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1.
Clin Oncol (R Coll Radiol) ; 35(1): e77-e84, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36115747

RESUMO

AIMS: There is a widespread belief that outcomes of cancer patients treated within clinical trials might not be representative of the outcomes obtained within standard clinical settings. We sought to investigate the effect of trial participation on biochemical recurrence (BCR) in localised, D'Amico intermediate- and high-risk prostate cancer patients treated with external beam radiotherapy (EBRT). MATERIALS AND METHODS: We relied on a study population treated with EBRT between January 2001 and January 2021 at a single tertiary care centre, stratified according to trial enrolment. Separate Kaplan-Meier and multivariable Cox regression models tested BCR-free survival at 60 months within intermediate- and high-risk EBRT patients, after adjustment for covariables. Additionally, the analyses were refitted after inverse probability treatment weighting was performed separately for both risk subgroups. RESULTS: Of 932 eligible patients, 635 (68%) and 297 (32%) had intermediate- and high-risk prostate cancer, respectively. Overall, 53% of patients were trial participants. BCR rates were 11 versus 5% (P = 0.27) and 12 versus 14% (P = 0.08) in trial participants versus non-participants for intermediate- and high-risk subgroups, respectively. Differences in patient and clinical characteristics were recorded. Trial participation status failed to reach predictor status in multivariable Cox regression models for BCR in both intermediate-risk (hazard ratio 1.34; 95% confidence interval 0.71-2.49; P = 0.4) and high-risk patients (hazard ratio 1.03; 95% confidence interval 0.45-2.34; P = 0.9). Virtually the same results were recorded in inverse probability treatment weighting cohorts. CONCLUSIONS: Relying on a large cohort of EBRT-treated intermediate- and high-risk patients, no BCR differences were recorded between trial participants and non-participants after accounting for confounders.


Assuntos
Braquiterapia , Neoplasias da Próstata , Humanos , Masculino , Braquiterapia/métodos , Modelos de Riscos Proporcionais , Antígeno Prostático Específico , Prostatectomia , Neoplasias da Próstata/cirurgia , Ensaios Clínicos como Assunto
2.
World J Urol ; 39(6): 1903-1909, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32747981

RESUMO

INTRODUCTION AND OBJECTIVES: To evaluate late complications in a large cohort of patients undergoing robot-assisted radical cystectomy (RARC) with totally intracorporeal urinary diversion (ICUD). MATERIALS AND METHODS: We prospectively enrolled patients who underwent RARC and ICUD between August 2012 and June 2019. We excluded patients with Ejection fraction < 36%, retinal vasculopathy, ventriculoperitoneal shunts, and those treated without curative intent. All complications and their onset date have been recorded, defined, and graded according to Clavien classification adapted for radical cystectomy. RESULTS: 210 patients were included, 76% of whom were men, with a mean age of 62 years. Urinary diversions used were Padua Ileal Bladder (PIB) in 80% of cases, and ileal conduit (IC) in 20% of patients (generally older and with more comorbidity). The mean follow-up was 30 ± 22 months. The stenosis rate of uretero-ileal anastomosis was 14%, while a reduction in eGFR (≥ 20%) was observed in about half of the cases. UTIs occurred in 37% of the patients, especially in the first 12 months. Only 2% of patients had bowel occlusion, whereas incisional hernia, lymphocele, and systemic events (metabolic acidosis and major cardiovascular events) occurred respectively in 20%, 10%, and 1% of cases. CONCLUSIONS: Our study evaluates first late complications in a cohort of patients who underwent RARC with ICUD. These data are encouraging and in line with findings from a historical series of open radical cystectomy (ORC). This study is a further step in supporting RARC as a safe and effective surgical option for the treatment of muscle-invasive bladder cancer (MIBC) in tertiary referral centers.


Assuntos
Cistectomia/efeitos adversos , Cistectomia/métodos , Complicações Pós-Operatórias/etiologia , Procedimentos Cirúrgicos Robóticos , Derivação Urinária/efeitos adversos , Derivação Urinária/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo
3.
World J Urol ; 38(4): 883-896, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31286194

RESUMO

PURPOSE: The aim of the present study is to investigate the impact of the near-infrared (NIRF) technology with indocyanine green (ICG) in robotic urologic surgery by performing a systematic literature review and to provide evidence-based expert recommendations on best practices in this field. METHODS: All English language publications on NIRF/ICG-guided robotic urologic procedures were evaluated. We followed the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement to evaluate PubMed®, Scopus® and Web of Science™ databases (up to April 2019). Experts in the field provided detailed pictures and intraoperative video-clips of different NIRF/ICG-guided robotic surgeries with recommendations for each procedure. A unique QRcode was generated and linked to each underlying video-clip. This new exclusive feature makes the present the first "dynamic paper" that merges text and figure description with their own video providing readers an innovative, immersive, high-quality and user-friendly experience. RESULTS: Our electronic search identified a total of 576 papers. Of these, 36 studies included in the present systematic review reporting the use of NIRF/ICG in robotic partial nephrectomy (n = 13), robotic radical prostatectomy and lymphadenectomy (n = 7), robotic ureteral re-implantation and reconstruction (n = 5), robotic adrenalectomy (n = 4), robotic radical cystectomy (n = 3), penectomy and robotic inguinal lymphadenectomy (n = 2), robotic simple prostatectomy (n = 1), robotic kidney transplantation (n = 1) and robotic sacrocolpopexy (n = 1). CONCLUSION: NIRF/ICG technology has now emerged as a safe, feasible and useful tool that may facilitate urologic robotic surgery. It has been shown to improve the identification of key anatomical landmarks and pathological structures for oncological and non-oncological procedures. Level of evidence is predominantly low. Larger series with longer follow-up are needed, especially in assessing the quality of the nodal dissection and the feasibility of the identification of sentinel nodes and the impact of these novel technologies on long-term oncological and functional outcomes.


Assuntos
Corantes , Verde de Indocianina , Imagem Óptica , Procedimentos Cirúrgicos Robóticos/métodos , Cirurgia Assistida por Computador/métodos , Procedimentos Cirúrgicos Urológicos/métodos , Consenso , Humanos , Imagem Óptica/normas , Guias de Prática Clínica como Assunto , Procedimentos Cirúrgicos Robóticos/normas , Cirurgia Assistida por Computador/normas , Procedimentos Cirúrgicos Urológicos/normas
4.
Eur J Surg Oncol ; 42(11): 1744-1750, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27593224

RESUMO

AIM: To compare the cancer specific survival (CSS) between p2-RCC and a Propensity Score Matched (PSM) cohort of cc-RCC patients. METHODS: Fifty-five (4.6%) patients with p2-RCC and 920 cc-RCC patients were identified within a prospectively maintained institutional dataset of 1205 histologically proved RCC patients treated with either RN or PN. Univariable and multivariable Cox regression analyses were used to identify predictors of CSS after surgical treatment. A 1:2 PSM analysis based on independent predictors of oncologic outcomes was employed and CSS was compared between PSM selected cc-RCC patients using Kaplan-Meier and Cox regression analysis. RESULTS: Overall, 55 (4.6%) p2-RCC and 920 (76.3%) cc-RCC patients were selected from the database; p2-RCC were significantly larger (p = 0.001), more frequently locally advanced (p < 0.001) and node positive (p < 0.001) and had significantly higher Fuhrman grade (p < 0.001) than cc-RCC. On multivariable Cox regression analysis age (p = 0.025), histologic subtype (p = 0.029), pN stage (p = 0.006), size, pT stage, cM stage, sarcomatoid features and Fuhrman grade (all p < 0.001) were independent predictors of CSS. After applying the PSM, 82 cc-RCC selected cases were comparable to 41 p2-RCC for age (p = 0.81), tumor size (p = 0.39), pT (p = 1.00) and pN (p = 0.62) stages, cM stage (p = 0.71) and Fuhrman grade (p = 1). In this PSM cohort, 5 yr CSS was significantly lower in the p2-RCC (63% vs 72.4%; p = 0.047). At multivariable Cox analysis p2 histology was an independent predictor of CSM (HR 2.46, 95% CI 1.04-5.83; p = 0.041). CONCLUSIONS: We confirmed the tendency of p2-RCC to present as locally advanced and metastatic disease more frequently than cc-RCC and demonstrated p2-RCC histology as an independent predictor of worse oncologic outcomes.


Assuntos
Carcinoma Papilar/mortalidade , Carcinoma de Células Renais/mortalidade , Neoplasias Renais/mortalidade , Adulto , Idoso , Carcinoma Papilar/patologia , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais
5.
Eur J Surg Oncol ; 42(11): 1729-1735, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27106494

RESUMO

AIM: Although extensively addressed in US registries, the utilization rate of Partial Nephrectomy has been poorly addressed in European settings. Our aim is to evaluate the impact of hospital volume on the use of PN for cT1 renal tumors. METHODS: 2526 patients with cT1N0M0 renal tumors treated with either PN or radical nephrectomy at 10 European centres in the last decade were included in the analysis. Joinpoint regression analysis was used to identify significant changes over time in linear slope of the trend for each center. The correlation between yearly caseload and the slopes was assessed with the non-parametric Spearman test. Coincident pairwise tests and regression analyses were used to generate and compare the trends of high-volume (HV), mid-volume (MV) and low-volume (LV) groups. RESULTS: Yearly caseload was significantly associated with increased use of PN (R = 0.69, p = 0.028). The utilization rate of PN was stable at LV centres (p = 0.67, p = 0.7, p = 0.76, for cT1, cT1a, and cT1b tumors, respectively), while increased significantly at MV (p = 0.002, 0.0005 and 0.007, respectively) and HV centers (all p < 0.0001). Regression analysis confirmed the trends for HV and MV as significantly different from those observed in LV centres (all p ≤ 0.002) and highlighted significant differences also between MV and HV centres (all p ≤ 0.03). CONCLUSIONS: We confirmed the association between caseload and the use of PN for cT1 tumors. Our findings suggest that a minimum caseload might turn the tide also in LV centres while a selective referral to HV centers for cT1b tumors should be considered.


Assuntos
Neoplasias Renais/cirurgia , Nefrectomia/métodos , Conjuntos de Dados como Assunto , Humanos , Análise de Regressão , Estudos Retrospectivos
6.
Oncogene ; 35(9): 1180-92, 2016 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-26073083

RESUMO

Although the development of bone metastasis is a major detrimental event in prostate cancer, the molecular mechanisms responsible for bone homing and destruction remain largely unknown. Here we show that loss of miR-15 and miR-16 in cooperation with increased miR-21 expression promote prostate cancer spreading and bone lesions. This combination of microRNA endows bone-metastatic potential to prostate cancer cells. Concomitant loss of miR-15/miR-16 and gain of miR-21 aberrantly activate TGF-ß and Hedgehog signaling, that mediate local invasion, distant bone marrow colonization and osteolysis by prostate cancer cells. These findings establish a new molecular circuitry for prostate cancer metastasis that was validated in patients' cohorts. Our data indicate a network of biomarkers and druggable pathways to improve patient treatment.


Assuntos
Biomarcadores Tumorais/biossíntese , Neoplasias Ósseas/genética , MicroRNAs/biossíntese , Neoplasias da Próstata/genética , Animais , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Proteínas Hedgehog/biossíntese , Humanos , Masculino , MicroRNAs/genética , Invasividade Neoplásica/genética , Neoplasias da Próstata/patologia , Transdução de Sinais/genética , Fator de Crescimento Transformador beta/biossíntese
7.
Eur J Pharm Biopharm ; 92: 112-9, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25769679

RESUMO

The aim of this work was to prepare chitosan (CH) based particulate formulations for colon delivery of vancomycin (VM). Chitosan microparticles (MPs) and nanoparticles (NPs) loaded with VM were prepared using different CH/tripolyphosphate (TPP) molar ratios and different technological processes. In particular, nanoparticles were prepared by ionic gelation and freeze-drying to recover these particles, or, alternatively, by spray-drying method. Microparticles were prepared using a different spray-dryer. Micro- and nanoparticles were characterized in terms of size distributions by photon correlation spectroscopy (PCS), while encapsulation and drug loading efficiencies were studied using a dialysis method. Fourier Transform Infrared Spectroscopy (FT-IR) was employed to determine the surface composition of the micro- and nanoparticles respectively, and the morphologies of the developed systems were studied by scanning electron microscopy (SEM). Water uptake as well as drug release profiles were also measured. Antibacterial activity against Staphylococcus aureus, a Gram-positive model strain, was evaluated. FT-IR results suggested an electrostatic interaction between VM and CH/TPP particles. Moreover, the particles were found to hold a positive zeta-potential, indicating the presence of CH on the particle surfaces. Particle size and encapsulation efficiency were mainly influenced by the different manufacturing processes employed. Nanoparticles obtained by spray-drying showed the best results in terms of water uptake and drug release rate. Moreover, they showed a good bactericidal activity against S. aureus.


Assuntos
Antibacterianos/administração & dosagem , Quitosana/química , Sistemas de Liberação de Medicamentos , Vancomicina/administração & dosagem , Antibacterianos/farmacocinética , Química Farmacêutica/métodos , Colo/metabolismo , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Liofilização , Microscopia Eletrônica de Varredura , Microesferas , Nanopartículas , Tamanho da Partícula , Polifosfatos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus/efeitos dos fármacos , Tecnologia Farmacêutica/métodos , Vancomicina/farmacocinética
8.
Eur J Surg Oncol ; 39(7): 792-8, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23562571

RESUMO

INTRODUCTION: Standardized methods of reporting complications after radical cystectomy (RC) and urinary diversions (UD) are necessary to evaluate the morbidity associated with this operation to evaluate the modified Clavien classification system (CCS) in grading perioperative complications of RC and UD in a real life cohort of patients with bladder cancer. MATERIALS AND METHODS: A consecutive series of patients treated with RC and UD from April 2011 to March 2012 at 19 centers in Italy was evaluated. Complications were recorded according to the modified CCS. Results were presented as complication rates per grade. Univariate and binary logistic regression analysis were used for statistical analysis. RESULTS AND LIMITATIONS: 467 patients were enrolled. Median age was 70 years (range 35-89). UD consisted in orthotopic neobladder in 112 patients, ileal conduit in 217 patients and cutaneous ureterostomy in 138 patients. 415 complications were observed in 302 patients and were classified as Clavien type I (109 patients) or II (220 patients); Clavien type IIIa (45 patients), IIIb (22 patients); IV (11 patients) and V (8 patients). Patients with cutaneous ureterostomy presented a lower rate (8%) of CCS type ≥IIIa (p = 0.03). A longer operative time was an independent risk factor of CCS ≥III (OR: 1.005; CI: 1.002-1.007 per minute; p = 0.0001). CONCLUSIONS: In our study, RC is associated with a significant morbidity (65%) and a reduced mortality (1.7%) when compared to previous experiences. The modified CCS represents an easily applicable tool to classify the complications of RC and UD in a more objective and detailed way.


Assuntos
Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/cirurgia , Cistectomia/efeitos adversos , Complicações Pós-Operatórias/classificação , Neoplasias da Bexiga Urinária/cirurgia , Derivação Urinária/efeitos adversos , Adulto , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/patologia , Estudos de Coortes , Cistectomia/métodos , Cistectomia/mortalidade , Cistoscopia/métodos , Intervalo Livre de Doença , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/patologia , Prognóstico , Medição de Risco , Taxa de Sobrevida , Resultado do Tratamento , Ureterostomia/efeitos adversos , Ureterostomia/métodos , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Derivação Urinária/métodos , Coletores de Urina/efeitos adversos
9.
J Nutr Health Aging ; 17(4): 378-84, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23538662

RESUMO

OBJECTIVES: The relative contributions of risk factors, as body mass index (BMI), depression, chronic diseases, smoking, and lifestyles (as physical and performance activity, social contacts and reading habit) to cognitive decline in the elderly are unclear. We explored these variables in relation to 7-year cognitive decline in long-lived Italian elderly. DESIGN: Secondary data analysis of a longitudinal study of a representative, age-stratified, population sample. SETTING: The TREVISO LONGEVA (TRELONG) Study, in Treviso, Italy. PARTICIPANTS: 120 men and 189 women, age 77 years and older (mean age 80.2 ± 6.9 years) survivors after seven years of follow up. MEASUREMENTS: Cognitive decline measured as difference between Mini-Mental State Examination (MMSE) score in 2003 and in 2010; Body mass index (BMI), handgrip, Short Physical Performance Battery (SPPB) score, social contacts, reading habit, sight, hearing, schooling, mediterranean diet and multiple clinical and survey data recorded at baseline in 2003. RESULTS: In separate univariate analyses, age, SPPB score < 5, depressive symptoms (GDS) and more comorbidities (CCI) were associated with greater cognitive decline. Otherwise higher BMI, higher handgrip, reading habit, non-deteriorated sight and hearing, and schooling were protective. In a final multivariate model, age and higher BMI were associated with greater cognitive decline while reading habits was protective. SPPB score < 5 tends, though weakly, to be associated with greater cognitive decline. These associations remained with multivariate adjustment for gender, schooling, Charlson co-morbidity index (CCI) and baseline MMSE. CONCLUSION: Age and higher baseline BMI, independent of gender, and other confounding factors, are risk factors for cognitive decline. Reading habit plays a protective role seven years later among northern Italian adults aged 70 years or older. Low physical performance tends, though weakly, to be associated with greater cognitive decline.


Assuntos
Índice de Massa Corporal , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/epidemiologia , Depressão/epidemiologia , Estilo de Vida , Atividade Motora , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Comorbidade , Depressão/diagnóstico , Dieta Mediterrânea , Escolaridade , Feminino , Seguimentos , Avaliação Geriátrica , Força da Mão , Humanos , Itália/epidemiologia , Modelos Lineares , Modelos Logísticos , Estudos Longitudinais , Masculino , Análise Multivariada , Estudos Prospectivos , Leitura , Fatores de Risco
10.
Neuroradiol J ; 25(5): 569-74, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24029092

RESUMO

Rosai-Dorfman disease (RDD) was firstly described in 1969 as a benign proliferative disorder of histiocytes with systemic symptoms and lymphadenopathy. This disease is of uncertain pathogenesis and mostly occurs in children and young adults. The typical clinical features of RDD include bilateral painless cervical lymphadenopathy, but extranodal involvement may also be present. The most common extranodal sites include organs such as the respiratory tract, skin, nasal cavity, orbit and bone. Isolated central nervous system (CNS) manifestations are extremely rare. In case of CNS involvement, the commonest imaging findings are dural-based extra-axial enhancing masses. We describe a case of intracranial RDD mimicking multiple meningiomas both clinically and radiologically in a 57-year-old man presenting with a six-year history of progressive right visual and hearing loss and tinnitus. In cases of multiple extra-axial lesions it is worth bearing in mind the possible differential diagnosis for intracranial RDD and eventually propose to the patient further investigations.

11.
Neuroradiol J ; 25(6): 684-94, 2012 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-24029182

RESUMO

Multiple sclerosis (MS) is an inflammatory CNS disease characterized by multifocal areas of demyelination; usually it arises in young adults, but can also occur in children (under the age of 10) and adolescents (under the age of 18). As in adult, pediatric MS (PMS) diagnosis is based on the demonstration of multiple demyelination episodes separated in time and spaces. Diagnostic criteria realized for childhood are similar to those employed for adults. Although clinical and imaging features of PMS can be similar to those of adults, the disease is often characterized by a more aggressive course and atypical imaging findings, with giant and pseudotumoral plaques. Differential diagnosis between PMS and ADEM could be difficult: clinical findings and MRI are necessary; sometimes MRI follow-up is required for definitive diagnosis.

12.
Neuroradiol J ; 25(6): 715-24, 2012 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-24029185

RESUMO

Central nervous system (CNS) vasculitis can affect both adults and children, but some of these occur almost exclusively in childhood. In children may develop as a primary condition or secondary to an underlying systemic disease. Cerebral vasculitis can be classified on the basis of the diameter of the involved vessels, although there is no univocal consensus. The diagnosis of CNS vasculitis is particularly difficult because the available investigative modalities have limited sensitivities and specificities. The most helpful diagnostic tests include cerebrospinal fluid analysis, MRI (MR angiography/venography (MRA/MRV) of the brain, and angiography. However, brain biopsy may be required to diagnose small vessel vasculitis in order to make differential diagnosis with a wide range of conditions, such as degenerative vasculopathies, embolic diseases, or coagulation disorders. This paper discusses on current understanding of most frequent primary and secondary central nervous system vasculitis in children in which are involved small vessel.

13.
Ann Oncol ; 23(3): 695-700, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21859900

RESUMO

BACKGROUND: The purpose of the study was to evaluate the benefit of adjuvant chemotherapy (AC) versus surgery alone in patients with muscle-invasive bladder cancer (MIBC). PATIENTS AND METHODS: One hundred and ninety-four patients with pT2G3, pT3-4, N0-2 transitional cell bladder carcinoma were randomly allocated to control (92 patients) or to four courses of AC (102 patients). These latter patients were further randomly assigned to receive gemcitabine 1000 mg/m(2) days 1, 8 and 15 and cisplatin 70 mg/m(2) day 2 or gemcitabine as above plus cisplatin 70 mg/m(2) day 15, every 28 days. RESULTS: At a median follow-up of 35 months, the 5-year overall survival (OS) was 48.5%, with no difference between the two arms [P = 0.24, hazard ratio (HR) 1.29, 95% confidence interval (CI) 0.84-1.99]. Mortality hazard was significantly correlated with Nodes (N) and Tumor (T) stage. The control and AC arms had comparable disease-free survival (42.3% and 37.2%, respectively; P = 0.70, HR 1.08, 95% CI 0.73-1.59). Only 62% of patients received the planned cycles. A significant higher incidence of thrombocytopenia was observed in patients receiving cisplatin on day 2 (P = 0.006). A similar global quality of life was observed in the two arms. CONCLUSION: The study was underpowered to demonstrate that AC with cisplatin and gemcitabine improves OS and disease-free survival in patients with MIBC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células de Transição/tratamento farmacológico , Desoxicitidina/análogos & derivados , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/cirurgia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Cistectomia , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Itália , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Recidiva , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/cirurgia , Gencitabina
14.
Mol Endocrinol ; 25(12): 2003-16, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22052999

RESUMO

We recently identified in prostate tumors (PCa) a transcriptional prognostic signature comprising a significant number of genes differentially regulated in patients with worse clinical outcome. Induction of up-regulated genes was due to chromatin remodeling by a combinatorial complex between estrogen receptor (ER)-ß and endothelial nitric oxide synthase (eNOS). Here we show that this complex can also repress transcription of prognostic genes that are down-regulated in PCa, such as the glutathione transferase gene GSTP1. Silencing of GSTP1 is a common early event in prostate carcinogenesis, frequently caused by promoter hypermethylation. We validated loss of glutathione transferase (GST) P1-1 expression in vivo, in tissue microarrays from a retrospective cohort of patients, and correlated it with decreased disease-specific survival. Furthermore, we show that in PCa cultured cells ERß/eNOS causes GSTP1 repression by being recruited at estrogen responsive elements in the gene promoter with consequential remodeling of local chromatin. Treatment with ERß antagonist or its natural ligand 5α-androstane-3ß,17ß-diol, eNOS inhibitors or ERß small interference RNA abrogated the binding and reversed GSTP1 silencing, demonstrating the direct involvement of the complex. In vitro, GSTP1 silencing by ERß/eNOS was specific for cells from patients with worse clinical outcome where it appeared the sole mechanism regulating GSTP1 expression because no promoter hypermethylation was present. However, in vivo chromatin immunoprecipitation assays on fresh PCa tissues demonstrated that silencing by ERß/eNOS can coexist with promoter hypermethylation. Our findings reveal that the ERß/eNOS complex can exert transcriptional repression and suggest that this may represent an epigenetic event favoring inactivation of the GSTP1 locus by methylation. Moreover, abrogation of ERß/eNOS function by 3ß-adiol emphasizes the significance of circulating or locally produced sex steroid hormones or their metabolites in PCa biology with relevant clinical/therapeutic implications.


Assuntos
Receptor beta de Estrogênio/metabolismo , Inativação Gênica , Glutationa S-Transferase pi/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Neoplasias da Próstata/genética , Androstano-3,17-diol/farmacologia , Androstano-3,17-diol/fisiologia , Linhagem Celular Tumoral , Movimento Celular , Montagem e Desmontagem da Cromatina , Metilação de DNA , Estradiol/farmacologia , Estradiol/fisiologia , Receptor beta de Estrogênio/agonistas , Glutationa S-Transferase pi/metabolismo , Humanos , Masculino , Prognóstico , Regiões Promotoras Genéticas , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/metabolismo , Transporte Proteico , Análise Serial de Tecidos , Transcrição Gênica/efeitos dos fármacos
15.
Eur Radiol ; 21(9): 2004-10, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21533865

RESUMO

OBJECTIVES: To determine whether Radiofrequency Ablation (RFA) followed by Radiotherapy (RT) (RFA-RT) produces better palliation in terms of pain than RT alone in patients with osteolytic bone metastases. METHODS: Patients with solitary bone metastases and a pain score of least 5 or more on the VAS scale were selected. Fifteen patients were treated with RFA-RT (20 Gy delivered in 5 fractions of 4 Gy over 1 week) and were compared with a matched group (30 subjects) treated by RT. RESULTS: A complete response in terms of pain relief at 12 weeks was documented in 16.6% (5/30) and 53.3% (8/15) of the subjects treated by RT or RFA-RT, respectively (p = 0.027). The overall response rate at 12 weeks was 93.3% (14 patients) in the group treated by RFA-RT and 59.9% (18 patients) in the group treated by RT (p = 0.048). Although recurrent pain was documented more frequently after RT (26.6%) than after RFA-RT (6.7%) the difference did not reach statistical significance. The morbidity related to RT did not significantly differ when this treatment was associated with RFA. CONCLUSIONS: Our results suggest that RFA-RT is safe and more effective than RT. The findings described here should serve as a framework around which to design future clinical trials.


Assuntos
Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/cirurgia , Ablação por Cateter/métodos , Cuidados Paliativos , Radioterapia/métodos , Idoso , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/secundário , Distribuição de Qui-Quadrado , Estudos de Coortes , Terapia Combinada , Intervalos de Confiança , Estudos de Viabilidade , Feminino , Humanos , Masculino , Osteólise/radioterapia , Osteólise/cirurgia , Manejo da Dor/métodos , Medição da Dor , Dor Intratável/radioterapia , Dor Intratável/cirurgia , Prognóstico , Medição de Risco , Estatísticas não Paramétricas , Análise de Sobrevida
17.
Minerva Pediatr ; 62(2): 217-21, 2010 Apr.
Artigo em Italiano | MEDLINE | ID: mdl-20440241

RESUMO

Infantile subglottic hemangioma is a pediatric tumor of endothelial cells characterized by an initial phase of rapid proliferation (around 6 months), followed by slow involution, often leading to complete regression following the first year of life. It is most frequently found in females and it usually it occurs also in the skin. From its position it can cause a progressive airway obstruction, so early diagnosis and treatment are very important. Many treatments have been described in the literature, including systemic steroids, intralesional steroid injection, carbon dioxide laser therapy, submucous resection, interferon alfa-2 and also tracheostomy as last approach. This case report discusses a 6-month old infant, that arrived to our attention for an acute two-way stridor. Laringoscopy under general anesthesia showed a subocclusive subglottic haemangioma that closed 70% of the laryngeal airway. In agreement with our ENT specialist it was decided to begin systemic steroid therapy, first by i.v. ingection during intensive therapy with rinotracheal intubation and mechanic ventilation; after the canula removal and the hemangioma reduction, the patient took oral steroids with a gradual reduction of the dose. This case evidences the importance of laryngoscopy in the diagnosis of subglottic haemangioma; it also proves the importance of multi-disciplinary collaboration with ENT specialist and dermatologist for the diagnosis and treatment of this kind of patient. It also shows that systemic steroids are an effective alternative in the management of obstructive pediatric subglottic hemangiomas.


Assuntos
Glote , Hemangioma/diagnóstico , Neoplasias Laríngeas/diagnóstico , Doença Aguda , Feminino , Hemangioma/complicações , Humanos , Lactente , Neoplasias Laríngeas/complicações , Sons Respiratórios/etiologia
18.
Clin Ter ; 160(1): 11-5, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19290406

RESUMO

OBJECTIVES: Cardiovascular disease (CVD) is the main cause of death among haemodialysis (HD) patients. Emerging cardiovascular risk factors such as oxidative stress and chronic inflammation are involved in these patients together with traditional risk factors. Here we investigate the effects of a short-term folate treatment on some markers of chronic inflammation in two groups of HD patients with and without vascular occlusive disease (VOD). PATIENTS AND METHODS: Homocysteine (HCy), C-reactive protein (CRP), Folate, fibrinogen and alpha1 acid glycoprotein (alpha1AGP) were dosed before and after a 3-month course of high-dose folate (25 mg intravenous calcium laevofolinate pentahydride once weekly) and again after a one-month washout in 15 HD patients with established VOD (group A) and in 15 comparable HD patients with no diagnosis of VOD (group B). RESULTS: Baseline HCy and CRP were significantly elevated in patients of both groups A and B compared to normal values. Folate treatment significantly reduced HCy in patients of both groups A and B and alpha1AGP only in patients of group A, while the other markers were not modified. After the one-month washout a significant raise of CRP could be observed in patients of group A; again, the other markers were not modified. CONCLUSIONS: Our results suggest that significant reduction of serum HCy can be achieved in both patients with or without VOD after administration of high-dose folic acid. Hence, folic acid supply is useful in the treatment of hyperhomocysteinemia in HD patients, although it is not sufficient to modify their chronic inflammatory status.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Ácido Fólico/uso terapêutico , Hiper-Homocisteinemia/tratamento farmacológico , Diálise Renal , Complexo Vitamínico B/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/etiologia , Feminino , Humanos , Hiper-Homocisteinemia/complicações , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Doenças Vasculares/complicações
19.
Urol Int ; 81(4): 437-40, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19077406

RESUMO

OBJECTIVES: We compared two different approaches to right laparoscopic transperitoneal adrenalectomy for large tumors (>5 cm): the anterior transperitoneal (AT) and lateral transperitoneal (LT) approaches. METHODS: 40 patients with a right large adrenal mass >5 cm underwent right adrenalectomy: 20 patients underwent the AT procedure and 20 patients the LT procedure. Preoperative characteristics were similar for both groups: mean tumor size for the AT and LT groups was 6.52 cm (range 5.2-8.5) and 6.59 cm (range 5.4-8.1), respectively. Mean patient's age was 53 years (23-75 in the AT group and 20-77 in the LT group). AT and LT approaches were compared in terms of operative time, intraoperative blood loss, time to first oral intake and postoperative convalescence. RESULTS: No difference was found between two groups in terms of estimated blood (100 ml for the AT group and 105.3 ml for the LT group), time to first oral intake (2.0 days for both groups) and convalescence (3.5 and 3 days, respectively). The mean operative times of the AT and LT procedures were 75.25 and 84.75 min, respectively: this difference was statistically significant at the Student's t test (p = 0.0423). CONCLUSIONS: Both approaches proved to be safe and minimally invasive. We believe that the shorter operative time of AT procedures was related to the better visibility of familiar anatomic landmarks, easier access to the vessels and a larger operative field. For these reasons, we prefer the AT approach in the management of large adrenal masses.


Assuntos
Doenças das Glândulas Suprarrenais/cirurgia , Neoplasias das Glândulas Suprarrenais/cirurgia , Glândulas Suprarrenais/patologia , Adrenalectomia/métodos , Laparoscopia/métodos , Administração Oral , Doenças das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Idoso , Feminino , Humanos , Complicações Intraoperatórias , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Operatórios/métodos , Resultado do Tratamento
20.
AJNR Am J Neuroradiol ; 29(9): 1684-91, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18599575

RESUMO

BACKGROUND AND PURPOSE: The higher relaxivity of gadobenate dimeglumine compared with gadodiamide is potentially advantageous for contrast-enhanced brain MR imaging. This study intraindividually compared 0.1-mmol/kg doses of these agents for qualitative and quantitative lesion enhancement. MATERIALS AND METHODS: Adult patients with suggested or known brain lesions underwent 2 identical MR imaging examinations at 1.5T, one with gadobenate dimeglumine and the other with gadodiamide. The agents were administered in randomized order separated by 3-14 days. Imaging sequences and postinjection acquisition timing were identical for the 2 examinations. Three blinded readers evaluated images qualitatively for diagnostic information (lesion extent, delineation, morphology, enhancement, and global preference) and quantitatively for contrast-to-noise ratio (CNR). RESULTS: One hundred thirteen of 138 enrolled patients successfully underwent both examinations. Final diagnoses were intra-axial tumor, metastasis, extra-axial tumor, or other (47, 27, 18, and 21 subjects, respectively). Readers 1, 2, and 3 demonstrated global preference for gadobenate dimeglumine in 63 (55.8%), 77 (68.1%), and 73 (64.6%) patients, respectively, compared with 3, 2, and 3 patients for gadodiamide (P < .0001, all readers). Highly significant (P < .0001, all readers) preference for gadobenate dimeglumine was demonstrated for all qualitative end points and for CNR (increases of 23.3%-34.7% and 42.4%-48.9% [spin-echo and gradient-refocused echo sequences, respectively] for gadobenate dimeglumine compared with gadodiamide). Inter-reader agreement was good for all evaluations (kappa = 0.47-0.69). Significant preference for gadobenate dimeglumine was demonstrated for all lesion subgroup analyses. CONCLUSION: Significantly greater diagnostic information and lesion enhancement are achieved on brain MR imaging with 0.1-mmol/kg gadobenate dimeglumine compared with gadodiamide at an equivalent dose.


Assuntos
Neoplasias Encefálicas/diagnóstico , Meios de Contraste , Gadolínio DTPA , Imageamento por Ressonância Magnética , Meglumina/análogos & derivados , Compostos Organometálicos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/patologia , Neoplasias Encefálicas/secundário , Estudos Cross-Over , Feminino , Humanos , Aumento da Imagem , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Sensibilidade e Especificidade , Adulto Jovem
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