Interhospital transfers resulting in liver transplantation: Clinical, regulatory, and economic issues.

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Tailored treatment of patients with hepatocellular carcinoma with portal vein invasion: experience from a multidisciplinary hepatobiliary tumor program within a NCI comprehensive cancer center.

BACKGROUND: Hepatocellular carcinoma (HCC) with portal vein invasion (PVI) has a poor prognosis with limited treatment options. Intra-arterial brachytherapy (IAB) and transarterial chemoembolization (TACE) yield local control but risk accelerating liver dysfunction. The outcomes, survival, and safety of selective liver-directed treatment are reported. METHODS: Thirty-seven consecutive patients with HCC and PVI treated between 2009 and 2015 were reviewed from a prospectively collected database. Univariate analysis, Kaplan-Meier plots using the log-rank method, and multivariate analyses were performed. Statistical significance was defined as P<0.05. Overall survival was reported in months (median; 95% CI). RESULTS: Most patients (59%) had PVI identified at initial HCC diagnosis. The liver-directed therapy group (n=22) demonstrated a survival advantage versus the systemic/supportive care group (n=14) [23.6 (5.8, 30.9) vs. 6.0 (3.5, 8.8) months]. Patients indicated for liver directed therapy had unilateral liver involvement (100% vs. 43%, P<0.0001), lower median alkaline phosphatase (105.5 vs. 208.0, P=0.002), and lower mean Child-Turcotte-Pugh (CTP) score (5.9 vs. 7.2, P=0.04) and tolerated treatment without serious complications. CONCLUSIONS: In HCC patients presenting with PVI, liver-directed therapy was safely performed in patients with limited venous involvement and preserved liver function. Liver-directed therapy extended survival for these patients indicated for palliative chemotherapy by traditional guidelines.

Antisense p53 transduction leads to overexpression of bcl-2 and dexamethasone resistance in multiple myeloma.

Multiple myeloma is a malignant proliferation of plasma cells which fail to undergo apoptosis. To understand events associated with lack of apoptosis in these cells, we studied effect of antisense p53 gene transduction in a multiple myeloma cell line, ARH77. Adeno-associated virus was used as a vector to introduce p53 cDNA in an antisense orientation driven by a herpes virus thymidine kinase promoter. We observed, that an antisense p53 (p53as) transduced cell line showed marked reduction in p53 mRNA and protein expression and increased growth when compared to the control cell lines transduced with neomycin-resistance gene or untransduced cells. There was a concomitant up-regulation of bcl-2 expression by over five-fold in p53as-transduced cells compared with controls; while there was no significant change in expression of c-myc and IL-6, genes implicated in myeloma growth. We measured apoptosis in the transduced cells by DNA end-labeling reaction which revealed decrease in apoptosis from 15.6% in control cells to 1.6% in p53as-transduced cells. Additionally, the p53as cells over expressing bcl-2 also showed resistance to killing by dexamethasone. In summary, our data demonstrates that loss of p53 function leads to myeloma cell progression and resistant phenotype through bcl-2-related mechanisms.