3 hemoglobin toxicity, which affected 9% in the S-1 group. Rates of hematologic adverse events such as leukocytopenia or thrombocytopenia were lower with S-1, compared with gemcitabine, but the S-1 group had slightly higher rates of GI side effects such as stomatitis or diarrhea, he said.

Twenty-eight percent of patients in the S-1 group and 42% in the gemcitabine discontinued treatment, mainly because of toxicity or cancer recurrence, Dr. Uesaka said.

Dr. Philip A. Philip, who discussed Dr. Uesaka’s study at the meeting, said it’s likely that S-1 will become the standard of care for pancreatic cancer treatment in Japan. "In my opinion, non-Japanese studies must be considered to define the role of S-1" in non-Japanese populations, said Dr. Philip, leader of the gastrointestinal cancer multidisciplinary team and professor of medicine and oncology at Wayne State University, Detroit.

Studies should examine the feasibility of using a lower dose of S-1 in non-Japanese populations, he suggested, and explore S-1 treatment for early- and late-stage pancreatic cancer, use of the drug with other cancer drugs or drug combinations, and potential biomarkers that might identify which patients will respond best to S-1.

In a press briefing before the meeting, Dr. Kenneth H. Yu called the results from Dr. Uesaka’s study "very impressive." The findings "will lead to a lot more discussion about whether or not S-1 can be developed for use in the U.S. population," said Dr. Yu of Memorial Sloan-Kettering Cancer Center, New York.

The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

Taiho Pharmaceutical Company, which makes S-1, funded the study. Dr. Uesaka has received honoraria from Taiho and Eli Lilly and Co. Some of his associates in the study have received honoraria or research funding from Taiho or other pharmaceutical companies. Dr. Philip disclosed financial relationships with multiple pharmaceutical companies, though not with Taiho.

[email protected]

On Twitter @SherryBoschert

PALM BEACH, FLA. – Add another notch to the evidence base for bariatric surgery as effective treatment for type 2 diabetes in obese patients.

Patients with type 2 diabetes who underwent any type of bariatric surgery had a 61%-78% relative risk reduction in their rate of macrovascular, microvascular, or vascular events during an average 20-month follow-up in a review of more than 15,000 cases in South Carolina.

"We are trying to get primary care physicians to spread the word [to patients] that bariatric surgery has come a long way over the past 30 or 40 years; the risk-to-reward ratio is much more beneficial to patients," Dr. John D. Scott said at the annual meeting of the Southern Surgical Association.

The new finding "adds to the extensive list of papers that show bariatric surgery mitigates the long-term effects of type 2 diabetes," Dr. Scott added in an interview. "Some front-line medical providers still see bariatric surgery as a procedure of last resort, but findings like ours show that a discussion [with patients on whether they should consider bariatric surgery] should happen a lot sooner."

Dr. Scott, a surgeon at University Medical Center in Greenville, S.C., recommended that patients with a body mass index of at least 35 kg/m² and two or more comorbidities be told that they have the option of undergoing bariatric surgery and reducing their risk.

"We have an epidemic [of obesity and type 2 diabetes], and for the first time since tuberculosis, this is an epidemic where surgery has a real opportunity to positively intervene," commented Dr. Josef E. Fischer, a professor of surgery at Harvard Medical School in Boston.

The study used hospital billing data collected by the South Carolina Office of Research and Statistics as well as state vital records data for 1995-2009. The analysis included 2,580 obese patients who underwent any type of bariatric surgery and 13,371 obese patients who did not have surgery. The researchers extracted the data from records of nearly 34,000 obese patients, but excluded patients with type 1 diabetes, patients with incomplete data, and patients with advanced cardiovascular or microvascular disease at the time of their surgery or entry into the state records during this period.

During a median follow-up of about 20 months, the rate of new-onset macro- or microvascular events was 2% in the bariatric surgery patients and 11% in the patients who did not undergo surgery. The rate of an incident vascular disease event was 2% in the patients who had surgery and 13% in those who did not. Macrovascular events included myocardial infarction, stroke, and all-cause death. Microvascular events included blindness in at least one eye, laser eye surgery, nontraumatic amputation, or placement of access for dialysis. Other vascular events included new-onset heart failure or angina, or revascularization of a coronary, carotid, or peripheral artery.

In a multivariate-adjusted analysis, patients who underwent bariatric surgery had a 61% reduction in macrovascular events, a 78% reduction in microvascular events, a 75% reduction in vascular events, and a 64% reduction in combined macro- and microvascular events, compared with patients who did not have this surgery – all statistically significant differences, reported Dr. Spence M. Taylor, a coinvestigator with Dr. Scott on the study. A propensity-score matched analysis that compared the bariatric surgery patients and matched nonsurgical patients showed very similar reductions in all three event categories.

"Bariatric surgery has a substantial and lasting mitigating association on major complications associated with type 2 diabetes in the obese population," concluded Dr. Taylor, chairman of surgery at the University Medical Center in Greenville.

Dr. Scott, Dr. Fischer, and Dr. Taylor had no relevant disclosures.

PALM BEACH, FLA. – Add another notch to the evidence base for bariatric surgery as effective treatment for type 2 diabetes in obese patients.

Patients with type 2 diabetes who underwent any type of bariatric surgery had a 61%-78% relative risk reduction in their rate of macrovascular, microvascular, or vascular events during an average 20-month follow-up in a review of more than 15,000 cases in South Carolina.

"We are trying to get primary care physicians to spread the word [to patients] that bariatric surgery has come a long way over the past 30 or 40 years; the risk-to-reward ratio is much more beneficial to patients," Dr. John D. Scott said at the annual meeting of the Southern Surgical Association.

The new finding "adds to the extensive list of papers that show bariatric surgery mitigates the long-term effects of type 2 diabetes," Dr. Scott added in an interview. "Some front-line medical providers still see bariatric surgery as a procedure of last resort, but findings like ours show that a discussion [with patients on whether they should consider bariatric surgery] should happen a lot sooner."

Dr. Scott, a surgeon at University Medical Center in Greenville, S.C., recommended that patients with a body mass index of at least 35 kg/m² and two or more comorbidities be told that they have the option of undergoing bariatric surgery and reducing their risk.

"We have an epidemic [of obesity and type 2 diabetes], and for the first time since tuberculosis, this is an epidemic where surgery has a real opportunity to positively intervene," commented Dr. Josef E. Fischer, a professor of surgery at Harvard Medical School in Boston.

The study used hospital billing data collected by the South Carolina Office of Research and Statistics as well as state vital records data for 1995-2009. The analysis included 2,580 obese patients who underwent any type of bariatric surgery and 13,371 obese patients who did not have surgery. The researchers extracted the data from records of nearly 34,000 obese patients, but excluded patients with type 1 diabetes, patients with incomplete data, and patients with advanced cardiovascular or microvascular disease at the time of their surgery or entry into the state records during this period.

During a median follow-up of about 20 months, the rate of new-onset macro- or microvascular events was 2% in the bariatric surgery patients and 11% in the patients who did not undergo surgery. The rate of an incident vascular disease event was 2% in the patients who had surgery and 13% in those who did not. Macrovascular events included myocardial infarction, stroke, and all-cause death. Microvascular events included blindness in at least one eye, laser eye surgery, nontraumatic amputation, or placement of access for dialysis. Other vascular events included new-onset heart failure or angina, or revascularization of a coronary, carotid, or peripheral artery.

In a multivariate-adjusted analysis, patients who underwent bariatric surgery had a 61% reduction in macrovascular events, a 78% reduction in microvascular events, a 75% reduction in vascular events, and a 64% reduction in combined macro- and microvascular events, compared with patients who did not have this surgery – all statistically significant differences, reported Dr. Spence M. Taylor, a coinvestigator with Dr. Scott on the study. A propensity-score matched analysis that compared the bariatric surgery patients and matched nonsurgical patients showed very similar reductions in all three event categories.

"Bariatric surgery has a substantial and lasting mitigating association on major complications associated with type 2 diabetes in the obese population," concluded Dr. Taylor, chairman of surgery at the University Medical Center in Greenville.

Dr. Scott, Dr. Fischer, and Dr. Taylor had no relevant disclosures.

PALM BEACH, FLA. – Add another notch to the evidence base for bariatric surgery as effective treatment for type 2 diabetes in obese patients.

Patients with type 2 diabetes who underwent any type of bariatric surgery had a 61%-78% relative risk reduction in their rate of macrovascular, microvascular, or vascular events during an average 20-month follow-up in a review of more than 15,000 cases in South Carolina.

"We are trying to get primary care physicians to spread the word [to patients] that bariatric surgery has come a long way over the past 30 or 40 years; the risk-to-reward ratio is much more beneficial to patients," Dr. John D. Scott said at the annual meeting of the Southern Surgical Association.

The new finding "adds to the extensive list of papers that show bariatric surgery mitigates the long-term effects of type 2 diabetes," Dr. Scott added in an interview. "Some front-line medical providers still see bariatric surgery as a procedure of last resort, but findings like ours show that a discussion [with patients on whether they should consider bariatric surgery] should happen a lot sooner."

Dr. Scott, a surgeon at University Medical Center in Greenville, S.C., recommended that patients with a body mass index of at least 35 kg/m² and two or more comorbidities be told that they have the option of undergoing bariatric surgery and reducing their risk.

"We have an epidemic [of obesity and type 2 diabetes], and for the first time since tuberculosis, this is an epidemic where surgery has a real opportunity to positively intervene," commented Dr. Josef E. Fischer, a professor of surgery at Harvard Medical School in Boston.

The study used hospital billing data collected by the South Carolina Office of Research and Statistics as well as state vital records data for 1995-2009. The analysis included 2,580 obese patients who underwent any type of bariatric surgery and 13,371 obese patients who did not have surgery. The researchers extracted the data from records of nearly 34,000 obese patients, but excluded patients with type 1 diabetes, patients with incomplete data, and patients with advanced cardiovascular or microvascular disease at the time of their surgery or entry into the state records during this period.

During a median follow-up of about 20 months, the rate of new-onset macro- or microvascular events was 2% in the bariatric surgery patients and 11% in the patients who did not undergo surgery. The rate of an incident vascular disease event was 2% in the patients who had surgery and 13% in those who did not. Macrovascular events included myocardial infarction, stroke, and all-cause death. Microvascular events included blindness in at least one eye, laser eye surgery, nontraumatic amputation, or placement of access for dialysis. Other vascular events included new-onset heart failure or angina, or revascularization of a coronary, carotid, or peripheral artery.

In a multivariate-adjusted analysis, patients who underwent bariatric surgery had a 61% reduction in macrovascular events, a 78% reduction in microvascular events, a 75% reduction in vascular events, and a 64% reduction in combined macro- and microvascular events, compared with patients who did not have this surgery – all statistically significant differences, reported Dr. Spence M. Taylor, a coinvestigator with Dr. Scott on the study. A propensity-score matched analysis that compared the bariatric surgery patients and matched nonsurgical patients showed very similar reductions in all three event categories.

"Bariatric surgery has a substantial and lasting mitigating association on major complications associated with type 2 diabetes in the obese population," concluded Dr. Taylor, chairman of surgery at the University Medical Center in Greenville.

Dr. Scott, Dr. Fischer, and Dr. Taylor had no relevant disclosures.

Videocapsule endoscopy’s success at identifying the cause of obscure gastrointestinal bleeding was found to be associated with markedly different clinical factors in two separate studies published in the December issue of Clinical Gastroenterology and Hepatology.

Capsule endoscopy allows visualization of the entire small bowel. Knowing which factors are associated with positive findings on capsule endoscopy would allow more appropriate patient selection for the procedure. This in turn would improve its diagnostic yield and maximize resource utilization.

Unfortunately, no single factor was found to accurately predict the success of this form of endoscopy in patients who presented with obscure gastrointestinal bleeding (OGIB) and who had negative or ambiguous findings on upper and lower endoscopies. In fact, the two studies identified entirely different predictors.

In the first study, Dr. Neal C. Shahidi and his associates at the University of British Columbia, Vancouver, reviewed the records of all 698 capsule endoscopies performed at St. Paul’s Hospital in 2001-2011 for the indication of OGIB. Mean patient age was 63 years, and the cohort was equally composed of men and women.

Approximately 48% of these study subjects presented with overt bleeding: hematemesis, hematochezia, or melena. The other 52% presented with occult bleeding evidenced by a positive fecal occult blood test (28%), iron deficiency anemia (21%), or an acute drop in hemoglobin (3%). No causes for the bleeding were identified on conventional esophagogastroduodenoscopy, intraoperative enteroscopy, or colonoscopy.

In approximately 4% of cases, capsule endoscopy failed for technical reasons, including limited visualization because of excessive debris, failure of the videocapsule to enter the small bowel within the procedure time, or inadequate viewing of the small bowel.

Capsule endoscopy definitively identified the cause of the bleeding – ulcerations/erosions, masses, vascular lesions, or visible blood – in 42% of these cases. Most were localized to the small bowel, although 18% were found in the stomach or cecum.

Even though the investigators "rigorously assessed" symptoms, other clinical factors, and patient characteristics such as smoking status, alcohol consumption, and a variety of comorbid conditions, the only factors found to be significantly associated with positive findings on capsule endoscopy were a high number of esophagogastroduodenoscopies leading up to the procedure (odds ratio 1.17), an increase in the need for transfusions (3-9 transfusions, OR 1.70; 10 or more, OR 2.72), and the presence of comorbid connective-tissue disease (OR 2.24).

This is the first report in the literature linking connective-tissue disease with positive findings on capsule endoscopy. There were 41 patients with rheumatoid arthritis, polymyalgia rheumatica, scleroderma, or other connective-tissue disorders in this series.

The increased frequency of positive capsule endoscopy in this subgroup of patients may be due in part to their predisposition to vascular lesions. Alternatively, connective-tissue disease may simply be a marker for the regular use of NSAIDs, Dr. Shahidi and his associates said.

Regarding the association with an increasing need for transfusions, "it is acceptable to presume that a patient’s transfusion requirements may be a marker for ongoing or severe pathology within the gastrointestinal tract," they noted.

Similarly, more frequent esophagogastroduodenoscopies may be another marker for ongoing GI bleeding, "as patients who continue to experience significant bleeding may undergo more endoscopic assessment," they added.

In the second study, Dr. Lucie Lepileur of the University of Rouen (France) and her colleagues reviewed the records on 911 capsule endoscopies performed for OGIB at two university referral centers during 2004-2010.

All the study subjects had undergone upper and lower endoscopies that were deemed negative or insufficient to explain their symptoms. A total of 41% presented with overt bleeding, chiefly melena and hematochezia, and the remaining 59% had occult bleeding.

Capsule endoscopy failed for technical reasons in approximately 1% of the cohort. It permitted a definitive diagnosis in 56%, including 203 angioectasias, 88 ulcerations, 70 tumors, 24 varices, and 6 diverticula of the small bowel. The procedure also identified lesions in the esophagus or stomach and the colon.

In another 8% of patients, capsule endoscopy revealed signs of suspected recent bleeding such as residual blood, clots, or red spots, but didn’t identify a specific lesion. The procedure failed to reveal any possible source of bleeding in the remaining 35% of cases.

The only factors found to be significantly associated with positive findings on capsule endoscopy were a history of overt bleeding (OR 3.8), male gender (OR 1.4), age of more than 60 years (OR 1.4), and inpatient status (OR 1.3). Conversely, female gender was the only factor found to be predictive of a nondiagnostic procedure.

The link with advanced age "can easily be explained by the more frequent occurrence of angioectasia in the elderly, which was the main bleeding lesion found in our series," Dr. Lepileur and her colleagues wrote.

The link with inpatient status likely reflects the more fragile health or more critical bleeding among patients who are hospitalized than among outpatients.

The finding that capsule endoscopy is more fruitful in men and less so in women suggests that the cause of chronic blood loss among women may be gynecologic rather than gastrointestinal in nature, the researchers said.

Neither Dr. Shahidi nor Dr. Lepileur reported any potential financial conflicts of interest.

Videocapsule endoscopy’s success at identifying the cause of obscure gastrointestinal bleeding was found to be associated with markedly different clinical factors in two separate studies published in the December issue of Clinical Gastroenterology and Hepatology.

Capsule endoscopy allows visualization of the entire small bowel. Knowing which factors are associated with positive findings on capsule endoscopy would allow more appropriate patient selection for the procedure. This in turn would improve its diagnostic yield and maximize resource utilization.

Unfortunately, no single factor was found to accurately predict the success of this form of endoscopy in patients who presented with obscure gastrointestinal bleeding (OGIB) and who had negative or ambiguous findings on upper and lower endoscopies. In fact, the two studies identified entirely different predictors.

In the first study, Dr. Neal C. Shahidi and his associates at the University of British Columbia, Vancouver, reviewed the records of all 698 capsule endoscopies performed at St. Paul’s Hospital in 2001-2011 for the indication of OGIB. Mean patient age was 63 years, and the cohort was equally composed of men and women.

Approximately 48% of these study subjects presented with overt bleeding: hematemesis, hematochezia, or melena. The other 52% presented with occult bleeding evidenced by a positive fecal occult blood test (28%), iron deficiency anemia (21%), or an acute drop in hemoglobin (3%). No causes for the bleeding were identified on conventional esophagogastroduodenoscopy, intraoperative enteroscopy, or colonoscopy.

In approximately 4% of cases, capsule endoscopy failed for technical reasons, including limited visualization because of excessive debris, failure of the videocapsule to enter the small bowel within the procedure time, or inadequate viewing of the small bowel.

Capsule endoscopy definitively identified the cause of the bleeding – ulcerations/erosions, masses, vascular lesions, or visible blood – in 42% of these cases. Most were localized to the small bowel, although 18% were found in the stomach or cecum.

Even though the investigators "rigorously assessed" symptoms, other clinical factors, and patient characteristics such as smoking status, alcohol consumption, and a variety of comorbid conditions, the only factors found to be significantly associated with positive findings on capsule endoscopy were a high number of esophagogastroduodenoscopies leading up to the procedure (odds ratio 1.17), an increase in the need for transfusions (3-9 transfusions, OR 1.70; 10 or more, OR 2.72), and the presence of comorbid connective-tissue disease (OR 2.24).

This is the first report in the literature linking connective-tissue disease with positive findings on capsule endoscopy. There were 41 patients with rheumatoid arthritis, polymyalgia rheumatica, scleroderma, or other connective-tissue disorders in this series.

The increased frequency of positive capsule endoscopy in this subgroup of patients may be due in part to their predisposition to vascular lesions. Alternatively, connective-tissue disease may simply be a marker for the regular use of NSAIDs, Dr. Shahidi and his associates said.

Regarding the association with an increasing need for transfusions, "it is acceptable to presume that a patient’s transfusion requirements may be a marker for ongoing or severe pathology within the gastrointestinal tract," they noted.

Similarly, more frequent esophagogastroduodenoscopies may be another marker for ongoing GI bleeding, "as patients who continue to experience significant bleeding may undergo more endoscopic assessment," they added.

In the second study, Dr. Lucie Lepileur of the University of Rouen (France) and her colleagues reviewed the records on 911 capsule endoscopies performed for OGIB at two university referral centers during 2004-2010.

All the study subjects had undergone upper and lower endoscopies that were deemed negative or insufficient to explain their symptoms. A total of 41% presented with overt bleeding, chiefly melena and hematochezia, and the remaining 59% had occult bleeding.

Capsule endoscopy failed for technical reasons in approximately 1% of the cohort. It permitted a definitive diagnosis in 56%, including 203 angioectasias, 88 ulcerations, 70 tumors, 24 varices, and 6 diverticula of the small bowel. The procedure also identified lesions in the esophagus or stomach and the colon.

In another 8% of patients, capsule endoscopy revealed signs of suspected recent bleeding such as residual blood, clots, or red spots, but didn’t identify a specific lesion. The procedure failed to reveal any possible source of bleeding in the remaining 35% of cases.

The only factors found to be significantly associated with positive findings on capsule endoscopy were a history of overt bleeding (OR 3.8), male gender (OR 1.4), age of more than 60 years (OR 1.4), and inpatient status (OR 1.3). Conversely, female gender was the only factor found to be predictive of a nondiagnostic procedure.

The link with advanced age "can easily be explained by the more frequent occurrence of angioectasia in the elderly, which was the main bleeding lesion found in our series," Dr. Lepileur and her colleagues wrote.

The link with inpatient status likely reflects the more fragile health or more critical bleeding among patients who are hospitalized than among outpatients.

The finding that capsule endoscopy is more fruitful in men and less so in women suggests that the cause of chronic blood loss among women may be gynecologic rather than gastrointestinal in nature, the researchers said.

Neither Dr. Shahidi nor Dr. Lepileur reported any potential financial conflicts of interest.

Videocapsule endoscopy’s success at identifying the cause of obscure gastrointestinal bleeding was found to be associated with markedly different clinical factors in two separate studies published in the December issue of Clinical Gastroenterology and Hepatology.

Capsule endoscopy allows visualization of the entire small bowel. Knowing which factors are associated with positive findings on capsule endoscopy would allow more appropriate patient selection for the procedure. This in turn would improve its diagnostic yield and maximize resource utilization.

Unfortunately, no single factor was found to accurately predict the success of this form of endoscopy in patients who presented with obscure gastrointestinal bleeding (OGIB) and who had negative or ambiguous findings on upper and lower endoscopies. In fact, the two studies identified entirely different predictors.

In the first study, Dr. Neal C. Shahidi and his associates at the University of British Columbia, Vancouver, reviewed the records of all 698 capsule endoscopies performed at St. Paul’s Hospital in 2001-2011 for the indication of OGIB. Mean patient age was 63 years, and the cohort was equally composed of men and women.

Approximately 48% of these study subjects presented with overt bleeding: hematemesis, hematochezia, or melena. The other 52% presented with occult bleeding evidenced by a positive fecal occult blood test (28%), iron deficiency anemia (21%), or an acute drop in hemoglobin (3%). No causes for the bleeding were identified on conventional esophagogastroduodenoscopy, intraoperative enteroscopy, or colonoscopy.

In approximately 4% of cases, capsule endoscopy failed for technical reasons, including limited visualization because of excessive debris, failure of the videocapsule to enter the small bowel within the procedure time, or inadequate viewing of the small bowel.

Capsule endoscopy definitively identified the cause of the bleeding – ulcerations/erosions, masses, vascular lesions, or visible blood – in 42% of these cases. Most were localized to the small bowel, although 18% were found in the stomach or cecum.

Even though the investigators "rigorously assessed" symptoms, other clinical factors, and patient characteristics such as smoking status, alcohol consumption, and a variety of comorbid conditions, the only factors found to be significantly associated with positive findings on capsule endoscopy were a high number of esophagogastroduodenoscopies leading up to the procedure (odds ratio 1.17), an increase in the need for transfusions (3-9 transfusions, OR 1.70; 10 or more, OR 2.72), and the presence of comorbid connective-tissue disease (OR 2.24).

This is the first report in the literature linking connective-tissue disease with positive findings on capsule endoscopy. There were 41 patients with rheumatoid arthritis, polymyalgia rheumatica, scleroderma, or other connective-tissue disorders in this series.

The increased frequency of positive capsule endoscopy in this subgroup of patients may be due in part to their predisposition to vascular lesions. Alternatively, connective-tissue disease may simply be a marker for the regular use of NSAIDs, Dr. Shahidi and his associates said.

Regarding the association with an increasing need for transfusions, "it is acceptable to presume that a patient’s transfusion requirements may be a marker for ongoing or severe pathology within the gastrointestinal tract," they noted.

Similarly, more frequent esophagogastroduodenoscopies may be another marker for ongoing GI bleeding, "as patients who continue to experience significant bleeding may undergo more endoscopic assessment," they added.

In the second study, Dr. Lucie Lepileur of the University of Rouen (France) and her colleagues reviewed the records on 911 capsule endoscopies performed for OGIB at two university referral centers during 2004-2010.

All the study subjects had undergone upper and lower endoscopies that were deemed negative or insufficient to explain their symptoms. A total of 41% presented with overt bleeding, chiefly melena and hematochezia, and the remaining 59% had occult bleeding.

Capsule endoscopy failed for technical reasons in approximately 1% of the cohort. It permitted a definitive diagnosis in 56%, including 203 angioectasias, 88 ulcerations, 70 tumors, 24 varices, and 6 diverticula of the small bowel. The procedure also identified lesions in the esophagus or stomach and the colon.

In another 8% of patients, capsule endoscopy revealed signs of suspected recent bleeding such as residual blood, clots, or red spots, but didn’t identify a specific lesion. The procedure failed to reveal any possible source of bleeding in the remaining 35% of cases.

The only factors found to be significantly associated with positive findings on capsule endoscopy were a history of overt bleeding (OR 3.8), male gender (OR 1.4), age of more than 60 years (OR 1.4), and inpatient status (OR 1.3). Conversely, female gender was the only factor found to be predictive of a nondiagnostic procedure.

The link with advanced age "can easily be explained by the more frequent occurrence of angioectasia in the elderly, which was the main bleeding lesion found in our series," Dr. Lepileur and her colleagues wrote.

The link with inpatient status likely reflects the more fragile health or more critical bleeding among patients who are hospitalized than among outpatients.

The finding that capsule endoscopy is more fruitful in men and less so in women suggests that the cause of chronic blood loss among women may be gynecologic rather than gastrointestinal in nature, the researchers said.

Neither Dr. Shahidi nor Dr. Lepileur reported any potential financial conflicts of interest.

Performance of either biliary endoscopic sphincterotomy alone or dual biliary and pancreatic sphincterotomy similarly prevented approximately half of idiopathic recurrent acute pancreatitis cases in a trial in which 89 patients were randomized to treatments based on the presence or absence of sphincter of Oddi dysfunction.

The study is "the largest randomized clinical trial studying ERCP [endoscopic retrograde cholangiopancreatography] with SOM [sphincter of Oddi manometry] in this population" with long-term follow-up data, Dr. Gregory A. Coté of Indiana University in Indianapolis and his colleagues reported in the December issue of Gastroenterology (2012 [doi: 10.1053/j.gastro.2012.09.006]).

Source: American Gastroenterological Institute

Finding therapeutic equivalence between biliary endoscopic sphincterotomy (BES) and dual endoscopic sphincterotomy (DES) in preventing at least one episode of acute pancreatitis during follow-up is important, because the addition of pancreatic sphincterotomy to ERCP carries the risk of post-ERCP pancreatitis, bleeding, perforation, and sphincter restenosis, according to Dr. Coté and his associates.

To assess the therapeutic value of two types of sphincterotomy and the prognostic value of pancreatic SOD for patients with idiopathic recurrent acute pancreatitis (RAP), the researchers randomized 69 adults with SOD to BES or DES. The other 20 patients who did not have SOD were randomized to BES or a sham therapy. SOD was defined as basal pressure of 40 mm Hg or greater, "sustained for at least 30 seconds across two transducers," the researchers noted.

The patients were aged 18 years and older, and those with chronic pancreatitis or an identified cause of RAP were excluded from the study.

Of the 69 patients with SOD, RAP occurred in 49% of patients who underwent BES and 47% who underwent DES. There was no significant difference in rates of RAP between non-SOD patients who had BES and those who had a sham procedure (27% vs. 11%, respectively).

The risk of RAP was approximately four times higher in patients with SOD than in those without SOD, they added.

"Most RAP events occurred within 30 months of randomization in all subgroups," the researchers said.

Overall, chronic pancreatitis developed in 17% of all patients over a median of 78 months, and there was no difference in the probability of developing chronic pancreatitis in patients with and without SOD.

The study was limited by several factors, including its small sample size for the non-SOD population and the impact of environmental and genetic risk factors on idiopathic RAP, the researchers noted.

The small sample of patients with normal SOM meant that the researchers could draw no conclusions about the benefit of BES in these patients, but the results "represent preliminary data for estimating the sample size of a future definitive trial of ERCP with empiric biliary sphincterotomy," they noted.

In addition, the findings suggest that SOD "may be a secondary marker of more significant inflammation related to previous acute pancreatitis," and that pancreatic sphincterotomy "cannot be recommended as a curative treatment of unexplained RAP alone," they wrote.

None of the study authors had any financial conflicts to disclose.

Performance of either biliary endoscopic sphincterotomy alone or dual biliary and pancreatic sphincterotomy similarly prevented approximately half of idiopathic recurrent acute pancreatitis cases in a trial in which 89 patients were randomized to treatments based on the presence or absence of sphincter of Oddi dysfunction.

The study is "the largest randomized clinical trial studying ERCP [endoscopic retrograde cholangiopancreatography] with SOM [sphincter of Oddi manometry] in this population" with long-term follow-up data, Dr. Gregory A. Coté of Indiana University in Indianapolis and his colleagues reported in the December issue of Gastroenterology (2012 [doi: 10.1053/j.gastro.2012.09.006]).

Source: American Gastroenterological Institute

Finding therapeutic equivalence between biliary endoscopic sphincterotomy (BES) and dual endoscopic sphincterotomy (DES) in preventing at least one episode of acute pancreatitis during follow-up is important, because the addition of pancreatic sphincterotomy to ERCP carries the risk of post-ERCP pancreatitis, bleeding, perforation, and sphincter restenosis, according to Dr. Coté and his associates.

To assess the therapeutic value of two types of sphincterotomy and the prognostic value of pancreatic SOD for patients with idiopathic recurrent acute pancreatitis (RAP), the researchers randomized 69 adults with SOD to BES or DES. The other 20 patients who did not have SOD were randomized to BES or a sham therapy. SOD was defined as basal pressure of 40 mm Hg or greater, "sustained for at least 30 seconds across two transducers," the researchers noted.

The patients were aged 18 years and older, and those with chronic pancreatitis or an identified cause of RAP were excluded from the study.

Of the 69 patients with SOD, RAP occurred in 49% of patients who underwent BES and 47% who underwent DES. There was no significant difference in rates of RAP between non-SOD patients who had BES and those who had a sham procedure (27% vs. 11%, respectively).

The risk of RAP was approximately four times higher in patients with SOD than in those without SOD, they added.

"Most RAP events occurred within 30 months of randomization in all subgroups," the researchers said.

Overall, chronic pancreatitis developed in 17% of all patients over a median of 78 months, and there was no difference in the probability of developing chronic pancreatitis in patients with and without SOD.

The study was limited by several factors, including its small sample size for the non-SOD population and the impact of environmental and genetic risk factors on idiopathic RAP, the researchers noted.

The small sample of patients with normal SOM meant that the researchers could draw no conclusions about the benefit of BES in these patients, but the results "represent preliminary data for estimating the sample size of a future definitive trial of ERCP with empiric biliary sphincterotomy," they noted.

In addition, the findings suggest that SOD "may be a secondary marker of more significant inflammation related to previous acute pancreatitis," and that pancreatic sphincterotomy "cannot be recommended as a curative treatment of unexplained RAP alone," they wrote.

None of the study authors had any financial conflicts to disclose.

Performance of either biliary endoscopic sphincterotomy alone or dual biliary and pancreatic sphincterotomy similarly prevented approximately half of idiopathic recurrent acute pancreatitis cases in a trial in which 89 patients were randomized to treatments based on the presence or absence of sphincter of Oddi dysfunction.

The study is "the largest randomized clinical trial studying ERCP [endoscopic retrograde cholangiopancreatography] with SOM [sphincter of Oddi manometry] in this population" with long-term follow-up data, Dr. Gregory A. Coté of Indiana University in Indianapolis and his colleagues reported in the December issue of Gastroenterology (2012 [doi: 10.1053/j.gastro.2012.09.006]).

Source: American Gastroenterological Institute

Finding therapeutic equivalence between biliary endoscopic sphincterotomy (BES) and dual endoscopic sphincterotomy (DES) in preventing at least one episode of acute pancreatitis during follow-up is important, because the addition of pancreatic sphincterotomy to ERCP carries the risk of post-ERCP pancreatitis, bleeding, perforation, and sphincter restenosis, according to Dr. Coté and his associates.

To assess the therapeutic value of two types of sphincterotomy and the prognostic value of pancreatic SOD for patients with idiopathic recurrent acute pancreatitis (RAP), the researchers randomized 69 adults with SOD to BES or DES. The other 20 patients who did not have SOD were randomized to BES or a sham therapy. SOD was defined as basal pressure of 40 mm Hg or greater, "sustained for at least 30 seconds across two transducers," the researchers noted.

The patients were aged 18 years and older, and those with chronic pancreatitis or an identified cause of RAP were excluded from the study.

Of the 69 patients with SOD, RAP occurred in 49% of patients who underwent BES and 47% who underwent DES. There was no significant difference in rates of RAP between non-SOD patients who had BES and those who had a sham procedure (27% vs. 11%, respectively).

The risk of RAP was approximately four times higher in patients with SOD than in those without SOD, they added.

"Most RAP events occurred within 30 months of randomization in all subgroups," the researchers said.

Overall, chronic pancreatitis developed in 17% of all patients over a median of 78 months, and there was no difference in the probability of developing chronic pancreatitis in patients with and without SOD.

The study was limited by several factors, including its small sample size for the non-SOD population and the impact of environmental and genetic risk factors on idiopathic RAP, the researchers noted.

The small sample of patients with normal SOM meant that the researchers could draw no conclusions about the benefit of BES in these patients, but the results "represent preliminary data for estimating the sample size of a future definitive trial of ERCP with empiric biliary sphincterotomy," they noted.

In addition, the findings suggest that SOD "may be a secondary marker of more significant inflammation related to previous acute pancreatitis," and that pancreatic sphincterotomy "cannot be recommended as a curative treatment of unexplained RAP alone," they wrote.

None of the study authors had any financial conflicts to disclose.

SAN ANTONIO – Earlier may be better when it comes to bariatric surgery for obesity.

Data increasingly suggest that surgery for extreme obesity during adolescence is associated with prevention or reversal of obesity-related health problems, including diabetes, frequently seen in those who remain obese into adulthood, Dr. Thomas Inge said at the annual meeting of the Obesity Society.

Currently, an estimated 4%-7% of adolescents are extremely obese, and a number of researchers have noted significant detrimental effects decades down the road and even early in adulthood for those affected by obesity and diabetes, he said.

These effects include years of life lost and "typical adult life complications of diabetes," such as amputation and renal disease, said Dr. Inge, a surgeon and director of the Center for Bariatric Research and Innovation at Cincinnati Children’s Hospital Medical Center.

Particularly disturbing is the fact that as many as 50% of children in some racial subgroups – including very young children – may develop diabetes in their lifetime, he added, noting that managing diabetes and obesity in this age group is quite challenging and that outcomes are often suboptimal.

Further, school-based studies suggest that morbidly obese children and teens tend to continue to gain weight over time, adding about 1 point of body mass index and 1 inch of waist circumference each year.

In a retrospective study designed to assess the association between adolescent weight status and adult health status, Dr. Inge found that obesity at age 18 based on participant recall increased the risk of diabetes and related comorbidities in adulthood by 37%, and increased the risk of renal disease fivefold.

The study, which involved nearly 1,500 adults who were part of the Longitudinal Assessment of Bariatric Surgery (LABS) 2 study, was reported in a poster at the meeting.

"By having been severely obese as an adolescent, they really did face quite significant problems later in life," he said.

The dilemma when it comes to treating obese adolescents is that medical treatment often fails. In one study, adolescents were found to have a greater risk of failure on metformin monotherapy at every time point compared with adults. Similar, but less striking, findings have been reported with rosiglitazone.

"One might propose, then, that adolescent diabetes is a more virulent condition, and if that’s the case, shouldn’t we really be thinking about more aggressive treatment – particularly today, in light of the fact that we do have surgical therapies with very high-powered evidence of demonstrated effectiveness?" he said.

Not only have studies in adults shown that gastric bypass surgery, for example, is highly effective for reducing fat mass and improving insulin resistance and beta-cell function, but adolescent data also show a benefit.

In a small retrospective study of 11 adolescent teens with type 2 diabetes and a preoperative BMI of about 50 kg/m², Dr. Inge found that BMI and weight decreased by 34% at 1 year follow-up.

Additionally, all participants were using medication at baseline, including one who was on insulin, and all but that one patient were off their medications at follow-up, he said, noting that the patient on insulin had successfully reduced medication dosages by 50% at follow-up. Mean glucose levels in the participants fell from 140 to 84 mmol/L, mean insulin values normalized, and insulin sensitivity measures improved dramatically. Glycosylated hemoglobin normalized, on average, and cardiovascular measures also improved.

"So this leads to the question: What could be responsible for the reduced efficacy of medical treatment in adolescents?" Dr. Inge said.

Because compliance has been good in the studies looking at this, it is possible that biological factors are involved that affect insulin resistance, and this suggests there may be an even greater role for surgery in adolescents. In both adults and adolescents, surgery has been found to dramatically improve insulin resistance.

In fact, in one study gastric bypass seemed to restore a more normal relationship between insulin sensitivity and the first-phase response – even though participants still had "impressive obesity," with a BMI of nearly 40 on average after surgery, he said.

This suggests that in adolescents something more happens as a result of bariatric surgery than just weight loss or "a change in the plumbing."

"It’s changing, perhaps, something more fundamentally important. I think it’s true that these operations are doing something fundamentally metabolic to improve the patient’s response to whatever this pathologic obesity milieu is," Dr. Inge said, noting that additional study via the Teen-LABS multisite consortium and registry is underway.

Teen-LABS, which aims to facilitate coordinated clinical, epidemiological, and behavioral research in the field of adolescent bariatric surgery, recently finished recruitment.

"We’re really testing the hypothesis that bariatric surgery earlier in life may be better than waiting until many more decades have eroded the important metabolic systems in the body," Dr. Inge said, concluding that the future health of obese and severely obese children is of great concern, and that aggressive intervention will be increasingly needed and warranted.

"We need to build upon the evidence base for this, and really describe in detail the risks and benefits to be expected. After gastric bypass, I’m becoming more and more convinced that metabolic defects can dramatically improve. We don’t know exactly why ... but for now, it is fairly clear that this is metabolic surgery," he said, adding that he expects surgical models will provide important clues to mechanisms which can be exploited to expand the armamentarium for fighting pediatric obesity.

Dr. Inge’s research is supported by the National Institutes of Health. He had no other disclosures to report.

SAN ANTONIO – Earlier may be better when it comes to bariatric surgery for obesity.

Data increasingly suggest that surgery for extreme obesity during adolescence is associated with prevention or reversal of obesity-related health problems, including diabetes, frequently seen in those who remain obese into adulthood, Dr. Thomas Inge said at the annual meeting of the Obesity Society.

Currently, an estimated 4%-7% of adolescents are extremely obese, and a number of researchers have noted significant detrimental effects decades down the road and even early in adulthood for those affected by obesity and diabetes, he said.

These effects include years of life lost and "typical adult life complications of diabetes," such as amputation and renal disease, said Dr. Inge, a surgeon and director of the Center for Bariatric Research and Innovation at Cincinnati Children’s Hospital Medical Center.

Particularly disturbing is the fact that as many as 50% of children in some racial subgroups – including very young children – may develop diabetes in their lifetime, he added, noting that managing diabetes and obesity in this age group is quite challenging and that outcomes are often suboptimal.

Further, school-based studies suggest that morbidly obese children and teens tend to continue to gain weight over time, adding about 1 point of body mass index and 1 inch of waist circumference each year.

In a retrospective study designed to assess the association between adolescent weight status and adult health status, Dr. Inge found that obesity at age 18 based on participant recall increased the risk of diabetes and related comorbidities in adulthood by 37%, and increased the risk of renal disease fivefold.

The study, which involved nearly 1,500 adults who were part of the Longitudinal Assessment of Bariatric Surgery (LABS) 2 study, was reported in a poster at the meeting.

"By having been severely obese as an adolescent, they really did face quite significant problems later in life," he said.

The dilemma when it comes to treating obese adolescents is that medical treatment often fails. In one study, adolescents were found to have a greater risk of failure on metformin monotherapy at every time point compared with adults. Similar, but less striking, findings have been reported with rosiglitazone.

"One might propose, then, that adolescent diabetes is a more virulent condition, and if that’s the case, shouldn’t we really be thinking about more aggressive treatment – particularly today, in light of the fact that we do have surgical therapies with very high-powered evidence of demonstrated effectiveness?" he said.

Not only have studies in adults shown that gastric bypass surgery, for example, is highly effective for reducing fat mass and improving insulin resistance and beta-cell function, but adolescent data also show a benefit.

In a small retrospective study of 11 adolescent teens with type 2 diabetes and a preoperative BMI of about 50 kg/m², Dr. Inge found that BMI and weight decreased by 34% at 1 year follow-up.

Additionally, all participants were using medication at baseline, including one who was on insulin, and all but that one patient were off their medications at follow-up, he said, noting that the patient on insulin had successfully reduced medication dosages by 50% at follow-up. Mean glucose levels in the participants fell from 140 to 84 mmol/L, mean insulin values normalized, and insulin sensitivity measures improved dramatically. Glycosylated hemoglobin normalized, on average, and cardiovascular measures also improved.

"So this leads to the question: What could be responsible for the reduced efficacy of medical treatment in adolescents?" Dr. Inge said.

Because compliance has been good in the studies looking at this, it is possible that biological factors are involved that affect insulin resistance, and this suggests there may be an even greater role for surgery in adolescents. In both adults and adolescents, surgery has been found to dramatically improve insulin resistance.

In fact, in one study gastric bypass seemed to restore a more normal relationship between insulin sensitivity and the first-phase response – even though participants still had "impressive obesity," with a BMI of nearly 40 on average after surgery, he said.

This suggests that in adolescents something more happens as a result of bariatric surgery than just weight loss or "a change in the plumbing."

"It’s changing, perhaps, something more fundamentally important. I think it’s true that these operations are doing something fundamentally metabolic to improve the patient’s response to whatever this pathologic obesity milieu is," Dr. Inge said, noting that additional study via the Teen-LABS multisite consortium and registry is underway.

Teen-LABS, which aims to facilitate coordinated clinical, epidemiological, and behavioral research in the field of adolescent bariatric surgery, recently finished recruitment.

"We’re really testing the hypothesis that bariatric surgery earlier in life may be better than waiting until many more decades have eroded the important metabolic systems in the body," Dr. Inge said, concluding that the future health of obese and severely obese children is of great concern, and that aggressive intervention will be increasingly needed and warranted.

"We need to build upon the evidence base for this, and really describe in detail the risks and benefits to be expected. After gastric bypass, I’m becoming more and more convinced that metabolic defects can dramatically improve. We don’t know exactly why ... but for now, it is fairly clear that this is metabolic surgery," he said, adding that he expects surgical models will provide important clues to mechanisms which can be exploited to expand the armamentarium for fighting pediatric obesity.

Dr. Inge’s research is supported by the National Institutes of Health. He had no other disclosures to report.

SAN ANTONIO – Earlier may be better when it comes to bariatric surgery for obesity.

Data increasingly suggest that surgery for extreme obesity during adolescence is associated with prevention or reversal of obesity-related health problems, including diabetes, frequently seen in those who remain obese into adulthood, Dr. Thomas Inge said at the annual meeting of the Obesity Society.

Currently, an estimated 4%-7% of adolescents are extremely obese, and a number of researchers have noted significant detrimental effects decades down the road and even early in adulthood for those affected by obesity and diabetes, he said.

These effects include years of life lost and "typical adult life complications of diabetes," such as amputation and renal disease, said Dr. Inge, a surgeon and director of the Center for Bariatric Research and Innovation at Cincinnati Children’s Hospital Medical Center.

Particularly disturbing is the fact that as many as 50% of children in some racial subgroups – including very young children – may develop diabetes in their lifetime, he added, noting that managing diabetes and obesity in this age group is quite challenging and that outcomes are often suboptimal.

Further, school-based studies suggest that morbidly obese children and teens tend to continue to gain weight over time, adding about 1 point of body mass index and 1 inch of waist circumference each year.

In a retrospective study designed to assess the association between adolescent weight status and adult health status, Dr. Inge found that obesity at age 18 based on participant recall increased the risk of diabetes and related comorbidities in adulthood by 37%, and increased the risk of renal disease fivefold.

The study, which involved nearly 1,500 adults who were part of the Longitudinal Assessment of Bariatric Surgery (LABS) 2 study, was reported in a poster at the meeting.

"By having been severely obese as an adolescent, they really did face quite significant problems later in life," he said.

The dilemma when it comes to treating obese adolescents is that medical treatment often fails. In one study, adolescents were found to have a greater risk of failure on metformin monotherapy at every time point compared with adults. Similar, but less striking, findings have been reported with rosiglitazone.

"One might propose, then, that adolescent diabetes is a more virulent condition, and if that’s the case, shouldn’t we really be thinking about more aggressive treatment – particularly today, in light of the fact that we do have surgical therapies with very high-powered evidence of demonstrated effectiveness?" he said.

Not only have studies in adults shown that gastric bypass surgery, for example, is highly effective for reducing fat mass and improving insulin resistance and beta-cell function, but adolescent data also show a benefit.

In a small retrospective study of 11 adolescent teens with type 2 diabetes and a preoperative BMI of about 50 kg/m², Dr. Inge found that BMI and weight decreased by 34% at 1 year follow-up.

Additionally, all participants were using medication at baseline, including one who was on insulin, and all but that one patient were off their medications at follow-up, he said, noting that the patient on insulin had successfully reduced medication dosages by 50% at follow-up. Mean glucose levels in the participants fell from 140 to 84 mmol/L, mean insulin values normalized, and insulin sensitivity measures improved dramatically. Glycosylated hemoglobin normalized, on average, and cardiovascular measures also improved.

"So this leads to the question: What could be responsible for the reduced efficacy of medical treatment in adolescents?" Dr. Inge said.

Because compliance has been good in the studies looking at this, it is possible that biological factors are involved that affect insulin resistance, and this suggests there may be an even greater role for surgery in adolescents. In both adults and adolescents, surgery has been found to dramatically improve insulin resistance.

In fact, in one study gastric bypass seemed to restore a more normal relationship between insulin sensitivity and the first-phase response – even though participants still had "impressive obesity," with a BMI of nearly 40 on average after surgery, he said.

This suggests that in adolescents something more happens as a result of bariatric surgery than just weight loss or "a change in the plumbing."

"It’s changing, perhaps, something more fundamentally important. I think it’s true that these operations are doing something fundamentally metabolic to improve the patient’s response to whatever this pathologic obesity milieu is," Dr. Inge said, noting that additional study via the Teen-LABS multisite consortium and registry is underway.

Teen-LABS, which aims to facilitate coordinated clinical, epidemiological, and behavioral research in the field of adolescent bariatric surgery, recently finished recruitment.

"We’re really testing the hypothesis that bariatric surgery earlier in life may be better than waiting until many more decades have eroded the important metabolic systems in the body," Dr. Inge said, concluding that the future health of obese and severely obese children is of great concern, and that aggressive intervention will be increasingly needed and warranted.

"We need to build upon the evidence base for this, and really describe in detail the risks and benefits to be expected. After gastric bypass, I’m becoming more and more convinced that metabolic defects can dramatically improve. We don’t know exactly why ... but for now, it is fairly clear that this is metabolic surgery," he said, adding that he expects surgical models will provide important clues to mechanisms which can be exploited to expand the armamentarium for fighting pediatric obesity.

Dr. Inge’s research is supported by the National Institutes of Health. He had no other disclosures to report.

BERLIN – A duodenal-jejunal liner seemed to improve glycemic control in patients with type 2 diabetes, a small prospective study has determined.

Among 16 patients who had the liner for 1 year, mean hemoglobin A_1c dropped more than 1% without any significant weight loss, Dr. Dimitri Pournaras said at the annual meeting of the European Association for the Study of Diabetes.

"Bypassing the gut seems to have an effect on glucose homeostasis that can’t be fully explained by weight loss," said Dr. Pournaras of Imperial College, London.

The flexible barrier attempts to mimic some of the benefits of gastric bypass without surgery, he said. The sleeve is endoscopically placed in the duodenal bulb and extends about 60 cm through the duodenum and proximal jejunum, preventing any nutrient contact with those regions.

Dr. Pournaras presented data on 16 nonobese patients with type 2 diabetes who had the gastric sleeve in place for 1 year.

At baseline, the patients had a body mass index of 23-36 kg/m² and were 35-65 years of age.

The mean duration of disease was 2 years, and HbA_1c at baseline was 7.5%-10.2%.

All of the patients were taking metformin; none were taking DPP-4 inhibitors, GLP-1 analogues, or insulin.

Investigators examined patients’ glycemic indicators at baseline and at 1, 12, and 52 weeks after the sleeve was placed.

After an overnight fast, patients consumed a 525-calorie liquid meal. Blood was drawn before the meal and at 30, 60, 90, and 120 minutes afterward.

There were no significant changes in weight at any time after the surgery. In fact, Dr. Pounaras said, no patient experienced a change in the amount of food consumed.

HbA_1c was significantly lower at 3 months and stayed low throughout the study.

At 52 weeks, the mean HbA_1c was 7.5%, compared with the mean of 8.6% at baseline.

More than half of the subjects (62%) reached a level of 7%.

Fasting glucose and acute glucose response improved significantly.

Insulin sensitivity improved early and that was maintained.

Insulin resistance, as measured by both the homeostasis model assessment of insulin resistance (HOMA-IR) and the Matsuda index, improved significantly by the end of the follow-up period. Insulin secretion and insulinogenic index were unchanged, as were C-peptide and fasting insulin, he reported.

Four patients experienced transient nausea and abdominal bloating after the sleeve was placed.

Dr. Pournaras did not say how many were able to come off of their metformin, nor did he mention the sleeve’s effect on any other drugs the patients may have been taking. In response to a question on this, he said that "metformin is a safe drug" that should not be used as the measure of diabetes remission.

The sleeve "opens the door to the possibility that we might one day be able to combine the duodenal-jejunal liner with medications such as GLP-1 agonists and DPP-4 inhibitors," Dr. Pournaras said.

The device is not approved for sale in the United States and is considered investigational. It is approved in Europe, and has pending approval in Australia, to treat patients with type 2 diabetes and/or obesity for 12 months.

GI Dynamics, the manufacturer of the device, sponsored the study. Dr. Pournaras did not present any financial disclosures.

BERLIN – A duodenal-jejunal liner seemed to improve glycemic control in patients with type 2 diabetes, a small prospective study has determined.

Among 16 patients who had the liner for 1 year, mean hemoglobin A_1c dropped more than 1% without any significant weight loss, Dr. Dimitri Pournaras said at the annual meeting of the European Association for the Study of Diabetes.

"Bypassing the gut seems to have an effect on glucose homeostasis that can’t be fully explained by weight loss," said Dr. Pournaras of Imperial College, London.

The flexible barrier attempts to mimic some of the benefits of gastric bypass without surgery, he said. The sleeve is endoscopically placed in the duodenal bulb and extends about 60 cm through the duodenum and proximal jejunum, preventing any nutrient contact with those regions.

Dr. Pournaras presented data on 16 nonobese patients with type 2 diabetes who had the gastric sleeve in place for 1 year.

At baseline, the patients had a body mass index of 23-36 kg/m² and were 35-65 years of age.

The mean duration of disease was 2 years, and HbA_1c at baseline was 7.5%-10.2%.

All of the patients were taking metformin; none were taking DPP-4 inhibitors, GLP-1 analogues, or insulin.

Investigators examined patients’ glycemic indicators at baseline and at 1, 12, and 52 weeks after the sleeve was placed.

After an overnight fast, patients consumed a 525-calorie liquid meal. Blood was drawn before the meal and at 30, 60, 90, and 120 minutes afterward.

There were no significant changes in weight at any time after the surgery. In fact, Dr. Pounaras said, no patient experienced a change in the amount of food consumed.

HbA_1c was significantly lower at 3 months and stayed low throughout the study.

At 52 weeks, the mean HbA_1c was 7.5%, compared with the mean of 8.6% at baseline.

More than half of the subjects (62%) reached a level of 7%.

Fasting glucose and acute glucose response improved significantly.

Insulin sensitivity improved early and that was maintained.

Insulin resistance, as measured by both the homeostasis model assessment of insulin resistance (HOMA-IR) and the Matsuda index, improved significantly by the end of the follow-up period. Insulin secretion and insulinogenic index were unchanged, as were C-peptide and fasting insulin, he reported.

Four patients experienced transient nausea and abdominal bloating after the sleeve was placed.

Dr. Pournaras did not say how many were able to come off of their metformin, nor did he mention the sleeve’s effect on any other drugs the patients may have been taking. In response to a question on this, he said that "metformin is a safe drug" that should not be used as the measure of diabetes remission.

The sleeve "opens the door to the possibility that we might one day be able to combine the duodenal-jejunal liner with medications such as GLP-1 agonists and DPP-4 inhibitors," Dr. Pournaras said.

The device is not approved for sale in the United States and is considered investigational. It is approved in Europe, and has pending approval in Australia, to treat patients with type 2 diabetes and/or obesity for 12 months.

GI Dynamics, the manufacturer of the device, sponsored the study. Dr. Pournaras did not present any financial disclosures.

BERLIN – A duodenal-jejunal liner seemed to improve glycemic control in patients with type 2 diabetes, a small prospective study has determined.

Among 16 patients who had the liner for 1 year, mean hemoglobin A_1c dropped more than 1% without any significant weight loss, Dr. Dimitri Pournaras said at the annual meeting of the European Association for the Study of Diabetes.

"Bypassing the gut seems to have an effect on glucose homeostasis that can’t be fully explained by weight loss," said Dr. Pournaras of Imperial College, London.

The flexible barrier attempts to mimic some of the benefits of gastric bypass without surgery, he said. The sleeve is endoscopically placed in the duodenal bulb and extends about 60 cm through the duodenum and proximal jejunum, preventing any nutrient contact with those regions.

Dr. Pournaras presented data on 16 nonobese patients with type 2 diabetes who had the gastric sleeve in place for 1 year.

At baseline, the patients had a body mass index of 23-36 kg/m² and were 35-65 years of age.

The mean duration of disease was 2 years, and HbA_1c at baseline was 7.5%-10.2%.

All of the patients were taking metformin; none were taking DPP-4 inhibitors, GLP-1 analogues, or insulin.

Investigators examined patients’ glycemic indicators at baseline and at 1, 12, and 52 weeks after the sleeve was placed.

After an overnight fast, patients consumed a 525-calorie liquid meal. Blood was drawn before the meal and at 30, 60, 90, and 120 minutes afterward.

There were no significant changes in weight at any time after the surgery. In fact, Dr. Pounaras said, no patient experienced a change in the amount of food consumed.

HbA_1c was significantly lower at 3 months and stayed low throughout the study.

At 52 weeks, the mean HbA_1c was 7.5%, compared with the mean of 8.6% at baseline.

More than half of the subjects (62%) reached a level of 7%.

Fasting glucose and acute glucose response improved significantly.

Insulin sensitivity improved early and that was maintained.

Insulin resistance, as measured by both the homeostasis model assessment of insulin resistance (HOMA-IR) and the Matsuda index, improved significantly by the end of the follow-up period. Insulin secretion and insulinogenic index were unchanged, as were C-peptide and fasting insulin, he reported.

Four patients experienced transient nausea and abdominal bloating after the sleeve was placed.

Dr. Pournaras did not say how many were able to come off of their metformin, nor did he mention the sleeve’s effect on any other drugs the patients may have been taking. In response to a question on this, he said that "metformin is a safe drug" that should not be used as the measure of diabetes remission.

The sleeve "opens the door to the possibility that we might one day be able to combine the duodenal-jejunal liner with medications such as GLP-1 agonists and DPP-4 inhibitors," Dr. Pournaras said.

The device is not approved for sale in the United States and is considered investigational. It is approved in Europe, and has pending approval in Australia, to treat patients with type 2 diabetes and/or obesity for 12 months.

GI Dynamics, the manufacturer of the device, sponsored the study. Dr. Pournaras did not present any financial disclosures.

BERLIN – In patients with type 1 diabetes and end-stage renal disease, a combined pancreas/kidney transplant was associated with significantly better 15-year survival than a single kidney graft alone.

Patients who got the simultaneous transplant were 30% more likely to survive to 15 years than were those who received a living donor kidney. Those patients who got a single kidney from a deceased donor, however, were 30% less likely to survive for 15 years after the operation, Dr. Trond Jenssen said at the annual meeting of the European Associations for the Study of Diabetes.

The combined graft is the preferred method of treating end-stage renal disease (ESRD) caused by diabetic nephropathy, said Dr. Jenssen of Oslo University. Not all patients are suited for it, however.

"According to the algorithm at our center, if you are older than 55 or too sick, you have to decide between the living and deceased donor single kidney graft. Patients who are younger and have less comorbidity are the ones considered for a combined transplant," he said.

Since those who have the dual-organ operation almost always normalize their glycemic values afterward, Dr. Jenssen said, it’s assumed that they will live longer than those who get only a kidney, but studies are divided on the finding.

"The literature over the past 10 years has differed," he said. Comparing studies among institutions is impossible because of the differences in surgical technique and immunosuppressive regimens; the patient populations can also vary widely.

Oslo University is in a unique place to study the issue, Dr. Jenssen suggested. The facility is the national transplant center, with nearly 30 years of full follow-up data on 630 type 1 diabetes patients who were transplanted for ESRD. All of the patients are followed at least annually and their information is entered into the Norwegian Renal Registry.

"Because patients in Norway tend to be very faithful to their doctors, we have not lost a single one of these to follow-up," he said.

Of the entire group, 222 received the simultaneous transplants, 171 received a living donor single kidney, and 237 got a deceased donor kidney. Patients who received the simultaneous transplant were younger than the living or deceased single graft groups (41 years vs. 45 and 55 years, respectively).

The study controlled for the evolution of surgical techniques and immunosuppressant regimens. Before 1989, all pancreases were transplanted with occluded ducts. From 1989 to 1999, the exocrine duct drained into the bladder, and since 2000, into the intestine. The pancreas has always been connected to the systemic circulation by the iliac artery and vein.

Before 2000, the immunosuppressive regiment consisted of cyclosporine and azathioprine; afterward, tacrolimus and mycophenolate. All patients from both eras take a daily dose of prednisone as well. There was no induction therapy before 2000, Dr. Jenssen said. After that time, patients receiving a single kidney began to receive basiliximab, and the dual-transplant patients got thymoglobulin.

The overall 15-year survival rate was 50% in the simultaneous-graft group, 30% in the living donor kidney group, and 12% in the deceased donor kidney group.

Dr. Jenssen presented two regression models. In the first, which controlled for recipient age, time on dialysis, and the transplant era, patients who got the dual graft were significantly more likely to survive to 15 years than were those who got the single live donor kidney (hazard ratio, 0.70). Patients who received a single deceased donor kidney were 31% less likely to survive (HR, 1.29). These differences were no longer significant in a second model, which also controlled for donor age, but Dr. Jenssen said the difference was not clinically meaningful.

Dr. Jenssen had no financial disclosures.

BERLIN – In patients with type 1 diabetes and end-stage renal disease, a combined pancreas/kidney transplant was associated with significantly better 15-year survival than a single kidney graft alone.

Patients who got the simultaneous transplant were 30% more likely to survive to 15 years than were those who received a living donor kidney. Those patients who got a single kidney from a deceased donor, however, were 30% less likely to survive for 15 years after the operation, Dr. Trond Jenssen said at the annual meeting of the European Associations for the Study of Diabetes.

The combined graft is the preferred method of treating end-stage renal disease (ESRD) caused by diabetic nephropathy, said Dr. Jenssen of Oslo University. Not all patients are suited for it, however.

"According to the algorithm at our center, if you are older than 55 or too sick, you have to decide between the living and deceased donor single kidney graft. Patients who are younger and have less comorbidity are the ones considered for a combined transplant," he said.

Since those who have the dual-organ operation almost always normalize their glycemic values afterward, Dr. Jenssen said, it’s assumed that they will live longer than those who get only a kidney, but studies are divided on the finding.

"The literature over the past 10 years has differed," he said. Comparing studies among institutions is impossible because of the differences in surgical technique and immunosuppressive regimens; the patient populations can also vary widely.

Oslo University is in a unique place to study the issue, Dr. Jenssen suggested. The facility is the national transplant center, with nearly 30 years of full follow-up data on 630 type 1 diabetes patients who were transplanted for ESRD. All of the patients are followed at least annually and their information is entered into the Norwegian Renal Registry.

"Because patients in Norway tend to be very faithful to their doctors, we have not lost a single one of these to follow-up," he said.

Of the entire group, 222 received the simultaneous transplants, 171 received a living donor single kidney, and 237 got a deceased donor kidney. Patients who received the simultaneous transplant were younger than the living or deceased single graft groups (41 years vs. 45 and 55 years, respectively).

The study controlled for the evolution of surgical techniques and immunosuppressant regimens. Before 1989, all pancreases were transplanted with occluded ducts. From 1989 to 1999, the exocrine duct drained into the bladder, and since 2000, into the intestine. The pancreas has always been connected to the systemic circulation by the iliac artery and vein.

Before 2000, the immunosuppressive regiment consisted of cyclosporine and azathioprine; afterward, tacrolimus and mycophenolate. All patients from both eras take a daily dose of prednisone as well. There was no induction therapy before 2000, Dr. Jenssen said. After that time, patients receiving a single kidney began to receive basiliximab, and the dual-transplant patients got thymoglobulin.

The overall 15-year survival rate was 50% in the simultaneous-graft group, 30% in the living donor kidney group, and 12% in the deceased donor kidney group.

Dr. Jenssen presented two regression models. In the first, which controlled for recipient age, time on dialysis, and the transplant era, patients who got the dual graft were significantly more likely to survive to 15 years than were those who got the single live donor kidney (hazard ratio, 0.70). Patients who received a single deceased donor kidney were 31% less likely to survive (HR, 1.29). These differences were no longer significant in a second model, which also controlled for donor age, but Dr. Jenssen said the difference was not clinically meaningful.

Dr. Jenssen had no financial disclosures.

BERLIN – In patients with type 1 diabetes and end-stage renal disease, a combined pancreas/kidney transplant was associated with significantly better 15-year survival than a single kidney graft alone.

Patients who got the simultaneous transplant were 30% more likely to survive to 15 years than were those who received a living donor kidney. Those patients who got a single kidney from a deceased donor, however, were 30% less likely to survive for 15 years after the operation, Dr. Trond Jenssen said at the annual meeting of the European Associations for the Study of Diabetes.

The combined graft is the preferred method of treating end-stage renal disease (ESRD) caused by diabetic nephropathy, said Dr. Jenssen of Oslo University. Not all patients are suited for it, however.

"According to the algorithm at our center, if you are older than 55 or too sick, you have to decide between the living and deceased donor single kidney graft. Patients who are younger and have less comorbidity are the ones considered for a combined transplant," he said.

Since those who have the dual-organ operation almost always normalize their glycemic values afterward, Dr. Jenssen said, it’s assumed that they will live longer than those who get only a kidney, but studies are divided on the finding.

"The literature over the past 10 years has differed," he said. Comparing studies among institutions is impossible because of the differences in surgical technique and immunosuppressive regimens; the patient populations can also vary widely.

Oslo University is in a unique place to study the issue, Dr. Jenssen suggested. The facility is the national transplant center, with nearly 30 years of full follow-up data on 630 type 1 diabetes patients who were transplanted for ESRD. All of the patients are followed at least annually and their information is entered into the Norwegian Renal Registry.

"Because patients in Norway tend to be very faithful to their doctors, we have not lost a single one of these to follow-up," he said.

Of the entire group, 222 received the simultaneous transplants, 171 received a living donor single kidney, and 237 got a deceased donor kidney. Patients who received the simultaneous transplant were younger than the living or deceased single graft groups (41 years vs. 45 and 55 years, respectively).

The study controlled for the evolution of surgical techniques and immunosuppressant regimens. Before 1989, all pancreases were transplanted with occluded ducts. From 1989 to 1999, the exocrine duct drained into the bladder, and since 2000, into the intestine. The pancreas has always been connected to the systemic circulation by the iliac artery and vein.

Before 2000, the immunosuppressive regiment consisted of cyclosporine and azathioprine; afterward, tacrolimus and mycophenolate. All patients from both eras take a daily dose of prednisone as well. There was no induction therapy before 2000, Dr. Jenssen said. After that time, patients receiving a single kidney began to receive basiliximab, and the dual-transplant patients got thymoglobulin.

The overall 15-year survival rate was 50% in the simultaneous-graft group, 30% in the living donor kidney group, and 12% in the deceased donor kidney group.

Dr. Jenssen presented two regression models. In the first, which controlled for recipient age, time on dialysis, and the transplant era, patients who got the dual graft were significantly more likely to survive to 15 years than were those who got the single live donor kidney (hazard ratio, 0.70). Patients who received a single deceased donor kidney were 31% less likely to survive (HR, 1.29). These differences were no longer significant in a second model, which also controlled for donor age, but Dr. Jenssen said the difference was not clinically meaningful.

Dr. Jenssen had no financial disclosures.