acute pancreatitis

Acute PancreatitisAcute Pancreatitis

Umit AkyuzUmit Akyuz, MD, MDGastroenterology Department,Yeditepe UniversityGastroenterology Department,Yeditepe University

IstanbulIstanbul

Acute Pancreatitis - ObjectivesAcute Pancreatitis - Objectives

Discuss basic physiologyDiscuss basic physiology

EtiologyEtiology

Clinical PresentationClinical Presentation

DiagnosisDiagnosis

PrognosisPrognosis

ManagementManagement

ComplicationsComplications

Pancreatic PhysiologyPancreatic Physiology

(1) Production of bicarbonate-rich fluid to (1) Production of bicarbonate-rich fluid to neutralize gastric fluid in the duodenum – neutralize gastric fluid in the duodenum – duct cells primarily (CFTR gene = duct cells primarily (CFTR gene = chloride / bicarbonate channel)chloride / bicarbonate channel)

(2) Synthesis of digestive enzymes – (2) Synthesis of digestive enzymes – acinar cellsacinar cells

(3) Insulin production = islet cells(3) Insulin production = islet cells


Most of the pancreas is made of acinar Most of the pancreas is made of acinar cellscells

The duct cells connect the acinar cells to The duct cells connect the acinar cells to the duodenum and as noted produces a the duodenum and as noted produces a bicarbonate rich fluid to “wash” the bicarbonate rich fluid to “wash” the enzymes into the duodenum (3000cc/day)enzymes into the duodenum (3000cc/day)

The islet cells function independently but The islet cells function independently but need remain in close proximity to the need remain in close proximity to the acinar cells to maintain normal gene acinar cells to maintain normal gene expressionexpression


Acinar enzymes are produced as Acinar enzymes are produced as zymogenszymogens

Zymogens are proenzymes that require Zymogens are proenzymes that require cleavage of a peptide by trypsin to cleavage of a peptide by trypsin to become activebecome active

Trypsinogen (zymogen of trypsin) is Trypsinogen (zymogen of trypsin) is activated by the intestinal brush boarder activated by the intestinal brush boarder enzyme enterokinase or by another trypsin enzyme enterokinase or by another trypsin moleculemolecule

Acute Pancreatitis – Acute Pancreatitis – EpidemiologyEpidemiology

>200,000 Hospital Admissions / Year>200,000 Hospital Admissions / Year

20% have a severe course20% have a severe course– 10-30% mortality for this group, which has not 10-30% mortality for this group, which has not

significantly changed during the past few significantly changed during the past few decades despite improvement in critical care decades despite improvement in critical care and other interventions and other interventions

Acute Pancreatitis – Acute Pancreatitis – PathophysiologyPathophysiology

An acute inflammatory process within the An acute inflammatory process within the pancreas with variable involvement of pancreas with variable involvement of localized tissues and remote organ localized tissues and remote organ systemssystemsIt can range from Mild It can range from Mild Severe with Severe with MOSF, necrosis, abscess, or a myriad of MOSF, necrosis, abscess, or a myriad of other complicationsother complicationsVigorous immune responseVigorous immune response– By the time pancreatitis is recognized By the time pancreatitis is recognized

clinically the inflammatory consequences clinically the inflammatory consequences dominate the clinical picturedominate the clinical picture


The vast majority of protection centers on The vast majority of protection centers on trypsin activation (or lack thereof)trypsin activation (or lack thereof)– (1) preventing trypsinogen activation (2) (1) preventing trypsinogen activation (2)

inactivating trypsin (3) “sweeping” trypsin out inactivating trypsin (3) “sweeping” trypsin out of the pancreasof the pancreas


EtiologyEtiology

EtiologyEtiology

Alcohol (40%)Alcohol (40%)– Mechanism not fully understoodMechanism not fully understood– Not all alcoholics get pancreatitis (only about Not all alcoholics get pancreatitis (only about

15%)15%)– This suggests a subset of the population This suggests a subset of the population

predisposed to pancreatitis, with alcohol predisposed to pancreatitis, with alcohol acting more as a co-precipitantacting more as a co-precipitant

Alcohol related pancreatitis - Alcohol related pancreatitis - CASECASE

26M presents for pseudocyst drainage – 26M presents for pseudocyst drainage – four weeks after severe pancreatitisfour weeks after severe pancreatitisHas had “abdominal symptoms” since Has had “abdominal symptoms” since childhoodchildhoodDoes admit to heavy alcohol use as young Does admit to heavy alcohol use as young adultadult– Strong family history of alcoholism and Strong family history of alcoholism and

pancreatitispancreatitis– Family history reveals a possible autosomal Family history reveals a possible autosomal

dominant abnormalitydominant abnormality

ERCP reveals chronic pancreatitisERCP reveals chronic pancreatitis

Alcohol related pancreatitis - Alcohol related pancreatitis - CASECASE

Answer:Answer:– A mutation (PRSS1) was found that alters the A mutation (PRSS1) was found that alters the

protein structure of trypsin producing a protein structure of trypsin producing a constant ON trypsin (auto-activation within the constant ON trypsin (auto-activation within the pancreas), resulting in frequent bouts of pancreas), resulting in frequent bouts of pancreatitis.pancreatitis.

EtiologyEtiology

Gallstones (35%)Gallstones (35%)– Gallstone pancreatitis risk is highest among Gallstone pancreatitis risk is highest among

patients with small GS < 5mm and with patients with small GS < 5mm and with microlithiasismicrolithiasis

– GS pancreatitis risk is also increased in white GS pancreatitis risk is also increased in white women > 60 yrswomen > 60 yrs

Etiology – Drugs and Toxins Etiology – Drugs and Toxins (5%)(5%)

AzathioprineAzathioprineCimetidineCimetidineEstrogensEstrogensEnalaprilEnalaprilErythromycinErythromycinFurosemideFurosemideMultiple HIV medicationsMultiple HIV medicationsScorpion BitesScorpion BitesSulfonamidesSulfonamidesThiazidesThiazidesTMP/SMXTMP/SMX

Etiology – TraumaEtiology – Trauma

Blunt TraumaBlunt Trauma– AutomobileAutomobile– Bicycle handlebar injuriesBicycle handlebar injuries– AbuseAbuse

Iatrogenic – ERCP (1-7%) Iatrogenic – ERCP (1-7%) – Likely secondary to contrast but also very Likely secondary to contrast but also very

operator dependantoperator dependant– Risk is also increased with Sphincter of Oddi Risk is also increased with Sphincter of Oddi

manometrymanometry

Etiology – Multi-System DiseaseEtiology – Multi-System Disease

Diabetic Ketoacidosis (10-15%)Diabetic Ketoacidosis (10-15%)Hemochromatosis Hemochromatosis HUSHUSHypercalcemia Hypercalcemia HyperparathyroidismHyperparathyroidismHypertriglyceridemiaHypertriglyceridemiaIBDIBDMalnutritionMalnutritionSevere PUDSevere PUDRenal FailureRenal FailureSIRSSIRSSLE and other connective tissue dissordersSLE and other connective tissue dissordersStatus-Post solid organ and BM transplantStatus-Post solid organ and BM transplantVasculitis Vasculitis

Etiology – Multi-System Disease Etiology – Multi-System Disease

Cystic FibrosisCystic Fibrosis– 2-15% of patients2-15% of patients– Ductal obstruction from thickened secetionsDuctal obstruction from thickened secetions

Etiology – Multi-System DiseaseEtiology – Multi-System Disease

Malnutrition and Re-feedingMalnutrition and Re-feeding

Anorexia NervosaAnorexia Nervosa– Pancreatic acinar cells atrophy but true cause Pancreatic acinar cells atrophy but true cause

of pancreatitis unknownof pancreatitis unknown

Etiology – InfectionEtiology – InfectionAscarisAscarisCampylobacterCampylobacterCMVCMVCoxsackie BCoxsackie BEBVEBVEnterovirusEnterovirusHIV/AIDSHIV/AIDSInfluenzaInfluenzaMACMACMeaslesMeaslesMumps RubellaMumps RubellaMycoplasma Mycoplasma Rubeola Rubeola Viral HepatitisViral HepatitisVaricellaVaricella

Etiology – Anatomical Etiology – Anatomical AnomaliesAnomalies

Pancreas DivisumPancreas Divisum– Failure of dorsal and ventral fusion (5-15% of Failure of dorsal and ventral fusion (5-15% of

population)population)

Annular Pancreas Annular Pancreas Any Ductal AnomaliesAny Ductal AnomaliesSphincter of Oddi dysfunctionSphincter of Oddi dysfunctionAlways consider a primary malignancy as Always consider a primary malignancy as a possible cause of new onset pancreatitis a possible cause of new onset pancreatitis in older patients without other obvious risk in older patients without other obvious risk factorsfactors

Etiology – GeneticEtiology – Genetic

CFTR heterozygote – “atypical” CFCFTR heterozygote – “atypical” CF

Other CFTR mutations – found in many Other CFTR mutations – found in many adult patients with more severe forms of adult patients with more severe forms of pancreatitis (we can test for a few hundred pancreatitis (we can test for a few hundred of the more than 1200 different mutations)of the more than 1200 different mutations)

SPINK1 mutations – most common cause SPINK1 mutations – most common cause of familial pancreatitis; causes a of familial pancreatitis; causes a predisposition for pancreatitis (other predisposition for pancreatitis (other trigger is usually present) trigger is usually present)

PRSS1 gene – Self-activating trypsin PRSS1 gene – Self-activating trypsin

Etiology - AutoimmuneEtiology - Autoimmune

Primarily a pancreatic disorder but . . .Primarily a pancreatic disorder but . . .

Can be associated with other diseases of Can be associated with other diseases of presumed autoimmune etiology including presumed autoimmune etiology including sclerosing cholangitis, primary biliary sclerosing cholangitis, primary biliary cirrhosis, retroperitoneal fibrosis, cirrhosis, retroperitoneal fibrosis, rheumatoid arthritis, sarcoidosis, and rheumatoid arthritis, sarcoidosis, and Sjögren's syndrome - some authors have Sjögren's syndrome - some authors have proposed that AIP represents a systemic proposed that AIP represents a systemic autoimmune diseaseautoimmune disease

Etiology - AutoimmuneEtiology - Autoimmune

(1) Diagnostic histology - dense (1) Diagnostic histology - dense lymphoplasmacytic infiltrate of the pancreatic lymphoplasmacytic infiltrate of the pancreatic parenchyma with secondary fibrosisparenchyma with secondary fibrosis

(2) Characteristic imaging with elevated IgG4 (2) Characteristic imaging with elevated IgG4 – focal or diffuse enlargement of the pancreas that is focal or diffuse enlargement of the pancreas that is

often sausage-shapedoften sausage-shaped– minimal pancreatic strandingminimal pancreatic stranding– calcifications or peripancreatic fluidcalcifications or peripancreatic fluid– uniform narrowing of the main pancreatic ductuniform narrowing of the main pancreatic duct– rim-like enhancement of the pancreatic head rim-like enhancement of the pancreatic head

(3) Response to steroid therapy(3) Response to steroid therapy

Etiology – IdiopathicEtiology – Idiopathic

Still accounts for ~20% of casesStill accounts for ~20% of cases

Etiology – IdiopathicEtiology – Idiopathic

Experts suggest that idiopathic Experts suggest that idiopathic pancreatitis should account for no more pancreatitis should account for no more than 5-10% of the total cases, yet the than 5-10% of the total cases, yet the broadly quoted percentage in the literature broadly quoted percentage in the literature at this time in the US is currently 20-25%.at this time in the US is currently 20-25%.


ClinicalClinical– Continuous mid-epigastric / peri-umbilical Continuous mid-epigastric / peri-umbilical

abdominal pain abdominal pain Radiating to back, lower Radiating to back, lower abdomen or chestabdomen or chest

– EmesisEmesis– FeverFever– Aggravated by eatingAggravated by eating– ProgressiveProgressive– Restless and uncomfortableRestless and uncomfortable


More severe casesMore severe cases– JaundiceJaundice– AscitesAscites– Pleural effusions – generally left-sidedPleural effusions – generally left-sided– Cullen’s sign – bluish peri-umbilical Cullen’s sign – bluish peri-umbilical

discolorationdiscoloration– Grey Turner’s sign – bluish discoloration of Grey Turner’s sign – bluish discoloration of

the flanksthe flanks

Diagnosis – Initial work-upDiagnosis – Initial work-up

GS history GS history Drug intake Drug intake Family HistoryFamily HistoryAlcohol intakeAlcohol intakeViral exposuresViral exposuresLipaseLipaseLFTsLFTsGB USGB US

Diagnosis – Follow up Diagnosis – Follow up investigationsinvestigations

Fasting liver profileFasting liver profile

Fasting plasma calcium – when wellFasting plasma calcium – when well

Viral titers as indicated by clinical Viral titers as indicated by clinical presentationpresentation

GB US – consider repeatingGB US – consider repeating

MRCPMRCP

CT pancreas (pancreas protocol)CT pancreas (pancreas protocol)

Diagnosis – Further Diagnosis – Further investigationsinvestigations

Appropriate for recurrent idiopathic acute Appropriate for recurrent idiopathic acute pancreatitispancreatitis– GB USGB US– EUS / ERCP – biliary and pancreatic cytologyEUS / ERCP – biliary and pancreatic cytology– Autoimmune markersAutoimmune markers– Sphincter of Oddi manometrySphincter of Oddi manometry– Functional testing / History to screen for Functional testing / History to screen for

sequela of chronic pancreatitis sequela of chronic pancreatitis

Diagnosis – AmylaseDiagnosis – Amylase

Elevates within HOURS and can remain Elevates within HOURS and can remain elevated for 4-5 dayselevated for 4-5 days

High specificity when using levels >3x High specificity when using levels >3x normalnormal

Many false positives (see next slide)Many false positives (see next slide)

Most specific = pancreatic isoamylase Most specific = pancreatic isoamylase (fractionated amylase)(fractionated amylase)

Diagnosis – Amylase ElevationDiagnosis – Amylase Elevation

Pancreatic SourcePancreatic Source– Biliary obstructionBiliary obstruction– Bowel obstructionBowel obstruction– Perforated ulcerPerforated ulcer– AppendicitisAppendicitis– Mesenteric ischemiaMesenteric ischemia– PeritonitisPeritonitis

SalivarySalivary– ParotitisParotitis– DKADKA– AnorexiaAnorexia– Fallopian tubeFallopian tube– MalignanciesMalignancies

Unknown SourceUnknown Source– Renal failureRenal failure– Head traumaHead trauma– BurnsBurns– PostoperativePostoperative

Diagnosis – LipaseDiagnosis – Lipase

The preferred test for diagnosisThe preferred test for diagnosis

Begins to increase 4-8H after onset of Begins to increase 4-8H after onset of symptoms and peaks at 24Hsymptoms and peaks at 24H

Remains elevated for daysRemains elevated for days

Sensitivity 86-100% and Specificity 60-Sensitivity 86-100% and Specificity 60-99%99%

>3X normal S&S ~100%>3X normal S&S ~100%

DiagnosisDiagnosis

Elevated ALT > 3x normal (in a non-Elevated ALT > 3x normal (in a non-alcoholic) has a positive predictive value of alcoholic) has a positive predictive value of 95% for GS pancreatitis95% for GS pancreatitis

Diagnosis – ImagingDiagnosis – Imaging

CTCT– Excellent pancreas imagingExcellent pancreas imaging– Recommended in all patients with persisting Recommended in all patients with persisting

organ failure, sepsis or deterioration in clinical organ failure, sepsis or deterioration in clinical status (6-10 days after admission)status (6-10 days after admission)

– Search for necrosis – will be present at least 4 Search for necrosis – will be present at least 4 days after onset of symptoms; if ordered too days after onset of symptoms; if ordered too early it will underestimate severityearly it will underestimate severity

– Follow-up months after presentation as Follow-up months after presentation as clinically warranted for CT severity index of >3clinically warranted for CT severity index of >3

Diagnosis - ImagingDiagnosis - Imaging

ERCP / EUSERCP / EUS– Diagnostic and TherapeuticDiagnostic and Therapeutic– Can see and treat:Can see and treat:

Ductal dilatationDuctal dilatation

StricturesStrictures

Filling defects / GSFilling defects / GS

Masses / BiopsyMasses / Biopsy

Diagnosis – ImagingDiagnosis – Imaging

ERCP indications (should be done in the first 72hr)ERCP indications (should be done in the first 72hr)– GS etiology with severe pancreatitis – needs sphincterotomyGS etiology with severe pancreatitis – needs sphincterotomy– CholangitisCholangitis– JaundiceJaundice– Dilated CBDDilated CBD– If no GS found sphincterotomy is indicated anywayIf no GS found sphincterotomy is indicated anyway– Poor surgical candidate for laparoscopic cholecystectomyPoor surgical candidate for laparoscopic cholecystectomy– Clinical course not improving sufficiently to allow timely laparoscopic Clinical course not improving sufficiently to allow timely laparoscopic

cholecystectomy and intraoperative cholangiogramcholecystectomy and intraoperative cholangiogram– Pregnant patientPregnant patient– Uncertainty regarding biliary etiology of pancreatitisUncertainty regarding biliary etiology of pancreatitis


PrognosisPrognosis

Prognosis – Ranson’s (Severe > 3)Prognosis – Ranson’s (Severe > 3)

Ranson’s ScoreRanson’s Score– 5 on Admission5 on Admission

Age > 55 yAge > 55 yGlucose >200Glucose >200WBC > 16000WBC > 16000LDH > 350LDH > 350ALT > 250ALT > 250

– 6 after 48 hours from presentation6 after 48 hours from presentationHct > 10% decreaseHct > 10% decreaseCalcium < 8Calcium < 8Base Deficit > 4Base Deficit > 4BUN > 5BUN > 5Fluid Sequestration > 6LFluid Sequestration > 6LPaO2 < 60PaO2 < 60

Prognosis – Atlanta CriteriaPrognosis – Atlanta Criteria

Severe Acute PancreatitisSevere Acute Pancreatitis– Early Prognostic SignsEarly Prognostic Signs

Ranson signs ≥3Ranson signs ≥3APACHE-II score ≥8APACHE-II score ≥8Organ Failure and/or Local Complications (persist >48 Organ Failure and/or Local Complications (persist >48 hr after admission)hr after admission)NecrosisNecrosisAbscessAbscessPseudocystPseudocyst

Organ Failure as Defined by Atlanta SymposiumOrgan Failure as Defined by Atlanta Symposium– Shock–systolic pressure Shock–systolic pressure <<90 mmH90 mmH– PaO2 ≤60 mmHgPaO2 ≤60 mmHg– Creatinine Creatinine >>2.0 mg/L after rehydration2.0 mg/L after rehydration– Gastrointestinal bleeding Gastrointestinal bleeding >>500 cc/24 h500 cc/24 h

Prognosis – CT Severity IndexPrognosis – CT Severity Index

CT GradeCT Grade– NormalNormal 0 points0 points– Focal or diffuse enlargementFocal or diffuse enlargement 1 point1 point– Intrinsic change or fat strandingIntrinsic change or fat stranding 2 points2 points– Single ill-defined fluid collectionSingle ill-defined fluid collection 3 points3 points– Multiple collections of fluid or gasMultiple collections of fluid or gas 4 points4 points

Necrosis ScoreNecrosis Score– NoneNone 0 points0 points– 1/3 of pancreas1/3 of pancreas 2 points2 points– 1/2 of pancreas1/2 of pancreas 4 points4 points– > 1/2 of pancrease> 1/2 of pancrease 6 points6 points

Severe = Score >Severe = Score > 6 (CT Grade + Necrosis) 6 (CT Grade + Necrosis)

Prognosis – CRP Prognosis – CRP

Santorini consensus and the World Santorini consensus and the World Association guidelines recommend a cut Association guidelines recommend a cut off of 10 - 15 mg/dloff of 10 - 15 mg/dl– This is checked 48 hours after admissionThis is checked 48 hours after admission

Management Management

All patients with biliary pancreatitis should All patients with biliary pancreatitis should undergo definitive treatment of gallstones undergo definitive treatment of gallstones during the same hospital admission, during the same hospital admission, unless a clear plan has been made for unless a clear plan has been made for definitive treatment within the next two definitive treatment within the next two weeksweeksDelay exposes the patient to the risk of Delay exposes the patient to the risk of potentially fatal recurrent acute potentially fatal recurrent acute pancreatitispancreatitisSurgery should be delayed in severe Surgery should be delayed in severe pancreatitis and ERCP is preferred pancreatitis and ERCP is preferred

ManagementManagement

Mainly supportiveMainly supportive– Hydration, pain relief, and pancreatic restHydration, pain relief, and pancreatic rest– NPO – to decrease pancreatic secretionNPO – to decrease pancreatic secretion– Remember stress ulcer prophylaxis alwaysRemember stress ulcer prophylaxis always– Look for complications!!!Look for complications!!!– No magic bullet – antiproteases, octreotide No magic bullet – antiproteases, octreotide

(antisecretory) or lexiafant (anti-inflammatory) (antisecretory) or lexiafant (anti-inflammatory) have all been disappointing in large trialshave all been disappointing in large trials

Management - AntibioticsManagement - Antibiotics

Infected necrosis has significant mortality (40%)Infected necrosis has significant mortality (40%)

No consensus at this time for prophylactic No consensus at this time for prophylactic antibiotics but the literature leans toward using antibiotics but the literature leans toward using them in severe pancreatitis with necrosisthem in severe pancreatitis with necrosis– Imipenum, cefuroxime, ceftazidime + amikacin + Imipenum, cefuroxime, ceftazidime + amikacin +

metro, Ofloxacin + metro, cipro + metro metro, Ofloxacin + metro, cipro + metro your your choicechoice

If used, it should be given no longer than 7 to 14 If used, it should be given no longer than 7 to 14 daysdays

Gut decontamination is not recommendedGut decontamination is not recommended

Management - FeedingsManagement - Feedings

Enteral nutrition is preferredEnteral nutrition is preferred

There is a push for nasojejunal feeds There is a push for nasojejunal feeds however nasogastric feeds have been however nasogastric feeds have been shown to be effective in 80% of casesshown to be effective in 80% of cases¶¶

NGTs should be used with caution in NGTs should be used with caution in patients with AMS howeverpatients with AMS however

More risk with TPN / IL but if cannot feed More risk with TPN / IL but if cannot feed enterally >5 days may be neededenterally >5 days may be needed

¶ Eatock FC. Nasogastric feeding in severe acute pancreatitis. Radiology 1994: 193, 297-306.

Management – Necrosis Management – Necrosis

All severe pancreatitis should be managed All severe pancreatitis should be managed in the ICU or Stepdown Unitin the ICU or Stepdown Unit

FNA recommended when >30% necrosis or FNA recommended when >30% necrosis or clinical suspicion of sepsis for a culture 7-14 clinical suspicion of sepsis for a culture 7-14 days after onset, if gas present assume days after onset, if gas present assume infected necrosis and treatinfected necrosis and treat

Infection generally requires debridement Infection generally requires debridement (surgical or IR)(surgical or IR)

Management – PainManagement – Pain

Morphine not ideal but can still be used – it Morphine not ideal but can still be used – it can theoretically worsen symptoms by can theoretically worsen symptoms by increasing spasm of the Sphincter of Oddiincreasing spasm of the Sphincter of OddiDemerol is a good opiate agonistDemerol is a good opiate agonistHydromorphone is also an excellent optionHydromorphone is also an excellent optionPCA is generally preferred in the PCA is generally preferred in the beginningbeginningAlways use the gut if you can to transition Always use the gut if you can to transition off IV pain medsoff IV pain medsDon’t forget aggressive bowel careDon’t forget aggressive bowel care

Infliximab, a monoclonal TNF antibody, was tested in 100 rats randomly assigned to 10 groups

In acute edematous pancreatitis and in severe necrotizing pancreatitis, the drug significantly decreased serum amylase activity and the histopathologic score

In severe necrotizing pancreatitis, it ameliorated both parenchymal and fatty tissue necrosis of the pancreas

It also alleviated alveolar edema and ARDS-like pulmonary complications, but this difference was not significant

Infliximab in Acute Pancreatitis Infliximab in Acute Pancreatitis

Oruc N, et al. Pancreas 2004; 28:E1-8. [26]

Treatment of Acute Treatment of Acute Pancreatitis with Protease Pancreatitis with Protease

InhibitorsInhibitors Ten articles of randomized controlled trials

evaluating the effects of protease inhibitors (Aprotinin and Gabexate) for acute pancreatitis were retrieved by systematically searching Medline, Cochrane Library and Ovid databases published from January 1966 through December 2003.

The main outcome of interest was the overall mortality rate from acute pancreatitis

When protease inhibitors were given to patients with mild pancreatitis, they were not significant (pooled RD 0.00; 95% CI from -0.04 to 0.05)

When protease inhibitors were given to patients with severe pancreatitis, the mortality rate decreased significantly (pooled RD -0.07; 95% CI from -0.13 to -0.01)

Seta T, et al. Eur J Gastroenterol Hepatol 2004; 16:1287-93. [37]

Zou WG, et al. J Surg Res 2002; 103:121-6. (modified) [29]

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60

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IL-10 Placebo

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Villoria A, et al. Pancreatology 2003; 3:466. [30]

Interleukin-10 in Acute Interleukin-10 in Acute PancreatitisPancreatitis

0

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40

60

80

100

0 1 2 3 4 5 6 7 8Days

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Efficacy in experimental study

No effect in humans

The utility of such experimental models might have limitation, and a full extrapolation of experimental data from laboratory animals to humans must be done with

cautionPastor CM, Frossard JL. FASEB J 2001; 15:893-7. [28]

Limitations of Experimental Models for Limitations of Experimental Models for the Treatment of Acute Pancreatitisthe Treatment of Acute Pancreatitis

Complications – LocalComplications – Local

NecrosisNecrosis– SterileSterile– Infected - abscessInfected - abscess

PseudocystPseudocyst

AscitesAscites

Intraperitoneal hemorrhageIntraperitoneal hemorrhage

ThrombosisThrombosis

Bowel infarctionBowel infarction

Obstructive jaundiceObstructive jaundice

Complications – SystemicComplications – Systemic

PulmonaryPulmonary– Pleural effusionsPleural effusions– AtelectasisAtelectasis– Mediastinal abscessMediastinal abscess– ARDSARDS

CardiovascularCardiovascular– HypotensionHypotension– Sudden deathSudden death– Pericardial effusionPericardial effusion

HematologicHematologic– DICDIC

GastrointestinalGastrointestinal– PUDPUD– Erosive gastritisErosive gastritis– Blood vessel erosionBlood vessel erosion– Portal vein thrombosisPortal vein thrombosis

RenalRenal– OliguriaOliguria– AzotemiaAzotemia– Renal artery/vein Renal artery/vein

throbosisthrobosis– ATNATN

Complications – Long TermComplications – Long Term

Chronic PancreatitisChronic Pancreatitis– Abdominal PainAbdominal Pain– SteatorrheaSteatorrhea– Exocrine insufficiency (pancreas has a 90% Exocrine insufficiency (pancreas has a 90%

reserve for the secretion of digestive reserve for the secretion of digestive enzymes)enzymes)

– Endocrine Insufficiency – less commonEndocrine Insufficiency – less common– PseudocystPseudocyst

ConclusionsConclusions

Do not assume alcohol is the primary cause of Do not assume alcohol is the primary cause of pancreatitispancreatitisAlways consider further work-up for “idiopathic” Always consider further work-up for “idiopathic” pancreatitis pancreatitis Severe acute pancreatitis should be managed in Severe acute pancreatitis should be managed in ICU/SDICU/SDInfected necrosis carries a high mortalityInfected necrosis carries a high mortalityAntibiotics for suspected infected necrosisAntibiotics for suspected infected necrosisTube feedings preferred Tube feedings preferred Always look for the myriad of complicationsAlways look for the myriad of complications

CHRONIC CHRONIC PANCREATITISPANCREATITIS

Progressive – Destructive InflammationProgressive – Destructive Inflammation

Permanent parenchymal loss Permanent parenchymal loss

Pancreatic endo + exo insufficiencyPancreatic endo + exo insufficiency

CausesCauses

• Alcohol Alcohol 80 % 80 % (Ten years (Ten years 60 gdL)60 gdL)

• Idiopathic Idiopathic 10%-20%10%-20%

• Rare biliary, pHTPRare biliary, pHTP

Chronic PancreatitisChronic Pancreatitis

Classic triadClassic triad SteatorrheaSteatorrhea

CalcificationCalcification

DiabetesDiabetes

Symptoms + SignsSymptoms + Signs

Abdominal PainAbdominal Pain

MalabsorptionMalabsorption

DiabetesDiabetes

JaundiceJaundice

PainPain

Mid-epigastrium; UpperquadrantMid-epigastrium; Upperquadrant

periumbilicalperiumbilical

Steady, boring, achy, Steady, boring, achy,

radiating to the back.radiating to the back.

Better! When Sitting.Better! When Sitting.

Diagnostic LaboratoryDiagnostic Laboratory

Amylase Slightly Lipase

Liver Fu. Tests Glucose AP Protrombin time

Diagnostic ImagingDiagnostic Imaging

CT: CT: Ductal dilatationDuctal dilatation

CalcificationCalcification

PseudocystsPseudocysts

ERCPERCP

Diagnostic TestsDiagnostic Tests

Pancreolauryl-TestPancreolauryl-Test

Secretin – Pancreocymin TestSecretin – Pancreocymin Test

PANCREATIC NLPPANCREATIC NLP1.1. Adeno – ca Adeno – ca -- 90%90%

2.2. Acinal cellAcinal cellGiant cellGiant cell 10%10%EpidermoidEpidermoidSarcomaSarcoma

3. Islet cell 3. Islet cell -- 5%5%

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acute pancreatitis

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time pancreatitis

trypsin activation

gallstone pancreatitis

sweeping trypsin

inactivating trypsin

frequent bouts of pancreatitis

trypsin autoactivation

protein structure of