Perfusion MR imaging at 3-Tesla: Can it predict tumor grade and histologic necrosis rate of musculoskeletal sarcoma?

PURPOSE: To identify quantitative perfusion parameters that are best associated with tumor grade and tumor necrosis at magnetic resonance (MR) imaging at 3-Tesla. METHODS: MR perfusion studies of 31 patients with a musculoskeletal sarcoma were retrospectively evaluated by two readers. There were 18 men and 13 women with a mean age of 34.9±24.4 (standard deviation [SD] years) (range: 6-87 years). All patients underwent carcinologic tumor resection less than 3 months after MR imaging. For all patients six perfusion parameters (three semi-quantitative and three permeability parameters) were analyzed. The percentage of tumor necrosis was estimated using MR imaging. Perfusion data were compared between groups of tumors with different grades and necrosis ratios. Interobserver variability was calculated using intraclass correlation coefficient (ICC). RESULTS: Interobserver variability among the perfusion parameters was good to excellent (ICC: 0.72-0.9). The area under the curve and maximum slope values showed a significant association with the degree of tumor necrosis (P=0.02-0.04). When tumors with low necrosis ratios were compared to those with high ratios the former parameter was 80% lower. In the same groups, the imaging necrosis index was 56.9-59.8% higher in patients with grade 2 necrosis (P=0.01). Extracellular space volume (Ve) was 31.4% to 55.8% lower in tumors with high grade while the backflow constant (Kep) was 33.6% to 40.1%% higher in tumors with high grade. CONCLUSION: Semi-quantitative MR perfusion parameters have an excellent reproducibility and are associated with the degree of histologic tumor necrosis in musculoskeletal sarcomas. The utility of permeability parameters for determining tumor grade needs further investigations.

Cell-to-cell heterogeneity of EWSR1-FLI1 activity determines proliferation/migration choices in Ewing sarcoma cells.

Ewing sarcoma is characterized by the expression of the chimeric EWSR1-FLI1 transcription factor. Proteomic analyses indicate that the decrease of EWSR1-FLI1 expression leads to major changes in effectors of the dynamics of the actin cytoskeleton and the adhesion processes with a shift from cell-to-cell to cell-matrix adhesion. These changes are associated with a dramatic increase of in vivo cell migration and invasion potential. Importantly, EWSR1-FLI1 expression, evaluated by single-cell RT-ddPCR/immunofluorescence analyses, and activity, assessed by expression of EWSR1-FLI1 downstream targets, are heterogeneous in cell lines and in tumours and can fluctuate along time in a fully reversible process between EWSR1-FLI1high states, characterized by highly active cell proliferation, and EWSR1-FLI1low states where cells have a strong propensity to migrate, invade and metastasize. This new model of phenotypic plasticity proposes that the dynamic fluctuation of the expression level of a dominant oncogene is an intrinsic characteristic of its oncogenic potential.

Chronic endocarditis due to Legionella anisa: a first case difficult to diagnose.

Endocarditis due to Legionella spp. is uncommon but presumably underestimated given the prevalence of Legionellae in the environment. We report a first and unusual case of chronic native valve endocarditis due to L. anisa and advocate that the diagnosis of endocarditis be made collaboratively between the cardiologist, surgeon, microbiologist and pathologist.

[Coronary stent evaluation with cardiac CT: Literature review]. / Évaluation des stents coronaires en scanner cardiaque: revue de la littérature.

Since the introduction of the 64-generation scanners, the accuracy and robustness of the diagnosis of coronary artery disease has progressed. The main advantage of cardiac CT is the exclusion of coronary artery disease by its excellent negative predictive value. Currently, cardiac CT applications extend thanks to innovations both in terms of technological development systems scanner or stents implanted. This is a literature review of stent evaluation with cardiac CT.

[Cardiac CT: new applications]. / Scanner cardiaque : nouvelles applications.

Since the introduction of the 64-generation scanners, the accuracy and robustness of the diagnosis of coronary artery disease has progressed. The main advantage of cardiac CT is the exclusion of coronary artery disease by its excellent negative predictive value. Currently, cardiac CT applications extend thanks to innovations both in terms of technological development systems scanner or stents implanted, that the evolution of surgical procedures such as TAVI.

Glucose metabolism and hexosamine pathway regulate oncogene-induced senescence.

Oncogenic stress-induced senescence (OIS) prevents the ability of oncogenic signals to induce tumorigenesis. It is now largely admitted that the mitogenic effect of oncogenes requires metabolic adaptations to respond to new energetic and bio constituent needs. Yet, whether glucose metabolism affects OIS response is largely unknown. This is largely because of the fact that most of the OIS cellular models are cultivated in glucose excess. In this study, we used human epithelial cells, cultivated without glucose excess, to study alteration and functional role of glucose metabolism during OIS. We report a slowdown of glucose uptake and metabolism during OIS. Increasing glucose metabolism by expressing hexokinase2 (HK2), which converts glucose to glucose-6-phosphate (G6P), favors escape from OIS. Inversely, expressing a glucose-6-phosphatase, [corrected] pharmacological inhibition of HK2, or adding nonmetabolizable glucose induced a premature senescence. Manipulations of various metabolites covering G6P downstream pathways (hexosamine, glycolysis, and pentose phosphate pathways) suggest an unexpected role of the hexosamine pathway in controlling OIS. Altogether, our results show that decreased glucose metabolism occurs during and participates to OIS.

[Cardiac magnetic resonance with a MRI compatible pacemaker]. / IRM cardiaque avec un stimulateur IRM compatible.

Patients with cardiac implantable electronic devices are usually excluded from MRI examinations due to contraindication for MRI. The MRI-conditional pacemaker system may allow the benefits of MRI (system 1.5T) to be more accessible to pacemaker patients. A 62-year-old man was admitted with acute coronary syndrome and atrial fibrillation. A conventional angiography showed normal coronaries. A cardiac cardioversion revealed a significant sinus node dysfunction and a magnetic resonance imaging (MRI) compatible dual chamber system was implanted. At 6-week follow-up, a cardiac MRI revealed a typical anterior myocardial infarction with diagnostic quality images despite pacemaker. This is one of the first reports of cardiovascular MRI in a patient with MRI-conditional pacing system.

[Cardiac MRI: technology, clinical applications, and future directions]. / IRM cardiaque : technologie actuelle, applications cliniques et perspectives futures.

The field of cardiovascular MRI has evolved rapidly over the past decade, feeding new applications across a broad spectrum of clinical and research areas. Advances in magnet hardware technology, and key developments such as segmented k-space acquisitions, advanced motion encoding techniques, ultra-rapid perfusion imaging and delayed myocardial enhancement imaging have all contributed to a revolution in how patients with ischemic and non-ischemic heart disease are diagnosed and treated. Actually, cardiac MRI is a widely accepted method as the "gold standard" for detection and characterization of many forms of cardiac diseases. The aim of this review is to present an overview of cardiac MRI technology, advances in clinical applications, and future directions.

Involvement of SMAp in the intention-related long latency stretch reflex modulation: a TMS study.

When our movement is perturbed by environmental forces, the Long Latency Stretch Reflex (LLSR), generated by a transcortical loop through the primary motor cortex (M1), is the fastest reaction adapted according to our prior intent. We investigated the involvement of the caudal part of the Supplementary Motor Area (SMAp) in this intention-related LLSR modulation. Subjects were instructed either to not react (i.e. to 'let-go') or to resist a mechanical perturbation extending the wrist and Transcranial Magnetic Stimulation (TMS) was used to transiently inactivate SMAp, either at the time of the LLSR generation (TMS was applied 50 ms before the perturbation), or at the end of the preparation period (TMS was applied 150 ms before the perturbation). The effect of SMAp transient inactivation on the LLSR modulation was compared to the effect of transient inactivation of M1 or of a Control area. Compared to the Control condition, the intention-related LLSR modulation decreased when TMS was applied either over SMAp or over M1 50 ms before perturbation occurrence, suggesting that SMAp, as M1, is involved in the LLSR modulation. Moreover, the LLSR modulation also decreased when TMS was applied over SMAp 150 ms before the perturbation, indicating that anticipatory processes taking place in SMAp participate to the LLSR modulation. In addition, TMS applied over SMAp elicited Motor-Evoked Potentials (MEPs) whose latency and shape were similar to MEPs evoked by TMS over M1, suggesting that they are due to direct corticospinal projections from SMAp. Interestingly, the SMAp MEPs amplitude was modulated depending on the subject's intention to resist or to let-go. Taken together these results strongly favor the idea that, during the expectation of a perturbation, SMAp is the seat of anticipatory processes that are specific to the subject's intent and that preset M1 in order to adapt the LLSR to this intention.

Corticomedullary mixed tumor of the adrenal gland-a clinical and pathological chameleon: case report and review of literature.

Adrenal tumors mostly present with specific and unique clinical features, regarding their endocrine metabolism. A 53-year-old man came to our Department for a left adrenal mass discovered incidentally. Biochemical and imaging findings were suspicious for a pheochromocytoma. The patient underwent a laparoscopic left adrenalectomy. A well-circumscribed 5.5-cm mass was removed. It was composed of adrenal cells intimately admixed with pheochromocytes. Immunohistochemical studies were positive both for cortical cells (inibin-α, synaptophysine and melan-A) and medullary cells (S-100 and chromogranine A). Final pathology was of corticomedullary mixed tumor (CMT). CMT is a rare tumor with 14 cases previously reported in literature, with wide variable biochemical behavior, such as his radiological and pathological features. Prevalence and actual malignant potential are yet unknown to our knowledge.

Hypercalcitonemia revealing a somatostatinoma.

Somatostatinoma are rare well-differentiated endocrine tumors with malignant behavior arising from the pancreas and duodenum. They are defined by somatostatin positive immunostaining of the majority of tumor cells. The main clinical features are diabetes, diarrhea and biliary lithiasis related to somatostatin production. Somatostatinoma secreting both calcitonin and somatostatin may be unrecognized as a small number of such observations have been published. We report the case of a 57- year-old woman referred for weight loss, diarrhea and worsening diabetes. Computer tomography scan revealed multiple hypervascular liver lesions suggestive of metastases. High plasma calcitonin level was evidenced, with normal chromogranin-A value, and high plasma somatostatin results lately communicated. Calcitonin secretion of extra-thyroidal origin was suspected leading to the identification of a pancreatic mass by further multiphase CT. The patient underwent left pancreatectomy with surgical hepatic resection. Histological and immunostaining studies confirmed definitive diagnosis of somatostatinoma secreting both somatostatin and calcitonin. Plasma calcitonin should be measured in the assessment of duodeno-pancreatic endocrine neoplasm. Calcitonin determination is available, more reproducible than other specific pancreatic endocrine markers and could be effective for diagnosis and follow-up of such foregut-derived endocrine neoplasia.

Crystalline ultrastructures, inflammatory elements, and neoangiogenesis are present in inconspicuous aortic valve tissue.

Morbidity from calcific aortic valve disease (CAVD) is increasing. Recent studies suggest early reversible changes involving inflammation and neoangiogenesis. We hypothesized that microcalcifications, chemokines, and growth factors are present in unaffected regions of calcific aortic valves. We studied aortic valves from 4 patients with CAVD and from 1 control, using immunohistochemistry, scanning electron microscopy, and infrared spectrography. We revealed clusters of capillary neovessels in calcified (ECC), to a lesser extent in noncalcified (ECN) areas. Endothelial cells proved constant expression of SDF-1 in ECC, ECN, and endothelial cells from valvular surface (ECS). Its receptor CXCR4 was expressed in ECC. IL-6 expression correlated with CXCR4 staining and presence of lymphocytes. VEGF was expressed by ECS, its receptor by ECC and ECN. Crystalline ultrastructures were found on the surface of histologically noncalcified areas (HNCAs), spectrography revealed calcium hydroxylapatite. Our results demonstrate that crystalline ultrastructures are present in HNCAs, undergoing neoangiogenesis in an inflammatory context. These alterations could be an early witness of disease and an opening to therapy.

Tumour growth and resistance to gemcitabine of pancreatic cancer cells are decreased by AP-2alpha overexpression.

BACKGROUND: Activator protein-2alpha (AP-2alpha) is a transcription factor that belongs to the family of AP-2 proteins that have essential roles in tumorigenesis. Indeed, AP-2alpha is considered as a tumour-suppressor gene in different tissues such as colonic, prostatic or breast epithelial cells. Moreover, AP-2alpha also participates in the control of colon and breast cancer cells sensitivity towards chemotherapeutic drugs. Despite its potential interest, very few data are available regarding the roles of AP-2alpha in pancreatic cancer. METHODS: We have developed a stable pancreatic CAPAN-1 cell line overexpressing AP-2alpha. Consequences of overexpression were studied in terms of in vivo cell growth, gene expression, migration capacity and chemosensitivity. RESULTS: In vivo tumour growth of CAPAN-1 cells overexpressing AP-2alpha was significantly decreased by comparison to control cells. An altered expression pattern of cell cycle-controlling factors (CDK-4, CDK-6, cyclin-G1, p27(kip1) and p57(kip2)) was observed in AP-2alpha-overexpressing clones by microarrays and western blot analysis. Promoter activity and ChIP analysis indicated that AP-2alpha induces p27(kip1) protein levels by direct binding to and transactivation of its promoter. Moreover, AP-2alpha overexpression increased the chemosensitivity of CAPAN-1 cells to low doses of gemcitabine and reduced their in vitro migration capacity. CONCLUSION: Our data suggested that AP-2alpha overexpression could be exploited to decrease in vivo tumour growth of pancreatic cancer cells and to increase their sensitivity to gemcitabine.

Neural networks underlying hyperkinetic seizures of "temporal lobe" origin.

PURPOSE: Hyperkinetic seizures are most often considered to originate from prefrontal cortex. Recently however, it has been suggested that hyperkinetic seizures can be found in patients with temporal lobe seizures. The objective of this study was to determine the features of temporal epilepsy with hyperkinetic seizures and the functional anatomy of involved brain networks. METHODS: We retrospectively identified patients investigated by depth electrodes (SEEG) in whom hyperkinetic manifestations were proved to be linked to initial temporal lobe involvement. Seizure organisation was determined according to the "Epileptogenicity Index" (EI), a new way to quantify rapid discharges at seizure onset. RESULTS: We found 7 patients among 130 SEEG investigations that fulfilled the inclusion criteria. Most of the patients presented with hyperkinetic occurring (or predominating) during sleep. SEEG signal analysis demonstrated a common temporo-frontal network in which the temporal pole played a central role. Major involvement of the orbito-frontal cortex and to a lesser extent the cingulate gyrus was also a particular feature of these seizures. DISCUSSION: Seizures originating in the temporal lobe must be recognized as an important cause of hyperkinetic seizures. The temporal pole and its connexions with medio-basal prefrontal cortex represent the main structures involved in epileptogenic networks.

[Seronegative myasthenia and myasthenia gravis with anti-MuSK antibody: a retrospective study of 20 cases]. / Myasthénie séronégative et myasthénie avec anticorps anti-MuSK : une série rétrospective de 20 cas.

INTRODUCTION: Despite the fact that anti-muscle specific tyrosine kinase (MuSK) antibodies have been discovered for seven years, only a few studies have, until now, focused on myasthenia without acetylcholine-receptors antibodies (ab) (formerly known as "seronegative myasthenia"), and among them, anti-MuSK-antibody-positive and -negative patients. METHOD: We retrospectively studied 20 patients with "seronegative" myasthenia gravis, eight of them being anti-MuSK-ab positive, the remaining twelve being negative. We searched for clinical, neurophysiological, and therapeutic differences between the two groups (anti-MuSK-ab positive: anti-MuSK+ versus anti-MuSK-ab negative: anti-MuSK-). RESULTS: Anti-MuSK+ patients had more predominantly bulbar involvement and had more severe disease (these patients required referral to intensive care more frequently). There was no difference between the two groups concerning treatment efficiency and tolerance. Most of our patients were treated with acetylcholinesterase-inhibitors, and immunomodulatory or immunosuppressive drugs that could indirectly reflect greater severity. However, there was no difference in treatments for anti-MuSK+ versus anti-MuSK- patients. CONCLUSION: These results both confirm and complete the preexisting data on RACh-negative myasthenia, and especially on myasthenia associated with MuSK antibodies.

Tei index to assess perioperative left ventricular systolic function in patients undergoing mitral valve repair.

BACKGROUND: Using echocardiography, perioperative assessment of systolic function by fractional area change (FAC) is questionable in patients suffering from mitral regurgitation (MR). Tei index, an index expressing global cardiac function, has been reported to be unchanged after mitral valve surgery. We tested the hypothesis where the Tei index could be useful in assessing the perioperative cardiac function in patients undergoing mitral valve repair (MVR). METHODS: Twenty-five patients were enrolled. Transoesophageal echocardiography was performed perioperatively before and after the correction of MR. We compared the impact of the MVR on the left ventricular FAC and the Tei index. FAC was calculated from the transgastric short-axis view and Tei index was determined from the four chambers and deep transgastric views. RESULTS: Two patients were excluded because of poor acoustic windows. FAC significantly decreased after MVR from 53 (9)% to 42 (10)% (P<0.001), while Tei index was unaffected [0.46 (0.16) vs 0.47 (0.17), NS]. A significant relationship was found between the preoperative Tei index and the postoperative FAC (R=-0.64, P<0.001). Moreover, a significant and clinically relevant relationship was determined between the predicted (using preoperative Tei index) and the measured postoperative FAC (R=0.64, P<0.001). CONCLUSIONS: FAC but not the Tei index is influenced by MVR. The preoperative determination of the Tei index allows predicting postoperative FAC and offers the opportunity to identify patients in whom a severe unsuspected systolic dysfunction could render difficult the weaning from cardiopulmonary bypass.

Endovascular treatment of descending aortic dissection (type B): short- and medium-term results.

BACKGROUND: Optimal treatment of type B dissections is open to debate. The use of endoprostheses is an option that requires evaluation. AIM: To report our experience with endoprostheses in type B aortic dissections. METHODS: We report our short- and medium-term results with covered prostheses for the treatment of acute (n=7) and chronic (n=28) type B aortic dissections. The criteria used to indicate treatment were the same as those usually used for surgery: acute complications or dilated aneurysm. Cover of the main intimal tear was obtained in all cases with an improvement in symptoms in patients with acute dissections. RESULTS: Early mortality was 14.3% (five patients), linked in three cases to the occurrence of a retrograde dissection of the ascending aorta. No neurological complications were observed. Four patients required an additional endovascular and/or surgical procedure. On early control scans, complete thrombosis of the false lumen at the thoracic level was observed in 40% of cases, partial thrombosis in 42.8% and an absence of thrombosis in 11.4%. After a mean follow-up of 20.8 months, one patient died of a pneumopathy. No secondary aneurysm expansion was noted at the thoracic stage whereas three patients presented with dilation of the abdominal aorta. CONCLUSION: The results of treatment of type B dissections with covered endoprostheses are encouraging. However, the morbimortality associated with treatment and the uncertainty of long-term results do not allow the use of this therapeutic option outside the criteria usually recognized to indicate surgery.

Bullet embolization from the left brachiocephalic vein to the right ventricle.

We present a rare case of bullet embolism from the left brachiocephalic vein to the right ventricle, following a chest gunshot wound, in a 56-year-old soldier. The bullet was accidentally discovered on a systematic chest X-ray. The bullet was very close to the tricuspid subvalvular apparatus and was about to come out from the ventricle. We removed it under cardiopulmonary bypass.