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... hepatocytes and G-cells of the thyroid gland [56]. It is an acute phase reactant that has been extensively investigated as earlymarker in systemic bacterial infection, sepsis, and multiorgan failure =-=[68]-=-. Because severe acute pancreatitis is associated with sepsis, infected pancreatic necrosis, and multiorgan failure, procalcitonin can be used as a useful marker in early prediction of severity [69]. ...

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...of AP over the last few decades, although the case fatality rate has remained unchanged [7]. This may either be due to increased incidence of gallstone disease or improvement in diagnostic modalities =-=[8]-=-. The revised Atlanta classification system has classified AP into mild, moderate, and severe [9, 10]. More than 80% of acute pancreatitis attacks are mild and self-limiting and resolve without seriou...

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... but reaches up to 30%–40% in patients with severe disease [13, 14]. Sepsis related multiorgan failure and infected pancreatic necrosis account for about 40–50% of all mortality in acute pancreatitis =-=[13, 15, 16]-=-. Mortality in AP occurs in two peaks [17–21]. Nearly 50% of deaths occur early within the first week due tomassive inflammatory responses leading to multiorgan failure. Septic complications related t...

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...rypsin in pancreatic parenchyma acting as the central step in the initiation of autodigestion of pancreatic tissue and subsequent local and systemic inflammation is presently the most accepted theory =-=[17, 18, 30, 31]-=-. Whatever is the initiating event, the disease progression can be viewed as a threephase continuum: local inflammation of the pancreas and a generalized inflammatory response followed by the final st...

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...rypsin in pancreatic parenchyma acting as the central step in the initiation of autodigestion of pancreatic tissue and subsequent local and systemic inflammation is presently the most accepted theory =-=[17, 18, 30, 31]-=-. Whatever is the initiating event, the disease progression can be viewed as a threephase continuum: local inflammation of the pancreas and a generalized inflammatory response followed by the final st...

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...thereby reducing the financial implications. 5. Role of Biomarkers in Prediction of Severe Acute Pancreatitis Severity assessment in acute pancreatitis was first started in 1974 by late Ranson et al. =-=[54]-=-. Since then a number of multifactorial scoring systems using common clinical and biochemical parameters have been described for prediction of severity. Ranson, Glasgow, andAPACHE II score are few of ...

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...related to infected pancreatic necrosis leading to multiorgan failure are the prime cause of death, late in the disease [17– 21]. The course and severity of AP can fluctuate rapidly and unpredictably =-=[1, 22]-=-. Despite the advances in investigational modalities and research techniques, the exact pathogenesis of AP is still unclear [18, 23–25]. Recent studies have suggested the role of inflammatorymediators...

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... and specificity of PCT for development of SAP were 73% and 87%, respectively, and overall area under curve (AUC) was 0.88. However, there was significant heterogeneity among individuals in the study =-=[73]-=-. In their study, Khanna et al. found 100% sensitivity of procalcitonin for prediction of organ failure andmortality, with a sensitivity of 86.4% for prediction of SAP [56]. Like that of Interleukin6,...

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...rypsin in pancreatic parenchyma acting as the central step in the initiation of autodigestion of pancreatic tissue and subsequent local and systemic inflammation is presently the most accepted theory =-=[17, 18, 30, 31]-=-. Whatever is the initiating event, the disease progression can be viewed as a threephase continuum: local inflammation of the pancreas and a generalized inflammatory response followed by the final st...

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...y Stratification and Its Assessment Acute pancreatitis is self-limiting in 75%–80% of cases and does not require any treatment other than parenteral intravenous fluid, analgesics, and supportive care =-=[4, 22, 23]-=-. The remaining may suffer from severe attacks, with the mortality reaching up to 30%–50% [18]. This subgroup of patients needs to be identified early in the course of the disease and needs to be aggr...

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... but reaches up to 30%–40% in patients with severe disease [13, 14]. Sepsis related multiorgan failure and infected pancreatic necrosis account for about 40–50% of all mortality in acute pancreatitis =-=[13, 15, 16]-=-. Mortality in AP occurs in two peaks [17–21]. Nearly 50% of deaths occur early within the first week due tomassive inflammatory responses leading to multiorgan failure. Septic complications related t...

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...rypsin in pancreatic parenchyma acting as the central step in the initiation of autodigestion of pancreatic tissue and subsequent local and systemic inflammation is presently the most accepted theory =-=[17, 18, 30, 31]-=-. Whatever is the initiating event, the disease progression can be viewed as a threephase continuum: local inflammation of the pancreas and a generalized inflammatory response followed by the final st...

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... may either be due to increased incidence of gallstone disease or improvement in diagnostic modalities [8]. The revised Atlanta classification system has classified AP into mild, moderate, and severe =-=[9, 10]-=-. More than 80% of acute pancreatitis attacks are mild and self-limiting and resolve without serious complications. In 20% of cases, however, it can be severe and complicated by major morbidity or mor...

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...than 80% of acute pancreatitis attacks are mild and self-limiting and resolve without serious complications. In 20% of cases, however, it can be severe and complicated by major morbidity or mortality =-=[3, 11, 12]-=-. Moderate acute pancreatitis is characterized by the presence of transient organ failure or local/systemic complications [10]. Persistent organ failure is the feature of severe acute pancreatitis whi...

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...46]. Sensitivity and specificity of amylase as a diagnostic test for AP depend on its threshold value. At a cut-off level of 1000 IU/L, it has a sensitivity of around 55–84% and specificity up to 95% =-=[36, 38, 46, 47]-=-. Journal of Biomarkers 3 Impaired Cell Membrane Trafficking Acinar cell damage (1) Fusion of lysosomal and zymogen grannule Trypsinogen Trypsin (2) Trypsin activates zymogen cascade (3) Secretory ves...

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...y Stratification and Its Assessment Acute pancreatitis is self-limiting in 75%–80% of cases and does not require any treatment other than parenteral intravenous fluid, analgesics, and supportive care =-=[4, 22, 23]-=-. The remaining may suffer from severe attacks, with the mortality reaching up to 30%–50% [18]. This subgroup of patients needs to be identified early in the course of the disease and needs to be aggr...

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...) or transabdominal ultrasonography. The pancreatic enzymes derived from pancreatic acinar cells [amylase, lipase, and the proenzyme trypsinogen] are the cornerstone in the laboratory diagnosis of AP =-=[36]-=-. Serum lipase is a more sensitive and specific biochemical marker of AP than the more frequently used amylase. Moreover, serum amylase level offers no additional advantage if simultaneously measured ...

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...le to either gallstone disease or alcohol abuse [3, 4]. The incidence is similar in both sexes, although alcohol abuse is the more common cause in men and gallstones is the more common cause in women =-=[5, 6]-=-. There is an upsurge in the incidence of AP over the last few decades, although the case fatality rate has remained unchanged [7]. This may either be due to increased incidence of gallstone disease o...

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...ue for assessing the same [65]. 5.2. C-Reactive Protein (CRP). CRP is an acute phase reactant synthesized by the hepatocytes and is usually elevated in Journal of Biomarkers 5 inflammatory conditions =-=[66]-=-. Cytokines like IL-6 are potent inducers of CRP synthesis in liver. It takes nearly 72 hours for the serum level of CRP to peak after the onset of symptoms [56]. It is the most frequently used single...

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...a predictor of severity in AP [56]. At this cut-off level, CRP has a sensitivity of 80–86% and specificity of 61–84% for diagnosing necrotizing pancreatitis within first 48 hours of onset of symptoms =-=[56, 67]-=-. In their study, Khanna et al. found a 100% sensitivity and 81.4% specificity for detection of pancreatic necrosis [56]. The demerit of CRP as marker is its delayed peak (48–72 hours) and its nonspec...

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...46]. Sensitivity and specificity of amylase as a diagnostic test for AP depend on its threshold value. At a cut-off level of 1000 IU/L, it has a sensitivity of around 55–84% and specificity up to 95% =-=[36, 38, 46, 47]-=-. Journal of Biomarkers 3 Impaired Cell Membrane Trafficking Acinar cell damage (1) Fusion of lysosomal and zymogen grannule Trypsinogen Trypsin (2) Trypsin activates zymogen cascade (3) Secretory ves...

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...ion for diagnosis of acute pancreatitis include pancreatic isoamylase, pancreatic elastase, serum trypsin, urinary trypsinogen activated peptide (TAP), Phospholipase A2, and Carboxypeptidase B (CAPB) =-=[39, 40]-=-. Serum trypsin and elastase are of particular interest because of their longer half-life which makes them useful in diagnosis during delayed presentations [41]. These tests, however, have not found m...

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...e A2, and Carboxypeptidase B (CAPB) [39, 40]. Serum trypsin and elastase are of particular interest because of their longer half-life which makes them useful in diagnosis during delayed presentations =-=[41]-=-. These tests, however, have not found much favor in clinical application because of a variety of reasons including inferior diagnostic accuracy compared to amylase and lipase, cumbersome techniques, ...

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...e, which is an integral part of severe acute pancreatitis [57]. Among various proinflammatory and antiinflammatory cytokines, IL-6 has the best sensitivity and specificity for early assessment of SAP =-=[58]-=-. With a cutoff value of 50 pg/mL, Jiang et al. have found a sensitivity and specificity of 100% and 89.7%, respectively [59]. With a similar cut-off level, Khanna et al. found a sensitivity of 93.1% ...

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... IL-6 has the best sensitivity and specificity for early assessment of SAP [58]. With a cutoff value of 50 pg/mL, Jiang et al. have found a sensitivity and specificity of 100% and 89.7%, respectively =-=[59]-=-. With a similar cut-off level, Khanna et al. found a sensitivity of 93.1% and specificity of 96.8% in their study [56]. The major drawback of IL-6 assay is that its serum concentration decreases very...

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...egative predictive values were 78% and 96%, respectively, and the area under the receiver operator curve was 0.956 [74]. Similar result has been found by Gross et al. and Wilson et al. in their study =-=[75, 76]-=-. More recent studies, however, by a Swiss group and the Japanese have yielded conflicting results [77, 78]. Domı́nguez-Muñoz et al. found quantification of plasma PMN elastase levels as a very accur...

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...atitis CAPAP level correlated well, with an accuracy of 92%, in predicting development of pancreatic necrosis, whereas the level of its proenzyme did not show any correlation with pancreatic necrosis =-=[87]-=-. Both CAPAP and urinary TAP are excellent prognostic markers, although TAP is a better marker on the day of admission [88]. 5.6.4. Trysinogen-2. In acute pancreatitis the level of trysinogen-2 rises ...

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...mmon cause in men and gallstones is the more common cause in women [5, 6]. There is an upsurge in the incidence of AP over the last few decades, although the case fatality rate has remained unchanged =-=[7]-=-. This may either be due to increased incidence of gallstone disease or improvement in diagnostic modalities [8]. The revised Atlanta classification system has classified AP into mild, moderate, and s...

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...than 80% of acute pancreatitis attacks are mild and self-limiting and resolve without serious complications. In 20% of cases, however, it can be severe and complicated by major morbidity or mortality =-=[3, 11, 12]-=-. Moderate acute pancreatitis is characterized by the presence of transient organ failure or local/systemic complications [10]. Persistent organ failure is the feature of severe acute pancreatitis whi...

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...creas and a generalized inflammatory response followed by the final stage of multiorgan dysfunction [17, 18, 30, 31]. Figure 1 illustrates the schematic overview of pathogenesis of acute pancreatitis =-=[32, 33]-=-. In the early phase, inflammation is usually localized to the pancreaswhich clinicallymanifests asmild acute pancreatitis. This usually resolves within a week without any local or systemic complicati...

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...t correlate with resolution of clinical symptoms [43]. Furthermore, the magnitude of the hyperamylasemia does not show significant statistical correlation with disease severity and ultimate prognosis =-=[44]-=-. In 19–32% of cases amylase activity may be normal at the time of hospital admission due to delayed presentation or exocrine pancreatic insufficiency (chronic alcoholism) [36, 43]. Raised serum amyla...

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...erity [69]. For faster result, PCT level can be measured by a semiquantitative strip test with a cut-off level of 0.5 ng/mL. Formore accuratemeasurements however fully automated assay should be opted =-=[70]-=-. An increased PCT level has been found to be an early predictor of severity, pancreatic necrosis, and organ failure in patients with AP [70–72]. In a recent meta-analysis, a subgroup of 8 studies usi...

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...s 0.956 [74]. Similar result has been found by Gross et al. and Wilson et al. in their study [75, 76]. More recent studies, however, by a Swiss group and the Japanese have yielded conflicting results =-=[77, 78]-=-. Domı́nguez-Muñoz et al. found quantification of plasma PMN elastase levels as a very accurate method for the early prognostic evaluation of AP and found its applicability in the clinical setting [7...

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...hemical markers in the diagnosis and severity evaluation in acute pancreatitis. 1. Introduction Acute pancreatitis (AP) is a potentially life threatening disease with varying severity of presentation =-=[1, 2]-=-. Nearly 60%–80% of all cases of AP in developed countries are attributable to either gallstone disease or alcohol abuse [3, 4]. The incidence is similar in both sexes, although alcohol abuse is the m...

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...re is the feature of severe acute pancreatitis which is associated with a high rate of mortality. The overall mortality of AP is about 10–15% but reaches up to 30%–40% in patients with severe disease =-=[13, 14]-=-. Sepsis related multiorgan failure and infected pancreatic necrosis account for about 40–50% of all mortality in acute pancreatitis [13, 15, 16]. Mortality in AP occurs in two peaks [17–21]. Nearly 5...

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...re is the feature of severe acute pancreatitis which is associated with a high rate of mortality. The overall mortality of AP is about 10–15% but reaches up to 30%–40% in patients with severe disease =-=[13, 14]-=-. Sepsis related multiorgan failure and infected pancreatic necrosis account for about 40–50% of all mortality in acute pancreatitis [13, 15, 16]. Mortality in AP occurs in two peaks [17–21]. Nearly 5...

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...Interleukins. Interleukin-6 (IL-6) is produced by a wide range of cells like monocytes, macrophage, endothelium, and fibroblast in response to potent proinflammatory stimulus like TNF-alpha and IL-1...

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...ion for diagnosis of acute pancreatitis include pancreatic isoamylase, pancreatic elastase, serum trypsin, urinary trypsinogen activated peptide (TAP), Phospholipase A2, and Carboxypeptidase B (CAPB) =-=[39, 40]-=-. Serum trypsin and elastase are of particular interest because of their longer half-life which makes them useful in diagnosis during delayed presentations [41]. These tests, however, have not found m...

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... to potent proinflammatory stimulus like TNF-alpha and IL-1...

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...of IL-6 is significantly elevated in SAP on the day of admission and tends to peak at 72 hrs after the clinical onset of disease, which makes IL-6 an excellent marker of early severity stratification =-=[56]-=-. In terms of predicting complications, IL-6 was found to be excellent in predicting remote organ failure, which is an integral part of severe acute pancreatitis [57]. Among various proinflammatory an...

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...g et al., IL-6, IL-8, and IL-10 have shown promising results in predicting severe acute pancreatitis. They, however, found a lack of consensus regarding the ideal cut-off value for assessing the same =-=[65]-=-. 5.2. C-Reactive Protein (CRP). CRP is an acute phase reactant synthesized by the hepatocytes and is usually elevated in Journal of Biomarkers 5 inflammatory conditions [66]. Cytokines like IL-6 are ...

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...level of its proenzyme did not show any correlation with pancreatic necrosis [87]. Both CAPAP and urinary TAP are excellent prognostic markers, although TAP is a better marker on the day of admission =-=[88]-=-. 5.6.4. Trysinogen-2. In acute pancreatitis the level of trysinogen-2 rises considerably more than that of trysinogen-1 [14]. High level of trypsinogen-2 can be found in both serum and urine. High se...

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...lowing ERCP induced pancreatitis [89–91]. High urinary trpsinogen-2 is used as a screening test for diagnosis of AP. A rapid dipstick method has been devised for rapid diagnosis of acute pancreatitis =-=[92]-=-. This test is particularly useful in rapid diagnosis of ERCP induced pancreatitis. Overall trysinogen-2 appears to be more useful as a diagnostic marker than as a predictor of severity [93]. 6 Journa...

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...creatitis [92]. This test is particularly useful in rapid diagnosis of ERCP induced pancreatitis. Overall trysinogen-2 appears to be more useful as a diagnostic marker than as a predictor of severity =-=[93]-=-. 6 Journal of Biomarkers 6. Emerging Potential Biomarkers for Prediction of Severity in AP 6.1. Tissue Factor. Tissue factor is a transmembrane glycoprotein involved in the initiation of coagulation ...

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...tentially life threatening disease with varying severity of presentation [1, 2]. Nearly 60%–80% of all cases of AP in developed countries are attributable to either gallstone disease or alcohol abuse =-=[3, 4]-=-. The incidence is similar in both sexes, although alcohol abuse is the more common cause in men and gallstones is the more common cause in women [5, 6]. There is an upsurge in the incidence of AP ove...

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...le to either gallstone disease or alcohol abuse [3, 4]. The incidence is similar in both sexes, although alcohol abuse is the more common cause in men and gallstones is the more common cause in women =-=[5, 6]-=-. There is an upsurge in the incidence of AP over the last few decades, although the case fatality rate has remained unchanged [7]. This may either be due to increased incidence of gallstone disease o...

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... may either be due to increased incidence of gallstone disease or improvement in diagnostic modalities [8]. The revised Atlanta classification system has classified AP into mild, moderate, and severe =-=[9, 10]-=-. More than 80% of acute pancreatitis attacks are mild and self-limiting and resolve without serious complications. In 20% of cases, however, it can be severe and complicated by major morbidity or mor...

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..., 13 pages http://dx.doi.org/10.1155/2015/519534 2 Journal of Biomarkers 2. Pathophysiology of Acute Pancreatitis Despite intense research over centuries, the exact pathogenesis of AP remains elusive =-=[3, 26]-=-. Although many theories have been proposed, none of them appear to be complete [3, 27]. Some of the propositions include abnormal biliopancreatic duct common pathway theory, pancreatic autodigestion ...

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...logy of Acute Pancreatitis Despite intense research over centuries, the exact pathogenesis of AP remains elusive [3, 26]. Although many theories have been proposed, none of them appear to be complete =-=[3, 27]-=-. Some of the propositions include abnormal biliopancreatic duct common pathway theory, pancreatic autodigestion theory, gallstone migration theory, enzyme activation theory, kinin and complement acti...

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...rse and relative inaccessibility of pancreatic tissue [3]. To overcome this problem, investigators have now taken to animal models to study the molecular aspects of pathogenesis of acute pancreatitis =-=[3, 28, 29]-=-. Further complicating the issue are the paradoxical results about the pathogenesis, obtained from different animals exposed to similar aetiology [5]. The premature activation of trypsin in pancreatic...

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...rse and relative inaccessibility of pancreatic tissue [3]. To overcome this problem, investigators have now taken to animal models to study the molecular aspects of pathogenesis of acute pancreatitis =-=[3, 28, 29]-=-. Further complicating the issue are the paradoxical results about the pathogenesis, obtained from different animals exposed to similar aetiology [5]. The premature activation of trypsin in pancreatic...

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...creatitis is usually based on a combination of clinical findings, laboratory investigations, and imaging techniques. There is no gold standard test available to diagnose acute pancreatitis at present =-=[34, 35]-=-. According to revised Atlanta classification, diagnosis of acute pancreatitis requires two of the following three criteria [1, 22]: (1) Abdominal pain characteristic of AP (acute onset of a persisten...

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...creatitis is usually based on a combination of clinical findings, laboratory investigations, and imaging techniques. There is no gold standard test available to diagnose acute pancreatitis at present =-=[34, 35]-=-. According to revised Atlanta classification, diagnosis of acute pancreatitis requires two of the following three criteria [1, 22]: (1) Abdominal pain characteristic of AP (acute onset of a persisten...

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...creatitis, the blood level of amylase rapidly increases within six hours of onset of disease, exhibits a half-life of 10–12 hours, remains elevated for 3–5 days, and finally is excreted by the kidney =-=[33, 36, 42]-=-. After reaching a peak level, subsequent return of serum amylase to its normal level does not correlate with resolution of clinical symptoms [43]. Furthermore, the magnitude of the hyperamylasemia do...

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...5 days, and finally is excreted by the kidney [33, 36, 42]. After reaching a peak level, subsequent return of serum amylase to its normal level does not correlate with resolution of clinical symptoms =-=[43]-=-. Furthermore, the magnitude of the hyperamylasemia does not show significant statistical correlation with disease severity and ultimate prognosis [44]. In 19–32% of cases amylase activity may be norm...

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...renal clearance. Macroamylasemia is a condition in which amylase remains bound to immunoglobulins or polysaccharides to form large molecular weight complexes leading to raised levels of serum amylase =-=[36, 45, 46]-=-. Hypertriglyceridemia competitively interferes with amylase assay, so a false low level of serum amylase can be found in patients having hypertriglyceridemia [36, 46]. Sensitivity and specificity of ...

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...renal clearance. Macroamylasemia is a condition in which amylase remains bound to immunoglobulins or polysaccharides to form large molecular weight complexes leading to raised levels of serum amylase =-=[36, 45, 46]-=-. Hypertriglyceridemia competitively interferes with amylase assay, so a false low level of serum amylase can be found in patients having hypertriglyceridemia [36, 46]. Sensitivity and specificity of ...

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...ailure and infection of pancreatic necrosis and sepsis with late complications of acute pancreatitis [32, 33]. 3.2. Lipase. Lipase assay has a sensitivity and specificity of 80% and 60%, respectively =-=[35, 48]-=-.The serum concentration of lipase increases within 3–6 hours of onset of disease and peaks within 24 hours [32]. The increased serum level stays for around 7–14 days before it comes down to the norma...

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...ts with delayed presentation [32, 36]. Pancreatic lipase is four times more active than amylase and it is less affected by exocrine pancreatic deficiency occurring in patients of chronic pancreatitis =-=[36, 49]-=-. Hypertriglyceridemia does not influence the serum lipase assay as happens in the case of serum amylase. Patients taking frusemide can show increased lipase activity [36]. Increased serum level of li...

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...me; MARS: mixed antagonist response syndrome; SIRS: systemic inflammatory response syndrome; Mild AP: mild acute pancreatitis [1]. however, serum lipase level’s sensitivity is limited between 55–100% =-=[36, 51]-=-. Like that of amylase, most studies suggest a poor correlation between lipase activity and disease severity [44]. 3.3. Trypsinogen. Trypsinogen is the zymogen of the pancreatic enzyme trypsin which i...

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...f the use of trypsinogen in the diagnosis and severity assessment of AP [32]. Both serum and urine concentrations risewithin fewhours of onset of disease anddecline to normal level within 3 to 5 days =-=[32, 36, 52]-=-. A dipstick method using urinary trysinogen-2 has been devised for rapid detection of AP [32, 53]. Because of its low sensitivity and less availability, this test is less frequently used in routine c...

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...centrations risewithin fewhours of onset of disease anddecline to normal level within 3 to 5 days [32, 36, 52]. A dipstick method using urinary trysinogen-2 has been devised for rapid detection of AP =-=[32, 53]-=-. Because of its low sensitivity and less availability, this test is less frequently used in routine clinical practice [32]. The greatest demerit of trypsinogen as a diagnostic test is its rapid clear...

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...lexity of assay [36]. IL-8 is the best characterized member of the chemokine family studied in acute pancreatitis. It is a powerful secondary chemoattractant of neutrophil in the inflammatory process =-=[60]-=-. Many studies have shown promising results in early prediction of SAP [60]. One study has shown its role in monitoring life threatening complications in patients of necrotizing pancreatitis with mult...

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...have shown promising results in early prediction of SAP [60]. One study has shown its role in monitoring life threatening complications in patients of necrotizing pancreatitis with multiorgan failure =-=[61]-=-. IL-12, IL-15, and IL-17 are proinflammatory cytokines which have been studied recently as potential biomarkers. Similar results have been seen in various studies as single biochemical markers on the...

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...e [68]. Because severe acute pancreatitis is associated with sepsis, infected pancreatic necrosis, and multiorgan failure, procalcitonin can be used as a useful marker in early prediction of severity =-=[69]-=-. For faster result, PCT level can be measured by a semiquantitative strip test with a cut-off level of 0.5 ng/mL. Formore accuratemeasurements however fully automated assay should be opted [70]. An i...

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...N Elastase). PMN Elastase is the protease released by activated neutrophil as a first line defense following tissue injury [36]. Granulocyte infiltration and activation occur in the early phase of AP =-=[74]-=-. So PMNElastase has been proved as an earlymarker of severe acute pancreatitis within 48 hours of onset of symptoms. With a cut-off level of 110 ...

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...egative predictive values were 78% and 96%, respectively, and the area under the receiver operator curve was 0.956 [74]. Similar result has been found by Gross et al. and Wilson et al. in their study =-=[75, 76]-=-. More recent studies, however, by a Swiss group and the Japanese have yielded conflicting results [77, 78]. Domı́nguez-Muñoz et al. found quantification of plasma PMN elastase levels as a very accur...

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...s 0.956 [74]. Similar result has been found by Gross et al. and Wilson et al. in their study [75, 76]. More recent studies, however, by a Swiss group and the Japanese have yielded conflicting results =-=[77, 78]-=-. Domı́nguez-Muñoz et al. found quantification of plasma PMN elastase levels as a very accurate method for the early prognostic evaluation of AP and found its applicability in the clinical setting [7...

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...al fluid. TAP activity increases early in the course of the disease and attains maximal value within 24–48 hours. Huang et al. did a meta-analysis on the role of urinary TAP in prediction of severity =-=[85]-=-. They found a sensitivity of 71% and specificity of 75% with an area under curve of 0.83 with a cut-off value of 35 nmol/L. This was comparable to the sensitivity and specificity of CRP and was bette...

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... potential severity stratification marker for acute pancreatitis [67, 85]. 5.6.3. Carboxypeptidase B Activation Peptide (CAPAP). It is the largest activation peptide amongst the pancreatic proenzymes =-=[86]-=-. This peptide is very stable in urine and serum. In a study of 85 patients with acute pancreatitis CAPAP level correlated well, with an accuracy of 92%, in predicting development of pancreatic necros...

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...und that TF as a predictor of severity is not as good as IL-6 or CRP. High serum level early in the course may suggest a role in the pathogenesis of AP and give a window for therapeutic interventions =-=[94]-=-. 6.2. Prealbumin to Fibrinogen Ratio. Prealbumin and Fibrinogen are acute phase reactants. Prealbumin is mostly used for assessment of nutritional status, whereas fibrinogen is usedmostly for assessm...

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... et al., it has superior sensitivity, specificity, positive predictive value (PPV), and NPV of 76.5%, 94.1%, 89.6%, and 85.6%, respectively, at a cut-off level of 31.70mg/g than other scoring systems =-=[95]-=-. 6.3. Cytokeratin 18. This is an epithelial cell structural protein, associatedwith apoptotic cell death. Recent animal studies have shown that wide apoptotic cell death is associated with a milder f...

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...el of cytokeratin 18 in patients with mild acute pancreatitis (271.2 ± 45.5 versus 152.6± 38.2 IU/L;...

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...le centre prospective study to assess its role in prediction of severity in AP. They found hepcidin is a better predictive marker for SAP compared to CRP with an AUC of 0.79 versus 0.69, respectively =-=[97]-=-. 6.5. Copeptin. Copeptin is a long amino acid peptide derived from a preprohormone consisting of neurophysin II, vasopressin, and copeptin. Its level rises during stress in critically ill patients. I...

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...admission in patients with SAP. Isman et al. also found that copeptin can be used as a novel prognostic marker for prediction of local complication, organ failure, and mortality in acute pancreatitis =-=[98]-=-. 6.6. Soluble E-Selectin (sES) and Soluble Thrombomodulin (sTM). Soluble ES is an endothelial activation marker, whereas soluble TM is an endothelial injury marker. During acute pancreatitis activate...

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...ing acute pancreatitis activated neutrophils release elastase which damages the endothelium. Ida et al. studied these two markers to find their significance in assessment of severe acute pancreatitis =-=[99]-=-. They concluded that those high levels of soluble ES can be found in all stages of the disease; therefore it can be used tomonitor the disease severity. SolubleTMcanbe used as a predictive parker of ...

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...lin have been found to be associated with acute pancreatitis with a strong correlation with the disease severity. High level of endothelin 1 can be used as a marker to monitor the disease progression =-=[100]-=-. 6.8. Melatonin Concentration. Melatonin plays a protective role in the early phase of acute pancreatitis in the form of an antioxidant or scavengers of free radicals, inhibition of nuclear factor ka...