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San Salvatore di Fitalia, Italy

Evangelista A.,Hospital Universitario Vall dHebron | Czerny M.,University of Zurich | Nienaber C.,University of Rostock | Schepens M.,A.Z. St. Jan Hospital | And 4 more authors.
European Journal of Cardio-thoracic Surgery | Year: 2014

An expert panel on the treatment of type B intramural haematoma (IMH) and penetrating atherosclerotic ulcer (PAU) consisting of cardiologists, cardiothoracic surgeons, vascular surgeons and interventional radiologists reviewed the literature to develop treatment algorithms using a consensus method. Data from 46 studies considered relevant were retrieved for a total of 1386 patients consisting of 925 with IMH, and 461 with PAU. The weighted mean 30-day mortality from IMH was 3.9%, 3-year aortic event-related mortality with medical treatment 5.4%, open surgery 23.2% and endovascular therapy 7.1%. In patients with PAU early and 3-year aortic event-mortality rates with open surgery were 15.9 and 25.0%, respectively, and with TEVAR were 7.2 and 10.4%, respectively. According to panel consensus statements, haemodynamic instability, persistent pain, signs of impending rupture and progressive periaortic haemorrhage in two successive imaging studies require immediate surgical or endovascular treatment. In the absence of these complications, medical treatment is warranted, with imaging control at 7 days, 3 and 6 months and annually thereafter. In the chronic phase, aortic diameter >55 mm or a yearly increase ≥5 mm should be considered indications for open surgery or thoracic endovascular treatment, with the latter being preferred. In complicated type B aortic PAU and IMH, endovascular repair is the best treatment option in the presence of suitable anatomy. © The Author 2014.

Chiang S.,Sloan Kettering Cancer Center | Staats P.N.,University of Maryland Baltimore County | Senz J.,Applied Genomics | Senz J.,Genetic Pathology Evaluation Center | And 6 more authors.
American Journal of Surgical Pathology | Year: 2015

Uterine tumors resembling ovarian sex cord tumors (UTROSCTs) are rare uterine neoplasms characterized by pure or predominant epithelial-like patterns that share morphologic, immunohistochemical, and ultrastructural features with ovarian sex cord tumors. FOXL2 immunoexpression has recently been found in sex cord stromal tumors of the ovary, including granulosa cell tumors, Sertoli-Leydig cell tumors, thecomas, and fibromas, but mutations have been identified mostly in adult granulosa cell tumors. In this study, we investigated FOXL2 mutation status and protein expression in UTROSCTs. Mutational analysis using a TaqMan real-time polymerase chain reaction-based allelic discrimination assay was performed on formalin-fixed, paraffin-embedded tissue from 15 UTROSCTs. FOXL2 mutation was absent in all tumors. FOXL2 immunoexpression was tested in all 15 tumors. Intensity of staining was scored as weak, moderate, or strong. Percentage of tumor cells with nuclear staining was recorded as follows: 0 (negative); 1+ (1% to 25%); 2+ (26% to 50%); 3+ (51% to 75%); and 4+ (76% to 100%). Nuclear expression of FOXL2 was present in 6 of 15 (40%) UTROSCTs. One tumor demonstrated strong 4+ staining. Moderate expression was seen in 3 cases, including 2 and 1 showing 2+ and 1+ staining, respectively. Weak expression was observed in 2 tumors demonstrating 3+ and 1+ staining. Although UTROSCTs show overlapping morphologic, immunohistochemical, and ultrastructural features with sex cord stromal tumors of the ovary, they do not harbor FOXL2 mutation despite focal immunoreactivity in a subset of these tumors. © 2014 Wolters Kluwer Health, Inc. All rights reserved.

Bossone E.,University of Salerno | Corteville D.C.,University of Michigan | Harris K.M.,Abbott Laboratories | Suzuki T.,University of Tokyo | And 11 more authors.
Circulation | Year: 2013

BACKGROUND - Stroke is a highly dreaded complication of type A acute aortic dissection (TAAAD). However, little data exist on its incidence and association with prognosis. METHODS AND RESULTS - We evaluated 2202 patients with TAAAD (mean age 62±14 years, 1487 [67.5%] men) from the International Registry of Acute Aortic Dissection to determine the incidence and prognostic impact of stroke in TAAAD. Stroke was present at arrival in 132 (6.0%) patients with TAAAD. These patients were older (65±12 versus 62±15 years; P=0.002) and more likely to have hypertension (86% versus 71%; P=0.001) or atherosclerosis (29% versus 22%; P=0.04) than patients without stroke. Chest pain at arrival was less common in patients with stroke (70% versus 82%; P<0.001), and patients with stroke presented more often with syncope (44% versus 15%; P<0.001), shock (14% versus 7%; P=0.005), or pulse deficit (51% versus 29%; P≤0.001). Arch vessel involvement was more frequent among patients with stroke (68% versus 37%; P<0.001). They had less surgical management (74% versus 85%; P<0.001). Hospital stay was significantly longer in patients with stroke (median 17.9 versus 13.3 days; P<0.001). In-hospital complications, such as hypotension, coma, and malperfusion syndromes, and in-hospital mortality (adjusted odds ratio, 1.62; 95% confidence interval, 0.99-2.65) were higher among patients with stroke. Among hospital survivors, follow-up mortality was similar between groups (adjusted hazard ratio, 1.15; 95% confidence interval, 0.46-2.89). CONCLUSIONS - Stroke occurred in >1 of 20 patients with TAAAD and was associated with increased in-hospital morbidity but not long-term mortality. Whether aggressive early invasive interventions will reduce negative outcomes remains to be evaluated in future studies. © 2013 American Heart Association, Inc.

Gravina G.L.,University of LAquila | Ranieri G.,San Salvatore Hospital | Muzi P.,General Pathology Laboratory | Marampon F.,University of LAquila | And 6 more authors.
Oncology Reports | Year: 2013

DNA methylation might be the earliest somatic genome changes in prostate cancer that also play an important role in the process of tumor invasion, growth and metastasis. In recent years, several inhibitors of DNA methyltransferases (DNMTis) have been developed and evaluated in pre-clinical models and in clinical trials. While these compounds are effective in the treatment of hematological conditions, clinical trials in solid tumors and in prostate cancer have shown limited or no efficacy. This may be attributed to inappropriate dose regimens leading to toxicity-related adverse events. As with other anti-target compounds, one of the obstacles encountered with DNMTis in prostate cancer could be the inability to select patients for the clinical studies as well as the inability to monitor the efficacy of the drug if not the conclusion of the study. Primary cultures derived from human prostatic tissues harvested from patients with benign prostatic hyper-plasia (BPH) and prostate cancer (PCa) as well as neoplastic and non-neoplastic prostate cell lines were tested for DNMT expression/activity and to monitor azacitidine molecular efficacy. We observed that in primary cultures the levels of DNMT activity as well as the protein levels of DNMT1, DNMT3a and DNMT3b were higher in cultures derived from PCa compared to BPH tissue samples and significantly higher in cultures derived from PCa with Gleason scores ≥7 compared to those observed in cultures derived from Gleason scores <7. In addition, DNMT activity as well as DNMT1, DNMT3a and DNMT3b levels were higher in PCa cell lines compared to their non-neoplastic counterparts. Although DNMT activity was higher in high tumorigenic/aggressive PCa cell lines compared to low tumorigenic/aggressive cell lines, only the levels of DNMT3a and DNMT3b were significantly higher in the first group of cells, suggesting that DNMT1 activity is related to the transition to non-neoplastic versus neoplastic phenotype whereas the de novo methylation enzymes were mainly related to progression. Nevertheless, the comparison in the more aggressive PC3 cell derivatives (PC3-LN4 cells) also possessed higher levels of DNMT1 compared to PC3 and PC3M from which these cells were derived. Collectively, our results confirm previous data on the increased methylation in more aggressive tumors supporting the use of DNMTis in advanced prostate cancer. In addition, since glutathione S-transferase-π (GSTP1) was re-expressed or its protein levels were increased after treatment with non-toxic azacitidine doses and since GSTP1 can easily be measured in patient sera, the monitoring of this protein may aide in the evaluation of therapy in future clinical trials.

Di Francesco A.,San Salvatore Hospital | Flamini S.,San Salvatore Hospital | Zugaro L.,San Salvatore Hospital | Zoccali C.,Italian National Cancer Institute
Acta Orthopaedica Belgica | Year: 2012

This study aimed to determine whether Radio-frequency Ablation (RFA) followed by prophylactic internal fixation produces better palliation in terms of pain and reduces the need for blood transfusion more than radiotherapy and surgical stabilization (RT-SS). Patients with solitary long bone metastases and a pain score of 5 or more on the VAS scale were selected. Fifteen patients were treated with RFA and surgical stabilization (RFA-SS) and were compared with a matched group (15 subjects) treated by radiotherapy and surgical stabilization (RT-SS). A complete response in terms of pain relief at 12 weeks was documented in 20% (3/15) and 53.3% (8/15) of the subjects treated by RT-SS or RFA-SS, respectively (p = 0.027). The overall response rate at 12 weeks was 93.3% (14 patients) in the group treated by RFA-SS and 59.9% (9 patients) in the group treated by RT-SS (p = 0.048). Although recurrent pain was documented more frequently after RT-SS (26.6%) than after RFASS (6.7%) the difference did not reach statistical significance. The morbidity related to RT-SS did not significantly differ when the treatment was associated with RFA. We observed a reduction in blood trans-fusion, as 3 patients in the RT-SS group required a blood transfusion, versus none in the RFA-SS group. Our results suggest that RFA-SS is safe and is more effective than RT-SS; furthermore, RFA may become an option for patients with metastases of the long bones to prevent tumour dissemination and reduce intraoperative blood loss. The findings described here should serve as a framework around which to design future clinical trials. © 2012, Acta Orthopædica Belgica.

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