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BACKGROUND: Prostate cancer (PCa) is the second most common neoplasm in male patients. To date, there's no certain indication about the maximum waiting time (WT) acceptable for treatment beginning and the impact on oncological and functional outcomes has not been well established. METHODS: Data from the National Research Council PCa monitoring multicenter project in Italy (Pros-IT CNR) were prospectively collected and analyzed. WT was defined as the time from the bioptical diagnosis of PCa to the first treatment received. Patients were divided in two groups, using a time frame of 90 days. Quality of life was measured through the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and of the Short-Form Health Survey (SF-12). The occurrence of upgrading, upstaging, presence of lymph node metastasis and positive surgical margins at the final histopathological diagnosis, and PSA at 12 months follow-up were evaluated. RESULTS: The overall median WT was 93 days. The logistic multivariable model confirmed that age, being resident in Southern regions of Italy and T staging at diagnosis were significantly associated with a WT>90 days. At 6 months from diagnosis the mean SF-12 score for the emotional-psychological component was significantly lower in WT≥90 days group (P=0.0428). Among patients treated with surgical approach, no significant differences in oncological outcomes were found in the two groups. CONCLUSIONS: In our study age, clinical T stage and provenance from Southern regions of Italy are associated with a WT>90 days. WT might have no impact on functional and oncological outcome.
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Intervención Coronaria Percutánea , Neoplasias de la Próstata , Humanos , Masculino , Próstata/patología , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/cirugía , Calidad de Vida , Listas de EsperaRESUMEN
PURPOSE: Therapeutic strategies for prostate cancer (PCa) have been evolving dramatically worldwide. The current article reports on the evolution of surgical management strategies for PCa in Italy. METHODS: The data from two independent Italian multicenter projects, the MIRROR-SIU/LUNA (started in 2007, holding data of 890 patients) and the Pros-IT-CNR project (started in 2014, with data of 692 patients), were compared. Differences in patients' characteristics were evaluated. Multivariable logistic regression models were used to identify characteristics associated with robot-assisted (RA) procedure, nerve sparing (NS) approach, and lymph node dissection (LND). RESULTS: The two cohorts did not differ in terms of age and prostate-specific antigen (PSA) levels at biopsy. Patients enrolled in the Pros-IT-CNR project more frequently were submitted to RA (58.8% vs 27.6%, p < 0.001) and NS prostatectomy (58.4% vs. 52.9%, p = 0.04), but received LND less frequently (47.7% vs. 76.7%, p < 0.001), as compared to the MIRROR-SIU/LUNA patients. At multivariate logistic models, Lower Gleason Scores (GS) and PSA levels were significantly associated with RA prostatectomy in both cohorts. As for the MIRROR-SIU/LUNA data, clinical T-stage was a predictor for NS (OR = 0.07 for T3, T4) and LND (OR = 2.41 for T2) procedures. As for Pros-IT CNR data, GS ≥ (4 + 3) and positive cancer cores ≥ 50% were decisive factors both for NS (OR 0.29 and 0.30) and LND (OR 7.53 and 2.31) strategies. CONCLUSIONS: PCa management has changed over the last decade in Italian centers: RA and NS procedures without LND have become the methods of choice to treat newly medium-high risk diagnosed PCa.
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Prostatectomía/métodos , Prostatectomía/tendencias , Neoplasias de la Próstata/cirugía , Anciano , Humanos , Italia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de TiempoRESUMEN
INTRODUCTION: We evaluate the clinical outcome of patients treated with conservative approach for small testicular masses (STMs). We analyzed the steps who brought to the selection of the therapeutic approach: starting from clinical presentation, through imaging and lab studies. METHODS: We considered 18 patients who underwent an organ-sparing approach for STMs from 2005 until 2014. The selection criteria were dimension of the mass and absence of clinical, laboratory and/or radiological malignancy suspicion. Preoperative scrotal ultrasound (US) was carried out in all the patients by the same radiologist. The postoperative fertility profile was evaluated in patients younger than 40 years. RESULTS: We performed 13 enucleations, one partial orchiectomy (PO) and four active surveillances. During surgery, a frozen section examination (FSE) was always requested and no discrepancies were noted between its results and the definitive histology. Only one seminomatous tumor was identified, while the remaining masses were four necrosis, four epidermoid cysts, three Leydig tumors, one Sertoli tumor and one chronic orchitis. After a mean follow-up of 41.6 ± 24.7 months, all the patients resulted free of disease and hypogonadism and five of them reached the fatherhood after surgery. CONCLUSIONS: The clinical and instrumental evaluation consented an accurate selection of patients eligible for the organ-preserving approach. We believe that testis-sparing surgery leads good functional and aesthetic results in patients with benign lesions; it is a safe option for STMs with a reliable pathologist performing FSE and is an important goal in young patients with fatherhood desire.
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Toma de Decisiones Clínicas , Tratamiento Conservador , Neoplasias de Células Germinales y Embrionarias/cirugía , Neoplasias Testiculares/cirugía , Adolescente , Adulto , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de Células Germinales y Embrionarias/patología , Tratamientos Conservadores del Órgano , Estudios Retrospectivos , Neoplasias Testiculares/patología , Adulto JovenRESUMEN
OBJECTIVE: To analyze the prevalence of cardiovascular disease (CVD) and osteoporosis in patients treated with androgen deprivation therapy (ADT) for prostate cancer (PCa) but not adherent to European Association of Urology (EAU) guidelines. MATERIALS AND METHODS: The CHOosIng Treatment for Prostate CanCEr (CHOICE) study was an Italian multicenter, cross-sectional study conducted from December 2010 to January 2012. A total of 1386 patients treated with ADT for PCa (first prescription or renewal of ADT) were selected. According to EAU guidelines, the cohort was categorized in discordant ADT (Group A) and concordant ADT (Group B). The prevalence of CVD and osteoporosis after ADT was recorded. RESULTS: The final cohort included 1075 patients. According to EAU guidelines adherence, 285 (26.51%) and 790 (73.49%) were considered discordant and concordant, respectively. The proportion of men with Charlson Comorbidity Index > 2 at baseline was statistically similar in Group A (81.8%) compared to Group B (80.8%) (P = .96). The number of complications reported at enrollment was as follows: cardiovascular in 351 (32.7%), endocrine in 166 (15.4%), sexual in 498 (46.3%), osteoporosis in 181 (16.8%), and gynecomastia in 274 (25.5%) subjects. At the multivariate logistic regression analysis adjusted for confounding factors, discordant ADT was associated with greater risk of cardiovascular complications (odds ratio: 2.07; P < .01) and osteoporosis (odds ratio: 1.75; P = .04). CONCLUSION: About one-third of patients with PCa received inappropriate ADT and showed a greater risk of CVD and osteoporosis. These results could be useful for setting better policy strategies to limit the inappropriateness of ADT prescription.
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Antagonistas de Andrógenos/administración & dosificación , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Hormona Liberadora de Gonadotropina/agonistas , Orquiectomía/efectos adversos , Osteoporosis/epidemiología , Osteoporosis/etiología , Neoplasias de la Próstata/terapia , Anciano , Anciano de 80 o más Años , Antagonistas de Andrógenos/efectos adversos , Estudios Transversales , Humanos , Masculino , PrevalenciaRESUMEN
Bladder cancer has an unexplained, high recurrence rate. Causes of recurrence might include the presence of sporadic tumor micro-foci in the residual urothelial tissue after surgery associated with an inverted ratio between intratumoral effector and regulatory T cell subsets. Hence, surgical specimens of both tumors and autologous, macroscopically/histologically free-of-tumor tissues were collected from 28 and 20 patients affected by bladder or renal cancer, respectively. The frequencies of effector (IFNγ+ and IL17+ T cells) and regulatory (CD4+CD25hiCD127lo and CD8+CD28-CD127loCD39+ Treg) T cell subpopulations among tumor infiltrating lymphocytes were analyzed by immunofluorescence, while the gene expression of MAGE-A1 and MAGE-A2 tumor-associated antigens was studied by RT-PCR. The results show that both the T cell infiltrate and the frequency of MAGE-A1/A2 gene expression were comparable in tumors and in autologous free-of-tumor tissues in bladder cancer, while the autologous free-of-tumor renal tissues showed reduced T cell infiltrate and frequency of MAGE gene expression as compared to the autologous tumors. Importantly, the intra-tumor T effector/Treg cell ratio was consistently <1 in bladder cancer patients (n. 7) who relapsed within two years, while it was always >1 in patients (n. 6) without recurrence (regardless of tumor stage) (P = 0.0006, Odds ratio = 195). These unprecedented findings clarify the pathogenic mechanism of bladder cancer recurrence and suggest that microscopically undetectable micro-foci of tumor may predispose to recurrence when associated with an inverted intratumoral T effector/Treg cell ratio.
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Linfocitos T CD8-positivos/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Recurrencia Local de Neoplasia/patología , Neoplasia Residual/patología , Linfocitos T Reguladores/inmunología , Neoplasias de la Vejiga Urinaria/patología , Estudios de Casos y Controles , Técnica del Anticuerpo Fluorescente , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Antígenos Específicos del Melanoma/genética , Antígenos Específicos del Melanoma/metabolismo , Clasificación del Tumor , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/metabolismo , Estadificación de Neoplasias , Neoplasia Residual/inmunología , Neoplasia Residual/metabolismo , Pronóstico , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias de la Vejiga Urinaria/inmunología , Neoplasias de la Vejiga Urinaria/metabolismoRESUMEN
OBJECTIVE: To evaluate both the patterns of prescription of androgen deprivation therapy (ADT) in patients with prostate cancer (PCa) and the adherence to European Association of Urology (EAU) guidelines for ADT prescription. METHODS: The Choosing Treatment for Prostate Cancer (CHOICE) study was an Italian multicentre cross-sectional study conducted between December 2010 and January 2012. A total of 1 386 patients, treated with ADT for PCa (first prescription or renewal of ADT), were selected. With regard to the EAU guidelines on ADT, the cohort was categorized into discordant ADT (Group A) and concordant ADT (Group B). RESULTS: The final cohort included 1 075 patients with a geographical distribution including North Italy (n = 627, 58.3%), Central Italy (n = 233, 21.7%) and South Italy (n = 215, 20.0%). In the category of patients treated with primary ADT, a total of 125 patients (56.3%) were classified as low risk according to D'Amico classification. With regard to the EAU guidelines, 285 (26.51%) and 790 patients (73.49%) were classified as discordant (Group A) and concordant (Group B), respectively. In Group A, patients were more likely to receive primary ADT (57.5%, 164/285 patients) than radical prostatectomy (RP; 30.9%, 88/285 patients), radiation therapy (RT; 6.7%, 19/285 patients) or RP + RT (17.7%, 14/285 patients; P < 0.01). Multivariate logistic regression analysis, adjusted for clinical and pathological variables, showed that patients from Central Italy (odds ratio [OR] 2.86; P < 0.05) and South Italy (OR 2.65; P < 0.05) were more likely to receive discordant ADT. CONCLUSION: EAU guideline adherence for ADT was low in Italy and was influenced by geographic area. Healthcare providers and urologists should consider these results in order to quantify the inadequate use of ADT and to set policy strategies to overcome this risk.
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Antagonistas de Andrógenos/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , Adhesión a Directriz , Recurrencia Local de Neoplasia/prevención & control , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/tratamiento farmacológico , Urología/tendencias , Anciano , Anciano de 80 o más Años , Terapia Combinada , Estudios Transversales , Humanos , Italia/epidemiología , Masculino , Recurrencia Local de Neoplasia/epidemiología , Selección de Paciente , Guías de Práctica Clínica como Asunto , Prescripciones , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/epidemiología , Factores de TiempoRESUMEN
PURPOSE: To describe the sonographic findings observed in the testis in patients who have undergone testicle-sparing surgery and surgical biopsies. METHODS: We reviewed the color Doppler sonographic findings from 14 patients after testicular interventions: 2 open biopsy procedures for infertility and 12 testicle-sparing surgical procedures (1 for spontaneous intratesticular hemorrhage and 11 for small tumors). Ten patients had benign tumors; one had a malignancy. Three patients were symptomatic; all others were studied as follow-up. RESULTS: Hypoechoic and hypovascular lesions at site of surgery were seen in 10 of the 11 patients after tumorectomy; no changes were observed in one patient. The lesions were either linear or an irregularly triangular shape, located at the surgical site, and interpreted as scars. Retraction of the testicular surface was detected in two cases. In the eight patients who underwent follow-up, lesions disappeared in one case, became smaller in two, and remained stable in five. Of the two patients who underwent biopsy, one developed peritesticular hematoma, and both had late hypoechoic scars in the testis. CONCLUSIONS: Hypoechoic and hypovascular scars are a "normal" postoperative pattern after testicle-sparing surgery. They are either linear or triangular, with rectilinear margins. Such findings need to be correctly interpreted and not misinterpreted as recurrences.
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Testículo/diagnóstico por imagen , Ultrasonografía , Estudios de Seguimiento , Humanos , Infertilidad/diagnóstico por imagen , Infertilidad/etiología , Masculino , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Neoplasias Testiculares/complicaciones , Neoplasias Testiculares/diagnóstico por imagen , Neoplasias Testiculares/cirugía , Testículo/cirugíaRESUMEN
Between 27% and 53% of all patients who undergo radical prostatectomy (RP) or radiation therapy (RT) as the first-line treatment of prostate cancer (PCa) develop a biochemical recurrence. Imaging plays a pivotal role in restaging by helping to distinguish between local relapse and metastatic disease (i.e., lymph-node and skeletal metastases). At present, the most promising tools for assessing PCa patients with biochemical recurrence are multiparametric magnetic resonance imaging (mpMRI) and positron emission tomography (PET)/computed tomography (CT) with radio-labeled choline derivatives. The main advantage of mpMRI is its high diagnostic accuracy in detecting local recurrence, while choline-PET/CT is able to identify lymph-node metastases when they are not suspicious on morphological imaging. The most recent advances in the field of fusion imaging have shown that multimodal co-registration, synchronized navigation, and combined interpretation are more valuable than the individual; separate assessment offered by different diagnostic techniques. The objective of the present essay was to describe the value of bimodal choline-PET/mpMRI fusion imaging and trimodal choline-PET/mpMRI/transrectal ultrasound (TRUS) in the assessment of PCa recurrence after RP and RT. Bimodal choline-PET/mpMRI fusion imaging allows morphological, functional, and metabolic information to be combined, thereby overcoming the limitations of each separate imaging modality. In addition, trimodal real-time choline-PET/mpMRI/TRUS fusion imaging may be useful for the planning and real-time guidance of biopsy procedures in order to obtain histological confirmation of the local recurrence.
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Recurrencia Local de Neoplasia/diagnóstico , Neoplasias de la Próstata/diagnóstico , Anciano , Anciano de 80 o más Años , Colina , Diagnóstico por Computador , Radioisótopos de Flúor , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Imagen Multimodal , Recurrencia Local de Neoplasia/diagnóstico por imagen , Estadificación de Neoplasias , Tomografía de Emisión de Positrones , Prostatectomía , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Radiofármacos , UltrasonografíaRESUMEN
OBJECTIVE: To evaluate the concordance and prognostic role of histologic variants of bladder urothelial carcinoma in transurethral resection of bladder tumor (TURBT) and radical cystectomy (RC) specimens. METHODS: Clinicopathologic information available at the time of RC and follow-up data from 4110 RC specimens, collected between January 2000 and December 2009 at 17 tertiary referral centers were retrospectively analyzed and evaluated for the presence or absence of uncommon variants of bladder urothelial carcinoma. The presence or absence of uncommon variants of bladder urothelial carcinoma was evaluated on previous TURBT specimens of patients undergoing RC. Cox regression was used to assess the impact of these parameters on cancer-specific survival, and the Kaplan-Meier test for disease-free survival was plotted for survival estimate. RESULTS: Of 4110 patients, 579 were found to have uncommon variants of bladder urothelial carcinoma at RC (14.1%), whereas 266 (6.4%) at TURBT. A lack of agreement about uncommon variants was observed between TURBT and RC specimens in the entire population (P <.001). The presence of uncommon variants at TURBT was associated with an increased risk of pathologic upstage (hazard ratio, 3.24; confidence interval, 1.19-6.37; P <.003) and significant decrease in cancer-specific survival and recurrence-free survival (P <.001). CONCLUSION: Although the concordance of presence of uncommon histologic variants of urothelial bladder carcinoma between TURBT and RC is low, the presence of uncommon histologic variants of urothelial bladder carcinoma at TURBT is associated with a less favorable clinical outcome.
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Cistectomía/métodos , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/cirugía , Anciano , Carcinoma/mortalidad , Carcinoma/patología , Carcinoma/cirugía , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Resultado del Tratamiento , Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/mortalidadRESUMEN
The management of prostate cancer (PCa) remains challenging because to date, there has been no way to distinguish between indolent and aggressive tumors. Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is implicated in the network of mechanisms that control androgen receptor (AR) expression. We studied the expression of the two proteins in PCa to evaluate their prognostic potential and elucidate the hnRNP K function in PCa progression. HnRNP K and AR expression were analyzed immunohistochemically in 105 patients who had undergone radical prostatectomy. The association between the expression of hnRNP K and/or AR and PSA progression or death was evaluated by univariate and multivariate analyses. The expression of hnRNP K was also investigated in vitro using the BPH-1 cell line and two different LNCaP populations that recapitulate the progression of PCa towards a more aggressive disease. AR and hnRNP K were differentially expressed between cancer and normal prostate tissues. A strong association with a good prognosis was evident in PCa exhibiting high percentage of AR-positive cells (>75%) (p≤0.005) and more interestingly, the combination of high AR and low cytoplasmic hnRNP K expression emerged as the most significant independent prognostic marker for PSA failure-free survival, in a multivariate analysis (p≤0.001). In vitro, a higher expression of hnRNP K and pERK was associated with higher PSA levels, suggesting a relationship between hnRNP K phosphorylation and AR-regulated genes. These results indicate that the interaction between the AR and hnRNP K has an important role in the progression of PCa. Changes of the expression of the two proteins are strongly associated with the clinical outcome and may be a potential prognostic marker.
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Ribonucleoproteína Heterogénea-Nuclear Grupo K/metabolismo , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Receptores Androgénicos/metabolismo , Anciano , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Fosforilación , Pronóstico , Antígeno Prostático Específico/metabolismo , Neoplasias de la Próstata/diagnósticoRESUMEN
We report a patient with myxoid liposarcoma of the spermatic cord in whom combined use of both ultrasound (US) and MRI helped to suggest the diagnosis. The lesion was solid at US and vascularized at color Doppler. T1-weighted MRI did not show fat within it; on T2-weighted images it had high signal intensity, with a cyst-like appearance. It is known that fat-poor myxoid liposarcomas with high water content may mimic a cystic lesion on non-contrast-enhanced MR; then, a combination of MRI findings, suggesting a cyst, and of US findings, showing the mass was actually solid and vascularized, allowed preoperatively the diagnosis of fat-poor myxoid liposarcoma.
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Neoplasias de los Genitales Masculinos/diagnóstico , Liposarcoma Mixoide/diagnóstico , Imagen por Resonancia Magnética , Cordón Espermático , Ultrasonografía Doppler en Color , Anciano , Humanos , Masculino , Cordón Espermático/diagnóstico por imagenRESUMEN
OBJECTIVE: This study aimed to evaluate the impact of abdominal obesity on preoperative features, complications and functional outcomes of men treated with radical prostatectomy (RP) for prostate cancer. MATERIAL AND METHODS: In 2006 a multicentre Italian report on RP evaluated the surgical and functional characteristics of prostate cancer and RP outcomes. Age and waist circumference (WC) were recorded. Abdominal obesity was defined as a WC of at least 102 cm. International Index of Erectile Function (IIEF) score, prostate-specific antigen, prostate volume, tumour characteristics, presence/absence of perioperative complications and the number of blood units transfused were recorded. Preoperative and postoperative continence status was evaluated. Spearman correlation coefficient and binary logistic regression analyses were conducted. RESULTS: In total, 470 men were recruited. A significant negative correlation between WC and preoperative IIEF scores was observed (r = -0.032, p < 0.001). Non-obese patients presented a preoperative IIEF score of 18.8 ± 6.0 and obese patients an IIEF score of 16.0 ± 7.0 (p < 0.001). Obese men are at three-fold greater risk of intraoperative complications and blood transfusions than those with a WC below 102 cm [adjusted odds ratio (OR) = 3.116, 95% confidence interval (CI) 0.281-16.348, p < 0.001, and OR = 2.763, 95% CI 0.518-3.843, p < 0.050, respectively]. A significant positive correlation between WC and postprostatectomy incontinence severity was observed. The risk of needing at least two pads per day is two and a half times greater in men with a WC of at least 102 cm than in those with a WC below 102 cm (adjusted OR = 2.435, 95% CI 0.321-7.668, p = 0.007). CONCLUSION: Abdominal obesity in a multicentre Italian cohort of patients treated with RP was associated with an increased risk of intraoperative and perioperative complications and with a worse functional outcome.
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Obesidad Abdominal/complicaciones , Complicaciones Posoperatorias/etiología , Prostatectomía , Neoplasias de la Próstata/cirugía , Anciano , Disfunción Eréctil/epidemiología , Humanos , Italia , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Estudios Prospectivos , Prostatectomía/métodos , Resultado del Tratamiento , Incontinencia Urinaria/epidemiología , Circunferencia de la CinturaRESUMEN
INTRODUCTION: Before radical prostatectomy (RP), a nomogram [Briganti et al., Eur Urol 2012;61:584-592] permits to measure the probability of specimen-confined (SC) disease (pT2-pT3a, node negative with negative margins) in high-risk prostate cancer (PCa). The aim of our study was to perform an external validation of this nomogram. MATERIALS AND METHODS: Between 2007 and 2011, 623 patients with high-risk PCa (prostate-specific antigen (PSA) >20 ng/ml and/or biopsy Gleason score ≥8 and/or clinical stage T3) underwent RP and pelvic lymph node dissection at tertiary referral centers. Multivariable logistic regression models predicting the presence of SC disease were built in; we then used the area under curve of the receiver operating characteristic analysis to quantify accuracy of the nomogram to predict SC disease. The extent of over- or underestimation was evaluated within calibration plots. RESULTS: 29% (181/623) of men had SC disease at RP. Preoperative PSA, biopsy Gleason score and stage differed significantly (all p < 0.001) between men with SC disease and those without. External validation of the nomogram showed an acceptable accuracy (area under curve: 66.3, 95% CI 62.4-70%) and a perfect calibration plot. CONCLUSIONS: The external cohort validates the original nomogram, with perfect calibration characteristics. The adequate although reduced accuracy may reflect the wide spectrum and behavior of the so-called high-risk PCa.
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Escisión del Ganglio Linfático/métodos , Prostatectomía/métodos , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Calibración , Estudios de Cohortes , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Nomogramas , Probabilidad , Antígeno Prostático Específico/metabolismo , Curva ROC , Análisis de Regresión , Reproducibilidad de los Resultados , Factores de Riesgo , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE: To analyze positive surgical margins (PSM) after radical prostatectomy (RP) in the overall population and in patients previously treated with transurethral resection of the prostate (TURP). MATERIALS AND METHODS: 2,408 patients treated with RP for clinically localized prostate cancer (PCa) were consecutively enrolled in 135 departments. We correlated PSM rates and all preoperative, surgical and pathological features. We stratified the site of PSM as unique or multifocal. Moreover, we analyzed differences between 75 patients who had undergone previous TURP and the remaining 2,333 patients. RESULTS: In the entire study population, we identified 702 patients with PSM (29%). Using univariate analysis, we reported a significant correlation between overall PSM and prostate-specific antigen (PSA), stage cT, biopsy Gleason score, number of biopsy cores, number of positive cores, percentage of positive cores and nerve-sparing approach. PSM proved to be strongly dependent on pT in particular in patients with pT2 PCa. When we compared the data from 75 patients previously treated with TURP and those from 2,333 without previous prostatic surgery, a statistically significant difference in margin localization was found. Moreover, we analyzed the 75 patients mentioned above, stratified in incidental PCa diagnosed at TURP or PCa detected with prostate biopsy for PSA rising during the post-TURP follow-up: no statistical differences were found between the 2 groups regarding margin status, even if PSM were more frequent in incidental PCa with no significance deriving from the stratification for PSM location at the apex or base. CONCLUSION: Men treated with TURP before RP presented an overall incidence of PSM similar to those without previous TURP, but with a higher risk of PSM at the bladder neck and a lower risk of PSM at the prostatic apex.
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Prostatectomía/métodos , Neoplasias de la Próstata/cirugía , Resección Transuretral de la Próstata/métodos , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Humanos , Italia , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Pronóstico , Próstata/patología , Próstata/cirugía , Antígeno Prostático Específico/sangre , Riesgo , Resultado del Tratamiento , Vejiga Urinaria/patologíaRESUMEN
BACKGROUND: Anti-tumor vaccination is a new frontier in cancer treatment applicable to immunogenic neoplasms such as prostate and renal cancers. GX301 is a vaccine constituted by four telomerase peptides and two adjuvants, Montanide ISA-51 and Imiquimod. OBJECTIVE: The aim of this study was to analyze safety and tolerability of GX301 in an open-label, phase I/II trial. Immunological and clinical responses were also evaluated as secondary endpoints. EXPERIMENTAL DESIGN: GX301 was administered by intradermally injecting 500 µg of each peptide (dissolved in Montanide ISA-51) in the skin of the abdomen. Imiquimod was applied as a cream at the injection sites. The protocol included 8 administrations at days 1, 3, 5, 7, 14, 21, 35, 63. Eligible patients were affected with stage IV prostate or renal cancer resistant to conventional treatments. Patients were clinically and immunologically monitored up to 6 months from the first immunization. RESULTS: No grade 3-4 adverse events were observed. Evidence of vaccine-specific immunological responses was detected in 100 % of patients. Disease stabilization occurred in 4 patients. Prolonged progression-free survival and overall survival were observed in patients showing a full pattern of vaccine-specific immunological responses. CONCLUSION: GX301 demonstrated to be safe and highly immunogenic. Further studies are needed to determine its clinical efficacy.
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Vacunas contra el Cáncer/administración & dosificación , Neoplasias Renales/inmunología , Neoplasias Renales/terapia , Péptidos/administración & dosificación , Neoplasias de la Próstata/inmunología , Neoplasias de la Próstata/terapia , Adyuvantes Inmunológicos , Anciano , Anciano de 80 o más Años , Aminoquinolinas/inmunología , Antígenos de Neoplasias/química , Antígenos de Neoplasias/inmunología , Vacunas contra el Cáncer/efectos adversos , Vacunas contra el Cáncer/inmunología , Proliferación Celular , Terapia Combinada , Citotoxicidad Inmunológica , Humanos , Imiquimod , Interferón gamma/metabolismo , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Masculino , Manitol/análogos & derivados , Manitol/inmunología , Persona de Mediana Edad , Estadificación de Neoplasias , Ácidos Oléicos/inmunología , Péptidos/efectos adversos , Péptidos/inmunología , Fenotipo , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Telomerasa/química , Telomerasa/inmunología , Resultado del TratamientoRESUMEN
PURPOSE: Women undergoing radical cystectomy (RC) and urinary diversion for bladder cancer experience substantial limitations in health-related quality of life (HRQOL). However, the level of discomfort caused by different urinary diversion has been never evaluated in long term survivors. The aim of this multicenter study is to evaluate differences in HRQOL among recurrence-free women undergoing cutaneous ureterostomy (CUS), Bricker's ileal conduit (BK-IC) and Orthotopic neobladder VIP (ONB-VIP) in disease-free females treated with radical cystectomy (RC), with long-term follow up (mean 60.1 months; range 36-122 months). MATERIALS AND METHODS: All consecutively treated female patients from two urological institutions who underwent RC and urinary diversion from January 2000 to December 2008, with no evidence of tumor recurrence at a minimum follow up of 36 months, were included. Patients received the European Organisation for Research and Treatment of Cancer (EORTC) generic (QLQ-C30) and bladder cancer-specific instruments (QLQ-BLM30) and the Functional Assessment of Cancer Therapy for Bladder Cancer (FACT-BL). Clinical data and questionnaire results were analyzed in order to evaluate the HRQOL differences among diversion groups. RESULTS: We identified 37 females (median age: 68, range 45-82 years), including 12 status-post CUS, 16 who underwent BK-IC, and 9 who underwent ONB-VIP. Most were healthy (24/37 with no comorbidities, 4/37 Charlson 1-2, 9/37 Charlson 3 or greater - we didn't considered bladder cancer in Charlson evaluation because bladder cancer was the main inclusion criteria). Women undergoing CUS endorsed worse FACT-BL scores compared with BK-IC and ONB-VIP patients, worse HRQOL regarding physical and emotional well-being (p=0.008 and p=0.02, respectively), and a trend toward worse EORTC QLQ-C30 scores for appetite loss and fatigue (p=0.05 for both). CONCLUSIONS: In our study long-term disease-free females treated with CUS endorsed worse HRQOL compared with women who underwent BK-IC or ONB-VIP, mostly due to worse physical and emotional perception of their body image.
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Calidad de Vida/psicología , Sobrevivientes/psicología , Neoplasias de la Vejiga Urinaria/psicología , Derivación Urinaria/psicología , Anciano , Anciano de 80 o más Años , Cistectomía/psicología , Femenino , Humanos , Persona de Mediana Edad , Encuestas y Cuestionarios , Factores de Tiempo , Ureterostomía/psicología , Neoplasias de la Vejiga Urinaria/cirugía , Derivación Urinaria/métodos , Reservorios Urinarios ContinentesRESUMEN
CD39 is an ectoenzyme, present on different immune cell subsets, which mediates immunosuppressive functions catalyzing ATP degradation. It is not known whether CD39 is expressed and implicated in the activity of CD8+ regulatory T lymphocytes (Treg). In this study, CD39 expression and function was analyzed in both CD8+ and CD4+CD25(hi) Treg from the peripheral blood of healthy donors as well as from tumor specimens. CD39 was found expressed by both CD8+ (from the majority of healthy donors and tumor patients) and CD4+CD25(hi) Treg, and CD39 expression correlated with suppression activity mediated by CD8+ Treg. Importantly, CD39 counteraction remarkably inhibited the suppression activity of CD8+ Treg (both from peripheral blood and tumor microenvironment) suggesting that CD39-mediated inhibition constitutes a prevalent hallmark of their function. Collectively, these findings, unveiling a new mechanism of action for CD8+ Treg, provide new knowledge on intratumoral molecular pathways related to tumor immune escape, which could be exploited in the future for designing new biological tools for anticancer immune intervention.
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Antígenos CD/metabolismo , Apirasa/metabolismo , Linfocitos T CD8-positivos/citología , Linfocitos Infiltrantes de Tumor/citología , Antineoplásicos/farmacología , Linfocitos T CD4-Positivos/citología , Proliferación Celular , Humanos , Tolerancia Inmunológica , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Microscopía Fluorescente , Fenotipo , Linfocitos T Reguladores/citologíaRESUMEN
OBJECTIVE: Presurgical, window of opportunity trials have been proposed as a model to assess the activity of preventive and therapeutic interventions in a cost-effective manner in prostate cancer (CaP). The aim of the study was to explore karyometry as a method for monitoring the efficacy of intervention with preventive agents in patients with CaP. MATERIALS AND METHODS: The material used in this investigation was from the 2F study, i.e., an Italian prospective randomized phase IIb presurgical study of finasteride vs. low-dose flutamide vs. placebo in men with CaP. Image analysis was performed in 16 cases treated with finasteride, 24 with flutamide, and 20 with placebo. For all these cases, CaP and normal looking secretory epithelium were present in the pretreatment biopsies as well as the post-treatment ex-vivo biopsies obtained from the radical prostatectomy specimens. RESULTS: To establish a direction of nuclear change from normal to malignancy, i.e., the so-called line of progression, a discriminant function was derived with the normal looking epithelium in the pretreatment biopsies as one endpoint, and the CaP in the pretreatment biopsies as the other. The discriminant function was then applied to the post-treatment groups. The increase in relative nuclear area was the dominant feature. In the placebo group, 15 out of 20 CaP (75%) cases had a higher discriminant function score at the end of study, with a significant increase of the mean score by 90%. The flutamide treated CaP cases had increased discriminant function scores in 19 out of 24 cases (79%) and an increase of the mean score by 43%; the 5 cases with lower scores involved only minor reductions. In contrast, the finasteride treated CaP cases had increased discriminant function scores for 8 out of 16 cases (50%), but the increase in the mean score was by only 8%. CONCLUSION: This exploratory study establishes that karyometric monitoring can track the results of subtle nuclear changes induced by preventive interventions in men with CaP, thus allowing assessment of agent activity in a cost-effective manner.
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Finasterida/uso terapéutico , Flutamida/uso terapéutico , Próstata/efectos de los fármacos , Neoplasias de la Próstata/tratamiento farmacológico , Inhibidores de 5-alfa-Reductasa/administración & dosificación , Inhibidores de 5-alfa-Reductasa/uso terapéutico , Anciano , Antagonistas de Andrógenos/administración & dosificación , Antagonistas de Andrógenos/uso terapéutico , Núcleo Celular/efectos de los fármacos , Núcleo Celular/genética , Núcleo Celular/metabolismo , Análisis Costo-Beneficio , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Finasterida/administración & dosificación , Flutamida/administración & dosificación , Humanos , Cariometría , Masculino , Persona de Mediana Edad , Periodo Preoperatorio , Estudios Prospectivos , Próstata/metabolismo , Próstata/patología , Neoplasias de la Próstata/economía , Neoplasias de la Próstata/genética , Resultado del TratamientoRESUMEN
PURPOSE: To perform a formal external validation of the preoperative Karakiewicz nomogram (KN) for the prediction of cancer-specific survival (CSS) using a large series of surgically treated patients diagnosed with organ-confined or metastatic renal cell carcinoma (RCC). METHODS: Patient population originated from a series of retrospectively gathered cases that underwent radical or partial nephrectomy between years 1995 and 2007 for suspicion of kidney cancer. The original Cox coefficients were used to generate the predicted risk of CSS at 1, 2, 5, and 10 years following surgery and compared to the observed risk of CSS in the current population. External validation was quantified using measures of predictive accuracy, defined as model discrimination and calibration. RESULTS: A total of 3,374 patients were identified. Relative to the original development cohort, the current sample population had a larger proportion of patients with localized (40.0 vs. 26.3 %, P < 0.001) and non-metastatic (92.2 vs. 88.1 %, P = 0.03) disease at presentation. Model discrimination for the prediction of CSS was 87.8 % (95 % CI, 84.4-91.4) at 1 year, 87.0 % (95 % CI, 84.4-89.5) at 2 years, 84.7 % (95 % CI, 82.3-87.1) at 5 years, and 85.9 % (95 % CI, 83.2-88.6) at 10 years. The relationship between predicted and observed CSS risk was adequate in the calibration plot. CONCLUSION: The use of the KN for the prediction of CSS in patients diagnosed with renal cell carcinoma was validated in the current study. In consequence, this tool may be recommended for routine clinical counseling in patients with various stages of RCC in the preoperative setting.
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Carcinoma de Células Renales/mortalidad , Neoplasias Renales/mortalidad , Nomogramas , Periodo Preoperatorio , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/epidemiología , Carcinoma de Células Renales/cirugía , Niño , Femenino , Humanos , Italia , Neoplasias Renales/epidemiología , Neoplasias Renales/cirugía , Masculino , Persona de Mediana Edad , Nefrectomía , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: Approximately 10-20% of recurrences in patients treated with nephrectomy for renal cell carcinoma (RCC) develop beyond 5 yr after surgery (late recurrence). OBJECTIVE: To determine features associated with late recurrence. DESIGN, SETTING, AND PARTICIPANTS: A total of 5009 patients from a multicenter database comprising 13 107 RCC patients treated surgically had a minimum recurrence-free survival of 60 mo (median follow-up [FU]: 105 mo [range: 78-135]); at last FU, 4699 were disease free (median FU: 103 mo [range: 78-134]), and 310 patients (6.2%) experienced disease recurrence (median FU: 120 mo [range: 93-149]). INTERVENTIONS: Patients underwent radical nephrectomy or nephron-sparing surgery. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable regression analyses identified features associated with late recurrence. Cox regression analyses evaluated the association of features with cancer-specific mortality (CSM). RESULTS AND LIMITATIONS: Lymphovascular invasion (LVI) (odds ratio [OR]: 3.07; p<0.001), Fuhrman grade 3-4 (OR: 1.60; p=0.001), and pT stage >pT1 (OR: 2.28; p<0.001) were significantly associated with late recurrence. Based on accordant regression coefficients, these parameters were weighted with point values (LVI: 2 points; Fuhrman grade 3-4: 1 point, pT stage >1: 2 points), and a risk score was developed for the prediction of late recurrences. The calculated values (0 points: late recurrence risk 3.1%; 1-3 points: 8.4%; 4-5 points: 22.1%) resulted in a good-, intermediate- and poor-prognosis group (area under the curve value for the model: 70%; 95% confidence interval, 67-73). Multivariable Cox regression analysis showed LVI (HR: 2.75; p<0.001), pT stage (HR: 1.24; p<0.001), Fuhrman grade (HR: 2.40; p<0.001), age (HR: 1.01; p<0.001), and gender (HR: 0.71; p=0.027) to influence CSM significantly. Limitations are based on the multicenter and retrospective study design. CONCLUSIONS: LVI, Fuhrman grade 3/4, and a tumor stage >pT1 are independent predictors of late recurrence after at least 5 yr from surgery in patients with RCC. We developed a risk score that allows for prognostic stratification and individualized aftercare of patients with regard to counseling, follow-up scheduling, and clinical trial design.