Dejan Radenkovic

D-dimer in acute pancreatitis: a new approach for an early assessment of organ failure.

Objectives: Studies on the clinical value of parameters of hemostasis in predicting pancreatitis-associated complications are still scarce. The aim of this prospective study was to identify the useful hemostatic markers for accurate determination of the subsequent development of organ failure (OF) during the very early course of acute pancreatitis (AP). Methods: In 91 consecutive primarily admitted patients with AP, prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin III, protein C, plasminogen activator inhibitor 1, d-dimer, and plasminogen were measured in plasma within the first 24 hours of admission and 24 hours thereafter. Two study groups comprising 24 patients with OF and 67 patients without OF were compared. Results: Levels of prothrombin time, fibrinogen, and d-dimer on admission were significantly different between the OF and non-OF groups, and all these parameters plus antithrombin III were significantly different 24 hours later. A d-dimer value of 414.00 &mgr;g/L on admission was the best cutoff value in predicting the development of OF with sensitivity, specificity, and positive and negative predictive values of 90%, 89%, 75%, and 96%, respectively. Conclusions: Measurement of plasma levels of d-dimer on the admission is an accurate method for the identification of patients who will develop OF in the further course of AP.Abbreviations: AP - acute pancreatitis, PT - prothrombin time, APTT - activated partial thromboplastin time, AT III - antithrombin III, PAI-1 - plasminogen activator inhibitor 1, ROC - receiver operating characteristic, AUC - area under the curve

Disorders of Hemostasis During the Surgical Management of Severe Necrotizing Pancreatitis

Objectives: Several clinical studies of severe necrotizing pancreatitis (SNP) suggest profound activation of coagulation as well as activation of the fibrinolytic system. The aim of this study was to evaluate the hemostatic derangements in patients who were managed for SNP. Methods: Forty-one operated-on patients with SNP were analyzed regarding clinical outcome and activation of the coagulation systems. Serial measurement of coagulation, anticoagulation, and fibrinolysis parameters: prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, antithrombin III (AT III), protein C, plasminogen activator inhibitor-1 (PAI-1), d-dimer, &agr;2-antiplasmin, and plasminogen were performed on days 1, 3, 5, 7, 10, and 14 after the initial operation. According to treatment outcome at the end of study, groups of 26 survivors and 15 nonsurvivors were compared. Results: Nonsurvivors had significantly lower levels of activity of protein C and AT III, and higher concentrations of d-dimer and PAI-1 than survivors. The other measured parameters did not show significant differences between the compared groups of patients. Conclusions: Changes in protein C, AT III, d-dimer and PAI-1 levels indicate exhaustion of fibrinolysis and coagulation inhibitors in patients with poor outcome during the course of SNP.

Severe acute pancreatitis: overall and early versus late mortality in intensive care units.

Objectives: To determine overall mortality and timing of death in patients with severe acute pancreatitis and factors affecting mortality. Methods: This was a retrospective, observational study of 110 patients admitted to a general intensive care unit (ICU) from January 2003 to January 2006. Results: The overall mortality rate was 53.6% (59/110); 25.4% (n = 15) of deaths were early (≤14 days after ICU admission). There were no significant differences in age, sex, or surgical/medical treatment between survivors and nonsurvivors. Median Acute Physiology and Chronic Health Evaluation (APACHE) II score was higher among nonsurvivors than survivors (score = 26 vs 19, respectively; P < 0.001), and the duration of hospitalization before ICU admission was significantly longer (4 vs 1 day; P < 0.001). Among the 59 patients who died, those in the early-mortality group were admitted to the ICU significantly earlier than those in the late-mortality group (3 vs 6.5 days; P < 0.05). Conclusions: Overall mortality and median APACHE II score were high. Death predominantly occurred late and was unaffected by patient age, length of stay in the ICU, or surgical/medical treatment. An APACHE II cutoff of 24.5 and pre-ICU admission time of 2.5 days were sensitive predictors of fatal outcome.

Decompressive laparotomy with temporary abdominal closure versus percutaneous puncture with placement of abdominal catheter in patients with abdominal compartment syndrome during acute pancreatitis: background and design of multicenter, randomised, controlled study

BackgroundDevelopment of abdominal compartment syndrome (ACS) in patients with severe acute pancreatitis (SAP) has a strong impact on the course of disease. Number of patients with this complication increases during the years due more aggressive fluid resuscitation, much bigger proportion of patients who is treated conservatively or by minimal invasive approach, and efforts to delay open surgery. There have not been standard recommendations for a surgical or some other interventional treatment of patients who develop ACS during the SAP. The aim of DECOMPRESS study was to compare decompresive laparotomy with temporary abdominal closure and percutaneus puncture with placement of abdominal catheter in these patients.MethodsOne hundred patients with ACS will be randomly allocated to two groups: I) decompresive laparotomy with temporary abdominal closure or II) percutaneus puncture with placement of abdominal catheter. Patients will be recruited from five hospitals in Belgrade during two years period. The primary endpoint is the mortality rate within hospitalization. Secondary endpoints are time interval between intervention and resolving of organ failure and multi organ dysfunction syndrome, incidence of infectious complications and duration of hospital and ICU stay. A total sample size of 100 patients was calculated to demonstrate that decompresive laparotomy with temporary abdominal closure can reduce mortality rate from 60% to 40% with 80% power at 5% alfa.ConclusionDECOMPRESS study is designed to reveal a reduction in mortality and major morbidity by using decompresive laparotomy with temporary abdominal closure in comparison with percutaneus puncture with placement of abdominal catheter in patients with ACS during SAP.Trial registrationClinicalTrials.gov Identifier: NTC00793715

Pancreatic anastomosis after pancreatoduodenectomy: A position statement by the International Study Group of Pancreatic Surgery (ISGPS).

Background. Clinically relevant postoperative pancreatic fistula (grades B and C of the ISGPS definition) remains the most troublesome complication after pancreatoduodenectomy. The approach to management of the pancreatic remnant via some form of pancreatico‐enteric anastomosis determines the incidence and severity of clinically relevant postoperative pancreatic fistula. Despite numerous trials comparing diverse pancreatico‐enteric anastomosis techniques and other adjunctive strategies (pancreatic duct stenting, somatostatin analogues, etc), currently, there is no clear consensus regarding the ideal method of pancreatico‐enteric anastomosis. Methods. An international panel of pancreatic surgeons working in well‐known, high‐volume centers reviewed the best contemporary literature concerning pancreatico‐enteric anastomosis and worked to develop a position statement on pancreatic anastomosis after pancreatoduodenectomy. Results. There is inherent risk assumed by creating a pancreatico‐enteric anastomosis based on factors related to the gland (eg, parenchymal texture, disease pathology). None of the technical variations of pancreaticojejunal or pancreaticogastric anastomosis, such as duct‐mucosa, invagination method, and binding technique, have been found to be consistently superior to another. Randomized trials and meta‐analyses comparing pancreaticogastrostomy versus pancreaticojejunostomy yield conflicting results and are inherently prone to bias due to marked heterogeneity in the studies. The benefit of stenting the pancreatico‐enteric anastomosis to decrease clinically relevant postoperative pancreatic fistula is not supported by high‐level evidence. While controversial, somatostatin analogues appear to decrease perioperative complications but not mortality, although consistent data across the more than 20 studies addressing this topic are lacking. The Fistula Risk Score is useful for predicting postoperative pancreatic fistula as well as for comparing outcomes of pancreatico‐enteric anastomosis across studies. Conclusion. Currently, no specific technique can eliminate development of clinically relevant postoperative pancreatic fistula. While consistent practice of any standardized technique may decrease the rate of clinically relevant postoperative pancreatic fistula, experienced surgeons can have lower postoperative pancreatic fistula rates performing a variety of techniques depending on the clinical situation. There is no clear evidence on the benefit of internal or external stenting after pancreatico‐enteric anastomosis. The use of somatostatin analogues may be important in decreasing morbidity after pancreatoduodenectomy, but it remains controversial. Future studies should focus on novel approaches to decrease the rate of clinically relevant postoperative pancreatic fistula with appropriate risk adjustment.

Protein C as an Early Marker of Severe Septic Complications in Diffuse Secondary Peritonitis

To evaluate the predictive value of protein C as a marker of severity in patients with diffuse peritonitis and abdominal sepsis, protein C levels were repeatedly determined and compared with serum levels of antithrombin III, plasminogen, α2-antiplasmin, Plasminogen activator inhibitor, D-dimer, C1-inhibitor, high molecular weight kininogen, and the C5a, C5b-9 fragments of the complement system. We carried out a prospective study from 44 patients with severe peritonitis confirmed by laparotomy and 15 patients undergoing elective ventral hernia repair who acted as controls. Analyzed biochemical parameters were determined before operations and on days 1, 2, 3, 5, 7, 10, and 14 after operations. For the study group, preoperative average protein C level was significantly lower in the patients who developed septic shock in the late course of the disease, with lethal outcome, than in the patients with severe peritonitis and sepsis who survived (p = 0.0001). In non-survivors, protein C activity remained decreased below 70%, whereas the course of survivors was characterized by increased values that were significantly higher (p < 0.03) at every time point than in those patients who died. Protein C was of excellent predictive value and achieved a sensitivity of 80% and a specificity of 87.5% in discriminating survivors from non-survivors within the first 48 hours of the study (AUC-0.917; p < 0.001), with a “cut-off” level of 66.0%. As for the control group, throughout the study period, protein C activity was permanently maintained within the range of normal, with significant differences with reference to the study group (p < 0.01). These results suggest that protein C represents a sensitive and early marker for the prediction of severe septic complications during diffuse peritonitis, and of outcome.

Planned staged reoperative necrosectomy using an abdominal zipper in the treatment of necrotizing pancreatitis

PurposeThe optimal operative treatment for severe necrotizing pancreatitis (SNP) still remains controversial. This article describes the operative approach with a planned staged necrosectomy using the “zipper” technique.MethodsBetween 1996 and 2000, 35 patients with SNP were treated with this approach. The patient demographics, etiology and severity of SNP, hospital course, and outcome were recorded and comparisons of several parameters were made between the patients who survived and those who died.ResultsHospital mortality was 34%. A total of 16 fistulae developed in 11 patients (31%), recurrent intra-abdominal abscesses in 4 (11%), and hemorrhaging in 5 (14%). The patients who died compared with those who survived had a higher Acute Physiology and Chronic Health Evaluation (APACHE)-II score on admission (14.5 vs 9, P < 0.001), extrapancreatic extension of necrosis more often (100% vs 65%, P = 0.02), and developed postoperative hemorrhaging more often (33% vs 4%, P = 0.038). A multivariate logistic analysis revealed an APACHE-II score of >13 on admission (P = 0.018) and an extension of necrosis behind both paracolic gutters (P < 0.001) to both be prognostic factors for mortality.ConclusionsSevere necrotizing pancreatitis still carries significant morbidity and mortality. This surgical approach facilitates the removal of all devitalized tissue and seems to decrease the incidence of recurrent intra-abdominal infection requiring reoperation. An APACHE-II score of ≥13 and an extension of necrosis behind both paracolic gutters was thus found to signify a worse outcome.

National surveillance reveals findings of Panton-Valentine leukocidin positive meticillin-resistant Staphylococcus aureus in Serbia.

Panton–Valentine leukocidin (PVL) has been the subject of worldwide attention due to its epidemiological linkage to community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA) (Tristan et al., 2007). Surveillance data for meticillin-resistant S. aureus (MRSA) has not been reported in Serbia before as the last report was before the splitting of Yugoslavia. We initiated MRSA surveillance in 2008 and report here what is to the best of our knowledge the first finding of PVL-positive MRSA in Serbia. The phenotypic and genotypic characteristics of the isolates and the clinical data related to them are reported in this article and compared to findings in other European and non-European countries.

CD117/KIT expression in pancreatic adenocarcinoma

Objective: CD117/KIT overexpression is common in neoplasms such as gastrointestinal stromal tumors and predicts clinical response to tyrosine kinase inhibitors. Pancreatic adenocarcinoma has a poor prognosis, and therefore, targeted molecular therapy may be beneficial. Marked differences in the incidence of CD117/KIT expression have been reported in pancreatic adenocarcinoma. The aim of this study was to test the hypothesis that CD117/KIT expression is unusual in pancreatic adenocarcinoma. Methods: CD117/KIT immunohistochemistry was performed on 23 archival pancreatic adenocarcinoma samples using 2 primary antibodies. Results: Satisfactory internal and external positive control labeling was achieved for both primary antibodies. No tumor cell labeling was identified using one primary antibody, whereas all cases showed cytoplasmic CD117/KIT staining with the second. However, CD117/KIT expression was also identified using the latter within nuclei and benign pancreatic epithelium, suggesting that artifactual staining was occurring. Conclusions: Pancreatic adenocarcinoma does not express CD117/KIT as assessed using the primary immunohistochemical antibody usually used in our laboratory for CD117/KIT detection. The variation in reported incidence of CD117/KIT expression in pancreatic adenocarcinoma is because of methodological differences in immunohistochemical technique. Ideally, immunohistochemical studies of this molecule should be combined with mutational status testing of the c-kit gene.

Interventional Treatment of Abdominal Compartment Syndrome during Severe Acute Pancreatitis: Current Status and Historical Perspective

Abdominal compartment syndrome (ACS) in patients with severe acute pancreatitis (SAP) is a marker of severe disease. It occurs as combination of inflammation of retroperitoneum, visceral edema, ascites, acute peripancreatic fluid collections, paralytic ileus, and aggressive fluid resuscitation. The frequency of ACS in SAP may be rising due to more aggressive fluid resuscitation, a trend towards conservative treatment, and attempts to use a minimally invasive approach. There remains uncertainty about the most appropriate surgical technique for the treatment of ACS in SAP. Some unresolved questions remain including medical treatment, indications, timing, and interventional techniques. This review will focus on interventional treatment of this serious condition. First line therapy is conservative treatment aiming to decrease IAP and to restore organ dysfunction. If nonoperative measures are not effective, early abdominal decompression is mandatory. Midline laparostomy seems to be method of choice. Since it carries significant morbidity we need randomized studies to establish firm advantages over other described techniques. After ACS resolves efforts should be made to achieve early primary fascia closure. Additional data are necessary to resolve uncertainties regarding ideal timing and indication for operative treatment.