Utility of EUS-guided Microbiopsies in Pancreatic Cystic Lesions
Utility of EUS-guided Microbiopsies in Pancreatic Cystic Lesions
The purpose of this study is to determine clinical impact of EUS-guided microbiopsy procedure
 and supplementary molecular analyses compared to standard diagnostic workup of pancreatic
 cysts. The hypothesis is that a combination of previously mentioned modalities may change the
 management of some pancreatic cystic lesions, increase the diagnostic accuracy and optimize
 the discrimination between high- and low-risk pancreatic cysts.
Pancreatic ductal adenocarcinoma (PDAC) accounts for 6% of all cancer related deaths in
 Denmark, and the 5-year survival rate is only 8%. PDAC develops from precursor lesions with
 pancreatic intraepithelial neoplasia (panIN) being the most common, and cystic lesions as a
 second precursor. Unlike panINs, which are too small for detection with current imaging
 modalities, cystic lesions of the pancreas are increasingly diagnosed due to the extended use
 of cross-sectional imaging. Pancreatic cystic lesions may be observed in up to 13.5% of all
 MRI scans and 3% of all CT scans. There are several types of pancreatic cysts and each of
 them requires individual management, ranging from no treatment over watchful waiting to
 surgical resection according to their malignant potential.

 Standard diagnostic workup includes cross-sectional imaging of the cystic lesions and, in
 selected cases endoscopic ultrasound (EUS) with aspiration of cyst fluid by fine needle
 aspiration (FNA), followed by cyst fluid cytology and tumor marker analysis. The diagnostic
 algorithm is based on International consensus guidelines established in 2006, and revised in
 2012 and 2017, integrating clinical features with EUS-findings. The level of evidence in
 these guidelines is unfortunately low. A recent meta-analysis concluded that EUS and cyst
 fluid cytology have low sensitivity (54-63%), whereas the specificity is acceptable (88-92%)
 for detection of mucinous cysts. Low sensitivity is mainly due to absence of sufficient
 cellular material in the cyst fluid for definite diagnosis. Tumor marker analysis of cyst
 fluid, such as carcinoembryonic antigen (CEA), CA 72.4, CA 125, CA 19.9, and CA 15.3, have
 been studied extensively with CEA being the most accurate marker. A cut-off value of 192
 ng/mL for CEA distinguishes mucinous from non-mucinous cysts with a good, albeit imperfect,
 accuracy of 80%. However, the value will not differentiate between IPMN and MCN, and more
 importantly, it does not correlate with the level of dysplasia or malignancy.

 EUS-guided through-the-needle microbiopsy using the Moray™ forceps is a novel adjunctive. The
 device can be inserted through a EUS-FNA needle and used to obtain microbiopsies from
 different tissues in relationship to the gastrointestinal system. This instrument can be used
 in combination with EUS-FNA to subsequently obtain microbiopsies from the pancreatic cyst
 wall. Microbiopsies seem to represent a break-through in pre-operative classification of
 pancreatic cysts, as they provide histological material for examination of tissue
 architecture not readily accessible in FNA material. However, very little experience has been
 obtained hitherto. Even though this technique is currently described only in a few studies,
 it seems feasible and theoretically offers a higher quality of material than what can be
 obtained by EUS-FNA alone.
Inclusion Criteria:

 -  Patients 18 years old or above

 -  Able to provide informed consent

 -  Pancreatic cyst with a diameter of 15 mm or above OR pancreatic cyst of any size with
 any one of either high-risk stigmata or worrisome features (obstructive jaundice in
 patients with a cyst in the head of the pancreas, solid component/mural nodule,
 thickened/enhancing cyst wall, main pancreatic duct ≥ 10 mm or abrupt change of main
 pancreatic duct diameter with distal atrophy)

 Exclusion Criteria:

 -  Lactating and pregnant females

 -  Cystic lesions with a predominantly solid component, suspected of malignancy

 -  Patients with uncorrected coagulopathy (international normalized ratio > 1.5 or
 platelet count < 50 109/L)

 -  Patients with previous history of pancreatic cancer

 -  Patients with a history of major stomach surgery (e.g. Billroth 1 and 2, gastrectomy,
 gastric bypass, esophagectomy, resection of the liver or pancreas)

 -  Patients with disseminated malignant disease

 -  Patients unfit for surgery

 -  Patients where EUS-guided puncture of the lesion is not presumed technically feasible
 and/or safe

 -  Patients with systemic immunosuppressive disease or receiving systemic
 immunosuppressive treatment

 -  Patients with a history of recent pancreatitis (within 3 months)