Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21
Filtrar
1.
J Nucl Med ; 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34649942

RESUMO

The role of prostate-specific membrane antigen (PSMA)-targeted PET in comparison to mpMRI in the evaluation of intraprostatic cancer foci is not well defined. The aim of our study was to compare the diagnostic performances of PSMA PET/CT, mpMRI and PSMA PET/CT+mpMRI using 3 independent blinded readers for each modality and with histopathology as gold standard in the detection, intra-prostatic localization and local extension of primary prostate cancer. Methods: Patients with intermediate- or high-risk prostate cancer who underwent a PSMA PET/CT as part of the prospective trial (NCT03368547) and a mpMRI prior to radical prostatectomy were included. Each imaging modality was interpreted by 3 blinded independent readers unaware of the other modality result. Central majority rule was applied (2:1). Whole-mount pathology was used as the gold-standard. Imaging scans and whole-mount pathology were interpreted using the same standardized approach on a segment- and lesion-level. A "neighboring" approach was used to define imaging/pathology correlation for the detection of individual prostate cancer foci. Accuracy in determining the location, extraprostatic extension (EPE) and seminal vesicle invasion (SVI) of prostate cancer foci was assessed using receiver operating characteristic (ROC) analysis. Inter-reader agreement was calculated using inter-class coefficient (ICC) analysis. Results: The final analysis included 74 patients (14/74 ( 19%) intermediate risk and 60/74 (81%) high risk). Cancer detection rate (lesion-based analysis) was 85%, 83% and 87 for PSMA PET/CT, mpMRI and PSMA PET/CT+mpMRI, respectively. ΔAUC between PSMA PET/CT+mpMRI and the two imaging modalities alone for delineation of tumor localization (segment-based analysis) was statistically significant (p<0.001), but not between PSMA PET/CT and mpMRI (P = 0.093). mpMRI outperformed PSMA PET/CT in detecting EPE (P = 0.002) and SVI (P = 0.001). On a segment-level analysis, ICC analysis showed moderate reliability among PSMA PET/CT and mpMRI readers using a 5-point Likert scale (range: 0.53 to 0.64). In the evaluation of T-staging, poor reliability was found among PSMA PET/CT readers and poor to moderate reliability was found for mpMRI readers. Conclusion: PSMA PET/CT and mpMRI have similar accuracy in the detection and intra-prostatic localization of prostate cancer foci. mpMRI performs better in identifying EPE and SVI. For the T-staging evaluation of intermediate to high-risk prostate cancer patients, mpMRI should still be considered the imaging modality of reference. Whenever available, PSMA PET/MRI or the co-registration/fusion of PSMA PET/CT and mpMRI (PSMA PET+mpMRI) should be used as it improves tumor extent delineation.

2.
Nat Commun ; 12(1): 4884, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34385460

RESUMO

Pathology is practiced by visual inspection of histochemically stained tissue slides. While the hematoxylin and eosin (H&E) stain is most commonly used, special stains can provide additional contrast to different tissue components. Here, we demonstrate the utility of supervised learning-based computational stain transformation from H&E to special stains (Masson's Trichrome, periodic acid-Schiff and Jones silver stain) using kidney needle core biopsy tissue sections. Based on the evaluation by three renal pathologists, followed by adjudication by a fourth pathologist, we show that the generation of virtual special stains from existing H&E images improves the diagnosis of several non-neoplastic kidney diseases, sampled from 58 unique subjects (P = 0.0095). A second study found that the quality of the computationally generated special stains was statistically equivalent to those which were histochemically stained. This stain-to-stain transformation framework can improve preliminary diagnoses when additional special stains are needed, also providing significant savings in time and cost.


Assuntos
Biópsia com Agulha de Grande Calibre/métodos , Aprendizado Profundo , Diagnóstico por Computador/métodos , Nefropatias/patologia , Rim/patologia , Coloração e Rotulagem/métodos , Algoritmos , Corantes/química , Corantes/classificação , Corantes/normas , Diagnóstico Diferencial , Humanos , Nefropatias/diagnóstico , Patologia Clínica/métodos , Patologia Clínica/normas , Padrões de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Coloração e Rotulagem/normas
3.
Transpl Infect Dis ; 23(4): e13656, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34176206

RESUMO

Mucormycosis is a rare fungal infection that typically affects severely immunocompromised individuals, often resulting in significant morbidity and mortality. Although early and aggressive intervention is necessary to prevent poor outcomes, diagnosis of this infection remains difficult. We report the first case, to our knowledge, of invasive gastrointestinal mucormycosis initially identified by next-generation sequencing of cfDNA from the blood, and discuss the various benefits and challenges which come with new molecular diagnostic techniques.


Assuntos
Ácidos Nucleicos Livres , Mucormicose , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hospedeiro Imunocomprometido , Mucormicose/diagnóstico , Mucormicose/tratamento farmacológico
4.
Urol Oncol ; 39(6): 327-337, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34034966

RESUMO

Kidney cancer is the 13th most common malignancy globally, and the incidence is rising. Papillary renal cell carcinoma is the second most common subtype, comprising 10-15% of renal cell carcinomas. Though the histologic features of this subtype were initially described in the 1990's, our understanding of the genetic and molecular characteristics of this disease have rapidly evolved over the past decade. In this review, we summarize the contemporary understanding of the clinical, morphologic, radiographic, and genetic characteristics of papillary renal cell carcinoma, as well as clinical considerations, current options for management, and prognosis.

5.
J Urol ; 206(3): 595-603, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33908801

RESUMO

PURPOSE: The appropriate number of systematic biopsy cores to retrieve during magnetic resonance imaging (MRI)-targeted prostate biopsy is not well defined. We aimed to demonstrate a biopsy sampling approach that reduces required core count while maintaining diagnostic performance. MATERIALS AND METHODS: We collected data from a cohort of 971 men who underwent MRI-ultrasound fusion targeted biopsy for suspected prostate cancer. A regional targeted biopsy (RTB) was evaluated retrospectively; only cores within 2 cm of the margin of a radiologist-defined region of interest were considered part of the RTB. We compared detection rates for clinically significant prostate cancer (csPCa) and cancer upgrading rate on final whole mount pathology after prostatectomy between RTB, combined, MRI-targeted, and systematic biopsy. RESULTS: A total of 16,459 total cores from 971 men were included in the study data sets, of which 1,535 (9%) contained csPCa. The csPCa detection rates for systematic, MRI-targeted, combined, and RTB were 27.0% (262/971), 38.3% (372/971), 44.8% (435/971), and 44.0% (427/971), respectively. Combined biopsy detected significantly more csPCa than systematic and MRI-targeted biopsy (p <0.001 and p=0.004, respectively) but was similar to RTB (p=0.71), which used on average 3.8 (22%) fewer cores per patient. In 102 patients who underwent prostatectomy, there was no significant difference in upgrading rates between RTB and combined biopsy (p=0.84). CONCLUSIONS: A RTB approach can maintain state-of-the-art detection rates while requiring fewer retrieved cores. This result informs decision making about biopsy site selection and total retrieved core count.


Assuntos
Imagem Multimodal/métodos , Próstata/patologia , Prostatectomia/estatística & dados numéricos , Neoplasias da Próstata/diagnóstico , Idoso , Biópsia com Agulha de Grande Calibre/métodos , Biópsia com Agulha de Grande Calibre/estatística & dados numéricos , Conjuntos de Dados como Assunto , Estudos de Viabilidade , Humanos , Biópsia Guiada por Imagem/métodos , Biópsia Guiada por Imagem/estatística & dados numéricos , Imagem por Ressonância Magnética Intervencionista/métodos , Imagem por Ressonância Magnética Intervencionista/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/estatística & dados numéricos , Imageamento por Ressonância Magnética Multiparamétrica/estatística & dados numéricos , Gradação de Tumores , Próstata/diagnóstico por imagem , Próstata/cirurgia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos , Análise Espacial , Ultrassonografia de Intervenção/estatística & dados numéricos
6.
Eur Urol ; 79(4): 456-465, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32631746

RESUMO

BACKGROUND: The potential for low-grade (grade group 1 [GG1]) prostate cancer (PCa) to progress to high-grade disease remains unclear. OBJECTIVE: To interrogate the molecular and biological features of low-grade PCa serially over time. DESIGN, SETTING, AND PARTICIPANTS: Nested longitudinal cohort study in an academic active surveillance (AS) program. Men were on AS for GG1 PCa from 2012 to 2017. INTERVENTION: Electronic tracking and resampling of PCa using magnetic resonance imaging/ultrasound fusion biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: ERG immunohistochemistry (IHC) and targeted DNA/RNA next-generation sequencing were performed on initial and repeat biopsies. Tumor clonality was assessed. Molecular data were compared between men who upgraded and those who did not upgrade to GG ≥ 2 cancer. RESULTS AND LIMITATIONS: Sixty-six men with median age 64 yr (interquartile range [IQR], 59-69) and prostate-specific antigen 4.9 ng/mL (IQR, 3.3-6.4) underwent repeat sampling of a tracked tumor focus (median interval, 11 mo; IQR, 6-13). IHC-based ERG fusion status was concordant at initial and repeat biopsies in 63 men (95% vs expected 50%, p < 0.001), and RNAseq-based fusion and isoform expression were concordant in nine of 13 (69%) ERG+ patients, supporting focal resampling. Among 15 men who upgraded with complete data at both time points, integrated DNA/RNAseq analysis provided evidence of shared clonality in at least five cases. Such cases could reflect initial undersampling, but also support the possibility of clonal temporal progression of low-grade cancer. Our assessment was limited by sample size and use of targeted sequencing. CONCLUSIONS: Repeat molecular assessment of low-grade tumors suggests that clonal progression could be one mechanism of upgrading. These data underscore the importance of serial tumor assessment in men pursuing AS of low-grade PCa. PATIENT SUMMARY: We performed targeted rebiopsy and molecular testing of low-grade tumors on active surveillance. Our findings highlight the importance of periodic biopsy as a component of monitoring for cancer upgrading during surveillance.

7.
J Urol ; 205(2): 444-451, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33026934

RESUMO

PURPOSE: Oncologic efficacy of focal therapies in prostate cancer depends heavily on accurate tumor size estimation. We aim to evaluate the agreement between radiologic tumor size and pathological tumor size, and identify predictors of pathological tumor size. MATERIALS AND METHODS: This single arm study cohort included all consecutive patients with biopsy proven prostate cancer and a corresponding PI-RADS®v2 3 or greater index tumor on multiparametric magnetic resonance imaging who subsequently underwent radical prostatectomy. Radiologic tumor size was defined as maximum tumor diameter on multiparametric magnetic resonance imaging and compared to whole mount histopathology tumor correlates. The difference between radiologic tumor size and pathological tumor size was assessed, and clinical, pathological and radiographic predictors of pathological tumor size were examined. RESULTS: A total of 461 consecutive lesions in 441 men were included for statistical analysis. Mean radiologic tumor size and pathological tumor size was 1.57 and 2.37 cm, respectively (p <0.001). Radiologic tumor size consistently underestimated pathological tumor size regardless of the preoperative covariates, and the degree of underestimation increased with smaller radiologic tumor size and lower PI-RADSv2 scores. Pathological tumor size was significantly larger for biopsy Gleason Grade Group (GG) 5 compared to GG1 (mean change 0.37 cm, p=0.014), PI-RADSv2 5 lesions compared to PI-RADSv2 4 (mean change 0.26, p=0.006) and higher prostate specific antigen density. The correlations between radiologic tumor size vs pathological tumor size according to biopsy GG and radiologic covariates were generally low with correlation coefficients ranging between 0.1 and 0.65. CONCLUSIONS: Multiparametric magnetic resonance imaging frequently underestimates pathological tumor size and the degree of underestimation increases with smaller radiologic tumor size and lower PI-RADSv2 scores. Therefore, a larger ablation margin may be required for smaller tumors and lesions with lower PI-RADSv2 scores. These variables must be considered when estimating treatment margins in focal therapy.


Assuntos
Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Período Pré-Operatório , Prostatectomia , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos , Carga Tumoral
8.
Radiology ; 296(2): 348-355, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32515678

RESUMO

Background Microstructural MRI has the potential to improve diagnosis and characterization of prostate cancer (PCa), but validation with histopathology is lacking. Purpose To validate ex vivo diffusion-relaxation correlation spectrum imaging (DR-CSI) in the characterization of microstructural tissue compartments in prostate specimens from men with PCa by using registered whole-mount digital histopathology (WMHP) as the reference standard. Materials and Methods Men with PCa who underwent 3-T MRI and robotic-assisted radical prostatectomy between June 2018 and January 2019 were prospectively studied. After prostatectomy, the fresh whole prostate specimens were imaged in patient-specific three-dimensionally printed molds by using 3-T MRI with DR-CSI and were then sliced to create coregistered WMHP slides. The DR-CSI spectral signal component fractions (fA, fB, fC) were compared with epithelial, stromal, and luminal area fractions (fepithelium, fstroma, flumen) quantified in PCa and benign tissue regions. A linear mixed-effects model assessed the correlations between (fA, fB, fC) and (fepithelium, fstroma, flumen), and the strength of correlations was evaluated by using Spearman correlation coefficients. Differences between PCa and benign tissues in terms of DR-CSI signal components and microscopic tissue compartments were assessed using two-sided t tests. Results Prostate specimens from nine men (mean age, 65 years ± 7 [standard deviation]) were evaluated; 20 regions from 17 PCas, along with 20 benign tissue regions of interest, were analyzed. Three DR-CSI spectral signal components (spectral peaks) were consistently identified. The fA, fB, and fC were correlated with fepithelium, fstroma, and flumen (all P < .001), with Spearman correlation coefficients of 0.74 (95% confidence interval [CI]: 0.62, 0.83), 0.80 (95% CI: 0.66, 0.89), and 0.67 (95% CI: 0.51, 0.81), respectively. PCa exhibited differences compared with benign tissues in terms of increased fA (PCa vs benign, 0.37 ± 0.05 vs 0.27 ± 0.06; P < .001), decreased fC (PCa vs benign, 0.18 ± 0.06 vs 0.31 ± 0.13; P = .01), increased fepithelium (PCa vs benign, 0.44 ± 0.13 vs 0.26 ± 0.16; P < .001), and decreased flumen (PCa vs benign, 0.14 ± 0.08 vs 0.27 ± 0.18; P = .004). Conclusion Diffusion-relaxation correlation spectrum imaging signal components correlate with microscopic tissue compartments in the prostate and differ between cancer and benign tissue. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Lee and Hectors in this issue.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Próstata/diagnóstico por imagem , Próstata/patologia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Idoso , Histocitoquímica , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes
9.
Proc Natl Acad Sci U S A ; 117(1): 563-572, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31871155

RESUMO

Small cell carcinoma of the bladder (SCCB) is a rare and lethal phenotype of bladder cancer. The pathogenesis and molecular features are unknown. Here, we established a genetically engineered SCCB model and a cohort of patient SCCB and urothelial carcinoma samples to characterize molecular similarities and differences between bladder cancer phenotypes. We demonstrate that SCCB shares a urothelial origin with other bladder cancer phenotypes by showing that urothelial cells driven by a set of defined oncogenic factors give rise to a mixture of tumor phenotypes, including small cell carcinoma, urothelial carcinoma, and squamous cell carcinoma. Tumor-derived single-cell clones also give rise to both SCCB and urothelial carcinoma in xenografts. Despite this shared urothelial origin, clinical SCCB samples have a distinct transcriptional profile and a unique transcriptional regulatory network. Using the transcriptional profile from our cohort, we identified cell surface proteins (CSPs) associated with the SCCB phenotype. We found that the majority of SCCB samples have PD-L1 expression in both tumor cells and tumor-infiltrating lymphocytes, suggesting that immune checkpoint inhibitors could be a treatment option for SCCB. We further demonstrate that our genetically engineered tumor model is a representative tool for investigating CSPs in SCCB by showing that it shares a similar a CSP profile with clinical samples and expresses SCCB-up-regulated CSPs at both the mRNA and protein levels. Our findings reveal distinct molecular features of SCCB and provide a transcriptional dataset and a preclinical model for further investigating SCCB biology.


Assuntos
Carcinoma de Células Pequenas/patologia , Carcinoma de Células de Transição/patologia , Transformação Celular Neoplásica/genética , Neoplasias da Bexiga Urinária/patologia , Bexiga Urinária/patologia , Urotélio/patologia , Animais , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Carcinoma de Células Pequenas/genética , Carcinoma de Células Pequenas/terapia , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/terapia , Transformação Celular Neoplásica/efeitos dos fármacos , Células Cultivadas , Cistectomia , Conjuntos de Dados como Assunto , Células Epiteliais , Regulação Neoplásica da Expressão Gênica , Engenharia Genética , Humanos , Linfócitos do Interstício Tumoral/metabolismo , Camundongos , Cultura Primária de Células , RNA-Seq , Bexiga Urinária/citologia , Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/terapia , Urotélio/citologia , Ensaios Antitumorais Modelo de Xenoenxerto
10.
J Pathol Inform ; 10: 31, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31620310

RESUMO

Background: The need for extending pathology diagnostic expertise to more areas is now being met by the maturation of technology that can effectively deliver this level of care. The experience and lessons learned from our successfully deployed International Telepathology Service (ITS) to a hospital system in China guided us in starting a domestic telepathology network, the California Telepathology Service (CTS). Many of the lessons learned from the ITS project informed our decision-making for the CTS. New challenges were recognized and overcome, such as addressing the complexity and cost-benefit tradeoffs involved in setting up a digital consultation system that competes with an established conventional glass slide delivery system. Methods: The CTS is based on a hub-and-spoke telepathology network using Leica Biosystems whole-slide image scanners and the eSlide Manager (eSM Version 12.3.3.7055, Leica Biosystems) digital image management software solution. The service currently comprises six spoke sites (UC San Diego [UCSD], UC Irvine [UCI], UC Davis, Northridge Hospital Medical Center [NHMC], Olive View Medical Center [OVMC], and Children's Hospital Los Angeles) and one central hub site (UCLA Medical Center). So far, five sites have been validated for telepathology case consultations following established practice guidelines, and four sites (UCI, UCSD, NHMC, and OVMC) have activated the service. Results: For the active spoke sites, we reviewed the volume, turnaround time (TAT), and case types and evaluated for utility and value. From May 2017 to July 2018, a total of 165 cases were submitted. Of note, digital consultations were particularly advantageous for preliminary kidney biopsy diagnoses (avg TAT 0.7 day). Conclusion: For spoke sites, telepathology provided shortened TAT and significant financial savings over hiring faculty with expertise to support a potentially low-volume service. For the hub site, the value includes exposure to educationally valuable cases, additional caseload volume to support specialized services, and improved communication with referring facilities over traditional carrier mail. The creation of a hub-and-spoke telepathology network is an expensive undertaking, and careful consideration needs to be given to support the needs of the clinical services, acquisition and effective deployment of the appropriate equipment, network requirements, and laboratory workflows to ensure a successful and cost-effective system.

11.
JAMA Netw Open ; 2(9): e1911019, 2019 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-31509206

RESUMO

Importance: Transrectal, ultrasonography-guided prostate biopsy often fails to disclose the severity of underlying pathologic findings for prostate cancer. Magnetic resonance imaging (MRI)-guided biopsy may improve the characterization of prostate pathologic results, but few studies have examined its use for the decision to enter active surveillance. Objective: To evaluate whether confirmatory biopsy findings by MRI guidance are associated with the risk of pathologic disease upgrading among patients with prostate cancer during active surveillance. Design, Settings, and Participants: This retrospective cohort study used prospectively obtained registry data from 332 men with prostate cancer of Gleason grade group (GG) 2 or lower who were referred for active surveillance at a large academic medical center from January 1, 2009, through December 31, 2017. Exposures: All confirmatory and follow-up biopsies were performed using MRI guidance with an MRI-ultrasonography fusion device. Patients underwent repeated MRI-guided biopsies every 12 to 24 months. At follow-up sessions, in addition to obtaining systematic samples, lesions seen on MRI were targeted and foci of low-grade prostate cancer were obtained again using tracking technology. Active surveillance was terminated with detection of at least GG3 disease or receipt of treatment. Main Outcomes and Measures: The primary outcome was upgrading to at least GG3 disease during active surveillance. Secondary outcomes were the associations of MRI lesion grade, prostate-specific antigen (PSA) level, PSA density, and biopsy method (targeted, systematic, or tracked) with the primary outcome. Results: Of 332 patients (mean [SD] age, 62.8 [7.6] years), 39 (11.7%) upgraded to at least GG3 disease during follow-up. The incidence of upgrading was 7.9% (9 of 114) when the confirmatory biopsy finding was normal, 11.4% (20 of 175) when the finding showed GG1 disease, and 23.3% (10 of 43) when the finding was GG2 disease (P = .03). Men with GG2 disease were almost 8 times more likely to upgrade during surveillance compared with those with normal findings but only among those with low PSA density (hazard ratio [HR], 7.82; 95% CI, 2.29-26.68). A PSA density of at least 0.15 ng/mL/mL was associated with increased risk of upgrading among patients with normal findings (HR, 7.21; 95% CI, 1.98-26.24) or GG1 disease (HR, 2.86; 95% CI, 1.16 to 7.03) on confirmatory biopsy. A total of 46% of pathologic disease upgrades would have been missed if only the targeted biopsy was performed and 65% of disease upgrades were detected only with tracked biopsy. Conclusions and Relevance: The findings suggest that confirmatory biopsy with MRI guidance is significantly associated with future disease upgrading of prostate cancer, especially when combined with PSA density, and should be considered as an appropriate entry point for active surveillance. Systematic and targeted biopsies were additive in detection of clinically significant cancers. Repeated biopsy at sites at which findings were previously abnormal (tracking biopsy) facilitated detection of cancers not suitable for continued active surveillance.


Assuntos
Neoplasias da Próstata/patologia , Conduta Expectante/métodos , Idoso , Estudos de Coortes , Humanos , Biópsia Guiada por Imagem , Calicreínas/sangue , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Modelos de Riscos Proporcionais , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/terapia , Estudos Retrospectivos , Ultrassonografia
12.
JAMA Surg ; 154(9): 811-818, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31188412

RESUMO

Importance: Magnetic resonance imaging (MRI) guidance improves the accuracy of prostate biopsy for the detection of clinically significant prostate cancer, but the optimal use of such guidance is not yet clear. Objective: To determine the cancer detection rate (CDR) of targeting MRI-visible lesions vs systematic prostate sampling in the diagnosis of clinically significant prostate cancer in men who were biopsy naive. Design, Setting, and Participants: This paired cohort trial, known as the Prospective Assessment of Image Registration in the Diagnosis of Prostate Cancer (PAIREDCAP) study, was conducted in an academic medical center from January 2015 to April 2018. Men undergoing first-time prostate biopsy were enrolled. Paired-cohort participants were a consecutive series of men with MRI-visible lesions (defined by a Prostate Imaging Reporting & Data System version 2 score ≥ 3), who each underwent 3 biopsy methods at the same sitting: first, a systematic biopsy; second, an MRI-lesion biopsy targeted by cognitive fusion; and third, an MRI-lesion targeted by software fusion. Another consecutive series of men without MRI-visible lesions underwent systematic biopsies to help determine the false-negative rate of MRI during the trial period. Main Outcomes and Measures: The primary end point was the detection rate of clinically significant prostate cancer (Gleason grade group ≥2) overall and by each biopsy method separately. The secondary end points were the effects of the Prostate Imaging Reporting & Data System version 2 grade, prostate-specific antigen density, and prostate volume on the primary end point. Tertiary end points were the false-negative rate of MRI and concordance of biopsy-method results by location of detected cancers within the prostate. Results: A total of 300 men participated; 248 had MRI-visible lesions (mean [SD] age, 65.5 [7.7] years; 197 were white [79.4%]), and 52 were control participants (mean [SD] age, 63.6 [5.9] years; 39 were white [75%]). The overall CDR was 70% in the paired cohort group, achieved by combining systematic and targeted biopsy results. The CDR by systematic sampling was 15% in the group without MRI-visible lesions. In the paired-cohort group, CDRs varied from 47% (116 of 248 men) when using cognitive fusion biopsy alone, to approximately 60% when using systematic biopsy (149 of 248 men) or either fusion method alone (154 of 248 men), to 70% (174 of 248 men) when combining systematic and targeted biopsy. Discordance of tumor locations suggests that the different biopsy methods detect different tumors. Thus, combining targeting and systematic sampling provide greatest sensitivity for detection of clinically significant prostate cancer. For all biopsy methods, the Prostate Imaging Reporting & Data System version 2 grade and prostate-specific antigen density were directly associated with CDRs, and prostate volume was inversely associated. Conclusions and Relevance: An MRI-visible lesion in men undergoing first-time prostate biopsy identifies those with a heightened risk of clinically significant prostate cancer. Combining targeted and systematic biopsy offers the best chances of detecting the cancer.


Assuntos
Biópsia Guiada por Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Sistema de Registros , Centros Médicos Acadêmicos , Fatores Etários , Idoso , Biópsia por Agulha/métodos , Estudos de Coortes , Reações Falso-Negativas , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/terapia , Medição de Risco , Sensibilidade e Especificidade , Análise de Sobrevida , Estados Unidos
13.
AJR Am J Roentgenol ; 213(3): W134-W142, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31216201

RESUMO

OBJECTIVE. The purpose of this study is to evaluate the performance of the apparent diffusion coefficient ratio (ADCratio; the ADC of the suspected prostate cancer [PCa] focus on MRI divided by the ADC in a noncancerous reference area) with that of conventional ADC for detection of high-grade PCa (Gleason score [GS] ≥ 3 + 4) versus low-grade PCa (GS = 3 + 3) with whole-mount (WM) histopathologic analysis used as a reference. MATERIALS AND METHODS. The cohort of this retrospective study included 218 men with 240 unilateral PCa lesions assessed by both 3-T multiparametric MRI and whole-mount histopathologic analysis. ROIs were placed on individual lesions verified by WM histopathologic analysis, to calculate the mean ADC (ADCtumor_mean) and lowest ADC within each lesion (ADCtumor_min), and within non-tumor-containing regions of the same tumor zone but on the contralateral side (ADCbenign), to calculate the background ADC. The ADCratio_mean (the ADCtumor_mean divided by the ADCbenign) was calculated. The performance of individual ADCtumor and ADCratio_mean values in discriminating PCa with a GS of 3 + 3 from PCa with a GS of 3 + 4 or greater was assessed using the AUC value. RESULTS. The ADCratio_mean had a higher AUC value for discriminating PCa lesions with a GS of 3 + 3 from those with a GS of 3 + 4 or greater (the AUC value increased from 0.70 using the ADCtumor_mean and 0.67 using the ADCtumor_min [the minimum ADC of the PCa lesion] to 0.80 for the ADCratio_mean and 0.72 for the ADCratio_min [the ADCtumor_min divided by the ADCbenign]; p = 0.043). When stratified by PCa zonal location, the ADCratio_mean had significantly more robust accuracy in the transition zone (the AUC value increased from 0.63 for ADCtumor_mean to 0.87 for ADCratio_mean; p = 0.019) compared with the peripheral zone (the AUC value increased from 0.74 for ADCtumor_mean to 0.78 for ADCratio_mean; p = 0.44). When analyzed on the basis of endorectal coil use, the ADCratio_mean performed nonsignificantly better in both the endorectal coil and non-endorectal coil subcohorts, although it performed better in the former. CONCLUSION. As an intrapatient-normalized diagnostic tool, the ADC ratio provided the best AUC value for discrimination of low-grade from high-grade PCa on 3-T MRI.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias da Próstata/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Meios de Contraste , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias da Próstata/patologia , Estudos Retrospectivos
14.
Nat Biomed Eng ; 3(6): 466-477, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31142829

RESUMO

The histological analysis of tissue samples, widely used for disease diagnosis, involves lengthy and laborious tissue preparation. Here, we show that a convolutional neural network trained using a generative adversarial-network model can transform wide-field autofluorescence images of unlabelled tissue sections into images that are equivalent to the bright-field images of histologically stained versions of the same samples. A blind comparison, by board-certified pathologists, of this virtual staining method and standard histological staining using microscopic images of human tissue sections of the salivary gland, thyroid, kidney, liver and lung, and involving different types of stain, showed no major discordances. The virtual-staining method bypasses the typically labour-intensive and costly histological staining procedures, and could be used as a blueprint for the virtual staining of tissue images acquired with other label-free imaging modalities.


Assuntos
Aprendizado Profundo , Processamento de Imagem Assistida por Computador , Coloração e Rotulagem , Algoritmos , Fluorescência , Humanos , Fígado/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Melaninas/metabolismo , Redes Neurais de Computação , Padrões de Referência
15.
BJU Int ; 124(2): 275-281, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30694605

RESUMO

OBJECTIVE: To study the relationship of maximum cancer core length (MCCL), on targeted biopsy (TB) of magnetic resonance imaging (MRI)-visible index lesions, to volume of that tumour found at radical prostatectomy (RP). PATIENTS AND METHODS: In all, 205 men undergoing fusion biopsy and RP were divided into two groups: 136 in whom the MCCL came from an index MRI-visible lesion (TB) and 69 in whom MCCL came from a non-targeted lesion (non-targeted biopsy [NTB]). MRI was 3-T multi-parametric and biopsy was via MRI-ultrasonography fusion. RESULTS: In the TB group, MCCL correlated with volume of clinically significant index tumours (ρ = 0.44-0.60, P < 0.01). The correlation was similar for first and repeat biopsy and for transition and peripheral zone lesions (ρ = 0.42-0.49, P < 0.01). No correlations were found in the NTB group. TB MCCL (6-10 and >10 mm) and MRI lesion diameter (>20 mm) were independently associated with tumour volume. TB MCCLs >10 mm and Gleason scores >7 were each associated with pathological T3 disease (odds ratios 5.73 and 5.04, respectively), but MRI lesion diameter lesion was not. CONCLUSIONS: MCCL on a TB from an MRI-visible lesion is an independent predictor of both cancer volume and pathological stage. This relationship does not exist for MCCL from a NTB core. Quantifying CCL on MRI-TBs may have a value, not previously described, to risk-stratify patients with prostate cancer before treatment.


Assuntos
Neoplasias da Próstata/patologia , Carga Tumoral , Idoso , Humanos , Biópsia Guiada por Imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prostatectomia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos , Ultrassonografia de Intervenção
16.
Eur Urol ; 76(1): 18-23, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30685078

RESUMO

Multiparametric magnetic resonance imaging (mpMRI) has transformed the management of localized prostate cancer by improving identification of clinically significant disease at diagnosis. Approximately 20% of primary prostate tumors are invisible to mpMRI, and we hypothesize that this invisibility reflects fundamental molecular properties of the tumor. We therefore profiled the genomes and transcriptomes of 40 International Society of Urological Pathology grade 2 tumors: 20 mpMRI-invisible (Prostate Imaging-Reporting and Data System [PI-RADS] v2 <3) and 20 mpMRI-visible (PI-RADS v2 5) tumors. mpMRI-visible tumors were enriched in hallmarks of nimbosus, an aggressive pathological, molecular, and microenvironmental phenomenon in prostate cancer. These hallmarks included genomes with increased mutation density, a higher prevalence of intraductal carcinoma/cribriform architecture pathology, and altered abundance of 102 transcripts, including overexpression of noncoding RNAs such as SCHLAP1. Multiple small nucleolar RNAs (snoRNAs) were identified, and a snoRNA signature synergized with nimbosus hallmarks to discriminate visible from invisible tumors. These data suggest a confluence of aggressive molecular and microenvironmental phenomena underlie mpMRI visibility of localized prostate cancer. PATIENT SUMMARY: We examined the correlation between tumor biology and magnetic resonance imaging (MRI) visibility in a group of patients with low- intermediate-risk prostate cancer. We observed that MRI findings are associated with biological features of aggressive prostate cancer.


Assuntos
Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/genética , RNA Longo não Codificante/genética , RNA Mensageiro/metabolismo , RNA Nuclear Pequeno/metabolismo , Idoso , Dosagem de Genes , Perfilação da Expressão Gênica , Genoma , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , RNA Longo não Codificante/metabolismo , Transcriptoma , Carga Tumoral , Microambiente Tumoral
17.
Abdom Radiol (NY) ; 44(3): 1052-1061, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30460528

RESUMO

PURPOSE: To determine the characteristics of missed prostate cancer (PCa) lesions on 3T multiparametric-MRI (mpMRI) based on PI-RADSv2 with whole-mount histopathology (WMHP) correlation. MATERIALS AND METHODS: This IRB-approved, HIPAA-compliant study, included 614 consecutive men with 3T mpMRI prior to prostatectomy at a single tertiary center between 12/2009 and 4/2017. Clinical, mpMRI, and pathologic features were obtained. PI-RADSv2-based MRI detected lesions were matched with previously finalized WMHP by a genitourinary (GU) radiologist and a GU pathologist. Patients with no mpMRI detected PCa lesion, but with at least one lesion ≥ 1 cm on WMHP, were reviewed retrospectively and assigned a PI-RADSv2 score. Tumor characteristics were compared between missed and detected lesions. RESULT: The final cohort included 518 patients with 1085 WMHP lesions. 51.9% (563/1085) of lesions were missed on 3T mpMRI. 71.4% (402/563), 21.7% (122/563), 4.4% (25/563), and 2.5% (14/563) of the missed lesions were Gleason scores (GS) 3 + 3, 3 + 4, 4 + 3, and 8 - 10, respectively. Missed PCa lesions had significantly lower proportion of GS ≥ 7 (p < 0.001) and smaller size for overall (p < 0.001) and index subcohorts (p < 0.001), as compared to detected lesions. 34.5% (194) of overall and 71.2% (79) index missed lesions were larger than 1 cm. In 13.7% (71/518) of patients without MR detected PCa, 149 lesions were detected on WMHP, with 70 (47%) lesions ≥ 1 cm. In retrospective review of these lesions, 42.9% (30), 18.6% (13), 21.5% (15), 10% (7), and 7% (5) were PI-RADSv2 1, 2, 3, 4, and 5, respectively. CONCLUSION: 3T mpMRI has an excellent per patients diagnostic performance for PCa and majority of missed lesions are clinically nonsignificant.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Erros de Diagnóstico/estatística & dados numéricos , Imageamento por Ressonância Magnética/métodos , Neoplasias da Próstata/diagnóstico por imagem , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos
18.
Urol Oncol ; 36(9): 401.e19-401.e25, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30064933

RESUMO

BACKGROUND: In the era of increasing scrutiny of delivery of quality care, efforts to decrease surgical overtreatment of insignificant prostate cancer (iCaP) continue. OBJECTIVE: To quantify the incidence of surgical overtreatment over time among a contemporary series of men diagnosed with CaP. METHODS: We retrospectively reviewed the medical records and pathologic specimens for men with CaP who underwent radical prostatectomy between January 2009 and December 2016 at a tertiary referral center. Overtreatment, defined as presence of iCaP in radical prostatectomy specimens, was the primary endpoint. iCaP was defined as a tumor of Gleason score no more than 6 and a tumor diameter ≤10mm (volume <0.5 cc). Independent predictors of iCaP were determined using a multivariable model. RESULTS: A total of 1,283 men were eligible for analysis. Overtreatment was found in 86 (6.7%) patients. The frequency of overtreatment significantly decreased from 15% (24/165) in 2009 to 3% (4/134) of patients in 2016 (P < 0.001). In the multivariable analysis, prostate-specific antigen density ≥0.15 vs. <0.15 (odds ratio [OR] 0.30, 95% confidence interval [CI] 0.15-0.64, P < 0.01), biopsy Gleason score 3+4 vs. 3+3 (OR 0.15, 95% CI 0.08-0.29, P < 0.01), African American vs. White ethnicity (OR 0.13, 95% CI 0.02-0.96, P = 0.045), and year of surgery (OR 0.88, 95% CI 0.77-0.99, P = 0.03) remained significant predictors of iCaP at surgery. Over the years of study, the odds of overtreatment decreased by 12% annually (OR 0.88, 95 CI 0.77-0.99, P = 0.03). At the same time, the pathological evidence of advanced disease at surgery (≥T3a with/without lymph node involvement) remained unchanged. COMMENT: Surgical overtreatment of CaP has declined to a rate of approximately 3% at this tertiary referral center; further decline is likely. The decline probably has a multifactorial explanation: decreased rate of overdiagnosis, better patient selection for surgery, or change in the referral pattern.


Assuntos
Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Idoso , História do Século XXI , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/patologia , Centros de Atenção Terciária
19.
J Urol ; 200(3): 564-572, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29524506

RESUMO

PURPOSE: Multiparametric magnetic resonance imaging and biopsy based molecular tests such as the 17-gene Oncotype DX® Genomic Prostate Score™ assay are increasingly performed to improve risk stratification in men with clinically localized prostate cancer. The prostate score assay was previously shown to be a significant independent predictor of adverse pathology findings at radical prostatectomy in men diagnosed by systematic biopsies only. Therefore, we investigated the ability of the prostate score assay to predict adverse pathology findings in the setting of magnetic resonance imaging guided prostate biopsy. MATERIALS AND METHODS: We identified men diagnosed with NCCN® (National Comprehensive Cancer Network®) very low, low or intermediate risk prostate cancer who underwent simultaneous multiparametric magnetic resonance imaging fusion targeted and systematic prostate biopsy with subsequent radical prostatectomy within 6 months. Prostate score assay testing was performed on biopsy tissue with the highest Gleason score. The primary outcome of the study was adverse pathology findings, defined as Gleason score 4 + 3 or greater disease and/or pT3+ at radical prostatectomy. Independent predictors of adverse pathology findings were determined in a multivariable model to adjust for clinical parameters. RESULTS: A total of 134 men were eligible for primary analysis. On univariable analysis the UCLA score, magnetic resonance imaging, prostate score assay results and biopsy Gleason score were significant predictors of adverse pathology findings. After multivariable adjustment prostate score assay values remained a significant predictor of adverse pathology results (prostate score assay per 20 U OR 3.28, 95% CI 1.74-6.62, p <0.001). A wide and overlapping distribution of prostate score assay results was seen across PI-RADS® (Prostate Imaging Reporting and Data System) version 2 scores. CONCLUSIONS: The prostate score assay result is an independent predictor of adverse pathology findings in patients who were diagnosed with very low, low or intermediate risk prostate cancer in the setting of multiparametric magnetic resonance imaging fusion prostate biopsy. This assay can be useful as an independent technology or an adjunct technology to multiparametric magnetic resonance imaging to individualize risk stratification of low and intermediate risk prostate cancer.


Assuntos
Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Genômica , Humanos , Biópsia Guiada por Imagem , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Valor Preditivo dos Testes , Neoplasias da Próstata/diagnóstico por imagem , Estudos Retrospectivos , Medição de Risco
20.
Urol Case Rep ; 14: 11-14, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28607878

RESUMO

Prostate specific membrane antigen (PSMA) scanning is a sensitive method of prostate cancer detection. In a 71 y.o. man with a PSA of 49 (6%F), 4 negative MRI studies and 6 negative biopsies over an 8 year interval, a 68Ga-PSMA PET/CT scan showed a PSMA-avid spot in the prostate. Using image fusion technology, the lesion was target-biopsied and Gleason 3 + 4 = 7 (cancer core length of 12 mm) was identified. This case may herald a new application for PSMA scanning and prostate cancer imaging.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...