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1.
Int J Pharm Compd ; 25(2): 94-98, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33798107

RESUMO

Even when a diagnosis of prostate cancer is anticipated, many patients are unprepared for the persistence and severity of sequelae such as erectile dysfunction, which frequently results from lifesaving treatment for that disease. Erectile dysfunction in particular can exert a powerful impact on quality of life as the patient's self-esteem diminishes, intimacy erodes, and a sustained level of stress and anxiety that impairs work performance and personal relationships becomes a part of his everyday experience. The Stanley Prostate-cancer Protocol for treating erectile dysfunction after prostatectomy and/or radiotherapy was developed to better assist the underserved patient population faced with that challenge. Feedback from patients and prescribers indicates that this program, even when initiated years after treatment for prostate cancer, is consistently effective in treating erectile dysfunction. The authors have also found that incorporating the Protocol into a range of pharmacy services can further the growth of a compounding practice. In this case report, the outcome of Stanley-Protocol therapy in a patient complaining of complete and persistent erectile dysfunction after prostate-cancer treatment is presented and formulations used in therapy for that disorder are provided.


Assuntos
Disfunção Erétil , Neoplasias , Protocolos Antineoplásicos , Disfunção Erétil/etiologia , Humanos , Masculino , Próstata , Prostatectomia , Qualidade de Vida
2.
Anticancer Res ; 41(4): 2183-2186, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33813431

RESUMO

BACKGROUND/AIM: The aim of this study was to identify simple and reliable factors to detect clinically insignificant prostate cancer (PC) for avoiding immediate prostate biopsies using biparametric magnetic resonance imaging (MRI), which consists of T2-weighted and diffusion-weighted imaging. PATIENTS AND METHODS: We retrospectively evaluated 427 men with suspected PC, who underwent biparametric MRI and standard 12-core transrectal prostate biopsy. MRI and prostate specific antigen density (PSAD) were analysed. To evaluate the combination of the two parameters, patients were divided into three groups (Group A: MRI negative and PSAD <0.23, Group B: MRI positive or PSAD ≥0.23, Group C: MRI positive and PSAD ≥0.23). A grade of ≥2 was defined as clinically significant PC. RESULTS: Clinically significant PC was detected in 46.5% of men with positive MRI findings, and 60.0% of men with PSAD ≥0.23. When combining MRI and PSAD, detection rates of clinically significant PC were 10.0%, 28.4% and 65.3% in group A, B and, C, respectively. CONCLUSION: Negative biparametric MRI findings with PSAD <0.23 might be a reliable evidence for avoiding immediate prostate biopsies.


Assuntos
Imagem por Ressonância Magnética/métodos , Antígeno Prostático Específico/análise , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia com Agulha de Grande Calibre/métodos , Imagem de Difusão por Ressonância Magnética , Humanos , Biópsia Guiada por Imagem , Testes Imunológicos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Cuidados Pré-Operatórios , Próstata/patologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/metabolismo , Estudos Retrospectivos , Carga Tumoral , Ultrassonografia de Intervenção
3.
Methods Mol Biol ; 2292: 105-113, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33651355

RESUMO

Prostate cancer antigen 3 (PCA3) is a urinary biomarker for prostate cancer and has demonstrated a good specificity and sensitivity representing a minimally invasive test.PCA3 assay could be useful in combination with PSA to suggest an eventual rebiopsy in men who have had one or more previous negative prostate biopsies.Combination of multiple tumor biomarkers will be the trend in the near future to achieve the goal of evaluate the aggressiveness of cancer and at the same time reducing the number of unnecessary biopsies.


Assuntos
Antígenos de Neoplasias/análise , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Biomarcadores Tumorais/análise , Biópsia/métodos , Humanos , Masculino
4.
Br J Radiol ; 94(1120): 20201014, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33733813

RESUMO

OBJECTIVES: In real-time portal dosimetry, thresholds are set for several measures of difference between predicted and measured images, and signals larger than those thresholds signify an error. The aim of this work is to investigate the use of an additional composite difference metric (CDM) for earlier detection of errors. METHODS: Portal images were predicted for the volumetric modulated arc therapy plans of six prostate patients. Errors in monitor units, aperture opening, aperture position and path length were deliberately introduced into all 180 segments of the treatment plans, and these plans were delivered to a water-equivalent phantom. Four different metrics, consisting of central axis signal, mean image value and two image difference measures, were used to identify errors, and a CDM was added, consisting of a weighted power sum of the individual metrics. To optimise the weights of the CDM and to evaluate the resulting timeliness of error detection, a leave-pair-out strategy was used. For each combination of four patients, the weights of the CDM were determined by an exhaustive search, and the result was evaluated on the remaining two patients. RESULTS: The median segment index at which the errors were identified was 87 (range 40-130) when using all of the individual metrics separately. Using a CDM as well as multiple separate metrics reduced this to 73 (35-95). The median weighting factors of the four metrics constituting the composite were (0.15, 0.10, 0.15, 0.00). Due to selection of suitable threshold levels, there was only one false positive result in the six patients. CONCLUSION: This study shows that, in conjunction with appropriate error thresholds, use of a CDM is able to identify increased image differences around 20% earlier than the separate measures. ADVANCES IN KNOWLEDGE: This study shows the value of combining difference metrics to allow earlier detection of errors during real-time portal dosimetry for volumetric modulated arc therapy treatment.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Radioterapia Guiada por Imagem/métodos , Radioterapia de Intensidade Modulada/métodos , Humanos , Masculino , Imagens de Fantasmas , Próstata/diagnóstico por imagem , Radiometria , Dosagem Radioterapêutica , Estudos Retrospectivos
5.
Br J Radiol ; 94(1119): 20200433, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33586999

RESUMO

OBJECTIVE: We aim to test the hypothesis that neurovascular bundle (NVB) displacement by rectal hydrogel spacer combined with NVB delineation as an organ at risk (OAR) is a feasible method for NVB-sparing stereotactic body radiotherapy. METHODS: Thirty-five men with low- and intermediate-risk prostate cancer who underwent rectal hydrogel spacer placement and pre-, post-spacer prostate MRI studies were treated with prostate SBRT (36.25 Gy in five fractions). A prostate radiologist contoured the NVB on both the pre- and post-spacer T2W MRI sequences that were then registered to the CT simulation scan for NVB-sparing radiation treatment planning. Three SBRT treatment plans were developed for each patient: (1) no NVB sparing, (2) NVB-sparing using pre-spacer MRI, and (3) NVB-sparing using post-spacer MRI. NVB dose constraints include maximum dose 36.25 Gy (100%), V34.4 Gy (95% of dose) <60%, V32Gy <70%, V28Gy <90%. RESULTS: Rectal hydrogel spacer placement shifted NVB contours an average of 3.1 ± 3.4 mm away from the prostate, resulting in a 10% decrease in NVB V34.4 Gy in non-NVB-sparing plans (p < 0.01). NVB-sparing treatment planning reduced the NVB V34.4 by 16% without the spacer (p < 0.01) and 25% with spacer (p < 0.001). NVB-sparing did not compromise PTV coverage and OAR endpoints. CONCLUSIONS: NVB-sparing SBRT with rectal hydrogel spacer significantly reduces the volume of NVB treated with high-dose radiation. Rectal spacer contributes to this effect through a dosimetrically meaningful displacement of the NVB that may significantly reduce RiED. These results suggest that NVB-sparing SBRT warrants further clinical evaluation. ADVANCES IN KNOWLEDGE: This is a feasibility study showing that the periprostatic NVBs can be spared high doses of radiation during prostate SBRT using a hydrogel spacer and nerve-sparing treatment planning.


Assuntos
Disfunção Erétil/prevenção & controle , Hidrogéis/uso terapêutico , Neoplasias da Próstata/radioterapia , Radiocirurgia/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Idoso , Estudos de Viabilidade , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Órgãos em Risco/diagnóstico por imagem , Próstata/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Dosagem Radioterapêutica , Reto/diagnóstico por imagem , Estudos Retrospectivos
6.
Br J Radiol ; 94(1120): 20201356, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33571001

RESUMO

OBJECTIVES: To investigate the impact of total variation regularized expectation maximization (TVREM) reconstruction on the image quality of 68Ga-PSMA-11 PET/CT using phantom and patient data. METHODS: Images of a phantom with small hot sphere inserts and 20 prostate cancer patients were acquired with a digital PET/CT using list-mode and reconstructed with ordered subset expectation maximization (OSEM) and TVREM with seven penalisation factors between 0.01 and 0.42 for 2 and 3 minutes-per-bed (m/b) acquisition. The contrast recovery (CR) and background variability (BV) of the phantom, image noise of the liver, and SUVmax of the lesions were measured. Qualitative image quality was scored by two radiologists using a 5-point scale (1-poor, 5-excellent). RESULTS: The performance of CR, BV, and image noise, and the gain of SUVmax was higher for TVREM 2 m/b groups with the penalization of 0.07 to 0.28 compared to OSEM 3 m/b group (all p < 0.05). The image noise of OSEM 3 m/b group was equivalent to TVREM 2 and 3 m/b groups with a penalization of 0.14 and 0.07, while lesions' SUVmax increased 15 and 20%. The highest qualitative score was attained at the penalization of 0.21 (3.30 ± 0.66) for TVREM 2 m/b groups and the penalization 0.14 (3.80 ± 0.41) for 3 m/b group that equal to or greater than OSEM 3 m/b group (2.90 ± 0.45, p = 0.2 and p < 0.001). CONCLUSIONS: TVREM improves lesion contrast and reduces image noise, which allows shorter acquisition with preserved image quality for PSMA PET/CT. ADVANCES IN KNOWLEDGE: TVREM reconstruction with optimized penalization factors can generate higher quality PSMA-PET images for prostate cancer diagnosis.


Assuntos
Ácido Edético/análogos & derivados , Interpretação de Imagem Assistida por Computador/métodos , Oligopeptídeos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Neoplasias da Próstata/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Próstata/diagnóstico por imagem , Reprodutibilidade dos Testes
7.
Br J Radiol ; 94(1120): 20201423, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33586998

RESUMO

OBJECTIVE: We determined the sensitivity and specificity of multiparametric magnetic resonance imaging (MP-MRI) in detection of locally recurrent prostate cancer and extra prostatic extension in the post-radical radiotherapy setting. Histopathological reference standard was whole-mount prostatectomy specimens. We also assessed for any added value of the dynamic contrast enhancement (DCE) sequence in detection and staging of local recurrence. METHODS: This was a single centre retrospective study. Participants were selected from a database of males treated with salvage prostatectomy for locally recurrent prostate cancer following radiotherapy. All underwent pre-operative prostate-specific antigen assay, positron emission tomography CT, MP-MRI and transperineal template prostate mapping biopsy prior to salvage prostatectomy. MP-MRI performance was assessed using both Prostate Imaging-Reporting and Data System v. 2 and a modified scoring system for the post-treatment setting. RESULTS: 24 patients were enrolled. Using Prostate Imaging-Reporting and Data System v. 2, sensitivity, specificity, positive predictive value and negative predictive value was 64%, 94%, 98% and 36%. MP-MRI under staged recurrent cancer in 63%. A modified scoring system in which DCE was used as a co-dominant sequence resulted in improved diagnostic sensitivity (61%-76%) following subgroup analysis. CONCLUSION: Our results show MP-MRI has moderate sensitivity (64%) and high specificity (94%) in detecting radio-recurrent intraprostatic disease, though disease tends to be under quantified and under staged. Greater emphasis on dynamic contrast images in overall scoring can improve diagnostic sensitivity. ADVANCES IN KNOWLEDGE: MP-MRI tends to under quantify and under stage radio-recurrent prostate cancer. DCE has a potentially augmented role in detecting recurrent tumour compared with the de novo setting. This has relevance in the event of any future modified MP-MRI scoring system for the irradiated gland.


Assuntos
Imageamento por Ressonância Magnética Multiparamétrica/métodos , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/cirurgia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Próstata/diagnóstico por imagem , Próstata/cirurgia , Prostatectomia , Neoplasias da Próstata/radioterapia , Estudos Retrospectivos , Terapia de Salvação , Sensibilidade e Especificidade
8.
Med Sci Monit ; 27: e929913, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33556045

RESUMO

BACKGROUND Two diagnostic models of prostate cancer (PCa) and clinically significant prostate cancer (CS-PCa) were established using clinical data of among patients whose prostate-specific antigen (PSA) levels are in the gray area (4.0-10.0 ng/ml). MATERIAL AND METHODS Data from 181 patients whose PSA levels were in the gray area were retrospectively analyzed, and the following data were collected: age, digital rectal examination, total PSA, PSA density (PSAD), free/total PSA (f/t PSA), transrectal ultrasound, multiparametric magnetic resonance imaging (mpMRI), and pathological reports. Patients were diagnosed with benign prostatic hyperplasia (BPH) and PCa by pathology reports, and PCa patients were separated into non-clinically significant PCa (NCS-PCa) and CS-PCa by Gleason score. Afterward, predictor models constructed by above parameters were researched to diagnose PCa and CS-PCa, respectively. RESULTS According to the analysis of included clinical data, there were 109 patients with BPH, 44 patients with NCS-PCa, and 28 patients with CS-PCa. Regression analysis showed PCa was correlated with f/t PSA, PSAD, and mpMRI (P<0.01), and CS-PCa was correlated with PSAD and mpMRI (P<0.01). The area under the receiver operating characteristic curves of 2 models for PCa (sensitivity=73.64%, specificity=64.23%) and for CS-PCa (sensitivity=71.41%, specificity=81.82%) were 0.79 and 0.87, respectively. CONCLUSIONS The prediction models had satisfactory diagnostic value for PCa and CS-PCa among patients with PSA in the gray area, and use of these models may help reduce overdiagnosis.


Assuntos
Calicreínas/sangue , Modelos Estatísticos , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/diagnóstico , Neoplasias da Próstata/diagnóstico , Fatores Etários , Idoso , Biópsia/estatística & dados numéricos , Diagnóstico Diferencial , Exame Retal Digital/estatística & dados numéricos , Humanos , Masculino , Sobremedicalização/prevenção & controle , Imageamento por Ressonância Magnética Multiparamétrica/estatística & dados numéricos , Gradação de Tumores , Próstata/diagnóstico por imagem , Próstata/patologia , Hiperplasia Prostática/sangue , Hiperplasia Prostática/patologia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Curva ROC , Valores de Referência , Estudos Retrospectivos , Medição de Risco/métodos , Ultrassonografia/estatística & dados numéricos
10.
Lancet Digit Health ; 3(3): e158-e165, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33549512

RESUMO

BACKGROUND: Accurate prognostication is crucial in treatment decisions made for men diagnosed with non-metastatic prostate cancer. Current models rely on prespecified variables, which limits their performance. We aimed to investigate a novel machine learning approach to develop an improved prognostic model for predicting 10-year prostate cancer-specific mortality and compare its performance with existing validated models. METHODS: We derived and tested a machine learning-based model using Survival Quilts, an algorithm that automatically selects and tunes ensembles of survival models using clinicopathological variables. Our study involved a US population-based cohort of 171 942 men diagnosed with non-metastatic prostate cancer between Jan 1, 2000, and Dec 31, 2016, from the prospectively maintained Surveillance, Epidemiology, and End Results (SEER) Program. The primary outcome was prediction of 10-year prostate cancer-specific mortality. Model discrimination was assessed using the concordance index (c-index), and calibration was assessed using Brier scores. The Survival Quilts model was compared with nine other prognostic models in clinical use, and decision curve analysis was done. FINDINGS: 647 151 men with prostate cancer were enrolled into the SEER database, of whom 171 942 were included in this study. Discrimination improved with greater granularity, and multivariable models outperformed tier-based models. The Survival Quilts model showed good discrimination (c-index 0·829, 95% CI 0·820-0·838) for 10-year prostate cancer-specific mortality, which was similar to the top-ranked multivariable models: PREDICT Prostate (0·820, 0·811-0·829) and Memorial Sloan Kettering Cancer Center (MSKCC) nomogram (0·787, 0·776-0·798). All three multivariable models showed good calibration with low Brier scores (Survival Quilts 0·036, 95% CI 0·035-0·037; PREDICT Prostate 0·036, 0·035-0·037; MSKCC 0·037, 0·035-0·039). Of the tier-based systems, the Cancer of the Prostate Risk Assessment model (c-index 0·782, 95% CI 0·771-0·793) and Cambridge Prognostic Groups model (0·779, 0·767-0·791) showed higher discrimination for predicting 10-year prostate cancer-specific mortality. c-indices for models from the National Comprehensive Cancer Care Network, Genitourinary Radiation Oncologists of Canada, American Urological Association, European Association of Urology, and National Institute for Health and Care Excellence ranged from 0·711 (0·701-0·721) to 0·761 (0·750-0·772). Discrimination for the Survival Quilts model was maintained when stratified by age and ethnicity. Decision curve analysis showed an incremental net benefit from the Survival Quilts model compared with the MSKCC and PREDICT Prostate models currently used in practice. INTERPRETATION: A novel machine learning-based approach produced a prognostic model, Survival Quilts, with discrimination for 10-year prostate cancer-specific mortality similar to the top-ranked prognostic models, using only standard clinicopathological variables. Future integration of additional data will likely improve model performance and accuracy for personalised prognostics. FUNDING: None.


Assuntos
Algoritmos , Aprendizado de Máquina , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Humanos , Masculino , Pessoa de Meia-Idade , Nomogramas , Prognóstico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Estados Unidos/epidemiologia
11.
Life Sci ; 271: 119180, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33571513

RESUMO

AIMS: N6-Methyladenosine (m6A) is the most frequent posttranscriptional modification and plays important roles in tumorigenesis and metastasis. The roles of fat mass and obesity-associated (FTO) in metabolic diseases have been widely explored. However, the molecular mechanisms and physiological functions of FTO in prostate cancer remain largely unknown. This study aimed to explore the exact functions of FTO in the progression of prostate cancer metastasis. MAIN METHODS: Dot blot and m6A RNA methylation quantification assays were performed to determine m6A levels. The protein and mRNA expression levels were detected using immunoblot (IB) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analyses. Cell invasion and migration abilities were measured using transwell and wound healing assays. Bioinformatics was used to measure the expression level of FTO and possible correlation between FTO levels and advanced tumor stage. Immunofluorescence (IF) was performed to measure the cellular localization of FTO. KEY FINDINGS: FTO was downregulated in prostate cancer tissues and cell lines, and the m6A content was increased. Importantly, patients with lower FTO expression had advanced tumor stage and higher Gleason scores. Gain- and loss-of-function assays revealed that FTO inhibits prostate cancer cell invasion and migration in vitro. Moreover, we confirmed that FTO can decrease the total m6A level. SIGNIFICANCE: The present study revealed that the FTO m6A demethylase inhibits prostate cancer cell invasion and migration by regulating total m6A levels.


Assuntos
Adenosina/análogos & derivados , Dioxigenase FTO Dependente de alfa-Cetoglutarato/biossíntese , Biomarcadores Tumorais/biossíntese , Movimento Celular/fisiologia , Neoplasias da Próstata/metabolismo , Adenosina/antagonistas & inibidores , Adenosina/biossíntese , Idoso , Carcinogênese/metabolismo , Carcinogênese/patologia , Linhagem Celular Tumoral , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/patologia
12.
Life Sci ; 271: 119198, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33577857

RESUMO

The aim of this study was to evaluate whether high levels of exogenous testosterone (T) interfere in prostate morphogenesis. Pregnant females were exposed to subcutaneous injections of T cypionate (500 µg/animal) at gestational days 20 and 22. Male and female pups were euthanized at postnatal days 1 and 15. 15-day-old males had only fibroblast growth factor 10 (FGF10) immunostaining and nuclear form factor altered by the treatment, whereas treated females (T1 and T15) had almost all analyzed parameters changed. T1 females showed an increased anogenital distance (AGD), whereas T15 females had both AGD and ovary weight increased. T1 females had a higher number of epithelial buds emerging from the urethral and vaginal epithelium. We observed ectopic prostatic tissue surrounding the vagina in both T1 and T15 females. Moreover, the ectopic acini of T15 females showed delayed luminal formation, and there was a thickening of the periacinar smooth muscle layer (SML). Finally, FGF10 immunostaining intensity decreased in both T15 male and female prostates. Indeed, Sonic hedgehog (Shh) was upregulated in T15 female prostates, whereas no difference was observed between the male groups. These data showed that exogenous T changed the nuclear morphology of prostate epithelial cells in both males and females. Surprisingly, smooth muscle hyperplasia was also observed in the ectopic female prostate. Moreover, T downregulated FGF10 in both male and female prostates. Interestingly, the results suggest that FGF10 downregulation is mediated by the upregulation of Shh in females. In conclusion, exogenous T disrupts prostate development, particularly, affecting, the female.


Assuntos
Epitélio/metabolismo , Fator 10 de Crescimento de Fibroblastos/biossíntese , Proteínas Hedgehog/biossíntese , Músculo Liso/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Próstata/metabolismo , Testosterona/toxicidade , Animais , Animais Recém-Nascidos , Epitélio/efeitos dos fármacos , Epitélio/patologia , Feminino , Fator 10 de Crescimento de Fibroblastos/genética , Regulação da Expressão Gênica no Desenvolvimento , Gerbillinae , Proteínas Hedgehog/genética , Masculino , Músculo Liso/citologia , Músculo Liso/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Próstata/efeitos dos fármacos , Próstata/patologia
13.
Nat Commun ; 12(1): 935, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568675

RESUMO

Black men die more often of prostate cancer yet, interestingly, may derive greater survival benefits from immune-based treatment with sipuleucel-T. Since no signatures of immune-responsiveness exist for prostate cancer, we explored race-based immune-profiles to identify vulnerabilities. Here we show in multiple independent cohorts comprised of over 1,300 patient samples annotated with either self-identified race or genetic ancestry, prostate tumors from Black men or men of African ancestry have increases in plasma cell infiltrate and augmented markers of NK cell activity and IgG expression. These findings are associated with improved recurrence-free survival following surgery and nominate plasma cells as drivers of prostate cancer immune-responsiveness.


Assuntos
Plasmócitos/imunologia , Neoplasias da Próstata/imunologia , Afro-Americanos/genética , Idoso , Movimento Celular , Estudos de Coortes , Humanos , Imunoglobulina G/genética , Imunoglobulina G/imunologia , Células Matadoras Naturais/imunologia , Masculino , Pessoa de Meia-Idade , Próstata/imunologia , Próstata/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/fisiopatologia
14.
Am J Vet Res ; 82(2): 144-151, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33480283

RESUMO

OBJECTIVE: To describe functional and anatomic changes of the lower urogenital tract of healthy male dogs during the sexually immature period and up to 2 years of age by urodynamic and morphometric assessment. ANIMALS: 6 sexually intact male Beagle littermates. PROCEDURES: Dogs underwent electromyography-coupled urodynamic tests, CT-assisted retrograde urethrography, prostatic washes, and blood sampling monthly from 4 through 12 months of age and then at 3-month intervals. Urodynamic and morphometric variables and serum canine prostate-specific esterase concentrations were analyzed by statistical methods. RESULTS: Integrated pressure of the urethra was significantly increased beginning at 8 months of age, compared with earlier time points. Urethral pressure peak amplitudes varied among anatomic regions. During bladder filling, few electromyographic signals were concurrent with urethral pressure peaks; these were most commonly detected in the penile portion of the urethra. Urethral length and prostate gland volume were significantly greater from 7 to 24 months of age than at younger ages. Urethral length was approximately 26 to 27 cm after 9 months, and prostate gland volume was approximately 11 to 12 cm3 after 11 months of age. Serum canine prostate-specific esterase concentrations correlated with prostate gland volume. Urinary bladder threshold volume was significantly increased at 6 months of age, compared with that at 4 months, with a maximum of 197.7 mL at 24 months. CONCLUSIONS AND CLINICAL RELEVANCE: Urethral resistance was acquired at approximately 8 months of age, when growth of the lower urinary tract was incomplete. Electromyographic and integrated pressure measurement results and the distribution and amplitude of urethral pressure peaks highlighted the potential role of the prostate gland and possibly the bulbocavernosus muscles in control of continence.


Assuntos
Urodinâmica , Sistema Urogenital , Animais , Cães , Masculino , Próstata , Uretra , Bexiga Urinária
15.
Br J Radiol ; 94(1119): 20201174, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33507812

RESUMO

OBJECTIVE: The optimal method for delineation of dominant intraprostatic lesions (DIL) for targeted radiotherapy dose escalation is unclear. This study evaluated interobserver and intermodality variability of delineations on biparametric MRI (bpMRI), consisting of T2 weighted (T2W) and diffusion-weighted (DWI) sequences, and 68Ga-PSMA-PET/CT; and compared manually delineated GTV contours with semi-automated segmentations based on quantitative thresholding of intraprostatic apparent diffusion coefficient (ADC) and standardised uptake values (SUV). METHODS: 16 patients who had bpMRI and PSMA-PET scanning performed prior to any treatment were eligible for inclusion. Four observers (two radiation oncologists, two radiologists) manually delineated the DIL on: (1) bpMRI (GTVMRI), (2) PSMA-PET (GTVPSMA) and (3) co-registered bpMRI/PSMA-PET (GTVFused) in separate sittings. Interobserver, intermodality and semi-automated comparisons were evaluated against consensus Simultaneous Truth and Performance Level Estimation (STAPLE) volumes, created from the relevant manual delineations of all observers with equal weighting. Comparisons included the Dice Similarity Coefficient (DSC), mean distance to agreement (MDA) and other metrics. RESULTS: Interobserver agreement was significantly higher (p < 0.05) for GTVPSMA (DSC: 0.822, MDA: 1.12 mm) and GTVFused (DSC: 0.787, MDA: 1.34 mm) than for GTVMRI (DSC: 0.705, MDA 2.44 mm). Intermodality agreement between GTVMRI and GTVPSMA was low (DSC: 0.440, MDA: 4.64 mm). Agreement between semi-automated volumes and consensus GTV was low for MRI (DSC: 0.370, MDA: 8.16 mm) and significantly higher for PSMA-PET (0.571, MDA: 4.45 mm, p < 0.05). CONCLUSION: 68Ga-PSMA-PET appears to improve interobserver consistency of DIL localisation vs bpMRI and may be more viable for simple quantitative delineation approaches; however, more sophisticated approaches to semi-automatic delineation factoring for patient- and disease-related heterogeneity are likely required. ADVANCES IN KNOWLEDGE: This is the first study to evaluate the interobserver variability of prostate GTV delineations with co-registered bpMRI and 68Ga-PSMA-PET.


Assuntos
Ácido Edético/análogos & derivados , Interpretação de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética/métodos , Oligopeptídeos , Tomografia por Emissão de Pósitrons/métodos , Neoplasias da Próstata/diagnóstico por imagem , Compostos Radiofarmacêuticos , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Próstata/diagnóstico por imagem , Reprodutibilidade dos Testes
18.
Int J Mol Sci ; 22(1)2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33466491

RESUMO

Androgens represent the main hormones responsible for maintaining hormonal balance and function in the prostate and testis. As they are involved in prostate and testicular carcinogenesis, more detailed information of their active concentration at the site of action is required. Since the introduction of the term intracrinology as the local formation of active steroid hormones from inactive precursors of the adrenal gland, mainly dehydroepiandrosterone (DHEA) and DHEA-S, it is evident that blood circulating levels of sex steroid hormones need not reflect their actual concentrations in the tissue. Here, we review and critically evaluate available methods for the analysis of human intraprostatic and intratesticular steroid concentrations. Since analytical approaches have much in common in both tissues, we discuss them together. Preanalytical steps, including various techniques for separation of the analytes, are compared, followed by the end-point measurement. Advantages and disadvantages of chromatography-mass spectrometry (LC-MS, GC-MS), immunoanalytical methods (IA), and hybrid (LC-IA) are discussed. Finally, the clinical information value of the determined steroid hormones is evaluated concerning differentiating between patients with cancer or benign hyperplasia and between patients with different degrees of infertility. Adrenal-derived 11-oxygenated androgens are mentioned as perspective prognostic markers for these purposes.


Assuntos
Glândulas Suprarrenais/metabolismo , Androgênios/metabolismo , Próstata/metabolismo , Testículo/metabolismo , Animais , Hormônios Esteroides Gonadais/metabolismo , Humanos , Masculino , Esteroides/metabolismo
19.
Cancer Radiother ; 25(2): 107-113, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33423967

RESUMO

PURPOSE: The use of MRI for radiotherapy planning purposes is growing but image acquisition using radiotherapy set-ups has impaired image quality. Whether differences in image acquisition set-up could modify organ contouring has not been evaluated. Therefore, we aimed to evaluate differences in contouring between paired of image sets that were acquired in the same scanning session using different parameters. MATERIAL AND METHODS: Ten patients underwent RT treatment planning with MRI co-registration. MRI was carried out using two different set-ups during the same session, MRI radiotherapy set-ups and MRI diagnostic set-ups. Prostates and rectums were retrospectively contoured in both image sets by 5 radiation oncologists and 4 radiologists. Intra-observer analysis was carried out comparing organ volumes, the Dice coefficient and hausdorff distance values between two contouring rounds. Inter-observer analysis was carried out by comparing individual contours to a generated STAPLE consensus contour, which is considered the gold standard reference. RESULTS: No significant differences were observed between MRI acquisition set-ups. Significant differences were observed for the dice and hausdorff parameters, comparing individual contours to the STAPLE consensus contour, when analysing diagnostic images between rounds, although raw values were similar. CONCLUSION: Prostate and rectum contours did not differ significantly when using diagnostic or radiotherapy MRI acquisition set-ups.


Assuntos
Imagem por Ressonância Magnética/métodos , Próstata/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Reto/diagnóstico por imagem , Algoritmos , Humanos , Masculino , Variações Dependentes do Observador , Órgãos em Risco/diagnóstico por imagem , Radio-Oncologistas , Radiologistas , Estudos Retrospectivos , Estatísticas não Paramétricas , Fluxo de Trabalho
20.
Cancer Radiother ; 25(2): 161-168, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33454191

RESUMO

PURPOSE: The aims of this study were: determination of the CTV to PTV margins for prostate and pelvic lymph nodes. Investigation of the impact of registration modality (pelvic bones or prostate) on the CTV to PTV margins of pelvic lymph nodes. Investigation of the variations of bladder and rectum over the treatment course. Investigation of the impact of bladder and rectum variations on prostate position. PATIENTS AND METHODS: This study included 15 patients treated for prostate adenocarcinoma. Daily kilo voltage images and weekly CBCT scans were performed to assess prostate displacements and common and external iliac vessels motion. These data was used to calculate the CTV to PTV margins using Van Herk equation in the setting of a daily bone registration. We also compared the CTV to PTV margins of pelvic lymph nodes according to registration method; based on pelvic bone or prostate. We delineated bladder and rectum on all CBCT scans to assess their variations over treatment course at 4 anatomic levels [1.5cm above pubic bone (PB), superior edge, mid- and inferior edge of PB]. RESULTS: Using Van Herk equation, the prostate CTV to PTV margins (bone registration) were 8.03mm, 5.42mm and 8.73mm in AP, ML and SI direction with more than 97% of prostate displacements were less than 5mm. The CTV to PTV margins ranged from 3.12mm to 3.25mm for external iliac vessels and from 3.12mm to 4.18mm for common iliac vessels. Compared to registration based on prostate alignment, bone registration resulted in an important reduction of the CTV to PTV margins up to 54.3% for external iliac vessels and up to 39.6% for common iliac vessels. There was no significant variation of the mean bladder volume over the treatment course. There was a significant variation of the mean rectal volume before and after the third week of treatment. After the third week, the mean rectal volume seemed to be stable. The uni- and multivariate analysis identified the anterior wall of rectum as independent factor acting on prostate motion in AP direction at 2 levels (superior edge of, mid PB). The right rectal wall influenced the prostate motion in ML direction at inferior edge of PB. The bladder volume tends toward significance as factor acting on prostate motion in AP direction. CONCLUSIONS: We recommend CTV to PTV margins of 8mm, 6mm and 9mm in AP, ML and SI directions for prostate. And, we suggest 4mm and 5mm for external and common iliac vessels respectively. We also prefer registration based on bony landmarks to minimize bowel irradiation. More CBCT scans should be performed during the first 3weeks and especially the first week to check rectum volume.


Assuntos
Adenocarcinoma/radioterapia , Linfonodos/diagnóstico por imagem , Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Reto/diagnóstico por imagem , Bexiga Urinária/diagnóstico por imagem , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Algoritmos , Análise de Variância , Antagonistas de Androgênios/uso terapêutico , Humanos , Artéria Ilíaca/diagnóstico por imagem , Veia Ilíaca/diagnóstico por imagem , Linfonodos/anatomia & histologia , Irradiação Linfática/métodos , Masculino , Movimentos dos Órgãos , Órgãos em Risco/anatomia & histologia , Órgãos em Risco/diagnóstico por imagem , Ossos Pélvicos/anatomia & histologia , Ossos Pélvicos/diagnóstico por imagem , Pelve , Estudos Prospectivos , Próstata/anatomia & histologia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Planejamento da Radioterapia Assistida por Computador/métodos , Erros de Configuração em Radioterapia , Radioterapia Conformacional , Radioterapia Guiada por Imagem , Reto/anatomia & histologia , Estatísticas não Paramétricas , Tomografia Computadorizada por Raios X , Carga Tumoral , Bexiga Urinária/anatomia & histologia
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