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!