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1.
Sci Rep ; 8(1): 8360, 2018 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-29849039

RESUMO

To evaluate the oncological results, associated complications, and postoperative health-related quality of life (HR-QoL) in patients treated with partial cystectomy (PC) for muscle-invasive bladder cancer (MIBC). 27 patients who underwent open PC for cT2 MIBC were included. A simple Cox's proportional hazards regression model was used to assess the association of several potential prognostic factors with survival. Postoperative HR-QoL was assessed with the EORTC (European Organisation for the Research and Treatment of Cancer) QLQ-C30 questionnaire version 3.0. Final pathological tumour stages in PC specimen were: pT0: 18.5%, non-MIBC: 3.7%, MIBC: 74.1%, pCIS: 14.8%. Estimated 5-year overall- and progression-free survival rates were 53.7% and 62.1%. Five (18.5%) patients experienced local recurrence with MIBC. Overall, the salvage cystectomy rate was 18.5%. The 90-day mortality rate was 0%. Significant risk factors for progression-free survival were vascular invasion (HR 5.33) and tumour multilocularity (HR 4.5) in the PC specimen, and a ureteric reimplantation during PC (HR 4.53). The rates of intraoperative complications, 30- and 90-day major complications were 7.4%, respectively and 14.8% for overall long-term complications. Postoperatively, median (IQR) global health status and QoL in our PC cohort was 79.2 (52.1-97.9). Open PC can provide adequate cancer control of MIBC with good HR-QoL in highly selected cases. Open PC can lead to long-term bladder preservation and shows an acceptable rate of severe perioperative complications, even in highly comorbid patients.


Assuntos
Cistectomia/efeitos adversos , Músculos/patologia , Complicações Pós-Operatórias/etiologia , Qualidade de Vida , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Cuidados Paliativos , Inquéritos e Questionários , Análise de Sobrevida , Resultado do Tratamento
2.
Oncotarget ; 8(29): 47110-47120, 2017 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-28445145

RESUMO

Both cholesterol levels and the use of statins have been described to influence the development and prognosis of prostate cancer (PC). In this retrospective, cross-sectional analysis of consecutive cases from a tertiary referral center we evaluated an association between hypercholesterolemia (≥5.0mmol/l), the use of statins, and advanced/aggressive PC in 767 men with histologically confirmed, clinically localized PC awaiting radical prostatectomy. We found that patients with HCE (n=287, 37.4%) had a significantly higher incidence of poorly differentiated PC (Gleason score ≥7b, 81.1% vs. 4.9%), advanced local tumor stage (≥pT3, 57.7% vs. 22.2%), and nodal involvement (19.8% vs. 1.6%). Multivariate logistic regression analysis identified hypercholesterolemia as a risk factor for aggressive and/or advanced PC (OR 2.01, p<0.001) whereas statin intake showed an odds ratio of 0.49 (p=0.005) indicating a negative association with high-risk PC. Despite a limited number of patients using statins (~9.5%), adjusted and weighed multivariate logistic regression models revealed that preoperative hypercholesterolemia is associated with a diagnosis of high-risk PC which is negatively influenced by statin intake.


Assuntos
Colesterol/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Estudos Transversais , Progressão da Doença , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/sangue , Hipercolesterolemia/complicações , Hipercolesterolemia/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Período Pós-Operatório , Período Pré-Operatório , Prognóstico , Prostatectomia , Neoplasias da Próstata/complicações , Neoplasias da Próstata/terapia , Curva ROC , Estudos Retrospectivos , Resultado do Tratamento
3.
World J Urol ; 34(5): 633-9, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26318637

RESUMO

PURPOSE: Failure of endocrine treatment in castration-resistant prostate cancer (CRPC) is often associated with the emergence of C-terminally truncated androgen receptor variants that function as constitutively active transcription factors (i.e., AR∆LBD). The mechanisms involved in the regulation of AR∆LBD signaling are largely unknown. Since the IGF-1 pathway was repeatedly shown to affect AR function, we studied whether an inhibition of IGF-1R could also affect AR∆LBD signaling. METHODS: Regulation of androgen receptor (AR) and AR∆LBD signaling was analyzed by reporter gene assays, immunoblotting, ELISA and quantitative RT-PCR. RESULTS: Inhibition of IGF-1R with the small-molecule inhibitor NVP-AEW541 reduced the transcriptional activity of the AR and its truncated counterparts Q640X and AR-V7. As shown in Q640X, the inhibition of transcriptional activity was paralleled by a decreased receptor phosphorylation. CONCLUSIONS: Inhibition of IGF-1R leads to a down-regulation of AR∆LBD signaling and provides a rationale for CRPC therapies targeting growth factor receptors.


Assuntos
Fator de Crescimento Insulin-Like I/fisiologia , Neoplasias de Próstata Resistentes à Castração/etiologia , Receptores Androgênicos/fisiologia , Transdução de Sinais , Humanos , Fator de Crescimento Insulin-Like I/antagonistas & inibidores , Masculino , Neoplasias de Próstata Resistentes à Castração/patologia , Células Tumorais Cultivadas
4.
World J Urol ; 34(3): 297-303, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26100946

RESUMO

Prostate cancer is the most prevalent non-skin cancer and the second leading cause of cancer death in men of the western world. As growth and differentiation of prostate cancer largely depend on androgens, inhibition of the androgen/androgen receptor signaling axis is the main treatment for locally advanced and/or metastatic tumors. Although first-line androgen deprivation therapies like chemical/surgical castration and/or administration of anti-androgens are able to control the disease for several years, prostate cancer almost invariably recurs as castration-resistant prostate cancer. This stage of the disease is characterized by a sustained AR-signaling despite castrate levels of circulating androgens. Various molecular mechanisms were shown to induce castration resistance. This review will discuss the most recent and relevant experimental findings on AR-signaling in castration-resistant prostate cancer in order to provide a comprehensive interpretation of the clinical behavior of this tumor entity following treatments with abiraterone, enzalutamide, ARN-509 or taxanes.


Assuntos
Androstenos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/metabolismo , Receptores Androgênicos/metabolismo , Benzamidas , Humanos , Masculino , Nitrilas , Feniltioidantoína/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Transdução de Sinais
5.
World J Urol ; 33(12): 1979-84, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25903805

RESUMO

BACKGROUND: There is evidence that obesity is associated with an aggressive prostate cancer (PC). Furthermore, preclinical studies suggest that oestrogens may play a pivotal role in this context. The biological processes underlying these observations are not fully understood. We prospectively evaluated whether obesity and/or preoperative estradiol levels are associated with high-grade cancer in patients with clinically localized PC at the time they underwent radical retropubic prostatectomy (RRP). METHODS: Preoperative sex hormone serum 17ß-estradiol (E2) as well as body mass index (BMI) and waist circumference (WC) were assessed in a cohort of 746 consecutive men treated with RP from February 2011 to October 2014. The data were correlated with patient-specific and clinicopathologic variables. RESULTS: A total of 746 patients underwent RRP. Median age was 68.0 years. Median E2 serum level was 18.3 ng/l (IQR 12.9-24.2 ng/l). Median BMI was 26.6 kg/m(2) (IQR 24.6-29.1 kg/m(2)), and the median WC was 103 cm (IQR 96-110 cm). Serum E2 below or above the normal range was not found more frequently in obese patients (high BMI: p = 0.62; large WC: p = 0.83). E2 was not associated with BMI in our cohort of patients (r = 0.07, p = 0.10) or WC (r = 0.07, p = 0.10). There was no association between preoperative serum E2 levels and tumour stage (p = 0.86, Fisher's exact), tumour grade (p = 0.37), lymph node involvement (p = 0.59) or Gleason score (p = 0.44). However, obesity correlated with tumour stage and grade (p = 0.036, Fisher's exact) and nodal metastasis (p = 0.039, Fishers' exact). CONCLUSION: Pretreatment serum 17ß-estradiol (E2) cannot be considered as a suitable marker for aggressive tumour disease in patients with localized prostate cancer.


Assuntos
Adenocarcinoma/sangue , Adenocarcinoma/patologia , Estradiol/sangue , Obesidade/complicações , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Adenocarcinoma/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Índice de Massa Corporal , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/patologia , Valor Preditivo dos Testes , Prostatectomia , Neoplasias da Próstata/complicações , Circunferência da Cintura
6.
Int Urol Nephrol ; 47(5): 765-70, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25787073

RESUMO

PURPOSE: The serum C-reactive protein (CRP) level correlates with the clinical prognosis in patients with kidney, penile and metastatic castration-resistant prostate cancer (PC). We prospectively evaluated the preoperative CRP level as a predictive marker for an advanced tumor stage or high-grade cancer in patients with clinically localized PC. METHODS: The study evaluated 629 patients with clinically localized PC who underwent radical prostatectomy between 2010 and 2013. Exclusion criteria were signs of systemic infection, symptoms of an autoimmune disease or neoadjuvant androgen deprivation. RESULTS: Poorly differentiated PC tends to be more common in patients with elevated CRP levels (15.5 vs. 9.5%, p = 0.08). Analogously, patients with a Gleason score ≥8 PC had significantly higher median CRP levels than those with a Gleason score ≤7 PC (1.9 vs. 1.2 mg/l, p = 0.03). However, neither uni- nor multivariate analysis showed an association between the preoperative CRP level and the presence of a locally advanced tumor stage, lymph node metastases or a positive surgical margin. CRP also failed to correlate with the initial PSA level and the clinical tumor-associated findings. Moreover, multivariate analysis relativized the association between an elevated CRP level and poor tumor differentiation. CONCLUSION: In patients with clinically localized PC, CRP does not appear to possess the predictive value and it was shown to have patients with other tumor entities or advanced PC.


Assuntos
Adenocarcinoma/sangue , Adenocarcinoma/secundário , Proteína C-Reativa/metabolismo , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Exame Retal Digital , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasia Residual , Valor Preditivo dos Testes , Período Pré-Operatório , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/cirurgia
7.
Urol J ; 11(3): 1569-74, 2014 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-25015600

RESUMO

PURPOSE: To examine whether surgical decompression of hematomas by capsulotomy can help to improve long-term renal function following extracorporeal shock wave lithotripsy (SWL). MATERIALS AND METHODS: This study retrospectively identified 7 patients who underwent capsulotomy for post SWL renal hematomas between 2008 and 2012. The control group comprised 8 conservatively treated patients. The median follow-up time was 22 months. RESULTS: The two groups were comparable in age, gender, body mass index, risk factors for developing hematomas (renal failure, urinary flow impairment, indwelling ureteral stent and diabetes mellitus) and the selected SWL modalities. Hematoma size was also similar. However, significantly more patients in the surgical group had purely intracapsular hematomas (85.7% vs. 37.5%) without a potentially pressure-relieving capsular rupture. There were no significant differences in the post-interventional drop in hemoglobin, rise in retention parameters or drop in glomerular filtration rate (GFR). No capsulotomy-related complications were observed, but surgery required a significantly longer hospital stay than conservative management (median, 9 days vs. 5 days). The two groups also showed comparable recovery of renal function at long-term follow-up (median change in GFR from baseline, 97.1% and 97.8%, respectively). CONCLUSION: Since renal function did not differ between the two treatment groups, the conservative management remains the standard treatment for post-SWL renal hematoma.


Assuntos
Síndromes Compartimentais/cirurgia , Descompressão Cirúrgica , Hematoma/cirurgia , Nefropatias/cirurgia , Litotripsia/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Síndromes Compartimentais/etiologia , Descompressão Cirúrgica/efeitos adversos , Feminino , Taxa de Filtração Glomerular , Hematoma/etiologia , Hemoglobinas/metabolismo , Humanos , Rim/fisiologia , Nefropatias/etiologia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Urolitíase/terapia
8.
Int J Urol ; 21(10): 980-6, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24865433

RESUMO

OBJECTIVES: To evaluate whether low testosterone levels or obesity, or both, are directly associated with tumor stage/grade in patients with clinically localized prostate cancer. METHODS: Preoperative androgen serum levels (total and free testosterone), sex hormone-binding globulin, body mass index and waist circumference were assessed in 510 consecutive European Caucasian men treated with radical prostatectomy. Hormone levels and body mass index/waist circumference were correlated with patient- and tumor-specific characteristics using multivariable logistic regression analysis. RESULTS: Even though we confirmed an inverse correlation between bodyweight and testosterone levels, only overweight - but not low testosterone - was associated with advanced disease and poor differentiation of prostate cancer. Using multivariate analyses, both body mass index ≥30 kg/m(2) and waist circumference >110 cm were associated with high-grade disease (Gleason score ≥8). A waist circumference >110 cm also correlated significantly with lymph node metastasis. CONCLUSIONS: This is the first study showing that obesity, but not low serum testosterone levels, is significantly associated with high grade and metastatic disease in men diagnosed with clinically localized prostate cancer. The present findings suggest that low androgen levels at diagnosis, which used to be held responsible for the development of aggressive prostate cancer, is only an epiphenomenon of obesity rather than the cause of prostate cancer development and/or progression.


Assuntos
Adenocarcinoma/complicações , Adenocarcinoma/secundário , Obesidade/complicações , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Testosterona/sangue , Adenocarcinoma/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/complicações , Globulina de Ligação a Hormônio Sexual/metabolismo , Circunferência da Cintura
9.
Eur Urol ; 65(1): 30-6, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23849416

RESUMO

BACKGROUND: Abiraterone, an androgen synthesis inhibitor, has been successfully used in the treatment of castration-resistant prostate cancer (CRPC) for 2 yr. Enzalutamide is a second-generation nonsteroidal antiandrogen that has recently been approved for the same indication. OBJECTIVE: This is the first study to evaluate the effectiveness of enzalutamide after failure of abiraterone. DESIGN, SETTING, AND PARTICIPANTS: Thirty-five patients were identified as having received sequential therapy with abiraterone followed by enzalutamide. All patients had undergone prior docetaxel chemotherapy, and no patient had received ketoconazole. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Posttreatment changes in prostate-specific antigen (PSA) were used to determine the activity of enzalutamide in patients who had received prior abiraterone. RESULTS AND LIMITATIONS: The median duration of abiraterone treatment was 9.0 mo (range: 2.0-19.0 mo). Of the 35 patients, 16 (45.7%) achieved a >50% decline in PSA, and 14 (40%) had a rising PSA as the best response. The median duration of subsequent enzalutamide treatment was 4.9 mo (Kaplan-Meier estimate; 95% confidence interval [CI], 2.4-7.4). Seven of 16 CRPC patients who were initially abiraterone-sensitive (43.8%) and 3 of 19 CRPC patients who were initially abiraterone-insensitive (15.8%) showed a >50% PSA decline while taking enzalutamide. Of the 35 patients, 17 (48.6%) were primarily enzalutamide-resistant and showed a rising PSA as the best response. Median time to progression was 4.0 mo (95% CI, 2.0-6.0) for 18 of 35 patients with at least one declining PSA value while taking enzalutamide (51.4%). Of the 17 patients who were assessable radiologically, only 1 (2.9%) attained a confirmed partial response. Small sample size was the major limitation. CONCLUSIONS: Enzalutamide treatment achieved only a modest response rate in patients progressing after abiraterone. Although cross-resistance between abiraterone and enzalutamide was a common phenomenon, it was not inevitable, and a small but significant number of patients showed significant benefit from sequential treatment.


Assuntos
Androstenóis/uso terapêutico , Antineoplásicos/uso terapêutico , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Androstenos , Benzamidas , Progressão da Doença , Docetaxel , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilas , Feniltioidantoína/uso terapêutico , Projetos Piloto , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/sangue , Falha de Tratamento
10.
BMC Urol ; 13: 53, 2013 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-24148787

RESUMO

BACKGROUND: The nodal status is a strong predictor for cancer specific death in patients with penile carcinoma, and the C-reactive protein (CRP) level at diagnosis has recently been shown to be associated with poor clinical outcome in various solid malignancies. Therefore, this retrospective study was performed to evaluate the association between preoperative CRP levels and the incidence of nodal metastasis in patients with squamous cell carcinoma (SCC) of the penis. METHODS: The analysis included 51 penile cancer patients who underwent either radical or partial penectomy for pT1-4 penile cancer between 1990 and 2010. The nodal status was correlated with patient and tumor specific characteristics. RESULTS: Sixteen (31%) patients had lymph node metastasis at the time of penile cancer surgery. Nodal status was associated with tumor stage but did not correlate significantly with tumor grade. In contrast, high presurgical CRP levels were significantly associated with the diagnosis of nodal involvement (p = 0.04). The optimal CRP cut-off value to predict lymph node metastasis was set at 20 mg/l based on ROC analysis. CONCLUSIONS: Since a high preoperative serum CRP level was closely correlated with nodal disease, it could be used as an additional marker to help identify patients with penile cancer who may benefit from inguinal lymph node dissection.


Assuntos
Biomarcadores Tumorais/sangue , Proteína C-Reativa/metabolismo , Carcinoma de Células Escamosas/secundário , Neoplasias Penianas/sangue , Neoplasias Penianas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/mortalidade , Alemanha/epidemiologia , Humanos , Incidência , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Taxa de Sobrevida
11.
BMC Cancer ; 13: 223, 2013 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-23642165

RESUMO

BACKGROUND: High levels of circulating C-reactive protein (CRP) have recently been linked to poor clinical outcome in various malignancies. The aim of this study was to evaluate the prognostic significance of the preoperative serum CRP level in patients with squamous cell carcinoma (SCC) of the penis. METHODS: This retrospective analysis included 79 penile cancer patients with information about their serum CRP value prior to surgery who underwent either radical or partial penectomy at two German high-volume centers (Ulm University Medical Center and Hannover Medical School) between 1990 and 2010. They had a median (mean) follow-up of 23 (32) months. RESULTS: A significantly elevated CRP level (>15 vs. ≤ 15 mg/l) was found more often in patients with an advanced tumor stage (≥pT2) (38.9 vs. 11.6%, p=0.007) and in those with nodal disease at diagnosis (50.0 vs. 14.6%, p=0.007). However, high CRP levels were not associated with tumor differentiation (p=0.53). The Kaplan-Meier 5-year cancer-specific survival (CSS) rate was 38.9% for patients with preoperative CRP levels above 15 mg/l and 84.3% for those with lower levels (p=0.001). Applying multivariate analysis and focusing on the subgroup of patients without metastasis at the time of penile surgery, both advanced local tumor stage (≥pT2; HR 8.8, p=0.041) and an elevated CRP value (>15 mg/l; HR 3.3, p=0.043) were identified as independent predictors of poor clinical outcome in patients with penile cancer. CONCLUSIONS: A high preoperative serum CRP level was associated with poor survival in patients with penile cancer. If larger patient populations confirm its prognostic value, its routine use could enable better risk stratification and risk-adjusted follow-up of patients with SCC of the penis.


Assuntos
Biomarcadores Tumorais/sangue , Proteína C-Reativa/metabolismo , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/secundário , Neoplasias Penianas/sangue , Neoplasias Penianas/patologia , Idoso , Carcinoma de Células Escamosas/cirurgia , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Neoplasias Penianas/cirurgia , Período Pré-Operatório , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida
12.
World J Urol ; 31(2): 253-9, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22763628

RESUMO

PURPOSE: To evaluate the clinical value of the pre-treatment calculated free testosterone (fT), total testosterone (tT), sexual hormone-binding globulin (SHBG) and estradiol (E2) levels as potential predictors of pathological stage and grade in patients with clinically localized prostate cancer. METHODS: Preoperative sex hormone serum levels were prospectively measured in 137 patients who underwent radical prostatectomy at the University Hospital Ulm from February 2011 to February 2012. We related sex hormone levels to clinicopathologic data including tumour stage, Gleason score and prostate specific antigen (PSA). (Non)parametric statistical tests and receiver operating characteristics (ROC) analyses were performed. RESULTS: Preoperative serum fT levels were significantly associated with advanced disease (pT3-4 and/or pN+; p = 0.047) and lymph node involvement (pN+) (p = 0.027). Patients with low (<0.047 µg/l) vs. normal fT values (≥0.047 µg/l) were associated with higher tumour stage (p = 0.049), positive lymph node status (pN+ , p = 0.038) and advance disease (p = 0.016). Moreover, low tT values (≤0.193 µg/l; p = 0.018) and elevated SHBG levels (>48.4 nmol/l, p = 0.043) correlated with a higher Gleason score. Conversely, E2 levels were not associated with tumour stage or grade. Applying multivariate analysis, unlike tT, SHBG, and E2 levels, low fT levels were a significant independent predictor of advanced disease (relative hazard ratio 3.05, p = 0.028). CONCLUSIONS: Low pre-treatment fT levels were significantly associated with tumour stage and extraprostatic tumour spread and might-in addition or combination with PSA-serve as a useful prognostic parameter for prostate cancer patients prior to radical prostatectomy.


Assuntos
Neoplasias da Próstata/sangue , Testosterona/sangue , Idoso , Estradiol/sangue , Humanos , Calicreínas/sangue , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Curva ROC , Globulina de Ligação a Hormônio Sexual/metabolismo
13.
ISRN Urol ; 2012: 304205, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22675643

RESUMO

Objective. To evaluate functional outcome of the retrourethral transobturator sling suspension (RTS) in the treatment of stress urinary incontinence (SUI) caused by prior prostate surgery. Methods. The RTS (AdVance male sling) was implanted in 32 patients who suffered from mild to severe postsurgical-treatment incontinence at the University Hospital Ulm from September 2010 to September 2011 including 10 patients with prior radiation therapy. Functional data (uroflowmetry, daily pad use, and postvoid residual urine) as well as quality of life with impact of urinary problems (ICIQ-UI SF) were prospectively assessed at baseline and during followup. Results. After a median followup of 9 months (range, 3-14) the incontinence cure rate (no pad usage) was 56.2% and the improvement rate (1-2 pads/day or ≥50% reduction) was 21.9%. No improvement was observed in 21.9%. Daily pad use and ICIQ-UI SF score improved significantly. No major perioperative complications occurred. Postoperatively, 15.6% of the patients exhibited transient acute urinary retention which resolved without further treatment after a maximum of 3 weeks. One patient underwent sling explantation due to dislocation and persistent perineal pain. Conclusions. The implantation of the RTS is a safe and effective procedure in selected patients with SUI resulting from prostate surgery.

14.
ISRN Urol ; 2012: 342796, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22523713

RESUMO

Objective. To evaluate and compare noncontinent and continent urinary diversion after radical cystectomy in patients with bladder cancer. Methods. A total of 301 patients submitted to radical cystectomy at the Charité-University Hospital Berlin from 1993 to 2007 including 146 with an ileal conduit and 115 with an ileal neobladder. Clinical and pathological data as well as oncological outcome were retrospectively analyzed and compared. Quality of life was analyzed using the EORTC QLQ-C30 and BLM30 questionnaires. Results. 69.1% and 69.6% of all patients who received an ileal conduit and ileal neobladder, respectively, developed early complications. The two groups differed significantly concerning the occurrence of postoperative ileus (P = 0.02) favoring patients who received an ileal conduit but not with regard to any other early-onset complication evaluated. Patients with ileal neobladder had a significantly better global health status and quality of life (P = 0.02), better physical functioning (P = 0.02), but also a higher rate of diarrhoea (P = 0.004). Conclusion. Cystectomy with any type of diversion remains a complication-prone surgery. Even if the patient groups are not homogeneous in all respects, there are many arguments in favor of the ileal neobladder as the urinary diversion of choice.

15.
World J Urol ; 30(6): 733-9, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22322390

RESUMO

PURPOSE: To assess long-term clinical and oncological outcome in women undergoing radical cystectomy and ileal neobladder reconstruction for invasive bladder cancer. METHODS: From 1995 to 2010, a total of 121 women with clinically organ-confined urothelial carcinoma underwent radical cystectomy with an orthotopic ileal neobladder. Median follow-up was 56 months. Clinical course, functional, pathological, and oncological outcome of these women were analyzed. RESULTS: Seventy-six patients (62.8%) experienced a complication of some type within 90 days of the procedure. 56 patients (46.3%) experienced minor complications, whereas 20 patients (16.5%) experienced major complications. Pathological subgroups included 70 patients (57.9%) with organ confined, lymph node-negative tumors, 24 (19.8%) with extravesical, lymph node-negative disease and 27 (22.3%) patients with lymph node-positive disease. The 5-year overall survival rate in patients with organ-confined (≤pT2, pN0), locally advanced (≥pT3, pN0), and metastatic disease was 80.2%, 81.9%, and 45.1%, respectively. 4 women (3.3%) experienced a local (pelvic) recurrence. One patient presented with a urethral recurrence (0.8%). Daytime and nighttime urinary continence (0-1 pad) was reported by 82.4 and 76.5%, respectively. Clean intermittent self-catheterization was required by 58.0%. The retrospective study design was the major limitation of the study. CONCLUSIONS: Despite a considerable complication rate, radical cystectomy with orthotopic diversion in female patients with bladder cancer may be considered a standard therapeutic option for selected patients with excellent oncological outcome including a low incidence of local and urethral recurrence.


Assuntos
Carcinoma de Células de Transição/cirurgia , Cistectomia/métodos , Íleo/cirurgia , Neoplasias da Bexiga Urinária/cirurgia , Bexiga Urinária/fisiologia , Derivação Urinária/métodos , Coletores de Urina , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/mortalidade , Feminino , Seguimentos , Humanos , Incidência , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/mortalidade , Incontinência Urinária/epidemiologia
16.
World J Urol ; 30(3): 333-9, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22362413

RESUMO

PURPOSE: A recently identified mechanism allowing prostate cancer (PCa) cells to grow in the absence of androgens is the expression of constitutively active, C-terminally truncated androgen receptor (AR) variants lacking vast parts of the ligand-binding domain. These AR variants termed ARΔLBD are either products of alternative splicing, point mutations leading to premature stop codons or proteolytic cleavage of the AR. Some controversies exist about the requirement of additional full-length AR for the full transcriptional activity of the ARΔLBD. On basis of a mutated, C-terminally truncated AR termed Q640X, we developed an experimental model for the study of ARΔLBD in PCa cells. METHODS: Activation of AR-dependent promoters was analyzed by reporter gene assays. Dimerization studies were conducted using a mammalian two-hybrid system. RESULTS: Although Q640X/Q640X homodimers were able to induce the expression of certain AR target genes, Q640X/AR heterodimers were necessary to activate the full panel of androgen-dependent genes under androgen-deprived conditions. CONCLUSIONS: The following study supports the hypothesis that castration-resistant prostate cancer (CRPC) cells are able to activate specific androgen-dependent genes by selective modulation of the ratio between ARΔLBD and their putative dimerization partners like the full-length AR or other ARΔLBD in the absence of androgens. The present data suggest that AR-mutant Q640X is a powerful experimental tool for the functional analysis of ARΔLBD in CRPC.


Assuntos
Variação Genética/genética , Modelos Biológicos , Mutação/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/fisiopatologia , Receptores Androgênicos/genética , Receptores Androgênicos/fisiologia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/fisiopatologia , Androgênios/genética , Androgênios/fisiologia , Castração , Linhagem Celular Tumoral , Dimerização , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Masculino , Neoplasias da Próstata/patologia , Transfecção , Falha de Tratamento
17.
World J Urol ; 30(4): 541-6, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21947551

RESUMO

OBJECTIVE: The risk of local recurrence after radical prostatectomy (RP) is considerably dependent on local tumor stage. To improve local staging, the aim of this study was to assess the feasibility of quantitative methylation-specific PCR (Q-MSP) for the identification of promoter hypermethylation of the detoxifying glutathione-S-transferase P1 gene (GSTP1) to detect occult prostate cancer (PCa) cells in the prostatic fossa after RP. METHODS: A total of 39 consecutive patients with clinically organ-confined PCa underwent RP. After gland excision, biopsies were obtained from eight defined areas of the prostatic fossa and bisected for both histopathological and molecular analyses. Results were related to clinicopathological data including tumor stage, Gleason score, prostate-specific antigen (PSA), and biochemical recurrence. RESULTS: Of 39 patients, 11 with PCa had at least one positive molecular margin status indicated by GSTP1 methylation. These included 5 of 17 (29.4%) with organ-confined and 6 of 22 (27.3%) with advanced (≥pT3 and/or pN+) PCa. GSTP1 methylation in surgical margins strongly correlated with histopathological R-status (P = 0.022) and preoperative PSA (P = 0.01) whereas no association with tumor stage (pT2 vs pT3), grade (Gleason score <7 vs ≥7), and lymph node status was found. No patient experienced biochemical relapse. CONCLUSIONS: GSTP1 hypermethylation detected by Q-MSP in prostatic fossa biopsies after RP is well suited for the detection of occult tumor cells in surgical margins. However, the limited number of patients and the short-term follow-up does not allow definite conclusions on the prognostic value of GSTP1 in surgical margins.


Assuntos
Ilhas de CpG/genética , Metilação de DNA , DNA de Neoplasias/genética , Glutationa S-Transferase pi/genética , Neoplasias Primárias Desconhecidas/patologia , Reação em Cadeia da Polimerase/métodos , Prostatectomia/métodos , Neoplasias da Próstata/patologia , Idoso , Biópsia , DNA de Neoplasias/metabolismo , Estudos de Viabilidade , Seguimentos , Glutationa S-Transferase pi/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Próstata/patologia , Próstata/cirurgia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/genética , Neoplasias da Próstata/cirurgia
18.
World J Surg Oncol ; 9: 126, 2011 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-21992771

RESUMO

BACKGROUND: Whenever technically feasible and oncologically justified, nephron-sparing surgery is the current standard of care for localized renal cell carcinomas (RCC). The main complications of partial nephrectomy, especially for large and centrally located tumors, are urinary leakage and parenchymal bleeding. We prospectively evaluated the pros and cons of using porcine small intestinal submucosa (SIS, Surgisis®) to close the renal defect after nephron-sparing surgery. METHODS: We used Surgisis® (Cook medical, Bloomington, IN, USA) to secure and compress the capsular defect after tumor resection in 123 patients submitted to 129 partial nephrectomies between August 2003 and February 2011. RESULTS: The median tumor size was 3.7 cm (range 1.1-13.0 cm). Procedures were performed with cold ischemia in 24 cases (18.2%), with warm ischemia in 46 (35.6%), and without ischemia in 59 cases (44.8%). In the total group of patients, 4 (3.1%) developed urinary fistula, and only 2 (1.6%) required postoperative transfusions due to hemorrhage after the application of the small intestinal submucosa membrane. CONCLUSION: Small intestinal submucosa is an easy-to-use biomaterial for preventing complications such as postoperative bleeding and urinary fistula in nephron-sparing surgery, especially in cases where tumor excision causes significant renal capsular and/or renal pelvic defects.


Assuntos
Curativos Biológicos , Carcinoma de Células Renais/cirurgia , Mucosa Intestinal , Intestino Delgado , Neoplasias Renais/cirurgia , Nefrectomia , Animais , Humanos , Estudos Prospectivos , Suínos , Estados Unidos , Isquemia Quente
20.
J Urol ; 185(2): 706-11, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21168877

RESUMO

PURPOSE: Sarcosine in prostate cancer tissue samples was recently reported to be increased during prostate cancer progression to metastasis and suggested to be a key metabolite of cancer cell invasion and aggressiveness. We reevaluated sarcosine in prostate cancer tissue samples as a potential indicator of tumor aggressiveness, and as a predictor of recurrence-free survival. MATERIALS AND METHODS: Sarcosine in matched samples of malignant and nonmalignant tissue from 92 patients with prostate cancer after radical prostatectomy was measured in the framework of a global metabolite profiling study of prostate cancer by gas chromatography/mass spectrometry. We related results to age, prostate volume, tumor stage, Gleason score, preoperative prostate specific antigen and biochemical recurrence, defined as a persistent prostate specific antigen increase of greater than 0.2 ng/ml. Nonparametric statistical tests, ROC curves and Kaplan-Meier analyses were done. RESULTS: Median sarcosine content in tissue was about 7% higher in matched malignant vs nonmalignant samples, which was significantly. Sarcosine values were not associated with tumor stage (pT2 vs pT3), tumor grade (Gleason score less than 7 vs 7 or greater) or biochemical recurrence. The lack of metastatic tissue samples was a study limitation. CONCLUSIONS: Sarcosine in prostate cancer tissue samples cannot be considered a suitable predictor of tumor aggressiveness or biochemical recurrence.


Assuntos
Biomarcadores Tumorais/metabolismo , Recidiva Local de Neoplasia/patologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Sarcosina/metabolismo , Idoso , Análise de Variância , Biomarcadores Tumorais/urina , Biópsia por Agulha , Estudos de Coortes , Diagnóstico Diferencial , Progressão da Doença , Intervalo Livre de Doença , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/fisiopatologia , Cuidados Pós-Operatórios/métodos , Cuidados Pré-Operatórios , Prognóstico , Modelos de Riscos Proporcionais , Antígeno Prostático Específico/sangue , Prostatectomia/métodos , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/fisiopatologia , Curva ROC , Valores de Referência , Sarcosina/urina , Sensibilidade e Especificidade , Análise de Sobrevida
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