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1.
Niger J Clin Pract ; 23(9): 1183-1187, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32913154

RESUMO

Aims: This study compared the analgesic effect of apical peri-prostatic block with that of intra-rectal xylocaine gel for trans-rectal ultrasound guided prostate biopsy (TRUS-PBx) in Nigeria. Methods: This is a prospective randomized comparative study carried out over one year in University of Benin Teaching Hospital, Edo State, Nigeria. The participants were randomized into two groups; Group A had 10 mls of intra-rectal xylocaine gel instillation while Group B had apical infiltration of 10 mls of 1% xylocaine all before TRUS-PBx. Result: There was a statistically significant difference in the mean pain score during and one hour after TRUS-PBx between Group A and Group B of the study population respectively (p < 0.0001). Those that had intra-rectal xylocaine gel (Group A) had more pain during and after biopsy. There was no difference in the mean pain score during probe insertion between the two groups (p = 0.952). Conclusion: This study demonstrated the superiority of apical peri-prostatic nerve block over intra rectal xylocaine gel instillation during TRUS-PBx with respect to its anesthetic efficacy. Therefore, centers providing TRUS-PBx in Nigeria should consider apical peri-prostatic nerve block as their mode of anesthesia for the procedure due to its efficacy and high safety profile.


Assuntos
Biópsia por Agulha/métodos , Biópsia Guiada por Imagem/métodos , Lidocaína/administração & dosagem , Bloqueio Nervoso/métodos , Dor/prevenção & controle , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Administração Retal , Idoso , Anestésicos Locais/administração & dosagem , Biópsia por Agulha/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Nigéria , Dor/etiologia , Medição da Dor , Estudos Prospectivos , Próstata/diagnóstico por imagem , Próstata/inervação , Reto/patologia , Ultrassonografia de Intervenção
2.
Anticancer Res ; 40(10): 5567-5575, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988880

RESUMO

BACKGROUND/AIM: Stage-specific embryonic antigen-4 (SSEA-4) expression is associated with malignant aggressiveness and is useful as a marker for identifying cancer stem cells. Our aim was to assess the relationship between hormonal therapy and SSEA-4 expression in prostate cancer (PC). MATERIALS AND METHODS: SSEA-4 expression in paired specimens from PC patients who underwent neoadjuvant hormonal therapy (NHT) and radical prostatectomy (60 pre-NHT specimens and 60 post-NHT specimens) was evaluated using immunohistochemistry. Proliferation index (PI) and apoptotic index (AI) were also evaluated. RESULTS: Post-NHT tissues had significantly elevated SSEA-4 expression whereas anti-tumor effects of NHT were inversely correlated with SSEA-4 expression level. SSEA-4 expression in post-NHT tissues was significantly associated with biochemical recurrence-free survival. SSEA-4 expression in the post-NHT tissues was positively associated with PI and negatively done with AI. CONCLUSION: SSEA-4 is a potential therapeutic target for limiting the malignant potential in hormone-naïve PC when considering the use of NHT.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Biomarcadores Tumorais/genética , Neoplasias da Próstata/tratamento farmacológico , Antígenos Embrionários Estágio-Específicos/genética , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Próstata/patologia , Prostatectomia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia
3.
Nat Commun ; 11(1): 4498, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32908142

RESUMO

The androgen receptor (AR) is the master regulator of prostate cancer (PCa) development, and inhibition of AR signalling is the most effective PCa treatment. AR is expressed in PCa cells and also in the PCa-associated stroma, including infiltrating macrophages. Macrophages have a decisive function in PCa initiation and progression, but the role of AR in macrophages remains largely unexplored. Here, we show that AR signalling in the macrophage-like THP-1 cell line supports PCa cell line migration and invasion in culture via increased Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) signalling and expression of its downstream cytokines. Moreover, AR signalling in THP-1 and monocyte-derived macrophages upregulates IL-10 and markers of tissue residency. In conclusion, our data suggest that AR signalling in macrophages may support PCa invasiveness, and blocking this process may constitute one mechanism of anti-androgen therapy.


Assuntos
Macrófagos/metabolismo , Neoplasias da Próstata/patologia , Receptores Androgênicos/metabolismo , Receptor Gatilho 1 Expresso em Células Mieloides/metabolismo , Idoso , Antagonistas de Androgênios/farmacologia , Antagonistas de Androgênios/uso terapêutico , Anilidas/farmacologia , Anilidas/uso terapêutico , Biópsia , Buffy Coat/citologia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/imunologia , Quimioterapia Adjuvante , Técnicas de Cocultura , Intervalo Livre de Doença , Humanos , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Invasividade Neoplásica/imunologia , Invasividade Neoplásica/prevenção & controle , Nitrilos/farmacologia , Nitrilos/uso terapêutico , Intervalo Livre de Progressão , Próstata/patologia , Próstata/cirurgia , Prostatectomia , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/terapia , Procedimentos Cirúrgicos Robóticos , Transdução de Sinais/imunologia , Análise de Célula Única , Células THP-1 , Compostos de Tosil/farmacologia , Compostos de Tosil/uso terapêutico
4.
Medicine (Baltimore) ; 99(37): e22059, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925739

RESUMO

Magnetic resonance imaging (MRI) targeted biopsy (TBx) of the prostate demonstrated to improve detection rate (DR) of clinically significant prostate cancer (csPCa) in biopsy-naive patients achieving strong level of evidence. Nevertheless, the csPCa yield for TBx alone versus TBx plus systematic biopsy (SBx) after accounting for overlapping of SBx cores with TBx cores, in prior-negative or active surveillance (AS) patients has not been well established.The objective of the study was to investigate benefits in terms of detection rate and pathological stratification of prostate cancer (PCa) using contextual SBx during MRI-TBx.Patients previously submitted to negative-SBx (cohort A) and those enrolled in an AS program (cohort B) who showed at least 1 suspicious area with a PIRADSv2 score ≥ 3 were prospectively and randomly assigned to only TBx strategy versus TBx plus SBx strategy. SBx locations could not encompass the TBx sites, so that the results of each type of biopsy were independent and did not overlap.A total of 312 patients were included in the 2 cohorts (cohort A: 213 cases; cohort B: 99 cases). No significant differences were found in terms of overall PCa-DR (77.6% vs 69.6% respectively; P = .36) and csPCa-DR (48.2% vs 60.9 respectively; P = .12). The MRI-TBx alone cohort showed higher csPCa/PCa ratio (87.5% vs 62.2%; P = .03). The MRI-TBx plus SBx group subanalysis showed significantly higher csPCa-DR obtained at the MRI-TBx cores when compared with the SBx cores (43.7% vs 24.1%, respectively; P = .01). Independently to age, prostatic-specific antigen and prostate imaging-reporting and data system score, either in rebiopsy (OR 0.43, 0.21-0.97) or AS (OR 0.46, 0.32-0.89) setting, SBx cores were negatively associated with the csPCa-DR when combined to TBx cores.MRI-TBx should be considered the elective method to perform prostate biopsy in patients with previous negative SBx and those considered for an AS program. Adding SBx samples to MRI-TBx did not improve detection rate of csPCa.


Assuntos
Biópsia Guiada por Imagem/métodos , Próstata/patologia , Neoplasias da Próstata/patologia , Idoso , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ultrassonografia , Conduta Expectante
5.
PLoS One ; 15(8): e0236553, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32756597

RESUMO

OBJECTIVES: The importance of clinical outcome prediction models using artificial intelligence (AI) is being emphasized owing to the increasing necessity of developing a clinical decision support system (CDSS) employing AI. Therefore, in this study, we proposed a "Dr. Answer" AI software based on the clinical outcome prediction model for prostate cancer treated with radical prostatectomy. METHODS: The Dr. Answer AI was developed based on a clinical outcome prediction model, with a user-friendly interface. We used 7,128 clinical data of prostate cancer treated with radical prostatectomy from three hospitals. An outcome prediction model was developed to calculate the probability of occurrence of 1) tumor, node, and metastasis (TNM) staging, 2) extracapsular extension, 3) seminal vesicle invasion, and 4) lymph node metastasis. Random forest and k-nearest neighbors algorithms were used, and the proposed system was compared with previous algorithms. RESULTS: Random forest exhibited good performance for TNM staging (recall value: 76.98%), while k-nearest neighbors exhibited good performance for extracapsular extension, seminal vesicle invasion, and lymph node metastasis (80.24%, 98.67%, and 95.45%, respectively). The Dr. Answer AI software consisted of three primary service structures: 1) patient information, 2) clinical outcome prediction, and outcomes according to the National Comprehensive Cancer Network guideline. CONCLUSION: The proposed clinical outcome prediction model could function as an effective CDSS, supporting the decisions of the physicians, while enabling the patients to understand their treatment outcomes. The Dr. Answer AI software for prostate cancer helps the doctors to explain the treatment outcomes to the patients, allowing the patients to be more confident about their treatment plans.


Assuntos
Inteligência Artificial , Sistemas de Apoio a Decisões Clínicas , Prognóstico , Neoplasias da Próstata/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Probabilidade , Próstata/patologia , Próstata/cirurgia , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/fisiopatologia , Neoplasias da Próstata/terapia , Glândulas Seminais/patologia , Glândulas Seminais/cirurgia , Resultado do Tratamento
6.
Niger Postgrad Med J ; 27(3): 242-247, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32687126

RESUMO

Giant prostatic enlargement often referred to as giant prostatic hyperplasia (GPH) is a rare condition described as a massive prostatic enlargement >500 g. Up until now, the total number of GPH reported worldwide in medical literature is < 30. To the best of our knowledge, only one case of a giant prostate has been reported in Nigeria. We report a case of a giant prostatic enlargement treated by open simple retropubic prostatectomy in a 73-year-old man who was suffering from lower urinary tract symptoms and persistent visible (gross) haematuria necessitating repeated blood transfusions. Transrectal ultrasound (TRUS) scan revealed a markedly enlarged prostate measuring 565 ml with a suspicious nodule and prostate-specific antigen level of 48.5 ng/ml. He had a 20-core TRUS-guided prostatic biopsy which showed benign prostatic hyperplasia. We performed a retropubic open simple prostatectomy for complete enucleation of the adenoma. Specimen weighed 512.5 g with dimensions of 17 cm × 16 cm and a volume of 528 ml. Histological examination showed prostatic fibromuscular hyperplasia with a focus of adenocarcinoma. The patient had an uneventful post-operative recovery and was discharged within a week post-surgery. Urethral catheter was removed after 2 weeks with satisfactory outcome.


Assuntos
Hematúria/etiologia , Prostatectomia , Hiperplasia Prostática/diagnóstico por imagem , Hiperplasia Prostática/cirurgia , Retenção Urinária/etiologia , Adenoma , Idoso , Humanos , Masculino , Nigéria , Próstata/patologia , Hiperplasia Prostática/patologia , Resultado do Tratamento , Ultrassonografia Doppler em Cores
7.
Br J Radiol ; 93(1112): 20200197, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32614607

RESUMO

OBJECTIVE: This study presents a methodology for voxel-based evaluation of two phase sequential radiotherapy treatment plans having conventional dose scheme in the first phase and subsequent hypofractionation dose scheme in the second phase based upon different priority [planning target volume (PTV), clinical target volume (CTV) and organs at risk (OAR)] of display modes. METHODS: A case of carcinoma prostate was selected for demonstration. Varian Eclipse treatment planning system (TPS) was used for contouring and planning. In the first phase, a dose of 52 Gy in 26 fractions to the PTV and in the second phase, a dose of 19.5 Gy in 3 fractions to the PTV Boost was planned on the same CT data set. Both the plans (Phase 1 and Phase 2) were exported and processed using "Voxel-based radiobiology display (VRb) tool". Plan Sum for Biologically effective dose (BED)-Cube and equivalent dose of 2Gy (EQD2)-Cube was reconstructed using a combination of linear quadratic (LQ) and linear quadratic-linear (LQ-L) radiobiological models. Tumor control probability (TCP) and normal tissue complication probability (NTCP) for different target volumes and organs were also calculated using EQD2-volume histograms of the Plan Sum. RESULTS: An in-house graphical user interface (GUI) is developed to present the qualitative and quantitative evaluation of the multiphase treatment plans with different display modes and dose regimens. The voxel based TCP obtained for the combined target volume was 90.56%. NTCP for the bladder and rectum was calculated from the Plan Sum histograms and found to be 0.33% and ~0.0% respectively. CONCLUSION: The proposed methodology using the VRb tool offers superior plan evaluation for multiphase sequential radiotherapy treatment plans over the existing methods. ADVANCES IN KNOWLEDGE: PTV, CTV and OAR priority based display modes in VRb tool offers better understanding of radiobiological evaluation of sequential radiotherapy treatment plans.


Assuntos
Fracionamento da Dose de Radiação , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Humanos , Masculino , Modelos Estatísticos , Próstata/patologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia
8.
PLoS One ; 15(7): e0232564, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32726309

RESUMO

BACKGROUND: The identity and spatial distribution of prostatic cell types has been determined in humans but not in dogs, even though aging- and prostate-related voiding disorders are common in both species and mechanistic factors, such as prostatic collagen accumulation, appear to be shared between species. In this publication we characterize the regional distribution of prostatic cell types in the young intact dog to enable comparisons with human and mice and we examine how the cellular source of procollagen 1A1 changes with age in intact male dogs. METHODS: A multichotomous decision tree involving sequential immunohistochemical stains was validated for use in dog and used to identify specific prostatic cell types and determine their distribution in the capsule, peripheral, periurethral and urethral regions of the young intact canine prostate. Prostatic cells identified using this technique include perivascular smooth muscle cells, pericytes, endothelial cells, luminal, intermediate, and basal epithelial cells, neuroendocrine cells, myofibroblasts, fibroblasts, fibrocytes, and other hematolymphoid cells. To enhance rigor and transparency, all high resolution images (representative images shown in the figures and biological replicates) are available through the GUDMAP database at https://doi.org/10.25548/16-WMM4. RESULTS: The prostatic peripheral region harbors the largest proportion of epithelial cells. Aging does not change the density of hematolymphoid cells, fibroblasts, and myofibroblasts in the peripheral region or in the fibromuscular capsule, regions where we previously observed aging- and androgen-mediated increases in prostatic collagen abundance Instead, we observed aging-related changes the procollagen 1A1 positive prostatic cell identity from a myofibroblast to a fibroblast. CONCLUSIONS: Hematolymphoid cells and myofibroblasts are often identified as sources of collagen in tissues prone to aging-related fibrosis. We show that these are not the likely sources of pathological collagen synthesis in older intact male dogs. Instead, we identify an aging-related shift in the prostatic cell type producing procollagen 1A1 that will help direct development of cell type and prostate appropriate therapeutics for collagen accumulation.


Assuntos
Envelhecimento/fisiologia , Fibroblastos/metabolismo , Miofibroblastos/metabolismo , Pró-Colágeno/biossíntese , Próstata/citologia , Bexiga Urinária/fisiopatologia , Envelhecimento/metabolismo , Envelhecimento/patologia , Animais , Suscetibilidade a Doenças , Cães , Imuno-Histoquímica , Masculino , Próstata/metabolismo , Próstata/patologia
10.
Gene ; 760: 144989, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32717307

RESUMO

Kinesin 14 family member KIFC1 is a mitotic kinesin which contains a C-terminal motor domain and plays a vital role for clustering the amplified centrosomes. Overexpression of KIFC1 in prostate cancer (PCa) cells showed resistance to docetaxel (DTX). The present study revealed that small KIFC1 inhibitor AZ82 suppresed the transcription and translation of KIFC1 significantly in PCa cells. AZ82 inhibited the KIFC1 expression both in the cytoplasm and nucleus of PCa cells. Inhibition of KIFC1 by AZ82 caused multipolar mitosis in PCa cells via de-clustering the amplified centrosomes and decreased the rate of cancer cell growth and proliferation. Moreover, depletion of KIFC1 reduced cells entering the cell cycle and caused PCa cells death through apoptosis by increasing the expression of Bax and Cytochrome C. Thereby, KIFC1 silencing and inhibition decreased the PCa cells survival by inducing multipolar mitosis as well as apoptosis, suggesting inhibition of KIFC1 using AZ82 might be a strategy to treat PCa by controlling the cancer cell proliferation.


Assuntos
Alanina/análogos & derivados , Centrossomo/efeitos dos fármacos , Cinesina/antagonistas & inibidores , Neoplasias da Próstata/tratamento farmacológico , Piridinas/farmacologia , Alanina/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Centrossomo/metabolismo , Dineínas/metabolismo , Humanos , Cinesina/genética , Cinesina/metabolismo , Masculino , Mitose/efeitos dos fármacos , Miosinas/metabolismo , Próstata/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia
11.
Medicine (Baltimore) ; 99(22): e18432, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481356

RESUMO

MicroRNA-93 (miR-93) has been found to be up-regulated in multiple malignancies. miR-93 might promote the proliferation and invasion of prostate cancer cell. In the present study, we aimed to investigate the expression level of miR-93 in prostate cancer tissues and its clinical and prognostic value in patients with prostate cancer.A total of 103 paired prostate cancer tissues and adjacent normal tissues were obtained from male patients who underwent surgical treatment in the department of urology, Huizhou Third People's Hospital, Guangzhou Medical University between July 2014 and March 2018. The correlation between prostate cancer characteristics and miR-93 expression was examined by chi-square test. Patient survival was evaluated using the Kaplan-Meier method and compared using log-rank test. Univariate and multivariate Cox regression analyses were performed for survival data.Compared to noncancerous prostate tissues, the expression levels of miR-93 in prostate cancer tissues were significantly increased (P < .001). High level of miR-93 expression was significantly correlated with Gleason score (P = .018), lymph node involvement (P = .026), bone metastasis (P < .001), and Tumor Node Metastasis (TNM) stage (P < .001). The 5-year overall survival rate in the high expression group was lower than that in the low expression group (log-rank test, P = .031). Multivariate Cox regression analysis showed that miR-93 expression level (HR = 2.181, 95% CI: 1.092-6.829, P = .028) was an independent factor in predicting the overall survival of prostate cancer patients.The present study demonstrated that increased expression of miR-93 correlates with progression and prognosis of prostate cancer. These fndings suggest miR-93 may serve as a novel target for prostate cancer prognosis and therapy.


Assuntos
MicroRNAs/metabolismo , Neoplasias da Próstata/metabolismo , Idoso , China/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Próstata/patologia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia
12.
Cancer Radiother ; 24(4): 323-331, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32532578

RESUMO

PURPOSE: The purpose of this study was to evaluate MRI and fluorocholine PET/CT diagnostic performances for the detection of local recurrence following prostate brachytherapy for localised prostate cancer. MATERIAL AND METHODS: In this single-centre study, we retrospectively reviewed data from 21 patients treated by brachytherapy for localised prostate cancer and diagnosed with biochemical recurrence according to Phoenix Criteria, who underwent MRI and fluorocholine PET/CT. We included patients with local relapse suspicion according to imaging exams, with biopsy for the final assessment of local recurrence. Patient analysis data were supplemented by segment analysis using an 8-segment model. RESULTS: The fluorocholine PET/CT was positive for 81% and negative for 19% of patients. The sensitivity and specificity were 92% and 33% with diagnosis accuracy of 67%. The MRI was positive for 57% and negative for 43% of patients. The sensitivity and specificity were 67% and 56% with diagnosis accuracy of 62%. There was no statistically significant difference between fluorocholine PET/CT and MRI accuracy (P=0.63). On a segment-based analysis, the sensitivity and specificity were 44% and 82% for fluorocholine PET/CT with diagnosis accuracy of 78%. For MRI, specificity was 91% diagnosis accuracy was 82%. CONCLUSION: Both MRI and fluorocholine PET/CT permit to highlight local recurrence sites after prostate brachytherapy. Confirmation biopsies are, however, necessary since this accuracy is insufficient.


Assuntos
Braquiterapia , Imagem por Ressonância Magnética/métodos , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Idoso , Biópsia , Colina/análogos & derivados , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Próstata/diagnóstico por imagem , Próstata/patologia , Neoplasias da Próstata/patologia , Compostos Radiofarmacêuticos , Dosagem Radioterapêutica , Estudos Retrospectivos , Sensibilidade e Especificidade
13.
Niger J Clin Pract ; 23(6): 754-758, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32525107

RESUMO

Background: To evaluate the extent of recall of consent information by daycare prostate biopsy patients in our low-literacy setting. And to evaluate the role of a 3rd party check on patient's recall of consent information. Subjects and Methods: As part of our standard of care, a formal informed consent session for day care prostate biopsy takes place 3 days prior to the procedure. For this study, before leaving the outpatient clinic the same day, the patient acknowledged before a third-party that his concerns were or were not satisfactorily addressed. The extent of recall of consent information was assessed on the morning of the procedure using a researcher-administered questionnaire. Consecutive patients participated in this cross-sectional study for day care prostate biopsy at a tertiary hospital in southeast Nigeria from February to November 2015 after obtaining due consent. Results: The recall of the risks associated with the planned procedure was poorer than the recall of the nature of the disease condition or the nature of the planned procedure. However, it was observed that aggregate recall was significantly poorer among patients who negatively attested to a satisfying consent session (OR 0.125; P < 0.0005). Conclusion: The use of a third-party in determining patient satisfaction after a consent session may be a better indicator of patient comprehension and subsequent recall of consent information, especially in low-literacy settings. Using a third-party, in this manner, may assist in checking paternalism inherent in the patient-doctor relationship.


Assuntos
Compreensão , Hospital Dia/estatística & dados numéricos , Consentimento Livre e Esclarecido , Rememoração Mental , Satisfação do Paciente , Próstata/patologia , Idoso , Idoso de 80 Anos ou mais , Biópsia , Estudos Transversais , Feminino , Pesquisas sobre Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Nigéria , Relações Médico-Paciente , Consentimento do Representante Legal
14.
J Cancer Res Clin Oncol ; 146(9): 2311-2317, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32583236

RESUMO

PURPOSE: We herein present the results of the first Italian Association of Radiotherapy and Clinical Oncology (AIRO) survey regarding salvage external beam re-irradiation of local prostate cancer relapse named PROLAPSE. METHODS: A questionnaire with 12 items was administered to the 775 Italian radiation oncologist members of the AIRO. RESULTS: One hundred of the members completed the survey. The survey highlighted that 59% of the participants are currently performing prostate re-EBRT, while nearly two-thirds (65%) affirmed that they are taking into consideration the procedure in case of intraprostatic relapse. Regarding the clinical target volume (CTV), only a minority (16%) declared to always prefer the partial prostate re-irradiation, while a consistent portion (nearly two-thirds) relied on clinical considerations of the choice towards partial or whole gland irradiation. The main techniques used for re-irradiation resulted to be intensity-modulated RT (IMRT)/volumetric modulated arc therapy (VMAT) and SBRT, having received approximately 40% of responses each. Regarding the criteria for patients' selection, more than 75% of responders agreed on the use of positron emission tomography (PET)/computed tomography (CT)-choline to exclude distant metastases and of multiparametric magnetic resonance imaging (mp-MRI) to detect intraprostatic recurrence. A sufficient timeframe (> 3 years) between primary RT and reirradiation was indicated by more than half of participants as an important driver in decision-making, while histological confirmation of the relapse was considered not essential by more than two-thirds. For the use of concomitant androgen deprivation therapy (ADT), most AIRO members (79%) agreed that the prescription should be based on a case-by-case analysis. Extreme hypofractionation (> 5 Gy/fraction) was preferred by the majority (52%) of the AIRO members. In most centers (more than 74%), the planning dose-volume constraints were generally extrapolated from the published data. In half of the cases, the interviewed responders affirmed that no major gastrointestinal (GI) and genitourinary (GU) toxicities were registered in the follow-up of their re-EBRT patients. Bladder complications represented the most commonly observed form of toxicity, with an incidence of 67%. CONCLUSION: This first AIRO survey about salvage prostate re-EBRT provides an interesting snapshot and suggests increasing interest in re-EBRT patients in Italy. Consensus about some aspects of patients' selection, the necessity of biopsy, fractionation, and highly selective techniques seems feasible, but other key points such as irradiated volume, dosimetry parameters, and hormonal treatment association need to be clarified.


Assuntos
Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Próstata/patologia , Próstata/efeitos da radiação , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Idoso , Biópsia/métodos , Fracionamento da Dose de Radiação , Humanos , Itália , Masculino , Oncologia/métodos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Prolapso , Radiocirurgia/métodos , Radioterapia de Intensidade Modulada/métodos , Reirradiação/métodos , Recidiva , Terapia de Salvação/métodos , Inquéritos e Questionários
15.
Prostate ; 80(12): 938-949, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32542667

RESUMO

BACKGROUND: The clinical manifestation of benign prostatic hyperplasia (BPH) is causally linked to the inflammatory microenvironment and proliferation of epithelial and stromal cells in the prostate transitional zone. The CXC-chemokine interleukin-8 (IL-8) contributes to inflammation. We evaluated the expression of inflammatory cytokines in clinical specimens, primary cultures, and prostatic lineage cell lines. We investigated whether IL-8 via its receptor system (IL-8 axis) promotes BPH. METHODS: The messenger RNA and protein expression of chemokines, including components of the IL-8 axis, were measured in normal prostate (NP; n = 7) and BPH (n = 21), urine (n = 24) specimens, primary cultures, prostatic lineage epithelial cell lines (NHPrE1, BHPrE1, BPH-1), and normal prostate cells (RWPE-1). The functional role of the IL-8 axis in prostate epithelial cell growth was evaluated by CRISPR/Cas9 gene editing. The effect of a combination with two natural compounds, oleanolic acid (OA) and ursolic acid (UA), was evaluated on the expression of the IL-8 axis and epithelial cell growth. RESULTS: Among the 19 inflammatory chemokines and chemokine receptors we analyzed, levels of IL-8 and its receptors (CXCR1, CXCR2), as well as, of CXCR7, a receptor for CXCL12, were 5- to 25-fold elevated in BPH tissues when compared to NP tissues (P ≤ .001). Urinary IL-8 levels were threefold to sixfold elevated in BPH patients, but not in asymptomatic males and females with lower urinary tract symptoms (P ≤ .004). The expression of the IL-8 axis components was confined to the prostate luminal epithelial cells in both normal and BPH tissues. However, these components were elevated in BPH-1 and primary explant cultures as compared to RWPE-1, NHPrE1, and BHPrE1 cells. Knockout of CXCR7 reduced IL-8, and CXCR1 expression by 4- to 10-fold and caused greater than or equal to 50% growth inhibition in BPH-1 cells. Low-dose OA + UA combination synergistically inhibited the growth of BPH-1 and BPH primary cultures. In the combination, the drug reduction indices for UA and OA were 16.4 and 7852, respectively, demonstrating that the combination was effective in inhibiting BPH-1 growth at significantly reduced doses of UA or OA alone. CONCLUSION: The IL-8 axis is a promotor of BPH pathogenesis. Low-dose OA + UA combination inhibits BPH cell growth by inducing autophagy and reducing IL-8 axis expression in BPH-epithelial cells.


Assuntos
Interleucina-8/metabolismo , Próstata/metabolismo , Próstata/patologia , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Receptores CXCR/metabolismo , Processos de Crescimento Celular/efeitos dos fármacos , Linhagem Celular , Células Cultivadas , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Epitélio/patologia , Humanos , Interleucina-8/biossíntese , Interleucina-8/genética , Masculino , Ácido Oleanólico/farmacologia , Próstata/efeitos dos fármacos , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores CXCR/biossíntese , Receptores CXCR/genética , Transdução de Sinais/efeitos dos fármacos , Triterpenos/farmacologia
16.
Br J Radiol ; 93(1112): 20200298, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32479105

RESUMO

OBJECTIVE: To compare the performance of Likert and Prostate Imaging-Reporting and Data System (PI-RADS) multiparametric (mp) MRI scoring systems for detecting clinically significant prostate cancer (csPCa). METHODS: 199 biopsy-naïve males undergoing prostate mpMRI were prospectively scored with Likert and PI-RADS systems by four experienced radiologists. A binary cut-off (threshold score ≥3) was used to analyze histological results by three groups: negative, insignificant disease (Gleason 3 + 3; iPCa), and csPCa (Gleason ≥3 +4). Lesion-level results and prostate zonal location were also compared. RESULTS: 129/199 (64.8%) males underwent biopsy, 96 with Likert or PI-RADS score ≥3, and 21 with negative MRI. A further 12 patients were biopsied during follow-up (mean 507 days). Prostate cancer was diagnosed in 87/199 (43.7%) patients, 65 with (33.6%) csPCa. 30/92 (32.6%) patients with negative MRI were biopsied, with an NPV of 83.3% for cancer and 86.7% for csPCa. Likert and PI-RADS score differences were observed in 92 patients (46.2%), but only for 16 patients (8%) at threshold score ≥3. Likert scoring had higher specificity than PI-RADS (0.77 vs 0.66), higher area under the curve (0.92 vs 0.87, p = 0.002) and higher PPV (0.66 vs 0.58); NPV and sensitivity were the same. Likert had more five score results (58%) compared to PI-RADS (36%), but with similar csCPa detection (81.0 and 80.6% respectively). Likert demonstrated lower proportion of false positive in the predominately AFMS-involving lesions. CONCLUSION: Likert and PI-RADS systems both demonstrate high cancer detection rates. Likert scoring had a higher AUC with moderately higher specificity and lower positive call rate and could potentially help to reduce the number of unnecessary biopsies performed. ADVANCES IN KNOWLEDGE: This paper illustrates that the Likert scoring system has potential to help urologists reduce the number of prostate biopsies performed.


Assuntos
Imagem por Ressonância Magnética , Neoplasias da Próstata/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Próstata/diagnóstico por imagem , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
17.
Toxicol Appl Pharmacol ; 401: 115102, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32512071

RESUMO

PURPOSE: Cadmium (Cd) is reported to be associated with carcinogenesis. The molecular mechanisms associated with Cd-induced prostate cancer (PCa) remain elusive. MATERIALS AND METHODS: RWPE1, PWR1E and DU 145 cells were used. RT2 Profiler Array, real-time-quantitative-PCR, immunofluorescence, cell cycle, apoptosis, proliferation and colony formation assays along with Gene Set Enrichment Analysis (GSEA) were performed. RESULT: Chronic Cd exposure of non-malignant RWPE1 and PWR1E cells promoted cell survival, proliferation and colony formation with inhibition of apoptosis. Even a two-week Cd exposure of PCa cell line (DU 145) significantly increased the proliferation and decreased apoptosis. RT2 profiler array of 84 genes involved in the Erk/MAPK pathway revealed induction of gene expression in Cd-RWPE1 cells compared to RWPE1. This was confirmed by individual TaqMan gene expression analysis in both Cd-RWPE1 and Cd-PWR1E cell lines. GSEA showed an enrichment of the Erk/MAPK pathway along with other pathways such as KEGG-ERBB, KEGG-Cell Cycle, KEGG-VEGF, KEGG-Pathways in cancer and KEGG-prostate cancer pathway. We randomly selected upregulated genes from Erk/MAPK pathway and performed profile analysis in a PCa data set from the TCGA/GDC data base. We observed upregulation of these genes in PCa compared to normal samples. An increase in phosphorylation of the Erk1/2 and Mek1/2 was observed in Cd-RWPE1 and Cd-PWR1E cells compared to parental cells, confirming that Cd-exposure induces activation of the Erk/MAPK pathway. CONCLUSION: This study demonstrates that Erk/MAPK signaling is a major pathway involved in Cd-induced malignant transformation of normal prostate cells. Understanding these dominant oncogenic pathways may help develop optimal therapeutic strategies for PCa.


Assuntos
Cádmio/toxicidade , Sistema de Sinalização das MAP Quinases/fisiologia , Próstata/efeitos dos fármacos , Próstata/enzimologia , Neoplasias da Próstata/induzido quimicamente , Neoplasias da Próstata/enzimologia , Carcinogênese/efeitos dos fármacos , Carcinogênese/metabolismo , Linhagem Celular Tumoral , Estudos de Coortes , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Próstata/patologia , Neoplasias da Próstata/patologia
18.
Urologe A ; 59(5): 617-625, 2020 May.
Artigo em Alemão | MEDLINE | ID: mdl-32377764

RESUMO

BACKGROUND: In recent years nuclear medicine theranostics using radiolabeled prostate-specific membrane antigen (PSMA) ligands have gained increasing importance in the management of prostate cancer. AIM: The aim of this work is to highlight the value of theranostic concepts using radiolabeled PSMA ligands for both the diagnostic work-up and treatment of advanced prostate cancer. MATERIAL AND METHODS: The currently available knowledge in the literature is summarized and presented. RESULTS: The use of PSMA in positron emission tomography-computed tomography (PET/CT) shows a high sensitivity and specificity for prostate cancer imaging, particularly in patients with biochemical recurrences. Furthermore, promising results are also reported for staging of primary prostate cancer and treatment monitoring. In addition, radioligand therapy using alpha and beta emitters is a promising third line treatment option in intensively pretreated patients with metastases. The reduction of side effects and optimization of the treatment sequence of radioligand therapy is of increasing importance. CONCLUSION: Nuclear medicine theranostics have an increasing clinical impact on the diagnostics and treatment of prostate cancer.


Assuntos
Antígenos de Superfície/metabolismo , Glutamato Carboxipeptidase II/metabolismo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/metabolismo , Nanomedicina Teranóstica/métodos , Diagnóstico por Imagem , Humanos , Ligantes , Masculino , Medicina de Precisão , Próstata/diagnóstico por imagem , Próstata/patologia , Neoplasias da Próstata/terapia , Ensaio Radioligante , Compostos Radiofarmacêuticos/uso terapêutico , Sensibilidade e Especificidade , Resultado do Tratamento
19.
Medicine (Baltimore) ; 99(19): e19946, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32384441

RESUMO

To conduct a STARD-compliant validity that the contrast-enhanced ultrasound (CEUS) evaluation of prostate for the improvement of positive rate of biopsy and diagnostic efficiency of prostate carcinoma (PCa).Data of 137 patients with suspected PCa who underwent relevant examinations and treatment were reviewed, and 82 of 137 patients were finally included. The patients consisted of Group 1 (26 patients) and Group 2 (42 patients) according to which they underwent transrectal ultrasound (TRUS) biopsy selected from CEUS evaluation of the prostate and who underwent TRUS-guided biopsy directly. A systematic 12-core biopsy was performed at first, and additional 1 to 2 cores biopsy was made in the suspected target area where CEUS had showed abnormal enhancement. The assumed diagnoses were compared with pathological findings.There were 37 patients with PCa and 31 patients with benign lesions; and 14 patients without biopsy after CEUS did not find PCa emerging in follow-up (18-47 months). The positive rates of biopsy-malignant lesions were 73.1% and 42.8% in Group 1 and Group 2, respectively. The positive rate of biopsy in Group 1 was significantly higher than that in Group 2 (P = .024). The sensitivity and accuracy of TRUS biopsy and a combination of TRUS biopsy after transrectal CEUS for the evaluation of prostate benign and malignant lesion were 60% and 66.7% (P=0.0139), and 94.4% and 88.5% (P=0.0453), respectively.CEUS evaluation of the prostate of PSA-elevated patient before biopsy can help select target patient with high risk of PCa, reduce unnecessary biopsy, increase detection rate of PCa, and improve diagnostic sensitivity and accuracy.


Assuntos
Carcinoma/diagnóstico por imagem , Meios de Contraste , Próstata/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Ultrassonografia/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Humanos , Biópsia Guiada por Imagem/métodos , Masculino , Pessoa de Meia-Idade , Próstata/patologia , Reto/cirurgia , Sensibilidade e Especificidade , Ultrassonografia/métodos , Ultrassonografia de Intervenção
20.
NPJ Syst Biol Appl ; 6(1): 13, 2020 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-32382028

RESUMO

Up to date, screening for prostate cancer (PCa) remains one of the most appealing but also a very controversial topics in the urological community. PCa is the second most common cancer in men worldwide and it is universally acknowledged as a complex disease, with a multi-factorial etiology. The pathway of PCa diagnosis has changed dramatically in the last few years, with the multiparametric magnetic resonance (mpMRI) playing a starring role with the introduction of the "MRI Pathway". In this scenario the basic tenet of network medicine (NM) that sees the disease as perturbation of a network of interconnected molecules and pathways, seems to fit perfectly with the challenges that PCa early detection must face to advance towards a more reliable technique. Integration of tests on body fluids, tissue samples, grading/staging classification, physiological parameters, MR multiparametric imaging and molecular profiling technologies must be integrated in a broader vision of "disease" and its complexity with a focus on early signs. PCa screening research can greatly benefit from NM vision since it provides a sound interpretation of data and a common language, facilitating exchange of ideas between clinicians and data analysts for exploring new research pathways in a rational, highly reliable, and reproducible way.


Assuntos
Detecção Precoce de Câncer/métodos , Neoplasias da Próstata/diagnóstico , Biomarcadores Tumorais , Humanos , Biópsia Guiada por Imagem/métodos , Imagem por Ressonância Magnética/métodos , Masculino , Gradação de Tumores/métodos , Valor Preditivo dos Testes , Próstata/patologia , Antígeno Prostático Específico/metabolismo
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