1 Differential Diagnosis of Differential Diagnosis of Neoplastic Pancreatic Cysts: Neoplastic Pancreatic Cysts: The Role of EUS with Guided The Role of EUS with Guided FNA FNA E.M.Santo,Y.Ron,O.Barkay,Y.Kopelman,M.Leshno,S.Marmor Dep. of Gastroenterology & Hepatology, Dep.of Pathology Tel-Aviv Sourasky Medical Center
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Differential Diagnosis of Neoplastic Pancreatic Cysts: The Role of EUS with Guided FNA
Differential Diagnosis of Neoplastic Pancreatic Cysts: The Role of EUS with Guided FNA. E.M.Santo,Y.Ron,O.Barkay,Y.Kopelman,M.Leshno,S.Marmor. Dep. of Gastroenterology & Hepatology, Dep.of Pathology Tel-Aviv Sourasky Medical Center. Introduction. - PowerPoint PPT Presentation
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Differential Diagnosis of Differential Diagnosis of Neoplastic Pancreatic Cysts:Neoplastic Pancreatic Cysts:The Role of EUS with Guided The Role of EUS with Guided
CEA in fluid - most accurate CEA in fluid - most accurate markermarker
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EUS – Serous cystEUS – Serous cyst
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EUS – Mucinous cystEUS – Mucinous cyst
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AIMAIM
Evaluation of the various Evaluation of the various parameters parameters (clinical,morphological,fluid (clinical,morphological,fluid content, cytology) and their content, cytology) and their contribution to the ability to contribution to the ability to distinguish between distinguish between serous serous and and mucinousmucinous cystic tumors cystic tumors
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AIMAIM
Validation of the current Validation of the current criteria used to distinguish criteria used to distinguish between various cystic between various cystic tumors (gold standard based tumors (gold standard based on surgical pathology )on surgical pathology )
Establishing new criteria Establishing new criteria with higher sensitivity and with higher sensitivity and specificityspecificity
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AIMAIM
Provide an algorithm for Provide an algorithm for the diagnosis and the diagnosis and treatment of pancreatic treatment of pancreatic cystic lesionscystic lesions
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Heuristics used in our Heuristics used in our InstituteInstitute for Dx of for Dx of SerousSerous
cystscysts
- Clinical Clinical - Microcystic morphologyMicrocystic morphology- CEA level CEA level < 5 ng / ml< 5 ng / ml- Histology- cuboidal, non Histology- cuboidal, non
septa, solid componentsepta, solid component- High viscosity (mucinous) High viscosity (mucinous)
fluidfluid- CEA - CEA - >140 ng/ml>140 ng/ml- Histology – columnar Histology – columnar
secreting epitheliumsecreting epithelium
Heuristics used in our Heuristics used in our InstituteInstitute for Dx of Mucinous for Dx of Mucinous
cystscysts
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MethodsMethods
1919
MethodsMethods
Retrospective study Retrospective study 170 patients between 1977-170 patients between 1977-
20062006 155 patients ,195 EUS exams155 patients ,195 EUS exams 40 patients – EUSx2 or more40 patients – EUSx2 or more 101 women, 54 men101 women, 54 men Mean age – 64.3Mean age – 64.3±14 years±14 years
2020
MethodsMethods
Demographic dataDemographic data Clinical presentationClinical presentation Imaging – US, CT , EUSImaging – US, CT , EUS FNAFNA Surgical findingsSurgical findings Follow up on all patients (Follow up on all patients (office visits , office visits ,
data from family physicians, data from family physicians, gastroenterologists, patient’s families)gastroenterologists, patient’s families)
– The agreement rate was 66% of the cases regarding mucinous vs. non-mucinous with kappa=0.33.
– Sensitivity and specificity of FNA are 59% and 80% respectively.
EUS-FNA vs. Surgical biopsy
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ResultsResults Mean of Ln(CEA)Mean of Ln(CEA)** levels were 2.6 and levels were 2.6 and
5.8 for non mucinous and mucinous 5.8 for non mucinous and mucinous cases respectively (p<0.0001)cases respectively (p<0.0001)
No statistically significant difference No statistically significant difference with all the other tumor markers with all the other tumor markers testedtested
Rate of solid component in cyst – the Rate of solid component in cyst – the difference was not statistically difference was not statistically significant (p=0.14)significant (p=0.14)
No difference concerning cyst size or No difference concerning cyst size or morphologymorphology*CEA is highly skewed distributed and therefore we *CEA is highly skewed distributed and therefore we transformed the CEA level to Ln(CEA)transformed the CEA level to Ln(CEA)
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10
Class
12.00
10.00
8.00
6.00
4.00
2.00
0.00
-2.00
lnC
EA
Mucinous
Ln
(CEA
) BoxPlot
Non-mucinous
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95% C.I.for OR
Variable B S.E.
p-value OR Lower Upper
log10CEA 1.818 0.727 0.012 6.2 1.48 25.6
Age -0.041 0.022 0.06 0.96 0.92 1.01
Logistic regression results
Note that CA-19 is highly correlated with CEA, and when CEA levels are unavailable the CA-19 level should play a role in the diagnostic process.
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1.00.80.60.40.20.0
1 - Specificity
1.0
0.8
0.6
0.4
0.2
0.0
Sensi
tivi
ty
ROC Curve
ROC of CEA classification of Mucinous vs. Serous
1-specificity
sen
sit
ivit
y
AUC=0.902 (CI=(0.79-1.0))
A Threshold of CEA=58
ng/ml yields 86.4% and
87.5% sensitivity
and specificity
respectively
A Threshold of CEA=58
ng/ml yields 86.4% and
87.5% sensitivity
and specificity
respectively
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ConclusionsConclusions EUS is a useful tool but it can not EUS is a useful tool but it can not
alonealone distinguish between cystic distinguish between cystic lesions with variable malignant lesions with variable malignant potential potential
EUS-FNA EUS-FNA alonealone is also limited in is also limited in its ability to correctly diagnose a its ability to correctly diagnose a cystic lesion – sensitivity 59% cystic lesion – sensitivity 59% specificity 80%specificity 80%
CombinationCombination of parameters – of parameters – cytology and CEA levels (or CA cytology and CEA levels (or CA 19-9 levels) can significantly 19-9 levels) can significantly increase the diagnostic yieldincrease the diagnostic yield
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A Practical Decision Algorithm based on
the Threshold Decision Model
Source: NEJM 1980; 302:1109-17
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For a patient with a pancreatic cyst there are several management options:For a patient with a pancreatic cyst there are several management options:
• Wait and watch approach with a follow up.
• An initial EUS-FNA is performed and patients with increased cyst fluid CEA or positive cytology undergo a surgical resection.
• Surgical resection of all cysts without prior EUS evaluation.
• Wait and watch approach with a follow up.
• An initial EUS-FNA is performed and patients with increased cyst fluid CEA or positive cytology undergo a surgical resection.
• Surgical resection of all cysts without prior EUS evaluation.
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Beside the preferences of the patient, the following parameters are relevant to the decision process:
Beside the preferences of the patient, the following parameters are relevant to the decision process:
• Age of the patient 60 year• 61-75 year• > 75 year
• Co-morbidity status (CV diseases, diabetes, other neoplastic diseases)
• No co-morbidity
• Co-morbidity
• Test results (CT, EUS)
• Age of the patient 60 year• 61-75 year• > 75 year
• Co-morbidity status (CV diseases, diabetes, other neoplastic diseases)
• No co-morbidity
• Co-morbidity
• Test results (CT, EUS)
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0
1000
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7000
8000
9000
10000
2005200320012000199919981997year
0
10
20
30
40
50
60
70
80
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Cy
st
siz
e (
mm
)
CEA in cyst
CA19-9 in blood
Cyst size
Natural history of mucinous cystic neoplasm 78 years old woman with incidental finding - 1977