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1.
Neurourol Urodyn ; 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31396992

RESUMO

AIMS: In recent years, the human brain-bladder control network has been visualized in different functional magnetic resonance imaging (fMRI) studies. The role of the brainstem and suprapontine regions has been elucidated. Especially the pontine region and the periaqueductal gray, as the central structures of the micturition circuit, were demonstrated. Detrusor sphincter dyssynergia (DSD) is a common problem in patients with neurological diseases. Residual urine and consecutive urinary tract infections with the risk of kidney damage remain a problem. In the present study, we used fMRI of the brain to compare the activation sites of patients with DSD with those of our previously published healthy controls with special emphasis on the brainstem region. METHODS: fMRI was performed in 11 patients with DSD who had an urge to void due to a filled bladder. In a nonvoiding model, they were instructed to contract or to relax the pelvic floor muscles repetitively. RESULTS: In patients with DSD, we could reproduce the activation sites found in healthy subjects, showing the regions in the brainstem as well as the other micturition-related areas. The activation of the pontine region was more rostral/dorsal compared with the healthy volunteers. CONCLUSION: Interestingly, we detected the well-known activation in the pontine region in the patients in the dorsal/rostral part compared with the more ventral activation in the healthy volunteers, suggesting that the L-region of the pontine micturition center is more prominent in cases of DSD.

2.
Int. braz. j. urol ; 45(3): 459-467, May-June 2019. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-1012312

RESUMO

ABSTRACT Purpose: 68Ga-PSMA PET/CT imaging is a promising modality for the staging of recurrent prostate cancer (PCa). Current evidence suggests limited diagnostic value of the 68Ga-PSMA PET/CT in PSA-levels ≤0.3ng/mL. Experimental data have demonstrated an increase in PSMA-expression in PCa metastases by androgen deprivation in vitro. The aim of the current study was to investigate a possible enhancing effect of PSMA with low-dose androgen deprivation in patients with BCR and low PSA-levels. Materials and Methods: Five patients with PCa and BCR, following radical prostatectomy, underwent 68Ga-PSMA PET/CT. A consecutive 68Ga-PSMA PET/CT was performed 6 to 11 days after injection of 80mg of Degarelix (Firmagon®). We recorded PSA and testosterone serum-levels and changes of PSMA-uptake in 68Ga-PSMA PET/CT images. Results: Median PSA prior 68Ga-PSMA PET/CT was 0.27ng/mL. All patients had a decrease in testosterone serum levels from median 2.95μg/l to 0.16μg/l following Degarelix injection. We observed an increase in the standardized uptake value (SUV) in PSMA-positive lymphogenous and osseous lesions in two patients following androgen deprivation. In another two patients, no PSMA positive signals were detected in either the first or the second scan. Conclusion: Our preliminary results of this feasibility assessment indicate a possible enhancing effect of PSMA-imaging induced by low-dose ADT. Despite several limitations and the small number of patients, this could be a new approach to improve staging by 68Ga-PSMA PET/CT in PCa patients with BCR after primary therapy. Further prospective studies with larger number of patients are needed to validate our findings.

3.
Medicine (Baltimore) ; 98(17): e15346, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31027111

RESUMO

To assess whether left and right-sided renal cell carcinoma (RCC) carry side-specific outcomes.Surgically treated RCC patients were included from the United States Surveillance, Epidemiology and End Results database (Surveillance, Epidemiology and End Results database [SEER]; 2013 version) and the German Centre for Cancer Registry Data (ZfKD; 2000-2014). Bilateral RCC, those with missing RCC staging, follow-up time, and survival status were excluded. Cancer-specific survival (CSS) according to RCC side was compared using multivariable Cox regression.Seventeen thousand seven hundred nine SEER patients and 41,967 ZfKD patients were included. In both datasets, patients with left-sided RCC had higher T status and more often presented with nodal positive or metastatic disease. In the SEER dataset 1258 (14.33%) patients with left-sided RCC underwent lymphadenectomy (LAD), compared to 908 (10.17%) LADs in right-sided RCC (P <.001). CSS was inferior for left-sided in both datasets after multivariable adjustment (SEER HR = 1.187, 95% CI 1.048-1.345, P = .007, P = .008; ZfKD HR = 1.155, 95% CI 1.046-1.275, P = .004).In the SEER population, site-specific CSS differences were driven by whether or not a LAD was performed. Among SEER patients with LAD no statistically significant differences in laterality were observed (HR 1.096, 95% CI 0.8977-1.337, P = .396) whereas, in absence of LAD, CSS was shorter for individuals with left-sided tumor (HR = 1.176, 95%CI 1.002-1.38, P = .0468).Although the overall survival difference was only marginal, left-sided RCC in surgically treated patients tends to present at more advanced stage and has in general worse CSS, especially in patients without LAD. Site-specific lymphogenic spread patterns might contribute to these findings. Further prospective studies should evaluate, whether side-adapted LAD protocols influence outcomes in RCC patients.


Assuntos
Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/mortalidade , Neoplasias Renais/diagnóstico , Neoplasias Renais/mortalidade , Idoso , Carcinoma de Células Renais/fisiopatologia , Feminino , Seguimentos , Humanos , Neoplasias Renais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Programa de SEER , Análise de Sobrevida
4.
Int Braz J Urol ; 45(3): 459-467, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30901173

RESUMO

PURPOSE: 68Ga-PSMA PET/CT imaging is a promising modality for the staging of recurrent prostate cancer (PCa). Current evidence suggests limited diagnostic value of the 68Ga-PSMA PET/CT in PSA-levels ≤0.3ng/mL. Experimental data have demonstrated na increase in PSMA-expression in PCa metastases by androgen deprivation in vitro. The aim of the current study was to investigate a possible enhancing effect of PSMA with low-dose androgen deprivation in patients with BCR and low PSA-levels. MATERIALS AND METHODS: Five patients with PCa and BCR, following radical prostatectomy, underwent 68Ga-PSMA PET/CT. A consecutive 68Ga-PSMA PET/CT was performed 6 to 11 days after injection of 80mg of Degarelix (Firmagon®). We recorded PSA and testosterone serum-levels and changes of PSMA-uptake in 68Ga-PSMA PET/CT images. RESULTS: Median PSA prior 68Ga-PSMA PET/CT was 0.27ng/mL. All patients had a decrease in testosterone serum levels from median 2.95µg/l to 0.16µg/l following Degarelix injection. We observed an increase in the standardized uptake value (SUV) in PSMA-positive lymphogenous and osseous lesions in two patients following androgen deprivation. In another two patients, no PSMA positive signals were detected in either the fi rst or the second scan. CONCLUSION: Our preliminary results of this feasibility assessment indicate a possible enhancing effect of PSMA-imaging induced by low-dose ADT. Despite several limitations and the small number of patients, this could be a new approach to improve staging by 68Ga-PSMA PET/CT in PCa patients with BCR after primary therapy. Further prospective studies with larger number of patients are needed to validate our findings.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Glicoproteínas de Membrana , Metástase Neoplásica/diagnóstico por imagem , Compostos Organometálicos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Neoplasias da Próstata/patologia , Compostos Radiofarmacêuticos , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/patologia , Oligopeptídeos/uso terapêutico , Antígeno Prostático Específico/sangue , Valores de Referência , Reprodutibilidade dos Testes , Fatores de Tempo
5.
Artigo em Inglês | MEDLINE | ID: mdl-30421149

RESUMO

Alzheimer's disease (AD) pathology precedes the onset of clinical symptoms by several decades. Thus, biomarkers are required to identify prodromal disease stages to allow for the early and effective treatment. The methoxy-X04-derivative BSC4090 is a fluorescent ligand which was designed to target neurofibrillary tangles in AD. BSC4090 staining was previously detected in post-mortem brains and olfactory mucosa derived from AD patients. We tested BSC4090 as a potential diagnostic marker of prodromal and early AD using olfactory mucosa biopsies from 12 individuals with AD, 13 with mild cognitive impairment (MCI), and 10 cognitively normal (CN) controls. Receiver-operating curve analysis revealed areas under the curve of 0.78 for AD versus CN and of 0.86 for MCI due to AD versus MCI of other causes. BSC4090 labeling correlated significantly with cerebrospinal fluid levels of tau protein phosphorylated at T181. Using NMR spectroscopy, we find that BSC4090 binds to fibrillar and pre-fibrillar but not to monomeric tau. Thus, BSC4090 may be an interesting candidate to detect AD at the early disease stages.

6.
Eur Radiol ; 2018 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-30255245

RESUMO

PURPOSE: To compare partial nephrectomy (PN), radiofrequency ablation (RFA), cryoablation (CRA) and microwave ablation (MWA) regarding oncologic, perioperative and functional outcomes. MATERIAL AND METHODS: The MEDLINE, EMBASE and COCHRANE libraries were searched for studies comparing PN, RFA, CRA or MWA and reporting on any-cause or cancer-specific mortality, local recurrence, complications or renal function. Network meta-analyses were performed. RESULTS: Forty-seven studies with 24,077 patients were included. Patients receiving RFA, CRA or MWA were older and had more comorbidities compared with PN. All-cause mortality was higher for CRA and RFA compared with PN (incidence rate ratio IRR = 2.58, IRR = 2.58, p < 0.001, respectively). No significant differences in cancer-specific mortality were evident. Local recurrence was higher for CRA, RFA and MWA compared with PN (IRR = 4.13, IRR = 1.79, IRR = 2.52, p < 0.05 respectively). A decline in renal function was less pronounced after RFA versus PN, CRA and MWA (mean difference in GFR MD = 6.49; MD = 5.82; MD = 10.89, p < 0.05 respectively). CONCLUSION: Higher overall survival and local control of PN compared with ablative therapies did not translate into significantly better cancer-specific mortality. Most studies carried a high risk of bias by selecting younger and healthier patients for PN, which may drive superior survival and local control. Physicians should be aware of the lack of high-quality evidence and the potential benefits of ablative techniques for certain patients, including a superior complication profile and renal function preservation. KEY POINTS: • Patients selected for ablation of small renal masses are older and have more comorbidities compared with those undergoing partial nephrectomy. • Partial nephrectomy yields lower all-cause mortality, which is probably biased by patient selection and does not translate into prolonged cancer-free survival. • The decline of renal function is smallest after radiofrequency ablation for small renal masses.

7.
Hum Pathol ; 2018 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-30121370

RESUMO

Papillary renal cell carcinoma (PRCC) is currently divided in two subtypes. We reviewed a large cohort of PRCC and correlated subtype, morphological features and diagnostic marker expression with overall survival (OS) to uncover differences between the two subtypes. 376 renal tumors initially diagnosed as PRCC with clinical and survival data were collected from the participating centers. 246 tumors were classified as PRCC1 (65.4%) and 130 as PRCC2 (34.6%) and graded according to the 2016 World Health Organization/International Society of Urological Pathology grading system. Morphological features (abundant cytoplasm, necrosis, fibrous stroma, foamy macrophages and psammoma bodies) were noted. Immunohistochemical stains (MIB1, p53, Racemase, EMA, CK7, CK20, E-Cadherin) were performed using tissue microarrays. χ2-tests, log rank tests and uni- and multivariate cox regression analysis were performed. Both subtypes displayed different morphological features and immunohistochemical profiles: Abundant cytoplasm was more frequent in PRCC2 while foamy macrophages were more common in PRCC1. Abundant cytoplasm and presence of psammoma bodies were associated with poorer OS. PRCC1 showed more frequent CK7 expression, PRCC2 more frequent E-Cadherin, p53 and higher MIB1 expression (>15%). Expression of Racemase and CK7 was associated with better OS, while high MIB1 (>15%) was associated with poorer OS. In multivariate analysis the only independent predictors of OS were proliferation (MIB1), tumor stage, metastasis and age at surgery. Subtype was not an independent prognostic factor. Therefore, PRCC subtype on its own is not suitable for estimating survival. More data focusing on PRCC tumor biology is needed to define prognostic subgroups, especially in PRCC2.

8.
Urol Case Rep ; 18: 64-66, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29785373

RESUMO

Primary Bladder Adenocarcinoma is a rare malignancy that has been observed in a heterogeneous patient population. This case report presents a 51 year old female with muscle-invasive primary bladder adenocarcinoma diagnosed in 2008. After transurethral resection and cystectomy with ileum neobladder adjuvant radiochemotherapy was administered. Two years later, a symptomatic fistula between neobladder and ileoileal anastomosis was excised, resulting in urinary incontinency. In 2016, the patient shows no signs of disease relapse but suffers from reduction of bladder capacity. This case report presents classical symptoms of adenocarcinoma of the bladder and a possible treatment regimen with associated side effects.

9.
J Urol ; 200(1): 48-60, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29477716

RESUMO

PURPOSE: We summarize the evidence on gender specific differences in disease-free, cancer specific and overall survival after radical cystectomy for bladder cancer. MATERIALS AND METHODS: We performed a systematic literature search of MEDLINE®, Embase® and the Cochrane Library in July 2017. Studies evaluating gender specific differences in disease-free, cancer specific or overall survival after radical cystectomy for bladder cancer were included in study. Analyses included random effect meta-analysis, subgroup analyses, meta-influence and cumulative meta-analyses. Funnel plots and the Egger test were used to assess publication bias. RESULTS: Of the 3,868 studies identified during the literature search 59 published between 1998 and 2017 were included in analysis. Of the studies 30 in a total of 38,321 patients evaluated disease-free survival, 44 in a total of 69,666 evaluated cancer specific survival and 26 in a total of 30,039 evaluated overall survival. Random effect meta-analyses revealed decreased disease-free, cancer specific survival and overall survival in female patients than in their male counterparts. Pooled estimates showed a HR of 1.16 (95% CI 1.06-1.27, p = 0.0018) for disease-free survival, 1.23 (95% CI 1.15-1.31, p <0.001) for cancer specific survival and 1.08 (95% CI 1.03-1.12, p = 0.0004) for overall survival. Subgroup analyses confirmed impaired disease-free, cancer specific and overall survival in female patients in all strata. Publication bias was evident only for studies of cancer specific survival (Egger test p = 0.0029). After adjusting for publication bias by the trim and fill method the corrected pooled estimated HR of cancer specific survival was 1.13 (95% CI 1.05-1.21, p = 0.0012). CONCLUSIONS: Female patients who underwent radical cystectomy for bladder cancer demonstrated worse disease-free, cancer specific and overall survival than their male counterparts. The multifactorial etiology might include epidemiological differences, gender specific health care discrepancies and hormonal influences.

10.
Health Qual Life Outcomes ; 16(1): 21, 2018 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-29357874

RESUMO

BACKGROUND: Patient-reported health-related quality of life (HRQOL) differs between treatment options for prostate carcinoma. Long-term HRQOL data in brachytherapy series are scarce. Therefore, we analyzed prostate-specific and general HRQOL in patients treated with brachytherapy for prostate carcinoma after long-term follow-up. METHODS: Two hundred ninety-six patients with prostate carcinoma were treated with brachytherapy (01/1998-11/2003). General and prostate-specific HRQOL were measured using EORTC-QLQ-C30 and EORTC-QLQ-PR25, respectively. Patients were asked to complete the questionnaires after a median follow-up of 141 (119-181) months. QLQ-C30 results were compared to the German reference population. QLQ-PR25 results were compared to an earlier follow-up after a median of 51 months (no published QLQ-PR25 reference population for comparison). Additionally, a literature review on HRQOL data in brachytherapy series was performed. RESULTS: One hundred six (35.8%) patients were lost to follow-up, 70 (23.6%) had died. 120 (40.5%) patients were contacted. 80 questionnaires were returned (27% of the original cohort; 91% of alive patients were ≥70 years). Sexual activity declined over time (mean scores: 40.5 vs. 45.5; p = 0.006), hormonal treatment-related symptoms, problems associated with incontinence aids, and burden of obstructive urinary symptoms did not differ significantly compared to the 51-month follow-up. General HRQOL was numerically better in our cohort as compared to the German reference population (> 16% relative difference for both age strata; < 70 and ≥70 years). CONCLUSIONS: Our results indicate that symptom-burden after long-term follow-up and associated prostate-specific HRQOL remains relatively stable from 51 to 141 months. General HRQOL in surviving patients was numerically better compared to the reference population.


Assuntos
Braquiterapia , Neoplasias da Próstata/radioterapia , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/efeitos adversos , Braquiterapia/métodos , Disfunção Erétil/psicologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Dosagem Radioterapêutica , Estatísticas não Paramétricas , Inquéritos e Questionários , Fatores de Tempo , Incontinência Urinária/psicologia
11.
Mol Oncol ; 12(2): 256-266, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29239100

RESUMO

Deregulation of the insulin-like growth factor (IGF) axis and dysbalance of components of the IGF system as potential therapeutic targets have been described in different tumor types. IGF2 is a major embryonic growth factor and an important activator of IGF signaling. It is regulated by imprinting in a development- and tissue-dependent manner and has been implicated in a broad range of malignancies including prostate cancer (PCa). Loss of imprinting (LOI) usually results in bi-allelic gene expression and increased levels of IGF2. However, the regulatory mechanisms and the pathophysiological impact of altered IGF2 expression in PCa remain elusive. Here, we show that in contrast to many other tumors, IGF2 mRNA and protein levels were decreased in 80% of PCa in comparison with non-neoplastic adjacent prostate and were independent of LOI status. Instead, IGF2 expression in both tumors and adjacent prostate depended on preferential usage of the IGF2 promoters P3 and P4. Decreased IGF2 expression in tumors was strongly related to hypermethylation of these two promoters. Methylation of the A region in promoter P4 correlated specifically with IGF2 expression in the 20% of PCa where IGF2 was higher in tumors than in adjacent prostate. We conclude that IGF2 is downregulated in most PCa and may be particularly relevant during early stages of tumor development or during chemotherapy and androgen deprivation. PCa differs from other tumors in that IGF2 expression is mainly regulated through methylation of promoter-specific and not by imprinting. Targeting of promoter-specific regions may have relevance for the adjuvant treatment of PCa.

12.
Cardiovasc Intervent Radiol ; 41(2): 277-283, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29075878

RESUMO

PURPOSE: To evaluate survival of patients with localized T1a clear cell renal cell carcinoma (ccRCC) who received cryosurgery or thermal ablation compared to deferred therapy. MATERIALS AND METHODS: We included 733 patients with histopathologically confirmed localized T1a ccRCC who either received cryosurgery (n = 315) or thermal ablation (n = 155), as well as patients who deferred therapy (n = 263) from the 2000-2013 Surveillance, Epidemiology, and End Results Program urinary cancer file. Cox proportional hazard models were used to compare cancer-specific survival (CSS) across subgroups. Sensitivity analyses were conducted to assess potential unmeasured confounding by comorbidities. RESULTS: Patients treated with cryosurgery and thermal ablation had a statistically significant CSS benefit compared to those who deferred therapy (cryosurgery HR 0.25, 95% CI 0.14-0.45, p < 0.001; thermal ablation HR 0.27, 95% CI 0.13-0.55, p < 0.001, after adjustment for age at diagnosis, tumor grade, and size). There was no significant difference in CSS comparing cryosurgery to thermal ablation (HR 1.03, 95% CI 0.45-2.3, p = 0.95, after adjustment for age at diagnosis, tumor grade, and size). These results proved robust upon sensitivity analyses: After adjustment for comorbidities with varying prevalence assumptions, the corrected hazard ratio (cHR) of cryosurgery versus deferred therapy ranged between HR 0.09 and 0.68. CONCLUSION: Local ablative techniques provide relevant survival benefit and are preferable alternatives over deferred therapy. Cryosurgery and thermal ablation yield comparable outcomes. LEVEL OF EVIDENCE: 2b according to the Oxford Centre for evidence-based medicine levels of evidence.


Assuntos
Carcinoma de Células Renais/cirurgia , Ablação por Cateter/métodos , Criocirurgia/métodos , Neoplasias Renais/cirurgia , Idoso , Feminino , Humanos , Masculino , Modelos de Riscos Proporcionais , Análise de Sobrevida , Fatores de Tempo
13.
Eur Urol Focus ; 2017 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-28888813

RESUMO

CONTEXT: The incidence of urothelial carcinoma of the bladder (UCB) is lower in women; however, women tend to present with more advanced disease. To date, there is no quantitative synthesis of studies reporting gender-specific outcomes in non-muscle-invasive UCB. OBJECTIVE: To conduct a meta-analysis evaluating gender-specific differences in recurrence of non-muscle-invasive urinary bladder cancer (NMIBC). EVIDENCE ACQUISITION: An unrestricted systematic literature search of the MEDLINE, EMBASE, and Cochrane libraries was conducted. Studies evaluating the impact of gender on disease recurrence after local treatment of NMIBC using multivariable Cox proportional hazard models were included. Random effect meta-analysis, subgroup analyses, meta-influence, and cumulative meta-analyses were conducted. Publication bias was assessed via a funnel plot and Eggers test. EVIDENCE SYNTHESIS: Of 609 studies screened, 27 comprising 23 754 patients were included. Random effect meta-analyses indicated women at increased risk for UCB recurrence compared with men (hazard ratio [HR]=1.11, 95% confidence interval [CI]: 1.01-1.23, p=0.03). Subgroup analyses yielded estimates between HR=0.99 and HR=1.68. Gender-specific differences in UCB recurrence were most pronounced in studies administering exclusively bacillus Calmette-Guerin (BCG; HR=1.64, 95% CI: 1.13-2.39, p=0.01), especially in a long-term treatment regimen (HR=1.68, 95% CI: 1.32-2.15, p<0.001). Sensitivity analyses confirmed female patients at increased risk for UCB recurrence. CONCLUSIONS: Women are at increased risk for disease recurrence after local treatment of NMIBC compared with male patients. Reduced effectiveness of BCG treatment might underlie this observation. Gender-specific differences were evident across various subgroups and proved robust upon sensitivity analyses. PATIENT SUMMARY: In this report, we combined several studies on gender-specific differences in relapse of superficial bladder cancer. Women were more likely to experience cancer relapse than men.

14.
Urol Int ; 99(2): 201-206, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28768259

RESUMO

OBJECTIVES: To evaluate in a prospective, controlled, nonrandomized study the surgical stress and acute-phase systemic response in robotic-assisted laparoscopic prostatectomy (RALP) compared to open radical retro-pubic prostatectomy (ORRP) by measuring humoral mediators. METHODS: Forty consecutive patients undergoing either RALP or ORRP were prospectively included to assess the extent of systemic response. Blood samples were collected before surgery (T1), at the time of prostatectomy (T2), at the time of wound closure (T3), and 12 h (T4), 24 h (T5), and 48 h (T6) after surgery, and assayed for interleukins (IL-6 and IL-10), C-reactive protein (CRP), and hemoglobin. A 2-sided p < 0.05 was considered to indicate significance. RESULTS: Baseline levels of IL-6, IL-10, and CRP were comparable in both arms of the study. IL-6 and IL-10 increased in both groups during surgery and reached maximum levels at 12 and 24 h after surgery. The RALP and RRP groups differed significantly at T2 (p = 0.009), T3 (p = 0.046), T5 (p = 0.05) and T6 (p = 0.0007) for IL-6, and at T3 (p = 0.05) and T4 (p = 0.05) for IL-10. CRP levels differed significantly at 48 h postoperative (p = 0.0053). The maximum levels of all 3 mediators in the RALP group were significantly lower than those in the open surgery group. Patients in the RALP group experienced less pain from day 2 to 4 according to the Visual Analog Scale (p < 0.05). CONCLUSIONS: The study suggests that IL-6 and IL-10 are useful objective markers for surgical stress and that tissue trauma and activation of post-aggression metabolism seem to be less in RALP compared to ORRP.


Assuntos
Laparoscopia , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos , Estresse Fisiológico , Idoso , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Hemoglobinas/metabolismo , Humanos , Mediadores da Inflamação/sangue , Interleucina-10/sangue , Interleucina-6/sangue , Laparoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Prostatectomia/efeitos adversos , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
15.
Prostate ; 76(8): 776-80, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26880517

RESUMO

BACKGROUND: Our study is the first evaluation of nodal metastatic prostate cancer (PCa) to mesorectal lymph nodes (MLN) detected by (68) Ga-PSMA-PET/CT. METHODS: We retrospectively analyzed 76 consecutive PCa patients who underwent (68) Ga-PSMA-PET/CT: 61 PCa patients with biochemical recurrence (BCR) after curative treatment and 15 high-risk PCa before primary therapy. We assessed PET-positive MLN, which are indicative for PCa. RESULTS: We detected PET-positive lesions for PCa in (68) Ga-PSMA-PET/CT in 66 of 76 (87%) patients. Nodal disease was imaged in 47 of 66 (71%) patients. Indicative mesorectal nodal lesions for PCa were detected in 12 of 76 (15.8%) patients. The median number of PET-positive MLN was one per patient. Seven of twelve patients had recurrent PCa after radical prostatectomy with a median PSA value of 1.84 ng/ml (range 0.31-13). Five of twelve patients had untreated first diagnosed high-risk PCa with median PSA value of 90 ng/ml (range 4.6-93) at PET/CT, respectively. For all PET positive MLN a morphological correlate was found in CT (shortest diameter median 4 mm [range 4-21]; longest diameter median 7.5 mm [range 5-25]). After PET/CT, four patients with recurrent PCa received hormonal therapy, one patient was treated with directed radiation therapy of MLN, one patient received chemotherapy, and one patient was treated with pelvic lymph node dissection. Three high-risk PCa patients received hormonal therapy, and two patients were treated with adjuvant hormonal therapy after radical prostatectomy. CONCLUSIONS: Detection and exact location of nodal metastasis for PCa is crucial for the choice of treatment and the patient's prognosis. (68) Ga-PSMA-PET/CT seems to improve the detection of nodal metastasis in PCa, especially concerning mesorectal lymph nodes.


Assuntos
Linfonodos/patologia , Metástase Linfática/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias da Próstata/patologia , Humanos , Masculino , Prostatectomia , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos
16.
Urol Ann ; 8(1): 66-9, 2016 Jan-Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26834405

RESUMO

INTRODUCTION: Comparison of Amplatz sheath percutaneous nephrolithotomy (Amplatz PCNL) and metal telescopic dilation PCNL (MTD PCNL) with respect to clinical outcomes and complications. MATERIALS AND METHODS: Single-institution retrospective chart review with 73 patients who underwent PCNL divided into two groups: Amplatz PCNL (n = 26) and MTD PCNL (n = 47). Efficacy (stone-free rate, residual stones, and surgical duration) and safety (transfusion rate and hemoglobin decrease) were evaluated. Complications were recorded and classified using the modified Clavien classification system. RESULTS: The two PCNL groups were similar regarding mean age, stone burden, side, stone location, and stone composition. There were no significant differences in surgery duration (101 ± 28 vs. 98 ± 30 min; P = 0.906), transfusion rate (3.9% vs. 4.3%; P = 0.382), and hemoglobin drop (0.9 ± 0.9 vs. 1 ± 0.7 g/dl; P = 0.424) for Amplatz and MTD PCNL, respectively. Stone-free rate (86% vs. 68%; P = 0.001) was significantly higher while residual fragments rate (37% vs. 60%; P = 0.001) was significantly lower in Amplatz PCNL compared to MTD PCNL. However, tube stay time (4.4 ± 1.8 vs. 5.8 ± 3.6 days; P = 0.005) and hospital time (8.6 ± 2.6 vs. 9.7 ± 5.5 days; P = 0.0001) were significantly longer in Amplatz PCNL compared to MTD PCNL. Clavien grading revealed a significantly higher rate of low-grade complications (I-III) for the MTD PCNL in comparison to Amplatz PCNL (10.6% vs. 3.9%, respectively; P = 0.011). There were no major complications and no tract dilation failure. CONCLUSION: The study demonstrates that Amplatz PCNL is a safe and effective procedure to remove large renal stones compared with MTD PCNL.

17.
Eur J Nucl Med Mol Imaging ; 43(5): 898-905, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26563122

RESUMO

PURPOSE: Binding of (68)Ga-PSMA-HBED-CC ((68)Ga-PSMA) at prostate cancer (PC) cells increases over time. A biphasic protocol may help separating benign from tumor lesions. The aim of this study was the retrospective evaluation of a diagnostic incremental value of a dual-time point (biphasic) (68)Ga-PSMA-PET/CT in patients with prostate cancer. METHODS: Retrospective analysis of 35 consecutive patients (49-78 years, median 71) with newly diagnosed PC (12/35) or recurrence of PC (23/35). PET/CT (Gemini TF16, Philips) was acquired 1 h and 3 h p. i. of 140-392 MBq (300 MBq median) (68)Ga-PSMA, followed by a diagnostic contrast CT. PET findings were correlated with histology or unequivocal CT findings. Semiquantitative PET data (SUVmax, SUV mean) were acquired and target-to-background-ratios (T/B-ratio) were calculated for benign and malign lesions for both time points. Size of lymph nodes (LN) on diagnostic CT was recorded. Statistical analysis was performed for assessment of significant changes of semiquantitative PET-parameters over time and for correlation of size and uptake of lymph nodes. RESULTS: One hundred and four lesions were evaluated. Sixty lesions were referenced by histology or unequivocal CT findings, including eight (13.3 %) histopathologically benign lymph nodes, 12 (20 %) histopathologically lymph node metastases, 12 (20 %) primary tumors, three (5 %) local recurrences, and 25 (41.7 %) bone metastases. Forty-four lesions were axillary LN with normal CT-appearance. Benign lesions had significantly lower SUVmax and T/B-ratios compared with malignant findings. Malign lesions showed a significant increase of both parameters over time compared to benign findings. There was no correlation between LN size and SUVmax. The sensitivity, specificity, the positive predictive value and negative predictive value of PET/CT regarding pelvic LN was 94 %, 99 %, 89 %, and 99.5 %, respectively. CONCLUSIONS: In contrast to benign tissues, the uptake of proven tumor lesions increases on (68)Ga-PSMA-PET/CT over time. A biphasic PET-study may lead to a better detection of tumor lesions in unequivocal findings.


Assuntos
Carcinoma/diagnóstico por imagem , Compostos Organometálicos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/diagnóstico por imagem , Compostos Radiofarmacêuticos , Adulto , Idoso , Ácido Edético/análogos & derivados , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Oligopeptídeos
18.
Urol Int ; 96(1): 57-64, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26139354

RESUMO

INTRODUCTION: We aimed at developing and validating a pre-cystectomy nomogram for the prediction of locally advanced urothelial carcinoma of the bladder (UCB) using clinicopathological parameters. MATERIALS AND METHODS: Multicenter data from 337 patients who underwent radical cystectomy (RC) for UCB were prospectively collected and eligible for final analysis. Univariate and multivariate logistic regression models were applied to identify significant predictors of locally advanced tumor stage (pT3/4 and/or pN+) at RC. Internal validation was performed by bootstrapping. The decision curve analysis (DCA) was done to evaluate the clinical value. RESULTS: The distribution of tumor stages pT3/4, pN+ and pT3/4 and/or pN+ at RC was 44.2, 27.6 and 50.4%, respectively. Age (odds ratio (OR) 0.980; p < 0.001), advanced clinical tumor stage (cT3 vs. cTa, cTis, cT1; OR 3.367; p < 0.001), presence of hydronephrosis (OR 1.844; p = 0.043) and advanced tumor stage T3 and/or N+ at CT imaging (OR 4.378; p < 0.001) were independent predictors for pT3/4 and/or pN+ tumor stage. The predictive accuracy of our nomogram for pT3/4 and/or pN+ at RC was 77.5%. DCA for predicting pT3/4 and/or pN+ at RC showed a clinical net benefit across all probability thresholds. CONCLUSION: We developed a nomogram for the prediction of locally advanced tumor stage pT3/4 and/or pN+ before RC using established clinicopathological parameters.


Assuntos
Cistectomia/métodos , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/cirurgia , Urotélio/patologia , Urotélio/cirurgia , Idoso , Algoritmos , Tomada de Decisões , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias/métodos , Nomogramas , Razão de Chances , Valor Preditivo dos Testes , Período Pré-Operatório , Estudos Prospectivos , Neoplasias da Bexiga Urinária/patologia
19.
J Immunother Cancer ; 3: 26, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26082837

RESUMO

BACKGROUND: CV9103 is a prostate-cancer vaccine containing self-adjuvanted mRNA (RNActive®) encoding the antigens PSA, PSCA, PSMA, and STEAP1. This phase I/IIa study evaluated safety and immunogenicity of CV9103 in patients with advanced castration-resistant prostate-cancer. METHODS: 44 Patients received up to 5 intra-dermal vaccinations. Three dose levels of total mRNA were tested in Phase I in cohorts of 3-6 patients to determine a recommended dose. In phase II, 32 additional patients were treated at the recommended dose. The primary endpoint was safety and tolerability, the secondary endpoint was induction of antigen specific immune responses monitored at baseline and at weeks 5, 9 and 17. RESULTS: The most frequent adverse events were grade 1/2 injection site erythema, injection site reactions, fatigue, pyrexia, chills and influenza-like illness. Possibly treatment related urinary retention occurred in 3 patients. The recommended dose was 1280 µg. A total of 26/33 evaluable patients treated at 1280 µg developed an immune response, directed against multiple antigens in 15 out of 33 patients. One patient showed a confirmed PSA response. In the subgroup of 36 metastatic patients, the Kaplan-Meier estimate of median overall survival was 31.4 months [95 % CI: 21.2; n.a]. CONCLUSIONS: The self-adjuvanted RNActive® vaccine CV9103 was well tolerated and immunogenic. The technology is a versatile, fast and cost-effective platform allowing for creation of vaccines. The follow-up vaccine CV9104 including the additional antigens prostatic acid phosphatase (PAP) and Muc1 is currently being tested in a randomized phase IIb trial to assess the clinical benefit induced by this new vaccination approach. TRIAL REGISTRATION: EU Clinical Trials Register: EudraCT number 2008-003967-37, registered 27 Jan 2009.

20.
Springerplus ; 3: 574, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25332874

RESUMO

Recent breakthrough therapies targeting androgen receptor signalling in castration resistant prostate cancer (CRPC) involve multifunctional androgen receptor (AR) blockade and exhaustive androgen deprivation. Nevertheless, limitations to an enduring effectiveness of new drugs are anticipated in resistance mechanisms occurring under such treatments. In this study we used CRPC cell models VCaP and LNCaP as well as AR-negative PC-3- and non-neoplastic epithelial BPH-1-cells treated with 5, 10 or 25 µmol/L abiraterone hydrolyzed from abiraterone acetate (AA). The origin of CYP17A1 up-regulation under AA treatment was investigated in CRPC cell models by qRT-PCR and western-blot procedures. AA treatments of AR positive CRPC cell models led to decreased expression of androgen regulated genes such as PSA. In these cells diminished expression of androgen regulated genes was accompanied by an up-regulation of CYP17A1 expression within short-term treatments. No such effects became evident in AR-negative PC-3 cells. AR directed siRNA (siAR) used in VCaP cells significantly reduced mRNA expression and AR protein abundance. Such interference with AR signalling in the absence of abiraterone acetate also caused a marked up-regulation of CYP17A1 expression. Down-regulation of androgen regulated genes occurs in spite of an elevated expression of CYP17A1, the very target enzyme for this drug. CYP17A1 up-regulation already takes place within such short treatments with AA and does not require adaptation events over several cell cycles. CYP17A1 is also up-regulated in the absence of AA when AR signalling is physically eliminated by siAR. These results reveal an immediate counter-regulation of CYP17A1 expression whenever AR-signalling is inhibited adequately but not a persisting adaptation yielding drug resistance.

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