This is a randomized trial to evaluate and directly compare the tissue quality, diagnostic sucess and safety profile of four different Fine Needle Biopsy needles.

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is currently the standard method for sampling solid pancreatic masses, with reported sensitivity for malignant cytology of 85-95%, specificity of 95-98% and diagnostic accuracy of 78-95%. Diagnostic failure of EUS-FNA can be due to inadequate targeting, inexperience of the endoscopist/pathologist, or necrotic or fibrotic tumors in which viable cells are difficult to obtain. The cellularity and architectural representation of the sample can also be determined by the needle used and its specific features. Recently, new needles known as "fine needle biopsy (FNB)" needles have become available that are specially designed to promote the collection of core tissue by unique designs of their needle tips. The advantages of FNB over FNA needles are that (a) the quality of tissue procured is superior: FNA needles yield cytology whereas FNB needles yield histology (b) molecular marker analysis can be performed more reliably on histology samples than cytology aspirates and (c) as histological tissue is greater in quantity than cytological aspirates, a quicker diagnosis with fewer passes can be established by histology than cytology.

Four different types of FNB needles are currently available - reverse-bevel tip (EchoTip ProCore HD Ultrasound Biopsy Needle, Cook Medical, Bloomington, IN), Menghini-tip (EZ shot, Olympus America, Center Valley, PA), Franseen tip (Acquire, Boston Scientific Corporation, Natick, MA) and fork-tip (SharkCore, Medtronic Corporation/Covidien, Newton, MA) needles, each with unique tip designs to facilitate procurement of histological core tissue. Although we have previously compared in randomized trials the diagnostic yield of Franseen and fork-tip FNB needles and have shown the two needles to be equivalent, there are currently no randomized trials directly comparing all four FNB needle types. EUS-guided tissue acquisition can also be performed using different techniques, including the use of suction, no use of suction and the stylet retraction technique. There are currently no studies comparing these different tissue acquisition techniques using the different FNB needles and no study has demonstrated the best technique for FNB.

Inclusion Criteria:

1. All patients referred for EUS-guided tissue acquisition of suspected or confirmed solid pancreatic mass lesions visualized on any radiological imaging
2. Able and willing to provide written or verbal consent
3. ≥ 18 years old
4. Able to undergo conscious sedation for EUS procedure

Exclusion Criteria:

1. <18 years old
2. Unable to obtain informed consent from the patient
3. Medically unfit for sedation
4. Pregnant patients
5. No pancreatic mass lesions visualized on EUS
6. Irreversible coagulopathy as determined by platelet count < 50,000/microL or International Normalized Ratio (INR) > 1.5
7. Unable to stop anti-platelet agents prior to the procedure

The patients, pathologists assessing the biopsy specimens and the research staff responsible for follow-up will be blinded to the FNB needle type utilized. Data will also be blinded for statistical analysis.