diagnosis of chronic pancreatitis christoph beglinger, university hospital basel, switzerland
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Diagnosis of chronic PancreatitisDiagnosis of chronic Pancreatitis
Christoph Beglinger, University Hospital Basel, SwitzerlandChristoph Beglinger, University Hospital Basel, Switzerland
PancreatitisPancreatitis
PancreasPancreas - - an organ that makes an organ that makes bicarbonatebicarbonate to neutralize gastric acid, to neutralize gastric acid, enzymesenzymes to digest the contents of a meal and to digest the contents of a meal and insulininsulin to signal the body to store ingested to signal the body to store ingested nutrients.nutrients.
Acute PancreatitisAcute Pancreatitis - An acute, potentially life-threatening condition presenting with - An acute, potentially life-threatening condition presenting with severe abdominal pain in which the pancreas appears to digest itself. It is severe abdominal pain in which the pancreas appears to digest itself. It is usually caused by gallstones, alcohol or is idiopathic.usually caused by gallstones, alcohol or is idiopathic.
Chronic Pancreatitis Chronic Pancreatitis - an- an irreversible scarring of the pancreas with permanent irreversible scarring of the pancreas with permanent loss of pancreatic function that typically causes unrelenting abdominal pain.loss of pancreatic function that typically causes unrelenting abdominal pain.
Hereditary Pancreatitis Hereditary Pancreatitis - a unusual form of acute and chronic pancreatitis that - a unusual form of acute and chronic pancreatitis that runs in families. The risk of pancreatic cancer is >50 times normal.runs in families. The risk of pancreatic cancer is >50 times normal.
PancreasPancreas
The PancreasThe Pancreas
Gross AnatomyGross Anatomy HeadHead BodyBody TailTail
1. History
Chronic pancreatitis: medical progress
« Since that early description (1788) of chronic pancreatitis, thousand of reports dealing with this disease have been published, yet chronic pancreatitis remains an enigmatic process of uncertain pathogenesis, unpredictable clinical course, and unclear treatment »
ML Steer, I Waxman, S Freedman
June 1995; 332: 1482-1490
DefinitionDefinition
A persistent inflammatory disease of the pancreas A persistent inflammatory disease of the pancreas IrreversibleIrreversible morphologic change morphologic change Typically causing pain and/or loss of digestive function Typically causing pain and/or loss of digestive function
Chronic PancreatitisChronic Pancreatitis
Progression from acute to chronic pancreatitis in humans ?
Chronic Pancreatitis: the main question:
OH
10 - 18 years
First attack
Pseudocysts
Cholestasis
10 years
Cirrhosis
Diabetes Steatorrhea
Chronic Pancreatitis: the natural history
Calcifications in CP
Exocrine Insufficiency in CP
Diabetes mellitus in CP
Normal Digestion and AbsorptionNormal Digestion and Absorption
Mechanical mixing Enzymes and bile salts Mucosal functions Blood supply Intestinal motility Bacterial flora
Fecal fat output vs Lipase
Lipase and Trypsin over Time
Gastric and duodenal pH in CP
Gastric Emptying in CP
Mechanisms of Fat MalabsorptionMechanisms of Fat Malabsorption
Pancreatic insufficiency Bile salt insufficiency Small intestinal bacterial overgrowth Reduced absorptive area Defects in enterocyte function Diseases of the lymph system
Mechanisms of CH MalabsorptionMechanisms of CH Malabsorption
Disaccharidase defect Reduced absorptive area Defects in enterocyte function Pancreatic insufficiency
Mechanismen der Protein MalabsorptionMechanismen der Protein Malabsorption
Reduced absorptive area Defects in enterocyte function Pancreatic insufficiency Protein-losing enteropathy
Chronic Pancreatitis: SymptomsChronic Pancreatitis: Symptoms
Clinical FeaturesClinical Features PainPain Exocrine Exocrine
pancreatic pancreatic insufficiencyinsufficiency
Endocrine Endocrine pancreatic pancreatic insufficiencyinsufficiency
Chronic Pancreatitis: DiagnosisChronic Pancreatitis: Diagnosis
Diagnosis: simpleDiagnosis: simple HistoryHistory ComplaintsComplaints X-ray, lab studiesX-ray, lab studies
Clinical PresentationClinical Presentation
Abdominal pain - primary feature Abdominal pain - primary feature ((15 – 25% CP may be painless)15 – 25% CP may be painless)
Malabsorption/steatorrhea – usually occurs Malabsorption/steatorrhea – usually occurs when enzyme secretion < 10% of normalwhen enzyme secretion < 10% of normal
Diabetes Diabetes
Jaundice, ascites, or pleural effusionsJaundice, ascites, or pleural effusions
DiagnosisDiagnosis
Frequently made by history alone Frequently made by history alone e.g. an alcoholic with recurrent attackse.g. an alcoholic with recurrent attacks
Plain abdominal X-ray - calcification in ~30%Plain abdominal X-ray - calcification in ~30% diagnostic in clinically suspected patientsdiagnostic in clinically suspected patients
“Screening” Tests“Screening” Tests
Blood tests Blood count Electrolytes, Mg, Phos, Ca Albumin, Protein Vitamin B12, Folate, Iron Liver tests Coagulation/INR, Cholesterol Glucose, HbA1c Beta-Carotin (?)
Stool tests Ova and Parasites Stool fat
Stool fat QuantitativeStool fat Quantitative
“Gold Standard” for Maldigestion
72 hrs collection optimal Normal < 7 gr/day Low importance in daily clinical life (stool
collection, -analysis)
Chronic Pancreatitis: ImagingChronic Pancreatitis: Imaging
HistologyHistology FibrosisFibrosis Scattered foci of chronic Scattered foci of chronic
inflammationinflammation Ducts & islets of Ducts & islets of
Langerhans persistLangerhans persist CalcificationsCalcifications
Imaging ModalitiesImaging Modalities
Abdominal ultrasoundAbdominal ultrasound Dilated pancreatic duct, calcifications, pseudocystsDilated pancreatic duct, calcifications, pseudocysts
(often incomplete exam due to overlying bowel (often incomplete exam due to overlying bowel gas)gas)
Abdominal CTAbdominal CTDilated pancreatic duct, atrophy of Dilated pancreatic duct, atrophy of pancreas, pseudocysts, calcifications pancreas, pseudocysts, calcifications
CT in chronic PancreatitisCT in chronic PancreatitisCT in chronic PancreatitisCT in chronic Pancreatitis
Imaging ModalitiesImaging Modalities
ERCPERCP Better test for defining the Better test for defining the ductal changesductal changes - stricture, ductal - stricture, ductal
irregularitiesirregularities Not for obtaining parenchymal informationNot for obtaining parenchymal information Provides therapeutics - dilation, stone extraction and Provides therapeutics - dilation, stone extraction and
stenting of ductstenting of duct
• MRCPMRCP• Imaging alternative for diagnostic purposes; secretin Imaging alternative for diagnostic purposes; secretin
stimulation ?stimulation ?
Chronic pancreatitisChronic pancreatitis
Imaging ModalitiesImaging Modalities
EUSEUS Duct & parenchyma – ductal dilatation, Duct & parenchyma – ductal dilatation,
irregularities, pseudocysts, stones, calcifications, irregularities, pseudocysts, stones, calcifications, parenchymal scarring evidenced by parenchymal scarring evidenced by heterogeneous echogenicityheterogeneous echogenicity
MassMass Identify early changes of chronic pancreatitisIdentify early changes of chronic pancreatitis Overall ~ 85% accurate in chronic pancreatitis Overall ~ 85% accurate in chronic pancreatitis
diagnosisdiagnosis
EUS: Chronic PancreatitisEUS: Chronic Pancreatitis
Pancreatic Function Tests
Indirect tests
• Stool tests (Elastase)
• Stool fat
• Breath tests etc.
Direct tests
Examination of pancreatic secretory responses
Why pancreatic function tests ?Why pancreatic function tests ?
Pancreatic function tests should be Pancreatic function tests should be performed if:performed if:
Diagnosis of CP is suspected andDiagnosis of CP is suspected and
Imaging tests normal or inconclusiveImaging tests normal or inconclusive
Indications for pancreatic function testsIndications for pancreatic function tests
Characterization of pancreatic function Characterization of pancreatic function in suspected pancreatic diseasein suspected pancreatic disease
Differential diagnosis in malabsorptionDifferential diagnosis in malabsorption
Assessment of adequacy of pancreatic Assessment of adequacy of pancreatic enzyme replacement therapyenzyme replacement therapy
Invasive tests are the Invasive tests are the
„Goldstandard“,„Goldstandard“,
but are they necessary?but are they necessary?
Requirements for Invasive Requirements for Invasive
Pancreatic Function TestsPancreatic Function Tests
Oro-duodenal intubationOro-duodenal intubation
Exogenous hormones (Secretin, Exogenous hormones (Secretin, Caerulein, CCK)Caerulein, CCK)
Expertise !Expertise !
Time ! Time ! ( PFTs are time consuming and ( PFTs are time consuming and expensive)expensive)
Should a marker be employed ?Should a marker be employed ?
Nonabsorbable marker perfused to the Nonabsorbable marker perfused to the duodenum (e.g. Polyethylene glycol, duodenum (e.g. Polyethylene glycol, PEG 4000)PEG 4000)
Precise quantification of pancreatic Precise quantification of pancreatic enzyme output/bicarbonate outputenzyme output/bicarbonate output
What type of stimulation should be used ?What type of stimulation should be used ?
Hormones (Secretin, CCK/Caerulein) ?Hormones (Secretin, CCK/Caerulein) ?
Meals ?Meals ?
Sensitivity and specifity of invasive PFTsSensitivity and specifity of invasive PFTs
90% sensitivity and 90% specificity for 90% sensitivity and 90% specificity for detecting CP with hormonal stimulidetecting CP with hormonal stimuli
Di Magno, N Engl J Med 1973Di Magno, N Engl J Med 1973
Lankisch, Gut 1982Lankisch, Gut 1982
Di Magno, Exocrine Pancreas Di Magno, Exocrine Pancreas 19931993
Secretin or secretin plus CCK ?Secretin or secretin plus CCK ?
SecretinSecretin Bicarbonate OutputBicarbonate Output
CCK CCK Enzyme OutputEnzyme Output
Problems associated with Problems associated with
enzyme measurementsenzyme measurements
Use/nonuse of a nonabsorbable Use/nonuse of a nonabsorbable markermarker
Collection of duodenal sampleCollection of duodenal sampless
Methods used to analyze enzyme Methods used to analyze enzyme concentrations (concentrations ( standardization has standardization has been extremely difficult !)been extremely difficult !)
Problems associated with stimuliProblems associated with stimuli
Stimulation of pancreatic function with Stimulation of pancreatic function with secretin/CCK = „Goldstandard“secretin/CCK = „Goldstandard“
Stimulation with meals/nutrients less Stimulation with meals/nutrients less specificspecific
(( they depend on adequate pancreatic they depend on adequate pancreatic stimulation) e.g. Celiac Diseasestimulation) e.g. Celiac Disease
Regan, Gastroenterology 1980Regan, Gastroenterology 1980
Lamers, Gastroenterology 1983Lamers, Gastroenterology 1983
Normal Ranges of invasive PFTs-1Normal Ranges of invasive PFTs-1
Volume (ml)Volume (ml) 117 - 392117 - 392
Bicarbonate ConcentrationBicarbonate Concentration
(mEq/l)(mEq/l) 88 - 13788 - 137
Bicarbonate OutputBicarbonate Output
(mEq/l)(mEq/l) 16 - 3316 - 33
Dreiling and Hollander 1950Dreiling and Hollander 1950
Normal Ranges in Secretin-TestNormal Ranges in Secretin-Test
in Baselin Basel
Bicarbonate ConcentrationBicarbonate Concentration
(mmol/L)(mmol/L) > 70> 70
Bicarbonate OutputBicarbonate Output
(mmol/hr)(mmol/hr) > 12> 12
Personal assessment of invasive PFTsPersonal assessment of invasive PFTs
Determination of bicarbonate Determination of bicarbonate concentration is sufficientconcentration is sufficient
Bicarbonate output determinationBicarbonate output determinationdoes not add any additional does not add any additional
pertinent informationpertinent information
Quantification of enzymes is not Quantification of enzymes is not necessarynecessary
Why pancreatic function tests ?Why pancreatic function tests ?
Pancreatic function tests should be Pancreatic function tests should be performed if:performed if:
Diagnosis of CP is suspected andDiagnosis of CP is suspected and
Imaging tests normal or inconclusiveImaging tests normal or inconclusive
Rapid Endoscopic PFTRapid Endoscopic PFT
Standard endoscopy under sedationStandard endoscopy under sedation
IV secretin (0.2 microgr/kg)IV secretin (0.2 microgr/kg)
Endoscopic fluid collection (0, 15, 30, Endoscopic fluid collection (0, 15, 30, 45 and 60 min)45 and 60 min)
Fluid analysis for bicarbonate concFluid analysis for bicarbonate conc
Conwell et al 2003; Stevens et al. 2006Conwell et al 2003; Stevens et al. 2006
Stevens et al. American J of Gastroenterology (2006) 101, 351–355
Standard vs Endoscopic PFT
Standard vs Endoscopic PFT
Conclusion from AuthorsConclusion from Authors
Simple test, safeSimple test, safe
Can be performed during endoscopyCan be performed during endoscopy
Rapid Endoscopic PFT - 2Rapid Endoscopic PFT - 2
Standard endoscopy under sedationStandard endoscopy under sedation
IV secretin (1 CU/kg)IV secretin (1 CU/kg)
Endoscopic fluid collection for 10 minEndoscopic fluid collection for 10 min
Fluid analysis for bicarb and enzyme Fluid analysis for bicarb and enzyme concconc
Raimondo M et al 2003; Clin Gastroenterol HepatolRaimondo M et al 2003; Clin Gastroenterol Hepatol
Patient groupsPatient groups
Chronic pancreatitis (N=72)Chronic pancreatitis (N=72)
Patients with normal pancreas (N=117)Patients with normal pancreas (N=117)
Overall accuracy of endoscopic PFTOverall accuracy of endoscopic PFT
79%79%
(negative PV 85%, positive PV 73%)(negative PV 85%, positive PV 73%)
That's all, folks!
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