CLASSIFICATION OF CLASSIFICATION OF CHRONIC PANCREATITISCHRONIC PANCREATITIS

EAGE, Podstgraduate Course,EAGE, Podstgraduate Course, Prague, April 2010. Prague, April 2010.

Tomica MilosavljevićTomica Milosavljević

School of Medicine, Clinical Center School of Medicine, Clinical Center University of Belgrade of University of Belgrade of Serbia ,Belgrade Serbia ,Belgrade

The phrase “chronic The phrase “chronic pancreatitis”pancreatitis”

in the clinical context:in the clinical context:

– syndrome of destructive,inflammatory syndrome of destructive,inflammatory conditions conditions

– many sequelae of long-standing pancreatic many sequelae of long-standing pancreatic injuryinjury

(irregular fibrosis, acinar cell loss, islet cell (irregular fibrosis, acinar cell loss, islet cell loss, and inflammatory cell infiltrates)loss, and inflammatory cell infiltrates)

Chronic pancreatitis, Chronic pancreatitis, morphologically morphologically

Irregular sclerosisIrregular sclerosis Destruction, permanent loss of the Destruction, permanent loss of the

exocrine parenchymaexocrine parenchyma May be either, focal, segmental or May be either, focal, segmental or

diffusediffuse Varying degrees of dilatation of Varying degrees of dilatation of

the duct systemthe duct system

Problems in definitionProblems in definition

Chronic pancreatitis implies Chronic pancreatitis implies longstandinglongstanding disease, both in disease, both in pathogenesis and effect.pathogenesis and effect.

Defining features Defining features ::– must consider the etiologymust consider the etiology– characteristic clinical evidencecharacteristic clinical evidence– sequelae of organ pathologysequelae of organ pathology– including complicationsincluding complications

Clasiffication 1Clasiffication 1

The clinical course is still The clinical course is still unpredictableunpredictable

The lack of the availability of a The lack of the availability of a clinical classificationclinical classification

Clasiffication 2Clasiffication 2 The King’s College Cambridge 1983 The King’s College Cambridge 1983

– clinically utilizable system clinically utilizable system – based on ERCPbased on ERCP

The MarseillesThe Marseilles 1963,19841963,1984– various subtypes and clinical entitiesvarious subtypes and clinical entities

Rome 1985: Rome 1985: pathogenesis and evolutionpathogenesis and evolution Zurich 1996 Zurich 1996

– alcohol relatedalcohol related– not provided prognostic information not provided prognostic information

Zurich Zurich international clasiffication (1997-98)international clasiffication (1997-98)

Clasiffication 3Clasiffication 3

TIGAR-O TIGAR-O (2001.)(2001.)

ABC criteria ABC criteria (Ramesh 2002)(Ramesh 2002)

Manchester Manchester 2006 (ABC)2006 (ABC)

M-ANNHEIM M-ANNHEIM 2007 (Schneider)2007 (Schneider)

Etiologic risk factors – TIGAR-O system

Toxic-metabolic– Alcochol– Tobacco– Hypercalcemia– Hyperlipidemia– Chronic renal

failure– Medications

(Phenacetin abuse)– Toxins( organotoni

n compounds)

Idiopathic

– Early onset– Late onset– Tropical

Tropical calc.pancr.

Fibrocalculous diab.

Other

Etiologic risk factors – TIGAR-O system Genetic

– Autosomal dominant Cationic

trypsinogen (Codon 29, 122 mut.)

– Autosomal recessive/modifier genes

CFTR mutations SPINK1 mutations Cationic

trypsinogen ( codon 16,22,23 mut.)

Alfa 1 antitrypsin defficiency (possible)

Autoimmune

– Isolated autoimmune

– Syndromic autoimmune

Sjogren IBD associated Prim.bill.cirrhosis

assoc.

Etiologic risk factors – TIGAR-O system

Recurrent and severe acute

– Postnecrotic acute

– Recurrent acute

– Vascular dis./ishemic

– Postirradiation

Obstructive– Pancreas divisum– Sphincter Oddi

disorders (controversial)

– Duct obstruction (tumor)

– Preampullar duodenal wall cyst

– Posttraumatic pancreatic duct scars

Why new clinical Why new clinical clasiffication?clasiffication? Clinical experience Clinical experience Progress in diagnostic methods Progress in diagnostic methods New molecular technologies New molecular technologies

for the assessmentfor the assessment Key clinical aspects is crucial Key clinical aspects is crucial

M W Büchler, M E Martignoni, H Friess, P Malfertheiner M W Büchler, M E Martignoni, H Friess, P Malfertheiner BMC BMC Gastroenterol. 2009; 9: 93. Gastroenterol. 2009; 9: 93.

Ideal Classification for Ideal Classification for chronic pancreatitis :chronic pancreatitis : User friendly,User friendly, transparent,transparent, relevant,relevant, prognosis- as well as treatment-prognosis- as well as treatment-

related related and offers a frame for future and offers a frame for future

disease evaluation.disease evaluation.M W Büchler, M E Martignoni, H Friess, P Malfertheiner BMC Gastroenterol. 2009; 9: 93. 2009

Facts and state-of-the-art Facts and state-of-the-art knowledge in chronic knowledge in chronic pancreatitis (I)pancreatitis (I) 1) Different 1) Different etiologiesetiologies

2) There are no serologic or blood 2) There are no serologic or blood markers markers

3) Pathognomonic lesions are detectable 3) Pathognomonic lesions are detectable by by imagingimaging

4) 4) LossLoss of exocrine and endocrine function of exocrine and endocrine function develops develops

Facts and state-of-the-art Facts and state-of-the-art knowledge in chronic knowledge in chronic pancreatitis (II)pancreatitis (II) 5) The end stage 5) The end stage steatorrhea and steatorrhea and

insulin-dependent diabetes insulin-dependent diabetes mellitus.mellitus.

6) 6) ComplicationsComplications are known such as are known such as common bile duct, duodenal, main common bile duct, duodenal, main pancreatic duct and vascular pancreatic duct and vascular obstruction/stenosis.obstruction/stenosis.

7) 7) Risk factor Risk factor for pancreatic cancer.for pancreatic cancer. 8) 8) Overall life expectancyOverall life expectancy is reduced. is reduced.

Unresolved issues in Unresolved issues in chronic pancreatitis (I)chronic pancreatitis (I)

1) 1) The relationship The relationship between acute and between acute and chronic pancreatitis is not completely chronic pancreatitis is not completely defined.defined.

2) 2) Disease progressionDisease progression, arrest and , arrest and regression of functional and morphologic regression of functional and morphologic findings occur is debated.findings occur is debated.

3) 3) Diagnosis Diagnosis of early chronic pancreatitis by of early chronic pancreatitis by imaging is not established.imaging is not established.

4) The role and validity of 4) The role and validity of exocrine exocrine pancreatic function tests pancreatic function tests in the diagnosis is in the diagnosis is not establishednot established..

Unresolved issues in Unresolved issues in chronic pancreatitis chronic pancreatitis (II)(II) 5) The 5) The pathogenesis of pain pathogenesis of pain is at least is at least

multifactorial and not defined.multifactorial and not defined. 6) The 6) The burn-out hypothesis burn-out hypothesis is still debated and not is still debated and not

defined with regard to time evolution in different defined with regard to time evolution in different etiologies.etiologies.

7) There is 7) There is disagreementdisagreement over whether to use over whether to use enzyme treatment to influence pain.enzyme treatment to influence pain.

8) The role of 8) The role of endoscopic intervention iendoscopic intervention is not s not defined under evidence-based criteria.defined under evidence-based criteria.

9) The role of 9) The role of surgery surgery is not defined under is not defined under evidence-based criteriaevidence-based criteria

Clinical CriteriaClinical Criteria pain pain

attacks of acute pancreatitis attacks of acute pancreatitis

complications of CP complications of CP

steatorrheasteatorrhea

diabetes mellitusdiabetes mellitus

Definition of Definition of complications (1)complications (1)

bile duct bile duct obstructionobstruction/stenosis with /stenosis with cholestasis or jaundice/cholestasis or jaundice/

duodenal obstructionduodenal obstruction/stenosis with /stenosis with clinical signs/ clinical signs/

vascular obstructionvascular obstruction/stenosis with /stenosis with clinical or morphological signs of clinical or morphological signs of portal/splenic vein hypertension portal/splenic vein hypertension

Definition of Definition of complications (2)complications (2)

pancreatic pancreatic pseudocystspseudocysts with clinical with clinical signs (compression of adjacent organs, signs (compression of adjacent organs, infection, bleeding, etc.)infection, bleeding, etc.)

pancreatic pancreatic fistulafistula (internal or external) (internal or external) pancreatogenic pancreatogenic ascites ascites other other rare complications rare complications related to related to

organs in vicinity (i.e., colonic stenosis, organs in vicinity (i.e., colonic stenosis, splenic pseudocyst, etc.)splenic pseudocyst, etc.)

Imaging criteria for Imaging criteria for chronic pancreatitischronic pancreatitis Ductal changes:Ductal changes: Irregularity Irregularity of the of the

main pancreatic duct or side branches main pancreatic duct or side branches ± intraductal filling defects, ± intraductal filling defects, calculicalculi, , duct duct obstruction obstruction (stricture), duct (stricture), duct dilatation dilatation (>3 mm)(>3 mm)

Parenchymal changes:Parenchymal changes: General or General or focal focal enlargementenlargement of the gland, of the gland, cystscysts, , calcificationscalcifications, heterogenous , heterogenous reflectivityreflectivity..

Etiology of chronic Etiology of chronic pancreatitispancreatitis alcohol alcohol idiopathic (unknown origin)idiopathic (unknown origin) hereditary autoimmune or in hereditary autoimmune or in

combination with specific diseases combination with specific diseases (Crohn's, PBC) (Crohn's, PBC)

tropicaltropical cystic fibrosiscystic fibrosis obstructive (pancreatic duct)obstructive (pancreatic duct) drugsdrugs

Specific definition of chronic Specific definition of chronic pancreatitis stage A (1)pancreatitis stage A (1) Stage AStage A: :

– the early stage , complications have the early stage , complications have not yet appeared, the clinical not yet appeared, the clinical exocrine and endocrine function is exocrine and endocrine function is preserved; preserved;

– subclinical signs (impaired glucose subclinical signs (impaired glucose tolerance, reduced exocrine function tolerance, reduced exocrine function but without steatorrhea) might but without steatorrhea) might already be apparent.already be apparent.

Specific definition of chronic Specific definition of chronic pancreatitis stage A (2)pancreatitis stage A (2)

Stage AStage A is accepted under the is accepted under the following conditions:following conditions:

– Pain of any type and degree and/or Pain of any type and degree and/or attacks of acute pancreatitis, attacks of acute pancreatitis,

– no complications , no complications , – no steatorrhea,no steatorrhea,– no insulin-dependent diabetes no insulin-dependent diabetes

mellitus.mellitus.

Specific definition of chronic Specific definition of chronic pancreatitis stage B (1)pancreatitis stage B (1)

Stage B:Stage B:

– the intermediate stage where the intermediate stage where chronic pancreatitis has led to chronic pancreatitis has led to complications,complications,

– but clinical exocrine and endocrine but clinical exocrine and endocrine function is still preserved.function is still preserved.

Specific definition of chronic Specific definition of chronic pancreatitis stage B (2)pancreatitis stage B (2)

The type of complication is specified The type of complication is specified (e.g., stage B, bile duct)(e.g., stage B, bile duct)

Stage BStage B is accepted under the is accepted under the following conditions:following conditions:– Patients with complications ,Patients with complications ,– but but without steatorrhea or diabetes without steatorrhea or diabetes

mellitusmellitus

Specific definition of chronic Specific definition of chronic pancreatitis stage C (1)pancreatitis stage C (1) Stage CStage C

– is is the end stage the end stage of chronic pancreatitis, of chronic pancreatitis, fibrosis has led to clinical exocrine fibrosis has led to clinical exocrine and/or endocrine pancreatic function and/or endocrine pancreatic function loss (steatorrhea and/or diabetes loss (steatorrhea and/or diabetes mellitus); complications of chronic mellitus); complications of chronic pancreatitis might or might not be pancreatitis might or might not be presentpresent

– the type of exocrine and/or endocrine the type of exocrine and/or endocrine pancreatic function loss is specified pancreatic function loss is specified (e.g., stage C, steatorrhea)(e.g., stage C, steatorrhea)

Specific definition of chronic Specific definition of chronic pancreatitis stage C (2)pancreatitis stage C (2) Stage CStage C can be sub classified into three categories: can be sub classified into three categories:

– C1: Patients C1: Patients with endocrine with endocrine function impairmentfunction impairment– C2: Patients C2: Patients with exocrine with exocrine function impairmentfunction impairment– C3: Patients with C3: Patients with exocrine/endocrineexocrine/endocrine function function

impairment and/or complications impairment and/or complications

Stage CStage C is accepted under the following conditions: is accepted under the following conditions:– Patients with clinical manifestation of end-stage Patients with clinical manifestation of end-stage

functional impairment with or without functional impairment with or without complications.complications.

Controversies in Controversies in chronic pancreatitis chronic pancreatitis clasifficatonclasifficaton Endoscopical interventionsEndoscopical interventions, ,

yes/no ?yes/no ?

Surgical Surgical dilemmadilemma-resection/drenaige ?-resection/drenaige ?

Follow-upFollow-up the patients and the patients and reconsider clasifficationreconsider clasiffication

Thank you very much Thank you very much for your attentionfor your attention

Prof. Dr Tomica MilosavljevićProf. Dr Tomica Milosavljević MD MD PhDPhDSchool of Medicine, Clinical Center School of Medicine, Clinical Center University of Belgrade of University of Belgrade of Serbia ,Belgrade Serbia ,Belgrade