THESIS ABSTRACTUniversity The University of ManchesterName Hussein Ahmed KhambaliaDegree Doctor of Philosophy, 2015Thesis Title Peri-Operative Assessment and Optimisation in Simultaneous Pancreas and Kidney TransplantationPancreas transplantation (PT) is considered a gold-standard cure for brittle insulin dependent diabetes mellitus. In over 90% of cases, this is conducted simultaneously with a kidney transplant, providing concurrent treatment for end-stage renal failure (Simultaneous pancreas and kidney transplantation, SPKT). However, since its inception in the 1960's, SPKT has been associated with considerable morbidity and mortality. Despite significant recent improvements in graft and patient survival, the multi-factorial nature of the procedure has resulted in persistently high peri-operative morbidity. This thesis has identified four areas to study in the peri-operative assessment and management of these patients, potentially resulting in improved clinical outcomes. 1. Pre-operative risk-prediction scoring systems aide in the consent process and the peri-operative planning of care following major surgery. In PT, multi-system risk-prediction tools are deficient. We therefore assessed the utility of commonly used general surgical risk prediction models in PT recipients. Our finding suggested that The Waterlow Score, a multi-system tool originally developed for predicting the development of decubitus skin ulcers, identified high-risk individuals and has value in predicting outcome following SPKT.2. Peri-operative physiological optimisation (Goal-directed therapy, GDT) is well-recognised to improve outcomes following major general surgery in high-risk individuals. A randomised controlled trial was therefore performed to investigate the benefits of GDT in the peri-operative period following SPKT. The findings demonstrated improved short-term outcomes following GDT in our cohort.3. The temporal evolution of biomarkers following major physiological stresses allow for application in the diagnosis, management surveillance and treatment of diseases. In our cohort the acute evolution of inflammatory and diabetes biomarkers were delineated and correlated to clinical outcome. We identified that cold ischaemic time is significantly negatively related to early pancreatic function and CRP provides an easily measurable predictor of recipient morbidity.4. The final study aimed to evaluate the feasibility and assess the benefits of contrast enhanced ultrasound (CEUS) in the immediate post-operative period following PT. We found CEUS to be a clinically useful adjunct in the post-operative assessment of allograft morphology and perfusion, although further validation and correlation with outcomes is required.