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1.
Int J Mol Sci ; 24(16)2023 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-37629155

RESUMO

PARPi, in combination with ionizing radiation, has demonstrated the ability to enhance cellular radiosensitivity in different tumors. The rationale is that the exposure to radiation leads to both physical and biochemical damage to DNA, prompting cells to initiate three primary mechanisms for DNA repair. Two double-stranded DNA breaks (DSB) repair pathways: (1) non-homologous end-joining (NHEJ) and (2) homologous recombination (HR); and (3) a single-stranded DNA break (SSB) repair pathway (base excision repair, BER). In this scenario, PARPi can serve as radiosensitizers by leveraging the BER pathway. This mechanism heightens the likelihood of replication forks collapsing, consequently leading to the formation of persistent DSBs. Together, the combination of PARPi and radiotherapy is a potent oncological strategy. This combination has proven its efficacy in different tumors. However, in prostate cancer, there are only preclinical studies to support it and, recently, an ongoing clinical trial. The objective of this paper is to perform a review of the current evidence regarding the use of PARPi and radiotherapy (RT) in PCa and to give future insight on this topic.


Assuntos
Neoplasias da Próstata , Radioterapia (Especialidade) , Humanos , Masculino , Reparo do DNA , Oncologia , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia
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.
Cancers (Basel) ; 15(3)2023 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-36765574

RESUMO

INTRODUCTION: Penile cancer (PC) is a rare malignancy with an overall incidence in Europe of 1/100,000 males/year. In Europe, few studies report the epidemiology, risk factors, clinical presentation, and treatment of PC. The aim of this study is to present an updated outlook on the aforementioned factors of PC in Spain. MATERIALS AND METHODS: A multicentric, retrospective, observational epidemiological study was designed, and patients with a new diagnosis of PC in 2015 were included. Patients were anonymously identified from the Register of Specialized Care Activity of the Ministry of Health of Spain. All Spanish hospitals recruiting patients in 2015 were invited to participate in the present study. We have followed a descriptive narration of the observed data. Continuous and categorical data were reported by median (p25th-p75th range) and absolute and relative frequencies, respectively. The incidence map shows differences between Spanish regions. RESULTS: The incidence of PC in Spain in 2015 was 2.55/100,000 males per year. A total of 586 patients were identified, and 228 patients from 61 hospitals were included in the analysis. A total of 54/61 (88.5%) centers reported ≤ 5 new cases. The patients accessed the urologist for visually-assessed penile lesions (60.5%), mainly localized in the glans (63.6%). Local hygiene, smoking habits, sexual habits, HPV exposure, and history of penile lesions were reported in 48.2%, 59.6%, 25%, 13.2%, and 69.7%. HPV-positive lesions were 18.1% (28.6% HPV-16). The majority of PC was squamous carcinoma (95.2%). PC was ≥cT2 in 45.2% (103/228) cases. At final pathology, PC was ≥pT2 in 51% of patients and ≥pN1 in 17% of cases. The most common local treatment was partial penectomy (46.9% cases). A total of 47/55 (85.5%) inguinal lymphadenectomies were open. Patients with ≥pN1 disease were treated with chemotherapy in 12/39 (40.8%) of cases. CONCLUSIONS: PC incidence is relatively high in Spain compared to other European countries. The risk factors for PC are usually misreported. The diagnosis and management of PC are suboptimal, encouraging the identification of referral centers for PC management.

4.
Sleep Med ; 91: 35-42, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35248939

RESUMO

BACKGROUND: Sleep-disordered breathing (SDB) has been associated with a greater aggressiveness of melanoma tumors, but the association with other cancers is unknown. This study investigates the relationship between the severity of SDB and the aggressiveness of prostate cancer (PC). METHODS: 165 patients under 66 years consecutively diagnosed with PC in three University Hospitals underwent a home respiratory polygraphy. SDB severity was assessed by means of the apnea-hypopnea index (AHI) as well as several oximetric parameters. The primary marker of the aggressiveness of PC was the Gleason score, while secondary markers included the tumor stage and metastatic spreading. RESULTS: The patients had a median (P 25-75) age of 60 (56-63) years, AHI of 13.3 (5.7-25.8), and 4% oxygen desaturation index of 8.7 (2.9-17.8). The prevalence of an AHI≥5 and AHI≥15 was 78.2% and 46.7%, respectively. The median AHI was similar in patients with Gleason 6 and > 6 [13.7 (5.6-28.7) vs 12.2 (5.7-23.2), p = 0.44], tumor stage I-II and III-IV [13.5 (5.3-26.5) vs 11.7 (7.8-21.1), p = 0.67], and presence or absence of metastasis [14.2 (9.6-31.8) vs 13.3 (5.2-24.6), p = 0.46]. The prevalence of an AHI≥5 and AHI≥15 was similar in patients with Gleason 6 and > 6 (79.2% vs 77.2%; p = 0.85, and 49.3% vs 44.33%; p = 0.53, respectively). These results did not change when different oximetric variables were analyzed instead of the AHI. CONCLUSIONS: Despite the high prevalence of SDB in patients with PC, our results do not support any association between the severity of SDB and PC aggressiveness.


Assuntos
Neoplasias da Próstata , Síndromes da Apneia do Sono , Humanos , Masculino , Pessoa de Meia-Idade , Oximetria , Prevalência , Neoplasias da Próstata/complicações , Síndromes da Apneia do Sono/complicações
6.
Rev. int. androl. (Internet) ; 19(1): 49-52, ene.-mar. 2021.
Artigo em Inglês | IBECS | ID: ibc-201670

RESUMO

INTRODUCTION: Adverse effects in the sexual sphere are common in patients who have undergone radical prostatectomy (RP). Climacturia, involuntary loss of urine during orgasm, occurs in 20-40% of cases after PR. We analyse its prevalence and associated risk factors after Robotic-assisted laparoscopic radical prostatectomy (RALRP). OBJECTIVES: We analyse the climacturia prevalence after robotic-assisted laparoscopic radical prostatectomy (RALRP) and the association with other related factors. MATERIALS AND METHODS: Retrospective study of 100 patients underwent PRLAR from May 2011 to July 2014. After excluding patients who received radiotherapy after surgery (17), those who did not have sexual activity (7) and those with whom it could not be possible contacted (14), a structured telephone interview was conducted in 62 patients, investigating: presence and intensity of climacturia, orgasmic quality, incontinence and erectile dysfunction (ED). Other factors analysed included neurovascular preservation and rehabilitative treatment for ED. The statistical analysis consisted of Chi2test and logistic regression to evaluate associated factors. RESULTS: The mean age was 56 vs 59 years and the mean follow-up time was 26.6 vs 20.3 months, in the group with climacturia and without climacturia, respectively. The prevalence of climacturia was 17.9% (slight leaks-82% and severe leaks-18%). In 37% of these patients occurred in all orgasms. The quality of orgasm after surgery was worse in 47%, better in 13% and equal in 40%. The quality of the orgasm worsened more frequently in the climacturia group (63% vs 37%). The urinary incontinence rate was 41%, always effort incontinence. It was more frequent in patients with climacturia (62% vs 38%). In all patients with climacturia, bilateral neurovascular bundles preservation was performed. 32% of the patients had undergone post-surgical erectile rehabilitation with oral drugs. No statistically significant differences were found between patients with or without climacturia respect to the parameters analysed. CONCLUSIONS: Climacturia rate after PRLAR in our series was 17.9%. Patients with climacturia presented worse quality orgasms and a higher incontinence rate (p> 0.05). None of the analysed parameters could be defined as predictors of climacturia


INTRODUCCIÓN: Los efectos adversos en la esfera sexual son comunes en pacientes sometidos a prostatectomía radical (PR). La climaturia, pérdida involuntaria de orina durante el orgasmo, se presenta en un 20-40% de casos tras PR. Analizamos su prevalencia y asociación con otros factores relacionados tras prostatectomía radical laparoscópica asistida por robot (PRLAR). OBJETIVOS: Analizamos la prevalencia de climaturia tras PRLAR y su asociación con otros posibles factores riesgo relacionados. MATERIAL Y MÉTODOS: Estudio retrospectivo de 100 pacientes, sometidos a PRLAR desde mayo-2011 a julio-2014. Tras excluir a pacientes que recibieron radioterapia tras la cirugía (17), a los que no tenían actividad sexual (7) y aquellos con los que no se pudo contactar (14), se realizó entrevista telefónica estructurada a 62 pacientes, indagando sobre: presencia e intensidad de climaturia, calidad orgásmica, incontinencia y disfunción eréctil (DE). Otros factores analizados incluyeron la preservación neurovascular y el tratamiento rehabilitador para DE. El análisis estadístico consistió en prueba de Chi2 y regresión logística para evaluar factores asociados. RESULTADOS: La edad media fue 56 vs 59 años y el tiempo medio de seguimiento de 26,6 vs 20,3 meses, en el grupo con climaturia y sin climaturia respectivamente. La prevalencia de climaturia fue del 17.9% (pérdidas leves el 82% y severas el 18%). En el 37% de estos pacientes ocurrió en todos los orgasmos. La calidad del orgasmo tras cirugía fue peor en el 47%, mejor en el 13% e igual en el 40%. La calidad del orgasmo empeoró con más frecuencia en el grupo con climaturia (63% vs 37%). La tasa de incontinencia urinaria fue del 41%, siempre de esfuerzo. Fue más frecuente en pacientes con climaturia (62% vs 38%). El 68% de los pacientes usaba fármacos para DE. En todos los pacientes con climaturia se realizó preservación nerviosa bilateral. El 32% de los pacientes habían realizado rehabilitación eréctil postquirúrgica con fármacos orales. No se encontraron diferencias estadísticamente significativas entre pacientes con o sin climaturia respecto a los parámetros analizados. CONCLUSIONES: La tasa de climaturia tras PRLAR en nuestra serie fue del 17,9%. Los pacientes con climaturia presentaron orgasmos de peor calidad y una tasa de incontinencia superior (p > 0,05). Ninguno de los parámetros analizados pudieron definirse como factores predictivos de climaturia


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Incontinência Urinária/etiologia , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Complicações Pós-Operatórias/fisiopatologia , Prostatectomia/efeitos adversos , Disfunção Erétil/diagnóstico , Procedimentos Cirúrgicos Robóticos/métodos , Prostatectomia/métodos , Fatores de Risco , Estudos Retrospectivos , Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/reabilitação
7.
Rev Int Androl ; 19(1): 49-52, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32147377

RESUMO

INTRODUCTION: Adverse effects in the sexual sphere are common in patients who have undergone radical prostatectomy (RP). Climacturia, involuntary loss of urine during orgasm, occurs in 20-40% of cases after PR. We analyse its prevalence and associated risk factors after Robotic-assisted laparoscopic radical prostatectomy (RALRP). OBJECTIVES: We analyse the climacturia prevalence after robotic-assisted laparoscopic radical prostatectomy (RALRP) and the association with other related factors. MATERIALS AND METHODS: Retrospective study of 100 patients underwent PRLAR from May 2011 to July 2014. After excluding patients who received radiotherapy after surgery (17), those who did not have sexual activity (7) and those with whom it could not be possible contacted (14), a structured telephone interview was conducted in 62 patients, investigating: presence and intensity of climacturia, orgasmic quality, incontinence and erectile dysfunction (ED). Other factors analysed included neurovascular preservation and rehabilitative treatment for ED. The statistical analysis consisted of Chi2test and logistic regression to evaluate associated factors. RESULTS: The mean age was 56 vs 59 years and the mean follow-up time was 26.6 vs 20.3 months, in the group with climacturia and without climacturia, respectively. The prevalence of climacturia was 17.9% (slight leaks-82% and severe leaks-18%). In 37% of these patients occurred in all orgasms. The quality of orgasm after surgery was worse in 47%, better in 13% and equal in 40%. The quality of the orgasm worsened more frequently in the climacturia group (63% vs 37%). The urinary incontinence rate was 41%, always effort incontinence. It was more frequent in patients with climacturia (62% vs 38%). In all patients with climacturia, bilateral neurovascular bundles preservation was performed. 32% of the patients had undergone post-surgical erectile rehabilitation with oral drugs. No statistically significant differences were found between patients with or without climacturia respect to the parameters analysed. CONCLUSIONS: Climacturia rate after PRLAR in our series was 17.9%. Patients with climacturia presented worse quality orgasms and a higher incontinence rate (p> 0.05). None of the analysed parameters could be defined as predictors of climacturia.


Assuntos
Disfunção Erétil , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Incontinência Urinária , Humanos , Masculino , Pessoa de Meia-Idade , Prostatectomia/efeitos adversos , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Incontinência Urinária/epidemiologia , Incontinência Urinária/etiologia
8.
Updates Surg ; 72(4): 1237-1246, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32488822

RESUMO

This is the phase 1 of a multicenter clinical trial (NCT03738488), which aims to assess the efficacy and efficiency of surgery planning with 3D models of renal cell carcinoma (RCC) with venous tumor thrombus extension (VTE) compared to the standard images (CT). The objective of this phase is to obtain a 3D printed model of RCC with VTE that is feasible, accurate, reproducible, suitable for surgical simulation, and affordable. A specific protocol was developed to obtain the computed tomography (CT) image: early arterial and nephrogenic phase. ITK-snap® and VirSSPA Software® were used to segment the areas of interest. The resulting 3D mesh was processed with MeshMixer® and Cura®. Ten models from seven different cases were segmented and printed using different 3D printers and materials. We evaluated the material, scale, wall thickness, anatomy printed, 3D conformation, accuracy compared to the CT, suitability to perform the surgery, material, cost, and time (segmentation + design + fabrication + finishing). The four selected models were printed with a BQ Witbox FDM printer in polyurethane filament with a 0.8 mm wall thickness and 100% scale. All the relevant anatomical structures could be correctly identified, the 3D conformation was maintained with good accuracy compared to the CT and the surgery could be performed on them. Mean design time, model cost and printing time were 8.3 h, 33.4 €, and 38.5 h respectively. Various feasible 3D models of RCC with VTE were obtained after a few attempts. The final models were proved to be reproducible, accurate compared to the CT, and suitable for surgery simulation. The printing process was standardized making it possible to manufacture affordable 3D printed models.


Assuntos
Carcinoma de Células Renais , Simulação por Computador , Cirurgia Geral/educação , Neoplasias Renais , Modelos Anatômicos , Impressão Tridimensional , Treinamento por Simulação/métodos , Software , Tomografia Computadorizada por Raios X/métodos , Trombose Venosa , Carcinoma de Células Renais/cirurgia , Humanos , Neoplasias Renais/cirurgia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
9.
Urol Int ; 104(3-4): 323-326, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31914452

RESUMO

Nivolumab is a fully human immunoglobulin G4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody that selectively blocks the interaction between PD-1, which is expressed on activated T cells, and its ligands PD-L1 and PD-L2, which are expressed on immune cells and tumour cells. Patients with severe renal dysfunction and haemodialysis are not enrolled in clinical trials. However, in daily clinical practice, we have patients with metastatic renal cell carcinoma (mRCC) and end-stage renal disease (ESRD). The scientific evidence about the efficacy and safety of nivolumab in these patients is scarce. We report three cases of mRCC patients with ESRD treated with second-line nivolumab therapy. They received both biweekly and monthly schemes. None of our patients showed grade 2-4 toxicities. Two patients achieved partial response and one progressive disease as best response. Our patients did not show increased toxicity by ESRD; also, two of the three patients had objectifiable clinical benefit. Nivolumab seems to be similarly safe for ESRD or dialysis patients as for patients without impaired kidney function (IKF). Dose adjustments might not be necessary. We suggest that patients on dialysis could be treated with nivolumab in the same way as populations without IKF.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Carcinoma de Células Renais/tratamento farmacológico , Falência Renal Crônica/complicações , Neoplasias Renais/tratamento farmacológico , Nivolumabe/administração & dosagem , Diálise Renal , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Carcinoma de Células Renais/secundário , Esquema de Medicação , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Resultado do Tratamento
10.
Arch Esp Urol ; 71(8): 639-650, 2018 Sep.
Artigo em Espanhol | MEDLINE | ID: mdl-30319124

RESUMO

OBJECTIVES: Castration resistant prostate cancer (CRPC) is an heterogeneous disease the molecular basis of which we are starting to know in depth. Currently, there are various pathways and targets under study, and probably many others to be characterized. In this paper, we review the most recent knowledge concerning the molecular biology of CRPC with a special focus on the therapeutic application of this knowledge. METHODS: We performed a bibliographic review using PUBMED as the search engine, including the following terms: "Castration resistant prostate cancer", "genomics", "molecular biology", "AR", "WNT", "mTOR", "PTEN", "cell-cycle", "DNA damage repair gene"and "chromatin modifier genes". RESULTS: CRPC has a high load of genetic alterations, probably derived from therapeutic pressure. The most frequent alterations involve the androgen receptor (RA) [60-70%] and the PI3K- AKT-mTOR [40-60%], even though other relevant pathways alterations have been identified such as those relative to cellular cycle [25%], DNA lesion repair genes [20%] and other pathway like WNT-ßcatenin [15-22%]. The knowledge of these pathways is helping as a base for development of new therapeutic targets with promising results and multiple ongoing studies. CONCLUSIONS: Over the last decade, the progress in the knowledge of the molecular bases of CRPC has been very relevant. Even though AR alterations are the most frequent and best characterized, anomalies in other pathways have been also identified as important in the biology of CRPC and derived a notable therapeutic development.


Assuntos
Neoplasias de Próstata Resistentes à Castração/genética , Proteínas de Ciclo Celular/genética , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/terapia , Via de Sinalização Wnt
11.
Arch. esp. urol. (Ed. impr.) ; 71(8): 639-650, oct. 2018. graf
Artigo em Espanhol | IBECS | ID: ibc-178742

RESUMO

OBJETIVOS: El cáncer de próstata resistente a la castración (CPRC) es una enfermedad heterogénea de la que estamos empezando a conocer sus bases moleculares en profundidad. Hay diversas vías y dianas en estudio en estos momentos y probablemente otras tantas por caracterizar. En este trabajo revisamos los conocimientos mas recientes relativos a la biología molecular del CPRC con un foco especial en la aplicación terapéutica de este conocimiento. Metodos: Se ha llevado a cabo una revisión de la literatura utilizando Pubmed como motor de búsqueda, incluyendo los siguientes términos: "castration-resistant prostate cáncer", "genomics", "molecular biology", "AR", "WNT", "mTOR", "PTEN", "cell-cycle", "DNA damage repair gene" y "chromatin modifier genes". RESULTADOS: El CPRC tiene una alta carga de alteraciones genéticas, probablemente derivadas de la presión terapéutica. Las alteraciones más frecuentes afectan al receptor androgénico (RA) [60-70%] y a la vía de PI3K-AKT-mTOR [40-60%], si bien se han identificado alteraciones relevantes de otras vías como aquellas relativas al control del ciclo celular [25%], en genes de reparación de lesiones en el ADN [20%] y en otras vías como la de WNT-betacatenina [15-22%]. El conocimiento de estas alteraciones esta sirviendo como base para el desarrollo de terapias especificas a nuevas dianas terapéuticas con resultados prometedores y multiples estudios en curso. CONCLUSIONES: En la ultima década el avance en el conocimiento de las bases moleculares del CPRC ha sido muy relevante. Si bien las alteraciones del RA son las mas frecuentes y mejor caracterizadas, anomalías en otras vías han sido también identificadas como destacadas en la biología del CRPC y han derivado en un desarrollo terapéutico notable


OBJECTIVES: Castration resistant prostate cancer (CRPC) is an heterogeneous disease the molecular basis of which we are starting to know in depth. Currently, there are various pathways and targets under study, and probably many others to be characterized. In this paper, we review the most recent knowledge concerning the molecular biology of CRPC with a special focus on the therapeutic application of this knowledge. METHODS: We performed a bibliographic review using PUBMED as the search engine, including the following terms: "Castration resistant prostate cancer", "genomics", "molecular biology", "AR", "WNT", "mTOR", "PTEN", cell-cycle", "DNA damage repair gene" and "chromatin modifier genea". RESULTS: CRPC has a high load of genetic alterations, probably derived from therapeutic pressure. The most frequent alterations involve the androgen receptor (RA) [60-70%] and the PI3K- AKT-mTOR [40-60%], even though other relevant pathways alterations have been identified such as those relative to cellular cycle [25%], DNA lesion repair genes [20%] and other pathway like WNT-Betacatenin [15-22%]. The knowledge of these pathways is helping as a base for development of new therapeutic targets with promising results and multiple ongoing studies. CONCLUSIONS: Over the last decade, the progress in the knowledge of the molecular bases of CRPC has been very relevant. Even though AR alterations are the most frequent and best characterized, anomalies in other pathways have been also identified as important in the biology of CRPC and derived a notable therapeutic development


Assuntos
Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/genética , Biologia Molecular/métodos , Neoplasias de Próstata Resistentes à Castração/terapia , Via de Sinalização Wnt
12.
J Immunother Cancer ; 5(1): 71, 2017 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-28923104

RESUMO

BACKGROUND: Enadenotucirev (formerly ColoAd1) is a tumor-selective chimeric adenovirus with demonstrated preclinical activity. This phase 1 Mechanism of Action study assessed intravenous (IV) delivery of enadenotucirev in patients with resectable colorectal cancer (CRC), non-small-cell lung cancer (NSCLC), urothelial cell cancer (UCC), and renal cell cancer (RCC) with a comparator intratumoral (IT) dosed CRC patient cohort. METHODS: Seventeen patients scheduled for primary tumor resection were enrolled. IT injection of enadenotucirev (CRC only) was administered as a single dose (≤ 3 × 1011 viral particles [vp]) on day 1, followed by resection during days 8-15. IV infusion of enadenotucirev was administered by three separate doses (1 × 1012 vp) on days 1, 3, and 5, followed by resection during days 8-15 (CRC) or days 10-25 (NSCLC, UCC, and RCC). Enadenotucirev activity was measured using immunohistochemical staining of nuclear viral hexon and quantitative polymerase chain reaction for viral genomic DNA. RESULTS: Delivery of enadenotucirev was observed in most tumor samples following IV infusion, with little or no demonstrable activity in normal tissue. This virus delivery (by both IV and IT dosing) was accompanied by high local CD8+ cell infiltration in 80% of tested tumor samples, suggesting a potential enadenotucirev-driven immune response. Both methods of enadenotucirev delivery were well tolerated, with no treatment-associated serious adverse events. CONCLUSIONS: This study provides key delivery and feasibility data to support the use of IV infusion of enadenotucirev, or therapeutic transgene-bearing derivatives of it, in clinical trials across a range of epithelial tumors, including the ongoing combination study of enadenotucirev with the checkpoint inhibitor nivolumab. It also provides insights into the potential immune-stimulating properties of enadenotucirev. TRIAL REGISTRATION: This MOA study was a phase 1, multicenter, non-randomized, open-label study to investigate the administration of enadenotucirev in a preoperative setting (ClinicalTrials.gov: NCT02053220).


Assuntos
Adenovírus Humanos/fisiologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma de Células Renais/terapia , Carcinoma de Células de Transição/terapia , Neoplasias Colorretais/terapia , Neoplasias Pulmonares/terapia , Adenovírus Humanos/genética , Administração Intravenosa , Linfócitos T CD8-Positivos/metabolismo , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma de Células Renais/imunologia , Carcinoma de Células de Transição/imunologia , Neoplasias Colorretais/imunologia , Terapia Combinada , DNA Viral/genética , Procedimentos Cirúrgicos do Sistema Digestório , Humanos , Neoplasias Pulmonares/imunologia , Terapia Viral Oncolítica , Vírus Oncolíticos/genética , Vírus Oncolíticos/fisiologia , Procedimentos Cirúrgicos Pulmonares , Resultado do Tratamento , Procedimentos Cirúrgicos Urológicos
13.
Int. braz. j. urol ; 43(2): 216-223, Mar.-Apr. 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-840817

RESUMO

ABSTRACT Introduction There is a growing interest in achieving higher survival rates with the lowest morbidity in localized prostate cancer (PC) treatment. Consequently, minimally invasive techniques such as low-dose rate brachytherapy (BT) and robotic-assisted prostatectomy (RALP) have been developed and improved. Comparative analysis of functional outcomes and quality of life in a prospective series of 51BT and 42Da Vinci prostatectomies DV Materials and Methods Comparative analysis of functional outcomes and quality of life in a prospective series of 93 patients with low-risk localized PC diagnosed in 2011. 51patients underwent low-dose rate BT and the other 42 patients RALP. IIEF to assess erectile function, ICIQ to evaluate continence and SF36 test to quality of life wee employed. Results ICIQ at the first revision shows significant differences which favour the BT group, 79% present with continence or mild incontinence, whereas in the DV group 45% show these positive results. Differences disappear after 6 months, with 45 patients (89%) presenting with continence or mild incontinence in the BT group vs. 30 (71%) in the DV group. 65% of patients are potent in the first revision following BT and 39% following DV. Such differences are not significant and cannot be observed after 6 months. No significant differences were found in the comparative analysis of quality of life. Conclusions ICIQ after surgery shows significant differences in favour of BT, which disappear after 6 months. Both procedures have a serious impact on erectile function, being even greater in the DV group. Differences between groups disappear after 6 months.


Assuntos
Humanos , Masculino , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/radioterapia , Qualidade de Vida , Braquiterapia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Complicações Pós-Operatórias , Prostatectomia/efeitos adversos , Fatores de Tempo , Incontinência Urinária/etiologia , Índice de Gravidade de Doença , Braquiterapia/efeitos adversos , Estudos Prospectivos , Inquéritos e Questionários , Resultado do Tratamento , Relação Dose-Resposta à Radiação , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Disfunção Erétil/etiologia , Pessoa de Meia-Idade
14.
Int Braz J Urol ; 43(2): 216-223, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28128908

RESUMO

INTRODUCTION: There is a growing interest in achieving higher survival rates with the lowest morbidity in localized prostate cancer (PC) treatment. Consequently, minimally invasive techniques such as low-dose rate brachytherapy (BT) and robotic-assisted prostatectomy (RALP) have been developed and improved. Comparative analysis of functional outcomes and quality of life in a prospective series of 51BT and 42Da Vinci prostatectomies DV Materials and Methods: Comparative analysis of functional outcomes and quality of life in a prospective series of 93 patients with low-risk localized PC diagnosed in 2011. 51patients underwent low-dose rate BT and the other 42 patients RALP. IIEF to assess erectile function, ICIQ to evaluate continence and SF36 test to quality of life wee employed. RESULTS: ICIQ at the first revision shows significant differences which favour the BT group, 79% present with continence or mild incontinence, whereas in the DV group 45% show these positive results. Differences disappear after 6 months, with 45 patients (89%) presenting with continence or mild incontinence in the BT group vs. 30 (71%) in the DV group. 65% of patients are potent in the first revision following BT and 39% following DV. Such differences are not significant and cannot be observed after 6 months. No significant differences were found in the comparative analysis of quality of life. CONCLUSIONS: ICIQ after surgery shows significant differences in favour of BT, which disappear after 6 months. Both procedures have a serious impact on erectile function, being even greater in the DV group. Differences between groups disappear after 6 months.


Assuntos
Braquiterapia/métodos , Prostatectomia/métodos , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Qualidade de Vida , Procedimentos Cirúrgicos Robóticos/métodos , Braquiterapia/efeitos adversos , Relação Dose-Resposta à Radiação , Disfunção Erétil/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Prospectivos , Prostatectomia/efeitos adversos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Índice de Gravidade de Doença , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Incontinência Urinária/etiologia
15.
Arch. esp. urol. (Ed. impr.) ; 64(9): 883-890, nov. 2011. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-92327

RESUMO

OBJETIVO: Analizar la relación existente entre trombocitosis y hematocrito prequirúrgicos y supervivencia en nuestra serie de pacientes tratados quirúrgicamente por adenocarcinoma renal.MÉTODO: Estudio retrospectivo con análisis descriptivo estadístico de 139 pacientes intervenidos quirúrgicamente en nuestro servicio en los últimos 4 años por adenocarcinoma renal. 116 (83,45%) presentaban al diagnóstico un estadio clínico localizado, y 23 (16,54%) un estadio localmente avanzado o metastásico. Fueron recogidos datos relativos a tiempo de seguimiento y supervivencia, características iconográficas e histológicas del tumor y parámetros analíticos. Los datos fueron analizados con estadístico SPSS.RESULTADOS: El recuento plaquetario medio previo a la intervención quirúrgica fue de 260930 cels/mm3. El hematocrito medio prequirúrgico fue de 41,10%. Se encontró una relación estadísticamente significativa (p=0,04) entre el recuento plaquetario al diagnóstico y la supervivencia. Pacientes con recuentos plaquetarios superiores a 350000/mm3 presentaban una supervivencia más baja (OR: 2,94; IC 95% 1,04- 8,27). Se objetivó una relación significativa (p=0,049) entre el hematocrito al diagnóstico y la supervivencia. A mayor hematocrito disminuyó el riesgo de muerte (OR: 0,92; IC 95% 0,85- 0,99). La supervivencia global en nuestro grupo fue del 88,4%. El análisis multivariante de la misma no arrojó datos estadísticamente significativos debido al escaso número de éxitus.CONCLUSIONES: La presencia de recuentos plaquetarios elevados o niveles de hematocrito bajos al diagnóstico se relacionan, en esta serie y de forma no independiente, con una disminución de la supervivencia en nuestro grupo de pacientes intervenidos por adenocarcinoma renal. Serían necesarios estudios con mayor seguimiento y muestras más amplias para aseverar estos hallazgos(AU)


OBJECTIVE: To examine the connection between preoperative thrombocytosis and hematocrit and survival in a group of patients operated for renal cell carcinoma.METHODS: Retrospective study with descriptive and statistical analysis of 139 patients with renal cell carcinoma treated surgically over the last 4 years in our Urology clinical unit. 116 (83,45%) were diagnosed at a localized clinical stage, whereas 23 (16,54%) presented as locally advanced or metastatic disease. We collected data about survival and time on surveillance, imaging and histological characteristics of the tumor and analytical parameters. Data were analyzed by the SPSS statistical software.RESULTS: The average platelet count and hematocrit before surgery were 260,930 cells/mm3 and 41.10%, respectively. We found a statistical correlation between platelet count at the time of diagnosis and survival. Patients with platelet counts higher than 350,000 cells/mm3 had a poor survival (OR: 2.94; CI 95% 1.04- 8.27). We also found that patients with high hematocrit at diagnosis presented a lower risk of death (OR: 0.92; CI 95% 0.85- 0.99). The global survival at the end of the study was 88.4%. Multivariate analysis did not show any significant result because of the low number of deaths.CONCLUSION: The presence of high platelet count or low hematocrit correlate with poor survival in a group of surgically treated renal cell carcinoma patients. Nevertheless more studies with longer surveillance and higher number of patients are needed(AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Laparoscopia/métodos , Urolitíase/cirurgia , /estatística & dados numéricos , Litotripsia , /estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia
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