Impact of pancreatic tumour biomechanics on diagnosis and post-operative complications.

756 Background: Around 600 people are diagnosed with pancreatic cancer in Ireland each year, with 90% of these having pancreatic ductal adenocarcinoma (PDAC). Five-year survival for PDAC is around 10%. PDAC upregulates stromal collagen formation which contributes to tissue stiffness. Stiffer pancreatic tumours have worse oncological outcomes due to faster progression and increased chemoresistance. Softer pancreata, conversely, are more likely to develop post-operative pancreatic fistulae (POPF), a significant post-pancreatectomy complication. While incorporated in risk scores, softness is currently determined by subjective intra-operative observation. Methods: Atomic force microscopy (AFM) is the gold standard technique used to measure biomechanics at a cellular length scale. We obtained fine needle biopsies (FNBs) of pancreatic tumours during diagnostic endoscopic ultrasound. This is the first time tissue biomechanics have been measured from pancreatic biopsies. Separately, we applied this technique to pancreatic tumours and adjacent normal tissue following resection. We also assessed collagen organisation in these pancreatic tumours to understand its contribution to the observed mechanical properties. Results: Of the patients with PDAC who underwent FNB, those presenting with metastatic disease had significantly stiffer tumours than those without, 1,490 Pa (SD 2,048.03 Pa) vs 250 Pa (SD 555.06 Pa) (p<0.0001). Neuroendocrine tumours exhibited larger variance compared to PDAC (p < 0.0001), SD 5,885.97 Pa vs SD 1,797.23 Pa. Regarding tumours which have undergone curative resection, tumour stroma is significantly stiffer than both cancer and benign epithelium. The collagen strands in this stroma are straighter, more numerous, and more packed than epithelial tissues. Pancreata which develop post-operative pancreatic fistulae (POPF) are softer than those which do not 96.42 Pa (SD 691.14 Pa) vs 343.99 Pa (SD 1,678.37 Pa). Conclusions: We describe a novel technique to measure the biomechanical properties of pancreatic biopsies. Using this technique, we now have the opportunity to measure these properties for the first time on all pancreatic tumours, including those presenting with unresectable disease. It is possible to distinguish between different types of tumour based on the biomechanical profile of biopsies. Previous ex vivo studies have linked stiffer tumours to a higher metastatic potential, and our results are the first to suggest that this may be true in a human population. In resected tumours, we confirm the anecdotal belief that softer pancreata are associated with POPF. Overall, this research demonstrates that tissue biomechanics has potential diagnostic and prognostic applications in pancreatic cancer.