Endoscopic ultrasound (EUS) is an indispensable tool for tissue acquisition for pancreatic lesions. Fine needle aspiration (FNA) is once considered as the first line diagnostic method especially when rapid on-site evaluation (ROSE) by cytopathologist is available.

However, FNA alone has several limitations including inadequate acquisition of cells, and unable to provide core tissue for further histological analysis. Furthermore, ROSE is not available in many endoscopic centres due to limited resources. Endosonographers around the world, are discovering methods to overcome the limitations, including the use of new on-site evaluation technique by endoscopists, new fine-needle biopsy (FNB) needles, contrast-enhanced harmonic EUS-guided FNB.

In this study, the investigators propose to compare the diagnostic performance between contrast-enhanced EUS-guided FNB versus conventional EUS-guided FNB technique with an aim to define the best EUS-guided tissue acquisition technique in the absence of ROSE. Results obtained from this research is expected to have significant impact in providing new insights on the best EUS-guided tissue acquisition method. It may replace FNA with ROSE as the gold standard for EUS-guided tissue acquisition in an affordable manner. It will also save the patients from unnecessary procedures and fasten the treatment pathways.

Seicean et al, in a prospective study, evaluated the diagnostic accuracy of EUS-FNA with CH-EUS using SonoVueTM versus EUS-FNA without CH-EUS. They found that the diagnostic accuracy of EUS-FNA with CH-EUS was higher than that of EUSFNA without CH-EUS (86.5% vs 78.4%). However, the difference did not reach the threshold required for statistical significance. Also, only FNA, but not FNB, was performed in this study.

The FNB needle was introduced to further improve upon EUS guided tissue sampling. It is designed to collect a larger amount of core sample tissue with preserved histological architecture for further analysis, including molecular analysis. Also the FNB needle has been shown to obtain samples with higher cellularity compared to the standard FNA needles. Compared with EUS-FNA, EUS-FNB had a better specimen adequacy, higher diagnostic accuracy, and fewer number of needle passes but no increase in complications rate.

The technique of macroscopic on-site evaluation (MOSE) has recently been advocated for estimating the adequacy of a core specimen obtained by EUS for histological diagnosis. MOSE involves immediate examination of the FNB specimen for the presence of a "macroscopic visible core" (MVC), which is defined as whitish or yellowish pieces of tissue with an apparent bulk. The total length of the MVC is then measured and the optimal cut-off MVC length was 4 mm. This study demonstrated that EUS-FNB with MOSE provided comparable diagnostic yield as EUS-FNB without MOSE (92.6% vs 89.3%) with fewer numbers of passes.

Puncturing avascular or necrotic area of a tumour could be the major reason of false negative rate during EUS-guided FNB. Contrast-enhanced harmonic EUS (CH-EUS) can define avascular or necrotic area inside a tumour which may improve the false negative rate during EUS-FNB. In this study, the investigators aim to evaluate the diagnostic performance of CH-EUS-guided FNB with MOSE for solid pancreatic masses. The investigators expect the study will define the best EUS-guided tissue acquisition technique in the absence of ROSE and replace FNA with ROSE as gold standard for tissue sampling for solid pancreatic masses.

Inclusion Criteria:

• referred for EUS-guided tissue acquisition for solid pancreatic lesions greater than 1cm in the largest diameter.

Exclusion Criteria:

• with coagulopathy, altered anatomy, contraindications for conscious sedation, pregnancy
• who cannot provide informed consent.