User login
More adenomas detected with FUSE endoscope
ORLANDO – Use of a novel colonoscope that offers 330-degree viewing, as compared to the 140- to 170-degree viewing of traditional forward-viewing colonoscopes, was associated with a 71% improvement in adenoma detection, according to late-breaking data from a randomized, prospective multicenter study reported at the annual Digestive Disease Week.
In addition to its expanded viewing capability, the device has the same technical features as traditional colonoscopes, including scope length and diameter, full tip deflection, working channel, suction, and forward water-jet irrigation, reported Dr. Ian M. Gralnek of the Technion-Israel Institute of Technology and Elisha Hospital, both in Haifa, Israel.
For the study, 185 patients underwent colonoscopies via both traditional forward-viewing and EndoChoice’s full-spectrum endoscopy (FUSE) colonoscopy in random order on the same day. The overall polyp detection rate was 52.5%, and the adenoma detection rate was 31.7%.
In 88 subjects who underwent traditional colonoscopy followed by FUSE colonoscopy, traditional colonoscopy detected 28 adenomas and the subsequent FUSE colonoscopy detected an additional 20 adenomas, for a 71.4% increase in adenomas found with subsequent FUSE colonoscopy.
In 97 subjects who were randomly assigned to receive FUSE colonoscopy first, 59 adenomas and 2 cancers were detected. On subsequent traditional colonoscopy, 5 additional adenomas were found, yielding an 8.2% increase in adenomas found with subsequent traditional colonoscopy.
Thus, significantly more adenomas were detected by FUSE colonoscopy than with traditional colonoscopy (71.4% vs. 8.2% incremental detection rates), and significantly fewer adenomas were missed by FUSE colonoscopy as compared with traditional colonoscopy (7.6% vs. 42%).
The differences were highly statistically significant, Dr. Gralnek said.
Study subjects were adults aged 18-70 years who were referred between January 2012 and March 2013 for colorectal cancer screening, polyp surveillance, or diagnostic evaluation to one of three sites in Israel, one site in the Netherlands, or two in the United States. Subjects were randomly assigned to receive FUSE or traditional colonoscopy, then to receive the alternative modality on the same day. The same endoscopist performed both examinations.
Though the study findings are limited by the lack of blinding, the fact that the same endoscopist performed both colonoscopies in each patient, and the lack of per-patient analysis, the results highlight the value of the improved visualization afforded by the FUSE colonoscope, Dr. Gralnek concluded.
Developed by EndoChoice, the FUSE colonoscope has a CE marking in Europe, and it recently received 510(k) marketing approval from the U.S. Food and Drug Administration. Commercial availability is expected as early as summer 2013.
The study was sponsored by EndoChoice.
Dr. Gralnek is a member of advisory committees or review panels for Given Imaging and Motus GI, and is a consultant for Given Imaging, Peer Medical, and AstraZeneca.
ORLANDO – Use of a novel colonoscope that offers 330-degree viewing, as compared to the 140- to 170-degree viewing of traditional forward-viewing colonoscopes, was associated with a 71% improvement in adenoma detection, according to late-breaking data from a randomized, prospective multicenter study reported at the annual Digestive Disease Week.
In addition to its expanded viewing capability, the device has the same technical features as traditional colonoscopes, including scope length and diameter, full tip deflection, working channel, suction, and forward water-jet irrigation, reported Dr. Ian M. Gralnek of the Technion-Israel Institute of Technology and Elisha Hospital, both in Haifa, Israel.
For the study, 185 patients underwent colonoscopies via both traditional forward-viewing and EndoChoice’s full-spectrum endoscopy (FUSE) colonoscopy in random order on the same day. The overall polyp detection rate was 52.5%, and the adenoma detection rate was 31.7%.
In 88 subjects who underwent traditional colonoscopy followed by FUSE colonoscopy, traditional colonoscopy detected 28 adenomas and the subsequent FUSE colonoscopy detected an additional 20 adenomas, for a 71.4% increase in adenomas found with subsequent FUSE colonoscopy.
In 97 subjects who were randomly assigned to receive FUSE colonoscopy first, 59 adenomas and 2 cancers were detected. On subsequent traditional colonoscopy, 5 additional adenomas were found, yielding an 8.2% increase in adenomas found with subsequent traditional colonoscopy.
Thus, significantly more adenomas were detected by FUSE colonoscopy than with traditional colonoscopy (71.4% vs. 8.2% incremental detection rates), and significantly fewer adenomas were missed by FUSE colonoscopy as compared with traditional colonoscopy (7.6% vs. 42%).
The differences were highly statistically significant, Dr. Gralnek said.
Study subjects were adults aged 18-70 years who were referred between January 2012 and March 2013 for colorectal cancer screening, polyp surveillance, or diagnostic evaluation to one of three sites in Israel, one site in the Netherlands, or two in the United States. Subjects were randomly assigned to receive FUSE or traditional colonoscopy, then to receive the alternative modality on the same day. The same endoscopist performed both examinations.
Though the study findings are limited by the lack of blinding, the fact that the same endoscopist performed both colonoscopies in each patient, and the lack of per-patient analysis, the results highlight the value of the improved visualization afforded by the FUSE colonoscope, Dr. Gralnek concluded.
Developed by EndoChoice, the FUSE colonoscope has a CE marking in Europe, and it recently received 510(k) marketing approval from the U.S. Food and Drug Administration. Commercial availability is expected as early as summer 2013.
The study was sponsored by EndoChoice.
Dr. Gralnek is a member of advisory committees or review panels for Given Imaging and Motus GI, and is a consultant for Given Imaging, Peer Medical, and AstraZeneca.
ORLANDO – Use of a novel colonoscope that offers 330-degree viewing, as compared to the 140- to 170-degree viewing of traditional forward-viewing colonoscopes, was associated with a 71% improvement in adenoma detection, according to late-breaking data from a randomized, prospective multicenter study reported at the annual Digestive Disease Week.
In addition to its expanded viewing capability, the device has the same technical features as traditional colonoscopes, including scope length and diameter, full tip deflection, working channel, suction, and forward water-jet irrigation, reported Dr. Ian M. Gralnek of the Technion-Israel Institute of Technology and Elisha Hospital, both in Haifa, Israel.
For the study, 185 patients underwent colonoscopies via both traditional forward-viewing and EndoChoice’s full-spectrum endoscopy (FUSE) colonoscopy in random order on the same day. The overall polyp detection rate was 52.5%, and the adenoma detection rate was 31.7%.
In 88 subjects who underwent traditional colonoscopy followed by FUSE colonoscopy, traditional colonoscopy detected 28 adenomas and the subsequent FUSE colonoscopy detected an additional 20 adenomas, for a 71.4% increase in adenomas found with subsequent FUSE colonoscopy.
In 97 subjects who were randomly assigned to receive FUSE colonoscopy first, 59 adenomas and 2 cancers were detected. On subsequent traditional colonoscopy, 5 additional adenomas were found, yielding an 8.2% increase in adenomas found with subsequent traditional colonoscopy.
Thus, significantly more adenomas were detected by FUSE colonoscopy than with traditional colonoscopy (71.4% vs. 8.2% incremental detection rates), and significantly fewer adenomas were missed by FUSE colonoscopy as compared with traditional colonoscopy (7.6% vs. 42%).
The differences were highly statistically significant, Dr. Gralnek said.
Study subjects were adults aged 18-70 years who were referred between January 2012 and March 2013 for colorectal cancer screening, polyp surveillance, or diagnostic evaluation to one of three sites in Israel, one site in the Netherlands, or two in the United States. Subjects were randomly assigned to receive FUSE or traditional colonoscopy, then to receive the alternative modality on the same day. The same endoscopist performed both examinations.
Though the study findings are limited by the lack of blinding, the fact that the same endoscopist performed both colonoscopies in each patient, and the lack of per-patient analysis, the results highlight the value of the improved visualization afforded by the FUSE colonoscope, Dr. Gralnek concluded.
Developed by EndoChoice, the FUSE colonoscope has a CE marking in Europe, and it recently received 510(k) marketing approval from the U.S. Food and Drug Administration. Commercial availability is expected as early as summer 2013.
The study was sponsored by EndoChoice.
Dr. Gralnek is a member of advisory committees or review panels for Given Imaging and Motus GI, and is a consultant for Given Imaging, Peer Medical, and AstraZeneca.
AT DDW 2013
Major finding: In 88 subjects who underwent traditional forward-viewing colonoscopy followed by FUSE colonoscopy, traditional colonoscopy detected 28 adenomas and the subsequent FUSE colonoscopy detected an additional 20 adenomas.
Data source: A randomized, prospective, multicenter study involving 185 patients who underwent both procedures on the same day, by the same endoscopist.
Disclosures: Dr. Gralnek is a member of advisory committees or review panels for Given Imaging and Motus GI, and is a consultant for Given Imaging, Peer Medical, and AstraZeneca.
Nighttime cholecystectomy may increase complication risk
ORLANDO – Older age and nighttime surgery were associated with an increased risk of complications in patients undergoing laparoscopic cholecystectomy at a high-volume safety net hospital, according to a retrospective study of cases.
Of 576 operations performed in consecutive patients for whom relevant data were available, 35% were performed at night, and although about 60% of procedures overall were nonelective, more than 90% of those performed at night were nonelective, meaning that most patients were admitted directly from the emergency department, Dr. Uma R. Phatak reported at the annual Digestive Disease Week.
A total of 35 complications occurred in 22 patients, including 18 undergoing nonelective surgery and 4 undergoing elective surgery.
Multivariate analysis demonstrated that age and nighttime surgery were significant predictors of complications, said Dr. Phatak of the University of Texas Health Science Center, Houston.
The probability of a complication increased with age for both the patients who underwent daytime surgery and those who underwent nighttime surgery, but the increase was greater in the nighttime surgery group, she said.
The predicted probability of a complication increased threefold for older patients who underwent surgery at night, according to an analysis by 10-year age intervals.
"At the upper end of the age spectrum, the predicted probability of a complication with surgery at night is about 30%, compared to about 10% in the daytime group," Dr. Phatak said.
This analysis did not adjust for disease severity, but a multivariate model that included the elective surgery patients showed that even in this group, an increased risk of a complication was associated with nighttime surgery and increasing age, she noted.
Patients included in the study underwent surgery during an 8-month period from October 2010 to May 2011 at a hospital with a large Hispanic population at high risk for gallstones where laparoscopic cholecystectomy is commonly performed at night. Most (84%) were women, and most (84%) were Hispanic.
The most common diagnoses were acute cholecystitis in the nighttime group and chronic cholecystitis in the daytime group.
Those who underwent nighttime surgery had a lower median age and a longer median length of stay, although it was unclear whether the length of stay was increased due to a delay in getting to the operating room.
The study is limited by its single-center retrospective design, which limits the generalizability. It also was underpowered to detect significant differences in complications other than surgical site infections, Dr. Phatak noted.
Nonetheless, the study demonstrates an increased risk of complications with nighttime surgery, suggesting that the benefits of early laparoscopic cholecystectomy for acute cholecystitis must be balanced against the risk of nighttime surgery, Dr. Phatak said.
"At our institution, new ambulatory operating rooms will be opening soon, decreasing the burden on the main operating room. This will allow for nonemergent cases to be booked during the daytime without imposing delays in the elective schedule," she said.
Providing increased space for elective operations, identifying high-risk patients, and prioritizing surgeries during the day for those patients may decrease the complication rate and improve outcomes, she concluded.
Dr. Phatak reported having no disclosures.
The report by Dr. Phatak and her colleagues
from the University of Texas (UT) Health
Science Center,
Houston, raises
a key issue with respect to the management of acute cholecystitis. Should these
operations be performed at night, especially in older patients? Multiple
prospective, randomized trials over the past 4 decades have concluded that
patients with acute cholecystitis who present within the first few days of the
illness should be managed urgently rather than undergo surgery 6 weeks later.
Nevertheless, a significant proportion of these operations are delayed in the United States.
The question then becomes why is evidence-based practice not being performed?
The answers probably include the surgeon’s schedule, daytime operating room
availability, and staff expertise and equipment availability at night. When an
urgent operation is delayed until the middle of the night, is the patient best
served if her surgeon is overly tired? Similarly, should the next morning’s
patient scheduled for an elective procedure undergo an operation by a surgeon
who has not had an adequate night’s sleep?
The obvious answers to these questions is no, but the
solutions are not simple. Multisurgeon groups and Acute Care Surgery services
may address these issues is schedules are constructed appropriately.
Similarly, efficient management of an operating room
during the day with flexibility for the add-on of urgent cases is ideal. In
addition, cross-training of operating room staff with knowledge and
availability of proper equipment at night is not trivial but is key for safe patient
care. Another important point is whether the findings of the report by Dr.
Phatak are generalizable. Certainly, her observations apply to safety-net
hospitals in cities with large Hispanic populations. However, a 60% incidence
of “nonelective” gallbladder surgery is unusual for the typical community
hospital, rural hospital, or academic medical center. In these settings,
appropriate management of acute cholecystitis is to have the patient take
nothing by mouth (NPO), to initiate appropriate medications, and to schedule
surgery semiurgently, ideally during the daytime. While this ideal situation
may not always be possible, insistence on daytime surgery should be a major
principle especially in older, more frail patients.
Dr. Henry
A. Pitt is an ACS Fellow and vice chairman of surgery at Indiana University, Indianapolis. Dr. Pitt has
no disclosures.
The report by Dr. Phatak and her colleagues
from the University of Texas (UT) Health
Science Center,
Houston, raises
a key issue with respect to the management of acute cholecystitis. Should these
operations be performed at night, especially in older patients? Multiple
prospective, randomized trials over the past 4 decades have concluded that
patients with acute cholecystitis who present within the first few days of the
illness should be managed urgently rather than undergo surgery 6 weeks later.
Nevertheless, a significant proportion of these operations are delayed in the United States.
The question then becomes why is evidence-based practice not being performed?
The answers probably include the surgeon’s schedule, daytime operating room
availability, and staff expertise and equipment availability at night. When an
urgent operation is delayed until the middle of the night, is the patient best
served if her surgeon is overly tired? Similarly, should the next morning’s
patient scheduled for an elective procedure undergo an operation by a surgeon
who has not had an adequate night’s sleep?
The obvious answers to these questions is no, but the
solutions are not simple. Multisurgeon groups and Acute Care Surgery services
may address these issues is schedules are constructed appropriately.
Similarly, efficient management of an operating room
during the day with flexibility for the add-on of urgent cases is ideal. In
addition, cross-training of operating room staff with knowledge and
availability of proper equipment at night is not trivial but is key for safe patient
care. Another important point is whether the findings of the report by Dr.
Phatak are generalizable. Certainly, her observations apply to safety-net
hospitals in cities with large Hispanic populations. However, a 60% incidence
of “nonelective” gallbladder surgery is unusual for the typical community
hospital, rural hospital, or academic medical center. In these settings,
appropriate management of acute cholecystitis is to have the patient take
nothing by mouth (NPO), to initiate appropriate medications, and to schedule
surgery semiurgently, ideally during the daytime. While this ideal situation
may not always be possible, insistence on daytime surgery should be a major
principle especially in older, more frail patients.
Dr. Henry
A. Pitt is an ACS Fellow and vice chairman of surgery at Indiana University, Indianapolis. Dr. Pitt has
no disclosures.
The report by Dr. Phatak and her colleagues
from the University of Texas (UT) Health
Science Center,
Houston, raises
a key issue with respect to the management of acute cholecystitis. Should these
operations be performed at night, especially in older patients? Multiple
prospective, randomized trials over the past 4 decades have concluded that
patients with acute cholecystitis who present within the first few days of the
illness should be managed urgently rather than undergo surgery 6 weeks later.
Nevertheless, a significant proportion of these operations are delayed in the United States.
The question then becomes why is evidence-based practice not being performed?
The answers probably include the surgeon’s schedule, daytime operating room
availability, and staff expertise and equipment availability at night. When an
urgent operation is delayed until the middle of the night, is the patient best
served if her surgeon is overly tired? Similarly, should the next morning’s
patient scheduled for an elective procedure undergo an operation by a surgeon
who has not had an adequate night’s sleep?
The obvious answers to these questions is no, but the
solutions are not simple. Multisurgeon groups and Acute Care Surgery services
may address these issues is schedules are constructed appropriately.
Similarly, efficient management of an operating room
during the day with flexibility for the add-on of urgent cases is ideal. In
addition, cross-training of operating room staff with knowledge and
availability of proper equipment at night is not trivial but is key for safe patient
care. Another important point is whether the findings of the report by Dr.
Phatak are generalizable. Certainly, her observations apply to safety-net
hospitals in cities with large Hispanic populations. However, a 60% incidence
of “nonelective” gallbladder surgery is unusual for the typical community
hospital, rural hospital, or academic medical center. In these settings,
appropriate management of acute cholecystitis is to have the patient take
nothing by mouth (NPO), to initiate appropriate medications, and to schedule
surgery semiurgently, ideally during the daytime. While this ideal situation
may not always be possible, insistence on daytime surgery should be a major
principle especially in older, more frail patients.
Dr. Henry
A. Pitt is an ACS Fellow and vice chairman of surgery at Indiana University, Indianapolis. Dr. Pitt has
no disclosures.
ORLANDO – Older age and nighttime surgery were associated with an increased risk of complications in patients undergoing laparoscopic cholecystectomy at a high-volume safety net hospital, according to a retrospective study of cases.
Of 576 operations performed in consecutive patients for whom relevant data were available, 35% were performed at night, and although about 60% of procedures overall were nonelective, more than 90% of those performed at night were nonelective, meaning that most patients were admitted directly from the emergency department, Dr. Uma R. Phatak reported at the annual Digestive Disease Week.
A total of 35 complications occurred in 22 patients, including 18 undergoing nonelective surgery and 4 undergoing elective surgery.
Multivariate analysis demonstrated that age and nighttime surgery were significant predictors of complications, said Dr. Phatak of the University of Texas Health Science Center, Houston.
The probability of a complication increased with age for both the patients who underwent daytime surgery and those who underwent nighttime surgery, but the increase was greater in the nighttime surgery group, she said.
The predicted probability of a complication increased threefold for older patients who underwent surgery at night, according to an analysis by 10-year age intervals.
"At the upper end of the age spectrum, the predicted probability of a complication with surgery at night is about 30%, compared to about 10% in the daytime group," Dr. Phatak said.
This analysis did not adjust for disease severity, but a multivariate model that included the elective surgery patients showed that even in this group, an increased risk of a complication was associated with nighttime surgery and increasing age, she noted.
Patients included in the study underwent surgery during an 8-month period from October 2010 to May 2011 at a hospital with a large Hispanic population at high risk for gallstones where laparoscopic cholecystectomy is commonly performed at night. Most (84%) were women, and most (84%) were Hispanic.
The most common diagnoses were acute cholecystitis in the nighttime group and chronic cholecystitis in the daytime group.
Those who underwent nighttime surgery had a lower median age and a longer median length of stay, although it was unclear whether the length of stay was increased due to a delay in getting to the operating room.
The study is limited by its single-center retrospective design, which limits the generalizability. It also was underpowered to detect significant differences in complications other than surgical site infections, Dr. Phatak noted.
Nonetheless, the study demonstrates an increased risk of complications with nighttime surgery, suggesting that the benefits of early laparoscopic cholecystectomy for acute cholecystitis must be balanced against the risk of nighttime surgery, Dr. Phatak said.
"At our institution, new ambulatory operating rooms will be opening soon, decreasing the burden on the main operating room. This will allow for nonemergent cases to be booked during the daytime without imposing delays in the elective schedule," she said.
Providing increased space for elective operations, identifying high-risk patients, and prioritizing surgeries during the day for those patients may decrease the complication rate and improve outcomes, she concluded.
Dr. Phatak reported having no disclosures.
ORLANDO – Older age and nighttime surgery were associated with an increased risk of complications in patients undergoing laparoscopic cholecystectomy at a high-volume safety net hospital, according to a retrospective study of cases.
Of 576 operations performed in consecutive patients for whom relevant data were available, 35% were performed at night, and although about 60% of procedures overall were nonelective, more than 90% of those performed at night were nonelective, meaning that most patients were admitted directly from the emergency department, Dr. Uma R. Phatak reported at the annual Digestive Disease Week.
A total of 35 complications occurred in 22 patients, including 18 undergoing nonelective surgery and 4 undergoing elective surgery.
Multivariate analysis demonstrated that age and nighttime surgery were significant predictors of complications, said Dr. Phatak of the University of Texas Health Science Center, Houston.
The probability of a complication increased with age for both the patients who underwent daytime surgery and those who underwent nighttime surgery, but the increase was greater in the nighttime surgery group, she said.
The predicted probability of a complication increased threefold for older patients who underwent surgery at night, according to an analysis by 10-year age intervals.
"At the upper end of the age spectrum, the predicted probability of a complication with surgery at night is about 30%, compared to about 10% in the daytime group," Dr. Phatak said.
This analysis did not adjust for disease severity, but a multivariate model that included the elective surgery patients showed that even in this group, an increased risk of a complication was associated with nighttime surgery and increasing age, she noted.
Patients included in the study underwent surgery during an 8-month period from October 2010 to May 2011 at a hospital with a large Hispanic population at high risk for gallstones where laparoscopic cholecystectomy is commonly performed at night. Most (84%) were women, and most (84%) were Hispanic.
The most common diagnoses were acute cholecystitis in the nighttime group and chronic cholecystitis in the daytime group.
Those who underwent nighttime surgery had a lower median age and a longer median length of stay, although it was unclear whether the length of stay was increased due to a delay in getting to the operating room.
The study is limited by its single-center retrospective design, which limits the generalizability. It also was underpowered to detect significant differences in complications other than surgical site infections, Dr. Phatak noted.
Nonetheless, the study demonstrates an increased risk of complications with nighttime surgery, suggesting that the benefits of early laparoscopic cholecystectomy for acute cholecystitis must be balanced against the risk of nighttime surgery, Dr. Phatak said.
"At our institution, new ambulatory operating rooms will be opening soon, decreasing the burden on the main operating room. This will allow for nonemergent cases to be booked during the daytime without imposing delays in the elective schedule," she said.
Providing increased space for elective operations, identifying high-risk patients, and prioritizing surgeries during the day for those patients may decrease the complication rate and improve outcomes, she concluded.
Dr. Phatak reported having no disclosures.
AT DDW 2013
Major finding: Older nighttime cholecystectomy patients had a threefold increased risk for complications.
Data source: A retrospective study of 576 cases.
Disclosures: Dr. Phatak reported having no disclosures.
Skip the sphincterotomy before bile duct stent placement
ORLANDO – Patients with unresectable pancreatic cancer may be safely spared from endoscopic sphincterotomy prior to stent placement, investigators said at the annual Digestive Disease Week.
Among patients undergoing placement of a self-expanding, 10-mm-diameter stent into the bile duct*, there were no differences in the rates of early or late complications between patients randomized to receive endoscopic sphincterotomy (ES) before stent placement and those who underwent stent placement alone, reported Dr. Tsuyoshi Hayashi from Sapporo Medical University in Japan.
"ES had no effect on not only the incidence of complications but also SEMS [self-expanding metal stent] patency and patient survival. ES is an unnecessary pretreatment prior to SEMS placement for distal biliary obstruction due to pancreatic cancer," Dr. Hayashi said.
Although endoscopic sphincterotomy is intended to prevent potential pancreatitis from the expansion forces of the stent on the opening of the pancreatic duct, it adds significantly to operative time and carries the risk of bleeding or perforation, Dr. Hayashi said.
To see whether the endoscopist could safely forego sphincterotomy, investigators in 25 hospitals on Japan’s northern island of Hokkaido enrolled a total of 200 patients into a randomized trial and assigned them to stent placement with or without sphincterotomy. Four patients assigned to sphincterotomy and two assigned to stenting alone were unable to undergo biliary cannulation, leaving 96 and 98 patients, respectively, for the analysis.
The authors found that sphincterotomy added significantly to the procedural time, at a mean of 577 (plus or minus 310) seconds, compared with 388 (plus or minus 203) seconds for the no-sphincterotomy procedures.
But when they looked at early complications (within 30 days of the procedure), they found that there were no significant between-group differences in the rates of mild to severe pancreatitis, moderate bleeding, mild perforation, moderate hepatic abscess, pain, or vomiting.
In addition, there were no significant between-group differences in late complications, including either mild to severe cholecystitis, pancreatitis, bleeding, or duodenal ulcer. Similarly, there were no significant differences between the sphincterotomy group and the no-sphincterotomy group in either median time to stent dysfunction (170.5 vs. 148.0 days, respectively) or median overall survival (242 vs. 202 days).
Causes of stent dysfunction, which occurred in 25 patients in each group, included food impaction, sludge formation, intestinal obstruction, migration, and tumor ingrowth or overgrowth, but there were no significant between-group differences in the causes.
The study funding source was not disclosed. Dr. Hayashi and his colleagues reported having no financial disclosures.
*Correction 7/25/2013: An earlier version of this story missnamed this duct and stent.
For patients with unresectable pancreatic cancer, self-expandable metallic stents (SEMS) are preferred to smaller-caliber, plastic stents for the palliation of jaundice. SEMS have longer patency rates and reduce the overall costs of care by obviating the need for stent exchanges in the majority of cases. Further, SEMS have largely replaced surgical bypass of the bile duct because of reduced morbidity and acceptable durability since most patients with unresectable pancreatic cancer are not expected to survive more than 1 year.
The decision to place a SEMS with complete or partial coating, primarily designed to reduce the likelihood of tumor ingrowth within the interstices of the stent, is more complex. Coating reduces ingrowth and modestly prolongs patency, but increases the likelihood of stent migration and possibly cholecystitis (due to occlusion of the cystic duct). Presumably due to their larger diameter than plastic stents, previous studies suggested a higher rate of post-ERCP (post-endoscopic retrograde cholangiopancreatography) pancreatitis, irrespective of preexisting endoscopic sphincterotomy.
|
| Dr. Gregory Cote |
Second, pancreatitis rates of 8%-9% are higher than expected for a low-risk indication such as malignant bile duct obstruction. The higher rates in this trial may be related to study design (patients in clinical trials are expected to have higher event rates due to meticulous follow-up compared with retrospective studies), use of SEMS in all patients, and specificity of the definition of post-ERCP pancreatitis in this population: Patients with pancreatic cancer are more likely to complain of pain following ERCP that is related to expansion of the metal stent, and a rise in serum pancreatic enzymes that may not necessarily connote true acute pancreatitis. This requires further investigation.
Third, bleeding and perforation are uncommon complications of ERCP with or without sphincterotomy when a high-volume physician performs the procedure. These data corroborate this - the argument that skipping the sphincterotomy will lower an already rare set of events is challenging. In fact, the only observed perforation occurred in a patient randomized to no sphincterotomy! Last, the higher rates (albeit not statistically significant) of hepatic abscess and cholecystitis among patients who did not undergo a sphincterotomy should not be ignored.
In some cases, sphincterotomy facilitates passage of the stent delivery catheter and tissue sampling devices, if needed. Nevertheless, endoscopists should be reassured by the equivalent rates of pancreatitis in this clinical trial. Based on these results, it seems appropriate to withhold sphincterotomy, at least in cases where bleeding may be high risk (e.g., with ongoing use of antiplatelet or anticoagulant medications).
Dr. Gregory A. Cote is an assistant professor of medicine in the department of medicine, division of gastroenterology and hepatology, Indiana University School of Medicine, Indianapolis. He is a consultant and member of the advisory board for Boston Scientific and a member of the advisory board for Olympus America.
For patients with unresectable pancreatic cancer, self-expandable metallic stents (SEMS) are preferred to smaller-caliber, plastic stents for the palliation of jaundice. SEMS have longer patency rates and reduce the overall costs of care by obviating the need for stent exchanges in the majority of cases. Further, SEMS have largely replaced surgical bypass of the bile duct because of reduced morbidity and acceptable durability since most patients with unresectable pancreatic cancer are not expected to survive more than 1 year.
The decision to place a SEMS with complete or partial coating, primarily designed to reduce the likelihood of tumor ingrowth within the interstices of the stent, is more complex. Coating reduces ingrowth and modestly prolongs patency, but increases the likelihood of stent migration and possibly cholecystitis (due to occlusion of the cystic duct). Presumably due to their larger diameter than plastic stents, previous studies suggested a higher rate of post-ERCP (post-endoscopic retrograde cholangiopancreatography) pancreatitis, irrespective of preexisting endoscopic sphincterotomy.
|
|
| Dr. Gregory Cote |
Second, pancreatitis rates of 8%-9% are higher than expected for a low-risk indication such as malignant bile duct obstruction. The higher rates in this trial may be related to study design (patients in clinical trials are expected to have higher event rates due to meticulous follow-up compared with retrospective studies), use of SEMS in all patients, and specificity of the definition of post-ERCP pancreatitis in this population: Patients with pancreatic cancer are more likely to complain of pain following ERCP that is related to expansion of the metal stent, and a rise in serum pancreatic enzymes that may not necessarily connote true acute pancreatitis. This requires further investigation.
Third, bleeding and perforation are uncommon complications of ERCP with or without sphincterotomy when a high-volume physician performs the procedure. These data corroborate this - the argument that skipping the sphincterotomy will lower an already rare set of events is challenging. In fact, the only observed perforation occurred in a patient randomized to no sphincterotomy! Last, the higher rates (albeit not statistically significant) of hepatic abscess and cholecystitis among patients who did not undergo a sphincterotomy should not be ignored.
In some cases, sphincterotomy facilitates passage of the stent delivery catheter and tissue sampling devices, if needed. Nevertheless, endoscopists should be reassured by the equivalent rates of pancreatitis in this clinical trial. Based on these results, it seems appropriate to withhold sphincterotomy, at least in cases where bleeding may be high risk (e.g., with ongoing use of antiplatelet or anticoagulant medications).
Dr. Gregory A. Cote is an assistant professor of medicine in the department of medicine, division of gastroenterology and hepatology, Indiana University School of Medicine, Indianapolis. He is a consultant and member of the advisory board for Boston Scientific and a member of the advisory board for Olympus America.
For patients with unresectable pancreatic cancer, self-expandable metallic stents (SEMS) are preferred to smaller-caliber, plastic stents for the palliation of jaundice. SEMS have longer patency rates and reduce the overall costs of care by obviating the need for stent exchanges in the majority of cases. Further, SEMS have largely replaced surgical bypass of the bile duct because of reduced morbidity and acceptable durability since most patients with unresectable pancreatic cancer are not expected to survive more than 1 year.
The decision to place a SEMS with complete or partial coating, primarily designed to reduce the likelihood of tumor ingrowth within the interstices of the stent, is more complex. Coating reduces ingrowth and modestly prolongs patency, but increases the likelihood of stent migration and possibly cholecystitis (due to occlusion of the cystic duct). Presumably due to their larger diameter than plastic stents, previous studies suggested a higher rate of post-ERCP (post-endoscopic retrograde cholangiopancreatography) pancreatitis, irrespective of preexisting endoscopic sphincterotomy.
|
|
| Dr. Gregory Cote |
Second, pancreatitis rates of 8%-9% are higher than expected for a low-risk indication such as malignant bile duct obstruction. The higher rates in this trial may be related to study design (patients in clinical trials are expected to have higher event rates due to meticulous follow-up compared with retrospective studies), use of SEMS in all patients, and specificity of the definition of post-ERCP pancreatitis in this population: Patients with pancreatic cancer are more likely to complain of pain following ERCP that is related to expansion of the metal stent, and a rise in serum pancreatic enzymes that may not necessarily connote true acute pancreatitis. This requires further investigation.
Third, bleeding and perforation are uncommon complications of ERCP with or without sphincterotomy when a high-volume physician performs the procedure. These data corroborate this - the argument that skipping the sphincterotomy will lower an already rare set of events is challenging. In fact, the only observed perforation occurred in a patient randomized to no sphincterotomy! Last, the higher rates (albeit not statistically significant) of hepatic abscess and cholecystitis among patients who did not undergo a sphincterotomy should not be ignored.
In some cases, sphincterotomy facilitates passage of the stent delivery catheter and tissue sampling devices, if needed. Nevertheless, endoscopists should be reassured by the equivalent rates of pancreatitis in this clinical trial. Based on these results, it seems appropriate to withhold sphincterotomy, at least in cases where bleeding may be high risk (e.g., with ongoing use of antiplatelet or anticoagulant medications).
Dr. Gregory A. Cote is an assistant professor of medicine in the department of medicine, division of gastroenterology and hepatology, Indiana University School of Medicine, Indianapolis. He is a consultant and member of the advisory board for Boston Scientific and a member of the advisory board for Olympus America.
ORLANDO – Patients with unresectable pancreatic cancer may be safely spared from endoscopic sphincterotomy prior to stent placement, investigators said at the annual Digestive Disease Week.
Among patients undergoing placement of a self-expanding, 10-mm-diameter stent into the bile duct*, there were no differences in the rates of early or late complications between patients randomized to receive endoscopic sphincterotomy (ES) before stent placement and those who underwent stent placement alone, reported Dr. Tsuyoshi Hayashi from Sapporo Medical University in Japan.
"ES had no effect on not only the incidence of complications but also SEMS [self-expanding metal stent] patency and patient survival. ES is an unnecessary pretreatment prior to SEMS placement for distal biliary obstruction due to pancreatic cancer," Dr. Hayashi said.
Although endoscopic sphincterotomy is intended to prevent potential pancreatitis from the expansion forces of the stent on the opening of the pancreatic duct, it adds significantly to operative time and carries the risk of bleeding or perforation, Dr. Hayashi said.
To see whether the endoscopist could safely forego sphincterotomy, investigators in 25 hospitals on Japan’s northern island of Hokkaido enrolled a total of 200 patients into a randomized trial and assigned them to stent placement with or without sphincterotomy. Four patients assigned to sphincterotomy and two assigned to stenting alone were unable to undergo biliary cannulation, leaving 96 and 98 patients, respectively, for the analysis.
The authors found that sphincterotomy added significantly to the procedural time, at a mean of 577 (plus or minus 310) seconds, compared with 388 (plus or minus 203) seconds for the no-sphincterotomy procedures.
But when they looked at early complications (within 30 days of the procedure), they found that there were no significant between-group differences in the rates of mild to severe pancreatitis, moderate bleeding, mild perforation, moderate hepatic abscess, pain, or vomiting.
In addition, there were no significant between-group differences in late complications, including either mild to severe cholecystitis, pancreatitis, bleeding, or duodenal ulcer. Similarly, there were no significant differences between the sphincterotomy group and the no-sphincterotomy group in either median time to stent dysfunction (170.5 vs. 148.0 days, respectively) or median overall survival (242 vs. 202 days).
Causes of stent dysfunction, which occurred in 25 patients in each group, included food impaction, sludge formation, intestinal obstruction, migration, and tumor ingrowth or overgrowth, but there were no significant between-group differences in the causes.
The study funding source was not disclosed. Dr. Hayashi and his colleagues reported having no financial disclosures.
*Correction 7/25/2013: An earlier version of this story missnamed this duct and stent.
ORLANDO – Patients with unresectable pancreatic cancer may be safely spared from endoscopic sphincterotomy prior to stent placement, investigators said at the annual Digestive Disease Week.
Among patients undergoing placement of a self-expanding, 10-mm-diameter stent into the bile duct*, there were no differences in the rates of early or late complications between patients randomized to receive endoscopic sphincterotomy (ES) before stent placement and those who underwent stent placement alone, reported Dr. Tsuyoshi Hayashi from Sapporo Medical University in Japan.
"ES had no effect on not only the incidence of complications but also SEMS [self-expanding metal stent] patency and patient survival. ES is an unnecessary pretreatment prior to SEMS placement for distal biliary obstruction due to pancreatic cancer," Dr. Hayashi said.
Although endoscopic sphincterotomy is intended to prevent potential pancreatitis from the expansion forces of the stent on the opening of the pancreatic duct, it adds significantly to operative time and carries the risk of bleeding or perforation, Dr. Hayashi said.
To see whether the endoscopist could safely forego sphincterotomy, investigators in 25 hospitals on Japan’s northern island of Hokkaido enrolled a total of 200 patients into a randomized trial and assigned them to stent placement with or without sphincterotomy. Four patients assigned to sphincterotomy and two assigned to stenting alone were unable to undergo biliary cannulation, leaving 96 and 98 patients, respectively, for the analysis.
The authors found that sphincterotomy added significantly to the procedural time, at a mean of 577 (plus or minus 310) seconds, compared with 388 (plus or minus 203) seconds for the no-sphincterotomy procedures.
But when they looked at early complications (within 30 days of the procedure), they found that there were no significant between-group differences in the rates of mild to severe pancreatitis, moderate bleeding, mild perforation, moderate hepatic abscess, pain, or vomiting.
In addition, there were no significant between-group differences in late complications, including either mild to severe cholecystitis, pancreatitis, bleeding, or duodenal ulcer. Similarly, there were no significant differences between the sphincterotomy group and the no-sphincterotomy group in either median time to stent dysfunction (170.5 vs. 148.0 days, respectively) or median overall survival (242 vs. 202 days).
Causes of stent dysfunction, which occurred in 25 patients in each group, included food impaction, sludge formation, intestinal obstruction, migration, and tumor ingrowth or overgrowth, but there were no significant between-group differences in the causes.
The study funding source was not disclosed. Dr. Hayashi and his colleagues reported having no financial disclosures.
*Correction 7/25/2013: An earlier version of this story missnamed this duct and stent.
AT DDW 2013
Major finding: There were no significant differences in early or late complications among patients with pancreatic cancer who underwent stent placement with or without sphincterotomy.
Data source: Randomized controlled trial in 200 patients from 25 treatment centers in Japan,
Disclosures: The study funding source was not disclosed. Dr. Hayashi and his colleagues reported having no financial disclosures.
Narrow-band imaging colonoscopy predicts histology of diminutive polyps
ORLANDO – Narrow-band imaging colonoscopy accurately predicts the histology of most diminutive polyps in the distal colon, according to findings from a multicenter prospective study.
Use of the technology, which has been promoted as a method for differentiating hypoplastic and adenomatous polyps, could reduce the costs associated with pathological examinations and polypectomy by 60% and 33%, respectively, Dr. Alessandro Repici reported at the annual Digestive Disease Week.
The findings suggest that narrow-band imaging colonoscopy allows high-confidence prediction of the histology of some polyps smaller than 5 mm and is ready for prime time, Dr. Repici said.
"According to our study, high-confidence narrow-band imaging characterization of polyps less than 5 mm was able to meet the criteria threshold for incorporating this kind of real-time histology analysis in clinical practice. This may result in significant reduction of costs in terms of reduction of polypectomy and pathology assessment, and we believe that, according to the present study, high-confidence narrow-band imaging prediction of diminutive polyps located in the distal colon appears ready to be incorporated in clinical practice," he said.
In 278 consecutive patients undergoing elective colonoscopy, a total of 574 polyps smaller than 10 mm, including 429 polyps smaller than 5 mm, were retrieved for histological analysis and were assigned a designation of high or low confidence; 60% of the diminutive polyps were adenomatous. Narrow-band imaging had a sensitivity of 90%, a specificity of 88%, a positive predictive value of 89%, a negative predictive value of 89% and an accuracy of 89% for high-confidence prediction of adenomatous histology in lesions smaller than 5 mm, said Dr. Repici of Istituto Clinico Humanitas, Milan.
Overall, narrow-band imaging had an 84% negative predictive value for diminutive polyps, but the negative predictive value was 92% for those in the distal colon. This met the 90% threshold established by the American Society for Gastrointestinal Endoscopy for adequacy, he said.
Furthermore, high-confidence characterization of polyps smaller than 5 mm predicted the correct surveillance interval in 92% and 99% of cases by American and European guidelines, respectively, he said.
On multivariate analysis, the only independent predictor of an incorrect characterization of polyp histology by narrow-band imaging was a low level of confidence (odds ratio, 3.8), Dr. Repici said.
Study subjects were adults with a mean age of 63 years who underwent elective colonoscopy between May 2011 and May 2012. More than half (58%) were men, and 22% had a family history of colorectal cancer. Participating endoscopists were required to pass a qualifying examination before the start of the study.
Dr. Repici has served on advisory committees or review panels for Boston Scientific and Almirall Prodesfarma, and has served as a consultant for Cosmo Technologies. He has received grant and/or research or other support from Ferring Pharmaceuticals, Olympus Europe, US Endoscopy, and Cook.
ORLANDO – Narrow-band imaging colonoscopy accurately predicts the histology of most diminutive polyps in the distal colon, according to findings from a multicenter prospective study.
Use of the technology, which has been promoted as a method for differentiating hypoplastic and adenomatous polyps, could reduce the costs associated with pathological examinations and polypectomy by 60% and 33%, respectively, Dr. Alessandro Repici reported at the annual Digestive Disease Week.
The findings suggest that narrow-band imaging colonoscopy allows high-confidence prediction of the histology of some polyps smaller than 5 mm and is ready for prime time, Dr. Repici said.
"According to our study, high-confidence narrow-band imaging characterization of polyps less than 5 mm was able to meet the criteria threshold for incorporating this kind of real-time histology analysis in clinical practice. This may result in significant reduction of costs in terms of reduction of polypectomy and pathology assessment, and we believe that, according to the present study, high-confidence narrow-band imaging prediction of diminutive polyps located in the distal colon appears ready to be incorporated in clinical practice," he said.
In 278 consecutive patients undergoing elective colonoscopy, a total of 574 polyps smaller than 10 mm, including 429 polyps smaller than 5 mm, were retrieved for histological analysis and were assigned a designation of high or low confidence; 60% of the diminutive polyps were adenomatous. Narrow-band imaging had a sensitivity of 90%, a specificity of 88%, a positive predictive value of 89%, a negative predictive value of 89% and an accuracy of 89% for high-confidence prediction of adenomatous histology in lesions smaller than 5 mm, said Dr. Repici of Istituto Clinico Humanitas, Milan.
Overall, narrow-band imaging had an 84% negative predictive value for diminutive polyps, but the negative predictive value was 92% for those in the distal colon. This met the 90% threshold established by the American Society for Gastrointestinal Endoscopy for adequacy, he said.
Furthermore, high-confidence characterization of polyps smaller than 5 mm predicted the correct surveillance interval in 92% and 99% of cases by American and European guidelines, respectively, he said.
On multivariate analysis, the only independent predictor of an incorrect characterization of polyp histology by narrow-band imaging was a low level of confidence (odds ratio, 3.8), Dr. Repici said.
Study subjects were adults with a mean age of 63 years who underwent elective colonoscopy between May 2011 and May 2012. More than half (58%) were men, and 22% had a family history of colorectal cancer. Participating endoscopists were required to pass a qualifying examination before the start of the study.
Dr. Repici has served on advisory committees or review panels for Boston Scientific and Almirall Prodesfarma, and has served as a consultant for Cosmo Technologies. He has received grant and/or research or other support from Ferring Pharmaceuticals, Olympus Europe, US Endoscopy, and Cook.
ORLANDO – Narrow-band imaging colonoscopy accurately predicts the histology of most diminutive polyps in the distal colon, according to findings from a multicenter prospective study.
Use of the technology, which has been promoted as a method for differentiating hypoplastic and adenomatous polyps, could reduce the costs associated with pathological examinations and polypectomy by 60% and 33%, respectively, Dr. Alessandro Repici reported at the annual Digestive Disease Week.
The findings suggest that narrow-band imaging colonoscopy allows high-confidence prediction of the histology of some polyps smaller than 5 mm and is ready for prime time, Dr. Repici said.
"According to our study, high-confidence narrow-band imaging characterization of polyps less than 5 mm was able to meet the criteria threshold for incorporating this kind of real-time histology analysis in clinical practice. This may result in significant reduction of costs in terms of reduction of polypectomy and pathology assessment, and we believe that, according to the present study, high-confidence narrow-band imaging prediction of diminutive polyps located in the distal colon appears ready to be incorporated in clinical practice," he said.
In 278 consecutive patients undergoing elective colonoscopy, a total of 574 polyps smaller than 10 mm, including 429 polyps smaller than 5 mm, were retrieved for histological analysis and were assigned a designation of high or low confidence; 60% of the diminutive polyps were adenomatous. Narrow-band imaging had a sensitivity of 90%, a specificity of 88%, a positive predictive value of 89%, a negative predictive value of 89% and an accuracy of 89% for high-confidence prediction of adenomatous histology in lesions smaller than 5 mm, said Dr. Repici of Istituto Clinico Humanitas, Milan.
Overall, narrow-band imaging had an 84% negative predictive value for diminutive polyps, but the negative predictive value was 92% for those in the distal colon. This met the 90% threshold established by the American Society for Gastrointestinal Endoscopy for adequacy, he said.
Furthermore, high-confidence characterization of polyps smaller than 5 mm predicted the correct surveillance interval in 92% and 99% of cases by American and European guidelines, respectively, he said.
On multivariate analysis, the only independent predictor of an incorrect characterization of polyp histology by narrow-band imaging was a low level of confidence (odds ratio, 3.8), Dr. Repici said.
Study subjects were adults with a mean age of 63 years who underwent elective colonoscopy between May 2011 and May 2012. More than half (58%) were men, and 22% had a family history of colorectal cancer. Participating endoscopists were required to pass a qualifying examination before the start of the study.
Dr. Repici has served on advisory committees or review panels for Boston Scientific and Almirall Prodesfarma, and has served as a consultant for Cosmo Technologies. He has received grant and/or research or other support from Ferring Pharmaceuticals, Olympus Europe, US Endoscopy, and Cook.
AT DDW 2013
Major finding: The negative predictive value of narrow-band imaging colonoscopy was 92% for polyps less than 5 mm in the distal colon.
Data source: A prospective multicenter study of 278 consecutive patients.
Disclosures: Dr. Repici has served on advisory committees or review panels for Boston Scientific and Almirall Prodesfarma and has served as a consultant for Cosmo Technologies. He has received grant and/or research or other support from Ferring Pharmaceuticals, Olympus Europe, US Endoscopy, and Cook.
Coffee protects against primary sclerosing cholangitis
Coffee consumption appears to protect against the development of primary sclerosing cholangitis, but not against the development of primary biliary cirrhosis, according to findings from a case-control study involving more than 1,300 subjects.
Average coffee consumption was 50 cups per month among 348 study subjects with primary sclerosing cholangitis (PSC), and those subjects spent an average of 50% of their life actively drinking coffee. Average coffee consumption among 456 healthy controls was 78 cups per month, and those subjects spent an average of 67% of their life actively drinking coffee, Dr. Craig Lammert reported during a press briefing held prior to the annual Digestive Disease Week where the findings will be presented.
The differences between the PSC patients and the controls were statistically significant after adjustment for age and sex, said Dr. Lammert of Mayo Clinic, Rochester, Minn.
The healthy controls and 530 subjects with primary biliary cirrhosis (PBC) did not differ significantly with respect to mean age when coffee drinking began, estimated lifetime cups of coffee per month, or percent of life spent actively drinking coffee.
Study subjects were adult patients with well-defined PBC and PSC, and healthy controls recruited between 2002 and 2013. All completed a questionnaire about their coffee drinking history and status.
The PBC patients and healthy controls differed in terms of sex (89% vs. 74% in the groups, respectively, were women), but were of similar age (66 years in both groups). The groups did not differ in terms of the percentages of current coffee drinkers and never coffee drinkers.
The PSC patient and healthy control groups differed significantly both in terms of sex composition and age (57 vs. 66 years, in the groups, respectively). Furthermore, 21% of PSC patients, compared with 13% of controls, reported never drinking coffee, and 67% of PSC patients, compared with 78% of controls, were current coffee drinkers. These differences were significant even after adjustment for age and sex.
Coffee consumption has been linked with numerous health benefits, including protective effects in the liver, but detailed evaluation of coffee use among patients with cholestatic liver disease has been lacking, according to Dr. Lammert.
These findings reveal an environmental effect divergence between PSC and PBC, which is interesting given that coffee was previously thought to be protective in advanced liver disease, said Dr. Larry Friedman, Digestive Disease Week Council chair and chair of the department of medicine at Newton-Wellesley Hospital in Newton, Mass.
"The key question to answer is, why is PBC different?" he asked, adding that PBC appears to be an "outlier that doesn’t follow the model or patterns reported to date."
Indeed, the findings are expected to spur new research into the environmental factors associated with complex liver disease, Dr. Lammert said.
As for whether patients with PSC should be encouraged to drink coffee, Dr. Lammert said the data are insufficient for making specific recommendations at this point.
"But I won’t discourage it by any means," he said.
This study was funded by grants from the National Institutes of Health and the American Liver Foundation. Dr. Lammert reported having no disclosures.
Coffee consumption appears to protect against the development of primary sclerosing cholangitis, but not against the development of primary biliary cirrhosis, according to findings from a case-control study involving more than 1,300 subjects.
Average coffee consumption was 50 cups per month among 348 study subjects with primary sclerosing cholangitis (PSC), and those subjects spent an average of 50% of their life actively drinking coffee. Average coffee consumption among 456 healthy controls was 78 cups per month, and those subjects spent an average of 67% of their life actively drinking coffee, Dr. Craig Lammert reported during a press briefing held prior to the annual Digestive Disease Week where the findings will be presented.
The differences between the PSC patients and the controls were statistically significant after adjustment for age and sex, said Dr. Lammert of Mayo Clinic, Rochester, Minn.
The healthy controls and 530 subjects with primary biliary cirrhosis (PBC) did not differ significantly with respect to mean age when coffee drinking began, estimated lifetime cups of coffee per month, or percent of life spent actively drinking coffee.
Study subjects were adult patients with well-defined PBC and PSC, and healthy controls recruited between 2002 and 2013. All completed a questionnaire about their coffee drinking history and status.
The PBC patients and healthy controls differed in terms of sex (89% vs. 74% in the groups, respectively, were women), but were of similar age (66 years in both groups). The groups did not differ in terms of the percentages of current coffee drinkers and never coffee drinkers.
The PSC patient and healthy control groups differed significantly both in terms of sex composition and age (57 vs. 66 years, in the groups, respectively). Furthermore, 21% of PSC patients, compared with 13% of controls, reported never drinking coffee, and 67% of PSC patients, compared with 78% of controls, were current coffee drinkers. These differences were significant even after adjustment for age and sex.
Coffee consumption has been linked with numerous health benefits, including protective effects in the liver, but detailed evaluation of coffee use among patients with cholestatic liver disease has been lacking, according to Dr. Lammert.
These findings reveal an environmental effect divergence between PSC and PBC, which is interesting given that coffee was previously thought to be protective in advanced liver disease, said Dr. Larry Friedman, Digestive Disease Week Council chair and chair of the department of medicine at Newton-Wellesley Hospital in Newton, Mass.
"The key question to answer is, why is PBC different?" he asked, adding that PBC appears to be an "outlier that doesn’t follow the model or patterns reported to date."
Indeed, the findings are expected to spur new research into the environmental factors associated with complex liver disease, Dr. Lammert said.
As for whether patients with PSC should be encouraged to drink coffee, Dr. Lammert said the data are insufficient for making specific recommendations at this point.
"But I won’t discourage it by any means," he said.
This study was funded by grants from the National Institutes of Health and the American Liver Foundation. Dr. Lammert reported having no disclosures.
Coffee consumption appears to protect against the development of primary sclerosing cholangitis, but not against the development of primary biliary cirrhosis, according to findings from a case-control study involving more than 1,300 subjects.
Average coffee consumption was 50 cups per month among 348 study subjects with primary sclerosing cholangitis (PSC), and those subjects spent an average of 50% of their life actively drinking coffee. Average coffee consumption among 456 healthy controls was 78 cups per month, and those subjects spent an average of 67% of their life actively drinking coffee, Dr. Craig Lammert reported during a press briefing held prior to the annual Digestive Disease Week where the findings will be presented.
The differences between the PSC patients and the controls were statistically significant after adjustment for age and sex, said Dr. Lammert of Mayo Clinic, Rochester, Minn.
The healthy controls and 530 subjects with primary biliary cirrhosis (PBC) did not differ significantly with respect to mean age when coffee drinking began, estimated lifetime cups of coffee per month, or percent of life spent actively drinking coffee.
Study subjects were adult patients with well-defined PBC and PSC, and healthy controls recruited between 2002 and 2013. All completed a questionnaire about their coffee drinking history and status.
The PBC patients and healthy controls differed in terms of sex (89% vs. 74% in the groups, respectively, were women), but were of similar age (66 years in both groups). The groups did not differ in terms of the percentages of current coffee drinkers and never coffee drinkers.
The PSC patient and healthy control groups differed significantly both in terms of sex composition and age (57 vs. 66 years, in the groups, respectively). Furthermore, 21% of PSC patients, compared with 13% of controls, reported never drinking coffee, and 67% of PSC patients, compared with 78% of controls, were current coffee drinkers. These differences were significant even after adjustment for age and sex.
Coffee consumption has been linked with numerous health benefits, including protective effects in the liver, but detailed evaluation of coffee use among patients with cholestatic liver disease has been lacking, according to Dr. Lammert.
These findings reveal an environmental effect divergence between PSC and PBC, which is interesting given that coffee was previously thought to be protective in advanced liver disease, said Dr. Larry Friedman, Digestive Disease Week Council chair and chair of the department of medicine at Newton-Wellesley Hospital in Newton, Mass.
"The key question to answer is, why is PBC different?" he asked, adding that PBC appears to be an "outlier that doesn’t follow the model or patterns reported to date."
Indeed, the findings are expected to spur new research into the environmental factors associated with complex liver disease, Dr. Lammert said.
As for whether patients with PSC should be encouraged to drink coffee, Dr. Lammert said the data are insufficient for making specific recommendations at this point.
"But I won’t discourage it by any means," he said.
This study was funded by grants from the National Institutes of Health and the American Liver Foundation. Dr. Lammert reported having no disclosures.
Major finding: Average coffee consumption was 50 vs. 78 cups per month, and percent of life actively drinking coffee was 50% vs. 67% in PSC cases vs. healthy controls, respectively.
Data source: A case-control study involving 1,334 subjects.
Disclosures: This study was funded by grants from the National Institutes of Health and the American Liver Foundation. Dr. Lammert reported having no disclosures.
Exhaled VOC concentrations provide childhood obesity clues
Concentrations of certain exhaled volatile organic compounds are significantly higher in obese children than in nonobese children, according to findings from a controlled study involving more than 100 children.
The findings could lead to improved understanding of the pathophysiologic processes and pathways leading to childhood obesity, according to Dr. Naim Alkhouri of Cleveland Clinic Children’s Hospital.
These "breath prints" also could lead to interventions for childhood obesity, Dr. Alkhouri said at a press briefing held in advance of the annual Digestive Disease Week, where the data will be presented.
Mass spectrometry in 60 obese children and 55 lean controls demonstrated differences in the concentrations of more than 50 volatile organic compounds (VOCs). Four ion peaks were shown to identify overweight/obese subjects with 92% accuracy, he said.
Further analysis showed significantly higher concentrations of four VOCs in the obese vs. nonobese children after adjustment for age, height, and race. These included breath isoprene (11.6 ppb vs. 6.2 ppb), 1-octene (7.7 ppb vs. 4.6 ppb), ammonia (67.4 ppb vs. 50.1 ppb), and hydrogen sulfide (0.49 vs. 0.35 ppb), he said.
Overweight and obese study subjects were children recruited from a pediatric preventive cardiology and metabolic clinic; healthy controls were recruited from a general pediatric clinic during well-child visits. All underwent a single exhaled breath collection using selective ion flow tube-mass spectrometry.
The obese and lean groups differed significantly in that those in the obese group were older (mean of 14.1 vs. 12.1 years), taller (mean of 164.9 vs. 153.3 cm), and more likely to be white (60% vs. 35.2%).
"Obesity continues to be an epidemic in the United States and worldwide. We estimate that 17% of children in the United States are obese, and 32% percent are overweight," Dr. Alkhouri said, adding that these children are at risk for serious health complications, such as diabetes, obstructive sleep apnea, nonalcoholic fatty liver disease, and cardiovascular disease.
"We believe that these breath prints will shed light on the causes and complications of childhood obesity. This could have implications for early interventions as well as new and easier ways to screen for obesity-related complications," he concluded.
Dr. Alkhouri disclosed ties with Gilead Sciences, Vertex Pharmaceuticals, and Merck.
Concentrations of certain exhaled volatile organic compounds are significantly higher in obese children than in nonobese children, according to findings from a controlled study involving more than 100 children.
The findings could lead to improved understanding of the pathophysiologic processes and pathways leading to childhood obesity, according to Dr. Naim Alkhouri of Cleveland Clinic Children’s Hospital.
These "breath prints" also could lead to interventions for childhood obesity, Dr. Alkhouri said at a press briefing held in advance of the annual Digestive Disease Week, where the data will be presented.
Mass spectrometry in 60 obese children and 55 lean controls demonstrated differences in the concentrations of more than 50 volatile organic compounds (VOCs). Four ion peaks were shown to identify overweight/obese subjects with 92% accuracy, he said.
Further analysis showed significantly higher concentrations of four VOCs in the obese vs. nonobese children after adjustment for age, height, and race. These included breath isoprene (11.6 ppb vs. 6.2 ppb), 1-octene (7.7 ppb vs. 4.6 ppb), ammonia (67.4 ppb vs. 50.1 ppb), and hydrogen sulfide (0.49 vs. 0.35 ppb), he said.
Overweight and obese study subjects were children recruited from a pediatric preventive cardiology and metabolic clinic; healthy controls were recruited from a general pediatric clinic during well-child visits. All underwent a single exhaled breath collection using selective ion flow tube-mass spectrometry.
The obese and lean groups differed significantly in that those in the obese group were older (mean of 14.1 vs. 12.1 years), taller (mean of 164.9 vs. 153.3 cm), and more likely to be white (60% vs. 35.2%).
"Obesity continues to be an epidemic in the United States and worldwide. We estimate that 17% of children in the United States are obese, and 32% percent are overweight," Dr. Alkhouri said, adding that these children are at risk for serious health complications, such as diabetes, obstructive sleep apnea, nonalcoholic fatty liver disease, and cardiovascular disease.
"We believe that these breath prints will shed light on the causes and complications of childhood obesity. This could have implications for early interventions as well as new and easier ways to screen for obesity-related complications," he concluded.
Dr. Alkhouri disclosed ties with Gilead Sciences, Vertex Pharmaceuticals, and Merck.
Concentrations of certain exhaled volatile organic compounds are significantly higher in obese children than in nonobese children, according to findings from a controlled study involving more than 100 children.
The findings could lead to improved understanding of the pathophysiologic processes and pathways leading to childhood obesity, according to Dr. Naim Alkhouri of Cleveland Clinic Children’s Hospital.
These "breath prints" also could lead to interventions for childhood obesity, Dr. Alkhouri said at a press briefing held in advance of the annual Digestive Disease Week, where the data will be presented.
Mass spectrometry in 60 obese children and 55 lean controls demonstrated differences in the concentrations of more than 50 volatile organic compounds (VOCs). Four ion peaks were shown to identify overweight/obese subjects with 92% accuracy, he said.
Further analysis showed significantly higher concentrations of four VOCs in the obese vs. nonobese children after adjustment for age, height, and race. These included breath isoprene (11.6 ppb vs. 6.2 ppb), 1-octene (7.7 ppb vs. 4.6 ppb), ammonia (67.4 ppb vs. 50.1 ppb), and hydrogen sulfide (0.49 vs. 0.35 ppb), he said.
Overweight and obese study subjects were children recruited from a pediatric preventive cardiology and metabolic clinic; healthy controls were recruited from a general pediatric clinic during well-child visits. All underwent a single exhaled breath collection using selective ion flow tube-mass spectrometry.
The obese and lean groups differed significantly in that those in the obese group were older (mean of 14.1 vs. 12.1 years), taller (mean of 164.9 vs. 153.3 cm), and more likely to be white (60% vs. 35.2%).
"Obesity continues to be an epidemic in the United States and worldwide. We estimate that 17% of children in the United States are obese, and 32% percent are overweight," Dr. Alkhouri said, adding that these children are at risk for serious health complications, such as diabetes, obstructive sleep apnea, nonalcoholic fatty liver disease, and cardiovascular disease.
"We believe that these breath prints will shed light on the causes and complications of childhood obesity. This could have implications for early interventions as well as new and easier ways to screen for obesity-related complications," he concluded.
Dr. Alkhouri disclosed ties with Gilead Sciences, Vertex Pharmaceuticals, and Merck.
Major finding: Concentrations of four VOCs were significantly higher in the overweight/obese vs. nonobese children after adjustment for age, height, and race. These included breath isoprene (11.6 ppb vs. 6.2 ppb), 1-octene (7.7 ppb vs. 4.6 ppb), ammonia (67.4 ppb vs. 50.1 ppb), and hydrogen sulfide (0.49 vs. 0.35 ppb).
Data source: A controlled study comparing exhaled VOC concentrations in overweight/obese and lean children.
Disclosures: Dr. Alkhouri disclosed ties with Gilead Sciences, Vertex Pharmaceuticals, and Merck.
New blood test could identify early pancreatic cancer
An investigational serum biomarker panel accurately identified potentially resectable cases of pancreatic cancer, opening up the possibility that a blood test could identify the cancer early and improve its dismal prognosis.
The panel measured four metabolites and had an overall sensitivity of 71% and a specificity of 78% for pancreatic cancer; the specificity for resectable tumors also approached 78%, reported Dr. Masaru Yoshida and his colleagues (Cancer Epidemiol. Biomarkers Prev. 2013 March 29 [doi: 10.1158/1055-9965.EPI-12-1033]).
The panel was more accurate than were any of the currently used biomarkers, including CA19-9 and CEA, said Dr. Yoshida, professor and chief of metabolomics research at Kobe University, Japan, and his colleagues.
"This novel diagnostic approach, which is safe and easy to apply as a screening method, is expected to improve the prognosis of patients with pancreatic cancer by detecting their cancers early, when still in a resectable and curable state," Dr. Yoshida said in a press statement.
The researchers created the panel based on a study of a cohort of 85 subjects: 43 with pancreatic cancer and 42 healthy controls. First, they pared down 113 potentially useful metabolites into a workable testing panel. Of the 45 candidate metabolites, four of them – xylitol, 1,5-anhydro-D-glucitol, histidine, and inositol – showed the highest variation between the healthy controls and the patients. In the training cohort, the panel of these four markers had a sensitivity of 86% and specificity of 88% for pancreatic cancer.
Next, the researchers evaluated a validation cohort of 42 cancer patients, 41 healthy controls, and 23 patients with chronic pancreatitis. In this cohort, with an area under the curve of 0.76, the panel’s sensitivity for pancreatic cancer was 71% and specificity, 78%. In contrast, the sensitivity of CA19-9 was 69% and specificity 86%; for CEA, those numbers were 36% and 80%, respectively.
In the subset of patients with resectable pancreatic cancer, the panel’s sensitivity was 78%, compared with 56% for CA19-9 and 44% for CEA.
The metabolic panel was also able to identify chronic pancreatitis, with a 17% rate of false positives, compared with a false-positive rate of 30% for CA19-9 and 44% for CEA.
A blood panel could address three key problems in the field of pancreatic cancer, Dr. Yoshida and his colleagues said. "The first is the difficulty of detecting pancreatic cancer early in resectable stages. A sensitivity and specificity of about 80% for resectable disease ... should be acceptable for clinical use, because most patients with resectable cancer have no symptoms, and blood examinations are useful tools for initial screening examinations."
The second problem is the difficulty in differentiating pancreatic cancer from chronic pancreatitis. "Many gastroenterologists follow up chronic pancreatitis with scheduled CT, magnetic resonance imaging (MRI), and endoscopic ultrasound scans (EUS); tumor marker tests; and endoscopic retrograde cholangiopancreatography (ERCP), but the initial malignant changes are frequently overlooked, and pancreatic tumors can rapidly become unresectable. In addition, unnecessary resections for benign inflammatory lesions are sometimes done because of false-positive results from CA19-9 and/or imaging examinations."
The third clinical problem is the risk of complications that result from pancreatic examinations. Serum samples are easy and safe to obtain, with a low risk of adverse events and, with this panel, a potentially good return of information. A blood test could also be a useful population screening tool, the researchers noted.
The metabolites probably reflect metabolic derangement that arises not only from focal tumorigenesis, but also from systemic reactions to pancreatic disease, Dr. Yoshida and his coinvestigators wrote. Pancreatic cancer causes significant decreases in some amino and fatty acids, probably because the tumor recruits these substances to aid its rapid cellular proliferation.
"Patients with pancreatic disease are also troubled by malnutrition because of pancreatic endocrine and exocrine insufficiency. Therefore, there is a possibility that the decreases in serum metabolite levels also reflect malnutrition."
Finally, they said, the decrease in 1,5-anhydro-D-glucitol indicates the presence of hyperglycemia and recent glycosuria. "These results suggest that glucose tolerance was impaired in these patients because of pancreatic insufficiency."
The authors reported no financial conflicts. The work was supported by grants administered by agencies of the Japanese government.
The results of Kobayashi et al. are encouraging in many respects, but need to be viewed with caution. The first question is whether the findings are repeatable in other populations. If so, their test may prove to be more sensitive and specific than CA19-9 and CEA for smaller pancreatic cancers, especially in the setting of chronic pancreatitis. Replication in larger studies is important because this study was relatively small, with only nine cases of cancer stage 0-IIB. Second, is the assay more rapid, reliable, robust, and/or significantly less expensive than CA19-9 and CEA? These factors are important for physician and health care system acceptance. Third, this approach has not been adequately tested in other disease states, with the important exception of chronic pancreatitis. Fourth, the test was done in the serum of patients who were already diagnosed with pancreatic cancer by other methods. Even in this setting, the sensitivity and specificity were inferior to clinical suspicion and imaging techniques.
The study was not designed to evaluate this test for early detection of pancreatic cancer, and with the current sensitivity and specificity, this test will have little if any value in screening of otherwise healthy populations. Finally, this approach did identify specific metabolites that were different between pancreatic cancer, chronic pancreatitis, and controls, which may provide further insights into the metabolic derangements of pancreatic cancer. Thus, it is too early to embrace or reject this new approach in the average clinic, but it does provide new insights and perspectives – and is moving us in a positive direction.
David C. Whitcomb, M.D., Ph.D., is the Giant Eagle Professor of Cancer Genetics; professor of medicine, cell biology, and physiology and human genetics; and chief of the division of gastroenterology, hepatology, and nutrition at the University of Pittsburgh and University of Pittsburgh Medical Center. He reports no significant financial conflicts.
The results of Kobayashi et al. are encouraging in many respects, but need to be viewed with caution. The first question is whether the findings are repeatable in other populations. If so, their test may prove to be more sensitive and specific than CA19-9 and CEA for smaller pancreatic cancers, especially in the setting of chronic pancreatitis. Replication in larger studies is important because this study was relatively small, with only nine cases of cancer stage 0-IIB. Second, is the assay more rapid, reliable, robust, and/or significantly less expensive than CA19-9 and CEA? These factors are important for physician and health care system acceptance. Third, this approach has not been adequately tested in other disease states, with the important exception of chronic pancreatitis. Fourth, the test was done in the serum of patients who were already diagnosed with pancreatic cancer by other methods. Even in this setting, the sensitivity and specificity were inferior to clinical suspicion and imaging techniques.
The study was not designed to evaluate this test for early detection of pancreatic cancer, and with the current sensitivity and specificity, this test will have little if any value in screening of otherwise healthy populations. Finally, this approach did identify specific metabolites that were different between pancreatic cancer, chronic pancreatitis, and controls, which may provide further insights into the metabolic derangements of pancreatic cancer. Thus, it is too early to embrace or reject this new approach in the average clinic, but it does provide new insights and perspectives – and is moving us in a positive direction.
David C. Whitcomb, M.D., Ph.D., is the Giant Eagle Professor of Cancer Genetics; professor of medicine, cell biology, and physiology and human genetics; and chief of the division of gastroenterology, hepatology, and nutrition at the University of Pittsburgh and University of Pittsburgh Medical Center. He reports no significant financial conflicts.
The results of Kobayashi et al. are encouraging in many respects, but need to be viewed with caution. The first question is whether the findings are repeatable in other populations. If so, their test may prove to be more sensitive and specific than CA19-9 and CEA for smaller pancreatic cancers, especially in the setting of chronic pancreatitis. Replication in larger studies is important because this study was relatively small, with only nine cases of cancer stage 0-IIB. Second, is the assay more rapid, reliable, robust, and/or significantly less expensive than CA19-9 and CEA? These factors are important for physician and health care system acceptance. Third, this approach has not been adequately tested in other disease states, with the important exception of chronic pancreatitis. Fourth, the test was done in the serum of patients who were already diagnosed with pancreatic cancer by other methods. Even in this setting, the sensitivity and specificity were inferior to clinical suspicion and imaging techniques.
The study was not designed to evaluate this test for early detection of pancreatic cancer, and with the current sensitivity and specificity, this test will have little if any value in screening of otherwise healthy populations. Finally, this approach did identify specific metabolites that were different between pancreatic cancer, chronic pancreatitis, and controls, which may provide further insights into the metabolic derangements of pancreatic cancer. Thus, it is too early to embrace or reject this new approach in the average clinic, but it does provide new insights and perspectives – and is moving us in a positive direction.
David C. Whitcomb, M.D., Ph.D., is the Giant Eagle Professor of Cancer Genetics; professor of medicine, cell biology, and physiology and human genetics; and chief of the division of gastroenterology, hepatology, and nutrition at the University of Pittsburgh and University of Pittsburgh Medical Center. He reports no significant financial conflicts.
An investigational serum biomarker panel accurately identified potentially resectable cases of pancreatic cancer, opening up the possibility that a blood test could identify the cancer early and improve its dismal prognosis.
The panel measured four metabolites and had an overall sensitivity of 71% and a specificity of 78% for pancreatic cancer; the specificity for resectable tumors also approached 78%, reported Dr. Masaru Yoshida and his colleagues (Cancer Epidemiol. Biomarkers Prev. 2013 March 29 [doi: 10.1158/1055-9965.EPI-12-1033]).
The panel was more accurate than were any of the currently used biomarkers, including CA19-9 and CEA, said Dr. Yoshida, professor and chief of metabolomics research at Kobe University, Japan, and his colleagues.
"This novel diagnostic approach, which is safe and easy to apply as a screening method, is expected to improve the prognosis of patients with pancreatic cancer by detecting their cancers early, when still in a resectable and curable state," Dr. Yoshida said in a press statement.
The researchers created the panel based on a study of a cohort of 85 subjects: 43 with pancreatic cancer and 42 healthy controls. First, they pared down 113 potentially useful metabolites into a workable testing panel. Of the 45 candidate metabolites, four of them – xylitol, 1,5-anhydro-D-glucitol, histidine, and inositol – showed the highest variation between the healthy controls and the patients. In the training cohort, the panel of these four markers had a sensitivity of 86% and specificity of 88% for pancreatic cancer.
Next, the researchers evaluated a validation cohort of 42 cancer patients, 41 healthy controls, and 23 patients with chronic pancreatitis. In this cohort, with an area under the curve of 0.76, the panel’s sensitivity for pancreatic cancer was 71% and specificity, 78%. In contrast, the sensitivity of CA19-9 was 69% and specificity 86%; for CEA, those numbers were 36% and 80%, respectively.
In the subset of patients with resectable pancreatic cancer, the panel’s sensitivity was 78%, compared with 56% for CA19-9 and 44% for CEA.
The metabolic panel was also able to identify chronic pancreatitis, with a 17% rate of false positives, compared with a false-positive rate of 30% for CA19-9 and 44% for CEA.
A blood panel could address three key problems in the field of pancreatic cancer, Dr. Yoshida and his colleagues said. "The first is the difficulty of detecting pancreatic cancer early in resectable stages. A sensitivity and specificity of about 80% for resectable disease ... should be acceptable for clinical use, because most patients with resectable cancer have no symptoms, and blood examinations are useful tools for initial screening examinations."
The second problem is the difficulty in differentiating pancreatic cancer from chronic pancreatitis. "Many gastroenterologists follow up chronic pancreatitis with scheduled CT, magnetic resonance imaging (MRI), and endoscopic ultrasound scans (EUS); tumor marker tests; and endoscopic retrograde cholangiopancreatography (ERCP), but the initial malignant changes are frequently overlooked, and pancreatic tumors can rapidly become unresectable. In addition, unnecessary resections for benign inflammatory lesions are sometimes done because of false-positive results from CA19-9 and/or imaging examinations."
The third clinical problem is the risk of complications that result from pancreatic examinations. Serum samples are easy and safe to obtain, with a low risk of adverse events and, with this panel, a potentially good return of information. A blood test could also be a useful population screening tool, the researchers noted.
The metabolites probably reflect metabolic derangement that arises not only from focal tumorigenesis, but also from systemic reactions to pancreatic disease, Dr. Yoshida and his coinvestigators wrote. Pancreatic cancer causes significant decreases in some amino and fatty acids, probably because the tumor recruits these substances to aid its rapid cellular proliferation.
"Patients with pancreatic disease are also troubled by malnutrition because of pancreatic endocrine and exocrine insufficiency. Therefore, there is a possibility that the decreases in serum metabolite levels also reflect malnutrition."
Finally, they said, the decrease in 1,5-anhydro-D-glucitol indicates the presence of hyperglycemia and recent glycosuria. "These results suggest that glucose tolerance was impaired in these patients because of pancreatic insufficiency."
The authors reported no financial conflicts. The work was supported by grants administered by agencies of the Japanese government.
An investigational serum biomarker panel accurately identified potentially resectable cases of pancreatic cancer, opening up the possibility that a blood test could identify the cancer early and improve its dismal prognosis.
The panel measured four metabolites and had an overall sensitivity of 71% and a specificity of 78% for pancreatic cancer; the specificity for resectable tumors also approached 78%, reported Dr. Masaru Yoshida and his colleagues (Cancer Epidemiol. Biomarkers Prev. 2013 March 29 [doi: 10.1158/1055-9965.EPI-12-1033]).
The panel was more accurate than were any of the currently used biomarkers, including CA19-9 and CEA, said Dr. Yoshida, professor and chief of metabolomics research at Kobe University, Japan, and his colleagues.
"This novel diagnostic approach, which is safe and easy to apply as a screening method, is expected to improve the prognosis of patients with pancreatic cancer by detecting their cancers early, when still in a resectable and curable state," Dr. Yoshida said in a press statement.
The researchers created the panel based on a study of a cohort of 85 subjects: 43 with pancreatic cancer and 42 healthy controls. First, they pared down 113 potentially useful metabolites into a workable testing panel. Of the 45 candidate metabolites, four of them – xylitol, 1,5-anhydro-D-glucitol, histidine, and inositol – showed the highest variation between the healthy controls and the patients. In the training cohort, the panel of these four markers had a sensitivity of 86% and specificity of 88% for pancreatic cancer.
Next, the researchers evaluated a validation cohort of 42 cancer patients, 41 healthy controls, and 23 patients with chronic pancreatitis. In this cohort, with an area under the curve of 0.76, the panel’s sensitivity for pancreatic cancer was 71% and specificity, 78%. In contrast, the sensitivity of CA19-9 was 69% and specificity 86%; for CEA, those numbers were 36% and 80%, respectively.
In the subset of patients with resectable pancreatic cancer, the panel’s sensitivity was 78%, compared with 56% for CA19-9 and 44% for CEA.
The metabolic panel was also able to identify chronic pancreatitis, with a 17% rate of false positives, compared with a false-positive rate of 30% for CA19-9 and 44% for CEA.
A blood panel could address three key problems in the field of pancreatic cancer, Dr. Yoshida and his colleagues said. "The first is the difficulty of detecting pancreatic cancer early in resectable stages. A sensitivity and specificity of about 80% for resectable disease ... should be acceptable for clinical use, because most patients with resectable cancer have no symptoms, and blood examinations are useful tools for initial screening examinations."
The second problem is the difficulty in differentiating pancreatic cancer from chronic pancreatitis. "Many gastroenterologists follow up chronic pancreatitis with scheduled CT, magnetic resonance imaging (MRI), and endoscopic ultrasound scans (EUS); tumor marker tests; and endoscopic retrograde cholangiopancreatography (ERCP), but the initial malignant changes are frequently overlooked, and pancreatic tumors can rapidly become unresectable. In addition, unnecessary resections for benign inflammatory lesions are sometimes done because of false-positive results from CA19-9 and/or imaging examinations."
The third clinical problem is the risk of complications that result from pancreatic examinations. Serum samples are easy and safe to obtain, with a low risk of adverse events and, with this panel, a potentially good return of information. A blood test could also be a useful population screening tool, the researchers noted.
The metabolites probably reflect metabolic derangement that arises not only from focal tumorigenesis, but also from systemic reactions to pancreatic disease, Dr. Yoshida and his coinvestigators wrote. Pancreatic cancer causes significant decreases in some amino and fatty acids, probably because the tumor recruits these substances to aid its rapid cellular proliferation.
"Patients with pancreatic disease are also troubled by malnutrition because of pancreatic endocrine and exocrine insufficiency. Therefore, there is a possibility that the decreases in serum metabolite levels also reflect malnutrition."
Finally, they said, the decrease in 1,5-anhydro-D-glucitol indicates the presence of hyperglycemia and recent glycosuria. "These results suggest that glucose tolerance was impaired in these patients because of pancreatic insufficiency."
The authors reported no financial conflicts. The work was supported by grants administered by agencies of the Japanese government.
Major finding: A serum panel of four metabolites had a 78% sensitivity for detecting resectable pancreatic cancers.
Data source: The panel was derived from a test cohort of 85, and a validation cohort of 42 cancer patients, 41 healthy controls, and 23 patients with chronic pancreatitis.
Disclosures: The authors had no financial disclosures. Japanese government agencies funded the study.
Early cholecystectomy beats delayed in acute cholecystitis
INDIANAPOLIS – Acute cholecystitis patients fared significantly better with early rather than delayed laparoscopic cholecystectomy in the largest-ever randomized trial addressing surgical timing for this common condition.
Patients assigned to early cholecystectomy – that is, surgery within 24 hours of presentation to the hospital – had one-third the morbidity, markedly shorter hospital lengths of stay, and correspondingly lower hospital costs compared with patients who underwent surgery on day 7-45, according to Dr. Markus W. Buchler of Heidelberg (Ger.) University.
"Early cholecystectomy in patients fit for surgery and in hospitals experienced in doing difficult laparoscopic cholecystectomies should become the standard of care in acute cholecystitis," he declared in presenting the results of the ACDC (Acute Cholecystitis: Early Versus Delayed Cholecystectomy) trial at the annual meeting of the American Surgical Association.
The optimal timing of surgical intervention in acute cholecystitis is a subject of long-standing controversy. The ACDC trial was conducted because in a Cochrane review of five smaller randomized trials totaling 451 acute cholecystitis patients, researchers concluded there was insufficient evidence to say which surgical strategy was best (Cochrane Database Syst. Rev. 2006 Oct 18;4:CD005440).
Dr. Buchler noted that surveys indicate many American surgeons prefer to delay laparoscopic cholecystectomy, while in Germany the surgical preference is for immediate surgery in patients with uncomplicated acute cholecystitis.
The ACDC trial involved 618 patients with uncomplicated acute cholecystitis who were placed on the same antibiotic – moxifloxacin – and randomized to early laparoscopic cholecystectomy or to delayed surgery on day 7-45. Pregnant patients were excluded from the trial, which was conducted at 35 European hospitals, including seven German university medical centers. All participating hospitals were staffed by surgical teams experienced in performing difficult laparoscopic cholecystectomies.
The primary endpoint was total morbidity within 75 days. This included cholangitis, pancreatitis, biliary leak, stroke, myocardial infarction, abscess, bleeding, peritonitis, infection, and renal failure. The rate was 11.6% in the early cholecystectomy group compared with 31.3% with delayed surgery. Among less challenging patients with an ASA score of 2 or less, the rates were 9.7% and 28.6%, respectively. Patients with an ASA score above 2 had an overall morbidity rate of 20% with early surgery compared with 47% with delayed laparoscopic cholecystectomy.
The rate of conversion to open surgery was 9.9% in the early laparoscopic cholecystectomy group and similar at 11.9% in the delayed surgery group. This came as a surprise to Dr. Buchler and his coinvestigators. They expected a significantly higher conversion rate in conjunction with delayed laparoscopic cholecystectomy.
"I think what this tells us is surgeons have gotten really good at laparoscopic cholecystectomy even in more difficult situations," he observed.
Total hospital stays averaged 5.4 days in the early surgery group compared with 10.0 days with delayed surgery. Mean total hospital costs calculated via the German DRG system were 2,919 euro in the early cholecystectomy group and 4,261 euro with delayed surgery.
Discussant Dr. Andrew L. Warshaw praised Dr. Buchler and his coworkers in the German surgical clinical trials study group for their "leadership in determining evidence-based standards of care."
"There’s no doubt in my mind that immediate cholecystectomy is superior in this patient population," said Dr. Warshaw, professor and chairman of the department of surgery at Harvard Medical School, Boston.
Noting that most acute cholecystitis patients are first seen by an internist or gastroenterologist who then makes the initial treatment decision, Dr. Warshaw asked Dr. Buchler if German internists and gastroenterologists have gotten on board this immediate surgery treatment pathway.
"Convincing internists and gastroenterologists will take a long time, at least in Germany," the surgeon replied. "It is much easier to convince the emergency department physicians to refer patients early to surgery; they’re much closer to the surgeons."
He noted that German surgical practice differs from that in the United States in several respects. For one, German patients routinely stay in the hospital longer, even if they don’t experience complications. That’s why the mean length of stay after cholecystectomy in ACDC was 4.68 days in the early surgery group and closely similar at 4.89 days in the delayed surgery group, even though the delayed surgery group had a threefold higher complication rate.
Another difference is that, unlike in this country, intraoperative cholangiography is rarely done in Germany.
"It’s the absolute exception that intraoperative cholangiography is used. It is used only when there’s a reason for it, such as jaundice. There was probably less than a 3% intraoperative cholangiography rate in this trial," said Dr. Buchler.
The ACDC trial was funded with government research grants. Dr. Buchler reported having no financial conflicts.
INDIANAPOLIS – Acute cholecystitis patients fared significantly better with early rather than delayed laparoscopic cholecystectomy in the largest-ever randomized trial addressing surgical timing for this common condition.
Patients assigned to early cholecystectomy – that is, surgery within 24 hours of presentation to the hospital – had one-third the morbidity, markedly shorter hospital lengths of stay, and correspondingly lower hospital costs compared with patients who underwent surgery on day 7-45, according to Dr. Markus W. Buchler of Heidelberg (Ger.) University.
"Early cholecystectomy in patients fit for surgery and in hospitals experienced in doing difficult laparoscopic cholecystectomies should become the standard of care in acute cholecystitis," he declared in presenting the results of the ACDC (Acute Cholecystitis: Early Versus Delayed Cholecystectomy) trial at the annual meeting of the American Surgical Association.
The optimal timing of surgical intervention in acute cholecystitis is a subject of long-standing controversy. The ACDC trial was conducted because in a Cochrane review of five smaller randomized trials totaling 451 acute cholecystitis patients, researchers concluded there was insufficient evidence to say which surgical strategy was best (Cochrane Database Syst. Rev. 2006 Oct 18;4:CD005440).
Dr. Buchler noted that surveys indicate many American surgeons prefer to delay laparoscopic cholecystectomy, while in Germany the surgical preference is for immediate surgery in patients with uncomplicated acute cholecystitis.
The ACDC trial involved 618 patients with uncomplicated acute cholecystitis who were placed on the same antibiotic – moxifloxacin – and randomized to early laparoscopic cholecystectomy or to delayed surgery on day 7-45. Pregnant patients were excluded from the trial, which was conducted at 35 European hospitals, including seven German university medical centers. All participating hospitals were staffed by surgical teams experienced in performing difficult laparoscopic cholecystectomies.
The primary endpoint was total morbidity within 75 days. This included cholangitis, pancreatitis, biliary leak, stroke, myocardial infarction, abscess, bleeding, peritonitis, infection, and renal failure. The rate was 11.6% in the early cholecystectomy group compared with 31.3% with delayed surgery. Among less challenging patients with an ASA score of 2 or less, the rates were 9.7% and 28.6%, respectively. Patients with an ASA score above 2 had an overall morbidity rate of 20% with early surgery compared with 47% with delayed laparoscopic cholecystectomy.
The rate of conversion to open surgery was 9.9% in the early laparoscopic cholecystectomy group and similar at 11.9% in the delayed surgery group. This came as a surprise to Dr. Buchler and his coinvestigators. They expected a significantly higher conversion rate in conjunction with delayed laparoscopic cholecystectomy.
"I think what this tells us is surgeons have gotten really good at laparoscopic cholecystectomy even in more difficult situations," he observed.
Total hospital stays averaged 5.4 days in the early surgery group compared with 10.0 days with delayed surgery. Mean total hospital costs calculated via the German DRG system were 2,919 euro in the early cholecystectomy group and 4,261 euro with delayed surgery.
Discussant Dr. Andrew L. Warshaw praised Dr. Buchler and his coworkers in the German surgical clinical trials study group for their "leadership in determining evidence-based standards of care."
"There’s no doubt in my mind that immediate cholecystectomy is superior in this patient population," said Dr. Warshaw, professor and chairman of the department of surgery at Harvard Medical School, Boston.
Noting that most acute cholecystitis patients are first seen by an internist or gastroenterologist who then makes the initial treatment decision, Dr. Warshaw asked Dr. Buchler if German internists and gastroenterologists have gotten on board this immediate surgery treatment pathway.
"Convincing internists and gastroenterologists will take a long time, at least in Germany," the surgeon replied. "It is much easier to convince the emergency department physicians to refer patients early to surgery; they’re much closer to the surgeons."
He noted that German surgical practice differs from that in the United States in several respects. For one, German patients routinely stay in the hospital longer, even if they don’t experience complications. That’s why the mean length of stay after cholecystectomy in ACDC was 4.68 days in the early surgery group and closely similar at 4.89 days in the delayed surgery group, even though the delayed surgery group had a threefold higher complication rate.
Another difference is that, unlike in this country, intraoperative cholangiography is rarely done in Germany.
"It’s the absolute exception that intraoperative cholangiography is used. It is used only when there’s a reason for it, such as jaundice. There was probably less than a 3% intraoperative cholangiography rate in this trial," said Dr. Buchler.
The ACDC trial was funded with government research grants. Dr. Buchler reported having no financial conflicts.
INDIANAPOLIS – Acute cholecystitis patients fared significantly better with early rather than delayed laparoscopic cholecystectomy in the largest-ever randomized trial addressing surgical timing for this common condition.
Patients assigned to early cholecystectomy – that is, surgery within 24 hours of presentation to the hospital – had one-third the morbidity, markedly shorter hospital lengths of stay, and correspondingly lower hospital costs compared with patients who underwent surgery on day 7-45, according to Dr. Markus W. Buchler of Heidelberg (Ger.) University.
"Early cholecystectomy in patients fit for surgery and in hospitals experienced in doing difficult laparoscopic cholecystectomies should become the standard of care in acute cholecystitis," he declared in presenting the results of the ACDC (Acute Cholecystitis: Early Versus Delayed Cholecystectomy) trial at the annual meeting of the American Surgical Association.
The optimal timing of surgical intervention in acute cholecystitis is a subject of long-standing controversy. The ACDC trial was conducted because in a Cochrane review of five smaller randomized trials totaling 451 acute cholecystitis patients, researchers concluded there was insufficient evidence to say which surgical strategy was best (Cochrane Database Syst. Rev. 2006 Oct 18;4:CD005440).
Dr. Buchler noted that surveys indicate many American surgeons prefer to delay laparoscopic cholecystectomy, while in Germany the surgical preference is for immediate surgery in patients with uncomplicated acute cholecystitis.
The ACDC trial involved 618 patients with uncomplicated acute cholecystitis who were placed on the same antibiotic – moxifloxacin – and randomized to early laparoscopic cholecystectomy or to delayed surgery on day 7-45. Pregnant patients were excluded from the trial, which was conducted at 35 European hospitals, including seven German university medical centers. All participating hospitals were staffed by surgical teams experienced in performing difficult laparoscopic cholecystectomies.
The primary endpoint was total morbidity within 75 days. This included cholangitis, pancreatitis, biliary leak, stroke, myocardial infarction, abscess, bleeding, peritonitis, infection, and renal failure. The rate was 11.6% in the early cholecystectomy group compared with 31.3% with delayed surgery. Among less challenging patients with an ASA score of 2 or less, the rates were 9.7% and 28.6%, respectively. Patients with an ASA score above 2 had an overall morbidity rate of 20% with early surgery compared with 47% with delayed laparoscopic cholecystectomy.
The rate of conversion to open surgery was 9.9% in the early laparoscopic cholecystectomy group and similar at 11.9% in the delayed surgery group. This came as a surprise to Dr. Buchler and his coinvestigators. They expected a significantly higher conversion rate in conjunction with delayed laparoscopic cholecystectomy.
"I think what this tells us is surgeons have gotten really good at laparoscopic cholecystectomy even in more difficult situations," he observed.
Total hospital stays averaged 5.4 days in the early surgery group compared with 10.0 days with delayed surgery. Mean total hospital costs calculated via the German DRG system were 2,919 euro in the early cholecystectomy group and 4,261 euro with delayed surgery.
Discussant Dr. Andrew L. Warshaw praised Dr. Buchler and his coworkers in the German surgical clinical trials study group for their "leadership in determining evidence-based standards of care."
"There’s no doubt in my mind that immediate cholecystectomy is superior in this patient population," said Dr. Warshaw, professor and chairman of the department of surgery at Harvard Medical School, Boston.
Noting that most acute cholecystitis patients are first seen by an internist or gastroenterologist who then makes the initial treatment decision, Dr. Warshaw asked Dr. Buchler if German internists and gastroenterologists have gotten on board this immediate surgery treatment pathway.
"Convincing internists and gastroenterologists will take a long time, at least in Germany," the surgeon replied. "It is much easier to convince the emergency department physicians to refer patients early to surgery; they’re much closer to the surgeons."
He noted that German surgical practice differs from that in the United States in several respects. For one, German patients routinely stay in the hospital longer, even if they don’t experience complications. That’s why the mean length of stay after cholecystectomy in ACDC was 4.68 days in the early surgery group and closely similar at 4.89 days in the delayed surgery group, even though the delayed surgery group had a threefold higher complication rate.
Another difference is that, unlike in this country, intraoperative cholangiography is rarely done in Germany.
"It’s the absolute exception that intraoperative cholangiography is used. It is used only when there’s a reason for it, such as jaundice. There was probably less than a 3% intraoperative cholangiography rate in this trial," said Dr. Buchler.
The ACDC trial was funded with government research grants. Dr. Buchler reported having no financial conflicts.
AT THE ASA ANNUAL MEETING
Major Finding: Acute cholecystitis patients randomized to laparoscopic cholecystectomy within 24 hours of hospital arrival had a 75-day total morbidity rate of 11.6% compared with 31.3% for those randomized to delayed laparoscopic cholecystectomy on days 7-45. Mean total hospital costs were one-third less in the early cholecystectomy group.
Data Source: ACDC trial of 618 randomized patients at 35 European medical centers.
Disclosures: The trial was funded by a German governmental research grant. The presenter reported having no conflict of interest.
Bariatric surgery advancement spurs guideline update
Weight loss surgery patients should get routine copper supplements along with other vitamins and minerals, according to newly updated bariatric surgery guidelines from the American Association of Clinical Endocrinologists, the Obesity Society, and the American Society for Metabolic and Bariatric Surgery.
The groups call for 2 mg/day to offset the potential for surgery to cause a deficiency. Although routine copper screening isn’t necessary after the procedure, copper levels should be assessed and treated as needed in patients with anemia, neutropenia, myeloneuropathy, and impaired wound healing.
The copper recommendations are new since the guidelines were last published in 2008. Other recommendations – there are 74 in all – have been revised to incorporate new advances in weight loss surgery and an improved evidence base. Changes are pointed out where they’ve been made, and the level of evidence cited for each assertion. Pre- and postoperative bariatric surgery checklists have been added as well, to help avoid errors.
"This is actually a very unique collaboration among the internists represented by the endocrinologists and the obesity people and the surgeons. We actually agreed on all these things. The main intent is to assist with clinical decision making," including selecting patients and procedures and perioperative management, said lead author Dr. Jeffrey Mechanick, president-elect of the American Association of Clinical Endocrinologists and director of metabolic support at the Mt. Sinai School of Medicine in New York.
"We scrutinized every recommendation one by one in the context of the new data. In many cases the recommendations changed," he said in an interview.
Another new recommendation is for patients to be followed by their primary care physicians and screened for cancer prior to surgery, as appropriate for age and risk. Dr. Mechanick and his colleagues have also given more attention to consent, behavioral, and psychiatric issues as well as weight loss surgery in patients with type 2 diabetes.
There’s more information on sleeve gastrectomy, as well. Considered experimental in 2008, it’s now "approved and being done more widely. There are some very nice data about its metabolic effects, independent from just the weight loss effect, effects on glycemic control, and cardiovascular risk. It was very important to devote a fair amount of time" to the procedure, he said.
The guidelines note that "sleeve gastrectomy has demonstrated benefits comparable to other bariatric procedures. ... A national risk-adjusted database positions [it] between the laparoscopic adjustable gastric band and laparoscopic Roux-en-Y gastric bypass in terms of weight loss, co-morbidity resolution, and complications."
"We [also] addressed two issues which were quite controversial, and are still rather unsettled. The first is the use of the lap band for mild obesity. The second is the use of these weight loss procedures specifically for patients with type 2 diabetes for glycemic control. Since 2008, there’ve been a lot more data" about the issues, he said, just as there’ve been more data about the need for copper supplementation.
As in 2008, the guidelines do not recommend bariatric surgery solely for glycemic control. "We still don’t have an absolute indication for ‘diabetes surgery,’ but we do recognize the existence of the salutary effects on glycemic control when these procedures are done for weight loss. It was important for the reader to be exposed to this information," Dr. Mechanick said.
Regarding surgery in the mildly obese, the guidelines note that patients with a body mass index of 30-34.9 kg/m2 with diabetes or metabolic syndrome "may also be offered a bariatric procedure, although current evidence is limited by the number of subjects studied and lack of long-term data demonstrating net benefit."
The guidelines will be published in the March/April 2013 issue of Endocrine Practice and March 2013 issue of Surgery for Obesity and Related Diseases.
Dr. Mechanick disclosed compensation from Abbott Nutrition for lectures and program development.
From preoperative evaluation through bariatric
surgery and onward through long-term postoperative health management, weight
loss surgery and the medical care associated with it is, obligatorily, a
thoroughly interdisciplinary effort. Endocrinologists and internists on the
bariatrics team spearhead lifestyle management, medical weight loss, and
long-term postoperative care and efforts to maintain durable weight loss.
Surgeons, endocrinologists, and internists work together to select patients
appropriate for bariatric surgery, to choose the weight-loss surgery best
suited to each individual patient, and to provide the proper preoperative
evaluation. Surgeons perform the appropriate bariatric operation and oversee
immediate postoperative and short-term perioperative care, and, frequently in
concert with gastroenterologists, internists, and endocrinologists, manage
complications that can result from bariatric surgery. Finally, long-term
continuity of medical care and durable maintenance of weight loss is again
directed by the endocrinologist and internist.
Thus, given that the entire bariatric care schema is
such an interdisciplinary effort, clinical practice guidelines for the
management of bariatric surgical patients must also be the product of an
analogous interdisciplinary effort. It is with this aim and in this spirit that
the American Association of Clinical Endocrinologists (AACE), The Obesity
Society (TOS), and American Society for Metabolic and Bariatric Surgery (AAMBS)
published their initial Medical Guidelines for Clinical Practice for the Perioperative
Nutritional, Metabolic, and Nonsurgical Support of the Bariatric Surgery
Patient in 2008. The same cooperating societies have just published their
sequel with numerous substantive additions, changes, and refinements. The
Clinical Practice Guidelines for the Perioperative Nutritional, Metabolic, and
Nonsurgical Support of the Bariatric Surgery Patient – 2013 Update: Cosponsored
by American Association of Clinical Endocrinologists, The Obesity Society, and
American Society for Metabolic & Bariatric Surgery was published jointly in
the March issue of Surgery for Obesity and Related Disease, and in the
March/April issue of Endocrine Practice.
Clearly, much has changed in the bariatric landscape
in the intervening half-decade. Laparoscopic gastric band surgery has declined,
while sleeve gastrectomy has gained traction as a restrictive bariatric
operation with more robust weight loss and glycemic effects. The
increasingly recognized impact of Roux-en-Y gastric bypass surgery not only on
weight loss, but also on glycemic control and other endocrinologic endpoints
has prompted studies to determine if such benefits might also result from
restrictive-only bariatric surgeries such as sleeve gastrectomy, and initial
results appear encouraging. The arrival of more and higher-quality data with
longer-term follow up of a greater variety of endpoints has led to the ability
of these updated guidelines to provide an increasing number of more specific,
data-driven recommendations related to the broader spectrum of bariatric
surgical procedures and anatomies managed by clinicians today. They cover every
aspect of the bariatric surgical patient, from preoperative evaluation through
surgery, to postoperative management, all with more solidly outcomes-based
recommendations from over 400 references, with user-friendly and more
error-proof preoperative and postoperative care checklists, while still
arriving at such expert guidelines through interdisciplinary study and
agreement in this timely update.
John A. Martin, M.D., is associate
professor of medicine and surgery and director of endoscopy, Northwestern
University Feinberg School of Medicine, Chicago.
From preoperative evaluation through bariatric
surgery and onward through long-term postoperative health management, weight
loss surgery and the medical care associated with it is, obligatorily, a
thoroughly interdisciplinary effort. Endocrinologists and internists on the
bariatrics team spearhead lifestyle management, medical weight loss, and
long-term postoperative care and efforts to maintain durable weight loss.
Surgeons, endocrinologists, and internists work together to select patients
appropriate for bariatric surgery, to choose the weight-loss surgery best
suited to each individual patient, and to provide the proper preoperative
evaluation. Surgeons perform the appropriate bariatric operation and oversee
immediate postoperative and short-term perioperative care, and, frequently in
concert with gastroenterologists, internists, and endocrinologists, manage
complications that can result from bariatric surgery. Finally, long-term
continuity of medical care and durable maintenance of weight loss is again
directed by the endocrinologist and internist.
Thus, given that the entire bariatric care schema is
such an interdisciplinary effort, clinical practice guidelines for the
management of bariatric surgical patients must also be the product of an
analogous interdisciplinary effort. It is with this aim and in this spirit that
the American Association of Clinical Endocrinologists (AACE), The Obesity
Society (TOS), and American Society for Metabolic and Bariatric Surgery (AAMBS)
published their initial Medical Guidelines for Clinical Practice for the Perioperative
Nutritional, Metabolic, and Nonsurgical Support of the Bariatric Surgery
Patient in 2008. The same cooperating societies have just published their
sequel with numerous substantive additions, changes, and refinements. The
Clinical Practice Guidelines for the Perioperative Nutritional, Metabolic, and
Nonsurgical Support of the Bariatric Surgery Patient – 2013 Update: Cosponsored
by American Association of Clinical Endocrinologists, The Obesity Society, and
American Society for Metabolic & Bariatric Surgery was published jointly in
the March issue of Surgery for Obesity and Related Disease, and in the
March/April issue of Endocrine Practice.
Clearly, much has changed in the bariatric landscape
in the intervening half-decade. Laparoscopic gastric band surgery has declined,
while sleeve gastrectomy has gained traction as a restrictive bariatric
operation with more robust weight loss and glycemic effects. The
increasingly recognized impact of Roux-en-Y gastric bypass surgery not only on
weight loss, but also on glycemic control and other endocrinologic endpoints
has prompted studies to determine if such benefits might also result from
restrictive-only bariatric surgeries such as sleeve gastrectomy, and initial
results appear encouraging. The arrival of more and higher-quality data with
longer-term follow up of a greater variety of endpoints has led to the ability
of these updated guidelines to provide an increasing number of more specific,
data-driven recommendations related to the broader spectrum of bariatric
surgical procedures and anatomies managed by clinicians today. They cover every
aspect of the bariatric surgical patient, from preoperative evaluation through
surgery, to postoperative management, all with more solidly outcomes-based
recommendations from over 400 references, with user-friendly and more
error-proof preoperative and postoperative care checklists, while still
arriving at such expert guidelines through interdisciplinary study and
agreement in this timely update.
John A. Martin, M.D., is associate
professor of medicine and surgery and director of endoscopy, Northwestern
University Feinberg School of Medicine, Chicago.
From preoperative evaluation through bariatric
surgery and onward through long-term postoperative health management, weight
loss surgery and the medical care associated with it is, obligatorily, a
thoroughly interdisciplinary effort. Endocrinologists and internists on the
bariatrics team spearhead lifestyle management, medical weight loss, and
long-term postoperative care and efforts to maintain durable weight loss.
Surgeons, endocrinologists, and internists work together to select patients
appropriate for bariatric surgery, to choose the weight-loss surgery best
suited to each individual patient, and to provide the proper preoperative
evaluation. Surgeons perform the appropriate bariatric operation and oversee
immediate postoperative and short-term perioperative care, and, frequently in
concert with gastroenterologists, internists, and endocrinologists, manage
complications that can result from bariatric surgery. Finally, long-term
continuity of medical care and durable maintenance of weight loss is again
directed by the endocrinologist and internist.
Thus, given that the entire bariatric care schema is
such an interdisciplinary effort, clinical practice guidelines for the
management of bariatric surgical patients must also be the product of an
analogous interdisciplinary effort. It is with this aim and in this spirit that
the American Association of Clinical Endocrinologists (AACE), The Obesity
Society (TOS), and American Society for Metabolic and Bariatric Surgery (AAMBS)
published their initial Medical Guidelines for Clinical Practice for the Perioperative
Nutritional, Metabolic, and Nonsurgical Support of the Bariatric Surgery
Patient in 2008. The same cooperating societies have just published their
sequel with numerous substantive additions, changes, and refinements. The
Clinical Practice Guidelines for the Perioperative Nutritional, Metabolic, and
Nonsurgical Support of the Bariatric Surgery Patient – 2013 Update: Cosponsored
by American Association of Clinical Endocrinologists, The Obesity Society, and
American Society for Metabolic & Bariatric Surgery was published jointly in
the March issue of Surgery for Obesity and Related Disease, and in the
March/April issue of Endocrine Practice.
Clearly, much has changed in the bariatric landscape
in the intervening half-decade. Laparoscopic gastric band surgery has declined,
while sleeve gastrectomy has gained traction as a restrictive bariatric
operation with more robust weight loss and glycemic effects. The
increasingly recognized impact of Roux-en-Y gastric bypass surgery not only on
weight loss, but also on glycemic control and other endocrinologic endpoints
has prompted studies to determine if such benefits might also result from
restrictive-only bariatric surgeries such as sleeve gastrectomy, and initial
results appear encouraging. The arrival of more and higher-quality data with
longer-term follow up of a greater variety of endpoints has led to the ability
of these updated guidelines to provide an increasing number of more specific,
data-driven recommendations related to the broader spectrum of bariatric
surgical procedures and anatomies managed by clinicians today. They cover every
aspect of the bariatric surgical patient, from preoperative evaluation through
surgery, to postoperative management, all with more solidly outcomes-based
recommendations from over 400 references, with user-friendly and more
error-proof preoperative and postoperative care checklists, while still
arriving at such expert guidelines through interdisciplinary study and
agreement in this timely update.
John A. Martin, M.D., is associate
professor of medicine and surgery and director of endoscopy, Northwestern
University Feinberg School of Medicine, Chicago.
Weight loss surgery patients should get routine copper supplements along with other vitamins and minerals, according to newly updated bariatric surgery guidelines from the American Association of Clinical Endocrinologists, the Obesity Society, and the American Society for Metabolic and Bariatric Surgery.
The groups call for 2 mg/day to offset the potential for surgery to cause a deficiency. Although routine copper screening isn’t necessary after the procedure, copper levels should be assessed and treated as needed in patients with anemia, neutropenia, myeloneuropathy, and impaired wound healing.
The copper recommendations are new since the guidelines were last published in 2008. Other recommendations – there are 74 in all – have been revised to incorporate new advances in weight loss surgery and an improved evidence base. Changes are pointed out where they’ve been made, and the level of evidence cited for each assertion. Pre- and postoperative bariatric surgery checklists have been added as well, to help avoid errors.
"This is actually a very unique collaboration among the internists represented by the endocrinologists and the obesity people and the surgeons. We actually agreed on all these things. The main intent is to assist with clinical decision making," including selecting patients and procedures and perioperative management, said lead author Dr. Jeffrey Mechanick, president-elect of the American Association of Clinical Endocrinologists and director of metabolic support at the Mt. Sinai School of Medicine in New York.
"We scrutinized every recommendation one by one in the context of the new data. In many cases the recommendations changed," he said in an interview.
Another new recommendation is for patients to be followed by their primary care physicians and screened for cancer prior to surgery, as appropriate for age and risk. Dr. Mechanick and his colleagues have also given more attention to consent, behavioral, and psychiatric issues as well as weight loss surgery in patients with type 2 diabetes.
There’s more information on sleeve gastrectomy, as well. Considered experimental in 2008, it’s now "approved and being done more widely. There are some very nice data about its metabolic effects, independent from just the weight loss effect, effects on glycemic control, and cardiovascular risk. It was very important to devote a fair amount of time" to the procedure, he said.
The guidelines note that "sleeve gastrectomy has demonstrated benefits comparable to other bariatric procedures. ... A national risk-adjusted database positions [it] between the laparoscopic adjustable gastric band and laparoscopic Roux-en-Y gastric bypass in terms of weight loss, co-morbidity resolution, and complications."
"We [also] addressed two issues which were quite controversial, and are still rather unsettled. The first is the use of the lap band for mild obesity. The second is the use of these weight loss procedures specifically for patients with type 2 diabetes for glycemic control. Since 2008, there’ve been a lot more data" about the issues, he said, just as there’ve been more data about the need for copper supplementation.
As in 2008, the guidelines do not recommend bariatric surgery solely for glycemic control. "We still don’t have an absolute indication for ‘diabetes surgery,’ but we do recognize the existence of the salutary effects on glycemic control when these procedures are done for weight loss. It was important for the reader to be exposed to this information," Dr. Mechanick said.
Regarding surgery in the mildly obese, the guidelines note that patients with a body mass index of 30-34.9 kg/m2 with diabetes or metabolic syndrome "may also be offered a bariatric procedure, although current evidence is limited by the number of subjects studied and lack of long-term data demonstrating net benefit."
The guidelines will be published in the March/April 2013 issue of Endocrine Practice and March 2013 issue of Surgery for Obesity and Related Diseases.
Dr. Mechanick disclosed compensation from Abbott Nutrition for lectures and program development.
Weight loss surgery patients should get routine copper supplements along with other vitamins and minerals, according to newly updated bariatric surgery guidelines from the American Association of Clinical Endocrinologists, the Obesity Society, and the American Society for Metabolic and Bariatric Surgery.
The groups call for 2 mg/day to offset the potential for surgery to cause a deficiency. Although routine copper screening isn’t necessary after the procedure, copper levels should be assessed and treated as needed in patients with anemia, neutropenia, myeloneuropathy, and impaired wound healing.
The copper recommendations are new since the guidelines were last published in 2008. Other recommendations – there are 74 in all – have been revised to incorporate new advances in weight loss surgery and an improved evidence base. Changes are pointed out where they’ve been made, and the level of evidence cited for each assertion. Pre- and postoperative bariatric surgery checklists have been added as well, to help avoid errors.
"This is actually a very unique collaboration among the internists represented by the endocrinologists and the obesity people and the surgeons. We actually agreed on all these things. The main intent is to assist with clinical decision making," including selecting patients and procedures and perioperative management, said lead author Dr. Jeffrey Mechanick, president-elect of the American Association of Clinical Endocrinologists and director of metabolic support at the Mt. Sinai School of Medicine in New York.
"We scrutinized every recommendation one by one in the context of the new data. In many cases the recommendations changed," he said in an interview.
Another new recommendation is for patients to be followed by their primary care physicians and screened for cancer prior to surgery, as appropriate for age and risk. Dr. Mechanick and his colleagues have also given more attention to consent, behavioral, and psychiatric issues as well as weight loss surgery in patients with type 2 diabetes.
There’s more information on sleeve gastrectomy, as well. Considered experimental in 2008, it’s now "approved and being done more widely. There are some very nice data about its metabolic effects, independent from just the weight loss effect, effects on glycemic control, and cardiovascular risk. It was very important to devote a fair amount of time" to the procedure, he said.
The guidelines note that "sleeve gastrectomy has demonstrated benefits comparable to other bariatric procedures. ... A national risk-adjusted database positions [it] between the laparoscopic adjustable gastric band and laparoscopic Roux-en-Y gastric bypass in terms of weight loss, co-morbidity resolution, and complications."
"We [also] addressed two issues which were quite controversial, and are still rather unsettled. The first is the use of the lap band for mild obesity. The second is the use of these weight loss procedures specifically for patients with type 2 diabetes for glycemic control. Since 2008, there’ve been a lot more data" about the issues, he said, just as there’ve been more data about the need for copper supplementation.
As in 2008, the guidelines do not recommend bariatric surgery solely for glycemic control. "We still don’t have an absolute indication for ‘diabetes surgery,’ but we do recognize the existence of the salutary effects on glycemic control when these procedures are done for weight loss. It was important for the reader to be exposed to this information," Dr. Mechanick said.
Regarding surgery in the mildly obese, the guidelines note that patients with a body mass index of 30-34.9 kg/m2 with diabetes or metabolic syndrome "may also be offered a bariatric procedure, although current evidence is limited by the number of subjects studied and lack of long-term data demonstrating net benefit."
The guidelines will be published in the March/April 2013 issue of Endocrine Practice and March 2013 issue of Surgery for Obesity and Related Diseases.
Dr. Mechanick disclosed compensation from Abbott Nutrition for lectures and program development.
Exenatide, sitagliptin associated with doubled risk for acute pancreatitis
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%).
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.
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%).
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.
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%).
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.
FROM JAMA INTERNAL MEDICINE
Major finding: Diabetes patients who took sitagliptin or exenatide faced twice the risk of being hospitalized for acute pancreatitis.
Data source: A case-control study based on the Blue Cross Blue Shield database comprising 1,269 cases and 1,269 controls treated from 2005 to 2008.
Disclosures: The study was sponsored by Johns Hopkins University and the National Institutes of Health. Dr. Singh 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.
