acute pancreatitis
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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
Pancreatic PhysiologyPancreatic Physiology
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
Pancreatic PhysiologyPancreatic Physiology
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 PancreatitisAcute Pancreatitis
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
Acute PancreatitisAcute Pancreatitis
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
Acute PancreatitisAcute Pancreatitis
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%.
Acute PancreatitisAcute Pancreatitis
Clinical PresentationClinical Presentation
Clinical PresentationClinical Presentation
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
Clinical PresentationClinical Presentation
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
Acute PancreatitisAcute 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]
0
20
40
60
80
100
IL-10 Placebo
New
org
an f
ailu
re (
%)
P NS
Villoria A, et al. Pancreatology 2003; 3:466. [30]
Interleukin-10 in Acute Interleukin-10 in Acute PancreatitisPancreatitis
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8Days
Sur
viva
l (%
)
IL-10Untreated
P<0.05
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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