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Background: Acute pancreatitis remains as one of the most difficult and challenging digestive disorder to predict in terms of clinical course and outcome. Every case has an individual course and therefore acute pancreatitis remains challenging and fascinating. Due to this variability, many different scoring systems have evolved during the last decades. Every scoring system has advantages and disadvantages. Not every scoring system is capable of assessing the clinical time course of the disease, some are only suitable for the time of initial presentation., Aim: This paper will give an overview on the development of different widely used scoring systems and their performance in assessing severity and prognosis of acute pancreatitis., Conclusion: Severity assessment means objective quantification of overall severity of illness. Early and reliable stratification of severity is required to decide best treatment of the individual patient, preparation for possible evolving complications or for referral to specialist centers. No single scoring system is able to cover the entire range of problems associated with treatment and assessment of acute pancreatitis. In our clinical experience, we recommend hematocrit upon admission, daily sequential organ failure assessment score and procalcitonin, C-reactive protein on day 3 and CT severity index beyond the first week. These scoring tools together with close clinical follow-up of the patient ultimately lead to an optimized treatment of this challenging disease.

The biomarker procalcitonin (PCT) has been used to diagnose and monitor a number of clinically significant infections. Serum levels of PCT are often increased in the presence of bacterial and fungal infections but not viral infections or noninfectious inflammation. Intra-abdominal infections (IAIs) are serious conditions that pose difficult challenges to physicians and the healthcare system. Researchers have evaluated PCT in the management of IAIs, both for diagnosis and for guiding antibiotic therapy. The studies have produced mixed results, leading to controversy on the utility of PCT in IAIs. PCT appears to be most useful in diagnosing postoperative infections and necrotizing pancreatitis. This review aims to summarize these data, explore the pathophysiology of PCT in sepsis from IAIs, discuss the strengths and weaknesses of PCT monitoring in IAIs, and provide guidance for the interpretation of PCT levels.

Background: Many studies have evaluated serum levels of procalcitonin (PCT) as a predictor in the development of severe acute pancreatitis (SAP) and infected pancreatic necrosis (IPN). This study assesses the value of PCT as a marker of development of SAP and IPN., Methods: Medline, Web of Science, the Cochrane clinical trials register, and international conference proceedings were searched systematically for prospective studies, which evaluated the usefulness of PCT as a marker of SAP and IPN. The sensitivity, specificity, and diagnostic odds ratios (DORs) were calculated for each study, and the study quality and heterogeneity among the studies were evaluated., Results: Twenty-four of 59 studies identified were included in data extraction. The sensitivity and specificity of PCT for development of SAP were 0.72 and 0.86, respectively (area under the curve [AUC] = 0.87; DOR = 14.9; 95% confidence interval [CI] = 5.6-39.8), albeit with a significant degree of heterogeneity (Q = 28.56, P < .01). The sensitivity and specificity of PCT for prediction of infected pancreatic necrosis were 0.80 and 0.91 (AUC = 0.91; DOR = 28.3; 95% CI = 13.8-58.3) with no significant heterogeneity (Q = 7.83, P = .18). No significant heterogeneity was observed among the studies when only higher quality studies (AUC = 0.91; DOR = 30.7; 95% CI = 10.7-87.8) or studies that used a cutoff PCT level >0.5 ng/mL (AUC = 0.88, 32.8; 95% CI = 10.1-106.6) were included., Conclusion: Serum measurements of PCT may be valuable in predicting the severity of acute pancreatitis and the risk of developing infected pancreatic necrosis.

Background/aims: Authors analyzed the clinical value of procalcitonin quick test (PCT-Q; BRAHMS Diagnostica, GmbH, Berlin) in infected pancreas necrosis verified by guided fine-needle aspiration (FNA)., Methodology: In the prospective, controlled study data of 24 patients were evaluated. PCT-Q was performed in patients with necrosis--verified on computer tomography (CT scan)--and/or sepsis. If PCT-Q test was positive or septic complication (infected necrosis or abscess) developed, CT or ultrasound (US) guided fine-needle aspiration was performed with Gram staining and bacteriology. Positive FNA result was indication for surgery with repeated staining and bacteriology of the surgical specimen., Results: Septic complications developed in 12 patients. Analyzing the results, fine-needle aspiration was more authentic with 92% sensitivity and 100% specificity, while sensitivity of PCT-Q test remained 75% and its specificity 83%. Comparing abscess with infected necrosis significantly higher procalcitonin values were detected in patients with necrosis., Conclusions: These results show that PCT-Q test is a possible non-invasive method which can be used besides fine-needle aspiration. Elevated levels of procalcitonin (higher than 2ng/mL) clearly suggest infection, while lower values do not exclude the possibility of local sepsis.

We compared the manually performed LUMItest procalcitonin (PCT) assay with the newly developed fully mechanized Kryptor PCT assay and determined the essential assay characteristics of this assay. The new Kryptor PCT assay was evaluated according to modified NCCLS EP-10/EP-6 protocols in five different laboratories. Samples from 696 patients were assayed using the original LUMItest PCT assay and the new Kryptor PCT assay. Possible interference by hemoglobin, triglycerides and bilirubin was evaluated by spiking patient plasma with the appropriate substances. The functional assay sensitivity (FAS) was determined by analyzing samples with low PCT concentrations. The FAS of the new Kryptor PCT assay was 0.04 ng/ml and the imprecision within- and between-series below 5% and below 10%, respectively. Within the smallest range of determination, from 0.3 ng/ml to 50 ng/ml, common to the LUMItest PCT assay (x) and the Kryptor PCT assay (y) the values correlated well: y=0.64+0.94x, s.xy=2.78 ng/ml. The performance characteristics of the Kryptor PCT assay are fully compatible with the intended clinical use. The assay allows determination of PCT in a turnaround time (TAT) of about 20 minutes and thus is adequate for STAT analyses.

Background: Infection of necrosis is a major risk factor in patients with acute pancreatitis. Systematic use of broad spectrum antibiotics has been recommended in these patients but may induce serious side effects. To better target patients in whom antibiotic prophylaxis could be beneficial, we evaluated whether early serum profiles of interleukin 6 (IL-6), tumor necrosis factor (TNF-alpha, C reactive protein (CRP) and procalcitonin (PCT) help to discriminate between patients who eventually develop infection of necrosis and those who do not., Methods: Forty-eight patients with acute pancreatitis and a computed tomography (CT) severity index score of more than 3 were prospectively screened. They were then separated into infected and non-infected groups according to the occurrence of infected pancreatic necrosis. The severity of illness was assessed with Ranson's classification and Simplified Acute Physiologic Score II. Serum levels of IL-6, TNF-alpha, CRP, and PCT were measured during the first 3 days after admission. CT-guided fine needle aspiration of pancreatic necrosis was performed to prove infection when sepsis of abdominal origin was suspected. Using the methodology of receiver operating curves, we determined the presence of a threshold for markers that would be predictive of the development of infected necrosis., Results: PCT and IL-6 were higher in the serum of patients who eventually developed infection of necrosis (P < 0.003 and < 0.04, respectively). No difference was noted between the 2 groups for TNF- alpha and CRP. The combination of IL-6 < 400 pg/l and PCT < 2 ng/L best identified patients who were not at risk for necrosis infection. The negative predictive value for these thresholds was 91%, whereas sensitivity and specificity were 75% and 84%., Conclusions: PCT and IL-6 serum levels were elevated very early in patients who eventually developed necrosis infection. A combination of PCT and IL-6 thresholds could be helpful in identifying a subgroup of patients in whom antibiotic prophylaxis is likely to be ineffective.

Procalcitonin (PCT). a new marker proposed as a diagnostic tool for bacterial infections, triggers a systemic-inflammatory reaction in the body (sepsis, septic shock) and has potential use in a wide range of patient settings. To interpret the results from PCT measurements, we depend on reference intervals established from relevant populations. PCT and C-reactive protein (CRP) concentrations were analysed in 47 patients with a normal postoperative course after major abdominal surgery. The mean concentration of PCT declines from the first day and reaches half its initial values on the second day after the operation. whereas the mean concentration of CRP increases in the first 48 h and reaches half its maximum value on the fifth day after the operation. We present a continuous reference interval for plasma PCT and CRP concentrations in the first week following major abdominal surgery. For PCT we also present a graphic display of expected mean and expected upper reference limits predicted from the value measured on the first postoperative day.

Procalcitonin test (PCT) has been proposed to check severity of generalized infections or sepsis. The authors measured the PCT values with PCT-Q quick test (BRAHMS DIAGNOSTICA GmbH, Berlin) at 14 surgical patients treated in their intensive care unit (7 sepsis, 4 peritonitis, 2 localized pancreatic abscess, 1 postoperative fever). At 3 septic patients (2 pancreatitis, 1 intestinal necrosis) they measured the PCT levels repeatedly during treatment. In 2 patients with localized pancreatic abscess and in 1 patient with postoperative fever without evidence of infection the PCT levels were low (< 0.5 ng/ml). At 4 patients with peritonitis following gastric or colon perforation the PCT levels were highly elevated (> 10 ng/ml). At 7 patients with severe sepsis the PCT values were high (> 2 ng/ml), except for 1 patient with intestinal necrosis. At this patient the PCT levels were repeatedly low. In 2 septic patients with pancreatitis elevated PCT levels indicated the need for surgery. In most patients PCT was a good indicator of generalized infections. PCT levels measured repeatedly in sepsis were lower than in patients with peritonitis.

Background: Infected pancreatic necrosis (IPN) is an absolute indication for surgical intervention, therefore an early and accurate laboratory diagnosis is necessary to confirm the infection. The aim of the study was to analyze the clinical value of procalcitonin (PCT) for the prediction of infected necrosis, in comparison with interleukin-6 (IL-6) and sICAM 1., Patients and Methods: A total of 30 patients were investigated; 10 patients with sterile pancreatic necrosis (SPN), 10 with IPN, and 10 with sepsis of different origin. The concentrations of PCT in the patients' sera were measured by immunoluminometric assay (BRAHMS Diagnostica, Berlin, Germany, PCT Lumitest), the IL-6 concentrations by bioassay, applying the B-9 cell line, and the sICAM-1 levels by enzyme-linked immunosorbent assay (ELISA) (R&D). PCT was determined in cell lysates by ECL Western blot., Results: PCT was found in relatively high concentrations (8.5 +/- 4.8 ng/mL) only in patients with infected pancreatic necrosis, and in patients with sepsis of different origin ( 15 +/- 5.4 ng/mL). Positive values (> 1 ng/mL) preceded positive bacterial results from either blood or surgical samples. None of the serum samples of patients with SPN exhibited PCT concentrations higher than 1.2 ng/mL. In contrast, IL-6 and sICAM-1 were overproduced in both types (infected and sterile) of pancreatic necrosis, and their levels remained elevated for several days even after surgical elimination of the infected focus (widespread necrosectomy and continuous lavage). Sensitivity, specificity, and positive predictive values for discriminating IPN from SPN was 90, 100, and 100% for PCT (p < 0.0001); 100, 20, and 55% for IL-6 (p 0.474 n.s.) and 90, 10, and 50% for sICAM-1 (p 1.000 n.s.). Immunoblotting revealed no PCT in patients' leukocytes, or in human endothelial cell lines., Conclusion: Elevated serum IL-6 and sICAM-1 levels are characteristic in systemic inflammatory response syndrome (SIRS) of either infectious or noninfectious origin. In contrast, the PCT level is an accurate, readily available parameter that allows the discrimination of IPN, and is a helpful marker facilitating a decision concerning surgical intervention.

Objective: Infection of pancreatic necrosis (IN) has a major impact on management and outcome in acute pancreatitis (AP). Currently, guided fine-needle aspiration (FNA) is the only means for an accurate diagnosis of IN. Procalcitonin (PCT), a 116 amino acid pro-peptide of calcitonin has been found in high concentrations in patients with sepsis. In the present study we analyzed the clinical value of serum PCT for predicting IN in AP and compared the results to guided FNA., Design: Clinical study., Setting: A collaborative study between the Departments of General Surgery and Clinical Chemistry/ Pathobiochemistry of the University of Ulm, Germany., Patients: 61 patients with AP entered this study and were stratified into three groups according to morphological and bacteriological data: I. 22 patients with edematous pancreatitis (AIP), II. 18 patients with sterile necrosis (SN), III. 21 patients with IN., Measurements and Results: During an observation period of 14 days PCT was measured by immunoluminometry, CRP was determined by lasernephelometry on a routine base. In patients with IN overall PCT concentrations were significantly higher than in those with SN, whereas CRP levels did not differ in both groups. In contrast, only low concentrations of both parameters were found in patients with AIP. By ROC analysis the best PCT cut-off level for predicting IN or persisting pancreatic sepsis was obtained at > or =1.8 ng/ml. If this cut-off was reached on at least two consecutive days, IN could be predicted with a sensitivity of 95%, a specificity, of 88%, and an accuracy of 90%. Guided FNA achieved a sensitivity, specificity, and accuracy of 91%. 79%, and 84% in differentiating IN from SN, respectively. After surgical treatment of IN median PCT values continued to be significantly higher in patients with persisting pancreatic sepsis (n=12) compared to those with an uneventful postoperative course (n=7). Our results demonstrate that monitoring of serum PCT could serve as a noninvasive and accurate method to predict IN in AP as well as to select patients with persisting septic complications after surgical debridement.

Background: Infected pancreatic necrosis (IPN) is the main cause of death in patients with severe acute pancreatitis. Therefore an early prediction of IPN is of utmost importance., Aim: Analysis of new blood variables as potential early predictors to differentiate between IPN and sterile pancreatic necrosis (SPN)., Patients: 64 consecutive patients with acute pancreatitis were enrolled in this prospective study; 29 were suffering from acute oedematous pancreatitis (AIP), and 35 from necrotising disease (NP) as diagnosed by contrast enhanced computed tomography., Methods: Procalcitonin (PCT) and granulocyte colony stimulating factor (G-CSF) in the serum were examined and compared with C reactive protein (CRP). CRP was measured with a turbidimetric immunoassay (Autokit CRP; Wako, Osaka, Japan), and PCT and G-CSF by ELISA (Lumitest PCT; Brahms Diagnostica, Berlin, Germany; G-CSF-Elisa; R&D Systems, Abingdon, Oxon, UK). Monitoring was performed daily and related to the onset of symptoms., Results: Within the first week, all three variables (CRP, PCT, and G-CSF) were significantly higher in patients with NP than in those with AIP (CRP, p<0.001; G-CSF, p<0. 001; PCT, p<0.001). During the course of the study, 12 of the 35 patients with NP developed late IPN after a median of 20.5 (range 3-49) days. Neither the peak nor the lowest concentrations during the monitoring period were of any value for predicting IPN (median peak values in SPN v IPN: PCT, 0.93 v 1.93 ng/ml; G-CSF, 347 v 421 pg/ml; CRP, 270 v 325 mg/l)., Conclusions: Serum PCT, G-CSF, and CRP concentrations are of similar value for early differentiation between mild and severe acute pancreatitis. However, these variables are not suitable for the early prediction of IPN.

Background: Infection of pancreatic necrosis has a major impact on clinical course, management, and outcome in acute pancreatitis. Currently, guided fine needle aspiration is the only means for an early and accurate diagnosis of infected necrosis. Procalcitonin (PCT), a 116 amino acid propeptide of calcitonin, and interleukin 8 (IL-8), a strong neutrophil activating cytokine, are markers of severe inflammation and sepsis., Aims: To analyse the clinical value of PCT and IL-8 as biochemical parameters for predicting infected necrosis in acute pancreatitis., Patients and Methods: Fifty patients with acute pancreatitis entered this prospective study and were stratified into three groups according to morphological and bacteriological findings: 18 patients with oedematous pancreatitis (group I), 14 patients with sterile necrosis (group II), and 18 patients who developed infected necrosis a median of 13.5 days after the onset of symptoms (group III). After admission serum samples were drawn daily for two weeks. Concentrations of PCT and IL-8 were measured by chemoluminescent immunoassays (upper reference range 0.5 ng/ml for PCT and 70 pg/ml for IL-8). The routine parameter C-reactive protein was determined by laser nephelometry (upper reference range 10 mg/l)., Results: Median concentrations of PCT and IL-8 were significantly higher in patients with infected necrosis than in those with sterile necrosis during the observation period, whereas there was no difference in C-reactive protein. In oedematous pancreatitis overall median concentrations of all three parameters were low. By receiver operating characteristics best cut off levels for predicting infected necrosis or persisting pancreatic sepsis were 1.8 ng/ml for PCT and 112 pg/ml for IL-8. If these cut off levels were reached on at least two days, sensitivity, specificity, and accuracy for the prediction of infected necrosis were 94%, 91%, and 92% for PCT and 72%, 75%, and 74% for IL-8, respectively. After surgical treatment of infected necrosis median PCT and IL-8 values continued to be significantly higher in patients with persisting pancreatic sepsis (n = 11) compared with those having an uneventful postoperative course (n = 7). For the preoperative differentiation between infected necrosis and sterile necrosis guided fine needle aspiration was performed in 24 patients with necrotising pancreatitis and reached a diagnostic accuracy of 84% compared with 87% for PCT, and 68% for IL-8. There was no correlation between the aetiology of acute pancreatitis or the extent of necrosis and PCT or IL-8., Conclusion: PCT and IL-8 are found in high concentrations in infected necrosis and associated systemic complications in patients with acute pancreatitis. The course of PCT shows the closest correlation with the presence of infected necrosis. Monitoring of serum PCT is a potential new marker for the non-invasive and accurate prediction of infected necrosis as well as for the selection of patients with persisting septic complications after surgical debridement.

Procalcitonin is a protein which is found in elevated concentrations in the blood circulation during systemic bacterial, fungal or protozoal infection. In contrast to classical acute-phase proteins like C-reactive protein or interleukin-6, it is not elevated after operative trauma. In this paper we present current opinions on the assumed induction mechanisms of the protein by cytokines and endotoxin. Furthermore, the clinical value for early detection of systemic infections in abdominal and transplantation surgery is demonstrated by examples from the literature. Our investigation shows that eight patients with necrotizing pancreatitis had a PCT mean value of 6.9 ng/ml on the day of admission. Seven patients with edematous pancreatitis had only a PCT mean value of 0.69 ng/ml. Despite these differences in the mean values, a significant difference between the normal value and the mean value of the group with necrotizing pancreatitis or edematous pancreatitis was not observed due to the wide range of PCT levels in the group of patients with necrotizing pancreatitis. The fact that only a few of the patients had a superinfected necrosis with systemic evasion of bacterias or their toxins may be the reason for this wide range. We suggest that a discrimination between superinfected necrotizing or sterile pancreatitis and edematous pancreatitis by PCT could be possible but more extensive studies with microbiological examination of the necrotic material are required to recognize the subgroups and to establish the real diagnostic efficiency of PCT in clinical practice, especially in the prediction of the outcome of acute pancreatitis.