Objective. Several tools have been developed for severity stratification in acute pancreatitis (AP). They include single biochemical markers and complex scoring systems, all of which aim at an early detection of severe AP to optimize monitoring and treatment of these patients. The aim of this study was to reassess and compare the value of some known and newly-introduced prognostic markers in the clinical context. Material and Methods. We have conducted a prospective observational study. One hundred and eight patients with a diagnosis of AP and onset of the disease within last 72 h were included in this study. Clinical data and expression results of some serum biochemical markers were used for statistical analysis. The diagnostic performance of scores predicting severity and progression of AP, cut-off values, specificity, and sensitivity were established using receiver operating characteristic curve analysis. Results. Among single biochemical markers, C-reactive protein remains the most useful. Despite its delayed increase, it is accurate, cheap, and widely available. Interleukin-6 and macrophage migration inhibitory factor seem to be new promising parameters for use in clinical routine. Pancreas specific scores (Imrie-Glasgow, pancreatitis outcome prediction) and scores assessing organ dysfunction (acute physiology and chronic health evaluation II, multiple organ dysfunction score, and Marshall score) remain of value in determining the severity, complications, and possible outcome of AP. Conclusions. Indication, timing, and consequences of the methods applied need to be carefully considered and incorporated into clinical assessments. Currently, there is no single prognostic marker that would cover the whole range of problems associated with the treatment of AP. The prediction of severity and progression of AP can be achieved using a series of accurate methods. The decision to undertake interventional or surgical treatment is the most complex task requiring both clinical judgment and meticulous monitoring of the patient.
Background. Acute pancreatitis is a potentially serious condition. It carries an overall mortality rate of 10–15%. Infectious complications account for approximately 80% of deaths from acute pancreatitis, and the question arises whether or not prophylactic antibiotics are useful in the prevention of these complications. Therefore, we performed an evidence-based analysis to assess the effect of available prophylactic antimicrobial treatment on the development of infected necrosis and sepsis, need for surgery, and mortality. Methods. A comprehensive PubMed search was performed evaluating the value of prophylactic administration of parenteral antibiotics in patients with acute necrotizing pancreatitis. Only articles published in English language between January 1990 and May 2006 were included. The search strategy initially generated 692 articles related to antibiotics in the treatment of acute pancreatitis. This number was reduced to 97 publications related to clinical trials on the same topic. Finally, 10 randomized clinical trials concerning prophylactic parenteral antibiotics in patients with acute necrotizing pancreatitis were identified. We have performed a meta-analysis using the random-effects model to assess the impact of prophylactic antibiotics on development of infected pancreatic necrosis and sepsis, need for surgery, and overall mortality. Results. Patients with necrotizing acute pancreatitis should receive effective antibiotic prophylaxis (i.e., carbapenems intravenously) to decrease the risk of infected necrosis and sepsis and need of surgery. Conclusions. While providing new insights into key aspects of antibiotic prophylaxis, this evidence-based analysis highlights the need for further clinical trials regarding the indications for antibiotic prophylaxis.
Pancreatic tumors are usually diagnosed at an advanced stage in the progression of the disease, thus reducing the survival chances of the patients. Non-invasive early detection would greatly enhance therapy and survival rates. Toward this aim, we investigated in a pilot study the power of methylation changes in whole blood as predictive markers for the detection of pancreatic tumors. We investigated methylation levels at selected CpG sites in the CpG rich regions at the promoter regions of p16, RARbeta, TNFRSF10C, APC, ACIN1, DAPK1, 3OST2, BCL2 and CD44 in the blood of 30 pancreatic tumor patients and in the blood of 49 matching controls. In addition, we studied LINE-1 and Alu repeats using degenerate amplification approach as a surrogate marker for genome-wide methylation. The site-specific methylation measurements at selected CpG sites were done by the SIRPH method. Our results show that in the patient’s blood, tumor suppressor genes were slightly but significantly higher methylated at several CpG sites, while repeats were slightly less methylated compared to control blood. This was found to be significantly associated with higher risk for pancreatic ductal adenocarcinoma. Additionally, high methylation levels at TNFRSCF10C were associated with positive perineural spread of tumor cells, while higher methylation levels of TNFRSF10C and ACIN1 were significantly associated with shorter survival. This pilot study shows that methylation changes in blood could provide a promising method for early detection of pancreatic tumors. However, larger studies must be carried out to explore the clinical usefulness of a whole blood methylation based test for non-invasive early detection of pancreatic tumors.
1 January 2007 in Scandinavian Journal of Gastroenterology
Objective. Fine-needle aspiration (FNA) is the procedure of choice for accurate diagnosis of infected necrosis. However, invasive procedures increase the risk of secondary pancreatic infection and the timing of FNA is still a matter for debate. Our objective was to assess the value of routine clinical tests to determine the minimal risk for infected necrosis, thereby optimizing timing and selection of patients for image-guided FNA. Material andmethods. This prospective, non-randomized study comprised 90 patients with acute necrotizing pancreatitis. The data of 52 patients were used for discriminant function analysis to determine the differences between patients with infected necrosis and those with sterile necrosis. Cut-off points for variables were established using receiver operating characteristic (ROC) curve analysis and logistic regression was performed to determine the risk of infected necrosis. The clinical relevance of the defined diagnostic system was prospectively tested in a further 38 consecutive patients with acute necrotizing pancreatitis (ANP). Results. Discriminant function analysis showed that C-reactive protein (CRP) and white blood cell (WBC) values were significant discriminators between patients with sterile necrosis and those with infected necrosis. Cut-off values of 81 mg/l for CRP and 13×109/l for WBC were established. The predicted risk for infected necrosis is approx. 1.4% if both tests are below the defined cut-off values. Consequently, we found FNA unnecessary in this subset of patients, unless otherwise indicated, as this invasive procedure per se carries a certain risk of bacterial contamination. Conclusions. Routine clinical tests are helpful in diagnosing the development of infected necrosis. Based on the application of classification functions, the timing and selection of patients for image-guided FNA can be optimized.