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Bezafibrate eased pruritus in patients with fibrosing cholangiopathies
Once-daily treatment with the lipid-lowering agent bezafibrate significantly reduced moderate to severe pruritis among patients with cholestasis, according to the findings of a multicenter, double-blind, randomized, placebo-controlled study (Fibrates for Itch, or FITCH).
Two weeks after completing treatment, 45% of bezafibrate recipients met the primary endpoint, reporting at least a 50% decrease in itch on a 10-point visual analog scale (VAS), compared with 11% of patients in the placebo group (P = .003). There was also a statistically significant decrease in serum alkaline phosphatase (ALP) levels from baseline (35% vs. 6%, respectively; P = .03) that corresponded with improved pruritus, and bezafibrate significantly improved both morning and evening pruritus. Bezafibrate was not associated with myalgia, rhabdomyolysis, or serum alanine transaminase elevations but did lead to a 3% increase in serum creatinine that “was not different from the placebo group,” wrote Elsemieke de Vries, MD, PhD, of the department of gastroenterology & hepatology at Tytgat Institute for Liver and Intestinal Research, Amsterdam, and of department of gastroenterology & metabolism at Amsterdam University Medical Centers, and associates. Their report is in Gastroenterology.
Up to 70% of patients with cholangitis experience pruritus. Current guidelines recommend management with cholestyramine, rifampin, naltrexone, or sertraline, but efficacy and tolerability are subpar, the investigators wrote. In a recent study, a selective inhibitor of an ileal bile acid transporter (GSK2330672) reduced pruritus in primary biliary cholangitis but frequently was associated with diarrhea. In another recent study of patients with primary biliary cholangitis who had responded inadequately to ursodeoxycholic acid (BEZURSO), bezafibrate induced biochemical responses that correlated with improvements in pruritis (a secondary endpoint).
Lysophosphatidic acid (LPA) has been implicated in cholangiopathy-associated pruritus but is not found in bile. However, biliary drainage rapidly improves severe itch in patients with primary biliary cholangitis. Therefore, Dr. de Vries and associates hypothesized that an as-yet unknown factor in bile contributes to pruritus in fibrosing cholangiopathies and that bezafibrate reduces itch by “alleviating hepatobiliary cholestasis and injury and, thereby, reducing formation and biliary secretion of this biliary factor X.”
The FITCH study, which was conducted at seven academic hospitals in the Netherlands and one in Spain, enrolled 74 patients 18 years and older with primary biliary cholangitis or primary or secondary sclerosing cholangitis who reported having pruritus with an intensity of at least 5 on the 10-point VAS at baseline (with 10 indicating “worst itch possible”; median, 7; interquartile range, 7-8). Patients with hepatocellular cholestasis caused by medications or pregnancy were excluded. Ages among most participants ranged from 30s to 50s, and approximately two-thirds were female. None had received another pruritus treatment within 10 days of enrollment, and prior treatment with bezafibrate was not allowed. Patients received once-daily bezafibrate (400 mg) or placebo tablets for 21 days, with visits to the outpatient clinic on days 0, 21, and 35.
There were no serious adverse events or new safety signals. One event of oral pain was considered possibly related to bezafibrate, and itch and jaundice worsened in two patients after completing treatment. As in the 24-month BEZURSO study, increases in serum creatinine were modest and similar between groups (3% with bezafibrate and 5% with placebo). Myalgia and increases in serum alanine transaminase were observed in BEZURSO but not in FITCH. However, the short treatment duration provides “no judgment on long-term safety [of bezafibrate] in complex diseases such as primary sclerosing cholangitis or primary biliary cholangitis,” the investigators wrote.
Four patients discontinued treatment – three stopped placebo because of “unbearable pruritus,” and one stopped bezafibrate after developing acute bacterial cholangitis that required emergency treatment. Although FITCH excluded patients whose estimated glomerular filtration rate was less than 60 mL/min per 1.73 m2, one such patient was accidentally enrolled. Her serum creatinine, measured in mmol/L, rose from 121 at baseline to 148 on day 21, and then dropped to 134 after 2 weeks off treatment.
The trial was supported by patient donations, the Netherlands Society of Gastroenterology, and Instituto de Salud Carlos III. The investigators reported having no conflicts of interest.
SOURCE: de Vries E et al. Gastroenterology. 2020 Oct 5. doi: 10.1053/j.gastro.2020.10.001.
Itch really matters to patients with cholestatic liver diseases, and effective treatment can make a significant difference to life quality. Although therapies exist for cholestatic itch (such as cholestyramine, rifampin, and naltrexone) recent data from the United Kingdom and United States suggest that therapy in practice is poor. It is likely that this results, at least in part, from the limitations of the existing treatments which can be unpleasant to take (cholestyramine) or difficult to use because of monitoring needs and side-effects (rifampin and naltrexone). Itch has therefore been identified as an area of real unmet need in cholestatic disease and there are a number of trials in progress or in set-up. This is extremely positive for patients.
The FITCH trial is one of the first of these “new generation” cholestatic itch trials to report and explore the efficacy of the PPAR-agonist bezafibrate in a mixed cholestatic population. Clear benefit was seen with around 50% of all disease groups meeting the primary endpoint and good drug tolerance. Is bezafibrate therefore the answer to cholestatic itch? The cautious answer is ... possibly, but more experience is needed. The trial duration was only 21 days, which means that long-term safety and efficacy remain to be explored. Bezafibrate is now being used in practice to treat cholestatic itch with effects similar to those reported in the trial. It is therefore clearly an important new option. Where it ultimately ends up in the treatment pathway only time and experience will tell.
David Jones, BM, BCh, PhD, is a professor of liver immunology at Newcastle University, Newcastle Upon Tyne, England. He reported having no disclosures relevant to this commentary.
Itch really matters to patients with cholestatic liver diseases, and effective treatment can make a significant difference to life quality. Although therapies exist for cholestatic itch (such as cholestyramine, rifampin, and naltrexone) recent data from the United Kingdom and United States suggest that therapy in practice is poor. It is likely that this results, at least in part, from the limitations of the existing treatments which can be unpleasant to take (cholestyramine) or difficult to use because of monitoring needs and side-effects (rifampin and naltrexone). Itch has therefore been identified as an area of real unmet need in cholestatic disease and there are a number of trials in progress or in set-up. This is extremely positive for patients.
The FITCH trial is one of the first of these “new generation” cholestatic itch trials to report and explore the efficacy of the PPAR-agonist bezafibrate in a mixed cholestatic population. Clear benefit was seen with around 50% of all disease groups meeting the primary endpoint and good drug tolerance. Is bezafibrate therefore the answer to cholestatic itch? The cautious answer is ... possibly, but more experience is needed. The trial duration was only 21 days, which means that long-term safety and efficacy remain to be explored. Bezafibrate is now being used in practice to treat cholestatic itch with effects similar to those reported in the trial. It is therefore clearly an important new option. Where it ultimately ends up in the treatment pathway only time and experience will tell.
David Jones, BM, BCh, PhD, is a professor of liver immunology at Newcastle University, Newcastle Upon Tyne, England. He reported having no disclosures relevant to this commentary.
Itch really matters to patients with cholestatic liver diseases, and effective treatment can make a significant difference to life quality. Although therapies exist for cholestatic itch (such as cholestyramine, rifampin, and naltrexone) recent data from the United Kingdom and United States suggest that therapy in practice is poor. It is likely that this results, at least in part, from the limitations of the existing treatments which can be unpleasant to take (cholestyramine) or difficult to use because of monitoring needs and side-effects (rifampin and naltrexone). Itch has therefore been identified as an area of real unmet need in cholestatic disease and there are a number of trials in progress or in set-up. This is extremely positive for patients.
The FITCH trial is one of the first of these “new generation” cholestatic itch trials to report and explore the efficacy of the PPAR-agonist bezafibrate in a mixed cholestatic population. Clear benefit was seen with around 50% of all disease groups meeting the primary endpoint and good drug tolerance. Is bezafibrate therefore the answer to cholestatic itch? The cautious answer is ... possibly, but more experience is needed. The trial duration was only 21 days, which means that long-term safety and efficacy remain to be explored. Bezafibrate is now being used in practice to treat cholestatic itch with effects similar to those reported in the trial. It is therefore clearly an important new option. Where it ultimately ends up in the treatment pathway only time and experience will tell.
David Jones, BM, BCh, PhD, is a professor of liver immunology at Newcastle University, Newcastle Upon Tyne, England. He reported having no disclosures relevant to this commentary.
Once-daily treatment with the lipid-lowering agent bezafibrate significantly reduced moderate to severe pruritis among patients with cholestasis, according to the findings of a multicenter, double-blind, randomized, placebo-controlled study (Fibrates for Itch, or FITCH).
Two weeks after completing treatment, 45% of bezafibrate recipients met the primary endpoint, reporting at least a 50% decrease in itch on a 10-point visual analog scale (VAS), compared with 11% of patients in the placebo group (P = .003). There was also a statistically significant decrease in serum alkaline phosphatase (ALP) levels from baseline (35% vs. 6%, respectively; P = .03) that corresponded with improved pruritus, and bezafibrate significantly improved both morning and evening pruritus. Bezafibrate was not associated with myalgia, rhabdomyolysis, or serum alanine transaminase elevations but did lead to a 3% increase in serum creatinine that “was not different from the placebo group,” wrote Elsemieke de Vries, MD, PhD, of the department of gastroenterology & hepatology at Tytgat Institute for Liver and Intestinal Research, Amsterdam, and of department of gastroenterology & metabolism at Amsterdam University Medical Centers, and associates. Their report is in Gastroenterology.
Up to 70% of patients with cholangitis experience pruritus. Current guidelines recommend management with cholestyramine, rifampin, naltrexone, or sertraline, but efficacy and tolerability are subpar, the investigators wrote. In a recent study, a selective inhibitor of an ileal bile acid transporter (GSK2330672) reduced pruritus in primary biliary cholangitis but frequently was associated with diarrhea. In another recent study of patients with primary biliary cholangitis who had responded inadequately to ursodeoxycholic acid (BEZURSO), bezafibrate induced biochemical responses that correlated with improvements in pruritis (a secondary endpoint).
Lysophosphatidic acid (LPA) has been implicated in cholangiopathy-associated pruritus but is not found in bile. However, biliary drainage rapidly improves severe itch in patients with primary biliary cholangitis. Therefore, Dr. de Vries and associates hypothesized that an as-yet unknown factor in bile contributes to pruritus in fibrosing cholangiopathies and that bezafibrate reduces itch by “alleviating hepatobiliary cholestasis and injury and, thereby, reducing formation and biliary secretion of this biliary factor X.”
The FITCH study, which was conducted at seven academic hospitals in the Netherlands and one in Spain, enrolled 74 patients 18 years and older with primary biliary cholangitis or primary or secondary sclerosing cholangitis who reported having pruritus with an intensity of at least 5 on the 10-point VAS at baseline (with 10 indicating “worst itch possible”; median, 7; interquartile range, 7-8). Patients with hepatocellular cholestasis caused by medications or pregnancy were excluded. Ages among most participants ranged from 30s to 50s, and approximately two-thirds were female. None had received another pruritus treatment within 10 days of enrollment, and prior treatment with bezafibrate was not allowed. Patients received once-daily bezafibrate (400 mg) or placebo tablets for 21 days, with visits to the outpatient clinic on days 0, 21, and 35.
There were no serious adverse events or new safety signals. One event of oral pain was considered possibly related to bezafibrate, and itch and jaundice worsened in two patients after completing treatment. As in the 24-month BEZURSO study, increases in serum creatinine were modest and similar between groups (3% with bezafibrate and 5% with placebo). Myalgia and increases in serum alanine transaminase were observed in BEZURSO but not in FITCH. However, the short treatment duration provides “no judgment on long-term safety [of bezafibrate] in complex diseases such as primary sclerosing cholangitis or primary biliary cholangitis,” the investigators wrote.
Four patients discontinued treatment – three stopped placebo because of “unbearable pruritus,” and one stopped bezafibrate after developing acute bacterial cholangitis that required emergency treatment. Although FITCH excluded patients whose estimated glomerular filtration rate was less than 60 mL/min per 1.73 m2, one such patient was accidentally enrolled. Her serum creatinine, measured in mmol/L, rose from 121 at baseline to 148 on day 21, and then dropped to 134 after 2 weeks off treatment.
The trial was supported by patient donations, the Netherlands Society of Gastroenterology, and Instituto de Salud Carlos III. The investigators reported having no conflicts of interest.
SOURCE: de Vries E et al. Gastroenterology. 2020 Oct 5. doi: 10.1053/j.gastro.2020.10.001.
Once-daily treatment with the lipid-lowering agent bezafibrate significantly reduced moderate to severe pruritis among patients with cholestasis, according to the findings of a multicenter, double-blind, randomized, placebo-controlled study (Fibrates for Itch, or FITCH).
Two weeks after completing treatment, 45% of bezafibrate recipients met the primary endpoint, reporting at least a 50% decrease in itch on a 10-point visual analog scale (VAS), compared with 11% of patients in the placebo group (P = .003). There was also a statistically significant decrease in serum alkaline phosphatase (ALP) levels from baseline (35% vs. 6%, respectively; P = .03) that corresponded with improved pruritus, and bezafibrate significantly improved both morning and evening pruritus. Bezafibrate was not associated with myalgia, rhabdomyolysis, or serum alanine transaminase elevations but did lead to a 3% increase in serum creatinine that “was not different from the placebo group,” wrote Elsemieke de Vries, MD, PhD, of the department of gastroenterology & hepatology at Tytgat Institute for Liver and Intestinal Research, Amsterdam, and of department of gastroenterology & metabolism at Amsterdam University Medical Centers, and associates. Their report is in Gastroenterology.
Up to 70% of patients with cholangitis experience pruritus. Current guidelines recommend management with cholestyramine, rifampin, naltrexone, or sertraline, but efficacy and tolerability are subpar, the investigators wrote. In a recent study, a selective inhibitor of an ileal bile acid transporter (GSK2330672) reduced pruritus in primary biliary cholangitis but frequently was associated with diarrhea. In another recent study of patients with primary biliary cholangitis who had responded inadequately to ursodeoxycholic acid (BEZURSO), bezafibrate induced biochemical responses that correlated with improvements in pruritis (a secondary endpoint).
Lysophosphatidic acid (LPA) has been implicated in cholangiopathy-associated pruritus but is not found in bile. However, biliary drainage rapidly improves severe itch in patients with primary biliary cholangitis. Therefore, Dr. de Vries and associates hypothesized that an as-yet unknown factor in bile contributes to pruritus in fibrosing cholangiopathies and that bezafibrate reduces itch by “alleviating hepatobiliary cholestasis and injury and, thereby, reducing formation and biliary secretion of this biliary factor X.”
The FITCH study, which was conducted at seven academic hospitals in the Netherlands and one in Spain, enrolled 74 patients 18 years and older with primary biliary cholangitis or primary or secondary sclerosing cholangitis who reported having pruritus with an intensity of at least 5 on the 10-point VAS at baseline (with 10 indicating “worst itch possible”; median, 7; interquartile range, 7-8). Patients with hepatocellular cholestasis caused by medications or pregnancy were excluded. Ages among most participants ranged from 30s to 50s, and approximately two-thirds were female. None had received another pruritus treatment within 10 days of enrollment, and prior treatment with bezafibrate was not allowed. Patients received once-daily bezafibrate (400 mg) or placebo tablets for 21 days, with visits to the outpatient clinic on days 0, 21, and 35.
There were no serious adverse events or new safety signals. One event of oral pain was considered possibly related to bezafibrate, and itch and jaundice worsened in two patients after completing treatment. As in the 24-month BEZURSO study, increases in serum creatinine were modest and similar between groups (3% with bezafibrate and 5% with placebo). Myalgia and increases in serum alanine transaminase were observed in BEZURSO but not in FITCH. However, the short treatment duration provides “no judgment on long-term safety [of bezafibrate] in complex diseases such as primary sclerosing cholangitis or primary biliary cholangitis,” the investigators wrote.
Four patients discontinued treatment – three stopped placebo because of “unbearable pruritus,” and one stopped bezafibrate after developing acute bacterial cholangitis that required emergency treatment. Although FITCH excluded patients whose estimated glomerular filtration rate was less than 60 mL/min per 1.73 m2, one such patient was accidentally enrolled. Her serum creatinine, measured in mmol/L, rose from 121 at baseline to 148 on day 21, and then dropped to 134 after 2 weeks off treatment.
The trial was supported by patient donations, the Netherlands Society of Gastroenterology, and Instituto de Salud Carlos III. The investigators reported having no conflicts of interest.
SOURCE: de Vries E et al. Gastroenterology. 2020 Oct 5. doi: 10.1053/j.gastro.2020.10.001.
FROM GASTROENTEROLOGY
FDA clears device to remove dead pancreatic tissue
The Food and Drug Administration has approved the EndoRotor System (Interscope, Inc.) for removal of necrotic tissue in patients with walled-off pancreatic necrosis (WOPN).
“This device has shown its potential to provide a minimally invasive way to remove harmful necrotic pancreatic tissue in patients with walled-off pancreatic necrosis,” Charles Viviano, MD, PhD, acting director, Reproductive, Gastro-Renal, Urological, General Hospital Device and Human Factors Office, FDA Center for Devices and Radiological Health, said in a statement.
“Currently, in order to remove dead tissue from a patient’s necrotic pancreatic cavity, health care providers need to perform an invasive surgery or use other endoscopic tools not specifically indicated to treat this condition. With [this] marketing authorization, patients with walled-off pancreatic necrosis now have a new treatment option,” said Dr. Viviano.
WOPN is a potentially deadly condition that occurs in about 15% of patients with severe pancreatitis. Often, the dead tissue must be removed.
The EndoRotor System is made up of a power console, foot control, specimen trap, and single-use catheter.
The device is used to perform endoscopic necrosectomy. In this procedure, a stent is used to create a portal between the stomach and the necrotic cavity in the pancreas to accommodate a standard endoscope through which the EndoRotor cuts and removes necrotized tissue.
The FDA approved the EndoRotor System on the basis of a clinical trial involving 30 patients with WOPN who underwent a total of 63 direct endoscopic necrosectomies with the EndoRotor System (average, 2.1 procedures per patient).
The effectiveness of the EndoRotor System was determined by how well it cleared pancreatic necrotic tissue measured during CT with contrast before and after the procedure, endoscopy, or MRI 14 to 28 days after the last procedure.
Results showed an average 85% reduction in the amount of necrotic tissue, with half of the patients having 98.5% clearance of necrotic tissue, the FDA said.
Three patients suffered procedure-related serious adverse events (10% complication rate). Two patients experienced gastrointestinal bleeding. One patient had a pneumoperitoneum and later died after suffering from sepsis and multiorgan system failure caused by massive collections of infected pancreatic necrotic tissue.
Other serious adverse events, which were thought to be due to the patient’s underlying condition and not related to the device or procedure, included hematemesis, deep vein thrombosis, and pancreatitis.
The EndoRotor System should not be used for patients with known or suspected pancreatic cancer, and the device will carry a boxed warning stating this.
The FDA said it knows of one patient who died from pancreatic cancer 3 months after having necrotic pancreatic tissue removed with the EndoRotor System.
“This patient did not have a diagnosis of pancreatic cancer prior to treatment, although the patient’s outcome is believed to be unrelated to the device or procedure,” the FDA said.
The EndoRotor System should be used only after patients have undergone other procedures to drain the WOPN.
It is also not appropriate for patients with walled-off necrosis who have a documented pseudoaneurysm greater than 1 cm within the cavity or with intervening gastric varices or unavoidable blood vessels within the access tract.
The EndoRotor System was approved under the de novo premarket review pathway for new low- to moderate-risk devices.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved the EndoRotor System (Interscope, Inc.) for removal of necrotic tissue in patients with walled-off pancreatic necrosis (WOPN).
“This device has shown its potential to provide a minimally invasive way to remove harmful necrotic pancreatic tissue in patients with walled-off pancreatic necrosis,” Charles Viviano, MD, PhD, acting director, Reproductive, Gastro-Renal, Urological, General Hospital Device and Human Factors Office, FDA Center for Devices and Radiological Health, said in a statement.
“Currently, in order to remove dead tissue from a patient’s necrotic pancreatic cavity, health care providers need to perform an invasive surgery or use other endoscopic tools not specifically indicated to treat this condition. With [this] marketing authorization, patients with walled-off pancreatic necrosis now have a new treatment option,” said Dr. Viviano.
WOPN is a potentially deadly condition that occurs in about 15% of patients with severe pancreatitis. Often, the dead tissue must be removed.
The EndoRotor System is made up of a power console, foot control, specimen trap, and single-use catheter.
The device is used to perform endoscopic necrosectomy. In this procedure, a stent is used to create a portal between the stomach and the necrotic cavity in the pancreas to accommodate a standard endoscope through which the EndoRotor cuts and removes necrotized tissue.
The FDA approved the EndoRotor System on the basis of a clinical trial involving 30 patients with WOPN who underwent a total of 63 direct endoscopic necrosectomies with the EndoRotor System (average, 2.1 procedures per patient).
The effectiveness of the EndoRotor System was determined by how well it cleared pancreatic necrotic tissue measured during CT with contrast before and after the procedure, endoscopy, or MRI 14 to 28 days after the last procedure.
Results showed an average 85% reduction in the amount of necrotic tissue, with half of the patients having 98.5% clearance of necrotic tissue, the FDA said.
Three patients suffered procedure-related serious adverse events (10% complication rate). Two patients experienced gastrointestinal bleeding. One patient had a pneumoperitoneum and later died after suffering from sepsis and multiorgan system failure caused by massive collections of infected pancreatic necrotic tissue.
Other serious adverse events, which were thought to be due to the patient’s underlying condition and not related to the device or procedure, included hematemesis, deep vein thrombosis, and pancreatitis.
The EndoRotor System should not be used for patients with known or suspected pancreatic cancer, and the device will carry a boxed warning stating this.
The FDA said it knows of one patient who died from pancreatic cancer 3 months after having necrotic pancreatic tissue removed with the EndoRotor System.
“This patient did not have a diagnosis of pancreatic cancer prior to treatment, although the patient’s outcome is believed to be unrelated to the device or procedure,” the FDA said.
The EndoRotor System should be used only after patients have undergone other procedures to drain the WOPN.
It is also not appropriate for patients with walled-off necrosis who have a documented pseudoaneurysm greater than 1 cm within the cavity or with intervening gastric varices or unavoidable blood vessels within the access tract.
The EndoRotor System was approved under the de novo premarket review pathway for new low- to moderate-risk devices.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved the EndoRotor System (Interscope, Inc.) for removal of necrotic tissue in patients with walled-off pancreatic necrosis (WOPN).
“This device has shown its potential to provide a minimally invasive way to remove harmful necrotic pancreatic tissue in patients with walled-off pancreatic necrosis,” Charles Viviano, MD, PhD, acting director, Reproductive, Gastro-Renal, Urological, General Hospital Device and Human Factors Office, FDA Center for Devices and Radiological Health, said in a statement.
“Currently, in order to remove dead tissue from a patient’s necrotic pancreatic cavity, health care providers need to perform an invasive surgery or use other endoscopic tools not specifically indicated to treat this condition. With [this] marketing authorization, patients with walled-off pancreatic necrosis now have a new treatment option,” said Dr. Viviano.
WOPN is a potentially deadly condition that occurs in about 15% of patients with severe pancreatitis. Often, the dead tissue must be removed.
The EndoRotor System is made up of a power console, foot control, specimen trap, and single-use catheter.
The device is used to perform endoscopic necrosectomy. In this procedure, a stent is used to create a portal between the stomach and the necrotic cavity in the pancreas to accommodate a standard endoscope through which the EndoRotor cuts and removes necrotized tissue.
The FDA approved the EndoRotor System on the basis of a clinical trial involving 30 patients with WOPN who underwent a total of 63 direct endoscopic necrosectomies with the EndoRotor System (average, 2.1 procedures per patient).
The effectiveness of the EndoRotor System was determined by how well it cleared pancreatic necrotic tissue measured during CT with contrast before and after the procedure, endoscopy, or MRI 14 to 28 days after the last procedure.
Results showed an average 85% reduction in the amount of necrotic tissue, with half of the patients having 98.5% clearance of necrotic tissue, the FDA said.
Three patients suffered procedure-related serious adverse events (10% complication rate). Two patients experienced gastrointestinal bleeding. One patient had a pneumoperitoneum and later died after suffering from sepsis and multiorgan system failure caused by massive collections of infected pancreatic necrotic tissue.
Other serious adverse events, which were thought to be due to the patient’s underlying condition and not related to the device or procedure, included hematemesis, deep vein thrombosis, and pancreatitis.
The EndoRotor System should not be used for patients with known or suspected pancreatic cancer, and the device will carry a boxed warning stating this.
The FDA said it knows of one patient who died from pancreatic cancer 3 months after having necrotic pancreatic tissue removed with the EndoRotor System.
“This patient did not have a diagnosis of pancreatic cancer prior to treatment, although the patient’s outcome is believed to be unrelated to the device or procedure,” the FDA said.
The EndoRotor System should be used only after patients have undergone other procedures to drain the WOPN.
It is also not appropriate for patients with walled-off necrosis who have a documented pseudoaneurysm greater than 1 cm within the cavity or with intervening gastric varices or unavoidable blood vessels within the access tract.
The EndoRotor System was approved under the de novo premarket review pathway for new low- to moderate-risk devices.
A version of this article first appeared on Medscape.com.
Endoscopic drainage of pancreatic fluid collections
Pancreatic fluid collections (PFCs) are common after acute pancreatitis but almost always resolve spontaneously. Persistent collections that cause symptoms, become infected, and/or compress vital structures require treatment. Open surgery had traditionally been considered the standard method for this indication;1 Given its inherently less invasive nature, endoscopic transmural drainage (ETMD) has become a mainstay of this step-up philosophy – it is now the dominant strategy for pseudocyst drainage and, on the basis of emerging randomized trial data, compares very favorably with surgery for the treatment of walled-off necrosis (WON).
According to the step-up approach, the initial treatment of symptomatic and/or infected collections that are within 4 weeks of an attack of pancreatitis involves conservative management because the wall of the collection is typically immature; the systemic inflammation may be significantly exacerbated by definitive drainage, particularly surgery. In this early phase, failure of conservative management is addressed by percutaneous catheter placement, stepping up to a minimally invasive operation if the response to percutaneous drainage and antibiotics is insufficient.
Collections that are at least 4 weeks from the onset of acute pancreatitis are considered mature and termed pseudocysts or WONs depending on whether they contain pure fluid or necrotic tissue. In this phase, endoscopic treatment plays a primary management role because these collections are generally adherent to the stomach or duodenal wall and their capsule is organized enough to withstand endoscopic intervention. If treatment can be held off until this phase, then percutaneous and surgical drainage can often be avoided.
In practice, the 4-week rule holds true for most, but not all, PFCs. ETMD can be performed in some particularly mature collections prior to 4 weeks if the indication is strong and the collection appears to have a mature wall. However, the potential for cyst wall perforation is higher and should be considered in the risk-benefit discussion. Conversely, some collections beyond 4 weeks lack an adequately organized wall and require additional time for maturation.
While endoscopic drainage of pseudocysts has essentially supplanted surgery, the management of WON is more complex and remains multidisciplinary. Two recent randomized trials demonstrated no difference in major complications and/or death between a surgical and endoscopic step-up strategy for WON.2,3 Rates of pancreatic fistulae, hospital stay, and overall treatment costs, however, favored endoscopy. Nevertheless, defining the ideal strategy for many of these patients with complexity requires multidisciplinary discussion. Surgery continues to play a primary role in several scenarios, including collections that are not close to the upper GI tract, those that are particularly complex and extend caudally, and situations in which the endoscopic progress is too slow.
The three most important questions when deciding to embark on ETMD are: (1) whether drainage is indicated (that is, is the patient symptomatic or is there evidence that the PFC is infected?), (2) whether the wall of the collection is adequately mature and apposed to the GI tract wall; and (3) whether the collection contains necrosis? This last question has critical implications in the technical approach to drainage. While CT scan with IV contrast is accurate for assessing wall maturity, it is inadequate to evaluate the presence or quantity of necrosum. Transabdominal ultrasound, endoscopic ultrasound, and MRI (on a T2 sequence) are all superior for this purpose. MRI has the additional benefit of assessing the pancreatic duct integrity, which may influence subsequent management.
Pseudocysts can be managed by cyst-gastrostomy or cyst-duodenostomy alone, whereas most WONs require the additional step of endoscopic necrosectomy – the process of entering the cyst cavity to mechanically debride necrotic tissue. Because of a higher rate of technical success, endoscopic ultrasound–directed creation of the transmural drainage pathway has become standard practice. In addition, it is likely safer, allowing for the identification and avoidance of interceding vessels and other vital structures. The role of endoscopic retrograde cholangiopancreatography with pancreatic stent placement as primary therapy for PFCs is limited to the drainage of small collections (<5 cm), for which it is the preferred treatment strategy. It is as effective as ETMD, which may not be feasible or safe for small PFCs.
Plastic double-pigtail stents have traditionally been used to maintain the transmural tract for both pseudocyst and WON. Recently, however, metallic stents have become more popular. Fully covered biliary self-expanding metallic stents (SEMS) are easier to place, have a larger lumen, and are associated with improved outcomes, compared with plastic stents in observational studies of pseudocyst drainage. Lumen-apposing metallic stents (LAMS) have become the preferred prosthesis for WON drainage given the ability to near-simultaneously establish access and deploy the stent, as well as their much larger caliber lumen which permits seamless entry into the cavity with an endoscope. Based on ease and efficiency of use, LAMS are also commonly employed for pseudocyst drainage, although entry into the cavity is unnecessary.
Plastic stents have been shown to be more cost effective than LAMS for pseudocyst drainage, although the economics around biliary SEMS in this context have not been explored. Robust comparative effectiveness data defining the optimal prostheses for pseudocysts are needed. The literature comparing LAMS to plastic stents for the management of WON is mixed. Studies have shown LAMS to be more cost effective, but a small randomized trial demonstrated no difference in clinical success or in the number of procedures to achieve WON resolution.4 We generally favor LAMS for WON since large-caliber balloon dilation of the tract seems safer within the lumen of the LAMS (which could seal small perforations and tamponade bleeding vessels) than within a freshly created tract.
Secondary infection of the cavity, usually because of stent occlusion, and bleeding are the most common complications of ETMD. Even in the absence of stent occlusion, contamination of the collection after ETMD is ubiquitous and, as such, we prescribe prophylactic antibiotics for 1-2 weeks after the procedure, although this practice is not evidence based. Hemorrhage appears to be increasing in frequency with the diffusion of LAMS; this has been postulated to be due to particularly rapid cyst cavity collapse resulting in erosion of the stent into contralateral cyst wall vessels. CT angiography followed by an embolization procedure for a possible pseudoaneurysm is the mainstay of treatment. Serious venous bleeding is more challenging to address because angiographic options are limited.
Despite tremendous recent advances, several important controversies in the endoscopic management of PFCs persist. The optimal prosthesis, the importance of first-session endoscopic necroscopy (compared with stepping up to endoscopic necroscopy only if necessary), the roles of adjunctive drain placement and chemical debridement (such as hydrogen peroxide), the need for concomitant pancreatic stent placement, and the preferred long-term management of a disconnected pancreatic duct are areas for which additional research is sorely needed. We further discuss these questions and many additional technical considerations pertaining to endoscopic drainage in a recent review.5
In summary, endoscopic transmural drainage of mature PFCs is effective and safe. Existing evidence supports its use as the favored treatment modality in appropriate candidates and has rendered it a mainstay of the therapeutic armamentarium for this disease. Further studies are needed to address critical unanswered questions and to develop a uniform endoscopic management paradigm.
References
1. van Santvoort HC et al. N Engl J Med. 2010;362(16):1491-502.
2. van Brunschot S et al. Lancet. 2018;391(10115):51-8.
3. Bang JY et al. Gastroenterology. 2019;156(4):1027-40.
4. Bang JY et al. Gut. 2019;68(7):1200-9.
5. Elmunzer BJ. Clin Gastroenterol Hepatol. 2018;16(12):1851-63.
Dr. Moran is assistant professor of medicine, division of gastroenterology and hepatology, Medical University of South Carolina, Charleston; Dr. Elmunzer is the Peter Cotton Professor of Medicine and Endoscopic Innovation, division of gastroenterology and hepatology, Medical University of South Carolina. The authors have no conflicts of interest pertaining to this review.
Pancreatic fluid collections (PFCs) are common after acute pancreatitis but almost always resolve spontaneously. Persistent collections that cause symptoms, become infected, and/or compress vital structures require treatment. Open surgery had traditionally been considered the standard method for this indication;1 Given its inherently less invasive nature, endoscopic transmural drainage (ETMD) has become a mainstay of this step-up philosophy – it is now the dominant strategy for pseudocyst drainage and, on the basis of emerging randomized trial data, compares very favorably with surgery for the treatment of walled-off necrosis (WON).
According to the step-up approach, the initial treatment of symptomatic and/or infected collections that are within 4 weeks of an attack of pancreatitis involves conservative management because the wall of the collection is typically immature; the systemic inflammation may be significantly exacerbated by definitive drainage, particularly surgery. In this early phase, failure of conservative management is addressed by percutaneous catheter placement, stepping up to a minimally invasive operation if the response to percutaneous drainage and antibiotics is insufficient.
Collections that are at least 4 weeks from the onset of acute pancreatitis are considered mature and termed pseudocysts or WONs depending on whether they contain pure fluid or necrotic tissue. In this phase, endoscopic treatment plays a primary management role because these collections are generally adherent to the stomach or duodenal wall and their capsule is organized enough to withstand endoscopic intervention. If treatment can be held off until this phase, then percutaneous and surgical drainage can often be avoided.
In practice, the 4-week rule holds true for most, but not all, PFCs. ETMD can be performed in some particularly mature collections prior to 4 weeks if the indication is strong and the collection appears to have a mature wall. However, the potential for cyst wall perforation is higher and should be considered in the risk-benefit discussion. Conversely, some collections beyond 4 weeks lack an adequately organized wall and require additional time for maturation.
While endoscopic drainage of pseudocysts has essentially supplanted surgery, the management of WON is more complex and remains multidisciplinary. Two recent randomized trials demonstrated no difference in major complications and/or death between a surgical and endoscopic step-up strategy for WON.2,3 Rates of pancreatic fistulae, hospital stay, and overall treatment costs, however, favored endoscopy. Nevertheless, defining the ideal strategy for many of these patients with complexity requires multidisciplinary discussion. Surgery continues to play a primary role in several scenarios, including collections that are not close to the upper GI tract, those that are particularly complex and extend caudally, and situations in which the endoscopic progress is too slow.
The three most important questions when deciding to embark on ETMD are: (1) whether drainage is indicated (that is, is the patient symptomatic or is there evidence that the PFC is infected?), (2) whether the wall of the collection is adequately mature and apposed to the GI tract wall; and (3) whether the collection contains necrosis? This last question has critical implications in the technical approach to drainage. While CT scan with IV contrast is accurate for assessing wall maturity, it is inadequate to evaluate the presence or quantity of necrosum. Transabdominal ultrasound, endoscopic ultrasound, and MRI (on a T2 sequence) are all superior for this purpose. MRI has the additional benefit of assessing the pancreatic duct integrity, which may influence subsequent management.
Pseudocysts can be managed by cyst-gastrostomy or cyst-duodenostomy alone, whereas most WONs require the additional step of endoscopic necrosectomy – the process of entering the cyst cavity to mechanically debride necrotic tissue. Because of a higher rate of technical success, endoscopic ultrasound–directed creation of the transmural drainage pathway has become standard practice. In addition, it is likely safer, allowing for the identification and avoidance of interceding vessels and other vital structures. The role of endoscopic retrograde cholangiopancreatography with pancreatic stent placement as primary therapy for PFCs is limited to the drainage of small collections (<5 cm), for which it is the preferred treatment strategy. It is as effective as ETMD, which may not be feasible or safe for small PFCs.
Plastic double-pigtail stents have traditionally been used to maintain the transmural tract for both pseudocyst and WON. Recently, however, metallic stents have become more popular. Fully covered biliary self-expanding metallic stents (SEMS) are easier to place, have a larger lumen, and are associated with improved outcomes, compared with plastic stents in observational studies of pseudocyst drainage. Lumen-apposing metallic stents (LAMS) have become the preferred prosthesis for WON drainage given the ability to near-simultaneously establish access and deploy the stent, as well as their much larger caliber lumen which permits seamless entry into the cavity with an endoscope. Based on ease and efficiency of use, LAMS are also commonly employed for pseudocyst drainage, although entry into the cavity is unnecessary.
Plastic stents have been shown to be more cost effective than LAMS for pseudocyst drainage, although the economics around biliary SEMS in this context have not been explored. Robust comparative effectiveness data defining the optimal prostheses for pseudocysts are needed. The literature comparing LAMS to plastic stents for the management of WON is mixed. Studies have shown LAMS to be more cost effective, but a small randomized trial demonstrated no difference in clinical success or in the number of procedures to achieve WON resolution.4 We generally favor LAMS for WON since large-caliber balloon dilation of the tract seems safer within the lumen of the LAMS (which could seal small perforations and tamponade bleeding vessels) than within a freshly created tract.
Secondary infection of the cavity, usually because of stent occlusion, and bleeding are the most common complications of ETMD. Even in the absence of stent occlusion, contamination of the collection after ETMD is ubiquitous and, as such, we prescribe prophylactic antibiotics for 1-2 weeks after the procedure, although this practice is not evidence based. Hemorrhage appears to be increasing in frequency with the diffusion of LAMS; this has been postulated to be due to particularly rapid cyst cavity collapse resulting in erosion of the stent into contralateral cyst wall vessels. CT angiography followed by an embolization procedure for a possible pseudoaneurysm is the mainstay of treatment. Serious venous bleeding is more challenging to address because angiographic options are limited.
Despite tremendous recent advances, several important controversies in the endoscopic management of PFCs persist. The optimal prosthesis, the importance of first-session endoscopic necroscopy (compared with stepping up to endoscopic necroscopy only if necessary), the roles of adjunctive drain placement and chemical debridement (such as hydrogen peroxide), the need for concomitant pancreatic stent placement, and the preferred long-term management of a disconnected pancreatic duct are areas for which additional research is sorely needed. We further discuss these questions and many additional technical considerations pertaining to endoscopic drainage in a recent review.5
In summary, endoscopic transmural drainage of mature PFCs is effective and safe. Existing evidence supports its use as the favored treatment modality in appropriate candidates and has rendered it a mainstay of the therapeutic armamentarium for this disease. Further studies are needed to address critical unanswered questions and to develop a uniform endoscopic management paradigm.
References
1. van Santvoort HC et al. N Engl J Med. 2010;362(16):1491-502.
2. van Brunschot S et al. Lancet. 2018;391(10115):51-8.
3. Bang JY et al. Gastroenterology. 2019;156(4):1027-40.
4. Bang JY et al. Gut. 2019;68(7):1200-9.
5. Elmunzer BJ. Clin Gastroenterol Hepatol. 2018;16(12):1851-63.
Dr. Moran is assistant professor of medicine, division of gastroenterology and hepatology, Medical University of South Carolina, Charleston; Dr. Elmunzer is the Peter Cotton Professor of Medicine and Endoscopic Innovation, division of gastroenterology and hepatology, Medical University of South Carolina. The authors have no conflicts of interest pertaining to this review.
Pancreatic fluid collections (PFCs) are common after acute pancreatitis but almost always resolve spontaneously. Persistent collections that cause symptoms, become infected, and/or compress vital structures require treatment. Open surgery had traditionally been considered the standard method for this indication;1 Given its inherently less invasive nature, endoscopic transmural drainage (ETMD) has become a mainstay of this step-up philosophy – it is now the dominant strategy for pseudocyst drainage and, on the basis of emerging randomized trial data, compares very favorably with surgery for the treatment of walled-off necrosis (WON).
According to the step-up approach, the initial treatment of symptomatic and/or infected collections that are within 4 weeks of an attack of pancreatitis involves conservative management because the wall of the collection is typically immature; the systemic inflammation may be significantly exacerbated by definitive drainage, particularly surgery. In this early phase, failure of conservative management is addressed by percutaneous catheter placement, stepping up to a minimally invasive operation if the response to percutaneous drainage and antibiotics is insufficient.
Collections that are at least 4 weeks from the onset of acute pancreatitis are considered mature and termed pseudocysts or WONs depending on whether they contain pure fluid or necrotic tissue. In this phase, endoscopic treatment plays a primary management role because these collections are generally adherent to the stomach or duodenal wall and their capsule is organized enough to withstand endoscopic intervention. If treatment can be held off until this phase, then percutaneous and surgical drainage can often be avoided.
In practice, the 4-week rule holds true for most, but not all, PFCs. ETMD can be performed in some particularly mature collections prior to 4 weeks if the indication is strong and the collection appears to have a mature wall. However, the potential for cyst wall perforation is higher and should be considered in the risk-benefit discussion. Conversely, some collections beyond 4 weeks lack an adequately organized wall and require additional time for maturation.
While endoscopic drainage of pseudocysts has essentially supplanted surgery, the management of WON is more complex and remains multidisciplinary. Two recent randomized trials demonstrated no difference in major complications and/or death between a surgical and endoscopic step-up strategy for WON.2,3 Rates of pancreatic fistulae, hospital stay, and overall treatment costs, however, favored endoscopy. Nevertheless, defining the ideal strategy for many of these patients with complexity requires multidisciplinary discussion. Surgery continues to play a primary role in several scenarios, including collections that are not close to the upper GI tract, those that are particularly complex and extend caudally, and situations in which the endoscopic progress is too slow.
The three most important questions when deciding to embark on ETMD are: (1) whether drainage is indicated (that is, is the patient symptomatic or is there evidence that the PFC is infected?), (2) whether the wall of the collection is adequately mature and apposed to the GI tract wall; and (3) whether the collection contains necrosis? This last question has critical implications in the technical approach to drainage. While CT scan with IV contrast is accurate for assessing wall maturity, it is inadequate to evaluate the presence or quantity of necrosum. Transabdominal ultrasound, endoscopic ultrasound, and MRI (on a T2 sequence) are all superior for this purpose. MRI has the additional benefit of assessing the pancreatic duct integrity, which may influence subsequent management.
Pseudocysts can be managed by cyst-gastrostomy or cyst-duodenostomy alone, whereas most WONs require the additional step of endoscopic necrosectomy – the process of entering the cyst cavity to mechanically debride necrotic tissue. Because of a higher rate of technical success, endoscopic ultrasound–directed creation of the transmural drainage pathway has become standard practice. In addition, it is likely safer, allowing for the identification and avoidance of interceding vessels and other vital structures. The role of endoscopic retrograde cholangiopancreatography with pancreatic stent placement as primary therapy for PFCs is limited to the drainage of small collections (<5 cm), for which it is the preferred treatment strategy. It is as effective as ETMD, which may not be feasible or safe for small PFCs.
Plastic double-pigtail stents have traditionally been used to maintain the transmural tract for both pseudocyst and WON. Recently, however, metallic stents have become more popular. Fully covered biliary self-expanding metallic stents (SEMS) are easier to place, have a larger lumen, and are associated with improved outcomes, compared with plastic stents in observational studies of pseudocyst drainage. Lumen-apposing metallic stents (LAMS) have become the preferred prosthesis for WON drainage given the ability to near-simultaneously establish access and deploy the stent, as well as their much larger caliber lumen which permits seamless entry into the cavity with an endoscope. Based on ease and efficiency of use, LAMS are also commonly employed for pseudocyst drainage, although entry into the cavity is unnecessary.
Plastic stents have been shown to be more cost effective than LAMS for pseudocyst drainage, although the economics around biliary SEMS in this context have not been explored. Robust comparative effectiveness data defining the optimal prostheses for pseudocysts are needed. The literature comparing LAMS to plastic stents for the management of WON is mixed. Studies have shown LAMS to be more cost effective, but a small randomized trial demonstrated no difference in clinical success or in the number of procedures to achieve WON resolution.4 We generally favor LAMS for WON since large-caliber balloon dilation of the tract seems safer within the lumen of the LAMS (which could seal small perforations and tamponade bleeding vessels) than within a freshly created tract.
Secondary infection of the cavity, usually because of stent occlusion, and bleeding are the most common complications of ETMD. Even in the absence of stent occlusion, contamination of the collection after ETMD is ubiquitous and, as such, we prescribe prophylactic antibiotics for 1-2 weeks after the procedure, although this practice is not evidence based. Hemorrhage appears to be increasing in frequency with the diffusion of LAMS; this has been postulated to be due to particularly rapid cyst cavity collapse resulting in erosion of the stent into contralateral cyst wall vessels. CT angiography followed by an embolization procedure for a possible pseudoaneurysm is the mainstay of treatment. Serious venous bleeding is more challenging to address because angiographic options are limited.
Despite tremendous recent advances, several important controversies in the endoscopic management of PFCs persist. The optimal prosthesis, the importance of first-session endoscopic necroscopy (compared with stepping up to endoscopic necroscopy only if necessary), the roles of adjunctive drain placement and chemical debridement (such as hydrogen peroxide), the need for concomitant pancreatic stent placement, and the preferred long-term management of a disconnected pancreatic duct are areas for which additional research is sorely needed. We further discuss these questions and many additional technical considerations pertaining to endoscopic drainage in a recent review.5
In summary, endoscopic transmural drainage of mature PFCs is effective and safe. Existing evidence supports its use as the favored treatment modality in appropriate candidates and has rendered it a mainstay of the therapeutic armamentarium for this disease. Further studies are needed to address critical unanswered questions and to develop a uniform endoscopic management paradigm.
References
1. van Santvoort HC et al. N Engl J Med. 2010;362(16):1491-502.
2. van Brunschot S et al. Lancet. 2018;391(10115):51-8.
3. Bang JY et al. Gastroenterology. 2019;156(4):1027-40.
4. Bang JY et al. Gut. 2019;68(7):1200-9.
5. Elmunzer BJ. Clin Gastroenterol Hepatol. 2018;16(12):1851-63.
Dr. Moran is assistant professor of medicine, division of gastroenterology and hepatology, Medical University of South Carolina, Charleston; Dr. Elmunzer is the Peter Cotton Professor of Medicine and Endoscopic Innovation, division of gastroenterology and hepatology, Medical University of South Carolina. The authors have no conflicts of interest pertaining to this review.
Identifying pancreatitis etiology may help prevent progression
Pancreatitis remains the third most common gastroenterological cause of hospital admission, and staying on top of the latest quality indicators is important for the care and safety of patients, said Jamie S. Barkin, MD, professor of medicine in the division of gastroenterology at the University of Miami, in a virtual presentation at the annual Digestive Diseases: New Advances conference jointly provided by Rutgers and Global Academy for Medical Education.
The basics of treatment have changed, said Dr. Barkin. “A large volume of ringers lactate intravenous fluids given within the first 24 hours of admission, as opposed to normal saline, may decrease the inflammatory response in patients with acute pancreatitis.” The preferred diagnostic method remains clinical evaluation along with use of serum lipase, which is more sensitive than serum amylase (97%) but with similar specificity (99%), and current wisdom does not support the need for an early CT for diagnosis unless there is a diagnostic dilemma.
Early establishment of disease etiology and its therapy is imperative to attempt to prevent recurrent episodes and progression to chronic pancreatitis, Dr. Barkin said. Genetic testing studies suggest that approximately 10% of acute pancreatitis cases are the result of genetic factors, and Dr. Barkin recommended performing genetic testing after a first attack of idiopathic acute pancreatitis, especially in younger patients.
There is an extensive list of medications that may cause acute pancreatitis, according to a recent study published in PLOS One, the most common of which include acetaminophen, amiodarone, azathioprine, and angiotensin-converting enzyme inhibitors, Dr. Barkin said. In addition, acute pancreatitis can be caused by isonicotinic acid hydrazide (INH), cannabis, L-asparaginase, metronidazole, mesalamine, simvastatin, sulindac, sitagliptin, thiazides, tigecycline, trans-retinoic acid, and valproic acid, among others.
Current recommendations for hospital treatment of acute pancreatitis include early large volume fluid replacement and initiation of per-oral nutrition as soon as able to be tolerated, as well as pain control, Dr. Barkin said. In addition, management includes strict glycemic and triglyceride control and performance of cholecystectomy for mild and or moderate biliary pancreatitis or endoscopic retrograde cholangiopancreatography (ERCP) if the patient is not an operative candidate during the same hospital stay.
Current recommendations for the prevention of acute pancreatitis include avoidance of irritants such as alcohol, nicotine, and drugs known to cause acute pancreatitis, including marijuana, said Dr. Barkin. In addition, controlling metabolic factors such as obesity, diabetes, and triglycerides can help reduce risk of recurrent episodes in susceptible patients. Several of these factors are also linked to increased risk for progression of acute pancreatitis to chronic pancreatitis.
For patients with biliary pancreatitis, Dr. Barkin noted that cholecystectomy should be performed prior to discharge during the index hospitalization. “In patients who cannot undergo surgery, endoscopic sphincterotomy should be performed to allow spontaneous passage of any stones still in the gallbladder,” he noted.
In addition, patients who have experienced an attack of acute pancreatitis should be screened long-term for development of pancreatic exocrine insufficiency, which may be present in approximately one-quarter of patients following an acute pancreatitis episode, and diabetes, Dr. Barkin said. He cited a population-based study published in the American Journal of Gastroenterology in 2019 in which individuals with postpancreatitis diabetes had significantly higher rates of all-cause mortality, as well as hospitalization for conditions including chronic pulmonary disease, severe renal disease, and infectious disease.
Finally, at the time of discharge, it is essential to evaluate acute pancreatitis patients for risk of readmission, Dr. Barkin said. In addition to severe disease and systemic inflammatory response syndrome at the time of patient discharge, several factors increase the likelihood of readmission including ongoing abdominal pain requiring use of pain medicine, obesity, and inability to tolerate solid food, he noted.
Global Academy for Medical Education and this news organization are owned by the same parent company.
Dr. Barkin had no relevant financial conflicts to disclose.
Share AGA GI Patient Center education on pancreatitis to help your patients understand testing and treatment options and possible complications at http://ow.ly/nsdn30rcz5A.
Pancreatitis remains the third most common gastroenterological cause of hospital admission, and staying on top of the latest quality indicators is important for the care and safety of patients, said Jamie S. Barkin, MD, professor of medicine in the division of gastroenterology at the University of Miami, in a virtual presentation at the annual Digestive Diseases: New Advances conference jointly provided by Rutgers and Global Academy for Medical Education.
The basics of treatment have changed, said Dr. Barkin. “A large volume of ringers lactate intravenous fluids given within the first 24 hours of admission, as opposed to normal saline, may decrease the inflammatory response in patients with acute pancreatitis.” The preferred diagnostic method remains clinical evaluation along with use of serum lipase, which is more sensitive than serum amylase (97%) but with similar specificity (99%), and current wisdom does not support the need for an early CT for diagnosis unless there is a diagnostic dilemma.
Early establishment of disease etiology and its therapy is imperative to attempt to prevent recurrent episodes and progression to chronic pancreatitis, Dr. Barkin said. Genetic testing studies suggest that approximately 10% of acute pancreatitis cases are the result of genetic factors, and Dr. Barkin recommended performing genetic testing after a first attack of idiopathic acute pancreatitis, especially in younger patients.
There is an extensive list of medications that may cause acute pancreatitis, according to a recent study published in PLOS One, the most common of which include acetaminophen, amiodarone, azathioprine, and angiotensin-converting enzyme inhibitors, Dr. Barkin said. In addition, acute pancreatitis can be caused by isonicotinic acid hydrazide (INH), cannabis, L-asparaginase, metronidazole, mesalamine, simvastatin, sulindac, sitagliptin, thiazides, tigecycline, trans-retinoic acid, and valproic acid, among others.
Current recommendations for hospital treatment of acute pancreatitis include early large volume fluid replacement and initiation of per-oral nutrition as soon as able to be tolerated, as well as pain control, Dr. Barkin said. In addition, management includes strict glycemic and triglyceride control and performance of cholecystectomy for mild and or moderate biliary pancreatitis or endoscopic retrograde cholangiopancreatography (ERCP) if the patient is not an operative candidate during the same hospital stay.
Current recommendations for the prevention of acute pancreatitis include avoidance of irritants such as alcohol, nicotine, and drugs known to cause acute pancreatitis, including marijuana, said Dr. Barkin. In addition, controlling metabolic factors such as obesity, diabetes, and triglycerides can help reduce risk of recurrent episodes in susceptible patients. Several of these factors are also linked to increased risk for progression of acute pancreatitis to chronic pancreatitis.
For patients with biliary pancreatitis, Dr. Barkin noted that cholecystectomy should be performed prior to discharge during the index hospitalization. “In patients who cannot undergo surgery, endoscopic sphincterotomy should be performed to allow spontaneous passage of any stones still in the gallbladder,” he noted.
In addition, patients who have experienced an attack of acute pancreatitis should be screened long-term for development of pancreatic exocrine insufficiency, which may be present in approximately one-quarter of patients following an acute pancreatitis episode, and diabetes, Dr. Barkin said. He cited a population-based study published in the American Journal of Gastroenterology in 2019 in which individuals with postpancreatitis diabetes had significantly higher rates of all-cause mortality, as well as hospitalization for conditions including chronic pulmonary disease, severe renal disease, and infectious disease.
Finally, at the time of discharge, it is essential to evaluate acute pancreatitis patients for risk of readmission, Dr. Barkin said. In addition to severe disease and systemic inflammatory response syndrome at the time of patient discharge, several factors increase the likelihood of readmission including ongoing abdominal pain requiring use of pain medicine, obesity, and inability to tolerate solid food, he noted.
Global Academy for Medical Education and this news organization are owned by the same parent company.
Dr. Barkin had no relevant financial conflicts to disclose.
Share AGA GI Patient Center education on pancreatitis to help your patients understand testing and treatment options and possible complications at http://ow.ly/nsdn30rcz5A.
Pancreatitis remains the third most common gastroenterological cause of hospital admission, and staying on top of the latest quality indicators is important for the care and safety of patients, said Jamie S. Barkin, MD, professor of medicine in the division of gastroenterology at the University of Miami, in a virtual presentation at the annual Digestive Diseases: New Advances conference jointly provided by Rutgers and Global Academy for Medical Education.
The basics of treatment have changed, said Dr. Barkin. “A large volume of ringers lactate intravenous fluids given within the first 24 hours of admission, as opposed to normal saline, may decrease the inflammatory response in patients with acute pancreatitis.” The preferred diagnostic method remains clinical evaluation along with use of serum lipase, which is more sensitive than serum amylase (97%) but with similar specificity (99%), and current wisdom does not support the need for an early CT for diagnosis unless there is a diagnostic dilemma.
Early establishment of disease etiology and its therapy is imperative to attempt to prevent recurrent episodes and progression to chronic pancreatitis, Dr. Barkin said. Genetic testing studies suggest that approximately 10% of acute pancreatitis cases are the result of genetic factors, and Dr. Barkin recommended performing genetic testing after a first attack of idiopathic acute pancreatitis, especially in younger patients.
There is an extensive list of medications that may cause acute pancreatitis, according to a recent study published in PLOS One, the most common of which include acetaminophen, amiodarone, azathioprine, and angiotensin-converting enzyme inhibitors, Dr. Barkin said. In addition, acute pancreatitis can be caused by isonicotinic acid hydrazide (INH), cannabis, L-asparaginase, metronidazole, mesalamine, simvastatin, sulindac, sitagliptin, thiazides, tigecycline, trans-retinoic acid, and valproic acid, among others.
Current recommendations for hospital treatment of acute pancreatitis include early large volume fluid replacement and initiation of per-oral nutrition as soon as able to be tolerated, as well as pain control, Dr. Barkin said. In addition, management includes strict glycemic and triglyceride control and performance of cholecystectomy for mild and or moderate biliary pancreatitis or endoscopic retrograde cholangiopancreatography (ERCP) if the patient is not an operative candidate during the same hospital stay.
Current recommendations for the prevention of acute pancreatitis include avoidance of irritants such as alcohol, nicotine, and drugs known to cause acute pancreatitis, including marijuana, said Dr. Barkin. In addition, controlling metabolic factors such as obesity, diabetes, and triglycerides can help reduce risk of recurrent episodes in susceptible patients. Several of these factors are also linked to increased risk for progression of acute pancreatitis to chronic pancreatitis.
For patients with biliary pancreatitis, Dr. Barkin noted that cholecystectomy should be performed prior to discharge during the index hospitalization. “In patients who cannot undergo surgery, endoscopic sphincterotomy should be performed to allow spontaneous passage of any stones still in the gallbladder,” he noted.
In addition, patients who have experienced an attack of acute pancreatitis should be screened long-term for development of pancreatic exocrine insufficiency, which may be present in approximately one-quarter of patients following an acute pancreatitis episode, and diabetes, Dr. Barkin said. He cited a population-based study published in the American Journal of Gastroenterology in 2019 in which individuals with postpancreatitis diabetes had significantly higher rates of all-cause mortality, as well as hospitalization for conditions including chronic pulmonary disease, severe renal disease, and infectious disease.
Finally, at the time of discharge, it is essential to evaluate acute pancreatitis patients for risk of readmission, Dr. Barkin said. In addition to severe disease and systemic inflammatory response syndrome at the time of patient discharge, several factors increase the likelihood of readmission including ongoing abdominal pain requiring use of pain medicine, obesity, and inability to tolerate solid food, he noted.
Global Academy for Medical Education and this news organization are owned by the same parent company.
Dr. Barkin had no relevant financial conflicts to disclose.
Share AGA GI Patient Center education on pancreatitis to help your patients understand testing and treatment options and possible complications at http://ow.ly/nsdn30rcz5A.
FROM DIGESTIVE DISEASES: NEW ADVANCES
Mounting data support COVID-19 acute pancreatitis
Mounting data support acute pancreatitis as one possible GI manifestation of COVID-19, according to investigators.
While previous case reports suggested that infection with SARS-CoV2 may lead to pancreatitis, this retrospective analysis, which is the largest to date, is the first to offer substantial evidence for this claim, reported lead author Sumant Inamdar, MBBS, of the University of Arkansas, Little Rock, and colleagues.
“It has become increasingly clear that COVID-19 has systemic effects that also includes the gastrointestinal and pancreaticobiliary systems,” the investigators wrote in Gastroenterology. “As islet cells of the pancreas contain ACE2 receptor proteins, SARS-CoV2 can bind to these receptors and cause pancreatic injury.”
For the present analysis, Dr. Inamdar and colleagues reviewed charts from 48,012 patients who were hospitalized in New York between March and June of this year. While pancreatitis is usually diagnosed based on two out of three criteria, disease classification in the study required all three: characteristic upper abdominal pain upon admission, lipase greater than three times the upper limit of normal, and evidence of pancreatitis on cross-sectional imaging.
“[B]y including all three criteria for pancreatitis in our definition, we may be underestimating the rate of pancreatitis,” the investigators wrote. “However, we felt including diagnostic lipase levels and imaging was important for the accuracy of the diagnosis.”
Primary outcomes included mechanical ventilation, length of stay, development of pancreatic necrosis, and mortality. Outcomes were compared between patients with and without COVID-19.
Out of 48,012 hospitalized patients, 11,883 (24.75%) tested positive for SARS-CoV2. Across the entire population, 189 patients had pancreatitis (0.39%), and of these, 32 (17%) also had COVID-19. This translates to a point prevalence for pancreatitis of 0.27% for patients hospitalized with COVID-19.
Among patients with pancreatitis who did not have COVID-19, the most common etiologies for pancreatitis were gallstones (34%) and alcohol (37%), compared with just 16% and 6% of SARS-CoV2-positive cases of pancreatitis, respectively. Idiopathic pancreatitis was significantly more common among patients with COVID-19 than those without (69% vs 21%; P less than .0001).
Black or Hispanic patients with pancreatitis were 4-5 times more likely to have COVID-19 than patients with pancreatitis who were white. Across all races/ethnicities, patients with pancreatitis and COVID-19 more often required mechanical ventilation (odds ratio [OR], 5.65) and longer hospital stays (OR, 3.22), compared with those who had pancreatitis alone. While rates of mortality and pancreatic necrosis showed similar trends, associations with COVID-19 were not statistically significant.
“These findings support the notion that pancreatitis should be included in the list of GI manifestations of COVID-19,” the investigators wrote.
When caring for patients with COVID-19, Dr. Inamdar and colleagues recommended that clinicians pay close attention to any history of abdominal pain, and consider testing serum lipase levels.
“Further large studies are needed to confirm our findings,” they concluded.
Avinash Ketwaroo, MD, of Baylor College of Medicine in Houston, agreed that more work is needed; in the meantime, he suggested that evidence is now strong enough for clinicians to take notice.
“Overall, this study adds further weight to COVID-19 acute pancreatitis,” he said. “Larger studies, and convincing pathophysiologic data, will be needed to confirm COVID-19 as a cause of acute pancreatitis. However, there appears to be enough circumstantial evidence to consider a COVID-19 diagnosis in patients presenting with acute pancreatitis.”
He noted that the new clinical evidence also stands on a solid theoretical foundation.
“Viruses, especially mumps and coxsackie, have long been known to cause acute pancreatitis,” he said. “Additionally, the ACE2 receptor is present on pancreatic beta-cells and may mediate COVID-19 induced pancreatitis.”
Along with larger observational studies, Dr. Ketwaroo suggested that a number of interventional questions remain unanswered.
“While most acute pancreatitis is treated with supportive care, could proven therapies for COVID-19, such as steroids, also mitigate COVID-19 acute pancreatitis?” he asked. “Is COVID-19 a cofactor for acute pancreatitis caused by alcohol or endoscopic retrograde cholangiopancreatography? We await further information from an active area of research.”
The investigators disclosed relationships with Boston Scientific, Olympus, Fujifilm, and others.
SOURCE: Inamdar S et al. Gastroenterology. 2020 Aug 26. doi: 10.1053/j.gastro.2020.08.044.
Share AGA GI Patient Center content to help your patients understand the symptoms and complications of pancreatitis at http://ow.ly/j1AN30r8ZDa.
This story was updated on 9/14/2020.
Mounting data support acute pancreatitis as one possible GI manifestation of COVID-19, according to investigators.
While previous case reports suggested that infection with SARS-CoV2 may lead to pancreatitis, this retrospective analysis, which is the largest to date, is the first to offer substantial evidence for this claim, reported lead author Sumant Inamdar, MBBS, of the University of Arkansas, Little Rock, and colleagues.
“It has become increasingly clear that COVID-19 has systemic effects that also includes the gastrointestinal and pancreaticobiliary systems,” the investigators wrote in Gastroenterology. “As islet cells of the pancreas contain ACE2 receptor proteins, SARS-CoV2 can bind to these receptors and cause pancreatic injury.”
For the present analysis, Dr. Inamdar and colleagues reviewed charts from 48,012 patients who were hospitalized in New York between March and June of this year. While pancreatitis is usually diagnosed based on two out of three criteria, disease classification in the study required all three: characteristic upper abdominal pain upon admission, lipase greater than three times the upper limit of normal, and evidence of pancreatitis on cross-sectional imaging.
“[B]y including all three criteria for pancreatitis in our definition, we may be underestimating the rate of pancreatitis,” the investigators wrote. “However, we felt including diagnostic lipase levels and imaging was important for the accuracy of the diagnosis.”
Primary outcomes included mechanical ventilation, length of stay, development of pancreatic necrosis, and mortality. Outcomes were compared between patients with and without COVID-19.
Out of 48,012 hospitalized patients, 11,883 (24.75%) tested positive for SARS-CoV2. Across the entire population, 189 patients had pancreatitis (0.39%), and of these, 32 (17%) also had COVID-19. This translates to a point prevalence for pancreatitis of 0.27% for patients hospitalized with COVID-19.
Among patients with pancreatitis who did not have COVID-19, the most common etiologies for pancreatitis were gallstones (34%) and alcohol (37%), compared with just 16% and 6% of SARS-CoV2-positive cases of pancreatitis, respectively. Idiopathic pancreatitis was significantly more common among patients with COVID-19 than those without (69% vs 21%; P less than .0001).
Black or Hispanic patients with pancreatitis were 4-5 times more likely to have COVID-19 than patients with pancreatitis who were white. Across all races/ethnicities, patients with pancreatitis and COVID-19 more often required mechanical ventilation (odds ratio [OR], 5.65) and longer hospital stays (OR, 3.22), compared with those who had pancreatitis alone. While rates of mortality and pancreatic necrosis showed similar trends, associations with COVID-19 were not statistically significant.
“These findings support the notion that pancreatitis should be included in the list of GI manifestations of COVID-19,” the investigators wrote.
When caring for patients with COVID-19, Dr. Inamdar and colleagues recommended that clinicians pay close attention to any history of abdominal pain, and consider testing serum lipase levels.
“Further large studies are needed to confirm our findings,” they concluded.
Avinash Ketwaroo, MD, of Baylor College of Medicine in Houston, agreed that more work is needed; in the meantime, he suggested that evidence is now strong enough for clinicians to take notice.
“Overall, this study adds further weight to COVID-19 acute pancreatitis,” he said. “Larger studies, and convincing pathophysiologic data, will be needed to confirm COVID-19 as a cause of acute pancreatitis. However, there appears to be enough circumstantial evidence to consider a COVID-19 diagnosis in patients presenting with acute pancreatitis.”
He noted that the new clinical evidence also stands on a solid theoretical foundation.
“Viruses, especially mumps and coxsackie, have long been known to cause acute pancreatitis,” he said. “Additionally, the ACE2 receptor is present on pancreatic beta-cells and may mediate COVID-19 induced pancreatitis.”
Along with larger observational studies, Dr. Ketwaroo suggested that a number of interventional questions remain unanswered.
“While most acute pancreatitis is treated with supportive care, could proven therapies for COVID-19, such as steroids, also mitigate COVID-19 acute pancreatitis?” he asked. “Is COVID-19 a cofactor for acute pancreatitis caused by alcohol or endoscopic retrograde cholangiopancreatography? We await further information from an active area of research.”
The investigators disclosed relationships with Boston Scientific, Olympus, Fujifilm, and others.
SOURCE: Inamdar S et al. Gastroenterology. 2020 Aug 26. doi: 10.1053/j.gastro.2020.08.044.
Share AGA GI Patient Center content to help your patients understand the symptoms and complications of pancreatitis at http://ow.ly/j1AN30r8ZDa.
This story was updated on 9/14/2020.
Mounting data support acute pancreatitis as one possible GI manifestation of COVID-19, according to investigators.
While previous case reports suggested that infection with SARS-CoV2 may lead to pancreatitis, this retrospective analysis, which is the largest to date, is the first to offer substantial evidence for this claim, reported lead author Sumant Inamdar, MBBS, of the University of Arkansas, Little Rock, and colleagues.
“It has become increasingly clear that COVID-19 has systemic effects that also includes the gastrointestinal and pancreaticobiliary systems,” the investigators wrote in Gastroenterology. “As islet cells of the pancreas contain ACE2 receptor proteins, SARS-CoV2 can bind to these receptors and cause pancreatic injury.”
For the present analysis, Dr. Inamdar and colleagues reviewed charts from 48,012 patients who were hospitalized in New York between March and June of this year. While pancreatitis is usually diagnosed based on two out of three criteria, disease classification in the study required all three: characteristic upper abdominal pain upon admission, lipase greater than three times the upper limit of normal, and evidence of pancreatitis on cross-sectional imaging.
“[B]y including all three criteria for pancreatitis in our definition, we may be underestimating the rate of pancreatitis,” the investigators wrote. “However, we felt including diagnostic lipase levels and imaging was important for the accuracy of the diagnosis.”
Primary outcomes included mechanical ventilation, length of stay, development of pancreatic necrosis, and mortality. Outcomes were compared between patients with and without COVID-19.
Out of 48,012 hospitalized patients, 11,883 (24.75%) tested positive for SARS-CoV2. Across the entire population, 189 patients had pancreatitis (0.39%), and of these, 32 (17%) also had COVID-19. This translates to a point prevalence for pancreatitis of 0.27% for patients hospitalized with COVID-19.
Among patients with pancreatitis who did not have COVID-19, the most common etiologies for pancreatitis were gallstones (34%) and alcohol (37%), compared with just 16% and 6% of SARS-CoV2-positive cases of pancreatitis, respectively. Idiopathic pancreatitis was significantly more common among patients with COVID-19 than those without (69% vs 21%; P less than .0001).
Black or Hispanic patients with pancreatitis were 4-5 times more likely to have COVID-19 than patients with pancreatitis who were white. Across all races/ethnicities, patients with pancreatitis and COVID-19 more often required mechanical ventilation (odds ratio [OR], 5.65) and longer hospital stays (OR, 3.22), compared with those who had pancreatitis alone. While rates of mortality and pancreatic necrosis showed similar trends, associations with COVID-19 were not statistically significant.
“These findings support the notion that pancreatitis should be included in the list of GI manifestations of COVID-19,” the investigators wrote.
When caring for patients with COVID-19, Dr. Inamdar and colleagues recommended that clinicians pay close attention to any history of abdominal pain, and consider testing serum lipase levels.
“Further large studies are needed to confirm our findings,” they concluded.
Avinash Ketwaroo, MD, of Baylor College of Medicine in Houston, agreed that more work is needed; in the meantime, he suggested that evidence is now strong enough for clinicians to take notice.
“Overall, this study adds further weight to COVID-19 acute pancreatitis,” he said. “Larger studies, and convincing pathophysiologic data, will be needed to confirm COVID-19 as a cause of acute pancreatitis. However, there appears to be enough circumstantial evidence to consider a COVID-19 diagnosis in patients presenting with acute pancreatitis.”
He noted that the new clinical evidence also stands on a solid theoretical foundation.
“Viruses, especially mumps and coxsackie, have long been known to cause acute pancreatitis,” he said. “Additionally, the ACE2 receptor is present on pancreatic beta-cells and may mediate COVID-19 induced pancreatitis.”
Along with larger observational studies, Dr. Ketwaroo suggested that a number of interventional questions remain unanswered.
“While most acute pancreatitis is treated with supportive care, could proven therapies for COVID-19, such as steroids, also mitigate COVID-19 acute pancreatitis?” he asked. “Is COVID-19 a cofactor for acute pancreatitis caused by alcohol or endoscopic retrograde cholangiopancreatography? We await further information from an active area of research.”
The investigators disclosed relationships with Boston Scientific, Olympus, Fujifilm, and others.
SOURCE: Inamdar S et al. Gastroenterology. 2020 Aug 26. doi: 10.1053/j.gastro.2020.08.044.
Share AGA GI Patient Center content to help your patients understand the symptoms and complications of pancreatitis at http://ow.ly/j1AN30r8ZDa.
This story was updated on 9/14/2020.
FROM GASTROENTEROLOGY
Diabetes plus weight loss equals increased risk of pancreatic cancer
A new study has linked recent-onset diabetes and subsequent weight loss to an increased risk of pancreatic cancer, indicating a distinct group of individuals to screen early for this deadly disease.
“The likelihood of a pancreatic cancer diagnosis was even further elevated among individuals with older age, healthy weight before weight loss, and unintentional weight loss,” wrote Chen Yuan, ScD, of the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston. The study was published in JAMA Oncology.
To determine whether an association exists between diabetes plus weight change and pancreatic cancer, the researchers analyzed decades of medical history data from the Nurses’ Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS). The study population from the NHS included 112,818 women with a mean age of 59 years; the population from the HPFS included 46,207 men with a mean age of 65 years. Since enrollment – the baseline was 1978 for the NHS and 1988 for the HPFS – participants have provided follow-up information via biennial questionnaires.
Recent diabetes onset, weight loss boost cancer risk
From those combined groups, 1,116 incident cases of pancreatic cancer (0.7%) were identified. Compared with patients with no diabetes, patients with recent-onset diabetes had triple the risk of pancreatic cancer (age-adjusted hazard ratio, 2.97; 95% confidence interval, 2.31-3.82) and patients with longstanding diabetes had more than double the risk (HR, 2.16; 95% CI, 1.78-2.60). Patients with longer disease duration also had more than twice the risk of pancreatic cancer, with HRs of 2.25 for those with diabetes for 4-10 years (95% CI, 1.74-2.92) and 2.07 for more than 10 years (95% CI, 1.61-2.66).
Compared with patients who hadn’t lost any weight, patients who reported a 1- to 4-pound weight loss (HR, 1.25; 95% CI, 1.03-1.52), a 5- to 8-pound weight loss (HR, 1.33; 95% CI, 1.06-1.66), and a more than 8-pound weight loss (HR, 1.92; 95% CI, 1.58-2.32) had higher risks of pancreatic cancer. Patients with recent-onset diabetes and a 1- to 8-pound weight loss (91 incident cases per 100,000 person-years; 95% CI, 55-151) or a weight loss of more than 8 pounds (164 incident cases per 100,000 person years; 95% CI, 114-238) had a much higher incidence of pancreatic cancer, compared with patients with neither (16 incident cases per 100,000 person-years; 95% CI, 14-17).
After stratified analyses of patients with both recent-onset diabetes and weight loss, rates of pancreatic cancer were also notably high in those 70 years or older (234 cases per 100,000 person years), those with a body mass index of less than 25 kg/m2 before weight loss (400 cases per 100,000 person years), and those with a low likelihood of intentional weight loss (334 cases per 100,000 person years).
“I like the study because it reminds us of the importance of not thinking everyone that presents with type 2 diabetes necessarily has garden-variety diabetes,” Paul Jellinger, MD, of the Center for Diabetes and Endocrine Care in Hollywood, Fla., said in an interview. “I have always been concerned when a new-onset diabetic individual presents with no family history of diabetes or prediabetes, especially if they’re neither overweight nor obese. I have sometimes screened those individuals for pancreatic abnormalities.”
A call for screening
“This study highlights the consideration for further screening to those with weight loss at the time of diabetes diagnosis, which is very sensible given how unusual weight loss is as a presenting symptom at the time of diagnosis of typical type 2 diabetes,” Dr. Jellinger added. “The combination of weight loss and no family history of diabetes at the time of diagnosis should be an even stronger signal for pancreatic cancer screening and potential detection at a much earlier stage.”
The authors acknowledged their study’s limitations, including some patients with pancreatic cancer not returning their questionnaires and the timing of the questionnaires meaning that patients could’ve developed diabetes after returning it. In addition, they recognized that the participants were “predominantly White health professionals” and recommended a study of “additional patient populations” in the future.
The authors noted numerous potential conflicts of interest, including receiving grants and personal fees from various initiatives, organizations, and pharmaceutical companies.
Review the “AGA Clinical Practice Update on Pancreas Cancer Screening in High-Risk Individuals: Expert Review” for best practice advice for clinicians screening and diagnosing pancreatic cancer in high-risk individuals. Learn more at http://ow.ly/vwTR30r4Zwu.
SOURCE: Yuan C et al. JAMA Oncol. 2020 Aug 13. doi: 10.1001/jamaoncol.2020.2948.
A new study has linked recent-onset diabetes and subsequent weight loss to an increased risk of pancreatic cancer, indicating a distinct group of individuals to screen early for this deadly disease.
“The likelihood of a pancreatic cancer diagnosis was even further elevated among individuals with older age, healthy weight before weight loss, and unintentional weight loss,” wrote Chen Yuan, ScD, of the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston. The study was published in JAMA Oncology.
To determine whether an association exists between diabetes plus weight change and pancreatic cancer, the researchers analyzed decades of medical history data from the Nurses’ Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS). The study population from the NHS included 112,818 women with a mean age of 59 years; the population from the HPFS included 46,207 men with a mean age of 65 years. Since enrollment – the baseline was 1978 for the NHS and 1988 for the HPFS – participants have provided follow-up information via biennial questionnaires.
Recent diabetes onset, weight loss boost cancer risk
From those combined groups, 1,116 incident cases of pancreatic cancer (0.7%) were identified. Compared with patients with no diabetes, patients with recent-onset diabetes had triple the risk of pancreatic cancer (age-adjusted hazard ratio, 2.97; 95% confidence interval, 2.31-3.82) and patients with longstanding diabetes had more than double the risk (HR, 2.16; 95% CI, 1.78-2.60). Patients with longer disease duration also had more than twice the risk of pancreatic cancer, with HRs of 2.25 for those with diabetes for 4-10 years (95% CI, 1.74-2.92) and 2.07 for more than 10 years (95% CI, 1.61-2.66).
Compared with patients who hadn’t lost any weight, patients who reported a 1- to 4-pound weight loss (HR, 1.25; 95% CI, 1.03-1.52), a 5- to 8-pound weight loss (HR, 1.33; 95% CI, 1.06-1.66), and a more than 8-pound weight loss (HR, 1.92; 95% CI, 1.58-2.32) had higher risks of pancreatic cancer. Patients with recent-onset diabetes and a 1- to 8-pound weight loss (91 incident cases per 100,000 person-years; 95% CI, 55-151) or a weight loss of more than 8 pounds (164 incident cases per 100,000 person years; 95% CI, 114-238) had a much higher incidence of pancreatic cancer, compared with patients with neither (16 incident cases per 100,000 person-years; 95% CI, 14-17).
After stratified analyses of patients with both recent-onset diabetes and weight loss, rates of pancreatic cancer were also notably high in those 70 years or older (234 cases per 100,000 person years), those with a body mass index of less than 25 kg/m2 before weight loss (400 cases per 100,000 person years), and those with a low likelihood of intentional weight loss (334 cases per 100,000 person years).
“I like the study because it reminds us of the importance of not thinking everyone that presents with type 2 diabetes necessarily has garden-variety diabetes,” Paul Jellinger, MD, of the Center for Diabetes and Endocrine Care in Hollywood, Fla., said in an interview. “I have always been concerned when a new-onset diabetic individual presents with no family history of diabetes or prediabetes, especially if they’re neither overweight nor obese. I have sometimes screened those individuals for pancreatic abnormalities.”
A call for screening
“This study highlights the consideration for further screening to those with weight loss at the time of diabetes diagnosis, which is very sensible given how unusual weight loss is as a presenting symptom at the time of diagnosis of typical type 2 diabetes,” Dr. Jellinger added. “The combination of weight loss and no family history of diabetes at the time of diagnosis should be an even stronger signal for pancreatic cancer screening and potential detection at a much earlier stage.”
The authors acknowledged their study’s limitations, including some patients with pancreatic cancer not returning their questionnaires and the timing of the questionnaires meaning that patients could’ve developed diabetes after returning it. In addition, they recognized that the participants were “predominantly White health professionals” and recommended a study of “additional patient populations” in the future.
The authors noted numerous potential conflicts of interest, including receiving grants and personal fees from various initiatives, organizations, and pharmaceutical companies.
Review the “AGA Clinical Practice Update on Pancreas Cancer Screening in High-Risk Individuals: Expert Review” for best practice advice for clinicians screening and diagnosing pancreatic cancer in high-risk individuals. Learn more at http://ow.ly/vwTR30r4Zwu.
SOURCE: Yuan C et al. JAMA Oncol. 2020 Aug 13. doi: 10.1001/jamaoncol.2020.2948.
A new study has linked recent-onset diabetes and subsequent weight loss to an increased risk of pancreatic cancer, indicating a distinct group of individuals to screen early for this deadly disease.
“The likelihood of a pancreatic cancer diagnosis was even further elevated among individuals with older age, healthy weight before weight loss, and unintentional weight loss,” wrote Chen Yuan, ScD, of the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston. The study was published in JAMA Oncology.
To determine whether an association exists between diabetes plus weight change and pancreatic cancer, the researchers analyzed decades of medical history data from the Nurses’ Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS). The study population from the NHS included 112,818 women with a mean age of 59 years; the population from the HPFS included 46,207 men with a mean age of 65 years. Since enrollment – the baseline was 1978 for the NHS and 1988 for the HPFS – participants have provided follow-up information via biennial questionnaires.
Recent diabetes onset, weight loss boost cancer risk
From those combined groups, 1,116 incident cases of pancreatic cancer (0.7%) were identified. Compared with patients with no diabetes, patients with recent-onset diabetes had triple the risk of pancreatic cancer (age-adjusted hazard ratio, 2.97; 95% confidence interval, 2.31-3.82) and patients with longstanding diabetes had more than double the risk (HR, 2.16; 95% CI, 1.78-2.60). Patients with longer disease duration also had more than twice the risk of pancreatic cancer, with HRs of 2.25 for those with diabetes for 4-10 years (95% CI, 1.74-2.92) and 2.07 for more than 10 years (95% CI, 1.61-2.66).
Compared with patients who hadn’t lost any weight, patients who reported a 1- to 4-pound weight loss (HR, 1.25; 95% CI, 1.03-1.52), a 5- to 8-pound weight loss (HR, 1.33; 95% CI, 1.06-1.66), and a more than 8-pound weight loss (HR, 1.92; 95% CI, 1.58-2.32) had higher risks of pancreatic cancer. Patients with recent-onset diabetes and a 1- to 8-pound weight loss (91 incident cases per 100,000 person-years; 95% CI, 55-151) or a weight loss of more than 8 pounds (164 incident cases per 100,000 person years; 95% CI, 114-238) had a much higher incidence of pancreatic cancer, compared with patients with neither (16 incident cases per 100,000 person-years; 95% CI, 14-17).
After stratified analyses of patients with both recent-onset diabetes and weight loss, rates of pancreatic cancer were also notably high in those 70 years or older (234 cases per 100,000 person years), those with a body mass index of less than 25 kg/m2 before weight loss (400 cases per 100,000 person years), and those with a low likelihood of intentional weight loss (334 cases per 100,000 person years).
“I like the study because it reminds us of the importance of not thinking everyone that presents with type 2 diabetes necessarily has garden-variety diabetes,” Paul Jellinger, MD, of the Center for Diabetes and Endocrine Care in Hollywood, Fla., said in an interview. “I have always been concerned when a new-onset diabetic individual presents with no family history of diabetes or prediabetes, especially if they’re neither overweight nor obese. I have sometimes screened those individuals for pancreatic abnormalities.”
A call for screening
“This study highlights the consideration for further screening to those with weight loss at the time of diabetes diagnosis, which is very sensible given how unusual weight loss is as a presenting symptom at the time of diagnosis of typical type 2 diabetes,” Dr. Jellinger added. “The combination of weight loss and no family history of diabetes at the time of diagnosis should be an even stronger signal for pancreatic cancer screening and potential detection at a much earlier stage.”
The authors acknowledged their study’s limitations, including some patients with pancreatic cancer not returning their questionnaires and the timing of the questionnaires meaning that patients could’ve developed diabetes after returning it. In addition, they recognized that the participants were “predominantly White health professionals” and recommended a study of “additional patient populations” in the future.
The authors noted numerous potential conflicts of interest, including receiving grants and personal fees from various initiatives, organizations, and pharmaceutical companies.
Review the “AGA Clinical Practice Update on Pancreas Cancer Screening in High-Risk Individuals: Expert Review” for best practice advice for clinicians screening and diagnosing pancreatic cancer in high-risk individuals. Learn more at http://ow.ly/vwTR30r4Zwu.
SOURCE: Yuan C et al. JAMA Oncol. 2020 Aug 13. doi: 10.1001/jamaoncol.2020.2948.
FROM JAMA ONCOLOGY
COVID-associated pancreatitis may disproportionately affect young, overweight men
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.
FROM GASTROENTEROLOGY
Observation pathway safely reduces acute pancreatitis hospitalization rate
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.
FROM JOURNAL OF CLINICAL GASTROENTEROLOGY
Key clinical point: For patients diagnosed with mild acute pancreatitis in the ED, an observation pathway may significantly reduce hospitalization rate and associated costs without compromising patient safety.
Major finding: An observational approach to mild acute pancreatitis reduced hospitalization rate by 31.2%.
Study details: A prospective trial involving 118 patients with mild acute pancreatitis.
Disclosures: The investigators reported no conflicts of interest.
Source: Ahmed A et al. J Clin Gastroenterol. 2020 Apr 14. doi: 10.1097/MCG.0000000000001354.
Genotyping improves accuracy of pancreatic cancer tumor markers
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.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Pancreatic enzyme replacement flunked randomized trial
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.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY