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Title: Novel approaches to the diagnosis and management of severe acute pancreatitis
Author: Miranda, Charles Joseph
ISNI:       0000 0004 5990 7344
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2016
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Severe Acute Pancreatitis (SAP) is the rapid onset of inflammation within the pancreatic organ. Unlike the milder form of this illness, SAP is associated with a high mortality and morbidity. No significant reduction in the outcomes of this disease has been made since the implementation of organ supportive management over two decades ago. This is due to difficulties in distinguishing between the milder form of the disease in the early period of the onset of symptoms when clinical intervention is most likely to prevent complications and death. Clinical equipoise exists in the management of one of these complications, namely Abdominal Compartment Syndrome (ACS) as the conventional management of surgery runs contrary to published evidence showing early abdominal surgery deteriorates clinical outcomes. Aims: Validation of the potential use of the Early Warning Score (EWS) as a predictor of SAP. Evaluation of the evidence for recombinant human protein C (Xigris™) in the early treatment of SAP. Determination of the safety profile of Xigris™ when given early in SAP. To determine if surgical management of ACS in SAP is of significant benefit compared to conventional management alone. Methods: Four studies were performed: A prospective observational study assessing the median EWS of patients admitted with acute pancreatitis; a systematic review of published evidence reporting the use of Xigris™ in SAP; a prospective cohort study using a 24 hour infusion of Xigris™ early in patients diagnosed with SAP and a pilot randomized controlled trial of targeted decompression in patients with ACS complicating SAP. Results: The highest EWS values for 130 patients with acute pancreatitis within the first 3 days of admission were not shown to have significant sensitivity and specificity in predicting an unfavourable outcome. A review of the published literature between from January 1985 to January 2011 supported the further investigation of Xigris™ as a treatment for SAP. No significant adverse events or differences in outcomes were evident in 19 patients who received a 24-hour infusion of Xigris™ early in SAP compared to matched historical controls. 22 patients were screened for the development of ACS. No patient developed ACS and consequently no randomization to either treatment arm was possible. Conclusion: With the recent advent of an updated classification system for the severity of acute pancreatitis, further prospective evaluation of the use of EWS in clinical practice is warranted. The results of the Phase 1 clinical trial of Xigris™ didnot reveal significant safety issues that might preclude the further investigation of Xigris™ as a specific therapy early in the onset of SAP. The absence of ACS inpatients with SAP lends support to a theory that ACS may be an epiphenomenon in the course of SAP.
Supervisor: Sibley, Colin ; Siriwardena, Ajith Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Pancreatitis ; Early warning score ; Activated protein C ; Xigris ; Abdominal compartment syndrome