Pancreas and Biliary Tract

SAN DIEGO – Patients on systemic anticoagulation had decreased odds of acute pancreatitis occurrence, reduced mortality, and improved outcomes, compared with patients who were not on systemic anticoagulation, results from a large retrospective analysis showed.

“Acute pancreatitis is a very common disease,” lead study author Yan Bi, MD, PhD, a senior associate consultant and assistant professor in the department of gastroenterology and hepatology at Mayo Clinic, Jacksonville, Fla., said in an interview in advance of the annual Digestive Disease Week. “It’s the number one GI cause for hospitalization. Unfortunately, even after decades of basic science and clinical research, there’s still no cure; there’s nothing to prevent it from happening. The only treatment we can offer is supportive care, which includes fluid hydration, pain control, and nutrition support.”

The pathogenesis of acute pancreatitis (AP) is complex, she continued, and represents a sequence of distinct and interconnected pathologic events. “Both animal data and human studies have shown that acute pancreatitis is a hypercoagulable state,” she said. “We hypothesize that coagulation plays important roles in the development of pancreatitis.”

To test their hypothesis, Dr. Bi and associates performed a retrospective study. They drew from the 2014 National Inpatient Sample to evaluate the effect of systemic anticoagulation prior to AP onset on outcomes of the condition. They used ICD-9 codes to identify patients with a primary diagnosis of AP as well as those who were taking systemic anticoagulation. The primary outcome was the odds of AP in patients taking systemic anticoagulation, compared with those who were not. Secondary outcomes were mortality, morbidity, length of hospital stay, and total hospitalization charges and costs. The researchers used propensity score matching to create a 1:1 matching population for sex, age, and Charlson Comorbidity Index, and multivariate regression to adjust for patient ZIP code, income, hospital region, location, size, and teaching status.


Dr. Bi presented results from 442,535 patients with AP. Of these, 12,735 were on systemic anticoagulation prior to AP. Their mean age was 66 and 47% were female. After adjustment for confounders, patients on systemic anticoagulation prior to AP onset displayed a decreased odds of AP occurrence, compared with those who were not on anticoagulation (OR 0.56; P less than .01). In addition, patients on anticoagulation displayed improved outcomes in a number of variables, compared with their counterparts who were not on anticoagulation: mortality (OR 0.65), shock (OR 0.68), acute kidney injury (OR 0.83), ICU admission (OR 0.57), multiorgan failure (OR 0.85), and hospital charges (a mean reduction of $9,275), as well as AP induced by alcohol use (OR 0.26; P less than .01 for all associations). “These data suggest that the majority of AP associated with alcohol was prevented by anticoagulation medication,” Dr. Bi said. “This is very striking. Anticoagulation may hold promise in both the prevention and treatment of AP.”

To further prove their points, Dr. Bi teamed with Baoan Ji, MD, PhD, a basic research scientist at Mayo Clinic, and developed a humanized AP animal model. With this model, they showed that Pradaxa, a Food and Drug Administration–approved anticoagulant, is effective in experimental AP prevention and treatment. “We are currently enrolling patients into a prospective clinical trial to further prove this in humans,” Dr. Bi said. The experimental therapeutic study will be reported at DDW on May 20.

She cautioned against using systemic anticoagulants in this patient population before results of the trial currently underway at Mayo Clinic’s Florida campus are known. “That should be sometime in mid-2020,” she said. “And the bleeding risk should be carefully monitored when using anticoagulants.”

The researchers were supported by funding from the Mayo Clinic and the Department of Defense.

dbrunk@mdedge.com

SOURCE: Bi Y et al. DDW 2019, Abstract Sa1381.

SAN DIEGO – Patients on systemic anticoagulation had decreased odds of acute pancreatitis occurrence, reduced mortality, and improved outcomes, compared with patients who were not on systemic anticoagulation, results from a large retrospective analysis showed.

“Acute pancreatitis is a very common disease,” lead study author Yan Bi, MD, PhD, a senior associate consultant and assistant professor in the department of gastroenterology and hepatology at Mayo Clinic, Jacksonville, Fla., said in an interview in advance of the annual Digestive Disease Week. “It’s the number one GI cause for hospitalization. Unfortunately, even after decades of basic science and clinical research, there’s still no cure; there’s nothing to prevent it from happening. The only treatment we can offer is supportive care, which includes fluid hydration, pain control, and nutrition support.”

The pathogenesis of acute pancreatitis (AP) is complex, she continued, and represents a sequence of distinct and interconnected pathologic events. “Both animal data and human studies have shown that acute pancreatitis is a hypercoagulable state,” she said. “We hypothesize that coagulation plays important roles in the development of pancreatitis.”

To test their hypothesis, Dr. Bi and associates performed a retrospective study. They drew from the 2014 National Inpatient Sample to evaluate the effect of systemic anticoagulation prior to AP onset on outcomes of the condition. They used ICD-9 codes to identify patients with a primary diagnosis of AP as well as those who were taking systemic anticoagulation. The primary outcome was the odds of AP in patients taking systemic anticoagulation, compared with those who were not. Secondary outcomes were mortality, morbidity, length of hospital stay, and total hospitalization charges and costs. The researchers used propensity score matching to create a 1:1 matching population for sex, age, and Charlson Comorbidity Index, and multivariate regression to adjust for patient ZIP code, income, hospital region, location, size, and teaching status.


Dr. Bi presented results from 442,535 patients with AP. Of these, 12,735 were on systemic anticoagulation prior to AP. Their mean age was 66 and 47% were female. After adjustment for confounders, patients on systemic anticoagulation prior to AP onset displayed a decreased odds of AP occurrence, compared with those who were not on anticoagulation (OR 0.56; P less than .01). In addition, patients on anticoagulation displayed improved outcomes in a number of variables, compared with their counterparts who were not on anticoagulation: mortality (OR 0.65), shock (OR 0.68), acute kidney injury (OR 0.83), ICU admission (OR 0.57), multiorgan failure (OR 0.85), and hospital charges (a mean reduction of $9,275), as well as AP induced by alcohol use (OR 0.26; P less than .01 for all associations). “These data suggest that the majority of AP associated with alcohol was prevented by anticoagulation medication,” Dr. Bi said. “This is very striking. Anticoagulation may hold promise in both the prevention and treatment of AP.”

To further prove their points, Dr. Bi teamed with Baoan Ji, MD, PhD, a basic research scientist at Mayo Clinic, and developed a humanized AP animal model. With this model, they showed that Pradaxa, a Food and Drug Administration–approved anticoagulant, is effective in experimental AP prevention and treatment. “We are currently enrolling patients into a prospective clinical trial to further prove this in humans,” Dr. Bi said. The experimental therapeutic study will be reported at DDW on May 20.

She cautioned against using systemic anticoagulants in this patient population before results of the trial currently underway at Mayo Clinic’s Florida campus are known. “That should be sometime in mid-2020,” she said. “And the bleeding risk should be carefully monitored when using anticoagulants.”

The researchers were supported by funding from the Mayo Clinic and the Department of Defense.

dbrunk@mdedge.com

SOURCE: Bi Y et al. DDW 2019, Abstract Sa1381.

SAN DIEGO – Patients on systemic anticoagulation had decreased odds of acute pancreatitis occurrence, reduced mortality, and improved outcomes, compared with patients who were not on systemic anticoagulation, results from a large retrospective analysis showed.

“Acute pancreatitis is a very common disease,” lead study author Yan Bi, MD, PhD, a senior associate consultant and assistant professor in the department of gastroenterology and hepatology at Mayo Clinic, Jacksonville, Fla., said in an interview in advance of the annual Digestive Disease Week. “It’s the number one GI cause for hospitalization. Unfortunately, even after decades of basic science and clinical research, there’s still no cure; there’s nothing to prevent it from happening. The only treatment we can offer is supportive care, which includes fluid hydration, pain control, and nutrition support.”

The pathogenesis of acute pancreatitis (AP) is complex, she continued, and represents a sequence of distinct and interconnected pathologic events. “Both animal data and human studies have shown that acute pancreatitis is a hypercoagulable state,” she said. “We hypothesize that coagulation plays important roles in the development of pancreatitis.”

To test their hypothesis, Dr. Bi and associates performed a retrospective study. They drew from the 2014 National Inpatient Sample to evaluate the effect of systemic anticoagulation prior to AP onset on outcomes of the condition. They used ICD-9 codes to identify patients with a primary diagnosis of AP as well as those who were taking systemic anticoagulation. The primary outcome was the odds of AP in patients taking systemic anticoagulation, compared with those who were not. Secondary outcomes were mortality, morbidity, length of hospital stay, and total hospitalization charges and costs. The researchers used propensity score matching to create a 1:1 matching population for sex, age, and Charlson Comorbidity Index, and multivariate regression to adjust for patient ZIP code, income, hospital region, location, size, and teaching status.


Dr. Bi presented results from 442,535 patients with AP. Of these, 12,735 were on systemic anticoagulation prior to AP. Their mean age was 66 and 47% were female. After adjustment for confounders, patients on systemic anticoagulation prior to AP onset displayed a decreased odds of AP occurrence, compared with those who were not on anticoagulation (OR 0.56; P less than .01). In addition, patients on anticoagulation displayed improved outcomes in a number of variables, compared with their counterparts who were not on anticoagulation: mortality (OR 0.65), shock (OR 0.68), acute kidney injury (OR 0.83), ICU admission (OR 0.57), multiorgan failure (OR 0.85), and hospital charges (a mean reduction of $9,275), as well as AP induced by alcohol use (OR 0.26; P less than .01 for all associations). “These data suggest that the majority of AP associated with alcohol was prevented by anticoagulation medication,” Dr. Bi said. “This is very striking. Anticoagulation may hold promise in both the prevention and treatment of AP.”

To further prove their points, Dr. Bi teamed with Baoan Ji, MD, PhD, a basic research scientist at Mayo Clinic, and developed a humanized AP animal model. With this model, they showed that Pradaxa, a Food and Drug Administration–approved anticoagulant, is effective in experimental AP prevention and treatment. “We are currently enrolling patients into a prospective clinical trial to further prove this in humans,” Dr. Bi said. The experimental therapeutic study will be reported at DDW on May 20.

She cautioned against using systemic anticoagulants in this patient population before results of the trial currently underway at Mayo Clinic’s Florida campus are known. “That should be sometime in mid-2020,” she said. “And the bleeding risk should be carefully monitored when using anticoagulants.”

The researchers were supported by funding from the Mayo Clinic and the Department of Defense.

dbrunk@mdedge.com

SOURCE: Bi Y et al. DDW 2019, Abstract Sa1381.

Introduction

Acute pancreatitis (AP) is a major clinical and financial burden in the United States. Several major clinical guidelines provide evidence-based recommendations for the clinical management decisions in AP, including those from the American College of Gastroenterology (ACG; 2013),¹ and the International Association of Pancreatology (IAP; 2013).² More recently, the American Gastroenterological Association (AGA) released their own set of guidelines.^3,4 In this update on AP, we review these guidelines and reference recent literature focused on epidemiology, risk factors, etiology, diagnosis, risk stratification, and recent advances in the early medical management of AP. Regarding the latter, we review six treatment interventions (pain management, intravenous fluid resuscitation, feeding, prophylactic antibiotics, probiotics, and timing of endoscopic retrograde cholangiopancreatography (ERCP) in acute biliary pancreatitis) and four preventive interventions (alcohol and smoking cessation, same-admission cholecystectomy for acute biliary pancreatitis, and chemoprevention and fluid administration for post-ERCP pancreatitis [PEP]). Updates on multidisciplinary management of (infected) pancreatic necrosis is beyond the scope of this review. Table 1 summarizes the concepts discussed in this article.

Recent advances in epidemiology and evaluation of AP

Epidemiology

AP is the third most common cause of gastrointestinal-related hospitalizations and fourth most common cause of readmission in 2014.⁵ Recent epidemiologic studies show conflicting trends for the incidence of AP, both increasing⁶ and decreasing,⁷ likely attributable to significant differences in study designs. Importantly, multiple studies have demonstrated that hospital length of stay, costs, and mortality have declined since 2009.^6,8-10

Persistent organ failure (POF), defined as organ failure lasting more than 48 hours, is the major cause of death in AP. POF, if only a single organ during AP, is associated with 27%-36% mortality; if it is multiorgan, it is associated with 47% mortality.^1,11 Other factors associated with increased hospital mortality include infected pancreatic necrosis,^12-14 diabetes mellitus,¹⁵ hospital-acquired infection,¹⁶ advanced age (70 years and older),¹⁷ and obesity.¹⁸ Predictive factors of 1-year mortality include readmission within 30 days, higher Charlson Comorbidity Index, and longer hospitalization.¹⁹

Risk factors

We briefly highlight recent insights into risk factors for AP (Table 1) and refer to a recent review for further discussion.²⁰ Current and former tobacco use are independent risk factors for AP.²¹ The dose-response relationship of alcohol to the risk of pancreatitis is complex,²² but five standard drinks per day for 5 years is a commonly used cut-off.^1,23 New evidence suggests that the relationship between the dose of alcohol and risk of AP differs by sex, linearly in men but nonlinearly (J-shaped) in women.²⁴ Risk of AP in women was decreased with alcohol consumption of up to 40 g/day (one standard drink contains 14 g of alcohol) and increased above this amount. Cannabis is a possible risk factor for toxin-induced AP and abstinence appears to abolish risk of recurrent attacks.²⁵

Patients with inflammatory bowel disease (IBD) have a 2.9-fold higher risk for AP versus non-IBD cohorts²⁶ with the most common etiologies are from gallstones and medications.²⁷ In patients with end-stage renal disease (ESRD), the risk of AP is higher in those who receive peritoneal dialysis, compared with hemodialysis^28-33 and who are women, older, or have cholelithiasis or liver disease.³⁴As recently reviewed,³⁵ pancreatic cancer appears to be associated with first-attack pancreatitis with few exceptions.³⁶ In this setting, the overall incidence of pancreatic cancer is low (1.5%). The risk is greatest within the first year of the attack of AP, negligible below age 40 years but steadily rising through the fifth to eighth decades.³⁷ Pancreatic cancer screening is a conditional recommendation of the ACG guidelines in patients with unexplained AP, particularly those aged 40 years or older.¹

Etiology and diagnosis

Alcohol and gallstones remain the most prevalent etiologies for AP.¹ While hypertriglyceridemia accounted for 9% of AP in a systematic review of acute pancreatitis in 15 different countries,³⁸ it is the second most common cause of acute pancreatitis in Asia (especially China).³⁹ Figure 1 provides a breakdown of the etiologies and risk factors of pancreatitis. Importantly, it remains challenging to assign several toxic-metabolic etiologies as either a cause or risk factor for AP, particularly with regards to alcohol, smoking, and cannabis to name a few.

Guidelines and recent studies of AP raise questions about the threshold above which hypertriglyceridemia causes or poses as an important cofactor for AP. American and European societies define the threshold for triglycerides at 885-1,000 mg/dL.^1,42,43 Pedersen et al. provide evidence of a graded risk of AP with hypertriglyceridemia: In multivariable analysis, adjusted hazard ratios for AP were much higher with nonfasting mild to moderately elevated plasma triglycerides (177-885 mg/dL), compared with normal values (below 89 mg/dL).⁴⁴ Moreover, the risk of severe AP (developing POF) increases in proportion to triglyceride value, independent of the underlying cause of AP.⁴⁵

Vidyard Video

Diagnosis of AP is derived from the revised Atlanta classification.⁴⁶ The recommended timing and indications for offering cross-sectional imaging are after 48-72 hours in patients with no improvement to initial care.¹ Endoscopic ultrasonography (EUS) has better diagnostic accuracy and sensitivity, compared with magnetic resonance cholangiopancreatography (MRCP) for choledocholithiasis, and has comparable specificity.^47,48 Among noninvasive imaging modalities, MRCP is more sensitive than computed tomography (CT) for diagnosing choledocholithiasis.⁴⁹ Despite guideline recommendations for more selective use of pancreatic imaging in the early assessment of AP, utilization of early CT or MRCP imaging (within the first 24 hours of care) remained high during 2014-2015, compared with 2006-2007.⁵⁰

Risk stratification

The goals of using risk stratification tools in AP are to identify patients at risk for developing major outcomes, including POF, infected pancreatic necrosis, and death, and to ensure timely triaging of patients to an appropriate level of care. Existing prediction models have only moderate predictive value.^53,54 Examples include simple risk stratification tools such as blood urea nitrogen (BUN) and hemoconcentration,^55,56 disease-modifying patient variables (age, obesity, etc.), biomarkers (i.e., angiopoietin 2),⁵⁷ and more complex clinical scoring systems such as Acute Physiology and Chronic Health Evaluation II (APACHE II), BISAP (BUN, impaired mental status, SIRS criteria, age, pleural effusion) score, early warning system (EWS), Glasgow-Imrie score, Japanese severity score, and recently the Pancreatitis Activity Scoring System (PASS).⁵⁸ Two recent guidelines affirmed the importance of predicting the severity of AP, using one or more predictive tools.^1,2 The recent 2018 AGA technical review does not debate this commonsense approach, but does highlight that there is no published observational study or randomized, controlled trial (RCT) investigating whether prediction tools affect clinical outcomes.⁴

Recent advances in early treatment of AP

Literature review and definitions

The AP literature contains heterogeneous definitions of severe AP and of what constitutes a major outcome in AP. Based on definitions of the 2013 revised Atlanta Criteria, the 2018 AGA technical review and clinical guidelines emphasized precise definitions of primary outcomes of clinical importance in AP, including death, persistent single organ failure, or persistent multiple organ failure, each requiring a duration of more than 48 hours, and infected pancreatic or peripancreatic necrosis or both (Table 2).^3,4

Pain management

Management of pain in AP is complex and requires a detailed discussion beyond the scope of this review, but recent clinical and translational studies raise questions about the current practice of using opioids for pain management in AP. A provocative, multicenter, retrospective cohort study reported lower 30-day mortality among critically ill patients who received epidural analgesia versus standard care without epidural analgesia.⁵⁹ The possible mechanism of protection and the drugs administered are unclear. An interesting hypothesis is that the epidural cohort may have received lower exposure to morphine, which may increase gut permeability, the risk of infectious complications, and severity of AP, based on a translational study in mice.⁶⁰

Intravenous fluid administration

Supportive care with the use of IV fluid hydration is a mainstay of treatment for AP in the first 12-24 hours. Table 3 summarizes the guidelines in regards to IV fluid administration as delineated by the ACG and AGA guidelines on the management of pancreatitis.^1,3 Guidelines advocate for early fluid resuscitation to correct intravascular depletion in order to reduce morbidity and mortality associated with AP.^1,2,4 The 2018 AGA guidelines endorse a conditional recommendation for using goal-directed therapy for initial fluid management,³ do not recommend for or against normal saline versus lactated Ringer’s (LR), but do advise against the use of hydroxyethyl starch fluids.³ Consistent with these recommendations, two recent RCTs published subsequent to the prespecified time periods of the AGA technical review and guideline, observed no significant differences between LR and normal saline on clinically meaningful outcomes.^61,62 The AGA guidelines acknowledge that evidence was of very-low quality in support of goal-directed therapy,^3,4 which has not been shown to have a significant reduction in persistent multiple organ failure, mortality, or pancreatic necrosis, compared with usual care. As the authors noted, interpretation of the data was limited by the absence of other critical outcomes in these trials (infected pancreatic necrosis), lack of uniformity of specific outcomes and definitions of transient and POF, few trials, and risk of bias. There is a clear need for a large RCT to provide evidence to guide decision making with fluid resuscitation in AP, particularly in regard to fluid type, volume, rate, duration, endpoints, and clinical outcomes.

Feeding

More recently, the focus of nutrition in the management of AP has shifted away from patients remaining nil per os (NPO). Current guidelines advocate for early oral feeding (within 24 hours) in mild AP,^3,4 in order to protect the gut-mucosal barrier. Remaining NPO when compared with early oral feeding has a 2.5-fold higher risk for interventions for necrosis.⁴ The recently published AGA technical review identified no significant impact on outcomes of early versus delayed oral feeding, which is consistent with observations of a landmark Dutch PYTHON trial entitled “Early versus on-demand nasoenteric tube feeding in acute pancreatitis.”^4,63 There is no clear cutoff point for initiating feeding for those with severe AP. A suggested practical approach is to initiate feeding within 24-72 hours and offer enteral nutrition for those intolerant to oral feeds. In severe AP and moderately severe AP, enteral nutrition is recommended over parenteral nutrition.^3,4 Enteral nutrition significantly reduces the risk of infected peripancreatic necrosis, single organ failure, and multiorgan failure.⁴ Finally, the AGA guidelines provide a conditional recommendation for providing enteral nutrition support through either the nasogastric or nasoenteric route.³ Further studies are required to determine the optimal timing, rate, and formulation of enteral nutrition in severe AP.

Antibiotics and probiotics

Current guidelines do not support the use of prophylactic antibiotics to prevent infection in necrotizing AP and severe AP.^1-3 The AGA technical review reported that prophylactic antibiotics did not reduce infected pancreatic or peripancreatic necrosis, persistent single organ failure, or mortality.⁴ Guidelines advocate against the use of probiotics for severe AP, because of increased mortality risk.¹

Timing of ERCP in acute biliary pancreatitis

There is universal agreement for offering urgent ERCP (within 24 hours) in biliary AP complicated by cholangitis.^1-3,64 Figure 2 demonstrates an example of a cholangiogram completed within 24 hours of presentation of biliary AP complicated by cholangitis.

In the absence of cholangitis, the timing of ERCP for AP with persistent biliary obstruction is less clear.^1-3 In line with recent guidelines, the 2018 AGA guidelines advocate against routine use of urgent ERCP for biliary AP without cholangitis,³ a conditional recommendation with overall low quality of data.⁴ The AGA technical review found that urgent ERCP, compared with conservative management in acute biliary pancreatitis without cholangitis had no significant effect on mortality, organ failure, infected pancreatic necrosis, and total necrotizing pancreatitis, but did significantly shorten hospital length of stay.⁴ There are limited data to guide decision making of when nonurgent ERCP should be performed in hospitalized patients with biliary AP with persistent obstruction and no cholangitis.^3,64

Alcohol and smoking cessation

The AGA technical review advocates for brief alcohol intervention during hospitalization for alcohol-induced AP on the basis of one RCT that addresses the impact of alcohol counseling on recurrent bouts of AP⁴ plus evidence from a Cochrane review of alcohol-reduction strategies in primary care populations.⁶⁵ Cessation of smoking – an established independent risk factor of AP – recurrent AP and chronic pancreatitis, should also be recommended as part of the management of AP.

Cholecystectomy

Evidence supports same-admission cholecystectomy for mild gallstone AP, a strong recommendation of published AGA guidelines.³ When compared with delayed cholecystectomy, same-admission cholecystectomy significantly reduced gallstone-related complications, readmissions for recurrent pancreatitis, and pancreaticobiliary complications, without having a significant impact on mortality during a 6-month follow-up period.⁶⁶ Delaying cholecystectomy 6 weeks in patients with moderate-severe gallstone AP appears to reduce morbidity, including the development of infected collections, and mortality.⁴ An ongoing RCT, the APEC trial, aims to determine whether early ERCP with biliary sphincterotomy reduces major complications or death when compared with no intervention for biliary AP in patients at high risk of complications.⁶⁷

Chemoprevention and IV fluid management of post-ERCP pancreatitis

Accumulating data support the effectiveness of chemoprevention, pancreatic stent placement, and fluid administration to prevent post-ERCP pancreatitis. Multiple RCTs, meta-analyses, and systematic reviews indicate that rectal NSAIDs) reduce post-ERCP pancreatitis onset^68-71 and moderate-severe post-ERCP pancreatitis. Additionally, placement of a pancreatic duct stent may decrease the risk of severe post-ERCP pancreatitis in high-risk patients.³ Guidelines do not comment on fluid administrations for prevention of post-ERCP pancreatitis, but studies have shown that greater periprocedural IV fluid was an independent protective factor against moderate to severe PEP⁷² and was associated with shorter hospital length of stay.⁷³ Recent meta-analyses and RCTs support using LR prior to ERCP to prevent PEP.^74-77 Interestingly, a recent RCT shows that the combination of rectal indomethacin and LR, compared with combination placebo and normal saline reduced the risk of PEP in high-risk patients.⁷⁸

Two ongoing multicenter RCTs will clarify the role of combination therapy. The Dutch FLUYT RCT aims to determine the optimal combination of rectal NSAIDs and periprocedural infusion of IV fluids to reduce the incidence of PEP and moderate-severe PEP⁷⁹ and the Stent vs. Indomethacin (SVI) trial aims to determine the whether combination pancreatic stent placement plus rectal indomethacin is superior to monotherapy indomethacin for preventing post-ERCP pancreatitis in high-risk cases.⁸⁰

Implications for clinical practice

The diagnosis and optimal management of AP require a systematic approach with multidisciplinary decision making. Morbidity and mortality in AP are driven by early or late POF, and the latter often is triggered by infected necrosis. Risk stratification of these patients at the point of contact is a commonsense approach to enable triaging of patients to the appropriate level of care. Regardless of pancreatitis severity, recommended treatment interventions include goal-directed IV fluid resuscitation, early feeding by mouth or enteral tube when necessary, avoidance of prophylactic antibiotics, avoidance of probiotics, and urgent ERCP for patients with acute biliary pancreatitis complicated by cholangitis. Key measures for preventing hospital readmission and pancreatitis include same-admission cholecystectomy for acute biliary pancreatitis and alcohol and smoking cessation. Preventive measures for post-ERCP pancreatitis in patients undergoing ERCP include rectal indomethacin, prophylactic pancreatic duct stent placement, and periprocedural fluid resuscitation.

Dr. Mandalia is a fellow, gastroenterology, department of internal medicine, division of gastroenterology, Michigan Medicine, Ann Arbor; Dr. DiMagno is associate professor of medicine, director, comprehensive pancreas program, department of internal medicine, division of gastroenterology, University of Michigan, Ann Arbor. Dr. Mandalia reports no conflicts of interest.

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70. Wan J et al. BMC Gastroenterol. 2017;17(1):43.

71. Yang C et al. Pancreatology. 2017;17(5):681-8.

72. DiMagno MJ et al. Pancreas. 2014;43(4):642-7.

73. Sagi SV et al. J Gastroenterol Hepatol. 2014;29(6):1316-20.

74. Choi JH et al. Clin Gastroenterol Hepatol. 2017;15(1):86-92.e1.

75. Wu D et al. J Clin Gastroenterol. 2017;51(8):e68-e76.

76. Zhang ZF et al. J Clin Gastroenterol. 2017;51(3):e17-e26.

77. Park CH et al. Endoscopy 2018 Apr;50(4):378-85.

78. Mok SRS et al. Gastrointest Endosc. 2017;85(5):1005-13.

79. Smeets XJN et al. Trials. 2018;19(1):207.

80. Elmunzer BJ et al. Trials. 2016;17(1):120.

Introduction

Acute pancreatitis (AP) is a major clinical and financial burden in the United States. Several major clinical guidelines provide evidence-based recommendations for the clinical management decisions in AP, including those from the American College of Gastroenterology (ACG; 2013),¹ and the International Association of Pancreatology (IAP; 2013).² More recently, the American Gastroenterological Association (AGA) released their own set of guidelines.^3,4 In this update on AP, we review these guidelines and reference recent literature focused on epidemiology, risk factors, etiology, diagnosis, risk stratification, and recent advances in the early medical management of AP. Regarding the latter, we review six treatment interventions (pain management, intravenous fluid resuscitation, feeding, prophylactic antibiotics, probiotics, and timing of endoscopic retrograde cholangiopancreatography (ERCP) in acute biliary pancreatitis) and four preventive interventions (alcohol and smoking cessation, same-admission cholecystectomy for acute biliary pancreatitis, and chemoprevention and fluid administration for post-ERCP pancreatitis [PEP]). Updates on multidisciplinary management of (infected) pancreatic necrosis is beyond the scope of this review. Table 1 summarizes the concepts discussed in this article.

Recent advances in epidemiology and evaluation of AP

Epidemiology

AP is the third most common cause of gastrointestinal-related hospitalizations and fourth most common cause of readmission in 2014.⁵ Recent epidemiologic studies show conflicting trends for the incidence of AP, both increasing⁶ and decreasing,⁷ likely attributable to significant differences in study designs. Importantly, multiple studies have demonstrated that hospital length of stay, costs, and mortality have declined since 2009.^6,8-10

Persistent organ failure (POF), defined as organ failure lasting more than 48 hours, is the major cause of death in AP. POF, if only a single organ during AP, is associated with 27%-36% mortality; if it is multiorgan, it is associated with 47% mortality.^1,11 Other factors associated with increased hospital mortality include infected pancreatic necrosis,^12-14 diabetes mellitus,¹⁵ hospital-acquired infection,¹⁶ advanced age (70 years and older),¹⁷ and obesity.¹⁸ Predictive factors of 1-year mortality include readmission within 30 days, higher Charlson Comorbidity Index, and longer hospitalization.¹⁹

Risk factors

We briefly highlight recent insights into risk factors for AP (Table 1) and refer to a recent review for further discussion.²⁰ Current and former tobacco use are independent risk factors for AP.²¹ The dose-response relationship of alcohol to the risk of pancreatitis is complex,²² but five standard drinks per day for 5 years is a commonly used cut-off.^1,23 New evidence suggests that the relationship between the dose of alcohol and risk of AP differs by sex, linearly in men but nonlinearly (J-shaped) in women.²⁴ Risk of AP in women was decreased with alcohol consumption of up to 40 g/day (one standard drink contains 14 g of alcohol) and increased above this amount. Cannabis is a possible risk factor for toxin-induced AP and abstinence appears to abolish risk of recurrent attacks.²⁵

Patients with inflammatory bowel disease (IBD) have a 2.9-fold higher risk for AP versus non-IBD cohorts²⁶ with the most common etiologies are from gallstones and medications.²⁷ In patients with end-stage renal disease (ESRD), the risk of AP is higher in those who receive peritoneal dialysis, compared with hemodialysis^28-33 and who are women, older, or have cholelithiasis or liver disease.³⁴As recently reviewed,³⁵ pancreatic cancer appears to be associated with first-attack pancreatitis with few exceptions.³⁶ In this setting, the overall incidence of pancreatic cancer is low (1.5%). The risk is greatest within the first year of the attack of AP, negligible below age 40 years but steadily rising through the fifth to eighth decades.³⁷ Pancreatic cancer screening is a conditional recommendation of the ACG guidelines in patients with unexplained AP, particularly those aged 40 years or older.¹

Etiology and diagnosis

Alcohol and gallstones remain the most prevalent etiologies for AP.¹ While hypertriglyceridemia accounted for 9% of AP in a systematic review of acute pancreatitis in 15 different countries,³⁸ it is the second most common cause of acute pancreatitis in Asia (especially China).³⁹ Figure 1 provides a breakdown of the etiologies and risk factors of pancreatitis. Importantly, it remains challenging to assign several toxic-metabolic etiologies as either a cause or risk factor for AP, particularly with regards to alcohol, smoking, and cannabis to name a few.

Guidelines and recent studies of AP raise questions about the threshold above which hypertriglyceridemia causes or poses as an important cofactor for AP. American and European societies define the threshold for triglycerides at 885-1,000 mg/dL.^1,42,43 Pedersen et al. provide evidence of a graded risk of AP with hypertriglyceridemia: In multivariable analysis, adjusted hazard ratios for AP were much higher with nonfasting mild to moderately elevated plasma triglycerides (177-885 mg/dL), compared with normal values (below 89 mg/dL).⁴⁴ Moreover, the risk of severe AP (developing POF) increases in proportion to triglyceride value, independent of the underlying cause of AP.⁴⁵

Vidyard Video

Diagnosis of AP is derived from the revised Atlanta classification.⁴⁶ The recommended timing and indications for offering cross-sectional imaging are after 48-72 hours in patients with no improvement to initial care.¹ Endoscopic ultrasonography (EUS) has better diagnostic accuracy and sensitivity, compared with magnetic resonance cholangiopancreatography (MRCP) for choledocholithiasis, and has comparable specificity.^47,48 Among noninvasive imaging modalities, MRCP is more sensitive than computed tomography (CT) for diagnosing choledocholithiasis.⁴⁹ Despite guideline recommendations for more selective use of pancreatic imaging in the early assessment of AP, utilization of early CT or MRCP imaging (within the first 24 hours of care) remained high during 2014-2015, compared with 2006-2007.⁵⁰

Risk stratification

The goals of using risk stratification tools in AP are to identify patients at risk for developing major outcomes, including POF, infected pancreatic necrosis, and death, and to ensure timely triaging of patients to an appropriate level of care. Existing prediction models have only moderate predictive value.^53,54 Examples include simple risk stratification tools such as blood urea nitrogen (BUN) and hemoconcentration,^55,56 disease-modifying patient variables (age, obesity, etc.), biomarkers (i.e., angiopoietin 2),⁵⁷ and more complex clinical scoring systems such as Acute Physiology and Chronic Health Evaluation II (APACHE II), BISAP (BUN, impaired mental status, SIRS criteria, age, pleural effusion) score, early warning system (EWS), Glasgow-Imrie score, Japanese severity score, and recently the Pancreatitis Activity Scoring System (PASS).⁵⁸ Two recent guidelines affirmed the importance of predicting the severity of AP, using one or more predictive tools.^1,2 The recent 2018 AGA technical review does not debate this commonsense approach, but does highlight that there is no published observational study or randomized, controlled trial (RCT) investigating whether prediction tools affect clinical outcomes.⁴

Recent advances in early treatment of AP

Literature review and definitions

The AP literature contains heterogeneous definitions of severe AP and of what constitutes a major outcome in AP. Based on definitions of the 2013 revised Atlanta Criteria, the 2018 AGA technical review and clinical guidelines emphasized precise definitions of primary outcomes of clinical importance in AP, including death, persistent single organ failure, or persistent multiple organ failure, each requiring a duration of more than 48 hours, and infected pancreatic or peripancreatic necrosis or both (Table 2).^3,4

Pain management

Management of pain in AP is complex and requires a detailed discussion beyond the scope of this review, but recent clinical and translational studies raise questions about the current practice of using opioids for pain management in AP. A provocative, multicenter, retrospective cohort study reported lower 30-day mortality among critically ill patients who received epidural analgesia versus standard care without epidural analgesia.⁵⁹ The possible mechanism of protection and the drugs administered are unclear. An interesting hypothesis is that the epidural cohort may have received lower exposure to morphine, which may increase gut permeability, the risk of infectious complications, and severity of AP, based on a translational study in mice.⁶⁰

Intravenous fluid administration

Supportive care with the use of IV fluid hydration is a mainstay of treatment for AP in the first 12-24 hours. Table 3 summarizes the guidelines in regards to IV fluid administration as delineated by the ACG and AGA guidelines on the management of pancreatitis.^1,3 Guidelines advocate for early fluid resuscitation to correct intravascular depletion in order to reduce morbidity and mortality associated with AP.^1,2,4 The 2018 AGA guidelines endorse a conditional recommendation for using goal-directed therapy for initial fluid management,³ do not recommend for or against normal saline versus lactated Ringer’s (LR), but do advise against the use of hydroxyethyl starch fluids.³ Consistent with these recommendations, two recent RCTs published subsequent to the prespecified time periods of the AGA technical review and guideline, observed no significant differences between LR and normal saline on clinically meaningful outcomes.^61,62 The AGA guidelines acknowledge that evidence was of very-low quality in support of goal-directed therapy,^3,4 which has not been shown to have a significant reduction in persistent multiple organ failure, mortality, or pancreatic necrosis, compared with usual care. As the authors noted, interpretation of the data was limited by the absence of other critical outcomes in these trials (infected pancreatic necrosis), lack of uniformity of specific outcomes and definitions of transient and POF, few trials, and risk of bias. There is a clear need for a large RCT to provide evidence to guide decision making with fluid resuscitation in AP, particularly in regard to fluid type, volume, rate, duration, endpoints, and clinical outcomes.

Feeding

More recently, the focus of nutrition in the management of AP has shifted away from patients remaining nil per os (NPO). Current guidelines advocate for early oral feeding (within 24 hours) in mild AP,^3,4 in order to protect the gut-mucosal barrier. Remaining NPO when compared with early oral feeding has a 2.5-fold higher risk for interventions for necrosis.⁴ The recently published AGA technical review identified no significant impact on outcomes of early versus delayed oral feeding, which is consistent with observations of a landmark Dutch PYTHON trial entitled “Early versus on-demand nasoenteric tube feeding in acute pancreatitis.”^4,63 There is no clear cutoff point for initiating feeding for those with severe AP. A suggested practical approach is to initiate feeding within 24-72 hours and offer enteral nutrition for those intolerant to oral feeds. In severe AP and moderately severe AP, enteral nutrition is recommended over parenteral nutrition.^3,4 Enteral nutrition significantly reduces the risk of infected peripancreatic necrosis, single organ failure, and multiorgan failure.⁴ Finally, the AGA guidelines provide a conditional recommendation for providing enteral nutrition support through either the nasogastric or nasoenteric route.³ Further studies are required to determine the optimal timing, rate, and formulation of enteral nutrition in severe AP.

Antibiotics and probiotics

Current guidelines do not support the use of prophylactic antibiotics to prevent infection in necrotizing AP and severe AP.^1-3 The AGA technical review reported that prophylactic antibiotics did not reduce infected pancreatic or peripancreatic necrosis, persistent single organ failure, or mortality.⁴ Guidelines advocate against the use of probiotics for severe AP, because of increased mortality risk.¹

Timing of ERCP in acute biliary pancreatitis

There is universal agreement for offering urgent ERCP (within 24 hours) in biliary AP complicated by cholangitis.^1-3,64 Figure 2 demonstrates an example of a cholangiogram completed within 24 hours of presentation of biliary AP complicated by cholangitis.

In the absence of cholangitis, the timing of ERCP for AP with persistent biliary obstruction is less clear.^1-3 In line with recent guidelines, the 2018 AGA guidelines advocate against routine use of urgent ERCP for biliary AP without cholangitis,³ a conditional recommendation with overall low quality of data.⁴ The AGA technical review found that urgent ERCP, compared with conservative management in acute biliary pancreatitis without cholangitis had no significant effect on mortality, organ failure, infected pancreatic necrosis, and total necrotizing pancreatitis, but did significantly shorten hospital length of stay.⁴ There are limited data to guide decision making of when nonurgent ERCP should be performed in hospitalized patients with biliary AP with persistent obstruction and no cholangitis.^3,64

Alcohol and smoking cessation

The AGA technical review advocates for brief alcohol intervention during hospitalization for alcohol-induced AP on the basis of one RCT that addresses the impact of alcohol counseling on recurrent bouts of AP⁴ plus evidence from a Cochrane review of alcohol-reduction strategies in primary care populations.⁶⁵ Cessation of smoking – an established independent risk factor of AP – recurrent AP and chronic pancreatitis, should also be recommended as part of the management of AP.

Cholecystectomy

Evidence supports same-admission cholecystectomy for mild gallstone AP, a strong recommendation of published AGA guidelines.³ When compared with delayed cholecystectomy, same-admission cholecystectomy significantly reduced gallstone-related complications, readmissions for recurrent pancreatitis, and pancreaticobiliary complications, without having a significant impact on mortality during a 6-month follow-up period.⁶⁶ Delaying cholecystectomy 6 weeks in patients with moderate-severe gallstone AP appears to reduce morbidity, including the development of infected collections, and mortality.⁴ An ongoing RCT, the APEC trial, aims to determine whether early ERCP with biliary sphincterotomy reduces major complications or death when compared with no intervention for biliary AP in patients at high risk of complications.⁶⁷

Chemoprevention and IV fluid management of post-ERCP pancreatitis

Accumulating data support the effectiveness of chemoprevention, pancreatic stent placement, and fluid administration to prevent post-ERCP pancreatitis. Multiple RCTs, meta-analyses, and systematic reviews indicate that rectal NSAIDs) reduce post-ERCP pancreatitis onset^68-71 and moderate-severe post-ERCP pancreatitis. Additionally, placement of a pancreatic duct stent may decrease the risk of severe post-ERCP pancreatitis in high-risk patients.³ Guidelines do not comment on fluid administrations for prevention of post-ERCP pancreatitis, but studies have shown that greater periprocedural IV fluid was an independent protective factor against moderate to severe PEP⁷² and was associated with shorter hospital length of stay.⁷³ Recent meta-analyses and RCTs support using LR prior to ERCP to prevent PEP.^74-77 Interestingly, a recent RCT shows that the combination of rectal indomethacin and LR, compared with combination placebo and normal saline reduced the risk of PEP in high-risk patients.⁷⁸

Two ongoing multicenter RCTs will clarify the role of combination therapy. The Dutch FLUYT RCT aims to determine the optimal combination of rectal NSAIDs and periprocedural infusion of IV fluids to reduce the incidence of PEP and moderate-severe PEP⁷⁹ and the Stent vs. Indomethacin (SVI) trial aims to determine the whether combination pancreatic stent placement plus rectal indomethacin is superior to monotherapy indomethacin for preventing post-ERCP pancreatitis in high-risk cases.⁸⁰

Implications for clinical practice

The diagnosis and optimal management of AP require a systematic approach with multidisciplinary decision making. Morbidity and mortality in AP are driven by early or late POF, and the latter often is triggered by infected necrosis. Risk stratification of these patients at the point of contact is a commonsense approach to enable triaging of patients to the appropriate level of care. Regardless of pancreatitis severity, recommended treatment interventions include goal-directed IV fluid resuscitation, early feeding by mouth or enteral tube when necessary, avoidance of prophylactic antibiotics, avoidance of probiotics, and urgent ERCP for patients with acute biliary pancreatitis complicated by cholangitis. Key measures for preventing hospital readmission and pancreatitis include same-admission cholecystectomy for acute biliary pancreatitis and alcohol and smoking cessation. Preventive measures for post-ERCP pancreatitis in patients undergoing ERCP include rectal indomethacin, prophylactic pancreatic duct stent placement, and periprocedural fluid resuscitation.

Dr. Mandalia is a fellow, gastroenterology, department of internal medicine, division of gastroenterology, Michigan Medicine, Ann Arbor; Dr. DiMagno is associate professor of medicine, director, comprehensive pancreas program, department of internal medicine, division of gastroenterology, University of Michigan, Ann Arbor. Dr. Mandalia reports no conflicts of interest.

References

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5. Peery AF et al. Gastroenterology. 2019 Jan;156(1):254-72.e11.

6. Krishna SG et al. Pancreas. 2017;46(4):482-8.

7. Sellers ZM et al. Gastroenterology. 2018;155(2):469-78.e1.

8. Brown A et al. JOP. 2008;9(4):408-14.

9. Fagenholz PJ et al. Ann Epidemiol. 2007;17(7):491.e1-.e8.

10. McNabb-Baltar J et al. Pancreas. 2014;43(5):687-91.

11. Johnson CD et al. Gut. 2004;53(9):1340-4.

12. Dellinger EP et al. Ann Surg. 2012;256(6):875-80.

13. Petrov MS et al. Gastroenterology. 2010;139(3):813-20.

14. Sternby H et al. Ann Surg. Apr 18. doi: 10.1097/SLA.0000000000002766.

15. Huh JH et al. J Clin Gastroenterol. 2018;52(2):178-83.

16. Wu BU et al. Gastroenterology. 2008;135(3):816-20.

17. Gardner TB et al. Clin Gastroenterol Hepatol. 2008;6(10):1070-6.

18. Krishna SG et al. Am J Gastroenterol. 2015;110(11):1608-19.

19. Lee PJ et al. Pancreas. 2016;45(4):561-4.

20. Mandalia A et al. F1000Research. 2018 Jun 28;7.

21. Majumder S et al. Pancreas. 2015;44(4):540-6.

22. DiMagno MJ. Clin Gastroenterol Hepatol. 2011;9(11):920-2.

23. Yadav D, Whitcomb DC. Nature Rev Gastroenterol Hepatol. 2010;7(3):131-45.

24. Samokhvalov AV et al. EBioMedicine. 2015;2(12):1996-2002.

25. Barkin JA et al. Pancreas. 2017;46(8):1035-8.

26. Chen Y-T et al. J Gastroenterol Hepatol. 2016;31(4):782-7.

27. Ramos LR et al. J Crohns Colitis. 2016;10(1):95-104.

28. Avram MM. Nephron. 1977;18(1):68-71.

29. Lankisch PG et al. Nephrol Dial Transplant. 2008;23(4):1401-5.

30. Owyang C et al. Mayo Clin Proc. 1979;54(12):769-73.

31. Owyang Cet al. Gut. 1982;23(5):357-61.

32. Quraishi ER et al. Am J Gastroenterol. 2005;100:2288.

33. Vaziri ND et al. Nephron. 1987;46(4):347-9.

34. Chen HJ et al. Nephrol Dial Transplant. 2017;32(10):1731-6.

35. Kirkegard J et al. Gastroenterology. 2018;May;154(6):1729-36.

36. Karlson BM, et al. Gastroenterology. 1997;113(2):587-92.

37. Munigala S et al. Clin Gastroenterol Hepatol. 2014;12(7):1143-50.e1.

38. Carr RA et al. Pancreatology. 2016;16(4):469-76.

39. Li X et al. BMC Gastroenterol. 2018;18(1):89.

40. Ahmed AU et al. Clin Gastroenterol Hepatol. 2016;14(5):738-46.

41. Sankaran SJ et al. Gastroenterology. 2015;149(6):1490-500.e1.

42. Berglund L et al. J Clin Endocrinol Metab. 2012;97(9):2969-89.

43. Catapano AL et al. Atherosclerosis. 2011;217(1):3-46.

44. Pedersen SB et al. JAMA Intern Med. 2016;176(12):1834-42.

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47. Kondo S et al. Eur J Radiol. 2005;54(2):271-5.

48. Meeralam Y et al. Gastrointest Endosc. 2017;86(6):986-93.

49. Stimac D et al. Am J Gastroenterol. 2007;102(5):997-1004.

50. Jin DX et al. Dig Dis Sci. 2017;62(10):2894-9.

51. Freeman ML. Gastrointest Endosc Clin N Am. 2012;22(3):567-86.

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53. Di MY et al. Ann Int Med. 2016;165(7):482-90.

54. Mounzer R et al. Gastroenterology. 2012;142(7):1476-82; quiz e15-6.

55. Koutroumpakis E et al. Am J Gastroenterol. 2015;110(12):1707-16.

56. Wu BU et al. Gastroenterology. 2009;137(1):129-35.

57. Buddingh KT et al. J Am Coll Surg. 2014;218(1):26-32.

58. Buxbaum J et al. Am J Gastroenterol. 2018;113(5):755-64.

59. Jabaudon M et al. Crit Car Med. 2018;46(3):e198-e205.

60. Barlass U et al. Gut. 2018;67(4):600-2.

61. Buxbaum JL et al. Am J Gastroenterol. 2017;112(5):797-803.

62. de-Madaria E et al. United Eur Gastroenterol J. 2018;6(1):63-72.

63. Bakker OJ et al. N Engl J Med. 2014;371(21):1983-93.

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69. Kubiliun NM et al. Clin Gastroenterol Hepatol. 2015;13(7):1231-9; quiz e70-1.

70. Wan J et al. BMC Gastroenterol. 2017;17(1):43.

71. Yang C et al. Pancreatology. 2017;17(5):681-8.

72. DiMagno MJ et al. Pancreas. 2014;43(4):642-7.

73. Sagi SV et al. J Gastroenterol Hepatol. 2014;29(6):1316-20.

74. Choi JH et al. Clin Gastroenterol Hepatol. 2017;15(1):86-92.e1.

75. Wu D et al. J Clin Gastroenterol. 2017;51(8):e68-e76.

76. Zhang ZF et al. J Clin Gastroenterol. 2017;51(3):e17-e26.

77. Park CH et al. Endoscopy 2018 Apr;50(4):378-85.

78. Mok SRS et al. Gastrointest Endosc. 2017;85(5):1005-13.

79. Smeets XJN et al. Trials. 2018;19(1):207.

80. Elmunzer BJ et al. Trials. 2016;17(1):120.

Introduction

Acute pancreatitis (AP) is a major clinical and financial burden in the United States. Several major clinical guidelines provide evidence-based recommendations for the clinical management decisions in AP, including those from the American College of Gastroenterology (ACG; 2013),¹ and the International Association of Pancreatology (IAP; 2013).² More recently, the American Gastroenterological Association (AGA) released their own set of guidelines.^3,4 In this update on AP, we review these guidelines and reference recent literature focused on epidemiology, risk factors, etiology, diagnosis, risk stratification, and recent advances in the early medical management of AP. Regarding the latter, we review six treatment interventions (pain management, intravenous fluid resuscitation, feeding, prophylactic antibiotics, probiotics, and timing of endoscopic retrograde cholangiopancreatography (ERCP) in acute biliary pancreatitis) and four preventive interventions (alcohol and smoking cessation, same-admission cholecystectomy for acute biliary pancreatitis, and chemoprevention and fluid administration for post-ERCP pancreatitis [PEP]). Updates on multidisciplinary management of (infected) pancreatic necrosis is beyond the scope of this review. Table 1 summarizes the concepts discussed in this article.

Recent advances in epidemiology and evaluation of AP

Epidemiology

AP is the third most common cause of gastrointestinal-related hospitalizations and fourth most common cause of readmission in 2014.⁵ Recent epidemiologic studies show conflicting trends for the incidence of AP, both increasing⁶ and decreasing,⁷ likely attributable to significant differences in study designs. Importantly, multiple studies have demonstrated that hospital length of stay, costs, and mortality have declined since 2009.^6,8-10

Persistent organ failure (POF), defined as organ failure lasting more than 48 hours, is the major cause of death in AP. POF, if only a single organ during AP, is associated with 27%-36% mortality; if it is multiorgan, it is associated with 47% mortality.^1,11 Other factors associated with increased hospital mortality include infected pancreatic necrosis,^12-14 diabetes mellitus,¹⁵ hospital-acquired infection,¹⁶ advanced age (70 years and older),¹⁷ and obesity.¹⁸ Predictive factors of 1-year mortality include readmission within 30 days, higher Charlson Comorbidity Index, and longer hospitalization.¹⁹

Risk factors

We briefly highlight recent insights into risk factors for AP (Table 1) and refer to a recent review for further discussion.²⁰ Current and former tobacco use are independent risk factors for AP.²¹ The dose-response relationship of alcohol to the risk of pancreatitis is complex,²² but five standard drinks per day for 5 years is a commonly used cut-off.^1,23 New evidence suggests that the relationship between the dose of alcohol and risk of AP differs by sex, linearly in men but nonlinearly (J-shaped) in women.²⁴ Risk of AP in women was decreased with alcohol consumption of up to 40 g/day (one standard drink contains 14 g of alcohol) and increased above this amount. Cannabis is a possible risk factor for toxin-induced AP and abstinence appears to abolish risk of recurrent attacks.²⁵

Patients with inflammatory bowel disease (IBD) have a 2.9-fold higher risk for AP versus non-IBD cohorts²⁶ with the most common etiologies are from gallstones and medications.²⁷ In patients with end-stage renal disease (ESRD), the risk of AP is higher in those who receive peritoneal dialysis, compared with hemodialysis^28-33 and who are women, older, or have cholelithiasis or liver disease.³⁴As recently reviewed,³⁵ pancreatic cancer appears to be associated with first-attack pancreatitis with few exceptions.³⁶ In this setting, the overall incidence of pancreatic cancer is low (1.5%). The risk is greatest within the first year of the attack of AP, negligible below age 40 years but steadily rising through the fifth to eighth decades.³⁷ Pancreatic cancer screening is a conditional recommendation of the ACG guidelines in patients with unexplained AP, particularly those aged 40 years or older.¹

Etiology and diagnosis

Alcohol and gallstones remain the most prevalent etiologies for AP.¹ While hypertriglyceridemia accounted for 9% of AP in a systematic review of acute pancreatitis in 15 different countries,³⁸ it is the second most common cause of acute pancreatitis in Asia (especially China).³⁹ Figure 1 provides a breakdown of the etiologies and risk factors of pancreatitis. Importantly, it remains challenging to assign several toxic-metabolic etiologies as either a cause or risk factor for AP, particularly with regards to alcohol, smoking, and cannabis to name a few.

Guidelines and recent studies of AP raise questions about the threshold above which hypertriglyceridemia causes or poses as an important cofactor for AP. American and European societies define the threshold for triglycerides at 885-1,000 mg/dL.^1,42,43 Pedersen et al. provide evidence of a graded risk of AP with hypertriglyceridemia: In multivariable analysis, adjusted hazard ratios for AP were much higher with nonfasting mild to moderately elevated plasma triglycerides (177-885 mg/dL), compared with normal values (below 89 mg/dL).⁴⁴ Moreover, the risk of severe AP (developing POF) increases in proportion to triglyceride value, independent of the underlying cause of AP.⁴⁵

Vidyard Video

Diagnosis of AP is derived from the revised Atlanta classification.⁴⁶ The recommended timing and indications for offering cross-sectional imaging are after 48-72 hours in patients with no improvement to initial care.¹ Endoscopic ultrasonography (EUS) has better diagnostic accuracy and sensitivity, compared with magnetic resonance cholangiopancreatography (MRCP) for choledocholithiasis, and has comparable specificity.^47,48 Among noninvasive imaging modalities, MRCP is more sensitive than computed tomography (CT) for diagnosing choledocholithiasis.⁴⁹ Despite guideline recommendations for more selective use of pancreatic imaging in the early assessment of AP, utilization of early CT or MRCP imaging (within the first 24 hours of care) remained high during 2014-2015, compared with 2006-2007.⁵⁰

Risk stratification

The goals of using risk stratification tools in AP are to identify patients at risk for developing major outcomes, including POF, infected pancreatic necrosis, and death, and to ensure timely triaging of patients to an appropriate level of care. Existing prediction models have only moderate predictive value.^53,54 Examples include simple risk stratification tools such as blood urea nitrogen (BUN) and hemoconcentration,^55,56 disease-modifying patient variables (age, obesity, etc.), biomarkers (i.e., angiopoietin 2),⁵⁷ and more complex clinical scoring systems such as Acute Physiology and Chronic Health Evaluation II (APACHE II), BISAP (BUN, impaired mental status, SIRS criteria, age, pleural effusion) score, early warning system (EWS), Glasgow-Imrie score, Japanese severity score, and recently the Pancreatitis Activity Scoring System (PASS).⁵⁸ Two recent guidelines affirmed the importance of predicting the severity of AP, using one or more predictive tools.^1,2 The recent 2018 AGA technical review does not debate this commonsense approach, but does highlight that there is no published observational study or randomized, controlled trial (RCT) investigating whether prediction tools affect clinical outcomes.⁴

Recent advances in early treatment of AP

Literature review and definitions

The AP literature contains heterogeneous definitions of severe AP and of what constitutes a major outcome in AP. Based on definitions of the 2013 revised Atlanta Criteria, the 2018 AGA technical review and clinical guidelines emphasized precise definitions of primary outcomes of clinical importance in AP, including death, persistent single organ failure, or persistent multiple organ failure, each requiring a duration of more than 48 hours, and infected pancreatic or peripancreatic necrosis or both (Table 2).^3,4

Pain management

Management of pain in AP is complex and requires a detailed discussion beyond the scope of this review, but recent clinical and translational studies raise questions about the current practice of using opioids for pain management in AP. A provocative, multicenter, retrospective cohort study reported lower 30-day mortality among critically ill patients who received epidural analgesia versus standard care without epidural analgesia.⁵⁹ The possible mechanism of protection and the drugs administered are unclear. An interesting hypothesis is that the epidural cohort may have received lower exposure to morphine, which may increase gut permeability, the risk of infectious complications, and severity of AP, based on a translational study in mice.⁶⁰

Intravenous fluid administration

Supportive care with the use of IV fluid hydration is a mainstay of treatment for AP in the first 12-24 hours. Table 3 summarizes the guidelines in regards to IV fluid administration as delineated by the ACG and AGA guidelines on the management of pancreatitis.^1,3 Guidelines advocate for early fluid resuscitation to correct intravascular depletion in order to reduce morbidity and mortality associated with AP.^1,2,4 The 2018 AGA guidelines endorse a conditional recommendation for using goal-directed therapy for initial fluid management,³ do not recommend for or against normal saline versus lactated Ringer’s (LR), but do advise against the use of hydroxyethyl starch fluids.³ Consistent with these recommendations, two recent RCTs published subsequent to the prespecified time periods of the AGA technical review and guideline, observed no significant differences between LR and normal saline on clinically meaningful outcomes.^61,62 The AGA guidelines acknowledge that evidence was of very-low quality in support of goal-directed therapy,^3,4 which has not been shown to have a significant reduction in persistent multiple organ failure, mortality, or pancreatic necrosis, compared with usual care. As the authors noted, interpretation of the data was limited by the absence of other critical outcomes in these trials (infected pancreatic necrosis), lack of uniformity of specific outcomes and definitions of transient and POF, few trials, and risk of bias. There is a clear need for a large RCT to provide evidence to guide decision making with fluid resuscitation in AP, particularly in regard to fluid type, volume, rate, duration, endpoints, and clinical outcomes.

Feeding

More recently, the focus of nutrition in the management of AP has shifted away from patients remaining nil per os (NPO). Current guidelines advocate for early oral feeding (within 24 hours) in mild AP,^3,4 in order to protect the gut-mucosal barrier. Remaining NPO when compared with early oral feeding has a 2.5-fold higher risk for interventions for necrosis.⁴ The recently published AGA technical review identified no significant impact on outcomes of early versus delayed oral feeding, which is consistent with observations of a landmark Dutch PYTHON trial entitled “Early versus on-demand nasoenteric tube feeding in acute pancreatitis.”^4,63 There is no clear cutoff point for initiating feeding for those with severe AP. A suggested practical approach is to initiate feeding within 24-72 hours and offer enteral nutrition for those intolerant to oral feeds. In severe AP and moderately severe AP, enteral nutrition is recommended over parenteral nutrition.^3,4 Enteral nutrition significantly reduces the risk of infected peripancreatic necrosis, single organ failure, and multiorgan failure.⁴ Finally, the AGA guidelines provide a conditional recommendation for providing enteral nutrition support through either the nasogastric or nasoenteric route.³ Further studies are required to determine the optimal timing, rate, and formulation of enteral nutrition in severe AP.

Antibiotics and probiotics

Current guidelines do not support the use of prophylactic antibiotics to prevent infection in necrotizing AP and severe AP.^1-3 The AGA technical review reported that prophylactic antibiotics did not reduce infected pancreatic or peripancreatic necrosis, persistent single organ failure, or mortality.⁴ Guidelines advocate against the use of probiotics for severe AP, because of increased mortality risk.¹

Timing of ERCP in acute biliary pancreatitis

There is universal agreement for offering urgent ERCP (within 24 hours) in biliary AP complicated by cholangitis.^1-3,64 Figure 2 demonstrates an example of a cholangiogram completed within 24 hours of presentation of biliary AP complicated by cholangitis.

In the absence of cholangitis, the timing of ERCP for AP with persistent biliary obstruction is less clear.^1-3 In line with recent guidelines, the 2018 AGA guidelines advocate against routine use of urgent ERCP for biliary AP without cholangitis,³ a conditional recommendation with overall low quality of data.⁴ The AGA technical review found that urgent ERCP, compared with conservative management in acute biliary pancreatitis without cholangitis had no significant effect on mortality, organ failure, infected pancreatic necrosis, and total necrotizing pancreatitis, but did significantly shorten hospital length of stay.⁴ There are limited data to guide decision making of when nonurgent ERCP should be performed in hospitalized patients with biliary AP with persistent obstruction and no cholangitis.^3,64

Alcohol and smoking cessation

The AGA technical review advocates for brief alcohol intervention during hospitalization for alcohol-induced AP on the basis of one RCT that addresses the impact of alcohol counseling on recurrent bouts of AP⁴ plus evidence from a Cochrane review of alcohol-reduction strategies in primary care populations.⁶⁵ Cessation of smoking – an established independent risk factor of AP – recurrent AP and chronic pancreatitis, should also be recommended as part of the management of AP.

Cholecystectomy

Evidence supports same-admission cholecystectomy for mild gallstone AP, a strong recommendation of published AGA guidelines.³ When compared with delayed cholecystectomy, same-admission cholecystectomy significantly reduced gallstone-related complications, readmissions for recurrent pancreatitis, and pancreaticobiliary complications, without having a significant impact on mortality during a 6-month follow-up period.⁶⁶ Delaying cholecystectomy 6 weeks in patients with moderate-severe gallstone AP appears to reduce morbidity, including the development of infected collections, and mortality.⁴ An ongoing RCT, the APEC trial, aims to determine whether early ERCP with biliary sphincterotomy reduces major complications or death when compared with no intervention for biliary AP in patients at high risk of complications.⁶⁷

Chemoprevention and IV fluid management of post-ERCP pancreatitis

Accumulating data support the effectiveness of chemoprevention, pancreatic stent placement, and fluid administration to prevent post-ERCP pancreatitis. Multiple RCTs, meta-analyses, and systematic reviews indicate that rectal NSAIDs) reduce post-ERCP pancreatitis onset^68-71 and moderate-severe post-ERCP pancreatitis. Additionally, placement of a pancreatic duct stent may decrease the risk of severe post-ERCP pancreatitis in high-risk patients.³ Guidelines do not comment on fluid administrations for prevention of post-ERCP pancreatitis, but studies have shown that greater periprocedural IV fluid was an independent protective factor against moderate to severe PEP⁷² and was associated with shorter hospital length of stay.⁷³ Recent meta-analyses and RCTs support using LR prior to ERCP to prevent PEP.^74-77 Interestingly, a recent RCT shows that the combination of rectal indomethacin and LR, compared with combination placebo and normal saline reduced the risk of PEP in high-risk patients.⁷⁸

Two ongoing multicenter RCTs will clarify the role of combination therapy. The Dutch FLUYT RCT aims to determine the optimal combination of rectal NSAIDs and periprocedural infusion of IV fluids to reduce the incidence of PEP and moderate-severe PEP⁷⁹ and the Stent vs. Indomethacin (SVI) trial aims to determine the whether combination pancreatic stent placement plus rectal indomethacin is superior to monotherapy indomethacin for preventing post-ERCP pancreatitis in high-risk cases.⁸⁰

Implications for clinical practice

The diagnosis and optimal management of AP require a systematic approach with multidisciplinary decision making. Morbidity and mortality in AP are driven by early or late POF, and the latter often is triggered by infected necrosis. Risk stratification of these patients at the point of contact is a commonsense approach to enable triaging of patients to the appropriate level of care. Regardless of pancreatitis severity, recommended treatment interventions include goal-directed IV fluid resuscitation, early feeding by mouth or enteral tube when necessary, avoidance of prophylactic antibiotics, avoidance of probiotics, and urgent ERCP for patients with acute biliary pancreatitis complicated by cholangitis. Key measures for preventing hospital readmission and pancreatitis include same-admission cholecystectomy for acute biliary pancreatitis and alcohol and smoking cessation. Preventive measures for post-ERCP pancreatitis in patients undergoing ERCP include rectal indomethacin, prophylactic pancreatic duct stent placement, and periprocedural fluid resuscitation.

Dr. Mandalia is a fellow, gastroenterology, department of internal medicine, division of gastroenterology, Michigan Medicine, Ann Arbor; Dr. DiMagno is associate professor of medicine, director, comprehensive pancreas program, department of internal medicine, division of gastroenterology, University of Michigan, Ann Arbor. Dr. Mandalia reports no conflicts of interest.

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IgG4-related disease can be grouped into four distinct clusters based on the distribution of organs involved, according to researchers who analyzed a large, multicenter cohort of patients with this heterogeneous, autoimmune-mediated condition.

The four groups also varied by age, race, sex, time to diagnosis, and concentration of serum IgG4, according to the investigators, led by Zachary S. Wallace, MD, of the division of rheumatology, allergy, and immunology at Massachusetts General Hospital and Harvard Medical School, both in Boston.

“These phenotypes may be used by clinicians to improve recognition of IgG4-related disease,” Dr. Wallace and his coauthors wrote in a report on the study that appears in the Annals of the Rheumatic Diseases.

First described in a Japanese population, IgG4-related disease has been subsequently seen in all racial and ethnic groups, according to the researchers. It is associated with organ failure and can affect nearly any organ or anatomic site, most notably the lungs, kidneys, lymph nodes, salivary glands, pancreatobiliary structures, and retroperitoneum.


In the present study, Dr. Wallace and his coinvestigators used a novel cluster analysis method, called latent class analysis, to categorize 765 cases of IgG4-related disease submitted by 52 investigators from 17 countries. The investigators included 493 of those cases in a primary study population, and the remaining 272 in a smaller cohort used to replicate the results.

In the larger, primary study cohort, about 65% of cases were male, 58% were non-Asian and 40% were white, and the mean age at diagnosis was 59.5 years. The replication cohort had similar characteristics, according to the investigators.

The clustering analysis revealed four distinct subgroups, characterized by pancreato-hepatobiliary, accounting for 31% of cases; retroperitoneal fibrosis and/or aortitis in 24%; disease generally limited to head and neck structures in 24%, and head and neck disease consistent with Mikulicz syndrome plus systemic involvement in 22%.

The highest IgG4 concentrations were seen in the group of patients with Mikulicz syndrome and systemic involvement, according to Dr. Wallace and his coauthors. The serum concentration was 1,170 mg/dL in that group, compared with 445 mg/dL in the group of patients with head and neck-limited disease, 316 mg/dL in the pancreato-hepatobiliary group, and just 178 mg/dL in the retroperitoneal fibrosis/aorta group.

Female and Asian patients were overrepresented in the group characterized by head and neck involvement, investigators also found. Moreover, that group had a significantly lower mean age at diagnosis than did the other groups.

Those variations suggested differences in genetic or environmental risk factors between clusters, according to the investigators.

“Given the similar distribution of subspecialists among investigators in this study practicing in Asian and non-Asian countries, the observed differences are unlikely to be the result of detection or selection biases,” they said in their report.

The findings of this study help to inform subsequent investigations intended to evaluate those factors in more detail, they said.

Dr. Wallace and his coauthors reported no conflicts of interest related to their work, which was previously presented at the American College of Rheumatology annual meeting.

SOURCE: Wallace ZS et al. Ann Rheum Dis. 2019 Jan 5. doi: 10.1136/annrheumdis-2018-214603

IgG4-related disease can be grouped into four distinct clusters based on the distribution of organs involved, according to researchers who analyzed a large, multicenter cohort of patients with this heterogeneous, autoimmune-mediated condition.

The four groups also varied by age, race, sex, time to diagnosis, and concentration of serum IgG4, according to the investigators, led by Zachary S. Wallace, MD, of the division of rheumatology, allergy, and immunology at Massachusetts General Hospital and Harvard Medical School, both in Boston.

“These phenotypes may be used by clinicians to improve recognition of IgG4-related disease,” Dr. Wallace and his coauthors wrote in a report on the study that appears in the Annals of the Rheumatic Diseases.

First described in a Japanese population, IgG4-related disease has been subsequently seen in all racial and ethnic groups, according to the researchers. It is associated with organ failure and can affect nearly any organ or anatomic site, most notably the lungs, kidneys, lymph nodes, salivary glands, pancreatobiliary structures, and retroperitoneum.


In the present study, Dr. Wallace and his coinvestigators used a novel cluster analysis method, called latent class analysis, to categorize 765 cases of IgG4-related disease submitted by 52 investigators from 17 countries. The investigators included 493 of those cases in a primary study population, and the remaining 272 in a smaller cohort used to replicate the results.

In the larger, primary study cohort, about 65% of cases were male, 58% were non-Asian and 40% were white, and the mean age at diagnosis was 59.5 years. The replication cohort had similar characteristics, according to the investigators.

The clustering analysis revealed four distinct subgroups, characterized by pancreato-hepatobiliary, accounting for 31% of cases; retroperitoneal fibrosis and/or aortitis in 24%; disease generally limited to head and neck structures in 24%, and head and neck disease consistent with Mikulicz syndrome plus systemic involvement in 22%.

The highest IgG4 concentrations were seen in the group of patients with Mikulicz syndrome and systemic involvement, according to Dr. Wallace and his coauthors. The serum concentration was 1,170 mg/dL in that group, compared with 445 mg/dL in the group of patients with head and neck-limited disease, 316 mg/dL in the pancreato-hepatobiliary group, and just 178 mg/dL in the retroperitoneal fibrosis/aorta group.

Female and Asian patients were overrepresented in the group characterized by head and neck involvement, investigators also found. Moreover, that group had a significantly lower mean age at diagnosis than did the other groups.

Those variations suggested differences in genetic or environmental risk factors between clusters, according to the investigators.

“Given the similar distribution of subspecialists among investigators in this study practicing in Asian and non-Asian countries, the observed differences are unlikely to be the result of detection or selection biases,” they said in their report.

The findings of this study help to inform subsequent investigations intended to evaluate those factors in more detail, they said.

Dr. Wallace and his coauthors reported no conflicts of interest related to their work, which was previously presented at the American College of Rheumatology annual meeting.

SOURCE: Wallace ZS et al. Ann Rheum Dis. 2019 Jan 5. doi: 10.1136/annrheumdis-2018-214603

IgG4-related disease can be grouped into four distinct clusters based on the distribution of organs involved, according to researchers who analyzed a large, multicenter cohort of patients with this heterogeneous, autoimmune-mediated condition.

The four groups also varied by age, race, sex, time to diagnosis, and concentration of serum IgG4, according to the investigators, led by Zachary S. Wallace, MD, of the division of rheumatology, allergy, and immunology at Massachusetts General Hospital and Harvard Medical School, both in Boston.

“These phenotypes may be used by clinicians to improve recognition of IgG4-related disease,” Dr. Wallace and his coauthors wrote in a report on the study that appears in the Annals of the Rheumatic Diseases.

First described in a Japanese population, IgG4-related disease has been subsequently seen in all racial and ethnic groups, according to the researchers. It is associated with organ failure and can affect nearly any organ or anatomic site, most notably the lungs, kidneys, lymph nodes, salivary glands, pancreatobiliary structures, and retroperitoneum.


In the present study, Dr. Wallace and his coinvestigators used a novel cluster analysis method, called latent class analysis, to categorize 765 cases of IgG4-related disease submitted by 52 investigators from 17 countries. The investigators included 493 of those cases in a primary study population, and the remaining 272 in a smaller cohort used to replicate the results.

In the larger, primary study cohort, about 65% of cases were male, 58% were non-Asian and 40% were white, and the mean age at diagnosis was 59.5 years. The replication cohort had similar characteristics, according to the investigators.

The clustering analysis revealed four distinct subgroups, characterized by pancreato-hepatobiliary, accounting for 31% of cases; retroperitoneal fibrosis and/or aortitis in 24%; disease generally limited to head and neck structures in 24%, and head and neck disease consistent with Mikulicz syndrome plus systemic involvement in 22%.

The highest IgG4 concentrations were seen in the group of patients with Mikulicz syndrome and systemic involvement, according to Dr. Wallace and his coauthors. The serum concentration was 1,170 mg/dL in that group, compared with 445 mg/dL in the group of patients with head and neck-limited disease, 316 mg/dL in the pancreato-hepatobiliary group, and just 178 mg/dL in the retroperitoneal fibrosis/aorta group.

Female and Asian patients were overrepresented in the group characterized by head and neck involvement, investigators also found. Moreover, that group had a significantly lower mean age at diagnosis than did the other groups.

Those variations suggested differences in genetic or environmental risk factors between clusters, according to the investigators.

“Given the similar distribution of subspecialists among investigators in this study practicing in Asian and non-Asian countries, the observed differences are unlikely to be the result of detection or selection biases,” they said in their report.

The findings of this study help to inform subsequent investigations intended to evaluate those factors in more detail, they said.

Dr. Wallace and his coauthors reported no conflicts of interest related to their work, which was previously presented at the American College of Rheumatology annual meeting.

SOURCE: Wallace ZS et al. Ann Rheum Dis. 2019 Jan 5. doi: 10.1136/annrheumdis-2018-214603

Compared with younger patients, elderly patients admitted for acute biliary pancreatitis have increased rates of severe acute pancreatitis and mortality, according to an analysis of a nationally representative database.

Mortality was almost three times as high in elderly patients after stringent matching for confounding variables, wrote researcher Kishan Patel, MD, of the Ohio State University, Columbus, and coauthors.

These findings represent a “current health care concern,” since the elderly population in the United States is expected to double within the next several decades and the prevalence of acute pancreatitis is on the rise, Dr. Patel and colleagues wrote in a report on the analysis in the Journal of Clinical Gastroenterology.

The analysis is the first, to the investigators’ knowledge, that addresses national-level outcomes associated with acute biliary pancreatitis in elderly patients.

To evaluate clinical outcomes of elderly patients with acute biliary pancreatitis, Dr. Patel and colleagues queried the Nationwide Readmissions Database, which is the largest inpatient readmission database in the United States.

The investigators looked at outcomes associated with index hospitalizations, defined as a patient’s first hospitalization in a calendar year, and found 184,763 adult patients who received a diagnosis of acute biliary pancreatitis between 2011 and 2014. Of those, 41% were elderly.

The mortality rate associated with the index admission was 1.96% (n = 356) for the elderly patients, compared with just 0.32% (n = 1,473) for nonelderly patients (P less than .001), according to the report.

Mortality was increased in the elderly versus nonelderly patients, with an odds ratio of 2.8 (95% CI, 2.2-3.5), according to results of a propensity score matched analysis. Likewise, severe acute pancreatitis was increased in the elderly, with an OR of 1.2 (95% CI: 1.1-1.3) in that analysis.

By contrast, patient age did not impact 30-day readmission rates, according to results of a multivariate analysis that adjusted for confounding factors.

Mortality and severe acute pancreatitis both increased with age within the elderly cohort, further multivariate analysis showed. For example, the ORs for mortality were 1.39 for patients aged 75-84 years and 2.21 for patients aged 85 years and older, the results show.

The elderly population in the United States is expected to almost double by 2050, rising from 48 to 88 million, Dr. Patel and colleagues said. The number of those aged 85 years or older is expected to increase from 5.9 to 18 million by 2050, at which time they will make up nearly 5% of the total U.S. population.

“This specific demographic is more susceptible to common medical ailments, more troubling is acute pancreatitis is one of the most frequent causes of hospitalization in gastroenterology,” Dr. Patel and colleagues wrote.

Dr. Patel and coauthors reported no conflicts of interest related to the analysis.

SOURCE: Patel K et al. J Clin Gastroenterol. 2018 Aug 28. doi: 10.1097/MCG.0000000000001108.

Compared with younger patients, elderly patients admitted for acute biliary pancreatitis have increased rates of severe acute pancreatitis and mortality, according to an analysis of a nationally representative database.

Mortality was almost three times as high in elderly patients after stringent matching for confounding variables, wrote researcher Kishan Patel, MD, of the Ohio State University, Columbus, and coauthors.

These findings represent a “current health care concern,” since the elderly population in the United States is expected to double within the next several decades and the prevalence of acute pancreatitis is on the rise, Dr. Patel and colleagues wrote in a report on the analysis in the Journal of Clinical Gastroenterology.

The analysis is the first, to the investigators’ knowledge, that addresses national-level outcomes associated with acute biliary pancreatitis in elderly patients.

To evaluate clinical outcomes of elderly patients with acute biliary pancreatitis, Dr. Patel and colleagues queried the Nationwide Readmissions Database, which is the largest inpatient readmission database in the United States.

The investigators looked at outcomes associated with index hospitalizations, defined as a patient’s first hospitalization in a calendar year, and found 184,763 adult patients who received a diagnosis of acute biliary pancreatitis between 2011 and 2014. Of those, 41% were elderly.

The mortality rate associated with the index admission was 1.96% (n = 356) for the elderly patients, compared with just 0.32% (n = 1,473) for nonelderly patients (P less than .001), according to the report.

Mortality was increased in the elderly versus nonelderly patients, with an odds ratio of 2.8 (95% CI, 2.2-3.5), according to results of a propensity score matched analysis. Likewise, severe acute pancreatitis was increased in the elderly, with an OR of 1.2 (95% CI: 1.1-1.3) in that analysis.

By contrast, patient age did not impact 30-day readmission rates, according to results of a multivariate analysis that adjusted for confounding factors.

Mortality and severe acute pancreatitis both increased with age within the elderly cohort, further multivariate analysis showed. For example, the ORs for mortality were 1.39 for patients aged 75-84 years and 2.21 for patients aged 85 years and older, the results show.

The elderly population in the United States is expected to almost double by 2050, rising from 48 to 88 million, Dr. Patel and colleagues said. The number of those aged 85 years or older is expected to increase from 5.9 to 18 million by 2050, at which time they will make up nearly 5% of the total U.S. population.

“This specific demographic is more susceptible to common medical ailments, more troubling is acute pancreatitis is one of the most frequent causes of hospitalization in gastroenterology,” Dr. Patel and colleagues wrote.

Dr. Patel and coauthors reported no conflicts of interest related to the analysis.

SOURCE: Patel K et al. J Clin Gastroenterol. 2018 Aug 28. doi: 10.1097/MCG.0000000000001108.

Compared with younger patients, elderly patients admitted for acute biliary pancreatitis have increased rates of severe acute pancreatitis and mortality, according to an analysis of a nationally representative database.

Mortality was almost three times as high in elderly patients after stringent matching for confounding variables, wrote researcher Kishan Patel, MD, of the Ohio State University, Columbus, and coauthors.

These findings represent a “current health care concern,” since the elderly population in the United States is expected to double within the next several decades and the prevalence of acute pancreatitis is on the rise, Dr. Patel and colleagues wrote in a report on the analysis in the Journal of Clinical Gastroenterology.

The analysis is the first, to the investigators’ knowledge, that addresses national-level outcomes associated with acute biliary pancreatitis in elderly patients.

To evaluate clinical outcomes of elderly patients with acute biliary pancreatitis, Dr. Patel and colleagues queried the Nationwide Readmissions Database, which is the largest inpatient readmission database in the United States.

The investigators looked at outcomes associated with index hospitalizations, defined as a patient’s first hospitalization in a calendar year, and found 184,763 adult patients who received a diagnosis of acute biliary pancreatitis between 2011 and 2014. Of those, 41% were elderly.

The mortality rate associated with the index admission was 1.96% (n = 356) for the elderly patients, compared with just 0.32% (n = 1,473) for nonelderly patients (P less than .001), according to the report.

Mortality was increased in the elderly versus nonelderly patients, with an odds ratio of 2.8 (95% CI, 2.2-3.5), according to results of a propensity score matched analysis. Likewise, severe acute pancreatitis was increased in the elderly, with an OR of 1.2 (95% CI: 1.1-1.3) in that analysis.

By contrast, patient age did not impact 30-day readmission rates, according to results of a multivariate analysis that adjusted for confounding factors.

Mortality and severe acute pancreatitis both increased with age within the elderly cohort, further multivariate analysis showed. For example, the ORs for mortality were 1.39 for patients aged 75-84 years and 2.21 for patients aged 85 years and older, the results show.

The elderly population in the United States is expected to almost double by 2050, rising from 48 to 88 million, Dr. Patel and colleagues said. The number of those aged 85 years or older is expected to increase from 5.9 to 18 million by 2050, at which time they will make up nearly 5% of the total U.S. population.

“This specific demographic is more susceptible to common medical ailments, more troubling is acute pancreatitis is one of the most frequent causes of hospitalization in gastroenterology,” Dr. Patel and colleagues wrote.

Dr. Patel and coauthors reported no conflicts of interest related to the analysis.

SOURCE: Patel K et al. J Clin Gastroenterol. 2018 Aug 28. doi: 10.1097/MCG.0000000000001108.

For the pancreatobiliary session, Michelle Ann Anderson, MD, of the University of Michigan, Ann Arbor, reminded us about appropriate patient selection given the risk of pancreatitis after endoscopic retrograde cholangiopancreatography pancreatitis, also known as post-ERCP pancreatitis. Strategies to prevent post-ERCP pancreatitis include using pancreatic duct stents and using wire rather than contrast for cannulation. She recommended rectal indomethacin for all patients. Because of encouraging data, she recommended 2-3 L of lactated Ringer’s solution during the procedure and recovery. 

Katie Morgan, MD, from the Medical University of South Carolina, Charleston, reviewed her group’s experience with 195 total pancreatectomies with islet autotransplants for chronic pancreatitis. Quality of life improved with major reductions in narcotic use, and 25% of patients were insulin free. 

Bret Petersen, MD, of Mayo Clinic, Rochester, Minn., discussed multidrug resistant infection in ERCP endoscopes. He reminded us of the risk of lapses in endoscope reprocessing steps and the need for monitoring. He commented on recent Food and Drug Administration’s culture guidance and new technologies in development. 

James Scheiman, MD, from the University of Virginia, Charlottesville, discussed pancreatic cysts. He reviewed the controversy between the more conservative American Gastroenterological Association guidelines and the more aggressive International Consensus guidelines. He advised considering patient preferences with a multidisciplinary approach.
For the liver session, Guadalupe García-Tsao, MD, of Yale University, New Haven, Conn., discussed the controversy regarding nonselective beta-blockers. She advised caution if refractory ascites are present because of risk for renal dysfunction, but she also highlighted the benefits including reduced first and recurrent variceal hemorrhage. 

Rohit Loomba, MD, from the University of California at San Diego addressed fibrosis assessments in fatty liver. In his algorithm, patients with low Nonalcoholic Fatty Liver Disease Fibrosis Score or Fibrosis-4 scores would have continued observation, while patients with medium or high scores would undergo transient elastography or magnetic resonance elastography. 

Patrick Northup, MD, from the University of Virginia discussed anticoagulation for portal vein thrombosis. He also discussed consideration of transjugular intrahepatic portosystemic shunt if there are high-risk varices. Duration of anticoagulation is controversial, but this strategy may prevent decompensation and affect transplant outcomes. 

Daryl Lau, MD, MSc, MPH, from Harvard Medical School, Boston, reviewed the hepatitis B virus therapy controversy for e-antigen–negative patients with prolonged viral suppression. She recommended caution in general and emphasized that stage 3-4 fibrosis patients should not discontinue therapy. 

The final talk was my review of hepatitis C virus treatment. I emphasized that pretreatment fibrosis assessments are critical given continued risk of hepatocellular carcinoma after cure. Challenges include identifying the remaining patients and supporting them through treatment. HCV therapies demonstrate what is possible when breakthroughs are translated to clinical care, and I was honored to participate in this course that highlighted many advances in our field.

Dr. Muir is a professor of medicine, director of gastroenterology & hepatology research at Duke Clinical Research Institute, and chief of the division of gastroenterology in the department of medicine at Duke University, all in Durham, N.C. He has received research grants from and served on the advisory boards for AbbVie, Gilead Sciences, Merck, and several other pharmaceutical companies. This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2018.

For the pancreatobiliary session, Michelle Ann Anderson, MD, of the University of Michigan, Ann Arbor, reminded us about appropriate patient selection given the risk of pancreatitis after endoscopic retrograde cholangiopancreatography pancreatitis, also known as post-ERCP pancreatitis. Strategies to prevent post-ERCP pancreatitis include using pancreatic duct stents and using wire rather than contrast for cannulation. She recommended rectal indomethacin for all patients. Because of encouraging data, she recommended 2-3 L of lactated Ringer’s solution during the procedure and recovery. 

Katie Morgan, MD, from the Medical University of South Carolina, Charleston, reviewed her group’s experience with 195 total pancreatectomies with islet autotransplants for chronic pancreatitis. Quality of life improved with major reductions in narcotic use, and 25% of patients were insulin free. 

Bret Petersen, MD, of Mayo Clinic, Rochester, Minn., discussed multidrug resistant infection in ERCP endoscopes. He reminded us of the risk of lapses in endoscope reprocessing steps and the need for monitoring. He commented on recent Food and Drug Administration’s culture guidance and new technologies in development. 

James Scheiman, MD, from the University of Virginia, Charlottesville, discussed pancreatic cysts. He reviewed the controversy between the more conservative American Gastroenterological Association guidelines and the more aggressive International Consensus guidelines. He advised considering patient preferences with a multidisciplinary approach.
For the liver session, Guadalupe García-Tsao, MD, of Yale University, New Haven, Conn., discussed the controversy regarding nonselective beta-blockers. She advised caution if refractory ascites are present because of risk for renal dysfunction, but she also highlighted the benefits including reduced first and recurrent variceal hemorrhage. 

Rohit Loomba, MD, from the University of California at San Diego addressed fibrosis assessments in fatty liver. In his algorithm, patients with low Nonalcoholic Fatty Liver Disease Fibrosis Score or Fibrosis-4 scores would have continued observation, while patients with medium or high scores would undergo transient elastography or magnetic resonance elastography. 

Patrick Northup, MD, from the University of Virginia discussed anticoagulation for portal vein thrombosis. He also discussed consideration of transjugular intrahepatic portosystemic shunt if there are high-risk varices. Duration of anticoagulation is controversial, but this strategy may prevent decompensation and affect transplant outcomes. 

Daryl Lau, MD, MSc, MPH, from Harvard Medical School, Boston, reviewed the hepatitis B virus therapy controversy for e-antigen–negative patients with prolonged viral suppression. She recommended caution in general and emphasized that stage 3-4 fibrosis patients should not discontinue therapy. 

The final talk was my review of hepatitis C virus treatment. I emphasized that pretreatment fibrosis assessments are critical given continued risk of hepatocellular carcinoma after cure. Challenges include identifying the remaining patients and supporting them through treatment. HCV therapies demonstrate what is possible when breakthroughs are translated to clinical care, and I was honored to participate in this course that highlighted many advances in our field.

Dr. Muir is a professor of medicine, director of gastroenterology & hepatology research at Duke Clinical Research Institute, and chief of the division of gastroenterology in the department of medicine at Duke University, all in Durham, N.C. He has received research grants from and served on the advisory boards for AbbVie, Gilead Sciences, Merck, and several other pharmaceutical companies. This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2018.

For the pancreatobiliary session, Michelle Ann Anderson, MD, of the University of Michigan, Ann Arbor, reminded us about appropriate patient selection given the risk of pancreatitis after endoscopic retrograde cholangiopancreatography pancreatitis, also known as post-ERCP pancreatitis. Strategies to prevent post-ERCP pancreatitis include using pancreatic duct stents and using wire rather than contrast for cannulation. She recommended rectal indomethacin for all patients. Because of encouraging data, she recommended 2-3 L of lactated Ringer’s solution during the procedure and recovery. 

Katie Morgan, MD, from the Medical University of South Carolina, Charleston, reviewed her group’s experience with 195 total pancreatectomies with islet autotransplants for chronic pancreatitis. Quality of life improved with major reductions in narcotic use, and 25% of patients were insulin free. 

Bret Petersen, MD, of Mayo Clinic, Rochester, Minn., discussed multidrug resistant infection in ERCP endoscopes. He reminded us of the risk of lapses in endoscope reprocessing steps and the need for monitoring. He commented on recent Food and Drug Administration’s culture guidance and new technologies in development. 

James Scheiman, MD, from the University of Virginia, Charlottesville, discussed pancreatic cysts. He reviewed the controversy between the more conservative American Gastroenterological Association guidelines and the more aggressive International Consensus guidelines. He advised considering patient preferences with a multidisciplinary approach.
For the liver session, Guadalupe García-Tsao, MD, of Yale University, New Haven, Conn., discussed the controversy regarding nonselective beta-blockers. She advised caution if refractory ascites are present because of risk for renal dysfunction, but she also highlighted the benefits including reduced first and recurrent variceal hemorrhage. 

Rohit Loomba, MD, from the University of California at San Diego addressed fibrosis assessments in fatty liver. In his algorithm, patients with low Nonalcoholic Fatty Liver Disease Fibrosis Score or Fibrosis-4 scores would have continued observation, while patients with medium or high scores would undergo transient elastography or magnetic resonance elastography. 

Patrick Northup, MD, from the University of Virginia discussed anticoagulation for portal vein thrombosis. He also discussed consideration of transjugular intrahepatic portosystemic shunt if there are high-risk varices. Duration of anticoagulation is controversial, but this strategy may prevent decompensation and affect transplant outcomes. 

Daryl Lau, MD, MSc, MPH, from Harvard Medical School, Boston, reviewed the hepatitis B virus therapy controversy for e-antigen–negative patients with prolonged viral suppression. She recommended caution in general and emphasized that stage 3-4 fibrosis patients should not discontinue therapy. 

The final talk was my review of hepatitis C virus treatment. I emphasized that pretreatment fibrosis assessments are critical given continued risk of hepatocellular carcinoma after cure. Challenges include identifying the remaining patients and supporting them through treatment. HCV therapies demonstrate what is possible when breakthroughs are translated to clinical care, and I was honored to participate in this course that highlighted many advances in our field.

Dr. Muir is a professor of medicine, director of gastroenterology & hepatology research at Duke Clinical Research Institute, and chief of the division of gastroenterology in the department of medicine at Duke University, all in Durham, N.C. He has received research grants from and served on the advisory boards for AbbVie, Gilead Sciences, Merck, and several other pharmaceutical companies. This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2018.

Long-term pancreatic surveillance of high-risk patients identified cancers while they were still resectable, and 85% of such patients remained alive 3 years after diagnosis, researchers reported.

iStock/ThinkStock

“Among individuals undergoing pancreatic surveillance, specific detectable lesions with worrisome features predicted neoplastic progression. The short-term outcomes of patients with screening-detected PDACs [pancreatic ductal adenocarcinomas] improved,” wrote Marcia Irene Canto, MD, MHS, of the Johns Hopkins University, Baltimore, together with her associates in the September issue of Gastroenterology.

The lifetime risk of PDAC is about 1.5%, the researchers noted. Consequently, the U.S. Preventive Services Task Force does not recommend pancreatic surveillance at a population level. However, pancreatic screening is being evaluated for individuals who are at significantly elevated risk of PDAC, including those with at least two first-degree relatives with PDAC or who have germline mutations in BRCA1, BRCA2, PALB2, PRSS1 (hereditary pancreatitis), CDKN2A, MLH1, MSH2, MSH6, PMS2 (Lynch syndrome), or STK11 (Peutz-Jeghers syndrome).

For the study, Dr. Canto and her associates analyzed data from 354 such high-risk individuals enrolled in the CAPS (Cancer of the Pancreas Screening) cohort studies, which were conducted at tertiary care academic centers during 1998-2014. All participants underwent endoscopic ultrasound at baseline, followed by surveillance with endoscopic ultrasound, magnetic resonance imaging, computed tomography, or some combination of these modalities. Patients who developed pancreatic cancer or high-grade dysplasia were offered surgery.

In all, 68 patients (19%) developed pancreatic lesions with worrisome features, such as solid masses, multiple cysts, mural nodules, thickened or enhancing walls, cysts exceeding 3 cm in size or that grew more than 4 mm annually, a greater than 5-mm dilation of the main pancreatic duct, or an abrupt change in duct caliber. The lesions developed over a median of 13.1 months (interquartile range, 0.2-52 months).

A total of 7% of patients had neoplastic progression, including 14 cases of PDAC and 10 cases of high-grade dysplasia. Median times from baseline to detection of PDAC were 4.8 years overall (IQR, 1.6-6.9 years), 1.7 years (IQR, 0.5-4.4 years) among patients aged at least 60 years at baseline, and 5.2 years among younger patients (IQR, 0.4-8 years). Patients developed PDAC at a median of 67 years old.

Among 10 PDACs detected by surveillance, 9 were resectable. Three patients subsequently died of PDAC, while one patient died of complications of gastric cancer surgery. However, 85% of patients survived for at least 3 years after surgical resection of PDAC. The remaining four cases of PDAC were detected outside surveillance or after patients stopped surveillance.

The 10 cases of high-grade dysplasia consisted of intraductal papillary mucinous neoplasm with high-grade dysplasia or high-grade pancreatic intraepithelial neoplasia. Patients whose PDAC or high-grade dysplasia was detected by surveillance survived a median of 5.3 years, while patients whose surveillance was late or stopped and who subsequently developed neoplasia survived a median of only 1.4 years after diagnosis (P less than .0001).

Funders included the Pancreatic Cancer Action Network, Lustgarten Foundation for Pancreatic Cancer Research, the John and Peter Hooven Memorial Endowment, Hugh and Rachel Victor, and ChiRhoClin. Dr. Canto had no disclosures. Three coinvestigators disclosed royalties for licensing of PALB2 as a pancreatic cancer susceptibility gene.

SOURCE: Canto MI et al. Gastroenterology. 2018 May 24. doi: 10.1053/j.gastro.2018.05.035

Long-term pancreatic surveillance of high-risk patients identified cancers while they were still resectable, and 85% of such patients remained alive 3 years after diagnosis, researchers reported.

iStock/ThinkStock

“Among individuals undergoing pancreatic surveillance, specific detectable lesions with worrisome features predicted neoplastic progression. The short-term outcomes of patients with screening-detected PDACs [pancreatic ductal adenocarcinomas] improved,” wrote Marcia Irene Canto, MD, MHS, of the Johns Hopkins University, Baltimore, together with her associates in the September issue of Gastroenterology.

The lifetime risk of PDAC is about 1.5%, the researchers noted. Consequently, the U.S. Preventive Services Task Force does not recommend pancreatic surveillance at a population level. However, pancreatic screening is being evaluated for individuals who are at significantly elevated risk of PDAC, including those with at least two first-degree relatives with PDAC or who have germline mutations in BRCA1, BRCA2, PALB2, PRSS1 (hereditary pancreatitis), CDKN2A, MLH1, MSH2, MSH6, PMS2 (Lynch syndrome), or STK11 (Peutz-Jeghers syndrome).

For the study, Dr. Canto and her associates analyzed data from 354 such high-risk individuals enrolled in the CAPS (Cancer of the Pancreas Screening) cohort studies, which were conducted at tertiary care academic centers during 1998-2014. All participants underwent endoscopic ultrasound at baseline, followed by surveillance with endoscopic ultrasound, magnetic resonance imaging, computed tomography, or some combination of these modalities. Patients who developed pancreatic cancer or high-grade dysplasia were offered surgery.

In all, 68 patients (19%) developed pancreatic lesions with worrisome features, such as solid masses, multiple cysts, mural nodules, thickened or enhancing walls, cysts exceeding 3 cm in size or that grew more than 4 mm annually, a greater than 5-mm dilation of the main pancreatic duct, or an abrupt change in duct caliber. The lesions developed over a median of 13.1 months (interquartile range, 0.2-52 months).

A total of 7% of patients had neoplastic progression, including 14 cases of PDAC and 10 cases of high-grade dysplasia. Median times from baseline to detection of PDAC were 4.8 years overall (IQR, 1.6-6.9 years), 1.7 years (IQR, 0.5-4.4 years) among patients aged at least 60 years at baseline, and 5.2 years among younger patients (IQR, 0.4-8 years). Patients developed PDAC at a median of 67 years old.

Among 10 PDACs detected by surveillance, 9 were resectable. Three patients subsequently died of PDAC, while one patient died of complications of gastric cancer surgery. However, 85% of patients survived for at least 3 years after surgical resection of PDAC. The remaining four cases of PDAC were detected outside surveillance or after patients stopped surveillance.

The 10 cases of high-grade dysplasia consisted of intraductal papillary mucinous neoplasm with high-grade dysplasia or high-grade pancreatic intraepithelial neoplasia. Patients whose PDAC or high-grade dysplasia was detected by surveillance survived a median of 5.3 years, while patients whose surveillance was late or stopped and who subsequently developed neoplasia survived a median of only 1.4 years after diagnosis (P less than .0001).

Funders included the Pancreatic Cancer Action Network, Lustgarten Foundation for Pancreatic Cancer Research, the John and Peter Hooven Memorial Endowment, Hugh and Rachel Victor, and ChiRhoClin. Dr. Canto had no disclosures. Three coinvestigators disclosed royalties for licensing of PALB2 as a pancreatic cancer susceptibility gene.

SOURCE: Canto MI et al. Gastroenterology. 2018 May 24. doi: 10.1053/j.gastro.2018.05.035

Long-term pancreatic surveillance of high-risk patients identified cancers while they were still resectable, and 85% of such patients remained alive 3 years after diagnosis, researchers reported.

iStock/ThinkStock

“Among individuals undergoing pancreatic surveillance, specific detectable lesions with worrisome features predicted neoplastic progression. The short-term outcomes of patients with screening-detected PDACs [pancreatic ductal adenocarcinomas] improved,” wrote Marcia Irene Canto, MD, MHS, of the Johns Hopkins University, Baltimore, together with her associates in the September issue of Gastroenterology.

The lifetime risk of PDAC is about 1.5%, the researchers noted. Consequently, the U.S. Preventive Services Task Force does not recommend pancreatic surveillance at a population level. However, pancreatic screening is being evaluated for individuals who are at significantly elevated risk of PDAC, including those with at least two first-degree relatives with PDAC or who have germline mutations in BRCA1, BRCA2, PALB2, PRSS1 (hereditary pancreatitis), CDKN2A, MLH1, MSH2, MSH6, PMS2 (Lynch syndrome), or STK11 (Peutz-Jeghers syndrome).

For the study, Dr. Canto and her associates analyzed data from 354 such high-risk individuals enrolled in the CAPS (Cancer of the Pancreas Screening) cohort studies, which were conducted at tertiary care academic centers during 1998-2014. All participants underwent endoscopic ultrasound at baseline, followed by surveillance with endoscopic ultrasound, magnetic resonance imaging, computed tomography, or some combination of these modalities. Patients who developed pancreatic cancer or high-grade dysplasia were offered surgery.

In all, 68 patients (19%) developed pancreatic lesions with worrisome features, such as solid masses, multiple cysts, mural nodules, thickened or enhancing walls, cysts exceeding 3 cm in size or that grew more than 4 mm annually, a greater than 5-mm dilation of the main pancreatic duct, or an abrupt change in duct caliber. The lesions developed over a median of 13.1 months (interquartile range, 0.2-52 months).

A total of 7% of patients had neoplastic progression, including 14 cases of PDAC and 10 cases of high-grade dysplasia. Median times from baseline to detection of PDAC were 4.8 years overall (IQR, 1.6-6.9 years), 1.7 years (IQR, 0.5-4.4 years) among patients aged at least 60 years at baseline, and 5.2 years among younger patients (IQR, 0.4-8 years). Patients developed PDAC at a median of 67 years old.

Among 10 PDACs detected by surveillance, 9 were resectable. Three patients subsequently died of PDAC, while one patient died of complications of gastric cancer surgery. However, 85% of patients survived for at least 3 years after surgical resection of PDAC. The remaining four cases of PDAC were detected outside surveillance or after patients stopped surveillance.

The 10 cases of high-grade dysplasia consisted of intraductal papillary mucinous neoplasm with high-grade dysplasia or high-grade pancreatic intraepithelial neoplasia. Patients whose PDAC or high-grade dysplasia was detected by surveillance survived a median of 5.3 years, while patients whose surveillance was late or stopped and who subsequently developed neoplasia survived a median of only 1.4 years after diagnosis (P less than .0001).

Funders included the Pancreatic Cancer Action Network, Lustgarten Foundation for Pancreatic Cancer Research, the John and Peter Hooven Memorial Endowment, Hugh and Rachel Victor, and ChiRhoClin. Dr. Canto had no disclosures. Three coinvestigators disclosed royalties for licensing of PALB2 as a pancreatic cancer susceptibility gene.

SOURCE: Canto MI et al. Gastroenterology. 2018 May 24. doi: 10.1053/j.gastro.2018.05.035

The number of U.S. emergency department visits for acute pancreatitis associated with alcohol abuse, chronic pancreatitis history, and younger age was on the rise in recent years, an analysis of a nationally representative database has suggested.

Katarzyna Bialasiewicz/Thinkstock

Meanwhile, hospital admissions and length of stay dropped, but ED and inpatient charges increased, according to the analysis by Sushil K. Garg, MD, of the division of gastroenterology and hepatology at the Mayo Clinic, Rochester, Minn., and his coauthors.

“This study identifies important patient populations, specifically young patients with alcohol abuse, to target in order to develop programs to assist in reduction of ED utilization for acute pancreatitis,” Dr. Garg and his colleagues reported in the Journal of Clinical Gastroenterology.

The retrospective analysis was focused on nearly 2.2 million ED visits during 2006-2012 in the National Emergency Department Sample (NEDS) database. The cohort was limited to adults at least 18 years of age with a primary diagnosis of acute pancreatitis.

Overall, there was a nonsignificant 5.5% increase in visits per 10,000 U.S. population during 2006-2012, the researchers found. However, the total number of ED visits in this sample increased significantly – from 292,902 in 2006 to a peak of 326,376, an average rate of increase of 7,213 visits per year (P = .0086), according to the report.

Younger patients had a significant increase in the number of pancreatitis-related ED visits over the study period, while older patients had a significant decrease, according to investigators. Visits were up 9.2% for patients aged 18-44 years and 8.6% for those aged 45-64 but down 13.4% for patients aged 65-84 years and 20.1% for those aged 85 years or older.

The incidence of visits secondary to biliary disease was virtually flat over time, Dr. Garg and his coinvestigators found when looking at visits grouped by the most common presenting etiologies. By contrast, there were significant increases in visits for acute pancreatitis associated with alcohol abuse or chronic pancreatitis.

Specifically, acute pancreatitis associated with biliary disease averaged 20.7% of yearly pancreatitis-related ED visits and did not significantly change over time, the researchers reported.

By contrast, acute pancreatitis associated with alcohol abuse, which accounted for 24.1% of visits on average, increased by 15.9% over the study period, an increase driven by an increase among age groups younger than 65 years.

Acute pancreatitis associated with chronic pancreatitis, which made up 11.5% of visits on average, increased “substantially” in all age groups, according to study authors, with the largest increase in the group aged 45-64 years. Overall, the percentage increase over 7 years was 59.5%.

Rates of hospitalization decreased significantly over time, from 76.2% in 2006 to 72.7% in 2012 (P = .0026), and likewise, the length of stay dropped from 5.36 to 4.64 days (P = .0001), according to the analysis.

Inpatient charges, adjusted for inflation and expressed in 2012 dollars, increased from $32,130.63 to $34,652.00 (P = .0011), an average rate of increase of $489/year.

Predictors of hospitalization included age older than 84 years, alcohol use, smoking, and a Charlson comorbidity score of 1 or greater, according to the results of a multivariate regression analysis.

“Factors which may place patients at higher risk for severe or complicated acute pancreatitis requiring admission, such as obesity, alcohol use, and increasing age, are identified and should be explored in further studies and potentially targeted to improve ED and inpatient care,” Dr. Garg and his coauthors said.

Dr. Garg and his coauthors had no disclosures related to the study.

Help your patients better understand pancreatitis and available tests and treatments by using AGA patient education materials, https://www.gastro.org/practice-guidance/gi-patient-center/topic/pancreatitis.

SOURCE: Garg SK et al. J Clin Gastroenterol. 2018 Apr 6. doi: 10.1097/MCG.0000000000001030.

The number of U.S. emergency department visits for acute pancreatitis associated with alcohol abuse, chronic pancreatitis history, and younger age was on the rise in recent years, an analysis of a nationally representative database has suggested.

Katarzyna Bialasiewicz/Thinkstock

Meanwhile, hospital admissions and length of stay dropped, but ED and inpatient charges increased, according to the analysis by Sushil K. Garg, MD, of the division of gastroenterology and hepatology at the Mayo Clinic, Rochester, Minn., and his coauthors.

“This study identifies important patient populations, specifically young patients with alcohol abuse, to target in order to develop programs to assist in reduction of ED utilization for acute pancreatitis,” Dr. Garg and his colleagues reported in the Journal of Clinical Gastroenterology.

The retrospective analysis was focused on nearly 2.2 million ED visits during 2006-2012 in the National Emergency Department Sample (NEDS) database. The cohort was limited to adults at least 18 years of age with a primary diagnosis of acute pancreatitis.

Overall, there was a nonsignificant 5.5% increase in visits per 10,000 U.S. population during 2006-2012, the researchers found. However, the total number of ED visits in this sample increased significantly – from 292,902 in 2006 to a peak of 326,376, an average rate of increase of 7,213 visits per year (P = .0086), according to the report.

Younger patients had a significant increase in the number of pancreatitis-related ED visits over the study period, while older patients had a significant decrease, according to investigators. Visits were up 9.2% for patients aged 18-44 years and 8.6% for those aged 45-64 but down 13.4% for patients aged 65-84 years and 20.1% for those aged 85 years or older.

The incidence of visits secondary to biliary disease was virtually flat over time, Dr. Garg and his coinvestigators found when looking at visits grouped by the most common presenting etiologies. By contrast, there were significant increases in visits for acute pancreatitis associated with alcohol abuse or chronic pancreatitis.

Specifically, acute pancreatitis associated with biliary disease averaged 20.7% of yearly pancreatitis-related ED visits and did not significantly change over time, the researchers reported.

By contrast, acute pancreatitis associated with alcohol abuse, which accounted for 24.1% of visits on average, increased by 15.9% over the study period, an increase driven by an increase among age groups younger than 65 years.

Acute pancreatitis associated with chronic pancreatitis, which made up 11.5% of visits on average, increased “substantially” in all age groups, according to study authors, with the largest increase in the group aged 45-64 years. Overall, the percentage increase over 7 years was 59.5%.

Rates of hospitalization decreased significantly over time, from 76.2% in 2006 to 72.7% in 2012 (P = .0026), and likewise, the length of stay dropped from 5.36 to 4.64 days (P = .0001), according to the analysis.

Inpatient charges, adjusted for inflation and expressed in 2012 dollars, increased from $32,130.63 to $34,652.00 (P = .0011), an average rate of increase of $489/year.

Predictors of hospitalization included age older than 84 years, alcohol use, smoking, and a Charlson comorbidity score of 1 or greater, according to the results of a multivariate regression analysis.

“Factors which may place patients at higher risk for severe or complicated acute pancreatitis requiring admission, such as obesity, alcohol use, and increasing age, are identified and should be explored in further studies and potentially targeted to improve ED and inpatient care,” Dr. Garg and his coauthors said.

Dr. Garg and his coauthors had no disclosures related to the study.

Help your patients better understand pancreatitis and available tests and treatments by using AGA patient education materials, https://www.gastro.org/practice-guidance/gi-patient-center/topic/pancreatitis.

SOURCE: Garg SK et al. J Clin Gastroenterol. 2018 Apr 6. doi: 10.1097/MCG.0000000000001030.

The number of U.S. emergency department visits for acute pancreatitis associated with alcohol abuse, chronic pancreatitis history, and younger age was on the rise in recent years, an analysis of a nationally representative database has suggested.

Katarzyna Bialasiewicz/Thinkstock

Meanwhile, hospital admissions and length of stay dropped, but ED and inpatient charges increased, according to the analysis by Sushil K. Garg, MD, of the division of gastroenterology and hepatology at the Mayo Clinic, Rochester, Minn., and his coauthors.

“This study identifies important patient populations, specifically young patients with alcohol abuse, to target in order to develop programs to assist in reduction of ED utilization for acute pancreatitis,” Dr. Garg and his colleagues reported in the Journal of Clinical Gastroenterology.

The retrospective analysis was focused on nearly 2.2 million ED visits during 2006-2012 in the National Emergency Department Sample (NEDS) database. The cohort was limited to adults at least 18 years of age with a primary diagnosis of acute pancreatitis.

Overall, there was a nonsignificant 5.5% increase in visits per 10,000 U.S. population during 2006-2012, the researchers found. However, the total number of ED visits in this sample increased significantly – from 292,902 in 2006 to a peak of 326,376, an average rate of increase of 7,213 visits per year (P = .0086), according to the report.

Younger patients had a significant increase in the number of pancreatitis-related ED visits over the study period, while older patients had a significant decrease, according to investigators. Visits were up 9.2% for patients aged 18-44 years and 8.6% for those aged 45-64 but down 13.4% for patients aged 65-84 years and 20.1% for those aged 85 years or older.

The incidence of visits secondary to biliary disease was virtually flat over time, Dr. Garg and his coinvestigators found when looking at visits grouped by the most common presenting etiologies. By contrast, there were significant increases in visits for acute pancreatitis associated with alcohol abuse or chronic pancreatitis.

Specifically, acute pancreatitis associated with biliary disease averaged 20.7% of yearly pancreatitis-related ED visits and did not significantly change over time, the researchers reported.

By contrast, acute pancreatitis associated with alcohol abuse, which accounted for 24.1% of visits on average, increased by 15.9% over the study period, an increase driven by an increase among age groups younger than 65 years.

Acute pancreatitis associated with chronic pancreatitis, which made up 11.5% of visits on average, increased “substantially” in all age groups, according to study authors, with the largest increase in the group aged 45-64 years. Overall, the percentage increase over 7 years was 59.5%.

Rates of hospitalization decreased significantly over time, from 76.2% in 2006 to 72.7% in 2012 (P = .0026), and likewise, the length of stay dropped from 5.36 to 4.64 days (P = .0001), according to the analysis.

Inpatient charges, adjusted for inflation and expressed in 2012 dollars, increased from $32,130.63 to $34,652.00 (P = .0011), an average rate of increase of $489/year.

Predictors of hospitalization included age older than 84 years, alcohol use, smoking, and a Charlson comorbidity score of 1 or greater, according to the results of a multivariate regression analysis.

“Factors which may place patients at higher risk for severe or complicated acute pancreatitis requiring admission, such as obesity, alcohol use, and increasing age, are identified and should be explored in further studies and potentially targeted to improve ED and inpatient care,” Dr. Garg and his coauthors said.

Dr. Garg and his coauthors had no disclosures related to the study.

Help your patients better understand pancreatitis and available tests and treatments by using AGA patient education materials, https://www.gastro.org/practice-guidance/gi-patient-center/topic/pancreatitis.

SOURCE: Garg SK et al. J Clin Gastroenterol. 2018 Apr 6. doi: 10.1097/MCG.0000000000001030.

Researchers have identified laminin 511 as a novel antigen in autoimmune pancreatitis (AIP). A truncated form of the antigen was found in about half of human patients, but fewer than 2% of controls, and mice that were immunized with the antigen responded with induced antibodies and suffered pancreatic injury.

Laminin 511 plays a key role in cell–extracellular matrix (ECM) adhesion in pancreatic tissue. The results, published in Science Translational Medicine, could improve the biologic understanding of AIP and could potentially be a useful diagnostic marker for the disease.

Some autoantibodies are known to be associated with AIP, but the seropositive frequency is low among patients.

The researchers previously demonstrated that injecting IgG from AIP patients into neonatal mice led to pancreatic injury. The IgG was bound to the basement membrane of the pancreatic acini, suggesting the presence of autoantibodies that recognize an antigen in the ECM.

The researchers then screened previously known proteins from the pancreatic ECM against sera from AIP patients, performing Western blot analyses and immunosorbent column chromatography with human and mouse pancreas extracts, and AIP patient IgG. But this approach yielded no results.

The team then conducted an enzyme-linked immunosorbent assay using known pancreatic ECM proteins, which included the laminin subunits 511-FL, 521-FL, 511-E8, 521-E8, 111-EI, 211-E8, and 332-E8. The E8 designates a truncated protein produced by pancreatic elastase that contains the integrin-binding site.

That experiment revealed that 511-E8 is a consistent autoantigen, and a survey of AIP patients found that 26 of 51 (51.0%) had autoantibodies against 511-E8, compared with just 2 of 122 (1.6%) of controls (P less than .001). Further immunohistochemistry studies confirmed that patient IgG binds to laminin in pancreatic tissue.

When the researchers injected 511-E8, 511-FL, 521-FL, or ovalbumin into 8-week-old mice, and then again after 28 days and 56 days, only those who received 511-E8 showed evidence of pancreatic injury 28 days after the final immunization. The mice generated autoantibodies to 511-E8 but not ovalbumin.

The findings may have clinical significance. Patients with antibodies to laminin 511-E8 had a lower frequency of malignancies (0% vs. 32%; P =.0017) and allergic diseases (12% vs. 48%; P =.0043) than patients with no laminin 511-E8 antibodies.

The study was funded by the Japan Society for the Promotion of Science; the Japanese Ministry of Health, Labour, and Welfare; the Practical Research Project for Rare/Intractable Diseases Grant,; the Agency for Medical Research and Development; and the Takeda Science Foundation. One of the authors has filed a patent related to the study results.

SOURCE: Shiokawa M et al. Sci. Transl. Med. 2018 Aug 8. doi: 10.1126/scitranslmed.aaq0997.

Researchers have identified laminin 511 as a novel antigen in autoimmune pancreatitis (AIP). A truncated form of the antigen was found in about half of human patients, but fewer than 2% of controls, and mice that were immunized with the antigen responded with induced antibodies and suffered pancreatic injury.

Laminin 511 plays a key role in cell–extracellular matrix (ECM) adhesion in pancreatic tissue. The results, published in Science Translational Medicine, could improve the biologic understanding of AIP and could potentially be a useful diagnostic marker for the disease.

Some autoantibodies are known to be associated with AIP, but the seropositive frequency is low among patients.

The researchers previously demonstrated that injecting IgG from AIP patients into neonatal mice led to pancreatic injury. The IgG was bound to the basement membrane of the pancreatic acini, suggesting the presence of autoantibodies that recognize an antigen in the ECM.

The researchers then screened previously known proteins from the pancreatic ECM against sera from AIP patients, performing Western blot analyses and immunosorbent column chromatography with human and mouse pancreas extracts, and AIP patient IgG. But this approach yielded no results.

The team then conducted an enzyme-linked immunosorbent assay using known pancreatic ECM proteins, which included the laminin subunits 511-FL, 521-FL, 511-E8, 521-E8, 111-EI, 211-E8, and 332-E8. The E8 designates a truncated protein produced by pancreatic elastase that contains the integrin-binding site.

That experiment revealed that 511-E8 is a consistent autoantigen, and a survey of AIP patients found that 26 of 51 (51.0%) had autoantibodies against 511-E8, compared with just 2 of 122 (1.6%) of controls (P less than .001). Further immunohistochemistry studies confirmed that patient IgG binds to laminin in pancreatic tissue.

When the researchers injected 511-E8, 511-FL, 521-FL, or ovalbumin into 8-week-old mice, and then again after 28 days and 56 days, only those who received 511-E8 showed evidence of pancreatic injury 28 days after the final immunization. The mice generated autoantibodies to 511-E8 but not ovalbumin.

The findings may have clinical significance. Patients with antibodies to laminin 511-E8 had a lower frequency of malignancies (0% vs. 32%; P =.0017) and allergic diseases (12% vs. 48%; P =.0043) than patients with no laminin 511-E8 antibodies.

The study was funded by the Japan Society for the Promotion of Science; the Japanese Ministry of Health, Labour, and Welfare; the Practical Research Project for Rare/Intractable Diseases Grant,; the Agency for Medical Research and Development; and the Takeda Science Foundation. One of the authors has filed a patent related to the study results.

SOURCE: Shiokawa M et al. Sci. Transl. Med. 2018 Aug 8. doi: 10.1126/scitranslmed.aaq0997.

Researchers have identified laminin 511 as a novel antigen in autoimmune pancreatitis (AIP). A truncated form of the antigen was found in about half of human patients, but fewer than 2% of controls, and mice that were immunized with the antigen responded with induced antibodies and suffered pancreatic injury.

Laminin 511 plays a key role in cell–extracellular matrix (ECM) adhesion in pancreatic tissue. The results, published in Science Translational Medicine, could improve the biologic understanding of AIP and could potentially be a useful diagnostic marker for the disease.

Some autoantibodies are known to be associated with AIP, but the seropositive frequency is low among patients.

The researchers previously demonstrated that injecting IgG from AIP patients into neonatal mice led to pancreatic injury. The IgG was bound to the basement membrane of the pancreatic acini, suggesting the presence of autoantibodies that recognize an antigen in the ECM.

The researchers then screened previously known proteins from the pancreatic ECM against sera from AIP patients, performing Western blot analyses and immunosorbent column chromatography with human and mouse pancreas extracts, and AIP patient IgG. But this approach yielded no results.

The team then conducted an enzyme-linked immunosorbent assay using known pancreatic ECM proteins, which included the laminin subunits 511-FL, 521-FL, 511-E8, 521-E8, 111-EI, 211-E8, and 332-E8. The E8 designates a truncated protein produced by pancreatic elastase that contains the integrin-binding site.

That experiment revealed that 511-E8 is a consistent autoantigen, and a survey of AIP patients found that 26 of 51 (51.0%) had autoantibodies against 511-E8, compared with just 2 of 122 (1.6%) of controls (P less than .001). Further immunohistochemistry studies confirmed that patient IgG binds to laminin in pancreatic tissue.

When the researchers injected 511-E8, 511-FL, 521-FL, or ovalbumin into 8-week-old mice, and then again after 28 days and 56 days, only those who received 511-E8 showed evidence of pancreatic injury 28 days after the final immunization. The mice generated autoantibodies to 511-E8 but not ovalbumin.

The findings may have clinical significance. Patients with antibodies to laminin 511-E8 had a lower frequency of malignancies (0% vs. 32%; P =.0017) and allergic diseases (12% vs. 48%; P =.0043) than patients with no laminin 511-E8 antibodies.

The study was funded by the Japan Society for the Promotion of Science; the Japanese Ministry of Health, Labour, and Welfare; the Practical Research Project for Rare/Intractable Diseases Grant,; the Agency for Medical Research and Development; and the Takeda Science Foundation. One of the authors has filed a patent related to the study results.

SOURCE: Shiokawa M et al. Sci. Transl. Med. 2018 Aug 8. doi: 10.1126/scitranslmed.aaq0997.

The number of U.S. emergency department visits for acute pancreatitis associated with alcohol abuse, chronic pancreatitis history, and younger age was on the rise in recent years, an analysis of a nationally representative database has suggested.

Katarzyna Bialasiewicz/Thinkstock

Help your patients better understand pancreatitis and available tests and treatments by using AGA patient education materials, https://www.gastro.org/practice-guidance/gi-patient-center/topic/pancreatitis.

SOURCE: Garg SK et al. J Clin Gastroenterol. 2018 Apr 6. doi: 10.1097/MCG.0000000000001030.

The number of U.S. emergency department visits for acute pancreatitis associated with alcohol abuse, chronic pancreatitis history, and younger age was on the rise in recent years, an analysis of a nationally representative database has suggested.

Katarzyna Bialasiewicz/Thinkstock

Help your patients better understand pancreatitis and available tests and treatments by using AGA patient education materials, https://www.gastro.org/practice-guidance/gi-patient-center/topic/pancreatitis.

SOURCE: Garg SK et al. J Clin Gastroenterol. 2018 Apr 6. doi: 10.1097/MCG.0000000000001030.

The number of U.S. emergency department visits for acute pancreatitis associated with alcohol abuse, chronic pancreatitis history, and younger age was on the rise in recent years, an analysis of a nationally representative database has suggested.

Katarzyna Bialasiewicz/Thinkstock

Help your patients better understand pancreatitis and available tests and treatments by using AGA patient education materials, https://www.gastro.org/practice-guidance/gi-patient-center/topic/pancreatitis.

SOURCE: Garg SK et al. J Clin Gastroenterol. 2018 Apr 6. doi: 10.1097/MCG.0000000000001030.

Patients with acute pancreatitis should receive “goal-directed” fluid therapy with normal saline or Ringer’s lactate solution rather than hydroxyethyl starch (HES) fluids, states a new guideline from the AGA Institute.

In a single-center randomized trial, hydroxyethyl starch fluids conferred a 3.9-fold increase in the odds of multiorgan failure (95% confidence interval for odds ratio, 1.2-12.0) compared with normal saline in patients with acute pancreatitis, wrote guideline authors Seth D. Crockett, MD, MPH, of the University of North Carolina, Chapel Hill, and his associates. This trial and another randomized study found no mortality benefit for HES compared with fluid resuscitation. The evidence is “very low quality” but mirrors the critical care literature, according to the experts. So far, Ringer’s lactate solution and normal saline have shown similar effects on the risk of organ failure, necrosis, and mortality, but ongoing trials should better clarify this choice, they noted (Gastroenterology. doi: 10.1053/j.gastro.2018.01.032).

The guideline addresses the initial 2-week period of treating acute pancreatitis. It defines goal-directed fluid therapy as titration based on meaningful targets, such as heart rate, mean arterial pressure, central venous pressure, urine output, blood urea nitrogen concentration, and hematocrit. Studies of goal-directed fluid therapy in acute pancreatitis have been unblinded, have used inconsistent outcome measures, and have found no definite benefits over nontargeted fluid therapy, note the guideline authors. Nevertheless, they conditionally recommend goal-directed fluid therapy, partly because a randomized, blinded trial of patients with severe sepsis or septic shock (which physiologically resembles acute pancreatitis) had in-hospital mortality rates of 31% when they received goal-directed fluid therapy and 47% when they received standard fluid therapy (P = .0009).

The guideline recommends against routine use of two interventions: prophylactic antibiotics and urgent endoscopic retrograde cholangiopancreatography (ERCP) for patients with acute pancreatitis. The authors note that no evidence supports routine prophylactic antibiotics for acute pancreatitis patients without cholangitis, and that urgent ERCP did not significantly affect the risk of mortality, multiorgan failure, single-organ failure, infected pancreatic and peripancreatic necrosis, or necrotizing pancreatitis in eight randomized controlled trials of patients with acute gallstone pancreatitis.

Source: Crockett SD et al. Gastroenterology. doi: 10.1053/j.gastro.2018.01.032.

Patients with acute pancreatitis should receive “goal-directed” fluid therapy with normal saline or Ringer’s lactate solution rather than hydroxyethyl starch (HES) fluids, states a new guideline from the AGA Institute.

In a single-center randomized trial, hydroxyethyl starch fluids conferred a 3.9-fold increase in the odds of multiorgan failure (95% confidence interval for odds ratio, 1.2-12.0) compared with normal saline in patients with acute pancreatitis, wrote guideline authors Seth D. Crockett, MD, MPH, of the University of North Carolina, Chapel Hill, and his associates. This trial and another randomized study found no mortality benefit for HES compared with fluid resuscitation. The evidence is “very low quality” but mirrors the critical care literature, according to the experts. So far, Ringer’s lactate solution and normal saline have shown similar effects on the risk of organ failure, necrosis, and mortality, but ongoing trials should better clarify this choice, they noted (Gastroenterology. doi: 10.1053/j.gastro.2018.01.032).

The guideline addresses the initial 2-week period of treating acute pancreatitis. It defines goal-directed fluid therapy as titration based on meaningful targets, such as heart rate, mean arterial pressure, central venous pressure, urine output, blood urea nitrogen concentration, and hematocrit. Studies of goal-directed fluid therapy in acute pancreatitis have been unblinded, have used inconsistent outcome measures, and have found no definite benefits over nontargeted fluid therapy, note the guideline authors. Nevertheless, they conditionally recommend goal-directed fluid therapy, partly because a randomized, blinded trial of patients with severe sepsis or septic shock (which physiologically resembles acute pancreatitis) had in-hospital mortality rates of 31% when they received goal-directed fluid therapy and 47% when they received standard fluid therapy (P = .0009).

The guideline recommends against routine use of two interventions: prophylactic antibiotics and urgent endoscopic retrograde cholangiopancreatography (ERCP) for patients with acute pancreatitis. The authors note that no evidence supports routine prophylactic antibiotics for acute pancreatitis patients without cholangitis, and that urgent ERCP did not significantly affect the risk of mortality, multiorgan failure, single-organ failure, infected pancreatic and peripancreatic necrosis, or necrotizing pancreatitis in eight randomized controlled trials of patients with acute gallstone pancreatitis.

Source: Crockett SD et al. Gastroenterology. doi: 10.1053/j.gastro.2018.01.032.

Patients with acute pancreatitis should receive “goal-directed” fluid therapy with normal saline or Ringer’s lactate solution rather than hydroxyethyl starch (HES) fluids, states a new guideline from the AGA Institute.

In a single-center randomized trial, hydroxyethyl starch fluids conferred a 3.9-fold increase in the odds of multiorgan failure (95% confidence interval for odds ratio, 1.2-12.0) compared with normal saline in patients with acute pancreatitis, wrote guideline authors Seth D. Crockett, MD, MPH, of the University of North Carolina, Chapel Hill, and his associates. This trial and another randomized study found no mortality benefit for HES compared with fluid resuscitation. The evidence is “very low quality” but mirrors the critical care literature, according to the experts. So far, Ringer’s lactate solution and normal saline have shown similar effects on the risk of organ failure, necrosis, and mortality, but ongoing trials should better clarify this choice, they noted (Gastroenterology. doi: 10.1053/j.gastro.2018.01.032).

The guideline addresses the initial 2-week period of treating acute pancreatitis. It defines goal-directed fluid therapy as titration based on meaningful targets, such as heart rate, mean arterial pressure, central venous pressure, urine output, blood urea nitrogen concentration, and hematocrit. Studies of goal-directed fluid therapy in acute pancreatitis have been unblinded, have used inconsistent outcome measures, and have found no definite benefits over nontargeted fluid therapy, note the guideline authors. Nevertheless, they conditionally recommend goal-directed fluid therapy, partly because a randomized, blinded trial of patients with severe sepsis or septic shock (which physiologically resembles acute pancreatitis) had in-hospital mortality rates of 31% when they received goal-directed fluid therapy and 47% when they received standard fluid therapy (P = .0009).

The guideline recommends against routine use of two interventions: prophylactic antibiotics and urgent endoscopic retrograde cholangiopancreatography (ERCP) for patients with acute pancreatitis. The authors note that no evidence supports routine prophylactic antibiotics for acute pancreatitis patients without cholangitis, and that urgent ERCP did not significantly affect the risk of mortality, multiorgan failure, single-organ failure, infected pancreatic and peripancreatic necrosis, or necrotizing pancreatitis in eight randomized controlled trials of patients with acute gallstone pancreatitis.

Source: Crockett SD et al. Gastroenterology. doi: 10.1053/j.gastro.2018.01.032.