Will Pass

For patients with relapsed or refractory mantle cell lymphoma (MCL), second generation Bruton’s tyrosine kinase (BTK) inhibitor acalabrutinib may offer increased response rates and better tolerability compared with other single-agent targeted therapies, based on a recent analysis.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

Improved safety could lead to long-term benefits resulting from extended treatment duration, according to lead author Claire Telford, PhD, of AstraZeneca in Gaithersburg, Md., and colleagues. AstraZeneca manufactures acalabrutinib (Calquence).

Currently, treatment for MCL is guided by a number of clinical considerations, the investigators explained in Clinical Therapeutics.

“The type of treatment recommended for relapsed/refractory MCL depends on multiple factors, namely time to the relapse, extent of disease, previous regimens, candidacy for allogeneic stem cell transplantation, and the patient’s overall health,” they wrote.

To determine how acalabrutinib stacks up with other options, the investigators drew data from the phase 2 ACE-LY-004 trial, which tested acalabrutinib in 124 patients with relapsed or refractory MCL. After matching, the investigators compared the ACE-LY-004 outcomes from 12 other trials, in which patients received different targeted therapies.

Results pointed to higher overall response and complete response rates for acalabrutinib, compared with other single-agent targeted therapy. Specifically, acalabrutinib had a higher overall response rate, compared with ibrutinib (9.3% higher), lenalidomide (38.1% higher), temsirolimus (40.7% higher), and bortezomib (50.6% higher). For each of these, complete responses also were higher.

There was no significant difference in overall response or complete response rates between acalabrutinib and rituximab combinations – bendamustine plus rituximab, ibrutinib plus rituximab, and lenalidomide plus rituximab.

The investigators also highlighted a number of safety advantages. Compared with ibrutinib, acalabrutinib was associated with significantly fewer instances of grade 3 or 4 atrial fibrillation. Risk of grade 3 or 4 thrombocytopenia was significantly lower with acalabrutinib than with ibrutinib, bortezomib, lenalidomide, and temsirolimus.

Still, in some instances, acalabrutinib was comparatively less tolerable. It was associated with a higher risk of grade 3 or 4 infections than bendamustine plus rituximab; and anemia was more common among patients receiving acalabrutinib than among those who had lenalidomide plus rituximab or ibrutinib plus rituximab.

“This comparison of targeted therapies used in the treatment of relapsed/refractory MCL has shown that acalabrutinib has the potential to provide higher response rates, with trends for longer [progression-free survival] and [overall survival], and an improved safety profile,” the investigators wrote.

The study was funded by AstraZeneca. Dr. Telford is an employee of AstraZeneca and other authors reported financial relationships with the company.

SOURCE: Telford C et al. Clin Ther. 2019 Nov 4. doi: 10.1016/j.clinthera.2019.09.012 .

For patients with relapsed or refractory mantle cell lymphoma (MCL), second generation Bruton’s tyrosine kinase (BTK) inhibitor acalabrutinib may offer increased response rates and better tolerability compared with other single-agent targeted therapies, based on a recent analysis.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

Improved safety could lead to long-term benefits resulting from extended treatment duration, according to lead author Claire Telford, PhD, of AstraZeneca in Gaithersburg, Md., and colleagues. AstraZeneca manufactures acalabrutinib (Calquence).

Currently, treatment for MCL is guided by a number of clinical considerations, the investigators explained in Clinical Therapeutics.

“The type of treatment recommended for relapsed/refractory MCL depends on multiple factors, namely time to the relapse, extent of disease, previous regimens, candidacy for allogeneic stem cell transplantation, and the patient’s overall health,” they wrote.

To determine how acalabrutinib stacks up with other options, the investigators drew data from the phase 2 ACE-LY-004 trial, which tested acalabrutinib in 124 patients with relapsed or refractory MCL. After matching, the investigators compared the ACE-LY-004 outcomes from 12 other trials, in which patients received different targeted therapies.

Results pointed to higher overall response and complete response rates for acalabrutinib, compared with other single-agent targeted therapy. Specifically, acalabrutinib had a higher overall response rate, compared with ibrutinib (9.3% higher), lenalidomide (38.1% higher), temsirolimus (40.7% higher), and bortezomib (50.6% higher). For each of these, complete responses also were higher.

There was no significant difference in overall response or complete response rates between acalabrutinib and rituximab combinations – bendamustine plus rituximab, ibrutinib plus rituximab, and lenalidomide plus rituximab.

The investigators also highlighted a number of safety advantages. Compared with ibrutinib, acalabrutinib was associated with significantly fewer instances of grade 3 or 4 atrial fibrillation. Risk of grade 3 or 4 thrombocytopenia was significantly lower with acalabrutinib than with ibrutinib, bortezomib, lenalidomide, and temsirolimus.

Still, in some instances, acalabrutinib was comparatively less tolerable. It was associated with a higher risk of grade 3 or 4 infections than bendamustine plus rituximab; and anemia was more common among patients receiving acalabrutinib than among those who had lenalidomide plus rituximab or ibrutinib plus rituximab.

“This comparison of targeted therapies used in the treatment of relapsed/refractory MCL has shown that acalabrutinib has the potential to provide higher response rates, with trends for longer [progression-free survival] and [overall survival], and an improved safety profile,” the investigators wrote.

The study was funded by AstraZeneca. Dr. Telford is an employee of AstraZeneca and other authors reported financial relationships with the company.

SOURCE: Telford C et al. Clin Ther. 2019 Nov 4. doi: 10.1016/j.clinthera.2019.09.012 .

For patients with relapsed or refractory mantle cell lymphoma (MCL), second generation Bruton’s tyrosine kinase (BTK) inhibitor acalabrutinib may offer increased response rates and better tolerability compared with other single-agent targeted therapies, based on a recent analysis.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

Improved safety could lead to long-term benefits resulting from extended treatment duration, according to lead author Claire Telford, PhD, of AstraZeneca in Gaithersburg, Md., and colleagues. AstraZeneca manufactures acalabrutinib (Calquence).

Currently, treatment for MCL is guided by a number of clinical considerations, the investigators explained in Clinical Therapeutics.

“The type of treatment recommended for relapsed/refractory MCL depends on multiple factors, namely time to the relapse, extent of disease, previous regimens, candidacy for allogeneic stem cell transplantation, and the patient’s overall health,” they wrote.

To determine how acalabrutinib stacks up with other options, the investigators drew data from the phase 2 ACE-LY-004 trial, which tested acalabrutinib in 124 patients with relapsed or refractory MCL. After matching, the investigators compared the ACE-LY-004 outcomes from 12 other trials, in which patients received different targeted therapies.

Results pointed to higher overall response and complete response rates for acalabrutinib, compared with other single-agent targeted therapy. Specifically, acalabrutinib had a higher overall response rate, compared with ibrutinib (9.3% higher), lenalidomide (38.1% higher), temsirolimus (40.7% higher), and bortezomib (50.6% higher). For each of these, complete responses also were higher.

There was no significant difference in overall response or complete response rates between acalabrutinib and rituximab combinations – bendamustine plus rituximab, ibrutinib plus rituximab, and lenalidomide plus rituximab.

The investigators also highlighted a number of safety advantages. Compared with ibrutinib, acalabrutinib was associated with significantly fewer instances of grade 3 or 4 atrial fibrillation. Risk of grade 3 or 4 thrombocytopenia was significantly lower with acalabrutinib than with ibrutinib, bortezomib, lenalidomide, and temsirolimus.

Still, in some instances, acalabrutinib was comparatively less tolerable. It was associated with a higher risk of grade 3 or 4 infections than bendamustine plus rituximab; and anemia was more common among patients receiving acalabrutinib than among those who had lenalidomide plus rituximab or ibrutinib plus rituximab.

“This comparison of targeted therapies used in the treatment of relapsed/refractory MCL has shown that acalabrutinib has the potential to provide higher response rates, with trends for longer [progression-free survival] and [overall survival], and an improved safety profile,” the investigators wrote.

The study was funded by AstraZeneca. Dr. Telford is an employee of AstraZeneca and other authors reported financial relationships with the company.

SOURCE: Telford C et al. Clin Ther. 2019 Nov 4. doi: 10.1016/j.clinthera.2019.09.012 .

Loss of pancreatic E-cadherin may interfere with normal growth and maintenance of the pancreas while contributing to multiple pathological processes, based on evidence from mouse models.

In the presence of an oncogene, E-cadherin may play a pivotal role in pancreatic tumor formation, according to lead author Yoshihiro Kaneta, of Yokohama (Japan) City University in Japan, and colleagues. These findings could lead to new treatment strategies for patients with pancreatic cancer who lack E-cadherin, they noted.

Previous studies have shown that E-cadherin is involved in tissue homeostasis, although exact mechanisms vary by organ, and have remained unclear in the pancreas, the investigators explained in Cellular and Molecular Gastroenterology and Hepatology.

According to the investigators, E-cadherin expression is up-regulated in chemically induced acute pancreatitis, while in chronic pancreatitis, which is associated with an increased risk of pancreatic adenocarcinoma, E-cadherin expression is either low or absent. Other research has pointed to a link between dysregulated E-cadherin expression and cancer progression, with a loss of E-cadherin implicated in development of diffuse-type gastric cancer; however, evidence of a similar process in pancreatic cancer has not been reported, the investigators wrote.

To determine the role of E-cadherin in pancreatic function and tumor development, the investigators conducted experiments with knockout mice lacking pancreatic E-cadherin.

For the first 2 days after birth, knockout mice were similar both phenotypically and histologically to control mice. But over time, differences became apparent. Starting at day 3, control mice were comparatively larger than knockout mice, and by day 12, knockout mice began to die, with none surviving beyond day 28. Starting at day 6, histologic changes were observed in the pancreatic tissue of knockout mice, specifically, with aberrant epithelial tubules that resembled acinar-to-ductal metaplasia (ADM). Moreover, acinar cells were dilated and lacked surface expression of E-cadherin.

“These results suggested that E-cadherin was not required for pancreatic development at the embryonic stage but was required for growth and maintenance of the pancreas in the postnatal stage,” the investigators wrote.

Additional analyses revealed further differences between pancreatic tissue from knockout mice and control mice. A variety of aberrant processes were observed in knockout mice, including replacement of acini with alpha-smooth muscle actin–positive fibrotic cells, an increased number of ductal-like structures, a reduced number of amylase-positive cells, and an increased number of cytokeratin-19–positive and CD45-positive cells. Messenger RNA expression levels were also abnormal in pancreatic tissue of knockout mice, with shifts across a variety of cytokines and chemokines. These trends toward inflammation and fibrosis were described by the investigators as pancreatitis-like changes, although they observed no pancreatic intraepithelial neoplasia (PanIN), which is a precursor of pancreatic ductal adenocarcinoma.

In the presence of an oncogene, however, loss of pancreatic E-cadherin did contribute to the development of pancreatic cancer. In the presence of a Kras mutation, knockout mice began to develop PanINs and ADMs as soon as day 4. By day 7, PanINs stained partially positive for E-cadherin, showed structural abnormalities, and exhibited decreased amylase and increased cytokeratin-19. Within a similar time frame, pancreatic tissue began to adhere to the intestine, resulting in ascites and death. No metastases to other organs were observed.

Further testing showed that pancreatic stroma contained tumor cells. While DNA double-strand breaks were scarce, the investigators pointed out that chemotherapy and radiotherapy are typically responsible for DNA damage. Based on previous research linking stem cell conversion with Kras-acquired resistance, the investigators tested markers of stem cells in pancreatic tissue of knockout mice, finding that CD44, KLF4, and KLF5 were increased.

“These observations suggested that loss of E-cadherin provided tumorigenic activity to pancreatic cells and contributed to PanIN formation,” the investigators wrote.

Additional experiments with cell lines supported the above results and added further insight. Of clinical relevance, the investigators suggested that targeting Hdac1 with histone deacetylase inhibitors may be a viable treatment strategy for patients lacking pancreatic E-cadherin.

The study was funded by the Japan Society for the Promotion of Science KAKENHI grant JP17K09465 and the Yokohama City University Kamome project. The investigators declared no conflicts of interest.

SOURCE: Kaneta Y et al. Cell Mol Gastroenterol Hepatol. 2019 Sep 14. doi: 10.1016/j.jcmgh.2019.09.001.

Loss of pancreatic E-cadherin may interfere with normal growth and maintenance of the pancreas while contributing to multiple pathological processes, based on evidence from mouse models.

In the presence of an oncogene, E-cadherin may play a pivotal role in pancreatic tumor formation, according to lead author Yoshihiro Kaneta, of Yokohama (Japan) City University in Japan, and colleagues. These findings could lead to new treatment strategies for patients with pancreatic cancer who lack E-cadherin, they noted.

Previous studies have shown that E-cadherin is involved in tissue homeostasis, although exact mechanisms vary by organ, and have remained unclear in the pancreas, the investigators explained in Cellular and Molecular Gastroenterology and Hepatology.

According to the investigators, E-cadherin expression is up-regulated in chemically induced acute pancreatitis, while in chronic pancreatitis, which is associated with an increased risk of pancreatic adenocarcinoma, E-cadherin expression is either low or absent. Other research has pointed to a link between dysregulated E-cadherin expression and cancer progression, with a loss of E-cadherin implicated in development of diffuse-type gastric cancer; however, evidence of a similar process in pancreatic cancer has not been reported, the investigators wrote.

To determine the role of E-cadherin in pancreatic function and tumor development, the investigators conducted experiments with knockout mice lacking pancreatic E-cadherin.

For the first 2 days after birth, knockout mice were similar both phenotypically and histologically to control mice. But over time, differences became apparent. Starting at day 3, control mice were comparatively larger than knockout mice, and by day 12, knockout mice began to die, with none surviving beyond day 28. Starting at day 6, histologic changes were observed in the pancreatic tissue of knockout mice, specifically, with aberrant epithelial tubules that resembled acinar-to-ductal metaplasia (ADM). Moreover, acinar cells were dilated and lacked surface expression of E-cadherin.

“These results suggested that E-cadherin was not required for pancreatic development at the embryonic stage but was required for growth and maintenance of the pancreas in the postnatal stage,” the investigators wrote.

Additional analyses revealed further differences between pancreatic tissue from knockout mice and control mice. A variety of aberrant processes were observed in knockout mice, including replacement of acini with alpha-smooth muscle actin–positive fibrotic cells, an increased number of ductal-like structures, a reduced number of amylase-positive cells, and an increased number of cytokeratin-19–positive and CD45-positive cells. Messenger RNA expression levels were also abnormal in pancreatic tissue of knockout mice, with shifts across a variety of cytokines and chemokines. These trends toward inflammation and fibrosis were described by the investigators as pancreatitis-like changes, although they observed no pancreatic intraepithelial neoplasia (PanIN), which is a precursor of pancreatic ductal adenocarcinoma.

In the presence of an oncogene, however, loss of pancreatic E-cadherin did contribute to the development of pancreatic cancer. In the presence of a Kras mutation, knockout mice began to develop PanINs and ADMs as soon as day 4. By day 7, PanINs stained partially positive for E-cadherin, showed structural abnormalities, and exhibited decreased amylase and increased cytokeratin-19. Within a similar time frame, pancreatic tissue began to adhere to the intestine, resulting in ascites and death. No metastases to other organs were observed.

Further testing showed that pancreatic stroma contained tumor cells. While DNA double-strand breaks were scarce, the investigators pointed out that chemotherapy and radiotherapy are typically responsible for DNA damage. Based on previous research linking stem cell conversion with Kras-acquired resistance, the investigators tested markers of stem cells in pancreatic tissue of knockout mice, finding that CD44, KLF4, and KLF5 were increased.

“These observations suggested that loss of E-cadherin provided tumorigenic activity to pancreatic cells and contributed to PanIN formation,” the investigators wrote.

Additional experiments with cell lines supported the above results and added further insight. Of clinical relevance, the investigators suggested that targeting Hdac1 with histone deacetylase inhibitors may be a viable treatment strategy for patients lacking pancreatic E-cadherin.

The study was funded by the Japan Society for the Promotion of Science KAKENHI grant JP17K09465 and the Yokohama City University Kamome project. The investigators declared no conflicts of interest.

SOURCE: Kaneta Y et al. Cell Mol Gastroenterol Hepatol. 2019 Sep 14. doi: 10.1016/j.jcmgh.2019.09.001.

Loss of pancreatic E-cadherin may interfere with normal growth and maintenance of the pancreas while contributing to multiple pathological processes, based on evidence from mouse models.

In the presence of an oncogene, E-cadherin may play a pivotal role in pancreatic tumor formation, according to lead author Yoshihiro Kaneta, of Yokohama (Japan) City University in Japan, and colleagues. These findings could lead to new treatment strategies for patients with pancreatic cancer who lack E-cadherin, they noted.

Previous studies have shown that E-cadherin is involved in tissue homeostasis, although exact mechanisms vary by organ, and have remained unclear in the pancreas, the investigators explained in Cellular and Molecular Gastroenterology and Hepatology.

According to the investigators, E-cadherin expression is up-regulated in chemically induced acute pancreatitis, while in chronic pancreatitis, which is associated with an increased risk of pancreatic adenocarcinoma, E-cadherin expression is either low or absent. Other research has pointed to a link between dysregulated E-cadherin expression and cancer progression, with a loss of E-cadherin implicated in development of diffuse-type gastric cancer; however, evidence of a similar process in pancreatic cancer has not been reported, the investigators wrote.

To determine the role of E-cadherin in pancreatic function and tumor development, the investigators conducted experiments with knockout mice lacking pancreatic E-cadherin.

For the first 2 days after birth, knockout mice were similar both phenotypically and histologically to control mice. But over time, differences became apparent. Starting at day 3, control mice were comparatively larger than knockout mice, and by day 12, knockout mice began to die, with none surviving beyond day 28. Starting at day 6, histologic changes were observed in the pancreatic tissue of knockout mice, specifically, with aberrant epithelial tubules that resembled acinar-to-ductal metaplasia (ADM). Moreover, acinar cells were dilated and lacked surface expression of E-cadherin.

“These results suggested that E-cadherin was not required for pancreatic development at the embryonic stage but was required for growth and maintenance of the pancreas in the postnatal stage,” the investigators wrote.

Additional analyses revealed further differences between pancreatic tissue from knockout mice and control mice. A variety of aberrant processes were observed in knockout mice, including replacement of acini with alpha-smooth muscle actin–positive fibrotic cells, an increased number of ductal-like structures, a reduced number of amylase-positive cells, and an increased number of cytokeratin-19–positive and CD45-positive cells. Messenger RNA expression levels were also abnormal in pancreatic tissue of knockout mice, with shifts across a variety of cytokines and chemokines. These trends toward inflammation and fibrosis were described by the investigators as pancreatitis-like changes, although they observed no pancreatic intraepithelial neoplasia (PanIN), which is a precursor of pancreatic ductal adenocarcinoma.

In the presence of an oncogene, however, loss of pancreatic E-cadherin did contribute to the development of pancreatic cancer. In the presence of a Kras mutation, knockout mice began to develop PanINs and ADMs as soon as day 4. By day 7, PanINs stained partially positive for E-cadherin, showed structural abnormalities, and exhibited decreased amylase and increased cytokeratin-19. Within a similar time frame, pancreatic tissue began to adhere to the intestine, resulting in ascites and death. No metastases to other organs were observed.

Further testing showed that pancreatic stroma contained tumor cells. While DNA double-strand breaks were scarce, the investigators pointed out that chemotherapy and radiotherapy are typically responsible for DNA damage. Based on previous research linking stem cell conversion with Kras-acquired resistance, the investigators tested markers of stem cells in pancreatic tissue of knockout mice, finding that CD44, KLF4, and KLF5 were increased.

“These observations suggested that loss of E-cadherin provided tumorigenic activity to pancreatic cells and contributed to PanIN formation,” the investigators wrote.

Additional experiments with cell lines supported the above results and added further insight. Of clinical relevance, the investigators suggested that targeting Hdac1 with histone deacetylase inhibitors may be a viable treatment strategy for patients lacking pancreatic E-cadherin.

The study was funded by the Japan Society for the Promotion of Science KAKENHI grant JP17K09465 and the Yokohama City University Kamome project. The investigators declared no conflicts of interest.

SOURCE: Kaneta Y et al. Cell Mol Gastroenterol Hepatol. 2019 Sep 14. doi: 10.1016/j.jcmgh.2019.09.001.

A single-use duodenoscope may reduce the risk of postendoscopic infections while maintaining a high level of user satisfaction, based on a recent multicenter case series study.

At six tertiary referral centers in the United States, seven expert endoscopists performed more than 70 procedures with disposable scopes, ultimately reporting a median satisfaction score of 9 out of 10, according to lead author Venkataraman Muthusamy, MD, of UCLA Health in Los Angeles, and colleagues.

Writing for Clinical Gastroenterology and Hepatology, the investigators noted that duodenoscope-related infections represent a serious threat to public health, particularly when considered in the context of antibiotic resistance and the high number of endoscopic procedures performed annually.

“Solutions to the duodenoscope contamination problem remain elusive,” the investigators wrote. “Evidence-based interventions are important to guard against labor-intensive measures that are unfeasible, unaffordable, and potentially ineffective.”

According to the investigators, routine culture surveillance and field investigations following suspected duodenoscope-related infections may fail to detect culprit bacteria or shortcomings in equipment reprocessing; and even when performed correctly, standard reprocessing can be insufficient.

“Using current reprocessing techniques, improved compliance with reprocessing guidelines is not a definitive solution because reusable duodenoscope contamination may be present even after high-level disinfection or sterilization,” the investigators wrote, going on to cite Food and Drug Administration–reported contamination rates of 5.4% for high-concern organisms.

To determine if a single-use endoscope could overcome such risks, the investigators first conducted preclinical testing with animal laboratories and simulations, finding that a single-use duodenoscope was comparable with three reusable scope models. The present study, which included 73 patients with normal pancreaticobiliary anatomy, evaluated clinical feasibility, safety, and performance. The single-use duodenoscope was a first-generation device by Boston Scientific named EXALT Model D.

Of the 73 patients, 13 underwent roll-in maneuvers and 60 underwent endoscopic retrograde cholangiopancreatography (ERCP). The most common cause for ERCP was exchange or removal of biliary stent (55.0%), followed by evaluation of biliary defect or stricture (26.7%), then bile duct stone clearance (18.3%). The majority of ERCPs had an American Society for Gastrointestinal Endoscopy (ASGE) procedural complexity grade of 2 (43.3%) or 3 (43.3%), while a minority were graded 1 (11.7%) or, most severe, 4 (1.7%).

Two ERCPs required crossover to a reusable duodenoscope for completion. In the first instance, crossover was needed because dilation of a biliary stricture was unsuccessful, with the endoscopist reporting difficulties maneuvering the disposable scope, possibly because of shaft stiffness. In the second case, crossover was elected because cannulation was unsuccessful with standard access techniques; however, cannulation also was not possible with the reusable scope, necessitating an alternative approach.

According to the investigators, safety signals were comparable with standard practice. No serious, scope-related adverse events were reported. Serious adverse events of any kind were relatively uncommon; three patients developed post-ERCP pancreatitis within 7 days of ERCP, one developed a postsphincterotomy bleed, and one had worsening of a preexisting infection that required hospitalization.

As described above, the endoscopists reported a median overall satisfaction score of 9 out of 10. Specifically, 17 out of 23 scored ERCP maneuvers (73.9%) received a median 5 out of 5 performance rating. Out of 1,289 total ratings, almost all (98.1%) received a performance rating of at least 3 out of 5. Low-scoring performance characteristics (receiving at least one “1” rating), included elevator function; aspects of positioning; visualization; image quality, brightness, or appearance; and ease and ability of passing ancillary devices through the channel of the single-use duodenoscope and into the papilla.

“The new device provides an alternative to reusable duodenoscopes that may harbor residual contamination despite appropriately implemented reprocessing,” the investigators concluded.

They also pointed out that switching to disposable scopes would not completely put an end to postendoscopic infections.

“The single-use duodenoscope is a timely and innovative option to improve exogenous infection control, and must be used with awareness of the continued risk of endogenous infection, with standard infection control precautions and continued diligence in the use of existing reusable devices,” they wrote.

The study was funded by Boston Scientific. The investigators reported additional relationships with Medtronic, Ethicon/Torax, CapsoVision, and others.

SOURCE: Muthusamy V et al. Clin Gastroenterol Hepatol. 2019 Oct 11. doi: 10.1016/j.cgh.2019.10.052.

A single-use duodenoscope may reduce the risk of postendoscopic infections while maintaining a high level of user satisfaction, based on a recent multicenter case series study.

At six tertiary referral centers in the United States, seven expert endoscopists performed more than 70 procedures with disposable scopes, ultimately reporting a median satisfaction score of 9 out of 10, according to lead author Venkataraman Muthusamy, MD, of UCLA Health in Los Angeles, and colleagues.

Writing for Clinical Gastroenterology and Hepatology, the investigators noted that duodenoscope-related infections represent a serious threat to public health, particularly when considered in the context of antibiotic resistance and the high number of endoscopic procedures performed annually.

“Solutions to the duodenoscope contamination problem remain elusive,” the investigators wrote. “Evidence-based interventions are important to guard against labor-intensive measures that are unfeasible, unaffordable, and potentially ineffective.”

According to the investigators, routine culture surveillance and field investigations following suspected duodenoscope-related infections may fail to detect culprit bacteria or shortcomings in equipment reprocessing; and even when performed correctly, standard reprocessing can be insufficient.

“Using current reprocessing techniques, improved compliance with reprocessing guidelines is not a definitive solution because reusable duodenoscope contamination may be present even after high-level disinfection or sterilization,” the investigators wrote, going on to cite Food and Drug Administration–reported contamination rates of 5.4% for high-concern organisms.

To determine if a single-use endoscope could overcome such risks, the investigators first conducted preclinical testing with animal laboratories and simulations, finding that a single-use duodenoscope was comparable with three reusable scope models. The present study, which included 73 patients with normal pancreaticobiliary anatomy, evaluated clinical feasibility, safety, and performance. The single-use duodenoscope was a first-generation device by Boston Scientific named EXALT Model D.

Of the 73 patients, 13 underwent roll-in maneuvers and 60 underwent endoscopic retrograde cholangiopancreatography (ERCP). The most common cause for ERCP was exchange or removal of biliary stent (55.0%), followed by evaluation of biliary defect or stricture (26.7%), then bile duct stone clearance (18.3%). The majority of ERCPs had an American Society for Gastrointestinal Endoscopy (ASGE) procedural complexity grade of 2 (43.3%) or 3 (43.3%), while a minority were graded 1 (11.7%) or, most severe, 4 (1.7%).

Two ERCPs required crossover to a reusable duodenoscope for completion. In the first instance, crossover was needed because dilation of a biliary stricture was unsuccessful, with the endoscopist reporting difficulties maneuvering the disposable scope, possibly because of shaft stiffness. In the second case, crossover was elected because cannulation was unsuccessful with standard access techniques; however, cannulation also was not possible with the reusable scope, necessitating an alternative approach.

According to the investigators, safety signals were comparable with standard practice. No serious, scope-related adverse events were reported. Serious adverse events of any kind were relatively uncommon; three patients developed post-ERCP pancreatitis within 7 days of ERCP, one developed a postsphincterotomy bleed, and one had worsening of a preexisting infection that required hospitalization.

As described above, the endoscopists reported a median overall satisfaction score of 9 out of 10. Specifically, 17 out of 23 scored ERCP maneuvers (73.9%) received a median 5 out of 5 performance rating. Out of 1,289 total ratings, almost all (98.1%) received a performance rating of at least 3 out of 5. Low-scoring performance characteristics (receiving at least one “1” rating), included elevator function; aspects of positioning; visualization; image quality, brightness, or appearance; and ease and ability of passing ancillary devices through the channel of the single-use duodenoscope and into the papilla.

“The new device provides an alternative to reusable duodenoscopes that may harbor residual contamination despite appropriately implemented reprocessing,” the investigators concluded.

They also pointed out that switching to disposable scopes would not completely put an end to postendoscopic infections.

“The single-use duodenoscope is a timely and innovative option to improve exogenous infection control, and must be used with awareness of the continued risk of endogenous infection, with standard infection control precautions and continued diligence in the use of existing reusable devices,” they wrote.

The study was funded by Boston Scientific. The investigators reported additional relationships with Medtronic, Ethicon/Torax, CapsoVision, and others.

SOURCE: Muthusamy V et al. Clin Gastroenterol Hepatol. 2019 Oct 11. doi: 10.1016/j.cgh.2019.10.052.

A single-use duodenoscope may reduce the risk of postendoscopic infections while maintaining a high level of user satisfaction, based on a recent multicenter case series study.

At six tertiary referral centers in the United States, seven expert endoscopists performed more than 70 procedures with disposable scopes, ultimately reporting a median satisfaction score of 9 out of 10, according to lead author Venkataraman Muthusamy, MD, of UCLA Health in Los Angeles, and colleagues.

Writing for Clinical Gastroenterology and Hepatology, the investigators noted that duodenoscope-related infections represent a serious threat to public health, particularly when considered in the context of antibiotic resistance and the high number of endoscopic procedures performed annually.

“Solutions to the duodenoscope contamination problem remain elusive,” the investigators wrote. “Evidence-based interventions are important to guard against labor-intensive measures that are unfeasible, unaffordable, and potentially ineffective.”

According to the investigators, routine culture surveillance and field investigations following suspected duodenoscope-related infections may fail to detect culprit bacteria or shortcomings in equipment reprocessing; and even when performed correctly, standard reprocessing can be insufficient.

“Using current reprocessing techniques, improved compliance with reprocessing guidelines is not a definitive solution because reusable duodenoscope contamination may be present even after high-level disinfection or sterilization,” the investigators wrote, going on to cite Food and Drug Administration–reported contamination rates of 5.4% for high-concern organisms.

To determine if a single-use endoscope could overcome such risks, the investigators first conducted preclinical testing with animal laboratories and simulations, finding that a single-use duodenoscope was comparable with three reusable scope models. The present study, which included 73 patients with normal pancreaticobiliary anatomy, evaluated clinical feasibility, safety, and performance. The single-use duodenoscope was a first-generation device by Boston Scientific named EXALT Model D.

Of the 73 patients, 13 underwent roll-in maneuvers and 60 underwent endoscopic retrograde cholangiopancreatography (ERCP). The most common cause for ERCP was exchange or removal of biliary stent (55.0%), followed by evaluation of biliary defect or stricture (26.7%), then bile duct stone clearance (18.3%). The majority of ERCPs had an American Society for Gastrointestinal Endoscopy (ASGE) procedural complexity grade of 2 (43.3%) or 3 (43.3%), while a minority were graded 1 (11.7%) or, most severe, 4 (1.7%).

Two ERCPs required crossover to a reusable duodenoscope for completion. In the first instance, crossover was needed because dilation of a biliary stricture was unsuccessful, with the endoscopist reporting difficulties maneuvering the disposable scope, possibly because of shaft stiffness. In the second case, crossover was elected because cannulation was unsuccessful with standard access techniques; however, cannulation also was not possible with the reusable scope, necessitating an alternative approach.

According to the investigators, safety signals were comparable with standard practice. No serious, scope-related adverse events were reported. Serious adverse events of any kind were relatively uncommon; three patients developed post-ERCP pancreatitis within 7 days of ERCP, one developed a postsphincterotomy bleed, and one had worsening of a preexisting infection that required hospitalization.

As described above, the endoscopists reported a median overall satisfaction score of 9 out of 10. Specifically, 17 out of 23 scored ERCP maneuvers (73.9%) received a median 5 out of 5 performance rating. Out of 1,289 total ratings, almost all (98.1%) received a performance rating of at least 3 out of 5. Low-scoring performance characteristics (receiving at least one “1” rating), included elevator function; aspects of positioning; visualization; image quality, brightness, or appearance; and ease and ability of passing ancillary devices through the channel of the single-use duodenoscope and into the papilla.

“The new device provides an alternative to reusable duodenoscopes that may harbor residual contamination despite appropriately implemented reprocessing,” the investigators concluded.

They also pointed out that switching to disposable scopes would not completely put an end to postendoscopic infections.

“The single-use duodenoscope is a timely and innovative option to improve exogenous infection control, and must be used with awareness of the continued risk of endogenous infection, with standard infection control precautions and continued diligence in the use of existing reusable devices,” they wrote.

The study was funded by Boston Scientific. The investigators reported additional relationships with Medtronic, Ethicon/Torax, CapsoVision, and others.

SOURCE: Muthusamy V et al. Clin Gastroenterol Hepatol. 2019 Oct 11. doi: 10.1016/j.cgh.2019.10.052.

The American Gastroenterological Association recently issued a clinical practice update for the management of pancreatic necrosis, including 15 recommendations based on a comprehensive literature review and the experiences of leading experts.

Recommendations range from the general, such as the need for a multidisciplinary approach, to the specific, such as the superiority of metal over plastic stents for endoscopic transmural drainage.

The expert review, which was conducted by lead author Todd H. Baron, MD, of the University of North Carolina in Chapel Hill and three other colleagues, was vetted by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board. In addition, the update underwent external peer review prior to publication in Gastroenterology.

In the update, the authors outlined the clinical landscape for pancreatic necrosis, including challenges posed by complex cases and a mortality rate as high as 30%.

“Successful management of these patients requires expert multidisciplinary care by gastroenterologists, surgeons, interventional radiologists, and specialists in critical care medicine, infectious disease, and nutrition,” the investigators wrote.

They went on to explain how management has evolved over the past 10 years.

“Whereby major surgical intervention and debridement was once the mainstay of therapy for patients with symptomatic necrotic collections, a minimally invasive approach focusing on percutaneous drainage and/or endoscopic drainage or debridement is now favored,” they wrote. They added that debridement is still generally agreed to be the best choice for cases of infected necrosis or patients with sterile necrosis “marked by abdominal pain, nausea, vomiting, and nutritional failure or with associated complications including gastrointestinal luminal obstruction, biliary obstruction, recurrent acute pancreatitis, fistulas, or persistent systemic inflammatory response syndrome (SIRS).”

Other elements of care, however, remain debated, the investigators noted, which has led to variations in multiple aspects of care, such as interventional timing, intravenous fluids, antibiotics, and nutrition. Within this framework, the present practice update is aimed at offering “concise best practice advice for the optimal management of patients with this highly morbid condition.”

Among these pieces of advice, the authors emphasized that routine prophylactic antibiotics and/or antifungals to prevent infected necrosis are unsupported by multiple clinical trials. When infection is suspected, the update recommends broad spectrum intravenous antibiotics, noting that, in most cases, it is unnecessary to perform CT-guided fine-needle aspiration for cultures and gram stain.

Regarding nutrition, the update recommends against “pancreatic rest”; instead, it calls for early oral intake and, if this is not possible, then initiation of total enteral nutrition. Although the authors deemed multiple routes of enteral feeding acceptable, they favored nasogastric or nasoduodenal tubes, when appropriate, because of ease of placement and maintenance. For prolonged total enteral nutrition or patients unable to tolerate nasoenteric feeding, the authors recommended endoscopic feeding tube placement with a percutaneous endoscopic gastrostomy tube for those who can tolerate gastric feeding or a percutaneous endoscopic jejunostomy tube for those who cannot or have a high risk of aspiration.

As described above, the update recommends debridement for cases of infected pancreatic necrosis. Ideally, this should be performed at least 4 weeks after onset, and avoided altogether within the first 2 weeks, because of associated risks of morbidity and mortality; instead, during this acute phase, percutaneous drainage may be considered.

For walled-off pancreatic necrosis, the authors recommended transmural drainage via endoscopic therapy because this mitigates risk of pancreatocutaneous fistula. Percutaneous drainage may be considered in addition to, or in absence of, endoscopic drainage, depending on clinical status.

The remainder of the update covers decisions related to stents, other minimally invasive techniques, open operative debridement, and disconnected left pancreatic remnants, along with discussions of key supporting clinical trials.

The investigators disclosed relationships with Cook Endoscopy, Boston Scientific, Olympus, and others.

SOURCE: Baron TH et al. Gastroenterology. 2019 Aug 31. doi: 10.1053/j.gastro.2019.07.064.

Review the Gastroenterology clinical guidelines collection for AGA Institute statements detailing preferred approaches to specific medical problems or issues based on the most current available data at https://www.gastrojournal.org/content/agai. 

The American Gastroenterological Association recently issued a clinical practice update for the management of pancreatic necrosis, including 15 recommendations based on a comprehensive literature review and the experiences of leading experts.

Recommendations range from the general, such as the need for a multidisciplinary approach, to the specific, such as the superiority of metal over plastic stents for endoscopic transmural drainage.

The expert review, which was conducted by lead author Todd H. Baron, MD, of the University of North Carolina in Chapel Hill and three other colleagues, was vetted by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board. In addition, the update underwent external peer review prior to publication in Gastroenterology.

In the update, the authors outlined the clinical landscape for pancreatic necrosis, including challenges posed by complex cases and a mortality rate as high as 30%.

“Successful management of these patients requires expert multidisciplinary care by gastroenterologists, surgeons, interventional radiologists, and specialists in critical care medicine, infectious disease, and nutrition,” the investigators wrote.

They went on to explain how management has evolved over the past 10 years.

“Whereby major surgical intervention and debridement was once the mainstay of therapy for patients with symptomatic necrotic collections, a minimally invasive approach focusing on percutaneous drainage and/or endoscopic drainage or debridement is now favored,” they wrote. They added that debridement is still generally agreed to be the best choice for cases of infected necrosis or patients with sterile necrosis “marked by abdominal pain, nausea, vomiting, and nutritional failure or with associated complications including gastrointestinal luminal obstruction, biliary obstruction, recurrent acute pancreatitis, fistulas, or persistent systemic inflammatory response syndrome (SIRS).”

Other elements of care, however, remain debated, the investigators noted, which has led to variations in multiple aspects of care, such as interventional timing, intravenous fluids, antibiotics, and nutrition. Within this framework, the present practice update is aimed at offering “concise best practice advice for the optimal management of patients with this highly morbid condition.”

Among these pieces of advice, the authors emphasized that routine prophylactic antibiotics and/or antifungals to prevent infected necrosis are unsupported by multiple clinical trials. When infection is suspected, the update recommends broad spectrum intravenous antibiotics, noting that, in most cases, it is unnecessary to perform CT-guided fine-needle aspiration for cultures and gram stain.

Regarding nutrition, the update recommends against “pancreatic rest”; instead, it calls for early oral intake and, if this is not possible, then initiation of total enteral nutrition. Although the authors deemed multiple routes of enteral feeding acceptable, they favored nasogastric or nasoduodenal tubes, when appropriate, because of ease of placement and maintenance. For prolonged total enteral nutrition or patients unable to tolerate nasoenteric feeding, the authors recommended endoscopic feeding tube placement with a percutaneous endoscopic gastrostomy tube for those who can tolerate gastric feeding or a percutaneous endoscopic jejunostomy tube for those who cannot or have a high risk of aspiration.

As described above, the update recommends debridement for cases of infected pancreatic necrosis. Ideally, this should be performed at least 4 weeks after onset, and avoided altogether within the first 2 weeks, because of associated risks of morbidity and mortality; instead, during this acute phase, percutaneous drainage may be considered.

For walled-off pancreatic necrosis, the authors recommended transmural drainage via endoscopic therapy because this mitigates risk of pancreatocutaneous fistula. Percutaneous drainage may be considered in addition to, or in absence of, endoscopic drainage, depending on clinical status.

The remainder of the update covers decisions related to stents, other minimally invasive techniques, open operative debridement, and disconnected left pancreatic remnants, along with discussions of key supporting clinical trials.

The investigators disclosed relationships with Cook Endoscopy, Boston Scientific, Olympus, and others.

SOURCE: Baron TH et al. Gastroenterology. 2019 Aug 31. doi: 10.1053/j.gastro.2019.07.064.

Review the Gastroenterology clinical guidelines collection for AGA Institute statements detailing preferred approaches to specific medical problems or issues based on the most current available data at https://www.gastrojournal.org/content/agai. 

The American Gastroenterological Association recently issued a clinical practice update for the management of pancreatic necrosis, including 15 recommendations based on a comprehensive literature review and the experiences of leading experts.

Recommendations range from the general, such as the need for a multidisciplinary approach, to the specific, such as the superiority of metal over plastic stents for endoscopic transmural drainage.

The expert review, which was conducted by lead author Todd H. Baron, MD, of the University of North Carolina in Chapel Hill and three other colleagues, was vetted by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board. In addition, the update underwent external peer review prior to publication in Gastroenterology.

In the update, the authors outlined the clinical landscape for pancreatic necrosis, including challenges posed by complex cases and a mortality rate as high as 30%.

“Successful management of these patients requires expert multidisciplinary care by gastroenterologists, surgeons, interventional radiologists, and specialists in critical care medicine, infectious disease, and nutrition,” the investigators wrote.

They went on to explain how management has evolved over the past 10 years.

“Whereby major surgical intervention and debridement was once the mainstay of therapy for patients with symptomatic necrotic collections, a minimally invasive approach focusing on percutaneous drainage and/or endoscopic drainage or debridement is now favored,” they wrote. They added that debridement is still generally agreed to be the best choice for cases of infected necrosis or patients with sterile necrosis “marked by abdominal pain, nausea, vomiting, and nutritional failure or with associated complications including gastrointestinal luminal obstruction, biliary obstruction, recurrent acute pancreatitis, fistulas, or persistent systemic inflammatory response syndrome (SIRS).”

Other elements of care, however, remain debated, the investigators noted, which has led to variations in multiple aspects of care, such as interventional timing, intravenous fluids, antibiotics, and nutrition. Within this framework, the present practice update is aimed at offering “concise best practice advice for the optimal management of patients with this highly morbid condition.”

Among these pieces of advice, the authors emphasized that routine prophylactic antibiotics and/or antifungals to prevent infected necrosis are unsupported by multiple clinical trials. When infection is suspected, the update recommends broad spectrum intravenous antibiotics, noting that, in most cases, it is unnecessary to perform CT-guided fine-needle aspiration for cultures and gram stain.

Regarding nutrition, the update recommends against “pancreatic rest”; instead, it calls for early oral intake and, if this is not possible, then initiation of total enteral nutrition. Although the authors deemed multiple routes of enteral feeding acceptable, they favored nasogastric or nasoduodenal tubes, when appropriate, because of ease of placement and maintenance. For prolonged total enteral nutrition or patients unable to tolerate nasoenteric feeding, the authors recommended endoscopic feeding tube placement with a percutaneous endoscopic gastrostomy tube for those who can tolerate gastric feeding or a percutaneous endoscopic jejunostomy tube for those who cannot or have a high risk of aspiration.

As described above, the update recommends debridement for cases of infected pancreatic necrosis. Ideally, this should be performed at least 4 weeks after onset, and avoided altogether within the first 2 weeks, because of associated risks of morbidity and mortality; instead, during this acute phase, percutaneous drainage may be considered.

For walled-off pancreatic necrosis, the authors recommended transmural drainage via endoscopic therapy because this mitigates risk of pancreatocutaneous fistula. Percutaneous drainage may be considered in addition to, or in absence of, endoscopic drainage, depending on clinical status.

The remainder of the update covers decisions related to stents, other minimally invasive techniques, open operative debridement, and disconnected left pancreatic remnants, along with discussions of key supporting clinical trials.

The investigators disclosed relationships with Cook Endoscopy, Boston Scientific, Olympus, and others.

SOURCE: Baron TH et al. Gastroenterology. 2019 Aug 31. doi: 10.1053/j.gastro.2019.07.064.

Review the Gastroenterology clinical guidelines collection for AGA Institute statements detailing preferred approaches to specific medical problems or issues based on the most current available data at https://www.gastrojournal.org/content/agai. 

The Canadian Association of Gastroenterology (CAG) recently published a clinical practice guideline for the management of bile acid diarrhea (BAD).

Given a minimal evidence base, 16 out of the 17 guideline recommendations are conditional, according to lead author Daniel C. Sadowski, MD, of Royal Alexandra Hospital, Edmonton, Alta., and colleagues. Considering the shortage of high-quality evidence, the panel called for more randomized clinical trials to address current knowledge gaps.

“BAD is an understudied, often underappreciated condition, and questions remain regarding its diagnosis and treatment,” the panelists wrote in Clinical Gastroenterology and Hepatology. “There have been guidelines on the management of chronic diarrhea from the American Gastroenterological Association, and the British Society of Gastroenterology, but diagnosis and management of BAD was not assessed extensively in these publications. The British Society of Gastroenterology updated guidelines on the investigation of chronic diarrhea in adults, published after the consensus meeting, addressed some issues related to BAD.”

For the current guideline, using available evidence and clinical experience, expert panelists from Canada, the United States, and the United Kingdom aimed to “provide a reasonable and practical approach to care for specialists.” The guideline was further reviewed by the CAG Practice Affairs and Clinical Affairs Committees and the CAG Board of Directors.

The guideline first puts BAD in clinical context, noting a chronic diarrhea prevalence rate of approximately 5%. According to the guideline, approximately 1 out of 4 of these patients with chronic diarrhea may have BAD and prevalence of BAD is likely higher among those with other conditions, such as terminal ileal disease.

While BAD may be relatively common, it isn’t necessarily easy to diagnose, the panelists noted.

“The diagnosis of BAD continues to be a challenge, although this may be improved in the future with the general availability of screening serologic tests and other diagnostic tests,” the panelists wrote. “Although a treatment trial with bile acid sequestrants therapy (BAST) often is used, this approach has not been studied adequately, and likely is imprecise, and may lead to both undertreatment and overtreatment.”

Instead, the panelists recommended testing for BAD with 75-selenium homocholic acid taurine (SeHCAT) or 7-alpha-hydroxy-4-cholesten-3-one.

After addressing treatable causes of BAD, the guideline recommends initial therapy with cholestyramine or, if this is poorly tolerated, switching to BAST. However, the panelists advised against BAST for patients with resection or ileal Crohn’s disease, for whom other antidiarrheal agents are more suitable. When appropriate, BAST should be given at the lowest effective dose, with periodic trials of on-demand, intermittent administration, the panelists recommended. When BAST is ineffective, the guideline recommends that clinicians review concurrent medications as a possible cause of BAD or reinvestigate.

Concluding the guideline, the panelists emphasized the need for more high-quality research.

“The group recognized that specific, high-certainty evidence was lacking in many areas and recommended further studies that would improve the data available in future methodologic evaluations,” the panelists wrote.

While improving diagnostic accuracy of BAD should be a major goal of such research, progress is currently limited by an integral shortcoming of diagnostic test accuracy (DTA) studies, the panelists wrote.

“The main challenge in conducting DTA studies for BAD is the lack of a widely accepted or universally agreed-upon reference standard because the condition is defined and classified based on pathophysiologic mechanisms and its response to treatment (BAST),” the panelists wrote. “In addition, the index tests (SeHCAT, C4, FGF19, fecal bile acid assay) provide a continuous measure of metabolic function. Hence, DTA studies are not the most appropriate study design.”

“Therefore, one of the research priorities in BAD is for the scientific and clinical communities to agree on a reference standard that best represents BAD (e.g., response to BAST), with full understanding that the reference standard is and likely will be imperfect.”

The guideline was funded by unrestricted grants from Pendopharm and GE Healthcare Canada. The panelists disclosed relationships with AstraZeneca, AbbVie, Merck, Pfizer, and others.

SOURCE: Sadowski DC et al. Clin Gastroenterol Hepatol. 2019 Sep 14. doi: 10.1016/j.cgh.2019.08.062.

The Canadian Association of Gastroenterology (CAG) recently published a clinical practice guideline for the management of bile acid diarrhea (BAD).

Given a minimal evidence base, 16 out of the 17 guideline recommendations are conditional, according to lead author Daniel C. Sadowski, MD, of Royal Alexandra Hospital, Edmonton, Alta., and colleagues. Considering the shortage of high-quality evidence, the panel called for more randomized clinical trials to address current knowledge gaps.

“BAD is an understudied, often underappreciated condition, and questions remain regarding its diagnosis and treatment,” the panelists wrote in Clinical Gastroenterology and Hepatology. “There have been guidelines on the management of chronic diarrhea from the American Gastroenterological Association, and the British Society of Gastroenterology, but diagnosis and management of BAD was not assessed extensively in these publications. The British Society of Gastroenterology updated guidelines on the investigation of chronic diarrhea in adults, published after the consensus meeting, addressed some issues related to BAD.”

For the current guideline, using available evidence and clinical experience, expert panelists from Canada, the United States, and the United Kingdom aimed to “provide a reasonable and practical approach to care for specialists.” The guideline was further reviewed by the CAG Practice Affairs and Clinical Affairs Committees and the CAG Board of Directors.

The guideline first puts BAD in clinical context, noting a chronic diarrhea prevalence rate of approximately 5%. According to the guideline, approximately 1 out of 4 of these patients with chronic diarrhea may have BAD and prevalence of BAD is likely higher among those with other conditions, such as terminal ileal disease.

While BAD may be relatively common, it isn’t necessarily easy to diagnose, the panelists noted.

“The diagnosis of BAD continues to be a challenge, although this may be improved in the future with the general availability of screening serologic tests and other diagnostic tests,” the panelists wrote. “Although a treatment trial with bile acid sequestrants therapy (BAST) often is used, this approach has not been studied adequately, and likely is imprecise, and may lead to both undertreatment and overtreatment.”

Instead, the panelists recommended testing for BAD with 75-selenium homocholic acid taurine (SeHCAT) or 7-alpha-hydroxy-4-cholesten-3-one.

After addressing treatable causes of BAD, the guideline recommends initial therapy with cholestyramine or, if this is poorly tolerated, switching to BAST. However, the panelists advised against BAST for patients with resection or ileal Crohn’s disease, for whom other antidiarrheal agents are more suitable. When appropriate, BAST should be given at the lowest effective dose, with periodic trials of on-demand, intermittent administration, the panelists recommended. When BAST is ineffective, the guideline recommends that clinicians review concurrent medications as a possible cause of BAD or reinvestigate.

Concluding the guideline, the panelists emphasized the need for more high-quality research.

“The group recognized that specific, high-certainty evidence was lacking in many areas and recommended further studies that would improve the data available in future methodologic evaluations,” the panelists wrote.

While improving diagnostic accuracy of BAD should be a major goal of such research, progress is currently limited by an integral shortcoming of diagnostic test accuracy (DTA) studies, the panelists wrote.

“The main challenge in conducting DTA studies for BAD is the lack of a widely accepted or universally agreed-upon reference standard because the condition is defined and classified based on pathophysiologic mechanisms and its response to treatment (BAST),” the panelists wrote. “In addition, the index tests (SeHCAT, C4, FGF19, fecal bile acid assay) provide a continuous measure of metabolic function. Hence, DTA studies are not the most appropriate study design.”

“Therefore, one of the research priorities in BAD is for the scientific and clinical communities to agree on a reference standard that best represents BAD (e.g., response to BAST), with full understanding that the reference standard is and likely will be imperfect.”

The guideline was funded by unrestricted grants from Pendopharm and GE Healthcare Canada. The panelists disclosed relationships with AstraZeneca, AbbVie, Merck, Pfizer, and others.

SOURCE: Sadowski DC et al. Clin Gastroenterol Hepatol. 2019 Sep 14. doi: 10.1016/j.cgh.2019.08.062.

The Canadian Association of Gastroenterology (CAG) recently published a clinical practice guideline for the management of bile acid diarrhea (BAD).

Given a minimal evidence base, 16 out of the 17 guideline recommendations are conditional, according to lead author Daniel C. Sadowski, MD, of Royal Alexandra Hospital, Edmonton, Alta., and colleagues. Considering the shortage of high-quality evidence, the panel called for more randomized clinical trials to address current knowledge gaps.

“BAD is an understudied, often underappreciated condition, and questions remain regarding its diagnosis and treatment,” the panelists wrote in Clinical Gastroenterology and Hepatology. “There have been guidelines on the management of chronic diarrhea from the American Gastroenterological Association, and the British Society of Gastroenterology, but diagnosis and management of BAD was not assessed extensively in these publications. The British Society of Gastroenterology updated guidelines on the investigation of chronic diarrhea in adults, published after the consensus meeting, addressed some issues related to BAD.”

For the current guideline, using available evidence and clinical experience, expert panelists from Canada, the United States, and the United Kingdom aimed to “provide a reasonable and practical approach to care for specialists.” The guideline was further reviewed by the CAG Practice Affairs and Clinical Affairs Committees and the CAG Board of Directors.

The guideline first puts BAD in clinical context, noting a chronic diarrhea prevalence rate of approximately 5%. According to the guideline, approximately 1 out of 4 of these patients with chronic diarrhea may have BAD and prevalence of BAD is likely higher among those with other conditions, such as terminal ileal disease.

While BAD may be relatively common, it isn’t necessarily easy to diagnose, the panelists noted.

“The diagnosis of BAD continues to be a challenge, although this may be improved in the future with the general availability of screening serologic tests and other diagnostic tests,” the panelists wrote. “Although a treatment trial with bile acid sequestrants therapy (BAST) often is used, this approach has not been studied adequately, and likely is imprecise, and may lead to both undertreatment and overtreatment.”

Instead, the panelists recommended testing for BAD with 75-selenium homocholic acid taurine (SeHCAT) or 7-alpha-hydroxy-4-cholesten-3-one.

After addressing treatable causes of BAD, the guideline recommends initial therapy with cholestyramine or, if this is poorly tolerated, switching to BAST. However, the panelists advised against BAST for patients with resection or ileal Crohn’s disease, for whom other antidiarrheal agents are more suitable. When appropriate, BAST should be given at the lowest effective dose, with periodic trials of on-demand, intermittent administration, the panelists recommended. When BAST is ineffective, the guideline recommends that clinicians review concurrent medications as a possible cause of BAD or reinvestigate.

Concluding the guideline, the panelists emphasized the need for more high-quality research.

“The group recognized that specific, high-certainty evidence was lacking in many areas and recommended further studies that would improve the data available in future methodologic evaluations,” the panelists wrote.

While improving diagnostic accuracy of BAD should be a major goal of such research, progress is currently limited by an integral shortcoming of diagnostic test accuracy (DTA) studies, the panelists wrote.

“The main challenge in conducting DTA studies for BAD is the lack of a widely accepted or universally agreed-upon reference standard because the condition is defined and classified based on pathophysiologic mechanisms and its response to treatment (BAST),” the panelists wrote. “In addition, the index tests (SeHCAT, C4, FGF19, fecal bile acid assay) provide a continuous measure of metabolic function. Hence, DTA studies are not the most appropriate study design.”

“Therefore, one of the research priorities in BAD is for the scientific and clinical communities to agree on a reference standard that best represents BAD (e.g., response to BAST), with full understanding that the reference standard is and likely will be imperfect.”

The guideline was funded by unrestricted grants from Pendopharm and GE Healthcare Canada. The panelists disclosed relationships with AstraZeneca, AbbVie, Merck, Pfizer, and others.

SOURCE: Sadowski DC et al. Clin Gastroenterol Hepatol. 2019 Sep 14. doi: 10.1016/j.cgh.2019.08.062.

The Canadian Association of Gastroenterology (CAG) recently co-published a clinical practice guideline for the management of bile acid diarrhea (BAD) in Clinical Gastroenterology and Hepatology and the Journal of the Canadian Association of Gastroenterology.

Given a minimal evidence base, 16 out of the 17 guideline recommendations are conditional, according to lead author Daniel C. Sadowski, MD, of Royal Alexandra Hospital, Edmonton, Alta., and colleagues. Considering the shortage of high-quality evidence, the panel called for more randomized clinical trials to address current knowledge gaps.

“BAD is an understudied, often underappreciated condition, and questions remain regarding its diagnosis and treatment,” the panelists wrote in Clinical Gastroenterology and Hepatology. “There have been guidelines on the management of chronic diarrhea from the American Gastroenterological Association, and the British Society of Gastroenterology, but diagnosis and management of BAD was not assessed extensively in these publications. The British Society of Gastroenterology updated guidelines on the investigation of chronic diarrhea in adults, published after the consensus meeting, addressed some issues related to BAD.”

For the current guideline, using available evidence and clinical experience, expert panelists from Canada, the United States, and the United Kingdom aimed to “provide a reasonable and practical approach to care for specialists.” The guideline was further reviewed by the CAG Practice Affairs and Clinical Affairs Committees and the CAG Board of Directors.

The guideline first puts BAD in clinical context, noting a chronic diarrhea prevalence rate of approximately 5%. According to the guideline, approximately 1 out of 4 of these patients with chronic diarrhea may have BAD and prevalence of BAD is likely higher among those with other conditions, such as terminal ileal disease.

While BAD may be relatively common, it isn’t necessarily easy to diagnose, the panelists noted.

“The diagnosis of BAD continues to be a challenge, although this may be improved in the future with the general availability of screening serologic tests and other diagnostic tests,” the panelists wrote. “Although a treatment trial with bile acid sequestrants therapy (BAST) often is used, this approach has not been studied adequately, and likely is imprecise, and may lead to both undertreatment and overtreatment.”

Instead, the panelists recommended testing for BAD with 75-selenium homocholic acid taurine (SeHCAT) or 7-alpha-hydroxy-4-cholesten-3-one.

After addressing treatable causes of BAD, the guideline recommends initial therapy with cholestyramine or, if this is poorly tolerated, switching to BAST. However, the panelists advised against BAST for patients with resection or ileal Crohn’s disease, for whom other antidiarrheal agents are more suitable. When appropriate, BAST should be given at the lowest effective dose, with periodic trials of on-demand, intermittent administration, the panelists recommended. When BAST is ineffective, the guideline recommends that clinicians review concurrent medications as a possible cause of BAD or reinvestigate.

Concluding the guideline, the panelists emphasized the need for more high-quality research.

“The group recognized that specific, high-certainty evidence was lacking in many areas and recommended further studies that would improve the data available in future methodologic evaluations,” the panelists wrote.

While improving diagnostic accuracy of BAD should be a major goal of such research, progress is currently limited by an integral shortcoming of diagnostic test accuracy (DTA) studies, the panelists wrote.

“The main challenge in conducting DTA studies for BAD is the lack of a widely accepted or universally agreed-upon reference standard because the condition is defined and classified based on pathophysiologic mechanisms and its response to treatment (BAST),” the panelists wrote. “In addition, the index tests (SeHCAT, C4, FGF19, fecal bile acid assay) provide a continuous measure of metabolic function. Hence, DTA studies are not the most appropriate study design.”

“Therefore, one of the research priorities in BAD is for the scientific and clinical communities to agree on a reference standard that best represents BAD (e.g., response to BAST), with full understanding that the reference standard is and likely will be imperfect.”

The guideline was funded by unrestricted grants from Pendopharm and GE Healthcare Canada. The panelists disclosed relationships with AstraZeneca, AbbVie, Merck, Pfizer, and others.

Review the AGA clinical practice guideline on the laboratory evaluation of functional diarrhea and diarrhea-predominan irritable bowel syndrome in adults at https:/www.gastrojournal.org/article/S0016-5085(19)41083-4/fulltext.

SOURCE: Sadowski DC et al. Clin Gastroenterol Hepatol. 2019 Sep 14. doi: 10.1016/j.cgh.2019.08.062.

The Canadian Association of Gastroenterology (CAG) recently co-published a clinical practice guideline for the management of bile acid diarrhea (BAD) in Clinical Gastroenterology and Hepatology and the Journal of the Canadian Association of Gastroenterology.

Given a minimal evidence base, 16 out of the 17 guideline recommendations are conditional, according to lead author Daniel C. Sadowski, MD, of Royal Alexandra Hospital, Edmonton, Alta., and colleagues. Considering the shortage of high-quality evidence, the panel called for more randomized clinical trials to address current knowledge gaps.

“BAD is an understudied, often underappreciated condition, and questions remain regarding its diagnosis and treatment,” the panelists wrote in Clinical Gastroenterology and Hepatology. “There have been guidelines on the management of chronic diarrhea from the American Gastroenterological Association, and the British Society of Gastroenterology, but diagnosis and management of BAD was not assessed extensively in these publications. The British Society of Gastroenterology updated guidelines on the investigation of chronic diarrhea in adults, published after the consensus meeting, addressed some issues related to BAD.”

For the current guideline, using available evidence and clinical experience, expert panelists from Canada, the United States, and the United Kingdom aimed to “provide a reasonable and practical approach to care for specialists.” The guideline was further reviewed by the CAG Practice Affairs and Clinical Affairs Committees and the CAG Board of Directors.

The guideline first puts BAD in clinical context, noting a chronic diarrhea prevalence rate of approximately 5%. According to the guideline, approximately 1 out of 4 of these patients with chronic diarrhea may have BAD and prevalence of BAD is likely higher among those with other conditions, such as terminal ileal disease.

While BAD may be relatively common, it isn’t necessarily easy to diagnose, the panelists noted.

“The diagnosis of BAD continues to be a challenge, although this may be improved in the future with the general availability of screening serologic tests and other diagnostic tests,” the panelists wrote. “Although a treatment trial with bile acid sequestrants therapy (BAST) often is used, this approach has not been studied adequately, and likely is imprecise, and may lead to both undertreatment and overtreatment.”

Instead, the panelists recommended testing for BAD with 75-selenium homocholic acid taurine (SeHCAT) or 7-alpha-hydroxy-4-cholesten-3-one.

After addressing treatable causes of BAD, the guideline recommends initial therapy with cholestyramine or, if this is poorly tolerated, switching to BAST. However, the panelists advised against BAST for patients with resection or ileal Crohn’s disease, for whom other antidiarrheal agents are more suitable. When appropriate, BAST should be given at the lowest effective dose, with periodic trials of on-demand, intermittent administration, the panelists recommended. When BAST is ineffective, the guideline recommends that clinicians review concurrent medications as a possible cause of BAD or reinvestigate.

Concluding the guideline, the panelists emphasized the need for more high-quality research.

“The group recognized that specific, high-certainty evidence was lacking in many areas and recommended further studies that would improve the data available in future methodologic evaluations,” the panelists wrote.

While improving diagnostic accuracy of BAD should be a major goal of such research, progress is currently limited by an integral shortcoming of diagnostic test accuracy (DTA) studies, the panelists wrote.

“The main challenge in conducting DTA studies for BAD is the lack of a widely accepted or universally agreed-upon reference standard because the condition is defined and classified based on pathophysiologic mechanisms and its response to treatment (BAST),” the panelists wrote. “In addition, the index tests (SeHCAT, C4, FGF19, fecal bile acid assay) provide a continuous measure of metabolic function. Hence, DTA studies are not the most appropriate study design.”

“Therefore, one of the research priorities in BAD is for the scientific and clinical communities to agree on a reference standard that best represents BAD (e.g., response to BAST), with full understanding that the reference standard is and likely will be imperfect.”

The guideline was funded by unrestricted grants from Pendopharm and GE Healthcare Canada. The panelists disclosed relationships with AstraZeneca, AbbVie, Merck, Pfizer, and others.

Review the AGA clinical practice guideline on the laboratory evaluation of functional diarrhea and diarrhea-predominan irritable bowel syndrome in adults at https:/www.gastrojournal.org/article/S0016-5085(19)41083-4/fulltext.

SOURCE: Sadowski DC et al. Clin Gastroenterol Hepatol. 2019 Sep 14. doi: 10.1016/j.cgh.2019.08.062.

The Canadian Association of Gastroenterology (CAG) recently co-published a clinical practice guideline for the management of bile acid diarrhea (BAD) in Clinical Gastroenterology and Hepatology and the Journal of the Canadian Association of Gastroenterology.

Given a minimal evidence base, 16 out of the 17 guideline recommendations are conditional, according to lead author Daniel C. Sadowski, MD, of Royal Alexandra Hospital, Edmonton, Alta., and colleagues. Considering the shortage of high-quality evidence, the panel called for more randomized clinical trials to address current knowledge gaps.

“BAD is an understudied, often underappreciated condition, and questions remain regarding its diagnosis and treatment,” the panelists wrote in Clinical Gastroenterology and Hepatology. “There have been guidelines on the management of chronic diarrhea from the American Gastroenterological Association, and the British Society of Gastroenterology, but diagnosis and management of BAD was not assessed extensively in these publications. The British Society of Gastroenterology updated guidelines on the investigation of chronic diarrhea in adults, published after the consensus meeting, addressed some issues related to BAD.”

For the current guideline, using available evidence and clinical experience, expert panelists from Canada, the United States, and the United Kingdom aimed to “provide a reasonable and practical approach to care for specialists.” The guideline was further reviewed by the CAG Practice Affairs and Clinical Affairs Committees and the CAG Board of Directors.

The guideline first puts BAD in clinical context, noting a chronic diarrhea prevalence rate of approximately 5%. According to the guideline, approximately 1 out of 4 of these patients with chronic diarrhea may have BAD and prevalence of BAD is likely higher among those with other conditions, such as terminal ileal disease.

While BAD may be relatively common, it isn’t necessarily easy to diagnose, the panelists noted.

“The diagnosis of BAD continues to be a challenge, although this may be improved in the future with the general availability of screening serologic tests and other diagnostic tests,” the panelists wrote. “Although a treatment trial with bile acid sequestrants therapy (BAST) often is used, this approach has not been studied adequately, and likely is imprecise, and may lead to both undertreatment and overtreatment.”

Instead, the panelists recommended testing for BAD with 75-selenium homocholic acid taurine (SeHCAT) or 7-alpha-hydroxy-4-cholesten-3-one.

After addressing treatable causes of BAD, the guideline recommends initial therapy with cholestyramine or, if this is poorly tolerated, switching to BAST. However, the panelists advised against BAST for patients with resection or ileal Crohn’s disease, for whom other antidiarrheal agents are more suitable. When appropriate, BAST should be given at the lowest effective dose, with periodic trials of on-demand, intermittent administration, the panelists recommended. When BAST is ineffective, the guideline recommends that clinicians review concurrent medications as a possible cause of BAD or reinvestigate.

Concluding the guideline, the panelists emphasized the need for more high-quality research.

“The group recognized that specific, high-certainty evidence was lacking in many areas and recommended further studies that would improve the data available in future methodologic evaluations,” the panelists wrote.

While improving diagnostic accuracy of BAD should be a major goal of such research, progress is currently limited by an integral shortcoming of diagnostic test accuracy (DTA) studies, the panelists wrote.

“The main challenge in conducting DTA studies for BAD is the lack of a widely accepted or universally agreed-upon reference standard because the condition is defined and classified based on pathophysiologic mechanisms and its response to treatment (BAST),” the panelists wrote. “In addition, the index tests (SeHCAT, C4, FGF19, fecal bile acid assay) provide a continuous measure of metabolic function. Hence, DTA studies are not the most appropriate study design.”

“Therefore, one of the research priorities in BAD is for the scientific and clinical communities to agree on a reference standard that best represents BAD (e.g., response to BAST), with full understanding that the reference standard is and likely will be imperfect.”

The guideline was funded by unrestricted grants from Pendopharm and GE Healthcare Canada. The panelists disclosed relationships with AstraZeneca, AbbVie, Merck, Pfizer, and others.

Review the AGA clinical practice guideline on the laboratory evaluation of functional diarrhea and diarrhea-predominan irritable bowel syndrome in adults at https:/www.gastrojournal.org/article/S0016-5085(19)41083-4/fulltext.

SOURCE: Sadowski DC et al. Clin Gastroenterol Hepatol. 2019 Sep 14. doi: 10.1016/j.cgh.2019.08.062.

The American Gastroenterological Association recently issued a clinical practice update for the management of pancreatic necrosis, including 15 recommendations based on a comprehensive literature review and the experiences of leading experts.

Recommendations range from the general, such as the need for a multidisciplinary approach, to the specific, such as the superiority of metal over plastic stents for endoscopic transmural drainage.

The expert review, which was conducted by lead author Todd H. Baron, MD, of the University of North Carolina in Chapel Hill and three other colleagues, was vetted by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board. In addition, the update underwent external peer review prior to publication in Gastroenterology.

In the update, the authors outlined the clinical landscape for pancreatic necrosis, including challenges posed by complex cases and a mortality rate as high as 30%.

“Successful management of these patients requires expert multidisciplinary care by gastroenterologists, surgeons, interventional radiologists, and specialists in critical care medicine, infectious disease, and nutrition,” the investigators wrote.

They went on to explain how management has evolved over the past 10 years.

“Whereby major surgical intervention and debridement was once the mainstay of therapy for patients with symptomatic necrotic collections, a minimally invasive approach focusing on percutaneous drainage and/or endoscopic drainage or debridement is now favored,” they wrote. They added that debridement is still generally agreed to be the best choice for cases of infected necrosis or patients with sterile necrosis “marked by abdominal pain, nausea, vomiting, and nutritional failure or with associated complications including gastrointestinal luminal obstruction, biliary obstruction, recurrent acute pancreatitis, fistulas, or persistent systemic inflammatory response syndrome (SIRS).”

Other elements of care, however, remain debated, the investigators noted, which has led to variations in multiple aspects of care, such as interventional timing, intravenous fluids, antibiotics, and nutrition. Within this framework, the present practice update is aimed at offering “concise best practice advice for the optimal management of patients with this highly morbid condition.”

Among these pieces of advice, the authors emphasized that routine prophylactic antibiotics and/or antifungals to prevent infected necrosis are unsupported by multiple clinical trials. When infection is suspected, the update recommends broad spectrum intravenous antibiotics, noting that, in most cases, it is unnecessary to perform CT-guided fine-needle aspiration for cultures and gram stain.

Regarding nutrition, the update recommends against “pancreatic rest”; instead, it calls for early oral intake and, if this is not possible, then initiation of total enteral nutrition. Although the authors deemed multiple routes of enteral feeding acceptable, they favored nasogastric or nasoduodenal tubes, when appropriate, because of ease of placement and maintenance. For prolonged total enteral nutrition or patients unable to tolerate nasoenteric feeding, the authors recommended endoscopic feeding tube placement with a percutaneous endoscopic gastrostomy tube for those who can tolerate gastric feeding or a percutaneous endoscopic jejunostomy tube for those who cannot or have a high risk of aspiration.

As described above, the update recommends debridement for cases of infected pancreatic necrosis. Ideally, this should be performed at least 4 weeks after onset, and avoided altogether within the first 2 weeks, because of associated risks of morbidity and mortality; instead, during this acute phase, percutaneous drainage may be considered.

For walled-off pancreatic necrosis, the authors recommended transmural drainage via endoscopic therapy because this mitigates risk of pancreatocutaneous fistula. Percutaneous drainage may be considered in addition to, or in absence of, endoscopic drainage, depending on clinical status.

The remainder of the update covers decisions related to stents, other minimally invasive techniques, open operative debridement, and disconnected left pancreatic remnants, along with discussions of key supporting clinical trials.

The investigators disclosed relationships with Cook Endoscopy, Boston Scientific, Olympus, and others.

SOURCE: Baron TH et al. Gastroenterology. 2019 Aug 31. doi: 10.1053/j.gastro.2019.07.064.

The American Gastroenterological Association recently issued a clinical practice update for the management of pancreatic necrosis, including 15 recommendations based on a comprehensive literature review and the experiences of leading experts.

Recommendations range from the general, such as the need for a multidisciplinary approach, to the specific, such as the superiority of metal over plastic stents for endoscopic transmural drainage.

The expert review, which was conducted by lead author Todd H. Baron, MD, of the University of North Carolina in Chapel Hill and three other colleagues, was vetted by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board. In addition, the update underwent external peer review prior to publication in Gastroenterology.

In the update, the authors outlined the clinical landscape for pancreatic necrosis, including challenges posed by complex cases and a mortality rate as high as 30%.

“Successful management of these patients requires expert multidisciplinary care by gastroenterologists, surgeons, interventional radiologists, and specialists in critical care medicine, infectious disease, and nutrition,” the investigators wrote.

They went on to explain how management has evolved over the past 10 years.

“Whereby major surgical intervention and debridement was once the mainstay of therapy for patients with symptomatic necrotic collections, a minimally invasive approach focusing on percutaneous drainage and/or endoscopic drainage or debridement is now favored,” they wrote. They added that debridement is still generally agreed to be the best choice for cases of infected necrosis or patients with sterile necrosis “marked by abdominal pain, nausea, vomiting, and nutritional failure or with associated complications including gastrointestinal luminal obstruction, biliary obstruction, recurrent acute pancreatitis, fistulas, or persistent systemic inflammatory response syndrome (SIRS).”

Other elements of care, however, remain debated, the investigators noted, which has led to variations in multiple aspects of care, such as interventional timing, intravenous fluids, antibiotics, and nutrition. Within this framework, the present practice update is aimed at offering “concise best practice advice for the optimal management of patients with this highly morbid condition.”

Among these pieces of advice, the authors emphasized that routine prophylactic antibiotics and/or antifungals to prevent infected necrosis are unsupported by multiple clinical trials. When infection is suspected, the update recommends broad spectrum intravenous antibiotics, noting that, in most cases, it is unnecessary to perform CT-guided fine-needle aspiration for cultures and gram stain.

Regarding nutrition, the update recommends against “pancreatic rest”; instead, it calls for early oral intake and, if this is not possible, then initiation of total enteral nutrition. Although the authors deemed multiple routes of enteral feeding acceptable, they favored nasogastric or nasoduodenal tubes, when appropriate, because of ease of placement and maintenance. For prolonged total enteral nutrition or patients unable to tolerate nasoenteric feeding, the authors recommended endoscopic feeding tube placement with a percutaneous endoscopic gastrostomy tube for those who can tolerate gastric feeding or a percutaneous endoscopic jejunostomy tube for those who cannot or have a high risk of aspiration.

As described above, the update recommends debridement for cases of infected pancreatic necrosis. Ideally, this should be performed at least 4 weeks after onset, and avoided altogether within the first 2 weeks, because of associated risks of morbidity and mortality; instead, during this acute phase, percutaneous drainage may be considered.

For walled-off pancreatic necrosis, the authors recommended transmural drainage via endoscopic therapy because this mitigates risk of pancreatocutaneous fistula. Percutaneous drainage may be considered in addition to, or in absence of, endoscopic drainage, depending on clinical status.

The remainder of the update covers decisions related to stents, other minimally invasive techniques, open operative debridement, and disconnected left pancreatic remnants, along with discussions of key supporting clinical trials.

The investigators disclosed relationships with Cook Endoscopy, Boston Scientific, Olympus, and others.

SOURCE: Baron TH et al. Gastroenterology. 2019 Aug 31. doi: 10.1053/j.gastro.2019.07.064.

The American Gastroenterological Association recently issued a clinical practice update for the management of pancreatic necrosis, including 15 recommendations based on a comprehensive literature review and the experiences of leading experts.

Recommendations range from the general, such as the need for a multidisciplinary approach, to the specific, such as the superiority of metal over plastic stents for endoscopic transmural drainage.

The expert review, which was conducted by lead author Todd H. Baron, MD, of the University of North Carolina in Chapel Hill and three other colleagues, was vetted by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board. In addition, the update underwent external peer review prior to publication in Gastroenterology.

In the update, the authors outlined the clinical landscape for pancreatic necrosis, including challenges posed by complex cases and a mortality rate as high as 30%.

“Successful management of these patients requires expert multidisciplinary care by gastroenterologists, surgeons, interventional radiologists, and specialists in critical care medicine, infectious disease, and nutrition,” the investigators wrote.

They went on to explain how management has evolved over the past 10 years.

“Whereby major surgical intervention and debridement was once the mainstay of therapy for patients with symptomatic necrotic collections, a minimally invasive approach focusing on percutaneous drainage and/or endoscopic drainage or debridement is now favored,” they wrote. They added that debridement is still generally agreed to be the best choice for cases of infected necrosis or patients with sterile necrosis “marked by abdominal pain, nausea, vomiting, and nutritional failure or with associated complications including gastrointestinal luminal obstruction, biliary obstruction, recurrent acute pancreatitis, fistulas, or persistent systemic inflammatory response syndrome (SIRS).”

Other elements of care, however, remain debated, the investigators noted, which has led to variations in multiple aspects of care, such as interventional timing, intravenous fluids, antibiotics, and nutrition. Within this framework, the present practice update is aimed at offering “concise best practice advice for the optimal management of patients with this highly morbid condition.”

Among these pieces of advice, the authors emphasized that routine prophylactic antibiotics and/or antifungals to prevent infected necrosis are unsupported by multiple clinical trials. When infection is suspected, the update recommends broad spectrum intravenous antibiotics, noting that, in most cases, it is unnecessary to perform CT-guided fine-needle aspiration for cultures and gram stain.

Regarding nutrition, the update recommends against “pancreatic rest”; instead, it calls for early oral intake and, if this is not possible, then initiation of total enteral nutrition. Although the authors deemed multiple routes of enteral feeding acceptable, they favored nasogastric or nasoduodenal tubes, when appropriate, because of ease of placement and maintenance. For prolonged total enteral nutrition or patients unable to tolerate nasoenteric feeding, the authors recommended endoscopic feeding tube placement with a percutaneous endoscopic gastrostomy tube for those who can tolerate gastric feeding or a percutaneous endoscopic jejunostomy tube for those who cannot or have a high risk of aspiration.

As described above, the update recommends debridement for cases of infected pancreatic necrosis. Ideally, this should be performed at least 4 weeks after onset, and avoided altogether within the first 2 weeks, because of associated risks of morbidity and mortality; instead, during this acute phase, percutaneous drainage may be considered.

For walled-off pancreatic necrosis, the authors recommended transmural drainage via endoscopic therapy because this mitigates risk of pancreatocutaneous fistula. Percutaneous drainage may be considered in addition to, or in absence of, endoscopic drainage, depending on clinical status.

The remainder of the update covers decisions related to stents, other minimally invasive techniques, open operative debridement, and disconnected left pancreatic remnants, along with discussions of key supporting clinical trials.

The investigators disclosed relationships with Cook Endoscopy, Boston Scientific, Olympus, and others.

SOURCE: Baron TH et al. Gastroenterology. 2019 Aug 31. doi: 10.1053/j.gastro.2019.07.064.

BOSTON – The Karnofsky Performance Status is predictive of 5-year survival among patients with autoimmune-related liver disease who undergo a transplant, based on a retrospective look at more than 6,500 patients.

Will Pass/MDedge News

The analysis also showed that African American patients had a 33% higher mortality risk than non-Hispanic white patients, reported lead author Artin Galoosian, MD, of California Pacific Medical Center in San Francisco, who presented findings at the annual meeting of the American Association for the Study of Liver Diseases.

According to Dr. Galoosian, previous research has shown that Karnofsky scores are a quick and reliable means of predicting survival with liver transplant, but minimal research has evaluated this clinical tool specifically for patients with autoimmune-related liver diseases, which prompted the present study.

Drawing data from the United Network for Organ Sharing (UNOS; 2004-2017), the investigators evaluated performance status and survival in 6,628 patients who underwent liver transplant for one of three diseases: autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC), or primary biliary cholangitis (PBC). Karnofsky scores were divided into quartiles 1 through 4, from best to worst functional status. The investigators used Kaplan-Meier methods and multivariate Cox proportional hazard ratios to determine relationships between disease etiology, Karnofsky score, and survival; in addition, they evaluated the impact of demographic factors on outcomes.

The population was predominantly non-Hispanic white (73.0%) with smaller proportions of African American (13.4%) and Hispanic patients (11.5%). Of the three diseases, PBC was most common (38.2%), followed by PSC (32.1%), then AIH (29.7%).

Across all etiologies, Karnofsky status was significantly associated with survival; a score of 4 came with a 90% increased risk of posttransplant death, compared with a score of 1. Patients with AIH were most likely to have poor pretransplant functional status, as 39.1% of these patients had a Karnofsky score of 4, compared with 31.9% of patients with PSC and 29.0% of patients with PBC. AIH was also associated with a significantly higher risk of posttransplant death; relative risks for PSC and PBC were 20% and 17% lower, respectively.

Five years after surgery, 84.9% of AIH patients with a Karnofsky score of 1 were alive, compared with 76.1% of patients who had a score of 4. A similar association with functional status was found for PSC (84.9% vs. 75.4%), while PBC had a narrower survival margin (88.7% vs. 86.9%).

Analysis also revealed a wide survival gap between patients of different ethnic backgrounds. Compared with white patients, African American patients had a 33% higher risk of dying on the wait list or after transplant.

“[This gap] could reflect a multitude of issues, one being delayed referral to a hepatologist and being listed for transplant much later, so [patients] tend to be more sick,” Dr. Galoosian said.

He also offered some insight into clinical relevance.

“A broader implication of this research could be in the primary care setting,” Dr. Galoosian said. “[Clinicians need to be] aware that someone’s functional status has a broader impact on their health and be aware that ethnic minorities need to be more vigilantly up to date on their health care maintenance and more vigilantly connected to social workers if needed, in terms of getting the resources that they need to help break the [chain] of worse outcomes.”

The investigators disclosed relationships with Gilead, Salix, and AbbVie.

SOURCE: Galoosian A et al. The Liver Meeting 2019. Abstract 1102.

BOSTON – The Karnofsky Performance Status is predictive of 5-year survival among patients with autoimmune-related liver disease who undergo a transplant, based on a retrospective look at more than 6,500 patients.

Will Pass/MDedge News

The analysis also showed that African American patients had a 33% higher mortality risk than non-Hispanic white patients, reported lead author Artin Galoosian, MD, of California Pacific Medical Center in San Francisco, who presented findings at the annual meeting of the American Association for the Study of Liver Diseases.

According to Dr. Galoosian, previous research has shown that Karnofsky scores are a quick and reliable means of predicting survival with liver transplant, but minimal research has evaluated this clinical tool specifically for patients with autoimmune-related liver diseases, which prompted the present study.

Drawing data from the United Network for Organ Sharing (UNOS; 2004-2017), the investigators evaluated performance status and survival in 6,628 patients who underwent liver transplant for one of three diseases: autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC), or primary biliary cholangitis (PBC). Karnofsky scores were divided into quartiles 1 through 4, from best to worst functional status. The investigators used Kaplan-Meier methods and multivariate Cox proportional hazard ratios to determine relationships between disease etiology, Karnofsky score, and survival; in addition, they evaluated the impact of demographic factors on outcomes.

The population was predominantly non-Hispanic white (73.0%) with smaller proportions of African American (13.4%) and Hispanic patients (11.5%). Of the three diseases, PBC was most common (38.2%), followed by PSC (32.1%), then AIH (29.7%).

Across all etiologies, Karnofsky status was significantly associated with survival; a score of 4 came with a 90% increased risk of posttransplant death, compared with a score of 1. Patients with AIH were most likely to have poor pretransplant functional status, as 39.1% of these patients had a Karnofsky score of 4, compared with 31.9% of patients with PSC and 29.0% of patients with PBC. AIH was also associated with a significantly higher risk of posttransplant death; relative risks for PSC and PBC were 20% and 17% lower, respectively.

Five years after surgery, 84.9% of AIH patients with a Karnofsky score of 1 were alive, compared with 76.1% of patients who had a score of 4. A similar association with functional status was found for PSC (84.9% vs. 75.4%), while PBC had a narrower survival margin (88.7% vs. 86.9%).

Analysis also revealed a wide survival gap between patients of different ethnic backgrounds. Compared with white patients, African American patients had a 33% higher risk of dying on the wait list or after transplant.

“[This gap] could reflect a multitude of issues, one being delayed referral to a hepatologist and being listed for transplant much later, so [patients] tend to be more sick,” Dr. Galoosian said.

He also offered some insight into clinical relevance.

“A broader implication of this research could be in the primary care setting,” Dr. Galoosian said. “[Clinicians need to be] aware that someone’s functional status has a broader impact on their health and be aware that ethnic minorities need to be more vigilantly up to date on their health care maintenance and more vigilantly connected to social workers if needed, in terms of getting the resources that they need to help break the [chain] of worse outcomes.”

The investigators disclosed relationships with Gilead, Salix, and AbbVie.

SOURCE: Galoosian A et al. The Liver Meeting 2019. Abstract 1102.

BOSTON – The Karnofsky Performance Status is predictive of 5-year survival among patients with autoimmune-related liver disease who undergo a transplant, based on a retrospective look at more than 6,500 patients.

Will Pass/MDedge News

The analysis also showed that African American patients had a 33% higher mortality risk than non-Hispanic white patients, reported lead author Artin Galoosian, MD, of California Pacific Medical Center in San Francisco, who presented findings at the annual meeting of the American Association for the Study of Liver Diseases.

According to Dr. Galoosian, previous research has shown that Karnofsky scores are a quick and reliable means of predicting survival with liver transplant, but minimal research has evaluated this clinical tool specifically for patients with autoimmune-related liver diseases, which prompted the present study.

Drawing data from the United Network for Organ Sharing (UNOS; 2004-2017), the investigators evaluated performance status and survival in 6,628 patients who underwent liver transplant for one of three diseases: autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC), or primary biliary cholangitis (PBC). Karnofsky scores were divided into quartiles 1 through 4, from best to worst functional status. The investigators used Kaplan-Meier methods and multivariate Cox proportional hazard ratios to determine relationships between disease etiology, Karnofsky score, and survival; in addition, they evaluated the impact of demographic factors on outcomes.

The population was predominantly non-Hispanic white (73.0%) with smaller proportions of African American (13.4%) and Hispanic patients (11.5%). Of the three diseases, PBC was most common (38.2%), followed by PSC (32.1%), then AIH (29.7%).

Across all etiologies, Karnofsky status was significantly associated with survival; a score of 4 came with a 90% increased risk of posttransplant death, compared with a score of 1. Patients with AIH were most likely to have poor pretransplant functional status, as 39.1% of these patients had a Karnofsky score of 4, compared with 31.9% of patients with PSC and 29.0% of patients with PBC. AIH was also associated with a significantly higher risk of posttransplant death; relative risks for PSC and PBC were 20% and 17% lower, respectively.

Five years after surgery, 84.9% of AIH patients with a Karnofsky score of 1 were alive, compared with 76.1% of patients who had a score of 4. A similar association with functional status was found for PSC (84.9% vs. 75.4%), while PBC had a narrower survival margin (88.7% vs. 86.9%).

Analysis also revealed a wide survival gap between patients of different ethnic backgrounds. Compared with white patients, African American patients had a 33% higher risk of dying on the wait list or after transplant.

“[This gap] could reflect a multitude of issues, one being delayed referral to a hepatologist and being listed for transplant much later, so [patients] tend to be more sick,” Dr. Galoosian said.

He also offered some insight into clinical relevance.

“A broader implication of this research could be in the primary care setting,” Dr. Galoosian said. “[Clinicians need to be] aware that someone’s functional status has a broader impact on their health and be aware that ethnic minorities need to be more vigilantly up to date on their health care maintenance and more vigilantly connected to social workers if needed, in terms of getting the resources that they need to help break the [chain] of worse outcomes.”

The investigators disclosed relationships with Gilead, Salix, and AbbVie.

SOURCE: Galoosian A et al. The Liver Meeting 2019. Abstract 1102.

BOSTON – ED-based screening is a feasible method of detecting hepatitis C virus (HCV) in high-risk populations, but linkage to care remains low, according to investigators.

Will Pass/MDedge News

An HCV screening program involving three Seattle hospitals and more than 4,000 patients showed that linkage to care was lowest among patients who were younger, homeless, or used injection drugs, reported lead author Charles S. Landis, MD, PhD, of the University of Washington, Seattle.

“In the U.S., rates of acute HCV infections are increasing in younger patients and in areas disproportionally affected by the opiate epidemic,” Dr. Landis said in a presentation at the annual meeting of the American Association for the Study of Liver Diseases. “In order to achieve a goal of elimination, HCV screening, appropriate linkage to care, and treatment will need to be directed toward younger, marginalized, and underserved populations.”

Dr. Landis explained that EDs are suitable for HCV screening because users of emergency services are disproportionately affected by HCV, compared with patients in primary and specialty care settings. Despite this, linkage to care remains historically higher in primary and specialty care settings at approximately 70%, compared with 30% via the ED, Dr. Landis said.

Historically, EDs have been resistant to HCV screening programs, Dr. Landis said, but with the model used in the present study, which relied upon a full-time staff member in each ED who was employed by the infectious disease or hepatology department, no ED resources were needed.

Participants were willing adults who had reliable contact information. Patients were excluded if they were non–English speaking, incarcerated, enrolled or expected to enroll in another clinical study which excludes coenrollment, planned to move out of the region in the next 6 months, admitted to the ED with an acute life-threatening illness, or admitted to the ED for sexual assault. The program had three objectives: Screening, linkage to care, and treatment, all of which were coordinated by the aforementioned case manager.

To date, 4,182 patients have been screened, 936 have been enrolled, 95 have tested positive for HCV RNA, 32 have been linked with care, and 19 have been treated.

“So you can see, a lot of squeeze for a just a little bit of juice here,” Dr. Landis said, referring to the relatively low number of treated patients, compared with how many were screened.

The prevalence of HCV infection based on RNA testing was 2%, though one hospital had a rate of 5%. “This [prevalence] compares to, but is maybe slightly less than, the prevalence seen in others studies based in the emergency department,” Dr. Landis said. “The thought is, not all emergency departments are equal in terms of the patient population that they serve.”

Data analysis showed that the overall linkage to care was 36%. “This is still suboptimal, from my perspective,” Dr. Landis said, “but it does compare with several other ED-based studies.”

A closer look at the data showed that linkage was not uniform across the population. Among patients with homes, linkage to care was 59%, compared with 20% for patients who were homeless (P = .02).

“Ultimately, we need to tailor our approaches for linking homeless patients differently than patients who are not homeless,” Dr. Landis said.

Patients who reported no injection-drug use had a linkage to care of 50%, which was numerically higher than the rate of 20% among users of injection drugs; this difference was not statistically significant, which Dr. Landis attributed to insufficient population size. Similarly, younger patients showed numerical trends toward lower linkage to care.

“Future work will attempt to optimize linkage to care strategies based on patient demographic factors, such as active injection drug use or homelessness,” Dr. Landis said.

During discussion, a conference attendee from the United States expressed skepticism of the program’s merits.

“I may be a glass-half-empty person, but is it worth all this effort?” the attendee asked. “In all honesty, you treated a few dozen [patients] for 180,000 visits [per year]. I’m really not sure it’s worth those efforts, and I’m wondering if those efforts could be placed in different areas, especially for a higher yield.”

“Point well taken,” Dr. Landis said. “I think that was the purpose of the study, to see if the emergency department is a place to screen and link patients to care, and we’re trying to optimize that. Remember, there were 4,000 patients, but for many of those, it took literally a minute to screen them.”

An attendee from Australia offered a slightly more positive take on the findings, followed by a suggestion to improve linkage in marginalized populations.

“I’m not sure I’d be pessimistic,” the attendee said. “I think you ought to be commended for getting that number of people to link, because it is very difficult when we are looking at linking people from a hospital-based setting who actually live in the community and suffer from homelessness and mental health issues and incarceration and a whole range of other things. ... Maybe we need to change our idea of having these centralized silos where people are referred, and go out into the community, much like [tuberculosis] clinics used to do, and track people down.”

The study was funded by Gilead. The investigators disclosed additional relationships with HighTide Therapeutics, Intercept, AbbVie, and others.

SOURCE: Landis CS et al. The Liver Meeting 2019, Abstract 168.

BOSTON – ED-based screening is a feasible method of detecting hepatitis C virus (HCV) in high-risk populations, but linkage to care remains low, according to investigators.

Will Pass/MDedge News

An HCV screening program involving three Seattle hospitals and more than 4,000 patients showed that linkage to care was lowest among patients who were younger, homeless, or used injection drugs, reported lead author Charles S. Landis, MD, PhD, of the University of Washington, Seattle.

“In the U.S., rates of acute HCV infections are increasing in younger patients and in areas disproportionally affected by the opiate epidemic,” Dr. Landis said in a presentation at the annual meeting of the American Association for the Study of Liver Diseases. “In order to achieve a goal of elimination, HCV screening, appropriate linkage to care, and treatment will need to be directed toward younger, marginalized, and underserved populations.”

Dr. Landis explained that EDs are suitable for HCV screening because users of emergency services are disproportionately affected by HCV, compared with patients in primary and specialty care settings. Despite this, linkage to care remains historically higher in primary and specialty care settings at approximately 70%, compared with 30% via the ED, Dr. Landis said.

Historically, EDs have been resistant to HCV screening programs, Dr. Landis said, but with the model used in the present study, which relied upon a full-time staff member in each ED who was employed by the infectious disease or hepatology department, no ED resources were needed.

Participants were willing adults who had reliable contact information. Patients were excluded if they were non–English speaking, incarcerated, enrolled or expected to enroll in another clinical study which excludes coenrollment, planned to move out of the region in the next 6 months, admitted to the ED with an acute life-threatening illness, or admitted to the ED for sexual assault. The program had three objectives: Screening, linkage to care, and treatment, all of which were coordinated by the aforementioned case manager.

To date, 4,182 patients have been screened, 936 have been enrolled, 95 have tested positive for HCV RNA, 32 have been linked with care, and 19 have been treated.

“So you can see, a lot of squeeze for a just a little bit of juice here,” Dr. Landis said, referring to the relatively low number of treated patients, compared with how many were screened.

The prevalence of HCV infection based on RNA testing was 2%, though one hospital had a rate of 5%. “This [prevalence] compares to, but is maybe slightly less than, the prevalence seen in others studies based in the emergency department,” Dr. Landis said. “The thought is, not all emergency departments are equal in terms of the patient population that they serve.”

Data analysis showed that the overall linkage to care was 36%. “This is still suboptimal, from my perspective,” Dr. Landis said, “but it does compare with several other ED-based studies.”

A closer look at the data showed that linkage was not uniform across the population. Among patients with homes, linkage to care was 59%, compared with 20% for patients who were homeless (P = .02).

“Ultimately, we need to tailor our approaches for linking homeless patients differently than patients who are not homeless,” Dr. Landis said.

Patients who reported no injection-drug use had a linkage to care of 50%, which was numerically higher than the rate of 20% among users of injection drugs; this difference was not statistically significant, which Dr. Landis attributed to insufficient population size. Similarly, younger patients showed numerical trends toward lower linkage to care.

“Future work will attempt to optimize linkage to care strategies based on patient demographic factors, such as active injection drug use or homelessness,” Dr. Landis said.

During discussion, a conference attendee from the United States expressed skepticism of the program’s merits.

“I may be a glass-half-empty person, but is it worth all this effort?” the attendee asked. “In all honesty, you treated a few dozen [patients] for 180,000 visits [per year]. I’m really not sure it’s worth those efforts, and I’m wondering if those efforts could be placed in different areas, especially for a higher yield.”

“Point well taken,” Dr. Landis said. “I think that was the purpose of the study, to see if the emergency department is a place to screen and link patients to care, and we’re trying to optimize that. Remember, there were 4,000 patients, but for many of those, it took literally a minute to screen them.”

An attendee from Australia offered a slightly more positive take on the findings, followed by a suggestion to improve linkage in marginalized populations.

“I’m not sure I’d be pessimistic,” the attendee said. “I think you ought to be commended for getting that number of people to link, because it is very difficult when we are looking at linking people from a hospital-based setting who actually live in the community and suffer from homelessness and mental health issues and incarceration and a whole range of other things. ... Maybe we need to change our idea of having these centralized silos where people are referred, and go out into the community, much like [tuberculosis] clinics used to do, and track people down.”

The study was funded by Gilead. The investigators disclosed additional relationships with HighTide Therapeutics, Intercept, AbbVie, and others.

SOURCE: Landis CS et al. The Liver Meeting 2019, Abstract 168.

BOSTON – ED-based screening is a feasible method of detecting hepatitis C virus (HCV) in high-risk populations, but linkage to care remains low, according to investigators.

Will Pass/MDedge News

An HCV screening program involving three Seattle hospitals and more than 4,000 patients showed that linkage to care was lowest among patients who were younger, homeless, or used injection drugs, reported lead author Charles S. Landis, MD, PhD, of the University of Washington, Seattle.

“In the U.S., rates of acute HCV infections are increasing in younger patients and in areas disproportionally affected by the opiate epidemic,” Dr. Landis said in a presentation at the annual meeting of the American Association for the Study of Liver Diseases. “In order to achieve a goal of elimination, HCV screening, appropriate linkage to care, and treatment will need to be directed toward younger, marginalized, and underserved populations.”

Dr. Landis explained that EDs are suitable for HCV screening because users of emergency services are disproportionately affected by HCV, compared with patients in primary and specialty care settings. Despite this, linkage to care remains historically higher in primary and specialty care settings at approximately 70%, compared with 30% via the ED, Dr. Landis said.

Historically, EDs have been resistant to HCV screening programs, Dr. Landis said, but with the model used in the present study, which relied upon a full-time staff member in each ED who was employed by the infectious disease or hepatology department, no ED resources were needed.

Participants were willing adults who had reliable contact information. Patients were excluded if they were non–English speaking, incarcerated, enrolled or expected to enroll in another clinical study which excludes coenrollment, planned to move out of the region in the next 6 months, admitted to the ED with an acute life-threatening illness, or admitted to the ED for sexual assault. The program had three objectives: Screening, linkage to care, and treatment, all of which were coordinated by the aforementioned case manager.

To date, 4,182 patients have been screened, 936 have been enrolled, 95 have tested positive for HCV RNA, 32 have been linked with care, and 19 have been treated.

“So you can see, a lot of squeeze for a just a little bit of juice here,” Dr. Landis said, referring to the relatively low number of treated patients, compared with how many were screened.

The prevalence of HCV infection based on RNA testing was 2%, though one hospital had a rate of 5%. “This [prevalence] compares to, but is maybe slightly less than, the prevalence seen in others studies based in the emergency department,” Dr. Landis said. “The thought is, not all emergency departments are equal in terms of the patient population that they serve.”

Data analysis showed that the overall linkage to care was 36%. “This is still suboptimal, from my perspective,” Dr. Landis said, “but it does compare with several other ED-based studies.”

A closer look at the data showed that linkage was not uniform across the population. Among patients with homes, linkage to care was 59%, compared with 20% for patients who were homeless (P = .02).

“Ultimately, we need to tailor our approaches for linking homeless patients differently than patients who are not homeless,” Dr. Landis said.

Patients who reported no injection-drug use had a linkage to care of 50%, which was numerically higher than the rate of 20% among users of injection drugs; this difference was not statistically significant, which Dr. Landis attributed to insufficient population size. Similarly, younger patients showed numerical trends toward lower linkage to care.

“Future work will attempt to optimize linkage to care strategies based on patient demographic factors, such as active injection drug use or homelessness,” Dr. Landis said.

During discussion, a conference attendee from the United States expressed skepticism of the program’s merits.

“I may be a glass-half-empty person, but is it worth all this effort?” the attendee asked. “In all honesty, you treated a few dozen [patients] for 180,000 visits [per year]. I’m really not sure it’s worth those efforts, and I’m wondering if those efforts could be placed in different areas, especially for a higher yield.”

“Point well taken,” Dr. Landis said. “I think that was the purpose of the study, to see if the emergency department is a place to screen and link patients to care, and we’re trying to optimize that. Remember, there were 4,000 patients, but for many of those, it took literally a minute to screen them.”

An attendee from Australia offered a slightly more positive take on the findings, followed by a suggestion to improve linkage in marginalized populations.

“I’m not sure I’d be pessimistic,” the attendee said. “I think you ought to be commended for getting that number of people to link, because it is very difficult when we are looking at linking people from a hospital-based setting who actually live in the community and suffer from homelessness and mental health issues and incarceration and a whole range of other things. ... Maybe we need to change our idea of having these centralized silos where people are referred, and go out into the community, much like [tuberculosis] clinics used to do, and track people down.”

The study was funded by Gilead. The investigators disclosed additional relationships with HighTide Therapeutics, Intercept, AbbVie, and others.

SOURCE: Landis CS et al. The Liver Meeting 2019, Abstract 168.

BOSTON – Exposure to heavy metals from natural and man-made sources may contribute to development of autoimmune liver disease, according to a recent U.K. study involving more than 3,500 patients.

Will Pass/MDedge News

Coal mines were particularly implicated, as they accounted for 39% of the risk of developing primary biliary cholangitis (PBC), reported lead author Jessica Dyson, MBBS, of Newcastle (England) University, and colleagues.

“We know that the etiology of autoimmune liver disease remains unclear, but we’re increasingly coming to understand that it’s likely to be a complex interplay between genetic and environmental factors,” Dr. Dyson said during a presentation at the annual meeting of the American Association for the Study of Liver Diseases. Showing a map of England, she pointed out how three autoimmune liver diseases – PBC, primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) – each have unique clusters of distribution. “This implies that environmental exposure may have a role in disease pathogenesis.”

To investigate this possibility, Dr. Dyson and colleagues used structural equation modeling to look for associations between the above three autoimmune liver diseases, socioeconomic status, and environmental factors. Specific environmental factors included soil concentrations of heavy metals (cadmium, arsenic, lead, manganese, and iron), coal mines, lead mines, quarries, urban areas, traffic, stream pH, and landfills.

The study was conducted in the northeast of England, where migration rates are low, Dr. Dyson said. From this region, the investigators identified patients with PBC (n = 2,150), AIH (n = 963), and PSC (n = 472). Conceptual models were used to examine relationships between covariates and prevalence of disease, with good models exhibiting a root-mean-square error of association less than 0.05 and a 95% covariate significance. After adjusting for population density, comparative fit was used to measure variation within each model.

The best model for PBC revealed the aforementioned link with coal mines, proximity to which accounted for 39% of the pathogenesis of PBC. High levels of cadmium in soil had an interactive role with coal mines, and itself directly contributed 22% of the risk of PBC; however, Dr. Dyson noted that, while many cadmium-rich areas had high rates of PBC, not all did.

“This demonstrates the complexity of causality of disease, and we certainly can’t say that cadmium, in its own right, is a direct cause and effect,” Dr. Dyson said. “But I think [cadmium] certainly potentially is one of the factors at play.”

For AIH, coal mines contributed less (6%), although cadmium still accounted for 22% of variation of disease, as did alkaline areas. Finally, a significant link was found between PSC and regions with high arsenic levels.

“To conclude, our data suggest that heavy metals may be risk factors for autoimmune liver disease,” Dr. Dyson said. “There are a number of exposure routes that may be pertinent to patients, from heavy metals occurring via natural sources, and also via virtue of human activity, such as burning of fossil fuels, heavy-metal production, and pesticides.” Dr. Dyson emphasized this latter route, as some rural areas, where pesticide use is common, had high prevalence rates of autoimmune liver disease.

Dr. Dyson went on to put her findings in context. “Heavy metals are a well-recognized cause of immune dysregulation and epithelial injury and are actually actively transported into the bile, and that may be particularly relevant in terms of cholangiopathies. And this leads us to the possibility of interventions to reduce toxic exposure that may modify risk of disease.”

Looking to the future, Dr. Dyson described plans to build on this research with measurements of heavy metals in tissues, serum, and urine.

The investigators reported no relevant disclosures.

SOURCE: Dyson J et al. The Liver Meeting 2019, Abstract 48.

BOSTON – Exposure to heavy metals from natural and man-made sources may contribute to development of autoimmune liver disease, according to a recent U.K. study involving more than 3,500 patients.

Will Pass/MDedge News

Coal mines were particularly implicated, as they accounted for 39% of the risk of developing primary biliary cholangitis (PBC), reported lead author Jessica Dyson, MBBS, of Newcastle (England) University, and colleagues.

“We know that the etiology of autoimmune liver disease remains unclear, but we’re increasingly coming to understand that it’s likely to be a complex interplay between genetic and environmental factors,” Dr. Dyson said during a presentation at the annual meeting of the American Association for the Study of Liver Diseases. Showing a map of England, she pointed out how three autoimmune liver diseases – PBC, primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) – each have unique clusters of distribution. “This implies that environmental exposure may have a role in disease pathogenesis.”

To investigate this possibility, Dr. Dyson and colleagues used structural equation modeling to look for associations between the above three autoimmune liver diseases, socioeconomic status, and environmental factors. Specific environmental factors included soil concentrations of heavy metals (cadmium, arsenic, lead, manganese, and iron), coal mines, lead mines, quarries, urban areas, traffic, stream pH, and landfills.

The study was conducted in the northeast of England, where migration rates are low, Dr. Dyson said. From this region, the investigators identified patients with PBC (n = 2,150), AIH (n = 963), and PSC (n = 472). Conceptual models were used to examine relationships between covariates and prevalence of disease, with good models exhibiting a root-mean-square error of association less than 0.05 and a 95% covariate significance. After adjusting for population density, comparative fit was used to measure variation within each model.

The best model for PBC revealed the aforementioned link with coal mines, proximity to which accounted for 39% of the pathogenesis of PBC. High levels of cadmium in soil had an interactive role with coal mines, and itself directly contributed 22% of the risk of PBC; however, Dr. Dyson noted that, while many cadmium-rich areas had high rates of PBC, not all did.

“This demonstrates the complexity of causality of disease, and we certainly can’t say that cadmium, in its own right, is a direct cause and effect,” Dr. Dyson said. “But I think [cadmium] certainly potentially is one of the factors at play.”

For AIH, coal mines contributed less (6%), although cadmium still accounted for 22% of variation of disease, as did alkaline areas. Finally, a significant link was found between PSC and regions with high arsenic levels.

“To conclude, our data suggest that heavy metals may be risk factors for autoimmune liver disease,” Dr. Dyson said. “There are a number of exposure routes that may be pertinent to patients, from heavy metals occurring via natural sources, and also via virtue of human activity, such as burning of fossil fuels, heavy-metal production, and pesticides.” Dr. Dyson emphasized this latter route, as some rural areas, where pesticide use is common, had high prevalence rates of autoimmune liver disease.

Dr. Dyson went on to put her findings in context. “Heavy metals are a well-recognized cause of immune dysregulation and epithelial injury and are actually actively transported into the bile, and that may be particularly relevant in terms of cholangiopathies. And this leads us to the possibility of interventions to reduce toxic exposure that may modify risk of disease.”

Looking to the future, Dr. Dyson described plans to build on this research with measurements of heavy metals in tissues, serum, and urine.

The investigators reported no relevant disclosures.

SOURCE: Dyson J et al. The Liver Meeting 2019, Abstract 48.

BOSTON – Exposure to heavy metals from natural and man-made sources may contribute to development of autoimmune liver disease, according to a recent U.K. study involving more than 3,500 patients.

Will Pass/MDedge News

Coal mines were particularly implicated, as they accounted for 39% of the risk of developing primary biliary cholangitis (PBC), reported lead author Jessica Dyson, MBBS, of Newcastle (England) University, and colleagues.

“We know that the etiology of autoimmune liver disease remains unclear, but we’re increasingly coming to understand that it’s likely to be a complex interplay between genetic and environmental factors,” Dr. Dyson said during a presentation at the annual meeting of the American Association for the Study of Liver Diseases. Showing a map of England, she pointed out how three autoimmune liver diseases – PBC, primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) – each have unique clusters of distribution. “This implies that environmental exposure may have a role in disease pathogenesis.”

To investigate this possibility, Dr. Dyson and colleagues used structural equation modeling to look for associations between the above three autoimmune liver diseases, socioeconomic status, and environmental factors. Specific environmental factors included soil concentrations of heavy metals (cadmium, arsenic, lead, manganese, and iron), coal mines, lead mines, quarries, urban areas, traffic, stream pH, and landfills.

The study was conducted in the northeast of England, where migration rates are low, Dr. Dyson said. From this region, the investigators identified patients with PBC (n = 2,150), AIH (n = 963), and PSC (n = 472). Conceptual models were used to examine relationships between covariates and prevalence of disease, with good models exhibiting a root-mean-square error of association less than 0.05 and a 95% covariate significance. After adjusting for population density, comparative fit was used to measure variation within each model.

The best model for PBC revealed the aforementioned link with coal mines, proximity to which accounted for 39% of the pathogenesis of PBC. High levels of cadmium in soil had an interactive role with coal mines, and itself directly contributed 22% of the risk of PBC; however, Dr. Dyson noted that, while many cadmium-rich areas had high rates of PBC, not all did.

“This demonstrates the complexity of causality of disease, and we certainly can’t say that cadmium, in its own right, is a direct cause and effect,” Dr. Dyson said. “But I think [cadmium] certainly potentially is one of the factors at play.”

For AIH, coal mines contributed less (6%), although cadmium still accounted for 22% of variation of disease, as did alkaline areas. Finally, a significant link was found between PSC and regions with high arsenic levels.

“To conclude, our data suggest that heavy metals may be risk factors for autoimmune liver disease,” Dr. Dyson said. “There are a number of exposure routes that may be pertinent to patients, from heavy metals occurring via natural sources, and also via virtue of human activity, such as burning of fossil fuels, heavy-metal production, and pesticides.” Dr. Dyson emphasized this latter route, as some rural areas, where pesticide use is common, had high prevalence rates of autoimmune liver disease.

Dr. Dyson went on to put her findings in context. “Heavy metals are a well-recognized cause of immune dysregulation and epithelial injury and are actually actively transported into the bile, and that may be particularly relevant in terms of cholangiopathies. And this leads us to the possibility of interventions to reduce toxic exposure that may modify risk of disease.”

Looking to the future, Dr. Dyson described plans to build on this research with measurements of heavy metals in tissues, serum, and urine.

The investigators reported no relevant disclosures.

SOURCE: Dyson J et al. The Liver Meeting 2019, Abstract 48.