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.
Aims: The kidney becomes atrophic in advanced chronic kidney disease, and renal size and parenchymal volume correlate with renal function. However, alterations in renal parenchymal volume have not been adequately studied in terms of the renal cortex and medulla. We investigated the relationship between the changes in the renal cortex and medulla and renal function. Methods: Renal ultrasound (US) parameters including renal length, parenchymal thickness, cortical thickness and medullary thickness were assessed in 176 subjects, who were categorized into 4 groups based on the estimated glomerular filtration rate (ml/min/1.73 m2): group 1, ≥90; group 2, ≥60 but <90; group 3, ≥30 but <60; and group 4, <30. Renal US parameters in both kidneys were compared among the 4 groups. Results: We found stepwise associations in renal length, cortical thickness and parenchymal thickness with decreased renal function. Medullary thickness showed no changes among groups 1-3. Multiple linear regression analysis including sex, age and renal US parameters showed that only renal length was an independent predictor of renal function. When analyzed in groups 1-3, cortical thickness was the strongest associated parameter. Lower cortical left/right ratio (left cortical thickness/right cortical thickness) showed a stepwise association with a decrease in renal function. Conclusion: Renal length and cortical thickness measured by US were correlated with renal function. In particular, left cortical thickness could help to detect early changes in renal function.
The purpose of this study was to evaluate the detection rate of tumor vessels and vascularity in hepatocellular carcinoma (HCC) by contrast-enhanced coded US using Levovist, and to compare with conventional color/power Doppler US (CDUS) and dynamic CT. Ninety nodules (72 hypo/isoechoic nodules, 18 hyperechoic nodules) in 61 patients were studied. We observed tumor vessels by continuous transmission at the early vascular phase (40 s following administration of Levovist) and vascularity by intermittent transmission (intervals of 2-3 s) at the late vascular phase (40 to approximately 120 s). The detection rate of tumor vessels at the early vascular phase was 97% in hypo/isoechoic nodules and 70% in hyperechoic nodules with high density in dynamic CT being higher than that by CDUS. Tumor vascularity at the late vascular phase in hypo/isoechoic and hyperechoic nodules was hyper-enhancement in 78 and 40%, iso-enhancement in 19 and 40%, and hypo-enhancement in 3 and 0%, respectively. The detection rates of tumor vessels and vascularity in hyperechoic nodules were similar to those by CDUS. The detection rates of tumor vessels and vascularity were not affected by the tumor size in HCC tumors with high density in dynamic CT. Contrast-enhanced US with Levovist was superior to CDUS and equal to dynamic CT to assess tumor vessels in hypo/isoechoic nodules. Although it was equal to CDUS for hyperechoic nodules, this modality is useful in evaluating tumor hemodynamics.
Renal shear wave velocity was not associated with advanced renal impairment. However, it reflected alteration of renal aging, and this technique may be useful to detect renal impairment in the earlier stages.
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