Effects of vacuum-assisted closure and Drotrecogin alpha on inflammatory markers in severe acute pancreatitis

In severe acute pancreatitis (SAP) inflammatory processes foster necrosis, cellular lysis and liberation of vasoactive substances associated with multiple organ failure. The effects of vacuum-assisted closure and Drotrecogin alpha on inflammatory cytokines were evaluated in SAP patients with infected necrosis. Methods: Forty-six patients were included in three groups: Group 1, necrosectomy and abdominal cavity washing;Group 2, necrosectomy plus vacuum-assisted closure (VAC), and Group 3, necrossectomy plus VAC plus Drotrecogin alpha. Immunoreactive IL-32, TNF-α, IL-6, TGF-β and IL-2 cytokines were quantified with ELISA method. Results: IL-32 was significantly increased in all patients, predominantly the non-survivor of Group 3 (p 0.0001). Group 2 maintained increased IL-32 levels throughout. Peak TNF-α was observed in non-survivors of Groups 1 and 2, with a frank tendency to decrease in Group 3. The IL-6 was increased, sustained throughout the study, peaking at the onset in non-survivors. At the end IL-6 tended to diminish, predominantly in survivors. TNF-α and IL-6 were significantly increased on hospitalization, with a maximum peak in non-survivors of all groups. Initial values of TGF-β were significantly increased in survivors of the three groups, and were significantly diminished in non-survivors;affecting pancreas regeneration and favoring systemic inflammation, with possible multiple-organ repercussions. IL-2 levels were elevated, predominantly in non-survivors of Group 1. There was positive correlation between the increase IL-32 and TNF-α, and negative correlation between the increase in TNF-α and decrease in TGF-β;and, a tendency for negative correlation between the IL-2 increased and TGF-β levels. Conclusion: We found a generalized, sustained inflammatory state that fosters a torpid outcome in SAP patients.

Alterations in fibrinolytic system proteins PAI-1,MMP-3,MMP-8,TIMP-1 and TIMP-2 in post-cholecystectomy bile duct injury

Introduction: In bile duct injuries (BDI), cholestasis and cholangitis can alter the fibrinolytic system by promoting an increase of extracellular matrix depositions which favor an imbalance between metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). Materials and Methods: Levels of PAI-1, MMP-3, MMP-8, TIMP-1 and TIMP-2 in 35 patients with post-cholecystectomy BDI by complete biliary obstruction were measured and compared to a healthy control group. Sirius red staining and immune staining for MMP-3 and MMP-8 were also undertaken in liver biopsies. Results: Levels of PAI-1, TIMP-1, TIMP-2 and MMP-8 were higher in BDI than healthy controls: 15 ± 2 ng/mL vs 7.1 ± 2 ng/mL (p 0.024);539 ± 64 ng/mL vs 256 ± 13 ng/mL (p p p 2 vs. 22865.7 ± 3865 μm2 in healthy controls (p 2 vs. 30744.2 ± 5810.2 μm2 (p 2 vs. 116337.9 ± 24803.3 μm2 (p 0.55). These results suggest an imbalance between fibrogenic/fibrinolytic protein levels. Interestingly, expression of the fibrinolytic protein MMP-8 was increased in serum and liver biopsies in BDI. Conclusion: We found an imbalance of profibrogenic molecules which promote extracellular matrix deposition. The over-expression of fibrinolytic proteins such as MMP-8 could limit liver fibrosis, preventing hepatic dysfunction in post-cholecystectomy BDI.