This study evaluates the use of contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) and cyst fluid molecular analysis in the differential diagnosis of pancreatic cysts and the detection of malignancy.

Pancreatic cyst are a frequent finding on cross-sectional imaging on general population. They are identified in up to 3% of the abdominal computed tomographies (CT) and 20% of magnetic resonance imaging (MRI) performed for other reasons but the risk of malignancy in pancreatic cysts discovered incidentally is low, representing 1-5% of the total malignant pancreatic neoplasms.

Pancreatic cysts are a broad group of pancreatic lesions that can be divided into benign and premalignant or malignant lesions. Pseudocyst and serous cystic neoplasm (SCN) don´t have malignant potential while others like mucinous cysts are premalignant lesions. But not all mucinous neoplasms have the same risk of malignancy. According to recent publications mucinous cystic neoplasm (MCN) have a potential for malignancy of around 15%, main duct intrapapillary mucinous neoplasm (MD-IPMN) of 62% and branch duct IPMN (BD-IPMN) of 25%. The correct identification of these premalignant lesions will allow to optimize the treatment and follow-up of these patients, but in many cases it is difficult to accurately differentiate between different types of cysts and their risk of malignancy. The differentiation between lmucinous and non-mucinous cysts is suboptimal, with diagnostic accuracy for CT and MRI of 61% and 50-73% with endoscopic ultrasound (EUS). The endosonographic characteristics that have been related with malignancy are the size larger than 3 cm, the presence of a solid component, wall thickening, Wirsung dilation, abrupt change of the size of the main pancreatic duct with distal atrophy of the gland and the presence of lymphadenopathies. However, endosonographic characteristics are not sufficient as an individual predictor of malignancy.

The puncture of the cyst and fine-needle aspiration (EUS-FNA) with biochemical and cytological assessment is generally indicated to differentiate between cysts and to asses for malignancy. The determination of carcinoembryonic antigen (CEA) and amylase have low specificity for the detection of malignancy and for mucinous cyst, and the cytological assessment is highly specific but lacks of sensibility (50%). So further methods are requested for an adequate detection of premalignant and malignant cyst.

Contrast-enhanced harmonic endoscopic ultrasound uses an ultrasonographic contrast agent to visualize blood flow in fine vessels and may aid in the diagnosis of pancreatic cysts by enabling assessment of the vascularization of structures such as cyst walls, septa, or mural nodules. Furthermore it allows the correct differentiation between contrast-enhanced mural nodules, that predict for malignancy, from non-enhancing mucus clots.

The molecular analysis of cyst fluid may detect mutations that are associated with premalignant cyst and with malignancy. Kirsten rat sarcoma (KRAS) gene has been related with mucinous cyst while von Hippel-Lindau gene (VHL) is present in serous cyst.

This study evaluates the use of contrast-enhanced EUS and the molecular analysis for pancreatic cyst diagnosis and malignant detection, and if their use may modify cyst management.

Inclusion Criteria:

• Indeterminate pancreatic cyst > 2cm
• Pancreatic cyst > 1cm with morphological diagnosis suspicious to be mucinous etiology
• Suitable for endoscopy

Exclusion Criteria:

• Contraindication for endoscopy
• Active anticoagulant or antiplatelet therapy
• Thrombocytopenia or coagulopathy in the absence of its correction prior to the procedure
• Abscence of informed consent
• Extrapancreatic cyst
• Known pancreatic pseudocyst

All patients with with an imaging diagnosing pancreatic cystic neoplasm, older than 18 years old, that come to our unit during the 18 months of the study without exclusion criteria.