Transcript Pancreatic Cancer: The Use of Endosonography

Evaluation of Pancreatic
Cystic Lesions
Peter Darwin, MD
Director, Therapeutic Endoscopy
University of Maryland Hospital
Division of Gastroenterology
Cystic Lesions of the Pancreas
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Case Presentations
Differential
EUS evaluation
Management
Complications
Case 1
• 27 year old woman referred for evaluation
of recurrent pancreatitis with a cystic lesion
– Initially admitted 1/03 with acute pancreatitis
and a 3 cm cyst of pancreatic body. MRCP – EUS/FNA 11/05 of a 4 cm cystic collection.
Histology showed histiocytes, inflammatory
cells and debris. Mucin stain negative. CEA
390 ng/ml, amylase 91,700 U/l.
– What is the most likely diagnosis?
Case 2
• 77 year old woman with virtual
colonoscopy that demonstrated a 1.5 cm
cystic lesion of the pancreatic head
• EUS/FNA showed a multi-septated cyst
with clear/thin fluid. Mucin stain was
positive and CEA in the fluid 546 ng/ml
• What is the appropriate next step?
Differential
– Simple (Congenital) Cyst
– Cystic Neoplasm
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Serous
Mucinous
Cystic degeneration
IPMT
– Inflammatory
• Pseudocyst
Simple Cyst (Retention cyst)
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Asymptomatic
Thin walled, no septations
Thin clear fluid
Collapses with FNA
No malignant potential
Simple Cyst
Serous Cystadenoma
• Usually found incidentally
• Microcystic with a “honeycomb”
appearance; rarely has a macrocystic
component; central calcification
• Thin, clear fluid
• Cuboidal epithelium that stains positive for
glycogen
• Little to no malignant potential
Mucinous Cystadenoma
• Usually found incidentally but can cause
abdominal pain and a palpable mass
• Macrocystic, occasionally septated; peripheral
calcifications, solid components
• Fluid: Viscous or stringy, clear
• Cytology: Mucinous columnar cells with variable
atypia; fluid stains positive for mucin
• Malignant potential: 30% lifetime risk
Cyst Adenocarcinoma
• Presents with painless jaundice,
abdominal/back pain or rarely pancreatitis
• Primarily solid mass with cystic spaces
• Bloody ± debris
• Malignant adenocarcinoma may be seen,
but varying degrees of atypia may be
present in the specimen
Inflammatory
• Pseudocyst
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History of moderate to severe pancreatitis
Anechoic, thick-walled, rare septations
Fibrous lining of cyst (no epithelium)
FNA-> Thin, muddy-brown fluid
Cytology-> Neutrophils, macrophages,
histiocytes; negative staining for mucin
– Malignant potential: None
Pseudocyst
Intraductal Papillary Mucinous
Neoplasm (IPMN)
• 3 types: main duct, branch type and mixed
• History of pancreatitis, abdominal pain, or found
incidentally
• Imaging: Dilated main pancreatic duct or side
branches
• Fluid: Viscous or stringy, clear
• Cytology: Mucinous columnar cells with variable
atypia; fluid stains positive for mucin
• Malignant potential 20 to 30% lifetime risk
IPMN main duct
IPMN side branch
Solid Pseudopapillary Neoplasm
• Usually found incidentally; rarely causes
abdominal discomfort
• Solid and cystic components
• Bloody + necrotic debris
• Monomorphic cells with round nuclei and
eosinophilic or foamy cytoplasm;
immunostaining
• Locally invasive (similar to Desmoids)
Pseudo
UM-130
UC-30P
7.5 / 12 MHz.
7.5 MHz.
Can EUS alone Differentiate
Between Malignant and Benign
Cystic Lesions ?
• 48 patients with surgical/pathologic
correlation
• EUS images reviewed 2 blinded
endosonographers
• Assessed for wall, solid component, septae,
lymphadenopathy and # of cysts
• EUS features cannot reliably differentiate
Ahmad N, Kochman M, Lewis J, Ginsberg G. Am J Gastro 2001;96:3229-30.
EUS-Guided FNA
• Results for FNA cytology are variable
– Mucinous vs nonmucinous epithelium
• Tumor Markers
– CEA, CA 72-4, CA 125,
– CA 19-9, CA 15-3
• Molecular analysis
Cyst Fluid Analysis in the
Differential Diagnosis of Pancreatic
Cystic Lesions: a Pooled Analysis
• Pub Med review of articles with cyst fluid
analysis
– At least 7 patients
– Diagnosis of cystadenoma made by pathology
– Pseudocyst diagnosed by history and follow up
van der Waaij L, van Dullemen H, Porte R. Gastro Endo 2005;62:383-389.
Pancreatic Cyst Fluid
DNA QUANTITY &
QUALITY REFLECT LINING
CELL PROLIFERATION
KRAS & GNAS POINT
MUTATION (ONCOGENE)
FREE DNA
CEA
LOSS OF
HETEROZYGOSITY (LOH)
MUTATIONS (25) (TUMOR
SUPPRESSOR GENES)
DETACHED LINING CELLS
Second line molecular analysis targets both cellular and free DNA designed to complement
cytology and other first line information. Multiple molecular parameters reflects multiple
pathways of neoplasia development and progression
PFTG – Pancreatic Cysts
Molecular criteriaa
Co-existing concerning
clinical featuresb
DNA lacks molecular criteria
Not required for diagnosis
Statistically indolent (SI)
DNA meets at least 1 molecular
criterion
Patient lacks concerning clinical
features
Statistically higher risk
(SHR)
DNA meets at least 1 molecular
criterion
Patient may have 1 or more
concerning clinical features
Aggressive
DNA meets at least 2 molecular
criteria
Not required for diagnosis
Diagnostic category
Benign
aMolecular
criteria that have been correlated with malignant or high-grade disease are: a single high-clonality
mutation; elevated level of high-quality DNA; multiple low-clonality mutations; and a single low-clonality
oncogene mutation.
bIncludes:
cyst size >3 cm, growth rate >3 mm/year, main or side branch duct dilation >1 cm,
carcinoembryonic antigen level >1000 ng/mL and/or cytologic evidence of high-grade dysplasia.
Complications of EUS
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Pancreatitis (2%-3%)
Hemorrhage within the cyst (<1%)
Infection (<1%)
The prevailing opinion is to administer an
antibiotic, e.g., a fluoroquinolone, prior to
aspiration and possibly several days post.
Serous Cystadenoma
• Management determined by symptoms,
progression, and lesion location.
• Symptomatic or enlarging serous
cystadenomas should be resected.
• Small, asymptomatic, and nonenlarging
serous cystadenomas can be observed
Mucinous Cystadenoma
• Consider for resection
• Potential for malignant change (30%
lifetime)
• Distal pancreatectomy should be performed
for lesions in the body or tail of the
pancreas
• Pancreaticoduodenectomy for lesions in the
pancreatic head.
Ethanol Lavage: Initial Pilot
Study
• Background: lavage ablates liver cysts
• Methods: post evacuation, lavaged with
ethanol (5% to 80%)
• Observations: 25 patients – no symptoms –
resolution in 8 patients (35%)
• Conclusions: subset had long-term
resolution. Further studies needed.
Gan S, Thompson C, Bounds B, Brugge W. Gastro Endo 2005;61:746-752.
Prospective multicenter randomized
double blinded study
EUS
lavage
Baseline
SA
Post procedure Complete Complications
SA
ablation
Saline
N=15
1.7 cm2
1.4 cm2
0/15
0
Ethanol (1)
N=36
1.5 cm2
1.1 cm2*
2/37
1
Ethanol (2)
N=23
1.4 cm2
1.0 cm2**
10/23
1
*P=.002 ** P=.0001 ETOH vs saline
Brugge W, et al. Am J of Gastro 2007;106:S192
Revised International Consensus Guidelines for the
Management of Patients With Mucinous Cysts
Tanaka M, et al. Panceatology 12(2012) 183-197
Solid Pseudopapillary Neoplasm
• Solid pseudopapillary neoplasms are locally
aggressive lesions, which should be
resected surgically if possible.
• The type of resection is determined by the
location of the tumor
Endoscopic Management of
Pseudocysts
• Can be considered for mature pseudocysts,
infected pseudocysts, and in selected cases of
organized necrosis.
• Symptomatic lesions= (abdominal pain, gastric
outlet obstruction, early satiety, weight loss, or
jaundice)
• 82-84% success rate
• Complication rates occurring in 5% to 16%
• Recurrence rates ranging from 4% to 18%
Endoscopic Management
• Prophylactic antibiotics
• Special care must be taken to avoid
drainage of cystic neoplasms,
pseudoaneurysms, duplication cysts, and
other noninflammatory fluid collections.
• Pseudocyst size is not an indication for
drainage
• ERCP prior
Hookey L, et. al. Gastro Endo 2006;63:635-43.
Complications of Drainage
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Bleeding
Infection
Perforation
Pancreatitis
Aspiration
Stent migration
Death