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Radiofrequency ablation with artificial pleural effusion is a safe and beneficial treatment option that offers excellent local control through visualization of hepato-cellular carcinomas under the diaphragm.

The aim of this study was to clarify the clinical features of patients with isolated HCC metastases to the heart. A 66-year-old female hospitalized with a hepatocellular carcinoma (HCC) ranging from the right to the left lobe and with a tumor thrombus in the main portal vein, was treated with intraarterial cisplatin, 5-fluouracil, adriamycin and mitomycin. Computed tomography (CT) one month later revealed that the HCC had progressed with multiple lung metastases and moderate ascites. The patient had no symptoms. Magnetic resonance imaging (MRI) and echocardiography revealed a round, movable tumor with a diameter of 2 cm in the right atrium (RA). The patient succumbed to HCC five months later. An autopsy revealed HCC with portal tumor thrombi and metastases to the lungs, inferior vena cava (IVC) and RA. The metastases in the RA and IVC were not continous with the intrahepatic tumor and were histologically attached to the endocardium and endothelium, respectively. An isolated metastasis of a HCC of the RA and IVC is extremely rare. In conclusion, although the majority of isolated metastases of HCC to the heart were diagnosed by echocardiography and were treated with mainly surgery, they had poor prognosis. The echocardiography should be performed for patients with advanced HCC. A novel treatment including molecular targeted drugs is required.

Purpose Ras/Raf/MEK/ERK signaling is critical for tumor cell proliferation and survival. Selumetinib is a potent, selective, and orally available MEK1/2 inhibitor. In the current study, we evaluated the therapeutic efficacy of selumetinib alone or with cediranib, an orally available potent inhibitor of all three VEGFR tyrosine kinases, in murine orthotopic NSCLC models. Experimental Design NCI-H441 or NCI-H460 KRAS-mutant human NSCLC cells were injected into the lungs of mice. Mice were randomly assigned to treatment with selumetinib, cediranib, paclitaxel, selumetinib plus cediranib, or control. When controls became moribund, all animals were sacrificed and assessed for lung tumor burden and locoregional metastasis. Lung tumors and adjacent normal tissues were subjected to immunohistochemical analyses. Results Selumetinib inhibited lung tumor growth and, particularly at higher dose, reduced locoregional metastasis, as did cediranib. Combining selumetinib and cediranib markedly enhanced their antitumor effects, with near complete suppression of metastasis. Immunohistochemistry of tumor tissues revealed that selumetinib alone or with cediranib reduced ERK phosphorylation, angiogenesis, and tumor cell proliferation and increased apoptosis. The antiangiogenic and apoptotic effects were substantially enhanced when the agents were combined. Selumetinib also inhibited lung tumor VEGF production and VEGFR signaling. Conclusions In the current study, we evaluated therapy directed against MEK combined with antiangiogenic therapy in distinct orthotopic NSCLC models. MEK inhibition resulted in potent antiangiogenic effects with decreased VEGF expression and signaling. Combining selumetinib with cediranib enhanced their anti-tumor and antiangiogenic effects. We conclude that combining selumetinib and cediranib represents a promising strategy for the treatment of NSCLC.