Windsor, JPhillips, ALoveday, Benjamin2012-05-092012http://hdl.handle.net/2292/17804BACKGROUND. Severe acute pancreatitis (AP) is associated with infected local complications. Many of the causative organisms are enteric, and translocated bacteria or toxic factors may be transported via mesenteric lymph (ML). It was hypothesised that ML can pass directly to the pancreas via lymphatic routes, and disease conditioning of ML affects bacterial growth. When local complications become infected then intervention is required. The role for minimal access treatment is uncertain as its efficacy is often limited. It was hypothesised that its efficacy could be enhanced by accelerating natural liquefaction of pancreatic necrosis. METHODS. Lymphatic infusions (e.g., dye, bacteria) were undertaken to identify lymphatic connections between pancreas and intestine. Bacteria were incubated in ML collected from disease models, to determine the effect of disease conditioning on bacterial growth. A review of guidelines and a survey of local surgeons determined the role of minimal access treatment to manage infected local complications of AP. A classification was developed for the range of interventions available. The liquefactive efficacy of proteolytic enzymes on pancreatic necrosum was investigated. RESULTS. ML could reach the pancreas directly via retrograde lymph flow, even at physiological pressures, when lymphatic valves were incompetent or absent. Bacterial growth in ML was dependent on the duration of incubation, the bacterial species and their initial concentration, and the presence of ML disease conditioning. Guidelines differed in their recommendations regarding minimal access treatment of the local complications of AP, while local opinion suggested these treatments have an increasingly important role. Collagen is a major component and key target for liquefaction of pancreatic necrosum, and proteolytic enzymes were more effective than saline at decreasing the total protein content of necrosum and altering its mechanical properties. CONCLUSIONS. The results demonstrating lymphatic connections between pancreas and intestine, and bacterial growth in disease conditioned ML, indicate that antibiotics that concentrate in ML need further investigation in the setting of bacterial translocation. The ability to enhance liquefaction of pancreatic necrosis gives support to the use of lavage either through percutaneous drains or following necrosectomy, while proteolytic enzymes may offer an advantage to the use of saline alone for lavage.Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher.https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htmhttp://creativecommons.org/licenses/by-nc-sa/3.0/nz/ThesisCopyright: The authorQ112890503