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1.
Psychooncology ; 31(2): 227-237, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34467601

RESUMO

OBJECTIVE: Men diagnosed with localized prostate cancer (lPCa) are confronted with the decision for a treatment strategy, potentially experiencing treatment side effects and psychological distress. The Common Sense Model proposes that coping with such challenges is related to illness representations: Beliefs regarding consequences, coherence, timeline, and controllability of the illness. We analyzed the interplay of illness representations, coping and anxiety over an 18-month period among men with lPCa undergoing different treatment options (Active Surveillance, curative treatment). METHODS: In this longitudinal study, 183 men (age M = 66.83) answered a questionnaire before starting treatment, and 6, 12, and 18 months later. We analyzed time trajectories with growth curve modeling and conducted mediation analyses to evaluate the influence of coping on the association of illness representations and anxiety. Using a novel methodological approach, we compared a classic parallel mediation model with a level-contrast approach for the correlated mediators problem- and emotion-focused coping. RESULTS: Independent of treatment (b = 1.31, p = 0.200) men reported an elevated level of anxiety after diagnosis which declined considerably within the following 6 months (b = -1.87, p = 0.009). The perceived seriousness of consequences was significantly associated with greater anxiety, at baseline (ß = 0.471) and over time (all ß ≥ 0.204). This association was mediated by coping: Using more emotion-than problem-focused coping was associated with higher anxiety. CONCLUSIONS: Receiving a lPCa diagnosis is associated with a phase of increased anxiety. In order to reduce anxiety, information provision should be accompanied by developing concrete action plans to enable problem-focused coping strategies.


Assuntos
Adaptação Psicológica , Neoplasias da Próstata , Ansiedade/psicologia , Pré-Escolar , Emoções , Humanos , Estudos Longitudinais , Masculino , Neoplasias da Próstata/terapia
2.
World J Urol ; 38(6): 1501-1507, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31463559

RESUMO

BACKGROUND: Patients with localized prostate cancer (PCa) experience biochemical recurrence (BCR) despite a curatively intended radical prostatectomy (RP). The aim of this study was to describe the quality of life (QoL) of patients with a BCR while identifying predictors of early (ER) and late recurrence (LR). METHODS: For this purpose, a total of 330 PCa patients with a BCR following RP at Charité University Hospital in Berlin were analyzed. BCR was defined as two consecutive PSA values ≥ 0.2 after a previous non-detectable level. LR was defined as a BCR after 3 years post-RP. Differences in overall survival (OS) were calculated using the log-rank testing. A logistic regression model was applied to identify predictors of ER and LR. We further evaluated difference between ER and LR with respect to functional outcomes in urinary and sexual domains as well as the patients QoL. RESULTS: Out of 330 patients, 180 patients showed late BCR. Patients rated their global QoL with 64.5% in ER and 68.8% LR as good (EORTC quality of life Questionnaire, question 29 and 30). The questionnaire did not reveal QoL differences in terms of sexual and urinary function within ER and LR. The main predictor for LR was preoperative serum prostate-specific antigen (PSA) levels with a relative risk (RR) of 0.96 (p = 0.011). OS for patients with LR was significant longer than for patients with ER (154.3 vs. 143.2 months, p = 0.018). CONCLUSION: Patients with a BCR show a good quality of life possibly irrespective of the time point of BCR. We further identified preoperative PSA levels as a predictor of LR and noted that patients with LR patients lived longer. Further studies are needed.


Assuntos
Recidiva Local de Neoplasia/sangue , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/cirurgia , Qualidade de Vida , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Prostatectomia/métodos , Estudos Retrospectivos , Fatores de Tempo
3.
N Engl J Med ; 375(23): 2246-2254, 2016 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-27718781

RESUMO

BACKGROUND: Sunitinib, a vascular endothelial growth factor pathway inhibitor, is an effective treatment for metastatic renal-cell carcinoma. We sought to determine the efficacy and safety of sunitinib in patients with locoregional renal-cell carcinoma at high risk for tumor recurrence after nephrectomy. METHODS: In this randomized, double-blind, phase 3 trial, we assigned 615 patients with locoregional, high-risk clear-cell renal-cell carcinoma to receive either sunitinib (50 mg per day) or placebo on a 4-weeks-on, 2-weeks-off schedule for 1 year or until disease recurrence, unacceptable toxicity, or consent withdrawal. The primary end point was disease-free survival, according to blinded independent central review. Secondary end points included investigator-assessed disease-free survival, overall survival, and safety. RESULTS: The median duration of disease-free survival was 6.8 years (95% confidence interval [CI], 5.8 to not reached) in the sunitinib group and 5.6 years (95% CI, 3.8 to 6.6) in the placebo group (hazard ratio, 0.76; 95% CI, 0.59 to 0.98; P=0.03). Overall survival data were not mature at the time of data cutoff. Dose reductions because of adverse events were more frequent in the sunitinib group than in the placebo group (34.3% vs. 2%), as were dose interruptions (46.4% vs. 13.2%) and discontinuations (28.1% vs. 5.6%). Grade 3 or 4 adverse events were more frequent in the sunitinib group (48.4% for grade 3 events and 12.1% for grade 4 events) than in the placebo group (15.8% and 3.6%, respectively). There was a similar incidence of serious adverse events in the two groups (21.9% for sunitinib vs. 17.1% for placebo); no deaths were attributed to toxic effects. CONCLUSIONS: Among patients with locoregional clear-cell renal-cell carcinoma at high risk for tumor recurrence after nephrectomy, the median duration of disease-free survival was significantly longer in the sunitinib group than in the placebo group, at a cost of a higher rate of toxic events. (Funded by Pfizer; S-TRAC ClinicalTrials.gov number, NCT00375674 .).


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma de Células Renais/tratamento farmacológico , Indóis/administração & dosagem , Neoplasias Renais/tratamento farmacológico , Nefrectomia , Pirróis/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Carcinoma de Células Renais/cirurgia , Quimioterapia Adjuvante , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Indóis/efeitos adversos , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Pirróis/efeitos adversos , Sunitinibe , Análise de Sobrevida , Adulto Jovem
4.
BMC Urol ; 19(1): 9, 2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30665424

RESUMO

BACKGROUND: Treatment for localized prostate cancer (PCa) can cause long-term changes in erectile functioning. However, data on the importance of sexuality and possible consequences of altered erectile functioning on self-esteem in men with localized PCa are lacking. METHODS: Self-report questionnaires were completed by 292 men with PCa, initially managed with active surveillance (AS) or radical prostatectomy (RP). Independent t-tests were conducted to evaluate group differences. A sequential multiple regression model was fitted to analyze the associations between the importance of sexuality, changes in erectile functioning and impairment of self-esteem. Interaction effects were tested using simple slope analyses. RESULTS: Participants were 70 ± 7.2 years old and 66.5% rated sex as being "rather/very important". The two groups differed markedly in changes in erectile functioning, importance of sexuality and impairment of self-esteem (p < .001), with higher values in RP patients. Regression analysis showed that after adjustment for control variables and importance of sexuality, changes in erectile functioning were still associated with impairment of self-esteem (B = .668, SE = .069, p < .001). The interaction of changes in erectile functioning and importance of sexuality reached significance (B = .318, SE = .062, p < .001). CONCLUSIONS: RP patients report more changes in erectile functioning than AS patients. Moreover, in men with localized PCa, erectile functioning and self-esteem are closely related. Sexuality seems to be important for the majority of these men. Physicians should address the possibility of erectile dysfunction and its potential effects on psychological well-being before the treatment decision.


Assuntos
Disfunção Erétil/cirurgia , Ereção Peniana/fisiologia , Neoplasias da Próstata/cirurgia , Autoimagem , Comportamento Sexual/fisiologia , Idoso , Idoso de 80 Anos ou mais , Disfunção Erétil/diagnóstico , Disfunção Erétil/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Ereção Peniana/psicologia , Estudos Prospectivos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/psicologia , Autorrelato , Comportamento Sexual/psicologia
5.
BJU Int ; 122(5): 774-782, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29633515

RESUMO

OBJECTIVE: To investigate non-inferiority of intermittent docetaxel compared to continuous docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC). PATIENT AND METHODS: The investigator initiated randomised phase III study included 187 chemotherapy-naïve patients with mCRPC who were allocated to two treatment arms: intermittent docetaxel and continuous docetaxel. Docetaxel was applied in both arms as weekly (35 mg/m2 ) or 3-weekly (75 mg/m2 ). The primary endpoint was 1-year survival, which was tested for non-inferiority (margin δ = 0.125). The secondary endpoints were: overall survival (OS), progression-free survival (PFS), median time to treatment failure (TTF), and toxicity. RESULTS: Of 156 eligible patients, 78 were allocated to each arm. The intermittent treatment met the non-inferiority criteria for 1-year survival (two-sided 95% confidence interval, -0.12, 18, P = 0.022), but not for OS, according to the result of a post hoc analysis. The differences between the study arms in PFS and TTF were not significant. The median (range) treatment holiday in the intermittent arm was 110 (13-486) days, or 38% of the overall treatment duration. Safety profiles of both study arms were comparable. The main limitation of this study was that the planned number of patients could not be recruited. CONCLUSION: Intermittent docetaxel chemotherapy was non-inferior to continuous therapy for 1-year survival; non-inferiority in regard to OS was not reached.


Assuntos
Docetaxel , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Docetaxel/administração & dosagem , Docetaxel/efeitos adversos , Docetaxel/uso terapêutico , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia
6.
Urol Int ; 101(3): 256-262, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30253389

RESUMO

INTRODUCTION: The purpose of this study was to evaluate whether the number of radical prostatectomies per hospital per year is associated with stage distribution, surgical techniques or quality related outcome in Germany. MATERIALS AND METHODS: A German Internet-based database was analyzed. Hospitals were categorized according to their yearly radical prostatectomy (RP) volume. Patient's characteristics, RP techniques, and outcome-related parameters were compared between the different hospital volume categories. RESULTS: A total of 6,447 patients were analyzed. The highest rate of organ-confined disease and the lowest rate of extracapsular invasion have been demonstrated in very low-volume centres (72.6%

Assuntos
Prostatectomia/efeitos adversos , Prostatectomia/estatística & dados numéricos , Neoplasias da Próstata/cirurgia , Idoso , Perda Sanguínea Cirúrgica , Alemanha , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Próstata/patologia , Próstata/cirurgia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia , Risco , Procedimentos Cirúrgicos Robóticos , Glândulas Seminais/patologia , Resultado do Tratamento
7.
Urol Int ; 98(2): 184-190, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-26963286

RESUMO

OBJECTIVES: Current evidence of sequence-targeted therapy (TT) for patients with metastatic renal cell carcinoma (mRCC) beyond fourth-line is sparse. The aim of this study was to describe the efficacy and toxicity of fifth-line TT in patients with mRCC. METHODS: Out of 406 patients treated in first-line, 25 patients (6.16%) with more than 4 lines of TT were retrospectively reviewed at a German academic high-volume cancer center. Response was assessed by the use of standard Response Evaluation Criteria in Solid Tumors version 1.0, and toxicity was graded according to the Common Toxicity Criteria for Adverse Events version 3.0. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Cox proportional hazard models were applied to explore predictors of PFS and OS in univariable and multivariable analyses. RESULTS: Disease control rate for fifth-line treatment was 20%. Median OS from the beginning of first-line therapy was 50.2 months (IQR (interquartile range) 38.9-76.7). Median OS from the time of initiation of fifth-line therapy was 6.2 months (IQR 3.1-23.8). Median PFS for fifth-line TT was 4.1 months (IQR 1.81-9.07) and did not correlate to treatment response in first-line TT. CONCLUSIONS: Highly selected patients might benefit from fifth-line treatment independently from treatment response in first-line TT.


Assuntos
Carcinoma de Células Renais/terapia , Neoplasias Renais/terapia , Idoso , Intervalo Livre de Doença , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Análise Multivariada , Nefrectomia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
8.
Urol Int ; 98(2): 191-197, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27732978

RESUMO

BACKGROUND: Cancer-related fatigue is a common symptom in patients with renal cell carcinoma (RCC) and can be similar to the fatigue found in late-onset hypogonadism (LOH). The aim of this study was to investigate the prevalence of LOH in patients with localized RCC (loRCC) and metastatic RCC (mRCC) disease under targeted therapy (TT) and compare the results to findings of epidemiologic studies. METHODS: A total of 51 mRCC patients under TT and 33 patients with loRCC undergoing nephrectomy were included. Total testosterone (tT) levels and clinical signs of LOH were recorded (testicular volume, body-mass index (BMI), hip-to-waist ratio, International Index of Erectile Function, IIEF-5, Androgen Deficiency in the Aging Male, ADAM, and quality of life questionnaire-C30). LOH was defined according to current guidelines. RESULTS: Morning tT and calculated free testosterone levels showed no significant difference in patients with mRCC and loRCC (p = 0.551 and p = 0.430). A significant difference was found for clinical signs and symptoms including the ADAM score (p = 0.003), hip-to-waist ratio (p = 0.017) and testicular volume (p < 0.001). IIEF-5 score and BMI were not significantly different. The prevalence of LOH according to the current EAU definition was 13.7 and 15.2% for the mRCC and loRCC cohort, respectively (p = 0.302). CONCLUSIONS: LOH was present in a significant proportion of RCC patients. Prevalence rates of LOH were higher in patients with RCC compared to patients without cancer.


Assuntos
Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/tratamento farmacológico , Hipogonadismo/complicações , Hipogonadismo/tratamento farmacológico , Neoplasias Renais/complicações , Neoplasias Renais/tratamento farmacológico , Idoso , Androgênios/uso terapêutico , Índice de Massa Corporal , Carcinoma de Células Renais/epidemiologia , Estudos de Coortes , Humanos , Hipogonadismo/epidemiologia , Neoplasias Renais/epidemiologia , Perda de Heterozigosidade , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prevalência , Estudos Prospectivos , Qualidade de Vida , Globulina de Ligação a Hormônio Sexual/metabolismo , Inquéritos e Questionários , Testículo/fisiologia , Testosterona/sangue , Testosterona/uso terapêutico
9.
Am J Physiol Renal Physiol ; 311(6): F1198-F1210, 2016 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-27681558

RESUMO

Activation of the thick ascending limb (TAL) Na+-K+-2Cl- cotransporter (NKCC2) by the antidiuretic hormone arginine vasopressin (AVP) is an essential mechanism of renal urine concentration and contributes to extracellular fluid and electrolyte homeostasis. AVP effects in the kidney are modulated by locally and/or by systemically produced epoxyeicosatrienoic acid derivates (EET). The relation between AVP and EET metabolism has not been determined. Here, we show that chronic treatment of AVP-deficient Brattleboro rats with the AVP V2 receptor analog desmopressin (dDAVP; 5 ng/h, 3 days) significantly lowered renal EET levels (-56 ± 3% for 5,6-EET, -50 ± 3.4% for 11,12-EET, and -60 ± 3.7% for 14,15-EET). The abundance of the principal EET-degrading enzyme soluble epoxide hydrolase (sEH) was increased at the mRNA (+160 ± 37%) and protein levels (+120 ± 26%). Immunohistochemistry revealed dDAVP-mediated induction of sEH in connecting tubules and cortical and medullary collecting ducts, suggesting a role of these segments in the regulation of local interstitial EET signals. Incubation of murine kidney cell suspensions with 1 µM 14,15-EET for 30 min reduced phosphorylation of NKCC2 at the AVP-sensitive threonine residues T96 and T101 (-66 ± 5%; P < 0.05), while 14,15-DHET had no effect. Concomitantly, isolated perfused cortical thick ascending limb pretreated with 14,15-EET showed a 30% lower transport current under high and a 70% lower transport current under low symmetric chloride concentrations. In summary, we have shown that activation of AVP signaling stimulates renal sEH biosynthesis and enzyme activity. The resulting reduction of EET tissue levels may be instrumental for increased NKCC2 transport activity during AVP-induced antidiuresis.


Assuntos
Desamino Arginina Vasopressina/farmacologia , Eicosanoides/metabolismo , Epóxido Hidrolases/metabolismo , Rim/efeitos dos fármacos , Membro 1 da Família 12 de Carreador de Soluto/metabolismo , Animais , Rim/metabolismo , Camundongos , Fosforilação/efeitos dos fármacos , Ratos , Ratos Brattleboro
10.
BJU Int ; 118(5): 750-757, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26915345

RESUMO

OBJECTIVES: To verify retrospectively the margin status and analyse the location and characteristics of positive surgical margins (PSMs) in patients undergoing radical prostatectomy (RP), by a central pathology review, based on the consensus conference 2009 updated margin criteria from the International Society of Urological Pathology (ISUP). PATIENTS AND METHODS: The detailed PSM characteristics of 441 patients who underwent laparoscopic RP (LRP) between 1999 and 2007 were centrally reviewed with regard to location, number, Gleason score at the PSM and tumour width. Predictors of PSMs and the impact of several PSM characteristics on clinical outcomes were examined. Patient characteristics were compared using the chi-squared test. Differences in recurrence-free survival (RFS) rates were analysed using the log-rank test and presented as Kaplan-Meier survival curves. Univariable and multivariable Cox regression analysis for the prediction of RFS was performed. RESULTS: Central pathology review using the updated PSM definition according to ISUP 2009, resulted in reclassification of a substantial number of patients with PSMs (n = 113, 26.6%) as R0. Several PSM characteristics with a higher risk of biochemical recurrence (BCR) were identified as the strongest independent predictors of RFS: pathological stage; Gleason score; and the presence of multiple PSMs (hazard ratio [HR] 1.78; 95% confidence interval [CI] 1.08-2.96; P = 0.025). Further analysis replacing the location of PSM by the width categories of PSM showed that a PSM >3 mm was an independent predictor of RFS (HR 1.72; 95% CI 1.08-2.72; P = 0.022). CONCLUSIONS: The impact of PSMs after LRP for prostate cancer remains unclear. PSMs in the present cohort of patients undergoing LRP had different characteristics and conferred different risks of BCR. A better understanding of PSM characteristics and a careful standardized pathological evaluation is needed to adequately counsel patients with respect to prognosis and adjuvant therapy after LRP.


Assuntos
Fidelidade a Diretrizes , Laparoscopia , Margens de Excisão , Prostatectomia/métodos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Adulto , Idoso , Conferências de Consenso como Assunto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
World J Urol ; 34(8): 1147-54, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26676614

RESUMO

INTRODUCTION: Evidence for sequencing targeted therapy (TT) in patients with metastatic renal cell carcinoma (mRCC) beyond third line is limited. Treatment decisions for these sequence options are largely based on individual preferences and experience. The aim of this study was to describe the efficacy and toxicity of fourth-line TT. MATERIALS AND METHODS: We retrospectively reviewed patients treated with fourth-line TT for mRCC after failure of previous treatment lines at a German academic high-volume center. Out of 406 patients treated in first line, 56 patients (14.8 %) were identified with more than three lines of TT. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Cox proportional hazards models were applied to explore predictors of PFS and OS in uni- and multivariable analysis. RESULTS: For the fourth-line treatment, disease control rate was 35.7 %. Median OS from beginning of first-line therapy was 47.4 months (IQR 31.0-76.5). Primary resistance at first-line TT, metastatic disease at initial diagnosis and an intermediate MSKCC score were independent predictors of shorter OS from start of first-line TT. Median OS from the time of initiation of fourth-line therapy was 10.5 months (IQR 5.6-22.6). The corresponding median PFS for fourth-line TT was 3.2 months (IQR 1.6-8.0) and was not correlated with treatment response in first-line TT. The rate of toxicity-induced treatment termination was 16.1 %. Limitations are the retrospective and unicentric design with a limited number of patients. CONCLUSIONS: Patients might benefit from subsequent treatment lines independently from treatment response in first line.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
12.
Urol Int ; 97(4): 450-456, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27577572

RESUMO

INTRODUCTION: The aim of the present study was to compare long-term donor outcomes after open and laparoscopic living donor nephrectomy. The focus was on pregnancy rates, hypertension and quality of life parameters. MATERIALS AND METHODS: Data were retrospectively collected using our institution's electronic database and a structured questionnaire. The study included 30 donors after open donor nephrectomy (ODN) and 131 donors after laparoscopic donor nephrectomy (LDN). RESULTS: Demographic data did not differ between groups. When asked for their preference, significantly more donors in the LDN group would choose the same surgical approach again. The overall frequency of postoperative complications was significantly lower in the LDN group. The incidence of grade III complications was 2% after LDN and 10% after ODN (p = 0.79). Only 2 out of 15 female donors aged between 18 and 45 years delivered a healthy child after DN. On interview, only 4 out of 15 female donors declared the desire to have children after DN. CONCLUSIONS: From the donor perspective, long-term outcomes after LDN are more favorable than after ODN. To ensure favorable functional outcomes, strict preoperative donor selection and diligent long-term donor follow-up are required.


Assuntos
Nefrectomia , Adolescente , Adulto , Feminino , Humanos , Hipertensão , Transplante de Rim , Laparoscopia , Doadores Vivos , Pessoa de Meia-Idade , Gravidez , Taxa de Gravidez , Qualidade de Vida , Adulto Jovem
13.
Cancer Immunol Immunother ; 64(11): 1487-94, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26289091

RESUMO

The efficacy of immunotherapy in cancer patients is influenced by differences in their immune status. An evaluation of immunocompetence before therapy may help to predict therapeutic success and guide the selection of appropriate regimens. We assessed the preexisting cellular immunity against prostate-specific antigen (PSA) in untreated prostate cancer patients and healthy controls through measurement of the phenotype and function of CD8(+) T cells. Our data show that the majority of healthy men possess functional PSA-specific CD8(+) T cells in contrast to cancer patients, where <50 % showed a CD8(+) T cell response. PSA146-154-specific CD8(+) T cells of these patients had a higher expression of the activation marker CD38 and the exhaustion marker Tim-3, indicating that PSA-specific cells are exhausted. The heterogeneity of the CD8(+) T cell response against PSA in prostate cancer patients may influence their response to therapy and is a factor to be taken into account while designing and selecting treatment regimens.


Assuntos
ADP-Ribosil Ciclase 1/análise , Linfócitos T CD8-Positivos/imunologia , Glicoproteínas de Membrana/análise , Proteínas de Membrana/análise , Antígeno Prostático Específico/imunologia , Neoplasias da Próstata/imunologia , Idoso , Receptor Celular 2 do Vírus da Hepatite A , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/química , Neoplasias da Próstata/terapia
14.
World J Urol ; 33(3): 397-402, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24853030

RESUMO

OBJECTIVES: To investigate pathological and oncological outcomes of obese patients who underwent robot-assisted radical prostatectomy (RARP) compared with laparoscopic radical prostatectomy (LRP) or open retropubic radical prostatectomy (RRP) since limited comparative data exist with regard to oncological and survival outcomes. METHODS: A total of 869 patients with body mass index ≥ 30 from two academic centers were identified. A total of 194 patients who underwent RARP were propensity score (PS) matched 1:1 to LRP or RRP cases. PS-matching variables included prostate-specific antigen (PSA), biopsy Gleason score, clinical stage, surgeon experience, and nerve-sparing technique. Predictors of positive surgical margins (PSMs) were analyzed using logistic regression. Predictors of recurrence-free survival (RFS) were analyzed within Cox regression models. Overall survival was compared with RFS using the log-rank test. RESULTS: Pathologic Gleason scores <7, =7, and >7 were found in 24.2, 63.6, and 11.7 % of patients, respectively. There were no statistically significant differences related to pathologic stage or lymph node metastases between surgical techniques. PSM for pT2 disease were observed in 22.9, 17.4, and 19.3 % of patients undergoing RARP, LRP, and RRP, respectively (not significantly different). Preoperative PSA and clinical stage cT2 disease were independently associated with PSM. There were no significant differences in mean 3-year RFS for RARP, LRP, and RRP (87.4, 91.0, and 85.7 %). Biopsy Gleason score >7, PSM, and clinical stage two were independent predictors of decreased RFS. CONCLUSIONS: RARP demonstrates similar pathological and oncological results compared with LRP or RRP for obese patients.


Assuntos
Laparoscopia/métodos , Obesidade/complicações , Prostatectomia/métodos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Idoso , Biópsia , Índice de Massa Corporal , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Próstata/patologia , Próstata/cirurgia , Antígeno Prostático Específico/sangue , Taxa de Sobrevida , Resultado do Tratamento
15.
Urol Int ; 94(1): 99-110, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-24662736

RESUMO

OBJECTIVE: Functional epigenetic studies aimed to re-express transcriptionally silenced genes in renal cell carcinoma (RCC) may facilitate the ongoing search for appropriate markers supporting clinical decision-making. METHODS: The RCC cell line A-498 was treated with the DNA methyltransferase inhibitor zebularine under low-cytotoxicity conditions. RNA chip analyses revealed several upregulated transcripts that were further validated by qPCR on 49 matched pairs of human kidney tissues to identify suitable marker candidates. RESULTS: Members of the metallothionein (MT) group were remarkably downregulated in tumor tissues. MT1G and MT1H expression was decreased in 98% of cases, whereas MT2A expression was downregulated in 73% of all cases. Comparison of 308 reactivated transcripts upregulated more than 1.5-fold to published data revealed a high number of shared candidates, which supports the consistency of this experimental approach. CONCLUSION: MTs were found to be transcriptionally inactivated in human RCC. Our observations support the hypothesis of a possible involvement of these metalloproteins in renal cell carcinogenesis. Additional functional studies of these genes may provide clues for understanding renal cancers as essentially metabolic diseases.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Transformação Celular Neoplásica/genética , Epigênese Genética , Perfilação da Expressão Gênica , Neoplasias Renais/genética , Metalotioneína/genética , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Citidina/análogos & derivados , Citidina/farmacologia , Metilases de Modificação do DNA/antagonistas & inibidores , Metilases de Modificação do DNA/metabolismo , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Epigênese Genética/efeitos dos fármacos , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , Metalotioneína/metabolismo , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase , RNA Mensageiro/metabolismo , Fatores de Tempo , Transcrição Gênica
16.
BJU Int ; 114(4): 517-21, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24112652

RESUMO

OBJECTIVE: To determine pathological and oncological outcomes of patients diagnosed with low-risk prostate cancer in two age cohorts who underwent radical prostatectomy (RP) and qualified for active surveillance (AS) according to Prostate Cancer Research International: Active Surveillance (PRIAS) criteria, as AS for low-risk prostate cancer represents an acceptable management strategy especially for older patients. PATIENTS AND METHODS: In all, 320 patients aged ≥65 years who underwent RP and were eligible for AS according to PRIAS criteria were propensity score matched 1:1 to patients aged <65 years. Patient characteristics were compared with chi-square, Kruskal-Wallis, and one-way anova tests. Predictors of RP pathological upgrading or upstaging were analysed using logistic regression. Recurrence-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Predictors of RFS were analysed within Cox regression models. RESULTS: Pathological upgrading and upstaging were significantly higher among older (≥65 years) vs younger (<65 years) patients (53.1% vs 44.1% and 12.2% vs 7.2%, respectively). Higher prostate-specific antigen levels and increasing age were independent predictors of upgrading among patients aged <65 years. There were no differences in RFS or OS between the two age groups. Positive surgical margin status was the only independent predictor of shorter RFS. CONCLUSIONS: Patients aged ≥65 years who are eligible for AS by PRIAS criteria have a higher risk of being upgraded and upstaged at RP than those aged <65 years. These findings should be taken into consideration when discussing treatment options for patients diagnosed with prostate cancer.


Assuntos
Vigilância da População , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Fatores Etários , Idoso , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/mortalidade , Análise de Sobrevida , Taxa de Sobrevida
17.
World J Urol ; 32(6): 1411-6, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24609219

RESUMO

PURPOSE: Comparative data related to the use of open and minimally invasive surgical approaches for the treatment of high-risk prostate cancer (PCa) remain limited. We determined outcomes of open radical prostatectomy (RRP), laparoscopic RP (LRP), and robot-assisted RP (RARP) in matched cohorts of patients with high-risk prostate cancer. MATERIALS AND METHODS: A total of 805 patients with high-risk PCa [prostate-specific antigen (PSA) >20 ng/mL, Gleason score ≥8, or clinical stage ≥cT2c] were identified. A total of 407 RRP cases were propensity score (PS) matched 1:1 to 398 LRP or RARP cases to yield 3 cohorts (RARP, LRP, and RRP) of 110 patients each for analysis. PS matching variables included the following: age, clinical stage, preoperative PSA, biopsy Gleason score, surgeon experience, and nerve-sparing technique. Overall survival (OS) and recurrence-free survival (RFS) were compared with log-rank test. RFS predictor analysis was calculated within Cox regression models. RESULTS: Pathological Gleason scores <7, =7, and >7 were found in 3.3, 50.9, and 45.8 % of patients. There were no statistically significant differences for pathological stage and positive surgical margins between surgical techniques. Mean 3-year RFS was 41.4, 77.9, and 54.1 %, for RARP, LRP, and RRP, respectively (p < 0.0001 for RARP vs. LRP). There were no significant differences for mean estimated 3-year OS for patients treated with RARP, LRP, or RRP (95.4, 98.1, and 100 %). CONCLUSIONS: RARP demonstrated similar oncologic outcomes compared to RRP and LRP in a PS-matched cohort of patients with high-risk prostate cancer.


Assuntos
Laparoscopia , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos , Idoso , Estudos de Coortes , Intervalo Livre de Doença , Humanos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Pontuação de Propensão , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Resultado do Tratamento
18.
BMC Urol ; 14: 18, 2014 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-24506815

RESUMO

BACKGROUND: Few studies to date have directly compared outcomes of retropubic (RRP) and laparoscopic (LRP) radical prostatectomy. We investigated a single institution experience with RRP and LRP with respect to functional and pathological outcomes. METHODS: 168 patients who underwent RRP were compared to 171 patients who underwent LRP at our institution. Pathological and functional outcomes including postoperative urinary incontinence and erectile dysfunction (ED) of the two cohorts were examined. RESULTS: Patients had bilateral, unilateral and no nerve sparing technique performed in 83.3%, 1.8% and 14.9% of cases for RRP and 23.4%, 22.8% and 53.8% of cases for LRP, respectively (p < 0.001). Overall positive surgical margin rates were 22.2% among patients who underwent RRP compared to 26.5% of patients who underwent LRP (p = 0.435). Based upon pads/day, urinary continence postoperatively was achieved in 83.2% and 82.8% for RRP and LRP, respectively (p = 0.872). Analysis on postoperative ED was limited due to lack of information on the preoperative erectile status. However, postoperatively there were no differences with respect to ED between the two cohorts (p = 0.151). Based on ICIQ-scores, surgeons with more experience had lower rates of postoperative incontinence irrespective of surgical technique (p = 0.001 and p < 0.001 for continuous and stratified data, respectively). CONCLUSIONS: RRP and LRP represent effective surgical approaches for the treatment of clinically localized prostate cancer. Pathological outcomes are excellent for both surgical techniques. Functional outcomes including postoperative urinary incontinence and ED are comparable between the cohorts. Surgeon experience is more relevant than surgical technique applied.


Assuntos
Disfunção Erétil/etiologia , Laparoscopia/efeitos adversos , Prostatectomia/métodos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Incontinência Urinária/etiologia , Adulto , Idoso , Disfunção Erétil/prevenção & controle , Alemanha , Humanos , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Prostatectomia/efeitos adversos , Recuperação de Função Fisiológica , Resultado do Tratamento , Incontinência Urinária/prevenção & controle
19.
BMC Urol ; 14: 92, 2014 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-25412566

RESUMO

BACKGROUND: In patients with localized high-risk prostate cancer awaiting radiation therapy, pelvic lymphadenectomy (PL) is a reliable minimally invasive staging procedure. We compared outcomes after laparoendoscopic single site PL (LESSPL) with those after conventional multiport laparoscopic PL (MLPL). METHODS: A retrospective case-control study was carried out at the authors' center. For LESSPL the reusable X-Cone single port was combined with straight and prebent laparoscopic instruments and an additional 3 mm needlescopic grasper. MLPL was performed via four trocars of different sizes using standard laparoscopic instruments. RESULTS: Patients who underwent either LESSPL (n = 20) or MLPL (n = 97) between January 2008 and July 2013, were included in the study. Demographic data were comparable between groups. Patients in the LESSPL group tended to be older and had a significantly higher ASA-score. The mean operating time was 172.4 ± 34.1 min for LESSPL and 116.6 ± 40.1 min for MLPL (P < .001). During LESSPL, no conversion to MLPL was necessary. An average of 12 lymph nodes per patient was retrieved, with no significant difference between study groups. Postoperative pain scores were similar between groups. The hospital stay was 2.3 ± 0.7 days after LESSPL and 3.1 ± 1.2 days after MLPL (P = .01). Two days postoperatively, significantly more patients after LESSPL than after MLPL recovered their normal physical activity (P < .001). Six months postoperatively, no complications were registered in the LESSPL group and cosmetic results were excellent. CONCLUSIONS: In the present study, shorter hospitalization and quicker postoperative recovery were major benefits of LESSPL over MLPL. In patients with localized prostate cancer, staging LESS pelvic lymphadenectomy may be a safe alternative to conventional multiport laparoscopy.


Assuntos
Laparoscopia/métodos , Excisão de Linfonodo/métodos , Estadiamento de Neoplasias/métodos , Próstata/patologia , Neoplasias da Próstata/patologia , Idoso , Estudos de Casos e Controles , Humanos , Laparoscopia/instrumentação , Tempo de Internação , Excisão de Linfonodo/instrumentação , Masculino , Estadiamento de Neoplasias/instrumentação , Duração da Cirurgia , Estudos Retrospectivos , Fatores de Risco
20.
Eur Urol Focus ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38688825

RESUMO

BACKGROUND AND OBJECTIVE: Accurate magnetic resonance imaging (MRI) reporting is essential for transperineal prostate biopsy (TPB) planning. Although approved computer-aided diagnosis (CAD) tools may assist urologists in this task, evidence of improved clinically significant prostate cancer (csPCa) detection is lacking. Therefore, we aimed to document the diagnostic utility of using Prostate Imaging Reporting and Data System (PI-RADS) and CAD for biopsy planning compared with PI-RADS alone. METHODS: A total of 262 consecutive men scheduled for TPB at our referral centre were analysed. Reported PI-RADS lesions and an US Food and Drug Administration-cleared CAD tool were used for TPB planning. PI-RADS and CAD lesions were targeted on TPB, while four (interquartile range: 2-5) systematic biopsies were taken. The outcomes were the (1) proportion of csPCa (grade group ≥2) and (2) number of targeted lesions and false-positive rate. Performance was tested using free-response receiver operating characteristic curves and the exact Fisher-Yates test. KEY FINDINGS AND LIMITATIONS: Overall, csPCa was detected in 56% (146/262) of men, with sensitivity of 92% and 97% (p = 0.007) for PI-RADS- and CAD-directed TPB, respectively. In 4% (10/262), csPCa was detected solely by CAD-directed biopsies; in 8% (22/262), additional csPCa lesions were detected. However, the number of targeted lesions increased by 54% (518 vs 336) and the false-positive rate doubled (0.66 vs 1.39; p = 0.009). Limitations include biopsies only for men at clinical/radiological suspicion and no multidisciplinary review of MRI before biopsy. CONCLUSIONS AND CLINICAL IMPLICATIONS: The tested CAD tool for TPB planning improves csPCa detection at the cost of an increased number of lesions sampled and false positives. This may enable more personalised biopsy planning depending on urological and patient preferences. PATIENT SUMMARY: The computer-aided diagnosis tool tested for transperineal prostate biopsy planning improves the detection of clinically significant prostate cancer at the cost of an increased number of lesions sampled and false positives. This may enable more personalised biopsy planning depending on urological and patient preferences.

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