Radioembolisation des tumeurs hépatiques par microsphères marquées à l’yttrium-90

This study is a retrospective analysis of 64 patients with a primary or secondary liver malignancy, referred for yttrium-90 radioembolisation between December 2006 and September 2010. Among these 64 patients, 54 received a total number of 69 injections (one to three treatments per patient). The mean activity injected per treatment was 3.1 ± 1.6 GBq. The liver targeted dose was 123.1 ± 39 Gy. Pulmonary shunt, detected in 55% of treatments, was 5.7% ± 7.4. The pulmonary dose was 4.7 ± 7.1 Gy. Overall, response rate per patient, evaluated at 3 months by EASL or modified RECIST criteria, was 72.9%, 70% for hepatocellular carcinoma. The complication rate was relatively low (17%) with only two serious events. ⁹⁰Y-microspheres radioembolisation of liver malignancies is an effective and well-tolerated therapy. Until now often used as a salvage therapy, the recent and ongoing studies should better define its place in the therapeutic strategy (adjuvant, neoadjuvant, first line) and possible association with chemotherapy and targeted therapies.     

Impact d’une méthode originale de synchronisation respiratoire sur la détection des lésions hépatiques en TEP/TDM au F-FDG

In ¹⁸F-Fluoro-Desoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT), respiratory motion induces bias in image interpretations. These movements can introduce organs misregistration between both modalities yielding erroneous attenuation correction and thus wrong maximum standardized uptake values (SUV_max). We present here the results of a clinical study which aims to assess the benefits of a novel respiratory gating method (CT-based) for liver lesions detection. Forty-nine patients planed to undergo hepatic surgery were addressed to our department for PET/CT examination before surgery. Each patient had both standard and CT-based protocols. Hepatic lesions described by two observers on PET images were compared with pathological analysis and intra-operative ultrasound. Sensitivities calculated for observer 1 were 60 and 64% for standard and CT-based, respectively. For the second observer, sensitivities were 58.7 and 72%. CT-based showed a significant increase (P < 0.01) of sensitivity on a per-lesion basis for one observer. CT-based did not improve inter-observer variability. At last, SUV_max were significantly higher with CT-based method (P < 0.001). Respiratory gating CT-based method is easily bearable by the patients. This procedure ensures good matching between both modalities and reduces motion-blurring effect in PET data. CT-based method improves liver lesions detectability and allows more accurate quantitation compared to non-gated FDG-PET/CT examinations.     

Is there a place for nuclear medicine in the radioembolization of liver tumors?

This is purposely an ultraprovocative title for the broad nuclear medicine community (including radiophysics and radiopharmacy) which leads us to ask questions about how we should correctly use ⁹⁰Yttrium (MSY90) microspheres in the treatment of liver tumors.     

Ammonium ions enhance the flow through the pyruvate dehydrogenase in Ehrlich ascites tumor cells

The flow through pyruvate dehydrogenase was assayed in glycolysing cells by the evolution of 14CO2 from [1-14C] pyruvate. Parallel incubations were carried out in high bicarbonate buffer (25 mM) and in bicarbonate-free buffer. The activation of the complex by NH+4 was only observed in high bicarbonate buffer, because the dilution of labelled CO2 in the presence of an excess of bicarbonate enables the quantitative determination of labelled CO2 evolved from pyruvate in the decarboxylase step. In the bicarbonate-free buffer the activation of the complex was not observed, because the 14CO2 evolved from pyruvate was consumed by biosynthetic processes inside the cell. On the contrary in isolated hepatocytes the NH+4 activation of the pyruvate dehydrogenase was observed in both buffers. In Ehrlich ascites cells, in common with other mammalian tissues, pyruvate dehydrogenase activity was found to be inversely correlated to the intramitochondrial ATP/ADP ratio.     

A hypercaloric diet induces hepatic oxidative stress,infiltration of lymphocytes,and mitochondrial reshuffle in Psammomys obesus,a murine model of insulin resistance

The aim of this study was to show, for the first time, the effect of a hypercaloric diet on the mitochondrial reshuffle of hepatocytes during the progression from steatosis to steatohepatitis to cirrhosis in Psammomys obesus, a typical animal model of the metabolic syndrome. Metabolic and oxidative stresses were induced by feeding the animal through a standard laboratory diet (SD) for nine months. Metabolic parameters, liver malondialdehyde (MDA) and glutathione (GSH), were evaluated. The pathological evolution was examined by histopathology and immunohistochemistry, using CD3 and CD20 antibodies. The dynamics of the mitochondrial structure was followed by transmission electron microscopy. SD induced a steatosis in this animal that evolved under the effect of oxidative and metabolic stress by the appearance of adaptive inflammation and fibrosis leading the animal to the cirrhosis stage with serious hepatocyte damage by the triggering, at first the mitochondrial fusion–fission cycles, which attempted to maintain the mitochondria intact and functional, but the hepatocellular oxidative damage was increased inducing a vicious circle of mitochondrial alteration and dysfunction and their elimination by mitophagy. P. obesus is an excellent animal model of therapeutic research that targets mitochondrial dysfunction in the progression of steatosis.