gitj club cp ns guidelines

Universitätsklinik für Viszerale Chirurgie und Medizin / www.chirurgiebern.ch

Pancreatic cysts


What type of pancreatic cysts exist ?

Acquired Cysts:

Congenital Cysts:

Cystic Neoplasms:

Post-inflammatory fluid collectionPseudo-,-PseudocystPostnecrotic sequestrumParasitic, Ecchinococcal etc.

True cystsEnterogenous cysts/ duplication cysts(Epi)dermoid cysts, EndometriosePolycystic diseases; Cystic Fibrosis

Cystic Neoplasms:- IPMN: Intraductal papillary mucinous neoplasm- MCN: Mucinous cystic neoplasm- SCN: Serous cystic adenoma/ neoplasm- SPN: Solid pseudopapillary neoplasm- CPEN: Cystic pancreatic endocrine neoplasm

Why is this differentiation important ?

Risk Malignancy

Benign


How frequent are neoplastic pancreatic cystic lesions ?

Average: 2.5%

Age > 70 years: 10-20%*

*: MRI in non-pancreatic disease: 20% of 1444 patients; Zhang XM et al. Radiology 2002


Key features: Serous Cystic Neoplasm

Malignant potential: Location: Demographics, rate: Morphology: micro-, oligo-, macrocystic

typically: multicystic cluster (each < 2 cm) = honeycumbed

No communication with pancreatic duct

Stroma: (central fibrous and) calcified (stellate scar)

NO

throughout the pancreas (older) women (80%), 15-20% of PCNs


Key features: IPMN

Types: Malignant potential: Location: Demographics, rate: Morphology:

Yes (esp. main/combined duct IPMN)

M: head BD: multifocal !!

Equal m/w, middle-age/old; >25% of PCNs

Main-, branch-duct, mixed type

Cystic dilatation main (> 6 mm) or side

branches; M: Fish-mouth, globules of mucin (= masses)

Stroma: Lack of ovarian stroma (vs. MCN)


Key features: MCN

Malignant potential: Location: Demographics, rate: Morphology:

Yes (but lower than IPMN)

Body/tail (95%), always single lesion!Middle-aged women (95%), 25% of PCNs

thick-walled single cyst, often septations

Epithelial layer with mucin-producing cells, ovarian-like stroma

No communication with pancreatic duct


Risk of malignancy in pancreatic neoplastic cysts ?

IPMN: BD-:

MD-:

MCN:

SCN:

SPN:

CPEN:

1: Sakorafas GH et al. Surg Oncol. 2011; 2 Sakorafas GH et al. Surg Oncol 2012

++ ̴ 40% (6-46%) Risk of HGD/ malignancy 1

++++ ̴ 65% (57-92%) Risk of HGD/ malignancy in 5 y 1

++ 6-36% Prevalence malignancy 1

(+) VERY low (malignant = serous cystadenocarcinoma)

+ Low malignant potential 2

Variable 2

What factors determine malignant risk in IPMN/MCN?

Size

Histopathological type


What are high-risk stigmata for malignancy in IPMN/MCN?

Obstructive jaundice (and cystic lesion of the pa-head)

Enhancing solid component within cyst

Main pancreatic duct > 10 mm in size

Consequence?

Consider surgery, if clinically appropriate


If no high-risk stigmata in IPMN/MCN:What are worrisome features ?

Clinical: PancreatitisImaging: Cyst > 3 cm

Thickened/enhancing cyst wallsMain duct size 5-9 mmNon-enhancing mural noduleAbrupt change in caliber of pancreatic ductwith distal pancreatic atrophy

Consequence?

Endo-Sonography


What are the advantages of EUS in diagnostic workup of pancreatic cysts ?

Superior, higher-resolution imaging of the pancreas

(ductal communication, additional (smaller) cysts, nodules etc.)

Fine-needle-aspiration (FNA): sampling fluid for

Cytology and tumor markers


Operator-Dependent Investigation Sampling Error Contamination (gastric wall) Low cellularity -> Low senstivity

e.g. SCN only 30-40% enough cells

diagnostic accuracy: 10-60%

often NON-diagnostic

What are drawbacks of EUS ?

Including high-grade

atypical epithelial cells:

diagnostic in mucinous cysts

diagnostic accuracy: 80%


What are EUS features leading to consider surgery ?

Define mural nodule(s): 3-9 fold risk malignancy Main duct features suspicious for involvement Cytology: suspicious or positive for malignancy


EUS-FNA: Fluid Analysis in Cysts

Typ SCN MCN IPMN SPN Pseudocyst

Viscosity

Mucin

Amylase

CytologyCytology negative or

Glyogen-con-taining cuboid

cells

mucin-

containing column cells

papillary clusters ofmucin-

column cells, atypia

Branching papillae

cuboid or cylindric cells, high cellularity, myxoid stroma

«dirty material»

Macrophages,Inflammatory cell

Viscosity Low High High NA Low

Mucin Low High High NA Low

Amylase < 250 U/L < 250 U/L < 250 U/La Low High


CEA in Cyst-Fluid: What for ? Useful ?

Mucinous vs. Non-mucinous (serous)

Cut-off unclear: e.g. > 800 ng/mL

No correlation with risk of malignancy


How to perform surveillance for BD-IPMN and MCN?

< 1 cm:

1-2 cm:

2-3 cm:

> 3 cm:

CT/MRI in 2-3 years

Close surveillancealternating MRI with EUS every 3-6 monthsStrongly consider surgery (in young, fit patients)

EUS in 3-6 monthsLengthen interval, alternating EUS and MRIConsider surgery in young, fit patients (long surveillance)

CT/MRI yearly (for 2 years) lengthen interval if no change


Which syndrome associates with multiple/oligocystic SCN ?

Hippel-Lindau-Syndrome


The role of endoscopy in the diagnosis and treatment of cystic pancreatic neoplasms

Volume 84, No. 1 : 2016 GASTROINTESTINAL ENDOSCOPY


Cyst fluid collection:

Often present a diagnostic / therapeutic challenge. They range from pseudocysts &pancreatic necrosis to benign & malignant neoplasms. May be encountered during the evaluation of pancreatitis or abdominal pain&found incidentally in 2.5% of abdominal imaging performed for unrelated reasons, increases 10% in 70 ys.Can be misclassified as pseudocysts.


EUS Findings:• Diagnostic accuracy 40-96%. • Sensitivity 56%, specifi city 45% for differentiating

mucinous cysts (mucinous cystic neoplasms/IPMNs) from nonmucinous cysts were low, resulting in poor overall accuracy 51%.

• The agreement of whether a cyst was neoplastic versus nonneoplastic was fair with moderate agreement for serous cystic neoplasms&for solid components.

• Small cyst size alone does not exclude malignancy. • 20% of lesions 2 cm or smaller were malignant&an

additional 45% of lesions had malignant potential. • Only 3.5% asymptomatic lesions < 2 cm was malignant.


EUS Findings:• Certain EUS features are more predictive of particular

types:• Multiple small (< 3 mm) compartments within a cystic

lesion (microcystic lesion), suggest a serous cystic neoplasm with an accuracy of 92-96% not seen in mucinous cystic neoplasms.

• Cysts without septations or solid components within a pancreas having parenchymal features of pancreatitis (calcifications, atrophy, change in echo texture) indicates a pseudocyst with sen of 94% &spec of 85%.

• EUS imaging cannot reliably distinguish benign from malignant IPMNs.


EUS Findings:• A mural nodule, MPD dilation, thickened septal walls,• cyst size > 3 cm on radiologic or EUS imaging were

independent predictors of malignant branch-duct IPMN.• A MPD 10 mm or the presence of an enhancing solid

component on radiologic imaging as high-risk stigmata. • Lower risk findings, categorized as worrisome features,

included a cyst size of 3 cm, thickened enhancing cyst walls, nonenhancing mural nodules, MPD size of 5 to 9 mm, an abrupt change in the MPD caliber with upstream pancreatic atrophy, or the presence of peripancreatic LAP.

• Distinguishing cyst wall nodules that are epithelial (neoplastic) from those that are mucinous (nonneoplastic) is critical to properly risk stratify PCNs.


EUS Findings:• EUS imaging of intracystic mucus appears as a smooth,

well-defined hyperechoic rim with a hypoechoic center compared with the surrounding parenchyma serves to distinguish mucus from true epithelial nodules, which have ill-defined borders &hyperechoic center.

• Intraductal US may identify malignant IPMN by the presence of protruding lesions 4 mm.

• Contrast-enhanced EUS, may aid in distinguishing infl ammatory cysts from cystic pancreatic neoplasms & vascular epithelial mural nodules from nonvascular mucous in IPMNs.


EUS -FNA:Analyzed for cytologic, chemical/or molecular studies. Any solid component or regional LNs aspirated for cytology or histology. A higher diagnostic yield when a solid component on EUS A dilated PD can be safely targeted for FNA when IPMN is suspected.FNA of the cyst wall may provide additional cyto material& increase the diagnostic yield for mucinous lesions by 37%.EUS-FNA + CT /MRI increased the overall accuracy for diagnosing cystic pancreatic neoplasms by 36% & 54%, respectively.FNA greatest in cysts containing imaging features most associated with malignancy, namely an epithelial nodule or mass lesion, cyst size > 3 cm, or MPD dilation.


Cytology:

Has pooled sensitivity of 63%/specificity of 88% & in other study were 54%/93%.Cytologic findings suggestive of a pseudocyst includemacrophages, histiocytes, neutrophils. The presence of mucin is suggestive of a mucinous neoplasm&seen in 35% or more of cases. Glycogen-rich cuboidal cells indicate a serous cystic neoplasm but are present only in 10% of cases.The diagnostic accuracy of cytology from EUS-FNA for cystic lesions ranges from 54-97%&may be lower in smaller cysts.Malignancy within a cystic neoplasm can be identified by cytology with 83-99% specificity, sensitivities 25- 88%. A Cytology brush limited benefit over standard EUS-FNA & potential increased risk of adverse events.


Chemistry & markers:

• Amylase, lipase, CEA. • Amylase < 250 U/L virtually excluded (specificity 98%) the• lesion as a pseudocyst. • CEA cutoff of 192 ng/mL for differentiating mucinous from

nonmucinous cysts, sensitivity of 75% /specificity 84%. When morphologic criteria (associated

• Higher CEA levels increase specificity for the diagnosis of a mucinous cyst but do not correlate with malignancy. Conversely, a CEA < 5 ng/mL was seen in only 7% of mucinous cystic neoplasms & all serous cystic neoplasms. CEA to have a sensitivity of 63% & specificity of 88% for the identification of mucinous cystic tumors.

• Other tumor markers CA 19-9, CA 125, CA 72-4,CA 15-3, but none of these appear accurate enough to provide a definitive diagnosis.


DNA & Molecular analysis:• Improve the limitations of cytology, chemical/or markers.

An K-ras mutation strongly associated with mucinous cysts & K-ras/allelic loss showed a specificity of 96% for malignancy.

• The CEA&DNA molecular analysis improved diagnostic accuracy compared to either test alone.

• Integrated molecular analysis of cyst fluid (ie,molecular analysis with imaging&clinical features) was able to better characterize the malignant potential of pancreatic cysts.

• Acquisition of cyst fluid via EUSFNA, duodenal collection of pancreatic juice for DNA analysis via an echoendoscope after secretin stimulation found GNAS mutations in 64.1%.

• Molecular analysis (requires only 200 m L of fluid) may be most useful in small cysts with nondiagnostic cytology, equivocal cyst fluid CEA results, or when insufficient fluid is present for CEA testing.


Emerging techniques:Direct optical & endomicroscopic examof pancreatic cysts has become feasible. Intracystic visualization &biopsy through a 19-gauge needle can be obtained with either a reusable 0.9-mm fiberoptic probe or via a dedicated system primarily indicated for single-operator cholangioscopy/pancreatography Real-time in vivo microscopic imaging via needle-based confocal laser endomicroscopy after IV fluorescein with presence of epithelial villous structures had a sensitivity of 59% &specificity of 100% for IPMN, MCN, or adenocarcinoma.A superficial vascular network seen only in serous cystic neoplasms with accuracy of 87%The combined findings of mucin (by transneedle cystoscopy), papillary projections& dark rings onconfocal laser endomicroscopy improved diagnosticaccuracy compared with either technique alone.


EUS Complications:• Abdominal pain• Pancreatitis• Intracystic hemorrhage

• ASGE suggest antibiotics for 3 -5 days after EUSFNA of a pancreatic cystic lesion.


EUS intervention:• EUS-guided cyst ablation with ethanol alone or + paclitaxel

for suspected pancreatic cystic neoplasms is performed only at select centers &might be considered for patients who refuse or are not candidates for surgery.


ASGE recommendations: 1. EUS-FNA of any pancreatic cystic lesion > 3 cm in diameter or when cross-sectional or EUS imaging confirms an epithelial nodule, dilated MPD, or suspicious mass lesion. 2. EUS-FNA is optional in asymptomatics in whom cross-sectional imaging demonstrates a cyst < 3 cm without either a mass and/or epithelial nodule or associated dilated MPD.3. We recommend initial testing of aspirated pancreaticcyst fluid for CEA, amylase&cytology. 4. We suggest that molecular testing of the cyst be considered when initial ancillary testing of cytology & CEA isinconclusive &when test results may alter management.5. Prophylactic antibiotics for patients undergoing EUS-FNA for the evaluation of cystic pancreatic neoplasms. 6. ERCP, pancreatoscopy& intraductal US may be helpful in the diagnosis and characterization of suspected MD IPMNs.

gitj club cp ns guidelines

Health & Medicine