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1.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 1520-1523, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018280

RESUMO

Multiparametric magnetic resonance (mpMR) images are increasingly being used for diagnosis and monitoring of prostate cancer. Detection of malignancy from prostate mpMR images requires expertise, is time consuming and prone to human error. The recent developments of U-net have demonstrated promising detection results in many medical applications. Straightforward use of U-net tends to result in over-detection in mpMR images. The recently developed attention mechanism can help retain only features relevant for malignancy detection, thus improving the detection accuracy. In this work, we propose a U-net architecture that is enhanced by the attention mechanism to detect malignancy in prostate mpMR images. This approach resulted in improved performance in terms of higher Dice score and reduced over-detection when compared to U-net in detecting malignancy.


Assuntos
Imagem por Ressonância Magnética , Neoplasias da Próstata , Diagnóstico por Computador , Humanos , Masculino , Neoplasias da Próstata/diagnóstico por imagem
2.
Medicine (Baltimore) ; 99(38): e22156, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957339

RESUMO

INTRODUCTION: The aim of this study was to correlate cribriform pattern (CP) with other parameters in a large prospective series of Gleason score ≥7/ISUP grade ≥2 prostate cancer (PC) cases undergoing radical prostatectomy (RP). METHODS: This is a prospective single-center study on 210 consecutive patients. Gleason pattern 4 and individual tumor growth patterns determination were performed either in biopsy or in surgical specimens for all patients. RESULTS: At multiparametric magnetic resonance, a higher percentage of PI-RADS 5 was associated to CP (53.3% vs 17.7%, P = .038). CP was significantly and inversely (r = -0.261; P = .001) correlated with perineural invasion (PNI) but not with other pathological parameters. Kaplan-Meier analysis showed that mean biochemical (Bp) and radiological (Rp) progression-free survival were similar (Bp = χ 0.906; P = .341; Rp = χ 1.880; P = .170) independently to CP. In PNI positive cases, Bp-free survival was higher (χ = 3.617; P = .057) in cases without CP. CONCLUSIONS: In a homogeneous population excluding ISUP 1 cases, CP showed limited prognostic value. We first described an association with PNI and a prognostic value influenced by PNI status.


Assuntos
Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Idoso , Biópsia , Humanos , Estimativa de Kaplan-Meier , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Estudos Prospectivos , Prostatectomia , Neoplasias da Próstata/diagnóstico por imagem
3.
Medicine (Baltimore) ; 99(37): e22189, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925793

RESUMO

Herein, a Harris corner detection algorithm is proposed based on the concepts of iterated threshold segmentation and adaptive iterative threshold (AIT-Harris), and a stepwise local stitching algorithm is used to obtain wide-field ultrasound (US) images.Cone-beam computer tomography (CBCT) and US images from 9 cervical cancer patients and 1 prostate cancer patient were examined. In the experiment, corner features were extracted based on the AIT-Harris, Harris, and Morave algorithms. Accordingly, wide-field ultrasonic images were obtained based on the extracted features after local stitching, and the corner matching rates of all tested algorithms were compared. The accuracies of the drawn contours of organs at risk (OARs) were compared based on the stitched ultrasonic images and CBCT.The corner matching rate of the Morave algorithm was compared with those obtained by the Harris and AIT-Harris algorithms, and paired sample t tests were conducted (t = 6.142, t = 31.859, P < .05). The results showed that the differences were statistically significant. The average Dice similarity coefficient between the automatically delineated bladder region based on wide-field US images and the manually delineated bladder region based on ground truth CBCT images was 0.924, and the average Jaccard coefficient was 0.894.The proposed algorithm improved the accuracy of corner detection, and the stitched wide-field US image could modify the delineation range of OARs in the pelvic cavity.


Assuntos
Algoritmos , Tomografia Computadorizada de Feixe Cônico/métodos , Processamento de Imagem Assistida por Computador/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias do Colo do Útero/diagnóstico por imagem , Feminino , Humanos , Masculino , Sensibilidade e Especificidade , Ultrassonografia/métodos
4.
Medicine (Baltimore) ; 99(36): e20755, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32898989

RESUMO

Ga-PSMA-11 positron emission computed tomography /computed tomography (PET/CT) is more sensitive than magnetic resonance imaging (MRI) in detecting prostate cancer (PCa). We evaluated the value of Ga-PSMA-11 PET/CT with MRI in treatment-naive PCa.This retrospective study was approved by the hospital ethics committee. The MRI and Ga-PSMA-11 PET/CT imaging data of 63 cases of highly suspected PCa were enrolled in this study. The SUVmax and apparent diffusion coefficient (ADC), and their ratio, were assessed as diagnostic markers to distinguish PCa from benign disease.There were 107 prostate lesions detected in 63 cases. Forty cases with 64 malignant primary lesions were confirmed PCa, whereas 23 cases had 43 benign lesions. PSMA-avid lesions correlated with hypointense signal on ADC maps and hyperintense signal on diffusion-weighted imaging. The ADC of PCa was lower than that of benign lesions, and SUVmax and SUVmax/ADC of PCa was higher than that of benign lesions (P < .01). ADC had significant negative correlation with Gleason score (GS) and SUVmax, SUVmax, and SUVmax/ADC positively correlated with GS. From ROC analysis, we established cutoff values of ADC, SUVmax, and SUVmax/ADC at 1.02 × 10mm/s, 11.72, and 12.35, respectively, to differentiate PCa from benign lesions. The sensitivity, specificity, and AUC were 90.6%, 58.1%, and 0.816 for ADC, 67.2%, 97.7%, and 0.905 for SUVmax, and 81.2%, 88.4%, and 0.929 for SUVmax/ADC, respectively.Ga-PSMA-11 PET/CT combined with MRI offers higher diagnostic efficacy in the detection of PCa than either modality alone.


Assuntos
Espectroscopia de Ressonância Magnética/métodos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Antígeno Prostático Específico/análise , Neoplasias da Próstata/patologia , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/diagnóstico por imagem , Estudos Retrospectivos
5.
Asia Pac J Clin Oncol ; 16 Suppl 3: 7-11, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32852899

RESUMO

The past decade has witnessed the rising popularity and acceptance of molecular definitions on disease management. Prostate-specific membrane antigen (PSMA), in light of its molecular nature and cytokinetic properties, has rapidly become the target for development of a variety of functional tracers for PET/CT evaluation of prostate cancer. The most commonly used PSMA-binding analog is 68 Ga-labeled PSMA-11, which is now widely applied in both research and clinical settings. Literature data in the recent years have been enriched by a number of meta-analyses and systemic reviews on the evolving role of PSMA PET in primary diagnosis, staging, detection of biochemical recurrence after primary cancer treatment, identification, and significance of oligometastasis, as well as in restaging and treatment monitoring. Being a highly sensitive and reasonably specific molecular tracer, PSMA-binding analogs have a high potential to possess the majority of imaging characteristics required for a variety of management decisions in prostate malignancy.


Assuntos
Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Neoplasias da Próstata/diagnóstico por imagem , Humanos , Masculino , Estadiamento de Neoplasias , Neoplasias da Próstata/patologia
6.
PLoS Med ; 17(8): e1003281, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32797086

RESUMO

BACKGROUND: Prostate cancer (PC) is the most frequently diagnosed cancer in North American men. Pathologists are in critical need of accurate biomarkers to characterize PC, particularly to confirm the presence of intraductal carcinoma of the prostate (IDC-P), an aggressive histopathological variant for which therapeutic options are now available. Our aim was to identify IDC-P with Raman micro-spectroscopy (RµS) and machine learning technology following a protocol suitable for routine clinical histopathology laboratories. METHODS AND FINDINGS: We used RµS to differentiate IDC-P from PC, as well as PC and IDC-P from benign tissue on formalin-fixed paraffin-embedded first-line radical prostatectomy specimens (embedded in tissue microarrays [TMAs]) from 483 patients treated in 3 Canadian institutions between 1993 and 2013. The main measures were the presence or absence of IDC-P and of PC, regardless of the clinical outcomes. The median age at radical prostatectomy was 62 years. Most of the specimens from the first cohort (Centre hospitalier de l'Université de Montréal) were of Gleason score 3 + 3 = 6 (51%) while most of the specimens from the 2 other cohorts (University Health Network and Centre hospitalier universitaire de Québec-Université Laval) were of Gleason score 3 + 4 = 7 (51% and 52%, respectively). Most of the 483 patients were pT2 stage (44%-69%), and pT3a (22%-49%) was more frequent than pT3b (9%-12%). To investigate the prostate tissue of each patient, 2 consecutive sections of each TMA block were cut. The first section was transferred onto a glass slide to perform immunohistochemistry with H&E counterstaining for cell identification. The second section was placed on an aluminum slide, dewaxed, and then used to acquire an average of 7 Raman spectra per specimen (between 4 and 24 Raman spectra, 4 acquisitions/TMA core). Raman spectra of each cell type were then analyzed to retrieve tissue-specific molecular information and to generate classification models using machine learning technology. Models were trained and cross-validated using data from 1 institution. Accuracy, sensitivity, and specificity were 87% ± 5%, 86% ± 6%, and 89% ± 8%, respectively, to differentiate PC from benign tissue, and 95% ± 2%, 96% ± 4%, and 94% ± 2%, respectively, to differentiate IDC-P from PC. The trained models were then tested on Raman spectra from 2 independent institutions, reaching accuracies, sensitivities, and specificities of 84% and 86%, 84% and 87%, and 81% and 82%, respectively, to diagnose PC, and of 85% and 91%, 85% and 88%, and 86% and 93%, respectively, for the identification of IDC-P. IDC-P could further be differentiated from high-grade prostatic intraepithelial neoplasia (HGPIN), a pre-malignant intraductal proliferation that can be mistaken as IDC-P, with accuracies, sensitivities, and specificities > 95% in both training and testing cohorts. As we used stringent criteria to diagnose IDC-P, the main limitation of our study is the exclusion of borderline, difficult-to-classify lesions from our datasets. CONCLUSIONS: In this study, we developed classification models for the analysis of RµS data to differentiate IDC-P, PC, and benign tissue, including HGPIN. RµS could be a next-generation histopathological technique used to reinforce the identification of high-risk PC patients and lead to more precise diagnosis of IDC-P.


Assuntos
Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Aprendizado de Máquina/normas , Microscopia Óptica não Linear/normas , Neoplasias da Próstata/diagnóstico por imagem , Idoso , Canadá/epidemiologia , Carcinoma Intraductal não Infiltrante/epidemiologia , Carcinoma Intraductal não Infiltrante/patologia , Estudos de Casos e Controles , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Microscopia Óptica não Linear/métodos , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Reprodutibilidade dos Testes , Estudos Retrospectivos
7.
PLoS One ; 15(8): e0237587, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32804986

RESUMO

In radiomics studies, researchers usually need to develop a supervised machine learning model to map image features onto the clinical conclusion. A classical machine learning pipeline consists of several steps, including normalization, feature selection, and classification. It is often tedious to find an optimal pipeline with appropriate combinations. We designed an open-source software package named FeAture Explorer (FAE). It was programmed with Python and used NumPy, pandas, and scikit-learning modules. FAE can be used to extract image features, preprocess the feature matrix, develop different models automatically, and evaluate them with common clinical statistics. FAE features a user-friendly graphical user interface that can be used by radiologists and researchers to build many different pipelines, and to compare their results visually. To prove the effectiveness of FAE, we developed a candidate model to classify the clinical-significant prostate cancer (CS PCa) and non-CS PCa using the PROSTATEx dataset. We used FAE to try out different combinations of feature selectors and classifiers, compare the area under the receiver operating characteristic curve of different models on the validation dataset, and evaluate the model using independent test data. The final model with the analysis of variance as the feature selector and linear discriminate analysis as the classifier was selected and evaluated conveniently by FAE. The area under the receiver operating characteristic curve on the training, validation, and test dataset achieved results of 0.838, 0.814, and 0.824, respectively. FAE allows researchers to build radiomics models and evaluate them using an independent testing dataset. It also provides easy model comparison and result visualization. We believe FAE can be a convenient tool for radiomics studies and other medical studies involving supervised machine learning.


Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Neoplasias da Próstata/diagnóstico por imagem , Humanos , Masculino , Imageamento por Ressonância Magnética Multiparamétrica , Curva ROC , Software , Aprendizado de Máquina Supervisionado
8.
Int J Nanomedicine ; 15: 5333-5344, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801692

RESUMO

Purpose: Cabazitaxel (CBZ) is a new taxane-based antitumor drug approved by the FDA for the treatment of prostate cancer, especially for patients with advanced prostate cancer for whom docetaxel is ineffective or causes aggravation. However, Tween 80 injection can cause serious allergic reactions, and CBZ itself has strong toxicity, adverse reactions, and poor tumor selectivity, which greatly limits its clinical applications. Therefore, the CBZ-loaded bovine serum albumin nanoparticles (CBZ-BSA-Gd-NPs) were developed to overcome the allergenic response of Tween 80 and realize the integration of diagnosis and treatment. Methods: CBZ-BSA-Gd-NPs were prepared by the biomineralization method. The characterization, magnetic resonance imaging (MRI), safety, and antitumor activity of the nanoparticles were evaluated in vitro and in vivo. Results: The prepared nanoparticles were uniform in size (166 nm), with good MRI performance and stability over 24 h. Compared with CBZ-Tween 80 injection, CBZ-BSA-Gd-NPs showed much lower hemolysis, similar tumor inhibition, and enhanced cellular uptake in vitro. The pharmacokinetic behavior of CBZ-BSA-Gd-NPs in rats showed that the retention time of the nanoparticles was prolonged, the clearance rate decreased, and the area under the drug-time curve increased. The distribution of CBZ-BSA-Gd-NPs in nude mice was characterized by UPLC-MS/MS and MRI, and the results showed that CBZ-BSA-Gd-NPs could effectively target tumor tissues with reduced distribution in the heart, liver, spleen, lungs, and kidneys compared with CBZ-Tween 80, which indicated that CBZ-BSA-Gd-NPs not only had a passive targeting effect on tumor tissue but also achieved the integration of diagnosis and treatment. In vivo, CBZ-BSA-Gd-NPs showed improved tumor inhibitory effect with a safer profile. Conclusion: In summary, CBZ-BSA-Gd-NPs can serve as an effective therapeutic drug carrier to deliver CBZ into prostate cancer, and realize the integration of diagnosis and therapy.


Assuntos
Antineoplásicos/administração & dosagem , Nanopartículas/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Soroalbumina Bovina/administração & dosagem , Taxoides/administração & dosagem , Animais , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Cromatografia Líquida , Meios de Contraste/administração & dosagem , Meios de Contraste/farmacocinética , Docetaxel , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Humanos , Imagem por Ressonância Magnética , Masculino , Camundongos Endogâmicos BALB C , Nanopartículas/química , Neoplasias da Próstata/diagnóstico por imagem , Ratos Sprague-Dawley , Soroalbumina Bovina/farmacocinética , Espectrometria de Massas em Tandem , Taxoides/farmacocinética , Distribuição Tecidual
9.
Cancer Radiother ; 24(5): 423-428, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32620459

RESUMO

Prostate cancer is the most common malignant tumour and represents the third cause of cancer-mortality in men. The management of prostate cancer has dramatically changed over the last decades, mainly due to improvement of diagnostic modalities and development of new therapeutic strategies. Imaging plays a key role in all the steps of prostate cancer management. In recent years, magnetic resonance imaging (MRI) and positron-emission tomography (PET) - computed tomography (CT) have emerged as two major tools for the detection of prostate cancer, tumour staging and treatment choice. Both MRI and PET-CT - using choline or prostate-specific membrane antigen (PSMA) as radiotracer - have become mandatory. This article presents the contribution of the latest advances in these two imaging techniques of prostate cancer and their future developments.


Assuntos
Antígenos de Superfície , Glutamato Carboxipeptidase II , Imagem por Ressonância Magnética/métodos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Neoplasias da Próstata/diagnóstico por imagem , Adenocarcinoma/química , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/radioterapia , Idoso , Radioisótopos de Carbono , Colina/análogos & derivados , Radioisótopos de Flúor , Humanos , Masculino , Imagem Multimodal/métodos , Recidiva Local de Neoplasia/diagnóstico por imagem , Neoplasias da Próstata/química , Neoplasias da Próstata/radioterapia , Compostos Radiofarmacêuticos , Ultrassonografia/métodos
10.
Medicine (Baltimore) ; 99(29): e20760, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702820

RESUMO

Intracavitary application of brachytherapy (BT) sources followed by external beam radiation is essential for the local treatment of carcinoma of the cervix, postate, and nasopharynx. Dose distribution of external beam radiation plus BT can be challenging for the planning system because of their dose calculation by 2 different treatment planning system (TPS). The aims of this study were to introduce a novel iterative method of dose calculation preformed in the Pinnacle plan and evaluate a combined dose distribution for external beam radiation and BT.Because it is often the goal of the planner to produce plan with uniform dose throughout the target volume and normal tissue, we present an Iridium-192 calculation program using American Association of Physicists in Medicine Task Group 43 formula and export it to other commercialized TPS though the combined dose distribution of external beam radiation and BT can be shown. To illustrate such an improved procedure, we present the treatment plans of 2 patients treated with external beam radiation plus BT.Dose distribution of the single BT source were calculated with the Plato post loading TPS and the program model, and the results of 2 methods were similar. A nasopharyngeal case and a cervical case were shown in Pinnacle with this program. The total dose distribution of BT combined with EBRT was showed in compute tomography images. And the corresponding dose volume histogram figures could be displayed correctly in Pinnacle TPS.We demonstrated a novel iterative method of dose calculation preformed in the Pinnacle plan to produce a combined dose distribution for external beam radiation and BT. We used it to evaluate the dose of target volume and normal tissues in the treatment of external beam radiation plus BT.


Assuntos
Braquiterapia/métodos , Carcinoma/radioterapia , Planejamento da Radioterapia Assistida por Computador/instrumentação , Algoritmos , Braquiterapia/tendências , Fracionamento da Dose de Radiação , Feminino , Humanos , Radioisótopos de Irídio/metabolismo , Masculino , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/patologia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Doses de Radiação , Dosagem Radioterapêutica/normas , Tomografia Computadorizada por Raios X/métodos , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/patologia
11.
Int J Nanomedicine ; 15: 4289-4309, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606678

RESUMO

Objective: To construct prostate-specific membrane antigen (PSMA)-targeting, indocyanine green (ICG)-loaded nanobubbles (NBs) for multimodal (ultrasound, photoacoustic and fluorescence) imaging of prostate cancer. Methods: The mechanical oscillation method was used to prepare ICG-loaded photoacoustic NBs (ICG NBs). Then, PSMA-binding peptides were connected to the surface of ICG NBs using the biotin-avidin method to make targeted photoacoustic NBs, namely, PSMAP/ICG NBs. Their particle sizes, zeta potentials, and in vitro ultrasound, photoacoustic and fluorescence imaging were examined. Confocal laser scanning microscopy and flow cytometry were used to detect the binding ability of the PSMAP/ICG NBs to PSMA-positive LNCaP cells, C4-2 cells, and PSMA-negative PC-3 cells. The multimodal imaging effects of PSMAP/ICG NBs and ICG NBs were compared in nude mouse tumor xenografts. Results: The particle size of the PSMAP/ICG NBs was approximately 457.7 nm, and the zeta potential was approximately -23.5 mV. Both confocal laser scanning microscopy and flow cytometry confirmed that the PSMAP/ICG NBs could specifically bind to both LNCaP and C4-2 cells, but they rarely bound to PC-3 cells. The ultrasound, photoacoustic and fluorescence imaging intensities of the PSMAP/ICG NBs in vitro positively correlated with their concentrations. The ultrasound and photoacoustic imaging effects of the PSMAP/ICG NBs in LNCaP and C4-2 tumor xenografts were significantly enhanced compared with those in PC-3 tumor xenografts, which were characterized by a significantly increased duration of ultrasound enhancement and heightened photoacoustic signal intensity (P < 0.05). Fluorescence imaging showed that PSMAP/ICG NBs could accumulate in LNCaP and C4-2 tumor xenografts for a relatively long period. Conclusion: The targeted photoacoustic nanobubbles prepared in this study can specifically bind to PSMA-positive prostate cancer cells and have the ability to enhance ultrasound, photoacoustic and fluorescence imaging of PSMA-positive tumor xenografts. Photoacoustic imaging could visually display the intensity of the red photoacoustic signal in the tumor region, providing a more intuitive imaging modality for targeted molecular imaging. This study presents a potential multimodal contrast agent for the accurate diagnosis and assessment of prostate cancer.


Assuntos
Verde de Indocianina/química , Nanopartículas/química , Imagem Óptica , Técnicas Fotoacústicas , Neoplasias da Próstata/diagnóstico por imagem , Ultrassonografia , Animais , Linhagem Celular Tumoral , Meios de Contraste/química , Fluorescência , Humanos , Masculino , Camundongos Nus , Nanopartículas/ultraestrutura , Tamanho da Partícula , Peptídeos/metabolismo , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/terapia , Ligação Proteica
12.
Prostate ; 80(13): 1071-1086, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32687633

RESUMO

BACKGROUND: The emergence of reactive stroma is a hallmark of prostate cancer (PCa) progression and a potential source for prognostic and diagnostic markers of PCa. Collagen is a main component of reactive stroma and changes systematically and quantitatively to reflect the course of PCa, yet has remained undefined due to a lack of tools that can define collagen protein structure. Here we use a novel collagen-targeting proteomics approach to investigate zonal regulation of collagen-type proteins in PCa prostatectomies. METHODS: Prostatectomies from nine patients were divided into zones containing 0%, 5%, 20%, 70% to 80% glandular tissue and 0%, 5%, 25%, 70% by mass of PCa tumor following the McNeal model. Tissue sections from zones were graded by a pathologist for Gleason score, percent tumor present, percent prostatic intraepithelial neoplasia and/or inflammation (INF). High-resolution accurate mass collagen targeting proteomics was done on a select subset of tissue sections from patient-matched tumor or nontumor zones. Imaging mass spectrometry was used to investigate collagen-type regulation corresponding to pathologist-defined regions. RESULTS: Complex collagen proteomes were detected from all zones. COL17A and COL27A increased in zones of INF compared with zones with tumor present. COL3A1, COL4A5, and COL8A2 consistently increased in zones with tumor content, independent of tumor size. Collagen hydroxylation of proline (HYP) was altered in tumor zones compared with zones with INF and no tumor. COL3A1 and COL5A1 showed significant changes in HYP peptide ratios within tumor compared with zones of INF (2.59 ± 0.29, P value: .015; 3.75 ± 0.96 P value .036, respectively). By imaging mass spectrometry COL3A1 showed defined localization and regulation to tumor pathology. COL1A1 and COL1A2 showed gradient regulation corresponding to PCa pathology across zones. Pathologist-defined tumor regions showed significant increases in COL1A1 HYP modifications compared with COL1A2 HYP modifications. Certain COL1A1 and COL1A2 peptides could discriminate between pathologist-defined tumor and inflammatory regions. CONCLUSIONS: Site-specific posttranslational regulation of collagen structure by proline hydroxylation may be involved in reactive stroma associated with PCa progression. Translational and posttranslational regulation of collagen protein structure has potential for new markers to understand PCa progression and outcomes.


Assuntos
Colágeno/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Processamento de Proteína Pós-Traducional , Idoso , Sequência de Aminoácidos , Autoantígenos , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Colágeno Tipo IV/metabolismo , Colágeno Tipo VIII/metabolismo , Progressão da Doença , Colágenos Fibrilares/metabolismo , Humanos , Hidroxilação , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Colágenos não Fibrilares , Prolina/metabolismo , Próstata/metabolismo , Prostatectomia , Neoplasias da Próstata/diagnóstico por imagem , Proteômica/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos
13.
PLoS One ; 15(7): e0235779, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32645056

RESUMO

BACKGROUND: To determine the added value of preoperative prostate multiparametric MRI (mpMRI) supplementary to clinical variables and their role in predicting post prostatectomy adverse findings and biochemically recurrent cancer (BCR). METHODS: All consecutive patients treated at HUS Helsinki University Hospital with robot assisted radical prostatectomy (RALP) between 2014 and 2015 were included in the analysis. The mpMRI data, clinical variables, histopathological characteristics, and follow-up information were collected. Study end-points were adverse RALP findings: extraprostatic extension, seminal vesicle invasion, lymph node involvement, and BCR. The Memorial Sloan Kettering Cancer Center (MSKCC) nomogram, Cancer of the Prostate Risk Assessment (CAPRA) score and the Partin score were combined with any adverse findings at mpMRI. Predictive accuracy for adverse RALP findings by the regression models was estimated before and after the addition of MRI results. Logistic regression, area under curve (AUC), decision curve analyses, Kaplan-Meier survival curves and Cox proportional hazard models were used. RESULTS: Preoperative mpMRI data from 387 patients were available for analysis. Clinical variables alone, MSKCC nomogram or Partin tables were outperformed by models with mpMRI for the prediction of any adverse finding at RP. AUC for clinical parameters versus clinical parameters and mpMRI variables were 0.77 versus 0.82 for any adverse finding. For MSKCC nomogram versus MSKCC nomogram and mpMRI variables the AUCs were 0.71 and 0.78 for any adverse finding. For Partin tables versus Partin tables and mpMRI variables the AUCs were 0.62 and 0.73 for any adverse finding. In survival analysis, mpMRI-projected adverse RP findings stratify CAPRA and MSKCC high-risk patients into groups with distinct probability for BCR. CONCLUSIONS: Preoperative mpMRI improves the predictive value of commonly used clinical variables for pathological stage at RP and time to BCR. mpMRI is available for risk stratification prebiopsy, and should be considered as additional source of information to the standard predictive nomograms.


Assuntos
Recidiva Local de Neoplasia/diagnóstico , Próstata/cirurgia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/cirurgia , Idoso , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Nomogramas , Cuidados Pré-Operatórios , Prognóstico , Próstata/diagnóstico por imagem , Prostatectomia , Neoplasias da Próstata/diagnóstico por imagem , Medição de Risco
14.
Prostate ; 80(13): 1118-1127, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32634262

RESUMO

BACKGROUND: Conventional systematic prostate biopsies (SBx) have multiple limitations, and magnetic resonance imaging (MRI)-ultrasound fusion targeting is increasingly applied (fusion biopsies [FBx]). In our previous studies, we have shown that loss of the tumor suppressor gene phosphatase and tensin homolog (PTEN) in radical prostatectomy (RP) specimens predicts poor disease-specific survival, and in active surveillance (AS), PTEN loss in SBx predicts an adverse AS outcome, although SBx PTEN status does not correlate well with the corresponding RP status. Here, we have hypothesized that PTEN and erythroblast transformation-specific related gene (ERG) status in FBx correlate better with RP than they would in SBx. METHODS: A total of 106 men, who had undergone FBx and subsequent RP in a single center between June 2015 and May 2017 were included. Fifty-three of the men had concomitant or previous SBx's. All biopsy and RP specimens were collected, and tissue microarrays (TMA) were constructed from RP specimens. Immunohistochemical stainings for PTEN and ERG expression were conducted on biopsies and RP TMAs and results were compared by using Fisher's exact test. RESULTS: The immunohistochemical predictive power of FBx, determined by the concordance of biopsy PTEN and ERG status with RP, is superior to SBx (77.6% vs 66.7% in PTEN, 92.4% vs 66.6% in ERG). FBx was superior to SBx in correlation with RP Gleason Grade Groups and MRI prostate imaging reporting and data system scores. CONCLUSION: FBx grading correlates with RP histology and MRI findings and predicts the biomarker status in the RP specimens more accurately than SBx. A longer follow-up is needed to evaluate if this translates to better prediction of disease outcomes, especially in AS and radiation therapy where prostatectomy specimens are not available for prognostication.


Assuntos
PTEN Fosfo-Hidrolase/biossíntese , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Idoso , Humanos , Biópsia Guiada por Imagem/métodos , Imuno-Histoquímica , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Prostatectomia , Neoplasias da Próstata/diagnóstico por imagem , Regulador Transcricional ERG/biossíntese , Ultrassonografia de Intervenção/métodos
15.
Br J Radiol ; 93(1114): 20200484, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32706988

RESUMO

With increasing evidence to support prostate artery embolization (PAE) in the treatment of benign prostatic hyperplasia (BPH)-induced lower urinary tract symptoms (LUTS), Interventional Radiologists have begun to play an important role in the management of these patients. One area of knowledge needed when developing a PAE practice is knowledge of prostate-specific antigen (PSA) and other biomarkers utilized to detect prostate cancer in this population and what role they should play in the work up and follow-up of patients presenting with presumed BPH-induced LUTS. Furthermore, understanding how to evaluate presumed BPH-induced LUTS and stratify the risk of prostate cancer is an important skill to develop. The goal of this review is to provide Interventional Radiologists who have begun or aim to begin a PAE practice with the information they need to know regarding PSA levels and prostate cancer risk stratification for this patient population.


Assuntos
Biomarcadores Tumorais/sangue , Sintomas do Trato Urinário Inferior/terapia , Hiperplasia Prostática/terapia , Radiografia Intervencionista , Humanos , Masculino , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico por imagem
16.
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
17.
AJR Am J Roentgenol ; 215(2): 267-276, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32551903

RESUMO

OBJECTIVE. The purpose of this article is to review the utility of 18F-fluciclovine PET/CT in the evaluation of recurrent prostate cancer. CONCLUSION. Fluorine-18-labeled fluciclovine PET/CT has shown promise in the evaluation of recurrent prostate cancer. Its performance has been superior to that of other imaging modalities. It has had good diagnostic accuracy, especially in the detection of extra-prostatic disease recurrence, and the findings have an impact on treatment planning. Gallium-68-labeled prostate-specific membrane antigen PET/CT has also had excellent performance in the detection of biochemically recurrent prostate cancer with detection rates superior to those of fluciclovine PET/CT.


Assuntos
Ácidos Carboxílicos , Ciclobutanos , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/diagnóstico por imagem , Humanos , Masculino , Recidiva Local de Neoplasia/sangue , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue
19.
Clin Nucl Med ; 45(8): e360-e362, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32520502

RESUMO

PSMA (prostate-specific membrane antigen) PET/CT scan is the imaging modality of choice for staging and restaging of carcinoma prostate. Although initially thought to be a tracer with high specificity for prostatic tissue, with its extensive clinical use, there has been a rise in published literature citing its uptake in nonprostatic conditions. We present a case where false-positive PSMA uptake was noted in glomus jugulare during staging workup for carcinoma prostate.


Assuntos
Antígenos de Superfície/metabolismo , Radioisótopos de Flúor , Glomo Jugular/metabolismo , Glutamato Carboxipeptidase II/metabolismo , Achados Incidentais , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Idoso , Transporte Biológico , Glomo Jugular/diagnóstico por imagem , Glomo Jugular/patologia , Humanos , Masculino , Estadiamento de Neoplasias , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia
20.
Clin Nucl Med ; 45(8): e349-e357, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32558706

RESUMO

OBJECTIVE: This study aims to investigate the value of Tc-MIP-1404 SPECT/CT for assessment of whole-body tumor burden and treatment response in patients with biochemical recurrence of prostate cancer who undergo androgen deprivation therapy (ADT) or external beam radiation therapy (EBRT). METHODS: A total of 125 patients with biochemical recurrence of prostate cancer underwent Tc-MIP-1404 SPECT/CT. All 364 prostate-specific membrane antigen (PSMA)-positive lesions in the field of view were assessed quantitatively to calculate PSMA-derived metabolic tumor parameters, including whole-body PSMA tumor volume and whole-body total lesion PSMA. These metrics were correlated with serum prostate-specific antigen (PSA) levels and Gleason scores. In a subset of 50 patients who underwent Tc-MIP-1404 SPECT/CT before the initiation of ADT or EBRT, TL-PSMA and SUVmax were compared with radiographic response assessment by CT based on RECIST 1.1 and to biochemical response (BR) determined by changes in serum PSA levels. RESULTS: Serum PSA levels correlated with SUVmax, whole-body PSMA tumor volume, and whole-body total lesion PSMA in patients with 1 and in those with more than 1 PSMA-positive lesion (P < 0.05). The correlations were significant for both well-differentiated (Gleason score ≤7) and poorly differentiated tumors (Gleason score ≥8) (P < 0.05). The agreement between TL-PSMA derived from SPECT and BR in patients who underwent Tc-MIP-1404 SPECT/CT before and after initiation of ADT was 80% (95% confidence interval [CI], 0.43-0.91; Cohen κ = 0.68; P < 0.05); in these patients, the agreement between TL-PSMA and CT was 60% (95% CI, 0.20-0.72; Cohen κ = 0.46; P < 0.05) and the agreement between BR and CT was 52% (0.07-0.61; Cohen κ = 0.34; P < 0.05). Comparable results were found for patients who underwent SPECT/CT before and after initiation of EBRT, with the strongest agreement between TL-PSMA and BR (80%; 95% CI, 0.38-0.93; Cohen κ = 0.66; P < 0.05) compared with the agreement between TL-PSMA and CT (60%; 95% CI, 0.13-0.69; Cohen κ = 0.69; P < 0.05) and between BR and CT (48%; 95% CI, 0-0.54; Cohen κ = 0.26; P = 0.11). Discordant findings between SPECT and CT were most likely due to limitations in the assessment of small lymph node metastases and bone involvement, which were detectable on SPECT but not on CT. CONCLUSIONS: The results of our study show that Tc-MIP-1404 SPECT/CT is a promising method for the evaluation of treatment response in patients with biochemical recurrence of prostate cancer who undergo either ADT or EBRT. TL-PSMA for assessment of treatment response has the strongest correlation with serum PSA levels, superior to SUVmax-based evaluation and response assessment based on CT data and RECIST 1.1.


Assuntos
Compostos de Organotecnécio , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/terapia , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Carga Tumoral , Idoso , Antagonistas de Androgênios/uso terapêutico , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Recidiva , Resultado do Tratamento
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