Hüdayi Korkusuz

PURPOSE: Microwave ablation (MWA) is a new minimally invasive method for thermal ablation of benign thyroid nodules with promising results. The aim of this study was to investigate whether MWA has an impact on thyroid function. MATERIALS AND METHODS: Thirty patients with a total of 34 benign thyroid nodules underwent MWA between January 2013 and July 2014. Serum levels of triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH), thyroglobuline (Tg) and additionally antibodies against Tg (anti-Tg), thyrotropin receptors (TRAb) and thyroid peroxidase (anti-TPO) were measured at enrolment, 24 h after MWA, as well as at the 3-month and 6-month follow-up. Moreover, the nodule volume was evaluated to determine effectiveness. RESULTS: Serum TSH, T4, T3 and Tg levels did not change significantly at the 3-month or 6-month follow-up (p > 0.05); thyroid function was not affected by MWA. Antibody levels did not change significantly either; however, two patients developed antibodies after treatment. A volume reduction of 51.4% or 7.85 mL could be demonstrated after 3 months and a reduction of 55.8% or 14.0 mL after 6 months. Slight complications such as mild pain during the ablation or superficial haematomas emerged. The development of Graves' disease and mild Horner's syndrome were observed as more severe side effects. CONCLUSIONS: The data suggest MWA as an alternative for the treatment of benign thyroid nodules. While first results for preservation of thyroid function are positive, further measurements of laboratory data and especially antibodies are necessary.

iRGD is a derivative of the integrin-binding peptide RGD, which selectively increases the penetrability of tumor tissue to various coadministered substances in several preclinical models. In this study, we investigated the ability of iRGD to improve the delivery of sorafenib and doxorubicin therapy in hepatocellular carcinoma (HCC) using established mouse models of the disease. A contrast-enhanced MRI method was developed in parallel to assess the in vivo effects of iRGD in this setting. We found that iRGD improved the delivery of marker substances to the tumors of HCC-bearing mice about three-fold without a parallel increase in normal tissues. Control peptides lacking the critical CendR motif had no effect. Similarly, iRGD also selectively increased the signal intensity from tumors in Gd-DTPA-enhanced MRI. In terms of antitumor efficacy, iRGD coadministration significantly augmented the individual inhibitory effects of sorafenib and doxorubicin without increasing systemic toxicity. Overall, our results offered a preclinical proof of concept for the use of iRGD coadministration as a strategy to widen the therapeutic window for HCC chemotherapy, as monitored by Gd-DTPA-enhanced MRI as a noninvasive, clinically applicable method to identify iRGD-reactive tumors.

OBJECTIVES: To evaluate the performance of late enhancement dual-energy CT (LE-DECT) for the detection of infarcted myocardium as compared with 1.5-T late enhancement magnetic resonance imaging (LE-MRI) in a porcine model of reperfused chronic myocardial infarction (MI), using histopathology as standard of reference. MATERIALS AND METHODS: In 8 healthy minipigs, MI was induced by 30-minute balloon occlusion of the left anterior descending coronary artery. Sixty-one ± 4 days after left anterior descending coronary artery occlusion, LE-DECT was performed 5, 10, and 15 minutes subsequent to contrast material injection. Therefore, a dual-source CT scanner (Somatom Definition, Siemens Healthcare, Forchheim, Germany) was used in dual-energy mode with the following protocol: tube potential/current 140 kV/95 mAs on tube A and 100 kV/165 mAs on tube B, collimation 2 × 32 × 0.6 mm, 1.5 mL/kg contrast material injected at 3 to 4 mL/s. Myocardial iodine distribution was calculated from the dual-energy data and superimposed on the gray scale multiplanar reformats of the heart in short-axis view. Fifty ± 12 minutes after LE-DECT imaging, 1.5-T LE-MRI (Magnetom Avanto, Siemens Healthcare, Forchheim, Germany) was performed 10 minutes successive to injection of contrast material using phase-sensitive inversion recovery sequences. For all pigs investigated, 2,3,5-triphenyltetrazolium chloride staining and histopathology of stained-tissue samples were acquired. Two experienced radiologists assessed all imaging studies in a random manner and were blinded to the results of the other techniques for the presence of late enhancement (LE). The American Heart Association 17-segment model was used to compare the results of LE-DECT, 100 kV grayscale LE images, LE-MRI, and histopathology. Size of MI was calculated for histopathological findings, LE-MRI, LE-DECT, and 100 kV grayscale LE images 10 minutes after contrast agent injection. Agreement between infarct size assessed with imaging modalities and histopathology was evaluated with Bland-Altman analysis. RESULTS: Of the 136 myocardial segments in 8 minipigs, histopathology found MI in 27 segments. Diagnostic per-segment sensitivities and specificities for 100 kV grayscale LE images, LE-DECT images, and MR images obtained 10 minutes after contrast agent injection for both the readers were 0.62, 0.77, 0.79 and 0.97, 0.92, 0.94, respectively. Although sensitivities were higher for LE-DECT and LE-MRI than for 100 kV grayscale images, no statistically significant difference for the diagnostic accuracies of 100 kV grayscale LE images, LE-DECT images, and MR images (0.9, 0.89, 0.9) existed 10 minutes successive to contrast agent injection (all P > 0.05). Infarct size for LE-MRI, LE-DECT, and 100 kV grayscale LE images correlated well with histopathological findings (r = 0.97, 0.96, and 0.94; all P < 0.01). CONCLUSIONS: This feasibility study shows a high accuracy and a good correlation of LE-DECT and LE-MRI to histopathology for the detection of LE in a porcine model of reperfused chronic MI.

Highly promising preclinical data obtained in cultured cells and in nude mice bearing xenografts contrast with the rather modest clinical efficacy of Polo-like kinase 1 (Plk1) inhibitors. In the present study, we investigated if Plk1 might be a suitable target in hepatocellular carcinoma (HCC) and if a genetically engineered mouse tumor model that well reflects the tumor cell and micro-environmental features of naturally occurring cancers might be suitable to study anti-Plk1 therapy. Analysis of Plk1 expression in human HCC samples confirmed that HCC express much higher Plk1 levels than the adjacent normal liver tissue. Inhibition of Plk1 by an adenovirus encoding for a short hairpin RNA against Plk1 or by the small-molecule inhibitor BI 2536 reduced the viability of HCC cell lines and inhibited HCC xenograft progression in nude mice. Treatment of transforming growth factor (TGF) α/c-myc bitransgenic mice with BI 2536 during hepatocarcinogenesis reduced the number of dysplastic foci and of Ki-67-positive cells within the foci, indicating diminished tumorigenesis. In contrast, BI 2536 had no significant effect on HCC progression in the transgenic mouse HCC model as revealed by magnetic resonance imaging. Measurement of BI 2536 by mass spectrometry revealed considerably lower BI 2536 levels in HCC compared with the adjacent normal liver tissue. In conclusion, low intratumoral levels are a novel mechanism of resistance to the Plk1 inhibitor BI 2536. Plk1 inhibitors achieving sufficient intratumoral levels are highly promising in HCC treatment.