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1.
Toxins (Basel) ; 15(11)2023 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-37999495

RESUMO

Sesquiterpene lactones (SLs), plant-derived metabolites with broad spectra of biological effects, including anti-tumor and anti-inflammatory, hold promise for drug development. Primary cilia, organelles extending from cell surfaces, are crucial for sensing and transducing extracellular signals essential for cell differentiation and proliferation. Their life cycle is linked to the cell cycle, as cilia assemble in non-dividing cells of G0/G1 phases and disassemble before entering mitosis. Abnormalities in both primary cilia (non-motile cilia) and motile cilia structure or function are associated with developmental disorders (ciliopathies), heart disease, and cancer. However, the impact of SLs on primary cilia remains unknown. This study evaluated the effects of selected SLs (grosheimin, costunolide, and three cyclocostunolides) on primary cilia biogenesis and stability in human retinal pigment epithelial (RPE) cells. Confocal fluorescence microscopy was employed to analyze the effects on primary cilia formation (ciliogenesis), primary cilia length, and stability. The effects on cell proliferation were evaluated by flow cytometry. All SLs disrupted primary cilia formation in the early stages of ciliogenesis, irrespective of starvation conditions or cytochalasin-D treatment, with no effect on cilia length or cell cycle progression. Interestingly, grosheimin stabilized and promoted primary cilia formation under cilia homeostasis and elongation treatment conditions. Thus, SLs have potential as novel drugs for ciliopathies and tumor treatment.


Assuntos
Ciliopatias , Neoplasias , Humanos , Cílios/metabolismo , Cílios/patologia , Neoplasias/metabolismo , Ciliopatias/metabolismo , Ciliopatias/patologia , Lactonas/farmacologia , Lactonas/metabolismo
2.
Eur Radiol ; 33(11): 7371-7379, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37280356

RESUMO

OBJECTIVES: The standard therapy for small renal masses (SRMs) remains partial nephrectomy (PN), which is associated with relatively high morbidity and complication rate. Therefore, percutaneous radiofrequency ablation (PRFA) emerges as an alternative therapy. This study aimed to compare the efficacy, safety, and oncological outcomes of PRFA versus PN. METHODS: A multicenter non-inferiority study with retrospective analysis of 291 patients with SRMs (N0M0), who underwent PN or PRFA (2:1), recruited prospectively from two hospitals in the Andalusian Public Health System, Spain, between 2014 and 2021. Comparisons of treatment features were evaluated using the t test, Wilcoxon-Mann-Whitney U test, chi-square test, Fisher test, and Cochran-Armitage trend test. Kaplan-Meier curves depicted overall survival (OS), local recurrence-free survival (LRFS), and metastasis-free survival (MFS) rates in the overall study population. RESULTS: A total of 291 consecutive patients were identified; 111 and 180 patients underwent PRFA and PN, respectively. Median follow-up time was 38 and 48 months, and mean hospitalization days were 1.04 and 3.57 days, respectively. The variables underpinned with high surgical risk were significantly increased in PRFA compared to those in PN (mean age was 64.56 and 57.47 years, the solitary kidney presence was 12.6% and 5.6%, ASA score ≥ 3 was 36% and 14.5%, respectively). The rest of oncological outcomes were comparable amongst PRFA and PN. Patients undergoing PRFA did not improve OS, LRFS, and MFS compared to those undergoing PN. Limitations comprise retrospective design and limited statistical power. CONCLUSION: PRFA for SMRs in high-risk patients is non-inferior in terms of oncological outcomes and safety compared to PN. CLINICAL RELEVANCE STATEMENT: Our study has a direct clinical application as it proves that radiofrequency ablation is an effective and uncomplicated therapeutic option for patients with small renal masses. KEY POINTS: •There are non-inferiority results in overall survival, local recurrence-free survival, and metastasis-free survival between PRFA and PN. •Our two-center study showed that PRFA is non-inferior to PN in oncological outcomes. •Contrast-enhanced power ultrasound-guided PRFA provides an effective therapy for T1 renal tumors.


Assuntos
Carcinoma de Células Renais , Ablação por Cateter , Neoplasias Renais , Ablação por Radiofrequência , Humanos , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/cirurgia , Estudos Retrospectivos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/cirurgia , Resultado do Tratamento , Nefrectomia/métodos , Ablação por Cateter/métodos
3.
Clin Genitourin Cancer ; 20(2): 197.e1-197.e10, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34920959

RESUMO

There was a high medical need for patients with non-metastatic castration-resistant prostate cancer (nmCRPC) when several next-generation anti-androgens (apalutamide, enzalutamide, and darolutamide) demonstrated clinically relevant delays in metastasis onset. However, to date, few publications have assessed the pooled effect of these treatments on overall survival (OS). We performed a systematic review and meta-analysis of all randomized, placebo-controlled studies investigating a systemic treatment in nmCRPC. Publications were identified by searching several databases on April 7, 2021. The primary objective of this analysis was to determine the OS benefit. Secondary outcomes included the relative risk (RR) of adverse events (AEs) and grade 3-4 AEs. A sensitivity analysis with simulated data was also conducted to examine the influence of the study designs on the results. Three randomized controlled studies (SPARTAN, PROSPER, ARAMIS) met our inclusion criteria. Pooled meta-analyses showed a significant benefit in OS with the active agents versus placebo (hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.65-0.83), as well as increased risk of any grade (RR 1.09, 95% CI 1.01-1.17) and grade 3-4 AEs (RR 1.50, 95% CI 1.23-1.83). The sensitivity analysis with SPARTAN-like simulated populations demonstrated that when using ARAMIS statistical design, OS would be statistically significant in 98.1% of the cases, at a shorter follow-up and with lower number of events. First-line treatment of nmCRPC patients with anti-androgens increased OS with an acceptable safety profile. In light of the different study designs and follow-up, results should be interpreted separately.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Antagonistas de Androgênios/uso terapêutico , Antagonistas de Receptores de Andrógenos/uso terapêutico , Humanos , Imunoterapia , Masculino , Modelos de Riscos Proporcionais , Neoplasias de Próstata Resistentes à Castração/patologia
5.
J Urol ; 206(4): 914-923, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34039013

RESUMO

PURPOSE: We performed an exploratory analysis of prostate cancer-related pain and fatigue on health-related quality of life in patients with metastatic castration-sensitive prostate cancer receiving apalutamide (240 mg/day) or placebo, with continuous androgen deprivation therapy (ADT), in the phase 3, randomized, double-blind, placebo controlled TITAN trial (NCT02489318). MATERIALS AND METHODS: Patient-reported outcomes for pain and fatigue were evaluated using the Brief Pain Inventory-Short Form and Brief Fatigue Inventory. Time to deterioration (TTD) was estimated by Kaplan-Meier method; hazard ratios and 95% confidence intervals were calculated using Cox proportional hazards model. General estimating equations for logistic regression estimated treatment-related differences in the likelihood of worsening pain or fatigue. RESULTS: Compliance for completing the Brief Pain Inventory-Short Form and Brief Fatigue Inventory was high (96% to 97%) in the first year. Median followup times were similar between treatments (19 to 22 months). Median pain TTD was longer with apalutamide than placebo for "pain at its least in the last 24 hours" (28.7 vs 21.8 months, respectively; p=0.0146), "pain interfered with mood" (not estimable vs 22.4 months; p=0.0017), "pain interfered with walking ability" (28.7 vs 20.2 months; p=0.0027), "pain interfered with relations" (not estimable vs 23.0 months; p=0.0139) and "pain interfered with sleep" (28.7 vs 20.9 months; p=0.0167). Likelihood for fatigue and worsening fatigue were similar between groups. CONCLUSIONS: Patients with metastatic castration-sensitive prostate cancer receiving apalutamide plus ADT vs placebo plus ADT reported consistently favorable TTD of pain. No difference for change in fatigue was observed with apalutamide vs placebo.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Dor do Câncer/tratamento farmacológico , Fadiga/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/administração & dosagem , Dor do Câncer/diagnóstico , Dor do Câncer/etiologia , Dor do Câncer/psicologia , Deterioração Clínica , Fadiga/diagnóstico , Fadiga/etiologia , Fadiga/psicologia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor/estatística & dados numéricos , Medidas de Resultados Relatados pelo Paciente , Intervalo Livre de Progressão , Neoplasias da Próstata/complicações , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Índice de Gravidade de Doença , Tioidantoínas/administração & dosagem
6.
Lancet Oncol ; 20(11): 1518-1530, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31578173

RESUMO

BACKGROUND: In the phase 3 TITAN study, the addition of apalutamide to androgen deprivation therapy (ADT) significantly improved the primary endpoints of overall survival and radiographic progression-free survival in patients with metastatic castration-sensitive prostate cancer. We aimed to assess health-related quality of life (HRQOL) in TITAN, including pain and fatigue. METHODS: In this randomised, placebo-controlled, double-blind, phase 3 study, patients with metastatic castration-sensitive prostate cancer (defined as not receiving ADT at the time of metastatic disease progression) aged 18 years and older, receiving continuous ADT (selected at the investigator's discretion), and with an Eastern Cooperative Oncology Group performance status score of 0 or 1 were randomly assigned (1:1), using an interactive web response system, to receive oral apalutamide (four 60 mg tablets, once daily) or matching placebo. Previous localised disease treatment or previous docetaxel for metastatic castration-sensitive prostate cancer were allowed. Randomisation was stratified by Gleason score at diagnosis, region, and previous docetaxel treatment. Randomisation was done using randomly permuted blocks (block size of four). Investigators, research staff, sponsor study team, and patients were masked to the identities of test and control treatments. Patient-reported outcomes were prespecified exploratory endpoints and were the Brief Pain Inventory-Short Form (BPI-SF), Brief Fatigue Inventory (BFI), Functional Assessment of Cancer Therapy-Prostate (FACT-P), and EuroQoL 5D questionnaire 5 level (EQ-5D-5L). BPI and BFI were completed for 7 consecutive days (days -6 to 1 inclusive of each cycle visit), then at months 4, 8, and 12 in follow-up. FACT-P and EQ-5D-5L were completed during cycles 1-7, then every other cycle until the end of treatment, and at months 4, 8, and 12 in follow-up. Analyses were based on the intention-to-treat population. Missing patient-reported outcome assessments were calculated as the expected number of assessments for a visit minus the actual number of assessments received for that visit. For time-to-event endpoints, when median values could not be calculated because less than 50% of patients had degradation, 25th percentiles were compared. This study is registered with ClinicalTrials.gov, number NCT02489318, and is ongoing. FINDINGS: Between Dec 9, 2015, and July 25, 2017, 1052 eligible patients were enrolled randomly assigned to apalutamide (n=525) or placebo (n=527). Data cutoff for this analysis of patient-reported outcomes was Nov 23, 2018. Median follow-up for time to pain-related endpoints ranged from 19·4 to 22·1 months. Patients were mostly asymptomatic at baseline: on the BPI-SF pain severity scale of 0-10, median pain scores (indicating worst pain in the past 24 h) were 1·14 (IQR 0-3·17) in the apalutamide group and 1·00 (0-2·86) in the placebo group, and median worst fatigue scores on the BFI were 1·29 (IQR 0-3·29) in the apalutamide group and 1·43 (0·14-3·14) in the placebo group. Patient experience of pain and fatigue (intensity and interference) did not differ between the groups for the duration of treatment. Median time to worst pain intensity progression was 19·09 months (95% CI 11·04-not reached) in the apalutamide group versus 11·99 months (8·28-18·46) in the placebo group (HR 0·89 [95% CI 0·75-1·06]; p=0·20). Median time to pain interference progression was not reached in either group (95% CI 28·58-not reached in the apalutamide group; not reached-not reached in the placebo group). 25th percentiles for time to pain interference progression were 9·17 months (5·55-11·96) in the apalutamide group and 6·24 months (4·63-7·43) in the placebo group (HR 0·90 [95% CI 0·73-1·10]; p=0·29). FACT-P total scores and EQ-5D-5L data showed preservation of HRQOL in both groups. The median time to deterioration as determined by FACT-P total score was 8·87 months (95% CI 4·70-11·10) in the apalutamide group and 9·23 months (7·39-12·91) in the placebo group (HR 1·02 [95% CI 0·85-1·22]; p=0·85). INTERPRETATION: Apalutamide with ADT is a well-tolerated and effective option for men with metastatic castration-sensitive prostate cancer. The combination significantly improves survival outcomes compared with ADT alone while maintaining HRQOL despite additive androgen blockade. FUNDING: Janssen Research & Development.


Assuntos
Antagonistas de Androgênios/administração & dosagem , Antagonistas de Receptores de Andrógenos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Orquiectomia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Qualidade de Vida , Tioidantoínas/administração & dosagem , Idoso , Antagonistas de Androgênios/efeitos adversos , Antagonistas de Receptores de Andrógenos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ásia , Quimioterapia Adjuvante , Progressão da Doença , Europa (Continente) , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , América do Norte , Orquiectomia/efeitos adversos , Intervalo Livre de Progressão , Neoplasias de Próstata Resistentes à Castração/diagnóstico , Neoplasias de Próstata Resistentes à Castração/mortalidade , América do Sul , Tioidantoínas/efeitos adversos , Fatores de Tempo
7.
N Engl J Med ; 381(1): 13-24, 2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-31150574

RESUMO

BACKGROUND: Apalutamide is an inhibitor of the ligand-binding domain of the androgen receptor. Whether the addition of apalutamide to androgen-deprivation therapy (ADT) would prolong radiographic progression-free survival and overall survival as compared with placebo plus ADT among patients with metastatic, castration-sensitive prostate cancer has not been determined. METHODS: In this double-blind, phase 3 trial, we randomly assigned patients with metastatic, castration-sensitive prostate cancer to receive apalutamide (240 mg per day) or placebo, added to ADT. Previous treatment for localized disease and previous docetaxel therapy were allowed. The primary end points were radiographic progression-free survival and overall survival. RESULTS: A total of 525 patients were assigned to receive apalutamide plus ADT and 527 to receive placebo plus ADT. The median age was 68 years. A total of 16.4% of the patients had undergone prostatectomy or received radiotherapy for localized disease, and 10.7% had received previous docetaxel therapy; 62.7% had high-volume disease, and 37.3% had low-volume disease. At the first interim analysis, with a median of 22.7 months of follow-up, the percentage of patients with radiographic progression-free survival at 24 months was 68.2% in the apalutamide group and 47.5% in the placebo group (hazard ratio for radiographic progression or death, 0.48; 95% confidence interval [CI], 0.39 to 0.60; P<0.001). Overall survival at 24 months was also greater with apalutamide than with placebo (82.4% in the apalutamide group vs. 73.5% in the placebo group; hazard ratio for death, 0.67; 95% CI, 0.51 to 0.89; P = 0.005). The frequency of grade 3 or 4 adverse events was 42.2% in the apalutamide group and 40.8% in the placebo group; rash was more common in the apalutamide group. CONCLUSIONS: In this trial involving patients with metastatic, castration-sensitive prostate cancer, overall survival and radiographic progression-free survival were significantly longer with the addition of apalutamide to ADT than with placebo plus ADT, and the side-effect profile did not differ substantially between the two groups. (Funded by Janssen Research and Development; TITAN ClinicalTrials.gov number, NCT02489318.).


Assuntos
Adenocarcinoma/tratamento farmacológico , Antagonistas de Androgênios/uso terapêutico , Antagonistas de Receptores de Andrógenos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Tioidantoínas/uso terapêutico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/efeitos adversos , Antagonistas de Receptores de Andrógenos/efeitos adversos , Método Duplo-Cego , Exantema/induzido quimicamente , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Intervalo Livre de Progressão , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Qualidade de Vida , Radiografia , Tioidantoínas/efeitos adversos
8.
Arch Esp Urol ; 72(2): 203-210, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30855022

RESUMO

There are multiple definitions of high risk prostate cancer and each definition is associated with a different prognosis. Men classified as having high-risk disease warrant treatment because durable outcomes can be achieved. Radical prostatectomy, radiation therapy and androgen deprivation therapy play pivotal roles in the management of men with high-risk disease, and potentially in men with metastatic disease.


Hay múltiples definiciones del cáncer de próstata de alto riesgo y cada definición se asocia con un pronóstico diferente. En varones con cáncer de próstata clasificado cómo enfermedad de alto riesgo se justifica el tratamiento porque se pueden conseguir resultados duraderos. La prostatectomía radical, la  radioterapia y el tratamiento de deprivación androgénica juegan un papel fundamental en el manejo de los pacientes con enfermedad de alto riesgo, y potencialmente en varones con enfermedad metastásica.


Assuntos
Antagonistas de Androgênios , Prostatectomia , Neoplasias da Próstata , Antagonistas de Androgênios/uso terapêutico , Humanos , Masculino , Prognóstico , Antígeno Prostático Específico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/cirurgia
9.
Arch. esp. urol. (Ed. impr.) ; 72(2): 203-210, mar. 2019. tab
Artigo em Inglês | IBECS | ID: ibc-185443

RESUMO

There are multiple definitions of high risk prostate cancer and each definition is associated with a different prognosis. Men classified as having high-risk disease warrant treatment because durable outcomes can be achieved. Radical prostatectomy, radiation therapy and androgen deprivation therapy play pivotal roles in the management of men with high-risk disease, and potentially in men with metastatic disease


Hay múltiples definiciones del cáncer de próstata de alto riesgo y cada definición se asocia con un pronóstico diferente. En varones con cáncer de próstata clasificado cómo enfermedad de alto riesgo se justifica el tratamiento porque se pueden conseguir resultados duraderos. La prostatectomía radical, la radioterapia y el tratamiento de deprivación androgénica juegan un papel fundamental en el manejo de los pacientes con enfermedad de alto riesgo, y potencialmente en varones con enfermedad metastásica


Assuntos
Humanos , Masculino , Antagonistas de Androgênios/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/cirurgia , Antígeno Prostático Específico , Prostatectomia , Prognóstico
10.
Arch Esp Urol ; 71(8): 651-663, 2018 Sep.
Artigo em Espanhol | MEDLINE | ID: mdl-30319125

RESUMO

OBJECTIVES: Prostate cancer is the most frequent neoplasia diagnosed in males. Treatment of metastatic prostate cancer is based on androgen deprivation therapy (ADT) up to its change to the castration resistance state. Recently, new molecules have been developed that significantly increase survival and quality of life of these patients. Abiraterone acetate in combination with prednisone is the first oral hormone therapy that contributed to this change in the approach of the disease. METHODS: Systematic bibliographic review about abiraterone in the treatment of metastatic castration resistant prostate cancer (CPRC), with data on efficacy, safety and quality of life. RESULTS: Treatment with abiraterone and prednisone has demonstrated a significant increase in overall survival (OS 34.7 vs 30.3 months) and radiologic progression free survival (RPFS 16.5 months vs 8.3 months) in comparison to placebo and prednisone in patients with metastatic castration resistant prostate cancer (mCPRC). It also demonstrated an increase in OS and RPFS compared to placebo plus prednisone in mCPRC patients after at least one cytotoxic chemotherapy based treatment (OS 15.8 vs 11.2 months; RPFS 5.6 vs 3.6 months). Side effects related to abiraterone therapy are mainly related with mineral corticoid excess (Hypertension, hypokalemia, fluid retention) and, to a lesser extent, transaminase alterations or cardiovascular effects. Perceived quality of life results show a benefit in the abiraterone treatment group. CONCLUSIONS: Abiraterone acetate is a new hormonal treatment for metastatic castration resistant prostate cancer both before and after chemotherapy. The results of the available studies demonstrate a significant improvement in terms of efficacy, with a tolerability profile generally acceptable, predictable and manageable, and an improvement in patient's perceived quality of life.


Assuntos
Androstenos/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Androstenos/efeitos adversos , Androstenos/farmacologia , Humanos , Masculino
11.
Arch. esp. urol. (Ed. impr.) ; 71(8): 651-663, oct. 2018. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-178743

RESUMO

OBJETIVO: El cáncer de próstata es la neoplasia más frecuentemente diagnosticada en varones. El tratamiento del cáncer de próstata metastásico se basa en la terapia de deprivación androgénica (TDA) hasta su paso a un estado de resistencia a la castración. Recientemente, se han desarrollado moléculas que han aumentado significativamente la supervivencia y la calidad de vida de estos pacientes. Acetato de abiraterona en combinación con prednisona es la primera hormonoterapia oral que ha contribuido a este cambio en el abordaje sobre la enfermedad. Metodos: Revisión sistemática de la literatura existente sobre abiraterona en el tratamiento del cáncer de próstata metastásico resistente a la castración, con datos de eficacia, seguridad y calidad de vida. RESULTADOS: El tratamiento con abiraterona y prednisona ha demostrado aumentar de manera significativa la supervivencia global (SG 34,7 vs 30,3 meses) y libre de progresión radiológica (SLPr: 16,5 meses vs 8,3 meses) respecto a placebo y prednisona de los pacientes con cáncer de próstata resistente a la castración metastásico. Asimismo, demostró aumentar la SG y SLPr frente a placebo más prednisona en pacientes con CPRCm tras al menos un tratamiento basado en quimioterapia citotóxica (SG 15,8 versus 11,2 meses; SLPr 5,6 versus 3,6 meses). Los efectos secundarios del tratamiento con abiraterona se relacionan fundamentalmente con el exceso de mineralcorticoides (hipertensión, hipopotasemia, retención de líquidos) y, en menor medida, alteraciones de las transaminasas o efectos cardiovasculares. Los resultados de calidad de vida percibidos por los pacientes muestran un beneficio en el grupo de tratamiento con abiraterona. CONCLUSIONES: Acetato de abiraterona es un nuevo tratamiento hormonal para el cáncer de próstata metastásico resistente a la castración tanto previamente como después de quimioterapia. Los resultados de los estudios existentes demuestran una mejoría significativa en términos de eficacia, con un perfil de tolerabilidad por lo general aceptable, predecible y manejable, y una mejora en la calidad de vida percibida por el paciente


OBJECTIVES: Prostate cancer is the most frequent neoplasia diagnosed in males. Treatment of metastatic prostate cancer is based on androgen deprivation therapy (ADT) up to its change to the castration resistance state. Recently, new molecules have been developed that significantly increase survival and quality of life of these patients. Abiraterone acetate in combination with prednisone is the first oral hormone therapy that contributed to this change in the approach of the disease. METHODS: Systematic bibliographic review about abiraterone in the treatment of metastatic castration resistant prostate cancer (CPRC), with data on efficacy, safety and quality of life. RESULTS: Treatment with abiraterone and prednisone has demonstrated a significant increase in overall survival (OS 34.7 vs 30.3 months) and radiologic progression free survival (RPFS 16.5 months vs 8.3 months) in comparison to placebo and prednisone in patients with metastatic castration resistant prostate cancer (mCPRC). It also demonstrated an increase in OS and RPFS compared to placebo plus prednisone in mCPRC patients after at least one cytotoxic chemotherapy based treatment (OS 15.8 vs 11.2 months; RPFS 5.6 vs 3.6 months). Side effects related to abiraterone therapy are mainly related with mineral corticoid excess (Hypertension, hypokalemia, fluid retention) and, to a lesser extent, transaminase alterations or cardiovascular effects. Perceived quality of life results show a benefit in the abiraterone treatment group. CONCLUSIONS: Abiraterone acetate is a new hormonal treatment for metastatic castration resistant prostate cancer both before and after chemotherapy. The results of the available studies demonstrate a significant improvement in terms of efficacy, with a tolerability profile generally acceptable, predictable and manageable, and an improvement in patient's perceived quality of life


Assuntos
Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Androstenos/uso terapêutico , Androstenos/efeitos adversos , Androstenos/farmacologia
12.
J Endourol ; 32(9): 859-864, 2018 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-30024301

RESUMO

OBJECTIVE: The aim of the study was to assess the feasibility of laparoscopic nephrectomy (LN) in the treatment of patients with xanthogranulomatous pyelonephritis (XGP). METHODS: Retrospective review of medical records of 17 patients (mean age 60.0 ± 13.3 years) who underwent LN by a single surgeon from 2010 to 2018. Sociodemographic and clinical data including diagnosis, presenting clinical features, surgical management, and postoperative course were analyzed. RESULTS: LN was successfully performed in 15 (88.2%) patients. Two (12.5%) patients with disseminated disease were electively converted to open nephrectomy (ON) due to failure to progress. Two (11.8%) patients experienced intraoperative complications (grades 3b and 4b). Among patients in whom LN was successfully performed (n = 15), the mean operative time was 198.0 ± 107.1 min and was shorter when no intraoperative complications occurred (169.0 ± 48.1 min). Three (20%) of these patients required transfusions and nine (60.0%) required postoperative pelvic drainage (PD). Six (40%) patients experienced postoperative complications: one grade 1, four grade 2, and one grade 5. Mean hospital stay was 4.4 ± 4.3 days, and 3.4 ± 2.2 for those experiencing manageable or no complications. Among patients without postoperative complications (n = 6), mean hospital stay was shorter when no PD was placed (1.6 vs 2.6 days). CONCLUSION: LN is a feasible surgical option in patients with XGP although given the nature of XGP, it is associated with complications-nearly all manageable-which makes it a challenging surgical procedure. Advanced laparoscopic skills and experiences are needed. Dissemination of the disease is associated with the occurrence of more severe complications and conversion to ON. PD placement seems associated with shorter hospital stay.


Assuntos
Laparoscopia/métodos , Nefrectomia/métodos , Pielonefrite Xantogranulomatosa/cirurgia , Adulto , Idoso , Transfusão de Sangue/estatística & dados numéricos , Conversão para Cirurgia Aberta , Drenagem , Estudos de Viabilidade , Feminino , Humanos , Complicações Intraoperatórias/etiologia , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
13.
Arch. esp. urol. (Ed. impr.) ; 71(1): 108-113, ene.-feb. 2018.
Artigo em Espanhol | IBECS | ID: ibc-171834

RESUMO

La urología es una especialidad médico-quirúrgica que se ocupa del estudio, diagnóstico y tratamiento de las afecciones médicas y quirúrgicas del aparato urinario y retroperitoneo en ambos sexos y del aparato genital masculino sin límite de edad, motivadas por padecimientos congénitos, traumáticos, sépticos, metabólicos, obstructivos y oncológicos. La oncologia- urológica es la parte de la Urología más amplia y donde la investigación y los nuevos avances hacen que sea imprescindible un aprendizaje continuo. En este capítulo abordamos todos los aspectos académicos relacionados con la formación en el campo de la uro-oncología (AU)


Urology is a medical-surgical specialty that deals with the study, diagnosis and treatment of the medical and surgical diseases of the urinary apparatus and retroperitoneum in both sexes and the male genital apparatus without age limit, due to congenital, traumatic, septic, metabolic, obstructive and oncological conditions. Urologic oncology is the broadest urological part, where research and new advances make continuous learning essential. In this chapter we treat all academic features related with training in the field of Urooncology (AU)


Assuntos
Educação Continuada , Urologia/tendências , Oncologia/tendências , Especialização/tendências , Aprendizagem , Cursos
14.
Arch Esp Urol ; 71(1): 108-113, 2018 Jan.
Artigo em Espanhol | MEDLINE | ID: mdl-29336339

RESUMO

Urology is a medical-surgical specialty that deals with the study, diagnosis and treatment of the medical and surgical diseases of the urinary apparatus and retroperitoneum in both sexes and the male genital apparatus without age limit, due to congenital, traumatic, septic, metabolic, obstructive and oncological conditions. Urologic oncology is the broadest urological part, where research and new advances make continuous learning essential. In this chapter we treat all academic features related with training in the field of Urooncology.


Assuntos
Oncologia/educação , Urologia/educação , Educação de Pós-Graduação em Medicina/tendências , Bolsas de Estudo , Previsões
15.
Arch Esp Urol ; 70(4): 429-435, 2017 May.
Artigo em Espanhol | MEDLINE | ID: mdl-28530622

RESUMO

OBJECTIVES: The most frequent ureteral lesions are iatrogenic, mainly due to gynecologic and urologic procedures. The resolution and repair of these lesions, when they require surgery, is often the performance of ureteroneocystostomy. We describe the technique for the repair of distal ureter lesions that preserves both anatomy and function of the urinary tract (1). The operation consists in dissection and extraction of the distal ureteral stump from its intramural tract to get at least 1 cm of free ureter, percutaneous insertion of a ureteral stent, checking the absence of tension between proximal ureter and distal dissected stump, end to end anastomosis and reinsertion of the distal ureter in the previously dissected bladder muscle layer. We present 4 cases of ureteral injury after laparoscopic simple total hysterectomy for uterine myomas with complete section of the distal ureter, that were operated 3-5 days after injury, performing laparoscopic repair surgery. We performed clinical and radiological control with intravenous urography demonstrating ureteral continuity normalization and good renal function. We believe that repair of the urinary tract with anatomical and physiological preservation must be the first option in the laparoscopic treatment of complete distal ureteral injuries, and intramural ureter dissection when needed avoids the performance of ureteroneocystostomy. It is necessary to keep progressing in the technique improvement, and to increase the number of cases and experience.


Assuntos
Complicações Intraoperatórias/cirurgia , Laparoscopia , Ureter/lesões , Ureter/cirurgia , Ureterostomia/métodos , Adulto , Feminino , Procedimentos Cirúrgicos em Ginecologia , Humanos , Doença Iatrogênica , Pessoa de Meia-Idade
16.
Arch. esp. urol. (Ed. impr.) ; 70(4): 429-435, mayo 2017. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-163828

RESUMO

OBJETIVO: Las lesiones ureterales más frecuentes son las iatrógenas, fundamentalmente debidas a procedimientos ginecológicos y urológicos. Habitualmente la resolución y reparación de estas lesiones, cuando precisan cirugía, es la realización de una ureteroneocistostomía. Describimos una técnica para la reparación de lesiones de ureter distal que preserva tanto la anatomía como la función de la vía urinaria (1). La cirugía consiste en la disección y extracción del muñón ureteral distal de su trayecto intramural, para conseguir al menos 1 centímetro de uréter libre, colocación de stent ureteral por vía percutánea, comprobación de ausencia de tensión entre uréter proximal y muñón distal disecado, anastomosis término-terminal y reinserción de uréter distal en capa muscular vesical previamente disecada para la anastomosis. Presentamos 4 casos de lesión ureteral tras histerectomía total simple laparoscópica por miomas con sección completa de uréter distal, que se intervienen entre 3 y 5 días tras la lesión, realizando cirugía de reparación por vía laparoscópica. Se realiza control clínico y radiológico con urografía observando normalización de la continuidad ureteral y buen funcionalismo renal. Pensamos que la reparación con preservación anatómica y fisiológica de la vía urinaria, debe ser la primera opción en el tratamiento laparoscópico de las lesiones completas de uréter distal, y que la disección del uréter intramural en casos necesarios evita la realización de una ureteroneocistostomía. Es preciso seguir avanzando en el perfeccionamiento de la técnica y aumentar el número de casos y la experiencia


OBJECTIVES: The most frequent ureteral lesions are iatrogenic, mainly due to gynecologic and urologic procedures. The resolution and repair of these lesions, when they require surgery, is often the performance of ureteroneocystostomy. We describe the technique for the repair of distal ureter lesions that preserves both anatomy and function of the urinary tract (1). The operation consists in dissection and extraction of the distal ureteral stump from its intramural tract to get at least 1 cm of free ureter, percutaneous insertion of a ureteral stent, checking the absence of tension between proximal ureter and distal dissected stump, end to end anastomosis and reinsertion of the distal ureter in the previously dissected bladder muscle layer. We present 4 cases of ureteral injury after laparoscopic simple total hysterectomy for uterine myomas with complete section of the distal ureter, that were operated 3-5 days after injury, performing laparoscopic repair surgery. We performed clinical and radiological control with intravenous urography demonstrating ureteral continuity normalization and good renal function. We believe that repair of the urinary tract with anatomical and physiological preservation must be the first option in the laparoscopic treatment of complete distal ureteral injuries, and intramural ureter dissection when needed avoids the performance of ureteroneocystostomy. It is necessary to keep progressing in the technique improvement, and to increase the number of cases and experience


Assuntos
Humanos , Feminino , Ureterostomia/métodos , Laparoscopia/métodos , Histerectomia/efeitos adversos , Ureter/lesões , Complicações Pós-Operatórias/cirurgia , Doença Iatrogênica , Stents , Derivação Urinária , Procedimentos de Cirurgia Plástica/métodos
17.
Arch Esp Urol ; 67(7): 628-33, 2014 Sep.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-25241836

RESUMO

OBJECTIVES: The objective of this work was to establish the analgesia protocols for different types of urological surgery and to analyze the impact on pain during the first 24 h after surgery. METHODS: The study included 186 patients undergoing urological surgery between 2011 and 2013. Seven analgesia protocols were established and applied according to the surgical procedure. At 24 h post-surgery, i.e., the initiation of analgesic treatment, patients` pain was evaluated by visual analog scale/numeric scale (VAS/NS), and their degree of satisfaction and nausea were assessed. RESULTS: The study sample comprised 137 males (73.7%) and 49 females (26.3%), with a mean age of 58.5 ± 14.7 yrs. Analgesia protocol 1 was applied in 5.9% of patients, protocol 2 in 17.8%, protocol 3 in 8.6%, protocol 4 in 38.9%, protocol 5 in 13.5%, protocol 6 in 14.6%, and protocol 7 in 0.5%. At 24 h post-surgery, the VAS/NS score was = 3 in 82.3% of patients; hence, only 17.7% required rescue analgesia; 71% of patients were highly satisfied with the treatment provided and 22.6% were satisfied. 6.4% were not satisfied. CONCLUSION: Establishing analgesia protocols according to the type of surgery is a valid and useful measure to control postoperative pain during the first 24 h and to provide appropriate treatment standardization and follow-up.


Assuntos
Analgesia , Protocolos Clínicos , Medição da Dor , Dor Pós-Operatória/prevenção & controle , Satisfação do Paciente , Procedimentos Cirúrgicos Urológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Fatores de Tempo
18.
Arch. esp. urol. (Ed. impr.) ; 67(7): 628-633, sept. 2014. ilus, graf
Artigo em Espanhol | IBECS | ID: ibc-128738

RESUMO

OBJETIVO: El objetivo de este estudio es establecer unos protocolos de analgesia distribuidos según tipos de cirugías urológicas y analizar el impacto sobre el dolor en las primeras 24 horas tras la cirugía. MÉTODOS: Estudio con 186 pacientes intervenidos de cirugía urológica entre 2011 y 2013 en los que se establecen 7 protocolos de analgesia según tipos de cirugía urológica. Analizamos a las 24 horas de la cirugía y de iniciar por tanto el tratamiento analgésico, el dolor mediante escala visual analógica/escala numérica y el grado de satisfacción del paciente y presencia de nauseas. RESULTADOS: La distribución de los pacientes según sexos fue de 137 hombres (73,7%) y 49 mujeres (26,3%), con una edad media de 58,5 ± 14,7 años. La distribución de los pacientes según el tipo de protocolo asignado fue la siguiente: 5,9% protocolo 1; 17,8% protocolo 2; 8,6% protocolo 3; 38,9% protocolo 4; 13,5% protocolo 5; 14,6% protocolo 6; 0,5% protocolo 7.Tras analizar a las 24 horas post-cirugía el nivel de dolor de los pacientes con la escala EVA/EN observamos que el 82,3% presentan un EVA/EN ≤ 3, por tanto sólo en el 17,7% de los pacientes fue preciso la utilización de analgesia de rescate. El 71% de los pacientes estaban muy satisfechos con el tratamiento pautado, y el 22,6% satisfechos. El 6,4 % no estaba satisfecho. CONCLUSIÓN: El establecimiento de protocolos de analgesia según tipos de cirugía es una medida válida, aceptable, que permite el control del dolor postoperatorio en las primeras 24 horas y que proporciona la estandarización del tratamiento y el control del mismo de forma adecuada


OBJECTIVES: The objective of this work was to establish the analgesia protocols for different types of urological surgery and to analyze the impact on pain during the first 24 h after surgery. METHODS: The study included 186 patients undergoing urological surgery between 2011 and 2013. Seven analgesia protocols were established and applied according to the surgical procedure. At 24 h post-surgery, i.e., the initiation of analgesic treatment, patients` pain was evaluated by visual analog scale/numeric scale (VAS/NS), and their degree of satisfaction and nausea were assessed. RESULTS: The study sample comprised 137 males (73.7%) and 49 females (26.3%), with a mean age of 58.5±14.7 yrs. Analgesia protocol 1 was applied in 5.9% of patients, protocol 2 in 17.8%, protocol 3 in 8.6%, protocol 4 in 38.9%, protocol 5 in 13.5%, protocol 6 in 14.6%, and protocol 7 in 0.5%.At 24 h post-surgery, the VAS/NS score was ≤ 3 in 82.3% of patients; hence, only 17.7% required rescue analgesia; 71% of patients were highly satisfied with the treatment provided and 22.6% were satisfied. 6.4% were not satisfied. CONCLUSION: Establishing analgesia protocols according to the type of surgery is a valid and useful measure to control postoperative pain during the first 24 h and to provide appropriate treatment standardization and follow-up


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Urológicos/métodos , Analgesia/métodos , Protocolos Clínicos , Satisfação do Paciente , Período Pós-Operatório , Manejo da Dor/métodos
19.
Can Urol Assoc J ; 8(5-6): E366-70, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24940468

RESUMO

We report 2 patients with ureteral injury after a simple total laparoscopic hysterectomy for uterine myoma with a complete resection of the distal ureter. One patient had unilateral injury and the other 2 patients had bilateral injury. The surgical laparoscopic repair procedure was carried out 3 to 5 days after the injury. Surgery involved intramural dissection of the distal ureteral stump to expose at least 1 cm of the ureter, percutaneous ureteral stent placement, elimination of tension between the proximal ureter and the dissected distal stump, end-to-end anastomosis, and reinsertion of the distal ureter into the bladder muscle layer, which was previously dissected for the anastomosis.

20.
Arch Ital Urol Androl ; 76(2): 75-9, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15270418

RESUMO

OBJECTIVES: Between January 1994 and February 2002, 9086 men underwent biplane TRUS at our institution for a variety of reasons. 781 of the 9086 men (8.6%) showed evidence of one or more intraprostatic cystic lesions. We propose a new classification of cystic structures located at the midline of the prostate. MATERIAL AND METHODS: We have designed a methodology that reclassifies cystic structures located at the prostate midline through the ultrasonically guided transrectal aspiration of the cystic structure, the analysis of the PSA level of the aspirated fluid and the presence of spermatozoa, radiological studies (cyst injection with contrast medium, vasography, retrograde and/or voiding cystourethrography and utricle injection with contrast medium) and endoscopic studies (cystourethroscopy). RESULTS: Upon completion of the methodology, we have classified and defined these structures as the following: simple prostatic cysts, cysts of the müllerian ducts, megautricle, megautricle with inclusion of the ejaculatory ducts, "pseudocystic" dilation of the ejaculatory ducts and utriculoceles. CONCLUSIONS: This new classification of cystic structures located at the prostate midline is simple, useful and steers one away from any possible confusion.


Assuntos
Cistos/classificação , Doenças Prostáticas/classificação , Humanos , Masculino
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