Acute pancreatitis: update on management.

Acute pancreatitis is a common acute surgical condition associated with high morbidity and mortality in severe cases. New guidelines for management have recently been published by the American College of Gastroenterology and by the International Association of Pancreatology in collaboration with the American Pancreatic Association. The main differences between the new and previous versions of the guidelines relate to the use of endoscopic retrograde cholangiopancreatography (ERCP) and the addition of the new severity category of 'moderately severe acute pancreatitis' All patients with pancreatitis should have its cause determined by features of the history, results of laboratory tests (liver function tests, serum calcium triglyceride levels) and findings on transabdominal ultrasound. Those with idiopathic pancreatitis should have endoscopic ultrasound as a first-line investigation. Acute pancreatitis should be managed with aggressive hydration with intravenous fluids and fasting. Oral feeding can be recommenced in mild pancreatitis once pain and nausea and vomiting have resolved. Patients with mild biliary pancreatitis should have a laparoscopic cholecystectomy during their index admission. In addition to aggressive intravenous fluid resuscitation and fasting, patients with severe pancreatitis should have enteral feeding (nasoenteric or nasogastric feeds) commenced 48 hours after presentation. Total parenteral nutrition should be avoided where possible. All patients with organ failure or severe pancreatitis as defined by the revised version of the Atlanta classification should be managed in an intensive care setting. Patients with biliary pancreatitis and concurrent cholangitis should have endoscopic retrograde cholangiopancreatography within 24 hours of presentation.

Gene Expression Profiling: Identification of Novel Pathways and Potential Biomarkers in Severe Acute Pancreatitis.

BACKGROUND: Determining the risk of developing severe acute pancreatitis (AP) on presentation to hospital is difficult but vital to enable early management decisions that reduce morbidity and mortality. The objective of this study was to determine global gene expression profiles of patients with different acute pancreatitis severity to identify genes and molecular mechanisms involved in the pathogenesis of severe AP. STUDY DESIGN: AP patients (n = 87) were recruited within 24 hours of admission to the Emergency Department and were confirmed to exhibit at least 2 of the following features: (1) abdominal pain characteristic of AP, (2) serum amylase and/or lipase more than 3-fold the upper laboratory limit considered normal, and/or (3) radiographically demonstrated AP on CT scan. Severity was defined according to the Revised Atlanta classification. Thirty-two healthy volunteers were also recruited and peripheral venous blood was collected for performing RNA-Seq. RESULTS: In severe AP, 422 genes (185 upregulated, 237 downregulated) were significantly differentially expressed when compared with moderately severe and mild cases. Pathway analysis revealed changes in specific innate and adaptive immune, sepsis-related, and surface modification pathways in severe AP. Data-driven approaches revealed distinct gene expression groups (endotypes), which were not entirely overlapping with the clinical Atlanta classification. Importantly, severe and moderately severe AP patients clustered away from healthy controls, whereas mild AP patients did not exhibit any clear separation, suggesting distinct underlying mechanisms that may influence severity of AP. CONCLUSION: There were significant differences in gene expression affecting the severity of AP, revealing a central role of specific immunological pathways. Despite the existence of patient endotypes, a 4-gene transcriptomic signature (S100A8, S100A9, MMP25, and MT-ND4L) was determined that can predict severe AP with an accuracy of 64%.

Anterior hippocampus in schizophrenia pathogenesis: molecular evidence from a proteome study.

OBJECTIVE: The purpose of the present study was to identify differentially expressed proteins in the anterior and posterior hippocampus of brains of schizophrenia patients compared to neurologically healthy controls. METHOD: Proteins extracted from fresh frozen post-mortem posterior and anterior hippocampus for nine schizophrenia and nine control individuals, and seven schizophrenia and seven control individuals, respectively, were screened for differential expression using 2-D gel electrophoresis and mass spectrometry. RESULTS: A significantly larger number of protein spots were differentially expressed in the anterior (n = 43) compared to the posterior (n = 16) hippocampus, representing 34 and 14 unique proteins, respectively. These proteins are involved in cytoskeleton structure and function, neurotransmission and mitochondrial function. CONCLUSION: Based on the aberrant protein expression profiles, the anterior hippocampus appears to be more involved in schizophrenia pathogenesis than the posterior hippocampus. Furthermore, consistent with previous findings, we found molecular evidence to support abnormal neuronal cytoarchitecture and function, neurotransmission and mitochondrial function in the schizophrenia hippocampus.

Study of the early management of acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a common acute surgical presentation with evidence-based guidelines for early management. The aim of this study was to assess the compliance to the published guidelines in patients presenting with AP in Western Sydney. METHODS: A retrospective case note audit was conducted for all patients with a confirmed diagnosis of AP from 2008 to 2011 in Western Sydney. RESULTS: There were 932 patients. The mortality was low for mild (0.7%) and severe (1.2%) AP. There was an under-utilization of ultrasound (U/S) with 239 (25.6%) patients not having a U/S. There was an over-utilization of early (within 72 h) computed tomography scanning for diagnosis (31.1%), assessment of severity (16.1%) and assessment for the presence of complications (7.3%). Inappropriate prophylactic antibiotic usage occurred in 15.3% patients. Of 373 cases of gallstone pancreatitis, only 231 (69.1%) had a cholecystectomy within 4 weeks of presentation. There was an under-utilization of early endoscopic retrograde cholangiopancreatography for associated cholangitis (12.5%). Only 16 (18.8%) patients with severe pancreatitis received enteric feeding. In patients with pancreatic necrosis, 50% had invasive intervention delayed beyond 4 weeks and 69% had minimally invasive procedures performed prior to necrosectomy. Patients having a minimally invasive procedure initially showed an improvement in mortality compared with those who had primary necrosectomy (0 versus 40%, P = 0.025). CONCLUSIONS: Although morbidity and mortality were acceptable, there was a failure to comply with evidence-based guidelines for the early management of pancreatitis. The results support for the development and auditing of protocols for the early assessment and treatment of AP in all hospitals.

Epidemiology, aetiology and outcomes of acute pancreatitis: A retrospective cohort study.

BACKGROUND: Acute pancreatitis is a common acute surgical presentation in Western Society. The causes and pattern of pancreatitis has not been previously documented for Western Sydney. As Western Sydney contains many areas of low socio-economic status with an expected high level of alcohol abuse, it was hypothesised that alcoholic pancreatitis would be more prevalent in this population. The aims of this study were to determine the epidemiology, aetiology and outcomes of acute pancreatitis. METHODS: A retrospective analysis of patients presenting with acute pancreatitis to four tertiary hospitals over a four-year period was undertaken. RESULTS: 932 patients presented with acute pancreatitis with a median age of 50 years (range 16-95); 470 (50.4%) were female. Almost half had gallstones (40%), 25.6% idiopathic, 22% alcohol induced and 3.9% post ERCP. 69 (7.4%) of patients were admitted to ICU/HDU, with a median length of stay in ICU was 6 days (range 1-106). 85 (11.1%) patients had severe pancreatitis (score ≥ 3). Mortality in this study was 1% (9). CONCLUSION: The majority of patients with acute pancreatitis in Western Sydney present with mild disease and have a low risk of morbidity or mortality. The ratio of gallstone to alcohol aetiology was 2:1. Idiopathic pancreatitis is responsible for more cases than expected.