A microenvironment-inspired synthetic three-dimensional model for pancreatic ductal adenocarcinoma organoids.

Experimental in vitro models that capture pathophysiological characteristics of human tumours are essential for basic and translational cancer biology. Here, we describe a fully synthetic hydrogel extracellular matrix designed to elicit key phenotypic traits of the pancreatic environment in culture. To enable the growth of normal and cancerous pancreatic organoids from genetically engineered murine models and human patients, essential adhesive cues were empirically defined and replicated in the hydrogel scaffold, revealing a functional role of laminin-integrin α3/α6 signalling in establishment and survival of pancreatic organoids. Altered tissue stiffness-a hallmark of pancreatic cancer-was recapitulated in culture by adjusting the hydrogel properties to engage mechano-sensing pathways and alter organoid growth. Pancreatic stromal cells were readily incorporated into the hydrogels and replicated phenotypic traits characteristic of the tumour environment in vivo. This model therefore recapitulates a pathologically remodelled tumour microenvironment for studies of normal and pancreatic cancer cells in vitro.

Using Laser Speckle Contrast Imaging to Quantify Perfusion Quality in Kidney and Pancreas Grafts on Vascular Reperfusion: A Proof-of-Principle Study.

The accuracy of intraoperative graft perfusion assessment still remains subjective, with doppler examination being the only objective adjunct. Laser speckle contrast imaging (LSCI) has been used to assess intraoperative blood flow in neurosurgery and in various surgical specialties. Despite its ability to accurately quantify perfusion at the microvascular level, it has not been clinically evaluated in kidney/kidney-pancreas transplantation for perfusion characterization. We aimed to evaluate the utility of LSCI and identify objective parameters that can be quantified at reperfusion. Methods: This study was registered in ClinicalTrials.gov (NCT04202237). The Moor FLPI-2 blood flow imager was used in 4 patients (1 Simultaneous Pancreas and Kidney, 2 deceased, and 1 living donor kidney transplants) during reperfusion to capture reperfusion data. The following parameters were measured: flux (average speed × concentration of moving red blood cells in the sample volume), doppler centroid, total and valid pixels, valid rate, and total and valid area. Flux data were analyzed with Moor FLPI analysis software. Results: The perfusion characteristics and flux images correlated with initial graft function. Conclusions: LSCI is a safe, noncontact imaging modality that provides real-time, accurate, high-resolution, full field blood flow images and a wide range of flux data to objectively quantify organ reperfusion intraoperatively in kidney/kidney-pancreas transplantation. This modality could be used to develop a robust numerical quantification system for the evaluation and reporting of intraoperative organ perfusion, and aid intraoperative decision-making. Perfusion data could be combined with biomarkers and immunological parameters to more accurately predict graft outcomes.

Patient understanding of liver cirrhosis and improvement using multimedia education.

OBJECTIVE: For patients to engage with the long-term management of liver cirrhosis, sufficient understanding of their condition is essential. The aim of this study was to assess baseline patient knowledge and to test whether a condition-specific multimedia screencast could improve this. DESIGN: Service quality improvement study. SETTING: A UK tertiary liver centre. Patients were recruited during 12 general hepatology outpatient clinics. PATIENTS: Fifty-two patients with liver cirrhosis were included. Sixty-two per cent were male; their median age was 56 years and their median clinic attendance period was 3 years. INTERVENTIONS: Participants completed a baseline questionnaire assessing their knowledge of the management and complications of cirrhosis. They then watched a tailored screencast discussing this condition, which had been developed by expert hepatologists in collaboration with patient representatives. Knowledge was reassessed using a new copy of the original questionnaire after an interval of at least one month. MAIN OUTCOME MEASURES: Patient scores on knowledge questionnaires at baseline and follow-up. RESULTS: Fifty-two patients achieved a median score of 25.0% before viewing the screencast. Thirty-five patients then completed a follow-up questionnaire after an interval period. The median questionnaire score in this group improved from 25.0% to 66.7%; an increase of 41.7% compared with baseline (p<0.001). CONCLUSIONS: Despite regular review at a specialist clinic, participants had poor baseline knowledge of liver cirrhosis. Delivering information by screencast led to a significant improvement. We therefore present an effective way to empower patients with accurate, up-to-date and retainable information that can easily be translated to many other conditions.