lesioni solide pancreatiche: la diagnosi differenziale - gastrolearning®
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Gastrolearning II modulo/3a lezione Lesioni solide pancreatiche: la diagnosi differenziale Prof. L. Frulloni - Università di VeronaTRANSCRIPT
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Lesioni solide pancreatiche:la diagnosi differenziale
Luca FrulloniCattedra di Gastroenterologia
Università di Verona
Gastrolearning 2014
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Infiammazione
Neoplasia
Chirurgia?
Lesioni Solide Pancreatiche“Il” Problema Clinico
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Lesioni Solide PancreaticheProblematiche per la Decisione Clinica
Frequenza di lesioni benigne
Performance dei test diagnostici
Costi
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Lesioni Solide PancreaticheDiagnosi Anatomo-Patologica su Pezzi Operatori
adenok panc56.6%
cholangiok7.0% adenok
papilla15.3%
en-docrino10,5%
metastasi1,6%
AIP2.9%
PP3.5%
CP1,6%Milza
Accessoria0,8%
CP = pancreatite cronicaPP = pancreatite paraduodenaleAIP = pancreatite autoimmune
373 pazientiResecati per sospetto di neoplasia
Vitali F, 2013; submittedMeinz (Germany) – Verona (Italy)
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Lesioni Solide PancreaticheFrequenza e Probabilità Diagnostica
Massa Pancreatica
Metastasi Neoplasia localmente avanzata
Resecabile
80% 20%
Infiammazione10%
Neoplasia90%
N. 100
Diagnosi di naturaChemioterapia
PalliazioneN. 80
ChirurgiaN.18
AltroN. 2
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Lesioni Solide PancreaticheFrequenza e Probabilità Diagnostica
Massa Pancreatica
Metastasi Neoplasia localmente avanzata
Resecabile
80% 20%
Infiammazione10%
Neoplasia90%
ChirurgiaN.90
AltroN. 10
N.100
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Lesioni Solide PancreaticheProbabilità di Natura Infiammatoria
Probabilità di Neoplasiapre-test = 90%
Test Diagnostico
Probabilità post-test o
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J Gastrointest Surg, 2013; 17: 1218–1223
101 pazienti
94 pazientieseguono almeno 1 esame
dopo index CT
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J Gastrointest Surg, 2013; 17: 1218–1223
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J Gastrointest Surg, 2013; 17: 1218–1223
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J Gastrointest Surg, 2013; 17: 1218–1223
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Biologia della Lesione
Benigna Vs Maligna
Timing della Chirurgia?
Lesioni Solide PancreaticheUn Secondo Problema Clinico
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Le Lesioni Solide PancreaticheDefinizione
Zona di tessuto pancreatico che all’imaging assume m.d.c. in maniera differente dal parenchima normale
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Le Lesioni Cistiche PancreaticheDefinizione
Zona di tessuto pancreatico che all’imaging NON assume m.d.c.
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arteriosa
pre-contrastografica
venosa
tardiva
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basale arteriosa venosa tardiva0
2
4
6
8
10
12
Fase
En
han
cem
ent
Imaging (TC, RM, CE-US, CE-EUS)Enhancement dopo m.d.c.
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Le Lesioni Solide PancreaticheTipologia all’Imaging con m.d.c.
IpovascolarizzateIpervascolarizzate
TCfase arteriosa
RM fase arteriosa
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Lesioni Solide Pancreatiche“Regole” all’Imaging con m.d.c.
Enhancement in fase arteriosa
Ipervascolarizzate
Ipoinitensoin fase arteriosa
Ipovascolarizzate
NO Enhancementin fase portale/tardiva
Ipointensoin fase arteriosa
Infiammazione
SI Enhancement in fase portale/tardiva
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basale arteriosa venosa tardiva0
5
10
15
20
25normaleipovascolarizzateipervascolarizzateinfiammazione
Fase
En
han
cem
ent
Imaging (TC, RM, CE-US, CE-EUS)Enhancement dopo m.d.c.
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La Pratica ClinicaNon è Sempre “Bianco o Nero”
Iper-vascolarizzazione
Ipo-vascolarizzazione
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Le Lesioni Solide PancreaticheRapporti con il Dotto Pancreatico Principale
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Le Lesioni Solide PancreaticheUn Primo Nodo Decisionale
Index Imaging
IpovascolarizzataIpervascolarizzata
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basale arteriosa venosa tardiva0
5
10
15
20
25
normaleipervascolarizzate
Fase
En
han
cem
ent
Lesioni Solide IpervascolarizzateEnhancement dopo m.d.c.
Prevalenza5-10%
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Lesioni Solide IpervascolarizzatePossibilità Diagnostiche
NeoplasiePancreatiche/Peripancreatiche
Lesioni non neoplastiche
Lesioni Vascolari
Endocrina Milza Accessoria(intra-/peri-pancreatica)
Aneurisma
Adenoma sieroso solido Amartoma pancreatico Pseudo-aneurisma
Neoplasia acinare pancreatica Malformazioni A-V
Pancreatoblastoma
Metastasi (carcinoma renale)
Tumore fibroso solitario
Paraglanglioma
Shwannoma
Gastrointestinal stromal tumor (GIST)
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Lesioni Solide IpervascolarizzatePossibilità Diagnostiche
NeoplasiePancreatiche/Peripancreatiche
Lesioni non neoplastiche
Lesioni Vascolari
Endocrina (90%) Milza Accessoria(intra-/peri-pancreatica)
Aneurisma
Adenoma sieroso solido Amartoma pancreatico Pseudo-aneurisma
Neoplasia acinare pancreatica Malformazioni A-V
Pancreatoblastoma
Metastasi (carcinoma renale)
Tumore fibroso solitario
Paraglanglioma
Shwannoma
Gastrointestinal stromal tumor (GIST)
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Raman SP et al, AJR, 2012; 199: 309–318
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Lesioni Solide IpervascolarizzateNodo Decisionale
TC/RM
Comportamento dopo m.d.c.
sovrapponibilealla milza
sovrapponibileai vasi arteriosi
autonomo
milza accessoria malformazioni vascolaripseudoaneurisma
aneurisma
neoplasia
Biopsia NO NO SI
Modificato da Bhosale PR et al, Abdom Imaging, 2013; 38: 802–817
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Lesioni Solide IpervascolarizzateIter Diagnostico nella Pratica Clinica
Lesione Ipervascolarizzata
BiopsiaTumore Endocrino
NO SI
Metastasi da carcinoma renale?
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basale arteriosa venosa tardiva0
2
4
6
8
10
12 normale
ipovascolarizzate
infiammazione
Fase
En
han
cem
ent
Prevalenza90-95%
Lesioni Solide IpovascolarizzateEnhancement dopo m.d.c.
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Lesioni Solide Pancreatiche ResecateProbabilità Diagnostiche
Chirurghi Tedeschi“E’ così alta la probabilità neoplastica che è opportuno resecare tutti”
Frulloni L et al, W J Gastroenterol, 2011; 17(16): 2076-2079
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Neo-plasia91,2%
AIP2.9%
PP3.5%
PC1,6%
Milzaaccessoria
0,8%
PC = pancreatite cronicaPP = pancreatite paraduodenaleAIP = pancreatite autoimmune
373 pazientiResecati per sospetto di neoplasia
Vitali F, 2013; Pancreas in pressMeinz (Germany) – Verona (Italy)
Lesioni Solide Pancreatiche ResecateFrequenza e Tipologia
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Lesioni Solide Pancreatiche InfiammatoriePancreatite Autoimmune
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Granulocytic Epithelial Lesion – GEL –Zamboni G et at, Vierchow Arch, 2004; 445: 552-563
Anatomia Patologica, Verona
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Anatomia Patologica, Verona
Pancreatite AutoimmunePlamacellule IgG4+ all’Immunoistochimica
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AIP Type 2
IdiopathicDuct-Centric Pancreatitis
(IDCP)
IgG4–– GEL+
Ulcerative Colitis
Relapses NOSteroids
AIP Type 1
Lympho-PlasmacyticSclerosing
Pancreatitis (LPSP)
IgG4+ – GEL–
IgG4 – systemic disease
Relapses YESSteroids
Def
init
ion
Pat
ho
log
yC
linic
Chari ST et al, Pancreatology, 2010; 10: 664-672
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Acronimo = ICDC
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Shimosegawa T et al, Pancreas, 2011: 40: 352-358
AIP type 1
AIP type 2
AIPNot Otherwise Specified
(NOS)
Pancreatite AutoimmuneAlgoritmo Classificativo con ICDC
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Pancreatite AutoimmuneRisposta a Terapia Steroidea
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Pancreatite AutoimmuneImaging (TC Addome o RM Addome)
FocaleN.
10855%
Dif-fusa
N. 8845%196 pazienti
Verona, 22.11.2013
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Pancreatite AutoimmuneReperti Clinici
N. 196
Età esordio 48 ± 16
Maschi 65%
Bevitori 23%
g of alcol /die 23 ± 24
Fumatori 24%
N. sigarette/day 16 ± 6
Dolore continuo 9%
Pancreatite 21%
Ittero 53%
Dimagrimento 72%
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Pancreatite Autoimmune“Il” Nodo Decisionale
Diagnosi
Evitare di trattare un“tumore” con steroidi
Evitare la chirurgiaper una malattia “inflammatoria”
che risponde agli steroidi
La pancreatite autoimmunesembra un tumore
Russell Crowe Ben Mckenzie
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Neoplasia Pancreatite autoimmune
Età >60 40-60
Fumo Si No
Familiarità Neoplasia panc –
Malattie associate – Autoimmuni
Dolore Si No
Ittero Si Si
Dimagrimento Si Si
Pancreatite No Rara
Astenia, anoressia Si No
Diabete recente insorgenza Si Si
Massa PancreaticaLa Clinica
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Pancreatite Autoimmune Tipo 1International Consensus Diagnostic Criteria (ICDC)
Criterion Level 1 Level 2
P (parenchimal imaging)
Diffuse enlargementDelayed enhancement
Segmental/focal enlargementDelayed enhancement
D (ductal imaging)
Single long stenosis of MPDMultiple stenosis of MPD
Segmental/focal narrowing without upstream dilation
S (serology)
sIgG4 > 2x UNL
sIgG4 1-2x UNL
OOI(other organ involvement)
Intrahepatic bile duct stricture(s)Retroperitoneal fibrosis
Salivary/lacrymal glandsKidney
H (histology)
3 criteria 2 criteria
Rt (response to steroids)
Resolution/marked improvement of the pancreatic/extrapancreatic involvement
Shimosegawa T et al, Pancreas, 2011: 40: 352-358
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Lesioni Solide Pancreatiche IpovascolarizzateL’Imaging
1. US, CE-US
2. TC Addome
3. RM Addome, RMCP+secretina
4. EUS, CE-EUS, EUS-elastosonografia
5. PET
ICDC
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Pancreatite AutoimmuneTC Addome
ArteriosaMassa ipodensa alla testa del pancreas
VenosaPresa di mdc, non più riconoscibile la lesione
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Lesioni Solide Pancreatiche IpovascolarizzateL’Imaging
1. US, CE-US
2. TC Addome
3. RM Addome, RMCP+secretina
4. EUS, CE-EUS, EUS-elastosonografia
5. PET
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AdenocarcinomaInfiammatoria
D’Onofrio M et al, W J Surg Pathol, 2006; 12: 4181-4184
Lesioni Solide Pancreatiche IpovascolarizzateCE-US
Sensitivity=88%Specificity=97%
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Lesioni Solide Pancreatiche IpovascolarizzateCE-EUS
Sensitivity=93%Specificity=93%
Gong T-t et al, Gastrointestinal End, 2012; 76: 301-9
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Pancreatite Autoimmune Tipo 1International Consensus Diagnostic Criteria (ICDC)
Criterion Level 1 Level 2
P (parenchimal imaging)
Diffuse enlargementDelayed enhancement
Segmental/focal enlargementDelayed enhancement
D (ductal imaging)
Single long stenosis of MPDMultiple stenosis of MPD
Segmental/focal narrowing without upstream dilation
S (serology)
sIgG4 > 2x UNL
sIgG4 1-2x UNL
OOI(other organ involvement)
Intrahepatic bile duct stricture(s)Retroperitoneal fibrosis
Salivary/lacrymal glandsKidney
H (histology)
3 criteria 2 criteria
Rt (response to steroids)
Resolution/marked improvement of the pancreatic/extrapancreatic involvement
Shimosegawa T et al, Pancreas, 2011: 40: 352-358
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Pancreatite AutoimmuneRMCP con Secretina
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Pancreatite AutoimmuneRMCP con Secretina
BasaleStenosi multiple dotto di Wirsung, nonmarcata dilatazione a monte
Secretina 6 minUlteriore stenosi alla testa
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Pancreatite AutoimmunePET-TC e RMCP con Secretina
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Pancreatite Autoimmune Tipo 1International Consensus Diagnostic Criteria (ICDC)
Criterion Level 1 Level 2
P (parenchimal imaging)
Diffuse enlargementDelayed enhancement
Segmental/focal enlargementDelayed enhancement
D (ductal imaging)
Single long stenosis of MPDMultiple stenosis of MPD
Segmental/focal narrowing without upstream dilation
S (serology)
sIgG4 > 2x UNL
sIgG4 1-2x UNL
OOI(other organ involvement)
Intrahepatic bile duct stricture(s)Retroperitoneal fibrosis
Salivary/lacrymal glandsKidney
H (histology)
3 criteria 2 criteria
Rt (response to steroids)
Resolution/marked improvement of the pancreatic/extrapancreatic involvement
Shimosegawa T et al, Pancreas, 2011: 40: 352-358
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Lesioni Solide Pancreatiche IpovascolarizzateIl Laboratorio
Ca 19-9 +
70%
IgG4 +
60%
Adenocarcinoma Pancreatite Autoimmune
Caveat:
IgG4 +
5-10%
Ca 19-9 +
20-40%
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Pancreatite Autoimmune Tipo 1International Consensus Diagnostic Criteria (ICDC)
Criterion Level 1 Level 2
P (parenchimal imaging)
Diffuse enlargementDelayed enhancement
Segmental/focal enlargementDelayed enhancement
D (ductal imaging)
Single long stenosis of MPDMultiple stenosis of MPD
Segmental/focal narrowing without upstream dilation
S (serology)
sIgG4 > 2x UNL
sIgG4 1-2x UNL
OOI(other organ involvement)
Intrahepatic bile duct stricture(s)Retroperitoneal fibrosis
Salivary/lacrymal glandsKidney
H (histology)
3 criteria 2 criteria
Rt (response to steroids)
Resolution/marked improvement of the pancreatic/extrapancreatic involvement
Shimosegawa T et al, Pancreas, 2011: 40: 352-358
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Zamboni G, Capelli P, Anatomia Patologica, Verona
Pancreatite AutoimmuneDiagnosi su pezzo operatorio
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Diagnosi di Pancreatite AutoimmuneBiopsia
Autore Anno Nazione Tipo N. Sensibilità
Fujii LL 2013 USA TCB 9 56%
Iwashita T 2012 Japan 19G 44 43%
Ishikawa T 2012 Japan 22G 47 37%1
Kanno A 2012 Japan 22G 25 80%2
Imai K 2011 Japan 22G 21 0%
Mizuno N 2009 Japan 22G/TCB 14 36%
Detlefsen S 2009 Europe Core/IO 37/7 50%
Bang S-J 2008 Korea Core/IO 19/3 27%
Zhang L 2007 USA Core 9 77%
Levy MJ 2005 USA TCB 3 66%
Desphande V 2005 USA – 16 0%
Zamboni G 2004 Europe Core/IO 9 22%
All – – – 266 30%
1 Type 1 AIP: 9 paz Level 1 5 paz Level 2 ICDC; Tipo 2 AIP: 3 paz Level 2 ICDC2 Type 1 AIP: 14 paz Level 1, 6 paz Level 2 ICDC; Tipo 2 AIP: 1 paz Level 1 ICDC
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Pancreatite Autoimmune Tipo 1International Consensus Diagnostic Criteria (ICDC)
Criterion Level 1 Level 2
P (parenchimal imaging)
Diffuse enlargementDelayed enhancement
Segmental/focal enlargementDelayed enhancement
D (ductal imaging)
Single long stenosis of MPDMultiple stenosis of MPD
Segmental/focal narrowing without upstream dilation
S (serology)
sIgG4 > 2x UNL
sIgG4 1-2x UNL
OOI(other organ involvement)
Intrahepatic bile duct stricture(s)Retroperitoneal fibrosis
Salivary/lacrymal glandsKidney
H (histology)
3 criteria 2 criteria
Rt (response to steroids)
Resolution/marked improvement of the pancreatic/extrapancreatic involvement
Shimosegawa T et al, Pancreas, 2011: 40: 352-358
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esordio
esordio
3 sett steroidi
3 sett steroidi
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LR = Sensitivity
1-Specificity
IgG4 sensitivity =70% (0.7)specificity = 95% (0.95)
LR per IgG4 =0.7
0.05= 14
--ProbabilitàAIP
Diagnosi di Pancreatite Autoimmune
Nomogramma di Fagan
+ malattia autoimmune
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--
Probabilità neoplasia
Diagnosi di Neoplasia
+ colite ulcerosa
LR = Sensitivity
1-Specificity
CA 19-9 sensitivity =70% (0.7)specificity = 80% (0.8)
LR per Ca 19.9=0.7
0.2= 3.5
In presenza di una massa, valutare fattori possibilmente associati a pancreatite autoimmune:
- età giovane- index imaging suggestiva- malattie autoimmuni associate
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LR = Sensitivity
1-Specificity
FNAC sensitivity = 85% (0.85)specificity = 98% (0.98)
LR per FNAC=0.85
0.02= 45
Hewitt MG et al, Gastrointest Endosc, 2012; 75: 319-31
Diagnosi di NeoplasiaFNA con EUS
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FNAC
YESCancer
NOCancer
ICDC
+
Diagnosis of AIP
Response toSteroids
YES
–
NO
SURGERY
Index Imagingfocal ± mass
suspicion for AIP
Algorithm to Diagnose Focal AIP in Verona
Frulloni L et al, World J Gastroenterol , 2011; 17(16): 2076-2079
Risk for cancer = HIGH
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Zona dellaGroove
Lesioni Solide Pancreatiche InfiammatoriePancreatite Paraduodenale
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Lesioni Solide Pancreatiche InfiammatoriePancreatite Paraduodenale
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Cystic Distrophy of the Duodenal WallEsperienza Francese
Flejou JF et al, Gut, 1993; 34; 343-3471° paper Potet F, Duclert N, Arch Fr Mal App Dig,1970: 59(4): 223-38.
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Groove PancreatitisEsperienza Tedesca
Becker V and Mischke U, Int J Pancreatol, 1991; 10(3/4): 173-182
“The term groove pancreatitis (Rinnenpankreatitis) is employed to
describe a special form of pancreatitis that results in scarring that extends, in particular, into the "groove" between the C-loop of the duodenum and the
head of the pancreas.”
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Macroscopically
• changes centred in the duodenal wall
• thickened and scarred duodenal wall
• cystic changes in the submucosa or the muscularis
Microscopically
• exuberant proliferation of myoid cells surrounding acini (“myoadenomatosis”)
• Brunner’s gland hyperplasia
• chronic inflammation often present
• clusters of eosinophils
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Pancreatite ParaduodenaleTipo Solido e Cistico
Casetti L et al, W J Surg, 2009; 33(12): 2664-9
cistico71%
solido29%
Verona, 2013
118 pazienti
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C=ciste freccia nera = parete duodenale normale
freccia bianca=parete duodenale ispessita
Pancreatite ParaduodenaleReperti EUS
Fuini A, Verona
C
C
Tipo Cistico Tipo Solido (o microcistico <1cm)
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PD
C
D
P
Pancreatite ParaduodenaleReperti TC
Tipo Cistico – Forma Pura
Radiologia, Verona
P=pancreas freccia bianca= arteria gastro-duodenal
D=duodeno
C =ciste
PD=parete duodenale
C
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GrooveZone
Dilatazione del W
Calcificazioni
D
Pancreatite ParaduodenaleReperti TC
Tipo Cistico – Coinvolgimento del Pancreas Proprio
Radiologia, Verona
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Anatomia Patologica e Radiologia, Verona
Pancreatite ParaduodenaleTipo Solido in DD con Neoplasia Pancreatica
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Pancreatite ParaduodenaleReperti Clinici
Reference Anno Rivista Serie PazN.
Maschi%
Etàesordio
Fumatori%
Bevitori%
Flejou et al 1993 Gut P 10 100 41 – 20
Procacci et al 1997 Radiology R 10 100 41 80 90
Vullierme et al 2000 J Comp Assist Tomogr S 20 90 44 – –
Jouannaud et al 2006 Gastroenterol Clin Biol M 23 87 45 – 100
Pessaux et al 2006 Gastroenterol Clin Biol S 11 92 41 – 75
Rebours et al 2007 Am J Gastr M-S 105 86 46 – 86
Tison et al 2007 Pancreas P 9 89 46 – 100
Rahman et al 2007 HPB S 11 91 – 91 100
Casetti et al 2009 World J Surg S 58 93 45 97 97
Tipo di Casistica:P=patologica; R=radiologica; M=medica; C=chirurgica
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N. 118
Età esordio 41.4 ± 10.3
Maschi 96%
Bevitori 96%
g of alcol /die 129.3 ± 65.4
Fumatori 97%
N. sigarette/day 29.2 ± 13.6
Dolore continuo 38%
Pancreatite 65%
Ittero 12%
Vomito 38%
Pancreatite ParaduodenaleReperti Clinici
Verona, Italy, 2013
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Author Journal Year N. Surgery Efficacy Follow-upmonths
Relapse
Levenick JM Dig Dis Sci 2012 5 5 100% – –
Kim DJ J Kor Surg Soc 2011 6 6 100% 32 0%
Casetti L World J Surg 2009 58 58 100% 96 24%
Rahaman SH HPB 2007 11 11 100% 52 0%
Tison C Pancreas 2007 9 9 100% 86 0%
Rebours V Am J Gastr 2007 105 17 100% – –
Jounnaud V Gastr Clin Biol 2006 23 11 100% 47 0%
Pessaux P Gastr Clin Biol 2006 11 11 100% 64 10%
Pancreatite ParaduodenaleResultati della Duodeno-Cefalo-Pancreasectomia
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Lesioni Solide Pancreatiche IpovascolarizzateIndicazione
Pancreatite Paraduodenale
Neoplasia
Chirurgia Resettiva
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Biologia della Lesione
Benigna Vs Maligna
Timing della Chirurgia?
Lesioni Solide PancreaticheUn Secondo Problema Clinico
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Lesioni Solide Pancreatiche IpovascolarizzateTerapia
Pancreatite Paraduodenale
Neoplasia
Chirurgia Resettiva
Programmata Entro 1 Mese
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Pancreatite ParaduodenaleMotivi per una Chirurgia Programmata
1. Pazienti spesso sottopeso
2. Presenza di infiammazione peripancreatica con alto rischio di complicazioni
3. La chirurgia per lesioni benigne può essere dilazionata nel tempo
4. Tentativo di evitare la chirurgia con approccio conservativo (astensione dall’alcol, octreotide)
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Lesioni Solide PancreaticheTake Home Messages
Massa pancreatica
Metastasi/localmente avanzataSI
NODg istologica
Palliazione/chemioterapia
IPO-vascolarizzata
Milza accessoriaLesione vascolare
Enhancement autonomo
IPER-vascolarizzata
BIOPSIA
Clinica/imaging/laboratorio
TIPICI
Clinica/imaging/laboratorio
ATIPICI
CHIRURGIA
Conferma ipotesi alternativa
SINO
Terapia appropriata