ruolo della ecoendoscopia nelia pancreatite cronica … nella pc e nei tumori... · ruolo della...
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Ruolo della ECOENDOSCOPIAnelIa pancreatite cronica e nelle neoplasie cistiche del pancreas
Ruolo della ECOENDOSCOPIAnelIa pancreatite cronica e nelle neoplasie cistiche del pancreas
Dr. L. CuocoU.O. Gastroenterologia
Ospedale S. Bortolo - Vicenza
Le pancreatiti: aspetti di diagnosi e terapiaVicenza 4 febbraio 2011
� Ottima tecnica per:
� Lo studio delle neoplasie esofagee, gastriche e ret tali
� Lo studio di alcune malattie biliari e pancreatiche come:
• Diagnosi e staging del carcinoma del pancreas
• Diagnosi e staging delle lesioni ampollari
• Diagnosi della litiasi della VBP
� La diagnosi dei tumori sottomucosi del tratto diges tivo e delle pliche gastriche giganti
� Anatomia EUS radiale
� Più semplice, necessita comunque di un training spec ifico
EUS RADIALE
� Come EUS radiale e in più
� Possibilità di:
� Biopsie EUS guidate di:
• Masse mediastiniche
• Linfonodi
• Neoplasie pancreatiche
• Masse extraparietali
� Terapie EUS guidate quali:
• Neurolisi del plesso celiaco
• Drenaggio di pseudocisti pancreatiche o di ascessi p elvici
• Iniezioni locali di farmaci
� Anatomia EUS lineare
� Più complessa, necessita anch’essa di un training sp ecifico
EUS LINEARE
EUS pancreatica
� DECUBITO LATERALE Sx
� DIGIUNO DA 8 ORE
�SEDAZIONE PROFONDA (assistenza anestesiologica) propofol
� SEDAZIONE COSCIENTE
�midazolam (0.3 mg/10 kg) + meperidina (0,5 mg/kg)
�SONDA LINEARE O RADIALE
�PROFILASSI (antibiotici, gabesato mesilato) se indic ata
Eus in:
• Cystic pancreatic neoplasms• Chronic pancreatitis
Prevalence of Pancreatic Cystic Neoplasms
• 300 consecutive autopsies
• 186 cystic lesions were found in 73 of 300 autopsies (24.3%)
• Epithelial atypia seen: atypical hyperplasia (16.4%); Ca in situ (3.4%)
• Incidental malignancies of the pancreas are usually cystic in origin
Kimura W et al. Cancer 1998
Morphology of pancreatic cyst lesions
How to think about pancreatic cystic tumors
Nat Rev Cancer
Qualsiasi lesione cistica del pancreas, specie in assenza di
un episodio di pancreatite acuta o di una riacutizzazione in
pancreatite cronica, deve essere considerata come
potenzialmente neoplastica
WHO Histological Classification of Cystic Pancreatic Neoplasms
• Mucinous cystic neoplasms� adenoma� with moderate dysplasia� carcinoma
• Intraductal papillarymucinous neoplasm (IPMN)� adenoma� with moderate dysplasia� carcinoma
NON-MUCINOUS(benign)
MUCINOUS(pre-malignant and malignant)
Kloppel G et al. WHO 1996
• Serous cystic tumors• Cystic endocrine tumors
Does exist a test able to
differentiate between
malignant and benign
cystic lesions of the
pancreas?
Characteristic of Pancreatic Cystic Neoplasms
• Location• Number• Size• Relations with
surrounding organs• Contour• Uni/multilocular• Wall thickness• Wall alterations• Septation• Mass protruding into
EUS provides many informations
98 CASES(48 SURGICAL/PATHOLOGICAL CORRELATION)
2 ENDOSONOGRAPHERS (A & B) REVIEWED IMAGESWALLSOLID COMPONENTSEPTAELYMPHOADENOPATHYNUMBER
Ahmad NA et al, Am J Gastroenterol 2001
Can EUS alone differentiate between
malignant and benign cystic lesions of the pancreas?
A: solid component by EUS as the only statistically signi ficantpredictor of malignancy (however 61% of patients with ben ignlesions were also interpreted by EUS to have solid component )
B: None of the features were found to be significant predi ctor of a malignant lesion
CAN EUS ALONE DIFFERENTIATE
BETWEEN MALIGNANT AND BENIGN
CYSTIC LESIONS OF PANCREAS ?
•The diagnostic accuracy of EUS morphology alone forpancreatic cystic neoplasms varies between 50% and 73 %
in different studies
•Highly operator-dependent
•The agreement among endosonographers is reported tobe poor
Ahmad NA et al. Am J Gastroenterol 2001 Brugge WR et al. Gastroenterology 2004
Frossard JL et al. Am J Gastroenterol 2003
EUS-guided Fine Needle Aspiration
•Cyst Fluid Cytology
•Tumor marker analysis
•Molecular analysis
127 pts (67 SURGICAL/PATHOLOGICAL CORRELATION)
EUS & EUS-FNA for cytological and tumor markers analysis
Results of EUS and EUS-FNA were compared with the final diagnosis
EUS EUS-FNA
sensitivity 71% 97%
specificity 30% 100%
Frossard JL et al. Am J Gastroenterol 2003
EUS / EUS-FNA Complications
10,731 conventional EUS: 5 (.046%) complications808 interventional EUS: 9 (1.11) complications
550/808 EUS guided procedures for pancreatic lesions
EUS-FNA of 479 solid lesions: 0.4% complicationsEUS-FNA of 71 cystic lesions: 8.4% complications
Needed prospective studies to determine the appropriateuse of antibiotic prophilaxis in EUS FNA of pancreatic cysts
Buscarini E et al Dig Liv Dis 2006 38: 762-67
185 patients with known or suspected pancreatic cancerNegative tissue sampling by ERCP or negative CT-guided FNA
EUS-FNA Negative CT-guidedFNA (n=58)
Negative ERCP tissuesampling (n=36)
sensitivity 90% 94%
accuracy 84% 92%
EUS-FNA of pancreatic masses accurately diagnoses pancrea ticmalignancy when prior biopsy techniques have been unsucces sful
Am J Gastroenterol 2002
American Joint Comittee on CancerEUS–FNA preferred sampling technique in pancreatic cancer
EUS - FNA vs US/TC - FNASeeding
Incidence of peritoneal carcinomatosis
• EUS – FNA 2.2%
• Percutaneous FNA 16.3%P < 0.025
C. Micames Gastrointest Endosc 2003
EUS-FNA COMPLICATIONS
Literature data suggest that EUS is associated with a similar rate of perforation compared withstandard endoscopy (<0.03%).No death are reported related tothe procedures, in the recentlarge series
EUS-FNA induced complicationconsists in:
• Pancreatitis (0-2%)• Hemorrhage (0-1,3%)• Infectious disease
Gastrointest Endosc 2005
Fernandez G, Endoscopy 2007Gress F, Gastrointest Endosc 2002O’Toole D, Gastrointest Endosc 2001
Al-Haddad M, Endoscopy 2008Affi A, Gastrointest Endosc 2001Eloubeidi M, Am J Gastroenterol 2003
Cytology
•A number of studies havereported varying accuracy of pancreatic cyst EUS-FNA cytology, but the overall accuracyis around 50%
•Columnar epithelial cells whichstain for mucin (MCN, IPMN)
•Cuboidal epithelial cells whichstain for glycogen (SCA)
van der Waaij LA, Gastrointest Endosc 2005
Tumor Marker Analysis
•Cyst fluid contains glycoproteins secreted from the epithelial lining that may help to differentiate betweenmucinous and non mucinous lesions
•Carcinoembryonic antigen (CEA), cancer antigen72.4, carbohydrate antigen (CA) 19.9, CA 15.3
•CEA appears to hold the most promise fordifferentiating benign from malignant lesions
•High viscosity cyst contents or the detection of extracellular mucin is generally indicative of a mucinous neoplasm
Brugge WR et al. N Engl J Med 2004
EUS CytologyCEA
(Cut-off 192 ng/mL)
Sensitivity (%)32/57 (56.1%)
19/55 (34.5%)
42/56 (75%)
Specificity (%)25/55 (45.4%)
45/54 (83.3%)
46/55 (83.6%)
Accuracy (%)57/112 (50.9%)
64/109 (58.7%)
88/111 (79.2%)*
Differentiating mucinous and non-mucinous lesions
Brugge WR et al. Gastroenterology 2004
The Cooperative Pancreatic Cyst Study341 patients (histology in 112)
*p<.001 vs Cytology, EUS
DNA AnalysisA detailed molecular analysis of pancreatic cystaspirated fluid may be helpful in differentiating
mucinous from non-mucinous lesions
Nonmucinous(25)
Mucinous(88)
p
Mean no. of Mutations
0.8 1.7 <0.001
K-rasmutations
1/25 40/88 <0.0001
K-ras mut. followed byallelic loss
0/25 17/88 <0.01
Khalid A et al. Gastrointest Endosc 2009
p-53 over-expression
MUC2 and MUC5AC in 80% IPMN (carcinoma)
Proteomics…
K-ras mutation:
sensitivity 91% specificity 93%
“Pseudosolid mass”
Cytology not diagnostic
Fluid analysis not possible in the absence of larger cysts
TRU-CUT BIOPSY
SEROUS CYSTADENOMA
SerousCystadenoma
• Microcystic• Glycogen-rich lesion• No ductal communication• Vascular• Benign• Fluid analysis: low fluid
viscosity, low CEA, low amylase
• Small cuboidal cells
MUCINOUS CYSTIC NEOPLASM
Mucinous Cystic Neoplasm
• Macrocystic lesions• No ductal communication• Body or tail• Woman (90%)• Mucin-secreting
epithelial cells, surrounded by an ovarian stroma
• High risk of malignant evolution
• Viscous, mucoid fluid• Fluid analysis: high CEA,
low amylase
Malignant EUS Features
•Calcifications•Thick wall (>2 mm)•Septations•Vegetations•Vascular involvement
EUS-Elastosonography
INTRADUCTAL PAPILLARY MUCINOUS NEOPLASM (IPMN)
Types of IPMN
MainMain ductduct typetype
BranchBranch ductduct typetype
Intraductal Papillary Mucinous Neoplasms (IPMN)
Dottoprincipale
diffuso segmentario
Dotticollaterali
macrocistico microcistico
Misto
Furukawa T, 1992
Kuroda A, 1997
IPMN• Men = women
• pancreatic head
• from hyperplasia…to
carcinoma (malignant potential)
• Viscous, mucoid fluid
• Fluid analysis: ↑↑↑↑ CEA
• Ductal communication
(proliferation of the ductal
epithelium, secretes mucin
causing dilation of pancreatic
ducts)
• main duct type tumor with MPD > 10mm
• branch duct type tumor lesion > 40 mmirregular septalarge mural nodules
Malignant EUS Features
H. Kubo et al. Am J Gastroenterol 2001;96:1429-34
Frequency of malignancy in MPD IPMN: 60-92%, 2/3 invasive
POST-OPERATIVE 5-YEAR SURVIVAL
~ 100% for benign tumors and
non invasive carcinoma.
~ 60% for invasive carcinoma
Main duct type (>1 cm): surgery
Branch duct type: surgery if
- Size >30 mm
- Mural nodules
- (Dilated MPD)
- Positive cytology
- Positive symptoms
INDICATIONS FOR SURGERY
Tanaka et al, INTERNATIONAL CONSENSUS GUIDELINES , Pancreatology 2006
Brugge 2010
Conclusions
• Imaging alone, performed with CT, MRI, or EUS, is not sufficient.
•Cyst fluid analysis can provide diagnostic findings(dedicated cytologists).
• Cyst fluid tumor markers, particularly CEA and CA 72-4, supplement the findings of cytology.
• Don’t forget clinical signs (red flags: i.e. weightloss or the rapid onset of diabetesis highlysuggestive of malignant degeneration)
EUS criteria ofChronic Pancreatitis
Jones SN, Clin Radiol 1988Wiersema MJ, Endoscopy 1993
EUSParenchymal criteria
EUSDuctal criteria
EUSvs.
everybody
• 126 pts ERCP followed by EUS
• EUS sensitivity was greater than 85% when diagnosis of CP was based on the presence of >3 criteria, but the specificity was less than 60%
• Moderate to severe CP was unlikely (NPV>85%) when <3 criteria were present
• EUS is the most useful SINGLE test for diagnosis of chronic pancreatitis*
Sahai A, Gastrointest Endosc 1998*Gardner T. Gastrointest Endosc 2010
EUS in CP: questions, limitations and controversies
• Ideal threshold number of EUS features
• Relative value of each EUS feature• Influence of factors (such age) in EUS features
• Poor interobserver agreement• Accuracy and safety of EUS-FNA
• Accuracy and safety of EUS-Tru-cut biopsy
MAIOR CRITERIA• Hyperechoic foci
with shadowing
• PD calculi• Lobularity with
honeycombing
MINOR CRITERIA• Cysts• Dilated ducts > 3.5 mm• Irregular PD contour• Dilated side branches >1
mm• Hyperechoic duct wall• Strands• Foci no shadowing• Lobularity non contiguous
Criteria based on expert opinion alone and not validated prospectively
The ↑↑↑↑ ↑↑↑↑ ↑↑↑↑ of diagnostic categories ↑↑↑↑ ↑↑↑↑ ↑↑↑↑ inter-observer variability and reduces reproducibility
interobserver agreement poor
κκκκ<0,4 for 7/9 features
EUS-FNA / EUS-TRU-CUT BIOPSY in CP
Not completely safe
Sample often inadequate
Patchy lesions
Gain of NPV in some studies
At this time EUS-FNA/TRU-CUT BIOPSY
cannot be advocated forthe diagnosis of CP
*Gardner T. Gastrointest Endosc 2010
PANCREATIC CANCER OR INFLAMMATORY MASS??
EUS in patients with non specificchange of the pancreas on CT
Author N°Patients FNA Rate of malignancy
Horwhat2009
69 patientsEnlarged pancreas
19/69 8.7% (6/69)
Singh2008
107 patientsEnlarged pancreas
??? 22%
Ho2006
50 patientsEnlarged pancreas
11/5022%
8%4/50
Horwart JD, JOP 2009 Singh S, Dis Dig Sci 2008
Ho S, Clin Gastroenterol Hepatol 2003
Power Doppler EUS for the Differential Diagnosis BetweenPancreatic Cancer and Pseudotumoral Chronic
Pancreatitis
Power doppler Peripancreatic
collaterals
Sensitivity 93% 97%
Specificity 77% 92%
Accuracy 88% 95%
• 42 patients with pancreatic mass• 29 pts final diagnosis of PC
Criteria for malignant lesions•No detectable vascularisationusing conventional power doppler•Appearance of arterial vessels using SonoVue
•No detectable venous vessels inside the lesion
EUS Contrast-enhanced
sens 73.2% 91.1%
spec 83.3% 93.3%
Dietrich CF, World J Gastroenterol 2006
Euselastosonography
differentiating pancreatic mass
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