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Corradini P.,Fondazione Istituto Nazionale Dei Tumori | Corradini P.,University of Milan | Vitolo U.,Ospedale San Giovanni Battista | Miceli R.,Biometry and Bioinformatics | And 13 more authors.
Leukemia | Year: 2014

Peripheral T-cell lymphomas (PTCLs) receiving conventional treatment have a poor clinical outcome. We conducted a phase II study to evaluate the feasibility and efficacy of chemo-immunotherapy in young (≤60 years old, Clin A study) and elderly (>60 and ≤75 years old, Clin B study) patients with newly diagnosed PTCL. Clin A patients (n=61) received two courses of CHOP (cyclophosphamide, adriamycin, vincristine, prednisone)-21 with alemtuzumab (AL, 30 mg) followed by two courses of high-dose chemotherapy. On the basis of donor availability, patients in response received allogeneic (allo) or autologous (auto) stem cell transplantation (SCT). Clin B patients (n=25) received six courses of CHOP-21 and AL (10 mg). Clin A responding patients were 38 of 61 (62%) and received alloSCT (n=23) or autoSCT (n=14); one complete remission (CR) patient was not transplanted. At a median follow-up of 40 months, the 4-year overall survival (OS), progression-free survival (PFS) and disease-free survival (DFS) rates were 49, 44 and 65%, respectively. In Clin B study, the response rate was 72%. At a median follow-up of 48 months, the 4-year OS, PFS and DFS rates were 31, 26 and 44%, respectively. In conclusion, front-line alloSCT or autoSCT is effective in prolonging DFS in young patients; AL in elderly improved response with no survival benefit. © 2014 Macmillan Publishers Limited. Source

Mellai M.,Neuro Bio Oncology Center | Monzeglio O.,Neuro Bio Oncology Center | Piazzi A.,University of Piemonte Orientale | Caldera V.,Neuro Bio Oncology Center | And 6 more authors.
Journal of Neuro-Oncology | Year: 2012

MGMT (O6-methylguanine-DNA methyltransferase) promoter hypermethylation is a helpful prognostic marker for chemotherapy of gliomas, although with some controversy for low-grade tumors. The objective of this study was to retrospectively investigate MGMT promoter hypermethylation status for a series of 350 human brain tumors, including 275 gliomas of different malignancy grade, 21 glioblastoma multiforme (GBM) cell lines, and 75 non-glial tumors. The analysis was performed by methylation-specific PCR and capillary electrophoresis. MGMT expression at the protein level was also evaluated by both immunohistochemistry (IHC) and western blotting analysis. Associations of MGMT hypermethylation with IDH1/IDH2 mutations, EGFR amplification, TP53 mutations, and 1p/19q co-deletion, and the prognostic significance of these, were investigated for the gliomas. MGMT promoter hypermethylation was identified in 37.8% of gliomas, but was not present in non-glial tumors, with the exception of one primitive neuroectodermal tumor (PNET). The frequency was similar for all the astrocytic gliomas, with no correlation with histological grade. Significantly higher values were obtained for oligodendrogliomas. MGMT promoter hypermethylation was significantly associated with IDH1/IDH2 mutations (P = 0.0207) in grade II-III tumors, whereas it had a borderline association with 1p deletion (P = 0.0538) in oligodendrogliomas. No other association was found. Significant correlation of MGMT hypermethylation with MGMT protein expression was identified by IHC in GBMs and oligodendrogliomas (P = 0.0001), but not by western blotting. A positive correlation between MGMT protein expression, as detected by either IHC or western blotting, was also observed. The latter was consistent with MGMT promoter hypermethylation status in GBM cell lines. In low-grade gliomas, MGMT hypermethylation, but not MGMT protein expression, was associated with a trend, only, toward better survival, in contrast with GBMs, for which it had favorable prognostic significance. © Springer Science+Business Media, LLC. 2012. Source

Gastaldi L.,Polytechnic University of Turin | Battezzato A.,Polytechnic University of Turin | Bernucci C.,Azienda Ospedaliera Santa Croce e Carle | Mannino M.,Azienda Ospedaliera Santa Croce e Carle | Pastorelli S.,Polytechnic University of Turin
ASME 2010 10th Biennial Conference on Engineering Systems Design and Analysis, ESDA2010 | Year: 2010

Image Guided Neurosurgery allows surgeons to navigate and localize lesion through the patient's cranium with a 3D image guidance. The model of the head is reconstructed using pre-operative Computed Tomography (CT) or Magnetic Resonance (MR) images and real and virtual spaces are aligned by means of fiducial markers placed on the patient. In the paper a new method for the optimal placement of the fiducial markers in order to reduce misalignment is presented. Using routine diagnostic images a customized 3D model of the patient's cranium is reconstructed. A genetic algorithm calculates optimal positions of the marker in order to minimize the Target Registration Error (TRE). The fiducial set is shown to the surgeons on the 3D model to help him/her in placement of them. © 2010 by ASME. Source

Pinna G.,Ospedale Cottolengo | Pascale C.,Ospedale Cottolengo | Fornengo P.,University of Turin | Arras S.,Ospedale Civile | And 16 more authors.
PLoS ONE | Year: 2014

Epidemiological data on the impact of hypertensive crises (emergencies and urgencies) on referral to the Emergency Departments (EDs) are lacking, in spite of the evidence that they may be life-threatening conditions. We performed a multicenter study to identify all patients aged 18 years and over who were admitted to 10 Italian EDs during 2009 for hypertensive crises (systolic blood pressure >220 mmHg and/or diastolic blood pressure >120 mmHg). We classified patients as affected by either hypertensive emergencies or hypertensive urgencies depending on the presence or the absence of progressive target organ damage, respectively. Logistic regression analysis was then performed to assess variables independently associated with hypertensive emergencies with respect to hypertensive urgencies. Of 333,407 patients admitted to the EDs over the one-year period, 1,546 had hypertensive crises (4.6/1,000, 95% CI 4.4-4.9), and 23% of them had unknown hypertension. Hypertensive emergencies (n = 391, 25.3% of hypertensive crises) were acute pulmonary edema (30.9%), stroke (22.0%,), myocardial infarction (17.9%), acute aortic dissection (7.9%), acute renal failure (5.9%) and hypertensive encephalopathy (4.9%). Men had higher frequency than women of unknown hypertension (27.9% vs 18.5%, p<0.001). Even among known hypertensive patients, a larger proportion of men than women reported not taking anti-hypertensive drug (12.6% among men and 9.4% among women (p<0.001). Compared to women of similar age, men had higher likelihood of having hypertensive emergencies than urgencies (OR = 1.34, 95% CI 1.06-1.70), independently of presenting symptoms, creatinine, smoking habit and known hypertension. This study shows that hypertensive crises involved almost 5 out of 1,000 patients-year admitted to EDs. Sex differences in frequencies of unknown hypertension, compliance to treatment and risk of hypertensive emergencies might have implications for public health programs. © 2014 Pinna et al. Source

Mellai M.,University of Turin | Caldera V.,University of Turin | Comino A.,Azienda Ospedaliera Santa Croce e Carle | Fortunato M.,Azienda Ospedaliera Santa Croce e Carle | And 2 more authors.
Clinical Neuropathology | Year: 2010

A case of peripheral PNET (PNET/ESFT) of the cranial vault is described. A 56-year-old woman showed a mass with a large cyst in the right temporal region, adherent to the meninges, which caused a left hemiparesis with headache and confusion. The mass was totally removed. The histological examination showed a dense proliferation of small elements, organized in lobules separated by reticulin septa. Many circumscribed necroses, vessels with a thick handcuff of reticulin, a diffuse mucous degeneration and abundant mitoses were present. The cells were positive for Vimentin and CD99. RT-PCR revealed the EWS/FLI1 fusion transcript of the t(11,22) (q24;q12) translocation. The patient presented is the oldest one of the rare cases of dura-based meningioma-mimicking pPNETs till now described. In line with the possible origin from peripheral nerves or roots of cauda equina of non-intracranial tumors, those of the vault may derive from peripheral sensory nerves of the dura. The differential diagnosis must be made with cPNETs which show a worse prognosis and both can benefit from a different chemotherapy. ©2010 Dustri-Verlag Dr. K. Feistle. Source

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