Laboratory Markers of Severe Acute Pancreatitis

Background: A large array of parameters has been proposed for the biochemical stratification of severity and prediction of complications in acute pancreatitis. However, the number of accurate and readily available variables for routine application is still limited. Methods: The literature was reviewed for laboratory markers of acute pancreatitis with special regard to their clinical usefulness and test performance for stratifying severity and monitoring disease progression. Results: Several parameters, such as trypsinogen and procarboxypeptidase B activation peptide, PMN-elastase, interleukin-6 (IL-6) and 8 (IL-8), serum amyloid A (SAA), and procalcitonin (PCT), can differentiate between mild and severe acute pancreatitis within 48 h of disease onset with favorable diagnostic accuracy. Because fully automated assays have become available, IL-6, IL-8, PCT, and SAA are the most interesting parameters in this respect. For monitoring disease progression beyond 48 h, acute-phase proteins, IL-6, IL-8, and PCT are valuable markers. PCT is the first biochemical variable for predicting severe pancreatic infections and overall prognosis throughout the course of acute pancreatitis with high sensitivity and specificity. Conclusions: Among all the biochemical variables available, C-reactive protein is still the standard for a fast, reliable, and cost-effective assessment of severity in acute pancreatitis. PCT substantially contributes to an improved stratification of patients at risk to develop major complications and deserves routine application.

[1]  R. Carter,et al.  Urinary trypsinogen activation peptide as a marker of severe acute pancreatitis , 2004, The British journal of surgery.

[2]  P. Malfertheiner,et al.  Gabexate mesilate in human acute pancreatitis. German Pancreatitis Study Group. , 1993, Gastroenterology.

[3]  H. Spiro,et al.  Ulcerative colitis and scleroderma. , 1965, Gastroenterology.

[4]  J. Norman.  The role of cytokines in the pathogenesis of acute pancreatitis. , 1998, American journal of surgery.

[5]  V. Valtonen,et al.  C-reactive protein (CRP) and serum phospholipase A2 in the assessment of the severity of acute pancreatitis. , 1987, Gut.

[6]  R. Pezzilli,et al.  Serum interleukin-6, interleukin-8, andβ2-Microglobulin in early assessment of severity of acute pancreatitis comparison with serum C-reactive protein , 1995, Digestive Diseases and Sciences.

[7]  F. Chang,et al.  Early Changes of Serum Proinflammatory and Anti-inflammatory Cytokines After Endoscopic Retrograde Cholangiopancreatography , 2003, Pancreas.

[8]  P. Malfertheiner,et al.  PMN‐Elastase in Comparison with CRP, Antiproteases, and LDH as Indicators of Necrosis in Human Acute Pancreatitis , 1991, Pancreas.

[9]  H. Repo,et al.  Procalcitonin, soluble interleukin-2 receptor, and soluble E-selectin in predicting the severity of acute pancreatitis , 2001, Critical care medicine.

[10]  G. Krejs,et al.  Relation of serial measurements of plasma-soluble intercellular adhesion molecule-1 to severity of acute pancreatitis , 1999, American Journal of Gastroenterology.

[11]  R. Pezzilli,et al.  Clinical usefulness of the serum carboxypeptidase B activation peptide in acute pancreatitis. , 2000, JOP : Journal of the pancreas.

[12]  C. Johnson,et al.  Painful ascites , 2004, Gut.

[13]  J. Grönroos,et al.  Pancreatic and synovial type phospholipases A2 in serum samples from patients with severe acute pancreatitis. , 1993, Gut.

[14]  A. Shenkin,et al.  Role of interleukin-6 in mediating the acute phase protein response and potential as an early means of severity assessment in acute pancreatitis. , 1993, Gut.

[15]  F. Carballo,et al.  Clinical usefulness of polymorphonuclear elastase in predicting the severity of acute pancreatitis: Results of a multicentre study , 1991, The British journal of surgery.

[16]  J. Neoptolemos,et al.  Severe Acute Pancreatitis Is Related to Increased Early Urinary Levels of the Activation Peptide of Pancreatic Phospholipase A2 , 2002, Pancreatology.

[17]  A. Shenkin,et al.  The Relationship Between Pancreatic Enzyme Release and Activation and the Acute‐Phase Protein Response in Patients with Acute Pancreatitis , 1995, Pancreas.

[18]  P. Banks,et al.  Early diagnosis of pancreatic infection by computed tomography-guided aspiration. , 1987, Gastroenterology.

[19]  M. Büchler,et al.  Bacterial contamination of pancreatic necrosis. A prospective clinical study. , 1986, Gastroenterology.

[20]  M. Wurfel,et al.  Lipopolysaccharide (LPS)-binding protein is carried on lipoproteins and acts as a cofactor in the neutralization of LPS , 1994, The Journal of experimental medicine.

[21]  S.‐D. Lee,et al.  Serum interleukin 10 and interleukin 11 in patients with acute pancreatitis , 1999, Gut.

[22]  B. Rau,et al.  CC-chemokine activation in acute pancreatitis: enhanced release of monocyte chemoattractant protein-1 in patients with local and systemic complications , 2003, Intensive Care Medicine.

[23]  G. Steinbach,et al.  Serum amyloid A versus C‐reactive protein in acute pancreatitis: Clinical value of an alternative acute‐phase reactant , 2000, Critical care medicine.

[24]  T. Yoshida.  Gabexate mesilate in human acute pancreatitis. , 1993, Gastroenterology.

[25]  J. Schölmerich,et al.  lnterleukin‐8 and neutrophil activation in acute pancreatitis , 1992, European journal of clinical investigation.

[26]  J. Trapnell.  The natural history and prognosis of acute pancreatitis. , 1966, Annals of the Royal College of Surgeons of England.

[27]  Proinflammatory cytokines in early assessment of the prognosis of acute pancreatitis , 1999 .

[28]  M. McMahon,et al.  Dynamic contrast enhanced computed tomography: a precise technique for identifying and localising pancreatic necrosis. , 1990, BMJ.

[29]  J. Ponsky,et al.  A randomized, double blind study of interleukin 10 for the prevention of ERCP-induced pancreatitis , 2001, American Journal of Gastroenterology.

[30]  S. Bank,et al.  Cytokines (IL-6, IL-8, TNF): Early and Reliable Predictors of Severe Acute Pancreatitis , 2003, Journal of clinical gastroenterology.

[31]  T. Lövgren,et al.  Immunoreactive phospholipase A2 in serum in acute pancreatitis and pancreatic cancer. , 1985, Clinical chemistry.

[32]  B. Rau,et al.  Early Severe Acute Pancreatitis: Characteristics of a New Subgroup , 2001, Pancreas.

[33]  C. Rollhauser.  Interleukin 10 and incidence of pancreatitis after therapeutic endoscopic retrograde cholangiopancreatography. , 2001, Gastroenterology.

[34]  Trapnell Je.  The natural history and prognosis of acute pancreatitis. , 1966 .

[35]  F. D. de Beer,et al.  Human serum amyloid A (SAA) protein: a prominent acute‐phase reactant for clinical practice , 1996, European journal of clinical investigation.

[36]  L. Osborn,et al.  Leukocyte adhesion to endothelium in inflammation , 1990, Cell.

[37]  M. Bhatia,et al.  Novel therapeutic targets for acute pancreatitis and associated multiple organ dysfunction syndrome. , 2002, Current drug targets. Inflammation and allergy.

[38]  J. Hermon-Taylor,et al.  Type 1-prophospholipase A2 propeptide immunoreactivity is released from activated granulocytes. , 1995, Clinical biochemistry.

[39]  M. Büchler,et al.  Serum levels of procarboxypeptidase B and its activation peptide in patients with acute pancreatitis and non-pancreatic diseases , 2002, Gut.

[40]  T. Kirikae,et al.  Bacterial endotoxin: molecular relationships of structure to activity and function , 1994, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[41]  R. Isenmann,et al.  Diagnosis, objective assessment of severity, and management of acute pancreatitis , 1999, International journal of pancreatology : official journal of the International Association of Pancreatology.

[42]  S. Uehara,et al.  Immune function in patients with acute pancreatitis , 2003, Journal of gastroenterology and hepatology.

[43]  A. Fürstenberg,et al.  Post-ERP pancreatitis as a model for cytokine induced acute phase response in acute pancreatitis. , 1997, Gut.

[44]  J. White,et al.  Calcitonin Precursors: Early Markers of Gut Barrier Dysfunction in Patients With Acute Pancreatitis , 2003, Pancreas.

[45]  B. Rau,et al.  Clinical relevance of caspase-1 activated cytokines in acute pancreatitis: High correlation of serum interleukin-18 with pancreatic necrosis and systemic complications , 2001, Critical care medicine.

[46]  F. Gorelick,et al.  Mechanisms of intracellular zymogen activation. , 1999, Bailliere's best practice & research. Clinical gastroenterology.

[47]  A. Dabrowski,et al.  Serum Profiles of E-Selectin, Interleukin-10, and Interleukin-6 and Oxidative Stress Parameters in Patients with Acute Pancreatitis and Nonpancreatic Acute Abdominal Pain , 2003, Pancreas.

[48]  S. Sarna,et al.  Plasma anti‐inflammatory cytokines and monocyte human leucocyte antigen‐DR expression in patients with acute pancreatitis , 2004, Scandinavian journal of gastroenterology.

[49]  J. Neoptolemos,et al.  Early prediction of severity in acute pancreatitis by urinary trypsinogen activation peptide: a multicentre study , 2000, The Lancet.

[50]  J. Sánchez-Payá,et al.  A Comparative Study of the Activation Peptide of Carboxypeptidase B and Trypsinogen as Early Predictors of the Severity of Acute Pancreatitis , 2004, Pancreas.

[51]  P. Galanaud,et al.  Pro- and anti-inflammatory cytokines during acute severe pancreatitis: an early and sustained response, although unpredictable of death. Parisian Study Group on Acute Pancreatitis. , 1999, Critical care medicine.

[52]  E. Vicaut,et al.  Inflammatory cytokines, C reactive protein, and procalcitonin as early predictors of necrosis infection in acute necrotizing pancreatitis. , 2003, Surgery.

[53]  J. Neoptolemos,et al.  Double blind, randomised, placebo controlled study of a platelet activating factor antagonist, lexipafant, in the treatment and prevention of organ failure in predicted severe acute pancreatitis , 2001, Gut.

[54]  R. Ulevitch,et al.  Structure and function of lipopolysaccharide binding protein. , 1990, Science.

[55]  C. Johnson,et al.  Activation peptide of carboxypeptidase B and anionic trypsinogen as early predictors of the severity of acute pancreatitis , 2001, The British journal of surgery.

[56]  C. Johnson,et al.  Platelet-Activating Factor and Platelet-Activating Factor Antagonists in Acute Pancreatitis , 1999, Digestive Surgery.

[57]  G. Steinbach,et al.  Multicenter evaluation of a new immunoassay for procalcitonin measurement on the Kryptor® System , 2004, Clinical chemistry and laboratory medicine.

[58]  F. Carballo,et al.  Monitoring of serum proteinase-antiproteinase balance and systemic inflammatory response in prognostic evaluation of acute pancreatitis , 1993, Digestive Diseases and Sciences.

[59]  J. Neoptolemos,et al.  Serum amyloid A is a better early predictor of severity than C‐reactive protein in acute pancreatitis , 2002, The British journal of surgery.

[60]  K. Fearon,et al.  Endothelial-derived selectins in the development of organ dysfunction in acute pancreatitis , 2001, Critical care medicine.

[61]  F. Gansauge,et al.  Inflammatory mediators in human acute pancreatitis: clinical and pathophysiological implications , 2000, Gut.

[62]  R. Sutton,et al.  Levels of the chemokines growth‐related oncogene α and epithelial neutrophil‐activating protein 78 are raised in patients with severe acute pancreatitis , 2002, The British journal of surgery.

[63]  E. Cooper,et al.  Relation of alpha 2-macroglobulin and other antiproteases to the clinical features of acute pancreatitis. , 1984, American Journal of Surgery.

[64]  J. Pugin,et al.  Compartmentalization of the Inflammatory Response during Acute Pancreatitis Correlation with Local and Systemic Complications Sampling Protocol and Cytokine Assays , 2022 .

[65]  I. Kushner,et al.  Acute-phase proteins and other systemic responses to inflammation. , 1999, The New England journal of medicine.

[66]  W. Uhl,et al.  Sensitivity of antiproteases, complement factors and C-reactive protein in detecting pancreatic necrosis. Results of a prospective clinical study , 1986, International journal of pancreatology : official journal of the International Association of Pancreatology.

[67]  J. Frossard.  Trypsin activation peptide (TAP) in acute pancreatitis: from pathophysiology to clinical usefulness. , 2001, JOP : Journal of the pancreas.

[68]  N. Bird,et al.  Serum phospholipase A2 activity in acute pancreatitis: An early guide to severity , 1989, The British journal of surgery.

[69]  M. Büchler,et al.  Role of activation peptides from pancreatic proenzymes in the diagnosis and prognosis of acute pancreatitis. , 2002, Surgery.

[70]  M. Assicot,et al.  High serum procalcitonin concentrations in patients with sepsis and infection , 1993, The Lancet.

[71]  A. Shenkin,et al.  C‐reactive protein, antiproteases and complement factors as objective markers of severity in acute pancreatitis , 1989, The British journal of surgery.

[72]  B. Austen,et al.  Trypsinogen activation peptides assay in the early prediction of severity of acute pancreatitis , 1990, The Lancet.

[73]  K. Boda,et al.  Diagnostic relevance of procalcitonin, IL-6, and sICAM-1 in the prediction of infected necrosis in acute pancreatitis , 2000, International journal of pancreatology : official journal of the International Association of Pancreatology.

[74]  B. Rau,et al.  Secretory Phospholipase A2 in Patients with Infected Pancreatic Necroses in Acute Pancreatitis , 1998, Pancreas.

[75]  B. Rau,et al.  Role of ultrasonographically guided fine‐needle aspiration cytology in the diagnosis of infected pancreatic necrosis , 1998, The British journal of surgery.

[76]  P. Malfertheiner,et al.  Identification of pancreas necrosis in severe acute pancreatitis: imaging procedures versus clinical staging. , 1986, Gut.

[77]  P. Banks,et al.  Urinary trypsinogen activation peptide (TAP) predicts severity in patients with acute pancreatitis , 1997, International journal of pancreatology : official journal of the International Association of Pancreatology.

[78]  J. Ross,et al.  Serum concentrations of inflammatory mediators related to organ failure in patients with acute pancreatitis , 1996, The British journal of surgery.

[79]  R. Pezzilli,et al.  Immune-manipulation of the inflammatory response in acute pancreatitis. What can be expected? , 2004, JOP : Journal of the pancreas.

[80]  G. Steinbach,et al.  Clinical value of lipopolysaccharide-binding protein (LBP) determinations in acute pancreatitis , 2003, Langenbeck's Archives of Surgery.

[81]  G. Steinbach,et al.  The potential role of procalcitonin and interleukin 8 in the prediction of infected necrosis in acute pancreatitis , 1997, Gut.

[82]  J. Schölmerich,et al.  Granulocyte elastase in assessment of severity of acute pancreatitis , 2005, Digestive Diseases and Sciences.

[83]  R. Pezzilli,et al.  Behavior of serum interleukin 12 in human acute pancreatitis. , 1999, Pancreas.

[84]  M. Lerch,et al.  Trypsin activity is not involved in premature, intrapancreatic trypsinogen activation. , 2002, American journal of physiology. Gastrointestinal and liver physiology.

[85]  A. Kingsnorth,et al.  Cytokine storm in acute pancreatitis. , 2002, Journal of hepato-biliary-pancreatic surgery.

[86]  U. Stenman,et al.  Serum complex of trypsin 2 and (alpha)(sub 1) antitrypsin as diagnostic and prognostic marker of acute pancreatitis: clinical study in consecutive patients , 1996, BMJ.

[87]  France Gauvin,et al.  Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[88]  H. Repo,et al.  Procalcitonin strip test in the early detection of severe acute pancreatitis , 2001, The British journal of surgery.

[89]  M. Büchler,et al.  Role of procalcitonin and granulocyte colony stimulating factor in the early prediction of infected necrosis in severe acute pancreatitis , 2000, Gut.

[90]  J. Neoptolemos,et al.  Severe acute pancreatitis is related to increased early urinary levels of the activation Peptide of pancreatic phospholipase A(2). , 2002, Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.].