Disclosure 6/13/2015. Acute Pancreatitis - Update. Causes of mortality DEATH

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1 Disclosure Acute Pancreatitis - Update Jamie S. Barkin, MD, MACP. MACP Professor of Medicine Division of Gastroenterology I do not have any relevant financial relationships with any commercial interests. 1 2 Acute Pancreatitis: Concepts 2015 Causes of mortality 1) Volume replacement administered within 24 hours of admission is the foundation of therapy DEATH 2) Establish severity, clinically and with labs No need for early CT to establish severity 3) Establish etiology Importance is to prevent recurrence 4) Biliary Pancreatitis Use laboratory markers & MRCP for diagnosing retained CBD stone ERCP is only for treating patients with cholangitis Cholecystectomy as soon as possible 5) Nutrition use enteral, feed (orally) early 6) Recognize complications 7) Delayed, minimally invasive intervention for infected walled-off necrosis 3 Early (< one week) Systemic inflammatory response syndrome (SIRS) Multiorgan failure Late (> one week) Multiorgan failure Pancreatic infections/sepsis 4 1

2 Acute Pancreatitis Mechanism of organ dysfunction Q 1. What is the definition of acute pancreatitis (regardless of etiology)? Volume depletion Visceral hypofusion Capillary permeability bowel permeability ( TNF, IL6, angioprotin adipokines) Bacterial translocation SIRS David Whitcomb, M.D. 5 6 Acute pancreatitis diagnosis: Serology The definition of acute pancreatitis is based on the fulfillment of 2 out of 3 of the following criteria: Clinical (upper abdominal pain) Laboratory (serum amylase or lipase >3 times the upper limit of normal) Imaging (computed tomography, magnetic resonance [MR], ultrasonography) criteria CT usually not required to diagnose acute pancreatitis except to confirm the diagnosis or clinical suspicion of duodenal perforation etc., and or normal enzymes Sensitivity of serum amylase estimation 85%, with a specificity of 91% Elevations may not occur (or be missed) especially - mild attacks acute flares superimposed acute pancreatitis on chronic pancreatitis marked hypertriglyceridemia in some patients Lipase may also be more sensitive than amylase as it remains elevated in the serum longer than amylase 7 Adaptation. AGA Institute Technical Review on Acute Pancreatitis. Gastroenterology 2007;132:

3 Causes of Increased Amylase and Lipase Levels Amylase Acute Pancreatitis (AP) Diseases that might mimic AP Pancreatic pseudocyst Chronic pancreatitis Pancreatic carcinoma Biliary tract disease (cholecystitis, cholangitis, choledocholithiasis) Intestinal obstruction, pseudoobstruction, ischemia or perforation Acute appendicitis Ectopic pregnancy Other disorders Renal failure Lipase Acute Pancreatitis Pancreatic pseudocyst Chronic pancreatitis Pancreatic carcinoma Biliary tract disease (cholecystitis, cholangitis, choledocholithiasis) Intestinal obstruction, pseudoobstruction, ischemia or perforation Head Trauma Renal failure Heparin activation of lipoprotein lipase Q 2. On admission, what should be done to determine the etiology of acute pancreatitis? Adaptation AGA Institute. Gastroenterology 2007;132: Causes of acute pancreatitis Association of drugs with acute pancreatitis Alcohol, arteritis, autoimmune Biliary, blunt trauma Congenital Pancreatic divisum, duodenal diverticulum Chemicals organophosphate, methanol, Zinc Drugs & venomous i.e. spider, diabetes type 2 drugs Eosinophilic ERCP Formations primary and metastatic tumors pancreatic and ampullary, IPMTs, strictures, SOD Genetic CFTR, SPINK Hypercalcemia usually secondary to hyperparathyroidism hypertriglyceridemia Infectious viral (measles, mumps, coxsackie A, HIV) Ischemia hypotension, embolic, i.e. catherization, vasculitis, i.e. lupus IBD Crohn's 4x Barkin JS: Miller School of Medicine, University of Miami 11 Definite Association Aminosalicylates (sulfasalazine, mesalamine) L-asparaginase Azathioprine Didanosine Estrogen Furosemide Probable Association Chlorthalidone Cyclosporine Ethacrynic acid FK-506 Acetaminophen Amiodarone Atenolol Carbamazepine Chlorpromazine Cholestryamine Cisplatin Contrast media Danazol Diazoxide Diphenoxylate Ergotamine Pentamidine Sulfonamide Tetracycline Thiazides Valporic acid Vinca alkaloids 6-Mercaptopurine Possible Association Adaptation : Runzi and Layer HMG-CoA redctase inhibitors Metronidazole Rifampin Steroids 12 3

4 Pancreatitis accompanying infections Viral (usually mild and self-limited) Mumps Hepatitis A, B,E Cytomegaly Varicella zoster Herpes simplex Echo and coxsackie virus HIV Bacteria Mycoplasma Legionella Campylobacter jejuni, salmonella spp Q 3. What further investigations are indicated in patients after a first or second attack of idiopathic acute pancreatitis? Adapted from Hasibeder WR. Anaesth Intensive Care 2009;37: Repeated right upper quadrant ultrasonography Review the ABCs Endoscopic ultrasonography to access for occult microlithiasis, neoplasms and chronic pancreatitis If EUS is negative, (secretin-stimulated) magnetic resonance cholangiopancreatography (MRCP) Genetic counseling (not necessarily genetic testing) should be considererd Q 4. What is the best score/marker (including cut-off value) to predict severe acute pancreatitis at admission and at 48 hours? Adapted: IAP/APA Working Group Acute Pancreatitis Guidelines. Pancreatology 2013;13:e1-e

5 Systemic inflammatory response syndrome (SIRS) is advised to predict severe acute pancreatitis at admission and persistent SIRS at 48 h. SIRS is defined by the presence of two or more of the following four criteria: 1. Temperature <36ºC (96.8ºF) or >38ºC(100.4ºF) 2. Heart rate >90/min 3. Respiratory rate >20/min 4. White blood cells (<4 x 10 9 /L(<4K/mm 3 ), >12 x 10 9 (>12K/mm 3 ) or 10% bands Persistent (>48 h) SIRS is associated with multi-organ failure and mortality in acute pancreatitis Persistent SIRS was associated with a mortality of 25% compared with 8% for transient SIRS The sensitivity of persistent SIRS for mortality is 77-89% and specificity 79-86% Clinical course of acute pancreatitis The initial phase of acute pancreatitis is characterized by pancreatic inflammation that usually presents as SIRS Persistent organ failure is the key determinant of mortality in acute pancreatitis and is associated with a mortality of 25% - 35% In theory, SIRS is followed by a state of immune suppression, making patients more susceptible for infections including infection of pancreatic necrosis 17 Schepers NY, et al. Best Practice & Research Clin Gastroenterol 27 (2013) Definitions in acute pancreatitis Interstitial edematous pancreatitis Necrotizing pancreatitis Severity Mild Moderate Severe Inflammation of pancreatic parenchyma and extrapancreatic tissue without necrosis Parenchymal and/or extrapancreatic necrosis No organ failure or local/systemic complication Transient organ failure or local/systemic complications Persistent organ failure (>48 h) Q 5. What is the best strategy to predict outcome of acute pancreatitis during admission? Schepers NY, et al. Best Practice & Research Clin Gastroenterol 27 (2013)

6 Acute Pancreatitis: Host risk factors of poor prognosis Evaluate: Host of risk factors (e.g. age, co-morbidity, body mass index) Clinical risk stratification (e.g. persistent SIRS) Monitoring response to initial therapy (e.g. persistent SIRS, blood urea nitrogen, creatinine) 1 of 2 Observe Age - > 65 years Visceral fat volume waist circumference Comorbid disease Vital signs Urine output Examine Presence of abdominal rebound tenderness or guarding Delirium Abdominal wall or flank bruising 21 Adaptation AGA Institute. Gastroenterology 2007;132: of 2 Acute pancreatitis: Assessment of poor prognosis Evaluate Hypoxemia (PaO2 <60 mm Hg) Hypotension (BP <90 mm Hg) Renal impairment (serum creatinine >2 mg/dl) Hemo-concentration Hct >45 Body mass index and the risk and prognosis of acute pancreatitis: a meta-analysis Results: Compared with normal weight individuals, obese individuals (BMI>30 kg/m 2 ) had an increased risk of AP development Obese patients developed significantly more severe AP (SRRs 1.82, 95% CI) severe complications, local complications and mortality (SRRs 2.21, 95%) Hong S, et al. Eur J Gastroenterol Hepatol 2011;23(12):

7 Metabolic acute pancreatitis Early changes in blood urea nitrogen predict mortality in acute pancreatitis AIM: To evaluate the accuracy of serial blood urea nitrogen (BUN) vs. serial hemoglobin (Hgb) measurement for prediction of in-hospital mortality in acute pancreatitis Excess Abdominal fat Metabolic Acute pancreatitis High blood triglycerides Methods: Observational cohort study Results: For every 5-mg/dl increase in BUN during the first 24 hours, the age- and gender-adjusted odds ratio for mortality increased by 2.2 (95% confidence limit, 1.8, 2.7) High Blood glucose Adaptation: Petrov MS. Am J Gastroenterol 2013;108: Conclusion: Serial BUN measurement identified as the most valuable single routine laboratory test for predicting mortality in AP GOAL to decrease BUN Nebiker CA, et al. Surgery 2009;145(3): Q 6. What is the indication for and timing of the initial CT assessment in acute pancreatitis? Indication for initial CT assessment in acute pancreatitis can be: 1. Diagnostic uncertainty 2. Confirmation of severity based on clinical predictors of severe pancreatitis or - 3. Failure to respond to conservative treatment or in the setting of clinical deterioration Optimal timing for initial CT assessment is at least h after onset of symptoms

8 For the majority of patients, CT is not required for the diagnosis of acute pancreatitis Routine early CT in acute pancreatitis is not recommended because: 1. There is no evidence that early CT improves clinical outcome or that early detection of necrosis will influence treatment 2. CT scoring systems are not superior to clinical scoring systems in predicting prognosis and severity of disease 3. There is evidence to suggest that an early (inappropriate) CT may increase the duration of hospital stay, has low yield without direct management implications, does not improve clinical outcomes, and poses risks of contrast allergy and nephrotoxicity CT/MRI during course of acute pancreatitis is indicated when there s a lack of: Clinical improvement Clinical deterioration When invasive intervention is considered Supportive measures of Acute Pancreatitis Volume replacement foundation Pain Therapy All opiates increase sphincter of Oddi peristalsis and biliary pressure Strict glycemic control Q 9. What is the best fluid to use for initial fluid resuscitation in acute pancreatitis? Q 10. What is the optimal fluid infusion rate and response measurement for initial fluid resuscitation? Stress ulcer prophylaxis In patients with signs of systemic inflammation and one or more organ dysfunctions Adapted from Hasibeder WR. Anaesth Intensive Care 2009;37:

9 a) Optimal infusion rate for initial fluid resuscitation of Ringer s lactate: goal directed intravenous fluid therapy with 5-10 ml/kg/h should be used initially until resuscitation goals are reached a total infusion of ml will suffice to reach the resuscitation goals within the first 24 h The rate of infusions must be interpreted with caution and needs to be tailored to the condition of the patient b) Measuring the response to fluid resuscitation Response to fluid resuscitation should be based on one or more of the following: 1. Non-invasive clinical targets of heart rate <120/min, mean arterial pressure between 65 and 85 mmhg ( kpa), and urinary output >0.5 1 ml/kg/h 2. Invasive clinical targets of stroke volume variation, and intrathoracic blood volume determination and 3. Biochemical targets of hematocrit 35-44% c) Blood urea nitrogen as a predictor of outcome but not on its value as a response measurement 33 Early fluid resuscitation reduces morbidity among patients with acute pancreatitis AIM: To investigate the association between early fluid resuscitation and outcome of patients admitted to the hospital with acute pancreatitis Methods: Retrospective study of patients 340 of whom received early and 94 late resuscitation Early resuscitation defined as receiving one-third of the total 72-hour fluid volume within 24 hours of presentation, whereas late resuscitation was defined as receiving one-third of the total 72-hour fluid volume Results: Early resuscitation was associated with decreased SIRS, compared with late resuscitation, at 24 hours (15% vs 32%, P=.001), 48 hours (14% vs 33%, P=.001) Reduced organ failure at 72 hours (5% vs 10%, P <.05) A lower rate of admission to the intensive care unit (6% vs 17%, P<.001) Reduced length of hospital stay (8 vs 11 days, P =.01) Conclusions: Early fluid resuscitation was associated with reduced incidence of SIRS and organ failure at 72 hours Warndorf MG, et al. Clin Gastroenterol Hepatol 2011;9(8): Q 11. What are the indications for admission to an intensive care unit in acute pancreatitis? 1. Pulse <40 or >150 beats/min 2. Systolic arterial pressure < 80mmHg (<10.7 kpa) or mean arterial pressure <60 mmhg (<8.0 kpa) or diastolic arterial pressure >120 mmhg (>16 kpa) 3. Respiratory rate > 35 breaths/min 4. pao 2 <50 mmhg (<6.7 kpa) 5. Acute pancreatitis (persistent organ failure should be treated in an intensive care setting 6. Persistent SIRS, the elderly, the obese, patients requiring ongoing volume resuscitation

10 Q 12. Can persistent SIRS/organ failure be prevented? Early fluid resuscitation within the first 24 h of admission for acute pancreatitis is associated with decreased rates of persistent SIRS and organ failure Persistent organ failure is the key determinant of mortality in acute pancreatitis Persistent SIRS resulted in a mortality of 25% compared to 8% with transient SIRS [17,38] Renal failure predicts mortality in severe acute pancreatitis Fluid resuscitation cannot prevent necrosis formation, but early fluid resuscitation is associated with reduced SIRS, organ failure and in-hospital mortality Systemic review and meta-analysis of antibiotic prophylaxis in severe acute pancreatitis Q 13. Is systemic antibiotic prophylaxis effective in preventing infectious complications in acute pancreatitis? Aim: To perform an updated systemic review and meta-analysis to provide evidence of the effect of antibiotic prophylaxis in severe acute pancreatitis (SAP) Method: review of randomized controlled trials in accordance with the Preferred Reporting Items for Systemic Reviews and Meta-analysis (PRISMA) Results: 841 patients in 14 trials The use of antibiotic prophylaxis was not associated with a statistically significant reduction in mortality (RR 0.74) in the incidence of infected pancreatic necrosis (RR 0.78), in the incidence of nonpancreatic infections, and in the surgical interventions Conclusion: There is no evidence to date, that supports the routine use of antibiotic prophylaxis in patients with SAP 39 Adaptation: Wittau M, et al. Scand J Gastroenterol 2011;46:

11 Q 14. When should oral feeding be restarted in patients with predicted mild pancreatitis? Oral feeding in predicted mild pancreatitis can be restarted when abdominal pain is decreasing Inflammatory markers are improving Patient is hungry When to feed patients with predicted mild acute pancreatitis Q 15. What is the indication for enteral tube feeding? A RCT by Li et al included a total of 149 patients and allocated patients to early introduction of stepwise oral feeding (defined by authors as when patient felt hungry) or conventional stepwise oral feeding (after resolution of abdominal pain and normalization of pancreatic enzymes) It was shown that commencement of oral feeding before normalization of pancreatic enzymes, resulted in a significantly reduced total length of hospital stay Li J, et al. Pancreas 2013;42:

12 Enteral feeding is superior to parenteral nutrition in severe acute pancreatitis Enteral tube feeding should be the primary therapy in patients with predicted severe acute pancreatitis who require nutritional support Remarks: Two meta-analyses demonstrated that enteral nutrition, as compared with parenteral nutrition, decreases systemic infections, multi-organ failure, need for surgical intervention, and mortality. RCT in 60 patients with severe acute pancreatitis found improved outcomes when enteral nutrition was started within 48 h as compared to after 7 days of fasting Significant reduction Risks of multiple organ failure Pancreatic infectious complications Mortality Mechanism - ability to maintain gut mucosal integrity, prevent bacterial translocation and thereby reduce pro-inflammatory mediators and as a result prevents organ dysfunction Amin P. Crit Carr Med 2011;39(3): Q 16. What type of enteral nutrition should be used? Either elemental or polymeric enteral nutrition formulations can be used meta-analysis including 20 RCTs

13 Q 17. What is the indication for ERCP and spincterotomy early in the course of biliary pancreatitis? Patients with biliary pancreatitis and cholangitis (Definite) Probably indicated - Biliary pancreatitis with common bile duct obstruction whereby LFTs are not improving and or MRCP-CBD stones, dilated CBD Remarks: meta-analysis of 7 RCTs including 757 patients found no evidence that early routine ERCP significantly affects mortality or local/systemic complications regardless of the predicted severity of biliary pancreatitis Q 18. What is the optimal timing of cholecystectomy? Cholecystectomy during index admission for mild biliary pancreatitis appears safe and is recommended Interval cholecystectomy -Associated with a substantial risk of readmission for recurrent biliary events, especially recurrent biliary pancreatitis Remarks: Review of nine studies including 998 patients found an 18% readmission rate for recurrent biliary events a median of 6 weeks after index admission for mild biliary pancreatitis

14 Recurrent biliary events in patients with biliary acute pancreatitis Cholecystectomy should be performed after biliary pancreatitis to reduce the risk of recurrent biliary events. Not just ERCP as cholecystitis and biliary colic can be <48 h Q 19. What is the role of cholecystectomy after endoscopic sphincterotomy in biliary pancreatitis? In mild pancreatitis, cholecystectomy should be performed as soon as possible after recovery In severe pancreatitis, cholecystectomy should be delayed until resolution of symptoms or when extra-peripancreatic collections are resolved Modified from: Schepers NY, et al. Best Practice & Research Clin Gastroenterol 27 (2013) Cholecystectomy is advised because ERCP and sphincterotomy prevent recurrence of biliary pancreatitis but not gallstone related gallbladder disease, i.e. biliary colic and cholecystitis Q 20. Do acute peripancreatic fluid collections usually resolve? Remarks: meta-analysis reported a 10% readmission rate after ERCP for mild biliary pancreatitis because of biliary colic and acute cholecystitis

15 Peripancreatic fluid collections of acute pancreatitis Evolution of fluid collections in acute pancreatitis Defined by the presence or absence of necrosis and/or infection Acute peripancreatic fluid collections occur in the first 4 weeks and are without necrosis Pseudocysts are encapsulated fluid collections that occur after 4 weeks, without necrosis Acute necrotic collections (ANCs) occur in first 4 weeks, with necrosis Walled-off necrosis (WON; encapsulated collections occur after 4 weeks and with necrosis) Pseudocysts APFC Interstitial Fluid Collection in Acute Pancreatitis Necrosis CT PNPFC (Solid to Liquid) Walled-off pancreatic necrosis Adaptation: Thoeni RF. Radiology 2012;262(3): Acute peripancreatic fluid collections (APFCs) The new term for acute fluid collections that are not associated with necrosis, have no solid component, and always lack a wall of granulation Occurs in 30% to 50% of patients with AP More than 50% of cases resolve spontaneously within the first several weeks Pathogenesis may be from a rupture of a small branch of the pancreatic duct or from edema to parenchymal and/or peripancreatic inflammation Natural history of pseudocysts Approximately 50% of pseudocysts resolve spontaneously Pseudocysts presenting for <6 weeks had a 40% resolution rate and 20% complication rate Those presenting for more than 12 weeks usually did not resolve and had a 67% complication rate Usually sterile Imaging studies indicate that APFCs are irregular in shape, may be multiple, lack a well-defined wall and have an indistinct interface between the fluid and adjacent organs Adaptation - Brun A, et al. J Clin Gastroenterol 2011;45: Adaptation - Brun A, et al. J Clin Gastroenterol 2011;45:

16 Diagnosis of pseudocysts Clinical manifestations of pseudocysts A pseudocyst is suspected when An episode of pancreatitis fails to resolve Serum amylase levels are persistently high Patient has continuous abdominal pain after clinical resolution of AP On CT scan a pseudocyst usually appears as round or oval, symmetric, thin-walled (1 to 2) capsule measuring <15 HU CT is the most accurate test for showing a pseudocyst with a sensitivity of 90% to 100% Related to local mass effect Symptoms include abdominal pain, early satiety, weight loss and fever Weight loss due to gastric or duodenal compression is observed in 20% of patients Jaundice from bile duct compression occurs in 10% Adaptation - Brun A, et al. J Clin Gastroenterol 2011;45: Adaptation - Brun A, et al. J Clin Gastroenterol 2011;45: Efficacy of conservative treatment, without necrosectomy, for infected pancreatic necrosis (IPN): A systematic review and meta-analysis Q 21. Should patients with infected pancreatic necrosis undergo surgical debridement ASAP? AIM: To perform a systematic review and meta-analysis of studies related to primary conservative management for IPN Methods: Conservative therapy for IPN included intensive care, combination antimicrobials and nutritional support, with or without drainage of the infected fluid collections Results: Conservative management was successful for 64% of patients Mortality was 12%, and 26% of patients required necrosectomy or additional surgery for complications A separate analysis of 4 studies that reported IPN following percutaneous drainage had compatible results; 50% had successful outcomes, mortality was 18%, and 38% required surgery 63 Mouli VP, et al. Gastroenterology 2013;144:

17 Step-up approach in patients with acute necrotizing pancreatitis Aimed at control of the sepsis rather than complete removal of the infected necrotic material and involved percutaneous or endoscopic drainage of the infected peri-pancreatic fluid collection initially If drainage did not lead to clinical improvement, the next step was minimally invasive retroperitoneal necrosectomy, followed by open necrosectomy as the last resort The Dutch Pancreatitis Study Group demonstrated that there was a significant reduction in the rate of the composite end point of major complications or death in the step-up approach group compared with that of the open necrosectomy group Adaptation: Lemaire LC, et al. J. Clin Immunol 1998;18(6): Van Santvoort HC, et al. N Engl J Med 2010;362(16): A step-up approach or open necrosectomy for necrotizing pancreatitis Background: Necrotizing pancreatitis with infected necrotic tissue is associated with a high rate of complications and death Standard treatment is open necrosectomy The outcome may be improved by a minimally invasive step-up approach Method: Random assignment of 88 patients with necrotizing pancreatitis and suspected or confirmed infected necrotic tissue to undergo primary open necrosectomy or a step-up approach to treatment Step-up approach consisted of percutaneous drainage followed by minimally invasive retroperitoneal necrosectomy The primary end point was a composite of major complications (new-onset multiple-organ failure or multiple systemic complications, perforation of a visceral organ or enterocutaneous fistula, or bleeding) or death Adaptation: van Santvoort HC, et al. N Engl J Med 2010;362(16): A step-up approach or open necrosectomy for necrotizing pancreatitis (Cont) Results: The primary end-point occurred in 31 of 45 patients (69%) assigned to open necrosectomy and in 17/43 patients (40%) assigned to the step-up approach (risk ratio with the step-up approach, 0.57 (P=0.006) Q 21. What are the indications for intervention in necrotizing pancreatitis? Of the patients assigned to the step-up approach, 35% were treated with percutaneous drainage only New-onset multiple-organ failure occurred less often in patients assigned to the step-up approach than open necrosectomy (12% vs. 40%, P=0.002) Conclusion: A minimally invasive step-up approach, as compared with open necrosectomy, reduced the rate of the composite end point of major complications or death among patients with necrotizing pancreatitis and infected necrotic tissue Adaptation: van Santvoort HC, et al. N Engl J Med 2010;362(16):

18 Clinical suspicion or documented, infected necrotizing pancreatitis with clinical deterioration, preferably when the necrosis has become walled-off On-going organ failure for several weeks after the onset of acute pancreatitis Abdominal compartment syndrome Q 22. What is the role of fine needle aspiration to diagnose infected necrotizing pancreatitis? Ongoing acute bleeding Bowel ischemia Ongoing gastric outlet, intestinal, or biliary obstruction due to mass effect from large walled-off necrosis Remarks: In patients who are operated on because of persistent illness, approximately 40% will have infected necrotizing pancreatitis Microbiologic analysis of peri-pancreatic fluid collected during EUS in patients with pancreatitis: Impact on antibiotic therapy Not indicated, because clinical signs (i.e. persistent fever, increasing inflammatory markers) and imaging signs (i.e. gas in peripancreatic collections) are accurate predictors of infected necrosis in the majority of patients Risk of false-negative results reported in 12%-25% of patients Remarks: FNA is indicated in patients without clinical improvement for several weeks in the absence of clear clinical and imaging signs of infected necrotizing pancreatitis Aim: To evaluate the role of routine microbiologic analysis of peri-pancreatic fluid collections (PPFC) and its impact on antibiotic therapy in patients with pancreatitis Method: A prospective, observational, multicenter study comprising 44 consecutive patients for endoscopic treatment of PPFCs Results: Colonization of PPFCs was found in 59% of PPFC cultures, whereas all but 2 concomitant blood cultures showed no microbial growth Risk factors for a colonization were the presence of necrosis (P = 006), acute pancreatitis (P =.033), leukocytosis (P =.001), elevated C-reactive protein levels (P =.003), fever (P =.02), turbid material (P =.031) and longer hospital stay (P =.003) In 23 patients with fluid colonization despite empiric antibiotic therapy, the treatment had to be adjusted in 18 (78%) patients according to the observed antibiotic susceptibility profile 71 Adaptation: Negm AA, et al. Gastrointest Endosc 2013;78:

19 Q 23. What are the indications for intervention in sterile necrotizing pancreatitis? Ongoing gastric outlet, intestinal or biliary obstruction due to mass effect of walled-off necrosis (>4 weeks after onset of acute pancreatitis Persistent symptoms (e.g. pain, persistent illness ) in patients with walledoff necrosis without signs of infection Disconnected duct syndrome with persisting symptomatic (e.g. pain, obstruction) collection(s) with necrosis without signs of infections Remarks: In an observational study in 639 patients, approximately 1% of patients with necrotizing pancreatitis will have symptoms of obstruction during the initial hospital admission necessitating intervention. In a recent study, 197 patients with follow-up after necrotizing pancreatitis found a disconnected duct syndrome in 40% and about half of these patients required an intervention more than 8 weeks after necrotizing pancreatitis Timing of surgical intervention in necrotizing pancreatitis Delayed where possible until at least 4 weeks after initial presentation to allow the collection to become walled-off Aim: To determine the effect of surgical intervention timing for necrotizing pancreatitis Design: Retrospective study of 53 patients Remarks: If initial percutaneous catheter drainage is undertaken early, necrosectomy should ideally still be delayed until the collection has become walled-off Results Median timing of the intervention was 28 days 83% of patients had infected necrosis and 55% had preoperative organ failure 16 patients were operated on within 14 days of initial admission; 11 from day 15-29, and 26 on day 30 or later 75 Adaptation: Besselink MGH, et al. Arch Surg 2007;142(12):

20 Timing of surgical intervention in necrotizing pancreatitis Cont Results Lowest mortality in the 30-day group (8% vs 75% in the 1 to 14- days group, and 45% in the 15 to 29-days group, P<.001) Q 25. Should catheter drainage (percutaneous or endoscopic transluminal) always be the first step for suspected or confirmed infected necrotizing pancreatitis? This difference persisted when outcome was stratified for preoperative organ failure Conclusion: While postponing necrosectomy until 30 days after initial hospital admission is associated with decreased mortality, it is also associated with prolonged use of antibiotic and increased incidence of Candida species and antibiotic resistant organisms Adaptation: Besselink MGH, et al. Arch Surg 2007;142(12): Minimally invasive necrosectomy Percutaneous catheter drainage alone will prevent 23%-50% of necrosectomies in patients with infected necrotizing pancreatitis Percutaneous catheter drainage is technically feasible in >95% of patients with infected necrosis Classified based on the method of visualization (open, radiologic, endoscopic, hybrid or other) Route (per oral, trans-papillary or transmural, percutaneous retroperitoneal, percutaneous trans-peritoneal, percutaneous transmural or other PCD increasingly used to stabilized critical patients both as a bridge to surgery and as definitive therapy Route for PCD is via flank approach through the retroperitoneum, because it avoids enteric leaks and dissemination of infected material into the peritoneal cavity 79 Modified from: Trikudanathan G, et al. Expert Rev. Gastroenterol Hepatol 2013;7(5):

21 Cont. Minimally invasive necrosectomy Approach to patients with necrotizing pancreatitis and infection Infection is considered proven if gas is present in the extrapancreatic collection or when fine-needle aspiration is positive for bacteria or fungi on gram stain and culture Allows the tract to be used as a guidance for retroperitoneal surgical video-assisted retroperitoneal necrosectomy (VARD) In the Dutch Pancreatitis study group, 63% (n=30) of patients underwent PCD; 35% of patients recovered without additional necrosectomy Persistent external fistulas occur in up to 27% of patients Drawbacks include limited ability to remove necrotic debris Modified from: Trikudanathan G, et al. Expert Rev. Gastroenterol Hepatol 2013;7(5): No need for routine fine-needle aspiration in patients with clear clinical or imaging signs of infected necrotizing pancreatitis Intravenous antibiotics in case of suspected infected necrosis to mitigate additional infectious complications Intervention to drain infected fluid or remove infected necrosis in patients with progressive clinical deterioration despite maximal supportive therapy Intervention should be delayed until approximately four weeks to minimize the risks of complications during intervention, particularly necrosectomy Infected necrosis should be treated by a step-up approach, consisting of catheter drainage, either percutaneously or endoscopic transluminal, if necessary, surgery Modified from: Schepers NY, et al. Best Practice & Research Clin Gastroenterol 27 (2013) Acute Pancreatitis: Concepts ) Volume replacement administered within 24 hours of admission is the foundation of therapy 2) Establish severity, clinically and with labs No need for early CT to establish severity 3) Establish etiology Importance is to prevent recurrence 4) Biliary Pancreatitis Use laboratory markers & MRCP for diagnosing retained CBD stone ERCP is only for treating patients with cholangitis Cholecystectomy as soon as possible 5) Nutrition use enteral, feed (orally) early 6) Recognize complications 7) Delayed, minimally invasive intervention for infected walled-off necrosis 83 21