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Acute PancreatitisAcute Pancreatitis Evidence Based ApproachEvidence Based Approach
Pankaj Singh MDDirector of Gastrointestinal Endoscopy
Central Texas VA Health System, TX
Assistant Professor
Texas A&M University
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Clinical CaseClinical Case
32-year-old man c/o acute onset abdominal pain
(presumed pancreatic origin)h/o alcohol intake
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What do you think?What do you think?Amylase or lipaseUltrasound or CT scan
– If yes, When?ICU or medical ward Enteral nutrition or TPNAntibioticsERCPSurgery
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Evidence Evidence
A. Proven – > 2 well designed trials, randomized
B. Possible/ Probable – 1 well designed study, randomized
C. Consensus – agreed opinion with no supportive evidence
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GuidelinesGuidelines
AtlantaBritish Society of GastroenterologyInternational Association of PancreasSantorini ConferenceWorld Congress of Gastroenterology
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BackgroundBackground
Potentially fatalMortality – 0-25%
Necrosis determines the prognosis
Panreas 1998 307-11
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BackgroundBackgroundMild AP (no necrosis) – 0%
Sterile necrosis – 10%
Infected necrosis – 25%
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DiagnosisDiagnosis
Laboratory– Amylase– Lipase
Radiological– US– CT scan
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Blood testsBlood testsAmylase and lipasePlasma level peak within 24 hourst1/2 of amylase << lipase
Sensitivity Specificity
Amylase 67-100 85-98
Lipase 82-100 86-100
Gut 1997,41:431-35; Br J Surg 1998,84:1665-69.
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Lipase has slightly higher sensitivity and specificity and greater overall accuracy than amylase (Evidence category A)
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Ultra Sound (US)Ultra Sound (US)
Little part in the diagnosis of the acute pancreatitis
Role in biliary pancreatitis – Stones in gallbladder– Common Bile Duct dilation
Br J Surg 1982;69:369-72
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US findings should be examined in all patients with possible acute pancreatitis on admission (Evidence category B)
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CT scanCT scan
Not necessary for the diagnosisDiagnostic doubt
– Atypical presentations– Asymptomatic hyperamylasaemia or
hyperlipasemia
Gastroenterol Clin N Am 1990;19:811-42
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Routine use of CT scan within 24-48 hours of admission (Evidence category C)
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Initial ManagementInitial Management
Monitoring – temp., pulse, blood pressure, and urine output
Treatment – – Cardiopulmonary care– Sufficient fluid resuscitation– Pain control
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Severity StratificationSeverity Stratification
RationaleDifferentiate mild from severe acute
pancreatitis
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Desirable features of Markers Desirable features of Markers of Severityof Severity
Accuracy - High sensitivity & PPVPredictability within 24 hours of
admissionEasy to use
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Clinical FeaturesClinical Features
Clinical examination– Age > 70 years– Abdominal findings
increased tenderness rebound distension hypoactive bowel sounds
In first 24 hours of admission - unreliableAfter 48 hours- as accurate as Ranson score
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Multiple Factors Scoring Multiple Factors Scoring SystemSystem
Ranson – Separate for alcohol and gallstone etiology– Score > 3 = severe acute pancreatitis
Glasgow – valid in all types of pancreatitis
Both of these systems require 48 hours from the admission for full assessment
Can J Gastroent 2003 325-328
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APACHE IIAPACHE II
Acute Physiology and Chronic Health Evaluation as good as the Ranson or Glasgow at 24 and
48 hours of the admission APACHE II score > 8 = Severe acute pancreatitis Cumbersome to use if one does not use a pc or
palm - where the formula is easily downloaded
Br J Surg 1997,84:1665-69
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If a multiple factor scoring system is to be used, the best choice at present appears to be APACHE II calculated at 24 hours - Evidence category A
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TestsTests
Trypsinogen Trypsinogen activation peptide (TAP) I Trypsin
Inflammatory cascade (IL6, IL-8, TNF-) II
C - reactive protein III
Pancreatic injury
Amylase, Lipase, Trypsinogen IV
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Markers for Leakage of Markers for Leakage of Pancreatic EnzymesPancreatic Enzymes
Amylase/ Lipase – Degree of elevation shows little correlation with
disease severity and prognosis– May have an inverse relationship with severity
Trypsinogen 2 – Excreted into the urine– Used as a screening test for acute
pancreatitis
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Trypsinogen activation Trypsinogen activation peptide (TAP)peptide (TAP)
– Small peptideAdvantage
– Appear very early during the diseaseDisadvantage
– Limited "diagnostic window". decrease very quickly irrespective of the course of
the disease
– Not suitable for rapid simple analysis
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Markers of InflammationMarkers of Inflammation
TNF-alpha – Major role in mediating inflammatory response– Conflicting reports as a predictor of severity
Interleukin-6 and 8.– Principal cytokine mediator – Measured in serum and urine – Discriminate severe from mild cases on day 1
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C-reactive protein (CRP)C-reactive protein (CRP)
Acute phase reactant Synthesized by the hepatocytesSynthesis is induced by the release of
interleukin 1 and 6 Peak in serum is three days after the onset
of painMost popular single test severity marker
used today
Isenmann et al Pancreas 1993;8:358-61
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C-reactive protein (CRP)C-reactive protein (CRP)
Gold standard for the prediction of the necrotizing course of the disease
Accuracy of 86%Readily available
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Advantage Used to monitor the clinical course of the
disease
Disadvantage Not always present on admissionLack specificity
C-reactive protein (CRP)C-reactive protein (CRP)
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CRP is currently the gold standardAmylase and lipase of no valueHigh likelihood that IL-6/ TAP will
replace the CRP
Recommendations
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CT ScanCT ScanNormal
– Homogeneous enhancement of the whole pancreas
Abnormal – Non-visualization of a part of the pancreas
Sensitivity of 90-95%Specificity – 100%
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RecommendationRecommendation
A dynamic CT scan should be performed in all (predicted) severe cases between 3 and 10 days after admission
(Evidence grade B)
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Is It Possible to Predict Severity Is It Possible to Predict Severity
Early in Acute Pancreatitis?Early in Acute Pancreatitis?
Good clinical judgment– Specificity - 80%– Sensitivity - 40%
Scoring or biochemical methods – Specificity – 60%– Sensitivity – 95%
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Etiological AssessmentEtiological Assessment
Needed in all patientsDifferentiate biliary from alcoholic
pancreatitisEarly abdominal US is recommended in
all patients (Evidence category A)
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Initial Management of acute Initial Management of acute pancreatitispancreatitis
NutritionProphylactic AntibioticsAcid suppressionERCPSurgery
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Nutrition - RationaleNutrition - Rationale
Hyper metabolic state– Total energy expenditure 1.5 x resting energy
requirementNutrition depletion
– Starvation– Preexisting protein-calorie malnutrition &
micronutrient deficiency
Crit care Med 1991;19:484-90; J parenter Enter Nutr 1989;13:26-29.
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Nutrition – who needs it?Nutrition – who needs it?
Mild AP– 70-80% recover within 4-7 days
Moderate to severe AP– Ranson score > 3– APACHE II > 8– Necrotic pancreas– Organ failure
Windsor et al. Gut 1998,42:431-35; Kalfatentzos et al. Br J Surg 1997,84:1665-69
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Parenteral nutritionParenteral nutrition
Rationale for - Pancreatic restInability to tolerate enteric feeding
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Parenteral NutritionParenteral Nutrition
Rationale against Pancreatic rest
– Poorly definedIncreased risk of sepsis
– Gut atrophy - increased bacterial translocation
– HyperglycemiaGreater costs
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Parenteral NutritionParenteral Nutrition
Nine uncontrolled retrospective studies Safe, well tolerated with few complicationsNo impact on the outcome
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TPNTPN
Prospective randomized controlled trial
54
TPN IV F
Duration of hospital stay 16 10Line sepsis 10 1
Sax et al. Am J Surg 1987,153:117-22
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Enteral NutritionEnteral Nutrition
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Enteral NutritionEnteral Nutrition
Rationale for Minimal effect on pancreatic secretionsPrevention of gut mucosal atrophyAvoid TPN related complications
– Line sepsis– Hyperglycemia
Arch Surg 1999;134:287-292
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Enteral NutritionEnteral Nutrition
Rationale againstSmall degree of pancreatic stimulationProximal displacement of the feeding
tube may worsen the disease outcome
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Enteral nutritionEnteral nutrition
4 prospective randomized controlled trials
Significantly lower Line sepsis Infections per patients Hyperglycemic episodes
Cost was significantly higher in TPN
No difference in mortality, ICU admissions, multi-organ failure
Gut 1998,42:431-35; Br J Surg 1997,84:1665-69 JPEN 1997,21:14-20; J Submicrosc Cytol Pathol 1996,28:61-74.
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Enteric feedingEnteric feeding
Enteral nutrition is feasible, well tolerated and improves nutritional status
Enteral nutrition is certainly no worse than TPN and is less costly
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How about Nasogastric How about Nasogastric feeding ?feeding ?
AimAssess the safety and practicability of NG
feeding in severe acute pancreatitis
Methods– Prospective study– 26 patients with severe acute pancreatitis– NG feeding within 48 hours of admission
Eatock et al. International Journal of Pancreatology, 2000
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Result– Pancreatic necrosis – 15 patients– Severe organ failure - 11 patients
Feeding– Well tolerated in 22 patients– No evidence of clinical or biochemical
deterioration on commencing NG feeding
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NG feeding appears safe, is well tolerated and is possible in severe acute pancreatitis
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Evolution in NutritionEvolution in Nutrition
FastingTPN is betterEarly jejunal feeding is safeEarly jejunal feeding is superiorGastric feeding is as good as jejunal
feeding
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Current RecommendationsCurrent Recommendations
Mild to moderate Ranson < 3
APACHE II < 8 do not require nutritional support
Severe Ranson >3
APACHE II >10 Organ failure Pancreatic necrosis nutritional support
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Current RecommendationsCurrent Recommendations
Jejunal feeding should be started within 48 hours
The optimal feeding formulae is unknownEnsure the jejunal placement of the tube Monitor for
– Hypertryglyceridemia/ hyperglycemiaTPN in patients who do not tolerate
enteral feeding
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AntibioticsAntibiotics
Sepsis– Accounts for > 80% of deaths
Intestinal flora– Gram negative bacteria
Mechanism – translocation of the bacteria across the gut wall
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Antibiotics - RationaleAntibiotics - Rationale
Early (1 week) Sterile necrosis – Massive inflammatory response – multi-system
organ failure (SIRS)
Late – – Infected necrosis
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Why the controversy ?Why the controversy ?
Early trials in 1970’s did not show the benefit of antibiotics
Antibiotics that did not penetrated the pancreatic tissue
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Evidence Evidence
8 clinical trials Five of these trials showed a significant reduction
in the incidence of pancreatic infections 1 trial showed a significant reduction in mortality Limitations
– Small sample size– None were double blinded randomized placebo
controlled trials
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RecommendationsRecommendations
Prophylactic antibacterial treatment is strongly recommended in severe pancreatitis (Evidence B)
No evidence when to start prophylactic treatment or how long to continue therapy
Appropriate antibiotics are those that are active against in particular gram-negative organisms
Commence as early as possible after the identification of a severe attack
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Is there a downside with Is there a downside with antibiotics ?antibiotics ?
Increased risk of fungal infections Associate with mortality as high as 85%
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Fungal InfectionFungal Infection
CandidaTorulopsisCommensal organism found in
human gastrointestinal tractIncidence 10-40%
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Fungal infectionFungal infection92 patients with infected pancreatic necrosis22 patients (24%) with Candida infectionPatients with Candida infections
– Suffered higher mortality (64% vs. 19%, p=.0001)– More systemic complications– Were given preoperative antibiotics for a longer
period (19 vs 6 days; p=.0001)
World J. Surg. 25,372-76
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Fungal InfectionFungal Infection
Antibiotics predispose to candida infection of the pancreatic tissue which increases the mortality substantially
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TherapyTherapy
Treatment– Antifungal therapy – definite role
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Acid suppressionAcid suppression
Several RCT’s of H 2 receptor antagonists failed to show any clinical benefits
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Management of the Biliary Management of the Biliary PancreatitisPancreatitis
Passage or impaction of a stone Women (age of 50-70) Mortality 6%
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??What are the diagnostic criteria of biliary
pancreatitis ?What is the optimal method for biliary tract
imaging ?When is early ERCP indicated ?
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What are the diagnostic criteria of What are the diagnostic criteria of biliary pancreatitis in patients with AP ?biliary pancreatitis in patients with AP ?
Abnormal liver function tests– ALT elevation of > 3 x normal
Ultrasound – Gallstone
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What is the optimal method for What is the optimal method for biliary tract imaging ?biliary tract imaging ?
ERCPUltrasoundMRCPEUS
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Endoscopic Retrograde Endoscopic Retrograde CholangiopancreatographyCholangiopancreatography
((ERCP)ERCP)
ERCP– Gold standard– Potential serious complications
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Abdominal UltrasoundAbdominal Ultrasound
Sensitivity GB stone 60-80% CBD stone 30-60%
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Magnetic Resonance Magnetic Resonance Cholangio-PancreatographyCholangio-Pancreatography
((MRCP)MRCP)
Sensitivity of > 90%
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Endoscopy Ultrasound Endoscopy Ultrasound (EUS)(EUS)
EUS– Sensitivity of > 95% – Specificity of > 95-
100%
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When is early ERCP When is early ERCP indicated ?indicated ?
Concomitant cholangitis (Evidence A)
Significant persistent biliary obstruction (bilirubin > 5 mg/ dl) (Evidence A)
ERCP in severe biliary pancreatitis without biliary sepsis or obstruction (Evidence B)
Neoptolemos et al 1988; Fan NEJM 1993; Folsch NEJM 1997
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When is early ERCP When is early ERCP NOTNOT indicated ?indicated ?
Mild pancreatitis of suspected or proven biliary etiology in the absence of the biliary obstruction (Evidence A)
Neoptolemos et al 1988; Fan NEJM 1993; Folsch NEJM 1997
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Pancreatic necrosisPancreatic necrosis
Sterile necrosis – Systemic Inflammatory Response Syndrome (SIRS) (First week)– Mortality rate of 10-40%
Infected necrosis – Sepsis (After 3 weeks)– Mortality – 20-70%
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Sterile necrosisSterile necrosis
Sterile pancreatic necrosis – surgery in selected cases
Selected cases Massive pancreatic necrosis (>50%) with a
deteriorating clinical course (Evidence C) Patients with progression of organ dysfunction No signs of the improvement (grade B)
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Infected necrosisInfected necrosis
CT guided FNA with gram stain and culture is a confirmatory test (Evidence A)
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Infected NecrosisInfected Necrosis
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Infected necrosisInfected necrosis
Suspect if: Exacerbation of clinical signs
– Laboratory blood test changes Shift to immature cells Elevation of CRP
– Increased APACHE II– Positive blood culture
Indication for Fine Needle Asperation (FNA)
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Infected NecrosisInfected Necrosis
Necrosectomy is indicated in a confirmed infected pancreatic necrosis
(Evidence A)
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Management of Acute PancreatitisManagement of Acute Pancreatitis
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Management of Acute PancreatitisManagement of Acute Pancreatitis
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June 10, 323 BC
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Clinical CaseClinical Case
32-year-old man c/o acute onset abdominal pain (presumed
pancreatic origin) h/o alcohol intake
ALEXANDER THE GREAT – DIAGNOSIS:
ALCOHOLIC PANCREATITIS
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The EndThe End
To take the post test for credit of attendanceDownload the post test, complete and Return to Dr. S.K. Oliver at
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Post test question onePost test question one
Which of the following has an Evidence category A:1. Lipase has slightly higher sensitivity and
specificity and greater overall accuracy than amylase
2. Amylase has higher sensitivity and specificity and greater overall accuracy than lipase
3. US findings should be examined in all patients with possible acute pancreatitis on admission
4. Routine use of CT scan within 24-48 hours of admission
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Post test question twoPost test question two
Which of the following is the most popular single test severity marker used today?
1. Trypsinogen activation peptide
2. TNF- alpha
3. C Reactive Protein
4. Interleukin 6&8
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Post test question threePost test question three
Which of the following is associated with gut atrophy?
1. NG feedings
2. Jejunal feedings
3. Parenteral feedings
4. Enteric feedings
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Post test question fourPost test question four
When is early ERCP not indicated?
1. Concomitant cholangitis
2. Mild pancreatitis of suspected or proven biliary etiology in the absence of the biliary obstruction
3. Significant persistent biliary obstruction (bilirubin > 5 mg/ dl)
4. ERCP in severe biliary pancreatitis without biliary sepsis or obstruction
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The EndThe End