Surgery
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The American Joint Committee on Cancer (AJCC) T classification system for cholangiocarcinoma does not take into account the unique pathologic features of the bile duct. As such, the current AJCC T classification for distal cholangiocarcinoma may be inaccurate. ⋯ The AJCC T classification for distal cholangiocarcinoma does not accurately predict prognosis. Depth of the bile duct carcinoma invasion is a better alternative method to determine prognosis and should be incorporated into the pathologic assessment of resected distal cholangiocarcinoma.
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Bone marrow mesenchymal stem cells (MSCs) may mediate their beneficial effects by paracrine mechanisms. Recently, we reported that tumor necrosis factor-alpha (TNF-alpha) increased the release of vascular endothelial growth factor (VEGF) from human MSCs and augmented transforming growth factor-alpha (TGF-alpha)-stimulated VEGF secretion. However, it is unknown whether TNF-alpha stimulates VEGF production via TNF receptor 1 (TNFR1) or 2 (TNFR2) and the mechanism by which TNF-alpha augments TGF-alpha (a ligand of epidermal growth factor receptor, EGFR) stimulated VEGF production. We hypothesized that the ablation of TNFR2 would decrease TNF-alpha-stimulated and/or TGF-alpha- stimulated VEGF production via MEK-dependent mechanisms. ⋯ TNFR2 plays a vital role in the effects of TNF-alpha and TGF-alpha on MSC VEGF production. The activation of MEK was implicated in this novel cross talk between TNFR2 and TGF-alpha-EGFR in regulating the production of VEGF in human MSCs.
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We have demonstrated previously that valproic acid (VPA), a histone deacetylase inhibitor, can improve survival in lethal models of hemorrhagic shock. This study investigated whether VPA treatment would improve survival in a clinically relevant large animal model of poly-trauma/hemorrhagic shock, and whether the protective effects are executed through the Akt survival pathway. ⋯ Treatment with VPA without blood transfusion improves early survival in a highly lethal poly-trauma and hemorrhagic shock model. The survival advantage is due not to improvement in resuscitation but to better tolerance of shock by the cells, in part due to the preservation of the Akt survival pathway.
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The aim of the current study was to determine the role of heparin-binding (HB) epidermal growth factor (EGF)-like growth factor as a mediator of gut barrier function after hemorrhagic shock and resuscitation (HS/R) in mice. ⋯ HB-EGF is essential for the preservation of gut barrier function after HS/R. These findings support the clinical use of HB-EGF in protection of the intestines from disease states associated with intestinal hypoperfusion injury.
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Studies of sexual dimorphism in trauma outcomes suggest that women have a survival advantage compared to equivalently injured men. It is unknown if this gender disparity is mediated by potentially life-threatening complications. ⋯ This study demonstrates that women are less likely than men to develop inpatient complications, suggesting that the survival advantage among women after traumatic injury may involve a reduced susceptibility to developing life-threatening complications.