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1.
NMR Biomed ; 30(10)2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28665041

RESUMO

The purpose of this study was to measure and model the diffusion time dependence of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) derived from conventional prostate diffusion-weighted imaging methods as used in recommended multiparametric MRI protocols. Diffusion tensor imaging (DTI) was performed at 9.4 T with three radical prostatectomy specimens, with diffusion times in the range 10-120 ms and b-values 0-3000 s/mm2 . ADC and FA were calculated from DTI measurements at b-values of 800 and 1600 s/mm2 . Independently, a two-component model (restricted isotropic plus Gaussian anisotropic) was used to synthesize DTI data, from which ADC and FA were predicted and compared with the measured values. Measured ADC and FA exhibited a diffusion time dependence, which was closely predicted by the two-component model. ADC decreased by about 0.10-0.15 µm2 /ms as diffusion time increased from 10 to 120 ms. FA increased with diffusion time at b-values of 800 and 1600 s/mm2 but was predicted to be independent of diffusion time at b = 3000 s/mm2 . Both ADC and FA exhibited diffusion time dependence that could be modeled as two unmixed water pools - one having isotropic restricted dynamics, and the other unrestricted anisotropic dynamics. These results highlight the importance of considering and reporting diffusion times in conventional ADC and FA calculations and protocol recommendations, and inform the development of improved diffusion methods for prostate cancer imaging.


Assuntos
Anisotropia , Imagem de Difusão por Ressonância Magnética/métodos , Modelos Biológicos , Próstata/anatomia & histologia , Difusão , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
2.
J Surg Oncol ; 115(3): 307-311, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27859276

RESUMO

BACKGROUND: Total cystectomy and subsequent reconstruction of the urinary tract may be required for primary malignancy of the bladder, or in the context of multi-visceral resection for more advanced pelvic tumors. Complications following urinary diversion are a major source of morbidity, particularly in pelvic exenteration (PE) patients. METHODS: All patients who underwent radical cystectomy alone or during PE at a single tertiary referral centre between 2008 and 2014 were reviewed. Postoperative urological complications were collected and compared between groups. RESULTS: Two hundred and thirty-one patients underwent en bloc cystectomy (98 cystectomy alone, 133 as part of a PE). Postoperative urological complications occurred in 33% of the cystectomy alone group and 59% of the PE group (P < 0.001). PE for recurrence had higher complications than PE for primary malignancy (67% vs. 48%, P = 0.035). Urological leaks occurred in 3%, 6%, and 14% of patient who had cystectomy alone, PE for primary malignancy and PE for recurrence. Major blood loss and previous pelvic radiotherapy independently predicted conduit-associated complications in PE patients (P = 0.002 and 0.035). CONCLUSIONS: Urological complications of cystectomy, particularly urine leaks and sepsis, are more common in patients undergoing PE compared to those with cystectomy alone. Prior pelvic radiotherapy, the extent of surgical resection and major blood loss may contribute to urological morbidity. J. Surg. Oncol. 2017;115:307-311. © 2016 Wiley Periodicals, Inc.


Assuntos
Cistectomia/efeitos adversos , Exenteração Pélvica/efeitos adversos , Neoplasias da Bexiga Urinária/cirurgia , Doenças Urológicas/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cistectomia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Exenteração Pélvica/métodos , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
3.
Magn Reson Med ; 76(2): 626-34, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26445008

RESUMO

PURPOSE: To investigate diffusion anisotropy in whole human prostate specimens METHODS: Seven whole radical prostatectomy specimens were obtained with informed patient consent and institutional ethics approval. Diffusion tensor imaging was performed at 9.4 Tesla. Diffusion tensors were calculated from the native acquired data and after progressive downsampling RESULTS: Fractional anisotropy (FA) decreased as voxel volume increased, and differed widely between prostates. Fixation decreased mean FA by ∼0.05-0.08 at all voxel volumes but did not alter principle eigenvector orientation. In unfixed tissue high FA (> 0.6) was found only in voxels of volume <0.5 mm(3) , and then only in a small fraction of all voxels. At typical clinical voxel volumes (4-16 mm(3) ) less than 50% of voxels had FA > 0.25. FA decreased at longer diffusion times (Δ = 60 or 80 ms compared with 20 ms), but only by ∼0.02 at typical clinical voxel volume. Peripheral zone FA was significantly lower than transition zone FA in five of the seven prostates CONCLUSION: FA varies widely between prostates. The very small proportion of clinical size voxels with high FA suggests that in clinical DWI studies ADC based on three-direction measurements will be minimally affected by anisotropy. Magn Reson Med 76:626-634, 2016. © 2015 Wiley Periodicals, Inc.


Assuntos
Artefatos , Interpretação de Imagem Assistida por Computador/métodos , Próstata/diagnóstico por imagem , Próstata/patologia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Idoso , Anisotropia , Difusão , Imagem de Difusão por Ressonância Magnética , Humanos , Aumento da Imagem/métodos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Razão Sinal-Ruído
4.
NMR Biomed ; 29(5): 660-71, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26999065

RESUMO

This study compares the theoretical information content of single- and multi-compartment models of diffusion-weighted signal attenuation in prostate tissue. Diffusion-weighted imaging (DWI) was performed at 9.4 T with multiple diffusion times and an extended range of b values in four whole formalin-fixed prostates. Ten models, including different combinations of isotropic, anisotropic and restricted components, were tested. Models were ranked using the Akaike information criterion. In all four prostates, two-component models, comprising an anisotropic Gaussian component and an isotropic restricted component, ranked highest in the majority of voxels. Single-component models, whether isotropic (apparent diffusion coefficient, ADC) or anisotropic (diffusion tensor imaging, DTI), consistently ranked lower than multi-component models. Model ranking trends were independent of voxel size and maximum b value in the range tested (1.6-16 mm(3) and 3000-10,000 s/mm(2)). This study characterizes the two major water components previously identified by biexponential models and shows that models incorporating both anisotropic and restricted components provide more information-rich descriptions of DWI signals in prostate tissue than single- or multi-component anisotropic models and models that do not account for restricted diffusion.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Modelos Anatômicos , Próstata/anatomia & histologia , Processamento de Sinais Assistido por Computador , Fixação de Tecidos , Humanos , Masculino , Pessoa de Meia-Idade
5.
Radiology ; 277(3): 751-62, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26110669

RESUMO

PURPOSE: To investigate the hypothesis that the clinically observed decrease in apparent diffusion coefficient (ADC) at diffusion-weighted magnetic resonance imaging with increasing prostate cancer Gleason grade can be attributed to an increasing volume of low-diffusivity epithelial cells and corresponding decreasing volumes of higher-diffusivity stroma and lumen space rather than to increased cell density. MATERIALS AND METHODS: Tissue samples were acquired after institutional ethics review committee approval and informed consent from patients were obtained. Nuclear count, nuclear area, and gland component volumes (epithelium, stroma, lumen space) were measured in tissue from 14 patients. Gland component volumes and cellularity metrics were correlated with Gleason pattern (Spearman rank correlation coefficient) and measured ADC (Pearson correlation coefficient) in six prostates ex vivo. Differences between metrics for cancerous tissue and those for normal tissue were assessed by using a two-tailed two-sample t test. Linear mixed models with a post hoc Fisher least significant difference test were used to assess differences between gland component volumes and cellularity metrics for multiple groups. To adjust for a clustering effect due to repeated measures, the organ mean value of the measured metric for each tissue type was used in the analysis. RESULTS: There were significant differences between Gleason patterns for gland component volumes (P < .05) but not nuclear count (P = .100) or area (P = .141). There was a stronger correlation of Gleason pattern with gland component volumes (n = 553) of epithelium (Spearman ρ = 0.898, P < .001), stroma (ρ = -0.651, P < .001), and lumen space (ρ = -0.912, P = .007) than with the cellularity metrics (n = 288) nuclear area (ρ = 0.422, P = .133) or nuclear count (ρ = 0.082, P = .780). There was a stronger correlation between measured ADC and lumen volume (r = 0.688, P < .001) and epithelium volume (r = -0.647, P < .001) than between ADC and nuclear count (r = -0.598, P < .001) or nuclear area (r = -0.569, P < .001) (n = 57). CONCLUSION: Differences in the gland compartment volumes of prostate tissue having distinct diffusivities, rather than changes in the conventionally cited "cellularity" metrics, are likely to be the major contributor to clinically observed variations of ADC in prostate tissue.


Assuntos
Imagem de Difusão por Ressonância Magnética , Próstata/patologia , Epitélio/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias da Próstata/patologia
6.
NMR Biomed ; 28(4): 486-95, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25802213

RESUMO

Non-Gaussian diffusion dynamics was investigated in the two distinct water populations identified by a biexponential model of diffusion in prostate tissue. Diffusion-weighted MRI (DWI) signal attenuation was measured ex vivo in two formalin-fixed prostates at 9.4 T with diffusion times Δ = 10, 20 and 40 ms, and b values in the range 0.017-8.2 ms/µm(2) . A conventional biexponential model was compared with models in which either the lower diffusivity component or both of the components of the biexponential were stretched. Models were compared using Akaike's Information Criterion (AIC) and a leave-one-out (LOO) test of model prediction accuracy. The doubly stretched (SS) model had the highest LOO prediction accuracy and lowest AIC (highest information content) in the majority of voxels at Δ = 10 and 20 ms. The lower diffusivity stretching factor (α2 ) of the SS model was consistently lower (range ~0.3-0.9) than the higher diffusivity stretching factor (α1 , range ~0.7-1.1), indicating a high degree of diffusion heterogeneity in the lower diffusivity environment, and nearly Gaussian diffusion in the higher diffusivity environment. Stretched biexponential models demonstrate that, in prostate tissue, the two distinct water populations identified by the simple biexponential model individually exhibit non-Gaussian diffusion dynamics.


Assuntos
Imagem de Difusão por Ressonância Magnética/estatística & dados numéricos , Próstata/anatomia & histologia , Água Corporal , Difusão , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Fatores de Tempo
7.
Magn Reson Med ; 72(5): 1418-26, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24302537

RESUMO

PURPOSE: To compare the theoretical information content of four popular models of diffusion-weighted signal attenuation. METHOD: Four whole prostates were imaged fresh unfixed and fixed at 9.4T. Biexponential, kurtosis, stretched exponential, and monoexponential models were ranked using Akaike's Information Criterion (AIC) with validation by a leave-one-out test of model prediction error. RESULTS: For unfixed tissue measurements (b-value range: 17-2104 s/mm(2)) the biexponential and kurtosis models had similar information content to each other and this was distinctly higher than for the stretched and monoexponential models. In fixed-tissue measurements (b-value range: 17-8252 s/mm(2)), the biexponential model had much higher information content than the three other models. CONCLUSION: AIC-based model ranking is consistent with an independent prediction accuracy test. Biexponential and kurtosis models consistently perform better than stretched and monoexponential models. The biexponential model has increasing superiority over all three other models as maximum b-value increases above ∼2000 s/mm(2).


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Próstata/anatomia & histologia , Algoritmos , Humanos , Processamento de Imagem Assistida por Computador , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Reprodutibilidade dos Testes
8.
Urol Case Rep ; 54: 102706, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38827535

RESUMO

This case report details a fatal rectal perforation and sepsis in a comorbid 96-year-old male after traumatic urinary catheterization, highlighting the risks of IDC management in elderly patients with complex health backgrounds. Despite maximal medical therapy, including escalated antibiotics and ICU care, the patient died from septic shock linked to improper catheter insertion by a non-specialist nurse in the community. This case emphasizes the urgent need for better catheterization practices, specialized nursing education, and clear guidelines to prevent such outcomes.

9.
Magn Reson Med ; 70(4): 1160-6, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23165964

RESUMO

PURPOSE: To evaluate the effect of formalin fixation on biexponential modeling of diffusion decay in prostate tissue. METHODS: Three whole prostate specimens were imaged unfixed immediately postsurgery, and again after formalin fixation. Diffusion-weighted imaging was performed over an extended range of b-values and a biexponential model fitted to the signal decay curves. RESULTS: Tissue fixation resulted in a 35%, 20%, and 20% reduction in mean apparent diffusion coefficient of the higher diffusivity fit component for the three organs, respectively, and a 64%, 57%, and 45% reduction in mean apparent diffusion coefficient of the lower diffusivity component. The mean signal fraction of the higher diffusivity component was increased by 23%, 5%, and 1%, respectively. The effect of fixation did not appear to vary according to tissue type or glandular zone. CONCLUSION: Formalin fixed tissue appears to provide a stable model for detailed investigation of the microscopic biophysical basis of diffusion phenomena observed in vivo. Diffusivity changes that result from fixation may provide information about the microscopic environments of the biexponential components.


Assuntos
Fixadores/química , Formaldeído/química , Interpretação de Imagem Assistida por Computador/métodos , Modelos Biológicos , Próstata/química , Próstata/patologia , Fixação de Tecidos/métodos , Simulação por Computador , Humanos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
10.
BJUI Compass ; 4(5): 597-604, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37636210

RESUMO

Objective: To describe a novel RoboSling technique performed at the time of robot-assisted radical prostatectomy (RARP) and its utility for enhancing urinary function recovery postoperatively. Materials and Methods: The surgical technique involves harvesting a vascularised, fascial flap from the peritoneum on the posterior aspect of the bladder. Following completion of prostatectomy, the autologous flap is tunnelled underneath the bladder and incorporated into the rectourethralis and vertical longitudinal detrusor fibres at the posterior bladder neck with a modified Rocco suture. After urethra-vesical anastomosis is completed, the corners of the flap are hitched up to Cooper's ligament bilaterally with V-Loc sutures, tensioned and secured creating a bladder neck sling. A prospective, longitudinal cohort study was performed of 193 consecutive patients undergoing RARP between December 2016 and September 2019. The first 163 patients underwent standard RARP, and the last 30 patients had the RoboSling technique performed concurrently. Continence outcomes were the primary outcomes assessed using pad number and Expanded Prostate Cancer Composite (EPIC)-urinary domain questionnaire. Operative time (OT), estimated blood loss (EBL), complications and oncological outcomes were secondary outcomes. Results: The two groups were comparable for demographics and clinicopathological variables. At 3 months, zero pad usage (p = 0.005) and continence rates, defined as EPIC score ≥ 85 (p = 0.007), were both higher in the RoboSling group. EBL, complication rate and positive surgical margin rate did not differ between the two groups. Superior zero pad usage was observed at 1 year in the RoboSling group (p = 0.029). The RoboSling technique added on average 16 min to OT. Conclusions: The RoboSling procedure at the time of RARP was associated with earlier return to continence without negatively impacting other postoperative outcomes. This improvement in continence outcomes was maintained long term.

11.
Res Rep Urol ; 15: 113-121, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36968628

RESUMO

Purpose: Renal angiomyolipoma (AML) is the most common benign renal tumor. Whilst generally asymptomatic, they can cause life-threatening bleeding. Selective angioembolization (SAE) may be used to treat large symptomatic and asymptomatic AMLs. We aimed to evaluate the efficacy of SAE for symptomatic and asymptomatic renal AMLs and determine characteristics that predict spontaneous bleeding. Patients and Methods: Data were retrospectively collected from a prospectively maintained database from July 2011 to April 2022. Patients were included if AML was >4cm and they underwent subsequent SAE. Follow-up imaging was analyzed to calculate mean reduction in AML size. Clinical notes were reviewed to analyze lesion characteristics including vascularity, fat content and presence of aneurysm as well as post-procedural complications. Results: 26 patients with 30 AMLs were identified. Interval of follow-up imaging ranged from 1 to 60 months. 25 AMLs were embolized electively with 5 emergency embolizations performed for bleeding. Mean reduction in AML volume was 41% at 3 months (p=0.013) and 63% at 12 months (p=0.007). All 5 bleeding AMLs had a rich vascularity with 60% also having either aneurysms or a low fat content. Complications included post-embolic syndrome (n=9), segmental renal parenchyma devascularization (n=3), acute bleeding requiring re-embolization (n=2), nephrectomy for ongoing bleeding (n=1) and delayed bleeding managed conservatively (n=1). No deterioration in renal function was observed. Conclusion: SAE is an effective procedure for managing symptomatic and asymptomatic renal AML, with minimal significant complications. AML vascularity, fat content and aneurysms may be useful characteristics to assess future risk of bleeding in patients with renal AML.

12.
Can Urol Assoc J ; 17(7): E176-E181, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37068151

RESUMO

INTRODUCTION: Renal colic is a common emergency department (ED) presentation. Variations in assessment and management of suspected renal colic may have significant implications on patient and hospital outcomes. We developed a clinical practice guideline to standardize the assessment and management of renal colic in the ED. We subsequently compared outcomes before and after guideline implementation. METHODS: The guideline standardizes the analgesia regimen, urology consult criteria, imaging modality, patient education, and followup instructions. This is a single-center, observational cohort study of patients presenting to the ED with renal colic prospectively collected after guideline implementation (December 2018 to May 2019) compared to a control group retrospectively collected before guideline implementation (December 2017 to May 2018). A total of 528 patients (pre-guideline n=283, post-guideline n=245) were included. Statistical analysis was performed with SPSS using multivariate linear regression. RESULTS: ED length of stay (LOS) was significantly shorter after guideline implementation (pre-guideline 295.82±178.8 minutes vs. post-guideline 253.2±118.2 minutes, p=0.017). The number of computed tomography (CT) scans patients received was significantly less after guideline implementation (pre guideline 1.35±1.34 vs. post-guideline 1.00±0.68, p=0.034). Patients discharged for conservative management had a lower re-presentation rate in the post-guideline group (12.6%) than the pre-guideline group (17.2%); however, this did not reach statistical significance (p=0.18). CONCLUSIONS: Implementation of a clinical practice guideline for ureteric stones reduces the ED LOS and the total number of CT scan in patients who present with renal colic. Standardizing assessment and management of ureteric stones can potentially improve patient and hospital outcomes without compromising the quality of care.

13.
Magn Reson Med ; 68(6): 1943-8, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22287422

RESUMO

Diffusion tensor microimaging at 16.4 T with 40 µm isotropic voxels was used to investigate anisotropic water diffusion in prostate tissue at spatial resolution approaching the cellular scale. Nine normal glandular tissue samples were collected from the peripheral zone of six formalin fixed radical prostatectomy specimens. Fibromuscular stromal tissue exhibited microscopic diffusion anisotropy (mean fractional anisotropy range 0.47-0.66) significantly higher (P < 0.01, Student's t-test) than in epithelium-containing voxels (mean fractional anisotropy range 0.31-0.54) in six of the seven normal tissue samples in which both compartments could be measured. Fiber tracking demonstrated principle stromal fiber directions consistent with myocyte orientation seen on light microscopy of the same sample. Diffusion tensor microimaging may be valuable for investigation of variable results from attempts to measure diffusion anisotropy in the prostate in vivo.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Fixadores/farmacologia , Formaldeído/farmacologia , Microscopia/métodos , Próstata/citologia , Próstata/efeitos dos fármacos , Anisotropia , Humanos , Masculino , Projetos Piloto , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
14.
Magn Reson Med ; 68(3): 954-9, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22162114

RESUMO

Magnetic resonance microimaging was used to measure diffusion decay over an extended b-factor range in a formalin-fixed normal prostate sample and a Gleason pattern 3+4 cancer tissue sample. The coefficients of biexponential fits to diffusion decay data from 1600 voxels of dimension 160 × 160 × 160 µm(3) in each sample were correlated with underlying epithelial and stromal compartment partial volumes estimated from high-resolution apparent diffusion coefficient (ADC) data (40 × 40 × 40 µm(3) voxels) from the same tissue. In the normal tissue sample, the signal fractions of the low and high ADC components of the biexponential fits correlated linearly with partial volumes of epithelial tissue (R(2) = 0.6) and stromal tissue (R(2) = 0.5), respectively. Similar but weaker correlations were observed in the cancer sample. Epithelium-containing high spatial resolution voxels appeared to be composed of ∼60% low ADC and ∼40% high ADC component. Stromal voxels appeared to be composed of ∼20% low ADC and ∼80% high ADC component. This preliminary report suggests that distinctly different diffusion properties in microscopically adjacent cell types contribute to the multiexponential diffusion decay phenomenon in prostate tissue.


Assuntos
Algoritmos , Interpretação de Imagem Assistida por Computador/métodos , Modelos Biológicos , Próstata/patologia , Próstata/fisiopatologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/fisiopatologia , Simulação por Computador , Difusão , Fixadores , Formaldeído , Humanos , Aumento da Imagem/métodos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Neoplasias da Próstata/química , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
15.
Magn Reson Med ; 68(2): 614-20, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22807067

RESUMO

MR microimaging at 16.4 T with 40-µm isotropic voxels was used to investigate compartmentation of water diffusion in formalin-fixed prostate tissue. Ten tissue samples (~ 28 mm(3) each) from five organs were imaged. The mean diffusivity of epithelial, stromal, and ductal/acinar compartments was estimated by two methods: (1) manual region of interest selection and (2) Gaussian fitting of voxel diffusivity histograms. For the region of interest-method, the means of the tissue sample compartment diffusivities were significantly different (P < 0.001): 0.54 ± 0.05 µm(2)/ms for epithelium-containing voxels, 0.91 ± 0.17 µm(2)/ms for stroma, and 2.20 ± 0.04 µm(2)/ms for saline-filled ducts. The means from the histogram method were also significantly different (P < 0.001): 0.45 ± 0.08 µm(2)/ms for epithelium-containing voxels, 0.83 ± 0.16 µm(2)/ms for stroma, 2.21 ± 0.02 µm(2)/ms for duct. Estimated partial volumes of epithelial, stromal, and ductal/acinar compartments in a "tissue only" subvolume of each sample were significantly different (P < 0.02) between cancer and normal tissue for all three compartments. It is concluded that the negative correlation between apparent diffusion coefficient and cancer Gleason grade observed in vivo results from an increase of partial volume of epithelial tissue and concomitant decrease of stromal tissue and ductal space.


Assuntos
Formaldeído , Interpretação de Imagem Assistida por Computador/métodos , Próstata/patologia , Neoplasias da Próstata/patologia , Fixadores , Humanos , Aumento da Imagem/métodos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
16.
Br J Nutr ; 108(3): 424-30, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22067725

RESUMO

We have developed a blend of food extracts commonly consumed in the Mediterranean and East Asia, named blueberry punch (BBP), with the ultimate aim to formulate a chemoprevention strategy to inhibit prostate cancer progression in men on active surveillance protocol. We demonstrated previously that BBP inhibited prostate cancer cell proliferation in vitro and in vivo. The purpose of this study was to determine the molecular mechanism responsible for the suppression of prostate cancer cell proliferation by BBP. Treatment of lymph node-metastasised prostate cancer cells (LNCaP) and bone-metastasised prostate cancer cells (PC-3 and MDA-PCa-2b) with BBP (up to 0·8 %) for 72 h increased the percentage of cells at the G0/G1 phase and decreased those at the S and G2/M phases. The finding was supported by the reduction in the percentage of Ki-67-positive cells and of DNA synthesis measured by the incorporation of 5-ethynyl-2'-deoxyuridine. Concomitantly, BBP treatment decreased the protein levels of phosphorylated retinoblastoma, cyclin D1 and E, cyclin-dependent kinase (CDK) 4 and 2, and pre-replication complex (CDC6 and MCM7) in LNCaP and PC-3 cells, whereas CDK inhibitor p27 was elevated in these cell lines. In conclusion, BBP exerts its anti-proliferative effect on prostate cancer cells by modulating the expression and phosphorylation of multiple regulatory proteins essential for cell proliferation.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Análise de Alimentos , Extratos Vegetais/farmacologia , Neoplasias da Próstata/prevenção & controle , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/química , Ciclo Celular/efeitos dos fármacos , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proteínas Inibidoras de Quinase Dependente de Ciclina/genética , Proteínas Inibidoras de Quinase Dependente de Ciclina/metabolismo , Quinases Ciclina-Dependentes/genética , Quinases Ciclina-Dependentes/metabolismo , Ciclinas/genética , Ciclinas/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Relação Dose-Resposta a Droga , Ásia Oriental , Regulação da Expressão Gênica/fisiologia , Humanos , Masculino , Região do Mediterrâneo , Componente 7 do Complexo de Manutenção de Minicromossomo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química
17.
Urol Case Rep ; 44: 102130, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35769131

RESUMO

Basal cell carcinoma (BCC) is rare on non-sun exposed skin such as the scrotum and thus diagnosis is often delayed. This case highlights an approach to scrotal skin lesions, risk factors and diagnostic features of BCC. Importantly, scrotal BCCs are more likely to metastasise than non-scrotal BCCs. Management should consist of wide local excision and recommended follow up with thorough clinical history, skin examination and imaging in high-risk patients.

18.
Biochim Biophys Acta ; 1801(7): 731-7, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20227521

RESUMO

The eicosanoid pathway is activated in many types of cancers including prostate. Eicosanoids are synthesized from intracellular arachidonic acid (AA), which is released from membrane glycerophospholipids mainly by the action of cytosolic phospholipase A(2)alpha (cPLA(2)alpha). Thus, targeting cPLA(2)alpha has been proposed as a treatment option. The aim of this study was to determine the effect of cPLA(2)alpha inhibition on cyclooxygenase (COX) expression and PGE(2) production. Inhibition of cPLA(2)alpha expression by siRNA or activity by Efipladib in prostate cancer cell lines (PC3 and LNCaP) led to an increase in COX-1 protein and PGE(2) levels in a dose-dependent manner from 24 to 72 h. The COX-2 response was less evident. Efipladib treatment increased COX-1 promoter transcriptional activity without changing the rate of COX-1 protein degradation. Treatment with Efipladib also led to a decrease in most LOX products (HETEs) as measured by LC/MS/MS. Replenishing 5- and 12-HETEs abolished Efipladib-induced COX-1 and PGE(2) levels. Decreasing 5- and 12-HETE production, as a result of treating cells with inhibitors MK886 and Baicalein, respectively, mimicked the effect of Efipladib on COX-1 and PGE(2) levels. Hence, the mechanism underlying the cPLA(2)alpha inhibition-induced COX-1 is likely due to a decrease in LOX products, which may exert a negative feedback on COX-1 gene expression in prostate cancer cells. Considering that PGE(2) is a potent promoter of cancer cell proliferation and survival, understanding the mechanism coupling cPLA(2)alpha with COX-1 is of potential clinical significance.


Assuntos
Ácido Araquidônico/metabolismo , Ciclo-Oxigenase 1/biossíntese , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Fosfolipases A2 do Grupo IV/biossíntese , Proteínas de Neoplasias/biossíntese , Neoplasias da Próstata/enzimologia , Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico/biossíntese , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2 , Dinoprostona/metabolismo , Inibidores Enzimáticos/farmacologia , Fosfolipases A2 do Grupo IV/antagonistas & inibidores , Humanos , Ácidos Hidroxieicosatetraenoicos/biossíntese , Masculino , Proteínas de Neoplasias/antagonistas & inibidores , Regiões Promotoras Genéticas , Neoplasias da Próstata/tratamento farmacológico , Transcrição Gênica/efeitos dos fármacos
19.
Magn Reson Med ; 66(1): 244-7, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21695726

RESUMO

Diffusion tensor microimaging was used to investigate the water diffusion properties of formalin-fixed prostate tissue at spatial resolution approaching the cellular scale. Diffusion tensor microimaging was performed at 16.4 T with 40 µm isotropic voxels. Diffusion tensor microimaging clearly demonstrated distinct microscopic diffusion environments and tissue architecture consistent with that seen on light microscopy of the same tissue. The most restricted diffusion environment is the secretory epithelial cell layer (voxel bulk mean diffusivity, D = 0.4 ± 0.1 × 10(-3) mm(2)/sec). Diffusion in the fibromuscular stromal matrix is relatively less restricted (D = 0.7 ± 0.1 × 10(-3) mm(2)/sec). In tumor tissue (Gleason pattern 4+4) distinct glandular and ductal structures are absent in the diffusion-weighted images and diffusivity is low (D = 0.5 ± 0.1 × 10(-3) mm(2)/sec). Distinct stromal and epithelial diffusion compartments are the most likely origin of biexponential diffusion decay observed in vivo.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias da Próstata/diagnóstico , Humanos , Masculino , Neoplasias da Próstata/patologia , Manejo de Espécimes
20.
Urol Case Rep ; 37: 101610, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33680852

RESUMO

A 41 years-old male patient presented acutely with severe right testicular pain, and fever for 48 hours. Patient had a backround of previous left orchidectomy for epididymo-orchitis and sexually-transmitted disease. A clinical diagnosis of right epididymo-orchitis was made and patient was treated with intravenous broad-spectrum antibiotic. However subsequent ultrasound revealed imminent testicular ischaemia. Given the challenging nature of the case, i.e. single testicle with testicular ischaemia, surgical exploration, fasciotomy and tunica vaginalis grafting was performed to the patient. The patient recovered fully post-operatively with ultrasound proving restoration of end-diastolic flow to the testicle.

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