ETS-related gene (ERG) undermines genome stability in mouse prostate progenitors via Gsk3β dependent Nkx3.1 degradation.

21q22.2-3 deletion is the most common copy number alteration in prostate cancer (PCa). The genomic rearrangement results in the androgen-dependent de novo expression of ETS-related gene (ERG) in prostate cancer cells, a condition promoting tumor progression to advanced stages of the disease. Interestingly, ERG expression characterizes 5-30% of tumor precursor lesions - High Grade Prostatic Intraepithelial Neoplasia (HGPIN) - where its role remains unclear. Here, by combining organoids technology with Click-chemistry coupled Mass Spectrometry, we demonstrate a prominent role of ERG in remodeling the protein secretome of prostate progenitors. Functionally, by lowering autocrine Wnt-4 signaling, ERG represses canonical Wnt pathway in prostate progenitors, and, in turn, promotes the accumulation of DNA double strand breaks via Gsk3β-dependent degradation of the tumor suppressor Nkx3.1. On the other hand, by shaping extracellular paracrine signals, ERG strengthens the pro-oxidative transcriptional signature of inflammatory macrophages, which we demonstrate to infiltrate pre-malignant ERG positive prostate lesions. These findings highlight previously unrecognized functions of ERG in undermining adult prostate progenitor niche through cell autonomous and non-autonomous mechanisms. Overall, by supporting the survival and proliferation of prostate progenitors in the absence of growth stimuli and promoting the accumulation of DNA damage through destabilization of Nkx3.1, ERG could orchestrate the prelude to neoplastic transformation

Patient-reported impact of spondyloarthritis on work disability and working life: The ATLANTIS survey

44noopenopenRamonda, Roberta; Marchesoni, Antonio; Carletto, Antonio; Bianchi, Gerolamo; Cutolo, Maurizio; Ferraccioli, Gianfranco; Fusaro, Enrico; De Vita, Salvatore; Galeazzi, Mauro; Gerli, Roberto; Matucci-Cerinic, Marco; Minisola, Giovanni; Montecucco, Carlomaurizio; Pellerito, Raffaele; Salaffi, Fausto; Paolazzi, Giuseppe; Sarzi-Puttini, Piercarlo; Scarpa, Raffaele; Bagnato, Gianfilippo; Triolo, Giovanni; Valesini, Guido; Punzi, Leonardo; Olivieri, Ignazio; Ortolan, Augusta; Lorenzin, Mariagrazia; Frallonardo, Paola; Giollo, Alessandro; Locaputo, Antonella; Paolino, Sabrina; Simone, Davide; Quartuccio, Luca; Bartoloni, Elena; Luca, Rossella De; Bartoli, Francesca; Sensi, Felice; Caporali, Roberto; Carlo, Marco Di; Roberto, Bortolotti; Atzeni, Fabiola; Costa, Luisa; Ciccia, Francesco; Perrotta, Fabio; Gilio, Michele; ATLANTIS study groupRamonda, Roberta; Marchesoni, Antonio; Carletto, Antonio; Bianchi, Gerolamo; Cutolo, Maurizio; Ferraccioli, Gianfranco; Fusaro, Enrico; De Vita, Salvatore; Galeazzi, Mauro; Gerli, Roberto; Matucci-Cerinic, Marco; Minisola, Giovanni; Montecucco, Carlomaurizio; Pellerito, Raffaele; Salaffi, Fausto; Paolazzi, Giuseppe; Sarzi-Puttini, Piercarlo; Scarpa, Raffaele; Bagnato, Gianfilippo; Triolo, Giovanni; Valesini, Guido; Punzi, Leonardo; Olivieri, Ignazio; Ortolan, Augusta; Lorenzin, Mariagrazia; Frallonardo, Paola; Giollo, Alessandro; Locaputo, Antonella; Paolino, Sabrina; Simone, Davide; Quartuccio, Luca; Bartoloni, Elena; Luca, Rossella De; Bartoli, Francesca; Sensi, Felice; Caporali, Roberto; Carlo, Marco Di; Roberto, Bortolotti; Atzeni, Fabiola; Costa, Luisa; Ciccia, Francesco; Perrotta, Fabio; Gilio, Michele; ATLANTIS study, Grou

Contrast-enhanced ultrasound applications in liver transplant imaging

Contrast-enhanced ultrasound (CEUS) is gaining ever-increasing acceptance in the preoperative and postoperative evaluation of liver-transplanted patients. While indications are still a matter of research, CEUS is used in tertiary centers to supplement ultrasound (US) and Color Doppler US examination, with the potential of providing a comprehensive first-line ultrasound-based diagnosis. Alternatively, CEUS is used as a problem-solving tool when previous cross-sectional or US imaging was inconclusive, especially in assessing hepatocellular carcinoma, parenchymal perfusion abnormalities, the vascular status, and even the biliary tree. This review describes the potential use for CEUS in the setting of orthotopic liver transplantation (OLT)

Differential Proteomic Analysis of Hepatocellular Carcinoma

10nonenoneCORONA G; DE LORENZO E; ELIA C; SIMULA MP; AVELLINI C; BACCARANI U; LUPO F; TIRIBELLI C; COLOMBATTI A; TOFFOLI GCorona, G; DE LORENZO, E; Elia, C; Simula, Mp; Avellini, C; Baccarani, Umberto; Lupo, F; Tiribelli, C; Colombatti, Alfonso; Toffoli, G

Cardiac-CT and Cardiac-MR examinations cost analysis, based on data of four Italian Centers

Purpose: To establish the appropriate number of Cardiac-CT and Cardio-MR examinations, to determine an economically justified and sustainable investment in these two technologies, for an exclusive cardiologic use. Materials and methods: From July 2013 to July 2014, through a survey in four different Italian Departments of Radiology, data on the costs of Cardiac-CT and Cardiac-MR examinations were collected. For the evaluation of the costs of examinations, it was used an analytical accounting system, considering only the direct costs (consumables, health personnel work time, equipment amortization/maintenance) and other costs (utilities, services, etc.). Indirect costs (general costs) were not assessed. It was made a simulation, assuming an exclusive use of the CT and MR equipments for Cardiac-CT and Cardiac-MR examinations, calculating the annual number necessary to arrive at the Break Even Point (BEP: the point at which cost or expenses and revenue are equal). Results: On the basis of the CT costs, in order to reach the BEP, performing only Cardiac-CT examinations, an average of 2641–2752 examinations/year is needed. The annual time commitment of the Medical Professional to ensure the number of examinations to reach the BEP is 2625–2750 h/year, equivalent to two Medical Doctors in a Cardiology Department. The recent Cardiac-CT Italian Registry, in the period January–June 2011, reports a number of examinations of 3455 patients in 47 different Centers, distributed throughout the whole national territory. With regard to MR, in order to reach the BEP, performing only Cardiac-MR examinations, an average of 2435–3123 examinations/year is needed. The annual time commitment of the Medical Professional to ensure the number of examinations to reach the BEP is 2437–3125 h/year, equivalent to two Medical Doctors in a Cardiology Department. The recent Cardiac-MR Italian Registry reports a number of examinations of 3776 patients in 40 Centers, distributed throughout the whole national territory. Conclusion: This research has shown that, only on the basis of costs, currently in Italy is anti-economic an exclusive use of CT or MR equipment for cardiac exams, unless it’s not decided, regardless of the recent guidelines and clinical indications, to submit all patients with cardiac diseases (diseases of the coronary arteries and cardiomyopathies) to Cardiac-CT and Cardiac-MR examinations. This might likely to increase both the inappropriate examinations and either health spending and in the case of CT with important repercussions, in terms of radio-exposure, subject to forensic procedures

The role of pancreatic leakage on rising of postoperative complications following pancreatic surgery

Introduction. The variations in methods of pancreatic stump management and the volume of literature available on both main pancreatic duct and pancreaticoenctric anastomosis leak indicates the concern associated with the leak and the continuing efforts to prevent it. Herein we analyzed the role of pancreatic leakage followed by pancreatic surgery on the incidence of postoperative morbidity. Patients and methods. From 1989 to 2005, we performed 76 pancreaticoduodenectomy (PD) and 26 distal pancreatectomy (DP), assumed as control case). During DP the parenchymal transection was performed with a linear stapler. The surgical reconstruction after PD was as follows: 11 manual nonabsorbable stitch closure of the main duct, 24 closure of the main duct with linear stapler, 17 temporary occlusion of the main duct with neoprene glue, and 24 duct-to-mucosa anastomosis. Results. In the PD group, morbidity rate was 60%, caused by pancreatic leakage, with an incidence of 48%, hemorrhagic complication, occurred in 10% of patients following surgical procedure and infectious complication, with an incidence of 15%. After distal pancreatectomy we recorded 80, 7% no complications, 3, 9% leakage, 15, 4% hemoperitoneum. By multivariate analysis bleeding complications, biliary anastomosis leakage, and infectious complications were consequences of pancreatic leakage (P = 0.025, P = 0.025, and P = 0.025, respectively). A significant statistical difference was recorded analyzing re-operation rates between closure of the main duct with linear stapler versus temporary occlusion of the main duct with neoprene glue (t = 0.049) and closure of the main duct with linear stapler versus duct-to-mucosa anastomosis (t = 0.003). Conclusions. On the ground of our results of bleeding complication, biliary anastomosis leakage and infectious complication were consequences of pancreatic leakage: failure of a surgical anastomosis has serious consequences, particularly in case of anastomosis of the pancreas to the small bowel,, because of the digestive capacities of activated pancreatic secretions. (c) 2008 Elsevier Inc. All rights reserved