l'eterogeneità della pancreatite cronica - gastrolearning®
DESCRIPTION
Gastrolearning VI lezione L'eterogeneità della pancreatite cronica - Prof. I. Vantini Università di Verona www.gastrolearning.itTRANSCRIPT
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Università di Verona Dipartimento di
Medicina
L’eterogeneitàdella pancreatite
cronica
AOUI di VeronaIstituto del Pancreas
Italo Vantini
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Conoscere una malattia - 1
• La conoscenza delle connotazioni di una malattia consente di fornire:– una descrizione utile per l’inquadramento
classificativo (nosologico) (che cosa è)• Etiopatogenetica• Clinica• Anatomopatologica• Fisiopatologica
– un “nome”’per la sua identificazione nosologica (condivisione di come si chiama)
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Conoscere una malattia - 2
• Una diagnosi– Matching, illness script, exemplars– Percorsi probabilistici– Criteri, strumenti, percorsi, processi
• La diagnosi non è “tanto” l’inserimento del paziente in una “casella nosologica, ma un giudizio basato su dati e criteri utili per assumere decisioni operative ai fini della:
• Prognosi• Terapia
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In principio…
Sarles H, Sarles JC, Camatte R, Muratore R, Gaini M, Guien C, Pastor J, Le Roy
FObservations on 205 confirmed cases of acute pancreatitis, recurring pancreatitis, and chronic pancreatitis.
Gut 1965; 6: 545-59.
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Chronic pancreatitis
Chronic process characterized by inflammatory and fibrotic changes of the pancreas.
Irreversible nature of structural changes and progressive
functional impairment
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Chronic pancreatitis
Fibrosis of the pancreas Damage to the acinar tissue Changes in ductal system• Calcifications
morphologically
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Chronic pancreatitis: progressive parenchymal changes
Normal pancreas
Moderate changes more or lessscattered troughout the pancreas
Advanced changes (fibrosis)
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Chronic pancreatitis: pancreatic duct
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Pancreatic calcification
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Chronic pancreatitis
• Recurrent or persistent pancreatic pain
clinically
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Pain in chronic pancreatitis
PATHOPHYSIOLOGY• Acute inflammation
• Ischemia• Increased intraductal and parenchymal pressure
• Mechanical compression (e.g. pseudocyst)Pancreatic neural remodelling and neuropathy
Clinical pictures Type 1pain recurrent with lasting
pain-free intervalsType 2 pain : frequent, persisting,
disabling pain
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Chronic pancreatitis• Recurrent or persistent
pancreatic pain Changes in ductal system• Fibrosis of the pancreas• calcification
• Deterioration in pancreatic function
(exocrine and endocrine)
clinically
morphologically
functionally
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Frequency of painful relapses/year in 199 patients with chronic pancreatitis
(non-operated upon) followed up to 20 years
0
1
2
3
4
5
N. p
ain
ful
rela
pse
s
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
25°
years since clinical onset
25°50°75°
percentiles
Calcification and dysfunction in time
Scuro LA et al , Am J Gastroenterol 1983; 78: 495-501. Ammann RW et al. Gastroenterology 1984, 86: 820-8..
early advanced late
Prevention andtreatment
of painful relapses and complications
treatment of relapsing
or persisting pain
Treatment ofexocrine failureand secondary
diabetes
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alcool
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Alcohol and chronic pancreatitis- relative risk -
0
2
4
6
8
10
12
14
16
0-40 41-80 81- 240
grams of alcohol/day
chronicpancreatitiscancer without CP
Durbec J, Sarles H: Digestion 1973Talamini G. et al Dig Dis Sci 1999
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pain
function
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Chronic Pancreatitis (“old concepts”) - 1
Chronic Pancreatitis (“old concepts”) - 1
a single and distinct entity
a well defined epidemiological
and clinical pattern
Male/female 4:1; age onset 47 year old
alcoholic in origin (in Western Countries)
Differs from Acute Pancreatitis(etiology, clinical outcome,prognosis)
Acute and chronic pancreatitis are two distinct entities
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Pancreatologia
felix
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Chronic PancreatitisAlcohol abuse in more recent studies
Chronic PancreatitisAlcohol abuse in more recent studies
0
1020
3040
50
6070
8090
100
Italy 2009° India 2008* USA 2008^ China 2009"
% o
f patien
ts
° Frulloni L et al, PanCroInfAISP, Dig Liv Dis 2009; 41: 311-317* Balakrishnan V et al, J Pancreas, 2008; 9: 593-600^ Withcomb DC et al, NAPS2, Pancreatol, 2008; 8: 520-531” Whang LW et al, Chinese CPSG, Pancreas, 2008; 38:248-54.
893 pts 1033 pts 540 pts 2008 pts
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Smoking and chronic pancreatitis: a meta-analysis
Andriulli A, Botteri E, Almasio PL, Vantini I, Uomo G, Maisonneuve P: Smoking as a
cofactor for causation of chronic pancreatitis. Pancreas 2010; 39: 1205- 1210
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Smoking and pancreatic calcification
Talamini G, Bassi C, Falconi M, Sartori N, Vaona B, Bovo P, Benini L, Cavallini G, Pederzoli P, Vantini I: Smoking cessation at the clinical onset of chronic pancreatitis and risk of pancreatic calcification.
Pancreas 2007; 35: 320-326.
Giving-up smoking within 5years since onset of CP reduces the risk of developing pancreatic
calcifications
Talamini G et al Pancreas. 2007 ;35:320-6.
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Pancreatic acinar cell damage in response to cigarette smoke components : sensitization to acinar cell injury, that can be
worsened by alcohol consumption
Alexander M et al Pancreatology; 2011: 11: 469-74
Cytoplasmic swelling
Trypsinogenbut not PSTI
similarto
experimentalacute
pancreatitis
oxidativestress andlipidperossidation
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Chronic Pancreatitis (“concepts”) -2
Chronic Pancreatitis (“concepts”) -2
a single and distinct entity
alcohol and smoke interact as risk factors
increased risk of pancreatic cancer
a single clinical pattern, though evolving in time
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Epidemiological and clinical features of chronic pancreatitis: the identikit
• Males (80%)• 45 year old at the clinical onset• Alcohol abusers (40-60%)• Smokers in (> 80%)• Pancreatic calcification (20% at onset)• Dilation/changes of pancreatic duct system• Painful relapses• Progressive pancreatic failure (exocrine and
endocrine)
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Chronic pancreatisprinciples of therapy-2
• Prevention of relapses– Alcohol withdrawal in an early stage
• Reduction in the risk of pancreatic calcifications and of the progression of the disease– Smoking withdrawal
• Reduction in the risk of pancreatic cancer (?) – Smoking withdrawal
• Treatment of relapses– Treatment of acute flares (starvation, IV fluids, analgesic drugs)
• Treatment of disabling and severe pain and/or of complications– Surgery (drainage or resection) (not “untimed”) associated with
alcohol withdrawal• Treatment of exocrine failure
– Enzyme-containing pancreatic supplements (enteric-coated)
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Pancreatologia triumphans
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a “new” pancreatitis ?
men heavy alcohol drinkers heavy smokers calcification (90%) dilation of the pancreatic duct (80%) aggressive painful pancreatitis, often
disabling (> 50%) vomiting, jaundice
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Cystic Type (75%) Solid Type (25%)
- pathology: cystic and solid types -
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cyst
cyst
Thickened duodenal wall
NormalDuodenal
Wall
EUS findings
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Cystic dystrophy of the duodenal wallThe “groove” area
BD
W
C
C
P
D = duodenum P = papilla of Vater BD = common bile duct W = Wirsung’s ductC = cyst
D
Groove Groove
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CYSTIC DYSTROPHY OF DUODENAL WALL
A bud of dorsal pancreas, associated to the Santorini's duct, entrapped within the duodenal wall
during organogenesis
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Paraduodenal pancreatitis(cystic or solid duodenal dystrophy)
almost all men
almost all heavy alcohol abusers almost all smokers calcification (90%)
disabling painful relapses vomiting, jaundice (at onset)
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Age of onset
M/F Heavy drinkers >80gr/day
Smokers Calcific. Pain Localcomplications
Survival
45-50 3:1 ++ ++ ++ ++ ++ affected
< 20 2:1 - - ++ + + unaffected
40-45 9:1 +++ +++ ++ +++ ++ affected
45-50 2:1 +/- +/- + + + unaffected
50-60 n.d. +/- +/- ++ - +/- unaffected
45-50 2:1 - +/- - +/- +/- unaffected
Main clinical features in different types ofchronic pancreatitis
Alcoholic
Hereditary
Paraduod.
Obstructive
Painless
AIP
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Alcoholic pancreatitis and paraduodenal pancreatitis (PDP)
• PDP pancreatitis shares the same risk factors and similar epidemiological and clinical pattern of alcoholic pancreatitis
• Morphologically is a distinc form of CP• PDP clinically behaves a severe clinical form of
alcoholic pancreatitis
• Though alcohol withdrawal can induce some clinical improvement, more than 50% of the patients are eligible for surgery because of invalidating pain and/or duodenal obstruction
• It is probable that old series of patients formerly classified as alcoholic pancreatitis were in fact PDP
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GrooveZone
Dilation of Wirsung
Head calcifications
D
D = duodenal lumenW=Wirsung’s duct
cysts of the duodenal wall and chronic pancreatitis
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Chronic pancreatitisClassification of Marseille-Rome 1990
• Alcoholic pancreatitis • Obstructive pancreatitis• Hereditary and familial pancreatitis• Idiopathic pancreatitis
– juvenile– senile (may be painless)
• Inflammatory pancreatitis
Sarles H, Scand J Gastroenterol, 1989; 24: 641-2
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Obstruction and chronic pancreatitis
• Several experimental data on different animal models show that chronic pancreatitis cannot develop, irrespective of the type of the experimental damage, without an obstruction of the duct system
• Periductal inflammation can lead, together with stellate cells activation, to periductal fibrosis that can induce changes in the pancreatic duct system
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Kloeppel G. et al. Pancreas, 1993; 8: 659-670
Necrosis-fibrosis mechanism in chronic pancreatitis
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Following an acute pancreatitis
Acute pancreatitis 8 months before
an acute attack ofpancreatitis 6 months before
Chronic pancreatitis can be theconsequence of a necrosis-fibrosis change, leading to
obstruction of pancreatic ductsystem, and then to inflammatory
and fibrotic changes.Acute necrotizing
pancreatitis can lead tochronic pancreatitis
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Lankish PG et al., Am J Gastroenterol, 2009; 104: 2796-2805
(19/88=22%)
Acute pancreatitis: frequency of chronicization
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32%
10%
Lankish PG et al. Am J Gastroenterol, 2009; 104: 2796-2805
Acute pancreatitis: frequency of relapsesfollowing the first episode
(alcoholic vs. non-alcoholic pancreatitis)
40%
15%
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“obstructive” pancreatitis
Factors (different fromslow-growing tumors) hampering
the pancreatic outflow cantrigger a process leading to
obstructive pancreatitis
A “dysfunction” at the Oddi’s sphincter (SOD)can lead to chronic pancreatitis obstructive
Oddi’s sphincter inflammation with altered outflowcan “trigger” chronic pancreatitis
An obstacle to the pancreatic outflow can be associated withrelapsing pancreatitis without evidence of ductal changes
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calcificazionecalcificazioneostruenteostruente
calcificazionecalcificazioneostruenteostruente
dilatazione duttaledilatazione duttaledilatazione duttaledilatazione duttale
Dilatazione duttale e singola calcificazioneostruente
Ricorrenzedolorose
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DLD 1999; 41. 311-17
Obstruction is the most frequentassociated factor in women (46%)
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Age of onset
M/F Heavy drinkers
Smokers Calcific. Pain Localcomplications
Survival
45-50 3:1 ++ ++ ++ ++ ++ affected
< 20 2:1 - - ++ + + unaffected
40-45 9:1 +++ +++ ++ +++ ++ affected
45-50 2:1 +/- +/- + + + unaffected
50-60 n.d. +/- +/- ++ - +/- unaffected
45-50 2:1 - +/- - +/- +/- unaffected
Main clinical features in different types ofchronic pancreatitis
Alcoholic
Hereditary
Paraduod.
Obstructive
Painless
AIP
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Pain in chronic pancreatitis
PATHOPHYSIOLOGY OF PAIN IN
“OBSTRUCTIVE PANCREATITIS”
Increased intraductal-parenchymal
pressure caused by decreased drainage of
pancreatic juice into the duodenum•
Clinical pictures Type 1pain recurrent with lasting
pain-free intervalsType 2 pain : frequent, persisting,
disabling pain
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The rationale of drainage surgery is a decompression within theductal system and reduction in pain in a substantiaòproprtion of patients
Uncomplicate chronic pancreatitis- Indication for surgery -
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ERCP following sphincterotomy,ESW and fragment extraction
Large stone in the duct
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Surgery (pancreatojejunostomy) vs. endoscopy (sphincterotomy) in chronic pancreatitis
NEJM 2007; 356: 676-84
Djuna L Cahen et al
Djuna L Cahen et al
but in 6/7 evaluable patientssubmitted to rescue surgery,
it was uneffective
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Who are the main clinical and morphological features of the patients with good results of
drainage surgery and poor after endotherapy ?
• Advanced chronic pancreatitis• Distal obstruction• Calcifications (> 90% of the cases)
• Severe, recurrent pain
• Not too enlarged head of the pancreas
In advanced chronic pancreatitiswith symptoms and distal
obstruction, drainage surgeryis superior to endoscopic
therapy
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Who are the patients with chronic pancreatitis in which the endoscopic therapy seems to be more effective ?
• single distal obstruction • single distal stone• short duration of the disease• more aggressive, repeated stenting strategy
– Pancreatic sphincterotomy– Stricture dilation– Repeated stenting
– Stone removal Farnbacher et al Gastrointest Endosc 2002; 56: 501-59Costamagna G et al Endoscopy 2006; 38: 254-59Dumonceau JM et al ESGE guidelines- Endoscopy 2012, 44. 784-96
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For treating uncomplicated chronic pancreatitis(aimed at relieving pain) ESGE recommends ESW/ERCP at the first-time interval option.The clinical response should be evaluated
at 6-8 weeks. If it is unsatisfactory the case
should be discussed in a multidisciplinaryteam.
Surgical options should be considered,in particular in patients with a predicted poor
outcome after endosopic therapy (RG B)
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Candidate parameters for selecting patients for appropriate treatment and timing
(a multidimensional approach)
• Aethiology, natural history• Duration of the disease (stage)• Clinical features (pain type, complications) and QOL scores• Morphological assessment
– Main pancreatic duct and secondary branches changes– Distal stenosis (main duct, Santorini)– “Dominant” duct stricture– Single or multiple obstructions-strictures– Upstream dilation (+/-)– Stone (single, distal, multiple)
– Ductal scars (necrosi/fibrosis)– Complications
• Technical aspects and aggressive strategy
However, paincan persist also following
effective treatment of stricture,or it can subside also
if the stricture is not disappeared
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Pain treatment: appropriate patient selection
• A proper patient selection is of vital importance in the indication and in the outcome of treatment, in particular case of endoscopic and surgical therapy
• A more aggressive endoscopic strategy probably will
give better results in properly selected patients
• Surgery should be timed and tailored to the clinical features and risk assessment, morphological pictures, and the best as possibile assessment about the presumptive origin of pain. Combination surgery should be considered
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“Small duct”pancreatitis
Chronic pancreatitis: ERCP
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Langenbecjs Arch Surg 2003; 388: 132-9
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Frequency of painful relapses/year in 199 patients with chronic pancreatitis
(non-operated upon) followed up to 20 years
0
1
2
3
4
5
N. p
ain
ful
rela
pse
s
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
25°
years since clinical onset
25°50°75°
percentiles
Calcification and dysfunction in time
Scuro LA et al , Am J Gastroenterol 1983; 78: 495-501. Ammann RW et al. Gastroenterology 1984, 86: 820-8..
early advanced lateEndotherapy
Medical treatment
Endoscopy-SurgeryMedical treatment
Medicaltreatment
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25 years ago…..
• Amman RW et al Gastroenterology 1986– in chronic pancreatiis early surgery is
associated with a poor cinical outcome– the natural history of CP indicates that in
almost 2/3 of the patients pain spontaneously subsides in long-term evolution
– Commentary (Gastronterology 1986)• “The patient patient and the impatient
surgeon”
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Chronic pancreatitisClassification of Marseille-Rome 1990
• Alcoholic pancreatitis • Hereditary and familial pancreatitis• Idiopathic pancreatitis
– juvenile–senile (may be painless)
• Obstructive pancreatitis• Inflammatory pancreatitis
Sarles H, Scand J Gastroenterol, 1989; 24: 641-2
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Cationic Trypsinogen – PRSS14,5
R122H, N29I, A16V, R116C, E79K, R112C, D22G, K23R
Pancreatic Secretory Trypsin Inhibitor (PSTI) – SPINK16,7
N34S, P55S, M1T, L14P, -53C>T, IVS3+2T>C
CFTR gene1-3 F508 (nel 50-70% dei casi), altre mutazioni
1 N Engl J Med, 1998: 339; 645-22 N Engl J Med, 1998; 339: 653-8 3 Eur J Hum Genet, 2003; 11: 543-64 Gut, 2002;50:271-2.5 Gut, 2002; 50:687-926 J Med Genet, 2000; 37:67-97 Gut, 2002; 50:675-81
Gene-mutation associated pancreatitis
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Hereditary-Familial
one or more relatives of the same familial kindred affected, at different or at the same generation,
No other risk factor of pancreatitis (complete work-up)
Juvenile onset < 10 years (< 20 years)
Recurrent episodes of mild pancreatitis
Progression of pancreatic calcifications
Slow progression toward pancreatic failure
Survival rate comparable to that of the general population
High risk of pancreatic cancer: the first cause of death in hereditary pancreatitis (30 years since the onset)
Gene-mutation associated pancreatitisMain features of Hereditary Pancreatitis
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Cumulative risk of cancer in patients with Hereditary Pancreatitis
(smokers vs. non smokers)
smokers
non-smokers
Lowenfels AB et al JAMA 2001; 286:169-70
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pancreatite associata a mutazione del CFTR
Pancreatite associata amutazione del gene SPINK 1
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SPINK1
SPINK1SPINK1
Chronic pancreatitis associated with gene mutation
Bull-eye signBull-eye sign
Graziani R. et al. Abdominal Radiology, 2010; 115: 885-888
CFTR
Frulloni L, et al. Pancreas. 2008:371-
6.
non smokers
smokers
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Chronic pancreatitisClassification of Marseille-Rome 1990
• Alcoholic pancreatitis • Hereditary and familial pancreatitis• Idiopathic pancreatitis
– juvenile–senile (may be painless)
• Obstructive pancreatitis• Inflammatory pancreatitis
Sarles H, Scand J Gastroenterol, 1989; 24: 641-2
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CFTR Normale86,7%
CFTR Normale95,7%
CFTR 1 Mutazione
13,3%
CFTR 1 Mutazione
5,3%
Pancreatite Cronica Idiopatica60 pazienti
Controlli600 pazientiRR = 2,52RR = 2,52
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SPINK1 Normale77%
SPINK1 Normale99,65%
SPINK1 Mutato
23% SPINK1 1 Mutazione
0,35%
Pancreatite Cronica Giovanile
96 pazienti
Controlli279 pazienti
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Chronic pancreatitis and gene mutations
• Mutation in PRSS1 is present in ¼ of patients with juvenile-type chronic pancreatitis
• Up to 30% of idiopathic pancreatitis have a mutation in the CFTR allele vs. 3-5% in the general population, though a single mutation alone cannot trigger pancreatitis
• 20-30% of Hereditary Pancreatitis do not have PRSS1 mutation
• Mutation in PRSS1 is found in 20% of subjects who do not have any sign of pancreatitis (carriers)
Rebours V et al DLD 2012; 44: 8-15
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SI (87%)
Età all’esordio28 ± 14 anni
NO (13%)Età all’esordio
44 ± 18 aa
Esordio clinico = Pancreatite acuta
p = 0.005
Clinica all’esordio: Dolore aspecifico (6) Dispepsia (2) Ittero (1) Altra patologia (2)
Clinica all’esordio: Dolore aspecifico (6) Dispepsia (2) Ittero (1) Altra patologia (2)
CFTR-S = 30 ± 14 anni
CFTR-D = 20 ± 12 anni
SPINK1 = 24 ± 14 anni
p = 0.027
CFTR-S = 30 ± 14 anni
CFTR-D = 20 ± 12 anni
SPINK1 = 24 ± 14 anni
p = 0.027 10 di 11 pazienti
= PC all’esordio
10 di 11 pazienti
= PC all’esordio
Pancreatite associata ad alterazioni geniche
STORIA NATURALE DELLA PANCREATITE ASSOCIATA A MUTAZIONI GENICHE
Giulia De MarchiTesi di Laurea, 2011
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Long time ago…. Long time ago….
Ludovico Antonio Scuro1924 – 1989
“Why should the pancreas be the only
human organ not involved by an autoimmune
process?”
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Autoimmune pancreatitis• Described by H. Sarles in 1961 yet, • More than 900 papers published (most since
’90s)• Accounts for
– 4-6 % of all the patients with chronic pancreatitis referring to a terziary centre and for
– about 20-40 % of idiopathic chronic pancreatitis
• Its aethiology is still unknown antibodies: CA II, Lactoferrin, SPTI antibodies
(against host antigens); genetics: association with haplotype DRB1 0405 DQB1 0401; Polymorfism of Cytotoxic Lymphocyte-associated antigen-4 49A
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No drinker and no smoker patients
Frequent association with other autoimmune diseases
Asymptomatic jaundice at onset (particularly in focal type)
“Atypical” pancreatitis at onset (particularly in diffuse type)
Dramatic, peculiar response to steroids
Autoimmune Pancreatitis Main Clinical Features
Autoimmune Pancreatitis Main Clinical Features
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AIP Type 2 (15-30%)
IdiopathicDuct-Centric Pancreatitis
(IDCP)
IgG4– (ICH) – GEL+
Inflammatory Bowel Disease
Relapses NOSteroids
AIP Type 1 (70-85%)
Lympho-PlasmacyticSclerosing
Pancreatitis (LPSP)
IgG4+ (ICH) – GEL– IgG4 systemic disease
Relapses YESSteroids
Def
init
ion
Pa
tho
log
yC
linic
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From Zamboni G et al
Autoimmune Pancreatitis is a chronic pancreatitis
LP . periductal inflammationIgG4 positive plasmacells
Duct desctruction and narrowingStoriform fibrosis
Type 1
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Granulocytic Epithelial Lesion – GEL –Zamboni G et at, Vierchow Arch, 2004; 445:
552-563
Type 2
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Sausage-like Irregular narrowing
swelling Capsule-like rim
Diffuse AIP
mild pancreatitis
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Narrowed and irregular duct in autoimmune chronic pancreatitis
Associated witha clinical picture
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Autoimmune pancreatitisFocal and mass forming
Early arterial phase
University of Verona: Dpt. of Radiology
jaundice
Focal
Mass forming
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Mass forming AIP
The problem is not to confirmhistologically AIP, but to exclude cancer
by US or EUS-guided biopsies
University of Verona: Dpt. of Radiology
mandatory
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Mass-forming AIP: response to steroid therapy
15 days after initiation of steroidsCT at admission
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01-2009
02-2009
Dopo terapiasteroidea
Repertodi base
Pancreatite acuta lieve seguitada precoce ricorrenza lieve e persistenza di moderataelevazione degli enzimi
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Shimosegawa T et al, Pancreas, 2011: 40: 352-358
ICDC Autoimmune pancreatitis type 1: cardinal diagnostic criteria and levels of reliability
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Shimosegawa T et al, Pancreas, 2011: 40: 352-358
ICDC Autoimmune pancreatitis type 2: cardinal diagnostic criteria and levels of reliability
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92 Pazienti
Tipi di pancreatite autoimmunedopo completo work-up (ICDC)
Tsukasa Ikeura et al 2013, submitted
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AIP type 1
AIP NOS
AIP type 2
Three types of AIP: overlaps amongdiagnostic features
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Gut Online First, published on December 11, 2012 as 10.1136/gutjnl-2012-30361
Phil A Hart et al: Long-term outcomes of autoimmune pancreatitis:a multicentre, international analysis
23 institutions10 countries
1064 patients
ICDCcriteria
Type 1978
Type 286
Relapse rate
Type 131%
Type 29%
(> in IgG4 –related sclerosing cholangitis)
* retreatment with steroids was equally effective
*
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Phil A Hart et al: Long-term outcomes of autoimmune pancreatitis:a multicentre, international analysis
Gut Online First, published on December 11, 2012 as 10.1136/gutjnl-2012-30361
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alcoholic
obstructive
AIP
paraduodenal
painless
genetic
Chronic pancreatitis
idiopatic
Eterogeneityand ovelap
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Classificazioni della pancreatite cronica• Etiologia, clinica e morfologia (nosografica)
– Marsiglia 1963– Cambridge, 1983 – Marsiglia 1984– Marsiglia-Roma 1988
• Per stadio di malattia (early, late, advanced)– Chari ST, Singer MV Scand J Gastroenterol 1994; 29: 949-60
• Per fattori di rischio– TIGAR-O Etemad B, Whitcomb DC. Gastroenterology. 2001
• Per approccio operativo-terapeutico– Cavallini G, 2000 (“classificazione di Verona”)
• Per probabilità di diagnosi (clinica, imaging, funzione, istologia)– Zurich 1997– JAP 1997
• Per combinazione di clinica, probabilità di diagnosi, stadiazione, severità + score– M-ANNEHEIM (Schneider A, Lohr JM, Singer MV. J Clin
Gastroenterol 2007; 42: 101-119)
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Classification by
• EZIOLOGICORisk factors
Probabaility of the diagnosis
Clinical features and stage
Severity
M-ANNHEIM classification of chronic pancreatits
M-ANNHEIM classification of chronic pancreatits
Schneider A, Löhr JM, Singer MV.The M-ANNHEIM classification of chronic pancreatitis: introduction of a unifying classification system based on a review of previous classifications of the disease.J Gastroenterol. 2007; 42:101-19.
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Chronic pancreatitis
- classifications and operative needs -
• Nosographic classification • Diagnostic matching with illness scripts,
exemplars,categories
• Operative classification• Operative diagnosis targeted to decisions
• Complexity/undefined aspets/variation in time• Diagnosis (disease) reliability : defined, probable,
possible, undefined
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EBM
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Evidence Level (EL) of the literature information/source of the
statements
0
5
1 0
1 5
2 0
2 5
3 0
3 5
4 0
% o f th e s ta te m e n ts
1 2 3 4 5
According to Oxford Centre for Evidence Based Medicine
EBM
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Recommendation strenght of the statements,and agreement (consensus) rate
0
5
1 0
1 5
2 0
2 5
3 0
3 5
4 0
% o f th e s ta te m e n ts
A B C D
According to Oxford Centre for Evidence Based Medicine
83% of the statements: agreement rate*> 80% * Agreement rate: “strongly agree or with minor reserve”
EBM
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In principio…
Sarles H, Sarles JC, Camatte R, Muratore R, Gaini M, Guien C, Pastor J, Le Roy
FObservations on 205 confirmed cases of acute pancreatitis, recurring pancreatitis, and chronic pancreatitis.
Gut 1965; 6: 545-59.
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1642
George Wirsung………Wirsung duct
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Padova: giardino dei semplici(botanic garden )
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