Exploration of factors affecting severity in acute pancreatitis

Acute Pancreatitis (AP) is associated with a significant mortality despite advances in critical care and surgical management of the disease. A significant subgroup of patients with AP will have complications including Multiple Organ Dysfunction Syndrome (MODS) and Infected Pancreatic Necrosis (IPN) which are associated with higher mortality rates. The pathophysiology of MODS is not yet fully understood but cytokines are known to play a role. Three factors influencing mortality in patients with acute pancreatitis have been identified. Firstly, the host response to acute inflammation, which determines the pattern of cytokine response and may be subject to genetic control. Secondly, the development of infected pancreatic necrosis and the influence of surgical strategies developed to deal with this. Thirdly, the nature of infecting organisms in patients with IPN. Aims The aims of this thesis are 1) To compare genetic polymorphisms in an interleukin-8 locus in a cohort of patients with AP and healthy controls with regard to severity and susceptibility 2) To examine a retrospective series of patients with infected pancreatic necrosis and compare open and percutaneous necrosectomy techniques with regard to organ dysfunction and mortality 3) To identify microbiological factors which may affect outcome in patients with infected pancreatic necrosis 1) Materials and Methods Previously collected DNA samples from 106 patients with predicted severe AP were subjected to sequence specific PCR of 6 Interleukin-8 single nucleotide polymorphisms (SNPs) and compared with 100 healthy control DNA samples. SNP frequencies were compared in patients with mild and severe disease and between patients and controls. Patients and Methods 2) Ninety-nine patients with infected pancreatic necrosis treated surgically at GRI between December 1989 and March 2002 were prospectively identified. Retrospective case note review was performed. Patients were divided into OPEN and PERC (percutaneous) groups for analysis. Outcome measures included mortality and ITU requirements. 3) The same IPN cohort was further analysed with respect to microbial spectrum, use of prophylactic antibiotics, development of resistant organisms and effect on mortality. Results 1) No differences in Interleukin-8 SNP frequencies were noted between mild and severe patients or between patients and controls. 2) Fifty-six and 49 patients underwent open and percutaneous pancreatic necrosectomy respectively. Mortality rates were similar in both groups. Significantly fewer patients in the PERC group required ICU post-operatively indicating a reduction in post-operative MODS. 3) The spectrum of microbial infection varied slightly over the study period. Prophylactic antibiotic usage has been avoided latterly in this unit but overall prophylactic antibiotic use has not changed significantly. Fungal infection was associated with higher mortality rates. Conclusions Several factors affecting severity have been identified in Acute Pancreatitis. From this work, it has been demonstrated that: 1) Six hiterleukin-8 polymorpliisms do not seem to be related to disease severity or susceptibility in a cohort of AP patients 2) Minimally invasive pancreatic necrosectomy reduces post-operative MODS in patients with IPN and may improve mortality with continued improvements in technique. 3) Fungal infection is associated with higher mortality rates in patients with IPN.