Omega-3 fatty acid (FA) emulsions reduce LPS-stimulated murine macrophage TNF-alpha production, but the exact mechanism has yet to be defined. The purpose of this study was to determine the mechanism for omega-3 FA inhibition of macrophage TNF-alpha production following LPS stimulation. RAW 264.7 cells were pretreated with isocaloric emulsions of omega-3 FA (Omegaven), omega-6 FA (Lipovenos), or DMEM and subsequently exposed to LPS. IkappaB-alpha and phospho-IkappaB-alpha were determined by Western blotting. NF-kappaB binding was assessed using the electromobility shift assay, and activity was measured using a luciferase reporter vector. RT-PCR and ELISA quantified TNF-alpha mRNA and protein levels, respectively. Pretreatment with omega-3 FA inhibited IkappaB phosphorylation and significantly decreased NF-kappaB activity. Moreover, omega-3-treated cells demonstrated significant decreases in both TNF-alpha mRNA and protein expression by 47 and 46%, respectively. These experiments demonstrate that a mechanism for proinflammatory cytokine inhibition in murine macrophages by omega-3 FA is mediated, in part, through inactivation of the NF-kappaB signal transduction pathway secondary to inhibition of IkappaB phosphorylation.

No abstract

Staging of hepatocellular carcinoma (HCC) is complex and relies on multiple factors including tumor extent and hepatic function. No single staging system is applicable to all patients with HCC. The staging of the American Joint Committee on Cancer / International Union for Cancer Control should be used to predict outcome following resection or liver transplantation. The Barcelona Clinic Liver Cancer scheme is appropriate in patients with advanced HCC not candidate for surgery. Dual phase computed tomography or magnetic resonance imaging can be used for pretreatment assessment of tumor extent but the accuracy of these methods remains poor to characterize < 1 cm lesions. Assessment of tumor response should not rely only on tumor size and new imaging methods are available to evaluate response to therapy in HCC patients. Liver volumetry is part of the preoperative assessment of patients with HCC candidate for resection as it reflects liver function. Preoperative portal vein embolization is indicated in patients with small future liver remnant (≤ 20% in normal liver; ≤ 40% in fibrotic or cirrhotic liver). Tumor size is not a contraindication to liver resection. Liver resection can be proposed in selected patients with multifocal HCC. Besides tumor extent, surgical resection of HCC may be performed in selected patients with chronic liver disease.

No abstract