Pancreatic stone protein (PSP) and pancreatitis-associated protein (PAP): a protocol of a cohort study on the diagnostic efficacy and prognostic value of PSP and PAP as postoperative markers of septic complications in patients undergoing abdominal surgery (PSP study)

Oliver Maximilian Fisher, Christian Eugen Oberkofler, Dimitri Aristotle Raptis, Christopher Soll, Markus Béchir, Marc Schiesser, Rolf Graf, Oliver Maximilian Fisher, Christian Eugen Oberkofler, Dimitri Aristotle Raptis, Christopher Soll, Markus Béchir, Marc Schiesser, Rolf Graf

Abstract

Introduction: Major abdominal surgery leads to a postoperative systemic inflammatory response, making it difficult to discriminate patients with systemic inflammatory response syndrome from those with a beginning postoperative infectious complication. At present, physicians have to rely on their clinical experience to differentiate between the two. Pancreatic stone protein (PSP) and pancreatitis-associated protein (PAP), both secretory proteins produced by the pancreas, are dramatically increased during pancreatic disease and have been shown to act as acute-phase proteins. Increased levels of PSP have been detected in polytrauma patients developing sepsis and PSP has shown a high diagnostic accuracy in discriminating the severity of peritonitis and in predicting death in intensive care unit patients. However, the prognostic value of PSP/PAP for infectious complications among patients undergoing major abdominal surgery is unknown.

Methods and analysis: 160 patients undergoing major abdominal surgery will be recruited preoperatively. On the day before surgery, baseline blood values are attained. Following surgery, daily blood samples for measuring regular inflammatory markers (c-reactive protein, procalcitonin, interleukin-6, tumour necrosis factor-α and leucocyte counts) and PSP/PAP will be acquired. PSP/PAP will be measured using a validated ELISA developed in our research laboratory. Patient's discharge marks the end of his/her trial participation. Complication grade including mortality and occurrence of infectious postoperative complications according to validated diagnostic criteria will be correlated with PSP/PAP values. Total intensive care unit days and total length of stay will be recorded as further outcome parameters.

Ethics and dissemination: The PSP trial is a prospective monocentric cohort study evaluating the prognostic value of PSP and PAP for postoperative infectious complications. In addition, a comparison with established inflammatory markers in patients undergoing major abdominal surgery will be performed to help evaluate the role of these proteins in predicting and diagnosing infectious and other postoperative complications.

Institution ethics board approval id: KEKZH-Nr. STV 11-2009.

Trial registration: ClinicalTrials.gov: NCT01258179.

Figures

Figure 1
Figure 1
Flowchart of patient recruitment and study participation. PAP, pancreatitis-associated protein; PSP, pancreatic stone protein.

References

    1. Gressner AM TL. Proteinstoffwechsel. Lehrbuch der Klinischen Chemie und Pathobiochemie. New York: Schattauer Stuttgart, 1989:152
    1. Andus T, Heinrich PC, Castell JC, et al. [Interleukin-6: a key hormone of the acute phase reaction]. Dtsch Med Wochenschr 1989;114:1710–16
    1. Staehler M, Hammer C, Meiser B, et al. Procalcitonin: a new marker for differential diagnosis of acute rejection and bacterial infection in heart transplantation. Transplant Proc 1997;29:584–5
    1. Oberhoffer M, Karzai W, Meier-Hellmann A, et al. Sensitivity and specificity of various markers of inflammation for the prediction of tumor necrosis factor-alpha and interleukin-6 in patients with sepsis. Crit Care Med 1999;27:1814–18
    1. Welsch T, Muller SA, Ulrich A, et al. C-reactive protein as early predictor for infectious postoperative complications in rectal surgery. Int J Colorectal Dis 2007;22:1499–507
    1. Dimopoulou I, Armaganidis A, Douka E, et al. Tumour necrosis factor-alpha (TNF alpha) and interleukin-10 are crucial mediators in post-operative systemic inflammatory response and determine the occurrence of complications after major abdominal surgery. Cytokine 2007;37:55–61
    1. Kemppainen E, Sand J, Puolakkainen P, et al. Pancreatitis associated protein as an early marker of acute pancreatitis. Gut 1996;39:675–8
    1. Iovanna J, Orelle B, Keim V, et al. Messenger RNA sequence and expression of rat pancreatitis-associated protein, a lectin-related protein overexpressed during acute experimental pancreatitis. J Biol Chem 1991;266:24664–9
    1. Bimmler D, Schiesser M, Perren A, et al. Coordinate regulation of PSP/reg and PAP isoforms as a family of secretory stress proteins in an animal model of chronic pancreatitis. J Surg Res 2004;118:122–35
    1. Graf R, Schiesser M, Scheele GA, et al. A family of 16-kDa pancreatic secretory stress proteins form highly organized fibrillar structures upon tryptic activation. J Biol Chem 2001;276:21028–38
    1. Iovanna JL, Keim V, Nordback I, et al. Serum levels of pancreatitis-associated protein as indicators of the course of acute pancreatitis. Multicentric Study Group on Acute Pancreatitis. Gastroenterology 1994;106:728–34
    1. Masciotra L, Lechene de la Porte P, Frigerio JM, et al. Immunocytochemical localization of pancreatitis-associated protein in human small intestine. Dig Dis Sci 1995;40:519–24
    1. Carroccio A, Iovanna JL, Iacono G, et al. Pancreatitis-associated protein in patients with celiac disease: serum levels and immunocytochemical localization in small intestine. Digestion 1997;58:98–103
    1. Li L, Bachem MG, Zhou S, et al. Pancreatitis-associated protein inhibits human pancreatic stellate cell MMP-1 and -2, TIMP-1 and -2 secretion and RECK expression. Pancreatology 2009;9: 99–110
    1. Keel M, Harter L, Reding T, et al. Pancreatic stone protein is highly increased during posttraumatic sepsis and activates neutrophil granulocytes. Crit Care Med 2009;37:1642–8
    1. Gukasjan R, Raptis DA, Schulz HU, et al. Pancreatic stone protein predicts outcome in patients with peritonitis in the ICU. Crit Care Med 2013;41:1027–36
    1. Boeck L, Graf R, Eggimann P, et al. Pancreatic stone protein: a marker of organ failure and outcome in ventilator-associated pneumonia. Chest 2011;140:925–32
    1. Que YA, Delodder F, Guessous I, et al. Pancreatic stone protein as an early biomarker predicting mortality in a prospective cohort of patients with sepsis requiring ICU management. Crit Care 2012;16:R114.
    1. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004;240:205–13
    1. Gesellschaft DS. Leitlinien Sepsis. Secondary Leitlinien Sepsis 2010. .
    1. [No authors listed] American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992;20:864–74
    1. Scherr A, Graf R, Bain M, et al. Pancreatic stone protein predicts positive sputum bacteriology in exacerbations of COPD. Chest 2013;143:379–87
    1. Sankar V, Webster NR. Clinical application of sepsis biomarkers. J Anesth 2013;27:269–83
    1. Moore LJ, Moore FA, Todd SR, et al. Sepsis in general surgery: the 2005-2007 national surgical quality improvement program perspective. Arch Surg 2010;145:695–700
    1. Moore LJ, Moore FA, Jones SL, et al. Sepsis in general surgery: a deadly complication. Am J Surg 2009;198:868–74

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다