Pancreas and Biliary Tract

Patients with COVID-19 develop a distinct subset of pancreatitis hallmarked by duodenal and periduodenal inflammation, according to a recent case series.

Although all five patients presented with multiple predictive markers of severe pancreatitis, the subsequent clinical pathway “was much more benign than anticipated,” reported lead author Peter Szatmary, MB, BChir, PhD, of the University of Liverpool (England) and colleagues. Still, they noted prolonged hospital stays because of persistent inflammation and poor diabetic control.

“As the global pandemic of SARS-CoV-2 continues, nuances of the disease it precipitates in humans continue to emerge,” the investigators wrote in Gastroenterology. “[A] group from Wuhan reported a series of 9 patients with purported pancreatic injury in the context of SARS-CoV-2 infection, but did not provide robust evidence for pancreatitis relying on mild hyperamylasemia alone.”

For the present series, Dr. Szatmary and colleagues restricted diagnosis of pancreatitis to international consensus guidelines, which require “abdominal pain consistent with pancreatitis, serum amylase/lipase greater than three times the upper limit of normal, and characteristic findings on cross-sectional imaging.”

From middle of March to late April, the investigators identified 35 patients with acute pancreatitis at Royal Liverpool (England) University Hospital, 25 of whom tested negative for SARS-CoV-2, which resulted in study exclusion. An additional five patients were excluded from the series as another etiology for pancreatitis was clearly present, such as gallstones.

“The remaining 5 patients, all with SARS-CoV-2, presented atypically yet homogenously with a distinct metabolic-pancreatitis phenotype,” the investigators wrote.

All five patients were obese or overweight young men with a median body mass index of 30 kg/m² and age of 42 years. On presentation, all patients had elevated, but nondiagnostic, levels of amylase (median, 149 U/L). Contrast-enhanced abdominal CT revealed moderate to severe hepatic steatosis (less than 104 HU), which rapidly regressed within a week among patients who underwent repeat imaging.

“The pattern of pancreatic inflammation was similarly unusual in these patients,” the investigators wrote, going on to describe “mild pancreatic edema without significant pancreatic or peripancreatic necrosis, with distinct duodenal/periduodenal inflammation involving the second and third part of the duodenum.”

According to Dr. Szatmary and colleagues, these findings were “accompanied by a profound systemic inflammatory response,” including 1-2 criteria for systemic inflammatory response syndrome that increased to 2-4 criteria within 48 hours. During hospitalization, patients also exhibited a “dramatic elevation” of C-reactive protein, from a median of 31 mg/L upon admission to 485 mg/L within 48 hours.

Although these markers predicted severe disease, all cases followed a clinical course similar to “a typical attack of moderate pancreatitis,” the investigators wrote.

All patients were treated with IV fluids, four out of five received broad-spectrum IV antibiotics for pneumonitis, three out of five received fibrate and/or insulin therapy, and two out of five received pancreatic enzyme replacement therapy. No patients required corticosteroids, organ support, or respiratory support beyond low-flow oxygen. Median hospital stay was 14 days.

“We ... propose the combination of male sex, abdominal pain, metabolic stress, and CT-findings of predominantly pancreatico-duodenal inflammation with steatosis represent a distinct subset of pancreatitis in patients infected with SARS-CoV-2,” the investigators wrote.

They suggested that the endocrine pancreas may be “particularly vulnerable to this infection,” citing prolonged hospital stays because of poor diabetic control.

“[T]ransient dyslipidemias and impaired glucose tolerance may be common in SARS-CoV-2 patients and warrant further investigation,” they concluded.

Oscar J. Hines, MD, chief of the division of general surgery at UCLA Medical Center and leader in the field of pancreatitis management, said that the case series has a limited impact.

“The findings are unlikely to change practice and only call attention for physicians to the possibility of pancreatitis in COVID-positive patients,” Dr. Hines said.

The investigators reported grants from NIHR, Wellcome Trust, Mylan, and others.

SOURCE: Szatmary P et al. Gastroenterology. 2020 Jun 1. doi: 10.1053/j.gastro.2020.05.069.

Patients with COVID-19 develop a distinct subset of pancreatitis hallmarked by duodenal and periduodenal inflammation, according to a recent case series.

Although all five patients presented with multiple predictive markers of severe pancreatitis, the subsequent clinical pathway “was much more benign than anticipated,” reported lead author Peter Szatmary, MB, BChir, PhD, of the University of Liverpool (England) and colleagues. Still, they noted prolonged hospital stays because of persistent inflammation and poor diabetic control.

“As the global pandemic of SARS-CoV-2 continues, nuances of the disease it precipitates in humans continue to emerge,” the investigators wrote in Gastroenterology. “[A] group from Wuhan reported a series of 9 patients with purported pancreatic injury in the context of SARS-CoV-2 infection, but did not provide robust evidence for pancreatitis relying on mild hyperamylasemia alone.”

For the present series, Dr. Szatmary and colleagues restricted diagnosis of pancreatitis to international consensus guidelines, which require “abdominal pain consistent with pancreatitis, serum amylase/lipase greater than three times the upper limit of normal, and characteristic findings on cross-sectional imaging.”

From middle of March to late April, the investigators identified 35 patients with acute pancreatitis at Royal Liverpool (England) University Hospital, 25 of whom tested negative for SARS-CoV-2, which resulted in study exclusion. An additional five patients were excluded from the series as another etiology for pancreatitis was clearly present, such as gallstones.

“The remaining 5 patients, all with SARS-CoV-2, presented atypically yet homogenously with a distinct metabolic-pancreatitis phenotype,” the investigators wrote.

All five patients were obese or overweight young men with a median body mass index of 30 kg/m² and age of 42 years. On presentation, all patients had elevated, but nondiagnostic, levels of amylase (median, 149 U/L). Contrast-enhanced abdominal CT revealed moderate to severe hepatic steatosis (less than 104 HU), which rapidly regressed within a week among patients who underwent repeat imaging.

“The pattern of pancreatic inflammation was similarly unusual in these patients,” the investigators wrote, going on to describe “mild pancreatic edema without significant pancreatic or peripancreatic necrosis, with distinct duodenal/periduodenal inflammation involving the second and third part of the duodenum.”

According to Dr. Szatmary and colleagues, these findings were “accompanied by a profound systemic inflammatory response,” including 1-2 criteria for systemic inflammatory response syndrome that increased to 2-4 criteria within 48 hours. During hospitalization, patients also exhibited a “dramatic elevation” of C-reactive protein, from a median of 31 mg/L upon admission to 485 mg/L within 48 hours.

Although these markers predicted severe disease, all cases followed a clinical course similar to “a typical attack of moderate pancreatitis,” the investigators wrote.

All patients were treated with IV fluids, four out of five received broad-spectrum IV antibiotics for pneumonitis, three out of five received fibrate and/or insulin therapy, and two out of five received pancreatic enzyme replacement therapy. No patients required corticosteroids, organ support, or respiratory support beyond low-flow oxygen. Median hospital stay was 14 days.

“We ... propose the combination of male sex, abdominal pain, metabolic stress, and CT-findings of predominantly pancreatico-duodenal inflammation with steatosis represent a distinct subset of pancreatitis in patients infected with SARS-CoV-2,” the investigators wrote.

They suggested that the endocrine pancreas may be “particularly vulnerable to this infection,” citing prolonged hospital stays because of poor diabetic control.

“[T]ransient dyslipidemias and impaired glucose tolerance may be common in SARS-CoV-2 patients and warrant further investigation,” they concluded.

Oscar J. Hines, MD, chief of the division of general surgery at UCLA Medical Center and leader in the field of pancreatitis management, said that the case series has a limited impact.

“The findings are unlikely to change practice and only call attention for physicians to the possibility of pancreatitis in COVID-positive patients,” Dr. Hines said.

The investigators reported grants from NIHR, Wellcome Trust, Mylan, and others.

SOURCE: Szatmary P et al. Gastroenterology. 2020 Jun 1. doi: 10.1053/j.gastro.2020.05.069.

Patients with COVID-19 develop a distinct subset of pancreatitis hallmarked by duodenal and periduodenal inflammation, according to a recent case series.

Although all five patients presented with multiple predictive markers of severe pancreatitis, the subsequent clinical pathway “was much more benign than anticipated,” reported lead author Peter Szatmary, MB, BChir, PhD, of the University of Liverpool (England) and colleagues. Still, they noted prolonged hospital stays because of persistent inflammation and poor diabetic control.

“As the global pandemic of SARS-CoV-2 continues, nuances of the disease it precipitates in humans continue to emerge,” the investigators wrote in Gastroenterology. “[A] group from Wuhan reported a series of 9 patients with purported pancreatic injury in the context of SARS-CoV-2 infection, but did not provide robust evidence for pancreatitis relying on mild hyperamylasemia alone.”

For the present series, Dr. Szatmary and colleagues restricted diagnosis of pancreatitis to international consensus guidelines, which require “abdominal pain consistent with pancreatitis, serum amylase/lipase greater than three times the upper limit of normal, and characteristic findings on cross-sectional imaging.”

From middle of March to late April, the investigators identified 35 patients with acute pancreatitis at Royal Liverpool (England) University Hospital, 25 of whom tested negative for SARS-CoV-2, which resulted in study exclusion. An additional five patients were excluded from the series as another etiology for pancreatitis was clearly present, such as gallstones.

“The remaining 5 patients, all with SARS-CoV-2, presented atypically yet homogenously with a distinct metabolic-pancreatitis phenotype,” the investigators wrote.

All five patients were obese or overweight young men with a median body mass index of 30 kg/m² and age of 42 years. On presentation, all patients had elevated, but nondiagnostic, levels of amylase (median, 149 U/L). Contrast-enhanced abdominal CT revealed moderate to severe hepatic steatosis (less than 104 HU), which rapidly regressed within a week among patients who underwent repeat imaging.

“The pattern of pancreatic inflammation was similarly unusual in these patients,” the investigators wrote, going on to describe “mild pancreatic edema without significant pancreatic or peripancreatic necrosis, with distinct duodenal/periduodenal inflammation involving the second and third part of the duodenum.”

According to Dr. Szatmary and colleagues, these findings were “accompanied by a profound systemic inflammatory response,” including 1-2 criteria for systemic inflammatory response syndrome that increased to 2-4 criteria within 48 hours. During hospitalization, patients also exhibited a “dramatic elevation” of C-reactive protein, from a median of 31 mg/L upon admission to 485 mg/L within 48 hours.

Although these markers predicted severe disease, all cases followed a clinical course similar to “a typical attack of moderate pancreatitis,” the investigators wrote.

All patients were treated with IV fluids, four out of five received broad-spectrum IV antibiotics for pneumonitis, three out of five received fibrate and/or insulin therapy, and two out of five received pancreatic enzyme replacement therapy. No patients required corticosteroids, organ support, or respiratory support beyond low-flow oxygen. Median hospital stay was 14 days.

“We ... propose the combination of male sex, abdominal pain, metabolic stress, and CT-findings of predominantly pancreatico-duodenal inflammation with steatosis represent a distinct subset of pancreatitis in patients infected with SARS-CoV-2,” the investigators wrote.

They suggested that the endocrine pancreas may be “particularly vulnerable to this infection,” citing prolonged hospital stays because of poor diabetic control.

“[T]ransient dyslipidemias and impaired glucose tolerance may be common in SARS-CoV-2 patients and warrant further investigation,” they concluded.

Oscar J. Hines, MD, chief of the division of general surgery at UCLA Medical Center and leader in the field of pancreatitis management, said that the case series has a limited impact.

“The findings are unlikely to change practice and only call attention for physicians to the possibility of pancreatitis in COVID-positive patients,” Dr. Hines said.

The investigators reported grants from NIHR, Wellcome Trust, Mylan, and others.

SOURCE: Szatmary P et al. Gastroenterology. 2020 Jun 1. doi: 10.1053/j.gastro.2020.05.069.

For patients diagnosed with mild acute pancreatitis (AP) in the ED, an observation pathway may significantly reduce hospitalization rate and associated costs without compromising patient safety or quality of care, according to investigators.

Over a 2-year period, the observation pathway at Beth Israel Deaconess Medical Center, Boston, reduced hospitalizations by 31.2%, reported lead author Awais Ahmed, MD, of Harvard Medical School, Boston, and colleagues.

“AP carries a significant burden on the health care system, accounting for the third most common reason for gastrointestinal-related admissions in the United States,” the investigators wrote in the Journal of Clinical Gastroenterology. “As such, streamlining care for AP patients to reduce admissions can reduce the associated financial burden.”

The investigators’ efforts to reduce admissions for patients with AP began in 2016, when they first implemented an observation pathway at Beth Israel. This 6-month pilot study demonstrated proof of concept because it reduced admissions by 22.2% and shortened average length of stay without negatively affecting rates of mortality or readmission.

Based on these encouraging results, the hospital implemented the observation pathway as a standard of care. The present study analyzed 2 years of data from patients diagnosed with AP following the end of the pilot study. The primary outcome was hospitalization rate. Secondary outcomes included health care utilization, 30-day mortality rate, 30-day readmission rate, and median length of stay.

Patients with mild AP entered the observation pathway at the discretion of the supervising clinician, as well as based on absence of exclusion criteria, such as end organ damage, chronic pancreatitis, cholangitis, and other considerations.

Over 2 years, 165 patients were diagnosed with AP in the ED, of whom 118 (71.5%) had mild AP. From this latter group, 54 (45.8%) entered the observation pathway, while 64 (54.2%) were admitted as inpatients, primarily (n = 58) because of exclusion criteria. Within the observation group, 45 out of 54 patients (83.3%) successfully completed the pathway and were discharged. Six of these patients were readmitted within 30 days. Among the 9 patients who did not complete the pathway, 6 failed to meet discharge criteria, resulting in admission, whereas 3 patients left the hospital against medical advice.

Combining data from this 2-year period and the pilot study, the hospitalization rate for mild AP was reduced by 31.2%. In the present study, hospitalization was reduced by 27% for patients with AP of any severity. This figure was steady over a 3-year period, at 25.8%.

Median length of stay for patients with mild AP was significantly shorter in the present study’s observation pathway than in a historical cohort (19.9 vs. 72.0 hours); this remained significant when also including patients from the pilot study (21.2 vs. 72.0 hours). Compared with the historic cohort, patients in the observation had significantly fewer radiographic studies, and more patients were discharged in less than 24 hours. Meanwhile, 30-day readmission and mortality rates remained unchanged.

“In summary, our long-term data of a single center emergency department–based observation management pathway for mild AP demonstrates durability over more than 2 years in maintaining its objective of reducing hospitalization,” the investigators concluded. “This is associated with a [shorter] length of stay, and reduced health care resource utilization, suggesting a possible decrease in financial cost of managing mild AP, without affecting readmission rates or mortality.”

These findings encourage further research, the investigators suggested, while noting that the observation pathway may not be appropriate for all treatment centers.

“The generalizability of the pathway is limited, given its single center location, and tertiary environment,” the investigators wrote. “Smaller hospitals, lacking multidisciplinary support for complications of AP, may find it challenging to implement such a pathway, and thus triage these patients for inpatient admission at their facility or to nearby tertiary centers.”The investigators reported no conflicts of interest.

SOURCE: Ahmed A et al. J Clin Gastroenterol. 2020 Apr 14. doi: 10.1097/MCG.0000000000001354.

Visit the AGA GI Patient Center for information on pancreatitis to share with your patients at https://www.gastro.org/practice-guidance/gi-patient-center/topic/pancreatitis.

For patients diagnosed with mild acute pancreatitis (AP) in the ED, an observation pathway may significantly reduce hospitalization rate and associated costs without compromising patient safety or quality of care, according to investigators.

Over a 2-year period, the observation pathway at Beth Israel Deaconess Medical Center, Boston, reduced hospitalizations by 31.2%, reported lead author Awais Ahmed, MD, of Harvard Medical School, Boston, and colleagues.

“AP carries a significant burden on the health care system, accounting for the third most common reason for gastrointestinal-related admissions in the United States,” the investigators wrote in the Journal of Clinical Gastroenterology. “As such, streamlining care for AP patients to reduce admissions can reduce the associated financial burden.”

The investigators’ efforts to reduce admissions for patients with AP began in 2016, when they first implemented an observation pathway at Beth Israel. This 6-month pilot study demonstrated proof of concept because it reduced admissions by 22.2% and shortened average length of stay without negatively affecting rates of mortality or readmission.

Based on these encouraging results, the hospital implemented the observation pathway as a standard of care. The present study analyzed 2 years of data from patients diagnosed with AP following the end of the pilot study. The primary outcome was hospitalization rate. Secondary outcomes included health care utilization, 30-day mortality rate, 30-day readmission rate, and median length of stay.

Patients with mild AP entered the observation pathway at the discretion of the supervising clinician, as well as based on absence of exclusion criteria, such as end organ damage, chronic pancreatitis, cholangitis, and other considerations.

Over 2 years, 165 patients were diagnosed with AP in the ED, of whom 118 (71.5%) had mild AP. From this latter group, 54 (45.8%) entered the observation pathway, while 64 (54.2%) were admitted as inpatients, primarily (n = 58) because of exclusion criteria. Within the observation group, 45 out of 54 patients (83.3%) successfully completed the pathway and were discharged. Six of these patients were readmitted within 30 days. Among the 9 patients who did not complete the pathway, 6 failed to meet discharge criteria, resulting in admission, whereas 3 patients left the hospital against medical advice.

Combining data from this 2-year period and the pilot study, the hospitalization rate for mild AP was reduced by 31.2%. In the present study, hospitalization was reduced by 27% for patients with AP of any severity. This figure was steady over a 3-year period, at 25.8%.

Median length of stay for patients with mild AP was significantly shorter in the present study’s observation pathway than in a historical cohort (19.9 vs. 72.0 hours); this remained significant when also including patients from the pilot study (21.2 vs. 72.0 hours). Compared with the historic cohort, patients in the observation had significantly fewer radiographic studies, and more patients were discharged in less than 24 hours. Meanwhile, 30-day readmission and mortality rates remained unchanged.

“In summary, our long-term data of a single center emergency department–based observation management pathway for mild AP demonstrates durability over more than 2 years in maintaining its objective of reducing hospitalization,” the investigators concluded. “This is associated with a [shorter] length of stay, and reduced health care resource utilization, suggesting a possible decrease in financial cost of managing mild AP, without affecting readmission rates or mortality.”

These findings encourage further research, the investigators suggested, while noting that the observation pathway may not be appropriate for all treatment centers.

“The generalizability of the pathway is limited, given its single center location, and tertiary environment,” the investigators wrote. “Smaller hospitals, lacking multidisciplinary support for complications of AP, may find it challenging to implement such a pathway, and thus triage these patients for inpatient admission at their facility or to nearby tertiary centers.”The investigators reported no conflicts of interest.

SOURCE: Ahmed A et al. J Clin Gastroenterol. 2020 Apr 14. doi: 10.1097/MCG.0000000000001354.

Visit the AGA GI Patient Center for information on pancreatitis to share with your patients at https://www.gastro.org/practice-guidance/gi-patient-center/topic/pancreatitis.

For patients diagnosed with mild acute pancreatitis (AP) in the ED, an observation pathway may significantly reduce hospitalization rate and associated costs without compromising patient safety or quality of care, according to investigators.

Over a 2-year period, the observation pathway at Beth Israel Deaconess Medical Center, Boston, reduced hospitalizations by 31.2%, reported lead author Awais Ahmed, MD, of Harvard Medical School, Boston, and colleagues.

“AP carries a significant burden on the health care system, accounting for the third most common reason for gastrointestinal-related admissions in the United States,” the investigators wrote in the Journal of Clinical Gastroenterology. “As such, streamlining care for AP patients to reduce admissions can reduce the associated financial burden.”

The investigators’ efforts to reduce admissions for patients with AP began in 2016, when they first implemented an observation pathway at Beth Israel. This 6-month pilot study demonstrated proof of concept because it reduced admissions by 22.2% and shortened average length of stay without negatively affecting rates of mortality or readmission.

Based on these encouraging results, the hospital implemented the observation pathway as a standard of care. The present study analyzed 2 years of data from patients diagnosed with AP following the end of the pilot study. The primary outcome was hospitalization rate. Secondary outcomes included health care utilization, 30-day mortality rate, 30-day readmission rate, and median length of stay.

Patients with mild AP entered the observation pathway at the discretion of the supervising clinician, as well as based on absence of exclusion criteria, such as end organ damage, chronic pancreatitis, cholangitis, and other considerations.

Over 2 years, 165 patients were diagnosed with AP in the ED, of whom 118 (71.5%) had mild AP. From this latter group, 54 (45.8%) entered the observation pathway, while 64 (54.2%) were admitted as inpatients, primarily (n = 58) because of exclusion criteria. Within the observation group, 45 out of 54 patients (83.3%) successfully completed the pathway and were discharged. Six of these patients were readmitted within 30 days. Among the 9 patients who did not complete the pathway, 6 failed to meet discharge criteria, resulting in admission, whereas 3 patients left the hospital against medical advice.

Combining data from this 2-year period and the pilot study, the hospitalization rate for mild AP was reduced by 31.2%. In the present study, hospitalization was reduced by 27% for patients with AP of any severity. This figure was steady over a 3-year period, at 25.8%.

Median length of stay for patients with mild AP was significantly shorter in the present study’s observation pathway than in a historical cohort (19.9 vs. 72.0 hours); this remained significant when also including patients from the pilot study (21.2 vs. 72.0 hours). Compared with the historic cohort, patients in the observation had significantly fewer radiographic studies, and more patients were discharged in less than 24 hours. Meanwhile, 30-day readmission and mortality rates remained unchanged.

“In summary, our long-term data of a single center emergency department–based observation management pathway for mild AP demonstrates durability over more than 2 years in maintaining its objective of reducing hospitalization,” the investigators concluded. “This is associated with a [shorter] length of stay, and reduced health care resource utilization, suggesting a possible decrease in financial cost of managing mild AP, without affecting readmission rates or mortality.”

These findings encourage further research, the investigators suggested, while noting that the observation pathway may not be appropriate for all treatment centers.

“The generalizability of the pathway is limited, given its single center location, and tertiary environment,” the investigators wrote. “Smaller hospitals, lacking multidisciplinary support for complications of AP, may find it challenging to implement such a pathway, and thus triage these patients for inpatient admission at their facility or to nearby tertiary centers.”The investigators reported no conflicts of interest.

SOURCE: Ahmed A et al. J Clin Gastroenterol. 2020 Apr 14. doi: 10.1097/MCG.0000000000001354.

Visit the AGA GI Patient Center for information on pancreatitis to share with your patients at https://www.gastro.org/practice-guidance/gi-patient-center/topic/pancreatitis.

Stratifying diagnostic cut-off values of tumor markers based on genetic variants may improve detection of pancreatic cancer, according to investigators.

Stratification had the greatest positive impact on accuracy of carbohydrate antigen 19-9 (CA19-9), reported lead author Toshiya Abe, MD, PhD, of Johns Hopkins Hospital, Baltimore, and colleagues.

“Despite the evidence that genetic factors influence tumor marker levels, the potential utility of using a genetic test to improve the interpretation of tumor markers has drawn limited attention,” the investigators wrote in Clinical Gastroenterology and Hepatology.

And improvements are needed, the investigators noted, particularly for early cancer detection in high-risk individuals.

“[T]he toughest hurdle for a pancreatic cancer detection blood test is the detection of stage I disease,” the investigators wrote. “Cancers generally shed biomarkers in proportion to their size, and small stage I pancreatic cancers shed fewer diagnostic biomarkers into the circulation, making diagnosis more difficult.”

Although a 2016 study by Dr. Guopei Luo and colleagues demonstrated that diagnostic accuracy of CA19-9 could be improved via genotyping, tumor marker performance was not characterized by high-specificity cut-off values, which the present study aimed to do.

The control group included 504 high-risk individuals who were prospectively enrolled in the Cancer of the Pancreas Screening (CAPS) studies from 2002 to 2018, while the case group included 245 patients with pancreatic ductal adenocarcinoma (PDAC) who underwent resection at Johns Hopkins from 2010 to 2017.

The control group was randomly divided into discovery and validation sets in order to achieve 99% specificity cut-off values, which were used to measure sensitivity in the case group. According to the investigators, high-specificity cut-off values are necessary for surveillance of asymptomatic high-risk individuals in order to minimize false-positive results.

In all patients, tumor markers and genotype were analyzed. Tumor markers included carcinoembryonic antigen (CEA), CA19-9, and cancer antigen 125 (CA-125). Genotyping included 16 single-nucleotide polymorphisms (SNPs) in 9 genes, including FUT2 and FUT3, which are known to influence levels of CA19-9.

In contrast with previous findings, which identified three relevant subgroups of FUT2/FUT3, the present study found that four distinct subgroups were significantly associated with CA19-9 levels: FUT3-null, FUT3+/-, FUT3+/+, and FUT2-null.

When CA19-9 cut-off levels were stratified by these four subgroups and applied to the 245 patients with pancreatic cancer, the investigators achieved a sensitivity of 60.8%, compared with 52.7% without stratification. The new cut-off values led to reclassification of 28 (11.4%) patients with pancreatic cancer, including 24 who switched from negative to positive, and 4 who switched from positive to negative.

Sensitivity of the SNP-adjusted CA19-9 test was improved to 66.4% when used exclusively in patients with functional FUT3 genes. Conversely, sensitivity was markedly lower, at 36.7%, when the test was used for patients with stage I disease.

While CA19-9 testing was notably improved by SNP-based stratification, results from CEA and CA-125 testing were more modest. Standard CEA testing had a sensitivity of 13.8%, compared with 15.9% when cut-off values were stratified by FUT2 status and ABO blood group. Similarly, modifying CA-125 values based on SNPs in GAL3ST2 raised sensitivity from 15.5% to 17.6%.

Although combining SNP-modified tumor marker results did increase overall sensitivity to as high as 66.1%, this also reduced specificity to as low as 95.4%

Still, Dr. Abe and colleagues suggested that the findings demonstrate proof of concept.

“Our results show that a tumor marker SNP test can improve the diagnostic accuracy of CA19-9 and, to a lesser extent, CEA and CA-125, but further work is needed to improve the diagnostic accuracy of our panel for the detection of early-stage pancreatic cancer,” they concluded.

The investigators also suggested that the technique could have value for surveillance of ovarian cancer; however, again, they emphasized the need for more research.The study was funded by the National Institutes of Health, Susan Wojcicki and Dennis Troper, the Pancreatic Cancer Action Network, and others. The investigators reported no conflicts of interest.

SOURCE: Abe T et al. Clin Gastro Hepatol. 2019 Oct 29. doi: 10.1016/j.cgh.2019.10.036.

Stratifying diagnostic cut-off values of tumor markers based on genetic variants may improve detection of pancreatic cancer, according to investigators.

Stratification had the greatest positive impact on accuracy of carbohydrate antigen 19-9 (CA19-9), reported lead author Toshiya Abe, MD, PhD, of Johns Hopkins Hospital, Baltimore, and colleagues.

“Despite the evidence that genetic factors influence tumor marker levels, the potential utility of using a genetic test to improve the interpretation of tumor markers has drawn limited attention,” the investigators wrote in Clinical Gastroenterology and Hepatology.

And improvements are needed, the investigators noted, particularly for early cancer detection in high-risk individuals.

“[T]he toughest hurdle for a pancreatic cancer detection blood test is the detection of stage I disease,” the investigators wrote. “Cancers generally shed biomarkers in proportion to their size, and small stage I pancreatic cancers shed fewer diagnostic biomarkers into the circulation, making diagnosis more difficult.”

Although a 2016 study by Dr. Guopei Luo and colleagues demonstrated that diagnostic accuracy of CA19-9 could be improved via genotyping, tumor marker performance was not characterized by high-specificity cut-off values, which the present study aimed to do.

The control group included 504 high-risk individuals who were prospectively enrolled in the Cancer of the Pancreas Screening (CAPS) studies from 2002 to 2018, while the case group included 245 patients with pancreatic ductal adenocarcinoma (PDAC) who underwent resection at Johns Hopkins from 2010 to 2017.

The control group was randomly divided into discovery and validation sets in order to achieve 99% specificity cut-off values, which were used to measure sensitivity in the case group. According to the investigators, high-specificity cut-off values are necessary for surveillance of asymptomatic high-risk individuals in order to minimize false-positive results.

In all patients, tumor markers and genotype were analyzed. Tumor markers included carcinoembryonic antigen (CEA), CA19-9, and cancer antigen 125 (CA-125). Genotyping included 16 single-nucleotide polymorphisms (SNPs) in 9 genes, including FUT2 and FUT3, which are known to influence levels of CA19-9.

In contrast with previous findings, which identified three relevant subgroups of FUT2/FUT3, the present study found that four distinct subgroups were significantly associated with CA19-9 levels: FUT3-null, FUT3+/-, FUT3+/+, and FUT2-null.

When CA19-9 cut-off levels were stratified by these four subgroups and applied to the 245 patients with pancreatic cancer, the investigators achieved a sensitivity of 60.8%, compared with 52.7% without stratification. The new cut-off values led to reclassification of 28 (11.4%) patients with pancreatic cancer, including 24 who switched from negative to positive, and 4 who switched from positive to negative.

Sensitivity of the SNP-adjusted CA19-9 test was improved to 66.4% when used exclusively in patients with functional FUT3 genes. Conversely, sensitivity was markedly lower, at 36.7%, when the test was used for patients with stage I disease.

While CA19-9 testing was notably improved by SNP-based stratification, results from CEA and CA-125 testing were more modest. Standard CEA testing had a sensitivity of 13.8%, compared with 15.9% when cut-off values were stratified by FUT2 status and ABO blood group. Similarly, modifying CA-125 values based on SNPs in GAL3ST2 raised sensitivity from 15.5% to 17.6%.

Although combining SNP-modified tumor marker results did increase overall sensitivity to as high as 66.1%, this also reduced specificity to as low as 95.4%

Still, Dr. Abe and colleagues suggested that the findings demonstrate proof of concept.

“Our results show that a tumor marker SNP test can improve the diagnostic accuracy of CA19-9 and, to a lesser extent, CEA and CA-125, but further work is needed to improve the diagnostic accuracy of our panel for the detection of early-stage pancreatic cancer,” they concluded.

The investigators also suggested that the technique could have value for surveillance of ovarian cancer; however, again, they emphasized the need for more research.The study was funded by the National Institutes of Health, Susan Wojcicki and Dennis Troper, the Pancreatic Cancer Action Network, and others. The investigators reported no conflicts of interest.

SOURCE: Abe T et al. Clin Gastro Hepatol. 2019 Oct 29. doi: 10.1016/j.cgh.2019.10.036.

Stratifying diagnostic cut-off values of tumor markers based on genetic variants may improve detection of pancreatic cancer, according to investigators.

Stratification had the greatest positive impact on accuracy of carbohydrate antigen 19-9 (CA19-9), reported lead author Toshiya Abe, MD, PhD, of Johns Hopkins Hospital, Baltimore, and colleagues.

“Despite the evidence that genetic factors influence tumor marker levels, the potential utility of using a genetic test to improve the interpretation of tumor markers has drawn limited attention,” the investigators wrote in Clinical Gastroenterology and Hepatology.

And improvements are needed, the investigators noted, particularly for early cancer detection in high-risk individuals.

“[T]he toughest hurdle for a pancreatic cancer detection blood test is the detection of stage I disease,” the investigators wrote. “Cancers generally shed biomarkers in proportion to their size, and small stage I pancreatic cancers shed fewer diagnostic biomarkers into the circulation, making diagnosis more difficult.”

Although a 2016 study by Dr. Guopei Luo and colleagues demonstrated that diagnostic accuracy of CA19-9 could be improved via genotyping, tumor marker performance was not characterized by high-specificity cut-off values, which the present study aimed to do.

The control group included 504 high-risk individuals who were prospectively enrolled in the Cancer of the Pancreas Screening (CAPS) studies from 2002 to 2018, while the case group included 245 patients with pancreatic ductal adenocarcinoma (PDAC) who underwent resection at Johns Hopkins from 2010 to 2017.

The control group was randomly divided into discovery and validation sets in order to achieve 99% specificity cut-off values, which were used to measure sensitivity in the case group. According to the investigators, high-specificity cut-off values are necessary for surveillance of asymptomatic high-risk individuals in order to minimize false-positive results.

In all patients, tumor markers and genotype were analyzed. Tumor markers included carcinoembryonic antigen (CEA), CA19-9, and cancer antigen 125 (CA-125). Genotyping included 16 single-nucleotide polymorphisms (SNPs) in 9 genes, including FUT2 and FUT3, which are known to influence levels of CA19-9.

In contrast with previous findings, which identified three relevant subgroups of FUT2/FUT3, the present study found that four distinct subgroups were significantly associated with CA19-9 levels: FUT3-null, FUT3+/-, FUT3+/+, and FUT2-null.

When CA19-9 cut-off levels were stratified by these four subgroups and applied to the 245 patients with pancreatic cancer, the investigators achieved a sensitivity of 60.8%, compared with 52.7% without stratification. The new cut-off values led to reclassification of 28 (11.4%) patients with pancreatic cancer, including 24 who switched from negative to positive, and 4 who switched from positive to negative.

Sensitivity of the SNP-adjusted CA19-9 test was improved to 66.4% when used exclusively in patients with functional FUT3 genes. Conversely, sensitivity was markedly lower, at 36.7%, when the test was used for patients with stage I disease.

While CA19-9 testing was notably improved by SNP-based stratification, results from CEA and CA-125 testing were more modest. Standard CEA testing had a sensitivity of 13.8%, compared with 15.9% when cut-off values were stratified by FUT2 status and ABO blood group. Similarly, modifying CA-125 values based on SNPs in GAL3ST2 raised sensitivity from 15.5% to 17.6%.

Although combining SNP-modified tumor marker results did increase overall sensitivity to as high as 66.1%, this also reduced specificity to as low as 95.4%

Still, Dr. Abe and colleagues suggested that the findings demonstrate proof of concept.

“Our results show that a tumor marker SNP test can improve the diagnostic accuracy of CA19-9 and, to a lesser extent, CEA and CA-125, but further work is needed to improve the diagnostic accuracy of our panel for the detection of early-stage pancreatic cancer,” they concluded.

The investigators also suggested that the technique could have value for surveillance of ovarian cancer; however, again, they emphasized the need for more research.The study was funded by the National Institutes of Health, Susan Wojcicki and Dennis Troper, the Pancreatic Cancer Action Network, and others. The investigators reported no conflicts of interest.

SOURCE: Abe T et al. Clin Gastro Hepatol. 2019 Oct 29. doi: 10.1016/j.cgh.2019.10.036.

Pancreatic enzyme replacement therapy (PERT) did not significantly alter body weight after pancreatoduodenectomy in the intention-to-treat analysis of a randomized, placebo-controlled trial.

After 3 months of treatment, the PERT group lost an average of 0.68 kg, and the placebo group lost an average of 1.19 kg (P = .302). Low adherence might explain this missed primary endpoint – the 31% of patients who did not adhere to PERT were about four times more likely to lose weight, compared with patients who adhered to PERT (hazard ratio, 4.1, 95% confidence interval, 2.1-7.6), even after possible confounders were controlled for.

In the per-protocol analysis, PERT was associated with an average gain of 1.09 kg in body weight, whereas placebo was associated with an average loss of 2.28 kg (P < .001 for difference between groups). Therefore, clinicians should consider “active education and monitoring” to increase adherence to PERT among patients with pancreatic enzyme insufficiency after pancreatoduodenectomy, wrote Hongbeom Kim of Seoul (South Korea) National University College of Medicine. The findings were published in Clinical Gastroenterology and Hepatology.

Nutritional deficiencies, steatorrhea, bowel issues, and flatulence undermine health and quality of life among these patients, the researchers noted. Although guidelines recommend PERT, doses and indications are not standardized because of insufficient data. To date, most studies have focused on PERT for patients with pancreatic enzyme insufficiency attributable to chronic pancreatitis, not surgery.

This double-blind trial enrolled 304 patients who underwent pancreatoduodenectomy for benign or malignant indications at seven tertiary referral hospitals in South Korea. All patients had a preoperative or postoperative fecal elastase level of 200 mg/g or less. They were randomly assigned to receive thrice-daily capsules with meals consisting of PERT (40,000 FIP lipase, 25,000 FIP amylase, and 1,500 FIP protease) or placebo.

To assess adherence, patients filled out medication diaries and the investigators counted the number of capsules left at 3-month follow-up. “Patients who took more than two-thirds of the total [PERT or placebo] dose without taking other digestive enzymes were considered to have completed the protocol,” the researchers wrote.

In all, 67 patients were excluded from the intention-to-treat analysis because they withdrew consent or were lost to follow-up. Among the remaining 237 patients, PERT did not significantly outperform placebo for the primary endpoint of body weight or for secondary endpoints, including nutritional status and quality of life. The study was powered to assess the intention-to-treat population and hence missed its primary endpoint.

The per-protocol analysis included 71 patients who adhered to PERT and 93 who adhered to placebo. Among these patients, adherence to PERT versus placebo was associated with a 3.37-kg absolute mean increase in body weight (P < .001). [The use] of PERT [also significantly] increased prealbumin and transferrin levels, reflecting short-term nutritional status,” the researchers wrote. “However, no difference in quality of life was observed.”

Subgroup analyses also favored PERT in the per-protocol analysis but not the intention-to-treat analysis, the researchers said. The use of PERT did not significantly affect the frequency of defecation in either the intention-to-treat or the per-protocol analysis.

Korea Pharmbio and the Ministry of Science and ICT provided funding. The researchers reported having no conflicts of interest.

SOURCE: Kim H et al. Clin Gastroenterol Hepatol. 2019 Sep 12. doi: 10.1016/j.cgh.2019.08.061.

Pancreatic enzyme replacement therapy (PERT) did not significantly alter body weight after pancreatoduodenectomy in the intention-to-treat analysis of a randomized, placebo-controlled trial.

After 3 months of treatment, the PERT group lost an average of 0.68 kg, and the placebo group lost an average of 1.19 kg (P = .302). Low adherence might explain this missed primary endpoint – the 31% of patients who did not adhere to PERT were about four times more likely to lose weight, compared with patients who adhered to PERT (hazard ratio, 4.1, 95% confidence interval, 2.1-7.6), even after possible confounders were controlled for.

In the per-protocol analysis, PERT was associated with an average gain of 1.09 kg in body weight, whereas placebo was associated with an average loss of 2.28 kg (P < .001 for difference between groups). Therefore, clinicians should consider “active education and monitoring” to increase adherence to PERT among patients with pancreatic enzyme insufficiency after pancreatoduodenectomy, wrote Hongbeom Kim of Seoul (South Korea) National University College of Medicine. The findings were published in Clinical Gastroenterology and Hepatology.

Nutritional deficiencies, steatorrhea, bowel issues, and flatulence undermine health and quality of life among these patients, the researchers noted. Although guidelines recommend PERT, doses and indications are not standardized because of insufficient data. To date, most studies have focused on PERT for patients with pancreatic enzyme insufficiency attributable to chronic pancreatitis, not surgery.

This double-blind trial enrolled 304 patients who underwent pancreatoduodenectomy for benign or malignant indications at seven tertiary referral hospitals in South Korea. All patients had a preoperative or postoperative fecal elastase level of 200 mg/g or less. They were randomly assigned to receive thrice-daily capsules with meals consisting of PERT (40,000 FIP lipase, 25,000 FIP amylase, and 1,500 FIP protease) or placebo.

To assess adherence, patients filled out medication diaries and the investigators counted the number of capsules left at 3-month follow-up. “Patients who took more than two-thirds of the total [PERT or placebo] dose without taking other digestive enzymes were considered to have completed the protocol,” the researchers wrote.

In all, 67 patients were excluded from the intention-to-treat analysis because they withdrew consent or were lost to follow-up. Among the remaining 237 patients, PERT did not significantly outperform placebo for the primary endpoint of body weight or for secondary endpoints, including nutritional status and quality of life. The study was powered to assess the intention-to-treat population and hence missed its primary endpoint.

The per-protocol analysis included 71 patients who adhered to PERT and 93 who adhered to placebo. Among these patients, adherence to PERT versus placebo was associated with a 3.37-kg absolute mean increase in body weight (P < .001). [The use] of PERT [also significantly] increased prealbumin and transferrin levels, reflecting short-term nutritional status,” the researchers wrote. “However, no difference in quality of life was observed.”

Subgroup analyses also favored PERT in the per-protocol analysis but not the intention-to-treat analysis, the researchers said. The use of PERT did not significantly affect the frequency of defecation in either the intention-to-treat or the per-protocol analysis.

Korea Pharmbio and the Ministry of Science and ICT provided funding. The researchers reported having no conflicts of interest.

SOURCE: Kim H et al. Clin Gastroenterol Hepatol. 2019 Sep 12. doi: 10.1016/j.cgh.2019.08.061.

Pancreatic enzyme replacement therapy (PERT) did not significantly alter body weight after pancreatoduodenectomy in the intention-to-treat analysis of a randomized, placebo-controlled trial.

After 3 months of treatment, the PERT group lost an average of 0.68 kg, and the placebo group lost an average of 1.19 kg (P = .302). Low adherence might explain this missed primary endpoint – the 31% of patients who did not adhere to PERT were about four times more likely to lose weight, compared with patients who adhered to PERT (hazard ratio, 4.1, 95% confidence interval, 2.1-7.6), even after possible confounders were controlled for.

In the per-protocol analysis, PERT was associated with an average gain of 1.09 kg in body weight, whereas placebo was associated with an average loss of 2.28 kg (P < .001 for difference between groups). Therefore, clinicians should consider “active education and monitoring” to increase adherence to PERT among patients with pancreatic enzyme insufficiency after pancreatoduodenectomy, wrote Hongbeom Kim of Seoul (South Korea) National University College of Medicine. The findings were published in Clinical Gastroenterology and Hepatology.

Nutritional deficiencies, steatorrhea, bowel issues, and flatulence undermine health and quality of life among these patients, the researchers noted. Although guidelines recommend PERT, doses and indications are not standardized because of insufficient data. To date, most studies have focused on PERT for patients with pancreatic enzyme insufficiency attributable to chronic pancreatitis, not surgery.

This double-blind trial enrolled 304 patients who underwent pancreatoduodenectomy for benign or malignant indications at seven tertiary referral hospitals in South Korea. All patients had a preoperative or postoperative fecal elastase level of 200 mg/g or less. They were randomly assigned to receive thrice-daily capsules with meals consisting of PERT (40,000 FIP lipase, 25,000 FIP amylase, and 1,500 FIP protease) or placebo.

To assess adherence, patients filled out medication diaries and the investigators counted the number of capsules left at 3-month follow-up. “Patients who took more than two-thirds of the total [PERT or placebo] dose without taking other digestive enzymes were considered to have completed the protocol,” the researchers wrote.

In all, 67 patients were excluded from the intention-to-treat analysis because they withdrew consent or were lost to follow-up. Among the remaining 237 patients, PERT did not significantly outperform placebo for the primary endpoint of body weight or for secondary endpoints, including nutritional status and quality of life. The study was powered to assess the intention-to-treat population and hence missed its primary endpoint.

The per-protocol analysis included 71 patients who adhered to PERT and 93 who adhered to placebo. Among these patients, adherence to PERT versus placebo was associated with a 3.37-kg absolute mean increase in body weight (P < .001). [The use] of PERT [also significantly] increased prealbumin and transferrin levels, reflecting short-term nutritional status,” the researchers wrote. “However, no difference in quality of life was observed.”

Subgroup analyses also favored PERT in the per-protocol analysis but not the intention-to-treat analysis, the researchers said. The use of PERT did not significantly affect the frequency of defecation in either the intention-to-treat or the per-protocol analysis.

Korea Pharmbio and the Ministry of Science and ICT provided funding. The researchers reported having no conflicts of interest.

SOURCE: Kim H et al. Clin Gastroenterol Hepatol. 2019 Sep 12. doi: 10.1016/j.cgh.2019.08.061.

Molecularly guided treatments may extend survival by more than a year for patients with pancreatic cancer who have actionable molecular alterations, according to a retrospective analysis of almost 2,000 patients in the Know Your Tumor registry.

While patients with actionable alterations remain in the minority, experts suggest the study’s results provide a ray of hope for treating a cancer that has historically been associated with a poor prognosis and disappointing clinical trials.

Patients with actionable molecular alterations who received matched therapies had a median overall survival of 2.58 years, compared with 1.51 years for those who received unmatched therapies, reported lead author Michael J. Pishvaian, MD, PhD, of MD Anderson Cancer Center in Houston, and colleagues.

“Our study provides strong rationale that tumor-based molecular profiling for patients with pancreatic cancer should be routinely performed and encourages prospective clinical trials based on this or similar platforms,” the investigators wrote in Lancet Oncology.

In an accompanying comment, Jörg Kleeff, MD, and Christoph W. Michalski, MD, of Martin-Luther University Halle-Wittenberg in Germany, supported this conclusion, calling the study “an encouraging starting point for a structured investigation of molecularly matched therapies.”

The authors also highlighted the untapped potential the trial uncovered, noting that only 4% of patients received a molecularly matched therapy, even though one-quarter had actionable alterations.

“These findings are important in that they define an estimation of the current number of potentially actionable targets and in that they provide a – rather disappointing – real-world assessment of the number of patients who actually received molecularly targeted treatment,” Dr. Kleeff and Dr. Michalski wrote.

They went on to describe a list of unanswered questions in the field, ranging from ethical dilemmas that may be encountered when choosing between targeted trials and chemotherapy for patients with targetable alterations, to more tangible subjects, such as genome sequencing techniques and therapeutic timing.

Their comment and the related study were published simultaneously with a series of pancreatic cancer articles in Lancet journals, which includes:

• A review outlining current and emerging therapies (Lancet Oncol. 2020 Mar;21[3]:e135-e145).
• A review of information on the metastatic cascade (EBioMedicine. 2020 Feb 28:102662. doi: 10.1016/j.ebiom.2020.102662).
• A review of disease biology (EBioMedicine. 2020 Feb 28:102655. doi: 10.1016/j.ebiom.2020.102655).
• A review of early detection strategies (Lancet Gastroenterol Hepatol. 2020 Mar 2. pii: S2468-1253[19]30416-9).

According to the authors of the therapeutic review, treatments for pancreatic cancer have “a bright future.”

“There is more optimism now than ever before that advances will be made by combining chemotherapy more effectively with agents that target the unique features of pancreatic ductal adenocarcinoma tumors,” the authors wrote. “The next 5-10 years should deliver major improvements in outcomes through the use of novel agents that specifically target pathological signaling pathways and genetic alterations.”

In an interview, Dana B. Cardin, MD, of the Vanderbilt-Ingram Cancer Center in Nashville, Tenn., shared this favorable outlook, which she said is particularly needed for a condition that has generally been left behind by the new era of personalized oncology treatments.

“There’s been a lot of frustration on the part of patients and doctors and everyone in the research community that there have been a lot of other tumor types [in which] learning about genetic changes in cancer cells has really revolutionized how patients are being treated,” Dr. Cardin said. “That is something that has really been elusive in pancreas cancer.”

The retrospective study by Dr. Pishvaian and colleagues serves as proof-of-concept by showing that large-scale genomic testing can also identify personalized treatments for patients with pancreatic cancer, Dr. Cardin said.

“When you do find them, even when it’s a small percentage of patients that may have actionable mutations, it really can make a huge difference in the outcomes for those patients,” she said. “We have to get rid of this sense of futility. If you’re not trying to look for those things, then you’re not ever going to find them.”

Regardless of whether a personalized treatment is available for a particular patient, Dr. Cardin emphasized the importance of a positive and active clinical mindset, as data suggest that existing supportive strategies can have a significant impact on patient health.

“We can make a difference for these patients,” Dr. Cardin said, “but we’re only going to make a difference if we try.”

Dr. Cardin, a National Comprehensive Cancer Network panelist for pancreatic cancer, went on to explain how outcomes in the control arm of pancreatic cancer clinical trials have been improving over the past decade, even though the standard control drug, gemcitabine, has stayed the same.

“It doesn’t mean that gemcitabine is better than it used to be,” Dr. Cardin said. “It probably means that we’re treating more patients, and we’re also doing a better job of supporting those patients.” She identified growth factors, nutritional support, and enzyme supplements as key ancillary treatments for those who need them.

Dr. Pishvaian and colleagues’ study was funded by Pancreatic Cancer Action Network and Perthera. The investigators disclosed relationships with Perthera and other companies. Dr. Kleeff, Dr. Michalski, and Dr. Cardin declared no conflicts of interest.

SOURCES: Pishvaian MJ et al. Lancet Oncol. 2020 Mar 2. doi: 10.1016/S1470-2045(20)30074-7; Kleeff J et al. Lancet Oncol. 2020 Mar 2. doi: 10.1016/S1470-2045(20)30148-0; Christenson ES et al. Lancet Oncol. 2020 Mar 2. doi: 10.1016/S1470-2045(19)30795-8.

Molecularly guided treatments may extend survival by more than a year for patients with pancreatic cancer who have actionable molecular alterations, according to a retrospective analysis of almost 2,000 patients in the Know Your Tumor registry.

While patients with actionable alterations remain in the minority, experts suggest the study’s results provide a ray of hope for treating a cancer that has historically been associated with a poor prognosis and disappointing clinical trials.

Patients with actionable molecular alterations who received matched therapies had a median overall survival of 2.58 years, compared with 1.51 years for those who received unmatched therapies, reported lead author Michael J. Pishvaian, MD, PhD, of MD Anderson Cancer Center in Houston, and colleagues.

“Our study provides strong rationale that tumor-based molecular profiling for patients with pancreatic cancer should be routinely performed and encourages prospective clinical trials based on this or similar platforms,” the investigators wrote in Lancet Oncology.

In an accompanying comment, Jörg Kleeff, MD, and Christoph W. Michalski, MD, of Martin-Luther University Halle-Wittenberg in Germany, supported this conclusion, calling the study “an encouraging starting point for a structured investigation of molecularly matched therapies.”

The authors also highlighted the untapped potential the trial uncovered, noting that only 4% of patients received a molecularly matched therapy, even though one-quarter had actionable alterations.

“These findings are important in that they define an estimation of the current number of potentially actionable targets and in that they provide a – rather disappointing – real-world assessment of the number of patients who actually received molecularly targeted treatment,” Dr. Kleeff and Dr. Michalski wrote.

They went on to describe a list of unanswered questions in the field, ranging from ethical dilemmas that may be encountered when choosing between targeted trials and chemotherapy for patients with targetable alterations, to more tangible subjects, such as genome sequencing techniques and therapeutic timing.

Their comment and the related study were published simultaneously with a series of pancreatic cancer articles in Lancet journals, which includes:

• A review outlining current and emerging therapies (Lancet Oncol. 2020 Mar;21[3]:e135-e145).
• A review of information on the metastatic cascade (EBioMedicine. 2020 Feb 28:102662. doi: 10.1016/j.ebiom.2020.102662).
• A review of disease biology (EBioMedicine. 2020 Feb 28:102655. doi: 10.1016/j.ebiom.2020.102655).
• A review of early detection strategies (Lancet Gastroenterol Hepatol. 2020 Mar 2. pii: S2468-1253[19]30416-9).

According to the authors of the therapeutic review, treatments for pancreatic cancer have “a bright future.”

“There is more optimism now than ever before that advances will be made by combining chemotherapy more effectively with agents that target the unique features of pancreatic ductal adenocarcinoma tumors,” the authors wrote. “The next 5-10 years should deliver major improvements in outcomes through the use of novel agents that specifically target pathological signaling pathways and genetic alterations.”

In an interview, Dana B. Cardin, MD, of the Vanderbilt-Ingram Cancer Center in Nashville, Tenn., shared this favorable outlook, which she said is particularly needed for a condition that has generally been left behind by the new era of personalized oncology treatments.

“There’s been a lot of frustration on the part of patients and doctors and everyone in the research community that there have been a lot of other tumor types [in which] learning about genetic changes in cancer cells has really revolutionized how patients are being treated,” Dr. Cardin said. “That is something that has really been elusive in pancreas cancer.”

The retrospective study by Dr. Pishvaian and colleagues serves as proof-of-concept by showing that large-scale genomic testing can also identify personalized treatments for patients with pancreatic cancer, Dr. Cardin said.

“When you do find them, even when it’s a small percentage of patients that may have actionable mutations, it really can make a huge difference in the outcomes for those patients,” she said. “We have to get rid of this sense of futility. If you’re not trying to look for those things, then you’re not ever going to find them.”

Regardless of whether a personalized treatment is available for a particular patient, Dr. Cardin emphasized the importance of a positive and active clinical mindset, as data suggest that existing supportive strategies can have a significant impact on patient health.

“We can make a difference for these patients,” Dr. Cardin said, “but we’re only going to make a difference if we try.”

Dr. Cardin, a National Comprehensive Cancer Network panelist for pancreatic cancer, went on to explain how outcomes in the control arm of pancreatic cancer clinical trials have been improving over the past decade, even though the standard control drug, gemcitabine, has stayed the same.

“It doesn’t mean that gemcitabine is better than it used to be,” Dr. Cardin said. “It probably means that we’re treating more patients, and we’re also doing a better job of supporting those patients.” She identified growth factors, nutritional support, and enzyme supplements as key ancillary treatments for those who need them.

Dr. Pishvaian and colleagues’ study was funded by Pancreatic Cancer Action Network and Perthera. The investigators disclosed relationships with Perthera and other companies. Dr. Kleeff, Dr. Michalski, and Dr. Cardin declared no conflicts of interest.

SOURCES: Pishvaian MJ et al. Lancet Oncol. 2020 Mar 2. doi: 10.1016/S1470-2045(20)30074-7; Kleeff J et al. Lancet Oncol. 2020 Mar 2. doi: 10.1016/S1470-2045(20)30148-0; Christenson ES et al. Lancet Oncol. 2020 Mar 2. doi: 10.1016/S1470-2045(19)30795-8.

Molecularly guided treatments may extend survival by more than a year for patients with pancreatic cancer who have actionable molecular alterations, according to a retrospective analysis of almost 2,000 patients in the Know Your Tumor registry.

While patients with actionable alterations remain in the minority, experts suggest the study’s results provide a ray of hope for treating a cancer that has historically been associated with a poor prognosis and disappointing clinical trials.

Patients with actionable molecular alterations who received matched therapies had a median overall survival of 2.58 years, compared with 1.51 years for those who received unmatched therapies, reported lead author Michael J. Pishvaian, MD, PhD, of MD Anderson Cancer Center in Houston, and colleagues.

“Our study provides strong rationale that tumor-based molecular profiling for patients with pancreatic cancer should be routinely performed and encourages prospective clinical trials based on this or similar platforms,” the investigators wrote in Lancet Oncology.

In an accompanying comment, Jörg Kleeff, MD, and Christoph W. Michalski, MD, of Martin-Luther University Halle-Wittenberg in Germany, supported this conclusion, calling the study “an encouraging starting point for a structured investigation of molecularly matched therapies.”

The authors also highlighted the untapped potential the trial uncovered, noting that only 4% of patients received a molecularly matched therapy, even though one-quarter had actionable alterations.

“These findings are important in that they define an estimation of the current number of potentially actionable targets and in that they provide a – rather disappointing – real-world assessment of the number of patients who actually received molecularly targeted treatment,” Dr. Kleeff and Dr. Michalski wrote.

They went on to describe a list of unanswered questions in the field, ranging from ethical dilemmas that may be encountered when choosing between targeted trials and chemotherapy for patients with targetable alterations, to more tangible subjects, such as genome sequencing techniques and therapeutic timing.

Their comment and the related study were published simultaneously with a series of pancreatic cancer articles in Lancet journals, which includes:

• A review outlining current and emerging therapies (Lancet Oncol. 2020 Mar;21[3]:e135-e145).
• A review of information on the metastatic cascade (EBioMedicine. 2020 Feb 28:102662. doi: 10.1016/j.ebiom.2020.102662).
• A review of disease biology (EBioMedicine. 2020 Feb 28:102655. doi: 10.1016/j.ebiom.2020.102655).
• A review of early detection strategies (Lancet Gastroenterol Hepatol. 2020 Mar 2. pii: S2468-1253[19]30416-9).

According to the authors of the therapeutic review, treatments for pancreatic cancer have “a bright future.”

“There is more optimism now than ever before that advances will be made by combining chemotherapy more effectively with agents that target the unique features of pancreatic ductal adenocarcinoma tumors,” the authors wrote. “The next 5-10 years should deliver major improvements in outcomes through the use of novel agents that specifically target pathological signaling pathways and genetic alterations.”

In an interview, Dana B. Cardin, MD, of the Vanderbilt-Ingram Cancer Center in Nashville, Tenn., shared this favorable outlook, which she said is particularly needed for a condition that has generally been left behind by the new era of personalized oncology treatments.

“There’s been a lot of frustration on the part of patients and doctors and everyone in the research community that there have been a lot of other tumor types [in which] learning about genetic changes in cancer cells has really revolutionized how patients are being treated,” Dr. Cardin said. “That is something that has really been elusive in pancreas cancer.”

The retrospective study by Dr. Pishvaian and colleagues serves as proof-of-concept by showing that large-scale genomic testing can also identify personalized treatments for patients with pancreatic cancer, Dr. Cardin said.

“When you do find them, even when it’s a small percentage of patients that may have actionable mutations, it really can make a huge difference in the outcomes for those patients,” she said. “We have to get rid of this sense of futility. If you’re not trying to look for those things, then you’re not ever going to find them.”

Regardless of whether a personalized treatment is available for a particular patient, Dr. Cardin emphasized the importance of a positive and active clinical mindset, as data suggest that existing supportive strategies can have a significant impact on patient health.

“We can make a difference for these patients,” Dr. Cardin said, “but we’re only going to make a difference if we try.”

Dr. Cardin, a National Comprehensive Cancer Network panelist for pancreatic cancer, went on to explain how outcomes in the control arm of pancreatic cancer clinical trials have been improving over the past decade, even though the standard control drug, gemcitabine, has stayed the same.

“It doesn’t mean that gemcitabine is better than it used to be,” Dr. Cardin said. “It probably means that we’re treating more patients, and we’re also doing a better job of supporting those patients.” She identified growth factors, nutritional support, and enzyme supplements as key ancillary treatments for those who need them.

Dr. Pishvaian and colleagues’ study was funded by Pancreatic Cancer Action Network and Perthera. The investigators disclosed relationships with Perthera and other companies. Dr. Kleeff, Dr. Michalski, and Dr. Cardin declared no conflicts of interest.

SOURCES: Pishvaian MJ et al. Lancet Oncol. 2020 Mar 2. doi: 10.1016/S1470-2045(20)30074-7; Kleeff J et al. Lancet Oncol. 2020 Mar 2. doi: 10.1016/S1470-2045(20)30148-0; Christenson ES et al. Lancet Oncol. 2020 Mar 2. doi: 10.1016/S1470-2045(19)30795-8.

Etiologies, demographics, management, and outcomes vary widely among patients with acute pancreatitis around the world, according to an analysis of data from the prospective, international APPRENTICE patient registry.

In some cases – particularly in regard to therapeutic interventions – the differences are “strikingly divergent” and demonstrate a “lag behind current evidence,” Bassem Matta, MD, of the University of Pittsburgh Medical Center, and colleagues reported in Clinical Gastroenterology and Hepatology.

Findings of a disproportionately higher rate of opioid prescribing during hospitalization and at discharge at North American sites are especially alarming, the investigators said.
 

Demographics and etiologies

The most common etiologies among 1,612 patients in the registry, which collects data from individuals with acute pancreatitis at six centers in Europe, three centers in India, five centers in Latin America, and eight centers in North America, were biliary (45%) and alcoholic (21%), and severity was mild in 65% of patients, moderate in 23%, and severe in 12%, they noted.

The predominant etiology in Latin America was biliary (78%), whereas the predominant etiology in India was alcoholic (45%).

The mean age of patients in Europe was 58 years, which is older than the mean age of 46 years for all regions represented in the registry, and comorbid conditions were also more common among patients in Europe (73% vs. 50% overall), the investigators found.

In addition to age differences, significant geographic differences were seen with respect to sex, ethnicity, and race distributions. Patients from Indian sites, for example, were mostly men (75%), were younger in age (median, 39 years), and were more likely to have alcoholic etiology (45% vs. 14% in the other areas). Most of the Latin American patients were women (67%), were young (median, 43 years), and most often had biliary etiology (78% vs. 37% elsewhere).

In contrast, European and North American subjects had a relatively equal sex distribution and an overall older age (median, 58 years).

“Observed differences in etiology and demographics likely reflect a tight interconnection between age, sex, and etiology,” the investigators wrote.
 

Management

Analgesic utilization was “markedly variable” across the world, they said, explaining that nonsteroidal anti-inflammatory drugs (NSAIDs) were the mainstay of pain management in Europe (68%), whereas Indian sites used tramadol in 91% of patients.

Latin American centers frequently used opioids (59%), NSAIDs (48%), and tramadol (34%).

However, opioid analgesics were used in 93% of patients in North America, compared with 27% of patients in the other regions, and 64% vs. 2.7% of patients in North American vs. the other regions were discharged on opioid analgesics.

This is of particular concern in light of a meta-analysis showing no difference in efficacy between opioids and nonsteroidal anti-inflammatory drugs for pain control in acute pancreatitis, the investigators said, noting that “[i]t is not entirely clear why such divergences exist between North American centers compared to the rest of the world.

“Notably, no clear statements are included in the current societal guidelines addressing optimal strategies for analgesia in [acute pancreatitis],” they added.

Also of note, the rate of endoscopic retrograde cholangiopancreatography (ERCP) – which guidelines based on strong evidence say should be limited to urgent cases among biliary acute pancreatitis patients with suspected cholangitis or biliary obstruction – was much higher at North American sites (44.7% vs. 21.9% overall) and post-ERCP pancreatitis was significantly more common at North American sites (19% vs. 2.8% in the other geographic areas), they said.

However, these differences were mostly driven by two North American sites, which classified 50 out of 90 and 22 out of 62 enrolled patients, respectively, as having post-ERCP pancreatitis.

Further, cholecystectomies were performed at the time of hospital admission in 60% of patients in Latin America, compared with 15% overall.

Another notable difference in management related to intravenous fluid use; similar amounts were administered during the first 24 hours in India and Latin America (3-3.2 liters), but in Europe the average was 2.5 liters, and while lactated Ringers and normal saline were the main types of fluid used, lactated Ringers was the dominant type used in India (92%), but was rarely used in Latin America (7%).
 

Outcomes

The overall median length of stay was 8 days, and overall mortality during hospitalization was 2.8%. In patients with mild disease, the shortest lengths of stay were in North America (4 vs. 7 days in other regions), and severe disease was more common in India (23% vs. 9% elsewhere).

Intensive care unit admissions were highest at Indian centers, and in-hospital mortality was highest in Europe (5.7%), compared with 3.3% in India, 2.3% in Latin America, and 0.6% in North America, they said.

Mortality during the initial hospital stay among patients with severe acute pancreatitis was 44% in Europe, compared with 15% in the other three regions.

Multivariable regression analyses adjusting for potential confounders such as age, sex, body mass index, Charlson score, etiology, and transfer status showed that the odds of severe acute pancreatitis were 11.2 times higher in Europe, 7 times higher in India, and 5.6 times higher in Latin America, compared with North America.

The odds ratios for mortality during hospitalization among patients with severe disease were 10.4 in Europe, 4.2 in India, and 8.3 in Latin America, compared with North America.
 

Implications of the findings

Around the world, acute pancreatitis is a leading cause of gastrointestinal-related hospital admissions, and incidence is reportedly increasing in the United States and Europe, the investigators said, noting that about 20% of patients develop severe disease with relatively high morbidity and mortality.

Multiple advances in management have emerged over the last decade, but it is unclear whether those recent advances have gained traction worldwide, they added.

The APPRENTICE registry was created as a response to the lack of prospective, multinational data and the current study aimed to assess the geographic differences in patient characteristics, management, and outcomes across four geographic areas.

The findings, which represent “a bird’s eye view” of regional variation, underscore a need for “adequately powered, multicenter, randomized controlled trials comparing the efficacy of different fluid resuscitation protocols” in acute pancreatitis patients, the investigators said.

Further, “the interventions specific to each region are in certain aspects strikingly divergent, and in many occasions lag behind current evidence,” they wrote, noting the largely variable length-of-stay outcomes and mortality rates.

“In addition to depicting key features of [acute pancreatitis], the results from this study may serve as a reference guide for designing future clinical trials,” they concluded.

The authors reported having no disclosures.

sworcester@mdedge.com

SOURCE: Matt B et al. Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2019.11.017.

Share AGA GI Patient Center education to help your patients understand acute versus chronic pancreatitis, testing, treatment, and potential complications at https://www.gastro.org/practice-guidance/gi-patient-center/topic/pancreatitis. 

Etiologies, demographics, management, and outcomes vary widely among patients with acute pancreatitis around the world, according to an analysis of data from the prospective, international APPRENTICE patient registry.

In some cases – particularly in regard to therapeutic interventions – the differences are “strikingly divergent” and demonstrate a “lag behind current evidence,” Bassem Matta, MD, of the University of Pittsburgh Medical Center, and colleagues reported in Clinical Gastroenterology and Hepatology.

Findings of a disproportionately higher rate of opioid prescribing during hospitalization and at discharge at North American sites are especially alarming, the investigators said.
 

Demographics and etiologies

The most common etiologies among 1,612 patients in the registry, which collects data from individuals with acute pancreatitis at six centers in Europe, three centers in India, five centers in Latin America, and eight centers in North America, were biliary (45%) and alcoholic (21%), and severity was mild in 65% of patients, moderate in 23%, and severe in 12%, they noted.

The predominant etiology in Latin America was biliary (78%), whereas the predominant etiology in India was alcoholic (45%).

The mean age of patients in Europe was 58 years, which is older than the mean age of 46 years for all regions represented in the registry, and comorbid conditions were also more common among patients in Europe (73% vs. 50% overall), the investigators found.

In addition to age differences, significant geographic differences were seen with respect to sex, ethnicity, and race distributions. Patients from Indian sites, for example, were mostly men (75%), were younger in age (median, 39 years), and were more likely to have alcoholic etiology (45% vs. 14% in the other areas). Most of the Latin American patients were women (67%), were young (median, 43 years), and most often had biliary etiology (78% vs. 37% elsewhere).

In contrast, European and North American subjects had a relatively equal sex distribution and an overall older age (median, 58 years).

“Observed differences in etiology and demographics likely reflect a tight interconnection between age, sex, and etiology,” the investigators wrote.
 

Management

Analgesic utilization was “markedly variable” across the world, they said, explaining that nonsteroidal anti-inflammatory drugs (NSAIDs) were the mainstay of pain management in Europe (68%), whereas Indian sites used tramadol in 91% of patients.

Latin American centers frequently used opioids (59%), NSAIDs (48%), and tramadol (34%).

However, opioid analgesics were used in 93% of patients in North America, compared with 27% of patients in the other regions, and 64% vs. 2.7% of patients in North American vs. the other regions were discharged on opioid analgesics.

This is of particular concern in light of a meta-analysis showing no difference in efficacy between opioids and nonsteroidal anti-inflammatory drugs for pain control in acute pancreatitis, the investigators said, noting that “[i]t is not entirely clear why such divergences exist between North American centers compared to the rest of the world.

“Notably, no clear statements are included in the current societal guidelines addressing optimal strategies for analgesia in [acute pancreatitis],” they added.

Also of note, the rate of endoscopic retrograde cholangiopancreatography (ERCP) – which guidelines based on strong evidence say should be limited to urgent cases among biliary acute pancreatitis patients with suspected cholangitis or biliary obstruction – was much higher at North American sites (44.7% vs. 21.9% overall) and post-ERCP pancreatitis was significantly more common at North American sites (19% vs. 2.8% in the other geographic areas), they said.

However, these differences were mostly driven by two North American sites, which classified 50 out of 90 and 22 out of 62 enrolled patients, respectively, as having post-ERCP pancreatitis.

Further, cholecystectomies were performed at the time of hospital admission in 60% of patients in Latin America, compared with 15% overall.

Another notable difference in management related to intravenous fluid use; similar amounts were administered during the first 24 hours in India and Latin America (3-3.2 liters), but in Europe the average was 2.5 liters, and while lactated Ringers and normal saline were the main types of fluid used, lactated Ringers was the dominant type used in India (92%), but was rarely used in Latin America (7%).
 

Outcomes

The overall median length of stay was 8 days, and overall mortality during hospitalization was 2.8%. In patients with mild disease, the shortest lengths of stay were in North America (4 vs. 7 days in other regions), and severe disease was more common in India (23% vs. 9% elsewhere).

Intensive care unit admissions were highest at Indian centers, and in-hospital mortality was highest in Europe (5.7%), compared with 3.3% in India, 2.3% in Latin America, and 0.6% in North America, they said.

Mortality during the initial hospital stay among patients with severe acute pancreatitis was 44% in Europe, compared with 15% in the other three regions.

Multivariable regression analyses adjusting for potential confounders such as age, sex, body mass index, Charlson score, etiology, and transfer status showed that the odds of severe acute pancreatitis were 11.2 times higher in Europe, 7 times higher in India, and 5.6 times higher in Latin America, compared with North America.

The odds ratios for mortality during hospitalization among patients with severe disease were 10.4 in Europe, 4.2 in India, and 8.3 in Latin America, compared with North America.
 

Implications of the findings

Around the world, acute pancreatitis is a leading cause of gastrointestinal-related hospital admissions, and incidence is reportedly increasing in the United States and Europe, the investigators said, noting that about 20% of patients develop severe disease with relatively high morbidity and mortality.

Multiple advances in management have emerged over the last decade, but it is unclear whether those recent advances have gained traction worldwide, they added.

The APPRENTICE registry was created as a response to the lack of prospective, multinational data and the current study aimed to assess the geographic differences in patient characteristics, management, and outcomes across four geographic areas.

The findings, which represent “a bird’s eye view” of regional variation, underscore a need for “adequately powered, multicenter, randomized controlled trials comparing the efficacy of different fluid resuscitation protocols” in acute pancreatitis patients, the investigators said.

Further, “the interventions specific to each region are in certain aspects strikingly divergent, and in many occasions lag behind current evidence,” they wrote, noting the largely variable length-of-stay outcomes and mortality rates.

“In addition to depicting key features of [acute pancreatitis], the results from this study may serve as a reference guide for designing future clinical trials,” they concluded.

The authors reported having no disclosures.

sworcester@mdedge.com

SOURCE: Matt B et al. Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2019.11.017.

Share AGA GI Patient Center education to help your patients understand acute versus chronic pancreatitis, testing, treatment, and potential complications at https://www.gastro.org/practice-guidance/gi-patient-center/topic/pancreatitis. 

Etiologies, demographics, management, and outcomes vary widely among patients with acute pancreatitis around the world, according to an analysis of data from the prospective, international APPRENTICE patient registry.

In some cases – particularly in regard to therapeutic interventions – the differences are “strikingly divergent” and demonstrate a “lag behind current evidence,” Bassem Matta, MD, of the University of Pittsburgh Medical Center, and colleagues reported in Clinical Gastroenterology and Hepatology.

Findings of a disproportionately higher rate of opioid prescribing during hospitalization and at discharge at North American sites are especially alarming, the investigators said.
 

Demographics and etiologies

The most common etiologies among 1,612 patients in the registry, which collects data from individuals with acute pancreatitis at six centers in Europe, three centers in India, five centers in Latin America, and eight centers in North America, were biliary (45%) and alcoholic (21%), and severity was mild in 65% of patients, moderate in 23%, and severe in 12%, they noted.

The predominant etiology in Latin America was biliary (78%), whereas the predominant etiology in India was alcoholic (45%).

The mean age of patients in Europe was 58 years, which is older than the mean age of 46 years for all regions represented in the registry, and comorbid conditions were also more common among patients in Europe (73% vs. 50% overall), the investigators found.

In addition to age differences, significant geographic differences were seen with respect to sex, ethnicity, and race distributions. Patients from Indian sites, for example, were mostly men (75%), were younger in age (median, 39 years), and were more likely to have alcoholic etiology (45% vs. 14% in the other areas). Most of the Latin American patients were women (67%), were young (median, 43 years), and most often had biliary etiology (78% vs. 37% elsewhere).

In contrast, European and North American subjects had a relatively equal sex distribution and an overall older age (median, 58 years).

“Observed differences in etiology and demographics likely reflect a tight interconnection between age, sex, and etiology,” the investigators wrote.
 

Management

Analgesic utilization was “markedly variable” across the world, they said, explaining that nonsteroidal anti-inflammatory drugs (NSAIDs) were the mainstay of pain management in Europe (68%), whereas Indian sites used tramadol in 91% of patients.

Latin American centers frequently used opioids (59%), NSAIDs (48%), and tramadol (34%).

However, opioid analgesics were used in 93% of patients in North America, compared with 27% of patients in the other regions, and 64% vs. 2.7% of patients in North American vs. the other regions were discharged on opioid analgesics.

This is of particular concern in light of a meta-analysis showing no difference in efficacy between opioids and nonsteroidal anti-inflammatory drugs for pain control in acute pancreatitis, the investigators said, noting that “[i]t is not entirely clear why such divergences exist between North American centers compared to the rest of the world.

“Notably, no clear statements are included in the current societal guidelines addressing optimal strategies for analgesia in [acute pancreatitis],” they added.

Also of note, the rate of endoscopic retrograde cholangiopancreatography (ERCP) – which guidelines based on strong evidence say should be limited to urgent cases among biliary acute pancreatitis patients with suspected cholangitis or biliary obstruction – was much higher at North American sites (44.7% vs. 21.9% overall) and post-ERCP pancreatitis was significantly more common at North American sites (19% vs. 2.8% in the other geographic areas), they said.

However, these differences were mostly driven by two North American sites, which classified 50 out of 90 and 22 out of 62 enrolled patients, respectively, as having post-ERCP pancreatitis.

Further, cholecystectomies were performed at the time of hospital admission in 60% of patients in Latin America, compared with 15% overall.

Another notable difference in management related to intravenous fluid use; similar amounts were administered during the first 24 hours in India and Latin America (3-3.2 liters), but in Europe the average was 2.5 liters, and while lactated Ringers and normal saline were the main types of fluid used, lactated Ringers was the dominant type used in India (92%), but was rarely used in Latin America (7%).
 

Outcomes

The overall median length of stay was 8 days, and overall mortality during hospitalization was 2.8%. In patients with mild disease, the shortest lengths of stay were in North America (4 vs. 7 days in other regions), and severe disease was more common in India (23% vs. 9% elsewhere).

Intensive care unit admissions were highest at Indian centers, and in-hospital mortality was highest in Europe (5.7%), compared with 3.3% in India, 2.3% in Latin America, and 0.6% in North America, they said.

Mortality during the initial hospital stay among patients with severe acute pancreatitis was 44% in Europe, compared with 15% in the other three regions.

Multivariable regression analyses adjusting for potential confounders such as age, sex, body mass index, Charlson score, etiology, and transfer status showed that the odds of severe acute pancreatitis were 11.2 times higher in Europe, 7 times higher in India, and 5.6 times higher in Latin America, compared with North America.

The odds ratios for mortality during hospitalization among patients with severe disease were 10.4 in Europe, 4.2 in India, and 8.3 in Latin America, compared with North America.
 

Implications of the findings

Around the world, acute pancreatitis is a leading cause of gastrointestinal-related hospital admissions, and incidence is reportedly increasing in the United States and Europe, the investigators said, noting that about 20% of patients develop severe disease with relatively high morbidity and mortality.

Multiple advances in management have emerged over the last decade, but it is unclear whether those recent advances have gained traction worldwide, they added.

The APPRENTICE registry was created as a response to the lack of prospective, multinational data and the current study aimed to assess the geographic differences in patient characteristics, management, and outcomes across four geographic areas.

The findings, which represent “a bird’s eye view” of regional variation, underscore a need for “adequately powered, multicenter, randomized controlled trials comparing the efficacy of different fluid resuscitation protocols” in acute pancreatitis patients, the investigators said.

Further, “the interventions specific to each region are in certain aspects strikingly divergent, and in many occasions lag behind current evidence,” they wrote, noting the largely variable length-of-stay outcomes and mortality rates.

“In addition to depicting key features of [acute pancreatitis], the results from this study may serve as a reference guide for designing future clinical trials,” they concluded.

The authors reported having no disclosures.

sworcester@mdedge.com

SOURCE: Matt B et al. Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2019.11.017.

Share AGA GI Patient Center education to help your patients understand acute versus chronic pancreatitis, testing, treatment, and potential complications at https://www.gastro.org/practice-guidance/gi-patient-center/topic/pancreatitis. 

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.

In the United States, endoscopists who participate in advanced endoscopy fellowship programs use rectal NSAIDs more often than pancreatic duct stent placement to prevent post-ERCP pancreatitis (PEP), according to research published online in Gastrointestinal Endoscopy. In addition, methods for PEP prophylaxis in clinical practice are not implemented to the extent that the current evidence warrants.

“Future studies should not only further clarify the optimal PEP prophylaxis strategy, but should also focus on strategies to improve the implementation of evidence-based PEP prophylaxis techniques,” wrote Patrick Avila, MD, MPH, gastroenterologist at the University of California, San Francisco, and colleagues.
 

A survey of American endoscopists

Approximately 4% of patients who undergo biliopancreatic endoscopy develop PEP, which has a mortality rate of 3%. The American Society for Gastrointestinal Endoscopy (ASGE) recommends prophylactic pancreatic duct stent placement and rectal NSAIDs to reduce the incidence and severity of PEP in patients at high risk. The ASGE further suggests that rectal indomethacin may decrease the risk and severity of PEP in patients at average risk.

The European Society for Gastrointestinal Endoscopy (ESGE) recommends rectal indomethacin for all patients undergoing ERCP (endoscopic retrograde cholangiopancreatography). Several surveys of European endoscopists, however, indicate that relatively few respondents have adopted the recommended prophylactic techniques. The literature does not contain information about practice patterns among American endoscopists, and Dr. Avila and colleagues decided to investigate this question.

The researchers developed a 16-question online survey to assess current practice patterns with regard to PEP prophylaxis. They defined ERCPs that entailed a high risk for PEP as any that involved pancreatic or precut sphincterotomy, traumatic biliary sphincterotomy, balloon dilation of the biliary sphincter, injection of the pancreatic duct, extensive pancreatic duct instrumentation, difficult cannulation, suspected sphincter of Oddi dysfunction, previous PEP, or a female patient. Dr. Avila and colleagues distributed the survey to 233 advanced endoscopists involved in advanced endoscopy fellowship training programs.
 

Respondents had years of experience

Sixty-two endoscopists (26.7%) completed the survey. Respondents’ mean age was 47 years, and most respondents (74.6%) had been performing ERCP for more than 5 years. Almost all respondents (95%) worked at a tertiary referral center, and all worked with fellows.

All respondents reported having used pancreatic duct stent placement to prevent PEP. Most responders (72%) used pancreatic duct stent placement only in patients at high risk of PEP, and 64% reported using pancreatic duct stent placement in 25% or less of the ERCPs that they had performed. Four respondents (6.8%) used pancreatic duct stent placement for PEP in more than half of ERCPs. Among endoscopists who rarely use pancreatic duct stent placement for PEP, the major reasons cited included concern about increased risk of PEP with failed pancreatic duct insertion, the belief that stents do not provide additional benefit beyond pharmacologic prophylaxis, and difficulties in following up patients to ensure stent passage.

About 98% of respondents reported using rectal NSAIDs for PEP. Thirty-four respondents (59.7%) used this treatment only for patients at high risk, and 23 respondents (40.1%) used it for patients at average risk. Among respondents who used rectal NSAIDs to prevent PEP, 67.8% used the treatment in half or more of ERCPs. The NSAID of choice was indomethacin for all respondents. One respondent reported never using rectal NSAIDs for PEP because of doubts about its efficacy, in addition to cost and availability.

In addition, 49 respondents (83.0%) reported using rapid intravenous fluids to prevent PEP. None reported using octreotide or antibiotics to prevent PEP.
 

Results may reflect recall bias

The survey reveals “a significant divergence from the scientific evidence in how PEP techniques are used in routine clinical practice,” wrote Dr. Avila and colleagues. Several studies, including a randomized controlled trial, support the use of rectal NSAIDs as prophylaxis as patients at average risk of PEP, but less than half of respondents reported using it. The ASGE guidelines state that this treatment is “reasonable,” but do not advocate for it. “If appropriate, adopting a stronger stance in our practice guidelines may lead to further widespread use of rectal NSAIDs in this group of patients,” wrote Dr. Avila and colleagues.

Pancreatic duct stent placement is a difficult procedure to perform. The success rate in one British study was 51%, and a study of expert pancreaticobiliary endoscopists found a failure rate of 7%. It therefore may not be surprising that pancreatic duct stent placement was used less often than rectal NSAIDs among respondents, according to the authors.

Dr. Avila and colleagues acknowledged that the survey’s low response rate could have introduced nonresponse bias into the findings. They also stated that the study may have been affected by selection and recall biases. The results thus may not be generalizable to other practice settings, they concluded.

The authors did not report any study funding or disclosures.

egreb@mdedge.com

SOURCE: Avila P et al. Gastrointest Endosc. 2019 Nov 16. doi: 10.1016/j.gie.2019.11.013.

AGA offers resources to help your patients understand ECRP and scope safety. Learn more at https://www.gastro.org/news/help-your-patients-understand-ercp-and-scope-safety.  

In the United States, endoscopists who participate in advanced endoscopy fellowship programs use rectal NSAIDs more often than pancreatic duct stent placement to prevent post-ERCP pancreatitis (PEP), according to research published online in Gastrointestinal Endoscopy. In addition, methods for PEP prophylaxis in clinical practice are not implemented to the extent that the current evidence warrants.

“Future studies should not only further clarify the optimal PEP prophylaxis strategy, but should also focus on strategies to improve the implementation of evidence-based PEP prophylaxis techniques,” wrote Patrick Avila, MD, MPH, gastroenterologist at the University of California, San Francisco, and colleagues.
 

A survey of American endoscopists

Approximately 4% of patients who undergo biliopancreatic endoscopy develop PEP, which has a mortality rate of 3%. The American Society for Gastrointestinal Endoscopy (ASGE) recommends prophylactic pancreatic duct stent placement and rectal NSAIDs to reduce the incidence and severity of PEP in patients at high risk. The ASGE further suggests that rectal indomethacin may decrease the risk and severity of PEP in patients at average risk.

The European Society for Gastrointestinal Endoscopy (ESGE) recommends rectal indomethacin for all patients undergoing ERCP (endoscopic retrograde cholangiopancreatography). Several surveys of European endoscopists, however, indicate that relatively few respondents have adopted the recommended prophylactic techniques. The literature does not contain information about practice patterns among American endoscopists, and Dr. Avila and colleagues decided to investigate this question.

The researchers developed a 16-question online survey to assess current practice patterns with regard to PEP prophylaxis. They defined ERCPs that entailed a high risk for PEP as any that involved pancreatic or precut sphincterotomy, traumatic biliary sphincterotomy, balloon dilation of the biliary sphincter, injection of the pancreatic duct, extensive pancreatic duct instrumentation, difficult cannulation, suspected sphincter of Oddi dysfunction, previous PEP, or a female patient. Dr. Avila and colleagues distributed the survey to 233 advanced endoscopists involved in advanced endoscopy fellowship training programs.
 

Respondents had years of experience

Sixty-two endoscopists (26.7%) completed the survey. Respondents’ mean age was 47 years, and most respondents (74.6%) had been performing ERCP for more than 5 years. Almost all respondents (95%) worked at a tertiary referral center, and all worked with fellows.

All respondents reported having used pancreatic duct stent placement to prevent PEP. Most responders (72%) used pancreatic duct stent placement only in patients at high risk of PEP, and 64% reported using pancreatic duct stent placement in 25% or less of the ERCPs that they had performed. Four respondents (6.8%) used pancreatic duct stent placement for PEP in more than half of ERCPs. Among endoscopists who rarely use pancreatic duct stent placement for PEP, the major reasons cited included concern about increased risk of PEP with failed pancreatic duct insertion, the belief that stents do not provide additional benefit beyond pharmacologic prophylaxis, and difficulties in following up patients to ensure stent passage.

About 98% of respondents reported using rectal NSAIDs for PEP. Thirty-four respondents (59.7%) used this treatment only for patients at high risk, and 23 respondents (40.1%) used it for patients at average risk. Among respondents who used rectal NSAIDs to prevent PEP, 67.8% used the treatment in half or more of ERCPs. The NSAID of choice was indomethacin for all respondents. One respondent reported never using rectal NSAIDs for PEP because of doubts about its efficacy, in addition to cost and availability.

In addition, 49 respondents (83.0%) reported using rapid intravenous fluids to prevent PEP. None reported using octreotide or antibiotics to prevent PEP.
 

Results may reflect recall bias

The survey reveals “a significant divergence from the scientific evidence in how PEP techniques are used in routine clinical practice,” wrote Dr. Avila and colleagues. Several studies, including a randomized controlled trial, support the use of rectal NSAIDs as prophylaxis as patients at average risk of PEP, but less than half of respondents reported using it. The ASGE guidelines state that this treatment is “reasonable,” but do not advocate for it. “If appropriate, adopting a stronger stance in our practice guidelines may lead to further widespread use of rectal NSAIDs in this group of patients,” wrote Dr. Avila and colleagues.

Pancreatic duct stent placement is a difficult procedure to perform. The success rate in one British study was 51%, and a study of expert pancreaticobiliary endoscopists found a failure rate of 7%. It therefore may not be surprising that pancreatic duct stent placement was used less often than rectal NSAIDs among respondents, according to the authors.

Dr. Avila and colleagues acknowledged that the survey’s low response rate could have introduced nonresponse bias into the findings. They also stated that the study may have been affected by selection and recall biases. The results thus may not be generalizable to other practice settings, they concluded.

The authors did not report any study funding or disclosures.

egreb@mdedge.com

SOURCE: Avila P et al. Gastrointest Endosc. 2019 Nov 16. doi: 10.1016/j.gie.2019.11.013.

AGA offers resources to help your patients understand ECRP and scope safety. Learn more at https://www.gastro.org/news/help-your-patients-understand-ercp-and-scope-safety.  

In the United States, endoscopists who participate in advanced endoscopy fellowship programs use rectal NSAIDs more often than pancreatic duct stent placement to prevent post-ERCP pancreatitis (PEP), according to research published online in Gastrointestinal Endoscopy. In addition, methods for PEP prophylaxis in clinical practice are not implemented to the extent that the current evidence warrants.

“Future studies should not only further clarify the optimal PEP prophylaxis strategy, but should also focus on strategies to improve the implementation of evidence-based PEP prophylaxis techniques,” wrote Patrick Avila, MD, MPH, gastroenterologist at the University of California, San Francisco, and colleagues.
 

A survey of American endoscopists

Approximately 4% of patients who undergo biliopancreatic endoscopy develop PEP, which has a mortality rate of 3%. The American Society for Gastrointestinal Endoscopy (ASGE) recommends prophylactic pancreatic duct stent placement and rectal NSAIDs to reduce the incidence and severity of PEP in patients at high risk. The ASGE further suggests that rectal indomethacin may decrease the risk and severity of PEP in patients at average risk.

The European Society for Gastrointestinal Endoscopy (ESGE) recommends rectal indomethacin for all patients undergoing ERCP (endoscopic retrograde cholangiopancreatography). Several surveys of European endoscopists, however, indicate that relatively few respondents have adopted the recommended prophylactic techniques. The literature does not contain information about practice patterns among American endoscopists, and Dr. Avila and colleagues decided to investigate this question.

The researchers developed a 16-question online survey to assess current practice patterns with regard to PEP prophylaxis. They defined ERCPs that entailed a high risk for PEP as any that involved pancreatic or precut sphincterotomy, traumatic biliary sphincterotomy, balloon dilation of the biliary sphincter, injection of the pancreatic duct, extensive pancreatic duct instrumentation, difficult cannulation, suspected sphincter of Oddi dysfunction, previous PEP, or a female patient. Dr. Avila and colleagues distributed the survey to 233 advanced endoscopists involved in advanced endoscopy fellowship training programs.
 

Respondents had years of experience

Sixty-two endoscopists (26.7%) completed the survey. Respondents’ mean age was 47 years, and most respondents (74.6%) had been performing ERCP for more than 5 years. Almost all respondents (95%) worked at a tertiary referral center, and all worked with fellows.

All respondents reported having used pancreatic duct stent placement to prevent PEP. Most responders (72%) used pancreatic duct stent placement only in patients at high risk of PEP, and 64% reported using pancreatic duct stent placement in 25% or less of the ERCPs that they had performed. Four respondents (6.8%) used pancreatic duct stent placement for PEP in more than half of ERCPs. Among endoscopists who rarely use pancreatic duct stent placement for PEP, the major reasons cited included concern about increased risk of PEP with failed pancreatic duct insertion, the belief that stents do not provide additional benefit beyond pharmacologic prophylaxis, and difficulties in following up patients to ensure stent passage.

About 98% of respondents reported using rectal NSAIDs for PEP. Thirty-four respondents (59.7%) used this treatment only for patients at high risk, and 23 respondents (40.1%) used it for patients at average risk. Among respondents who used rectal NSAIDs to prevent PEP, 67.8% used the treatment in half or more of ERCPs. The NSAID of choice was indomethacin for all respondents. One respondent reported never using rectal NSAIDs for PEP because of doubts about its efficacy, in addition to cost and availability.

In addition, 49 respondents (83.0%) reported using rapid intravenous fluids to prevent PEP. None reported using octreotide or antibiotics to prevent PEP.
 

Results may reflect recall bias

The survey reveals “a significant divergence from the scientific evidence in how PEP techniques are used in routine clinical practice,” wrote Dr. Avila and colleagues. Several studies, including a randomized controlled trial, support the use of rectal NSAIDs as prophylaxis as patients at average risk of PEP, but less than half of respondents reported using it. The ASGE guidelines state that this treatment is “reasonable,” but do not advocate for it. “If appropriate, adopting a stronger stance in our practice guidelines may lead to further widespread use of rectal NSAIDs in this group of patients,” wrote Dr. Avila and colleagues.

Pancreatic duct stent placement is a difficult procedure to perform. The success rate in one British study was 51%, and a study of expert pancreaticobiliary endoscopists found a failure rate of 7%. It therefore may not be surprising that pancreatic duct stent placement was used less often than rectal NSAIDs among respondents, according to the authors.

Dr. Avila and colleagues acknowledged that the survey’s low response rate could have introduced nonresponse bias into the findings. They also stated that the study may have been affected by selection and recall biases. The results thus may not be generalizable to other practice settings, they concluded.

The authors did not report any study funding or disclosures.

egreb@mdedge.com

SOURCE: Avila P et al. Gastrointest Endosc. 2019 Nov 16. doi: 10.1016/j.gie.2019.11.013.

AGA offers resources to help your patients understand ECRP and scope safety. Learn more at https://www.gastro.org/news/help-your-patients-understand-ercp-and-scope-safety.  

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.