Thermotherapy using magnetic nanoparticles is a new technique for interstitial hyperthermia and thermoablation based on magnetic field-induced excitation of biocompatible superparamagnetic nanoparticles. To evaluate the potential of this technique for minimally invasive treatment, we carried out a systematic analysis of its effects on experimental glioblastoma multiforme in a rat tumor model. Tumors were induced by implantation of RG-2-cells into the brains of 120 male Fisher rats. Animals were randomly allocated to 10 groups of 12 rats each, including controls. Animals received two thermotherapy treatments following a single intratumoral injection of two different magnetic fluids (dextran- or aminosilane-coated iron-oxide nanoparticles). Treatment was carried out on days four and six after tumor induction using an alternating magnetic field applicator system operating at a frequency of 100 kHz and variable field strength of 0-18 kA/m. The effectiveness of treatment was determined by the survival time of the animals and histopathological examinations of the brain and the tumor.Thermotherapy with aminosilane-coated nanoparticles led up to 4.5-fold prolongation of survival over controls, while the dextran-coated particles did not indicate any advantage. Intratumoral deposition of the aminosilane-coated particles was found to be stable, allowing for serial thermotherapy treatments without repeated injection. Histological and immunohistochemical examinations after treatment revealed large necrotic areas close to particle deposits, a decreased proliferation rate and a reactive astrogliosis adjacent to the tumor.Thus, localized interstitial thermotherapy with magnetic nanoparticles has an antitumoral effect on malignant brain tumors. This method is suitable for clinical use and may be a novel strategy for treating malignant glioma, which cannot be treated successfully today. The optimal treatment schedules and potential combinations with other therapies need to be defined in further studies.

PI-RADS v2 improved diagnostic performance for the assessment of suspicious intraprostatic lesions identified in PI-RADS v1 for both readers and led to higher inter-reader reliability. These results suggest that PI-RADS v2 is a reliable and replicable reporting system for the assessment of prostate cancer.

Using a prospectively collected database of patients undergoing diagnostic or therapeutic angiography via transfemoral access, we sought to determine those patients who may benefit from ultrasound-guided puncture of the femoral artery. One-hundred-twelve patients with normal anticoagulation parameters were randomized in two groups. Fifty-six patients received ultrasound-guided puncture of the femoral artery, 56 patients underwent traditional palpation-guided vessel cannulation. Parameters assessed included procedure-time, number of attempts for successful puncture, intensity of the arterial pulse, previous ipsilateral punctures, history and risk factors of arteriosclerosis and leg circumference at the site of puncture. The data was analyzed by using outcome measures according to evidence-based medicine criteria. Only in patients with weak arterial pulse and thoses with a leg circumference of 60 cm or greater ultrasound guidance significantly decreased the number of attempts needed as well as the time for successful arterial puncture. In both patient subgroups, the number needed to treat (NNT) was 2, the absolute benefit increase (ABI) was 50 and 57%, respectively. In contrast, time for vessel cannulation was increased in patients with strong arterial pulse using ultrasound guidance. No significant differences were found with respect to diminished complications neither comparing both patient groups nor comparing risk subgroups. In conclusion ultrasound guidance for femoral artery access is recommended only in patients with a weak or absent arterial pulse and obese patients.

So far, the therapeutic outcome of hyperthermia has shown heterogeneous responses depending on how thermal stress is applied. We studied whether extrinsic heating (EH, hot air) and intrinsic heating (magnetic heating [MH] mediated by nanoparticles) induce distinct effects on pancreatic cancer cells (PANC-1 and BxPC-3 cells). The impact of MH (100 µg magnetic nanoparticles [MNP]/mL; H=23.9 kA/m; f=410 kHz) was always superior to that of EH. The thermal effects were confirmed by the following observations: 1) decreased number of vital cells, 2) altered expression of pro-caspases, and 3) production of reactive oxygen species, and 4) altered mRNA expression of Ki-67, TOP2A, and TPX2. The MH treatment of tumor xenografts significantly ( P ≤0.05) reduced tumor volumes. This means that different therapeutic outcomes of hyperthermia are related to the different responses cells exert to thermal stress. In particular, intratumoral MH is a valuable tool for the treatment of pancreatic cancers.

To evaluate the technical and clinical success of embolisation in patients with lifethreatening spontaneous retroperitoneal haematoma (SRH) and to assess predictors of clinical outcome.MATERIALS AND METHODS: Thirty patients (mean age: 71.9AE9.8 years) with SRH underwent digital subtraction angiography (DSA). All patients received anticoagulant or antiplatelet medication or a combination of both at the time the SRH occurred.RESULTS: Pre-interventional computed tomography angiography (CTA) revealed active retroperitoneal bleeding in 28 of 30 (93.3%) patients. DSA identified active haemorrhage in 22 of 30 patients (73.3%). Twenty-nine of 30 (96.7%) patients underwent embolisation. n-Butyl-2cyanoacrylate (NBCA) was used in 15 patients (51.7%), coils were used in 10 patients (34.5%), and both embolic agents were used in four patients (13.8%). The technical success rate was 100%. Pre-interventional haemoglobin levels increased significantly after embolotherapy from 70.9AE16.1 g/l to 87AE11.3 g/l (p<0.001), whereas partial thromboplastin time decreased from 58AE38 to 30AE9 seconds (p<0.001) after embolotherapy. The need for transfusion of concentrated red cells decreased from 3AE2.2 to 1AE1.1 units (p<0.001) after the intervention. Clinical success was achieved in 19 of 29 (65.5%) patients. No major procedure-related complications occurred. Seven patients (24.1%) died within 30 days after the procedure.CONCLUSION: Embolotherapy in patients with life-threatening SRH leads to a high technical success rate and is a safe therapeutic option. The clinical success rate was acceptable and

Despite intensive research and medical advances met, metastatic disease remains the most common cause of death in cancer patients. This results from late diagnosis, poor therapeutic response and undetected micrometastases and tumor margins during surgery. One approach to overcome these challenges involves fluorescence imaging, which exploits the properties of fluorescent probes for diagnostic detection of molecular structures at the onset of transformation and for intraoperative detection of metastases and tumor margins in real time. Considering these benefits, many contrast agents suitable for fluorescence imaging have been reported. However, most reports only demonstrate the detection of primary tumors and not the detection of metastases or their application in models of image-guided surgery. In this work, we demonstrate the influence of fibroblast activation protein (FAP) on the metastatic potential of fibrosarcoma cells and elucidate the efficacy of activatable FAP-targeting immunoliposomes (FAP-IL) for image-guided detection of the spontaneous metastases in mice models. Furthermore, we characterized the biodistribution and cellular localization of the liposomal fluorescent components in mice organs and traced their excretion over time in urine and feces. Taken together, activatable FAP-IL enhances intraoperative imaging of metastases. Their high accumulation in metastases, subsequent localization in the bile canaliculi and liver kupffer cells and suitable excretion in feces substantiates their potency as contrast agents for intraoperative imaging.

This work demonstrates the design of activatable bispecific liposomes aimed to target HER2, a poor prognosis tumor marker in many tumor types, and fibroblast activation protein (FAP), a universal tumor marker overexpressed on tumor fibroblasts and pericytes of almost all solid tumors. Encapsulating liposomes with a quenched concentration of a NIRF dye which only fluoresced after cellular degradation and activation enabled reliable visualization of the destination of the cargo in cells and animal studies. Conjugating single chain antibody fragments directed to FAP, together with Trastuzumab, a humanized monoclonal antibody for HER2 resulted in the activatable bispecific liposomes. In animal models of xenografted human breast tumors, the remarkable ability of the bispecific probes to simultaneously deliver the encapsulated dye into the nuclei of target tumor cells and tumor fibroblasts could be demonstrated. Hence, the bispecific probes represent model tools with high significance to address tumor heterogeneity and manage Trastuzumab resistance in the future.

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