Treatment of drug-eluting stents in-stent restenosis with paclitaxel-coated balloon angioplasty: Insights from the French "real-world" prospective GARO Registry.

BACKGROUND: Data about paclitaxel-eluting balloon (PCB) angioplasty to treat drug-eluting stents (DES) in-stent restenosis (ISR) were mainly collected in selected patient populations in the setting of randomized trials. The main goal of this prospective registry was to confirm the positive findings of these studies in an unselected population in clinical practice. METHODS: Consecutive patients with DES-ISR treated by PCB angioplasty were recruited in this prospective real-world registry. The primary endpoint was clinically driven target-lesion revascularization (TLR) at 9 months. Secondary endpoints included acute technical success, in-hospital outcomes, 9-month major adverse cardiac events (MACE) a composite of death, myocardial infarction (MI) and TLR and the occurrence of target vessel revascularization. RESULTS: A total of 206 patients (67.7 ± 10.2 years, 80.6% male, 41.3% diabetics) with 210 lesions were recruited. Unstable coronary artery disease was present in 55.3% of patients. The time from DES implantation to DES-ISR was 3.0 ± 2.4 years. Quantitative analyses revealed that patterns of treated DES-ISR were focal in 55.7% and diffuse in 44.3%. The reference diameter was 2.76 ± 0.64 mm. The 9-month follow-up rate was 90.8% (187/206). At 9 months, the TLR rate was 7.0% (13/187) whereas the rates for MACE, MI and cardiac death were 10.7% (20/187), 4.8% (9/187) and 2.1% (4/187) respectively. Results were consistent in patients with paclitaxel and non-paclitaxel-eluting stents (PES) ISR. CONCLUSION: This large prospective registry demonstrated acceptable rates of TLR and MACE at 9 months after treatment of DES-ISR by PCB angioplasty. PCB angioplasty was equally effective in patients with PES-ISR and non PES-ISR.

The EGFR family members sustain the neoplastic phenotype of ALK+ lung adenocarcinoma via EGR1.

In non-small cell lung cancer (NSCLC), receptor tyrosine kinases (RTKs) stand out among causal dominant oncogenes, and the ablation of RTK signaling has emerged as a novel tailored therapeutic strategy. Nonetheless, long-term RTK inhibition leads invariably to acquired resistance, tumor recurrence and metastatic dissemination. In ALK+ cell lines, inhibition of ALK signaling was associated with coactivation of several RTKs, whose pharmacological suppression reverted the partial resistance to ALK blockade. Remarkably, ERBB2 signaling synergized with ALK and contributed to the neoplastic phenotype. Moreover, the engagement of wild-type epidermal growth factor receptor or MET receptors could sustain cell viability through early growth response 1 (EGR1) and/or Erk1/2; Akt activation and EGR1 overexpression prevented cell death induced by combined ALK/RTK inhibition. Membrane expression of ERBB2 in a subset of primary naive ALK+ NSCLC could be relevant in the clinical arena. Our data demonstrate that the neoplastic phenotype of ALK-driven NSCLC relays 'ab initio' on the concomitant activation of multiple RTK signals via autocrine/paracrine regulatory loops. These findings suggest that molecular and functional signatures are required in de novo lung cancer patients for the design of efficacious and multi-targeted 'patient-specific' therapies.

EuroClonality/BIOMED-2 guidelines for interpretation and reporting of Ig/TCR clonality testing in suspected lymphoproliferations.

PCR-based immunoglobulin (Ig)/T-cell receptor (TCR) clonality testing in suspected lymphoproliferations has largely been standardized and has consequently become technically feasible in a routine diagnostic setting. Standardization of the pre-analytical and post-analytical phases is now essential to prevent misinterpretation and incorrect conclusions derived from clonality data. As clonality testing is not a quantitative assay, but rather concerns recognition of molecular patterns, guidelines for reliable interpretation and reporting are mandatory. Here, the EuroClonality (BIOMED-2) consortium summarizes important pre- and post-analytical aspects of clonality testing, provides guidelines for interpretation of clonality testing results, and presents a uniform way to report the results of the Ig/TCR assays. Starting from an immunobiological concept, two levels to report Ig/TCR profiles are discerned: the technical description of individual (multiplex) PCR reactions and the overall molecular conclusion for B and T cells. Collectively, the EuroClonality (BIOMED-2) guidelines and consensus reporting system should help to improve the general performance level of clonality assessment and interpretation, which will directly impact on routine clinical management (standardized best-practice) in patients with suspected lymphoproliferations.

Relationship between post-treatment platelet reactivity and ischemic and bleeding events at 1-year follow-up in patients receiving prasugrel.

BACKGROUND: Post-treatment platelet reactivity (PR) is associated with ischemic and bleeding events in patients receiving P2Y12 receptor antagonists. OBJECTIVES: We aimed to study the relationship between post-treatment PR after a 60-mg loading dose (LD) of prasugrel and 1-year thrombotic and bleeding events. METHOD: Patients were prospectively included in this multicenter study if they had a successful percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) and received prasugrel. The platelet reactivity index (PRI) was measured using the Vasodilator-Stimulated Phosphoprotein index (VASP) after a prasugrel LD. Endpoints included the rate of thrombotic events and bleeding events at 1 year. RESULTS: Among the 301 patients enrolled, 9 (3%) were lost to follow-up at 1 year. The rates of thrombotic and bleeding events at 1 year were of 7.5% and 6.8%, respectively. Receiver-operating curve (ROC) analysis demonstrated an optimal cut-off value of 53.5% of PRI to predict thrombotic events at 1 year. Using this cut-off value we observed that patients exhibiting high on-treatment platelet reactivity (HTPR) had a higher rate of thrombotic events (22.4% vs. 2.9%; P < 0.001). In parallel the optimal cut-off value of PRI to predict bleeding was 16%. Patients with a PRI ≤ 16% had a higher rate of bleeding events compared with those with a PRI > 16% (15.6% vs. 3.3%; P < 0.001). In multivariate analysis, the PRI predicted both thrombotic and bleeding events (OR: 1.44, 95% confidence interval [CI]: 1.2-1.72; P < 0.001 and OR: 0.75, 95% CI: 0.59-0.96; P = 0.024 [respectively, per 10% increase]). CONCLUSION: Platelet reactivity measurement after a prasugrel LD predicts both ischemic and bleeding events at 1 year follow-up for ACS patients undergoing PCI.

Solitary fibrous tumours: unusual aspects of a rare disease.

BACKGROUND: In literature there are only a few descriptions of the typical presentation of solitary fibrous tumours (SFT) and only a few case reports showing its unusual clinical and radiological features. METHODS: We retrospectively evaluated the computed tomography scans of 36 patients presenting with a histological diagnosis of SFT between 1998 and 2008. RESULTS: We present five cases of SFT with an atypical clinical presentation and radiological features. CONCLUSIONS: SFT can occasionally present with unusual radiological features making a differential diagnosis difficult. Even thought imaging plays a fundamental role in the initial diagnostic approach, final diagnosis in only confirmed by biopsy and histology.

[Role of angioplasty in the treatment of renal artery stenosis]. / Place de l'angioplastie des artères rénales.

Atherosclerotic renal artery stenosis is frequent and is associated with a high incidence of morbidity and mortality, with a strong correlation with coronary artery disease, (Kalra et al., 2005; Cheung et al., 2002; Guo et al., 2007 [1-3]). The atherosclerotic renal artery stenosis is an independent predictive factor of death (Conlon et al., 1998 [4]). The treatment of this lesion does not have strong evidence. A lot of studies in this area suggest the angioplasty is superior in a big majority between surgery, and angioplasty with stent is superior between balloon angioplasty, but some studies fail to prove the superiority of angioplasty versus medical treatment. These studies have sadly a lot of mistakes and nowadays we don't know what is the treatment for our patients in a lot of cases. The angioplasty is indicated when there is a failure of antihypertensive medications for control of blood pressure, when it is associated with a renal insufficiency quickly progressive or when there is a lesion on each renal artery. Other studies must be organized for prove the superiority of angioplasty when there is a real stenosis, maybe with the use of fractional flow reserve.

Breast MR with special focus on DW-MRI and DCE-MRI.

The use of magnetic resonance imaging (MRI) for the assessment of breast lesions was first described in the 1970s; however, its wide application in clinical routine is relatively recent. The basic principles for diagnosis of a breast lesion rely on the evaluation of signal intensity in T2-weighted sequences, on morphologic assessment and on the evaluation of contrast enhancement behaviour. The quantification of dynamic contrast behaviour by dynamic contrast-enhanced (DCE) MRI and evaluation of the diffusivity of water molecules by means of diffusion-weighted MRI (DW-MRI) have shown promise in the work-up of breast lesions. Therefore, breast MRI has gained a role for all indications that could benefit from its high sensitivity, such as detection of multifocal lesions, detection of contralateral carcinoma and in patients with familial disposition. Breast MRI has been shown to have a role in monitoring of neoadjuvant chemotherapy, for the evaluation of therapeutic results during the course of therapy. Breast MRI can improve the determination of the remaining tumour size at the end of therapy in patients with a minor response. DCE-MRI and DW-MRI have shown potential for improving the early assessment of tumour response to therapy and the assessment of residual tumour after the end of therapy. Breast MRI is important in the postoperative work-up of breast cancers. High sensitivity and specificity have been reported for the diagnosis of recurrence; however, pitfalls such as liponecrosis and changes after radiation therapy have to be carefully considered.

Breast ductal carcinoma and metastatic lymphoma to the contralateral breast in patient with cutaneous non-Hodgkin lymphoma.

Breast lymphoma is a rare condition, both as a primary and a metastatic manifestation. The primary form has an incidence ranging from 0.04% to 0.5% of all breast neoplasms, whereas the metastatic form has an incidence of 0.07%. We hereby report a clinical case of a patient who presented with cutaneous non-Hodgkin lymphoma (NHL) in the left scapulohumeral region treated with surgery followed by radiotherapy (40 Gy total). Three years following radiotherapy, the patient was diagnosed with a left breast infiltrating ductal carcinoma, treated with conservative surgery and adjuvant therapy. The following year, i.e. four years after the initial diagnosis of NHL, two lymphoproliferative relapses occurred: in the left cutaneous scapulohumeral region at the original site of disease, and in the right breast. The aim of this paper is to highlight an uncommon oncologic disorder such as breast lymphoma, highlighting its clinical and radiological manifestations. Some studies reported a possible aetiological role of radiotherapy in the development of breast cancer following treatment of NHL, and in the development of breast cancer following treatment of Hodgkin lymphoma, which could potentially explain our findings.

Intraobserver and interobserver variability in the calculation of apparent diffusion coefficient (ADC) from diffusion-weighted magnetic resonance imaging (DW-MRI) of breast tumours.

PURPOSE: This study evaluated intraobserver and interobserver variability in the measurement of apparent diffusion coefficient (ADC) values in breast carcinomas. MATERIALS AND METHODS: Twenty-eight patients with solid breast lesions >10 mm underwent conventional contrast-enhanced magnetic resonance imaging (MRI) and diffusion-weighted MRI (DW-MRI). Two observers (expert and trainee) segmented the lesion from the surrounding breast tissue on DW images with high b-value (1,000 s/mm(2)). This analysis was repeated by the expert reader after 6 months. Volumes were analysed to obtain mean, median and standard deviation (SD) of the ADC values. Interobserver and intraobserver variation was analysed using the Bland-Altman graph. RESULTS: All lesions were breast carcinomas, with a mean ADC value of 1.07 × 10(-3) mm(2)/s. The mean of the differences was 0.012 × 10(-3) mm(2)/s, corresponding to an intraobserver variability of 1.1% (limits of agreement: -5%/+8%). The mean interobserver difference was 0.022 × 10(-3) mm(2)/s, corresponding to an interobserver variability of 2% (limits of agreement: -9%/+14%). CONCLUSIONS: We found a low intraobserver and interobserver variability in calculating ADC in breast carcinomas, which supports its potential use in routine clinical practice.

CD38 increases CXCL12-mediated signals and homing of chronic lymphocytic leukemia cells.

Homing of chronic lymphocytic leukemia (CLL) cells to sites favoring growth, a critical step in disease progression, is principally coordinated by the CXCL12/CXCR4 axis. A cohort of 62 CLL patients was divided into migrating and nonmigrating subsets according to chemotaxis toward CXCL12. Migrating patients phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) proteins more than nonmigrating patients (P<0.0002). CD38 expression was the parameter most strongly associated with heightened CXCL12 signaling (P<0.0001), confirmed by independent statistical approaches. Consistent with this observation, CD38(-) CLL cells in samples with bimodal CD38 expression responded less to CXCL12 than the intact clone (P=0.003). Furthermore, lentivirus-induced de novo expression of CD38 was paralleled by increased responses to CXCL12, as compared with cells infected with a control virus. CD38 ligation with agonistic monoclonal antibodies (mAbs) enhanced CXCL12 signaling, whereas blocking anti-CD38 mAbs inhibited chemokine effects in vitro. This is attributed to physical proximity on the membrane between CD38 and CXCR4 (the CXCL12 receptor), as shown by (i) coimmunoprecipitation and (ii) confocal microscopy experiments. Blocking anti-CD38 mAbs significantly compromised homing of CLL cells from blood to lymphoid organs in a mouse model. These results indicate that CD38 synergizes with the CXCR4 pathway and support the working hypothesis that migration is a central step in disease progression.

Perfusion CT in solid body-tumours. Part II: Clinical applications and future development.

Perfusion computed tomography (CTP) has shown great potential in diagnosing tumours and evaluating and predicting treatment response and has been the subject of numerous experimental and clinical studies. Its increasing availability and simplicity allow it to be performed alongside morphological imaging to complete the evaluation of neoplastic lesions. The aim of this paper is to describe our personal experience and review the literature on the applications of CTP in tumours of different body regions, with particular regard to fields of development for new research. Increased clinical application is desirable, especially in relation to a wider use of antiangiogenic drugs. Additional and ideally multicentre studies are necessary to define the role of this technique.

Role of operator experience in ultrasound-guided fine-needle aspiration biopsy of the thyroid.

PURPOSE: Thyroid nodules are commonly encountered in clinical practice, and ultrasound (US)-guided fine-needle aspiration biopsy (FNAB) is the gold standard in diagnosing the pathological nature of undetermined thyroid nodules. The aim of this study was to evaluate whether operator experience influences the diagnostic accuracy of US-guided FNAB. MATERIALS AND METHODS: A total of 700 consecutive US-guided FNAB done by a single radiologist between 2000 and 2007 were retrospectively analysed. The same freehand technique and capillary-action technique with 22- or 25-gauge needles was used for all nodules, All specimens were prepared and fixed without the cytologist on site and were subsequently analysed by two expert cytologists. The procedures were chronologically divided into seven groups and classified as diagnostic or nondiagnostic. RESULTS: The rate of nondiagnostic procedures for each group was 32% in group 1, 13% in group 2, 17% in group 3, 11% in group 4, 10% in group 5, 5% in group 6 and 8% in group 7. No major complications were recorded. CONCLUSIONS: The rate of nondiagnostic US-guided FNAB is heavily dependent on the operator's experience. We estimated that at least 200 procedures need to be performed in order to achieve the levels of diagnostic accuracy reported in the literature. We therefore suggest specific training before operators routinely perform this procedure in clinical practice.

CT perfusion in solid-body tumours. Part I: Technical issues.

Functional imaging is becoming increasingly important in both research and clinical diagnostic radiology. Perfusion computed tomography (CTP) is a readily available and widely used tool that allows an objective measurement of tissue perfusion through the mathematical analysis of data obtained from repeated scans performed after administration of contrast agent. Recently, CTP has been increasingly used in the oncological field, being studied as a potential marker of neoplastic angiogenesis, which is one of the main targets of new tumour therapies. The aim of this paper was to provide the theoretical background and practical guidance for accurately performing CTP and interpreting results of examinations in solid-body tumours. CTP could be a valid tool for functional imaging of tumours if the acquisition technique is robust, if image and data analysis is accurate and if interpretation of results is adequately inserted within a clinical context.

CT perfusion in oncology: how to do it.

Robust technique and accurate data analysis are required for reliable computed tomography perfusion (CTp) imaging. Multislice CT is required for high temporal resolution scanning; 16-slice (or 64-slice) scanners are preferred for adequate volume coverage. After tumour localization, the volume of CTp imaging has to be positioned to include the maximum visible area of the tumour and an adequate arterial vessel. Dynamic scans at high temporal resolution (at least 1-s gantry rotation time) are performed to visualize the first pass of contrast agent within the tumour; repeated scans with low temporal resolution can be planned for late enhancement assessment. A short bolus of conventional iodinated contrast agent, preferably with high iodine concentration, is power injected at a high flow rate (>4 ml/s) in the antecubital vein. The breath-hold technique is required for CTp imaging of the chest and upper abdomen to avoid respiratory motion; free breathing is adequate for CTp imaging of the head, neck and pelvis. Using dedicated software, a region of interest (ROI) has to be placed in an adequate artery (as arterial input) to obtain density-time curves; according to different kinetic models, colour maps of different CTp parameters are generated and generally overlaid on CT images. Additional ROIs can be positioned in the tumour, and in all other parts of the CTp volume, to obtain the values of the CTp parameters within the ROI.

Peritoneal carcinomatosis from ovarian cancer: the role of CT and [¹8F]FDG-PET/CT.

PURPOSE: The diagnosis of peritoneal carcinomatosis secondary to ovarian cancer is a real challenge in the cancer imaging field. In this retrospective study, we evaluate the accuracy of Single Detector Computed Tomography (SDCT), Multi Detector Computed Tomography (MDCT), and Positron Emission Tomography-Computed Tomography with F18-fluorodeoxyglucose ([¹8F]FDG-PET/CT) in the diagnosis of peritoneal seeding and we evaluate the possible applications of MDCT to predict the complete surgical removal of the peritoneal deposits. METHODS AND MATERIALS: A total of 228 scans (91 SDCT, 89 MDCT, and 48 [¹8F]FDG-PET/CT) of patients with peritoneal carcinomatosis secondary to ovarian cancer proved at laparoscopy and confirmed by histopathology were retrospectively reviewed by two independent groups of Radiologists and Nuclear Medicine Physicians for the evaluation of ascites, peritoneal nodules, and omental cake signs. RESULTS: MDCT showed 81% of true positives, SDCT 72.5%, and [¹8F]FDG-PET/CT 77%. False negatives were 19% for MDCT, 27.5% for SDCT, and 23% for [¹8F]FDG-PET/CT. CONCLUSION: From our results, we concluded that MDCT is the technique of choice in the diagnosis of peritoneal seeding, while [¹8F]FDG-PET/CT, though showing similar accuracy, remains the most accurate technique for monitoring therapeutic response and disease recurrence. MDCT could play an important role due to its ability to predict the possibility of complete surgical removal of disease thus influencing the treatment plan aimed to improve quality of life.

The standardized Ginkgo biloba extract Egb-761 protects vascular endothelium exposed to oxidized low density lipoproteins.

Dietary antioxidants are frequently proposed as protective agents for the vascular endothelium during the onset of atherosclerosis. This protection may occur at two distinct levels. First, they prevent oxidative modification of atherogenic lipoproteins (LDL). Second, they can provide a cellular protection against oxidized LDL-mediated endothelium dysfunction, although this mechanism remains poorly considered in many instances. To gain insight into the mechanism underlying such cellular protection against oxidized LDL, we examined the impact of a popular traditional medicine, an extract from Ginkgo biloba with well-known antioxidant properties, on two endothelial cells properties: cell adhesion and ionic homeostasis. Cellular lipoperoxides levels were also measured as a marker of cellular oxidative stress. Human umbilical-vein endothelial cells were exposed to native (nat-) or oxidized (ox-) LDL, the latter prepared to be compatible with clinically observed levels of oxidation. Although nat-LDL had little effect, ox-LDL increased endothelial adhesive properties (35%, p<0.01) and lipoperoxidation (45%, p<0.01). Na,K-ATPase activity, a key regulator of ionic homeostasis, was significantly decreased after exposure to nat-LDL (30%, p<0.01) and dramatically depressed after exposure to ox-LDL (65%, p<0.001). The standardized preparation of Ginkgo biloba EGb-761 totally protected adhesive properties and endothelial lipoperoxide levels. Moreover, it limited the decrease in Na,K-ATPase activity induced by ox-LDL to levels similar to nat-LDL. This suggests that EGb-761 protects endothelial adhesive properties and helps prevent the disruption of ionic homeostasis. The EGb-761-mediated inhibition of ox-LDL-induced lipoperoxide levels in endothelial cells appears to be an important mechanism by which Ginkgo biloba extract protects endothelial properties.

CD146-based immunomagnetic enrichment followed by multiparameter flow cytometry: a new approach to counting circulating endothelial cells.

BACKGROUND: Circulating endothelial cells (CECs) have emerged as non-invasive biomarkers of vascular dysfunction. The most widely used method for their detection is CD146-based immunomagnetic separation (IMS). Although this approach has provided consensus values in both normal and pathologic situations, it remains tedious and requires a trained operator. OBJECTIVES: Our objective was to evaluate a new hybrid assay for CEC measurement using a combination of pre-enrichment of CD146+ circulating cells and multiparametric flow cytometry measurement (FCM). PATIENTS AND METHODS: CECs were determined in peripheral blood from 20 healthy volunteers, 12 patients undergoing coronary angioplasty, and 30 renal transplant recipients, and blood spiked with cultured endothelial cells. CD146+ cells were isolated using CD146-coated magnetic nanoparticles and labeled using CD45-fluorescein isothiocyanate and CD146-PE or isotype control antibody and propidium iodide before FCM. The same samples were also processed using CD146-based immunomagnetic separation as the reference method. RESULTS: The hybrid assay detected CECs, identified as CD45(dim)/CD146(bright)/propidium iodide(+), with high size-related scatter characteristics, and clearly discriminated these from CD45(bright)/CD146(dim) activated T lymphocytes. The method demonstrated both high recovery efficiency and good reproducibility. Both IMS and the hybrid assay similarly identified increased CEC levels in patients undergoing coronary angioplasty and renal transplantation, when compared to healthy controls. In patients, CEC values from these two methods were of the same order of magnitude and highly correlated. Bland-Altman analysis revealed poor statistical agreement between methods, flerrofluid-FCM providing higher values than IMS. CONCLUSION: This new hybrid FCM assay constitutes an accurate alternative to visual counting of CECs following CD146-based IMS.

Severity of periodontal disease correlates to inflammatory systemic status and independently predicts the presence and angiographic extent of stable coronary artery disease.

BACKGROUND: Periodontal disease (PD) has been recognized as a risk factor for systemic diseases, but its involvement in the pathogenesis of coronary artery disease (CAD) remains debated. OBJECTIVES: We sought to evaluate the potential relations between severity of the PD, inflammatory response and angiographic lesions extent in patients with stable CAD. DESIGN: A total of 131 subjects referred to our centre for coronary angiography were evaluated for presence and extension of CAD, then divided into two groups, one with presence of lesions (cases, n = 85) and other one with absence of lesions (controls, n = 46). Mean periodontal pocket depth (PPkD), high sensitivity C reactive protein (hs-CRP), serum amyloid A protein (SAA) and fibrinogen levels were measured in all patients. RESULTS: Cases and controls did not differ according to their baseline characteristics and prevalence of traditional cardiovascular risk factors. PPkD was greater in patients with CAD than in controls (2.24 +/- 1.28 mm vs 1.50 +/- 0.93 mm, P < 0.001 by Student's t-test). Systemic inflammatory response was more pronounced in cases than in controls, with higher values of hs-CRP, SAA and fibrinogen. Furthermore, PPkD values correlated with hs-CRP (r = 0.80, P < 0.001), SAA (r = 0.71, P < 0.001), fibrinogen levels (r = 0.72, P < 0.001) and the American College of Cardiology/American Heart Association angiographic score (r = 0.68, P < 0.001) in cases. Multivariate analysis indicated a persistent independent correlation between PPkD and angiographic score after adjustment for inflammatory markers levels. CONCLUSION: In the present study, PD lesions predicted presence of CAD stenosis in patients with cardiovascular risk factors. PD severity was correlated to angiographic extent of coronary lesions, independent of systemic inflammatory status. Those results suggest that these patients might benefit from an intensive periodontal therapy to prevent CAD progression.

Spontaneous osteoclastogenesis is a predictive factor for bone metastases from non-small cell lung cancer.

Lung cancer is a widespread disease and its incidence is growing. Since therapies have increased the life expectancy of lung cancer patients, the development of bone osteolytic metastases is becoming a common cause of morbidity. Osteolysis is caused by an increased osteoclast activity and may be reduced by inhibiting their formation and activity. We studied 60 male patients affected by NSCLC, divided in early and advanced stage disease. Patients' blood and urinary samples were collected at tumor diagnosis and at follow-up. PBMCs were cultured to investigate the spontaneous osteoclastogenesis. IL-7 was dosed in serum and its quantitative gene expression was evaluated on tumor and healthy tissues by RQ-PCR. Both at diagnosis and follow-up, osteolytic bone patients showed high spontaneous osteoclastogenesis level compared to non-bone metastatic and healthy controls. The presence of spontaneous osteoclastogenesis correlated with urinary crosslinks increase. Serum IL-7 levels were higher in bone metastatic patients than in patients without bone lesions and healthy controls. The serum IL-7 increase correlated with the osteoclastogenesis and, at least in part, depended on an increased IL-7 production by tumor cells. At follow-up, patients with increased osteoclastogenesis and serum IL-7 levels, were subjected to standard clinical analysis, which showed early secondary bone lesions. The in vitro assay for spontaneous osteoclastogenesis and serum IL-7 dosage could be useful for diagnostic purposes and it might be able to monitor cancer patients with a high risk to develop osteolytic metastases at follow-up, especially after a curative treatment.

Covered stent for closure of symptomatic plexus-like coronary fistula.

Coronary to pulmonary artery fistula are the most frequent congenital anomalies of the coronary arteries. When they are symptomatic they have to be treated in order to prevent complications such as sudden death or myocardial infarction. Surgery is the gold standard for their closure. However an increasing number of reports have shown that interventional cardiology could be a safe and efficient alternative. Plexus-like fistula are composed of multiples and tortuous branches that make them difficult to treat. We report the use of polytetrafluoroethylene-covered (PTFE) stent to cure a plexus-like coronary to pulmonary artery fistula, without associated atherosclerosis, responsible for myocardial ischemia.