Calprotectin and Calgranulin C as Biomarkers of Pancreatic Tumors: Baseline Levels and Level Changes after Surgery.

Pancreatic tumors and their surgical resection are associated with significant morbidity and mortality, and the biomarkers currently used for these conditions have limited sensitivity and specificity. Because calprotectin and calgranulin C serum levels have been demonstrated to be potential biomarkers of certain cancers and complications of major surgery, the levels of both proteins were tested in the current study in patients with benign and malignant pancreatic tumors that were surgically removed. The baseline serum levels and kinetics of calprotectin and calgranulin C during the 7-day postoperative period were evaluated with immunoassays in 98 adult patients who underwent pancreatic surgery. The baseline serum levels of calprotectin and calgranulin C in patients with malignant (n = 84) and benign tumors (n = 14) were significantly higher (p < 0.01) when compared to those in the healthy controls (n = 26). The serum levels of both proteins were also significantly (p < 0.05) higher in patients with benign tumors than in those with malignant tumors. After surgery, the serum levels of calprotectin and calgranulin C were significantly (p < 0.01) higher than their baseline values, and this elevation persisted throughout the seven days of the follow-up period. Interestingly, starting on day 1 of the postoperative period, the serum levels of both proteins were significantly (p < 0.05) higher in the 37 patients who developed postoperative pancreatic fistulas (POPFs) than in the patients who had uneventful recoveries (n = 61). Moreover, the serum levels of calprotectin and calgranulin C demonstrated a significant predictive value for the development of POPF; the predictive values of these two proteins were better than those of the serum level of C-reactive protein and the white blood cell count. Taken together, the results of this study suggest that calprotectin and calgranulin C serum levels are potential biomarkers for pancreatic tumors, surgical injury to the pancreatic tissue and the development of POPFs.

Fractionated plasmatic separation and adsorption does not alter haemodynamic parameters in experimental acute liver failure.

OBJECTIVE: Acute liver failure (ALF) is a rare disease with a bad prognosis. Its start is accompanied by haemodynamic instability. The aim of our study was to evaluate the influence of fractionated plasmatic separation and adsorption (FPSA) on body haemodynamics using a large animal experimental model of ALF. METHODS: ALF was induced by the devascularisation of 21 laboratory pigs. FPSA was applied in 14 animals and seven animals formed a control group. Values of systemic vascular resistance index (SVRI), heart rate (HR), pulmonary artery wedge pressure (PAWP) and cardiac index (CI) at hours 3, 6, 9 and 12 of the experiment were compared. The values from laboratory tests conducted with FPSA-treated vs. untreated ALF animals were compared using Student's t-test, paired or unpaired, as required, and Mann-Whitney U-test using EXCEL and QUATRO spreadsheet applications. RESULTS: We found no significant differences in mean arterial pressure, SVRI, or plasma lactate (p>0.05) in the FPSA-treated group but there was a significant decrease(p<0.05) in intracranial pressure (ICP). Furthermore, we observed a significant decrease in HR at hour 3. A significant increase in CI at hour 9 and a significant decrease in pulmonary artery wedge pressure at hours 6 and 12 were also observed. CONCLUSION: Our study of FPSA application (Prometheus device) for treatment of experimental ALF in a large animal model did not confirm the earlier reported development of changes in body haemodynamics.

Cerebral microdialysis reflects the neuroprotective effect of fractionated plasma separation and adsorption in acute liver failure better and earlier than intracranial pressure: a controlled study in pigs.

BACKGROUND: Cerebral edema is a well-recognized and potentially fatal complication of acute liver failure (ALF). The effectiveness of treatments that address intracranial hypertension is generally assessed by measuring intracranial pressure (ICP). The aim of this study was to determine the role of cerebral microdialysis in monitoring the efficacy of fractionated plasma separation and adsorption (FPSA) treatment for ALF. We hypothesized that in ALF cerebral microdialysis reflects the benefits of FPSA treatment on cerebral edema before ICP. METHODS: A surgical resection model of ALF was used in 21 pigs. We measured plasma ammonia concentration, brain concentrations of glucose, lactate, pyruvate, glutamate and glutamine, and ICP. Animals were randomized into three groups: in one group eight animals received 6 hours of FPSA treatment 2 hours after induction of ALF; in another group 10 animals received supportive treatment for ALF only; and in the final group three underwent sham surgery. RESULTS: The ICP was significantly higher in the ALF group than in the FPSA group 9 hours after surgery. The lactate/pyruvate (L/P) ratio was significantly lower in the FPSA group than the ALF group 5 hours after surgery, before any significant difference in ICP was detected. Indeed, significant changes in the L/P ratio could be observed within 1 hour of treatment. Glutamine levels were significantly lower in the FPSA group than the ALF group between 6 hours and 10 hours after surgery. CONCLUSIONS: Brain lactate/pyruvate ratio and concentration of glutamine measured by cerebral microdialysis reflected the beneficial effects of FPSA treatment on cerebral metabolism more precisely and rapidly than ICP in pigs with fulminant ALF. The role of glutamine as a marker of the efficacy of FPSA treatment for ALF appears promising, but needs further evaluation.

Artificial liver support system reduces intracranial pressure more effectively than bioartificial system: an experimental study.

OBJECTIVES: Extracorporeal liver support (ELS) may play a role in bridging therapy in patients with acute liver failure (ALF). The aim of this study was to compare the influence of nonbiological and biological methods on intracranial pressure (ICP) in an animal model of ALF. METHODS: A surgical devascularization model of ALF in pigs (35-40 kg) was used. Elimination therapy started after the onset of hypoglycemia. Biochemical parameters (bilirubin, ammonia, lactate, etc.) as well as ICP and cerebral perfusion pressure (CPP) were monitored for 12 hours. Of the total 31 pigs with ALF, 14 animals were treated by fractionated plasma separation and absorption (FPSA), 10 were treated with a bioartificial liver (BAL), and 7 animals were used as a control group. RESULTS: FPSA and BAL treatment started on average 3 hours 17 minutes and 2 hours 21 minutes, after devascularization and lasted for 5 hours 54 minutes and 5 hours 43 minutes, respectively. Ammonia levels were lower in the FPSA group, and bilirubin levels differed significantly in both the FPSA and BAL groups compared with controls. However, ICP values were reduced more effectively in pigs treated by FPSA: 19.1 vs. 27.0 mm Hg at 9 hours, 22.5 vs. 28.7 mm Hg at 11 hours, and 24.0 vs. 33.0 mm Hg at 12 hours (p<0.05). CONCLUSIONS: The artificial liver support system FPSA reduced ICP values more effectively than the Performer O. Liver RanD BAL system. Compared with this BAL system, the nonbiological elimination method of FPSA is a simpler application with the advantage that it can be applied in a more continuous way.

S-adenosylmethionine does not reduce ischaemia-reperfusion injury to a marginal liver graft in an in vivo experiment.

BACKGROUND/AIMS: There are a limited number of appropriate cadaver liver donors. One possible solution is the use of marginal liver grafts from cadaver donors for liver transplantation. METHODOLOGY: Rats with liver steatosis were divided into four containing seven animals each: I-a: steatotic liver grafts; +S-adenosylmethionine; I-b: steatotic liver grafts were transplanted; no S-adenosylmethionine; II-a: normal liver grafts, +S-adenosylmethionine; II-b: normal liver grafts. Blood samples were taken at days -1, 3 and 14. RESULTS: ALT values at day 14: 1.75 ± 1.10µkat/L (in group I-a), 1.91 ± 1.41µkat/L (in group I-b), 2.13±1.85µkat/L (in group II-a) and 2.08 ± 1.35µkat/L (in group II-b). There were no significant differences between these values. GSH values at day 14 post-transplantation were: 44.90 ± 8.61µM/mg (in group I-a), 43.82±8.58µM/mg (in group I-b), 41.65 ± 4.87µM/mg (in group II-a) and 42.71 ± 4.17µM/mg (in control group II-b). CONCLUSIONS: Our study did not demonstrate the positive effect of S-adenosylmethionine on ischaemia-reperfusion injury during liver transplantation in rats.