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1.
Eur Urol Open Sci ; 25: 5-10, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34337498

RESUMO

Background: Primary flexible ureterorenoscopy (URS) and extracorporeal shock wave lithotripsy (SWL) are treatment options in patients with renal calculi of 5-15 mm. Objective: To compare effectiveness, complication rates, and pain scores between primary URS and SWL. Design setting and participants: Between 2011 and 2016, patients with renal calculi between 5 and 15 mm were randomized to undergo either primary URS or SWL. Outcome measurements and statistical analysis: Stone-free rate and size of residual fragments assessed by computed tomography after 3 mo, complications, and pain scores were evaluated. Results and limitations: The study was prematurely closed after randomizing 44 patients due to poor accrual. The 3-mo stone-free rate and mean residual stone size were, respectively, 61% and 1.8 mm after URS and 48% and 2.4 mm after SWL. Early post-treatment pain scores were significantly higher after URS than after SWL on day 1 (3.3 vs 1.6, p = 0.02) and day 7 (5.2 vs 3.4, p = 0.04), but were no longer detectable after 3 wk and 3 mo, respectively. One Clavien-Dindo grade II complication was observed after URS (5%) and SWL (4%), while one (4%) grade IIIb complication was observed after SWL. Conclusions: URS appears to be associated with higher early post-treatment discomfort, which could be associated with routine postoperative stenting. Owing to premature closure of this trial, the power was insufficient to formally compare URS and SWL; however, the present data might be informative to counsel patients about treatment outcomes and allow future meta-analyses. Patient summary: This study was ended prematurely, but it contributes data about efficacy and side effects of different treatment options in patients with renal calculi.

2.
Praxis (Bern 1994) ; 110(10): 565-570, 2021 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-34344187

RESUMO

Dignity of Small Renal Masses: Implications for Diagnostics and Therapy Abstract. The ubiquitous availability of radiological imaging has increased the diagnosis of renal incidentalomas with a diameter ≤4 cm. If malignancy is suspected, these are often treated surgically without prior biopsy. However, several studies demonstrate a relevant proportion of benign tumors, equating to a degree of overtreatment. There are no Swiss data available. Renal tumors resected in our center between 2006 and 2014 (n = 404) were retrospectively examined for size on cross-sectional imaging and their respective histology, identifying 221 (54.7 %) small renal masses with a diameter ≤4 cm. Of these, 62 (28 %) were benign and three (1.4 %) were of unclear or low malignant potential. Among the remaining 156 malignancies, 116 (74.4 %) were classified as prognostically favorable, allowing for active surveillance, if the patient's clinical context allows.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/epidemiologia , Humanos , Rim , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/epidemiologia , Nefrectomia , Respeito , Estudos Retrospectivos
3.
Cancer Rep (Hoboken) ; : e1418, 2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34008909

RESUMO

BACKGROUND: Dutasteride has been shown to increase expression of the prostate-specific membrane antigen (PSMA) in prostate cancer cells in previous in vitro studies. This 5-alpha-reductase inhibitor is commonly used for the treatment of symptomatic benign prostatic enlargement. The modulation of PSMA expression might affect PSMA-based prostate cancer imaging and therapy. AIM: The purpose of this work was to further analyze concentration-dependent effects of Dutasteride on PSMA expression in a mouse xenograft model. METHODS AND RESULTS: Four groups of mice bearing LNCaP xenografts were treated for 14 days with daily intraperitoneal injections of either vehicle control or different concentrations of Dutasteride (0.1, 1, 10 mg/kg). Total expression of PSMA, androgen receptor (AR), and caspase-3 protein was analyzed using immunoblotting (WES). In addition, PSMA, cleaved caspase-3 and Ki-67 expression was assessed and quantified by immunohistochemistry. Tumor size was measured by caliper on day 7 and 14, tumor weight was assessed following tissue harvesting. The mean PSMA protein expression in mice increased significantly after treatment with 1 mg/kg (10-fold) or 10 mg/kg (sixfold) of Dutasteride compared to vehicle control. The mean fluorescence intensity significantly increased by daily injections of 0.1 mg/kg Dutasteride (1.6-fold) as well as 1 and 10 mg/kg Dutasteride (twofold). While the reduction in tumor volume following treatment with high concentrations of 10 mg/kg Dutasteride was nonsignificant, no changes in AR, caspase-3, cleaved caspase-3, and Ki-67 expression were observed. CONCLUSION: Short-term Dutasteride treatments with concentrations of 1 and 10 mg/kg significantly increase the total PSMA protein expression in a mouse LNCaP xenograft model. PSMA fluorescence intensity increases significantly even using lower daily concentrations of 0.1 mg/kg Dutasteride. Further investigations are needed to elucidate the impact of Dutasteride treatment on PSMA expression in patients.

4.
Prostate ; 81(5): 286-294, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33599318

RESUMO

BACKGROUND: The therapeutic role of extended (ePLND) versus nonextended pelvic lymph node dissection (nePLND) to remove occult micrometastases in men undergoing radical prostatectomy for localized prostate cancer (PC) is conflicting. Therefore, our aim was to quantify the direct effect of ePLND versus nePLND (removal of occult micrometastases), which is not mediated through the detection of nodal disease and potential adjuvant therapy (indirect effect). METHODS: Retrospective, bi-center cohort study of consecutive patients undergoing radical prostatectomy and PLND for PC (January 2006 and December 2016). Patients were followed until April 2018 for the occurrence of either biochemical recurrence or secondary therapy (composite outcome). ePLND was compared to nePLND by unweighted and weighted survival analysis (total effect) as well as by causal mediation analysis (direct and indirect effect). RESULTS: Positive nodal disease was detected in 71 (7%) out of 1008 patients undergoing radical prostatectomy and PLND for PC (ePLND: 368 [36.5%]; nePLND: 640 [63.5%]). Survival analysis demonstrated results in favor of ePLND (unweighted hazard ratio: 0.77 [95% confidence interval: 0.59-1.01], p = .056; weighted hazard ratio: 0.75 [0.56-0.99], p = .044). The causal mediation analysis confirmed the total effect of 0.77 (0.71-0.82). After disentangling this total effect into an indirect effect (via detection of nodal disease and potential adjuvant therapy) and a direct effect (via removal of occult micrometastases), we identified an even more protective direct effect of 0.69 (0.63-0.75). CONCLUSIONS: Our results not only indicate the utility of ePLND but also that its impact is not restricted to a staging benefit and probably involves a therapeutic benefit mediated through the removal of occult micrometastases.


Assuntos
Excisão de Linfonodo/métodos , Análise de Mediação , Prostatectomia/métodos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Idoso , Estudos de Coortes , Humanos , Metástase Linfática/patologia , Metástase Linfática/terapia , Masculino , Pessoa de Meia-Idade , Micrometástase de Neoplasia/patologia , Micrometástase de Neoplasia/terapia , Pelve , Estudos Retrospectivos , Resultado do Tratamento
5.
World J Urol ; 39(1): 97-103, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32240349

RESUMO

PURPOSE: To report the incidence of urinary tract malignancies (UTM) and to compare the diagnostic accuracy of cytology with cystoscopy, renal ultrasound (US) and computed tomography (CT) in patients with hematuria. METHODS: A retrospective analysis was conducted of patients who underwent cystoscopy, cytology, US and CT for hematuria between 2011 and 2017. Age, gender, BMI, smoking status, and results of further diagnostic interventions including transurethral resection of the bladder (TURB), ureterorenoscopy (URS), renal biopsy and imaging were extracted from medical charts. Logistic regression to identify risk factors for UTM was performed. Discriminatory accuracy of US, CT and cytology was assessed by 2 × 2 tables. RESULTS: Of 847 patients, 432 (51%) presented with non-visible hematuria (NVH) and 415 (49%) with visible hematuria (VH). Of all patients with NVH, seven (1.6%) had bladder cancer (BCA), three (< 1%) had renal cell cancer (RCC) and no single patient had upper tract urothelial cancer (UTUC). Of the patients with VH, 62 (14.9%) were diagnosed with BCA, 7 (1.6%) with RCC and 4 (< 1%) with UTUC. In multivariable analysis VH, higher age, smoking and lower BMI were associated with an increased risk for UTM. The specificity/negative predictive value of US for the detection of RCC or UTUC in patients with NVH and VH were 96%/100% and 95%/99%, respectively. CONCLUSION: Due to the low incidence of UTM, the necessity of further diagnostics should be questioned in patients with NVH. In contrast, patients with VH are at considerable risk for BCA, and cystoscopy and upper tract imaging is justified.


Assuntos
Neoplasias Urológicas/diagnóstico , Adulto , Idoso , Cistoscopia , Feminino , Hematúria/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Ultrassonografia , Neoplasias Urológicas/complicações , Neoplasias Urológicas/patologia
6.
J Cancer Res Clin Oncol ; 146(11): 2829-2841, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32719989

RESUMO

PURPOSE: Testicular granulosa cell tumors (tGrCT) are rare sex cord-stromal tumors. This review aims to synthesize the available evidence regarding the clinical presentation and clinicopathological characteristics, treatment and outcomes. METHODS: We conducted a systematic literature search using the most important research databases. Whenever feasible, we extracted the data on individual patient level. RESULTS: From 7863 identified records, we included 88 publications describing 239 patients with tGrCT. The majority of the cases were diagnosed with juvenile tGrCT (166/239, 69%), while 73/239 (31%) patients were diagnosed with adult tGrCT. Mean age at diagnosis was 1.5 years (± 5 SD) for juvenile tGrCT, and 42 years (± 19 SD) for adult tGrCT. Information on primary treatment was available in 231/239 (97%), of which 202/231 (87%) were treated with a radical orchiectomy and 20/231 (9%) received testis sparing surgery (TSS). Local recurrence after TSS was observed in 1/20 (5%) cases. Metastatic disease was never observed in men with juvenile tGrCT but in 7/73 (10%) men with adult tGrCT. In 5/7 men with metastatic tGrCT, metastases were diagnosed at initial staging, while 2/7 patients developed metastases after 72 and 121 months of follow-up, respectively. Primary site of metastasis is represented by the retroperitoneal lymph nodes, but other sites including lungs, liver, bone and inguinal lymph nodes can also be affected. In comparison with non-metastatic adult tGrCT, men with metastatic adult tGrCT had significantly larger primary tumors (70 vs 24 mm, p 0.001), and were more likely to present with angiolymphatic invasion (57% vs 4%, p 0.002) or gynecomastia (29% vs 3%, p 0.019). In five out of seven men with metastatic disease, resection of metastases or platinum-based chemotherapy led to complete remission. CONCLUSION: Juvenile tGrCT represent a benign entity whereas adult tGCTs have metastatic potential. Tumor size, presence of angiolymphatic invasion or gynecomastia represent risk factors for metastatic disease. The published literature supports the use of testis sparing surgery but there is only limited experience with adjuvant therapies. In the metastatic setting, the reviewed literature suggests that aggressive surgical and systemic treatment might cure patients.


Assuntos
Tumor de Células da Granulosa/patologia , Tumor de Células da Granulosa/terapia , Neoplasias Testiculares/patologia , Neoplasias Testiculares/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
7.
Urol Oncol ; 38(8): 683.e19-683.e26, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32466878

RESUMO

BACKGROUND: ARN-509 (Apalutamide) is a unique androgen receptor (AR) antagonist for the treatment of castration-resistant (CR) prostate cancer (PC). It inhibits AR nuclear translocation, DNA binding and transcription of AR gene targets. As dysregulation of autophagy has been detected in PC, the targeting of autophagy is a potential approach to overcome early therapeutic resistance. Therefore, we investigated the characteristics of autophagic response to ARN-509 treatment and evaluated the potential effect of a combination with autophagy inhibition. METHODS: Human prostate cancer cells (LNCaP) were cultivated in a steroid-free medium. Cells were treated with ARN-509 (50 µM) alone or in combination with the autophagy inhibitors 3-methyladenine (3MA, 5 mM) or chloroquine (Chl, 20 µM) or with ATG5 siRNA knock-down. Cell viability and apoptosis were measured by flow cytometry and fluorescence microscopy. Autophagy was monitored by immunohistochemistry, AUTOdot and immunoblotting (WES). RESULTS: Treatment with ARN-509 led to cell death of up to 37% with 50 µM and 60% with 100 µM by day 7. The combination of 50 µM ARN-509 with autophagy inhibitors produced a further increase in cell death by day 7. Immunostaining results showed that ARN-509 induced autophagy in LNCaP cells as evidenced by elevated levels of ATG5, Beclin 1 and LC3 punctuation and by an increase in the LC3-II band detected by WES. Autophagic flux was restored by the treatment of cells with Chl, intensifying the LC3-II band. These findings were further supported by an enhanced autophagosome punctuation observed by Autodot staining. CONCLUSIONS: These data demonstrate that treatment with ARN-509 leads to increased autophagy levels in LNCaP cells. Furthermore, in combination with autophagy inhibitors, ARN-509 provided a significantly elevated antitumor effect, thus providing a new therapeutic approach potentially translatable to patients.


Assuntos
Adenina/análogos & derivados , Autofagia/efeitos dos fármacos , Cloroquina/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Tioidantoínas/administração & dosagem , Adenina/administração & dosagem , Adenina/farmacologia , Cloroquina/farmacologia , Combinação de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Masculino , Neoplasias da Próstata/patologia , Tioidantoínas/farmacologia , Resultado do Tratamento , Células Tumorais Cultivadas
8.
Clin J Am Soc Nephrol ; 15(6): 822-829, 2020 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-32381585

RESUMO

BACKGROUND AND OBJECTIVES: The general rule that every active malignancy is an absolute contraindication for kidney transplantation is challenged by kidney failure patients diagnosed with active surveillance-eligible prostate cancer during pretransplantation workup. Interdisciplinary treatment teams therefore often face the challenge of balancing the benefits of early kidney transplantation and the risk of metastatic progression. Hence, we compared the quality-adjusted life expectancy of different management strategies in kidney failure patients diagnosed with active surveillance-eligible prostate cancer during pretransplantation workup. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A discrete event simulation model was developed on the basis of a systematic literature search, clinical guidelines, and expert opinion. After model validation and calibration, we simulated four management strategies in a hypothetical cohort of 100,000 patients: Definitive treatment (surgery or radiation therapy) and listing after a waiting period of 2 years, definitive treatment and immediate listing, active surveillance and listing after a waiting period of 2 years, and active surveillance and immediate listing. Individual patient results (quality-adjusted life years; QALYs) were aggregated into strategy-specific means (± SEs). RESULTS: Active surveillance and immediate listing yielded the highest amount of quality-adjusted life expectancy (6.97 ± 0.01 QALYs) followed by definitive treatment and immediate listing (6.75 ± 0.01 QALYs). These two strategies involving immediate listing not only outperformed those incorporating a waiting period of 2 years (definitive treatment: 6.32 ± 0.01 QALYs; active surveillance: 6.59 ± 0.01 QALYs) but also yielded a higher proportion of successfully performed transplantations (72% and 74% versus 56% and 59%), with less time on hemodialysis on average (4.02 and 3.81 years versus 4.80 and 4.65 years). CONCLUSIONS: Among kidney failure patients diagnosed with active surveillance-eligible prostate cancer during pretransplantation workup, the active surveillance and immediate listing strategy outperformed the alternative management strategies from a quality of life expectancy perspective, followed by definitive treatment and immediate listing.

9.
Oncologist ; 25(7): 585-590, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32043680

RESUMO

BACKGROUND: Sertoli cell tumors (SCTs) of the testes are rare, and the literature provides only weak evidence concerning their clinical course and management. The objective of this study was to summarize evidence on SCTs' clinical presentation, clinicopathological risk factors for malignancy, treatment options, and oncological outcomes. MATERIALS AND METHODS: Data sources included Medline, Embase, Scopus, the Cochrane Database of Systematic Reviews, and Web of Science. Published case reports, case series, and cohorts were included. Data on clinicopathological variables, treatment of local or metastatic disease, site of metastasis, or survival were extracted from each study considered in this paper, and associations between clinicopathological variables and metastatic disease were analyzed. Whenever feasible, data on individual patients were collected. RESULTS: Of the 435 patients included, only one (<1%) showed local recurrence after testis-sparing surgery (TSS). Three patients underwent adjuvant retroperitoneal lymphadenectomy. Fifty patients presented with metastases, located in the retroperitoneal lymph nodes (76%), lungs (36%), and bones (16%); median time to recurrence was 12 months. Risk factors for metastatic disease included age, tumor size, necrosis, tumor extension to the spermatic cord, angiolymphatic invasion, and mitotic index. Patients with metastases had a median life expectancy of 20 months. In six patients, metastasectomy resulted in complete remission. CONCLUSION: Our findings suggest that few local recurrences result after TSS, and no adjuvant therapy can be regarded as a standard of care. Several risk factors are predictive of metastatic disease. Surgery leads to remission in metastatic disease, whereas systemic treatment alone does not result in long-term remission. IMPLICATIONS FOR PRACTICE: Testicular Sertoli cell tumors usually present without metastatic disease and show low local recurrence rates after testis-sparing surgery; no adjuvant therapy option can be regarded as a standard of care. Patients with risk factors should undergo staging investigations. Those with metastatic disease have poor prognoses, and metastasectomy may be offered in selected cases.


Assuntos
Tumor de Células de Sertoli , Neoplasias Testiculares , Humanos , Excisão de Linfonodo , Masculino , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Revisões Sistemáticas como Assunto , Neoplasias Testiculares/patologia , Neoplasias Testiculares/cirurgia
11.
World J Urol ; 38(3): 741-746, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31087122

RESUMO

PURPOSE: To investigate the outcomes of comparative studies on photoselective vaporization of the prostate (PVP) as a function of risk of bias (RoB), conflicts of interest (COI), and industrial sponsorship (IS). METHODS: We performed a systematic literature search for comparative studies on PVP [randomized controlled trials (RCTs) and non-randomized comparative studies (NRCSs)]. Study selection as well as comprehensive assessment of RoB, COIs, and IS were performed in duplicate. The identified studies were further rated by two independent board-certified urologists as either PVP-favourable or PVP-unfavourable. Descriptive statistics were performed among all identified studies and among the subgroups of studies rated as favourable and unfavourable, respectively. RESULTS: Sixty-five studies qualified for inclusion (25 RTCs and 40 NRCSs) of which 56 (86%) were rated favourable and 9 (14%) unfavourable. A majority of all studies mentioned the absence/presence of potential COIs (78%). In contrast, a sponsorship statement was only found in 29% of the investigations. Studies rated favourable demonstrated a higher percentage of COIs (39% versus 22%). IS was exclusively found among favourable studies. Furthermore, a serious or critical RoB was more often found in favourably rated NRCSs. CONCLUSIONS: COIs and IS seem to be associated with favourable study outcomes in comparative studies on PVP. The transparency of the whole research process from study conception to the dissemination of the results has to be further improved to prevent a harmful effect of COIs and IS on the internal validity of studies.


Assuntos
Conflito de Interesses , Terapia a Laser , Sintomas do Trato Urinário Inferior/cirurgia , Hiperplasia Prostática/cirurgia , Apoio à Pesquisa como Assunto , Ressecção Transuretral da Próstata , Viés , Revelação , Setor de Assistência à Saúde , Humanos , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Hiperplasia Prostática/complicações
12.
J Urol ; 203(4): 719-726, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31651228

RESUMO

PURPOSE: We sought to externally validate recently published prostate cancer risk calculators incorporating multiparametric magnetic resonance imaging to predict clinically significant prostate cancer. We also compared the performance of these calculators to that of multiparametric magnetic resonance imaging naïve prostate cancer risk calculators. MATERIALS AND METHODS: We identified men without a previous prostate cancer diagnosis who underwent transperineal template saturation prostate biopsy with fusion guided targeted biopsy between November 2014 and March 2018 at our academic tertiary referral center. Any Gleason pattern 4 or greater was defined as clinically significant prostate cancer. Predictors, which were patient age, prostate specific antigen, digital rectal examination, prostate volume, family history, previous prostate biopsy and the highest region of interest according to the PI-RADS™ (Prostate Imaging Reporting and Data System), were retrospectively collected. Four multiparametric magnetic resonance imaging prostate cancer risk calculators and 2 multiparametric magnetic resonance imaging naïve prostate cancer risk calculators were evaluated for discrimination, calibration and the clinical net benefit using ROC analysis, calibration plots and decision curve analysis. RESULTS: Of the 468 men 193 (41%) were diagnosed with clinically significant prostate cancer. Three multiparametric magnetic resonance imaging prostate cancer risk calculators showed similar discrimination with a ROC AUC significantly higher than that of the other prostate cancer risk calculators (AUC 0.83-0.85 vs 0.69-0.74). Calibration in the large showed 2% deviation from the true amount of clinically significant prostate cancer for 2 multiparametric magnetic resonance imaging risk calculators while the other calculators showed worse calibration at 11% to 27%. A clinical net benefit was observed only for 3 multiparametric magnetic resonance imaging risk calculators at biopsy thresholds of 15% or greater. None of the 6 investigated prostate cancer risk calculators demonstrated clinical usefulness against a biopsy all strategy at thresholds less than 15%. CONCLUSIONS: The performance of multiparametric magnetic resonance imaging prostate cancer risk calculators varies but they generally outperform multiparametric magnetic resonance imaging naïve prostate cancer risk calculators in regard to discrimination, calibration and clinical usefulness. External validation in other biopsy settings is highly encouraged.


Assuntos
Imageamento por Ressonância Magnética Multiparamétrica , Próstata/diagnóstico por imagem , Neoplasias da Próstata/epidemiologia , Idoso , Biópsia com Agulha de Grande Calibre/métodos , Humanos , Biópsia Guiada por Imagem/métodos , Calicreínas , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prevalência , Próstata/patologia , Antígeno Prostático Específico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Curva ROC , Estudos Retrospectivos , Medição de Risco/métodos
13.
World J Urol ; 38(10): 2485-2491, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31865534

RESUMO

OBJECTIVES: To analyze the influence of aspirin (ASA) intake on PSA values and prostate cancer (PCa) development in a prospective screening study cohort. METHODS: 4314 men from the Swiss section of the European Randomized Study of Screening for Prostate Cancer (ERSPC) were included. A transrectal prostate biopsy was performed in men with a PSA level ≥ 3 ng/ml. Mortality data were obtained through registry linkages. PCa incidence and grade, total PSA, free-to-total PSA and overall survival were compared between ASA users and non-users. RESULTS: Median follow-up time was 9.6 years. In 789 men (18.3%) using aspirin [ASA +], the overall PCa incidence was significantly lower (6.8% vs. 9.6%, p = 0.015), but the multivariate Cox regression analysis showed no significant decrease in risk of PCa diagnosis (HR 0.84, p = 0.297). Total PSA values were significantly lower in ASA users for both baseline (1.6 vs. 1.8 ng/ml, p = 0.007) and follow-up visits (1.75 vs. 2.1 ng/ml, p < 0.001). Multivariate Cox regression analysis predicted significantly higher overall mortality risk among ASA users (HR 1.46, p = 0.009). CONCLUSIONS: In our study population, PCa incidence was significantly reduced among patients on aspirin. While we did not observe a statistically significant PCa risk reduction during the follow-up period, we found lower PSA values among ASA users compared to non-users, with a more distinct difference after 4 years of ASA intake, suggesting a cumulative effect and a potential protective association between regular ASA intake and PCa development. As for clinical practice, lowering PSA cutoff values by 0.4 ng/ml could be considered in long-term ASA users to avoid a potential bias towards delayed PCa detection.


Assuntos
Aspirina/farmacologia , Detecção Precoce de Câncer , Antígeno Prostático Específico/sangue , Antígeno Prostático Específico/efeitos dos fármacos , Neoplasias da Próstata/sangue , Neoplasias da Próstata/epidemiologia , Idoso , Aspirina/uso terapêutico , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Taxa de Sobrevida , Suíça/epidemiologia
14.
J Urol ; 203(5): 949-956, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31845841

RESUMO

PURPOSE: Leydig cell tumors are rare but they are the most common nongerm cell testicular tumors. Only limited evidence exists for reliably differentiating between benign and malignant Leydig cell tumors and for optimally managing the different types and stages of this rare disease. In this review we synthesize the available evidence on the clinical presentation and clinicopathological characteristics associated with Leydig cell tumor malignancy and management. MATERIALS AND METHODS: We analyzed published case series data on Leydig cell tumors. The association between clinicopathological variables and the presence of metastatic disease was assessed using regression analyses. RESULTS: We included 357 reports, reviewing available data from 1,375 patients (median age 34 years). Testis sparing surgery was performed in 463 patients. Local recurrence after testis sparing surgery occurred in 8 of 121 (7%) patients with available followup information. Metastases were found in 101 patients and were most often located in the retroperitoneal lymph nodes (60%), lungs (38%) and/or liver (29%). The multivariable models with or without multiple imputation predicting metastatic disease included older age, larger tumor size, presence of any adverse factor (larger tumor diameter, necrosis, angiolymphatic invasion, pleomorphism, high mitotic index, atypia) and any protective factor (Reinke crystals, lipofuscin pigments, gynecomastia) with model AUCs of 0.93. Durable remission after resection of metastases or use of platinum based chemotherapy was rarely seen. CONCLUSIONS: Our risk tables using clinicopathological parameters can help identify patients with malignant tumors. These patients should undergo disease staging and be followed or receive further treatment. In some patients with metastatic disease surgical and systemic treatment might result in disease control.


Assuntos
Tumor de Células de Leydig/terapia , Neoplasias Testiculares/terapia , Terapia Combinada , Saúde Global , Humanos , Tumor de Células de Leydig/diagnóstico , Tumor de Células de Leydig/epidemiologia , Masculino , Morbidade/tendências , Fatores de Risco , Taxa de Sobrevida/tendências , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/epidemiologia , Resultado do Tratamento
15.
J Cancer Res Clin Oncol ; 145(12): 3037-3045, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31646373

RESUMO

INTRODUCTION: Because spermatocytic tumors of the testis are rare, only limited evidence exists regarding the malignant potential and the optimal management of localized and metastatic disease. MATERIALS AND METHODS: We performed a systematic review through MEDLINE, EMBASE, Scopus, Cochrane Database of Systematic Reviews and Web of Science to identify reports including patients with testicular spermatocytic tumors. RESULTS: From originally 7863 studies, we extracted data of 146 patients of which 99% were treated with radical orchiectomy. Metastases in patients with initially localised disease were diagnosed in 7% of patients and detected after a median follow-up of 5.5 months (range 2-21 months). Patients with aggressive histology (sarcoma or anaplastic subtype) were more likely to have metastatic disease (6/124 (5%) vs 9/22 (41%), p < 0.001). Patients with metastatic disease had larger primary tumors (92.5 vs 67.5 mm, p = 0.05). Life expectancy in patients with metastatic disease ranged from 1 to 25 months. CONCLUSION: The published literature does neither support the use of testis sparing surgery nor adjuvant therapy. Patients with aggressive variants or larger tumors were more likely to have metastases and develop recurrences within the first few years. Patients with metastatic disease have a limited life expectancy and metastatic spermatocytic tumors are not as responsive to chemotherapy as germ cell cancers.


Assuntos
Metástase Neoplásica/tratamento farmacológico , Espermatócitos/efeitos dos fármacos , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/cirurgia , Testículo/efeitos dos fármacos , Testículo/cirurgia , Humanos , Masculino , Neoplasias Primárias Múltiplas/tratamento farmacológico , Neoplasias Primárias Múltiplas/cirurgia , Resultado do Tratamento
16.
BMC Cancer ; 19(1): 802, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31412792

RESUMO

BACKGROUND: To validate the utility of the chemokine ligand 12 (CXCL12) as prognostic marker in patients with localized and metastatic germ cell tumors (GCT). METHODS: CXCL12 expression was analyzed on a tissue microarray consisting of 750 tissue cores of different histological tumor components, Germ cell neoplasia in situ (GCNIS) and adjacent normal tissue of 263 testicular cancer patients using a semi-quantitative score. The association between CXCL12 expression and recurrence-free survival (RFS) as well as overall survival (OS) was assessed using Kaplan-Meier curves with log-rank tests. RESULTS: CXCL12 expression was absent in all seminomas but was found in 52 of 99 (52.5%) non-seminomas. Follow-up was available for 260 patients of which 36 (13.8%) recurred. In patients with stage 1 non-seminoma GCT, CXCL12 expression was not associated with higher risk of disease recurrence (p = 0.270). In contrast, post chemotherapy RFS of patients with metastatic non-seminoma and positive CXCL12 expression was significantly shorter compared to CXCL12 negative patients (p = 0.003). OS differences were not statistically different between patients with CXCL12 positive or negative tumors for either localized or metastatic disease. CONCLUSIONS: CXCL12 is almost exclusively expressed in non-seminoma. Pure seminoma, GCNIS and adjacent normal testicular tissue are CXCL12 negative. Our analysis suggests that patients with metastatic disease and a CXCL12-positive non-seminoma are at higher risk for disease recurrence after first-line chemotherapy and might thus be candidates for more intensive treatment and/or closer follow-up.


Assuntos
Quimiocina CXCL12/genética , Quimiocina CXCL12/metabolismo , Recidiva Local de Neoplasia , Neoplasias Embrionárias de Células Germinativas/fisiopatologia , Neoplasias Testiculares/fisiopatologia , Adolescente , Adulto , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Embrionárias de Células Germinativas/metabolismo , Prognóstico , Seminoma/diagnóstico , Seminoma/fisiopatologia , Seminoma/terapia , Análise de Sobrevida , Neoplasias Testiculares/genética , Neoplasias Testiculares/metabolismo , Adulto Jovem
17.
Prostate ; 79(12): 1450-1456, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31233227

RESUMO

BACKGROUND: Prostate-specific membrane antigen (PSMA)-based imaging and therapy are increasingly used in the management of prostate cancer. However, low PSMA surface expression in certain patients is a limitation for PSMA-based technologies. We have previously shown that high doses of dutasteride, a 5α-reductase inhibitor generally used for the treatment of benign prostatic enlargement, increase the PSMA expression in vitro. We now further analyzed the concentration- and time-dependent effects of dutasteride in LNCaP cells. METHODS: Androgen receptor (AR) expressing prostate cancer cells (LNCaP) were treated for 7 to 14 days with vehicle control (0.1% dimethyl sulfoxide) or different concentrations of dutasteride (0.25 , 0.5 , 1 , and 5 µM). In addition to cell proliferation, PSMA surface expression was assessed using flow cytometry (FACS) and immunocytochemistry. Total PSMA and AR expression was analyzed by capillary western immunoassay (WES). In addition, tumor cell uptake and internalization assays of 177 Lu-PSMA-617 were performed. RESULTS: Dutasteride treatment resulted in a significant upregulation of PSMA surface expression compared to vehicle control after 7 days in all tested concentrations. After 14 days a further, concentration-dependent increase of PSMA surface expression was detectable. Total PSMA protein expression significantly increased after treatment of cells with high concentrations of dutasteride using 5 µM for 7 or 14 days. However, when lower concentrations were used total PSMA expression was not significantly altered compared to vehicle control. Further testing revealed a dose-dependent increase in uptake and internalization of 177Lu -PSMA-617 after 7 and 14 days. Though, a significantly increased uptake was only observed using a 5 µM dutasteride concentration for 7 days as well as 1 and 5 µM for 14 days. CONCLUSION: Our investigations revealed a concentration- and time-dependent effect of dutasteride on PSMA expression and uptake of 177Lu -PSMA-617 in LNCaP cells. A short-term treatment of patients with high doses of dutasteride might increase the detection rate of PSMA-based imaging and increase the effect of 177Lu -PSMA-617 therapy via upregulation of PSMA expression.


Assuntos
Inibidores de 5-alfa Redutase/farmacologia , Antígenos de Superfície/biossíntese , Dutasterida/farmacologia , Glutamato Carboxipeptidase II/biossíntese , Próstata/efeitos dos fármacos , Neoplasias da Próstata/metabolismo , Linhagem Celular Tumoral , Dipeptídeos/metabolismo , Relação Dose-Resposta a Droga , Compostos Heterocíclicos com 1 Anel/metabolismo , Humanos , Lutécio/metabolismo , Masculino , Próstata/metabolismo , Radioisótopos/metabolismo , Receptores Androgênicos/biossíntese , Regulação para Cima
18.
J Urol ; 202(4): 717-724, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31042109

RESUMO

PURPOSE: Clinically significant, localized prostate cancer is currently treated with whole gland therapy. This approach is effective but associated with genitourinary and rectal side effects. Focal therapy of prostate cancer has been proposed as an alternative. The aim of this study was to determine the oncologic and functional outcomes of focal high intensity focused ultrasound therapy of prostate cancer. MATERIALS AND METHODS: In this single center, prospective study 75 men were treated between April 2014 and April 2018. Multiparametric magnetic resonance imaging and transperineal template saturation prostate biopsy were performed to localize prostate cancer, followed by focal ablation with high intensity focused ultrasound. The study primary end point was the detection of clinically significant prostate cancer, defined as Gleason score 7 or greater, at 6-month followup transperineal template saturation prostate biopsy. Genitourinary side effects were of secondary interest. RESULTS: Median patient age was 67 years (IQR 60-71) and median prostate specific antigen was 5.87 ng/ml (IQR 4.65-7.44). There were 5 low risk (6.7%) and 70 intermediate risk (93.3%) cancers. Clinically significant prostate cancer was detected in 41% of the men (95% CI 30.3-53.0) who underwent biopsy at 6 months and the median number of sampled cores was 44 (IQR 36-44). Prostate specific antigen (OR 1.17, IQR 0.49-2.85, p=0.71) and multiparametric magnetic resonance imaging (14.3% sensitivity, IQR 6.7-31.5) performed poorly to predict positive biopsies. Pad-free continence and erection sufficient for penetration were preserved in 63 of 64 (98.4%) and 31 of 45 patients (68.9%), respectively. CONCLUSIONS: Focal therapy with high intensity focused ultrasound leads to a low rate of genitourinary side effects. Followup biopsy of treated and untreated prostates remains the only modality to adequately select men in need of early salvage treatment.


Assuntos
Tratamentos com Preservação do Órgão/métodos , Próstata/patologia , Neoplasias da Próstata/terapia , Terapia por Ultrassom/métodos , Idoso , Biópsia com Agulha de Grande Calibre , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão/efeitos adversos , Órgãos em Risco/efeitos da radiação , Seleção de Pacientes , Ereção Peniana/efeitos da radiação , Estudos Prospectivos , Próstata/diagnóstico por imagem , Próstata/efeitos da radiação , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Resultado do Tratamento , Terapia por Ultrassom/efeitos adversos , Incontinência Urinária/epidemiologia , Incontinência Urinária/etiologia
20.
J Endourol ; 33(2): 107-112, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30612441

RESUMO

INTRODUCTION AND OBJECTIVES: Bipolar plasma vaporization (BPV) has been shown to be a low-morbidity alternative to conventional transurethral resection of the prostate (TURP). Improved functional short-term outcome and a postoperative prostate volume reduction comparable to TURP have been reported. However, comprehensive mid- or long-term results following BPV are still lacking. METHODS: A consecutive series of men who underwent pure BPV in a tertiary care academic center was prospectively investigated. Clinical parameters [International Prostate Symptom Score with Quality-of-Life domain, peak urinary flow rate (Qmax), postvoid residual volume, and prostate-specific antigen] as well as prostate volume (assessed by planimetric volumetry following transrectal 3D-ultrasound) were recorded preoperatively and regularly after BPV (after catheter removal, 6 weeks, 6 months, 1 year, and 3 years). Statistical analysis was performed using the Wilcoxon signed-rank test. All p-values ≤0.05 were considered significant. RESULTS: Seventy-five men were included in this prospective investigation. Their median (interquartile range) prostate volume was 41.0 mL (30.6-57.4 mL). In the first year after BPV, the prostate volume continuously decreased over time and the relative volume reduction was 52.2% after 12 months. Subsequently, the volume reduction remained stable with 50.7% after 3 years. All investigated outcome parameters improved significantly after the procedure and remained so after 3 years. Reoperations due to persistent or regrown adenoma were not necessary. Six (8.0%) and five patients (6.6%) developed a de novo urethral stricture or bladder neck contracture, respectively. CONCLUSIONS: Three years after pure BPV of the prostate, a durable prostate volume reduction in combination with a stable improvement of functional outcome parameters was detectable in our prospective study. The low morbidity of the procedure and the possibility to perform BPV under ongoing platelet aggregation inhibition confirms its role as minimally invasive alternative to conventional TURP.


Assuntos
Eletrocirurgia , Hiperplasia Prostática/cirurgia , Idoso , Humanos , Calicreínas/sangue , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Complicações Pós-Operatórias , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/sangue , Qualidade de Vida , Resultado do Tratamento , Volatilização
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