Carr-Purcell-Meiboom-Gill imaging of prostate cancer: quantitative T2 values for cancer discrimination.

PubMed

Roebuck, Joseph R; Haker, Steven J; Mitsouras, Dimitris; Rybicki, Frank J; Tempany, Clare M; Mulkern, Robert V

2009-05-01

Quantitative, apparent T(2) values of suspected prostate cancer and healthy peripheral zone tissue in men with prostate cancer were measured using a Carr-Purcell-Meiboom-Gill (CPMG) imaging sequence in order to assess the cancer discrimination potential of tissue T(2) values. The CPMG imaging sequence was used to image the prostates of 18 men with biopsy-proven prostate cancer. Whole gland coverage with nominal voxel volumes of 0.54 x 1.1 x 4 mm(3) was obtained in 10.7 min, resulting in data sets suitable for generating high-quality images with variable T(2)-weighting and for evaluating quantitative T(2) values on a pixel-by-pixel basis. Region-of-interest analysis of suspected healthy peripheral zone tissue and suspected cancer, identified on the basis of both T(1)- and T(2)-weighted signal intensities and available histopathology reports, yielded significantly (P<.0001) longer apparent T(2) values in suspected healthy tissue (193+/-49 ms) vs. suspected cancer (100+/-26 ms), suggesting potential utility of this method as a tissue specific discrimination index for prostate cancer. We conclude that CPMG imaging of the prostate can be performed in reasonable scan times and can provide advantages over T(2)-weighted fast spin echo (FSE) imaging alone, including quantitative T(2) values for cancer discrimination as well as proton density maps without the point spread function degradation associated with short effective echo time FSE sequences.

Carr-Purcell-Meiboom-Gill (CPMG) Imaging of Prostate Cancer: Quantitative T2 Values for Cancer Discrimination

PubMed Central

Roebuck, Joseph R.; Haker, Steven J.; Mitsouras, Dimitris; Rybicki, Frank J.; Tempany, Clare M.; Mulkern, Robert V.

2009-01-01

Quantitative, apparent T2 values of suspected prostate cancer and healthy peripheral zone tissue in men with prostate cancer were measured using a Carr-Purcell-Meiboom-Gill (CPMG) imaging sequence in order to assess the cancer discrimination potential of tissue T2 values. The CPMG imaging sequence was used to image the prostates of 18 men with biopsy proven prostate cancer. Whole gland coverage with nominal voxel volumes of 0.54 × 1.1 × 4 mm3 was obtained in 10.7 minutes, resulting in data sets suitable for generating high quality images with variable T2-weighting and for evaluating quantitative T2 values on a pixel-by-pixel basis. Region-of-interest analysis of suspected healthy peripheral zone tissue and suspected cancer, identified on the basis of both T1- and T2-weighted signal intensities and available histopathology reports, yielded significantly (p < 0.0001) longer apparent T2 values in suspected healthy tissue (193 ± 49 ms) vs. suspected cancer (100 ± 26 ms), suggesting potential utility of this method as a tissue specific discrimination index for prostate cancer. We conclude that CPMG imaging of the prostate can be performed in reasonable scan times and can provide advantages over T2-weighted fast spin echo imaging alone, including quantitative T2 values for cancer discrimination as well as proton density maps without the point spread function degradation associated with short effective echo time fast spin echo (FSE) sequences. PMID:18823731

Peripheral zone lesions of intermediary risk in multiparametric prostate MRI: Frequency and validation of the PI-RADSv2 risk stratification algorithm based on focal contrast enhancement.

PubMed

Benndorf, Matthias; Waibel, Lorenz; Krönig, Malte; Jilg, Cordula Annette; Langer, Mathias; Krauss, Tobias

2018-02-01

To validate the risk stratification algorithm of the Prostate Imaging Reporting and Data System (PI-RADSv2) for intermediary risk lesions (PI-RADSv2 category 3) in the peripheral zone based on focal contrast enhancement and to compare cancer rates in category 3, upgraded category 4 and category 4 based on markedly low ADC value. We retrospectively analyze 172 consecutive patients undergoing prostate MRI with 315 histopathologically verified lesions. We select all lesions either assigned category 3 or category 4 in the peripheral zone for further analysis. We compare cancer rates with the two-sided chi-squared test. To determine inter-observer agreement about contrast enhancement two blinded radiologists evaluate the subset of category 3 lesions based on the diffusion weighted sequence. The frequency of peripheral PI-RADS 3, upgraded PI-RADS 4 and PI-RADS 4 lesions based on markedly low ADC value is 10.8%, 10.8% and 20.3%, respectively. Cancer rates (significant cancer only) in these subgroups are 8.8% (3/34), 23.5% (8/34) and 40.6% (26/64), P < 0.01. Inter-observer agreement is moderate for evaluation of contrast enhancement with kappa values between 0.46 and 0.5. We demonstrate a trend of increasing cancer rate from PI-RADSv2 category 3 to upgraded category 4 to category 4 based on markedly low ADC value. Peripheral lesions of intermediary risk in the diffusion weighted sequence account for 21.6% of all prostate lesions encountered. Since it is likely that patient management recommendations will be linked to assessment categories in future versions of PI-RADS, cancer rates in upgraded category 4 and category 4 based on markedly low ADC values should be in a similar range. We conclude that in future studies of PI-RADSv2 upgraded category 4 and category 4 based on markedly low ADC value should be reported separately to generate a database for meta-analysis of cancer rates. Copyright © 2017 Elsevier B.V. All rights reserved.

Detection of prostate cancer in peripheral zone: comparison of MR diffusion tensor imaging, quantitative dynamic contrast-enhanced MRI, and the two techniques combined at 3.0 T.

PubMed

Li, Chunmei; Chen, Min; Li, Saying; Zhao, Xuna; Zhang, Chen; Luo, Xiaojie; Zhou, Cheng

2014-03-01

Previous studies have shown that the diagnostic accuracy for prostate cancer improved with diffusion tensor imaging (DTI) or quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) only. However, the efficacy of combined DTI and quantitative DCE-MRI in detecting prostate cancer at 3.0 T is still indeterminate. To investigate the utility of diffusion tensor imaging (DTI), quantitative DCE-MRI, and the two techniques combined at 3.0 T in detecting prostate cancer of the peripheral zone (PZ). DTI and DCE-MRI of 33 patients was acquired prior to prostate biopsy. Regions of interest (ROIs) were drawn according to biopsy zones which were apex, mid-gland, and base on each side of the PZ. Apparent diffusion coefficient (ADC), fractional anisotropy (FA), volume transfer constant (K(trans)), and rate constant (kep) values of cancerous sextants and non-cancerous sextants in PZ were calculated. Logistic regression models were generated for DTI, DCE-MRI, and DTI + DCE-MRI. Receiver-operating characteristic (ROC) curves were used to compare the ability of these models to differentiate cancerous sextants from non-cancerous sextants of PZ. There were significant differences in the ADC, FA, K(trans), and kep values between cancerous sextants and non-cancerous sextants in PZ (P < 0.0001, P < 0.0001, P < 0.0001, and P < 0.0001, respectively). The area under curve (AUC) for DTI + DCE-MRI was significantly greater than that for either DTI (0.93 vs. 0.86, P = 0.0017) or DCE-MRI (0.93 vs. 0.84, P = 0.0034) alone. The combination of DTI and quantitative DCE-MRI has better diagnostic performance in detecting prostate cancer of the PZ than either technique alone.

The role of different PI-RADS versions in prostate multiparametric magnetic resonance tomography assessment.

PubMed

Aliukonis, Paulius; Letauta, Tadas; Briedienė, Rūta; Naruševičiūtė, Ieva; Letautienė, Simona

2017-01-01

Background . Standardised Prostate Imaging Reporting and Data System (PI-RADS) guidelines for the assessment of prostate alterations were designed for the assessment of prostate pathology. Published by the ESUR in 2012, PI-RADS v1 was based on the total score of different MRI sequences with subsequent calculation. PI-RADS v2 was published by the American College of Radiology in 2015 and featured different assessment criteria for prostate peripheral and transitory zones. Aim . To assess the correlations of PI-RADS v1 and PI-RADS v2 with Gleason score values and to define their predictive values of the diagnosis of prostate cancer. Materials and methods . A retrospective analysis of 66 patients. Prostate specific antigen (PSA) value and the Gleason score (GS) were assessed. One the most malignant focal lesion was selected in the peripheral zone of each lobe of the prostate (91 in total). Statistical analysis was carried out applying SPSS software, v.23, p < 0.05. Results . Focal lesions assessed by PI-RADS v1 score: 10% - 1, 12% - 2, 41% - 3, 23% - 4, 14% - 5. Assessment applying PI-RADS v.2: 20% - 1, 7.5% - 2, 26%, 29.5%, and 17% were assessed by 3, 4, and 5 scores. Statistically relevant correlation was found only between GS and PI-RADS ( p = 0.033). The positive predictive value of both versions of PI-RADS - 75%, negative predictive value of PI-RADS v1 - 46%, PI-RADS v2 - 43%. Conclusions . PI-RADS v1 was more statistically relevant in assessing the grade of tumour. Prediction values were similar in both versions.

Characterization of an ICII82, 780-Induced, Estrogen Receptor (ER)-beta Mediated Apoptotic Pathway in Prostate Cancer Cells and Establishment of (ER)-beta-Regulated Electrophile-Processing Phase II Enzyme Downregulation as a Promotional Factor in Human Prostatic Carcinogenesis

DTIC Science & Technology

2001-05-01

absent in higher-grade cancers. ERP3 expression reappeared in metastatic prostatic carcinomas . The results were also compared to ERMo and androgen...metastatic prostatic carcinomas in bone and lymph nodes. The results were compared to ERax and androgen receptor expressions in those samples. Taken... carcinomas of the peripheral zone were in contrast strongly positive for the 13 receptor whereas its expression in grade 415 cancers was negligible to

A Multireader Exploratory Evaluation of Individual Pulse Sequence Cancer Detection on Prostate Multiparametric Magnetic Resonance Imaging (MRI).

PubMed

Gaur, Sonia; Harmon, Stephanie; Gupta, Rajan T; Margolis, Daniel J; Lay, Nathan; Mehralivand, Sherif; Merino, Maria J; Wood, Bradford J; Pinto, Peter A; Shih, Joanna H; Choyke, Peter L; Turkbey, Baris

2018-04-25

To determine independent contribution of each prostate multiparametric magnetic resonance imaging (mpMRI) sequence to cancer detection when read in isolation. Prostate mpMRI at 3-Tesla with endorectal coil from 45 patients (n = 30 prostatectomy cases, n = 15 controls with negative magnetic resonance imaging [MRI] or biopsy) were retrospectively interpreted. Sequences (T2-weighted [T2W] MRI, diffusion-weighted imaging [DWI], and dynamic contrast-enhanced [DCE] MRI; N = 135) were separately distributed to three radiologists at different institutions. Readers evaluated each sequence blinded to other mpMRI sequences. Findings were correlated to whole-mount pathology. Cancer detection sensitivity, positive predictive value for whole prostate (WP), transition zone, and peripheral zone were evaluated per sequence by reader, with reader concordance measured by index of specific agreement. Cancer detection rates (CDRs) were calculated for combinations of independently read sequences. 44 patients were evaluable (cases median prostate-specific antigen 6.83 [ range 1.95-51.13] ng/mL, age 62 [45-71] years; controls prostate-specific antigen 6.85 [2.4-10.87] ng/mL, age 65.5 [47-71] years). Readers had highest sensitivity on DWI (59%) vs T2W MRI (48%) and DCE (23%) in WP. DWI-only positivity (DWI+/T2W-/DCE-) achieved highest CDR in WP (38%), compared to T2W-only (CDR 24%) and DCE-only (CDR 8%). DWI+/T2W+/DCE- achieved CDR 80%, an added benefit of 56.4% from T2W-only and of 42% from DWI-only (P < .0001). All three sequences interpreted independently positive gave highest CDR of 90%. Reader agreement was moderate (index of specific agreement: T2W = 54%, DWI = 58%, DCE = 33%). When prostate mpMRI sequences are interpreted independently by multiple observers, DWI achieves highest sensitivity and CDR in transition zone and peripheral zone. T2W and DCE MRI both add value to detection; mpMRI achieves highest detection sensitivity when all three mpMRI sequences are positive. Published by Elsevier Inc.

Automated prostate cancer localization without the need for peripheral zone extraction using multiparametric MRI.

PubMed

Liu, Xin; Yetik, Imam Samil

2011-06-01

Multiparametric magnetic resonance imaging (MRI) has been shown to have higher localization accuracy than transrectal ultrasound (TRUS) for prostate cancer. Therefore, automated cancer segmentation using multiparametric MRI is receiving a growing interest, since MRI can provide both morphological and functional images for tissue of interest. However, all automated methods to this date are applicable to a single zone of the prostate, and the peripheral zone (PZ) of the prostate needs to be extracted manually, which is a tedious and time-consuming job. In this paper, our goal is to remove the need of PZ extraction by incorporating the spatial and geometric information of prostate tumors with multiparametric MRI derived from T2-weighted MRI, diffusion-weighted imaging (DWI) and dynamic contrast enhanced MRI (DCE-MRI). In order to remove the need of PZ extraction, the authors propose a new method to incorporate the spatial information of the cancer. This is done by introducing a new feature called location map. This new feature is constructed by applying a nonlinear transformation to the spatial position coordinates of each pixel, so that the location map implicitly represents the geometric position of each pixel with respect to the prostate region. Then, this new feature is combined with multiparametric MR images to perform tumor localization. The proposed algorithm is applied to multiparametric prostate MRI data obtained from 20 patients with biopsy-confirmed prostate cancer. The proposed method which does not need the masks of PZ was found to have prostate cancer detection specificity of 0.84, sensitivity of 0.80 and dice coefficient value of 0.42. The authors have found that fusing the spatial information allows us to obtain tumor outline without the need of PZ extraction with a considerable success (better or similar performance to methods that require manual PZ extraction). Our experimental results quantitatively demonstrate the effectiveness of the proposed method, depicting that the proposed method has a slightly better or similar localization performance compared to methods which require the masks of PZ.

Transrectal real-time elastography of the prostate: Normal patterns

PubMed Central

Goddi, A.; Sacchi, A.; Magistretti, G.; Almolla, J.

2011-01-01

Introduction Given the growing importance in clinical practice of transrectal real-time sonoelastography of the prostate, it is important to define normal patterns correlated to volume growth and reconsider the technical problems. Materials and methods We selected a sample of 100 men aged 30 to 87 with prostate volumes ranging from 20 to 100 cc. Strain images were obtained using an end-fire convex probe. The elasticity patterns of the various anatomical zones of the prostate were compared with the volume. Results The peripheral zone showed intermediate elasticity in 100% of cases regardless of the volume. We found some rare small areas of more limited elasticity in 23% of cases, among patients over 40. The posterior side of the central zone exhibited intermediate elasticity, and relative inelasticity was observed on the lateral side and at the base in 79% of cases. The entire central zone appeared compliant in 15% of cases and inelastic in 6%. The transition zone findings were stratified according to gland volume. When the volume was less than 45 cc, the transition zone was elastic in 67% of cases, inhomogeneously inelastic in 22%, and uniformly inelastic in 11%. In glands larger than 45 cc, the appearance was mainly elastic in 31% of cases, inhomogeneously inelastic in 57%, and uniformly inelastic in 12%. Conclusions Real-time elastography can distinguish the elastic properties of the prostate and define the normal patterns associated with increases in gland volume. PMID:23396618

Building a high-resolution T2-weighted MR-based probabilistic model of tumor occurrence in the prostate.

PubMed

Nagarajan, Mahesh B; Raman, Steven S; Lo, Pechin; Lin, Wei-Chan; Khoshnoodi, Pooria; Sayre, James W; Ramakrishna, Bharath; Ahuja, Preeti; Huang, Jiaoti; Margolis, Daniel J A; Lu, David S K; Reiter, Robert E; Goldin, Jonathan G; Brown, Matthew S; Enzmann, Dieter R

2018-02-19

We present a method for generating a T2 MR-based probabilistic model of tumor occurrence in the prostate to guide the selection of anatomical sites for targeted biopsies and serve as a diagnostic tool to aid radiological evaluation of prostate cancer. In our study, the prostate and any radiological findings within were segmented retrospectively on 3D T2-weighted MR images of 266 subjects who underwent radical prostatectomy. Subsequent histopathological analysis determined both the ground truth and the Gleason grade of the tumors. A randomly chosen subset of 19 subjects was used to generate a multi-subject-derived prostate template. Subsequently, a cascading registration algorithm involving both affine and non-rigid B-spline transforms was used to register the prostate of every subject to the template. Corresponding transformation of radiological findings yielded a population-based probabilistic model of tumor occurrence. The quality of our probabilistic model building approach was statistically evaluated by measuring the proportion of correct placements of tumors in the prostate template, i.e., the number of tumors that maintained their anatomical location within the prostate after their transformation into the prostate template space. Probabilistic model built with tumors deemed clinically significant demonstrated a heterogeneous distribution of tumors, with higher likelihood of tumor occurrence at the mid-gland anterior transition zone and the base-to-mid-gland posterior peripheral zones. Of 250 MR lesions analyzed, 248 maintained their original anatomical location with respect to the prostate zones after transformation to the prostate. We present a robust method for generating a probabilistic model of tumor occurrence in the prostate that could aid clinical decision making, such as selection of anatomical sites for MR-guided prostate biopsies.

In-gantry MRI guided prostate biopsy diagnosis of prostatitis and its relationship with PIRADS V.2 based score.

PubMed

Jyoti, Rajeev; Jina, Noel Hamesh; Haxhimolla, Hodo Z

2017-04-01

The recent literature has focussed predominantly on prostate cancer detection which has been revolutionized by multiparametric magnetic resonance imaging (mpMRI). Due to an overlap of features, prostatitis may mimic prostate cancer on MRI, especially in patients with chronic prostatitis. We retrospectively analysed our in-gantry MRI-guided biopsy (MRGB) results to determine incidental detection rate of prostatitis in Prostate Imaging Reporting and Data System (PIRADS) 3, 4 and 5 foci reported on diagnostic MRI of the prostate. About 137 patients underwent in-gantry MRGB for lesions with PIRADS score of 3 or above. All the biopsies were performed utilizing the dynaTRIM™ system (Invio Inc, Germany) on a three-tesla MRI scanner (Ingenia 3.0T, Philips, Netherlands) by a Radiologist and a Urologist. We biopsied 228 lesions in 137 patients. There were 55 lesions that returned positive for prostate cancer with a Gleason Score of 3 + 3 = 6 or above. There were 62 lesions that showed inflammation. The distribution of these lesions was 3 (5%) in the central zone, 32 (52%) in the transitional zone and 27 (43%) in the peripheral zone. Inflammation was found in 36 (58%) PIRADS 3 lesions, 24 (39%) PIRADS 4 lesions and 2 (3%) PIRADS 5 lesions on pre biopsy MRI evaluation. In our series, biopsies which showed inflammation had a radiological appearance on mpMRI more likely of a PIRADS 3 or 4 lesions with only 3% of PIRADS 5 biopsies showing inflammation. This would suggest that a higher PIRADS score can more reliably differentiate between prostate cancer and prostatitis. © 2016 The Royal Australian and New Zealand College of Radiologists.

Magnetic resonance spectroscopic imaging of benign prostatic tissue: findings at 3.0 T compared to 1.5 T—initial experience☆

PubMed Central

Chitkara, Munish; Westphalen, Antonio; Kurhanewicz, John; Qayyum, Aliya; Poder, Liina; Reed, Galen; Coakley, Fergus V.

2013-01-01

In a retrospective study of 71 voxels of benign peripheral zone tissue from 3 men who underwent endorectal magnetic resonance (MR) spectroscopic imaging of the prostate at both 1.5 and 3 T, 21 voxels that appeared more malignant at 3 T to either of two readers demonstrated significantly higher levels of choline and polyamines at 3 T compared to 1.5 T using a Wilcoxon ranked-sum test; awareness of this selective amplification of these metabolic signals at high field strength may help avoid overdiagnosis of prostate cancer. PMID:21724122

Contrast-enhanced transrectal ultrasound for prediction of prostate cancer aggressiveness: The role of normal peripheral zone time-intensity curves.

PubMed

Huang, Hui; Zhu, Zheng-Qiu; Zhou, Zheng-Guo; Chen, Ling-Shan; Zhao, Ming; Zhang, Yang; Li, Hong-Bo; Yin, Li-Ping

2016-12-08

To assess the role of time-intensity curves (TICs) of the normal peripheral zone (PZ) in the identification of biopsy-proven prostate nodules using contrast-enhanced transrectal ultrasound (CETRUS). This study included 132 patients with 134 prostate PZ nodules. Arrival time (AT), peak intensity (PI), mean transit time (MTT), area under the curve (AUC), time from peak to one half (TPH), wash in slope (WIS) and time to peak (TTP) were analyzed using multivariate linear logistic regression and receiver operating characteristic (ROC) curves to assess whether combining nodule TICs with normal PZ TICs improved the prediction of prostate cancer (PCa) aggressiveness. The PI, AUC (p < 0.001 for both), MTT and TPH (p = 0.011 and 0.040 respectively) values of the malignant nodules were significantly higher than those of the benign nodules. Incorporating the PI and AUC values (both, p < 0.001) of the normal PZ TIC, but not the MTT and TPH values (p = 0.076 and 0.159 respectively), significantly improved the AUC for prediction of malignancy (PI: 0.784-0.923; AUC: 0.758-0.891) and assessment of cancer aggressiveness (p < 0.001). Thus, all these findings indicate that incorporating normal PZ TICs with nodule TICs in CETRUS readings can improve the diagnostic accuracy for PCa and cancer aggressiveness assessment.

68Ga-PSMA PET/MR-Positive, Histopathology-Proven Prostate Cancer in a Patient With Negative Multiparametric Prostate MRI.

PubMed

Muehlematter, Urs J; Rupp, Niels J; Mueller, Julian; Eberli, Daniel; Burger, Irene A

2018-05-25

Multiparametric MRI incorporating T2-weighted, diffusion-weighted, and dynamic contrast material-enhanced sequences is currently used for detection and localization of clinically important prostate cancer (PCa). The Ga-labeled PET tracer targeting the prostate-specific membrane antigen (PSMA, Ga-PSMA-11) is a promising diagnostic approach for staging and restating PCa. Recent studies suggest that Ga-PSMA could also be used for primary PCa detection and localization. We report a case of a Ga-PSMA PET/MR-positive lesion of the peripheral zone in a 73-year-old man with a negative preceding multiparametric MRI. Radical prostatectomy and subsequent histopathologic examination confirmed a Gleason 4 + 4 PCa.

Anatomical and metabolic assessment of prostate using a 3-Tesla MR scanner with a custom-made external transceive coil: healthy volunteer study.

PubMed

Kaji, Yasushi; Kuroda, Kagayaki; Maeda, Takaki; Kitamura, Yuri; Fujiwara, Toshitaka; Matsuoka, Yuichiro; Tamura, Mitsuru; Takei, Naoyuki; Matsuda, Tsuyoshi; Sugimura, Kazuro

2007-03-01

To examine the possibility of using a 3 Tesla (T) magnetic resonance (MR) scanner with a custom-made external coil to obtain ductal details of the prostate, high-quality spectra, and metabolite mapping corresponding to prostate zonal anatomy in healthy volunteers. MRI and two-dimensional (2D) chemical shift imaging (CSI) were performed in 16 healthy volunteers using a 3T scanner with a custom-made external transmit-receive (transceive) coil. Visualization of the prostatic duct-like structure was analyzed on T2-weighted (T2W) images. The resolution of the metabolite peaks and the distribution of metabolites in CSI were also assessed. In the axial plane, 3-mm-thick images were better than 4-mm-thick images with the same voxel volume for assessing duct-like structures and prostatic urethra. Differentiation between inner and outer citrate (Cit) peaks was frequently observed (29 out of 30). The mean peak area ratio of choline (Cho) plus creatine (Cr) over Cit in the peripheral zone (PZ) was significantly lower than in the transition zone (TZ) (P = 0.014). 3T MR examinations of the prostate using an external coil allow information to be collected about the details of duct-like structures, the high-quality spectra of Cit, and the zone-specific distribution of metabolites.

Everyman's prostate phantom: kiwi-fruit substitute for human prostates at magnetic resonance imaging, diffusion-weighted imaging and magnetic resonance spectroscopy.

PubMed

Mueller-Lisse, Ullrich G; Murer, Sophie; Mueller-Lisse, Ulrike L; Kuhn, Marissa; Scheidler, Juergen; Scherr, Michael

2017-08-01

To apply an easy-to-assemble phantom substitute for human prostates in T2-weighted magnetic resonance imaging (T2WI), diffusion-weighted imaging (DWI) and 3D magnetic resonance spectroscopy (MRS). Kiwi fruit were fixed with gel hot and cold compress packs on two plastic nursery pots, separated by a plastic plate, and submerged in tap water inside a 1-L open-spout plastic watering can for T2WI (TR/TE 7500/101 ms), DWI (5500/61 ms, ADC b50-800 s/mm 2 map) and MRS (940/145 ms) at 3.0 T, with phased array surface coils. One green kiwi fruit was additionally examined with an endorectal coil. Retrospective comparison with benign peripheral zone (PZ) and transitional zone (TZ) of prostate (n = 5), Gleason 6-7a prostate cancer (n = 8) and Gleason 7b-9 prostate cancer (n = 7) validated the phantom. Mean contrast between central placenta (CP) and outer pericarp (OP, 0.346-0.349) or peripheral placenta (PP, 0.364-0.393) of kiwi fruit was similar to Gleason 7b-9 prostate cancer and PZ (0.308) in T2WI. ADC values of OP and PP (1.27 ± 0.07-1.37 ± 0.08 mm 2 /s × 10 -3 ) resembled PZ and TZ (1.39 ± 0.17-1.60 ± 0.24 mm 2 /s × 10 -3 ), while CP (0.91 ± 0.14-0.99 ± 0.10 mm 2 /s × 10 -3 ) resembled Gleason 7b-9 prostate cancer (1.00 ± 0.25 mm 2 /s × 10 -3 ). MR spectra showed peaks of citrate and myo-inositol in kiwi fruit, and citrate and "choline+creatine" in prostates. The phantom worked with an endorectal coil, too. The kiwi fruit phantom reproducibly showed zones similar to PZ, TZ and cancer in human prostates in T2WI and DWI and two metabolite peaks in MRS and appears suitable to compare different MR protocols, coil systems and scanners. • Kiwi fruit appear suitable as phantoms for human prostate in MR examinations. • Kiwi fruit show zonal anatomy like human prostates in T2-weighted MRI and DWI. • MR spectroscopy reliably shows peaks in kiwi fruit (citrate/inositol) and human prostates (citrate/choline+creatine). • The kiwi fruit phantom works both with and without an endorectal coil. • EU regulation No. 543/2011 specifies physical and biochemical properties of kiwi fruit.

Diffusion-weighted imaging of the prostate: should we use quantitative metrics to better characterize focal lesions originating in the peripheral zone?

PubMed

Pierre, Thibaut; Cornud, Francois; Colléter, Loïc; Beuvon, Frédéric; Foissac, Frantz; Delongchamps, Nicolas B; Legmann, Paul

2018-05-01

To compare inter-reader concordance and accuracy of qualitative diffusion-weighted (DW) PIRADSv2.0 score with those of quantitative DW-MRI for the diagnosis of peripheral zone prostate cancer. Two radiologists independently assigned a DW-MRI-PIRADS score to 92 PZ-foci, in 74 patients (64.3±5.6 years old; median PSA level: 8 ng/ml, normal DRE in 70 men). A standardised ADCmean and nine ADC-derived parameters were measured, including ADCratios with the whole-prostate (WP-ADCratio) or the mirror-PZ (mirror-ADCratio) as reference areas. Surgical histology and MRI-TRUS fusion-biopsy were the reference for tumours and benign foci, respectively. Inter-reader agreement was assessed by the Cohen-kappa-coefficient and the intraclass correlation coefficient (ICC). Univariate-multivariate regressions determined the most predictive factor for cancer. Fifty lesions were malignant. Inter-reader concordance was fair for qualitative assessment, but excellent for quantitative assessment for all quantitative variables. At univariate analysis, ADCmean, WP-ADCratio and WL-ADCmean performed equally, but significantly better than the mirror-ADCratio (p<0.001). At multivariate analysis, the only independent variable significantly associated with malignancy was the whole-prostate-ADCratio. At a cut-off value of 0.68, sensitivity was 94-90 % and specificity was 60-38 % for readers 1 and 2, respectively. The whole-prostate-ADCratio improved the qualitative inter-reader concordance and characterisation of focal PZ-lesions. • Inter-reader concordance of DW PI-RADSv2.0 score for PZ lesions was only fair. • Using a standardised ADCmean measurement and derived DW-quantitative parameters, concordance was excellent. • The whole-prostate ADCratio performed significantly better than the mirror-ADCratio for cancer detection. • At a cut-off of 0.68, sensitivity values of WP-ADCratio were 94-90 %. • The whole-prostate ADCratio may circumvent variations of ADC metrics across centres.

Haralick textural features on T2 -weighted MRI are associated with biochemical recurrence following radiotherapy for peripheral zone prostate cancer.

PubMed

Gnep, Khémara; Fargeas, Auréline; Gutiérrez-Carvajal, Ricardo E; Commandeur, Frédéric; Mathieu, Romain; Ospina, Juan D; Rolland, Yan; Rohou, Tanguy; Vincendeau, Sébastien; Hatt, Mathieu; Acosta, Oscar; de Crevoisier, Renaud

2017-01-01

To explore the association between magnetic resonance imaging (MRI), including Haralick textural features, and biochemical recurrence following prostate cancer radiotherapy. In all, 74 patients with peripheral zone localized prostate adenocarcinoma underwent pretreatment 3.0T MRI before external beam radiotherapy. Median follow-up of 47 months revealed 11 patients with biochemical recurrence. Prostate tumors were segmented on T 2 -weighted sequences (T 2 -w) and contours were propagated onto the coregistered apparent diffusion coefficient (ADC) images. We extracted 140 image features from normalized T 2 -w and ADC images corresponding to first-order (n = 6), gradient-based (n = 4), and second-order Haralick textural features (n = 130). Four geometrical features (tumor diameter, perimeter, area, and volume) were also computed. Correlations between Gleason score and MRI features were assessed. Cox regression analysis and random survival forests (RSF) were performed to assess the association between MRI features and biochemical recurrence. Three T 2 -w and one ADC Haralick textural features were significantly correlated with Gleason score (P < 0.05). Twenty-eight T 2 -w Haralick features and all four geometrical features were significantly associated with biochemical recurrence (P < 0.05). The most relevant features were Haralick features T 2 -w contrast, T 2 -w difference variance, ADC median, along with tumor volume and tumor area (C-index from 0.76 to 0.82; P < 0.05). By combining these most powerful features in an RSF model, the obtained C-index was 0.90. T 2 -w Haralick features appear to be strongly associated with biochemical recurrence following prostate cancer radiotherapy. 3 J. Magn. Reson. Imaging 2017;45:103-117. © 2016 International Society for Magnetic Resonance in Medicine.

Integration of Diagnostic and Interventional MRI for the Study of Persistent Prostate Cancer after External Beam Radiotherapy

DTIC Science & Technology

2009-10-01

1500 ms). A clinical pilot study reported equivalence between central gland (CG) and peripheral zone (PZ) T1 values (CG: 1321±45 ms, n=14; PZ: 1359...across variable TI, the period of longitudinal recovery is kept independent of TI selection for any TR. Central to T1prep is RF cycling of an...pilot study A clinical pilot study involved 15 patients with low or intermediate risk localized prostate cancer and no history of prior therapy. The

Is there a role for anterior zone sampling as part of saturation trans-rectal ultrasound guided prostate biopsy?

PubMed

Cole, Eric; Margel, David; Greenspan, Michael; Shayegan, Bobby; Matsumoto, Edward; Fischer, Marc A; Patlas, Michael; Daya, Dean; Pinthus, Jehonathan H

2014-05-03

The prostatic anterior zone (AZ) is not targeted routinely by TRUS guided prostate biopsy (TRUS-Pbx). MRI is an accurate diagnostic tool for AZ tumors, but is often unavailable due to cost or system restrictions. We examined the diagnostic yield of office based AZ TRUS-Pbx. 127 men at risk for AZ tumors were studied: Patients with elevated PSA and previous extended negative TRUS-Pbx (group 1, n = 78) and actively surveyed low risk prostate cancer patients (group 2, n = 49). None of the participants had a previous AZ biopsy. Biopsy template included suspicious ultrasonic areas, 16 peripheral zone (PZ), 4 transitional zone (TZ) and 6 AZ cores. All biopsies were performed by a single urologist under local peri-prostatic anaesthetic, using the B-K Medical US System, an end-firing probe 4-12 MHZ and 18 ga/25 cm needle. All samples were reviewed by a single specialized uro-pathologist. Multivariate analysis was used to detect predictors for AZ tumors accounting for age, PSA, PSA density, prostate volume, BMI, and number of previous biopsies. Median PSA was 10.4 (group 1) and 7.3 (group 2). Age (63.9, 64.5), number of previous biopsies (1.5) and cores (17.8, 21.3) and prostate volume (56.4 cc, 51 cc) were similar for both groups. The overall diagnostic yield was 34.6% (group 1) and 85.7% (group 2). AZ cancers were detected in 21.8% (group 1) and 34.7% (group 2) but were rarely the only zone involved (1.3% and 4.1% respectively). Gleason ≥ 7 AZ cancers were often accompanied by equal grade PZ tumors. In multivariate analysis only prostate volume predicted for AZ tumors. Patients detected with AZ tumors had significantly smaller prostates (36.9 cc vs. 61.1 cc p < 0.001). Suspicious AZ ultrasonic findings were uncommon (6.3%). TRUS-Pbx AZ sampling rarely improves the diagnostic yield of extended PZ sampling in patients with elevated PSA and previous negative biopsies. In low risk prostate cancer patients who are followed by active surveillance, AZ sampling changes risk stratification in 6% but larger studies are needed to define the role of AZ sampling in this population and its correlation with prostatectomy final pathological specimens.

Intracellular Propionibacterium acnes Infection in Glandular Epithelium and Stromal Macrophages of the Prostate with or without Cancer

PubMed Central

Bae, Yuan; Ito, Takashi; Iida, Tadatsune; Uchida, Keisuke; Sekine, Masaki; Nakajima, Yutaka; Kumagai, Jiro; Yokoyama, Tetsuji; Kawachi, Hiroshi; Akashi, Takumi; Eishi, Yoshinobu

2014-01-01

Background Recent reports on Propionibacterium acnes (P. acnes) suggest that this bacterium is prevalent in the prostate, is associated with acute and chronic prostatic inflammation, and might have a role in prostate carcinogenesis. Methods To evaluate the pathogenic role of this indigenous bacterium, we screened for the bacterium in radical prostatectomy specimens using enzyme immunohistochemistry with a novel P. acnes-specific monoclonal antibody (PAL antibody), together with an anti-nuclear factor-kappa B (NF-κB) antibody. We examined formalin-fixed and paraffin-embedded tissue sections of radical prostatectomy specimens from 28 patients with prostate cancer and 18 age-matched control patients with bladder cancer, but without prostate cancer. Results Immunohistochemistry with the PAL antibody revealed small round bodies within some non-cancerous glandular epithelium and stromal macrophages in most prostate samples. Prostate cancer samples had higher frequencies of either cytoplasmic P. acnes or nuclear NF-κB expression of glandular epithelium and higher numbers of stromal macrophages with P. acnes than control samples. These parameters were also higher in the peripheral zone than in the transitional zone of the prostate, especially in prostate cancer samples. Nuclear NF-κB expression was more frequent in glands with P. acnes than in glands without P. acnes. The number of stromal macrophages with the bacterium correlated with the grade of chronic inflammation in both the PZ and TZ areas and with the grade of acute inflammation in the TZ area. Conclusions Immunohistochemical analysis with a novel monoclonal antibody for detecting P. acnes in the prostate suggested that intraepithelial P. acnes infection in non-cancerous prostate glands and inflammation caused by the bacterium may contribute to the development of prostate cancer. PMID:24587325

[Comparative study of histological results between resection and biopsy of the prostate].

PubMed

Mathieu, R; Tibari, Y; Verhoest, G; Vincendeau, S; Manunta, A; Rioux-Leclercq, N; Bensalah, K

2014-05-01

To evaluate the histological correlation between transuretral resection chips and biopsy cores within a population of patients who underwent resection of prostate (TURP) and prostate biopsies (BPx). Clinical and tumoral data of 77 patients who had both procedures simultaneously or with a slight delay were collected. According to the presence of prostate cancer (Pca), 4 groups were defined: group 1 (TURP and BPx negative), group 2 (TURP positive, BPx negative), group 3 (TURP negative, BPx positive), group 4 (TURP and BPx positive). Means and proportions were compared using Anova and χ(2) test, respectively. The patients were older in groups 3 and 4 (79 and 76 respectively, P=0.65). The PSA was higher in the groups 3 and 4 (64 and 55 ng/mL) than the groups 1 and 2 (10.6 et 16 respectively, P=0.23). The number of positive biopsy was higher in the group 4 than the group 3 (5.6 vs. 4.6, P<0.0001), the chips were more invaded in the group 4 than the group 2 (41% vs. 11% P<0.0001), the Gleason score at TURP was higher in the group 4 than the group 2 (7.5 vs. 6.2 P<0.0001). Our study underlines that the Pca of transition and peripheral zones seems to have distinct characteristics. When chips of TURP and BPx were both invaded, it was due to an aggressive cancer. The decision to explore the peripheral zone in the case of positive TURP must take clinical context into consideration. Copyright © 2013. Published by Elsevier Masson SAS.

Testosterone and dihydrotestosterone levels in the transition zone correlate with prostate volume.

PubMed

Pejčić, Tomislav; Tosti, Tomislav; Tešić, Živoslav; Milković, Borivoj; Dragičević, Dejan; Kozomara, Milutin; Čekerevac, Milica; Džamić, Zoran

2017-07-01

There is still no consensus regarding intraprostatic androgen levels and the accumulation of androgens in the hyperplastic prostatic tissue. The current opinion is that intraprostatic dihydrotestosterone (DHT) concentrations are maintained but not elevated in benign prostatic hyperplasia (BPH), while there is no similar data concerning intraprostatic testosterone (T). Tissue T (tT) and tissue DHT (tDHT) concentration were determined in 93 patients scheduled for initial prostate biopsy. The criteria for biopsy were abnormal DRE and/or PSA > 4 ng/mL. Total prostate volume (TPV) was determined by transrectal ultrasound (TRUS). During TRUS- guided prostate biopsy, 10-12 samples were collected from the peripheral zone (PZ) and two additional samples were collected from the transition zone (TZ). The samples from the TZ were immediately frozen in liquid nitrogen at -70°C, and transported for tissue androgen determination, using liquid chromatography mass spectrometry (LC-MS). Pathological analysis revealed that prostate cancer (PCa) was present in 45 and absent in 48 patients. In the whole group, there were 42 men with small prostate (TPV < 30 mL) and 51 with enlarged prostate (TPV ≥ 31 mL). The overall average tT level was 0.79 ± 0.66 ng/g, while the average tDHT level was 10.27 ± 7.15 ng/g. There were no differences in tT and tDHT level in prostates with and without PCa. However, tT and tDHT levels were significantly higher in larger, than in smaller prostates (tT: 1.05 ± 0.75 and 0.46 ± 0.29 ng/g, and tDHT: 15.0 ± 6.09 and 4.51 ± 2.75 ng/g, respectively). There were strong correlations between tT and TPV (r = 0.71), and tDHT and TPV (r = 0.74). The present study confirmed that both T and DHT accumulated in the stroma of enlarged prostates; the degree of accumulation correlated with prostate volume. © 2017 Wiley Periodicals, Inc.

Is contrast enhancement needed for diagnostic prostate MRI?

PubMed Central

Rondoni, Valeria; Aisa, Maria Cristina; Martorana, Eugenio; D’Andrea, Alfredo; Malaspina, Corrado Maria; Orlandi, Agostino; Galassi, Giorgio; Orlandi, Emanuele; Scialpi, Pietro; Dragone, Michele; Palladino, Diego; Simeone, Annalisa; Amenta, Michele; Bianchi, Giampaolo

2017-01-01

Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) provides clinical guidelines for multiparametric magnetic resonance imaging (mpMRI) [T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)] of prostate. However, DCE-MRI seems to show a limited contribution in prostate cancer (PCa) detection and management. In our experience, DCE-MRI, did not show significant change in diagnostic performance in addition to DWI and T2WI [biparametric MRI (bpMRI)] which represent the predominant sequences to detect suspected lesions in peripheral and transitional zone (TZ). In this article we reviewed the role of DCE-MRI also indicating the potential contribute of bpMRI approach (T2WI and DWI) and lesion volume evaluation in the diagnosis and management of suspected PCa. PMID:28725592

Is contrast enhancement needed for diagnostic prostate MRI?

PubMed

Scialpi, Michele; Rondoni, Valeria; Aisa, Maria Cristina; Martorana, Eugenio; D'Andrea, Alfredo; Malaspina, Corrado Maria; Orlandi, Agostino; Galassi, Giorgio; Orlandi, Emanuele; Scialpi, Pietro; Dragone, Michele; Palladino, Diego; Simeone, Annalisa; Amenta, Michele; Bianchi, Giampaolo

2017-06-01

Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) provides clinical guidelines for multiparametric magnetic resonance imaging (mpMRI) [T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)] of prostate. However, DCE-MRI seems to show a limited contribution in prostate cancer (PCa) detection and management. In our experience, DCE-MRI, did not show significant change in diagnostic performance in addition to DWI and T2WI [biparametric MRI (bpMRI)] which represent the predominant sequences to detect suspected lesions in peripheral and transitional zone (TZ). In this article we reviewed the role of DCE-MRI also indicating the potential contribute of bpMRI approach (T2WI and DWI) and lesion volume evaluation in the diagnosis and management of suspected PCa.

Peripheral Zone Inflammation Is Not Strongly Associated With Lower Urinary Tract Symptom Incidence and Progression in the Placebo Arm of the Prostate Cancer Prevention Trial .

PubMed

Kulac, Ibrahim; Gumuskaya, Berrak; Drake, Charles G; Gonzalez, Beverly; Arnold, Kathryn B; Goodman, Phyllis J; Kristal, Alan R; Lucia, M Scott; Thompson, Ian M; Isaacs, William B; De Marzo, Angelo M; Platz, Elizabeth A

2016-11-01

Intraprostatic inflammation has been associated with lower urinary tract symptom (LUTS) progression. However, prior studies used tissue removed for clinical indications, potentially skewing inflammation extent or biasing the association. We, therefore, evaluated inflammation and LUTS incidence and progression in men who underwent biopsy of the prostate peripheral zone irrespective of indication. We developed nested case-control sets in men in the placebo arm of the Prostate Cancer Prevention Trial who were free of clinical BPH and had a protocol-directed year 7 biopsy. Cases had baseline IPSS <15 and year 7 IPSS of 8-14 (low, N = 47), 15-19 (incident moderate, N = 42), or ≥20 (incident high, N = 44). Controls had baseline and year 7 IPSS <8 (N = 41). For progression from IPSS <8, cases had baseline to year 7 IPSS slope >75th percentile (N = 46) and controls had a slope <25th percentile (N = 45). For progression from IPSS = 8-14, cases had a slope >75th percentile (N = 46) and controls had a slope <25th percentile (N = 46). We reviewed three H&E-stained biopsy cores per man to determine prevalence of ≥1 core with inflammation and mean extent (%) of tissue area with inflammation. Inflammation prevalence in low cases (64%) was similar to controls (66%), but higher in moderate (69%) and high (73%) cases (P-trend = 0.4). Extent did not differ across LUTS categories (P-trend = 0.5). For progression from IPSS < 8, prevalence (65%, P = 0.9) and extent (2.5%, P = 0.8) in cases did not differ from controls (64%, 2.7%). For progression from IPSS 8-14, prevalence in cases (52%) was lower than in controls (78%, P = 0.009), while extent was higher in cases (5.3%) than controls (3.6%), especially in men with ≥1 core with inflammation (10.1% versus 4.6%, P = 0.06). Peripheral zone intraprostatic inflammation is not strongly associated with LUTS incidence or progression. Prostate 76:1399-1408, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Prostate cancer localization with endorectal MR imaging and MR spectroscopic imaging: effect of clinical data on reader accuracy.

PubMed

Dhingsa, Rajpal; Qayyum, Aliya; Coakley, Fergus V; Lu, Ying; Jones, Kirk D; Swanson, Mark G; Carroll, Peter R; Hricak, Hedvig; Kurhanewicz, John

2004-01-01

To determine the effect of digital rectal examination findings, sextant biopsy results, and prostate-specific antigen (PSA) levels on reader accuracy in the localization of prostate cancer with endorectal magnetic resonance (MR) imaging and MR spectroscopic imaging. This was a retrospective study of 37 patients (mean age, 57 years) with biopsy-proved prostate cancer. Transverse T1-weighted, transverse high-spatial-resolution, and coronal T2-weighted MR images and MR spectroscopic images were obtained. Two independent readers, unaware of clinical data, recorded the size and location of suspicious peripheral zone tumor nodules on a standardized diagram of the prostate. Readers also recorded their degree of diagnostic confidence for each nodule on a five-point scale. Both readers repeated this interpretation with knowledge of rectal examination findings, sextant biopsy results, and PSA level. Step-section histopathologic findings were the reference standard. Logistic regression analysis with generalized estimating equations was used to correlate tumor detection with clinical data, and alternative free-response receiver operating characteristic (AFROC) curve analysis was used to examine the overall effect of clinical data on all positive results. Fifty-one peripheral zone tumor nodules were identified at histopathologic evaluation. Logistic regression analysis showed awareness of clinical data significantly improved tumor detection rate (P <.02) from 15 to 19 nodules for reader 1 and from 13 to 19 nodules for reader 2 (27%-37% overall) by using both size and location criteria. AFROC analysis showed no significant change in overall reader performance because there was an associated increase in the number of false-positive findings with awareness of clinical data, from 11 to 21 for reader 1 and from 16 to 25 for reader 2. Awareness of clinical data significantly improves reader detection of prostate cancer nodules with endorectal MR imaging and MR spectroscopic imaging, but there is no overall change in reader accuracy, because of an associated increase in false-positive findings. A stricter definition of a true-positive result is associated with reduced sensitivity for prostate cancer nodule detection. Copyright RSNA, 2004

SU-F-J-171: Robust Atlas Based Segmentation of the Prostate and Peripheral Zone Regions On MRI Utilizing Multiple MRI System Vendors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Padgett, K; Pollack, A; Stoyanova, R

Purpose: Automatically generated prostate MRI contours can be used to aid in image registration with CT or ultrasound and to reduce the burden of contouring for radiation treatment planning. In addition, prostate and zonal contours can assist to automate quantitative imaging features extraction and the analyses of longitudinal MRI studies. These potential gains are limited if the solutions are not compatible across different MRI vendors. The goal of this study is to characterize an atlas based automatic segmentation procedure of the prostate collected on MRI systems from multiple vendors. Methods: The prostate and peripheral zone (PZ) were manually contoured bymore » an expert radiation oncologist on T2-weighted scans acquired on both GE (n=31) and Siemens (n=33) 3T MRI systems. A leave-one-out approach was utilized where the target subject is removed from the atlas before the segmentation algorithm is initiated. The atlas-segmentation method finds the best nine matched atlas subjects and then performs a normalized intensity-based free-form deformable registration of these subjects to the target subject. These nine contours are then merged into a single contour using Simultaneous Truth and Performance Level Estimation (STAPLE). Contour comparisons were made using Dice similarity coefficients (DSC) and Hausdorff distances. Results: Using the T2 FatSat (FS) GE datasets the atlas generated contours resulted in an average DSC of 0.83±0.06 for prostate, 0.57±0.12 for PZ and 0.75±0.09 for CG. Similar results were found when using the Siemens data with a DSC of 0.79±0.14 for prostate, 0.54±0.16 and 0.70±0.9. Contrast between prostate and surrounding anatomy and between the PZ and CG contours for both vendors demonstrated superior contrast separation; significance was found for all comparisons p-value < 0.0001. Conclusion: Atlas-based segmentation yielded promising results for all contours compared to expertly defined contours in both Siemens and GE 3T systems providing fast and automatic segmentation of the prostate. Funding Support, Disclosures, and Conflict of Interest: AS Nelson is a partial owner of MIM Software, Inc. AS Nelson, and A Swallen are current employees at MIM Software, Inc.« less

Efficient 3D multi-region prostate MRI segmentation using dual optimization.

PubMed

Qiu, Wu; Yuan, Jing; Ukwatta, Eranga; Sun, Yue; Rajchl, Martin; Fenster, Aaron

2013-01-01

Efficient and accurate extraction of the prostate, in particular its clinically meaningful sub-regions from 3D MR images, is of great interest in image-guided prostate interventions and diagnosis of prostate cancer. In this work, we propose a novel multi-region segmentation approach to simultaneously locating the boundaries of the prostate and its two major sub-regions: the central gland and the peripheral zone. The proposed method utilizes the prior knowledge of the spatial region consistency and employs a customized prostate appearance model to simultaneously segment multiple clinically meaningful regions. We solve the resulted challenging combinatorial optimization problem by means of convex relaxation, for which we introduce a novel spatially continuous flow-maximization model and demonstrate its duality to the investigated convex relaxed optimization problem with the region consistency constraint. Moreover, the proposed continuous max-flow model naturally leads to a new and efficient continuous max-flow based algorithm, which enjoys great advantages in numerics and can be readily implemented on GPUs. Experiments using 15 T2-weighted 3D prostate MR images, by inter- and intra-operator variability, demonstrate the promising performance of the proposed approach.

Apparent Diffusion Coefficient Values of the Benign Central Zone of the Prostate: Comparison With Low- and High-Grade Prostate Cancer.

PubMed

Gupta, Rajan T; Kauffman, Christopher R; Garcia-Reyes, Kirema; Palmeri, Mark L; Madden, John F; Polascik, Thomas J; Rosenkrantz, Andrew B

2015-08-01

The apparent diffusion coefficient (ADC) values for benign central zone (CZ) of the prostate were compared with ADC values of benign peripheral zone (PZ), benign transition zone (TZ), and prostate cancer, using histopathologic findings from radical prostatectomy as the reference standard. The study included 27 patients with prostate cancer (mean [± SD] age, 60.0 ± 7.6 years) who had 3-T endorectal coil MRI of the prostate performed before undergoing prostatectomy with whole-mount histopathologic assessment. Mean ADC values were recorded from the ROI within the index tumor and within benign CZ, PZ, and TZ, with the use of histopathologic findings as the reference standard. ADC values of the groups were compared using paired t tests and ROC curve analysis. The ADC of benign CZ in the right (1138 ± 123 × 10(-6) mm(2)/s) and left (1166 ± 141 × 10(-6) mm(2)/s) lobes was not significantly different (p = 0.217). However, the ADC of benign CZ (1154 ± 129 × 10(-6) mm(2)/s) was significantly lower (p < 0.001) than the ADCs of benign PZ (1579 ± 197 × 10(-6) mm(2)/s) and benign TZ (1429 ± 180 × 10(-6) mm(2)/s). Although the ADC of index tumors (1042 ± 134 × 10(-6) mm(2)/s) was significantly lower (p = 0.002) than the ADC of benign CZ there was no significant difference (p = 0.225) between benign CZ and tumors with a Gleason score of 6 (1119 ± 87 × 10(-6) mm(2)/s). In 22.2% of patients (6/27), including five patients who had tumors with a Gleason score greater than 6, the ADC was lower in benign CZ than in the index tumor. The AUC of ADC for the differentiation of benign CZ from index tumors was 72.4% (sensitivity, 70.4%; specificity, 51.9%), and the AUC of ADC for differentiation from tumors with a Gleason score greater than 6 was 76.7% (sensitivity, 75.0%; specificity, 65.0%). The ADC of benign CZ is lower than the ADC of other zones of the prostate and overlaps with the ADC of prostate cancer tissue, including high-grade tumors. Awareness of this potential diagnostic pitfall is important to avoid misinterpreting the normal CZ as suspicious for tumor.

Biparametric 3T Magnetic Resonance Imaging for prostatic cancer detection in a biopsy-naïve patient population: a further improvement of PI-RADS v2?

PubMed

Stanzione, Arnaldo; Imbriaco, Massimo; Cocozza, Sirio; Fusco, Ferdinando; Rusconi, Giovanni; Nappi, Carmela; Mirone, Vincenzo; Mangiapia, Francesco; Brunetti, Arturo; Ragozzino, Alfonso; Longo, Nicola

2016-12-01

To prospectively determine the diagnostic accuracy of a biparametric 3T magnetic resonance imaging protocol (BP-MRI) for prostatic cancer detection, compared to a multiparametric MRI protocol (MP-MRI), in a biopsy naïve patient population. Eighty-two untreated patients (mean age 65±7.6years) with clinical suspicion of prostate cancer and/or altered prostate-specific antigen (PSA) levels underwent a MP-MRI, including T2-weighted imaging, diffusion-weighted imaging (with the correspondent apparent diffusion coefficient maps) and dynamic contrast enhanced sequence, followed by prostate biopsy. Two radiologists reviewed both the BP-MRI and the MP-MRI protocols to establish a radiological diagnosis. Receiver operating characteristics curves were obtained to determine the diagnostic performance of the two protocols. The mean PSA level was 8.8±8.1ng/ml. A total of 34 prostatic tumors were identified, with a Gleason score that ranged from 3+3 to 5+4. Of these 34 tumors, 29 were located within the peripheral zone and 5 in the transitional zone. BP-MRI and MP-MRI showed a similar performance in terms of overall diagnostic accuracy, with an area under the curve of 0.91 and 0.93, respectively (p=n.s.). BP-MRI prostate protocol is feasible for prostatic cancer detection compared to a standard MP-MRI protocol, requiring a shorter acquisition and interpretation time, with comparable diagnostic accuracy to the conventional protocol, without the administration of gadolinium-based contrast agent. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Evaluation of the normal-to-diseased apparent diffusion coefficient ratio as an indicator of prostate cancer aggressiveness.

PubMed

Lebovici, Andrei; Sfrangeu, Silviu A; Feier, Diana; Caraiani, Cosmin; Lucan, Ciprian; Suciu, Mihai; Elec, Florin; Iacob, Gheorghita; Buruian, Mircea

2014-05-10

We tested the feasibility of a simple method for assessment of prostate cancer (PCa) aggressiveness using diffusion-weighted magnetic resonance imaging (MRI) to calculate apparent diffusion coefficient (ADC) ratios between prostate cancer and healthy prostatic tissue. The requirement for institutional review board approval was waived. A set of 20 standardized core transperineal saturation biopsy specimens served as the reference standard for placement of regions of interest on ADC maps in tumorous and normal prostatic tissue of 22 men with PCa (median Gleason score: 7; range, 6-9). A total of 128 positive sectors were included for evaluation. Two diagnostic ratios were computed between tumor ADCs and normal sector ADCs: the ADC peripheral ratio (the ratio between tumor ADC and normal peripheral zone tissue, ADC-PR), and the ADC central ratio (the ratio between tumor ADC and normal central zone tissue, ADC-CR). The performance of the two ratios in detecting high-risk tumor foci (Gleason 8 and 9) was assessed using the area under the receiver operating characteristic curve (AUC). Both ADC ratios presented significantly lower values in high-risk tumors (0.48 ± 0.13 for ADC-CR and 0.40 ± 0.09 for ADC-PR) compared with low-risk tumors (0.66 ± 0.17 for ADC-CR and 0.54 ± 0.09 for ADC-PR) (p < 0.001) and had better diagnostic performance (ADC-CR AUC = 0.77, sensitivity = 82.2%, specificity = 66.7% and ADC-PR AUC = 0.90, sensitivity = 93.7%, specificity = 80%) than stand-alone tumor ADCs (AUC of 0.75, sensitivity = 72.7%, specificity = 70.6%) for identifying high-risk lesions. The ADC ratio as an intrapatient-normalized diagnostic tool may be better in detecting high-grade lesions compared with analysis based on tumor ADCs alone, and may reduce the rate of biopsies.

Evaluation of the normal-to-diseased apparent diffusion coefficient ratio as an indicator of prostate cancer aggressiveness

PubMed Central

2014-01-01

Background We tested the feasibility of a simple method for assessment of prostate cancer (PCa) aggressiveness using diffusion-weighted magnetic resonance imaging (MRI) to calculate apparent diffusion coefficient (ADC) ratios between prostate cancer and healthy prostatic tissue. Methods The requirement for institutional review board approval was waived. A set of 20 standardized core transperineal saturation biopsy specimens served as the reference standard for placement of regions of interest on ADC maps in tumorous and normal prostatic tissue of 22 men with PCa (median Gleason score: 7; range, 6–9). A total of 128 positive sectors were included for evaluation. Two diagnostic ratios were computed between tumor ADCs and normal sector ADCs: the ADC peripheral ratio (the ratio between tumor ADC and normal peripheral zone tissue, ADC-PR), and the ADC central ratio (the ratio between tumor ADC and normal central zone tissue, ADC-CR). The performance of the two ratios in detecting high-risk tumor foci (Gleason 8 and 9) was assessed using the area under the receiver operating characteristic curve (AUC). Results Both ADC ratios presented significantly lower values in high-risk tumors (0.48 ± 0.13 for ADC-CR and 0.40 ± 0.09 for ADC-PR) compared with low-risk tumors (0.66 ± 0.17 for ADC-CR and 0.54 ± 0.09 for ADC-PR) (p < 0.001) and had better diagnostic performance (ADC-CR AUC = 0.77, sensitivity = 82.2%, specificity = 66.7% and ADC-PR AUC = 0.90, sensitivity = 93.7%, specificity = 80%) than stand-alone tumor ADCs (AUC of 0.75, sensitivity = 72.7%, specificity = 70.6%) for identifying high-risk lesions. Conclusions The ADC ratio as an intrapatient-normalized diagnostic tool may be better in detecting high-grade lesions compared with analysis based on tumor ADCs alone, and may reduce the rate of biopsies. PMID:24885552

The Accumulation of Versican in the Nodules of Benign Prostatic Hyperplasia

PubMed Central

True, Lawrence D.; Hawley, Sarah; Norwood, Thomas H.; Braun, Kathleen R.; Evanko, Stephen P.; Chan, Christina K.; LeBaron, Richard C.; Wight, Thomas N.

2014-01-01

Background Proteoglycans, a complex group of extracellular matrix (ECM) molecules, are elevated in benign prostatic hyperplasia (BPH). Versican is a stromal proteoglycan present in prostate tissue. Versican expression is elevated in tissues with increased proliferation. Based on these observations, we determined the extent and distribution of versican expression in prostates with BPH. Methods The involvement of versican in BPH nodules was compared with levels in non-nodular transition (TZ) and peripheral zone (PZ) tissues from 18 human prostate glands using immunohistochemistry, Northern blots and/or QRTPCR to localize versican and quantify versican mRNA transcript levels, and Western blots to assess gene product levels. Results Increased versican immunoreactivity was observed in the stroma of BPH nodules. Higher steady state levels of versican variants V0, V1, and V3 mRNA transcript and gene product were detected in the nodular tissues than in the non-nodular TZ or PZ parenchyma. Conclusions These results suggest that versican may play a role in nodule formation in BPH. PMID:18819099

TU-CD-BRA-04: Evaluation of An Atlas-Based Segmentation Method for Prostate and Peripheral Zone Regions On MRI

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nelson, AS; Piper, J; Curry, K

2015-06-15

Purpose: Prostate MRI plays an important role in diagnosis, biopsy guidance, and therapy planning for prostate cancer. Prostate MRI contours can be used to aid in image fusion for ultrasound biopsy guidance and delivery of radiation. Our goal in this study is to evaluate an automatic atlas-based segmentation method for generating prostate and peripheral zone (PZ) contours on MRI. Methods: T2-weighted MRIs were acquired on 3T-Discovery MR750 System (GE, Milwaukee). The Volumes of Interest (VOIs): prostate and PZ were outlined by an expert radiation oncologist and used to create an atlas library for atlas-based segmentation. The atlas-segmentation accuracy was evaluatedmore » using a leave-one-out analysis. The method involved automatically finding the atlas subject that best matched the test subject followed by a normalized intensity-based free-form deformable registration of the atlas subject to the test subject. The prostate and PZ contours were transformed to the test subject using the same deformation. For each test subject the three best matches were used and the final contour was combined using Majority Vote. The atlas-segmentation process was fully automatic. Dice similarity coefficients (DSC) and mean Hausdorff values were used for comparison. Results: VOIs contours were available for 28 subjects. For the prostate, the atlas-based segmentation method resulted in an average DSC of 0.88+/−0.08 and a mean Hausdorff distance of 1.1+/−0.9mm. The number of patients (#) in DSC ranges are as follows: 0.60–0.69(1), 0.70–0.79(2), 0.80–0.89(13), >0.89(11). For the PZ, the average DSC was 0.72+/−0.17 and average Hausdorff of 0.9+/−0.9mm. The number of patients (#) in DSC ranges are as follows: <0.60(4), 0.60–0.69(6), 0.70–0.79(7), 0.80–0.89(9), >0.89(1). Conclusion: The MRI atlas-based segmentation method achieved good results for both the whole prostate and PZ compared to expert defined VOIs. The technique is fast, fully automatic, and has the potential to provide significant time savings for prostate VOI definition. AS Nelson and J Piper are partial owners of MIM Software, Inc. AS Nelson, J Piper, K Curry, and A Swallen are current employees at MIM Software, Inc.« less

The 3-dimensional structure of isolated and small foci of prostatic adenocarcinoma: the morphologic relationship between prostatic adenocarcinoma and prostatic intraepithelial neoplasia.

PubMed

Mai, Kien T; Burns, Bruce F; Stinson, William A; Morash, Christopher

2007-03-01

Transitional histopathologic changes from high-grade prostatic intraepithelial neoplasia (HGPIN) into early prostatic adenocarcinoma (PAC) have not been well studied to date. To investigate the histogenesis of PAC, we examined isolated and small foci of PAC (ISPAC) found in prostatectomy specimens and the 3-dimensional structure of these foci. Twelve consecutive radical prostatectomy specimens having ISPAC, performed for peripheral zone PAC (10 cases) and for transitional zone PAC (2 cases), of Gleason score were studied. One to 2 tissue blocks with representative sections were used. Eight ISPAC, with Gleason score 3 + 3 had complete serial sections of the entire lesion. PAC consisted of continuous, tortuous and branching tubules and acini arising from benign ducts displaying: (a) HGPIN in 5 ISPAC and (b) no HGPIN in 3 ISAPC. At the junctions between benign epithelia with or without HGPIN and malignant epithelia, there were transitional lesions with HGPIN involving small ducts and acini. PAC develops as a result of multiple outpouchings of the epithelium with formation of small ducts and acini showing cytologic atypia and gradual or abrupt loss of basal cells. Grade 3 ISPAC consists of a system of continuous duct pushing into the stroma. There is also evidence suggestive of HGPIN as being both a precursor lesion and an accompanying lesion of PAC.

Diffusion anisotropy in fresh and fixed prostate tissue ex vivo.

PubMed

Bourne, Roger M; Bongers, Andre; Chatterjee, Aritrick; Sved, Paul; Watson, Geoffrey

2016-08-01

To investigate diffusion anisotropy in whole human prostate specimens 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 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 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. © 2015 Wiley Periodicals, Inc.

Sampling of the anterior apical region results in increased cancer detection and upgrading in transrectal repeat saturation biopsy of the prostate.

PubMed

Seles, Maximilian; Gutschi, Thomas; Mayrhofer, Katrin; Fischereder, Katja; Ehrlich, Georg; Gallé, Guenter; Gutschi, Stefan; Pachernegg, Oliver; Pummer, Karl; Augustin, Herbert

2016-04-01

To evaluate whether biopsy cores taken via a transrectal approach from the anterior apical region of the prostate in a repeat-biopsy population can result in an increased overall cancer detection rate and in more accurate assessment of the Gleason score. The study was a prospective, randomised (end-fire vs side-fire ultrasound probe) evaluation of 288 men by repeat transrectal saturation biopsy with 28 cores taken from the transition zone, base, mid-lobar, anterior and the anterior apical region located ventro-laterally to the urethra of the peripheral zone. The overall prostate cancer detection rate was 44.4%. Improvement of the overall detection rate by 7.8% could be achieved with additional biopsies of the anterior apical region. Two tumours featuring a Gleason score 7 could only be detected in the anterior apical region. In three cases (2.34%) Gleason score upgrading was achieved by separate analysis of each positive core of the anterior apical region. A five-fold higher cancer detection rate in the anterior apical region compared with the transition zone could be shown. Sampling of the anterior apical region results in higher overall cancer detection rate in repeat transrectal saturation biopsies of the prostate. Specimens from this region can detect clinically significant cancer, improve accuracy of the Gleason Scoring and therefore may alter therapy. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

Time-dependent change of blood flow in the prostate treated with high-intensity focused ultrasound.

PubMed

Shoji, Sunao; Tonooka, Akiko; Hashimoto, Akio; Nakamoto, Masahiko; Tomonaga, Tetsuro; Nakano, Mayura; Sato, Haruhiro; Terachi, Toshiro; Koike, Junki; Uchida, Toyoaki

2014-09-01

Avascular areas on contrast-enhanced magnetic resonance imaging have been considered to be areas of localized prostate cancer successfully treated by high-intensity focused ultrasound. However, the optimal timing of magnetic resonance imaging has not been discussed. The thermal effect of high-intensity focused ultrasound is degraded by regional prostatic blood flow. Conversely, the mechanical effect of high-intensity focused ultrasound (cavitation) is not affected by blood flow, and can induce vessel damage. In this series, the longitudinal change of blood flow on contrast-enhanced magnetic resonance imaging was observed from postoperative day 1 to postoperative day 14 in 10 patients treated with high-intensity focused ultrasound. The median rates of increase in the non-enhanced volume of the whole gland, transition zone and peripheral zone from postoperative day 1 to postoperative day 14 were 36%, 39%, and 34%, respectively. In another pathological analysis of the prostate tissue of 17 patients immediately after high-intensity focused ultrasound without neoadjuvant hormonal therapy, we observed diffuse coagulative degeneration and partial non-coagulative prostate tissue around arteries with vascular endothelial cell detachment. These observations on contrast-enhanced magnetic resonance imaging support a time-dependent change of the blood flow in the prostate treated with high-intensity focused ultrasound. Additionally, our pathological findings support the longitudinal changes of these magnetic resonance imaging findings. Further large-scale studies will investigate the most appropriate timing of contrast-enhanced magnetic resonance imaging for evaluation of the effectiveness of high-intensity focused ultrasound for localized prostate cancer. © 2014 The Japanese Urological Association.

Phosphorus magnetic resonance spectroscopic imaging at 7 T in patients with prostate cancer.

PubMed

Lagemaat, Miriam W; Vos, Eline K; Maas, Marnix C; Bitz, Andreas K; Orzada, Stephan; van Uden, Mark J; Kobus, Thiele; Heerschap, Arend; Scheenen, Tom W J

2014-05-01

The aim of this study was to identify characteristics of phosphorus (P) spectra of the human prostate and to investigate changes of individual phospholipid metabolites in prostate cancer through in vivo P magnetic resonance spectroscopic imaging (MRSI) at 7 T. In this institutional review board-approved study, 15 patients with biopsy-proven prostate cancer underwent T2-weighted magnetic resonance imaging and 3-dimensional P MRSI at 7 T. Voxels were selected at the tumor location, in normal-appearing peripheral zone tissue, normal-appearing transition zone tissue, and in the base of the prostate close to the seminal vesicles. Phosphorus metabolite ratios were determined and compared between tissue types. Signals of phosphoethanolamine (PE) and phosphocholine (PC) were present and well resolved in most P spectra in the prostate. Glycerophosphocholine signals were observable in 43% of the voxels in malignant tissue, but in only 10% of the voxels in normal-appearing tissue away from the seminal vesicles. In many spectra, independent of tissue type, 2 peaks resonated in the chemical shift range of inorganic phosphate, possibly representing 2 separate pH compartments. The PC/PE ratio in the seminal vesicles was highly elevated compared with the prostate in 5 patients. A considerable overlap of P metabolite ratios was found between prostate cancer and normal-appearing prostate tissue, preventing direct discrimination of these tissues. The only 2 patients with high Gleason scores tumors (≥4+5) presented with high PC and glycerophosphocholine levels in their cancer lesions. Phosphorus MRSI at 7 T shows distinct features of phospholipid metabolites in the prostate gland and its surrounding structures. In this exploratory study, no differences in P metabolite ratios were observed between prostate cancer and normal-appearing prostate tissue possibly because of the partial volume effects of small tumor foci in large MRSI voxels.

Regular transition zone biopsy during active surveillance for prostate cancer may improve detection of pathological progression.

PubMed

Wong, Lih-Ming; Toi, Ants; Van der Kwast, Theodorus; Trottier, Greg; Alibhai, Shabbir M H; Timilshina, Narhari; Evans, Andrew; Zlotta, Alexandre; Fleshner, Neil; Finelli, Antonio

2014-10-01

We investigated the frequency of cancer and pathological progression in transition zone biopsies in men undergoing multiple rebiopsies while on active surveillance. Eligibility criteria of the active surveillance prostate cancer database (1997 to 2012) at our tertiary center includes prostate specific antigen 10 ng/ml or less, cT2 or less, no Gleason grade 4 or 5, 3 or fewer positive cores, no core with greater than 50% involvement, patient age 75 years or less and 1 or more biopsies after initial diagnostic biopsy. We excluded from analysis men with fewer than 10 cores at diagnostic biopsy and/or confirmatory biopsy greater than 24 months after diagnostic biopsy. Multiparametric magnetic resonance imaging was performed selectively to investigate incongruity between prostate specific antigen and biopsy findings. Pathological progression was defined by grade and/or volume (greater than 50% of core involved). Transition zone progression was subdivided into exclusively transition zone and combined transition zone (transition and peripheral zones). A multivariate Cox proportional hazards model was used to determine predictors of transition zone progression. A total of 392 men were considered in analysis. Median followup was 45.5 months. At each biopsy during active surveillance (confirmatory biopsy to biopsy 5+) there were transition zone positive cores in 18.6% to 26.7% of cases, all transition zone progression in 5.9% to 11.1% and exclusively transition zone progression in 2.7% to 6.7%. Volume related progression was noted more frequently than grade related progression (24 vs 9 cases). Predictors of only transition zone progression were the maximum percent in a single core (HR 1.99, 95% CI 1.30-3.04, p = 0.002) and cancer on magnetic resonance imaging (HR 3.19, 95% CI 1.23-8.27, p = 0.02). Across multiple active surveillance biopsies 2.7% to 6.7% of men had only transition zone progression. We recommend that transition zone biopsy be considered in all men at confirmatory biopsy. Positive magnetic resonance imaging findings or a high percent of core involvement may subsequently be useful to identify patients at risk. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Quantification of phase I / II metabolizing enzyme gene expression and polycyclic aromatic hydrocarbon-DNA adduct levels in human prostate

PubMed Central

John, Kaarthik; Ragavan, Narasimhan; Pratt, M. Margaret; Singh, Paras B.; Al-Buheissi, Salah; Matanhelia, Shyam S.; Phillips, David H.; Poirier, Miriam C.; Martin, Francis L.

2008-01-01

BACKGROUND Studies of migrant populations suggest that dietary and/or environmental factors play a crucial role in the aetiology of prostatic adenocarcinoma (CaP). The human prostate consists of the peripheral zone (PZ), transition zone (TZ) and central zone (CZ); CaP occurs most often in the PZ. METHODS To investigate the notion that an underlying differential expression of phase I/II genes, and/or the presence of polycyclic aromatic hydrocarbon (PAH)-DNA adducts might explain the elevated PZ susceptibility, we examined prostate tissues (matched tissue sets consisting of PZ and TZ) from men undergoing radical retropubic prostatectomy for CaP (n=26) or cystoprostatectomy (n=1). Quantitative gene expression analysis was employed for cytochrome P450 (CYP) isoforms CYP1A1, CYP1B1 and CYP1A2, as well as N-acetyltransferase 1 and 2 (NAT1 and NAT2) and catechol-O-methyl transferase (COMT). RESULTS CYP1B1, NAT1 and COMT were expressed in all tissue sets; levels of CYP1B1 and NAT1 were consistently higher in the PZ compared to TZ. Immunohistochemistry confirmed the presence of CYP1B1 (nuclear-associated and primarily in basal epithelial cells) and NAT1. Tissue sections from 23 of these aforementioned 27 matched tissue sets were analyzed for PAH-DNA adduct levels using antiserum elicited against DNA modified with r7, t8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydro-benzo[a]pyrene (BPDE). PAH-DNA adduct levels were highest in glandular epithelial cells, but a comparison of PZ and TZ showed no significant differences. CONCLUSION Although expression of activating and/or detoxifying enzymes may be higher in the PZ, PAH-DNA adduct levels appear to be similar in both zones. Therefore, factors other than PAH-DNA adducts may be responsible for promotion of tumour formation in the human prostate. PMID:19143007

MRI to predict prostate growth and development in children, adolescents and young adults.

PubMed

Ren, Jing; Liu, Huijia; Wang, He; Wen, Didi; Huang, Xufang; Ren, Fang; Huan, Yi

2015-02-01

The purpose of this study was to investigate the use of MRI in predicting prostate growth and development. A total of 1,500 healthy male volunteers who underwent MRI of the pelvis were included in this prospective study. Subjects were divided into five groups according to age (group A, 2-5 years; group B, 6-10 years; group C, 11-15 years; group D, 16-20 years; group E, 21-25 years). Total prostate volume (TPV) as well as prostate central zone (CZ) and peripheral zone (PZ) were measured and evaluated on MRI. Data of the different groups were compared using variance analysis, Scheffé's method, Kruskal-Wallis H-test, and Pearson's correlation. Statistical significance was inferred at P < 0.05. In groups A and B, the prostates were barely visible. In group C, although TPV was measured, it was hard to distinguish CZ and PZ. In group D, 136 CZ and PZ were clearly visible. In group E, 377 CZ and PZ were clearly visible on T2-weighted imaging (T2WI). The median TPVs of groups A, B, C, D, and E were 0.00 cm(3), 0.05 cm(3), 2.83 cm(3), 8.32 cm(3,) and 11.56 cm(3), respectively, and the median prostate development scores were 0.08, 0.69, 1.56, 2.38, and 2.74, respectively. Both TPVs and zonal anatomy scores varied significantly among the five groups (P = 0.000). TPV and zonal anatomy score increased with increasing age. MRI provides a reliable quantitative reference for prostate growth and development. • When and how the prostate develops after birth remains unclear. • Prostate volume increases rapidly after the age of 10 years. • MRI provides a reliable objective and quantitative reference for prostate growth and development.

A comprehensive review of the role of zinc in normal prostate function and metabolism; and its implications in prostate cancer☆

PubMed Central

Costello, Leslie C.; Franklin, Renty B.

2016-01-01

The human prostate gland contains extremely high zinc levels; which is due to the specialized zinc-accumulating acinar epithelial of the peripheral zone. These cells evolved for their unique capability to produce and secrete extremely levels of citrate, which is achieved by the high cellular zinc level effects on the cell metabolism. This review highlights the specific functional and metabolic alterations that result from the accumulation of the high zinc levels, especially its effects on mitochondrial citrate metabolism and terminal oxidation. The implications of zinc in the development and progression of prostate cancer are described, which is the most consistent hallmark characteristic of prostate cancer. The requirement for decreased zinc resulting from down regulation of ZIP1 to prevent zinc cytotoxicity in the malignant cells is described as an essential early event in prostate oncogenesis. This provides the basis for the concept that an agent (such as the zinc ionophore, clioquinol) that facilitates zinc uptake and accumulation in ZIP1-deficient prostate tumors cells will markedly inhibit tumor growth. In the current absence of an efficacious chemotherapy for advanced prostate cancer, and for prevention of early development of malignancy; a zinc treatment regimen is a plausible approach that should be pursued. PMID:27132038

A Bayesian nonrigid registration method to enhance intraoperative target definition in image-guided prostate procedures through uncertainty characterization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pursley, Jennifer; Risholm, Petter; Fedorov, Andriy

2012-11-15

Purpose: This study introduces a probabilistic nonrigid registration method for use in image-guided prostate brachytherapy. Intraoperative imaging for prostate procedures, usually transrectal ultrasound (TRUS), is typically inferior to diagnostic-quality imaging of the pelvis such as endorectal magnetic resonance imaging (MRI). MR images contain superior detail of the prostate boundaries and provide substructure features not otherwise visible. Previous efforts to register diagnostic prostate images with the intraoperative coordinate system have been deterministic and did not offer a measure of the registration uncertainty. The authors developed a Bayesian registration method to estimate the posterior distribution on deformations and provide a case-specific measuremore » of the associated registration uncertainty. Methods: The authors adapted a biomechanical-based probabilistic nonrigid method to register diagnostic to intraoperative images by aligning a physician's segmentations of the prostate in the two images. The posterior distribution was characterized with a Markov Chain Monte Carlo method; the maximum a posteriori deformation and the associated uncertainty were estimated from the collection of deformation samples drawn from the posterior distribution. The authors validated the registration method using a dataset created from ten patients with MRI-guided prostate biopsies who had both diagnostic and intraprocedural 3 Tesla MRI scans. The accuracy and precision of the estimated posterior distribution on deformations were evaluated from two predictive distance distributions: between the deformed central zone-peripheral zone (CZ-PZ) interface and the physician-labeled interface, and based on physician-defined landmarks. Geometric margins on the registration of the prostate's peripheral zone were determined from the posterior predictive distance to the CZ-PZ interface separately for the base, mid-gland, and apical regions of the prostate. Results: The authors observed variation in the shape and volume of the segmented prostate in diagnostic and intraprocedural images. The probabilistic method allowed us to convey registration results in terms of posterior distributions, with the dispersion providing a patient-specific estimate of the registration uncertainty. The median of the predictive distance distribution between the deformed prostate boundary and the segmented boundary was Less-Than-Or-Slanted-Equal-To 3 mm (95th percentiles within {+-}4 mm) for all ten patients. The accuracy and precision of the internal deformation was evaluated by comparing the posterior predictive distance distribution for the CZ-PZ interface for each patient, with the median distance ranging from -0.6 to 2.4 mm. Posterior predictive distances between naturally occurring landmarks showed registration errors of Less-Than-Or-Slanted-Equal-To 5 mm in any direction. The uncertainty was not a global measure, but instead was local and varied throughout the registration region. Registration uncertainties were largest in the apical region of the prostate. Conclusions: Using a Bayesian nonrigid registration method, the authors determined the posterior distribution on deformations between diagnostic and intraprocedural MR images and quantified the uncertainty in the registration results. The feasibility of this approach was tested and results were positive. The probabilistic framework allows us to evaluate both patient-specific and location-specific estimates of the uncertainty in the registration result. Although the framework was tested on MR-guided procedures, the preliminary results suggest that it may be applied to TRUS-guided procedures as well, where the addition of diagnostic MR information may have a larger impact on target definition and clinical guidance.« less

A Bayesian nonrigid registration method to enhance intraoperative target definition in image-guided prostate procedures through uncertainty characterization

PubMed Central

Pursley, Jennifer; Risholm, Petter; Fedorov, Andriy; Tuncali, Kemal; Fennessy, Fiona M.; Wells, William M.; Tempany, Clare M.; Cormack, Robert A.

2012-01-01

Purpose: This study introduces a probabilistic nonrigid registration method for use in image-guided prostate brachytherapy. Intraoperative imaging for prostate procedures, usually transrectal ultrasound (TRUS), is typically inferior to diagnostic-quality imaging of the pelvis such as endorectal magnetic resonance imaging (MRI). MR images contain superior detail of the prostate boundaries and provide substructure features not otherwise visible. Previous efforts to register diagnostic prostate images with the intraoperative coordinate system have been deterministic and did not offer a measure of the registration uncertainty. The authors developed a Bayesian registration method to estimate the posterior distribution on deformations and provide a case-specific measure of the associated registration uncertainty. Methods: The authors adapted a biomechanical-based probabilistic nonrigid method to register diagnostic to intraoperative images by aligning a physician's segmentations of the prostate in the two images. The posterior distribution was characterized with a Markov Chain Monte Carlo method; the maximum a posteriori deformation and the associated uncertainty were estimated from the collection of deformation samples drawn from the posterior distribution. The authors validated the registration method using a dataset created from ten patients with MRI-guided prostate biopsies who had both diagnostic and intraprocedural 3 Tesla MRI scans. The accuracy and precision of the estimated posterior distribution on deformations were evaluated from two predictive distance distributions: between the deformed central zone-peripheral zone (CZ-PZ) interface and the physician-labeled interface, and based on physician-defined landmarks. Geometric margins on the registration of the prostate's peripheral zone were determined from the posterior predictive distance to the CZ-PZ interface separately for the base, mid-gland, and apical regions of the prostate. Results: The authors observed variation in the shape and volume of the segmented prostate in diagnostic and intraprocedural images. The probabilistic method allowed us to convey registration results in terms of posterior distributions, with the dispersion providing a patient-specific estimate of the registration uncertainty. The median of the predictive distance distribution between the deformed prostate boundary and the segmented boundary was ⩽3 mm (95th percentiles within ±4 mm) for all ten patients. The accuracy and precision of the internal deformation was evaluated by comparing the posterior predictive distance distribution for the CZ-PZ interface for each patient, with the median distance ranging from −0.6 to 2.4 mm. Posterior predictive distances between naturally occurring landmarks showed registration errors of ⩽5 mm in any direction. The uncertainty was not a global measure, but instead was local and varied throughout the registration region. Registration uncertainties were largest in the apical region of the prostate. Conclusions: Using a Bayesian nonrigid registration method, the authors determined the posterior distribution on deformations between diagnostic and intraprocedural MR images and quantified the uncertainty in the registration results. The feasibility of this approach was tested and results were positive. The probabilistic framework allows us to evaluate both patient-specific and location-specific estimates of the uncertainty in the registration result. Although the framework was tested on MR-guided procedures, the preliminary results suggest that it may be applied to TRUS-guided procedures as well, where the addition of diagnostic MR information may have a larger impact on target definition and clinical guidance. PMID:23127078

Correlation of apparent diffusion coefficient ratio on 3.0 T MRI with prostate cancer Gleason score.

PubMed

Jyoti, Rajeev; Jain, Tarun Pankaj; Haxhimolla, Hodo; Liddell, Heath; Barrett, Sean Edward

2018-01-01

The purpose was to investigate the usefulness of ADC ratio on Diffusion MRI to discriminate between benign and malignant lesions of Prostate. Images of patients who underwent in-gantry MRI guided prostate lesion biopsy were retrospectively analyzed. Prostate Cancers with 20% or more Gleason score (GS) pattern 3 + 3 = 6 in each core or any volume of higher Gleason score pattern were included. ADC ratio was calculated by two reviewers for each lesion. The ADC ratio was calculated for each lesion by dividing the lowest ADC value in a lesion and highest ADC value in normal prostate in peripheral zone (PZ). ADC ratio values were compared with the biopsy result. Data was analysed using independent samples T-test, Spearman correlation, intra-class correlation coefficient (ICC) and Receiver operating characteristic (ROC) curve. 45 lesions in 33 patients were analyzed. 12 lesions were in transitional zone (TZ) and 33 in perpheral zone PZ. All lesions demonstrated an ADC ratio of 0.45 or lower. GS demonstrated a negative correlation with both the ADC value and ADC ratio . However, ADC ratio (p < 0.001) demonstrated a stronger correlation compared to ADC value alone (p = 0.014). There was no significant statistical difference between GS 3 + 4 and GS 4 + 3 mean ADC tumour value (p = 0.167). However when using ADC ratio , there was a significant difference (p = 0.032). ROC curve analysis demonstrated an area under the curve of 0.83 using ADC ratio and 0.76 when using ADC tumour value when discriminating Gleason 6 from Gleason ≥7 tumours. Inter-observer reliability in the calculation of ADC ratios was excellent, with ICC of 0.964. ADC ratio is a reliable and reproducible tool in quantification of diffusion restriction for clinically significant prostate cancer foci.

[Testosterone replacement therapy for late-onset hypogonadism after radical prostatectomy: a case report].

PubMed

Nakano, Kosuke; Kiuchi, Hiroshi; Miyagawa, Yasushi; Tsujimura, Akira; Nonomura, Norio

2014-08-01

A 53-year-old man presented to our hospital with a few-month history of fatigue and anorexia. His aging male's symptoms (AMS) score was 57, and the free testosterone value was low (6.5 pg/ml). He was diagnosed with severe late-onset hypogonadism indicative of androgen replacement therapy (ART). His serum prostate specific antigen was 8.7 ng/ml, and pelvic magnetic resonance imaging showed a low intensity area in the peripheral zone of the prostate. A systematic 10-core prostate biopsy revealed one core of adenocarcinoma with a Gleason score of 3 + 3=6. Imaging examination revealed organ-confined prostate cancer that was cT2aN0M0. Given his desire for ART for the treatment of hypogonadism, the patient underwent open radical prostatectomy. Pathologic examination demonstrated prostate adenocarcinoma that was pT2aN0, and Gleason score of 3 + 3=6. After confirming that the prostate specific antigen value was under 0.01 ng/ml for three years after prostatectomy, the patient received 125 mg methyltestosterone monthly. His hypogonadism-related symptoms diminished and AMS score dropped to 48. During a three-year follow-up of ART, no biochemical recurrence was found.

Epigenetics-related genes in prostate cancer: expression profile in prostate cancer tissues, androgen-sensitive and -insensitive cell lines.

PubMed

Shaikhibrahim, Zaki; Lindstrot, Andreas; Ochsenfahrt, Jacqueline; Fuchs, Kerstin; Wernert, Nicolas

2013-01-01

Epigenetic changes have been suggested to drive prostate cancer (PCa) development and progression. Therefore, in this study, we aimed to identify novel epigenetics-related genes in PCa tissues, and to examine their expression in metastatic PCa cell lines. We analyzed the expression of epigenetics-related genes via a clustering analysis based on gene function in moderately and poorly differentiated PCa glands compared to normal glands of the peripheral zone (prostate proper) from PCa patients using Whole Human Genome Oligo Microarrays. Our analysis identified 12 epigenetics-related genes with a more than 2-fold increase or decrease in expression and a p-value <0.01. In modera-tely differentiated tumors compared to normal glands of the peripheral zone, we found the genes, TDRD1, IGF2, DICER1, ADARB1, HILS1, GLMN and TRIM27, to be upregulated, whereas TNRC6A and DGCR8 were found to be downregulated. In poorly differentiated tumors, we found TDRD1, ADARB and RBM3 to be upregulated, whereas DGCR8, PIWIL2 and BC069781 were downregulated. Our analysis of the expression level for each gene in the metastatic androgen-sensitive VCaP and LNCaP, and -insensitive PC3 and DU-145 PCa cell lines revealed differences in expression among the cell lines which may reflect the different biological properties of each cell line, and the potential role of each gene at different metastatic sites. The novel epigenetics-related genes that we identified in primary PCa tissues may provide further insight into the role that epigenetic changes play in PCa. Moreover, some of the genes that we identified may play important roles in primary PCa and metastasis, in primary PCa only, or in metastasis only. Follow-up studies are required to investigate the functional role and the role that the expression of these genes play in the outcome and progression of PCa using tissue microarrays.

MR Imaging of the Prostate and Adjacent Anatomic Structures before, during, and after Ejaculation: Qualitative and Quantitative Evaluation1

PubMed Central

Medved, Milica; Sammet, Steffen; Yousuf, Ambereen; Oto, Aytekin

2015-01-01

Purpose To determine the possibility of obtaining high-quality magnetic resonance (MR) images before, during, and immediately after ejaculation and detecting measurable changes in quantitative MR imaging parameters after ejaculation. Materials and Methods In this prospective, institutional review board–approved, HIPAA-compliant study, eight young healthy volunteers (median age, 22.5 years), after providing informed consent, underwent MR imaging while masturbating to the point of ejaculation. A 1.5-T MR imaging unit was used, with an eight-channel surface coil and a dynamic single-shot fast spin-echo sequence. In addition, a quantitative MR imaging protocol that allowed calculation of T1, T2, and apparent diffusion coefficient (ADC) values was applied before and after ejaculation. Volumes of the prostate and seminal vesicles (SV) were calculated by using whole-volume segmentation on T2-weighted images, both before and after ejaculation. Pre- and postejaculation changes in quantitative MR parameters and measured volumes were evaluated by using the Wilcoxon signed rank test with Bonferroni adjustment. Results There was no significant change in prostate volumes on pre- and postejaculation images, while the SV contracted by 41% on average (median, 44.5%; P = .004). No changes before and after ejaculation were observed in T1 values or in T2 and ADC values in the central gland, while T2 and ADC values were significantly reduced in the peripheral zone by 12% and 14%, respectively (median, 13% and 14.5%, respectively; P = .004). Conclusion Successful dynamic MR imaging of ejaculation events and the ability to visualize internal sphincter closure, passage of ejaculate, and significant changes in SV volumes were demonstrated. Significant changes in peripheral zone T2 and ADC values were observed. PMID:24495265

Relationship between intraprostatic tracer deposits and sentinel lymph node mapping in prostate cancer patients.

PubMed

Buckle, Tessa; Brouwer, Oscar R; Valdés Olmos, Renato A; van der Poel, Henk G; van Leeuwen, Fijs W B

2012-07-01

Intraprostatic injection of the hybrid tracer indocyanine green (ICG)-(99m)Tc-nanocolloid enables both preoperative sentinel node (SN) identification and intraoperative visualization of the SN. Relating the fluorescence deposits in embedded prostate tissue specimens to the preoperatively detected SNs also provides the opportunity to study the influence of their placement on lymphatic drainage pattern. Nineteen patients with prostate carcinoma scheduled for robot-assisted laparoscopic prostatectomy and lymph node (LN) dissection were included. ICG-(99m)Tc-nanocolloid was injected intraprostatically, guided by ultrasound. SN biopsy was performed using a combination of radioguidance and fluorescence guidance. Tracer distribution was visualized in paraffin-embedded prostate samples using ex vivo fluorescence imaging. This distribution was correlated to the number and location of the SNs identified on preoperative lymphoscintigraphy and SPECT/CT. ICG-(99m)Tc-nanocolloid helped guide surgical excision of the SNs. Ex vivo fluorescence imaging revealed a large variation in the locations of intraprostatic tracer deposits among patients. Tracer deposits in the peripheral zone correlated with a higher number of visualized LNs than deposits in the central zone (on average, 4.7 vs. 2.4 LNs per patient). Furthermore, tracer deposits in the mid gland correlated with a higher number of visualized LNs than deposits near the base or apex of the prostate (on average, 6 vs. 3.5 LNs per patient). The hybrid nature of the tracer not only enables surgical guidance but also provides an opportunity to study the correlation between the location of tracer deposits within the prostate and the number and location of preoperatively visualized SNs. These data suggest that the location at which a tracer deposit is placed influences the lymphatic drainage pattern.

Prostate thermal therapy with catheter-based ultrasound devices and MR thermal monitoring

NASA Astrophysics Data System (ADS)

Diederich, Chris J.; Nau, Will H.; Kinsey, Adam; Ross, Tony; Wootton, Jeff; Juang, Titania; Butts-Pauly, Kim; Ricke, Viola; Liu, Erin H.; Chen, Jing; Bouley, Donna M.; Van den Bosch, Maurice; Sommer, Graham

2007-02-01

Four types of transurethral applicators were devised for thermal ablation of prostate combined with MR thermal monitoring: sectored tubular transducer devices with directional heating patterns; planar and curvilinear devices with narrow heating patterns; and multi-sectored tubular devices capable of dynamic angular control without applicator movement. These devices are integrated with a 4 mm delivery catheter, incorporate an inflatable cooling balloon (10 mm OD) for positioning within the prostate and capable of rotation via an MR-compatible motor. Interstitial devices (2.4 mm OD) have been developed for percutaneous implantation with directional or dynamic angular control. In vivo experiments in canine prostate under MR temperature imaging were used to evaluate the heating technology and develop treatment control strategies. MR thermal imaging in a 0.5 T interventional MRI was used to monitor temperature and thermal dose in multiple slices through the target volume. Sectored tubular, planar, and curvilinear transurethral devices produce directional coagulation zones, extending 15-20 mm radial distance to the outer prostate capsule. Sequential rotation and modulated dwell time can conform thermal ablation to selected regions. Multi-sectored transurethral applicators can dynamically control the angular heating profile and target large regions of the gland in short treatment times without applicator manipulation. Interstitial implants with directional devices can be used to effectively ablate the posterior peripheral zone of the gland while protecting the rectum. The MR derived 52 °C and lethal thermal dose contours (t 43=240 min) allowed for real-time control of the applicators and effectively defined the extent of thermal damage. Catheter-based ultrasound devices, combined with MR thermal monitoring, can produce relatively fast and precise thermal ablation of prostate, with potential for treatment of cancer or BPH.

Transrectal ultrasound (TRUS) findings of the prostate gland in late onset hypogonadism with testosterone supplementation in correlation with clinical outcome.

PubMed

Phongkitkarun, Sith; Rassameepong, Apinan; Permpongkosol, Sompol; Taphey, Mayureewan; Wibulpolprasert, Bussanee

2012-07-01

To determine the TRUS findings of the prostate and correlation of ultrasoundfindings with clinical outcomes in late-onset hypogonadal (LOH) men with testosterone supplementation. Between January 2007 and September 2010, TRUS findings and clinical outcomes of 16 from 226 subjects were studied The demographic data, ultrasound parameters as prostate volume and vascularity, and clinical parameters were evaluated Correlation between ultrasound and clinical parameters were analyzed using Pearson correlation analysis. During mean time follow-up of 6.48 months, the volume of the central gland (CG) significantly increased (p = 0.02), the volume of the total gland (TG) increased, and the volume of the peripheral zone (PZ) slightly decreased. The vascularity of the TG, CG, and PZ were significantly increased. The periurethral region vascularity was not significantly increased (p = 0.06), whereas total serum testosterone, prostate specific antigen (PSA), and PSA density were increased The International Prostate Symptom Score (IPSS) was significantly decreased (p < 0.001). There was a significant correlation between increased prostate volume and increased serum PSA. Testosterone supplementation in LOH men was found to cause an increase in TG volume during the first six months. The preferentially increased CG volume and prostatic vascularity might be due to exogenous testosterone. The authors observed a significantly increased PSA with a strong correlation between serum PSA and prostate volume.

Application of Prostate Imaging Reporting and Data System Version 2 (PI-RADS v2): Interobserver Agreement and Positive Predictive Value for Localization of Intermediate- and High-Grade Prostate Cancers on Multiparametric Magnetic Resonance Imaging.

PubMed

Chen, Frank; Cen, Steven; Palmer, Suzanne

2017-09-01

To evaluate interobserver agreement with the use of and the positive predictive value (PPV) of Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) for the localization of intermediate- and high-grade prostate cancers on multiparametric magnetic resonance imaging (mpMRI). In this retrospective, institutional review board-approved study, 131 consecutive patients who had mpMRI followed by transrectal ultrasound-MR imaging fusion-guided biopsy of the prostate were included. Two readers who were blinded to initial mpMRI reports, clinical data, and pathologic outcomes reviewed the MR images, identified all prostate lesions, and scored each lesion based on the PI-RADS v2. Interobserver agreement was assessed by intraclass correlation coefficient (ICC), and PPV was calculated for each PI-RADS category. PI-RADS v2 was found to have a moderate level of interobserver agreement between two readers of varying experience, with ICC of 0.74, 0.72, and 0.67 for all lesions, peripheral zone lesions, and transitional zone lesions, respectively. Despite only moderate interobserver agreement, the calculated PPV in the detection of intermediate- and high-grade prostate cancers for each PI-RADS category was very similar between the two readers, with approximate PPV of 0%, 12%, 64%, and 87% for PI-RADS categories 2, 3, 4, and 5, respectively. In our study, PI-RADS v2 has only moderate interobserver agreement, a similar finding in studies of the original PI-RADS and in initial studies of PI-RADS v2. Despite this, PI-RADS v2 appears to be a useful system to predict significant prostate cancer, with PI-RADS scores correlating well with the likelihood of intermediate- and high-grade cancers. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Association of quantitative magnetic resonance imaging parameters with histological findings from MRI/ultrasound fusion prostate biopsy.

PubMed

Dianat, Seyed Saeid; Carter, H Ballentine; Schaeffer, Edward M; Hamper, Ulrik M; Epstein, Jonathan I; Macura, Katarzyna J

2015-10-01

Purpose of this pilot study was to correlate quantitative parameters derived from the multiparametric magnetic resonance imaging (MP-MRI) of the prostate with results from MRI guided transrectal ultrasound (MRI/TRUS) fusion prostate biopsy in men with suspected prostate cancer. Thirty-nine consecutive patients who had 3.0T MP-MRI and subsequent MRI/TRUS fusion prostate biopsy were included and 73 MRI-identified targets were sampled by 177 cores. The pre-biopsy MP-MRI consisted of T2-weighted, diffusion weighted (DWI), and dynamic contrast enhanced (DCE) images. The association of quantitative MRI measurements with biopsy histopathology findings was assessed by Mann-Whitney U- test and Kruskal-Wallis test. Of 73 targets, biopsy showed benign prostate tissue in 46 (63%), cancer in 23 (31.5%), and atypia/high grade prostatic intraepithelial neoplasia in four (5.5%) targets. The median volume of cancer-positive targets was 1.3 cm3. The cancer-positive targets were located in the peripheral zone (56.5%), transition zone (39.1%), and seminal vesicle (4.3%). Nine of 23 (39.1%) cancer-positive targets were higher grade cancer (Gleason grade > 6). Higher grade targets and cancer-positive targets compared to benign lesions exhibited lower mean apparent diffusion coefficient (ADC) value (952.7 < 1167.9 < 1278.9), and lower minimal extracellular volume fraction (ECF) (0.13 < 0.185 < 0.213), respectively. The difference in parameters was more pronounced between higher grade cancer and benign lesions. Our findings from a pilot study indicate that quantitative MRI parameters can predict malignant histology on MRI/TRUS fusion prostate biopsy, which is a valuable technique to ensure adequate sampling of MRI-visible suspicious lesions under TRUS guidance and may impact patient management. The DWI-based quantitative measurement exhibits a stronger association with biopsy findings than the other MRI parameters.

Development of a Combined MR Fingerprinting and Diffusion Examination for Prostate Cancer.

PubMed

Yu, Alice C; Badve, Chaitra; Ponsky, Lee E; Pahwa, Shivani; Dastmalchian, Sara; Rogers, Matthew; Jiang, Yun; Margevicius, Seunghee; Schluchter, Mark; Tabayoyong, William; Abouassaly, Robert; McGivney, Debra; Griswold, Mark A; Gulani, Vikas

2017-06-01

Purpose To develop and evaluate an examination consisting of magnetic resonance (MR) fingerprinting-based T1, T2, and standard apparent diffusion coefficient (ADC) mapping for multiparametric characterization of prostate disease. Materials and Methods This institutional review board-approved, HIPAA-compliant retrospective study of prospectively collected data included 140 patients suspected of having prostate cancer. T1 and T2 mapping was performed with fast imaging with steady-state precession-based MR fingerprinting with ADC mapping. Regions of interest were drawn by two independent readers in peripheral zone lesions and normal-appearing peripheral zone (NPZ) tissue identified on clinical images. T1, T2, and ADC were recorded for each region. Histopathologic correlation was based on systematic transrectal biopsy or cognitively targeted biopsy results, if available. Generalized estimating equations logistic regression was used to assess T1, T2, and ADC in the differentiation of (a) cancer versus NPZ, (b) cancer versus prostatitis, (c) prostatitis versus NPZ, and (d) high- or intermediate-grade tumors versus low-grade tumors. Analysis was performed for all lesions and repeated in a targeted biopsy subset. Discriminating ability was evaluated by using the area under the receiver operating characteristic curve (AUC). Results In this study, 109 lesions were analyzed, including 39 with cognitively targeted sampling. T1, T2, and ADC from cancer (mean, 1628 msec ± 344, 73 msec ± 27, and 0.773 × 10 -3 mm 2 /sec ± 0.331, respectively) were significantly lower than those from NPZ (mean, 2247 msec ± 450, 169 msec ± 61, and 1.711 × 10 -3 mm 2 /sec ± 0.269) (P < .0001 for each) and together produced the best separation between these groups (AUC = 0.99). ADC and T2 together produced the highest AUC of 0.83 for separating high- or intermediate-grade tumors from low-grade cancers. T1, T2, and ADC in prostatitis (mean, 1707 msec ± 377, 79 msec ± 37, and 0.911 × 10 -3 mm 2 /sec ± 0.239) were significantly lower than those in NPZ (P < .0005 for each). Interreader agreement was excellent, with an intraclass correlation coefficient greater than 0.75 for both T1 and T2 measurements. Conclusion This study describes the development of a rapid MR fingerprinting- and diffusion-based examination for quantitative characterization of prostatic tissue. © RSNA, 2017 Online supplemental material is available for this article.

Specimen Orientation by Marking the Peripheral End: (Potential) Clinical Advantages in Prostate Biopsy

PubMed Central

Galosi, Andrea Benedetto; Muzzonigro, Giovanni; Lacetera, Vito; Mazzucchelli, Roberta

2011-01-01

The aim of this paper is to identify advantages that could be obtained by orientation of the biopsy specimen using the marking technique. We reviewed our experience (4,500 cases) and the published literature. The peripheral (proximal) end of the fresh specimen is marked with ink soon after needle delivering in a few minutes. It is performed easily in association with pre-embedding method. Five potential clinical advantages were identified: (1) tumor localization, (2) atypical lesions localization and planning rebiopsy strategy, (3) planning surgical strategy, (4) selection criteria for focal therapy and active surveillance, and (5) cost reduction. Peripheral end marking is low cost, easy and reproducible. It drives several potential advantages in cancer diagnosis or isolated atypical lesions, in particular, spatial localization within the biopsy (transition versus peripheral zone, anterior versus posterior, subcapsular versus intraparenchima, and extraprostatic extension) should be easy and reliable. We can add a new pathological parameter: pathological orientation or biopsy polarity. PMID:22096654

Dual optimization based prostate zonal segmentation in 3D MR images.

PubMed

Qiu, Wu; Yuan, Jing; Ukwatta, Eranga; Sun, Yue; Rajchl, Martin; Fenster, Aaron

2014-05-01

Efficient and accurate segmentation of the prostate and two of its clinically meaningful sub-regions: the central gland (CG) and peripheral zone (PZ), from 3D MR images, is of great interest in image-guided prostate interventions and diagnosis of prostate cancer. In this work, a novel multi-region segmentation approach is proposed to simultaneously segment the prostate and its two major sub-regions from only a single 3D T2-weighted (T2w) MR image, which makes use of the prior spatial region consistency and incorporates a customized prostate appearance model into the segmentation task. The formulated challenging combinatorial optimization problem is solved by means of convex relaxation, for which a novel spatially continuous max-flow model is introduced as the dual optimization formulation to the studied convex relaxed optimization problem with region consistency constraints. The proposed continuous max-flow model derives an efficient duality-based algorithm that enjoys numerical advantages and can be easily implemented on GPUs. The proposed approach was validated using 18 3D prostate T2w MR images with a body-coil and 25 images with an endo-rectal coil. Experimental results demonstrate that the proposed method is capable of efficiently and accurately extracting both the prostate zones: CG and PZ, and the whole prostate gland from the input 3D prostate MR images, with a mean Dice similarity coefficient (DSC) of 89.3±3.2% for the whole gland (WG), 82.2±3.0% for the CG, and 69.1±6.9% for the PZ in 3D body-coil MR images; 89.2±3.3% for the WG, 83.0±2.4% for the CG, and 70.0±6.5% for the PZ in 3D endo-rectal coil MR images. In addition, the experiments of intra- and inter-observer variability introduced by user initialization indicate a good reproducibility of the proposed approach in terms of volume difference (VD) and coefficient-of-variation (CV) of DSC. Copyright © 2014 Elsevier B.V. All rights reserved.

Can Apparent Diffusion Coefficient Values Assist PI-RADS Version 2 DWI Scoring? A Correlation Study Using the PI-RADSv2 and International Society of Urological Pathology Systems.

PubMed

Gaur, Sonia; Harmon, Stephanie; Rosenblum, Lauren; Greer, Matthew D; Mehralivand, Sherif; Coskun, Mehmet; Merino, Maria J; Wood, Bradford J; Shih, Joanna H; Pinto, Peter A; Choyke, Peter L; Turkbey, Baris

2018-05-07

The purposes of this study were to assess correlation of apparent diffusion coefficient (ADC) and normalized ADC (ratio of tumor to nontumor tissue) with the Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) and updated International Society of Urological Pathology (ISUP) categories and to determine how to optimally use ADC metrics for objective assistance in categorizing lesions within PI-RADSv2 guidelines. In this retrospective study, 100 patients (median age, 62 years; range, 44-75 years; prostate-specific antigen level, 7.18 ng/mL; range, 1.70-84.56 ng/mL) underwent 3-T multiparametric MRI of the prostate with an endorectal coil. Mean ADC was extracted from ROIs based on subsequent prostatectomy specimens. Histopathologic analysis revealed 172 lesions (113 peripheral, 59 transition zone). Two radiologists blinded to histopathologic outcome assigned PI-RADSv2 categories. Kendall tau was used to correlate ADC metrics with PI-RADSv2 and ISUP categories. ROC curves were used to assess the utility of ADC metrics in differentiating each reader's PI-RADSv2 DWI category 4 or 5 assessment in the whole prostate and by zone. ADC metrics negatively correlated with ISUP category in the whole prostate (ADC, τ = -0.21, p = 0.0002; normalized ADC, τ = -0.21, p = 0.0001). Moderate negative correlation was found in expert PI-RADSv2 DWI categories (ADC, τ = -0.34; normalized ADC, τ = -0.31; each p < 0.0001) maintained across zones. In the whole prostate, AUCs of ADC and normalized ADC were 87% and 82% for predicting expert PI-RADSv2 DWI category 4 or 5. A derived optimal cutoff ADC less than 1061 and normalized ADC less than 0.65 achieved positive predictive values of 83% and 84% for correct classification of PI-RADSv2 DWI category 4 or 5 by an expert reader. Consistent relations and predictive values were found by an independent novice reader. ADC and normalized ADC inversely correlate with PI-RADSv2 and ISUP categories and can serve as quantitative metrics to assist with assigning PI-RADSv2 DWI category 4 or 5.

NF-κB and androgen receptor variant expression correlate with human BPH progression.

PubMed

Austin, David C; Strand, Douglas W; Love, Harold L; Franco, Omar E; Jang, Alex; Grabowska, Magdalena M; Miller, Nicole L; Hameed, Omar; Clark, Peter E; Fowke, Jay H; Matusik, Robert J; Jin, Ren J; Hayward, Simon W

2016-04-01

Benign prostatic hyperplasia (BPH) is a common, chronic progressive disease. Inflammation is associated with prostatic enlargement and resistance to 5α-reductase inhibitor (5ARI) therapy. Activation of the nuclear factor-kappa B (NF-κB) pathway is linked to both inflammation and ligand-independent prostate cancer progression. NF-κB activation and androgen receptor variant (AR-V) expression were quantified in transition zone tissue samples from patients with a wide range of AUASS from incidental BPH in patients treated for low grade, localized peripheral zone prostate cancer to advanced disease requiring surgical intervention. To further investigate these pathways, human prostatic stromal and epithelial cell lines were transduced with constitutively active or kinase dead forms of IKK2 to regulate canonical NF-κB activity. The effects on AR full length (AR-FL) and androgen-independent AR-V expression as well as cellular growth and differentiation were assessed. Canonical NF-κB signaling was found to be upregulated in late versus early stage BPH, and to be strongly associated with non-insulin dependent diabetes mellitus. Elevated expression of AR-variant 7 (AR-V7), but not other AR variants, was found in advanced BPH samples. Expression of AR-V7 significantly correlated with the patient AUASS and TRUS volume. Forced activation of canonical NF-κB in human prostatic epithelial and stromal cells resulted in elevated expression of both AR-FL and AR-V7, with concomitant ligand-independent activation of AR reporters. Activation of NF-κB and over expression of AR-V7 in human prostatic epithelial cells maintained cell viability in the face of 5ARI treatment. Activation of NF-κB and AR-V7 in the prostate is associated with increased disease severity. AR-V7 expression is inducible in human prostate cells by forced activation of NF-κB resulting in resistance to 5ARI treatment, suggesting a potential mechanism by which patients may become resistant to 5ARI therapy. © 2015 Wiley Periodicals, Inc.

Performance Comparison of 1.5 T Endorectal Coil MRI with Non-Endorectal Coil 3.0 T MRI in Patients with Prostate Cancer

PubMed Central

Shah, Zarine K.; Elias, Saba N.; Abaza, Ronney; Zynger, Debra L.; DeRenne, Lawrence A.; Knopp, Michael V.; Guo, Beibei; Schurr, Ryan; Heymsfield, Steven B.; Jia, Guang

2015-01-01

Rationale and Objectives To compare prostate morphology, image quality, and diagnostic performance of 1.5 T endorectal coil MRI and 3.0 T non-endorectal coil MRI in patients with prostate cancer. Materials and Methods MR images obtained of 83 patients with prostate cancer using 1.5 T MRI systems with an endorectal coil were compared to images collected from 83 patients with a 3.0 T MRI system. Prostate diameters were measured and image quality was evaluated by one ABR-certified radiologist (Reader 1) and one ABR-certified diagnostic medical physicist (Reader 2). The likelihood of the peripheral zone cancer presence in each sextant and local extent were rated and compared with histopathologic findings. Results Prostate anterior-posterior diameter measured by both readers was significantly shorter with 1.5 T endorectal MRI than with 3.0 T MRI. The overall image quality score difference was significant only for Reader 1. Both readers found that the two MRI systems provided similar diagnostic accuracy in cancer localization, extraprostatic extension, and seminal vesicle involvement. Conclusion Non-endorectal coil 3.0 T MRI provides prostate images that are natural in shape and that have comparable image quality to those obtained at 1.5 T with an endorectal coil, but not superior diagnostic performance. These findings suggest an opportunity exists for improving technical aspects of 3.0 T prostate MRI. PMID:25579637

Optical biopsy of the prostate: can we TRUST (trans-rectal ultrasound-coupled spectral tomography)?

NASA Astrophysics Data System (ADS)

Piao, Daqing; Jiang, Zhen; Bartels, Kenneth E.; Holyoak, G. Reed; Ritchey, Jerry W.; Rock, Kendra; Ownby, Charlotte L.; Bunting, Charles F.; Slobodov, Gennady

2011-03-01

Needle-based core-biopsy to locate prostate cancer relies heavily upon trans-rectal ultrasound (TRUS) imaging guidance. Ultrasonographic findings of classic hypoechoic peripheral zone lesions have a low specificity of ~28%, a low positive predictive value of ~29%, and an overall accuracy of ~43%, in prostate cancer diagnosis. The prevalence of isoechoic or nearly invisible prostate cancers on ultrasonography ranges from 25 to 42%. As a result, TRUS is useful and convenient to direct the needle trajectory following a systematic biopsy sampling template rather than to target only the potentially malignant lesion for focal-biopsy. To address this deficiency in the first-line of prostate cancer imaging, a trans-rectal ultrasound-coupled spectral tomography (TRUST) approach is being developed to non-invasively resolve the likely optical signatures of prostate malignancy. The approach has evolved from using one NIR wavelength to two NIR bands, and recently to three bands of NIR spectrum information. The concept has been evaluated on one normal canine prostate and three dogs with implanted prostate tumor developed as a model. The initial results implementing TRUST on the canine prostate tumor model includes: (1) quantifying substantially increased total hemoglobin concentration over the time-course of imaging in a rapidly growing prostate tumor; (2) confirming hypoxia in a prostatic cystic lesion; and (3) imaging hypoxic changes of a necrotic prostate tumor. Despite these interesting results, intensive technologic development is necessary for translating the approach to benefiting clinical practice, wherein the ultimate utility is not possibly to eliminate needle-biopsy but to perform focal-biopsy that is only necessary to confirm the cancer, as well as to monitor and predict treatment responses.

Computerized whole slide quantification shows increased microvascular density in pT2 prostate cancer as compared to normal prostate tissue.

PubMed

van Niekerk, Cornelis G; van der Laak, Jeroen A W M; Börger, M Elisa; Huisman, Henk-Jan; Witjes, J Alfred; Barentsz, Jelle O; Hulsbergen-van de Kaa, Christina A

2009-01-01

Contrast enhanced imaging enables powerful, non-invasive diagnostics, important for detection and staging of early prostate cancer. The uptake of contrast agent is increased in prostate cancer as compared to normal prostate tissue. To reveal the underlying physiological mechanisms, quantification of tissue components in pathology specimens may yield important information. Aim of this study was to investigate whether microvascularity is increased in prostate confined cancer (pT2). Radical prostatectomy specimens of 26 patients were selected for organ confined peripheral zone tumors which were restricted to one side of the prostate. Microvessels were visualized by immunohistochemistry against CD31. Specimens were scanned using a computer controlled microscope and scanning stage and vessels were recognized automatically. Pseudocolor mappings were produced showing number of vascular profiles (MVD), vascular area (MVA) and perimeter (MVP) in an overview of the entire prostate transection. MVD is a common measure for vascularity, whereas MVA represents the 3D vascular volume and MVP the perfused surface area. Mean, coefficient of variation and 75th percentile of these parameters were calculated automatically in manually indicated areas, consisting of the entire tumor area and the corresponding normal area in the contra lateral side of the prostate. The mappings clearly indicate areas of increased vascularity in prostate transections. In tumor tissue an increase was found compared to normal tissue of 81%, 49%, and 62% for mean MVD, mean MVA and mean MVP, respectively (P < 0.001 for all comparisons). In contrast, the heterogeneity in tumor vasculature was significantly decreased as compared to normal prostate (P < 0.001). Characteristics of microvasculature deviated significantly in pT2 prostate tumor as compared to normal tissue. Copyright 2008 Wiley-Liss, Inc.

Molecular pathology of prostate cancer.

PubMed

Cazares, L H; Drake, R R; Esquela-Kirscher, A; Lance, R S; Semmes, O J; Troyer, D A

2010-01-01

This chapter includes discussion of the molecular pathology of tissue, blood, urine, and expressed prostatic secretions. Because we are unable to reliably image the disease in vivo, a 12 core method that oversamples the peripheral zone is widely used. This generates large numbers of cores that need to be carefully processed and sampled. In spite of the large number of tissue cores, the amount of tumor available for study is often quite limited. This is a particular challenge for research, as new biomarker assays will need to preserve tissue architecture intact for histopathology. Methods of processing and reporting pathology are discussed. With the exception of ductal variants, recognized subtypes of prostate cancer are largely confined to research applications, and most prostate cancers are acinar. Biomarker discovery in urine and expressed prostatic secretions would be useful since these are readily obtained and are proximate fluids. The well-known challenges of biomarker discovery in blood and urine are referenced and discussed. Mediators of carcinogenesis can serve as biomarkers as exemplified by mutations in PTEN and TMPRSS2:ERG fusion. The use of proteomics in biomarker discovery with an emphasis on imaging mass spectroscopy of tissues is discussed. Small RNAs are of great interest, however, their usefulness as biomarkers in clinical decision making remains the subject of ongoing research. The chapter concludes with an overview of blood biomarkers such as circulating nucleic acids and tumor cells and bound/free isoforms of prostate specific antigen (PSA).

Effect of intravascular contrast agent on diffusion and perfusion fraction coefficients in the peripheral zone and prostate cancer.

PubMed

Mazaheri, Yousef; Hötker, Andreas M; Shukla-Dave, Amita; Akin, Oguz; Hricak, Hedvig

2018-09-01

To determine whether water diffusion and the perfusion fraction coefficients in prostate peripheral zone (PZ) and prostate cancer (PCa) are affected by intravenous contrast injection and explore the potential mechanism behind previously reported differences between pre- and post-contrast ADC values. Our institutional review board waived informed consent for this HIPAA-compliant, retrospective study, which included 32 patients (median age, 63 years; range, 47-77 years) with biopsy-proven, untreated PCa who underwent 3-Tesla MRI, including DW-MRI at b-values 0, 400, 700, 1000 s/mm 2 before and after gadolinium injection. For regions of interest (ROIs) in presumed benign PZ and PZ PCa, apparent diffusion coefficient (ADC), perfusion fraction f, and diffusion coefficient D were estimated voxel-wise, and signal-to-noise ratio (SNR) and contrast-to-noise (CNR) were estimated. Pre- and post-contrast measurements were compared by Wilcoxon signed-rank test; P < 0.05 was considered significant. In PZ, f (P = 0.002) was significantly higher on post-contrast imaging than on pre-contrast imaging, but ADC and D values did not change significantly (P = 0.562 and 0.295 respectively). In PCa, all parameters differed significantly between post-contrast and pre-contrast imaging (P < 0.0001 for ADC, P = 0.0084 for D, and P = 0.029 for f). On post-contrast imaging, SNR was not significantly different in PZ (P = 0.260) but was significantly lower in PCa (P < 0.0001); CNR did not change significantly (P = 0.059). After contrast injection, ADC and D declined significantly in PCa only, while f increased significantly in both PCa and PZ. Pre- and post-contrast diffusion parameters cannot be used interchangeably for diagnostic purposes that require quantitative diffusion estimates. Copyright © 2018. Published by Elsevier Inc.

Correlation of Peripheral Vein Tumour Marker Levels, Internal Iliac Vein Tumour Marker Levels and Radical Prostatectomy Specimens in Patients with Prostate Cancer and Borderline High Prostate-Specific Antigen: A Pilot Study.

PubMed

Farrelly, Cormac; Lal, Priti; Trerotola, Scott O; Nadolski, Gregory J; Watts, Micah M; Gorrian, Catherine Mc; Guzzo, Thomas J

2016-05-01

To correlate prostate-specific antigen (PSA), free to total PSA percentage (fPSA%) and prostatic acid phosphatase (PAP) levels from peripheral and pelvic venous samples with prostatectomy specimens in patients with prostate adenocarcinoma and borderline elevation of PSA. In this prospective institutional review board approved study, 7 patients with biopsy proven prostate cancer had a venous sampling procedure prior to prostatectomy (mean 3.2 days, range 1-7). Venous samples were taken from a peripheral vein (PVS), the right internal iliac vein, a deep right internal iliac vein branch, left internal iliac vein and a deep left internal iliac vein branch. Venous sampling results were compared to tumour volume, laterality, stage and grade in prostatectomy surgical specimens. Mean PVS PSA was 4.29, range 2.3-6 ng/ml. PSA and PAP values in PVS did not differ significantly from internal iliac or deep internal iliac vein samples (p > 0.05). fPSA% was significantly higher in internal iliac (p = 0.004) and deep internal iliac (p = 0.003) vein samples compared to PVS. One of 7 patients had unilateral tumour only. This patient, with left-sided tumour, had a fPSA% of 6, 6, 6, 14 and 12 in his peripheral, right internal iliac, deep right internal iliac branch, left internal iliac and deep left internal iliac branch samples respectively. There were no adverse events. fPSA%, unlike total PSA or PAP, is significantly higher in pelvic vein compared to peripheral vein samples when prostate cancer is present. Larger studies including patients with higher PSA values are warranted to further investigate this counterintuitive finding.

High activity Rhenium-186 HEDP with autologous peripheral blood stem cell rescue: a phase I study in progressive hormone refractory prostate cancer metastatic to bone

PubMed Central

O'Sullivan, J M; McCready, V R; Flux, G; Norman, A R; Buffa, F M; Chittenden, S; Guy, M; Pomeroy, K; Cook, G; Gadd, J; Treleaven, J; Al-Deen, A; Horwich, A; Huddart, R A; Dearnaley, D P

2002-01-01

We tested the feasibility and toxicity of high activities Rhenium-186 hydroxyethylidene diphosphonate, with peripheral blood stem cell rescue in patients with progressive hormone refractory prostate cancer metastatic to bone. Twenty-five patients received between 2500 and 5000 MBq of Rhenium-186 hydroxyethylidene diphosphonate followed 14 days later by the return of peripheral blood peripheral blood stem cells. Activity limiting toxicity was defined as grade III haematological toxicity, lasting at least 7 days, or grade IV haematological toxicity of any duration or any serious unexpected toxicity. Activity limiting toxicity occurred in two of six who received activities of 5000 MBq and maximum tolerated activity was defined at this activity level. Prostate specific antigen reductions of 50% or more lasting at least 4 weeks were seen in five of the 25 patients (20%) all of whom received more than 3500 MBq of Rhenium-186 hydroxyethylidene diphosphonate. The actuarial survival at 1 year is 54%. Administered activities of 5000 MBq of Rhenium-186 hydroxyethylidene diphosphonate are feasible using autologous peripheral blood peripheral blood stem cell rescue in patients with progressive hormone refractory prostate cancer metastatic to bone. The main toxicity is thrombocytopaenia, which is short lasting. A statistically significant activity/prostate specific antigen response was seen. We have now commenced a Phase II trial to further evaluate response rates. British Journal of Cancer (2002) 86, 1715–1720. doi:10.1038/sj.bjc.6600348 www.bjcancer.com © 2002 Cancer Research UK PMID:12087455

Multiparametric magnetic resonance imaging findings of prostatic pure leiomyomas.

PubMed

Mussi, Thais Caldara; Costa, Yves Bohrer; Obara, Marcos Takeo; Queiroz, Marcos Roberto Gomes de; Garcia, Rodrigo Gobbo; Longo, José Antonio Domingos Cianciarulo; Lemos, Gustavo Caserta; Baroni, Ronaldo Hueb

2016-01-01

To describe the imaging findings of prostatic tumors nonadenocarcinoma on multiparametric magnetic resonance imaging. A total of 200 patients underwented multiparametric magnetic resonance imaging of the prostate for screening for prostate cancer, from August 2013 to September 2014, followed by biopsy with ultrasound/magnetic resonance imaging fusion. We found three pathologic proved cases of prostatic pure leiomyomas (0.02%) in our series and described the multiparametric magnetic resonance imaging features of these prostatic leiomyomas. The imaging findings had similar features to lesions with moderate or high suspicion for significant cancer (Likert 4 or 5) when localized both in the transitional zone or in the peripheral zone of the gland. Pure prostatic leiomyomas had imaging findings on multiparametric magnetic resonance imaging that mimicked usual adenocarcinomas on this test. Radiologists, urologists and pathologists must be aware of this entity and its imaging features. Descrever os achados de imagem de tumores prostáticos não adenocarcinoma na ressonância magnética multiparamétrica. Realizaram ressonância magnética multiparamétrica da próstata para detecção de câncer de próstata 200 pacientes de agosto de 2013 a setembro de 2014, seguida por biópsia com fusão de imagens de ultrassonografia/ressonância magnética. Encontramos três casos confirmados histologicamente de leiomiomas prostáticos puros (0,02%) em nossa casuística e descrevemos os achados da ressonância magnética multiparamétrica destes casos de leiomiomas. Os achados de imagem foram semelhantes aos de lesões com moderada ou alta suspeição para neoplasia clinicamente significante (Likert 4 ou 5) quando localizados na zona de transição ou zona periférica da próstata. Leiomiomas puros da próstata tiveram achados de imagem na ressonância magnética multiparamétrica que mimetizaram adenocarcinomas. Radiologistas, urologistas e patologistas devem estar cientes destas entidades e seus achados de imagem.

Biparametric MRI of the prostate.

PubMed

Scialpi, Michele; D'Andrea, Alfredo; Martorana, Eugenio; Malaspina, Corrado Maria; Aisa, Maria Cristina; Napoletano, Maria; Orlandi, Emanuele; Rondoni, Valeria; Scialpi, Pietro; Pacchiarini, Diamante; Palladino, Diego; Dragone, Michele; Di Renzo, Giancarlo; Simeone, Annalisa; Bianchi, Giampaolo; Brunese, Luca

2017-12-01

Biparametric Magnetic Resonance Imaging (bpMRI) of the prostate combining both morphologic T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) is emerging as an alternative to multiparametric MRI (mpMRI) to detect, to localize and to guide prostatic targeted biopsy in patients with suspicious prostate cancer (PCa). BpMRI overcomes some limitations of mpMRI such as the costs, the time required to perform the study, the use of gadolinium-based contrast agents and the lack of a guidance for management of score 3 lesions equivocal for significant PCa. In our experience the optimal and similar clinical results of the bpMRI in comparison to mpMRI are essentially related to the DWI that we consider the dominant sequence for detection suspicious PCa both in transition and in peripheral zone. In clinical practice, the adoption of bpMRI standardized scoring system, indicating the likelihood to diagnose a clinically significant PCa and establishing the management of each suspicious category (from 1 to 4), could represent the rationale to simplify and to improve the current interpretation of mpMRI based on Prostate Imaging and Reporting Archiving Data System version 2 (PI-RADS v2). In this review article we report and describe the current knowledge about bpMRI in the detection of suspicious PCa and a simplified PI-RADS based on bpMRI for management of each suspicious PCa categories to facilitate the communication between radiologists and urologists.

Biparametric MRI of the prostate

PubMed Central

Scialpi, Michele; D’Andrea, Alfredo; Martorana, Eugenio; Malaspina, Corrado Maria; Aisa, Maria Cristina; Napoletano, Maria; Orlandi, Emanuele; Rondoni, Valeria; Scialpi, Pietro; Pacchiarini, Diamante; Palladino, Diego; Dragone, Michele; Di Renzo, Giancarlo; Simeone, Annalisa; Bianchi, Giampaolo; Brunese, Luca

2017-01-01

Biparametric Magnetic Resonance Imaging (bpMRI) of the prostate combining both morphologic T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) is emerging as an alternative to multiparametric MRI (mpMRI) to detect, to localize and to guide prostatic targeted biopsy in patients with suspicious prostate cancer (PCa). BpMRI overcomes some limitations of mpMRI such as the costs, the time required to perform the study, the use of gadolinium-based contrast agents and the lack of a guidance for management of score 3 lesions equivocal for significant PCa. In our experience the optimal and similar clinical results of the bpMRI in comparison to mpMRI are essentially related to the DWI that we consider the dominant sequence for detection suspicious PCa both in transition and in peripheral zone. In clinical practice, the adoption of bpMRI standardized scoring system, indicating the likelihood to diagnose a clinically significant PCa and establishing the management of each suspicious category (from 1 to 4), could represent the rationale to simplify and to improve the current interpretation of mpMRI based on Prostate Imaging and Reporting Archiving Data System version 2 (PI-RADS v2). In this review article we report and describe the current knowledge about bpMRI in the detection of suspicious PCa and a simplified PI-RADS based on bpMRI for management of each suspicious PCa categories to facilitate the communication between radiologists and urologists. PMID:29201499

MR elastography to measure the effects of cancer and pathology fixation on prostate biomechanics, and comparison with T 1, T 2 and ADC

NASA Astrophysics Data System (ADS)

McGrath, Deirdre M.; Lee, Jenny; Foltz, Warren D.; Samavati, Navid; van der Kwast, Theo; Jewett, Michael A. S.; Chung, Peter; Ménard, Cynthia; Brock, Kristy K.

2017-02-01

MRI is under evaluation for image-guided intervention for prostate cancer. The sensitivity and specificity of MRI parameters is determined via correlation with the gold-standard of histopathology. Whole-mount histopathology of prostatectomy specimens can be digitally registered to in vivo imaging for correlation. When biomechanical-based deformable registration is employed to account for deformation during histopathology processing, the ex vivo biomechanical properties are required. However, these properties are altered by pathology fixation, and vary with disease. Hence, this study employs magnetic resonance elastography (MRE) to measure ex vivo prostate biomechanical properties before and after fixation. A quasi-static MRE method was employed to measure high resolution maps of Young’s modulus (E) before and after fixation of canine prostate and prostatectomy specimens (n  =  4) from prostate cancer patients who had previously received radiation therapy. For comparison, T 1, T 2 and apparent diffusion coefficient (ADC) were measured in parallel. E (kPa) varied across clinical anatomy and for histopathology-identified tumor: peripheral zone: 99(±22), central gland: 48(±37), tumor: 85(±53), and increased consistently with fixation (factor of 11  ±  5 p  <  0.02). T 2 decreased consistently with fixation, while changes in T 1 and ADC were more complex and inconsistent. The biomechanics of the clinical prostate specimens varied greatly with fixation, and to a lesser extent with disease and anatomy. The data obtained will improve the precision of prostate pathology correlation, leading to more accurate disease detection and targeting.

Clinical utility of apparent diffusion coefficient values obtained using high b-value when diagnosing prostate cancer using 3 tesla MRI: comparison between ultra-high b-value (2000 s/mm²) and standard high b-value (1000 s/mm²).

PubMed

Kitajima, Kazuhiro; Takahashi, Satoru; Ueno, Yoshiko; Yoshikawa, Takeshi; Ohno, Yoshiharu; Obara, Makoto; Miyake, Hideaki; Fujisawa, Masato; Sugimura, Kazuro

2012-07-01

To determine whether the apparent diffusion coefficient (ADC) obtained using b = 2000 s/mm(2) upon 3 Tesla (T) diffusion-weighted MRI is superior to b = 1000 s/mm(2) for discriminating malignant from normal prostate tissue and predicting the aggressiveness of prostate cancer, using histopathological findings of radical prostatectomy as a reference. Eighty prostate cancer patients underwent preoperative 3T MRI including diffusion weighted imaging with b-values of 0, 1000, and 2000 s/mm(2) . ADCs were measured for malignant lesions and normal sites on three sets of ADC maps calculated with monoexponential fitting between b = 0 and 1000, 0 and 2000, and 1000 and 2000, respectively. The relationship between the ADC and Gleason score was evaluated. The areas under the ROC curves for b = 0,1000, b = 0,2000, and b = 1000,2000 were 0.896, 0.937, and 0.857, respectively, in the peripheral zone (PZ) and 0.877, 0.889, and 0.731, respectively, in the transition zone (TZ). The difference between b = 0,1000 and b = 0,2000 was significant in PZ (P = 0.033), but not in TZ (P = 0.84). Weak but significant negative correlations were identified between ADCs and Gleason score in both PZ and TZ cancer at b = 0,1000 and b = 0,2000 (r = -0.323 to -0.341). For 3T MRI, ADCs using b = 0,2000 are more accurate than b = 0,1000 for diagnosing PZ cancer, and as accurate for TZ cancer. Copyright © 2012 Wiley Periodicals, Inc.

Patient-specific pharmacokinetic parameter estimation on dynamic contrast-enhanced MRI of prostate: Preliminary evaluation of a novel AIF-free estimation method.

PubMed

Ginsburg, Shoshana B; Taimen, Pekka; Merisaari, Harri; Vainio, Paula; Boström, Peter J; Aronen, Hannu J; Jambor, Ivan; Madabhushi, Anant

2016-12-01

To develop and evaluate a prostate-based method (PBM) for estimating pharmacokinetic parameters on dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) by leveraging inherent differences in pharmacokinetic characteristics between the peripheral zone (PZ) and transition zone (TZ). This retrospective study, approved by the Institutional Review Board, included 40 patients who underwent a multiparametric 3T MRI examination and subsequent radical prostatectomy. A two-step PBM for estimating pharmacokinetic parameters exploited the inherent differences in pharmacokinetic characteristics associated with the TZ and PZ. First, the reference region model was implemented to estimate ratios of K trans between normal TZ and PZ. Subsequently, the reference region model was leveraged again to estimate values for K trans and v e for every prostate voxel. The parameters of PBM were compared with those estimated using an arterial input function (AIF) derived from the femoral arteries. The ability of the parameters to differentiate prostate cancer (PCa) from benign tissue was evaluated on a voxel and lesion level. Additionally, the effect of temporal downsampling of the DCE MRI data was assessed. Significant differences (P < 0.05) in PBM K trans between PCa lesions and benign tissue were found in 26/27 patients with TZ lesions and in 33/38 patients with PZ lesions; significant differences in AIF-based K trans occurred in 26/27 and 30/38 patients, respectively. The 75 th and 100 th percentiles of K trans and v e estimated using PBM positively correlated with lesion size (P < 0.05). Pharmacokinetic parameters estimated via PBM outperformed AIF-based parameters in PCa detection. J. Magn. Reson. Imaging 2016;44:1405-1414. © 2016 International Society for Magnetic Resonance in Medicine.

Patient-Specific Pharmacokinetic Parameter Estimation on Dynamic Contrast-Enhanced MRI of Prostate: Preliminary Evaluation of a Novel AIF-Free Estimation Method

PubMed Central

Ginsburg, Shoshana B.; Taimen, Pekka; Merisaari, Harri; Vainio, Paula; Boström, Peter J.; Aronen, Hannu J.; Jambor, Ivan; Madabhushi, Anant

2017-01-01

Purpose To develop and evaluate a prostate-based method (PBM) for estimating pharmacokinetic parameters on dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) by leveraging inherent differences in pharmacokinetic characteristics between the peripheral zone (PZ) and transition zone (TZ). Materials and Methods This retrospective study, approved by the Institutional Review Board, included 40 patients who underwent a multiparametric 3T MRI examination and subsequent radical prostatectomy. A two-step PBM for estimating pharmacokinetic parameters exploited the inherent differences in pharmacokinetic characteristics associated with the TZ and PZ. First, the reference region model was implemented to estimate ratios of Ktrans between normal TZ and PZ. Subsequently, the reference region model was leveraged again to estimate values for Ktrans and ve for every prostate voxel. The parameters of PBM were compared with those estimated using an arterial input function (AIF) derived from the femoral arteries. The ability of the parameters to differentiate prostate cancer (PCa) from benign tissue was evaluated on a voxel and lesion level. Additionally, the effect of temporal downsampling of the DCE MRI data was assessed. Results Significant differences (P < 0.05) in PBM Ktrans between PCa lesions and benign tissue were found in 26/27 patients with TZ lesions and in 33/38 patients with PZ lesions; significant differences in AIF-based Ktrans occurred in 26/27 and 30/38 patients, respectively. The 75th and 100th percentiles of Ktrans and ve estimated using PBM positively correlated with lesion size (P < 0.05). Conclusion Pharmacokinetic parameters estimated via PBM outperformed AIF-based parameters in PCa detection. PMID:27285161

Correlation of Peripheral Vein Tumour Marker Levels, Internal Iliac Vein Tumour Marker Levels and Radical Prostatectomy Specimens in Patients with Prostate Cancer and Borderline High Prostate-Specific Antigen: A Pilot Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farrelly, Cormac, E-mail: farrellycormac@gmail.com; Lal, Priti; Trerotola, Scott O.

PurposeTo correlate prostate-specific antigen (PSA), free to total PSA percentage (fPSA%) and prostatic acid phosphatase (PAP) levels from peripheral and pelvic venous samples with prostatectomy specimens in patients with prostate adenocarcinoma and borderline elevation of PSA.Materials and MethodsIn this prospective institutional review board approved study, 7 patients with biopsy proven prostate cancer had a venous sampling procedure prior to prostatectomy (mean 3.2 days, range 1–7). Venous samples were taken from a peripheral vein (PVS), the right internal iliac vein, a deep right internal iliac vein branch, left internal iliac vein and a deep left internal iliac vein branch. Venous sampling resultsmore » were compared to tumour volume, laterality, stage and grade in prostatectomy surgical specimens.ResultsMean PVS PSA was 4.29, range 2.3–6 ng/ml. PSA and PAP values in PVS did not differ significantly from internal iliac or deep internal iliac vein samples (p > 0.05). fPSA% was significantly higher in internal iliac (p = 0.004) and deep internal iliac (p = 0.003) vein samples compared to PVS. One of 7 patients had unilateral tumour only. This patient, with left–sided tumour, had a fPSA% of 6, 6, 6, 14 and 12 in his peripheral, right internal iliac, deep right internal iliac branch, left internal iliac and deep left internal iliac branch samples respectively. There were no adverse events.ConclusionfPSA%, unlike total PSA or PAP, is significantly higher in pelvic vein compared to peripheral vein samples when prostate cancer is present. Larger studies including patients with higher PSA values are warranted to further investigate this counterintuitive finding.« less

Interrelationships among angiogenesis, proliferation, and apoptosis in the tumor microenvironment during N-methyl-N-nitrosourea androgen-induced prostate carcinogenesis in rats.

PubMed

Liao, Zhiming; Boileau, Thomas W-M; Erdman, John W; Clinton, Steven K

2002-10-01

Proliferation, apoptosis and angiogenesis are critical biologic processes altered during carcinogenesis. Surrogate biomarkers of these processes represent potential intermediate endpoints for short-term intervention studies with preventive and therapeutic agents. We examined the interrelationships among these processes during prostate carcinogenesis induced by N-methyl-N-nitrosourea (MNU) in male Wistar-Unilever rats. Immunohistochemical and digital image analysis techniques were used to evaluate the proliferation index, the apoptotic index and microvessel density (MVD) in tissue representing stages of prostate carcinogenesis. The proliferation index in the normal glandular epithelium of the prostate is lower than that observed in hyperplastic foci and atypical hyperplasia (P < 0.01) and is further increased in carcinoma (P < 0.01). Apoptosis in the normal prostate epithelium or hyperplastic lesions is lower than in adenocarcinoma (P < 0.01). In parallel to proliferation index, MVD increases as prostate cancer progresses. As tumors enlarge, we observed a predictable change in biomarker expression within the tumor microenvironment. We examined prostate tumors vertical line 1 cm in diameter and biomarker expression was quantified within the peripheral (outer 1-2 mm), central (perinecrotic) and intermediate (remaining) areas of each tumor. The proliferation index is higher (P < 0.01) in the intermediate area than either in the peripheral area or central area. Similarly, the vascular density in the intermediate area is higher (P < 0.01) than either in the peripheral or central area. The apoptotic index is higher (P < 0.05) in the central perinecrotic core than that in either the intermediate or the peripheral area. In conclusion, we observe that angiogenesis, proliferation and apoptosis are linked biological processes predictably altered temporally and spatially during prostate carcinogenesis in the MNU model. These biomarker changes are similar to those reported in human prostate carcinogenesis and represent potential biomarkers for the assessment of dietary, chemopreventive and therapeutic agents.

Impact of a Structured Reporting Template on Adherence to Prostate Imaging Reporting and Data System Version 2 and on the Diagnostic Performance of Prostate MRI for Clinically Significant Prostate Cancer.

PubMed

Shaish, Hiram; Feltus, Whitney; Steinman, Jonathan; Hecht, Elizabeth; Wenske, Sven; Ahmed, Firas

2018-05-01

The aim of this study was to assess the impact of a structured reporting template on adherence to the Prostate Imaging Reporting and Data System (PI-RADS) version 2 lexicon and on the diagnostic performance of prostate MRI to detect clinically significant prostate cancer (CS-PCa). An imaging database was searched for consecutive patients who underwent prostate MRI followed by MRI-ultrasound fusion biopsy from October 2015 through October 2017. The initial MRI reporting template used included only subheadings. In July 2016, the template was changed to a standardized PI-RADS-compliant structured template incorporating dropdown menus. Lesion, patient characteristics, pathology, and adherence to the PI-RADS lexicon were extracted from MRI reports and patient charts. Diagnostic performance of prostate MRI to detect CS-PCa using combined ultrasound-MRI fusion and systematic biopsy as a reference standard was assessed. Three hundred twenty-four lesions in 202 patients (average age, 67 years; average prostate-specific antigen level, 5.9 ng/mL) were analyzed, including 217 MRI peripheral zone (PZ) lesions, 84 MRI non-PZ lesions, and 23 additional PZ lesions found on systematic biopsy but missed on MRI. Thirty-three percent (106 of 324) were CS-PCa. Adherence to the PI-RADS lexicon improved from 32.9% (50 of 152) to 88.4% (152 of 172) (P < .0001) after introduction of the structured template. The sensitivity of prostate MRI for CS-PCa in the PZ increased from 53% to 70% (P = .011). There was no significant change in specificity (60% versus 55%, P = .458). A structured template with dropdown menus incorporating the PI-RADS lexicon and classification rules improves adherence to PI-RADS and may increase the diagnostic performance of prostate MRI for CS-PCa. Copyright © 2018 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Determination of the Association Between T2-weighted MRI and Gleason Sub-pattern: A Proof of Principle Study.

PubMed

Downes, Michelle R; Gibson, Eli; Sykes, Jenna; Haider, Masoom; van der Kwast, Theo H; Ward, Aaron

2016-11-01

The study aimed to determine the relationship between T2-weighted magnetic resonance imaging (MRI) signal and histologic sub-patterns in prostate cancer areas with different Gleason grades. MR images of prostates (n = 25) were obtained prior to radical prostatectomy. These were processed as whole-mount specimens with tumors and the peripheral zone was annotated digitally by two pathologists. Gleason grade 3 was the most prevalent grade and was subdivided into packed, intermediate, and sparse based on gland-to-stroma ratio. Large cribriform, intraductal carcinoma, and small cribriform glands (grade 4 group) were separately annotated but grouped together for statistical analysis. The log MRI signal intensity for each contoured region (n = 809) was measured, and pairwise comparisons were performed using the open-source software R version 3.0.1. Packed grade 3 sub-pattern has a significantly lower MRI intensity than the grade 4 group (P < 0.00001). Sparse grade 3 has a significantly higher MRI intensity than the packed grade 3 sub-pattern (P < 0.0001). No significant difference in MRI intensity was observed between the Gleason grade 4 group and the sparse sub-pattern grade 3 group (P = 0.54). In multivariable analysis adjusting for peripheral zone, the P values maintained significance (packed grade 3 group vs grade 4 group, P < 0.001; and sparse grade 3 sub-pattern vs packed grade 3 sub-pattern, P < 0.001). This study demonstrated that T2-weighted MRI signal is dependent on histologic sub-patterns within Gleason grades 3 and 4 cancers, which may have implications for directed biopsy sampling and patient management. Copyright © 2016 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Normal Central Zone of the Prostate and Central Zone Involvement by Prostate Cancer: Clinical and MR Imaging Implications

PubMed Central

Akin, Oguz; Franiel, Tobias; Goldman, Debra A.; Udo, Kazuma; Touijer, Karim A.; Reuter, Victor E.; Hricak, Hedvig

2012-01-01

Purpose: To describe the anatomic features of the central zone of the prostate on T2-weighted and diffusion-weighted (DW) magnetic resonance (MR) images and evaluate the diagnostic performance of MR imaging in detection of central zone involvement by prostate cancer. Materials and Methods: The institutional review board waived informed consent and approved this retrospective, HIPAA-compliant study of 211 patients who underwent T2-weighted and DW MR imaging of the prostate before radical prostatectomy. Whole-mount step-section pathologic findings were the reference standard. Two radiologists independently recorded the visibility, MR signal intensity, size, and symmetry of the central zone and scored the likelihood of central zone involvement by cancer on T2-weighted MR images and on T2-weighted MR images plus apparent diffusion coefficient (ADC) maps generated from the DW MR images. Descriptive summary statistics were calculated for central zone imaging features. Sensitivity, specificity, and area under the curve were used to evaluate reader performance in detecting central zone involvement. Results: For readers 1 and 2, the central zone was visible, at least partially, in 177 (84%) and 170 (81%) of 211 patients, respectively. The most common imaging appearance of the central zone was symmetric, homogeneous low signal intensity. Cancers involving the central zone had higher prostate-specific antigen values, Gleason scores, and rates of extracapsular extension and seminal vesicle invasion compared with cancers not involving the central zone (P < .05). Area under the curve, sensitivity, and specificity in detecting central zone involvement were 0.70, 0.30, and 0.96 for reader 1 and 0.65, 0.35, and 0.93 for reader 2, and these values did not differ significantly between T2-weighted imaging and T2-weighted imaging plus ADC maps. Conclusion: The central zone was visualized in most patients. Cancers involving the central zone were associated with more aggressive disease than those without central zone involvement. © RSNA, 2012 PMID:22357889

Chemical species of sulfur in prostate cancer cells studied by XANES spectroscopy

NASA Astrophysics Data System (ADS)

Czapla, Joanna; Kwiatek, Wojciech M.; Lekki, Janusz; Dulińska-Litewka, Joanna; Steininger, Ralph; Göttlicher, Jörg

2013-12-01

The role of sulfur in prostate cancer progression may be significant for understanding the process of carcinogenesis. This work, based on X-ray Absorption Near Edge Structure (XANES) spectroscopy, is focused on determination of sulfur chemical species occurring in prostate cancer cell lines. The experimental material consisted of four commercially available cell lines: three from metastasized prostate cancer (PC3, LNCaP, and DU145) and one, used as a control, from the non-tumourigenic peripheral zone of the prostate (PZ-HPV-7). The experiment was performed at the SUL-X beamline of the synchrotron radiation source ANKA, Karlsruhe (Germany). The K-edge XANES spectra of sulfur were analyzed by deconvolution in order to establish sulfur species that occur in prostate cancer cells and to find out whether there are any differences in their content between various cell lines. Experimental spectra were fitted in two ways: with two Gaussian peaks and one arctangent step function, and additionally by a Linear Combination Fit with spectra of reference compounds in order to obtain quantitative chemical information. All fitting procedures were performed with the Athena code (Ravel and Newville, 2005) and the results of deconvolution were used to determine the fraction of each sulfur form. The results of data analysis showed that cell lines from different metastasis had different ratio of reduced to oxidized sulfur species. The LCF analysis demonstrated that the highest content of GSH, one of the most important sulfur-bearing compounds in cells, was observed in DU145 cells. These findings may confirm the hypothesis of changes in redox balance in case of cancer initiation and progression.

Thermoacoustic imaging of prostate cancer: comparison to histology

NASA Astrophysics Data System (ADS)

Patch, S. K.; Griep, S. K.; Jacobsohn, K.; See, W. A.; Hull, D.

2014-03-01

Ex vivo imaging of fresh prostate specimens was performed to test the hypothesis that the thermoacoustic (TA) contrast mechanism generated with very high frequency electromagnetic (EM) irradiation is sensitive to prostate cancer. Ex vivo imaging was performed immediately after radical prostatectomy, performed as part of normal care. Irradiation pulsewidth was 700 ns and duty cycle was extremely low. Typical specific absorption rate (SAR) throughout the prostate was 70-90 kW/kg during pulsing, but time-averaged SAR was below 2 W/kg. TA pressure pulses generated by rapid heating due to EM energy deposition were detected using single element transducers. 15g/L glycine powder mixed into DI water served as acoustic couplant, which was chilled to prevent autolysis. Spatial encoding was performed by scanning in tomographic "step-and-shoot" mode, with 3 mm translation between slices and 1.8-degree rotation between tomographic views. Histology slides for 3 cases scanned with 2.25 MHz transducers were marked for comparison to TA reconstructions. These three cases showed little, moderate, and severe involvement in the histology levels surrounding the verumontanum. TA signal strength decreased with percent cancerous involvement. When VHF is used for tissue heating, the TA contrast mechanism is driven by ionic content and we observed suppressed TA signal from diseased prostate tissue in the peripheral zone. For the 45 regions of interest analyzed, a reconstruction value of 0.4 mV provides 100% sensitivity but only 29% specificity.

Prostate stem cell antigen (PSCA) mRNA expression in peripheral blood in patients with benign prostatic hyperplasia and/or prostate cancer.

PubMed

Fawzy, Mohamed S; Mohamed, Randa H; Elfayoumi, Abdel-Rahman R

2015-03-01

The aim of this study was to determine whether detection of prostate stem cell antigen (PSCA) expression in BPH might be associated with the subsequent presence of Prostate cancer (PCa) and also to determine whether detection of PSCA expression has potential for prognosis in PCa. This study was comprised of 112 PCa patients, 111 BPH patients and 120 control subjects. We employed reverse-transcriptase polymerase chain reaction (RT-PCR) to detect PSCA mRNA-bearing cells in peripheral blood. PSCA mRNA was detected in the peripheral blood of 71.4% PCa patients and in 13.5% of patients with BPH by RT-PCR. PSCA was positive in 80% of high-grade diseases compared with 20% of low-grade diseases (P = 0.01). Whereas only 38.8% of prostate-confined diseases were PSCA positive, 61.2% of extraprostatic diseases were PSCA positive (P < 0.001). Patients with a lymphovascular invasion of tumor emboli tended to be PSCA positive (P = 0.02). BPH patients with RT-PCR PSCA positive were significantly more likely to develop prostate cancer (OR = 16, 95% CI = 8.1-31.6, P < 0.001). In conclusion, RT-PCR PSCA positivity is significantly associated with the Gleason score, LV tumor emboli and whether or not the tumor was organ confined. In this study, RT-PCR PSCA detection may be a promising tumor marker of diagnostic and metastasis detection for patients with prostate cancer. Also, it may be an important test for predicting BPH patients who are at high risk of subsequent cancer development.

Targeted Prostate Thermal Therapy with Catheter-Based Ultrasound Devices and MR Thermal Monitoring

NASA Astrophysics Data System (ADS)

Diederich, Chris; Ross, Anthony; Kinsey, Adam; Nau, Will H.; Rieke, Viola; Butts Pauly, Kim; Sommer, Graham

2006-05-01

Catheter-based ultrasound devices have significant advantages for thermal therapy procedures, including potential for precise spatial and dynamic control of heating patterns to conform to targeted volumes. Interstitial and transurethral ultrasound applicators, with associated treatment strategies, were developed for thermal ablation of prostate combined with MR thermal monitoring. Four types of multielement transurethral applicators were devised, each with different levels of selectivity and intended therapeutic goals: sectored tubular transducer devices with fixed directional heating patterns; planar and lightly focused curvilinear devices with narrow heating patterns; and multi-sectored tubular devices capable of dynamic angular control without applicator movement. These devices are integrated with a 4 mm delivery catheter, incorporate an inflatable cooling balloon (10 mm OD) for positioning within the prostate and capable of rotation via an MR-compatible motor. Similarly, interstitial devices (2.4 mm OD) have been developed for percutaneous implantation with fixed directional heating patterns (e.g., 180 deg.). In vivo experiments in canine prostate (n=15) under MR temperature imaging were used to evaluate the heating technology and develop treatment strategies. MR thermal imaging in a 0.5 T interventional MRI was used to monitor temperature contours and thermal dose in multiple slices through the target volume. Sectored transurethral devices produce directional coagulation zones, extending 15-20 mm radial distance to the outer prostate capsule. The curvilinear applicator produces distinct 2-3 mm wide lesions, and with sequential rotation and modulated dwell time can precisely conform thermal ablation to selected areas or the entire prostate gland. Multi-sectored transurethral applicators can dynamically control the angular heating profile and target large regions of the gland in short treatment times without applicator manipulation. Interstitial implants with directional devices can be used to effectively ablate the posterior peripheral zone of the gland while protecting the rectum. An implant with multi-sectored interstitial devices can effectively control the angular heating pattern without applicator rotation. The MR derived 52 °C and lethal thermal dose contours (t43=240 min) allowed for real-time control of the applicators and effectively defined the extent of thermal damage. Catheter-based ultrasound devices, combined with MR thermal monitoring, can produce relatively fast and precise thermal ablation of prostate, with potential for treatment of cancer or BPH.

Computer-aided detection of prostate cancer in T2-weighted MRI within the peripheral zone

NASA Astrophysics Data System (ADS)

Rampun, Andrik; Zheng, Ling; Malcolm, Paul; Tiddeman, Bernie; Zwiggelaar, Reyer

2016-07-01

In this paper we propose a prostate cancer computer-aided diagnosis (CAD) system and suggest a set of discriminant texture descriptors extracted from T2-weighted MRI data which can be used as a good basis for a multimodality system. For this purpose, 215 texture descriptors were extracted and eleven different classifiers were employed to achieve the best possible results. The proposed method was tested based on 418 T2-weighted MR images taken from 45 patients and evaluated using 9-fold cross validation with five patients in each fold. The results demonstrated comparable results to existing CAD systems using multimodality MRI. We achieved an area under the receiver operating curve (A z ) values equal to 90.0%+/- 7.6% , 89.5%+/- 8.9% , 87.9%+/- 9.3% and 87.4%+/- 9.2% for Bayesian networks, ADTree, random forest and multilayer perceptron classifiers, respectively, while a meta-voting classifier using average probability as a combination rule achieved 92.7%+/- 7.4% .

Real-time computed tomography dosimetry during ultrasound-guided brachytherapy for prostate cancer.

PubMed

Kaplan, Irving D; Meskell, Paul; Oldenburg, Nicklas E; Saltzman, Brian; Kearney, Gary P; Holupka, Edward J

2006-01-01

Ultrasound-guided implantation of permanent radioactive seeds is a treatment option for localized prostate cancer. Several techniques have been described for the optimal placement of the seeds in the prostate during this procedure. Postimplantation dosimetric calculations are performed after the implant. Areas of underdosing can only be corrected with either an external beam boost or by performing a second implant. We demonstrate the feasibility of performing computed tomography (CT)-based postplanning during the ultrasound-guided implant and subsequently correcting for underdosed areas. Ultrasound-guided brachytherapy is performed on a modified CT table with general anesthesia. The postplanning CT scan is performed after the implant, while the patient is still under anesthesia. Additional seeds are implanted into "cold spots," and the resultant dosimetry confirmed with CT. Intraoperative postplanning was successfully performed. Dose-volume histograms demonstrated adequate dose coverage during the initial implant, but on detailed analysis, for some patients, areas of underdosing were observed either at the apex or the peripheral zone. Additional seeds were implanted to bring these areas to prescription dose. Intraoperative postplanning is feasible during ultrasound-guided brachytherapy for prostate cancer. Although the postimplant dose-volume histograms for all patients, before the implantation of additional seeds, were adequate according to the American Brachytherapy Society criteria, specific critical areas can be underdosed. Additional seeds can then be implanted to optimize the dosimetry and reduce the risk of underdosing areas of cancer.

Blue nevus of the prostate: incidental finding in radical prostatectomy specimen with a pre-operative echographic image of peripheral hypoechogenic nodule.

PubMed

Raspollini, Maria Rosaria; Masieri, Lorenzo; Tosi, Nicola; Santucci, Marco

2011-12-01

Blue nevus is a stromal melanin deposition, which is microscopically characterized by deeply pigmented melanin-filled spindle cells within the fibromuscular stroma. Cases with prominent melanosis such as those with grossly visible pigment are uncommon. Melanocytic lesions of the prostate are incidental findings with no evidence of malignant transformation. There have only been very few reports of a malignant melanoma of primary prostatic origin. We report an incidental finding of a blue nevus of the prostate, in a radical prostatectomy specimen, in a 64-years-old man with a pre-operative ecographic image of peripheral hypoechogenic nodule. The are very few reports of blue nevi associated to prostatic adenocarcinoma, but none has been evidentiated before surgery as a distinct ultrasound lesion interpreted as adenocarcinoma, therefore inducing the clinician to perform biopsies and consequently a radical prostatectomy.

Identifying the Presence of Prostate Cancer in Individuals with PSA Levels <20 ng ml-1 Using Computational Data Extraction Analysis of High Dimensional Peripheral Blood Flow Cytometric Phenotyping Data.

PubMed

Cosma, Georgina; McArdle, Stéphanie E; Reeder, Stephen; Foulds, Gemma A; Hood, Simon; Khan, Masood; Pockley, A Graham

2017-01-01

Determining whether an asymptomatic individual with Prostate-Specific Antigen (PSA) levels below 20 ng ml -1 has prostate cancer in the absence of definitive, biopsy-based evidence continues to present a significant challenge to clinicians who must decide whether such individuals with low PSA values have prostate cancer. Herein, we present an advanced computational data extraction approach which can identify the presence of prostate cancer in men with PSA levels <20 ng ml -1 on the basis of peripheral blood immune cell profiles that have been generated using multi-parameter flow cytometry. Statistical analysis of immune phenotyping datasets relating to the presence and prevalence of key leukocyte populations in the peripheral blood, as generated from individuals undergoing routine tests for prostate cancer (including tissue biopsy) using multi-parametric flow cytometric analysis, was unable to identify significant relationships between leukocyte population profiles and the presence of benign disease (no prostate cancer) or prostate cancer. By contrast, a Genetic Algorithm computational approach identified a subset of five flow cytometry features ( CD 8 + CD 45 RA - CD 27 - CD 28 - ( CD 8 + Effector Memory cells); CD 4 + CD 45 RA - CD 27 - CD 28 - ( CD 4 + Terminally Differentiated Effector Memory Cells re-expressing CD45RA); CD 3 - CD 19 + (B cells); CD 3 + CD 56 + CD 8 + CD 4 + (NKT cells)) from a set of twenty features, which could potentially discriminate between benign disease and prostate cancer. These features were used to construct a prostate cancer prediction model using the k-Nearest-Neighbor classification algorithm. The proposed model, which takes as input the set of flow cytometry features, outperformed the predictive model which takes PSA values as input. Specifically, the flow cytometry-based model achieved Accuracy = 83.33%, AUC = 83.40%, and optimal ROC points of FPR = 16.13%, TPR = 82.93%, whereas the PSA-based model achieved Accuracy = 77.78%, AUC = 76.95%, and optimal ROC points of FPR = 29.03%, TPR = 82.93%. Combining PSA and flow cytometry predictors achieved Accuracy = 79.17%, AUC = 78.17% and optimal ROC points of FPR = 29.03%, TPR = 85.37%. The results demonstrate the value of computational intelligence-based approaches for interrogating immunophenotyping datasets and that combining peripheral blood phenotypic profiling with PSA levels improves diagnostic accuracy compared to using PSA test alone. These studies also demonstrate that the presence of cancer is reflected in changes in the peripheral blood immune phenotype profile which can be identified using computational analysis and interpretation of complex flow cytometry datasets.

Clinical performance of serum [-2]proPSA derivatives, %p2PSA and PHI, in the detection and management of prostate cancer.

PubMed

Huang, Ya-Qiang; Sun, Tong; Zhong, Wei-De; Wu, Chin-Lee

2014-01-01

Prostate-specific antigen (PSA) has been widely used as a serum marker for prostate cancer (PCa) screening or progression monitoring, which dramatically increased rate of early detection while significantly reduced PCa-specific mortality. However, a number of limitations of PSA have been noticed. Low specificity of PSA may lead to overtreatment in men who presenting with a total PSA (tPSA) level of < 10 ng/mL. As a type of free PSA (fPSA), [-2]proPSA is differentially expressed in peripheral zone of prostate gland and found to be elevated in serum of men with PCa. Two p2PSA-based derivatives, prostate health index (PHI) and %p2PSA, which were defined as [(p2PSA/fPSA) × √ tPSA] and [(p2PSA/fPSA) × 100] respectively, have been suggested to be increased in PCa and can better distinguish PCa from benign prostatic diseases than tPSA or fPSA. We performed a systematic review of the available scientific evidences to evaluate the potentials of %p2PSA and PHI in clinical application. Mounting evidences suggested that both %p2PSA and PHI possess higher area under the ROC curve (AUC) and better specificity at a high sensitivity for PCa detection when compare with tPSA and %fPSA. It indicated that measurements of %p2PSA and PHI significantly improved the accuracy of PCa detection and diminished unnecessary biopsies. Furthermore, elevations of %p2PSA and PHI are related to more aggressive diseases. %p2PSA and PHI might be helpful in reducing overtreatment on indolent cases or assessing the progression of PCa in men who undergo active surveillance. Further studies are needed before being applied in routine clinical practice.

T2-weighted prostate MRI at 7 Tesla using a simplified external transmit-receive coil array: correlation with radical prostatectomy findings in two prostate cancer patients.

PubMed

Rosenkrantz, Andrew B; Zhang, Bei; Ben-Eliezer, Noam; Le Nobin, Julien; Melamed, Jonathan; Deng, Fang-Ming; Taneja, Samir S; Wiggins, Graham C

2015-01-01

To report design of a simplified external transmit-receive coil array for 7 Tesla (T) prostate MRI, including demonstration of the array for tumor localization using T2-weighted imaging (T2WI) at 7T before prostatectomy. Following simulations of transmitter designs not requiring parallel transmission or radiofrequency-shimming, a coil array was constructed using loop elements, with anterior and posterior rows comprising one transmit-receive element and three receive-only elements. This coil structure was optimized using a whole-body phantom. In vivo sequence optimization was performed to optimize achieved flip angle (FA) and signal to noise ratio (SNR) in prostate. The system was evaluated in a healthy volunteer at 3T and 7T. The 7T T2WI was performed in two prostate cancer patients before prostatectomy, and localization of dominant tumors was subjectively compared with histopathological findings. Image quality was compared between 3T and 7T in these patients. Simulations of the B1(+) field in prostate using two-loop design showed good magnitude (B1(+) of 0.245 A/m/w(1/2)) and uniformity (nonuniformity [SD/mean] of 10.4%). In the volunteer, 90° FA was achieved in prostate using 225 v 1 ms hard-pulse (indicating good efficiency), FA maps confirmed good uniformity (14.1% nonuniformity), and SNR maps showed SNR gain of 2.1 at 7T versus 3T. In patients, 7T T2WI showed excellent visual correspondence with prostatectomy findings. 7T images demonstrated higher estimated SNR (eSNR) in benign peripheral zone (PZ) and tumor compared with 3T, but lower eSNR in fat and slight decreases in tumor-to-PZ contrast and PZ-homogeneity. We have demonstrated feasibility of a simplified external coil array for high-resolution T2-weighted prostate MRI at 7T. © 2013 Wiley Periodicals, Inc.

Head-To-Head Comparison Between High- and Standard-b-Value DWI for Detecting Prostate Cancer: A Systematic Review and Meta-Analysis.

PubMed

Woo, Sungmin; Suh, Chong Hyun; Kim, Sang Youn; Cho, Jeong Yeon; Kim, Seung Hyup

2018-01-01

The purpose of this study was to perform a head-to-head comparison between high-b-value (> 1000 s/mm 2 ) and standard-b-value (800-1000 s/mm 2 ) DWI regarding diagnostic performance in the detection of prostate cancer. The MEDLINE and EMBASE databases were searched up to April 1, 2017. The analysis included diagnostic accuracy studies in which high- and standard-b-value DWI were used for prostate cancer detection with histopathologic examination as the reference standard. Methodologic quality was assessed with the revised Quality Assessment of Diagnostic Accuracy Studies tool. Sensitivity and specificity of all studies were calculated and were pooled and plotted in a hierarchic summary ROC plot. Meta-regression and multiple-subgroup analyses were performed to compare the diagnostic performances of high- and standard-b-value DWI. Eleven studies (789 patients) were included. High-b-value DWI had greater pooled sensitivity (0.80 [95% CI, 0.70-0.87]) (p = 0.03) and specificity (0.92 [95% CI, 0.87-0.95]) (p = 0.01) than standard-b-value DWI (sensitivity, 0.78 [95% CI, 0.66-0.86]); specificity, 0.87 [95% CI, 0.77-0.93] (p < 0.01). Multiple-subgroup analyses showed that specificity was consistently higher for high- than for standard-b-value DWI (p ≤ 0.05). Sensitivity was significantly higher for high- than for standard-b-value DWI only in the following subgroups: peripheral zone only, transition zone only, multiparametric protocol (DWI and T2-weighted imaging), visual assessment of DW images, and per-lesion analysis (p ≤ 0.04). In a head-to-head comparison, high-b-value DWI had significantly better sensitivity and specificity for detection of prostate cancer than did standard-b-value DWI. Multiple-subgroup analyses showed that specificity was consistently superior for high-b-value DWI.

Antigen specific T-cell responses against tumor antigens are controlled by regulatory T cells in patients with prostate cancer.

PubMed

Hadaschik, Boris; Su, Yun; Huter, Eva; Ge, Yingzi; Hohenfellner, Markus; Beckhove, Philipp

2012-04-01

Immunotherapy is a promising approach in an effort to control castration resistant prostate cancer. We characterized tumor antigen reactive T cells in patients with prostate cancer and analyzed the suppression of antitumor responses by regulatory T cells. Peripheral blood samples were collected from 57 patients with histologically confirmed prostate cancer, 8 patients with benign prostatic hyperplasia and 16 healthy donors. Peripheral blood mononuclear cells were isolated and antigen specific interferon-γ secretion of isolated T cells was analyzed by enzyme-linked immunospot assay. T cells were functionally characterized and T-cell responses before and after regulatory T-cell depletion were compared. As test tumor antigens, a panel of 11 long synthetic peptides derived from a total of 8 tumor antigens was used, including prostate specific antigen and prostatic acid phosphatase. In patients with prostate cancer we noted a 74.5% effector T-cell response rate compared with only 25% in patients with benign prostatic hyperplasia and 31% in healthy donors. In most patients 2 or 3 tumor antigens were recognized. Comparing various disease stages there was a clear increase in the immune response against prostate specific antigens from intermediate to high risk tumors and castration resistant disease. Regulatory T-cell depletion led to a significant boost in effector T-cell responses against prostate specific antigen and prostatic acid phosphatase. Tumor specific effector T cells were detected in most patients with prostate cancer, especially those with castration resistant prostate cancer. Since effector T-cell responses against prostate specific antigens strongly increased after regulatory T-cell depletion, our results indicate that immunotherapy efficacy could be enhanced by decreasing regulatory T cells. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Prostate cancer antigen 3 gene expression in peripheral blood and urine sediments from prostate cancer and benign prostatic hyperplasia patients versus healthy individuals.

PubMed

Moradi Sardareh, Hemen; Goodarzi, Mohammad Taghi; Yadegar-Azari, Reza; Poorolajal, Jalal; Mousavi-Bahar, Seyed Habibollah; Saidijam, Massoud

2014-11-30

To determine the expression of prostate cancer antigen 3 (PCA3) gene in peripheral blood and urine sediments from patients with prostate cancer (PCa) and benign prostatic hyperplasia (BPH) and normal subjects. A total number of 48 patients [24 with biopsy proven prostate cancer (PCa) and 24 with benign prostate hyperplasia (BPH)] were studied. Twenty-four healthy individuals were also recruited as control group. After blood and urine sampling, total RNA was extracted and cDNA was synthesized. Expression of PCA3 gene was assessed by quantitative reverse transcription polymerase chain reaction. Comparison of PCA3 gene expression between control and BPH groups indicated no statistically significant differences in both urine and blood samples. Patients with PCa demonstrated an increased PCA3 gene expression rate compared to control and BPH groups (10.64 and 7.17 folds, respectively). The rate of fold increased PCA3 gene expression in urine was 20.90, 20.90, and 20.35 in patients with PCa, BPH and normal subjects, respectively. Evaluation of PCA3 gene expression can be considered as a reliable marker for detection of PCa. Increased level of this marker in urine sediments is more sensitive than blood for distinguishing between cancerous and non-cancerous groups. 

18F-DCFBC Prostate-Specific Membrane Antigen-Targeted PET/CT Imaging in Localized Prostate Cancer: Correlation With Multiparametric MRI and Histopathology.

PubMed

Turkbey, Baris; Mena, Esther; Lindenberg, Liza; Adler, Stephen; Bednarova, Sandra; Berman, Rose; Ton, Anita T; McKinney, Yolanda; Eclarinal, Philip; Hill, Craig; Afari, George; Bhattacharyya, Sibaprasad; Mease, Ronnie C; Merino, Maria J; Jacobs, Paula M; Wood, Bradford J; Pinto, Peter A; Pomper, Martin G; Choyke, Peter L

2017-10-01

To assess the ability of (N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4-F-fluorobenzyl-L-cysteine) (F-DCFBC), a prostate-specific membrane antigen-targeted PET agent, to detect localized prostate cancer lesions in correlation with multiparametric MRI (mpMRI) and histopathology. This Health Insurance Portability and Accountability Act of 1996-compliant, prospective, institutional review board-approved study included 13 evaluable patients with localized prostate cancer (median age, 62.8 years [range, 51-74 years]; median prostate-specific antigen, 37.5 ng/dL [range, 3.26-216 ng/dL]). Patients underwent mpMRI and F-DCFBC PET/CT within a 3 months' window. Lesions seen on mpMRI were biopsied under transrectal ultrasound/MRI fusion-guided biopsy, or a radical prostatectomy was performed. F-DCFBC PET/CT and mpMRI were evaluated blinded and separately for tumor detection on a lesion basis. For PET image analysis, MRI and F-DCFBC PET images were fused by using software registration; imaging findings were correlated with histology, and uptake of F-DCFBC in tumors was compared with uptake in benign prostatic hyperplasia nodules and normal peripheral zone tissue using the 80% threshold SUVmax. A total of 25 tumor foci (mean size, 1.8 cm; median size, 1.5 cm; range, 0.6-4.7 cm) were histopathologically identified in 13 patients. Sensitivity rates of F-DCFBC PET/CT and mpMRI were 36% and 96%, respectively, for all tumors. For index lesions, the largest tumor with highest Gleason score, sensitivity rates of F-DCFBC PET/CT and mpMRI were 61.5% and 92%, respectively. The average SUVmax for primary prostate cancer was higher (5.8 ± 4.4) than that of benign prostatic hyperplasia nodules (2.1 ± 0.3) or that of normal prostate tissue (2.1 ± 0.4) at 1 hour postinjection (P = 0.0033). The majority of index prostate cancers are detected with F-DCFBC PET/CT, and this may be a prognostic indicator based on uptake and staging. However, for detecting prostate cancer with high sensitivity, it is important to combine prostate-specific membrane antigen PET/CT with mpMRI.

Prostate-specific membrane antigen PET/MRI validation of MR textural analysis for detection of transition zone prostate cancer.

PubMed

Bates, Anthony; Miles, Kenneth

2017-12-01

To validate MR textural analysis (MRTA) for detection of transition zone (TZ) prostate cancer through comparison with co-registered prostate-specific membrane antigen (PSMA) PET-MR. Retrospective analysis was performed for 30 men who underwent simultaneous PSMA PET-MR imaging for staging of prostate cancer. Thirty texture features were derived from each manually contoured T2-weighted, transaxial, prostatic TZ using texture analysis software that applies a spatial band-pass filter and quantifies texture through histogram analysis. Texture features of the TZ were compared to PSMA expression on the corresponding PET images. The Benjamini-Hochberg correction controlled the false discovery rate at <5%. Eighty-eight T2-weighted images in 18 patients demonstrated abnormal PSMA expression within the TZ on PET-MR. 123 images were PSMA negative. Based on the corrected p-value of 0.005, significant differences between PSMA positive and negative slices were found for 16 texture parameters: Standard deviation and mean of positive pixels for all spatial filters (p = <0.0001 for both at all spatial scaling factor (SSF) values) and mean intensity following filtration for SSF 3-6 mm (p = 0.0002-0.0018). Abnormal expression of PSMA within the TZ is associated with altered texture on T2-weighted MR, providing validation of MRTA for the detection of TZ prostate cancer. • Prostate transition zone (TZ) MR texture analysis may assist in prostate cancer detection. • Abnormal transition zone PSMA expression correlates with altered texture on T2-weighted MR. • TZ with abnormal PSMA expression demonstrates significantly reduced MI, SD and MPP.

Evaluation of different mathematical models and different b-value ranges of diffusion-weighted imaging in peripheral zone prostate cancer detection using b-value up to 4500 s/mm2

PubMed Central

Feng, Zhaoyan; Min, Xiangde; Margolis, Daniel J. A.; Duan, Caohui; Chen, Yuping; Sah, Vivek Kumar; Chaudhary, Nabin; Li, Basen; Ke, Zan; Zhang, Peipei; Wang, Liang

2017-01-01

Objectives To evaluate the diagnostic performance of different mathematical models and different b-value ranges of diffusion-weighted imaging (DWI) in peripheral zone prostate cancer (PZ PCa) detection. Methods Fifty-six patients with histologically proven PZ PCa who underwent DWI-magnetic resonance imaging (MRI) using 21 b-values (0–4500 s/mm2) were included. The mean signal intensities of the regions of interest (ROIs) placed in benign PZs and cancerous tissues on DWI images were fitted using mono-exponential, bi-exponential, stretched-exponential, and kurtosis models. The b-values were divided into four ranges: 0–1000, 0–2000, 0–3200, and 0–4500 s/mm2, grouped as A, B, C, and D, respectively. ADC, , D*, f, DDC, α, Dapp, and Kapp were estimated for each group. The adjusted coefficient of determination (R2) was calculated to measure goodness-of-fit. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic performance of the parameters. Results All parameters except D* showed significant differences between cancerous tissues and benign PZs in each group. The area under the curve values (AUCs) of ADC were comparable in groups C and D (p = 0.980) and were significantly higher than those in groups A and B (p< 0.05 for all). The AUCs of ADC and Kapp in groups B and C were similar (p = 0.07 and p = 0.954), and were significantly higher than the other parameters (p< 0.001 for all). The AUCs of ADC in group D was slightly higher than Kapp (p = 0.002), and both were significantly higher than the other parameters (p< 0.001 for all). Conclusions ADC derived from conventional mono-exponential high b-value (3200 s/mm2) models is an optimal parameter for PZ PCa detection. PMID:28199367

Prostate-specific antigen density values among patients with symptomatic prostatic enlargement in Nigeria.

PubMed

Udeh, Emeka I; Nnabugwu, Ikenna I; Ozoemena, Francis O; Ugwumba, Fred O; Aderibigbe, Adesina S O; Ohayi, Samuel R; Echetabu, Kevin N

2016-06-29

This study aims to estimate the prostate-specific antigen density (PSAD) cutoff level for detecting prostate cancer (CAP) in Nigerian men with "grey zone PSA" (4-10 ng/ml) and normal digital rectal examination findings. We addressed this research question: Is the international PSAD cutoff of 0.15 ideal for detecting CAP in our symptomatic patients with "grey zone PSA?" To estimate the prostate-specific antigen density (PSAD) cutoff level for detecting CAP in Nigerian men with "grey zone PSA" (4-10 ng/ml) and normal digital rectal examination findings. Prospective. A tertiary medical center in Enugu, Nigeria. Two hundred and fifty-four men with either benign prostatic hyperplasia (BPH) or CAP were recruited. Patients with PSA above 4 ng/ml or abnormal digital rectal examination or hypoechoic lesion in the prostate were biopsied. PSAD and histology report of BPH or CAP. Ninety-seven patients had CAP while 157 had benign prostatic hyperplasia (BPH). Seventy-two patients had their serum PSA value within the range of 4.0 and 10 ng/ml. PSAD cutoff level to detect CAP was 0.04 (sensitivity 95.88 %; specificity 28.7 %). The PSAD cutoff level generated for Nigerian men in this study is 0.04 which is relatively different from international consensus. This PSAD cutoff level has a positive correlation with histology and could detect patients with CAP who have "grey zone PSA."

Computer-aided diagnosis of prostate cancer in the peripheral zone using multiparametric MRI

NASA Astrophysics Data System (ADS)

Niaf, Emilie; Rouvière, Olivier; Mège-Lechevallier, Florence; Bratan, Flavie; Lartizien, Carole

2012-06-01

This study evaluated a computer-assisted diagnosis (CADx) system for determining a likelihood measure of prostate cancer presence in the peripheral zone (PZ) based on multiparametric magnetic resonance (MR) imaging, including T2-weighted, diffusion-weighted and dynamic contrast-enhanced MRI at 1.5 T. Based on a feature set derived from grey-level images, including first-order statistics, Haralick features, gradient features, semi-quantitative and quantitative (pharmacokinetic modelling) dynamic parameters, four kinds of classifiers were trained and compared : nonlinear support vector machine (SVM), linear discriminant analysis, k-nearest neighbours and naïve Bayes classifiers. A set of feature selection methods based on t-test, mutual information and minimum-redundancy-maximum-relevancy criteria were also compared. The aim was to discriminate between the relevant features as well as to create an efficient classifier using these features. The diagnostic performances of these different CADx schemes were evaluated based on a receiver operating characteristic (ROC) curve analysis. The evaluation database consisted of 30 sets of multiparametric MR images acquired from radical prostatectomy patients. Using histologic sections as the gold standard, both cancer and nonmalignant (but suspicious) tissues were annotated in consensus on all MR images by two radiologists, a histopathologist and a researcher. Benign tissue regions of interest (ROIs) were also delineated in the remaining prostate PZ. This resulted in a series of 42 cancer ROIs, 49 benign but suspicious ROIs and 124 nonsuspicious benign ROIs. From the outputs of all evaluated feature selection methods on the test bench, a restrictive set of about 15 highly informative features coming from all MR sequences was discriminated, thus confirming the validity of the multiparametric approach. Quantitative evaluation of the diagnostic performance yielded a maximal area under the ROC curve (AUC) of 0.89 (0.81-0.94) for the discrimination of the malignant versus nonmalignant tissues and 0.82 (0.73-0.90) for the discrimination of the malignant versus suspicious tissues when combining the t-test feature selection approach with a SVM classifier. A preliminary comparison showed that the optimal CADx scheme mimicked, in terms of AUC, the human experts in differentiating malignant from suspicious tissues, thus demonstrating its potential for assisting cancer identification in the PZ.

Chronological changes of radiofrequency ablation zone in rabbit liver: an in vivo correlation between gross pathology and histopathology

PubMed Central

Song, Kyoung D; Rhim, Hyunchul; Kang, Tae Wook; Cha, Dong Ik; Yang, Jehoon

2017-01-01

Objective: To examine the gross pathology and histopathology of ablation zones created from radiofrequency (RF) ablation and to correlate their chronological changes. Methods: A total of 48 in vivo ablation zones (16 rabbit livers) were obtained immediately after and also 30 min, 1 h and 2 h after RF ablation and were subjected to haematoxylin and eosin (H&E) staining, nicotinamide adenine dinucleotide (NADH) diaphorase staining, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining. Chronological changes in gross pathology and histopathology were evaluated and correlated with each other. Results: Peripheral red zones on gross pathology correlated with peripheral zones on H&E staining, lightly stained peripheral zones on NADH staining and peripheral positive zones on TUNEL staining. Central white zones on gross pathology correlated with combined central and border zones on H&E staining, central negative zones on NADH staining and combined central-positive and middle-negative zones on TUNEL staining. Boundary visibility between central white and peripheral red zones on gross pathology was significantly higher at 1 and 2 h than immediately after RF ablation. As time increased after RF ablation, visibility of the border zone on H&E staining and the grade of positively stained hepatocytes in the peripheral zone on TUNEL staining increased. Conclusion: Chronological changes in gross pathology of RF ablation zones correlated well with histopathology. The boundary between the central white and peripheral red zones tended to become clear at 1 h after RF ablation. Advances in knowledge: (1) RF ablation zones show chronological changes on gross pathology and histopathology. (2) Gross pathology and histopathology correlate well with each other. PMID:28139942

Aging up-regulates ARA55 in stromal cells, inducing androgen-mediated prostate cancer cell proliferation and migration.

PubMed

Zou, Qingsong; Cui, Di; Liang, Shengjie; Xia, Shujie; Jing, Yifeng; Han, Bangmin

2016-06-01

Stromal cells in the peripheral zone (PZ) of the prostate from older males (PZ-old) could significantly promote Prostate cancer (PCa) growth compared with stromal cells from young males (PZ-young). But the mechanism is still unknown. In the co-culture system with PZ-old cells, Pc3/Du145 cells showed advanced proliferation and migration after Dihydrotestosterone (DHT) incubation, but DHT didn't show the similar effect in PZ-young co-culture system. Also, higher androgen/AR signal pathway activity and AR-related cytokines secretion (FGF-2, KGF, IGF-1) were found in PZ-old cells. As AR exprssison was equivalent in PZ-old and PZ-young cells, we focused on Androgen receptor associated protein-55(ARA55), a stromal-specific androgen receptor (AR) coactivator. ARA55 expression was higher in PZ-old cells compared with PZ-young cells in vitro. After knocking down ARA55 expression in PZ-old cells, the PCa growth- promoting effect from the PZ-old cells was diminished, which may be explained by the decreased the progressive cytokines secretion (FGF-2, KGF, IGF-1) from PZ-old stromal cells. In vivo, the consistent results were also found: PZ-old cells promoted prostate cancer cells growth, but this effect receded when knocking down ARA55 expression in PZ-old cells. From our study, we found PZ stromal cells presented age-related effects in proliferation and migration of prostate cancer cells in the androgen/AR dependent manner. As aging increased, more ARA55 were expressed in PZ stromal cells, leading to more sensitive androgen/androgen receptor (AR) signal pathway, then constituting a more feasible environment to cancer cells.

Phase I/II trial of single-fraction high-dose-rate brachytherapy-boosted hypofractionated intensity-modulated radiation therapy for localized adenocarcinoma of the prostate.

PubMed

Myers, Michael A; Hagan, Michael P; Todor, Dorin; Gilbert, Lynn; Mukhopadhyay, Nitai; Randolf, Jessica; Heimiller, Jeffrey; Anscher, Mitchell S

2012-01-01

A Phase I/II protocol was conducted to examine the toxicity and efficacy of the combination of intensity-modulated radiation therapy (IMRT) with a single-fraction high-dose-rate (HDR) brachytherapy implant. From 2001 through 2006, 26 consecutive patients were treated on the trial. The primary objective was to demonstrate a high rate of completion without experiencing a treatment-limiting toxicity. Eligibility was limited to patients with T stage ≤2b, prostate-specific antigen (PSA) ≤20, and Gleason score ≤7. Treatment began with a single HDR fraction of 6Gy to the entire prostate and 9Gy to the peripheral zone, followed by IMRT optimized to deliver in 28 fractions with a normalized total dose of 70Gy. Patients received 50.4Gy to the pelvic lymph node. The prostate dose (IMRT and HDR) resulted in an average biologic equivalent dose >128Gy (α/β=3). Patients whose pretreatment PSA was ≥10ng/mL, Gleason score 7, or stage ≥T2b received short-term androgen ablation. Median followup was 53 months (9-68 months). There were no biochemical failures by either the American Society of Therapeutic Radiology and Oncology or the Phoenix definitions. The median nadir PSA was 0.32ng/mL. All the 26 patients completed the treatment as prescribed. The rate of Grade 3 late genitourinary toxicity was 3.8% consisting of a urethral stricture. There was no other Grade 3 or 4 genitourinary or gastrointestinal toxicities. Single-fraction HDR-boosted IMRT is a safe effective method of dose escalation for localized prostate cancer. Copyright © 2012 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Poster — Thur Eve — 77: Implanted Brachythearpy Seed Movement due to Transrectal Ultrasound Probe-Induced Prostate Deformation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, D; Usmani, N; Sloboda, R

The study investigated the movement of implanted brachytherapy seeds upon transrectal US probe removal, providing insight into the underlying prostate deformation and an estimate of the impact on prostate dosimetry. Implanted seed distributions, one obtained with the prostate under probe compression and another with the probe removed, were reconstructed using C-arm fluoroscopy imaging. The prostate, delineated on ultrasound images, was registered to the fluoroscopy images using seeds and needle tracks identified on ultrasound. A deformation tensor and shearing model was developed to correlate probe-induced seed movement with position. Changes in prostate TG-43 dosimetry were calculated. The model was used tomore » infer the underlying prostate deformation and to estimate the location of the prostate surface in the absence of probe compression. Seed movement patterns upon probe removal reflected elastic decompression, lateral shearing, and rectal bending. Elastic decompression was characterized by expansion in the anterior-posterior direction and contraction in the superior-inferior and lateral directions. Lateral shearing resulted in large anterior movement for extra-prostatic seeds in the lateral peripheral region. Whole prostate D90 increased up to 8 Gy, mainly due to the small but systematic seed movement associated with elastic decompression. For selected patients, lateral shearing movement increased prostate D90 by 4 Gy, due to increased dose coverage in the anterior-lateral region at the expense of the posterior-lateral region. The effect of shearing movement on whole prostate D90 was small compared to elastic decompression due to the subset of peripheral seeds involved, but is expected to have greater consequences for local dose coverage.« less

[Anatomo-functional changes in the prostate and seminal vesicles with aging].

PubMed

Mantovani, F; Mastromarino, G; Colombo, F; Canclini, L; Fenice, O

1993-10-01

The anatomo-functional modifications of the prostate and the seminal pathways during the genital apparatus aging, (prostatic hyperplasia and hypotrophy of the seminal pathways and testis), are caused by hormonal modifications (inconstant increase of the gonadotropins LH-FSH, decrease of the peripheric utilization of testosterone, alterations of the adrenal secretion), by anatomical involutions (degenerations of the glandular, stromal and vascular components).

Enhancing the Efficacy of Prostate Cancer Immunotherapy by Manipulating T-Cell Receptor Signaling in Order to Alter Peripheral Regulatory T-Cell Activity

DTIC Science & Technology

2009-07-01

27] Ross S, Spencer SD, Holcomb I, Tan C, Hongo J, Devaux B, et al. Prostate stem cell antigen as therapy target: tissue expression and in vivo...Holcomb I, Tan C, Hongo J, Devaux B, et al. Prostate stem cell antigen as therapy target: tissue expression and in vivo efficacy of an immunoconjugate

Color Doppler quantitative measures to predict outcome of biopsies in prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Strigari, Lidia; Marsella, Annelisa; Canitano, Stefano

2008-11-15

Purpose: The aim was to correlate the color Doppler flow activity pre- and postradiotherapy, using transrectal color Doppler ultrasonography (CDUS) and the 2 year positive biopsy rate after radiotherapy in patients with prostate cancer. Methods and materials: Analysis was carried out in 69 out of 160 patients who had undergone treatment with 3D-conformal radiotherapy (3D-CRT) to prostate and seminal vesicles. Patients were randomized to receive 80 Gy in 40 fractions in 8 weeks (arm A) and 62 Gy in 20 fractions in 5 weeks, 4 fractions per week (arm B). Color Doppler flow activity (CDFA) was evaluated calculating the vascularizationmore » index (VI), defined as the ratio between the colored and total pixels in the whole and peripheral prostate, delineated by a radiation oncologist on CDUS images, using EcoVasc a home-made software. The difference between the 2 year post- and pre-3D-CRT maximum VI (VI{sub max}), named {Delta}VI{sub max}, was calculated in the whole and peripheral prostate for each patient. Then, {Delta}VI{sub max} and the detected 2 year biopsy outcome were analyzed using the receiver operating characteristics (ROC) technique. Results: The VI{sub max} increased or decreased in patients with positive or negative biopsies, respectively, compared to the value before RT in both arms. The area under the ROC curve for {Delta}VI{sub max} in the whole and peripheral prostate is equal to 0.790 and 0.884, respectively. Conclusion: The {Delta}VI{sub max} index, comparing CDFA at 2 years compared to that before RT, allows the 2 year postradiotherapy positive biopsy rate to be predicted.« less

Quantitative diffusion MRI using reduced field-of-view and multi-shot acquisition techniques: Validation in phantoms and prostate imaging.

PubMed

Zhang, Yuxin; Holmes, James; Rabanillo, Iñaki; Guidon, Arnaud; Wells, Shane; Hernando, Diego

2018-09-01

To evaluate the reproducibility of quantitative diffusion measurements obtained with reduced Field of View (rFOV) and Multi-shot EPI (msEPI) acquisitions, using single-shot EPI (ssEPI) as a reference. Diffusion phantom experiments, and prostate diffusion-weighted imaging in healthy volunteers and patients with known or suspected prostate cancer were performed across the three different sequences. Quantitative diffusion measurements of apparent diffusion coefficient, and diffusion kurtosis parameters (healthy volunteers), were obtained and compared across diffusion sequences (rFOV, msEPI, and ssEPI). Other possible confounding factors like b-value combinations and acquisition parameters were also investigated. Both msEPI and rFOV have shown reproducible quantitative diffusion measurements relative to ssEPI; no significant difference in ADC was observed across pulse sequences in the standard diffusion phantom (p = 0.156), healthy volunteers (p ≥ 0.12) or patients (p ≥ 0.26). The ADC values within the non-cancerous central gland and peripheral zone of patients were 1.29 ± 0.17 × 10 -3  mm 2 /s and 1.74 ± 0.23 × 10 -3  mm 2 /s respectively. However, differences in quantitative diffusion parameters were observed across different number of averages for rFOV, and across b-value groups and diffusion models for all the three sequences. Both rFOV and msEPI have the potential to provide high image quality with reproducible quantitative diffusion measurements in prostate diffusion MRI. Copyright © 2018 Elsevier Inc. All rights reserved.

A Younger Man With Localized Prostate Cancer Asks, "Which Type of Radiation Is Right for Me?"

PubMed

Bekelman, Justin E

2018-06-20

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 61-year-old man presents with stage II prostate cancer after a period of active surveillance. Work-up reveals T1cN0M0 carcinoma, a prostate-specific antigen (PSA) level of 4.8 ng/mL, and Grade Group II (highest Gleason 3+4) in three cores of 12 taken, at the right mid-gland and right apex. The patient has been on active surveillance for the past 16 months. He was originally diagnosed after biopsy for an elevated PSA with stage I prostate cancer, T1cN0M0; PSA, 4.5 ng/mL; Grade Group 1 (Gleason 3+3) in one core of 12 taken, also at the right mid-gland. A multiparametric magnetic resonance imaging scan showed a heterogeneous peripheral zone without a dominant lesion and a calculated prostate volume of 28 mL. His medical history includes hypercholesterolemia, for which he takes atorvastatin. He is otherwise healthy and has no other significant medical or surgical history. His father had prostate cancer in his 70s and died of other causes at 89 years of age. The patient reports 2- to 3-hour urinary frequency and 0 to 1 nocturia, and has no difficulty obtaining or maintaining an erection. After meeting with his urologist, he sees a radiation oncologist.

Comparison of stretched-Exponential and monoexponential model diffusion-Weighted imaging in prostate cancer and normal tissues.

PubMed

Liu, Xiaohang; Zhou, Liangping; Peng, Weijun; Wang, He; Zhang, Yong

2015-10-01

To compare stretched-exponential and monoexponential model diffusion-weighted imaging (DWI) in prostate cancer and normal tissues. Twenty-seven patients with prostate cancer underwent DWI exam using b-values of 0, 500, 1000, and 2000 s/mm(2) . The distributed diffusion coefficients (DDC) and α values of prostate cancer and normal tissues were obtained with stretched-exponential model and apparent diffusion coefficient (ADC) values using monoexponential model. The ADC, DDC (both in 10(-3) mm(2)/s), and α values (range, 0-1) were compared among different prostate tissues. The ADC and DDC were also compared and correlated in each tissue, and the standardized differences between DDC and ADC were compared among different tissues. Data were obtained for 31 cancers, 36 normal peripheral zone (PZ) and 26 normal central gland (CG) tissues. The ADC (0.71 ± 0.12), DDC (0.60 ± 0.18), and α value (0.64 ± 0.05) of tumor were all significantly lower than those of the normal PZ (1.41 ± 0.22, 1.47 ± 0.20, and 0.85 ± 0.09) and CG (1.25 ± 0.14, 1.32 ± 0.13, and 0.82 ± 0.06) (all P < 0.05). ADC was significantly higher than DDC in cancer, but lower than DDC in the PZ and CG (all P < 0.05). The ADC and DDC were strongly correlated (R(2)  = 0.99, 0.98, 0.99, respectively, all P < 0.05) in all the tissue, and standardized difference between ADC and DDC of cancer was slight but significantly higher than that in normal tissue. The stretched-exponential model DWI provides more parameters for distinguishing prostate cancer and normal tissue and reveals slight differences between DDC and ADC values. © 2015 Wiley Periodicals, Inc.

Elastic registration of prostate MR images based on state estimation of dynamical systems

NASA Astrophysics Data System (ADS)

Marami, Bahram; Ghoul, Suha; Sirouspour, Shahin; Capson, David W.; Davidson, Sean R. H.; Trachtenberg, John; Fenster, Aaron

2014-03-01

Magnetic resonance imaging (MRI) is being increasingly used for image-guided biopsy and focal therapy of prostate cancer. A combined rigid and deformable registration technique is proposed to register pre-treatment diagnostic 3T magnetic resonance (MR) images, with the identified target tumor(s), to the intra-treatment 1.5T MR images. The pre-treatment 3T images are acquired with patients in strictly supine position using an endorectal coil, while 1.5T images are obtained intra-operatively just before insertion of the ablation needle with patients in the lithotomy position. An intensity-based registration routine rigidly aligns two images in which the transformation parameters is initialized using three pairs of manually selected approximate corresponding points. The rigid registration is followed by a deformable registration algorithm employing a generic dynamic linear elastic deformation model discretized by the finite element method (FEM). The model is used in a classical state estimation framework to estimate the deformation of the prostate based on a similarity metric between pre- and intra-treatment images. Registration results using 10 sets of prostate MR images showed that the proposed method can significantly improve registration accuracy in terms of target registration error (TRE) for all prostate substructures. The root mean square (RMS) TRE of 46 manually identified fiducial points was found to be 2.40+/-1.20 mm, 2.51+/-1.20 mm, and 2.28+/-1.22mm for the whole gland (WG), central gland (CG), and peripheral zone (PZ), respectively after deformable registration. These values are improved from 3.15+/-1.60 mm, 3.09+/-1.50 mm, and 3.20+/-1.73mm in the WG, CG and PZ, respectively resulted from rigid registration. Registration results are also evaluated based on the Dice similarity coefficient (DSC), mean absolute surface distances (MAD) and maximum absolute surface distances (MAXD) of the WG and CG in the prostate images.

Prostatic adenocarcinoma with glomeruloid features.

PubMed

Pacelli, A; Lopez-Beltran, A; Egan, A J; Bostwick, D G

1998-05-01

A wide variety of architectural patterns of adenocarcinoma may be seen in the prostate. We have recently encountered a hitherto-undescribed pattern of growth characterized by intraluminal ball-like clusters of cancer cells reminiscent of renal glomeruli, which we refer to as prostatic adenocarcinoma with glomeruloid features. To define the architectural features, frequency, and distribution of prostatic adenocarcinoma with glomeruloid features, we reviewed 202 totally embedded radical prostatectomy specimens obtained between October 1992 and April 1994 from the files of the Mayo Clinic. This series was supplemented by 100 consecutive needle biopsies with prostatic cancer from January to February 1996. Prostatic adenocarcinoma with glomeruloid features was characterized by round to oval epithelial tufts growing within malignant acini, often supported by a fibrovascular core. The epithelial cells were sometimes arranged in semicircular concentric rows separated by clefted spaces. In the radical prostatectomy specimens, nine cases (4.5%) had glomeruloid features. The glomeruloid pattern constituted 5% to 20% of each cancer (mean, 8.33%) and was usually located at the apex or in the peripheral zone of the prostate. Seven cases were associated with a high Gleason score (7 or 8), one with a score of 6, and one with a score of 5. All cases were associated with high-grade prostatic intraepithelial neoplasia and extensive perineural invasion. Pathological stages included T2c (three cases), T3b (four cases), and T3c (two cases); one of the T3b cases had lymph node metastases (N1). Three (3%) of 100 consecutive routine needle biopsy specimens with cancer showed glomeruloid features, and this pattern constituted 5% to 10% of each cancer (mean, 6.7%). The Gleason score was 6 for two cases and 8 for one case. Two cases were associated with high-grade prostatic intraepithelial neoplasia, and one case had perineural invasion. Glomeruloid features were not observed in any benign or premalignant lesions, including hyperplasia and intraepithelial neoplasia. Glomeruloid structures in the prostate represent an uncommon but distinctive pattern of growth that is specific for malignancy. Glomeruloid features may be a useful diagnostic clue for malignancy, particularly in some challenging needle biopsy specimens. This pattern of growth is usually seen in high-grade adenocarcinoma, often with extraprostatic extension. Further investigations are required to determine its independent predictive value and correlation with stage and Gleason score.

MR elastography of prostate cancer: quantitative comparison with histopathology and repeatability of methods.

PubMed

Sahebjavaher, Ramin S; Nir, Guy; Honarvar, Mohammad; Gagnon, Louis O; Ischia, Joseph; Jones, Edward C; Chang, Silvia D; Fazli, Ladan; Goldenberg, S Larry; Rohling, Robert; Kozlowski, Piotr; Sinkus, Ralph; Salcudean, Septimiu E

2015-01-01

The purpose of this work was to assess trans-perineal prostate magnetic resonance elastography (MRE) for (1) repeatability in phantoms/volunteers and (2) diagnostic power as correlated with histopathology in prostate cancer patients. The three-dimensional (3D) displacement field was obtained using a fractionally encoded gradient echo sequence using a custom-made transducer. The repeatability of the method was assessed based on three repeat studies and by changing the driving frequency by 3% in studies on a phantom and six healthy volunteers. Subsequently, 11 patients were examined with MRE prior to radical prostatectomy. The areas under the receiver operating characteristic curves were calculated using a windowed voxel-to-voxel approach by comparing the 2D registered slides, masked with the Gleason score. For the repeatability study, the average intraclass correlation coefficient for elasticity images was 99% for repeat phantom studies, 98% for ±6 Hz phantom studies, 95% for volunteer repeat studies with 2 min acquisition time, 82% for ±2 Hz volunteer studies with 2 min acquisition time and 73% for repeat volunteer studies with 8 min acquisition time. For the patient study, the average elasticity was 8.2 ± 1.7 kPa in the prostate capsule, 7.5 ± 1.9 kPa in the peripheral zone (PZ), 9.7 ± 3.0 kPa in the central gland (CG) and 9.0 ± 3.4 kPa in the transition zone. In the patient study, cancerous tissue with Gleason score at least 3 + 3 was significantly (p < 0.05) different from normal tissue in 10 out of 11 cases with tumors in the PZ, and 6 out of 9 cases with tumors in the CG. However, the overall case-averaged area under the curve was 0.72 in the PZ and 0.67 in the CG. Cancerous tissue was not always stiffer than normal tissue. The inversion algorithm was sensitive to (i) vibration amplitude and displacement nodes and (ii) misalignment of the 3D wave field due to subject movement. Copyright © 2014 John Wiley & Sons, Ltd.

MiR-139-5p is Increased in the Peripheral Blood of Patients with Prostate Cancer.

PubMed

Pang, Cheng; Liu, Ming; Fang, Weiwei; Guo, Jun; Zhang, Zhipeng; Wu, Pengjie; Zhang, Yaoguang; Wang, Jianye

2016-01-01

Emerging evidence suggested that microRNAs (miRNAs) play a causal role in cancer tumorigenesis. Aberrant expression of miRNA (miR)-139-5p has been observed in various types of cancers. The present study evaluated the relationship between miR-139-5p expression levels and prostate cancer (PCa), to assess the feasibility of using peripheral blood miR-139-5p as a potential non-invasive biomarker for PCa. Total RNA was extracted from peripheral whole blood samples from 45 PCa patients, 45 benign prostatic hyperplasia (BPH) patients and 50 healthy controls (HC). The expression of miR-139-5p was assessed by reverse transcription quantitative polymerase chain reaction. MiR-139-5p in peripheral blood was significantly higher in PCa patients than in patients with BPH and HC individuals (P<0.001). Higher miR-139-5p expression was observed to be associated with certain clinicopathological parameters, including PSA>20ng/ml (P<0.05), pathological tumor stage 3/4 (P<0.05) and Gleason score >7 (P<0.01). A receiver operating characteristic (ROC) curve analysis revealed that miR-139-5p distinguished PCa patients from BPH patients [area under the curve (AUC), 0.936; 95% CI, 0.878-0.993; P<0.001]. Peripheral blood miR-139-5p may be utilized as a potential novel non-invasive biomarker for PCa screening. © 2016 The Author(s) Published by S. Karger AG, Basel.

Interstitial laser prostatectomy

NASA Astrophysics Data System (ADS)

Johnson, Douglas E.; Cromeens, Douglas M.; Price, Roger E.

1994-05-01

Interstitial laser coagulation of the canine prostate using the Sharplan interstitial thermal therapy fiber (Model 25432) was performed in 9 adult dogs and the subsequent gross and histopathologic changes occurring in the prostate were studied at intervals ranging from 1 hour to 5 weeks. A large well-demarcated area of acute coagulative necrosis developed around each fiber tract which in turn was surrounded by a prominent narrow zone of marked tissue disruption and an outer zone of hemorrhage. Liquefaction developed within the coagulative areas within 24 hours and by 4 days, each prostatic lobe contained an irregular cavity which became lined by normal-appearing transitional epithelium and that by 5 weeks, communicated with the prostatic urethra. These changes, similar to those reported following transurethral visual laser ablation of the prostate, suggest that interstitial laser thermal therapy may provide an alternative means for treating selected patients suffering from prostatic enlargement.

WE-A-17A-11: Implanted Brachytherapy Seed Movement Due to Transrectal Ultrasound Probe-Induced Prostate Deformation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, D; Usmani, N; Sloboda, R

Purpose: To characterize the movement of implanted brachytherapy seeds due to transrectal ultrasound probe-induced prostate deformation and to estimate the effects on prostate dosimetry. Methods: Implanted probe-in and probe-removed seed distributions were reconstructed for 10 patients using C-arm fluoroscopy imaging. The prostate was delineated on ultrasound and registered to the fluoroscopy seeds using a visible subset of seeds and residual needle tracks. A linear tensor and shearing model correlated the seed movement with position. The seed movement model was used to infer the underlying prostate deformation and to simulate the prostate contour without probe compression. Changes in prostate and surrogatemore » urethra dosimetry were calculated. Results: Seed movement patterns reflecting elastic decompression, lateral shearing, and rectal bending were observed. Elastic decompression was characterized by anterior-posterior expansion and superior-inferior and lateral contractions. For lateral shearing, anterior movement up to 6 mm was observed for extraprostatic seeds in the lateral peripheral region. The average intra-prostatic seed movement was 1.3 mm, and the residual after linear modeling was 0.6 mm. Prostate D90 increased by 4 Gy on average (8 Gy max) and was correlated with elastic decompression. For selected patients, lateral shearing resulted in differential change in D90 of 7 Gy between anterior and posterior quadrants, and increase in whole prostate D90 of 4 Gy. Urethra D10 increased by 4 Gy. Conclusion: Seed movement upon probe removal was characterized. The proposed model captured the linear correlation between seed movement and position. Whole prostate dose coverage increased slightly, due to the small but systematic seed movement associated with elastic decompression. Lateral shearing movement increased dose coverage in the anterior-lateral region, at the expense of the posterior-lateral region. The effect on whole prostate D90 was smaller due to the subset of peripheral seeds involved, but lateral shearing movement can have greater consequences for local dose coverage.« less

Targeting Peripheral-Derived Regulatory T Cells as a Means of Enhancing Immune Responses Directed against Prostate Cancer

DTIC Science & Technology

2017-08-01

Award Number: W81XWH-15-1-0328 TITLE: Targeting Peripheral-Derived Regulatory T Cells as a Means of Enhancing Immune Responses Directed against...1 August 2016 - 31 July 2017 4. TITLE AND SUBTITLE Targeting Peripheral-Derived Regulatory T Cells as a Means of Enhancing Immune Responses Directed...discovered that a subset of regulatory T cells (Tregs), termed peripheral-derived Tregs (pTregs), impair immune responses directed against tumor

Phenotypic analysis of prostate-infiltrating lymphocytes reveals TH17 and Treg skewing.

PubMed

Sfanos, Karen Sandell; Bruno, Tullia C; Maris, Charles H; Xu, Lauren; Thoburn, Christopher J; DeMarzo, Angelo M; Meeker, Alan K; Isaacs, William B; Drake, Charles G

2008-06-01

Pathologic examination of prostate glands removed from patients with prostate cancer commonly reveals infiltrating CD4+ and CD8+ T cells. Little is known about the phenotype of these cells, despite accumulating evidence suggesting a potential role for chronic inflammation in the etiology of prostate cancer. We developed a technique that samples the majority of the peripheral prostate through serial needle aspirates. CD4+ prostate-infiltrating lymphocytes (PIL) were isolated using magnetic beads and analyzed for subset skewing using both flow cytometry and quantitative reverse transcription-PCR. The transcriptional profile of fluorescence-activated cell sorted prostate-infiltrating regulatory T cells (CD4+, CD25+, GITR+) was compared with naïve, peripheral blood T cells using microarray analysis. CD4+ PIL showed a paucity of TH2 (interleukin-4-secreting) cells, a surprising finding given the generally accepted association of these cells with chronic, smoldering inflammation. Instead, CD4+ PIL seemed to be skewed towards a regulatory Treg phenotype (FoxP3+) as well as towards the TH17 phenotype (interleukin-17+). We also found that a preponderance of TH17-mediated inflammation was associated with a lower pathologic Gleason score. These protein level data were reflected at the message level, as analyzed by quantitative reverse transcription-PCR. Microarray analysis of pooled prostate-infiltrating T(reg) revealed expected Treg-associated transcripts (FoxP3, CTLA-4, GITR, LAG-3) as well as a number of unique cell surface markers that may serve as additional Treg markers. Taken together, these data suggest that TH17 and/or Treg CD4+ T cells (rather than TH2 T cells) may be involved in the development or progression of prostate cancer.

Phenotypic Analysis of Prostate-Infiltrating Lymphocytes Reveals TH17 and Treg Skewing

PubMed Central

Sfanos, Karen Sandell; Bruno, Tullia C.; Maris, Charles H.; Xu, Lauren; Thoburn, Christopher J.; DeMarzo, Angelo M.; Meeker, Alan K.; Isaacs, William B.; Drake, Charles G.

2011-01-01

Purpose Pathologic examination of prostate glands removed from patients with prostate cancer commonly reveals infiltrating CD4+ and CD8+ T cells. Little is known about the phenotype of these cells, despite accumulating evidence suggesting a potential role for chronic inflammation in the etiology of prostate cancer. Experimental Design We developed a technique that samples the majority of the peripheral prostate through serial needle aspirates. CD4+ prostate-infiltrating lymphocytes (PIL) were isolated using magnetic beads and analyzed for subset skewing using both flow cytometry and quantitative reverse transcription-PCR. The transcriptional profile of fluorescence-activated cell sorted prostate-infiltrating regulatory T cells (CD4+, CD25+, GITR+) was compared with naïve, peripheral blood T cells using microarray analysis. Results CD4+ PIL showed a paucity of TH2 (interleukin-4– secreting) cells, a surprising finding given the generally accepted association of these cells with chronic, smoldering inflammation. Instead, CD4+ PIL seemed to be skewed towards a regulatory Treg phenotype (FoxP3+) as well as towards the TH17 phenotype (interleukin-17+). We also found that a preponderance of TH17-mediated inflammation was associated with a lower pathologic Gleason score. These protein level data were reflected at the message level, as analyzed by quantitative reverse transcription-PCR. Microarray analysis of pooled prostate-infiltrating Treg revealed expected Treg-associated transcripts (FoxP3, CTLA-4, GITR, LAG-3) as well as a number of unique cell surface markers that may serve as additional Treg markers. Conclusion Taken together, these data suggest that TH17 and/or Treg CD4+ T cells (rather than TH2 T cells) may be involved in the development or progression of prostate cancer. PMID:18519750

[Application evaluation of multi-parametric MRI in the diagnosis and differential diagnosis of early prostate cancer and prostatitis].

PubMed

Li, P; Huang, Y; Li, Y; Cai, L; Ji, G H; Zheng, Y; Chen, Z Q

2016-10-11

Objective: To evaluate the value of multi-parametric MRI (Mp-MRI) in the diagnosis and differential diagnosis of early prostate cancer(PCa) in the peripheral zone(PZ) and low T 2 WI signal intensity of prostatitis. Methods: A total of 40 patients with PZ early PCa and 37 with prostatitis of hypointense T 2 WI signal in PZ were retrospectively analyzed, which were collected from the General Hospital of Ningxia Medical University from Janurary 2009 to June 2015, who underwent T 2 WI, DWI, and DCE-MRI examination and all patients were confirmed by pathology. All the data was transferred to GE Advanced Workstation AW4.3, the indexes divided into cancerous and prostatitis regions were calculated by Functool2 of signal intensity-time(SI-T) curve and ADC value, to calcuate the time to minimum(T max ), the whole enhancment degree (SI max ). ROC cure was used to determine the cutoff value for PCa detection with the ADC value. Result: On T 2 WI, 57.5% of PCa (23/40) showed focal nodular homogeneous low signal intensity, 70.3% of prostatitis(26/37) showed diffuse inhomogeneous low signal intensity. DCE-MRI, the distribution of curve types for malignant tumors was type Ⅰ 2.5%(1/40), typeⅡ32.5%(13/40) and type Ⅲ 65.0% (26/40). While the numbers for prostatitis was type Ⅰ 16.2%(6/37) , type Ⅱ 56.8% (21/37) and type Ⅲ 27.0% (10/37)respectively.The patterns of curve types in malignant lesions were different from benign lesions significantly(χ 2 =12.32, P <0.01). The mean values of T max , SI max in cancerous and prostatitis regions were (17.96±2.91)s, 1.76%±0.23% and (21.19±3.59)s, 1.53%±0.18%, respectively ( t =5.37, 6.10; P <0.01). On DWI, The mean ADC values in cancerous and prostatitis regions were (0.95±0.13)×10 -3 mm 2 /s and (1.12±0.13)×10 -3 mm 2 /s, respectively ( t =7.10, P <0.01). According to the ROC analysis, when the cutoff value was 1.01×10 -3 mm 2 /s, the early PCa of diagnostic sensitivity, specificity and accuracy was 79.1%, 72.7% and 76.1% respectively. Conclusion: Combined with morphology and signal characteristics of conventional T 2 WI, DWI and DCE-MRI improve the power of MR imaging in discriminating prostatitis from early PCa.

Vascular pericyte density and angiogenesis associated with adenocarcinoma of the prostate.

PubMed

Killingsworth, Murray C; Wu, Xiaojuan

2011-01-01

Angiogenesis facilitates metabolism, proliferation and metastasis of adenocarcinoma cells in the prostate, as without the development of new vasculature tumor growth cannot be sustained. However, angiogenesis is variable with the well-known phenomenon of vascular 'hotspots' seen associated with viable tumor cell mass. With the recent recognition of pericytes as molecular regulators of angiogenesis, we have examined the interaction of these cells in actively growing new vessels. Pericyte interactions with developing new vessels were examined using transmission electron microscopy. Pericyte distribution was mapped from α-SMA+ immunostained histological sections and quantified using image analysis. Data was obtained from peripheral and more central regions of 27 cases with Gleason scores of 4-9. Pericyte numbers were increased around developing new vessel sprouts at sites of luminal maturation. Numbers were reduced around the actively growing tips of migrating endothelial cells and functional new vessels. Tumor regions internal to a 500-μm peripheral band showed higher microvessel pericyte density than the peripheral region. Pericytes were found to be key cellular components of developing new vessels in adenocarcinoma of the prostate. Their numbers increased at sites of luminal maturation with these cells displaying an activated phenotype different to quiescent pericytes. Increased pericyte density was found internal to the peripheral region, suggesting more mature vessels lie more centrally. Copyright © 2011 S. Karger AG, Basel.

"Textural analysis of multiparametric MRI detects transition zone prostate cancer".

PubMed

Sidhu, Harbir S; Benigno, Salvatore; Ganeshan, Balaji; Dikaios, Nikos; Johnston, Edward W; Allen, Clare; Kirkham, Alex; Groves, Ashley M; Ahmed, Hashim U; Emberton, Mark; Taylor, Stuart A; Halligan, Steve; Punwani, Shonit

2017-06-01

To evaluate multiparametric-MRI (mpMRI) derived histogram textural-analysis parameters for detection of transition zone (TZ) prostatic tumour. Sixty-seven consecutive men with suspected prostate cancer underwent 1.5T mpMRI prior to template-mapping-biopsy (TPM). Twenty-six men had 'significant' TZ tumour. Two radiologists in consensus matched TPM to the single axial slice best depicting tumour, or largest TZ diameter for those with benign histology, to define single-slice whole TZ-regions-of-interest (ROIs). Textural-parameter differences between single-slice whole TZ-ROI containing significant tumour versus benign/insignificant tumour were analysed using Mann Whitney U test. Diagnostic accuracy was assessed by receiver operating characteristic area under curve (ROC-AUC) analysis cross-validated with leave-one-out (LOO) analysis. ADC kurtosis was significantly lower (p < 0.001) in TZ containing significant tumour with ROC-AUC 0.80 (LOO-AUC 0.78); the difference became non-significant following exclusion of significant tumour from single-slice whole TZ-ROI (p = 0.23). T1-entropy was significantly lower (p = 0.004) in TZ containing significant tumour with ROC-AUC 0.70 (LOO-AUC 0.66) and was unaffected by excluding significant tumour from TZ-ROI (p = 0.004). Combining these parameters yielded ROC-AUC 0.86 (LOO-AUC 0.83). Textural features of the whole prostate TZ can discriminate significant prostatic cancer through reduced kurtosis of the ADC-histogram where significant tumour is included in TZ-ROI and reduced T1 entropy independent of tumour inclusion. • MR textural features of prostate transition zone may discriminate significant prostatic cancer. • Transition zone (TZ) containing significant tumour demonstrates a less peaked ADC histogram. • TZ containing significant tumour reveals higher post-contrast T1-weighted homogeneity. • The utility of MR texture analysis in prostate cancer merits further investigation.

The 3DBiopsy Prostate Biopsy System: Preclinical Investigation of a Needle, Actuator, and Specimen Collection Device Allowing Sampling of Individualized Prostate Lengths Between 20 and 60 mm.

PubMed

Stone, Nelson N; Mouraviev, Vladimir; Schechter, David; Lucia, M Scott; Smith, Elizabeth E; Arangua, Paul; Hoenemeyer, John; Rosa, Jim; Bawa, Rajan; Crawford, E David

2017-09-01

To increase the likelihood of detecting anterior cancers within the prostate and provide a specimen that spans the length of the gland. Newly designed 17- and 15-gauge (G) biopsy needles, a variable actuator, and an integrated pathology system intended for the longer cores were developed and tested for this purpose. Testing was performed comparing 2 common cannula tip grinds, a Vet-point (sharp tip) and a Menghini-point (atraumatic tip), and were tested against 18-G Bard Monopty in porcine kidney. A variable actuator was developed to fire the needle 20-60 mm and tested in cadaver prostates. The aggregate firings for 3 different shot lengths comparing the Vet- with the Menghini-tip cannulas demonstrated 91% vs 85.2% fill (length of specimen/length of core bed, P = .007). A 15-G trocar needle with the Vet-tip cannula also had the best performance, with an aggregate standard deviation of 6.4% across 3 firing ranges and a minimum to maximum specimen length of 81%-105% of potential fill. Cadaver testing with the Vet-tip needles in the actuator for the transrectal (17-G) and transperineal (15-G) biopsies demonstrated mean fills of 93.3% and 76.5%, respectively. The new transrectal ultrasound needle obtained a 2-fold increase in specimen length over the standard Bard device (P <.001). Longer and consistent cores were obtained using the new biopsy needles. Combined with an adjustable actuator, the physician can obtain specimens that include peripheral and anterior zone tissue in 1 core. Determination of cancer location on the longer specimens could enhance focal therapy planning. Copyright © 2017 Elsevier Inc. All rights reserved.

Ultrahigh b-values MRI in normal human prostate: Initial research on reproducibility and age-related differences.

PubMed

Shi, Changzheng; Zhang, Dong; Xiao, Zeyu; Wang, Li; Ma, Rong; Chen, Hanwei; Luo, Liangping

2017-09-01

To investigate the reproducibility of diffusion-weighted imaging (DWI) with ultrahigh b-values, and analyze the age-related differences in normal prostates. In all, 67 healthy participants were divided into three age groups (group A, 15-30 years; group B, 31-50 years; group C, ≥51 years), and underwent DWI scanning twice with 15 b-factors from 0 to 3000 at 3.0T. Triexponential fits were applied to calculate the molecular diffusion coefficient (D), the pseudo-diffusion coefficient (D*), the ultrahigh apparent diffusion coefficient (ADC uh ), and perfusion fraction (f). The interobserver and short-term interscan reproducibility were evaluated, and the change in these parameters with age were assessed. The D, ADC uh , and f values presented good to excellent reproducibility. With increasing age, a trend of increasing D values was observed, with significant difference in both peripheral zone (PZ, P = 0.01) and central gland (CG, P = 0.01) of normal prostate tissue. The f value increased in the CG beginning at 50 years of age while the ADC uh value decreased in the PZ after 50 years of age; all of them showed significant differences between groups A and C and groups B and C (P = 0.01/0.01). The D, ADC uh , and f values have good to excellent reproducibility in the normal prostate, and these values change with age. The ultrahigh b-values magnetic resonance imaging (MRI) can provide additional information (ADC uh ), which is different from the IVIM (intravoxel incoherent motion)-derived parameters. 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:801-812. © 2017 International Society for Magnetic Resonance in Medicine.

Prostatic abscess: diagnosis and management in the modern antibiotic era.

PubMed

Tiwari, Punit; Pal, Dilip K; Tripathi, Astha; Kumar, Suresh; Vijay, Mukesh; Goel, Amit; Sharma, Pramod; Dutta, Arindam; Kundu, Anup K

2011-03-01

This retrospective study was aimed at analyzing the clinical findings and therapeutic strategies in 24 patients who were admitted with prostatic abscess, during the period from 1999 to 2008. The diagnosis of prostatic abscesses was made clinically by digital rectal palpation based on the presence of positive fluctuation with tenderness. All cases were confirmed by trans-rectal ultrasound (TRUS), and only positive cases were included in this study. The diagnostic work-up included analysis of midstream urine and abscess fluid culture for pathogens. Therapeutic options included endoscopic trans-urethral incision or trans-perineal aspiration under ultrasound guidance, or conservative therapy. Of the 24 patients studied, 45.83% of the cases had a pre-disposing factor, and diabetes mellitus (37.50%) was the most common. Digital rectal palpation revealed fluctuation in 70.83% of the cases. Trans-abdominal ultrasonography missed the condition in 29.16% of the cases. On TRUS, all the study patients showed hypo-echoic zones, while nine others showed internal septations. In most of the cases, the lesion was peripheral. A causative pathogen could be identified in 70.83% of the cases. Surgical drainage of the abscess by trans-urethral deroofing was performed in 17 cases (including one with failed aspiration), trans-perineal aspiration under TRUS guidance was performed in three cases and conservative therapy was followed in five cases. Our data confirms the importance of predisposing factors in the pathogenesis of prostatic abscess. In most of the cases, the clue to diagnosis is obtained by digital rectal palpation. TRUS gives the definite diagnosis and also helps in follow-up of patients. Trans-urethral deroofing is the ideal therapy where the abscess cavity is more than 1 cm, although in some selected cases, TRUS-guided aspiration or conservative therapy does have a role in treatment.

The eternal enigma in prostatic biopsy access route.

PubMed

Fabiani, Andrea; Principi, Emanuele; Filosa, Alessandra; Servi, Lucilla

2017-10-03

Dear Editors,We read with interest the article by Di Franco and co-workers (1). The introduction of prostatic magnetic resonance and the relative fusion-biopsy have not yet allowed the expected improvements in prostate biopsy. To our knowledge, there are no works that demonstrate the superiority of fusion techniques on the remaining ultrasound guided prostate biopsies that are still the widely used in the diagnosis of prostate cancer. Furthemore, these technologies are expensive exams and they are not yet available in all centers, especially in those minors. We work at a "minor" center and we always keep in mind that the goal of  prostatic biopsy is the diagnosis and the staging of prostatic neoplasms.. However, it remains uncertain which of the two techniques, transperineal (TP) or transrectal (TR), is superior in terms of detection rate during first biopsy setting. Several studies have compared the prostate cancer detection rate but TR and TP access route in prostatic gland sampling seems to be equivalent in terms of efficiency and complications, as reported by Shen PF et al. (2), despite several methodological limitations recognized in their work. The results reported by Di Franco CA et al. represent the real life experience of most urologists that perform the PB based on their own training experience and available technical devices. From an historical viewpoint, the TP route has been the first one to be used to reach the prostate, both for diagnostic and therapeutic purposes. To date, because it seems to be more invasive and difficult, the TP route is less used worldwide than the TR one (2). Theoretically, the TP approach should detect more prostate cancer than the TR way  because the cores of the TP approach are directed longitudinally to the peripheral zone and the anterior part of the prostate (4). The results reported by Di Franco et al. seems to confirm these considerations. However, our real life experience differ from the conclusions reached in their work. We recently conducted a prospective evaluation of 352 patients who underwent their first prostate biopsy because of a suspicious of prostate cancer (elevated prostate specific antigen (PSA) and/or abnormal digital rectal examination and/or abnormal findings on transrectal prostatic ultrasound). Patients was randomized as following. A total of 187 patients (Group A) underwent a prostatic biopsy with a transperineal approach in a lithotomic position,  using a biplane probe (8818 BK Medical, Denmark) and a fan technique with a single perineal median access (5). The remnants 165 patients (Group B) underwent a transrectal ultrasound guided prostate biopsy in a left lateral position, using a end fire probe configuration (8818 BK Medical, Denmark) and a sagittal technique. The bioptic prostatic mapping was performed with a 12-core scheme sec. Gore (3) by a single experienced operator and the histopathologic evaluation was performed by a single dedicated uro-pathologist. Statistical evaluations were made with a T Student test  (p<0,005). Group A and Group B was similar in term of mean patient age (67,9 years and 67 years respectively), mean total PSA (12,1 ng/ml vs 12 ng/ml) and digital rectal examination positivity (22% vs 29%).  The global cancer detection rate was 33,69% (63/187) in the transperineal prostate biopsy group and 48,48 % (80/165) in the transrectal approach (p=0.0047).  No significant statistical differences were found in the complications rates between the two groups. Statistical evaluation of site of tumor localization reveal only a trend to statistical significance in apical site tumors diagnosed with the TR approach versus the TP technique. The TR approach had a better diagnostic accuracy than TP technique in case of PSA<4 ng/ml, intermediate prostate volume (30 and 50 ml), normal digital rectal examination without any relationship with the patient age. In our experience, two aspect may explain the difference between the two group in term of global detection rate. First, we usually perform transrectal biopsy with a sagittal technique that simulates the transperineal way of needle incidence with the prostatic gland. The lateral and anterior gland portions may be sampled more accurately. Second, our transperineal approach consists in a single perineal median access that can make more difficult the gland sampling between the two lobes. However, there was no significant difference in core positivity rate at the peripheral zone, medium gland, apex or any other site such as reported in many randomized clinical trials (2). Unlike the conclusions reported by Di Franco et al., in our experience we found a statistically significant difference between the TR and TP approach, at the first biopsy setting, in term of global cancer detection rate. No differences were found in terms of complications. Moreover, our data suggest that TR approach had a better diagnostic accuracy than TP technique in case of  PSA<4 ng/ml, prostate volume 30-50 ml, normal digital rectal examination without any relationship with the patient age. The further step of the statistical evaluation of our data will be the definition of the possibility that the TR biopsy determine a better staging of prostate cancer than TP approach as first procedure.    REFERENCES 1)      Di Franco CA, Jallous H., Porru D. et al. A retrospective comparison between transrectal and transperineal prostate biopsy in the detection of prostate cancer Arch Ital Urol Androl 2017; 89(1), 55-92)      Shen FP, Zhu YC, Wei WR et al. The results of transperineal vs transrectal prostate biopsy: a systematic review and meta-analysis. Asian Journal of Androl 2012; 14: 310-15.3)      Gore JL., Shariat SF, Miles BJ., et al. Optimal combinations of systematic sextant and laterally directed biopsies for the detection of prostate cancer. J Urol 2001; 165: 1554-59.  4)      Abdollah F., Novara G., Briganti A. et al. Trasrectal versus transperineal saturation re biopsy of the prostate: is there a difference in cancer detection rate? Urology 2011; 77:9215)      Novella G, Ficarra V, Galfano A, et al. Pain assessment after original transperineal prostate biopsy using a coaxial needle. Urology. 2003; 62 : 689-92.

Transrectal real-time tissue elastography targeted biopsy coupled with peak strain index improves the detection of clinically important prostate cancer.

PubMed

Ma, Qi; Yang, Dong-Rong; Xue, Bo-Xin; Wang, Cheng; Chen, Han-Bin; Dong, Yun; Wang, Cai-Shan; Shan, Yu-Xi

2017-07-01

The focus of the present study was to evaluate transrectal real-time tissue elastography (RTE)-targeted two-core biopsy coupled with peak strain index for the detection of prostate cancer (PCa) and to compare this method with 10-core systematic biopsy. A total of 141 patients were enrolled for evaluation. The diagnostic value of peak strain index was assessed using a receiver operating characteristic curve. The cancer detection rates of the two approaches and corresponding positive cores and Gleason score were compared. The cancer detection rate per core in the RTE-targeted biopsy (44%) was higher compared with that in systematic biopsy (30%). The peak strain index value of PCa was higher compared with that of the benign lesion. PCa was detected with the highest sensitivity (87.5%) and specificity (85.5%) using the threshold value of a peak strain index of ≥5.97 with an area under the curve value of 0.95. When the Gleason score was ≥7, RTE-targeted biopsy coupled with peak strain index detected 95.6% of PCa cases, but 84.4% were detected using systematic biopsy. Peak strain index as a quantitative parameter may improve the differentiation of PCa from benign lesions in the prostate peripheral zone. Transrectal RTE-targeted biopsy coupled with peak strain index may enhance the detection of clinically significant PCa, particularly when combined with systematic biopsy.

Reduced Field-of-View Diffusion-Weighted Magnetic Resonance Imaging of the Prostate at 3 Tesla: Comparison With Standard Echo-Planar Imaging Technique for Image Quality and Tumor Assessment.

PubMed

Tamada, Tsutomu; Ream, Justin M; Doshi, Ankur M; Taneja, Samir S; Rosenkrantz, Andrew B

The purpose of this study was to compare image quality and tumor assessment at prostate magnetic resonance imaging (MRI) between reduced field-of-view diffusion-weighted imaging (rFOV-DWI) and standard DWI (st-DWI). A total of 49 patients undergoing prostate MRI and MRI/ultrasound fusion-targeted biopsy were included. Examinations included st-DWI (field of view [FOV], 200 × 200 mm) and rFOV-DWI (FOV, 140 × 64 mm) using a 2-dimensional (2D) spatially-selective radiofrequency pulse and parallel transmission. Two readers performed qualitative assessments; a third reader performed quantitative evaluation. Overall image quality, anatomic distortion, visualization of capsule, and visualization of peripheral/transition zone edge were better for rFOV-DWI for reader 1 (P ≤ 0.002), although not for reader 2 (P ≥ 0.567). For both readers, sensitivity, specificity, and accuracy for tumor with a Gleason Score (GS) of 3 + 4 or higher were not different (P ≥ 0.289). Lesion clarity was higher for st-DWI for reader 2 (P = 0.008), although similar for reader 1 (P = 0.409). Diagnostic confidence was not different for either reader (P ≥ 0.052). Tumor-to-benign apparent diffusion coefficient ratio was not different (P = 0.675). Potentially improved image quality of rFOV-DWI did not yield improved tumor assessment. Continued optimization is warranted.

PI-RADS version 2: evaluation of diffusion-weighted imaging interpretation between b = 1000 and b = 1500 s mm-2.

PubMed

Kwon, Mi-Ri; Kim, Chan Kyo; Kim, Jae-Hun

2017-11-01

To investigate the variability of diffusion-weighted imaging (DWI) interpretation of Prostate Imaging Reporting and Data System (PI-RADS) version 2 (v2) in evaluating prostate cancer (PCa). 154 patients with PCa underwent multiparametric 3T MRI, followed by radical prostatectomy. DWI with different b values (b = 0, 100, 1000 and 1500 s mm - 2 ) was obtained. Using the PI-RADS v2, two radiologists independently scored suspicious lesions in each patient and compared DWI of b = 1000 (DWI 1000 ) with 1500 (DWI 1500 ) s mm - 2 . On DWI 1000 and DWI 1500 , the intermethod and interobserver agreements of DWI scores were excellent in all patients (κ ≥ 0.873). In each peripheral zone and transition zone DWI scores, both observers showed excellent intermethod agreement between DWI 1000 and DWI 1500 (κ ≥ 0.897), and interobserver agreement for DWI 1000 and DWI 1500 was good to excellent (κ ≥ 0.796). For estimating clinically significant cancer, the area under receiver operating characteristics curves of DWI 1000 and DWI 1500 were 0.710 and 0.724 for observer 1 (p = 0.11), and 0.649 and 0.656 for observer 2 (p = 0.12), respectively. The PI-RADS v2 scoring at 3T shows excellent agreement between DWI 1000 and DWI 1500 in evaluating PCa, with excellent inter-observer agreement. Advance in knowledge: DWI using b = 1000 s mm -2 instead of b = 1500 s mm -2 reduces examination time or image distortion, with improved the signal-to-noise ratio.

High serum concentration of estradiol may be a risk factor of prostate enlargement in aging male in China.

PubMed

Xu, Ding; Wu, Yu; Shen, Haibo; Qian, Subo; Qi, Jun

2018-06-18

Assess the association between serum sex hormone level and prostate volume in men with benign prostatic hyperplasia (BPH). The study involved 239 BPH patients from January 2013 to June 2015 in our hospital. Each patient collected age, medical history, height, weight, body mass index, as well as a full examination of sex hormones, and transrectal ultrasound results. Estradiol (E2) was significantly associated with prostate volume (r = 0.151, p = .02) and transitional zone volume (r = 0.136, p = .035). The association was more significant after adjusting age and BMI (r = 0.253 and 0.250, p <.001). Patients were divided into two groups according to prostate volume and E2, respectively. E2 in patients with prostate volume ≤50 ml was significantly lower than those with prostate volume >50 ml. Prostate volume, transitional zone volume and age were all significantly higher in the patients with E2 ≥ 160 umol/l than those in the patients with E2 < 160 umol/l. Through logistics regression, E2 (p = .012, OR = 1.004) are the only independent risk factor for prostate volume. E2 is significantly associated with prostate volume. High concentrations of E2 may be a risk factor for the large volume of prostate.

Intrafraction Prostate Translations and Rotations During Hypofractionated Robotic Radiation Surgery: Dosimetric Impact of Correction Strategies and Margins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Water, Steven van de, E-mail: s.vandewater@erasmusmc.nl; Valli, Lorella; Alma Mater Studiorum, Department of Physics and Astronomy, Bologna University, Bologna

Purpose: To investigate the dosimetric impact of intrafraction prostate motion and the effect of robot correction strategies for hypofractionated CyberKnife treatments with a simultaneously integrated boost. Methods and Materials: A total of 548 real-time prostate motion tracks from 17 patients were available for dosimetric simulations of CyberKnife treatments, in which various correction strategies were included. Fixed time intervals between imaging/correction (15, 60, 180, and 360 seconds) were simulated, as well as adaptive timing (ie, the time interval reduced from 60 to 15 seconds in case prostate motion exceeded 3 mm or 2° in consecutive images). The simulated extent of robot corrections was alsomore » varied: no corrections, translational corrections only, and translational corrections combined with rotational corrections up to 5°, 10°, and perfect rotational correction. The correction strategies were evaluated for treatment plans with a 0-mm or 3-mm margin around the clinical target volume (CTV). We recorded CTV coverage (V{sub 100%}) and dose-volume parameters of the peripheral zone (boost), rectum, bladder, and urethra. Results: Planned dose parameters were increasingly preserved with larger extents of robot corrections. A time interval between corrections of 60 to 180 seconds provided optimal preservation of CTV coverage. To achieve 98% CTV coverage in 98% of the treatments, translational and rotational corrections up to 10° were required for the 0-mm margin plans, whereas translational and rotational corrections up to 5° were required for the 3-mm margin plans. Rectum and bladder were spared considerably better in the 0-mm margin plans. Adaptive timing did not improve delivered dose. Conclusions: Intrafraction prostate motion substantially affected the delivered dose but was compensated for effectively by robot corrections using a time interval of 60 to 180 seconds. A 0-mm margin required larger extents of additional rotational corrections than a 3-mm margin but resulted in lower doses to rectum and bladder.« less

Prostate-Specific Membrane Antigen Expression in Adrenocortical Carcinoma on 68Ga-Prostate-Specific Membrane Antigen PET/CT.

PubMed

Arora, Saurabh; Damle, Nishikant Avinash; Aggarwal, Sameer; Passah, Averilicia; Behera, Abhishek; Arora, Geetanjali; Bal, Chandrasekhar; Tripathi, Madhavi

2018-06-01

We present here a case of metastatic adrenocortical carcinoma with bilateral lung nodules. The patient had been treated with mitotane therapy initially and then was later referred for chemotherapy. There was progression of disease noted on the F-FDG PET/CT. Ga prostate-specific membrane antigen (PSMA) PET/CT was planned to explore the possibility of future treatment with Lu-DKFZ-PSMA-617. It revealed peripheral increased uptake of Ga-HBED-CC-PSMA equal to liver uptake.

Colour Doppler and microbubble contrast agent ultrasonography do not improve cancer detection rate in transrectal systematic prostate biopsy sampling.

PubMed

Taverna, Gianluigi; Morandi, Giovanni; Seveso, Mauro; Giusti, Guido; Benetti, Alessio; Colombo, Piergiuseppe; Minuti, Francesco; Grizzi, Fabio; Graziotti, Pierpaolo

2011-12-01

What's known on the subject? and What does the study add? Transrectal gray-scale ultrasonography guided prostate biopsy sampling is the method for diagnosing prostate cancer (PC) in patients with an increased prostate specific antigen level and/or abnormal digital rectal examination. Several imaging strategies have been proposed to optimize the diagnostic value of biopsy sampling, although at the first biopsy nearly 10-30% of PC still remains undiagnosed. This study compares the PC detection rate when employing Colour Doppler ultransongraphy with or without the injection of SonoVue™ microbubble contrast agent, versus the transrectal ultrasongraphy-guided systematic biopsy sampling. The limited accuracy, sensitivity, specificity and the additional cost of using the contrast agent do not justify its routine application in PC detection. • To compare prostate cancer (PC) detection rate employing colour Doppler ultrasonography with or without SonoVue™ contrast agent with transrectal ultrasonography-guided systematic biopsy sampling. • A total of 300 patients with negative digital rectal examination and transrectal grey-scale ultrasonography, with PSA values ranging between 2.5 and 9.9 ng/mL, were randomized into three groups: 100 patients (group A) underwent transrectal ultrasonography-guided systematic bioptic sampling; 100 patients (group B) underwent colour Doppler ultrasonography, and 100 patients (group C) underwent colour Doppler ultrasonography before and during the injection of SonoVue™. • Contrast-enhanced targeted biopsies were sampled into hypervascularized areas of peripheral, transitional, apical or anterior prostate zones. • All the patients included in Groups B and C underwent a further 13 systematic prostate biopsies. The cancer detection rate was calculated for each group. • In 88 (29.3%) patients a histological diagnosis of PC was made, whereas 22 (7.4%) patients were diagnosed with high-grade prostatic intraepithelial neoplasia or atypical small acinar proliferation. • No significant differences were found among the three groups for cancer detection rate (P= 0.329). • Additionally, low sensitivity, specificity and accuracy of colour Doppler with or without SonoVue™ contrast agent were found. • Prostate cancer detection rate does not significantly improve with the use of colour Doppler ultrasonography with or without SonoVue™. • Although no collateral effects have been highlighted, the combined use of colour Doppler ultrasonography and SonoVue™ determines adjunctive costs and increases the mean time for taking a single prostate biopsy. © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

The therapeutic potential of royal jelly in benign prostatic hyperplasia. Comparison with contemporary literature.

PubMed

Pajovic, Bogdan; Radojevic, Nemanja; Dimitrovski, Antonio; Tomovic, Savo; Vukovic, Marko

2016-09-01

The aim of this study is to establish the scientific benefit of royal jelly (RJ) on prostatic-specific antigen (PSA), post-void residual (PVR) volume and International Prostate Symptom Score (IPSS) in benign prostatic hyperplasia. For the study, a group of 40 men were administered 38 mg of RJ over a period of three months, their PSA values, prostate volumes and the volumes of their transitory prostate zones, PVR and IPPS values were measured at the end of the first month, and at the end of the third month. The results of this study confirm the potential of RJ in reducing PSA scores and improving IPSS values. Since the use of RJ did not lead to any significant reduction in PVR, prostate volume, or to any involution of the transitory zone, it appears that it may only affect the blood marker of prostatic hyperplasia and to improve quality-of-life (QoL) in those patients. Overall, in comparison to phytotherapy and conventional therapy, RJ had similar positive effects on QoL in patients with BPH, however it exhibited markedly better effects on reducing PSA levels in blood. The therapeutical use of RJ exhibited no side effects.

Performance of Ultrafast DCE-MRI for Diagnosis of Prostate Cancer.

PubMed

Chatterjee, Aritrick; He, Dianning; Fan, Xiaobing; Wang, Shiyang; Szasz, Teodora; Yousuf, Ambereen; Pineda, Federico; Antic, Tatjana; Mathew, Melvy; Karczmar, Gregory S; Oto, Aytekin

2018-03-01

This study aimed to test high temporal resolution dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for different zones of the prostate and evaluate its performance in the diagnosis of prostate cancer (PCa). Determine whether the addition of ultrafast DCE-MRI improves the performance of multiparametric MRI. Patients (n = 20) with pathologically confirmed PCa underwent preoperative 3T MRI with T2-weighted, diffusion-weighted, and high temporal resolution (~2.2 seconds) DCE-MRI using gadoterate meglumine (Guerbet, Bloomington, IN) without an endorectal coil. DCE-MRI data were analyzed by fitting signal intensity with an empirical mathematical model to obtain parameters: percent signal enhancement, enhancement rate (α), washout rate (β), initial enhancement slope, and enhancement start time along with apparent diffusion coefficient (ADC) and T2 values. Regions of interests were placed on sites of prostatectomy verified malignancy (n = 46) and normal tissue (n = 71) from different zones. Cancer (α = 6.45 ± 4.71 s -1 , β = 0.067 ± 0.042 s -1 , slope = 3.78 ± 1.90 s -1 ) showed significantly (P <.05) faster signal enhancement and washout rates than normal tissue (α = 3.0 ± 2.1 s -1 , β = 0.034 ± 0.050 s -1 , slope = 1.9 ± 1.4 s -1 ), but showed similar percentage signal enhancement and enhancement start time. Receiver operating characteristic analysis showed area under the curve for DCE parameters was comparable to ADC and T2 in the peripheral (DCE 0.67-0.82, ADC 0.80, T2 0.89) and transition zones (DCE 0.61-0.72, ADC 0.69, T2 0.75), but higher in the central zone (DCE 0.79-0.88, ADC 0.45, T2 0.45) and anterior fibromuscular stroma (DCE 0.86-0.89, ADC 0.35, T2 0.12). Importantly, combining DCE with ADC and T2 increased area under the curve by ~30%, further improving the diagnostic accuracy of PCa detection. Quantitative parameters from empirical mathematical model fits to ultrafast DCE-MRI improve diagnosis of PCa. DCE-MRI with higher temporal resolution may capture clinically useful information for PCa diagnosis that would be missed by low temporal resolution DCE-MRI. This new information could improve the performance of multiparametric MRI in PCa detection. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Comparison of prostate cancer gene 3 score, prostate health index and percentage free prostate-specific antigen for differentiating histological inflammation from prostate cancer and other non-neoplastic alterations of the prostate at initial biopsy.

PubMed

De Luca, Stefano; Passera, Roberto; Bollito, Enrico; Manfredi, Matteo; Scarpa, Roberto Mario; Sottile, Antonino; Randone, Donato Franco; Porpiglia, Francesco

2014-12-01

To determine if prostate cancer gene 3 (PCA3) score, Prostate Health Index (PHI), and percent free prostate-specific antigen (%fPSA) may be used to differentiate prostatitis from prostate cancer (PCa), benign prostatic hyperplasia (BPH) and high-grade prostate intraepithelial neoplasia (HG-PIN) in patients with elevated PSA and negative digital rectal examination (DRE). in the present prospective study, 274 patients, undergoing PCA3 score, PHI and %fPSA assessments before initial biopsy, were enrolled. Three multivariate logistic regression models were used to test PCA3 score, PHI and %fPSA as risk factors for prostatitis vs. PCa, vs. BPH, and vs. HG-PIN. All the analyses were performed for the whole patient cohort and for the 'gray zone' of PSA (4-10 ng/ml) cohort (188 individuals). The determinants for prostatitis vs. PCa were PCA3 score, PHI and %fPSA (Odds Ratio [OR]=0.97, 0.96 and 0.94, respectively). Unit increase of PHI was the only risk factor for prostatitis vs. BPH (OR=1.06), and unit increase of PCA3 score for HG-PIN vs. prostatitis (OR=0.98). In the 'gray zone' PSA cohort, the determinants for prostatitis vs. PCa were PCA3 score, PHI and %fPSA (OR=0.96, 0.94 and 0.92, respectively), PCA3 score and PHI for prostatitis vs. BPH (OR=0.96 and 1.08, respectively), and PCA3 score for prostatitis vs. HG-PIN (OR=0.97). The clinical benefit of using PCA3 score and PHI to estimate prostatitis vs. PCa was comparable; even %fPSA had good diagnostic performance, being a faster and cheaper marker. PHI was the only determinant for prostatitis vs. BPH, while PCA3 score for prostatitis vs. HG-PIN. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

[Will the climate change affect the mortality from prostate cancer?].

PubMed

Santos Arrontes, Daniel; García González, Jesús Isidro; Martín Muñoz, Manuel Pablo; Castro Pita, Miguel; Mañas Pelillo, Antonio; Paniagua Andrés, Pedro

2007-03-01

The global heating of the atmosphere, as well as the increase of the exposition to sunlight, will be associated with a decrease of the mortality from prostate cancer, due to an increase of the plasmatic levels of vitamin D. To evaluate if climatological factors (temperature, rainfall, and number of sunlight hours per year) may influence the mortality associated with prostate cancer over a five-year period. In this ecology type study we will evaluate the trends of prostate tumors associated mortality in the period between January 1st 1998 and December 31st 2002, in the geographic area of Spain (17 Autonomic communities-CA-and 2 Autonomic cities- Ceuta and Melilla-, 43 million inhabitants). Demographic and mortality data were obtained from the National Institute of Statistics (INE) and climatological data about temperature and rainfall were obtained from the National Institute of Meteorology (INM). The provinces were classified using the climatic index of Martonne (defined as the quotient between annual rainfall and mean annual temperature plus 10). Areas with a quotient below 5 ml/m2/o C are considered extremely arid zones; between 5 and 15 ml/m2/o C are considered arid zones, between 15 and 20 ml/m2/o C semiarid zones; between 20 and 30 ml/m2/o C subhumid zones; between 30 and 60 ml/m2/o C humid zones; and over 60 ml/m2/o C superhumid zones. We compared mortality rates between different climatic areas using the Jonckheere-Terpstra test for six independent samples following the index of Martonne. All calculations were performed using the SPSS v 13.0 for Windows software. A logistic regression model was performed to identify climate factors associated with prostate cancer mortality. A likeliness of the null hypotheses inferior to 0.05 was considered significant. Prostate cancer mortality presented statistically significant differences, being higher in provinces with higher Martonne index (p < 0.001) and lower in areas with a greater number of sunlight hours per year (p = 0.041). The adjusted mortality rate associated with extreme aridity regions and was 21.51 cases/100,000 males year, whereas in humid zones it was 35.87 cases/100,000 males years. Mortality associated with prostate cancer is significantly superior in regions with less exposition to the sunlight. The climate change may lead to a modification of the main epidemiologic patterns, and it may be associated with a modification of cancer mortality rates. Nevertheless, these results should be taken with caution and should be confirmed by prospective studies.

Validation of tissue change monitoring (TCM) on the Sonablate® 500 during high intensity focused ultrasound (HIFU) treatment of prostate cancer with real-time thermometry

NASA Astrophysics Data System (ADS)

Chen, Wo-Hsing; Sanghvi, Narendra T.; Carlson, Roy; Schatzl, Georg; Marberger, Michael

2012-10-01

The Sonablate® 500 has quantitative, real-time Tissue Change Monitoring (TCM) software that estimates changes in tissue properties due to HIFU treatment of prostate cancer. This study validates the Sonablate 500 TCM system using real-time thermometry. Five patients with histologically confirmed, organ-confined prostate cancer were enrolled. Four patients with focal cancer had hemiablation and one had whole gland ablation. TCM generates energy reading based on spectral analysis on the RF backscattered ultrasound signals; results are used as an estimator of tissue temperature. Needle thermocouples were placed transperineally under TRUS guidance in the prostate to monitor temperatures from focal zone, posterior to the focal zone and on the lateral gland where no HIFU was applied. The HIFU treatments averaged 37, 35 and 19.7 Watts for the treatment for anterior, middle and posterior zones. The measured temperatures (Average, Max, and Min) in the HIFU treatment zones were 84, 114 and 70 degrees C. The temperature estimated by TCM energy readings were 83% 75-100 degrees C and 17% 60-75 degrees C with an average of 91 degrees C. Outside the focal zone, average recorded temperature was 50 degrees C. Average temperature in the lateral lobe where no HIFU was applied was 40.7 degrees C.

Optimization of prostate biopsy: the role of magnetic resonance imaging targeted biopsy in detection, localization and risk assessment.

PubMed

Bjurlin, Marc A; Meng, Xiaosong; Le Nobin, Julien; Wysock, James S; Lepor, Herbert; Rosenkrantz, Andrew B; Taneja, Samir S

2014-09-01

Optimization of prostate biopsy requires addressing the shortcomings of standard systematic transrectal ultrasound guided biopsy, including false-negative rates, incorrect risk stratification, detection of clinically insignificant disease and the need for repeat biopsy. Magnetic resonance imaging is an evolving noninvasive imaging modality that increases the accurate localization of prostate cancer at the time of biopsy, and thereby enhances clinical risk assessment and improves the ability to appropriately counsel patients regarding therapy. In this review we 1) summarize the various sequences that comprise a prostate multiparametric magnetic resonance imaging examination along with its performance characteristics in cancer detection, localization and reporting standards; 2) evaluate potential applications of magnetic resonance imaging targeting in prostate biopsy among men with no previous biopsy, a negative previous biopsy and those with low stage cancer; and 3) describe the techniques of magnetic resonance imaging targeted biopsy and comparative study outcomes. A bibliographic search covering the period up to October 2013 was conducted using MEDLINE®/PubMed®. Articles were reviewed and categorized based on which of the 3 objectives of this review was addressed. Data were extracted, analyzed and summarized. Multiparametric magnetic resonance imaging consists of anatomical T2-weighted imaging coupled with at least 2 functional imaging techniques. It has demonstrated improved prostate cancer detection sensitivity up to 80% in the peripheral zone and 81% in the transition zone. A prostate cancer magnetic resonance imaging suspicion score has been developed, and is depicted using the Likert or PI-RADS (Prostate Imaging Reporting and Data System) scale for better standardization of magnetic resonance imaging interpretation and reporting. Among men with no previous biopsy, magnetic resonance imaging increases the frequency of significant cancer detection to 50% in low risk and 71% in high risk patients. In low risk men the negative predictive value of a combination of negative magnetic resonance imaging with prostate volume parameters is nearly 98%, suggesting a potential role in avoiding biopsy and reducing over detection/overtreatment. Among men with a previous negative biopsy 72% to 87% of cancers detected by magnetic resonance imaging guidance are clinically significant. Among men with a known low risk cancer, repeat biopsy using magnetic resonance targeting demonstrates a high likelihood of confirming low risk disease in low suspicion score lesions and of upgrading in high suspicion score lesions. Techniques of magnetic resonance imaging targeted biopsy include visual estimation transrectal ultrasound guided biopsy; software co-registered magnetic resonance imaging-ultrasound, transrectal ultrasound guided biopsy; and in-bore magnetic resonance imaging guided biopsy. Although the improvement in accuracy and efficiency of visual estimation biopsy compared to systematic appears limited, co-registered magnetic resonance imaging-ultrasound biopsy as well as in-bore magnetic resonance imaging guided biopsy appear to increase cancer detection rates in conjunction with increasing suspicion score. Use of magnetic resonance imaging for targeting prostate biopsies has the potential to reduce the sampling error associated with conventional biopsy by providing better disease localization and sampling. More accurate risk stratification through improved cancer sampling may impact therapeutic decision making. Optimal clinical application of magnetic resonance imaging targeted biopsy remains under investigation. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Impact of PSA density of transition zone as a potential parameter in reducing the number of unnecessary prostate biopsies in patients with psa levels between 2.6 and 10.0 ng/mL.

PubMed

Castro, Hugo A Socrates; Iared, Wagner; Santos, José Eduardo Mourão; Solha, Raphael Sandes; Shigueoka, David Carlos; Ajzen, Sergio Aron

2018-04-10

To assess the accuracy of prostate-specific antigen (PSA) adjusted for the transition zone volume (PSATZ) in predicting prostate cancer by comparing the ability of several PSA parameters in predicting prostate cancer in men with intermediate PSA levels of 2.6 - 10.0 ng/mL and its ability to reduce unnecessary biopsies. This study included 656 patients referred for prostate biopsy who had a serum PSA of 2.6 - 10.0 ng/mL. Total prostate and transition zone volumes were measured by transrectal ultrasound using the prolate ellipsoid method. The clinical values of PSA, free-to-total (F/T) ratio, PSA density (PSAD) and PSATZ for the detection of prostate cancer were calculated and statistical comparisons between biopsy-positive (cancer) and biopsy-negative (benign) were conducted. Cancer was detected in 172 patients (26.2%). Mean PSA, PSATZ, PSAD and F/T ratio were 7.5 ng/mL, 0.68 ng/mL/cc. 0.25 ng/mL/cc and 0.14 in patients with prostate cancer and 6.29 ng/mL, 0.30 ng/mL/cc, 0.16 ng/mL/cc and 0.22 in patients with benign biopsies, respectively. ROC curves analysis demonstrated that PSATZ had a higher area under curve (0,838) than F/T ratio (0,806) (P<0.001) and PSAD (0,806) (P<0.001). With a cut-off value of 0.22 ng/mL/cc, PSATZ had 100% of sensitivity and could have prevented 24% of unnecessary biopsies. PSATZ may be useful in enhancing the specificity of serum PSA. Compared to other PSA related parameters, it was better in differentiating between prostate cancer and benign prostatic enlargement. Also, PSATZ could reduce a significant number of unnecessary biopsies. Copyright® by the International Brazilian Journal of Urology.

Correlation of p63 immunohistochemistry with histology and contrast enhanced MRI in characteristic lesions induced by minimally invasive thermal treatments in a dog prostate

NASA Astrophysics Data System (ADS)

Pascal, A.; Butts-Pauly, K.; Plata, J.; Sommer, G.; Daniel, B.; Bouley, D. M.

2017-03-01

Thermal ablation techniques are important tools to treat low grade tumors in the prostate gland. The use of Magnetic Resonance Imaging (MRI) has been an excellent tool to visualize and assess the thermally ablated areas in real time. In this study slides from dog prostates previously treated with cryoablation or High Intensity Focal Ultrasound (HIFU) were immunohistochemically stained with the biomarker p63, in order to determine if this marker would be helpful for differentiatiating between viable, sub lethally damaged and normal glands. Digitized slides were analyzed using Sedeen Viewer software, and compared with corresponding representative H&E slides and MR images. p63 staining in the cryoablated acute duration prostates was negative in the coagulation necrosis zone (region of interest subjected to the coldest temperatures). In acute duration HIFU treated prostates, the central heat-fixed zone (region of interest subjected to the hottest temperatures) still displayed + p63 staining. Cryoablated or HIFU subacute duration treated prostates were very hemorrhagic, but presented the same stain pattern in the treated areas as the acute duration prostates, and in chronic duration prostates, whether treated with cryo or HIFU, glands displayed robust p63 staining most prevalent in the outer edges of the lesion where there was extensive glandular regeneration. In conclusion, this study demonstrates the value of p63 IHC and its usefulness in detecting viable prostate basal cells in normal dog prostates following either cryoablation of HIFU. Our results suggest that the portions of the lesion with complete loss of p63 staining correspond well to the non-enhancing region in cryoablated prostates, as viewed with MRI. However, p63 staining in the heat-fixed zone in acute harvested HIFU treated prostates remains positive, suggesting either inadequate heat to destroy basal cells, or heat-fixation of the p63 antigen and false positive staining. Therefore p63 staining does not appear to be beneficial in determining cell viability in HIFU-treated tissues, and would not aid in predicting if unwanted tumor cells in a similarly treated area could regenerate.

TU-CD-BRB-12: Radiogenomics of MRI-Guided Prostate Cancer Biopsy Habitats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stoyanova, R; Lynne, C; Abraham, S

2015-06-15

Purpose: Diagnostic prostate biopsies are subject to sampling bias. We hypothesize that quantitative imaging with multiparametric (MP)-MRI can more accurately direct targeted biopsies to index lesions associated with highest risk clinical and genomic features. Methods: Regionally distinct prostate habitats were delineated on MP-MRI (T2-weighted, perfusion and diffusion imaging). Directed biopsies were performed on 17 habitats from 6 patients using MRI-ultrasound fusion. Biopsy location was characterized with 52 radiographic features. Transcriptome-wide analysis of 1.4 million RNA probes was performed on RNA from each habitat. Genomics features with insignificant expression values (<0.25) and interquartile range <0.5 were filtered, leaving total of 212more » genes. Correlation between imaging features, genes and a 22 feature genomic classifier (GC), developed as a prognostic assay for metastasis after radical prostatectomy was investigated. Results: High quality genomic data was derived from 17 (100%) biopsies. Using the 212 ‘unbiased’ genes, the samples clustered by patient origin in unsupervised analysis. When only prostate cancer related genomic features were used, hierarchical clustering revealed samples clustered by needle-biopsy Gleason score (GS). Similarly, principal component analysis of the imaging features, found the primary source of variance segregated the samples into high (≥7) and low (6) GS. Pearson’s correlation analysis of genes with significant expression showed two main patterns of gene expression clustering prostate peripheral and transitional zone MRI features. Two-way hierarchical clustering of GC with radiomics features resulted in the expected groupings of high and low expressed genes in this metastasis signature. Conclusions: MP-MRI-targeted diagnostic biopsies can potentially improve risk stratification by directing pathological and genomic analysis to clinically significant index lesions. As determinant lesions are more reliably identified, targeting with radiotherapy should improve outcome. This is the first demonstration of a link between quantitative imaging features (radiomics) with genomic features in MRI-directed prostate biopsies. The research was supported by NIH- NCI R01 CA 189295 and R01 CA 189295; E Davicioni is partial owner of GenomeDx Biosciences, Inc. M Takhar, N Erho, L Lam, C Buerki and E Davicioni are current employees at GenomeDx Biosciences, Inc.« less

Biexponential characterization of prostate tissue water diffusion decay curves over an extended b-factor range.

PubMed

Mulkern, Robert V; Barnes, Agnieszka Szot; Haker, Steven J; Hung, Yin P; Rybicki, Frank J; Maier, Stephan E; Tempany, Clare M C

2006-06-01

Detailed measurements of water diffusion within the prostate over an extended b-factor range were performed to assess whether the standard assumption of monoexponential signal decay is appropriate in this organ. From nine men undergoing prostate MR staging examinations at 1.5 T, a single 10-mm-thick axial slice was scanned with a line scan diffusion imaging sequence in which 14 equally spaced b factors from 5 to 3,500 s/mm(2) were sampled along three orthogonal diffusion sensitization directions in 6 min. Due to the combination of long scan time and limited volume coverage associated with the multi-b-factor, multidirectional sampling, the slice was chosen online from the available T2-weighted axial images with the specific goal of enabling the sampling of presumed noncancerous regions of interest (ROIs) within the central gland (CG) and peripheral zone (PZ). Histology from prescan biopsy (n=9) and postsurgical resection (n=4) was subsequently employed to help confirm that the ROIs sampled were noncancerous. The CG ROIs were characterized from the T2-weighted images as primarily mixtures of glandular and stromal benign prostatic hyperplasia, which is prevalent in this population. The water signal decays with b factor from all ROIs were clearly non-monoexponential and better served with bi- vs. monoexponential fits, as tested using chi(2)-based F test analyses. Fits to biexponential decay functions yielded intersubject fast diffusion component fractions in the order of 0.73+/-0.08 for both CG and PZ ROIs, fast diffusion coefficients of 2.68+/-0.39 and 2.52+/-0.38 microm(2)/ms and slow diffusion coefficients of 0.44+/-0.16 and 0.23+/-0.16 um(2)/ms for CG and PZ ROIs, respectively. The difference between the slow diffusion coefficients within CG and PZ was statistically significant as assessed with a Mann-Whitney nonparametric test (P<.05). We conclude that a monoexponential model for water diffusion decay in prostate tissue is inadequate when a large range of b factors is sampled and that biexponential analyses are better suited for characterizing prostate diffusion decay curves.

Early Choline Levels From 3-Tesla MR Spectroscopy After Exclusive Radiation Therapy in Patients With Clinically Localized Prostate Cancer are Predictive of Plasmatic Levels of PSA at 1 Year

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crehange, Gilles, E-mail: gcrehange@cgfl.fr; Maingon, Philippe; Gauthier, Melanie

2011-11-15

Purpose: To investigate the time course response of prostate metabolism to irradiation using magnetic resonance spectroscopy (MRS) at 3-month intervals and its impact on biochemical control. Methods and Materials: Between January 2008 and April 2010, 24 patients with localized prostate cancer were prospectively enrolled in the Evaluation of the Response to Irradiation with MR Spectroscopy (ERIS) trial. All the patients had been treated with intensity-modulated radiation therapy with or without long-term adjuvant hormonal therapy (LTHT) and underwent 3-T MRS and prostate-specific antigen (PSA) assays at baseline and every 3 months thereafter up to 12 months. Results: After radiation, the meanmore » normalized citrate level (citrate/water) decreased significantly over time, both in the peripheral zone (PZ) (p = 0.0034) and in the entire prostate (p = 0.0008), whereas no significant change was observed in mean normalized choline levels (choline/water) in the PZ (p = 0.84) and in the entire prostate (p = 0.95). At 6 months after radiation, the mean choline level was significantly lower in the PZ for patients with a PSA value of {<=}0.5 ng/mL at 12 months (4.9 {+-} 1.7 vs. 7.1 {+-} 1.5, p = 0.0378). Similar results were observed at 12 months in the PZ (6.2 {+-} 2.3 vs. 11.4 {+-} 4.1, p = 0.0117 for choline level and 3.4 {+-} 0.7 vs. 16.1 {+-} 6.1, p = 0.0054 for citrate level) and also in the entire prostate (6.2 {+-} 1.9 vs. 10.4 {+-} 3.2, p = 0.014 for choline level and 3.0 {+-} 0.8 vs. 13.3 {+-} 4.7, p = 0.0054 for citrate level). For patients receiving LTHT, there was no correlation between choline or citrate levels and PSA value, either at baseline or at follow-up. Conclusions: Low normalized choline in the PZ, 6 months after radiation, predicts which patients attained a PSA {<=}0.5 ng/mL at 1 year. Further analyses with longer follow-up times are warranted to determine whether or not these new biomarkers can conclusively predict the early radiation response and the clinical outcome for patients with or without LTHT.« less

MRI signal intensity based B-spline nonrigid registration for pre- and intraoperative imaging during prostate brachytherapy.

PubMed

Oguro, Sota; Tokuda, Junichi; Elhawary, Haytham; Haker, Steven; Kikinis, Ron; Tempany, Clare M C; Hata, Nobuhiko

2009-11-01

To apply an intensity-based nonrigid registration algorithm to MRI-guided prostate brachytherapy clinical data and to assess its accuracy. A nonrigid registration of preoperative MRI to intraoperative MRI images was carried out in 16 cases using a Basis-Spline algorithm in a retrospective manner. The registration was assessed qualitatively by experts' visual inspection and quantitatively by measuring the Dice similarity coefficient (DSC) for total gland (TG), central gland (CG), and peripheral zone (PZ), the mutual information (MI) metric, and the fiducial registration error (FRE) between corresponding anatomical landmarks for both the nonrigid and a rigid registration method. All 16 cases were successfully registered in less than 5 min. After the nonrigid registration, DSC values for TG, CG, PZ were 0.91, 0.89, 0.79, respectively, the MI metric was -0.19 +/- 0.07 and FRE presented a value of 2.3 +/- 1.8 mm. All the metrics were significantly better than in the case of rigid registration, as determined by one-sided t-tests. The intensity-based nonrigid registration method using clinical data was demonstrated to be feasible and showed statistically improved metrics when compare to only rigid registration. The method is a valuable tool to integrate pre- and intraoperative images for brachytherapy.

New technologies in benign prostatic hyperplasia management.

PubMed

Roberts, William W

2016-05-01

Surgical debulking of the adenoma/transition zone has been the fundamental principle which underpins transurethral resection of the prostate - still acknowledged to be the gold-standard therapy for benign prostatic hyperplasia (BPH). However, there has been a recent resurgence in development of new BPH technologies driven by enhanced understanding of prostate pathophysiology, development of new ablative technologies, and the need for less morbid alternatives as the mean age and complexity of the treatment population continues to increase. The objective of this review is to highlight new BPH technologies and review their available clinical data with specific emphasis on unique features of the technology, procedural effectiveness and safety, and potential impact on current treatment paradigms. New technologies have emerged that alter the shape of the prostate to decrease urinary obstruction and enhance delivery of a lethal thermal dose by steam injection into the transition zone of the prostate. Energy can be delivered to the prostate via a beam of high-pressure saline or focused acoustic energy to mechanically disintegrate prostate tissue. Methods of cell death are being targeted with selectivity by the arterial supply with embolization and specific to prostate cells via injectable biological therapies. A number of new technologies are at various stages of development and improve on the transurethral resection of the prostate paradigm by moving closer to the ideal BPH therapy which is definitive, can be performed in minutes, in the office setting, with only local anesthesia and oral sedation.

Multivariate modelling of prostate cancer combining magnetic resonance derived T2, diffusion, dynamic contrast-enhanced and spectroscopic parameters.

PubMed

Riches, S F; Payne, G S; Morgan, V A; Dearnaley, D; Morgan, S; Partridge, M; Livni, N; Ogden, C; deSouza, N M

2015-05-01

The objectives are determine the optimal combination of MR parameters for discriminating tumour within the prostate using linear discriminant analysis (LDA) and to compare model accuracy with that of an experienced radiologist. Multiparameter MRIs in 24 patients before prostatectomy were acquired. Tumour outlines from whole-mount histology, T2-defined peripheral zone (PZ), and central gland (CG) were superimposed onto slice-matched parametric maps. T2, Apparent Diffusion Coefficient, initial area under the gadolinium curve, vascular parameters (K(trans),Kep,Ve), and (choline+polyamines+creatine)/citrate were compared between tumour and non-tumour tissues. Receiver operating characteristic (ROC) curves determined sensitivity and specificity at spectroscopic voxel resolution and per lesion, and LDA determined the optimal multiparametric model for identifying tumours. Accuracy was compared with an expert observer. Tumours were significantly different from PZ and CG for all parameters (all p < 0.001). Area under the ROC curve for discriminating tumour from non-tumour was significantly greater (p < 0.001) for the multiparametric model than for individual parameters; at 90 % specificity, sensitivity was 41 % (MRSI voxel resolution) and 59 % per lesion. At this specificity, an expert observer achieved 28 % and 49 % sensitivity, respectively. The model was more accurate when parameters from all techniques were included and performed better than an expert observer evaluating these data. • The combined model increases diagnostic accuracy in prostate cancer compared with individual parameters • The optimal combined model includes parameters from diffusion, spectroscopy, perfusion, and anatominal MRI • The computed model improves tumour detection compared to an expert viewing parametric maps.

AgNOR histochemical expression in benign prostatic hyperplasia and prostatic adenocarcinoma

NASA Astrophysics Data System (ADS)

Rita, R.; Delyuzar; Laksmi, L. I.

2018-03-01

Benign prostatic hyperplasia and prostatic adenocarcinoma were common diseases and usually occurred after the 5th decade of life. The problem in diagnosing using Hematoxylin and Eosin staining was how to differentiate whether it is benign or malignant zone. Therefore, proliferating markers, such as AgNOR, could be helping to over this difficulty. A descriptive study using consecutive sampling as the method of sample recruiting was conducted to describe AgNOR histochemical expression in benign prostatic hyperplasia and prostatic adenocarcinoma. AgNOR staining was done in 13 benign prostatic hyperplasia samples and 7 prostatic adenocarcinoma samples, which have been confirmed using p63 immunohistochemical staining before. Benign prostatic hyperplasia usually showed lower AgNOR proliferating activity while all of theprostatic adenocarcinoma (100%) had high AgNOR proliferating activity.

Analysis of the spatial distribution of prostate cancer obtained from histopathological images

NASA Astrophysics Data System (ADS)

Diaz, Kristians; Castaneda, Benjamin; Montero, Maria Luisa; Yao, Jorge; Joseph, Jean; Rubens, Deborah; Parker, Kevin J.

2013-03-01

Understanding the spatial distribution of prostate cancer and how it changes according to prostate specific antigen (PSA) values, Gleason score, and other clinical parameters may help comprehend the disease and increase the overall success rate of biopsies. This work aims to build 3D spatial distributions of prostate cancer and examine the extent and location of cancer as a function of independent clinical parameters. The border of the gland and cancerous regions from wholemount histopathological images are used to reconstruct 3D models showing the localization of tumor. This process utilizes color segmentation and interpolation based on mathematical morphological distance. 58 glands are deformed into one prostate atlas using a combination of rigid, affine, and b-spline deformable registration techniques. Spatial distribution is developed by counting the number of occurrences in a given position in 3D space from each registered prostate cancer. Finally a difference between proportions is used to compare different spatial distributions. Results show that prostate cancer has a significant difference (SD) in the right zone of the prostate between populations with PSA greater and less than 5ng/ml. Age does not have any impact in the spatial distribution of the disease. Positive and negative capsule-penetrated cases show a SD in the right posterior zone. There is SD in almost all the glands between cases with tumors larger and smaller than 10% of the whole prostate. A larger database is needed to improve the statistical validity of the test. Finally, information from whole-mount histopathological images may provide better insight into prostate cancer.

Association between pathology and texture features of multi parametric MRI of the prostate

NASA Astrophysics Data System (ADS)

Kuess, Peter; Andrzejewski, Piotr; Nilsson, David; Georg, Petra; Knoth, Johannes; Susani, Martin; Trygg, Johan; Helbich, Thomas H.; Polanec, Stephan H.; Georg, Dietmar; Nyholm, Tufve

2017-10-01

The role of multi-parametric (mp)MRI in the diagnosis and treatment of prostate cancer has increased considerably. An alternative to visual inspection of mpMRI is the evaluation using histogram-based (first order statistics) parameters and textural features (second order statistics). The aims of the present work were to investigate the relationship between benign and malignant sub-volumes of the prostate and textures obtained from mpMR images. The performance of tumor prediction was investigated based on the combination of histogram-based and textural parameters. Subsequently, the relative importance of mpMR images was assessed and the benefit of additional imaging analyzed. Finally, sub-structures based on the PI-RADS classification were investigated as potential regions to automatically detect maligned lesions. Twenty-five patients who received mpMRI prior to radical prostatectomy were included in the study. The imaging protocol included T2, DWI, and DCE. Delineation of tumor regions was performed based on pathological information. First and second order statistics were derived from each structure and for all image modalities. The resulting data were processed with multivariate analysis, using PCA (principal component analysis) and OPLS-DA (orthogonal partial least squares discriminant analysis) for separation of malignant and healthy tissue. PCA showed a clear difference between tumor and healthy regions in the peripheral zone for all investigated images. The predictive ability of the OPLS-DA models increased for all image modalities when first and second order statistics were combined. The predictive value reached a plateau after adding ADC and T2, and did not increase further with the addition of other image information. The present study indicates a distinct difference in the signatures between malign and benign prostate tissue. This is an absolute prerequisite for automatic tumor segmentation, but only the first step in that direction. For the specific identified signature, DCE did not add complementary information to T2 and ADC maps.

Detection of prostate cancer with multiparametric MRI (mpMRI): effect of dedicated reader education on accuracy and confidence of index and anterior cancer diagnosis

PubMed Central

Garcia-Reyes, Kirema; Passoni, Niccolò M.; Palmeri, Mark L.; Kauffman, Christopher R.; Choudhury, Kingshuk Roy; Polascik, Thomas J.; Gupta, Rajan T.

2015-01-01

Purpose To evaluate the impact of dedicated reader education on accuracy/confidence of peripheral zone index cancer and anterior prostate cancer (PCa) diagnosis with mpMRI; secondary aim was to assess the ability of readers to differentiate low-grade cancer (Gleason 6 or below) from high-grade cancer (Gleason 7+). Materials and methods Five blinded radiology fellows evaluated 31 total prostate mpMRIs in this IRB-approved, HIPAA-compliant, retrospective study for index lesion detection, confidence in lesion diagnosis (1–5 scale), and Gleason grade (Gleason 6 or lower vs. Gleason 7+). Following a dedicated education program, readers reinterpreted cases after a memory extinction period, blinded to initial reads. Reference standard was established combining whole mount histopathology with mpMRI findings by a board-certified radiologist with 5 years of prostate mpMRI experience. Results Index cancer detection: pre-education accuracy 74.2%; post-education accuracy 87.7% (p = 0.003). Confidence in index lesion diagnosis: pre-education 4.22 ± 1.04; post-education 3.75 ± 1.41 (p = 0.0004). Anterior PCa detection: pre-education accuracy 54.3%; post-education accuracy 94.3% (p = 0.001). Confidence in anterior PCa diagnosis: pre-education 3.22 ± 1.54; post-education 4.29 ± 0.83 (p = 0.0003). Gleason score accuracy: pre-education 54.8%; post-education 73.5% (p = 0.0005). Conclusions A dedicated reader education program on PCa detection with mpMRI was associated with a statistically significant increase in diagnostic accuracy of index cancer and anterior cancer detection as well as Gleason grade identification as compared to pre-education values. This was also associated with a significant increase in reader diagnostic confidence. This suggests that substantial interobserver variability in mpMRI interpretation can potentially be reduced with a focus on education and that this can occur over a fellowship training year. PMID:25034558

Why prostate tumour delineation based on apparent diffusion coefficient is challenging: an exploration of the tissue microanatomy.

PubMed

Borren, Alie; Moman, Maaike R; Groenendaal, Greetje; Boeken Kruger, Arto E; van Diest, Paul J; van der Groep, Petra; van der Heide, Uulke A; van Vulpen, Marco; Philippens, Marielle E P

2013-11-01

Focal boosting of prostate tumours to improve outcome, requires accurate tumour delineation. For this, the apparent diffusion coefficient (ADC) derived from diffusion-weighted MR imaging (DWI) seems a useful tool. On voxel level, the relationship between ADC and histological presence of tumour is, however, ambiguous. Therefore, in this study the relationship between ADC and histological variables was investigated on voxel level to understand the strengths and limitations of DWI for prostate tumour delineation. Twelve radical prostatectomy patients underwent a pre-operative 3.0T DWI exam and the ADC was calculated. From whole-mount histological sections cell density and glandular area were retrieved for every voxel. The distribution of all variables was described for tumour, peripheral zone (PZ) and central gland (CG) on regional and voxel level. Correlations between variables and differences between regions were calculated. Large heterogeneity of ADC on voxel level was observed within tumours, between tumours and between patients. This heterogeneity was reflected by the distribution of cell density and glandular area. On regional level, tumour was different from PZ having higher cell density (p = 0.007), less glandular area (p = 0.017) and lower ADCs (p = 0.017). ADC was correlated with glandular area (r = 0.402) and tumour volume (r = -0.608), but not with Gleason score. ADC tended to decrease with increasing cell density (r = -0.327, p = 0.073). On voxel level, correlations between ADC and histological variables varied among patients, for cell density ranging from r = -0.439 to r = 0.261 and for glandular area from r = 0.593 to r = 0.207. The variation in ADC can to a certain extent be explained by the variation in cell density and glandular area. The ADC is highly heterogeneous, which reflects the heterogeneity of malignant and benign prostate tissue. This heterogeneity might however obscure small tumours or parts of tumours. Therefore, DWI has to be used in the context of multiparametric MRI.

Dynamic contrast enhanced MRI of the prostate: comparison of gadobutrol and Gd-DTPA.

PubMed

Durmus, T; Vollnberg, B; Schwenke, C; Kilic, E; Huppertz, A; Taupitz, M; Franiel, T

2013-09-01

To evaluate the enhancement profile of the macrocyclic contrast medium (CM) gadobutrol in comparison to linear CM Gd-DTPA in DCE-MRI of the prostate. In total 53 patients with prostata cancer (PCa) were included, who received a radical prostatectomy after multiparametric MRI of the prostate including DCE-MRI. Using circular regions of interests normal peripheral zone (PZ) and PCa foci > 5 mm in diameter (42 and 34 foci in Gd-DTPA and gadobutrol group, respectively) were analysed in DCE-MRI. Enhancement curves (Type I, II and III) and pharmacokinetic parameters were analyzed qualitatively and quantitatively and compared using mixed linear models (two sided p-values < 0.05 were regarded significant). There was no significant difference in frequencies of curve types I, II or III in the normal PZ (p = 0.63) or in PCa foci (p = 0.75). PCa with a Gleason score ≥ 7 had in comparison to Gleason ≤ 6 significantly more often a Wash-Out-curve (Type III) with both CM (p = 0.02). The relative peak enhancement was in the PZ (Gd-DTPA 1.4 a. u. [1.20; 1.59], gadobutrol 1.58 a. u. [1.37; 1.78]) and in PCa foci (Gd-DTPA 1.56 a. u. [1.41; 1.71], gadobutrol 1.76 a. u. [1.59; 1.94]) significantly higher with gadobutrol (p = 0.04). The pharmacokinetic parameters Ktrans und kep were higher in PCa foci than in PZ (p < 0.0001 and p = 0.002, respectively) without significant difference of the parameter values between both CM (p = 0.65). [corrected] This study is the first systematic comparison of gadobutrol and Gd-DTPA in DCE-MRI of the prostate. The relative peak enhancement is higher using gadobutrol compared to Gd-DTPA in DCE-MRI. There was no statistically significant difference in curve types or the pharmacokinetic parameters in PCa or normal PZ between both CM. © Georg Thieme Verlag KG Stuttgart · New York.

Imaging of prostate cancer: a platform for 3D co-registration of in-vivo MRI ex-vivo MRI and pathology

NASA Astrophysics Data System (ADS)

Orczyk, Clément; Mikheev, Artem; Rosenkrantz, Andrew; Melamed, Jonathan; Taneja, Samir S.; Rusinek, Henry

2012-02-01

Objectives: Multi-parametric MRI is emerging as a promising method for prostate cancer diagnosis. prognosis and treatment planning. However, the localization of in-vivo detected lesions and pathologic sites of cancer remains a significant challenge. To overcome this limitation we have developed and tested a system for co-registration of in-vivo MRI, ex-vivo MRI and histology. Materials and Methods: Three men diagnosed with localized prostate cancer (ages 54-72, PSA levels 5.1-7.7 ng/ml) were prospectively enrolled in this study. All patients underwent 3T multi-parametric MRI that included T2W, DCEMRI, and DWI prior to robotic-assisted prostatectomy. Ex-vivo multi-parametric MRI was performed on fresh prostate specimen. Excised prostates were then sliced at regular intervals and photographed both before and after fixation. Slices were perpendicular to the main axis of the posterior capsule, i.e., along the direction of the rectal wall. Guided by the location of the urethra, 2D digital images were assembled into 3D models. Cancer foci, extra-capsular extensions and zonal margins were delineated by the pathologist and included in 3D histology data. A locally-developed software was applied to register in-vivo, ex-vivo and histology using an over-determined set of anatomical landmarks placed in anterior fibro-muscular stroma, central. transition and peripheral zones. The mean root square distance across corresponding control points was used to assess co-registration error. Results: Two specimens were pT3a and one pT2b (negative margin) at pathology. The software successfully fused invivo MRI. ex-vivo MRI fresh specimen and histology using appropriate (rigid and affine) transformation models with mean square error of 1.59 mm. Coregistration accuracy was confirmed by multi-modality viewing using operator-guided variable transparency. Conclusion: The method enables successful co-registration of pre-operative MRI, ex-vivo MRI and pathology and it provides initial evidence of feasibility of MRI-guided surgical planning.

Evaluation of primary prostate cancer using 11C-methionine-PET/CT and 18F-FDG-PET/CT.

PubMed

Shiiba, Masato; Ishihara, Keiichi; Kimura, Go; Kuwako, Tomoyuki; Yoshihara, Hisashi; Yoshihara, Naohisa; Sato, Hidetaka; Kondo, Yukihiro; Tsuchiya, Shin-ichi; Kumita, Shin-ichiro

2012-02-01

The objective of this study was to evaluate the capability of (11)C-methionine (MET)-PET/CT and (18)F-2-deoxy-2-fluoro-D: -glucose (FDG)-PET/CT to diagnose primary prostate cancer using recently developed Gemini TF PET/CT (Philips Healthcare, Cleveland, OH). Twenty men who had been referred for a diagnostic work-up for prostate cancer were enrolled in this study. MET- and FDG-PET/CT by high-resolution mode were carried out on the same day prior to prostate biopsy and each maximum standardized uptake value (SUVmax) was compared with the pathological findings. The regions of interest (about 100 mm(2) small round) were placed at standard 6 points of the peripheral zone and 4 points in the apex of the transitional zone in cases that had undergone biopsy of the internal gland. We summed two scores if a specimen had inhomogeneous Gleason scores (e.g. GS 7; 4 + 3) and doubled the score when the Gleason score was the same (e.g. GS 8; 4 × 2). We divided the tumors into three groups. If the summed Gleason score of the specimens was 5 or less, they were grouped as NG (no grade with the Gleason score). If the summed Gleason score was 6 or 7, the tumors were defined as LG (low Gleason score group), and if the summed Gleason score was 8, 9 or 10, the tumors were classified as HG (high Gleason score group). The mean SUVmax was calculated and one-way analysis of variance or Kruskal-Wallis test and the Tukey post hoc test were performed for statistical comparisons. The capabilities of MET and FDG for diagnosing prostate cancer were evaluated through analysis of the area under the curve of the receiver operating characteristic (ROC) curve. The cut-off levels of SUVmax for the highest accuracy were determined by the results of the ROC analysis, and the sensitivity, specificity and accuracy were calculated. The PET images, obtained with Gemini TF PET/CT, allowed visual identification of anatomical locations within the prostate gland. Among the mean SUVmax of MET, FDG early phase and FDG delayed phase, the differences between NG and HG were all statistically significant (P < 0.01). With MET the difference between NG and LG was also significant (P < 0.05). And for the elevation rate from FDG early to delayed phase, the difference between NG and HG was significant (P < 0.05). The cut-off SUVmax, sensitivity, specificity, accuracy for distinguishing between NG and LG + HG by MET, FDG early and delayed phase were 3.15/78.7/75.6/78.3, 2.81/61.7/80.0/70.7 and 3.00/62.8/78.9/70.7, respectively. And the same factors between NG + LG and HG were 3.76/70.1/89.7/82.6, 2.88/70.1/82.9/78.3 and 3.47/62.7/86.3/77.7, respectively. In terms of the capability to diagnose prostate cancer of high Gleason score (≥8), there was no significant difference between MET and FDG. MET appears to be useful for detecting prostate cancer of both low and high Gleason score.

Functional anatomy of the prostate: implications for treatment planning.

PubMed

McLaughlin, Patrick W; Troyer, Sara; Berri, Sally; Narayana, Vrinda; Meirowitz, Amichay; Roberson, Peter L; Montie, James

2005-10-01

To summarize the functional anatomy relevant to prostate cancer treatment planning. Coronal, axial, and sagittal T2 magnetic resonance imaging (MRI) and MRI angiography were fused by mutual information and registered with computed tomography (CT) scan data sets to improve definition of zonal anatomy of the prostate and critical adjacent structures. The three major prostate zones (inner, outer, and anterior fibromuscular) are visible by T2 MRI imaging. The bladder, bladder neck, and internal (preprostatic) sphincter are a continuous muscular structure and clear definition of the preprostatic sphincter is difficult by MRI. Transition zone hypertrophy may efface the bladder neck and internal sphincter. The external "lower" sphincter is clearly visible by T2 MRI with wide variations in length. The critical erectile structures are the internal pudendal artery (defined by MRI angiogram or T2 MRI), corpus cavernosum, and neurovascular bundle. The neurovascular bundle is visible along the posterior lateral surface of the prostate on CT and MRI, but its terminal branches (cavernosal nerves) are not visible and must be defined by their relationship to the urethra within the genitourinary diaphragm. Visualization of the ejaculatory ducts within the prostate is possible on sagittal MRI. The anatomy of the prostate-rectum interface is clarified by MRI, as is the potentially important distinction of rectal muscle and rectal mucosa. Improved understanding of functional anatomy and imaging of the prostate and critical adjacent structures will improve prostate radiation therapy by improvement of dose and toxicity correlation, limitation of dose to critical structures, and potential improvement in post therapy quality of life.

Prostate health index and prostate cancer gene 3 score but not percent-free Prostate Specific Antigen have a predictive role in differentiating histological prostatitis from PCa and other nonneoplastic lesions (BPH and HG-PIN) at repeat biopsy.

PubMed

De Luca, Stefano; Passera, Roberto; Fiori, Cristian; Bollito, Enrico; Cappia, Susanna; Mario Scarpa, Roberto; Sottile, Antonino; Franco Randone, Donato; Porpiglia, Francesco

2015-10-01

To determine if prostate health index (PHI), prostate cancer antigen gene 3 (PCA3) score, and percentage of free prostate-specific antigen (%fPSA) may be used to differentiate asymptomatic acute and chronic prostatitis from prostate cancer (PCa), benign prostatic hyperplasia (BPH), and high-grade prostate intraepithelial neoplasia (HG-PIN) in patients with elevated PSA levels and negative findings on digital rectal examination at repeat biopsy (re-Bx). In this prospective study, 252 patients were enrolled, undergoing PHI, PCA3 score, and %fPSA assessments before re-Bx. We used 3 multivariate logistic regression models to test the PHI, PCA3 score, and %fPSA as risk factors for prostatitis vs. PCa, vs. BPH, and vs. HG-PIN. All the analyses were performed for the whole patient cohort and for the "gray zone" of PSA (4-10ng/ml) cohort (171 individuals). Of the 252 patients, 43 (17.1%) had diagnosis of PCa. The median PHI was significantly different between men with a negative biopsy and those with a positive biopsy (34.9 vs. 48.1, P<0.001), as for the PCA3 score (24 vs. 54, P<0.001) and %fPSA (11.8% vs. 15.8%, P = 0.012). The net benefit of using PCA3 and PHI to differentiate prostatitis and PCa was moderate, although it extended to a good range of threshold probabilities (40%-100%), whereas that from using %fPSA was negligible: this pattern was reported for the whole population as for the "gray zone" PSA cohort. In front of a good diagnostic performance of all the 3 biomarkers in distinguishing negative biopsy vs. positive biopsy, the clinical benefit of using the PCA3 score and PHI to estimate prostatitis vs. PCa was comparable. PHI was the only determinant for prostatitis vs. BPH, whereas no biomarkers could differentiate prostate inflammation from HG-PIN. Copyright © 2015 Elsevier Inc. All rights reserved.

Biexponential Characterization of Prostate Tissue Water Diffusion Decay Curves Over an Extended b-factor Range

PubMed Central

Mulkern, Robert V.; Barnes, Agnieszka Szot; Haker, Steven J.; Hung, Yin P.; Rybicki, Frank J.; Maier, Stephan E.; Tempany, Clare M.C.

2006-01-01

Detailed measurements of water diffusion within the prostate over an extended b-factor range were performed to assess whether the standard assumption of monoexponential signal decay is appropriate in this organ. From nine men undergoing prostate MR staging exams at 1.5 T, a single 10 mm thick axial slice was scanned with a line scan diffusion imaging (LSDI) sequence in which 14 equally spaced b- factors from 5 to 3500 s/mm2 were sampled along three orthogonal diffusion sensitization directions in 6 minutes. Due to the combination of long scan time and limited volume coverage associated with the multi-b- factor, multi-directional sampling, the slice was chosen online from the available T2-weighted axial images with the specific goal of enabling the sampling of presumed non-cancerous regions of interest (ROI’s) within the central gland (CG) and peripheral zone (PZ). Histology from pre-scan biopsy (N = 9) and post-surgical resection (N = 4) was subsequently employed to help confirm that the ROIs sampled were non-cancerous. The CG ROIs were characterized from the T2-weighted images as primarily mixtures of glandular and stromal benign prostatic hyperplasia (BPH) which is prevalent in this population. The water signal decays with b- factor from all ROI’s were clearly non-monoexponential and better served with bi- vs monoexponential fits, as tested using λ2 based F-test analyses. Fits to biexponential decay functions yielded inter-subject fast diffusion component fractions on the order of 0.73 ± 0.08 for both CG and PZ ROIs, fast diffusion coefficients of 2.68 ± 0.39 and 2.52 ± 0.38 μm2/ms and slow diffusion coefficients of 0.44 ± 0.16 and 0.23 ± 0.16 um2/ms for CG and PZ ROI’s, respectively. The difference between the slow diffusion coefficients within CG and PZ was statistically significant as assessed with a Mann-Whitney non-parametric test (P < 0.05). We conclude that a monoexponential model for water diffusion decay in prostate tissue is inadequate when a large range of b- factors is sampled and that biexponential analyses are better suited for characterizing prostate diffusion decay curves. PMID:16735177

Prostate-cancer diagnosis by non-invasive prostatic Zinc mapping using X-Ray Fluorescence (XRF)

NASA Astrophysics Data System (ADS)

Cortesi, Marco

At present, the major screening tools (PSA, DRE, TRUS) for prostate cancer lack sensitivity and specificity, and none can distinguish between low-grade indolent cancer and high-grade lethal one. The situation calls for the promotion of alternative approaches, with better detection sensitivity and specificity, to provide more efficient selection of patients to biopsy and with possible guidance of the biopsy needles. The prime objective of the present work was the development of a novel non-invasive method and tool for promoting detection, localization, diagnosis and follow-up of PCa. The method is based on in-vivo imaging of Zn distribution in the peripheral zone of the prostate, by a trans-rectal X-ray fluorescence (XRF) probe. Local Zn levels, measured in 1--4 mm3 fresh tissue biopsy segments from an extensive clinical study involving several hundred patients, showed an unambiguous correlation with the histological classification of the tissue (Non-Cancer or PCa), and a systematic positive correlation of its depletion level with the cancer-aggressiveness grade (Gleason classification). A detailed analysis of computer-simulated Zn-concentration images (with input parameters from clinical data) disclosed the potential of the method to provide sensitive and specific detection and localization of the lesion, its grade and extension. Furthermore, it also yielded invaluable data on some requirements, such as the image resolution and counting-statistics, requested from a trans-rectal XRF probe for in-vivo recording of prostatic-Zn maps in patients. By means of systematic table-top experiments on prostate-phantoms comprising tumor-like inclusions, followed by dedicated Monte Carlo simulations, the XRF-probe and its components have been designed and optimized. Multi-parameter analysis of the experimental data confirmed the simulation estimations of the XRF detection system in terms of: delivered dose, counting statistics, scanning resolution, target-volume size and the accuracy of locating at various depths of small-volume tumor-like inclusions in tissue-phantoms. The clinical study, the Monte Carlo simulations and the analysis of Zn-map images provided essential information and promising vision on the potential performance of the Zn-based PCa detection concept. Simulations focusing on medical-probe design and its performance at permissible radiation doses yielded positive results - confirmed by a series of systematic laboratory experiments with a table-top XRF system.

Effect of intravenous gadolinium-DTPA on diffusion-weighted imaging for prostate lesions and normal tissue at 3.0-Tesla magnetic resonance imaging.

PubMed

Liu, Xiaohang; Zhou, Liangping; Peng, Weijun; Qian, Min

2011-06-01

Post-contrast diffusion-weighted imaging (DWI) is occasionally necessary when the results of the pre-contrast DWI differ from that of the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), however, the effects of contrast material on DWI image and apparent diffusion coefficient (ADC) values have not been fully examined. To assess whether the administration of gadolinium-DTPA (Gd-DTPA) significantly affects the DWI of prostate lesions or normal tissue at the 3.0 Tesla magnetic resonance imaging (3.0 T MRI). Fifty-one patients with 52 prostate lesions, including 32 prostate cancer (25 in the peripheral zone [PZ] and seven that could not be confidently located) and 20 benign lesions (11 in PZ and nine in central grand [CG]), underwent echo-planar imaging (EPI)-DWI with b values of 0, 1000 s/mm(2) before and after administration of Gd-DTPA at 3.0 T MRI. Regions of interest (ROI) were drawn in all lesions, 42 normal PZ, 44 CG tissue and air to calculate the signal-to-noise ratio (SNR) and ADC values of lesions and normal tissue, and contrast-to-noise ratio (CNR) of lesions for pre- and post-contrast images. Statistical differences between pre- and post-contrast data were assessed by use of a paired t test. No significant differences between pre- and post-contrast images were found in the CNR of lesions and SNR of all the tissue except CG, which showed a statistically significant decline (9.6%, p < 0.0001) in SNR after contrast relative to the pre-contrast images. The post-contrast ADC values were statistically significantly lower than pre-contrast for prostate cancer (0.80 ± 0.11 mm(2)/s Vs 0.89 ± 0.12 mm(2)/s, p < 0.0001) and benign lesions (1.14 ± 0.30 mm(2)/s vs. 1.2 ± 0.29 mm(2)/s, p < 0.0001). No significant differences were detected for normal tissue. The administration of Gd-DTPA can slightly affect the DWI image quality of the prostate and reduce the ADC value of lesions at 3.0T MRI. Applications of post-contrast DWI require caution in interpretation.

A pilot study evaluating a new questionnaire for prostatic symptom scoring, the SPSS, and its sensitivity as constructed to objective measures of outflow obstruction.

PubMed

Yano, Masataka; Kitahara, Satoshi; Yasuda, Kosaku; Yamanishi, Tomonori; Nakai, Hideo; Yanagisawa, Ryouzo; Morozumi, Makoto; Homma, Yukio

2004-05-01

To evaluate the extent to which our newly developed questionnaire, the Saitama Prostate Symptom Score (SPSS), for prostatic symptom scoring reflects objective findings in benign prostatic hyperplasia (clinical BPH) and to compare it with the International Prostate Symptom Score (IPSS) with regard to diagnostic sensitivity in clinical BPH. In this study, both the SPSS and the IPSS were self-administered by patients. Free uroflowmetry, a pressure-flow study and the measurement of prostatic volume were carried out. There was no significant correlation between the results of the IPSS questionnaire and the urethral obstruction grade estimated by Schaefer or Abrams-Griffiths nomograms. The total score of the SPSS was correlated with these nomograms (P = 0.0487 and P = 0.0413, respectively). There was no significant correlation between the results of the IPSS questionnaire and the total volume or transition zone volume of the prostate, whereas the total score of the SPSS correlated with the total volume of the gland and transition zone volume (P = 0.0044 and P= 0.0051, respectively). This study revealed the SPSS to correlate with objective findings satisfactorily. However, there are still several aspects of the SPSS which need to be improved upon, and the questionnaire should be studied in larger numbers of patients suffering from lower urinary tract symptoms.

Evaluation of radiation necrosis and malignant glioma in rat models using diffusion tensor MR imaging

PubMed Central

Wang, Silun; Chen, Yifei; Lal, Bachchu; Ford, Eric; Tryggestad, Erik; Armour, Michael; Yan, Kun; Laterra, John; Zhou, Jinyuan

2011-01-01

Standard MRI cannot distinguish between radiation necrosis and tumor progression; however, this distinction is critical in the assessment of tumor response to therapy. In this study, one delayed radiation necrosis model (dose, 40 Gy; radiation field, 10 × 10 mm2; n = 13) and two orthotopic glioma models in rats (9L gliosarcoma, n = 8; human glioma xenografts, n = 5) were compared using multiple DTI indices. A visible isotropic apparent diffusion coefficient (ADC) pattern was observed in the lesion due to radiation necrosis, which consisted of a hypointense central zone and a hyperintense peripheral zone. There were significantly lower ADC, parallel diffusivity, and perpendicular diffusivity in the necrotic central zone than in the peripheral zone (all p < 0.001). When radiation-induced necrosis was compared with viable tumor, radiation necrosis had significantly lower ADC than 9L gliosarcoma and human glioma xenografts (both p < 0.01) in the central zone, and significantly lower FA than 9L gliosarcoma (p = 0.005) and human glioma xenografts (p = 0.012) in the peripheral zone. Histological analysis revealed parenchymal coagulative necrosis in the central zone, and damaged vessels and reactive astrogliosis in the peripheral zone. These data suggest that qualitative and quantitative analysis of the DTI maps can provide useful information by which to distinguish between radiation necrosis and viable glioma. PMID:21948114

Clinical map document based on XML (cMDX): document architecture with mapping feature for reporting and analysing prostate cancer in radical prostatectomy specimens.

PubMed

Eminaga, Okyaz; Hinkelammert, Reemt; Semjonow, Axel; Neumann, Joerg; Abbas, Mahmoud; Koepke, Thomas; Bettendorf, Olaf; Eltze, Elke; Dugas, Martin

2010-11-15

The pathology report of radical prostatectomy specimens plays an important role in clinical decisions and the prognostic evaluation in Prostate Cancer (PCa). The anatomical schema is a helpful tool to document PCa extension for clinical and research purposes. To achieve electronic documentation and analysis, an appropriate documentation model for anatomical schemas is needed. For this purpose we developed cMDX. The document architecture of cMDX was designed according to Open Packaging Conventions by separating the whole data into template data and patient data. Analogue custom XML elements were considered to harmonize the graphical representation (e.g. tumour extension) with the textual data (e.g. histological patterns). The graphical documentation was based on the four-layer visualization model that forms the interaction between different custom XML elements. Sensible personal data were encrypted with a 256-bit cryptographic algorithm to avoid misuse. In order to assess the clinical value, we retrospectively analysed the tumour extension in 255 patients after radical prostatectomy. The pathology report with cMDX can represent pathological findings of the prostate in schematic styles. Such reports can be integrated into the hospital information system. "cMDX" documents can be converted into different data formats like text, graphics and PDF. Supplementary tools like cMDX Editor and an analyser tool were implemented. The graphical analysis of 255 prostatectomy specimens showed that PCa were mostly localized in the peripheral zone (Mean: 73% ± 25). 54% of PCa showed a multifocal growth pattern. cMDX can be used for routine histopathological reporting of radical prostatectomy specimens and provide data for scientific analysis.

Clinical map document based on XML (cMDX): document architecture with mapping feature for reporting and analysing prostate cancer in radical prostatectomy specimens

PubMed Central

2010-01-01

Background The pathology report of radical prostatectomy specimens plays an important role in clinical decisions and the prognostic evaluation in Prostate Cancer (PCa). The anatomical schema is a helpful tool to document PCa extension for clinical and research purposes. To achieve electronic documentation and analysis, an appropriate documentation model for anatomical schemas is needed. For this purpose we developed cMDX. Methods The document architecture of cMDX was designed according to Open Packaging Conventions by separating the whole data into template data and patient data. Analogue custom XML elements were considered to harmonize the graphical representation (e.g. tumour extension) with the textual data (e.g. histological patterns). The graphical documentation was based on the four-layer visualization model that forms the interaction between different custom XML elements. Sensible personal data were encrypted with a 256-bit cryptographic algorithm to avoid misuse. In order to assess the clinical value, we retrospectively analysed the tumour extension in 255 patients after radical prostatectomy. Results The pathology report with cMDX can represent pathological findings of the prostate in schematic styles. Such reports can be integrated into the hospital information system. "cMDX" documents can be converted into different data formats like text, graphics and PDF. Supplementary tools like cMDX Editor and an analyser tool were implemented. The graphical analysis of 255 prostatectomy specimens showed that PCa were mostly localized in the peripheral zone (Mean: 73% ± 25). 54% of PCa showed a multifocal growth pattern. Conclusions cMDX can be used for routine histopathological reporting of radical prostatectomy specimens and provide data for scientific analysis. PMID:21078179

PI-RADS v2 and ADC values: is there room for improvement?

PubMed

Jordan, Eric J; Fiske, Charles; Zagoria, Ronald; Westphalen, Antonio C

2018-03-17

To determine the diagnostic accuracy of ADC values in combination with PI-RADS v2 for the diagnosis of clinically significant prostate cancer (CS-PCa) compared to PI-RADS v2 alone. This retrospective study included 155 men whom underwent 3-Tesla prostate MRI and subsequent MR/US fusion biopsies at a single non-academic center from 11/2014 to 3/2016. All scans were performed with a surface coil and included T2, diffusion-weighted, and dynamic contrast-enhanced sequences. Suspicious findings were classified using Prostate Imaging Reporting and Data System (PI-RADS) v2 and targeted using MR/US fusion biopsies. Mixed-effect logistic regression analyses were used to determine the ability of PIRADS v2 alone and combined with ADC values to predict CS-PCa. As ADC categories are more practical in clinical situations than numeric values, an additional model with ADC categories of ≤ 800 and > 800 was performed. A total of 243 suspicious lesions were included, 69 of which were CS-PCa, 34 were Gleason score 3+3 PCa, and 140 were negative. The overall PIRADS v2 score, ADC values, and ADC categories are independent statistically significant predictors of CS-PCa (p < 0.001). However, the area under the ROC of PIRADS v2 alone and PIRADS v2 with ADC categories are significantly different in both peripheral and transition zone lesions (p = 0.026 and p = 0.03, respectively) Further analysis of the ROC curves also shows that the main benefit of utilizing ADC values or categories is better discrimination of PI-RADS v2 4 lesions. ADC values and categories help to diagnose CS-PCa when lesions are assigned a PI-RADS v2 score of 4.

Multiparametric Magnetic Resonance Imaging of the Prostate for Tumour Detection and Local Staging: Imaging in 1.5T and Histopathologic Correlation.

PubMed

Loggitsi, Dimitra; Gyftopoulos, Anastasios; Economopoulos, Nikolaos; Apostolaki, Aikaterini; Kalogeropoulos, Theodoros; Thanos, Anastasios; Alexopoulou, Efthimia; Kelekis, Nikolaos L

2017-11-01

The study sought to prospectively evaluate which technique among T2-weighted images, dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI), diffusion-weighted (DW) MRI, or a combination of the 2, is best suited for prostate cancer detection and local staging. Twenty-seven consecutive patients with biopsy-proven adenocarcinoma of the prostate underwent MRI on a 1.5T scanner with a surface phased-array coil prior radical prostatectomy. Combined anatomical and functional imaging was performed with the use of T2-weighted sequences, DCE MRI, and DW MRI. We compared the imaging results with whole mount histopathology. For the multiparametric approach, significantly higher sensitivity values, that is, 53% (95% confidence interval [CI]: 41.0-64.1) were obtained as compared with each modality alone or any combination of the 3 modalities (P < .05). The specificity for this multiparametric approach, being 90.3% (95% CI: 86.3-93.3) was not significantly higher (P < .05) as compared with the values of the combination of T2+DCE MRI, DW+DCE MRI, or DCE MRI alone. Among the 3 techniques, DCE had the best performance for tumour detection in both the peripheral and the transition zone. High negative predictive value rates (>86%) were obtained for both tumour detection and local staging. The combination of T2-weighted sequences, DCE MRI, and DW MRI yields higher diagnostic performance for tumour detection and local staging than can any of these techniques alone or even any combination of them. Copyright © 2017 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

Diffusion-prepared stimulated-echo turbo spin echo (DPsti-TSE): An eddy current-insensitive sequence for three-dimensional high-resolution and undistorted diffusion-weighted imaging.

PubMed

Zhang, Qinwei; Coolen, Bram F; Versluis, Maarten J; Strijkers, Gustav J; Nederveen, Aart J

2017-07-01

In this study, we present a new three-dimensional (3D), diffusion-prepared turbo spin echo sequence based on a stimulated-echo read-out (DPsti-TSE) enabling high-resolution and undistorted diffusion-weighted imaging (DWI). A dephasing gradient in the diffusion preparation module and rephasing gradients in the turbo spin echo module create stimulated echoes, which prevent signal loss caused by eddy currents. Near to perfect agreement of apparent diffusion coefficient (ADC) values between DPsti-TSE and diffusion-weighted echo planar imaging (DW-EPI) was demonstrated in both phantom transient signal experiments and phantom imaging experiments. High-resolution and undistorted DPsti-TSE was demonstrated in vivo in prostate and carotid vessel wall. 3D whole-prostate DWI was achieved with four b values in only 6 min. Undistorted ADC maps of the prostate peripheral zone were obtained at low and high imaging resolutions with no change in mean ADC values [(1.60 ± 0.10) × 10 -3 versus (1.60 ± 0.02) × 10 -3  mm 2 /s]. High-resolution 3D DWI of the carotid vessel wall was achieved in 12 min, with consistent ADC values [(1.40 ± 0.23) × 10 -3  mm 2 /s] across different subjects, as well as slice locations through the imaging volume. This study shows that DPsti-TSE can serve as a robust 3D diffusion-weighted sequence and is an attractive alternative to the traditional two-dimensional DW-EPI approaches. Copyright © 2017 John Wiley & Sons, Ltd.

The CYP3A4 *1B polymorphism and prostate cancer susceptibility in a Portuguese population.

PubMed

Nogal, Ana; Coelho, Ana; Catarino, Raquel; Morais, António; Lobo, Francisco; Medeiros, Rui

2007-09-01

Testosterone exposure has been implicated in prostate carcinogenesis, and genes that alter its metabolism, such as CYP3A4, have been associated with prostate cancer susceptibility. The aim of our study was to assess the relationship between the CYP3A4 *1B polymorphism and its possible role in the development of prostate cancer. DNA samples obtained from the peripheral blood cells of 414 individuals diagnosed with prostate cancer and 337 healthy male donors were used in this case-control study. The CYP3A4*1B polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism methodology. We found no statistically significant differences in the distribution of the CYP3A4*1B genotypes between cases and controls (P = 0.470; odds ratio = 1.191; 95% confidence interval=0.740-1.918), as well as after the stratification of our analysis, according to important clinicopathologic parameters of prostate cancer. Our results suggest that the CYP3A4*1B polymorphism is not associated with prostate cancer risk within the Portuguese population.

Clinicopathological importance of anterior prostate cancer in Japanese Men.

PubMed

Sato, Shun; Takahashi, Hiroyuki; Kimura, Takahiro; Egawa, Shin; Furusato, Bungo; Ikegami, Masahiro

2017-03-01

Prostate cancer of transition zone origin or anterior location has been recognized as infrequent, smaller in size and indolent, whereas, our previous report showed that transition zone/anterior cancer was frequently experienced in Japanese men. The current study was conducted to show clinicopathological characteristics of transition zone/anterior cancer. A total of 201 radical prostatectomy specimens were categorized as cancer of anterior or posterior prostate where more than two thirds of the tumor existed in the specific area. Clinicopathological characteristics including Gleason score, pathological stage, lymph node metastasis, extraprostatic extension, surgical incision into the prostate (shown as pT2+), and surgical margin status were compared between anterior and posterior cases. Cases were divided as 83, 73, and 45 of anterior, posterior cancer, and no dominance, respectively. Anterior cancers included significant numbers of high grade tumors (13/83 cases: 15.7%), which was less than posterior cancers (28.8%: 21/73). The cases in pT2+ were significantly more frequent in anterior cases than posterior ones (22.9% vs. 4.1%). No seminal vesicle invasion was shown in anterior cases. Thus, although anterior cancers are less aggressive than posterior cancers, a significant numbers of clinically important cancers were located in the anterior portion in Japanese men. © 2017 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

MRI Signal Intensity Based B-Spline Nonrigid Registration for Pre- and Intraoperative Imaging During Prostate Brachytherapy

PubMed Central

Oguro, Sota; Tokuda, Junichi; Elhawary, Haytham; Haker, Steven; Kikinis, Ron; Tempany, Clare M.C.; Hata, Nobuhiko

2009-01-01

Purpose To apply an intensity-based nonrigid registration algorithm to MRI-guided prostate brachytherapy clinical data and to assess its accuracy. Materials and Methods A nonrigid registration of preoperative MRI to intraoperative MRI images was carried out in 16 cases using a Basis-Spline algorithm in a retrospective manner. The registration was assessed qualitatively by experts’ visual inspection and quantitatively by measuring the Dice similarity coefficient (DSC) for total gland (TG), central gland (CG), and peripheral zone (PZ), the mutual information (MI) metric, and the fiducial registration error (FRE) between corresponding anatomical landmarks for both the nonrigid and a rigid registration method. Results All 16 cases were successfully registered in less than 5 min. After the nonrigid registration, DSC values for TG, CG, PZ were 0.91, 0.89, 0.79, respectively, the MI metric was −0.19 ± 0.07 and FRE presented a value of 2.3 ± 1.8 mm. All the metrics were significantly better than in the case of rigid registration, as determined by one-sided t-tests. Conclusion The intensity-based nonrigid registration method using clinical data was demonstrated to be feasible and showed statistically improved metrics when compare to only rigid registration. The method is a valuable tool to integrate pre- and intraoperative images for brachytherapy. PMID:19856437

SU-E-T-611: Photon and Neutron Peripheral Dose Ratio for Low (6 MV) and High (15 MV) Energy for Treatment Selection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Irazola, L; Sanchez-Doblado, F; Servicio de Radiofisica, Hospital Universitario Virgen Macarena, Seville

2015-06-15

Purpose: Differences between radiotherapy techniques and energies, can offer improvements in tumor coverage and organs at risk preservation. However, a more complete decision should include peripheral doses delivered to the patient. The purpose of this work is the balance of photon and neutron peripheral doses for a prostate case solved with 6 different treatment modalities. Methods: Inverse and Forward IMRT and 3D-CRT in 6 and 15 MV for a Siemens Primus linac, using the same CT data set and contours. The methodology described in [1], was used with the TNRD thermal neutron detector [2] for neutron peripheral dose estimation atmore » 7 relevant organs (colon, esophagus, stomach, liver, lung, thyroid and skin). Photon doses were estimated for these organs by terms of the algorithm proposed in [3]. Plans were optimized with the same restrictions and limited to 30 segments in the Inverse case. Results: A similar photon peripheral dose was found comparing 6 and 15 MV cases with slightly higher values of (1.9 ± 1.6) % in mean, for the 6 MV cases. Neutron presence when using 15 MV, represents an increase in peripheral dose of (18 ± 17) % in average. Due to the higher number of MU used in Inverse IMRT, an increasing of (22 ± 3) % in neutron dose is found related to Forward and 3D-CRT plans. This corresponds to photon doses within 44 and 255 mSv along the organs, for a dose prescription of 68 Gy at the isocenter. Conclusion: Neutron and photon peripheral doses for a prostate treatment planified in 6 different techniques have been analyzed. 6 MV plans are slightly more demanding in terms of photon peripheral doses. Inverse technique in 15 MV has Result to be the most demanding one in terms of total peripheral doses, including neutrons and photons.« less

Convective Water Vapor Energy for Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia.

PubMed

DeLay, Kenneth Jackson; McVary, Kevin T

2016-08-01

Benign prostatic hyperplasia (BPH) refers to proliferation of smooth muscle and epithelial cells within the transition zone of the prostate. Half of men over 40 develop histologic BPH. About half of men with BPH develop an enlarged prostate gland, called benign prostatic enlargement; among these, about half develop some degree of bladder outlet obstruction. Bladder outlet obstruction and changes in smooth muscle tone and resistance may result in lower urinary tract symptoms, including storage disturbances (such as daytime urinary urgency, frequency, and nocturia) and voiding disturbances (such as urinary hesitancy, weak urinary stream, straining to void, and prolonged voiding). Copyright © 2016 Elsevier Inc. All rights reserved.

Peripheral Retinal Changes Associated with Age-Related Macular Degeneration in the Age-Related Eye Disease Study 2: Age-Related Eye Disease Study 2 Report Number 12 by the Age-Related Eye Disease Study 2 Optos PEripheral RetinA (OPERA) Study Research Group.

PubMed

Domalpally, Amitha; Clemons, Traci E; Danis, Ronald P; Sadda, SriniVas R; Cukras, Catherine A; Toth, Cynthia A; Friberg, Thomas R; Chew, Emily Y

2017-04-01

To compare rates of peripheral retinal changes in Age-Related Eye Disease Study 2 (AREDS2) participants with at least intermediate age-related macular degeneration (AMD) with control subjects without intermediate age-related changes (large drusen). Cross-sectional evaluation of clinic-based patients enrolled in AREDS2 and a prospective study. Participants from prospective studies. The 200° pseudocolor and fundus autofluorescence (FAF) images were captured on the Optos 200 Tx Ultrawide-field device (Optos, Dunfermline, Scotland) by centering on the fovea and then steering superiorly and inferiorly. The montaged images were graded at a reading center with the images divided into 3 zones (zone 1 [posterior pole], zone 2 [midperiphery], and zone 3 [far periphery]) to document the presence of peripheral lesions. Peripheral retinal lesions: drusen, hypopigmentary/hyperpigmentary changes, reticular pseudodrusen, senile reticular pigmentary changes, cobblestone degeneration, and FAF abnormalities. A total of 484 (951 eyes) AREDS2 participants with AMD (cases) and 89 (163 eyes) controls without AMD had gradable color and FAF images. In zones 2 and 3, neovascularization and geographic atrophy (GA) were present, ranging from 0.4% to 6% in eyes of cases, respectively, and GA was present in 1% of eyes of controls. Drusen were detected in 97%, 78%, and 64% of eyes of cases and 48%, 21%, and 9% of eyes of controls in zones 2 and 3 superior and 3 inferior, respectively (P < 0.001 for all). Peripheral reticular pseudodrusen were seen in 15%. Senile reticular pigmentary change was the predominant peripheral change seen in 48% of cases and 16% of controls in zone 2 (P < 0.001). Nonreticular pigment changes were less frequent in the periphery than in the posterior pole (46% vs. 76%) and negligible in controls. Peripheral retinal changes are more prevalent in eyes with AMD than in control eyes. Drusen are seen in a majority of eyes with AMD in both the mid and far periphery, whereas pigment changes and features of advanced AMD are less frequent. Age-related macular degeneration may be more than a "macular" condition but one that involves the entire retina. Future longitudinal studies of peripheral changes in AMD and their impact on visual function may contribute to understanding AMD pathogenesis. Published by Elsevier Inc.

Correlation of contrast-enhanced MR images with the histopathology of minimally invasive thermal and cryoablation cancer treatments in normal dog prostates

NASA Astrophysics Data System (ADS)

Bouley, D. M.; Daniel, B.; Butts Pauly, K.; Liu, E.; Kinsey, A.; Nau, W.; Diederich, C. J.; Sommer, G.

2007-02-01

Magnetic Resonance Imaging (MRI) is a promising tool for visualizing the delivery of minimally invasive cancer treatments such as high intensity ultrasound (HUS) and cryoablation. We use an acute dog prostate model to correlate lesion histopathology with contrast-enhanced (CE) T1 weighted MR images, to aid the radiologists in real time interpretation of in vivo lesion boundaries and pre-existing lesions. Following thermal or cryo treatments, prostate glands are removed, sliced, stained with the vital dye triphenyl tetrazolium chloride, photographed, fixed and processed in oversized blocks for routine microscopy. Slides are scanned by Trestle Corporation at .32 microns/pixel resolution, the various lesions traced using annotation software, and digital images compared to CE MR images. Histologically, HUS results in discrete lesions characterized by a "heat-fixed" zone, in which glands subjected to the highest temperatures are minimally altered, surrounded by a rim or "transition zone" composed of severely fragmented, necrotic glands, interstitial edema and vascular congestion. The "heat-fixed" zone is non-enhancing on CE MRI while the "transition zone" appears as a bright, enhancing rim. Likewise, the CE MR images for cryo lesions appear similar to thermally induced lesions, yet the histopathology is significantly different. Glands subjected to prolonged freezing appear totally disrupted, coagulated and hemorrhagic, while less intensely frozen glands along the lesion edge are partially fragmented and contain apoptotic cells. In conclusion, thermal and cryo-induced lesions, as well as certain pre-existing lesions (cystic hyperplasia - non-enhancing, chronic prostatitis - enhancing) have particular MRI profiles, useful for treatment and diagnostic purposes.

Genome-wide DNA methylation measurements in prostate tissues uncovers novel prostate cancer diagnostic biomarkers and transcription factor binding patterns.

PubMed

Kirby, Marie K; Ramaker, Ryne C; Roberts, Brian S; Lasseigne, Brittany N; Gunther, David S; Burwell, Todd C; Davis, Nicholas S; Gulzar, Zulfiqar G; Absher, Devin M; Cooper, Sara J; Brooks, James D; Myers, Richard M

2017-04-17

Current diagnostic tools for prostate cancer lack specificity and sensitivity for detecting very early lesions. DNA methylation is a stable genomic modification that is detectable in peripheral patient fluids such as urine and blood plasma that could serve as a non-invasive diagnostic biomarker for prostate cancer. We measured genome-wide DNA methylation patterns in 73 clinically annotated fresh-frozen prostate cancers and 63 benign-adjacent prostate tissues using the Illumina Infinium HumanMethylation450 BeadChip array. We overlaid the most significantly differentially methylated sites in the genome with transcription factor binding sites measured by the Encyclopedia of DNA Elements consortium. We used logistic regression and receiver operating characteristic curves to assess the performance of candidate diagnostic models. We identified methylation patterns that have a high predictive power for distinguishing malignant prostate tissue from benign-adjacent prostate tissue, and these methylation signatures were validated using data from The Cancer Genome Atlas Project. Furthermore, by overlaying ENCODE transcription factor binding data, we observed an enrichment of enhancer of zeste homolog 2 binding in gene regulatory regions with higher DNA methylation in malignant prostate tissues. DNA methylation patterns are greatly altered in prostate cancer tissue in comparison to benign-adjacent tissue. We have discovered patterns of DNA methylation marks that can distinguish prostate cancers with high specificity and sensitivity in multiple patient tissue cohorts, and we have identified transcription factors binding in these differentially methylated regions that may play important roles in prostate cancer development.

Reliability of Pentacam HR Thickness Maps of the Entire Cornea in Normal, Post-Laser In Situ Keratomileusis, and Keratoconus Eyes.

PubMed

Xu, Zhe; Peng, Mei; Jiang, Jun; Yang, Chun; Zhu, Weigen; Lu, Fan; Shen, Meixiao

2016-02-01

To measure the repeatability and reproducibility of Pentacam HR system thickness maps for the entire cornea in normal, post-laser in situ keratomileusis (post-LASIK), and keratoconus (KC) eyes. Reliability study. Sixty normal subjects (60 eyes), 30 post-LASIK subjects (60 eyes), and 14 KC patients (27 eyes) were imaged with the Pentacam HR system by 2 well-trained operators. For pachymetry the cornea was divided into 4 zones: a central zone (2-mm diameter) and concentric pericentral zone (2-5 mm), transitional zone (5-7 mm), and peripheral zone (7-10 mm). The 3 concentric zones were subdivided into 8 sectors. Intraobserver repeatability and interobserver reproducibility of entire corneal thickness maps were tested by the repeatability and reproducibility coefficients, intraclass correlation coefficients, coefficient of variation, and 95% limits of agreement. From central to peripheral zones, the precision of corneal thickness measurements became gradually smaller. Central zone repeatability and reproducibility were the best in the normal, post-LASIK, and KC groups. The peripheral superior sectors showed poorer repeatability and reproducibility for all subjects. The intraobserver repeatability and interobserver reproducibility for all zones were ≤19.3 μm, ≤22.1 μm, and ≤20.7 μm, in the normal, post-LASIK, and KC groups, respectively. The intraobserver and interobserver coefficients of variation for all zones were ≤1.3%, ≤1.6%, and ≤1.6% for all 3 groups. Pentacam HR system pachymetry of the entire cornea provided good precision in normal, post-LASIK, and KC corneas. Thickness measurements in the peripheral cornea should be interpreted with caution in abnormal corneas after surgery or with diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of dietary selenium and cancer cell xenograft on peripheral T and B lymphocytes in adult nude mice.

PubMed

Cheng, Wen-Hsing; Holmstrom, Alexandra; Li, Xiangdong; Wu, Ryan T Y; Zeng, Huawei; Xiao, Zhengguo

2012-05-01

Selenium (Se) is known to regulate tumorigenesis and immunity at the nutritional and supranutritional levels. Because the immune system provides critical defenses against cancer and the athymic, immune-deficient NU/J nude mice are known to gradually develop CD8(+) and CD4(+) T cells, we investigated whether B and T cell maturation could be modulated by dietary Se and by tumorigenesis in nude mice. Fifteen homozygous nude mice were fed a Se-deficient, Torula yeast basal diet alone (Se-) or supplemented with 0.15 (Se+) or 1.0 (Se++) mg Se/kg (as Na(2)SeO(4)) for 6 months, followed by a 7-week time course of PC-3 prostate cancer cell xenograft (2 × 10(6) cells/site, 2 sites/mouse). Here, we show that peripheral B cell levels decreased in nude mice fed the Se -  or Se++ diet and the CD4(+) T cell levels increased in mice fed the Se++ diet. During the PC-3 cell tumorigenesis, dietary Se status did not affect peripheral CD4(+) or CD8(+) T cells in nude mice whereas mice fed with the Se++ diet appeared to exhibit greater peripheral CD25(+)CD4(+) T cells on day 9. Dietary Se status did not affect spleen weight in nude mice 7 weeks after the xenograft. Spleen weight was associated with frequency of peripheral CD4(+), but not CD8(+) T cells. Taken together, dietary Se at the nutritional and supranutritional levels regulates peripheral B and T cells in adult nude mice before and after xenograft with PC-3 prostate cancer cells.

Increased oncogenic microRNA-18a expression in the peripheral blood of patients with prostate cancer: A potential novel non-invasive biomarker.

PubMed

Al-Kafaji, Ghada; Al-Naieb, Ziad Tariq; Bakhiet, Moiz

2016-02-01

MicroRNAs have been demonstrated to be stably detectable in peripheral blood, thus representing important sources of non-invasive biomarkers of various diseases, including cancer. Recently, microRNA-18a (miR-18a) has been revealed to be highly expressed in prostate cancer (PC) tissues, acting as an oncogenic miRNA. The present study evaluated miR-18a expression in the peripheral blood of patients with PC, patients with benign prostatic hyperplasia (BPH), and healthy individuals, to assess the feasibility of using peripheral blood miR-18a as a potential non-invasive biomarker for PC. Total RNA was extracted from peripheral whole blood samples from 24 PC patients, 24 BPH patients and 23 healthy control individuals. The expression of miR-18a was assessed by reverse transcription quantitative polymerase chain reaction. The results revealed that miR-18a expression was significantly higher in PC patients than in BPH patients and healthy controls [fold change (mean ± standard deviation), 5.5±1.4 for PC, 1.5±0.5 for BPH and 1.2±0.6 for controls; P<0.005]. Higher miR-18a expression was strongly associated with PC [odds ratio (OR), 4.602; 95% confidence interval (CI), 2.194-9.654; P=0.001], but was not significantly associated with BPH (OR, 1.2; 95% CI, 0.7-2.02; P=0.332). Despite the small number of patients, which limits the statistical power of the study, higher miR-18a expression was observed to be significantly correlated with certain clinicopathological parameters, including Gleason score >7 and pathological tumor stage 3/4 (P<0.005). A receiver operating characteristic (ROC) analysis revealed that miR-18a discriminated PC patients from BPH patients and healthy controls [area under the curve (AUC), 0.805; 95% CI, 0.704-0.906). Furthermore, use of the ROC curve to discriminate PC from BPH patients yielded an AUC of 0.878 (95% CI, 0.783-0.972). In summary, the present results indicate that miR-18a expression is significantly increased in peripheral blood of patients with PC compared with that of BPH patients and healthy individuals, and that higher miR-18a expression is associated with progression of PC. Peripheral blood oncogenic miR-18a may serve as a potential novel non-invasive biomarker for PC that also facilitates discrimination between PC and BPH.

Elevated hardness of peripheral gland on real-time elastography is an independent marker for high-risk prostate cancers.

PubMed

Zhang, Qi; Yao, Jing; Cai, Yehua; Zhang, Limin; Wu, Yishuo; Xiong, Jingyu; Shi, Jun; Wang, Yuanyuan; Wang, Yi

2017-12-01

To examine the role of quantitative real-time elastography (RTE) features on differentiation between high-risk prostate cancer (PCA) and non-high-risk prostatic diseases in the initial transperineal biopsy setting. We retrospectively included 103 patients with suspicious PCA who underwent both RTE and initial transperineal prostate biopsy. Patients were grouped into high-risk and non-high-risk categories according to the D'Amico's risk stratification. With computer assistance based on MATLAB programming, three features were extracted from RTE, i.e., the median hardness within peripheral gland (PG) (H med ), the ratio of the median hardness within PG to that outside PG (H ratio ), and the ratio of the hard area within PG to the total PG area (H ar ). A multiple regression model incorporating an RTE feature, age, transrectal ultrasound finding, and prostate volume was used to identify markers for high-risk PCA. Forty-seven patients (45.6%) were diagnosed with PCA and 34 (33.0%) were diagnosed with high-risk PCA. Three RTE features were all statistically higher in high-risk PCA than in non-high-risk diseases (p < 0.001), indicating that the PGs in high-risk PCA patients were harder than those in non-high-risk patients. A high H ratio , high age, and low prostate volume were found to be independent markers for PCAs (p < 0.05), among which the high H ratio was the only independent marker for high-risk PCAs (p = 0.012). When predicting high-risk PCAs, the multiple regression achieved an area under receiver operating characteristic curve of 0.755, sensitivity of 73.5%, and specificity of 71.0%. The elevated hardness of PG identified high-risk PCA and served as an independent marker of high-risk PCA. As a non-invasive imaging modality, the RTE could be potentially used in routine clinical practice for the detection of high-risk PCA to decrease unnecessary biopsies and reduce overtreatment.

High intensity focused ultrasound (HIFU).

PubMed

Barkin, Jack

2011-04-01

Curative treatments for localized prostate cancer, from least invasive to most invasive, include brachytherapy, cryosurgery, three-dimensional conformal radiation therapy, external beam radiation therapy, and radical prostatectomy. A patient with localized, low risk or intermediate risk prostate cancer who is diagnosed at an early age and receives one of these treatments has only an approximately 50% chance of maintaining an undetectable prostate-specific antigen (PSA) level, good spontaneous erections, and total continence by 5 years after treatment. This article discusses transrectal high intensity focused ultrasound (HIFU) treatment of localized prostate cancer using the Sonablate 500 (Focus Surgery, Indianapolis, IN, USA) device, which the author has adopted in favor of the Ablatherm (EDAP, TMS S. A., Lyons, France) device, the other HIFU device approved for use in Canada. Characteristics of the ideal prostate cancer include stage T1-T2b, less than 40 cc in size, and with an anterior-posterior dimension of up to 35 mm high. The anterior zone of the prostate is treated before the posterior zone. The procedure involves 2 to 3 second bursts of ultrasound energy, followed by 3 second cooling cycles. In each treatment lesion, the physician achieves a temperature of 100 C at the focal point. The device allows for real-time visualization of tissue response following the delivery of ultrasound energy. HIFU is a minimally invasive, outpatient treatment for localized prostate cancer that provides similar short term and medium term cure rates and considerably less morbidity and side effects than other treatments. Although the effectiveness of HIFU has not yet been demonstrated in large, long term studies, this treatment option should be discussed with patients who have just been diagnosed with low risk or intermediate risk prostate cancer and desire aggressive, noninvasive, curative therapy, with potentially a lower incidence of side effects compared to conventional therapy.

TGFβ1 alters androgenic metabolites and hydroxysteroid dehydrogenase enzyme expression in human prostate reactive stromal primary cells: Is steroid metabolism altered by prostate reactive stromal microenvironment?

PubMed Central

Piao, Yun-shang; Wiesenfeld, Paddy; Sprando, Robert; Arnold, Julia T.

2013-01-01

The inflammatory tissue microenvironment can be an active promoter in preneoplastic cancer lesions. Altered steroid hormone metabolism as induced by the inflammatory microenvironment may contribute to epithelial cancer progression. Dehydroepiandrosterone sulfate (DHEAS) is the most abundant endogenous steroid hormone present in human serum and can be metabolized to DHEA, androgens and/or estrogens in peripheral tissues. We have previously reported that TGFβ1-induced reactive prostate stromal cells increase DHEA metabolism to active androgens and alter prostate cancer cell gene expression. While much of the focus on mechanisms of prostate cancer and steroid metabolism is in the epithelial cancer cells, this study focuses on TGFβ1-induced effects on DHEA metabolic pathways and enzymes in human prostate stromal cells. In DHEA-treated primary prostate stromal cells, TGFβ1 produced time- and dose-dependent increases in metabolism of DHEA to androstenedione and testosterone. Also TGFβ1-treated prostate stromal cells exhibited changes in the gene expression of enzymes involved in steroid metabolism including up-regulation of 3β hydroxysteroid dehydrogenase (HSD), and down-regulation of 17βHSD5, and 17βHSD2. These studies suggest that reactive prostate stroma and the inflammatory microenvironment may contribute to altered steroid metabolism and increased intratumoral androgens. PMID:23770322

TGFβ1 alters androgenic metabolites and hydroxysteroid dehydrogenase enzyme expression in human prostate reactive stromal primary cells: Is steroid metabolism altered by prostate reactive stromal microenvironment?

PubMed

Piao, Yun-shang; Wiesenfeld, Paddy; Sprando, Robert; Arnold, Julia T

2013-11-01

The inflammatory tissue microenvironment can be an active promoter in preneoplastic cancer lesions. Altered steroid hormone metabolism as induced by the inflammatory microenvironment may contribute to epithelial cancer progression. Dehydroepiandrosterone sulfate (DHEAS) is the most abundant endogenous steroid hormone present in human serum and can be metabolized to DHEA, androgens and/or estrogens in peripheral tissues. We have previously reported that TGFβ1-induced reactive prostate stromal cells increase DHEA metabolism to active androgens and alter prostate cancer cell gene expression. While much of the focus on mechanisms of prostate cancer and steroid metabolism is in the epithelial cancer cells, this study focuses on TGFβ1-induced effects on DHEA metabolic pathways and enzymes in human prostate stromal cells. In DHEA-treated primary prostate stromal cells, TGFβ1 produced time- and dose-dependent increases in metabolism of DHEA to androstenedione and testosterone. Also TGFβ1-treated prostate stromal cells exhibited changes in the gene expression of enzymes involved in steroid metabolism including up-regulation of 3β hydroxysteroid dehydrogenase (HSD), and down-regulation of 17βHSD5, and 17βHSD2. These studies suggest that reactive prostate stroma and the inflammatory microenvironment may contribute to altered steroid metabolism and increased intratumoral androgens. Published by Elsevier Ltd.

Activation of innate immunity by prostate specific antigen (PSA).

PubMed

Kodak, James A; Mann, Dean L; Klyushnenkova, Elena N; Alexander, Richard B

2006-11-01

Prostate specific antigen (PSA) is a serine protease secreted by the prostatic epithelium. The only known function of the protein is to cleave seminogelin. We wished to determine if PSA activated peripheral blood mononuclear cells (PBMC). PBMC and selected sub-populations were cultured with purified PSA. Secretion of IFNgamma was measured by cytokine capture flow cytometry and enzyme-linked immunosorbent assay. We observed secretion of IFNgamma and a proliferative response in PBMC cultured with PSA. We found that NK cells were the source of the IFNgamma but NK cells were not directly stimulated by PSA. Rather, a soluble factor secreted primarily by CD14 monocytes in response to PSA stimulated NK cells to secrete IFNgamma. PSA induces a pro-inflammatory response that results in the secretion of INFgamma by NK cells. The presence of large amounts of PSA could contribute to the common finding of inflammatory infiltrates in the prostate.

Minimally invasive ultrasound thermal therapy with MR thermal monitoring and guidance

NASA Astrophysics Data System (ADS)

Diederich, Chris J.; Stafford, R. Jason; Price, Roger E.; Nau, William H.; Tyreus, Per Daniel; Rivera, Belinda; Schomer, Donald; Olsson, Lars; Hazle, John D.

2001-06-01

In this study both transurethral and interstitial ultrasound thermal therapy were applied to thermally coagulate targeted portions of the canine prostate or brain and implanted TVT tumors while using MRI-based thermal mapping techniques to monitor the therapy. MRI was also used for target definition, positioning of the applicator, and evaluation of target viability post-therapy. The complex phase-difference mapping technique using an iGE-EPI sequence with lipid suppression was used for determining temperature elevations within the in vivo prostate or brain and surrounding structures. Calculated temperature distributions, thermal dose exposures, T2-wieghted & T1-contrast enhanced images, gross inspection, and histology of sectioned prostates and brains were in good agreement with each other in defining destroyed tissue zones. Interstitial and transurethral ultrasound applicators produce directed zones of thermal coagulation within targeted tissue and implanted tumor, which can be accurately monitored and evaluated by MRI.

Role of monocyte-lineage cells in prostate cancer cell invasion and tissue factor expression.

PubMed

Lindholm, Paul F; Lu, Yi; Adley, Brian P; Vladislav, Tudor; Jovanovic, Borko; Sivapurapu, Neela; Yang, Ximing J; Kajdacsy-Balla, André

2010-11-01

Tissue factor (TF) is a cell surface glycoprotein intricately related to blood coagulation and inflammation. This study was performed to investigate the role of monocyte-lineage cells in prostate cancer cell TF expression and cell invasion. Prostate cancer cell invasion was tested with and without added peripheral blood monocytes or human monocyte-lineage cell lines. TF neutralizing antibodies were used to determine the TF requirement for prostate cancer cell invasion activity. Immunohistochemistry was performed to identify prostate tissue CD68 positive monocyte-derived cells and prostate epithelial TF expression. Co-culture of PC-3, DU145, and LNCaP cells with isolated human monocytes significantly stimulated prostate cancer cell invasion activity. TF expression was greater in highly invasive prostate cancer cells and was induced in PC-3, DU145, and LNCaP cells by co-culture with U-937 cells, but not with THP-1 cells. TF neutralizing antibodies inhibited PC-3 cell invasion in co-cultures with monocyte-lineage U-937 or THP-1 cells. Prostate cancer tissues contained more CD68 positive cells in the stroma and epithelium (145 ± 53/mm(2)) than benign prostate (108 ± 31/mm(2)). Samples from advanced stage prostate cancer tended to contain more CD68 positive cells when compared with lower stage lesions. Prostatic adenocarcinoma demonstrated significantly increased TF expression compared with benign prostatic epithelium. This study shows that co-culture with monocyte-lineage cells induced prostate cancer cell invasion activity. PC-3 invasion and TF expression was induced in co-culture with U-937 cells and partially inhibited with TF neutralizing antibodies.

Prostate-specific antigen 1.5-4.0 ng/mL: a diagnostic challenge and danger zone.

PubMed

Crawford, E David; Moul, Judd W; Rove, Kyle O; Pettaway, Curtis A; Lamerato, Lois E; Hughes, Alexa

2011-12-01

What's known on the subject? and What does the study add? Large population screening trials like the ERSPC, PCPT and PLCO have noted that men with seemingly low PSA (even as low as 0.5 ng/dL) still can have prostate cancer. Despite these findings, PSA is still predominantly used as a current indicator for possible presence of prostate cancer rather than also serving as a prognostic marker. This study examines a larger number of men in a diverse US population to determine the prognostic value of a man's baseline or first PSA. • To assess the value of a PSA threshold of 1.5 ng/mL as a predictor of increased prostate cancer risk over a four-year period based on a man's first PSA test, including racial differences. • To review the risk of progression of benign prostatic hyperplasia (BPH) based on a similar PSA threshold. • A retrospective review involving 21,502 men from a large Midwestern health system was performed. • Men at least 40 years old with baseline PSA values between 0 and 4.0 ng/mL and at least four years of follow-up after initial PSA test were included. • Optimal PSA threshold and predictive value of PSA for development of prostate cancer were calculated. • Prostate cancer rates were 15-fold higher in patients with PSA ≥1.5 ng/mL vs patients with PSA <1.5 ng/mL (7.85% vs 0.51%). • African American patients with baseline PSA <1.5 ng/mL faced prostate cancer rates similar to the whole study population (0.54% vs 0.51%, respectively), while African American patients with PSA 1.5-4.0 ng/mL faced a 19-fold increase in prostate cancer. • Both Caucasian and African American men with baseline PSA values between 1.5 and 4.0 ng/mL are at increased risk for future prostate cancer compared with those who have an initial PSA value below the 1.5 ng/mL threshold. • Based on a growing body of literature and this analysis, it is recommended that a first PSA test threshold of 1.5 ng/mL and above, or somewhere between 1.5 and 4.0 ng/mL, represent the Early-Warning PSA Zone (EWP Zone). • This should serve to inform patients and clinicians alike to future clinical activities with respect to prostate cancer and BPH. © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

Quantitative analysis of peripheral vasculitis, ischemia, and vascular leakage in uveitis using ultra-widefield fluorescein angiography.

PubMed

Karampelas, Michael; Sim, Dawn A; Chu, Colin; Carreno, Ester; Keane, Pearse A; Zarranz-Ventura, Javier; Westcott, Mark; Lee, Richard W J; Pavesio, Carlos E

2015-06-01

To investigate the relationships between peripheral vasculitis, ischemia, and vascular leakage in uveitis using ultra-widefield fluorescein angiography (FA). Cross-sectional, consecutive case series. Consecutive ultra-widefield FA images were collected from 82 uveitis patients (82 eyes) in a single center. The extent of peripheral vasculitis, capillary nonperfusion, and vessel leakage were quantified. Parameters included: (1) foveal avascular zone area and macular leakage, (2) peripheral diffuse capillary leakage and ischemia, (3) peripheral vasculitis, and (4) leakage from neovascularization. Central macular thickness measurements were derived with optical coherence tomography. Main outcome measures were correlations between central and peripheral fluorangiographic changes as well as associations between visual function, ultra-widefield FA-derived metrics, and central macular thickness. Although central leakage was associated with peripheral leakage (r = 0.553, P = .001), there was no association between foveal avascular zone size and peripheral ischemia (r = 0.114, P = .324), regardless of the underlying uveitic diagnosis. Peripheral ischemia was, however, correlated to neovascularization-related leakage (r = 0.462, P = .001) and focal vasculitis (r = 0.441, P = .001). Stepwise multiple regression analysis revealed that a poor visual acuity was independently associated with foveal avascular zone size and central macular thickness (R(2)-adjusted = 0.45, P = .001). We present a large cohort of patients with uveitis imaged with ultra-widefield FA and further describe novel methods for quantification of peripheral vascular pathology, in an attempt to identify visually significant parameters. Although we observed that relationships exist between peripheral vessel leakage, vasculitis, and ischemia, it was only macular ischemia and increased macular thickness that were independently associated with a reduced visual acuity. Copyright © 2015 Elsevier Inc. All rights reserved.

A three-gene panel on urine increases PSA specificity in the detection of prostate cancer.

PubMed

Rigau, Marina; Ortega, Israel; Mir, Maria Carmen; Ballesteros, Carlos; Garcia, Marta; Llauradó, Marta; Colás, Eva; Pedrola, Núria; Montes, Melania; Sequeiros, Tamara; Ertekin, Tugce; Majem, Blanca; Planas, Jacques; Ruiz, Anna; Abal, Miguel; Sánchez, Alex; Morote, Juan; Reventós, Jaume; Doll, Andreas

2011-12-01

Several studies have demonstrated the usefulness of monitoring an RNA transcript, such as PCA3, in post-prostate massage (PM) urine for increasing the specificity of prostate-specific antigen (PSA) in the detection of prostate cancer (PCa). However, a single marker may not necessarily reflect the multifactorial nature of PCa. We analyzed post-PM urine samples from 154 consecutive patients, who presented for prostate biopsies because of elevated serum PSA (>4 ng/ml) and/or abnormal digital rectal exam. We tested whether the putative PCa biomarkers PSMA, PSGR, and PCA3 could be detected by quantitative real-time PCR in post-PM urine sediment. We combined these findings to test if a combination of these biomarkers could improve the specificity of actual diagnosis. Afterwards, we specifically tested our model for clinical usefulness in the PSA diagnostic "gray zone" (4-10 ng/ml) on a target subset of 82 men with no prior biopsy. By univariate analysis, we found that the PSMA, PSGR, and PCA3 scores were significant predictors of PCa. Using a multiplex model, the area under the multi receiver-operating characteristic curve was 0.74 versus 0.82 in the diagnostic "gray zone." Fixing the sensitivity at 96%, we obtained a specificity of 34% and 50% in the gray zone. Taken together, these results provide a strategy for the development of a more accurate model for PCa diagnosis. In the future, a multiplexed, urine-based diagnostic test for PCa with a higher specificity, but the same sensitivity as the serum-PSA test, could be used to determine better which patients should undergo biopsy. Copyright © 2011 Wiley Periodicals, Inc.

MR Elastography and Diffusion-Weighted Imaging of ex-vivo Prostate Cancer: quantitative comparison to histopathology

PubMed Central

Nir, Guy; Gagnon, Louis O.; Ischia, Joseph; Jones, Edward C.; Chang, Silvia; Yung, Andrew; Honarvar, Mohammad; Fazli, Ladan; Goldenberg, Larry; Rohling, Robert; Sinkus, Ralph; Kozlowski, Piotr

2017-01-01

Purpose 1) to develop a Magnetic Resonance Elastography (MRE) system for imaging of the ex-vivo human prostate, 2) to assess the diagnostic power of mono-frequency and multi-frequency MRE and diffusion weighted imaging (DWI) alone and combined as correlated with histopathology in a patient study. Materials and Methods An electromagnetic driver was designed specifically for MRE studies in small-bore MR scanners. Ex-vivo prostate specimens (post-fixation) of fourteen patients who underwent radical prostatectomy were imaged with MRE at 7 T (nine cases had DWI). In six patients, the MRE examination was performed at three frequencies (600, 800, 1000 Hz) to extract the power-law exponent Gamma. The images were registered to wholemount pathology slides marked with the Gleason score. The areas under the Receiver-Operator-Characteristic curves (AUC) were calculated. Results The methods were validated in a phantom study and demonstrated that (i) the driver does not interfere with the acquisition process, (ii) the driver can generate amplitudes greater than 100 μm for frequencies <1kHz. In the quantitative study, cancerous tissue with Gleason score at least 3+3 was distinguished from normal tissue in the peripheral zone with an average AUC of 0.75 (Gd), 0.75 (Gl), 0.70 (Gamma-Gd), 0.68 (ADC), and 0.82 (Gd+Gl+ADC). The differentiation between PZ and CG was modest for Gd (p<0.07), Gl (p<0.06) but not significant for Gamma (p<0.2). A correlation of 0.4 kPa/h was found between fixation time of the prostate specimen to the stiffness of the tissue which could affect the diagnostic power results. Conclusion DWI and MRE may provide complementary information; in fact MRE performed better than ADC in distinguishing normal from cancerous tissue in some cases. Multi-frequency (Gamma) analysis did not appear to improve the results. However, in light of effect of tissue fixation, the clinical implication of our results may be inconclusive and more experiments are needed. PMID:25382459

Induction at high incidence of ductal prostate adenocarcinomas in NBL/Cr and Sprague-Dawley Hsd:SD rats treated with a combination of testosterone and estradiol-17 beta or diethylstilbestrol.

PubMed

Bosland, M C; Ford, H; Horton, L

1995-06-01

This study determined the incidence of prostate adenocarcinoma following long-term treatment of NBL and Sprague-Dawley rats with estradiol-17 beta or diethylstilbestrol (DES) plus testosterone and it defined the origin of these tumors. NBL and Sprague-Dawley rats were treated with two Silastic tubing implants (i.d. 1.6 mm, o.d. 3.2 mm) containing a 2 cm long filling of testosterone and one implant containing a 1 cm long filling of estradiol-17 beta or DES. Control animals received empty implants. Treated animals were killed when moribund and controls were killed at 91 (NBL) or 75 (Sprague-Dawley) weeks after initiation of treatment and accessory sex glands were sampled for histopathological examination of multiple step sections. Prostatic adenocarcinoma occurred in 100% of NBL rats after treatment with estradiol-17 beta or DES plus testosterone for 44 and 59 weeks (group means) respectively. Adenocarcinoma incidences were lower in Sprague-Dawley rats. The adenocarcinomas were small, microscopic, invasive tumors and they were spatially closely associated with the periurethral ducts of the dorsal, lateral and/or anterior (= coagulating gland) prostate, but never with the ducts of the ventral lobe and seminal vesicles. One adenocarcinoma was of uncertain origin. Duct-acinar dysplastic lesions occurred in the periphery of the dorsal and lateral prostate of all hormone-treated NBL and many Sprague-Dawley rats, but did not appear to give rise to carcinoma. Although some adenocarcinomas were contiguous with dysplastic ducts of the peripheral dorsolateral prostate, the main mass of these neoplasms was located in the periurethral area. Also, most adenocarcinomas were only connected with the periurethral ducts, in which atypical hyperplasia occurred following hormone treatment for 36 weeks or longer. Thus atypical hyperplasia of the periurethral prostate ducts, but not peripheral duct-acinar dysplasia, appeared to be the likely precursor of the induced carcinomas. Testosterone plus DES, but not estradiol-17 beta, induced marked dysplasia-like lesions in the acini of the ventral prostate of all NBL and many Sprague-Dawley rats. These lesions had progressed to carcinoma in situ (or adenoma) in 46% of NBL rats.

Hair-cell counts and afferent innervation patterns in the cristae ampullares of the squirrel monkey with a comparison to the chinchilla

NASA Technical Reports Server (NTRS)

Fernandez, C.; Lysakowski, A.; Goldberg, J. M.

1995-01-01

1. The numbers of type I and type II hair cells were estimated by dissector techniques applied to semithin, stained sections of the horizontal, superior, and posterior cristae in the squirrel monkey and the chinchilla. 2. The crista in each species was divided into concentrically arranged central, intermediate, and peripheral zones of equal areas. The three zones can be distinguished by the sizes of individual hair cells and calyx endings, by the density of hair cells, and by the relative frequency of calyx endings innervating single or multiple type I hair cells. 3. In the monkey crista, type I hair cells outnumber type II hair cells by a ratio of almost 3:1. The ratio decreases from 4-5:1 in the central and intermediate zones to under 2:1 in the peripheral zone. For the chinchilla, the ratio is near 1:1 for the entire crista and decreases only slightly between the central and peripheral zones. 4. Nerve fibers supplying the cristae in the squirrel monkey were labeled by extracellular injections of horseradish peroxidase (HRP) into the vestibular nerve. Peripheral terminations of individual fibers were reconstructed and related to the zones of the cristae they innervated and to the sizes of their parent axons. Results were similar for the horizontal, superior, and posterior cristae. 5. Axons seldom bifurcate below the neuroepithelium. Most fibers begin branching shortly after crossing the basement membrane. Their terminal arbors are compact, usually extending no more than 50-100 microns from the parent exon. A small number of long intraepithelial fibers enter the intermediate and peripheral zones of the cristae near its base, then run unbranched for long distances through the neuroepithelium to reach the central zone. 6. There are three classes of afferent fibers innervating the monkey crista. Calyx fibers terminate exclusively on type I hair cells, and bouton fibers end only on type II hair cells. Dimorphic fibers provide a mixed innervation, including calyx endings to type I hair cells and bouton endings to type II hair cells. Long intraepithelial fibers are calyx and dimorphic units, whose terminal fields are similar to those of other fibers. The central zone is innervated by calyx and dimorphic fibers; the peripheral zone, by bouton and dimorphic fibers; and the intermediate zone, by all three kinds of fibers. Internal (axon) diameters are largest for calyx fibers and smallest for bouton fibers. Of the entire sample of 286 labeled fibers, 52% were dimorphic units, 40% were calyx units, and 8% were bouton units.(ABSTRACT TRUNCATED AT 400 WORDS).

Quantitation of circulating tumor cells in blood samples from ovarian and prostate cancer patients using tumor-specific fluorescent ligands.

PubMed

He, Wei; Kularatne, Sumith A; Kalli, Kimberly R; Prendergast, Franklyn G; Amato, Robert J; Klee, George G; Hartmann, Lynn C; Low, Philip S

2008-10-15

Quantitation of circulating tumor cells (CTCs) can provide information on the stage of a malignancy, onset of disease progression and response to therapy. In an effort to more accurately quantitate CTCs, we have synthesized fluorescent conjugates of 2 high-affinity tumor-specific ligands (folate-AlexaFluor 488 and DUPA-FITC) that bind tumor cells >20-fold more efficiently than fluorescent antibodies. Here we determine whether these tumor-specific dyes can be exploited for quantitation of CTCs in peripheral blood samples from cancer patients. A CTC-enriched fraction was isolated from the peripheral blood of ovarian and prostate cancer patients by an optimized density gradient centrifugation protocol and labeled with the aforementioned fluorescent ligands. CTCs were then quantitated by flow cytometry. CTCs were detected in 18 of 20 ovarian cancer patients (mean 222 CTCs/ml; median 15 CTCs/ml; maximum 3,118 CTCs/ml), whereas CTC numbers in 16 gender-matched normal volunteers were negligible (mean 0.4 CTCs/ml; median 0.3 CTCs/ml; maximum 1.5 CTCs/ml; p < 0.001, chi(2)). CTCs were also detected in 10 of 13 prostate cancer patients (mean 26 CTCs/ml, median 14 CTCs/ml, maximum 94 CTCs/ml) but not in 18 gender-matched healthy donors (mean 0.8 CTCs/ml, median 1, maximum 3 CTC/ml; p < 0.0026, chi(2)). Tumor-specific fluorescent antibodies were much less efficient in quantitating CTCs because of their lower CTC labeling efficiency. Use of tumor-specific fluorescent ligands to label CTCs in peripheral blood can provide a simple, accurate and sensitive method for determining the number of cancer cells circulating in the bloodstream.

Hi-tech of the prostate: interstitial laser coagulation of benign prostatic hypertrophy

NASA Astrophysics Data System (ADS)

Muschter, Rolf; Hofstetter, Alfons G.; Hessel, Stefan F. F.; Keiditsch, Ernst; Rothenberger, Karl-Heinz; Schneede, Peter; Frank, Klaus H.

1992-06-01

We report on the new technique of interstitial laser coagulation of the prostate (ILCP) in the treatment of benign prostatic hyperplasia (BPH). Basic experiments by use of a Nd:YAG laser in combination with a newly designed fiber tip homogeneously distributing the laser irradiation have been performed in potato, muscle, liver, and surgically removed human BPH-tissue to determine the volume of coagulation. The coagulation zone surrounding the probe was well defined and homogeneous. The size was dependent on laser power and irradiation time. Carbonization was never present except in darker tissues irradiated with high energy. Volume and time resolved measurements correlated well with the size of coagulation. 10 W and 5 minutes, for example, resulted in a coagulation zone of 17 X 15 mm. Comparable results have been seen in in-vivo experiments in surgically exposed canine prostates. Specimen for macroscopic and microscopic examination were taken immediately after treatment and after 5 and 35 days. The well demarked coagulation necrosis of the early stage resulted in cystic degeneration and fibrosis in the later stages. This was combined with shrinkage and reduction in volume. The urothelium of the urethra, the external sphincter and the rectum showed no damage. Until now, 15 patients suffering from obstructive symptoms due to BPH have been treated with interstitial laser coagulation. The probes were inserted from the perineum into the center of each lateral lobe of the prostate by transrectal ultrasound guidance, while the median lobe was treated by urethroscopic guidance, while the median lobe was treated by urethroscopic control. Dependent on the size of the prostate irradiation, time was 5 to 10 minutes per lobe at a power setting of 5 to 10 W.

Splenic marginal zone lymphoma.

PubMed

Piris, Miguel A; Onaindía, Arantza; Mollejo, Manuela

Splenic marginal zone lymphoma (SMZL) is an indolent small B-cell lymphoma involving the spleen and bone marrow characterized by a micronodular tumoral infiltration that replaces the preexisting lymphoid follicles and shows marginal zone differentiation as a distinctive finding. SMZL cases are characterized by prominent splenomegaly and bone marrow and peripheral blood infiltration. Cells in peripheral blood show a villous cytology. Bone marrow and peripheral blood characteristic features usually allow a diagnosis of SMZL to be performed. Mutational spectrum of SMZL identifies specific findings, such as 7q loss and NOTCH2 and KLF2 mutations, both genes related with marginal zone differentiation. There is a striking clinical variability in SMZL cases, dependent of the tumoral load and performance status. Specific molecular markers such as 7q loss, p53 loss/mutation, NOTCH2 and KLF2 mutations have been found to be associated with the clinical variability. Distinction from Monoclonal B-cell lymphocytosis with marginal zone phenotype is still an open issue that requires identification of precise and specific thresholds with clinical meaning. Copyright © 2016 Elsevier Ltd. All rights reserved.

Biomarkers of Selenium Action in Prostate Cancer

DTIC Science & Technology

2006-03-01

without BPH) transition zone tissue of a 42-year-old man ac- cording to previously described methods [4]. The pre- sence of contaminating epithelial...protein secreted by cells using a sensitive ELISA method . Replicating the conditions used for the microarray analyses, cells were fed fresh medium...4 Introduction Biomarkers of selenium actions in prostate tissue would be of great value in stratifying patients

A short-term intervention with selenium affects expression of genes implicated in the epithelial-to-mesenchymal transition in the prostate

PubMed Central

Kok, Dieuwertje E.G.; Kiemeney, Lambertus A.L.M.; Verhaegh, Gerald W.; Schalken, Jack A.; van Lin, Emile N.J.T.; Michiel Sedelaar, J.P.; Alfred Witjes, J.; Hulsbergen - van de Kaa, Christina A.; van't Veer, Pieter; Kampman, Ellen; Afman, Lydia A.

2017-01-01

In parallel with the inconsistency in observational studies and chemoprevention trials, the mechanisms by which selenium affects prostate cancer risk have not been elucidated. We conducted a randomized, placebo-controlled trial to examine the effects of a short-term intervention with selenium on gene expression in non-malignant prostate tissue. Twenty-three men received 300 μg selenium per day in the form of selenized yeast (n=12) or a placebo (n=11) during 5 weeks. Prostate biopsies collected from the transition zone before and after intervention were analysed for 15 participants (n=8 selenium, n=7 placebo). Pathway analyses revealed that the intervention with selenium was associated with down-regulated expression of genes involved in cellular migration, invasion, remodeling and immune responses. Specifically, expression of well-established epithelial markers, such as E-cadherin and epithelial cell adhesion molecule EPCAM, was up-regulated, while the mesenchymal markers vimentin and fibronectin were down-regulated after intervention with selenium. This implies an inhibitory effect of selenium on the epithelial-to-mesenchymal transition (EMT). Moreover, selenium was associated with down-regulated expression of genes involved in wound healing and inflammation; processes which are both related to EMT. In conclusion, our explorative data showed that selenium affected expression of genes implicated in EMT in the transition zone of the prostate. PMID:28076331

A short-term intervention with selenium affects expression of genes implicated in the epithelial-to-mesenchymal transition in the prostate.

PubMed

Kok, Dieuwertje E G; Kiemeney, Lambertus A L M; Verhaegh, Gerald W; Schalken, Jack A; van Lin, Emile N J T; Sedelaar, J P Michiel; Witjes, J Alfred; Hulsbergen-van de Kaa, Christina A; van 't Veer, Pieter; Kampman, Ellen; Afman, Lydia A

2017-02-07

In parallel with the inconsistency in observational studies and chemoprevention trials, the mechanisms by which selenium affects prostate cancer risk have not been elucidated. We conducted a randomized, placebo-controlled trial to examine the effects of a short-term intervention with selenium on gene expression in non-malignant prostate tissue. Twenty-three men received 300 µg selenium per day in the form of selenized yeast (n=12) or a placebo (n=11) during 5 weeks. Prostate biopsies collected from the transition zone before and after intervention were analysed for 15 participants (n=8 selenium, n=7 placebo). Pathway analyses revealed that the intervention with selenium was associated with down-regulated expression of genes involved in cellular migration, invasion, remodeling and immune responses. Specifically, expression of well-established epithelial markers, such as E-cadherin and epithelial cell adhesion molecule EPCAM, was up-regulated, while the mesenchymal markers vimentin and fibronectin were down-regulated after intervention with selenium. This implies an inhibitory effect of selenium on the epithelial-to-mesenchymal transition (EMT). Moreover, selenium was associated with down-regulated expression of genes involved in wound healing and inflammation; processes which are both related to EMT. In conclusion, our explorative data showed that selenium affected expression of genes implicated in EMT in the transition zone of the prostate.

Targeting the Neural Microenvironment in Prostate Cancer

DTIC Science & Technology

2016-10-01

neurotrophic factor (GDNF), which is expressed by peripheral nerves. GDNF binds to RET, a receptor tyrosine kinase, in conjunction with its co-receptor...kinase, in conjunction with its co- receptor GFRα1 and activates cellular signaling. Studies in pancreatic cancer strongly implicate RET signaling as

20180312 - Development of a Human 3D Prostate Microtissue Assay for Anti-androgen Screening (SOT)

EPA Science Inventory

Altered androgen hormone biosynthesis and metabolism can modulate androgen levels, contributing to endocrine disruption that may result in impaired reproductive and sexual development. Steroid 5α-reductase isozymes are expressed in key peripheral tissues and catalyze the co...

Peripheral Changes Associated With Delayed Dark Adaptation in Age-related Macular Degeneration.

PubMed

Laíns, Inês; Park, Dong Ho; Mukai, Ryo; Silverman, Rebecca; Oellers, Patrick; Mach, Steven; Kim, Ivana K; Vavvas, Demetrios G; Miller, Joan W; Miller, John B; Husain, Deeba

2018-06-01

To study the association between peripheral changes in age-related macular degeneration (AMD) and dark adaptation (DA). Prospective, cross-sectional study. We recruited patients with AMD and a control group (>50 years) without any vitreoretinal disease. Ultra-widefield (UWF) pseudocolor and fundus autofluorescence (FAF) were obtained, and were assessed by 2 graders for the presence of several peripheral changes in perimacular, midperipheral, and far-peripheral zones. All participants were also imaged with 7-field color fundus photographs used for AMD staging (Age-Related Eye Disease Study classification system). Both eyes of study participants were tested with a dark adaptation (DA) extended protocol (20 minutes). Multilevel mixed-effect models (accounting for correlated outcomes between 2 eyes) were used for analyses. We included 128 eyes (n = 72 patients), 75% with AMD and the remainder controls. The presence of reticular pigmentary changes in the midperipheral (ß = 4.3, P = .012) and far-peripheral zones (ß = 8.4, P < .001) was associated with delayed rod-intercept times (RITs), even after adjusting for confounding factors. The presence, number, and extent of peripheral classic drusen did not show a similar association (P ≥ .148). The presence of a mottled decreased FAF pattern in the midperipheral zone was also associated with prolonged RITs (β = 4.4, P = .031). Our results suggest an association between DA and the presence of peripheral reticular pigmentary changes, as well as the presence of a peripheral mottled decreased FAF pattern. This provides new insights on the clinical significance of peripheral changes in AMD, and their contribution to impairments on DA. Copyright © 2018 Elsevier Inc. All rights reserved.

Detection of high GS risk group prostate tumors by diffusion tensor imaging and logistic regression modelling.

PubMed

Ertas, Gokhan

2018-07-01

To assess the value of joint evaluation of diffusion tensor imaging (DTI) measures by using logistic regression modelling to detect high GS risk group prostate tumors. Fifty tumors imaged using DTI on a 3 T MRI device were analyzed. Regions of interests focusing on the center of tumor foci and noncancerous tissue on the maps of mean diffusivity (MD) and fractional anisotropy (FA) were used to extract the minimum, the maximum and the mean measures. Measure ratio was computed by dividing tumor measure by noncancerous tissue measure. Logistic regression models were fitted for all possible pair combinations of the measures using 5-fold cross validation. Systematic differences are present for all MD measures and also for all FA measures in distinguishing the high risk tumors [GS ≥ 7(4 + 3)] from the low risk tumors [GS ≤ 7(3 + 4)] (P < 0.05). Smaller value for MD measures and larger value for FA measures indicate the high risk. The models enrolling the measures achieve good fits and good classification performances (R 2 adj  = 0.55-0.60, AUC = 0.88-0.91), however the models using the measure ratios perform better (R 2 adj  = 0.59-0.75, AUC = 0.88-0.95). The model that employs the ratios of minimum MD and maximum FA accomplishes the highest sensitivity, specificity and accuracy (Se = 77.8%, Sp = 96.9% and Acc = 90.0%). Joint evaluation of MD and FA diffusion tensor imaging measures is valuable to detect high GS risk group peripheral zone prostate tumors. However, use of the ratios of the measures improves the accuracy of the detections substantially. Logistic regression modelling provides a favorable solution for the joint evaluations easily adoptable in clinical practice. Copyright © 2018 Elsevier Inc. All rights reserved.

Selective nanoparticle-directed photothermal ablation of the canine prostate

NASA Astrophysics Data System (ADS)

Schwartz, Jon A.; Price, Roger E.; Gill-Sharp, Kelly L.; Sang, Krystina L.; Khorchani, Jennifer D.; Payne, J. Donald; Goodwin, Bradford S.

2011-03-01

This study adapted AuroLase® Therapy, previously reported for the treatment of brain tumors, to the treatment of prostate disease by 1) using normal canine prostate in vivo, directly injected with a solution of nanoparticles as a proxy for prostate tumor and, 2) developing an appropriate laser dosimetry for prostate which is which is subablative in native prostate while simultaneously producing photothermal coagulation in prostate tissue containing therapeutic nanoshells. Healthy, mixed-breed hound dogs were given surgical laparotomies during which nanoshells were injected directly into one or both prostate hemispheres. Laser energy was delivered percutaneously to the parenchyma of the prostate along 1-5 longitudinal tracts via a liquid-cooled optical fiber catheter terminated with a 1-cm isotropic diffuser after which the incision was closed and sutured using standard surgical techniques. The photothermal lesions were permitted to resolve for up to 8 days, after which each animal was euthanized, necropsied, and the prostate taken for histopathological analysis. We developed a laser dosimetry which is sub- to marginally ablative in native prostate and simultaneously ablative of prostate tissue containing nanoshells which would indicate a viable means of treating tumors of the prostate which are known from other studies to accumulate nanoshells. Secondly, we determined that multiple laser treatments of nanoshell-containing prostate tissue could be accomplished while sparing the urethra and prostate capsule thermal damage. Finally, we determined that the extent of damage zone radii correlate positively with nanoshell concentration, and negatively to the length of time between nanoshell injection and laser treatment.

Effects of a saw palmetto herbal blend in men with symptomatic benign prostatic hyperplasia.

PubMed

Marks, L S; Partin, A W; Epstein, J I; Tyler, V E; Simon, I; Macairan, M L; Chan, T L; Dorey, F J; Garris, J B; Veltri, R W; Santos, P B; Stonebrook, K A; deKernion, J B

2000-05-01

We tested the effects of a saw palmetto herbal blend in men with symptomatic benign prostatic hyperplasia (BPH) via a randomized, placebo controlled trial. We randomized 44 men 45 to 80 years old with symptomatic BPH into a trial of a saw palmetto herbal blend versus placebo. End points included routine clinical measures (symptom score, uroflowmetry and post-void residual urine volume), blood chemistry studies (prostate specific antigen, sex hormones and multiphasic analysis), prostate volumetrics by magnetic resonance imaging, and prostate biopsy for zonal tissue morphometry and semiquantitative histology studies. Saw palmetto herbal blend and placebo groups had improved clinical parameters with a slight advantage in the saw palmetto group (not statistically significant). Neither prostate specific antigen nor prostate volume changed from baseline. Prostate epithelial contraction was noted, especially in the transition zone, where percent epithelium decreased from 17.8% at baseline to 10.7% after 6 months of saw palmetto herbal blend (p <0.01). Histological studies showed that the percent of atrophic glands increased from 25. 2% to 40.9% after treatment with saw palmetto herbal blend (p <0.01). The mechanism of action appeared to be nonhormonal but it was not identified by tissue studies of apoptosis, cellular proliferation, angiogenesis, growth factors or androgen receptor expression. We noted no adverse effects of saw palmetto herbal blend. When the study was no longer blinded, 41 men elected to continue therapy in an open label extension. Saw palmetto herbal blend appears to be a safe, highly desirable option for men with moderately symptomatic BPH. The secondary outcome measures of clinical effect in our study were only slightly better for saw palmetto herbal blend than placebo (not statistically significant). However, saw palmetto herbal blend therapy was associated with epithelial contraction, especially in the transition zone (p <0.01), indicating a possible mechanism of action underlying the clinical significance detected in other studies.

Effect of Pulsed Electromagnetic Field Therapy on Prostate Volume and Vascularity in the Treatment of Benign Prostatic Hyperplasia: A Pilot Study in a Canine Model

PubMed Central

Leoci, Raffaella; Aiudi, Giulio; Silvestre, Fabio; Lissner, Elaine; Lacalandra, Giovanni Michele

2014-01-01

BACKGROUND Benign prostatic hyperplasia (BPH) is a result of urogenital aging. Recent studies suggest that an age-related impairment of the blood supply to the lower urinary tract plays a role in the development of BPH and thus may be a contributing factor in the pathogenesis of BPH. The canine prostate is a model for understanding abnormal growth of the human prostate gland. We studied the efficacy of pulsed electromagnetic field therapy (PEMF) in dogs to modify prostate blood flow and evaluated its effect on BPH. METHODS PEMF (5 min, twice a day for 3 weeks) was performed on 20 dogs affected by BPH. Prostatic volume, Doppler assessment by ultrasonography, libido, semen quality, testosterone levels, and seminal plasma volume, composition and pH were evaluated before and after treatment. RESULTS The 3 weeks of PEMF produced a significant reduction in prostatic volume (average 57%) without any interference with semen quality, testosterone levels or libido. Doppler parameters showed a reduction of peripheral resistances and a progressive reduction throughout the trial of the systolic peak velocity, end-diastolic velocity, mean velocity, mean, and peak gradient of the blood flow in the dorsal branch of the prostatic artery. The pulsatility index and the resistance index did not vary significantly over time. CONCLUSIONS The efficacy of PEMF on BPH in dogs, with no side effects, suggests the suitability of this treatment in humans and supports the hypothesis that impairment of blood supply to the lower urinary tract may be a causative factor in the development of BPH. Prostate 74:1132–1141, 2014. © 2014 The Authors. The Prostate published by Wiley Periodicals, Inc. PMID:24913937

High serum dihydrotestosterone examined by ultrasensitive LC-MS/MS as a predictor of benign prostatic hyperplasia or Gleason score 6 cancer in men with prostate-specific antigen levels of 3-10 ng/mL.

PubMed

Miyoshi, Y; Uemura, H; Suzuki, K; Shibata, Y; Honma, S; Harada, M; Kubota, Y

2017-03-01

There has been no consensus on the role of serum androgen concentrations in prostate cancer detection in men with prostate-specific antigen levels of 3-10 ng/mL. In this study, testosterone and dihydrotestosterone concentrations in blood were examined by a newly developed method using ultrasensitive liquid chromatography with two serially linked mass spectrometers (LC-MS/MS). We investigated the correlation between serum androgen levels and Gleason scores at biopsy. We analyzed data of 157 men with a total prostate-specific antigen range of 3-10 ng/mL who underwent initial systematic prostate needle biopsy for suspected prostate cancer between April 2000 and July 2003. Peripheral blood testosterone and dihydrotestosterone concentrations were determined by LC-MS/MS. Blood levels of testosterone and dihydrotestosterone were compared with pathological findings by multivariate analyses. Median values of prostate-specific antigen and prostate volume measured by ultrasound were 5.7 ng/mL and 31.4 cm 3 , respectively. Benign prostatic hyperplasia was diagnosed in 97 patients (61.8%), and prostate cancer was diagnosed in 60 (38.2%) patients, including 31 (19.7%) patients with a Gleason score of 6 and 29 (18.5%) patients with a Gleason score of 7-10. Median values of testosterone and dihydrotestosterone in blood were 3798.7 and 371.7 pg/mL, respectively. There was a strong correlation between serum testosterone and dihydrotestosterone. In multivariate analysis, age, prostate volume, and serum dihydrotestosterone were significant predictors of benign prostatic hyperplasia or prostate cancer with a Gleason score of 6. The area under the receiver operating characteristics curve for age, prostate volume, and serum dihydrotestosterone were 0.67, 0.67, and 0.67, respectively . We confirmed that high dihydrotestosterone blood levels can predict benign prostatic hyperplasia or prostate cancer with a Gleason score of 6 in men with prostate-specific antigen levels of 3-10 ng/mL. © 2016 American Society of Andrology and European Academy of Andrology.

[The value of PHI/PCA3 in the early diagnosis of prostate cancer].

PubMed

Tan, S J; Xu, L W; Xu, Z; Wu, J P; Liang, K; Jia, R P

2016-01-12

To investigate the value of prostate health index (PHI) and prostate cancer gene 3 (PCA3) in the early diagnosis of prostate cancer (PCa). A total of 190 patients with abnormal serum prostate specific antigen (PSA) or abnormal digital rectal examination were enrolled. They were all underwent initial biopsy and 11 of them were also underwent repeated biopsy. In addition, 25 healthy cases (with normal digital rectal examination and PSA<4 ng/ml) were the control group.The PHI and PCA3 were detected by using immunofluorescence and Loop-Mediated Isothermal Amplification (LAMP). The sensitivity and specificity of diagnosis were determined by ROC curve.In addition, the relationship between PHI/PSA and the Gleason score and clinical stage were analyzed. A total of 89 patients were confirmed PCa by Pathological diagnosis. The other 101 patients were diagnosed as benign prostatic hyperplasia (BPH). The sensitivity and specificity of PCA3 test were 85.4% was 92.1%. Area under curve (AUC) of PHI is higher than AUC of PSA (0.727>0.699). The PHI in peripheral blood was positively correlated with Gleason score and clinical stage. The detection of PCA3 and PHI shows excellent detecting effectiveness. Compared with single PSA, the combined detection of PHI and PCA3 improved the diagnostic specificity. It can provide a new method for the early diagnosis in prostate cancer and avoid unnecessary biopsies.

Symptomatic and asymptomatic benign prostatic hyperplasia: Molecular differentiation by using microarrays

NASA Astrophysics Data System (ADS)

Prakash, Kulkarni; Pirozzi, Gregorio; Elashoff, Michael; Munger, William; Waga, Iwao; Dhir, Rajiv; Kakehi, Yoshiyuki; Getzenberg, Robert H.

2002-05-01

Benign prostatic hyperplasia (BPH) is a disease of unknown etiology that significantly affects the quality of life in aging men. Histologic BPH may present itself either as symptomatic or asymptomatic in nature. To elucidate the molecular differences underlying BPH, gene expression profiles from the prostate transition zone tissue have been analyzed by using microarrays. A set of 511 differentially expressed genes distinguished symptomatic and asymptomatic BPH. This genetic signature separates BPH from normal tissue but does not seem to change with age. These data could provide novel approaches for alleviating symptoms and hyperplasia in BPH.

Tumor-associated myeloid cells promote tumorigenesis of non-tumorigenic human and murine prostatic epithelial cell lines.

PubMed

Sass, Stephanie N; Ramsey, Kimberley D; Egan, Shawn M; Wang, Jianmin; Cortes Gomez, Eduardo; Gollnick, Sandra O

2018-06-01

The etiology of prostate cancer is poorly understood, but it is a multi-step process that has been linked to environmental factors that induce inflammation within the gland. Glands of prostate cancer patients frequently contain multiple zones of disease at various stages of progression. The factors that drive disease progression from an indolent benign stage to aggressive disease are not well-defined. Prostate inflammation and carcinoma are associated with high levels of myeloid cell infiltration; these cells are linked to disease progression in other cancers, but their role in prostate cancer is unclear. To determine whether myeloid cells contribute to prostate cancer progression, the ability of prostate tumor-associated CD11b + cells (TAMC) to drive prostate epithelial cell tumorigenesis was tested. Co-culture of CD11b + TAMC with non-tumorigenic genetically primed prostate epithelial cells resulted in stable transformation and induction of tumorigenesis. RNA sequencing identified the IL-1α pathway as a potential molecular mechanism responsible for tumor promotion by TAMC. Inhibition of IL-1α delayed growth of TAMC-induced tumors. Further analysis showed that IL-1α inhibition led to decreased angiogenesis within tumors, suggesting that IL-1α promotes prostate tumor progression, potentially through augmentation of angiogenesis.

KTP laser selective vaporization of the prostate in the management of urinary retention due to BPH

NASA Astrophysics Data System (ADS)

Kleeman, M. W.; Nseyo, Unyime O.

2003-06-01

High-powered photoselective vaporization of the prostate (PVP) is a relatively new addition in the armamentarium against bladder outlet obstruction due to BPH. With BPH, the prostate undergoes stromal and epithelial hyperplasia, particularly in the transitional zone, mediated by dihydrotestosterone (DHT). This periurethral enlargement can compress the prostatic urethra leading to bladder outlet obstruction and eventually urinary retention. Treatment of uncomplicated symptomatic BPH has evolved from the standard transurethral resection of the prostate (TURP) to multiple medical therapies and the putative minimally invasive surgical procedures. These include microwave ablation, needle ablation, balloon dilation, stents, as well as fluid based thermo-therapy, ultrasound therapy and cryotherapy. Different forms of lasers have been applied to treat BPH with variable short and long term benefits of urinary symptoms. However, the controversy remains about each laser regarding its technical applicability and efficacy.

Chronic Pelvic Pain Development and Prostate Inflammation in Strains of Mice With Different Susceptibility to Experimental Autoimmune Prostatitis.

PubMed

Breser, Maria L; Motrich, Ruben D; Sanchez, Leonardo R; Rivero, Virginia E

2017-01-01

Experimental autoimmune prostatitis (EAP) is an autoimmune inflammatory disease of the prostate characterized by peripheral prostate-specific autoimmune responses associated with prostate inflammation. EAP is induced in rodents upon immunization with prostate antigens (PAg) plus adjuvants and shares important clinical and immunological features with the human disease chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). EAP was induced in young NOD, C57BL/6, and BALB/c male mice by immunization with PAg plus complete Freund́s adjuvant. Tactile allodynia was assessed using Von Frey fibers as a measure of pelvic pain at baseline and at different time points after immunization. Using conventional histology, immunohistochemistry, FACS analysis, and protein arrays, an interstrain comparative study of prostate cell infiltration and inflammation was performed. Chronic pelvic pain development was similar between immunized NOD and C57BL/6 mice, although the severity of leukocyte infiltration was greater in the first case. Coversely, minimal prostate cell infiltration was observed in immunized BALB/c mice, who showed no pelvic pain development. Increased numbers of mast cells, mostly degranulated, were detected in prostate samples from NOD and C57BL/6 mice, while lower total counts and resting were observed in BALB/c mice. Prostate tissue from NOD mice revealed markedly increased expression levels of inflammatory cytokines, chemokines, adhesion molecules, vascular endothelial growth factor, and metalloproteinases. Similar results, but to a lesser extent, were observed when analyzing prostate tissue from C57BL/6 mice. On the contrary, the expression of the above mediators was very low in prostate tissue from immunized BALB/c mice, showing significantly slight increments only for CXCL1 and IL4. Our results provide new evidence indicating that NOD, C57BL/6, and BALB/c mice develop different degrees of chronic pelvic pain, type, and amount of prostate cell infiltration and secretion of inflammatory mediators. Our results corroborate and support the notion that mice with different genetic background have different susceptibility to EAP induction. Prostate 77:94-104, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Three-dimensional analysis of vestibular efferent neurons innervating semicircular canals of the gerbil

NASA Technical Reports Server (NTRS)

Purcell, I. M.; Perachio, A. A.

1997-01-01

Anterograde labeling techniques were used to examine peripheral innervation patterns of vestibular efferent neurons in the crista ampullares of the gerbil. Vestibular efferent neurons were labeled by extracellular injections of biocytin or biotinylated dextran amine into the contralateral or ipsilateral dorsal subgroup of efferent cell bodies (group e) located dorsolateral to the facial nerve genu. Anterogradely labeled efferent terminal field varicosities consist mainly of boutons en passant with fewer of the terminal type. The bouton swellings are located predominately in apposition to the basolateral borders of the afferent calyces and type II hair cells, but several boutons were identified close to the hair cell apical border on both types. Three-dimensional reconstruction and morphological analysis of the terminal fields from these cells located in the sensory neuroepithelium of the anterior, horizontal, and posterior cristae were performed. We show that efferent neurons densely innervate each end organ in widespread terminal fields. Subepithelial bifurcations of parent axons were minimal, with extensive collateralization occurring after the axons penetrated the basement membrane of the neuroepithelium. Axonal branching ranged between the 6th and 27th orders and terminal field collecting area far exceeds that of the peripheral terminals of primary afferent neurons. The terminal fields of the efferent neurons display three morphologically heterogeneous types: central, peripheral, and planum. All cell types possess terminal fields displaying a high degree of anisotropy with orientations typically parallel to or within +/-45 degrees of the longitudinal axis if the crista. Terminal fields of the central and planum zones predominately project medially toward the transverse axis from the more laterally located penetration of the basement membrane by the parent axon. Peripheral zone terminal fields extend predominately toward the planum semilunatum. The innervation areas of efferent terminal fields display a trend from smallest to largest for the central, peripheral, and planum types, respectively. Neurons that innervate the central zone of the crista do not extend into the peripheral or planum regions. Conversely, those neurons with terminal fields in the peripheral or planum regions do not innervate the central zone of the sensory neuroepithelium. The central zone of the crista is innervated preferentially by efferent neurons with cell bodies located in the ipsilateral group e. The peripheral and planum zones of the crista are innervated preferentially by efferent neurons with cell bodies located in the contralateral group e. A model incorporating our anatomic observations is presented describing an ipsilateral closed-loop feedback between ipsilateral efferent neurons and the periphery and an open-loop feed-forward innervation from contralateral efferent neurons. A possible role for the vestibular efferent neurons in the modulation of semicircular canal afferent response dynamics is proposed.

The influence of prostatic anatomy and neurotrophins on basal prostate epithelial progenitor cells.

PubMed

Höfner, Thomas; Klein, Corinna; Eisen, Christian; Rigo-Watermeier, Teresa; Haferkamp, Axel; Trumpp, Andreas; Sprick, Martin R

2016-01-01

Based on findings of surface marker, protein screens as well as the postulated near-urethral location of the prostate stem cell niche, we were interested whether androgen ablation, distinct anatomic regions within the prostate or neurotrophins have an influence on basal prostate epithelial progenitor cells (PESCs). Microdissection of the prostate, enzymatic digestion, and preparation of single cells was performed from murine and human prostates. Adult PESC marker expressions were compared between a group of C57BL/6 mice and a separate group of castrated C57BL/6 mice. Surface markers CD13/CD271 on human prostate epithelial progenitor cells were evaluated by FACS analyses in cells cultured under novel stem cell conditions. The effect of neurotrophins NGF, NT3, and BDNF were evaluated with respect to their influence on proliferation and activation of human basal PESCs in vitro. We demonstrate the highest percentage of CD49f+ and Trop2+ expressing cells in the urethra near prostatic regions of WT mice (Trop2+ proximal: 10% vs. distal to the urethra: 3%, P < 0.001). While a marked increase of Trop2 expressing cells can be measured both in the proximal and distal prostatic regions after castration, the most prominent increase in Trop2+ cells can be measured in the prostatic tissue distant to the urethra. Furthermore, we demonstrate that the proportion of syndecan-1 expressing cells greatly increases in the regions proximal to the urethra after castration (WT: 5% vs. castrated: 40%). We identified heterogeneous CD13 and nerve growth factor receptor (p75(NGFR), CD271) expression on CD49f(+)/TROP2(high) human basal PESCs. Addition of the neurotrophins NT3, BDNF, and NGF to the stem cell media led to a marked temporary increase in the proliferation of human basal PESCs. Our results in mice support the model, in which the proximal urethral region contains the prostate stem cell niche while a stronger androgen-dependent regulation of adult prostate stem cells can be found in the peripheral prostatic tissue. Neutrophin signaling via nerve growth factor receptor is possibly involved in human prostate stem cell homeostasis. © 2015 Wiley Periodicals, Inc.

Prostatome: A combined anatomical and disease based MRI atlas of the prostate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rusu, Mirabela; Madabhushi, Anant, E-mail: anant.madabhushi@case.edu; Bloch, B. Nicolas

Purpose: In this work, the authors introduce a novel framework, the anatomically constrained registration (AnCoR) scheme and apply it to create a fused anatomic-disease atlas of the prostate which the authors refer to as the prostatome. The prostatome combines a MRI based anatomic and a histology based disease atlas. Statistical imaging atlases allow for the integration of information across multiple scales and imaging modalities into a single canonical representation, in turn enabling a fused anatomical-disease representation which may facilitate the characterization of disease appearance relative to anatomic structures. While statistical atlases have been extensively developed and studied for the brain,more » approaches that have attempted to combine pathology and imaging data for study of prostate pathology are not extant. This works seeks to address this gap. Methods: The AnCoR framework optimizes a scoring function composed of two surface (prostate and central gland) misalignment measures and one intensity-based similarity term. This ensures the correct mapping of anatomic regions into the atlas, even when regional MRI intensities are inconsistent or highly variable between subjects. The framework allows for creation of an anatomic imaging and a disease atlas, while enabling their fusion into the anatomic imaging-disease atlas. The atlas presented here was constructed using 83 subjects with biopsy confirmed cancer who had pre-operative MRI (collected at two institutions) followed by radical prostatectomy. The imaging atlas results from mapping thein vivo MRI into the canonical space, while the anatomic regions serve as domain constraints. Elastic co-registration MRI and corresponding ex vivo histology provides “ground truth” mapping of cancer extent on in vivo imaging for 23 subjects. Results: AnCoR was evaluated relative to alternative construction strategies that use either MRI intensities or the prostate surface alone for registration. The AnCoR framework yielded a central gland Dice similarity coefficient (DSC) of 90%, and prostate DSC of 88%, while the misalignment of the urethra and verumontanum was found to be 3.45 mm, and 4.73 mm, respectively, which were measured to be significantly smaller compared to the alternative strategies. As might have been anticipated from our limited cohort of biopsy confirmed cancers, the disease atlas showed that most of the tumor extent was limited to the peripheral zone. Moreover, central gland tumors were typically larger in size, possibly because they are only discernible at a much later stage. Conclusions: The authors presented the AnCoR framework to explicitly model anatomic constraints for the construction of a fused anatomic imaging-disease atlas. The framework was applied to constructing a preliminary version of an anatomic-disease atlas of the prostate, the prostatome. The prostatome could facilitate the quantitative characterization of gland morphology and imaging features of prostate cancer. These techniques, may be applied on a large sample size data set to create a fully developed prostatome that could serve as a spatial prior for targeted biopsies by urologists. Additionally, the AnCoR framework could allow for incorporation of complementary imaging and molecular data, thereby enabling their careful correlation for population based radio-omics studies.« less

Prospective study of DNA methylation at chromosome 8q24 in peripheral blood and prostate cancer risk.

PubMed

Barry, Kathryn Hughes; Moore, Lee E; Sampson, Joshua N; Koutros, Stella; Yan, Liying; Meyer, Ann; Reddy, Mahitha; Oler, Andrew J; Cook, Michael B; Fraumeni, Joseph F; Yeager, Meredith; Amundadottir, Laufey T; Berndt, Sonja I

2017-05-23

Chromosome 8q24 has emerged as an important genetic susceptibility region for several cancers, including prostate cancer; however, little is known about the contribution of DNA methylation in this region to risk. We prospectively evaluated DNA methylation at 8q24 in relation to prostate cancer using pre-diagnostic blood samples from 694 prostate cancer cases (including 172 aggressive cases) and 703 controls in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We used logistic regression to estimate odds ratios and 95% confidence intervals. Although none remained significant after adjustment for multiple testing (q>0.05), of the 50 CpG sites meeting quality control, we identified 8 sites that were nominally associated with prostate cancer (P trend <0.05), including 6 correlated (Spearman ρ: 0.20-0.52) sites in POU5F1B and 2 intergenic sites (most significant site: Chr8:128428897 in POU5F1B, P trend =0.01). We also identified two correlated (ρ=0.39) sites in MYC (Chr8:128753187 and Chr8:128753154) that were associated with aggressive (P trend =0.02 and 0.03), but not non-aggressive disease (P trend =0.70 and 0.20; P heterogeneity =0.01 and 4.6 × 10 -3 ). These findings persisted after adjustment for the top 8q24 prostate cancer variants in our study. Although requiring replication, our findings provide some evidence that 8q24 DNA methylation levels may be associated with prostate cancer risk.

Unshielded asymmetric transmit-only and endorectal receive-only radiofrequency coil for (23) Na MRI of the prostate at 3 tesla.

PubMed

Farag, Adam; Peterson, Justin Charles; Szekeres, Trevor; Bauman, Glenn; Chin, Joseph; Romagnoli, Cesare; Bartha, Robert; Scholl, Timothy J

2015-08-01

To develop and optimize radiofrequency (RF) hardware for the detection of endogenous sodium ((23) Na) by 3.0 Tesla (T) MRI in the human prostate. A transmit-only receive-only (TORO) RF system of resonators consisting of an unshielded, asymmetric, quadrature birdcage (transmit), and an endorectal (ER), linear, surface (receive) coil were developed and tested on a 3T MRI scanner. Two different ER receivers were constructed; a single-tuned ((23) Na) and a dual-tuned ((1) H/(23) Na). Both receivers were evaluated by the measurements of signal-to-noise ratio (SNR) and B1 homogeneity. For tissue sodium concentration (TSC) quantification, vials containing known sodium concentrations were incorporated into the ER. The system was used to measure the prostate TSC of three men (age 55 ± 5 years) with biopsy-proven prostate cancer. B1 field inhomogeneity of the asymmetric transmitter was estimated to be less than 5%. The mean SNR measured in a region of interest within the prostate using the single-tuned ER coil was 54.0 ± 4.6. The mean TSC in the central gland was 60.2 ± 5.7 mmol/L and in the peripheral gland was 70.5 ± 9.0 mmol/L. A TORO system was developed and optimized for (23) Na MRI of the human prostate which showed good sensitivity throughout the prostate for quantitative measurement of TSC. © 2014 Wiley Periodicals, Inc.

MR elastography and diffusion-weighted imaging of ex vivo prostate cancer: quantitative comparison to histopathology.

PubMed

Sahebjavaher, Ramin S; Nir, Guy; Gagnon, Louis O; Ischia, Joseph; Jones, Edward C; Chang, Silvia D; Yung, Andrew; Honarvar, Mohammad; Fazli, Ladan; Goldenberg, S Larry; Rohling, Robert; Sinkus, Ralph; Kozlowski, Piotr; Salcudean, Septimiu E

2015-01-01

The purpose of this work was (1) to develop a magnetic resonance elastography (MRE) system for imaging of the ex vivo human prostate and (2) to assess the diagnostic power of mono-frequency and multi-frequency MRE and diffusion weighted imaging (DWI) alone and combined as correlated with histopathology in a patient study. An electromagnetic driver was designed specifically for MRE studies in small-bore MR scanners. Ex vivo prostate specimens (post-fixation) of 14 patients who underwent radical prostatectomy were imaged with MRE at 7 T (nine cases had DWI). In six patients, the MRE examination was performed at three frequencies (600, 800, 1000 Hz) to extract the power-law exponent Gamma. The images were registered to wholemount pathology slides marked with the Gleason score. The areas under the receiver-operator-characteristic curves (AUC) were calculated. The methods were validated in a phantom study and it was demonstrated that (i) the driver does not interfere with the acquisition process and (ii) the driver can generate amplitudes greater than 100 µm for frequencies less than 1 kHz. In the quantitative study, cancerous tissue with Gleason score at least 3 + 3 was distinguished from normal tissue in the peripheral zone (PZ) with an average AUC of 0.75 (Gd ), 0.75 (Gl ), 0.70 (Gamma-Gd ), 0.68 (apparent diffusion coefficient, ADC), and 0.82 (Gd  + Gl  + ADC). The differentiation between PZ and central gland was modest for Gd (p < 0.07), Gl (p < 0.06) but not significant for Gamma (p < 0.2). A correlation of 0.4 kPa/h was found between the fixation time of the prostate specimen and the stiffness of the tissue, which could affect the diagnostic power results. DWI and MRE may provide complementary information; in fact MRE performed better than ADC in distinguishing normal from cancerous tissue in some cases. Multi-frequency (Gamma) analysis did not appear to improve the results. However, in light of the effect of tissue fixation, the clinical implication of our results may be inconclusive and more experiments are needed. Copyright © 2014 John Wiley & Sons, Ltd.

MR-perfusion (MRP) and diffusion-weighted imaging (DWI) in prostate cancer: quantitative and model-based gadobenate dimeglumine MRP parameters in detection of prostate cancer.

PubMed

Scherr, M K; Seitz, M; Müller-Lisse, U G; Ingrisch, M; Reiser, M F; Müller-Lisse, U L

2010-12-01

Various MR methods, including MR-spectroscopy (MRS), dynamic, contrast-enhanced MRI (DCE-MRI), and diffusion-weighted imaging (DWI) have been applied to improve test quality of standard MRI of the prostate. To determine if quantitative, model-based MR-perfusion (MRP) with gadobenate dimeglumine (Gd-BOPTA) discriminates between prostate cancer, benign tissue, and transitional zone (TZ) tissue. 27 patients (age, 65±4 years; PSA 11.0±6.1 ng/ml) with clinical suspicion of prostate cancer underwent standard MRI, 3D MR-spectroscopy (MRS), and MRP with Gd-BOPTA. Based on results of combined MRI/MRS and subsequent guided prostate biopsy alone (17/27), biopsy and radical prostatectomy (9/27), or sufficient negative follow-up (7/27), maps of model-free, deconvolution-based mean transit time (dMTT) were generated for 29 benign regions (bROIs), 14 cancer regions (cROIs), and 18 regions of transitional zone (tzROIs). Applying a 2-compartment exchange model, quantitative perfusion analysis was performed including as parameters: plasma flow (PF), plasma volume (PV), plasma mean transit time (PMTT), extraction flow (EFL), extraction fraction (EFR), interstitial volume (IV) and interstitial mean transit time (IMTT). Two-sided T-tests (significance level p<0.05) discriminated bROIs vs. cROIs and cROIs vs. tzROIs, respectively. PMTT discriminated best between bROIs (11.8±3.0 s) and cROIs (24.3±9.6 s) (p<0.0001), while PF, PV, PS, EFR, IV, IMTT also differed significantly (p 0.00002-0.0136). Discrimination between cROIs and tzROIs was insignificant for all parameters except PV (14.3±2.5 ml vs. 17.6±2.6 ml, p<0.05). Besides MRI, MRS and DWI quantitative, 2-compartment MRP with Gd-BOPTA discriminates between prostate cancer and benign tissue with several parameters. However, distinction of prostate cancer and TZ does not appear to be reliable. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

TRPM8 and prostate: a cold case?

PubMed

Noyer, Lucile; Grolez, Guillaume P; Prevarskaya, Natalia; Gkika, Dimitra; Lemonnier, Loic

2018-06-20

While originally cloned from the prostate in 2001, transient receptor potential, melastatin member 8 (TRPM8) has since been identified as the cold/menthol receptor in the peripheral nervous system. This discovery has led to hundreds of studies regarding the role of this channel in pain and thermosensation phenomena, while relegating TRPM8 involvement in cancer to a secondary role. Despite these findings, there is growing evidence that TRPM8 should be carefully studied within the frame of carcinogenesis, especially in the prostate, where it is highly expressed and where many teams have confirmed variations in its expression during cancer progression. Its regulation by physiological factors, such as PSA and androgens, has proved that TRPM8 can exhibit an activity beyond that of a cold receptor, thus explaining how the channel can be activated in organs not exposed to temperature variations. With this review, we aim to provide a brief overview of the current knowledge regarding the complex roles of TRPM8 in prostate carcinogenesis and to show that this research path still represents a "hot" topic with potential clinical applications in the short term.

Noninvasive prostate cancer screening based on serum surface-enhanced Raman spectroscopy and support vector machine

NASA Astrophysics Data System (ADS)

Li, Shaoxin; Zhang, Yanjiao; Xu, Junfa; Li, Linfang; Zeng, Qiuyao; Lin, Lin; Guo, Zhouyi; Liu, Zhiming; Xiong, Honglian; Liu, Songhao

2014-09-01

This study aims to present a noninvasive prostate cancer screening methods using serum surface-enhanced Raman scattering (SERS) and support vector machine (SVM) techniques through peripheral blood sample. SERS measurements are performed using serum samples from 93 prostate cancer patients and 68 healthy volunteers by silver nanoparticles. Three types of kernel functions including linear, polynomial, and Gaussian radial basis function (RBF) are employed to build SVM diagnostic models for classifying measured SERS spectra. For comparably evaluating the performance of SVM classification models, the standard multivariate statistic analysis method of principal component analysis (PCA) is also applied to classify the same datasets. The study results show that for the RBF kernel SVM diagnostic model, the diagnostic accuracy of 98.1% is acquired, which is superior to the results of 91.3% obtained from PCA methods. The receiver operating characteristic curve of diagnostic models further confirm above research results. This study demonstrates that label-free serum SERS analysis technique combined with SVM diagnostic algorithm has great potential for noninvasive prostate cancer screening.

Differential blood-based diagnosis between benign prostatic hyperplasia and prostate cancer: miRNA as source for biomarkers independent of PSA level, Gleason score, or TNM status.

PubMed

Leidinger, Petra; Hart, Martin; Backes, Christina; Rheinheimer, Stefanie; Keck, Bastian; Wullich, Bernd; Keller, Andreas; Meese, Eckart

2016-08-01

Since the benefit of prostate-specific antigen (PSA) screening remains controversial, new non-invasive biomarkers for prostate carcinoma (PCa) are still required. There is evidence that microRNAs (miRNAs) in whole peripheral blood can separate patients with localized prostate cancer from healthy individuals. However, the potential of blood-based miRNAs for the differential diagnosis of PCa and benign prostatic hyperplasia (BPH) has not been tested. We compared the miRNome from blood of PCa and BPH patients and further investigated the influence of the tumor volume, tumor-node-metastasis (TNM) classification, Gleason score, pretreatment risk status, and the pretreatment PSA value on the miRNA pattern. By microarray approach, we identified seven miRNAs that were significantly deregulated in PCa patients compared to BPH patients. Using quantitative real time PCR (qRT-PCR), we confirmed downregulation of hsa-miR-221* (now hsa-miR-221-5p) and hsa-miR-708* (now hsa-miR-708-3p) in PCa compared to BPH. Clinical parameters like PSA level, Gleason score, or TNM status seem to have only limited impact on the overall abundance of miRNAs in patients' blood, suggesting a no influence of these factors on the expression of deregulated miRNAs.

Apoptosis-induced CXCL5 accelerates inflammation and growth of prostate tumor metastases in bone.

PubMed

Roca, Hernan; Jones, Jacqueline D; Purica, Marta C; Weidner, Savannah; Koh, Amy J; Kuo, Robert; Wilkinson, John E; Wang, Yugang; Daignault-Newton, Stephanie; Pienta, Kenneth J; Morgan, Todd M; Keller, Evan T; Nör, Jacques E; Shea, Lonnie D; McCauley, Laurie K

2018-01-02

During tumor progression, immune system phagocytes continually clear apoptotic cancer cells in a process known as efferocytosis. However, the impact of efferocytosis in metastatic tumor growth is unknown. In this study, we observed that macrophage-driven efferocytosis of prostate cancer cells in vitro induced the expression of proinflammatory cytokines such as CXCL5 by activating Stat3 and NF-κB(p65) signaling. Administration of a dimerizer ligand (AP20187) triggered apoptosis in 2 in vivo syngeneic models of bone tumor growth in which apoptosis-inducible prostate cancer cells were either coimplanted with vertebral bodies, or inoculated in the tibiae of immunocompetent mice. Induction of 2 pulses of apoptosis correlated with increased infiltration of inflammatory cells and accelerated tumor growth in the bone. Apoptosis-induced tumors displayed elevated expression of the proinflammatory cytokine CXCL5. Likewise, CXCL5-deficient mice had reduced tumor progression. Peripheral blood monocytes isolated from patients with bone metastasis of prostate cancer were more efferocytic compared with normal controls, and CXCL5 serum levels were higher in metastatic prostate cancer patients relative to patients with localized prostate cancer or controls. Altogether, these findings suggest that the myeloid phagocytic clearance of apoptotic cancer cells accelerates CXCL5-mediated inflammation and tumor growth in bone, pointing to CXCL5 as a potential target for cancer therapeutics.

Radiographic and anatomic basis for prostate contouring errors and methods to improve prostate contouring accuracy.

PubMed

McLaughlin, Patrick W; Evans, Cheryl; Feng, Mary; Narayana, Vrinda

2010-02-01

Use of highly conformal radiation for prostate cancer can lead to both overtreatment of surrounding normal tissues and undertreatment of the prostate itself. In this retrospective study we analyzed the radiographic and anatomic basis of common errors in computed tomography (CT) contouring and suggest methods to correct them. Three hundred patients with prostate cancer underwent CT and magnetic resonance imaging (MRI). The prostate was delineated independently on the data sets. CT and MRI contours were compared by use of deformable registration. Errors in target delineation were analyzed and methods to avoid such errors detailed. Contouring errors were identified at the prostatic apex, mid gland, and base on CT. At the apex, the genitourinary diaphragm, rectum, and anterior fascia contribute to overestimation. At the mid prostate, the anterior and lateral fasciae contribute to overestimation. At the base, the bladder and anterior fascia contribute to anterior overestimation. Transition zone hypertrophy and bladder neck variability contribute to errors of overestimation and underestimation at the superior base, whereas variable prostate-to-seminal vesicle relationships with prostate hypertrophy contribute to contouring errors at the posterior base. Most CT contouring errors can be detected by (1) inspection of a lateral view of prostate contours to detect projection from the expected globular form and (2) recognition of anatomic structures (genitourinary diaphragm) on the CT scans that are clearly visible on MRI. This study shows that many CT prostate contouring errors can be improved without direct incorporation of MRI data. Copyright 2010 Elsevier Inc. All rights reserved.

Ghrelin O-acyltransferase (GOAT) is expressed in prostate cancer tissues and cell lines and expression is differentially regulated in vitro by ghrelin.

PubMed

Seim, Inge; Jeffery, Penny L; de Amorim, Laura; Walpole, Carina M; Fung, Jenny; Whiteside, Eliza J; Lourie, Rohan; Herington, Adrian C; Chopin, Lisa K

2013-07-23

Ghrelin is a 28 amino acid peptide hormone that is expressed in the stomach and a range of peripheral tissues, where it frequently acts as an autocrine/paracrine growth factor. Ghrelin is modified by a unique acylation required for it to activate its cognate receptor, the growth hormone secretagogue receptor (GHSR), which mediates many of the actions of ghrelin. Recently, the enzyme responsible for adding the fatty acid residue (octanoyl/acyl group) to the third amino acid of ghrelin, GOAT (ghrelin O-acyltransferase), was identified. We used cell culture, quantitative real-time reverse transcription (RT)-PCR and immunohistochemistry to demonstrate the expression of GOAT in prostate cancer cell lines and tissues from patients. Real-time RT-PCR was used to demonstrate the expression of prohormone convertase (PC)1/3, PC2 and furin in prostate cancer cell lines. Prostate-derived cell lines were treated with ghrelin and desacyl ghrelin and the effect on GOAT expression was measured using quantitative RT-PCR. We have demonstrated that GOAT mRNA and protein are expressed in the normal prostate and human prostate cancer tissue samples. The RWPE-1 and RWPE-2 normal prostate-derived cell lines and the LNCaP, DU145, and PC3 prostate cancer cell lines express GOAT and at least one other enzyme that is necessary to produce mature, acylated ghrelin from proghrelin (PC1/3, PC2 or furin). Finally, ghrelin, but not desacyl ghrelin (unacylated ghrelin), can directly regulate the expression of GOAT in the RWPE-1 normal prostate derived cell line and the PC3 prostate cancer cell line. Ghrelin treatment (100nM) for 6 hours significantly decreased GOAT mRNA expression two-fold (P < 0.05) in the PC3 prostate cancer cell line, however, ghrelin did not regulate GOAT expression in the DU145 and LNCaP prostate cancer cell lines. This study demonstrates that GOAT is expressed in prostate cancer specimens and cell lines. Ghrelin regulates GOAT expression, however, this is likely to be cell-type specific. The expression of GOAT in prostate cancer supports the hypothesis that the ghrelin axis has autocrine/paracrine roles. We propose that the RWPE-1 prostate cell line and the PC3 prostate cancer cell line may be useful for investigating GOAT regulation and function.

Genome Wide Association Study to Identify SNPs and CNPs Associated with Development of Radiation Injury in Prostate Cancer Patients Treated with Radiotherapy

DTIC Science & Technology

2012-10-01

catalyzes the oxidative metabolism of androgens and estrogens in human peripheral tissues18. Other physiological functions included cell adhesion... aldosterone (CNKSR3)21. The Ingenuity Pathway Analysis software (Ingenuity Systems, Inc., Redwood City, CA) grouped 11 of these 12 genes into a

A steep peripheral ring in irregular cornea topography, real or an instrument error?

PubMed

Galindo-Ferreiro, Alicia; Galvez-Ruiz, Alberto; Schellini, Silvana A; Galindo-Alonso, Julio

2016-01-01

To demonstrate that the steep peripheral ring (red zone) on corneal topography after myopic laser in situ keratomileusis (LASIK) could possibly due to instrument error and not always to a real increase in corneal curvature. A spherical model for the corneal surface and modifying topography software was used to analyze the cause of an error due to instrument design. This study involved modification of the software of a commercially available topographer. A small modification of the topography image results in a red zone on the corneal topography color map. Corneal modeling indicates that the red zone could be an artifact due to an instrument-induced error. The steep curvature changes after LASIK, signified by the red zone, could be also an error due to the plotting algorithms of the corneal topographer, besides a steep curvature change.

Statistical Validation of Image Segmentation Quality Based on a Spatial Overlap Index1

PubMed Central

Zou, Kelly H.; Warfield, Simon K.; Bharatha, Aditya; Tempany, Clare M.C.; Kaus, Michael R.; Haker, Steven J.; Wells, William M.; Jolesz, Ferenc A.; Kikinis, Ron

2005-01-01

Rationale and Objectives To examine a statistical validation method based on the spatial overlap between two sets of segmentations of the same anatomy. Materials and Methods The Dice similarity coefficient (DSC) was used as a statistical validation metric to evaluate the performance of both the reproducibility of manual segmentations and the spatial overlap accuracy of automated probabilistic fractional segmentation of MR images, illustrated on two clinical examples. Example 1: 10 consecutive cases of prostate brachytherapy patients underwent both preoperative 1.5T and intraoperative 0.5T MR imaging. For each case, 5 repeated manual segmentations of the prostate peripheral zone were performed separately on preoperative and on intraoperative images. Example 2: A semi-automated probabilistic fractional segmentation algorithm was applied to MR imaging of 9 cases with 3 types of brain tumors. DSC values were computed and logit-transformed values were compared in the mean with the analysis of variance (ANOVA). Results Example 1: The mean DSCs of 0.883 (range, 0.876–0.893) with 1.5T preoperative MRI and 0.838 (range, 0.819–0.852) with 0.5T intraoperative MRI (P < .001) were within and at the margin of the range of good reproducibility, respectively. Example 2: Wide ranges of DSC were observed in brain tumor segmentations: Meningiomas (0.519–0.893), astrocytomas (0.487–0.972), and other mixed gliomas (0.490–0.899). Conclusion The DSC value is a simple and useful summary measure of spatial overlap, which can be applied to studies of reproducibility and accuracy in image segmentation. We observed generally satisfactory but variable validation results in two clinical applications. This metric may be adapted for similar validation tasks. PMID:14974593

Machine learning-based analysis of MR radiomics can help to improve the diagnostic performance of PI-RADS v2 in clinically relevant prostate cancer.

PubMed

Wang, Jing; Wu, Chen-Jiang; Bao, Mei-Ling; Zhang, Jing; Wang, Xiao-Ning; Zhang, Yu-Dong

2017-10-01

To investigate whether machine learning-based analysis of MR radiomics can help improve the performance PI-RADS v2 in clinically relevant prostate cancer (PCa). This IRB-approved study included 54 patients with PCa undergoing multi-parametric (mp) MRI before prostatectomy. Imaging analysis was performed on 54 tumours, 47 normal peripheral (PZ) and 48 normal transitional (TZ) zone based on histological-radiological correlation. Mp-MRI was scored via PI-RADS, and quantified by measuring radiomic features. Predictive model was developed using a novel support vector machine trained with: (i) radiomics, (ii) PI-RADS scores, (iii) radiomics and PI-RADS scores. Paired comparison was made via ROC analysis. For PCa versus normal TZ, the model trained with radiomics had a significantly higher area under the ROC curve (Az) (0.955 [95% CI 0.923-0.976]) than PI-RADS (Az: 0.878 [0.834-0.914], p < 0.001). The Az between them was insignificant for PCa versus PZ (0.972 [0.945-0.988] vs. 0.940 [0.905-0.965], p = 0.097). When radiomics was added, performance of PI-RADS was significantly improved for PCa versus PZ (Az: 0.983 [0.960-0.995]) and PCa versus TZ (Az: 0.968 [0.940-0.985]). Machine learning analysis of MR radiomics can help improve the performance of PI-RADS in clinically relevant PCa. • Machine-based analysis of MR radiomics outperformed in TZ cancer against PI-RADS. • Adding MR radiomics significantly improved the performance of PI-RADS. • DKI-derived Dapp and Kapp were two strong markers for the diagnosis of PCa.

Microstructural and Compositional Features of the Fibrous and Hyaline Cartilage on the Medial Tibial Plateau Imply a Unique Role for the Hopping Locomotion of Kangaroo

PubMed Central

He, Bo; Wu, Jian Ping; Xu, Jiake; Day, Robert E.; Kirk, Thomas Brett

2013-01-01

Hopping provides efficient and energy saving locomotion for kangaroos, but it results in great forces in the knee joints. A previous study has suggested that a unique fibrous cartilage in the central region of the tibial cartilage could serve to decrease the peak stresses generated within kangaroo tibiofemoral joints. However, the influences of the microstructure, composition and mechanical properties of the central fibrous and peripheral hyaline cartilage on the function of the knee joints are still to be defined. The present study showed that the fibrous cartilage was thicker and had a lower chondrocyte density than the hyaline cartilage. Despite having a higher PG content in the middle and deep zones, the fibrous cartilage had an inferior compressive strength compared to the peripheral hyaline cartilage. The fibrous cartilage had a complex three dimensional collagen meshwork with collagen bundles parallel to the surface in the superficial zone, and with collagen bundles both parallel and perpendicular to the surface in the middle and deep zones. The collagen in the hyaline cartilage displayed a typical Benninghoff structure, with collagen fibres parallel to the surface in the superficial zone and collagen fibres perpendicular to the surface in the deep zone. Elastin fibres were found throughout the entire tissue depth of the fibrous cartilage and displayed a similar alignment to the adjacent collagen bundles. In comparison, the elastin fibres in the hyaline cartilage were confined within the superficial zone. This study examined for the first time the fibrillary structure, PG content and compressive properties of the central fibrous cartilage pad and peripheral hyaline cartilage within the kangaroo medial tibial plateau. It provided insights into the microstructure and composition of the fibrous and peripheral hyaline cartilage in relation to the unique mechanical properties of the tissues to provide for the normal activities of kangaroos. PMID:24058543

Microstructural and compositional features of the fibrous and hyaline cartilage on the medial tibial plateau imply a unique role for the hopping locomotion of kangaroo.

PubMed

He, Bo; Wu, Jian Ping; Xu, Jiake; Day, Robert E; Kirk, Thomas Brett

2013-01-01

Hopping provides efficient and energy saving locomotion for kangaroos, but it results in great forces in the knee joints. A previous study has suggested that a unique fibrous cartilage in the central region of the tibial cartilage could serve to decrease the peak stresses generated within kangaroo tibiofemoral joints. However, the influences of the microstructure, composition and mechanical properties of the central fibrous and peripheral hyaline cartilage on the function of the knee joints are still to be defined. The present study showed that the fibrous cartilage was thicker and had a lower chondrocyte density than the hyaline cartilage. Despite having a higher PG content in the middle and deep zones, the fibrous cartilage had an inferior compressive strength compared to the peripheral hyaline cartilage. The fibrous cartilage had a complex three dimensional collagen meshwork with collagen bundles parallel to the surface in the superficial zone, and with collagen bundles both parallel and perpendicular to the surface in the middle and deep zones. The collagen in the hyaline cartilage displayed a typical Benninghoff structure, with collagen fibres parallel to the surface in the superficial zone and collagen fibres perpendicular to the surface in the deep zone. Elastin fibres were found throughout the entire tissue depth of the fibrous cartilage and displayed a similar alignment to the adjacent collagen bundles. In comparison, the elastin fibres in the hyaline cartilage were confined within the superficial zone. This study examined for the first time the fibrillary structure, PG content and compressive properties of the central fibrous cartilage pad and peripheral hyaline cartilage within the kangaroo medial tibial plateau. It provided insights into the microstructure and composition of the fibrous and peripheral hyaline cartilage in relation to the unique mechanical properties of the tissues to provide for the normal activities of kangaroos.

Feasibility of Dual Optics/Ultrasound Imaging and Contrast Media for the Detection and Characterization of Prostate Cancer

DTIC Science & Technology

2009-03-01

acousto - optic effect will be used to only modulate light (at the ultrasound frequency) which propagates through a small ultrasound focal zone. This...DOD Idea Development Award is concerned with the development of a novel acousto - optic detection idea based on quadrature measurements with a gain...perform acousto - optic molecular imaging of prostate cancer with incoherent photons using endogenous contrast, e.g. hypoxia, and with fluorescent probes and microbubbles for increased specificity and signal enhancement.

Extraglandular and intraglandular vascularization of canine prostate.

PubMed

Stefanov, Miroslav

2004-03-01

The literature on the vascularization of the canine prostate is reviewed and the clinical significance of prostate morphology is described. Scanning Electron Microscopy (SEM), combined with improved corrosion casting methods, reveal new morphological details that promise better diagnostics and treatment but also require expansion of clinical nomenclature. A proposal is made for including two previously unnamed veins in Nomina Anatomica Veterinaria (NAV). The canine prostate has two lobes with independent vascularization. Each lobe is supplied through the left and right a. prostatica, respectively. The a. prostatica sprouts three small vessels (cranial, middle, and caudal) towards the prostate gland. A. prostatica is a small-size artery whose wall structure is similar to the arteries of the muscular type. V. prostatica is a small-size valved vein. The canine prostate has capsular, parenchymal, and urethral vascular zones. The surface vessels of the capsule are predominantly veins and the diameter of arterial vessels is larger than that of the veins. The trabecular vessels are of two types: direct and branched. The prostate parenchyma is supplied by branches of the trabecular vessels. The periacinary capillaries are fenestrated and form a net in a circular pattern. The processes of the myoepithelial cells embrace both the acins and the periacinar capillaries. In the prostate ductal system. there are spermatozoa. The prostatic part of the urethra is supplied by an independent branch of a. prostatica. The prostatic urethral part is drained by v. prostatica, the vein of the urethral bulb and the ventral prostate veins. M. urethralis begins as early as the urethral prostatic part. The greater part of the white muscle fibers in m. urethralis suggest an enhanced anaerobic metabolism. Copyright 2004 Wiley-Liss, Inc.

A transfer learning approach for classification of clinical significant prostate cancers from mpMRI scans

NASA Astrophysics Data System (ADS)

Chen, Quan; Xu, Xiang; Hu, Shiliang; Li, Xiao; Zou, Qing; Li, Yunpeng

2017-03-01

Deep learning has shown a great potential in computer aided diagnosis. However, in many applications, large dataset is not available. This makes the training of a sophisticated deep learning neural network (DNN) difficult. In this study, we demonstrated that with transfer learning, we can quickly retrain start-of-the-art DNN models with limited data provided by the prostateX challenge. The training data consists of 330 lesions, only 78 were clinical significant. Efforts were made to balance the data during training. We used ImageNet pre-trained inceptionV3 and Vgg-16 model and obtained AUC of 0.81 and 0.83 respectively on the prostateX test data, good for a 4th place finish. We noticed that models trained for different prostate zone has different sensitivity. Applying scaling factors before merging the result improves the AUC for the final result.

Logistic regression model for diagnosis of transition zone prostate cancer on multi-parametric MRI.

PubMed

Dikaios, Nikolaos; Alkalbani, Jokha; Sidhu, Harbir Singh; Fujiwara, Taiki; Abd-Alazeez, Mohamed; Kirkham, Alex; Allen, Clare; Ahmed, Hashim; Emberton, Mark; Freeman, Alex; Halligan, Steve; Taylor, Stuart; Atkinson, David; Punwani, Shonit

2015-02-01

We aimed to develop logistic regression (LR) models for classifying prostate cancer within the transition zone on multi-parametric magnetic resonance imaging (mp-MRI). One hundred and fifty-five patients (training cohort, 70 patients; temporal validation cohort, 85 patients) underwent mp-MRI and transperineal-template-prostate-mapping (TPM) biopsy. Positive cores were classified by cancer definitions: (1) any-cancer; (2) definition-1 [≥Gleason 4 + 3 or ≥ 6 mm cancer core length (CCL)] [high risk significant]; and (3) definition-2 (≥Gleason 3 + 4 or ≥ 4 mm CCL) cancer [intermediate-high risk significant]. For each, logistic-regression mp-MRI models were derived from the training cohort and validated internally and with the temporal cohort. Sensitivity/specificity and the area under the receiver operating characteristic (ROC-AUC) curve were calculated. LR model performance was compared to radiologists' performance. Twenty-eight of 70 patients from the training cohort, and 25/85 patients from the temporal validation cohort had significant cancer on TPM. The ROC-AUC of the LR model for classification of cancer was 0.73/0.67 at internal/temporal validation. The radiologist A/B ROC-AUC was 0.65/0.74 (temporal cohort). For patients scored by radiologists as Prostate Imaging Reporting and Data System (Pi-RADS) score 3, sensitivity/specificity of radiologist A 'best guess' and LR model was 0.14/0.54 and 0.71/0.61, respectively; and radiologist B 'best guess' and LR model was 0.40/0.34 and 0.50/0.76, respectively. LR models can improve classification of Pi-RADS score 3 lesions similar to experienced radiologists. • MRI helps find prostate cancer in the anterior of the gland • Logistic regression models based on mp-MRI can classify prostate cancer • Computers can help confirm cancer in areas doctors are uncertain about.

Focal Laser Ablation of Prostate Cancer: Feasibility of Magnetic Resonance Imaging-Ultrasound Fusion for Guidance.

PubMed

Natarajan, Shyam; Jones, Tonye A; Priester, Alan M; Geoghegan, Rory; Lieu, Patricia; Delfin, Merdie; Felker, Ely; Margolis, Daniel J A; Sisk, Anthony; Pantuck, Allan; Grundfest, Warren; Marks, Leonard S

2017-10-01

Focal laser ablation is a potential treatment in some men with prostate cancer. Currently focal laser ablation is performed by radiologists in a magnetic resonance imaging unit (in bore). We evaluated the safety and feasibility of performing focal laser ablation in a urology clinic (out of bore) using magnetic resonance imaging-ultrasound fusion for guidance. A total of 11 men with intermediate risk prostate cancer were enrolled in this prospective, institutional review board approved pilot study. Magnetic resonance imaging-ultrasound fusion was used to guide laser fibers transrectally into regions of interest harboring intermediate risk prostate cancer. Thermal probes were inserted for real-time monitoring of intraprostatic temperatures during laser activation. Multiparametric magnetic resonance imaging (3 Tesla) was done immediately after treatment and at 6 months along with comprehensive fusion biopsy. Ten of 11 patients were successfully treated while under local anesthesia. Mean procedure time was 95 minutes (range 71 to 105). Posttreatment magnetic resonance imaging revealed a confined zone of nonperfusion in all 10 men. Mean zone volume was 4.3 cc (range 2.1 to 6.0). No CTCAE grade 3 or greater adverse events developed and no changes were observed in urinary or sexual function. At 6 months magnetic resonance imaging-ultrasound fusion biopsy of the treatment site showed no cancer in 3 patients, microfocal Gleason 3 + 3 in another 3 and persistent intermediate risk prostate cancer in 4. Focal laser ablation of prostate cancer appears safe and feasible with the patient under local anesthesia in a urology clinic using magnetic resonance imaging-ultrasound fusion for guidance and thermal probes for monitoring. Further development is necessary to refine out of bore focal laser ablation and additional studies are needed to determine appropriate treatment margins and oncologic efficacy. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Using the prostate imaging reporting and data system version 2 (PI-RIDS v2) to detect prostate cancer can prevent unnecessary biopsies and invasive treatment.

PubMed

Liu, Chang; Liu, Shi-Liang; Wang, Zhi-Xian; Yu, Kai; Feng, Chun-Xiang; Ke, Zan; Wang, Liang; Zeng, Xiao-Yong

2018-04-13

Prostate cancer (PCa) is one of the most common cancers among men globally. The authors aimed to evaluate the ability of the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) to classify men with PCa, clinically significant PCa (CSPCa), or no PCa, especially among those with serum total prostate-specific antigen (tPSA) levels in the "gray zone" (4-10 ng ml -1 ). A total of 308 patients (355 lesions) were enrolled in this study. Diagnostic efficiency was determined. Univariate and multivariate analyses, receiver operating characteristic curve analysis, and decision curve analysis were performed to determine and compare the predictors of PCa and CSPCa. The results suggested that PI-RADS v2, tPSA, and prostate-specific antigen density (PSAD) were independent predictors of PCa and CSPCa. A PI-RADS v2 score ≥4 provided high negative predictive values (91.39% for PCa and 95.69% for CSPCa). A model of PI-RADS combined with PSA and PSAD helped to define a high-risk group (PI-RADS score = 5 and PSAD ≥0.15 ng ml -1 cm -3 , with tPSA in the gray zone, or PI-RADS score ≥4 with high tPSA level) with a detection rate of 96.1% for PCa and 93.0% for CSPCa while a low-risk group with a detection rate of 6.1% for PCa and 2.2% for CSPCa. It was concluded that the PI-RADS v2 could be used as a reliable and independent predictor of PCa and CSPCa. The combination of PI-RADS v2 score with PSA and PSAD could be helpful in the prediction and diagnosis of PCa and CSPCa and, thus, may help in preventing unnecessary invasive procedures.

3D Registration of mpMRI for Assessment of Prostate Cancer Focal Therapy.

PubMed

Orczyk, Clément; Rosenkrantz, Andrew B; Mikheev, Artem; Villers, Arnauld; Bernaudin, Myriam; Taneja, Samir S; Valable, Samuel; Rusinek, Henry

2017-12-01

This study aimed to assess a novel method of three-dimensional (3D) co-registration of prostate magnetic resonance imaging (MRI) examinations performed before and after prostate cancer focal therapy. We developed a software platform for automatic 3D deformable co-registration of prostate MRI at different time points and applied this method to 10 patients who underwent focal ablative therapy. MRI examinations were performed preoperatively, as well as 1 week and 6 months post treatment. Rigid registration served as reference for assessing co-registration accuracy and precision. Segmentation of preoperative and postoperative prostate revealed a significant postoperative volume decrease of the gland that averaged 6.49 cc (P = .017). Applying deformable transformation based on mutual information from 120 pairs of MRI slices, we refined by 2.9 mm (max. 6.25 mm) the alignment of the ablation zone, segmented from contrast-enhanced images on the 1-week postoperative examination, to the 6-month postoperative T2-weighted images. This represented a 500% improvement over the rigid approach (P = .001), corrected by volume. The dissimilarity by Dice index of the mapped ablation zone using deformable transformation vs rigid control was significantly (P = .04) higher at the ablation site than in the whole gland. Our findings illustrate our method's ability to correct for deformation at the ablation site. The preliminary analysis suggests that deformable transformation computed from mutual information of preoperative and follow-up MRI is accurate in co-registration of MRI examinations performed before and after focal therapy. The ability to localize the previously ablated tissue in 3D space may improve targeting for image-guided follow-up biopsy within focal therapy protocols. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Urinary MicroRNAs of Prostate Cancer: Virus-Encoded hsv1-miRH18 and hsv2-miR-H9-5p Could Be Valuable Diagnostic Markers.

PubMed

Yun, Seok Joong; Jeong, Pildu; Kang, Ho Won; Kim, Ye-Hwan; Kim, Eun-Ah; Yan, Chunri; Choi, Young-Ki; Kim, Dongho; Kim, Jung Min; Kim, Seon-Kyu; Kim, Seon-Young; Kim, Sang Tae; Kim, Won Tae; Lee, Ok-Jun; Koh, Gou-Young; Moon, Sung-Kwon; Kim, Isaac Yi; Kim, Jayoung; Choi, Yung-Hyun; Kim, Wun-Jae

2015-06-01

MicroRNAs (miRNAs) in biological fluids are potential biomarkers for the diagnosis and assessment of urological diseases such as benign prostatic hyperplasia (BPH) and prostate cancer (PCa). The aim of the study was to identify and validate urinary cell-free miRNAs that can segregate patients with PCa from those with BPH. In total, 1,052 urine, 150 serum, and 150 prostate tissue samples from patients with PCa or BPH were used in the study. A urine-based miRNA microarray analysis suggested the presence of differentially expressed urinary miRNAs in patients with PCa, and these were further validated in three independent PCa cohorts, using a quantitative reverse transcriptionpolymerase chain reaction analysis. The expression levels of hsa-miR-615-3p, hsv1-miR-H18, hsv2-miR-H9-5p, and hsa-miR-4316 were significantly higher in urine samples of patients with PCa than in those of BPH controls. In particular, herpes simplex virus (hsv)-derived hsv1-miR-H18 and hsv2-miR-H9-5p showed better diagnostic performance than did the serum prostate-specific antigen (PSA) test for patients in the PSA gray zone. Furthermore, a combination of urinary hsv2-miR-H9-5p with serum PSA showed high sensitivity and specificity, providing a potential clinical benefit by reducing unnecessary biopsies. Our findings showed that hsv-encoded hsv1-miR-H18 and hsv2-miR-H9-5p are significantly associated with PCa and can facilitate early diagnosis of PCa for patients within the serum PSA gray zone.

Urinary MicroRNAs of Prostate Cancer: Virus-Encoded hsv1-miRH18 and hsv2-miR-H9-5p Could Be Valuable Diagnostic Markers

PubMed Central

Yun, Seok Joong; Jeong, Pildu; Kang, Ho Won; Kim, Ye-Hwan; Kim, Eun-Ah; Yan, Chunri; Choi, Young-Ki; Kim, Dongho; Kim, Jung Min; Kim, Seon-Kyu; Kim, Seon-Young; Kim, Sang Tae; Kim, Won Tae; Lee, Ok-Jun; Koh, Gou-Young; Moon, Sung-Kwon; Kim, Isaac Yi; Kim, Jayoung; Choi, Yung-Hyun; Kim, Wun-Jae

2015-01-01

Purpose: MicroRNAs (miRNAs) in biological fluids are potential biomarkers for the diagnosis and assessment of urological diseases such as benign prostatic hyperplasia (BPH) and prostate cancer (PCa). The aim of the study was to identify and validate urinary cell-free miRNAs that can segregate patients with PCa from those with BPH. Methods: In total, 1,052 urine, 150 serum, and 150 prostate tissue samples from patients with PCa or BPH were used in the study. A urine-based miRNA microarray analysis suggested the presence of differentially expressed urinary miRNAs in patients with PCa, and these were further validated in three independent PCa cohorts, using a quantitative reverse transcriptionpolymerase chain reaction analysis. Results: The expression levels of hsa-miR-615-3p, hsv1-miR-H18, hsv2-miR-H9-5p, and hsa-miR-4316 were significantly higher in urine samples of patients with PCa than in those of BPH controls. In particular, herpes simplex virus (hsv)-derived hsv1-miR-H18 and hsv2-miR-H9-5p showed better diagnostic performance than did the serum prostate-specific antigen (PSA) test for patients in the PSA gray zone. Furthermore, a combination of urinary hsv2-miR-H9-5p with serum PSA showed high sensitivity and specificity, providing a potential clinical benefit by reducing unnecessary biopsies. Conclusions: Our findings showed that hsv-encoded hsv1-miR-H18 and hsv2-miR-H9-5p are significantly associated with PCa and can facilitate early diagnosis of PCa for patients within the serum PSA gray zone. PMID:26126436

DCE-MRI of the prostate using shutter-speed vs. Tofts model for tumor characterization and assessment of aggressiveness.

PubMed

Hectors, Stefanie J; Besa, Cecilia; Wagner, Mathilde; Jajamovich, Guido H; Haines, George K; Lewis, Sara; Tewari, Ashutosh; Rastinehad, Ardeshir; Huang, Wei; Taouli, Bachir

2017-09-01

To quantify Tofts model (TM) and shutter-speed model (SSM) perfusion parameters in prostate cancer (PCa) and noncancerous peripheral zone (PZ) and to compare the diagnostic performance of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to Prostate Imaging and Reporting and Data System (PI-RADS) classification for the assessment of PCa aggressiveness. Fifty PCa patients (mean age 60 years old) who underwent MRI at 3.0T followed by prostatectomy were included in this Institutional Review Board-approved retrospective study. DCE-MRI parameters (K trans , v e , k ep [TM&SSM] and intracellular water molecule lifetime τ i [SSM]) were determined in PCa and PZ. Differences in DCE-MRI parameters between PCa and PZ, and between models were assessed using Wilcoxon signed-rank tests. Receiver operating characteristic (ROC) analysis for differentiation between PCa and PZ was performed for individual and combined DCE-MRI parameters. Diagnostic performance of DCE-MRI parameters for identification of aggressive PCa (Gleason ≥8, grade group [GG] ≥3 or pathology stage pT3) was assessed using ROC analysis and compared with PI-RADSv2 scores. DCE-MRI parameters were significantly different between TM and SSM and between PZ and PCa (P < 0.037). Diagnostic performances of TM and SSM for differentiation of PCa from PZ were similar (highest AUC TM: K trans +k ep 0.76, SSM: τ i +k ep 0.80). PI-RADS outperformed TM and SSM DCE-MRI for identification of Gleason ≥8 lesions (AUC PI-RADS: 0.91, highest AUC DCE-MRI: K trans +τ i SSM 0.61, P = 0.002). The diagnostic performance of PI-RADS and DCE-MRI for identification of GG ≥3 and pT3 PCa was not significantly different (P > 0.213). SSM DCE-MRI did not increase the diagnostic performance of DCE-MRI for PCa characterization. PI-RADS outperformed both TM and SSM DCE-MRI for identification of aggressive cancer. 3 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:837-849. © 2017 International Society for Magnetic Resonance in Medicine.

Risk Stratification Among Men With Prostate Imaging Reporting and Data System Version 2 Category 3 Transition Zone Lesions: Is Biopsy Always Necessary?

PubMed Central

Felker, Ely R.; Raman, Steven S.; Margolis, Daniel J.; Lu, David S. K.; Shaheen, Nicholas; Natarajan, Shyam; Sharma, Devi; Huang, Jiaoti; Dorey, Fred; Marks, Leonard S.

2017-01-01

OBJECTIVE The objective of our study was to determine the clinical and MRI characteristics of clinically significant prostate cancer (PCA) (Gleason score ≥ 3 + 4) in men with Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) category 3 transition zone (TZ) lesions. MATERIALS AND METHODS From 2014 to 2016, 865 men underwent prostate MRI and MRI/ultrasound (US) fusion biopsy (FB). A subset of 90 FB-naïve men with 96 PI-RADSv2 category 3 TZ lesions was identified. Patients were imaged at 3 T using a body coil. Images were assigned a PI-RADSv2 category by an experienced radiologist. Using clinical data and imaging features, we performed univariate and multivariate analyses to identify predictors of clinically significant PCA. RESULTS The mean patient age was 66 years, and the mean prostate-specific antigen density (PSAD) was 0.13 ng/mL2. PCA was detected in 34 of 96 (35%) lesions, 14 of which (15%) harbored clinically significant PCA. In univariate analysis, DWI score, prostate volume, and PSAD were significant predictors (p < 0.05) of clinically significant PCA with a suggested significance for apparent diffusion coefficient (ADC) and prostate-specific antigen value (p < 0.10). On multivariate analysis, PSAD and lesion ADC were the most important covariates. The combination of both PSAD of 0.15 ng/mL2 or greater and an ADC value of less than 1000 mm2/s yielded an AUC of 0.91 for clinically significant PCA (p < 0.001). If FB had been restricted to these criteria, only 10 of 90 men would have undergone biopsy, resulting in diagnosis of clinically significant PCA in 60% with eight men (9%) misdiagnosed (false-negative). CONCLUSION The yield of FB in men with PI-RADSv2 category 3 TZ lesions for clinically significant PCA is 15% but significantly improves to 60% (AUC > 0.9) among men with PSAD of 0.15 ng/mL2 or greater and lesion ADC value of less than 1000 mm2/s. PMID:28858541

Expression and localization of GLUT1 and GLUT12 in prostate carcinoma.

PubMed

Chandler, Jenalle D; Williams, Elizabeth D; Slavin, John L; Best, James D; Rogers, Suzanne

2003-04-15

Increased glucose consumption is a characteristic of malignant cells and in prostate carcinoma is associated with the proliferation of both androgen-dependent and independent cells. Transport of polar glucose across the nonpolar membrane relies on glucose transporter proteins, known as GLUTs. Increased expression of GLUT1 is a characteristic of many malignant cells. The authors characterized and cloned the cDNA for a novel glucose transporter, GLUT12, which was identified initially in malignant breast epithelial cells. To the authors' knowledge, there have been no reports on the expression of glucose transporters in the human prostate or human prostate carcinoma cells. The authors evaluated GLUT1 and GLUT12 expression in human prostate carcinoma cells. Reverse transcription-polymerase chain reaction was performed on total RNA extracted from cultured prostate carcinoma cells LNCaP, C4, C4-2, and C4-2B using primers to amplify GLUT1, GLUT12, or the housekeeping gene, 36B4. Total protein extracted from prostate carcinoma cell lines was assessed for GLUT12 protein by Western blot analysis. Cultured cell monolayers were incubated with antibodies to GLUT1 or GLUT12 and a peripheral Golgi protein, Golgi 58K, for detection by immunofluorescent confocal microscopy. Sections of benign prostatic hyperplasia and human prostate carcinoma were stained for immunohistochemical detection of GLUT1 and GLUT12. GLUT1 and GLUT12 mRNA and protein were detected in all cell lines evaluated. Immunofluorescence staining demonstrated both GLUT1 and GLUT12 on the plasma membrane and in the cytoplasm in all cultured prostate carcinoma cell lines, with GLUT1 but not GLUT12 appearing to colocalize with the Golgi. Immunohistochemical staining of benign prostatic hyperplasia indicated expression of GLUT1 but not GLUT12. Malignant tissue stained for GLUT12 but was negative for GLUT1. GLUT1 and GLUT12 are expressed in human prostate carcinoma cells. One possible rationale for the GLUT1 Golgi association is that it may supply glucose to the Golgi for byproduct incorporation into the prostatic secretory fluid. Further work will investigate the importance of glucose transport and GLUT1 and GLUT12 in prostate carcinoma cell growth. Copyright 2003 American Cancer Society.

A new model consists of intravesical prostatic protrusion, prostate volume and serum prostatic-specific antigen in the evaluation of prostate cancer.

PubMed

Xu, Ding; Yu, Yongjiang; Zhu, Yunkai; Huang, Tao; Chen, Yaqing; Qi, Jun

2014-04-01

The Prostate-specific antigen (PSA) level is largely used to diagnose prostate cancer (PCa) in last decades. However, its specificity is low in patients with a PSA level ranging from 4.0 to 10.0 ng/ml. This study aims to define the correlation between intravesical prostatic protrusion (IPP) and PSA and to establish a new model to predict PCa. A total of 339 patients order than 45 years examined between October 2010 and June 2012 were enrolled. Eligible patients were recommended for transrectal ultrasonography (TRUS)-guided prostate biopsies after measuring total prostate volume (TPV), tranzisional zone volume (TZV) and IPP. The levels of total PSA (tPSA), free PSA (fPSA) were analyzed by using Hybritech calibrated Access tPSA and fPSA assays. A new mathematical model, named IPP removed PCa predicting score (IRPPS), consists of tPSA, TZV and IPP was established. The predictive accuracy of IRPPS, PSA density (PSAD), %PSA and tPSA were compared using receiver-operator characteristic (ROC) analysis. Eighty-six patients had PSA levels of 4.0-10.0 ng/ml. Twenty of them were diagnosed as PCa. Using ROC curves, the areas under the curve for IRPPS, PSAD and %PSA and tPSA were 0.786, 0.768 and 0.664 and 0.585, respectively. We suggested IPP grade had a significant relationship with serum tPSA levels. The predictive accuracy of IRPPS was higher than the other 3 indictors.

Efficacy of Intravitreal Bevacizumab for Stage 3+ Retinopathy of Prematurity

PubMed Central

Mintz-Hittner, Helen A.; Kennedy, Kathleen A.; Chuang, Alice Z.

2011-01-01

BACKGROUND Retinopathy of prematurity is a leading cause of childhood blindness worldwide. Peripheral retinal ablation with conventional (confluent) laser therapy is destructive, causes complications, and does not prevent all vision loss, especially in cases of retinopathy of prematurity affecting zone I of the eye. Case series in which patients were treated with vascular endothelial growth factor inhibitors suggest that these agents may be useful in treating retinopathy of prematurity. METHODS We conducted a prospective, controlled, randomized, stratified, multicenter trial to assess intravitreal bevacizumab monotherapy for zone I or zone II posterior stage 3+ (i.e., stage 3 with plus disease) retinopathy of prematurity. Infants were randomly assigned to receive intravitreal bevacizumab (0.625 mg in 0.025 ml of solution) or conventional laser therapy, bilaterally. The primary ocular outcome was recurrence of retinopathy of prematurity in one or both eyes requiring retreatment before 54 weeks’ postmenstrual age. RESULTS We enrolled 150 infants (total sample of 300 eyes); 143 infants survived to 54 weeks’ postmenstrual age, and the 7 infants who died were not included in the primary-outcome analyses. Retinopathy of prematurity recurred in 4 infants in the bevacizumab group (6 of 140 eyes [4%]) and 19 infants in the laser-therapy group (32 of 146 eyes [22%], P = 0.002). A significant treatment effect was found for zone I retinopathy of prematurity (P = 0.003) but not for zone II disease (P = 0.27). CONCLUSIONS Intravitreal bevacizumab monotherapy, as compared with conventional laser therapy, in infants with stage 3+ retinopathy of prematurity showed a significant benefit for zone I but not zone II disease. Development of peripheral retinal vessels continued after treatment with intravitreal bevacizumab, but conventional laser therapy led to permanent destruction of the peripheral retina. This trial was too small to assess safety. PMID:21323540

Cell membrane water exchange effects in prostate DCE-MRI

NASA Astrophysics Data System (ADS)

Li, Xin; Priest, Ryan A.; Woodward, William J.; Siddiqui, Faisal; Beer, Tomasz M.; Garzotto, Mark G.; Rooney, William D.; Springer, Charles S.

2012-05-01

Prostate Dynamic-Contrast-Enhanced (DCE) MRI often exhibits fast and extensive global contrast reagent (CR) extravasation - measured by Ktrans, a pharmacokinetic parameter proportional to its rate. This implies that the CR concentration [CR] is high in the extracellular, extravascular space (EES) during a large portion of the DCE-MRI study. Since CR is detected indirectly, through water proton signal change, the effects of equilibrium transcytolemmal water exchange may be significant in the data and thus should be admitted in DCE-MRI pharmacokinetic modeling. The implications for parameter values were investigated through simulations, and analyses of actual prostate data, with different models. Model parameter correlation and precision were also explored. A near-optimal version of the exchange-sensitized model was found. Our results indicate that ΔKtrans (the Ktrans difference returned by this version and a model assuming exchange to be effectively infinitely fast) may be a very useful biomarker for discriminating malignant from benign prostate tissue. Using an exchange-sensitized model, we find that the mean intracellular water lifetime (τi) - an exchange measure - can be meaningfully mapped for the prostate. Our results show prostate glandular zone differences in τi values.

[Peripheral refraction and retinal contour in congenital and acquired high myopia].

PubMed

Tarutta, E P; Markosyan, G A; Milash, S V

to perform a comparative study of peripheral refraction and retinal contour in patients with congenital versus acquired high myopia. A total of 30 patients (60 eyes) with high myopia aged 8 to 18 years (11.2±0.32 years on average) were examined. The patients were divided into 2 groups. Group 1 consisted of 21 patients (42 eyes) with acquired myopia of -6.0 to -10.25 diopters (-7.55±0.17 diopters on average), group 2 - of 9 patients (18 eyes) with congenital myopia of -8.75 to -28.75 diopters (-16.39±1.24 diopters on average). Using the Grand Seiko WR-5100K binocular open-field autoref/keratometer (Japan), relative peripheral refraction was assessed with account to relative peripheral eye length measured by the IOL Master partial coherent interferometer ('Carl Zeiss', Germany) at 15° and 30° nasally and temporally from the foveal center along the horizontal meridian. In acquired myopia, relative peripheral refraction and relative peripheral eye length readings evidenced the formation of peripheral hyperopic defocus in all examined zones. Congenital high myopia cases were notable for myopic defocus at 15° of the nasal retina (N15 zone): -0.67±0.33 diopters against the eye length change of -0.33±0.13 mm. The research helped identify retinal contour changes characteristic of congenital myopia and indicative of posterior pole irregularity.

Clinical correlates of enlarged prostate size in subjects with sexual dysfunction

PubMed Central

Corona, Giovanni; Gacci, Mauro; Maseroli, Elisa; Rastrelli, Giulia; Vignozzi, Linda; Sforza, Alessandra; Forti, Gianni; Mannucci, Edoardo; Maggi, Mario

2014-01-01

Digito-rectal examination (DRE) of the prostate provides useful information on the state of prostate growth and on the presence of suspected peripheral nodules. The aim of this study is to describe the clinical and biochemical correlates of finding an enlarged prostate size at DRE in subjects with sexual dysfunction (SD). A consecutive series of 2379 patients was retrospectively studied. The analysis was focused on a subset of subjects (n = 1823; mean age 54.7 ± 11.4) selected for being free from overt prostatic diseases. Several parameters were investigated. After adjusting for confounders, the presence of an enlarged prostate size at DRE was associated with a higher risk of metabolic syndrome (HR = 1.346 (1.129–1.759); P = 0.030), type 2 diabetes mellitus (HR = 1.489 (1.120–1.980); P = 0.006), increased LDL cholesterol (>100 mg dl−1; HR = 1.354 (1.018–1.801); P = 0.037) and increased mean blood pressure (BP) values (HR = 1.017 (1.007–1.027) for each mmHg increment; P = 0.001). Accordingly, enlarged prostate size was also associated with a higher risk of arteriogenic erectile dysfunction (ED), as well as with other andrological conditions, such as varicocele and premature ejaculation (PE). PSA levels were significantly higher in subjects with enlarged prostate size when compared to the rest of the sample (HR = 3.318 (2.304; 4.799) for each log unit increment in PSA levels; P < 0.0001). Arteriogenic ED, according to different criteria, was also associated with increased PSA levels. In conclusion, our data support the need to examine prostate size either by clinical (DRE) or biochemical (PSA) inspection in subjects with SD, in order to have insights into the nature of the SD and the metabolic and cardiovascular (CV) background of the patient. PMID:24830688

Increased PSA expression on prostate cancer exosomes in in vitro condition and in cancer patients.

PubMed

Logozzi, Mariantonia; Angelini, Daniela F; Iessi, Elisabetta; Mizzoni, Davide; Di Raimo, Rossella; Federici, Cristina; Lugini, Luana; Borsellino, Giovanna; Gentilucci, Alessandro; Pierella, Federico; Marzio, Vittorio; Sciarra, Alessandro; Battistini, Luca; Fais, Stefano

2017-09-10

Prostate specific antigen (PSA) test is the most common, clinically validated test for the diagnosis of prostate cancer (PCa). While neoplastic lesions of the prostate may cause aberrant levels of PSA in the blood, the quantitation of free or complexed PSA poorly discriminates cancer patients from those developing benign lesions, often leading to invasive and unnecessary surgical procedures. Microenvironmental acidity increases exosome release by cancer cells. In this study we evaluated whether acidity, a critical phenotype of malignancy, could influence exosome release and increase the PSA expression in nanovesicles released by PCa cells. To this aim, we exploited Nanoparticle Tracking Analysis (NTA), an immunocapture-based ELISA, and nanoscale flow-cytometry. The results show that microenvironmental acidity induces an increased release of nanovesicles expressing both PSA and the exosome marker CD81. In order to verify whether the changes induced by the local selective pressure of extracellular acidity may correspond to a clinical pathway we used the same approach to evaluate the levels of PSA-expressing exosomes in the plasma of PCa patients and controls, including subjects with benign prostatic hypertrophy (BPH). The results show that only PCa patients have high levels of nanovesicles expressing both CD81 and PSA. This study shows that tumor acidity exerts a selective pressure leading to the release of extracellular vesicles that express both PSA and exosome markers. A comparable scenario was shown in the plasma of prostate cancer patients as compared to both BPH and healthy controls. These results suggest that microenvironmental acidity may represent a key factor which determines qualitatively and quantitatively the release of extracellular vesicles by malignant tumors, including prostate cancer. This condition leads to the spill-over of nanovesicles into the peripheral blood of prostate cancer patients, where the levels of tumor biomarkers expressed by exosomes, such as PSA-exosomes, may represent a novel, non-invasive clinical tool for the screening and early diagnosis of prostate cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

[Prostatic granulomas revealing a peripheral T-cell lymphoma].

PubMed

Foguem, C; Curlier, E; Rouamba, M-M; Regent, A; Philippe, P

2009-02-01

The presence of granulomas on tissue biopsie has been reported in a wide range of disorders. The clinical presentation and the diagnostic work-up of granulomatosis can be difficult as it is illustrated in the following report. A 59-year-old patient was referred in 2002 for a granulomatous prostatitis. Physical examination was normal. Except for the increase of prostate-specific antigen (which motivated a biopsy), the laboratory results were normal. Thoracic CT-scan disclosed mediastinal lymph nodes. A minor salivary gland biopsy was consistent with the diagnosis of sarcoidosis. In 2004, the patient presented an epidermal necrolysis, and in 2005 the deterioration of general status raised suspicion of a lymphoproliferative disorder. Liver and bone marrow biopsies revealed a granulomatous process. Despite steroid therapy, the patient died. Autopsy discloses a anaplasic T cell lymphoma. This report illustrates the relationship between sarcoidosis and lymphoma as a mode of presentation, a complication, or an accidental but misleading association? The association between anaplastic lymphoma and sarcoidosis is exceptional.

Ghrelin O-acyltransferase (GOAT) is expressed in prostate cancer tissues and cell lines and expression is differentially regulated in vitro by ghrelin

PubMed Central

2013-01-01

Background Ghrelin is a 28 amino acid peptide hormone that is expressed in the stomach and a range of peripheral tissues, where it frequently acts as an autocrine/paracrine growth factor. Ghrelin is modified by a unique acylation required for it to activate its cognate receptor, the growth hormone secretagogue receptor (GHSR), which mediates many of the actions of ghrelin. Recently, the enzyme responsible for adding the fatty acid residue (octanoyl/acyl group) to the third amino acid of ghrelin, GOAT (ghrelin O-acyltransferase), was identified. Methods We used cell culture, quantitative real-time reverse transcription (RT)-PCR and immunohistochemistry to demonstrate the expression of GOAT in prostate cancer cell lines and tissues from patients. Real-time RT-PCR was used to demonstrate the expression of prohormone convertase (PC)1/3, PC2 and furin in prostate cancer cell lines. Prostate-derived cell lines were treated with ghrelin and desacyl ghrelin and the effect on GOAT expression was measured using quantitative RT-PCR. Results We have demonstrated that GOAT mRNA and protein are expressed in the normal prostate and human prostate cancer tissue samples. The RWPE-1 and RWPE-2 normal prostate-derived cell lines and the LNCaP, DU145, and PC3 prostate cancer cell lines express GOAT and at least one other enzyme that is necessary to produce mature, acylated ghrelin from proghrelin (PC1/3, PC2 or furin). Finally, ghrelin, but not desacyl ghrelin (unacylated ghrelin), can directly regulate the expression of GOAT in the RWPE-1 normal prostate derived cell line and the PC3 prostate cancer cell line. Ghrelin treatment (100nM) for 6 hours significantly decreased GOAT mRNA expression two-fold (P < 0.05) in the PC3 prostate cancer cell line, however, ghrelin did not regulate GOAT expression in the DU145 and LNCaP prostate cancer cell lines. Conclusions This study demonstrates that GOAT is expressed in prostate cancer specimens and cell lines. Ghrelin regulates GOAT expression, however, this is likely to be cell-type specific. The expression of GOAT in prostate cancer supports the hypothesis that the ghrelin axis has autocrine/paracrine roles. We propose that the RWPE-1 prostate cell line and the PC3 prostate cancer cell line may be useful for investigating GOAT regulation and function. PMID:23879975

Cyclophosphamide augments antitumor immunity: studies in an autochthonous prostate cancer model.

PubMed

Wada, Satoshi; Yoshimura, Kiyoshi; Hipkiss, Edward L; Harris, Tim J; Yen, Hung-Rong; Goldberg, Monica V; Grosso, Joseph F; Getnet, Derese; Demarzo, Angelo M; Netto, George J; Anders, Robert; Pardoll, Drew M; Drake, Charles G

2009-05-15

To study the immune response to prostate cancer, we developed an autochthonous animal model based on the transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse in which spontaneously developing tumors express influenza hemagglutinin as a unique, tumor-associated antigen. Our prior studies in these animals showed immunologic tolerance to hemagglutinin, mirroring the clinical situation in patients with cancer who are generally nonresponsive to their disease. We used this physiologically relevant animal model to assess the immunomodulatory effects of cyclophosphamide when administered in combination with an allogeneic, cell-based granulocyte-macrophage colony-stimulating factor-secreting cancer immunotherapy. Through adoptive transfer of prostate/prostate cancer-specific CD8 T cells as well as through studies of the endogenous T-cell repertoire, we found that cyclophosphamide induced a marked augmentation of the antitumor immune response. This effect was strongly dependent on both the dose and the timing of cyclophosphamide administration. Mechanistic studies showed that immune augmentation by cyclophosphamide was associated with a transient depletion of regulatory T cells in the tumor draining lymph nodes but not in the peripheral circulation. Interestingly, we also noted effects on dendritic cell phenotype; low-dose cyclophosphamide was associated with increased expression of dendritic cell maturation markers. Taken together, these data clarify the dose, timing, and mechanism of action by which immunomodulatory cyclophosphamide can be translated to a clinical setting in a combinatorial cancer treatment strategy.

Cell intrinsic abrogation of TGFβ signaling delays but does not prevent dysfunction of self/tumor specific CD8 T cells in a murine model of autochthonous prostate cancer

PubMed Central

Chou, Cassie K.; Schietinger, Andrea; Liggitt, H. Denny; Tan, Xiaoxia; Funk, Sarah; Freeman, Gordon J.; Ratliff, Timothy L.; Greenberg, Norman M.; Greenberg, Philip D.

2012-01-01

Adoptive T cell therapy (ACT) for the treatment of established cancers is actively being pursued in clinical trials. However, poor in vivo persistence and maintenance of anti-tumor activity of transferred T cells remain major problems. Transforming growth factor beta (TGFβ) is a potent immunosuppressive cytokine that is often expressed at high levels within the tumor microenvironment, potentially limiting T cell mediated anti-tumor activity. Here, we used a model of autochthonous murine prostate cancer to evaluate the effect of cell intrinsic abrogation of TGFβ signaling in self/tumor specific CD8 T cells used in ACT to target the tumor in situ. We found that persistence and anti-tumor activity of adoptively transferred effector T cells deficient in TGFβ signaling was significantly improved in the cancerous prostate. However, over time, despite persistence in peripheral lymphoid organs, the numbers of transferred cells in the prostate decreased and the residual prostate infiltrating T cells were no longer functional. These findings reveal that TGFβ negatively regulates the accumulation and effector function of transferred self/tumor specific CD8 T cells and highlight that, when targeting a tumor antigen that is also expressed as a self-protein, additional substantive obstacles are operative within the tumor microenvironment, potentially hampering the success of ACT for solid tumors. PMID:22984076

Peripheral structures of the Rio Grande Rift in the Sangre de Cristo Mountains, around the Colorado-New Mexico border

NASA Astrophysics Data System (ADS)

Fridrich, C. J.; Workman, J. B.

2009-12-01

Recently active faults of the Rio Grande rift near the Colorado-New Mexico border are almost entirely limited to the San Luis basin. In contrast, the early (≈26 to ≈10 Ma) structure of the rift in this area is significantly broader. A wide zone of abandoned, peripheral extensional structures is exposed on the eastern flank of the San Luis basin—in the west half of the Sangre de Cristo Mountains, known in this area as the southern Culebra and northern Taos Ranges. New detailed mapping shows that the eastern limit of the zone of early peripheral extension is marked by an aligned series of north-trending grabens, including the Devil’s Park, Valle Vidal, and Moreno Valley basins. Master faults of these intermontaine basins are partly localized along, and evidently reactivated moderate- to high-angle Laramide (≈70 to ≈40 Ma) reverse faults of the Sangre de Cristo Mountains. Between these grabens and the San Luis basin lies a structural zone that varies in style from block faulting, in the north, to more closely spaced tilted-domino-style faulting in the Latir volcanic field, to the south. Additional early rift structures include several long northwest-striking faults, the largest of which are interpreted to have accommodated significant right-lateral strike-slip, based on abrupt southwestward increase in the magnitude of extension across them. These faults evidently transferred strain from the axial part of the rift into the zone of early peripheral extension, and accommodated lateral changes in structural style. Throughout the area of early peripheral extension, there is a correlation between the magnitude of local volcanism and the degree of extension; however, it is unclear if extension drove volcanism—via mantle upwelling, or if extension was maximized where the crust was weakest, owing to the presence of magma and hot rock at shallow depths.

Distribution of serine/threonine kinase SAD-B in mouse peripheral nerve synapse.

PubMed

Hagiwara, Akari; Harada, Kenu; Hida, Yamato; Kitajima, Isao; Ohtsuka, Toshihisa

2011-05-11

The serine/threonine kinase SAD regulates neural functions such as axon/dendrite polarization and neurotransmitter release. In the vertebrate central nervous system, SAD-B, a homolog of Caenorhabditis elegans SAD-1, is associated with synaptic vesicles and the active zone cytomatrix in nerve terminals. However, the distribution of SAD-B in the peripheral nervous system remains elusive. Here, we show that SAD-B is specifically localized to neuromuscular junctions. Although the active zone protein bassoon showed a punctated signal indicating its localization to motor end plates, SAD-B shows relatively diffuse localization indicating its association with both the active zone and synaptic vesicles. Therefore, SAD kinase may regulate neurotransmitter release from motor end plates in a similar manner to its regulation of neurotransmitter release in the central nervous system.

A Pilot Study of Perceptual-Motor Training for Peripheral Prisms

PubMed Central

Houston, Kevin E.; Bowers, Alex R.; Fu, Xianping; Liu, Rui; Goldstein, Robert B.; Churchill, Jeff; Wiegand, Jean-Paul; Soo, Tim; Tang, Qu; Peli, Eli

2016-01-01

Purpose Peripheral prisms (p-prisms) shift peripheral portions of the visual field of one eye, providing visual field expansion for patients with hemianopia. However, patients rarely show adaption to the shift, incorrectly localizing objects viewed within the p-prisms. A pilot evaluation of a novel computerized perceptual-motor training program aiming to promote p-prism adaption was conducted. Methods Thirteen patients with hemianopia fitted with 57Δ oblique p-prisms completed the training protocol. They attended six 1-hour visits reaching and touching peripheral checkerboard stimuli presented over videos of driving scenes while fixating a central target. Performance was measured at each visit and after 3 months. Results There was a significant reduction in touch error (P = 0.01) for p-prism zone stimuli from pretraining median of 16.6° (IQR 12.1°–19.6°) to 2.7° ( IQR 1.0°–8.5°) at the end of training. P-prism zone reaction times did not change significantly with training (P > 0.05). P-prism zone detection improved significantly (P = 0.01) from a pretraining median 70% (IQR 50%–88%) to 95% at the end of training (IQR 73%–98%). Three months after training improvements had regressed but performance was still better than pretraining. Conclusions Improved pointing accuracy for stimuli detected in prism-expanded vision of patients with hemianopia wearing 57Δ oblique p-prisms is possible and training appears to further improve detection. Translational Relevance This is the first use of this novel software to train adaptation of visual direction in patients with hemianopia wearing peripheral prisms. PMID:26933522

Regional analysis of whole cell currents from hair cells of the turtle posterior crista.

PubMed

Brichta, Alan M; Aubert, Anne; Eatock, Ruth Anne; Goldberg, Jay M

2002-12-01

The turtle posterior crista is made up of two hemicristae, each consisting of a central zone containing type I and type II hair cells and a surrounding peripheral zone containing only type II hair cells and extending from the planum semilunatum to the nonsensory torus. Afferents from various regions of a hemicrista differ in their discharge properties. To see if afferent diversity is related to the basolateral currents of the hair cells innervated, we selectively harvested type I and II hair cells from the central zone and type II hair cells from two parts of the peripheral zone, one near the planum and the other near the torus. Voltage-dependent currents were studied with the whole cell, ruptured-patch method and characterized in voltage-clamp mode. We found regional differences in both outwardly and inwardly rectifying voltage-sensitive currents. As in birds and mammals, type I hair cells have a distinctive outwardly rectifying current (I(K,L)), which begins activating at more hyperpolarized voltages than do the outward currents of type II hair cells. Activation of I(K,L) is slow and sigmoidal. Maximal outward conductances are large. Outward currents in type II cells vary in their activation kinetics. Cells with fast kinetics are associated with small conductances and with partial inactivation during 200-ms depolarizing voltage steps. Almost all type II cells in the peripheral zone and many in the central zone have fast kinetics. Some type II cells in the central zone have large outward currents with slow kinetics and little inactivation. Although these currents resemble I(K,L), they can be distinguished from the latter both electrophysiologically and pharmacologically. There are two varieties of inwardly rectifying currents in type II hair cells: activation of I(K1) is rapid and monoexponential, whereas that of I(h) is slow and sigmoidal. Many type II cells either have both inward currents or only have I(K1); very few cells only have I(h). Inward currents are less conspicuous in type I cells. Type II cells near the torus have smaller outwardly rectifying currents and larger inwardly rectifying currents than those near the planum, but the differences are too small to account for variations in discharge properties of bouton afferents innervating the two regions of the peripheral zone. The large outward conductances seen in central cells, by lowering impedances, may contribute to the low rotational gains of some central-zone afferents.

Patients with elevated serum PSA and indwelling catheter after acute urinary retention: prospective study of 63 patients with 7-year follow-up.

PubMed

Kravchick, Sergey; Bunkin, Igor; Peled, Ronit; Yulish, Eugeny; Ben-Dor, David; Kravchenko, Yakov; Cytron, Shmuel

2007-10-01

Elevated PSA value in the presence of an indwelling catheter is still an enigma. The aims of this prospective study were: to investigate the reliability of elevated PSA levels in patients with normal DRE and indwelling catheter after AUR; to assess the impact of preoperative TRUS-biopsy in detecting prostate cancer in such circumstances; to estimate the crucial duration of follow-up period. 63 patients were included in the study. PSA was assessed 5 days after catheter insertion. All patients failed to void without catheter and have been scheduled for surgery. TRUS-biopsy was performed before operation. All patients underwent surgery at least two weeks after prostate biopsies. Postoperative follow-up visits continued for at least 7 years. Biopsies were taken when indicated by persistently elevated PSA or an abnormal DRE. Mean PSA before catheter insertion differed significantly from PSA obtained on the 5(th) day after AUR (p = 0.001). Mean prostate volume calculated on TRUS was 80.5 +/- 28 ml. Mean duration of indwelling catheter placement was 37.8 +/- 7.97 days. Mean delay in operative treatment as a result of preoperative evaluation was 23.548 +/- 2.487 days. Carcinoma was detected in 13 patients, while clinically insignificant cancer was present in 31% (4 patients). It must be also emphasized that 38% of patients with carcinoma were >70 year-old. Preoperative TRUS-biopsy and postoperative pathologic exam diagnosed carcinoma in 5 patients (2 and 3 respectively). During 42 months of 7-year follow-up cancer was revealed in 8 patients. Mean PSA value in the follow-up period was significantly elevated in patients with carcinoma: 5.99 +/- 3.34 v/s 2.34 +/- 1.68 ng/ml (p = 0.007) and was the strongest predictor for cancer detection (p = 0.001). The detection rate of clinically significant cancer on preoperative biopsies postoperative pathologic exam in patients with AUR and indwelling catheter is low. These patients could be safely operated on without any delay. However, in order to detect clinically important cancer in the peripheral zone a postoperative monitoring period of should be recommended: starting 6 months after operation and continuing subsequently for at least 4 years. Postoperative PSA level is the strongest predictor of cancer detection and could be usefully employed in these patients. AUR and in the patients with large prostate cause elevated PSA. Cancer detection rate on preoperative biopsies is low in these patients. Long postoperative monitoring period should be strongly recommended.

Peripheral photon and neutron doses from prostate cancer external beam irradiation.

PubMed

Bezak, Eva; Takam, Rundgham; Marcu, Loredana G

2015-12-01

Peripheral photon and neutron doses from external beam radiotherapy (EBRT) are associated with increased risk of carcinogenesis in the out-of-field organs; thus, dose estimations of secondary radiation are imperative. Peripheral photon and neutron doses from EBRT of prostate carcinoma were measured in Rando phantom. (6)LiF:Mg,Cu,P and (7)LiF:Mg,Cu,P glass-rod thermoluminescence dosemeters (TLDs) were inserted in slices of a Rando phantom followed by exposure to 80 Gy with 18-MV photon four-field 3D-CRT technique. The TLDs were calibrated using 6- and 18-MV X-ray beam. Neutron dose equivalents measured with CR-39 etch-track detectors were used to derive readout-to-neutron dose conversion factor for (6)LiF:Mg,Cu,P TLDs. Average neutron dose equivalents per 1 Gy of isocentre dose were 3.8±0.9 mSv Gy(-1) for thyroid and 7.0±5.4 mSv Gy(-1) for colon. For photons, the average dose equivalents per 1 Gy of isocentre dose were 0.2±0.1 mSv Gy(-1) for thyroid and 8.1±9.7 mSv Gy(-1) for colon. Paired (6)LiF:Mg,Cu,P and (7)LiF:Mg,Cu,P TLDs can be used to measure photon and neutron doses simultaneously. Organs in close proximity to target received larger doses from photons than those from neutrons whereas distally located organs received higher neutron versus photon dose. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Androgen Ablation Augments Prostate Cancer Vaccine Immunogenicity Only When Applied After Immunization

PubMed Central

Koh, Yi T.; Gray, Andrew; Higgins, Sean A.; Hubby, Bolyn; Kast, W. Martin

2009-01-01

Background Androgen ablation (AA) causes apoptosis of normal and neoplastic prostate cells. It is a standard treatment for advanced prostate cancer. Androgen ablation-mediated immunological effects include bone marrow hyperplasia, thymic regeneration, T and B cell lymphopoeisis and restoration of age-related peripheral T cell dysfunction. Androgens also regulate the transcription of several cytokines. Dendritic cells (DC) are the most potent antigen presenting cells that can activate antigen-specific naïve T cells. Despite myriad clinical trials involving DC-based prostate cancer immunotherapies, the effects of AA on DC function remain largely uncharacterized. Therefore, we investigated the effects of AA on DC and whether it could improve the efficacy of prostate cancer immunotherapy. Methods Cytokine expression changes due to AA were quantified by multiplex ELISA. Flow cytometry was used to assess AA-mediated effects on DC maturation and expression of costimulatory markers. Mixed leukocyte reactions and cell-mediated lysis assays elucidated the role of androgens in DC function. The effect of AA on the efficacy of vaccination against a prostate tumor-associated antigen was tested using Elispot assays. Results Androgen ablation increased dendritic cell maturation and costimulatory marker expression, but had no effect on DC costimulatory function. However, DC isolated from castrated mice increased the expression of key cytokines by antigen-experienced T cells while decreasing their expression in naïve cells. Finally, androgen ablation improved immune responses to vaccination only when applied after immunization. Conclusion Androgen ablation causes differential effects of DC on primary and secondary T cell responses, thus augmenting vaccine immunogenicity only when applied after immunization. PMID:19143030

Diagnostic and prognostic significance of prostate specific antigen and serum interleukin 18 and 10 in patients with locally advanced prostate cancer: a prospective study.

PubMed

Dwivedi, Shailendra; Goel, Apul; Natu, Shanker M; Mandhani, Anil; Khattri, Sanjay; Pant, Kamlesh K

2011-01-01

Prostate cancer is one of the most common cancers afflicting men today. Prostate biopsy, an invasive procedure is generally used for diagnoses but attempts are being made to find accurate and precise non-invasive biomarkers. Diagnostic accuracy of prostate specific antigen (PSA) has been well documented. Serum interleukin-18 (IL-18) and interleukin-10 (IL-10) have shown their diagnostic ability in other cancers but not investigated well in prostate cancer. This study, thus determines the diagnostic and prognostic significance of PSA, IL-18 and IL-10 prospectively in patients with carcinoma prostate. A total of 149 patients, aged 40-84 yrs were investigated during April 2007 to July 2010 and recruited for this study after Institutional ethical approval. Of the total of 149 patients, 71 had biopsy proven prostate cancers (TNM stage: T2=17, T3=26 and T4=28) and 78 clinical benign prostate hyperplasia (BPH). Peripheral blood samples of all patients and 71 age matched control subjects were obtained at baseline and estimation of PSA, IL-18 and IL-10 was done by enzyme linked immunosorbent assay (ELISA). Carcinoma prostate patients were followed for three years. Data were analyzed with ANOVA, ROC curve analysis and survival analysis. The baseline levels of PSA, IL-18 and IL-10 in all groups of carcinoma prostate were found to be significantly (p<0.01) higher than both Control and BPH. The levels of IL-18 and IL-10 also found to be elevated significantly in stage T3 (p<0.05) and T4 (p<0.01) as compared to stage T2. The levels especially of IL-18 is found to be well associated with progression of the disease of various groups (r=0.84, p<0.01). In contrast, IL-10 showed significant direct association with progression of carcinoma (r=0.84, p<0.01) while inverse relation with survival duration (r=-0.48, p<0.01) and survival rate (χ2=8.98, p=0.0027; Hazard ratio=0.37, 95% CI=0.18-0.69). Study concluded that serum IL-18 has potential to be a better diagnostic marker with higher specificity and sensitivity and IL-10 may be valuable as a prognostic marker than PSA in carcinoma prostate.

Differentiation of prostatitis and prostate cancer using the Prostate Imaging-Reporting and Data System (PI-RADS).

PubMed

Meier-Schroers, Michael; Kukuk, Guido; Wolter, Karsten; Decker, Georges; Fischer, Stefan; Marx, Christian; Traeber, Frank; Sprinkart, Alois Martin; Block, Wolfgang; Schild, Hans Heinz; Willinek, Winfried

2016-07-01

To determine if prostate cancer (PCa) and prostatitis can be differentiated by using PI-RADS. 3T MR images of 68 patients with 85 cancer suspicious lesions were analyzed. The findings were correlated with histopathology. T2w imaging (T2WI), diffusion weighted imaging (DWI), dynamic contrast enhancement (DCE), and MR-Spectroscopy (MRS) were acquired. Every lesion was given a single PI-RADS score for each parameter, as well as a sum score and a PI-RADS v2 score. Furthermore, T2-morphology, ADC-value, perfusion type, citrate/choline-level, and localization were evaluated. 44 of 85 lesions showed PCa (51.8%), 21 chronic prostatitis (24.7%), and 20 other benign tissue such as hyperplasia or fibromuscular tissue (23.5%). The single PI-RADS score for T2WI, DWI, DCE, as well as the aggregated score including and not including MRS, and the PI-RADS v2-score were all significantly higher for PCa than for prostatitis or other tissue (p<0.001). The single PI-RADS score for MRS and the PI-RADS sum score including MRS were significantly higher for prostatitis than for other tissue (p=0.029 and p=0.020), whereas the other parameters were not different. Prostatitis usually presented borderline pathological PI-RADS scores, showed restricted diffusion with ADC≥900mm(2)/s in 100% of cases, was more often indistinctly hypointense on T2WI (66.7%), and localized in the transitional zone (57.1%). An ADC≥900mm(2)/s achieved the highest predictive value for prostatitis (AUC=0.859). Prostatitis can be differentiated from PCa using PI-RADS, since all available parameters are more distinct in cases of cancer. However, there is significant overlap between prostatitis and other benign findings, thus PI-RADS is only suitable to a limited extent for the primary assessment of prostatitis. Restricted diffusion with ADC≥900mm(2)/s is believed to be a good indicator for prostatitis. MRS can help to distinguish between prostatitis and other tissue. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Prospective validation of %p2PSA and the Prostate Health Index, in prostate cancer detection in initial prostate biopsies of Asian men, with total PSA 4-10 ng ml-1.

PubMed

Tan, Lincoln Gl; Tan, Yung Khan; Tai, Bee Choo; Tan, Karen Ml; Gauhar, Vineet; Tiong, Ho Yee; Hawkins, Robert Cw; Thamboo, Thomas P; Hong, Felicia Sk; Chiong, Edmund

2017-01-01

Despite its widespread use for prostate cancer screening, low specificity makes PSA a suboptimal biomarker, especially in the diagnostic "gray zone" of 4-10 ng ml-1 . False-positives lead to unnecessary biopsies with attendant morbidities. This is the first prospective validation study of %p2PSA and the Prostate Health Index (PHI) in Asian men presenting with a total PSA between 4.0 and 10 ng ml-1 . We studied 157 Asian men between 50 and 75 years old, with normal per rectal prostate examinations, undergoing their first prostate biopsy, using a standardized biopsy protocol, for PSA levels of 4-10 ng ml-1 . Thirty (19.1%) were found to have prostate cancer on biopsy. Statistically significant differences between patients with and without prostate cancer were found for total PSA, p2PSA, %p2PSA, and PHI. The areas under the curve of the receiver operating characteristic curve for total PSA, %fPSA, %p2PSA, and PHI were 0.479, 0.420, 0.695, and 0.794, respectively. PHI predicts prostatic biopsies results best. At a sensitivity of 90%, the specificity (95% CI) of PHI was 58.3%, more than triple the specificity of total PSA at 17.3%, potentially avoiding 77 (49%) unnecessary biopsies. Similar to studies in mainly Caucasian populations, we have prospectively shown that %p2PSA and PHI greatly outperform total and free to total PSA ratio, in the detection of prostate cancer at first biopsy. Higher PHI levels also correspond to increasing the risk of detecting GS ≥7 cancers. We have validated the use of PHI to aid decision-making regarding prostate biopsies in Asian men with serum PSA between 4 and 10 ng ml-1 .

Methodology to study the three-dimensional spatial distribution of prostate cancer and their dependence on clinical parameters

PubMed Central

Rojas, Kristians Diaz; Montero, Maria L.; Yao, Jorge; Messing, Edward; Fazili, Anees; Joseph, Jean; Ou, Yangming; Rubens, Deborah J.; Parker, Kevin J.; Davatzikos, Christos; Castaneda, Benjamin

2015-01-01

Abstract. A methodology to study the relationship between clinical variables [e.g., prostate specific antigen (PSA) or Gleason score] and cancer spatial distribution is described. Three-dimensional (3-D) models of 216 glands are reconstructed from digital images of whole mount histopathological slices. The models are deformed into one prostate model selected as an atlas using a combination of rigid, affine, and B-spline deformable registration techniques. Spatial cancer distribution is assessed by counting the number of tumor occurrences among all glands in a given position of the 3-D registered atlas. Finally, a difference between proportions is used to compare different spatial distributions. As a proof of concept, we compare spatial distributions from patients with PSA greater and less than 5  ng/ml and from patients older and younger than 60 years. Results suggest that prostate cancer has a significant difference in the right zone of the prostate between populations with PSA greater and less than 5  ng/ml. Age does not have any impact in the spatial distribution of the disease. The proposed methodology can help to comprehend prostate cancer by understanding its spatial distribution and how it changes according to clinical parameters. Finally, this methodology can be easily adapted to other organs and pathologies. PMID:26236756

Prostatic Artery Embolization (PAE) for Symptomatic Benign Prostatic Hyperplasia (BPH): Part 1, Pathological Background and Clinical Implications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Fei, E-mail: feisun@ccmijesususon.com; Crisóstomo, Verónica, E-mail: crisosto@ccmijesususon.com; Báez-Díaz, Claudia, E-mail: cbaez@ccmijesususon.com

Pathological features of benign prostatic hyperplasia (BPH) dictate various responses to prostatic artery embolization (PAE). Typically, BPH originates in the transition zone and periurethral region, where should be considered the primary target area in PAE procedures. Given that histological heterogeneity of components in hyperplasia nodules, epithelial or stromal, identifying the more responsive nodules to PAE will have clinical implications. Since some lower urinary tract symptoms (LUTS) in patients with BPH are usually related to bladder outlet obstruction-induced changes in bladder function rather than to outflow obstruction directly, proper selection of candidate patients prior to PAE is of great clinical importance.more » BPH is a typical chronic progressive condition, suggesting PAE could aim not only to relieve LUTS but also to delay or prevent the clinical progression. Awareness of the pathological background of BPH is essential for interventional radiologists to improve clinical outcomes and develop new treatment strategies in clinical practice of PAE.« less

Benign prostatic hyperplasia.

PubMed

Chughtai, Bilal; Forde, James C; Thomas, Dominique Dana Marie; Laor, Leanna; Hossack, Tania; Woo, Henry H; Te, Alexis E; Kaplan, Steven A

2016-05-05

Benign prostatic hyperplasia (BPH), which causes lower urinary tract symptoms (LUTS), is a common diagnosis among the ageing male population with increasing prevalence. Many risks factors, both modifiable and non-modifiable, can increase the risk of development and progression of BPH and LUTS. The symptoms can be obstructive (resulting in urinary hesitancy, weak stream, straining or prolonged voiding) or irritative (resulting in increased urinary frequency and urgency, nocturia, urge incontinence and reduced voiding volumes), or can affect the patient after micturition (for example, postvoid dribble or incomplete emptying). BPH occurs when both stromal and epithelial cells of the prostate in the transitional zone proliferate by processes that are thought to be influenced by inflammation and sex hormones, causing prostate enlargement. Patients with LUTS undergo several key diagnostic investigations before being diagnosed with BPH. Treatment options for men with BPH start at watchful waiting and progress through medical to surgical interventions. For the majority of patients, the starting point on the treatment pathway will be dictated by their symptoms and degree of bother.

Prostatic Artery Embolization (PAE) for Symptomatic Benign Prostatic Hyperplasia (BPH): Part 1, Pathological Background and Clinical Implications.

PubMed

Sun, Fei; Crisóstomo, Verónica; Báez-Díaz, Claudia; Sánchez, Francisco M

2016-01-01

Pathological features of benign prostatic hyperplasia (BPH) dictate various responses to prostatic artery embolization (PAE). Typically, BPH originates in the transition zone and periurethral region, where should be considered the primary target area in PAE procedures. Given that histological heterogeneity of components in hyperplasia nodules, epithelial or stromal, identifying the more responsive nodules to PAE will have clinical implications. Since some lower urinary tract symptoms (LUTS) in patients with BPH are usually related to bladder outlet obstruction-induced changes in bladder function rather than to outflow obstruction directly, proper selection of candidate patients prior to PAE is of great clinical importance. BPH is a typical chronic progressive condition, suggesting PAE could aim not only to relieve LUTS but also to delay or prevent the clinical progression. Awareness of the pathological background of BPH is essential for interventional radiologists to improve clinical outcomes and develop new treatment strategies in clinical practice of PAE.

Parathyroid Hormone-Related Peptide Elicits Peripheral TRPV1-dependent Mechanical Hypersensitivity

PubMed Central

Shepherd, Andrew J.; Mickle, Aaron D.; Kadunganattil, Suraj; Hu, Hongzhen; Mohapatra, Durga P.

2018-01-01

Bone metastasis in breast, prostate and lung cancers often leads to chronic pain, which is poorly managed by existing analgesics. The neurobiological mechanisms that underlie chronic pain associated with bone-metastasized cancers are not well understood, but sensitization of peripheral nociceptors by tumor microenvironment factors has been demonstrated to be important. Parathyroid hormone-related peptide (PTHrP) is highly expressed in bone-metastasized breast and prostate cancers, and is critical to growth and proliferation of these tumors in the bone tumor microenvironment. Previous studies have suggested that PTHrP could sensitize nociceptive sensory neurons, resulting in peripheral pain hypersensitivity. In this study, we found that PTHrP induces both heat and mechanical hypersensitivity, that are dependent on the pain-transducing transient receptor potential channel family vanilloid, member-1 (TRPV1), but not the mechano-transducing TRPV4 and TRPA1 ion channels. Functional ratiometric Ca2+ imaging and voltage-clamp electrophysiological analysis of cultured mouse DRG neurons show significant potentiation of TRPV1, but not TRPA1 or TRPV4 channel activation by PTHrP. Interestingly, PTHrP exposure led to the slow and sustained activation of TRPV1, in the absence of any exogenous channel agonist, and is dependent on the expression of the type-1 parathyroid hormone receptor (PTH1), as well as on downstream phosphorylation of the channel by protein kinase C (PKC). Accordingly, local administration of specific small-molecule antagonists of TRPV1 to mouse hindpaws after the development of PTHrP-induced mechanical hypersensitivity led to its significant attenuation. Collectively, our findings suggest that PTHrP/PTH1-mediated flow activation of TRPV1 channel contributes at least in part to the development and maintenance of peripheral mechanical pain hypersensitivity, and could therefore constitute a mechanism for nociceptor sensitization in the context of metastatic bone cancer pain. PMID:29497363

Bendamustine Hydrochloride, Etoposide, Dexamethasone, and Filgrastim For Peripheral Blood Stem Cell Mobilization in Treating Patients With Refractory or Recurrent Lymphoma or Multiple Myeloma

ClinicalTrials.gov

2017-04-14

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Multiple Myeloma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

Genetically Modified Peripheral Blood Stem Cell Transplant in Treating Patients With HIV-Associated Non-Hodgkin or Hodgkin Lymphoma

ClinicalTrials.gov

2015-05-06

Adult Nasal Type Extranodal NK/T-cell Lymphoma; AIDS-related Diffuse Large Cell Lymphoma; AIDS-related Diffuse Mixed Cell Lymphoma; AIDS-related Diffuse Small Cleaved Cell Lymphoma; AIDS-related Immunoblastic Large Cell Lymphoma; AIDS-related Lymphoblastic Lymphoma; AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Small Noncleaved Cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; HIV-associated Hodgkin Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage I AIDS-related Lymphoma; Stage II AIDS-related Lymphoma; Stage III AIDS-related Lymphoma; Stage IV AIDS-related Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

Hepatobiliary fascioliasis in non-endemic zones: a surprise diagnosis.

PubMed

Jha, Ashish Kumar; Goenka, Mahesh Kumar; Goenka, Usha; Chakrabarti, Amrita

2013-03-01

Fascioliasis is a zoonotic infection caused by Fasciola hepatica. Because of population migration and international food trade, human fascioliasis is being an increasingly recognised entity in nonendemic zones. In most parts of Asia, hepatobiliary fascioliasis is sporadic. Human hepatobiliary infection by this trematode has two distinct phases: an acute hepatic phase and a chronic biliary phase. Hepatobiliary infection is mostly associated with intense peripheral eosinophilia. In addition to classically defined hepatic phase and biliary phase fascioliasis, some cases may have an overlap of these two phases. Chronic liver abscess formation is a rare presentation. We describe a surprise case of hepatobiliary fascioliasis who presented to us with liver abscess without intense peripheral eosinophilia, a rare presentation of human fascioliasis especially in non-endemic zones. Copyright © 2013 Arab Journal of Gastroenterology. Published by Elsevier Ltd. All rights reserved.

Anatomy-aware measurement of segmentation accuracy

NASA Astrophysics Data System (ADS)

Tizhoosh, H. R.; Othman, A. A.

2016-03-01

Quantifying the accuracy of segmentation and manual delineation of organs, tissue types and tumors in medical images is a necessary measurement that suffers from multiple problems. One major shortcoming of all accuracy measures is that they neglect the anatomical significance or relevance of different zones within a given segment. Hence, existing accuracy metrics measure the overlap of a given segment with a ground-truth without any anatomical discrimination inside the segment. For instance, if we understand the rectal wall or urethral sphincter as anatomical zones, then current accuracy measures ignore their significance when they are applied to assess the quality of the prostate gland segments. In this paper, we propose an anatomy-aware measurement scheme for segmentation accuracy of medical images. The idea is to create a "master gold" based on a consensus shape containing not just the outline of the segment but also the outlines of the internal zones if existent or relevant. To apply this new approach to accuracy measurement, we introduce the anatomy-aware extensions of both Dice coefficient and Jaccard index and investigate their effect using 500 synthetic prostate ultrasound images with 20 different segments for each image. We show that through anatomy-sensitive calculation of segmentation accuracy, namely by considering relevant anatomical zones, not only the measurement of individual users can change but also the ranking of users' segmentation skills may require reordering.

Zoledronic acid induces a significant decrease of circulating endothelial cells and circulating endothelial precursor cells in the early prostate cancer neoadjuvant setting.

PubMed

Santini, Daniele; Zoccoli, Alice; Gregorj, Chiara; Di Cerbo, Melania; Iuliani, Michele; Pantano, Francesco; Zamarchi, Rita; Sergi, Federico; Flammia, Gerardo; Buscarini, Maurizio; Rizzo, Sergio; Cicero, Giuseppe; Russo, Antonio; Vincenzi, Bruno; Avvisati, Giuseppe; Tonini, Giuseppe

2013-01-01

Published data demonstrated that zoledronic acid (ZOL) exhibits antiangiogenetic effects. A promising tool for monitoring antiangiogenic therapies is the measurement of circulating endothelial cells (CECs) and circulating endothelial precursor cells (CEPs) in the peripheral blood of patients. Our aim was to investigate the effects of ZOL on levels of CECs and CEPs in localized prostate cancer. Ten consecutive patients with a histologic diagnosis of low-risk prostate adenocarcinoma were enrolled and received an intravenous infusion of ZOL at baseline (T0), 28 days (T28) and 56 days (T56). Blood samples were collected at the following times: T0 (before the first infusion of ZOL), T3 (72 h after the first dose), T28, T56 (both just before the ZOL infusion) and T84 (28 days after the last infusion of ZOL) and CEC/CEP levels were directly quantified by flow cytometry at all these time points. Our analyses highlighted a significant reduction of mean percentage of CECs and CEPs after initiation of ZOL treatment [p = 0.014 (at day 3) and p = 0.012 (at day 84), respectively]. These preliminary results demonstrate that ZOL could exert an antiangiogenic effect in early prostate cancer through CEP and CEC modulation.

Heterogeneous PSMA expression on circulating tumor cells - a potential basis for stratification and monitoring of PSMA-directed therapies in prostate cancer

PubMed Central

Gorges, Tobias M.; Riethdorf, Sabine; von Ahsen, Oliver; Nastały, Paulina; Röck, Katharina; Boede, Marcel; Peine, Sven; Kuske, Andra; Schmid, Elke; Kneip, Christoph; König, Frank; Rudolph, Marion; Pantel, Klaus

2016-01-01

The prostate specific membrane antigen (PSMA) is the only clinically validated marker for therapeutic decisions in prostate cancer (PC). Characterization of circulating tumor cells (CTCs) obtained from the peripheral blood of PC patients might provide an alternative to tissue biopsies called “liquid biopsy”. The aim of this study was to develop a reliable assay for the determination of PSMA on CTCs. PSMA expression was analyzed on tissue samples (cohort one, n = 75) and CTCs from metastatic PC patients (cohort two, n = 29). Specific signals for the expression of PSMA could be seen for different prostate cancer cell line cells (PC3, LaPC4, 22Rv1, and LNCaP) by Western blot, immunohistochemistry (IHC), immunocytochemistry (ICC), and FACS. PSMA expression was found to be significantly increased in patients with higher Gleason grade (p = 0.0011) and metastases in lymph nodes (p = 0.0000085) or bone (p = 0.0020) (cohort one). In cohort two, CTCs were detectable in 20 out of 29 samples (69 %, range from 1 - 1000 cells). Twelve out of 20 CTC-positive patients showed PSMA-positive CTCs (67 %, score 1+ to 3+). We found intra-patient heterogeneity regarding the PSMA status between CTCs and the corresponding primary tumors. The results of our study could help to address the question whether treatment decisions based on CTC PSMA profiling will lead to a measurable benefit in clinical outcome for prostate cancer patients in the near future. PMID:27145459

Fast Conformal Thermal Ablation in the Prostate with Transurethral Multi-Sectored Ultrasound Devices and MR Guidance

NASA Astrophysics Data System (ADS)

Kinsey, Adam M.; Diederich, Chris J.; Nau, William H.; Ross, Anthony B.; Pauly, Kim Butts; Rieke, Viola; Sommer, Graham

2007-05-01

Transurethral ultrasound applicators incorporating an array of multisectored tubular transducers were evaluated in theoretical simulations and in vivo canine prostates under MR guidance as a method for fast, conformal thermal therapy of the prostate. Comprehensive simulations with a biothermal model investigated the effect on lesion creation of sector size, perfusion, treatment time, rectal cooling, prostate target dimensions, and feedback controller parameters (maximum temperature, pilot points at boundary, update times). In vivo canine prostates (n = 4) were treated with trisectored ultrasound transducers (3 mm OD) under MR temperature monitoring to contour the ablation zone (>52 C for 1-2 min) to the boundary of the prostate. Contiguous thermal lesions extended 2 cm in radius from the urethra in less than 15 min and independent sector control simultaneously allowed for conformal treatment in the angular dimension. Experiments investigated sequential translation of the transducer assembly within the catheter for tailoring heat treatments to different partitions in the prostate (base, apex) without changing the initial setup. This treatment method offered greater lesion shape control in three dimensions and slightly lengthened the overall treatment time. The MR temperature images correlated with post-treatment histology and accurately controlled the heating to the target boundary. MR-based control of transurethral ultrasound devices appeared more practical with multisectored transducers compared to rotating curvilinear and planar applicators due to less stringent requirements on spatial and temporal MR parameters. This study demonstrated the applicability of these devices in the prostate for anterior-lateral BPH treatment, and whole gland or quadrant target volumes for cancer treatment.

Ultrasound image features of intravesical prostatic protrusion indicated failure of medication therapy of finasteride and doxazosin in patients with benign prostatic hyperplasia (LUTS/BPH).

PubMed

Liu, Qiang; Zhu, Yunkai; Liu, Jianping; Qi, Jun; Kang, Jian

2017-03-01

Intravesical prostatic protrusion (IPP) is a type of benign prostatic hyperplasia (BPH) adenoma, and it plays a critical role in the pathogenesis of bladder outlet obstruction in patients with lower urinary tract syndromes (LUTS/BPH). The goal of this study was to investigate the effect of a combination therapy with finasteride and doxazosin on IPP in BPU/LUTS patients. A total of 322 BPH patients with enlarged prostatic volume as well as moderate to severe symptom scores were enrolled and divided into four groups according to the degree of IPP (IPP > 10 mm, 5-10 mm, <5 mm and no IPP) in this study. Aggravated International Prostatic Symptom Score (IPSS), acute urinary retention or relevant urinary complications were considered as failure of the therapy. The degrees of IPP were recorded before and after 6 months of treatment. Student's t test and χ 2 were performed between the baseline and endpoint of the therapy. The results showed that the total prostate volume (TPV) and transition zone volume (TZV) of the prostate decreased significantly after 6-month combination therapy (P < 0.05), while no significant changes in IPP were observed at that point (P > 0.05). Failure rates of the medication differed significantly among the four groups. The study indicated that the combination therapy using finasteride and doxazosin could not reduce the degree of IPP. LUTS/BPH patients with IPP which contributes to the failure of medication tend to have a higher risk of progression.

A telemedicine system for enabling teaching activities.

PubMed

Masero, V; Sanchez, F M; Uson, J

2000-01-01

In order to improve the distance teaching of minimally invasive surgery techniques, an integrated system has been developed. It comprises a telecommunications system, a server, a workstation, some medical peripherals and several computer applications developed in the Minimally Invasive Surgery Centre. The latest peripherals, such as robotized teleoperating systems for telesurgery and virtual reality peripherals, have been added. The visualization of the zone to be treated, along with the teacher's explanations, enables the student to understand the procedures of the operation much better.

Impact of maternal and postnatal zinc dietary status on the prostate of pubescent and adult rats.

PubMed

Camora, Lucas F; Silva, Ana Priscila G; Santos, Sérgio A A; Justulin, Luis A; Perobelli, Juliana E; Barbisan, Luis Fernando; Scarano, Wellerson R

2017-11-01

Zinc is important for cell physiology and alteration of its levels during development can modulate a series of biological events. The aim of this study was to investigate whether dietary zinc deficiency or supplementation during morphogenesis and early postnatal development could interfere in prostate maturation. Pregnant rats were exposed to a standard diet (NZ:35 mg Zn/kg chow), low-zinc diet (LZ:3 mg of Zn/kg chow) and zinc-supplemented diet (HZ:180 mg/Kg chow) from gestational day 10 (GD10) through postnatal day 21 (PND21). After weaning, male offspring were divided into three groups that were submitted to the same food conditions as their mothers until PND53. The animals were euthanized at PND53 and PND115. The ventral prostate was removed, weighed and its fragments were subjected to histological, western blot and zymography analysis. PND53: body and prostate weight were lower in LZ compared to NZ; the epithelial compartment was reduced while the stromal compartment was increased in LZ compared to NZ; there was an increase in the amount of collagen and reduction in AR and SIRT1 expression in LZ compared to NZ. PND115: body weight was lower in LZ compared to NZ and prostate weight was similar among the groups; peripheral physiological hyperplasia was observed, as well as an increased epithelial proliferation index and reduced PAR4 expression in LZ and HZ compared to NZ. Zinc deficiency during prostate morphogenesis and differentiation is potentially harmful to its morphology, however, by restoring the standard dietary environment, the gland responds to the new microenvironment independent of the previous dietary condition. © 2017 International Federation for Cell Biology.

DNA methylation levels at chromosome 8q24 in peripheral blood are associated with 8q24 cancer susceptibility loci.

PubMed

Barry, Kathryn Hughes; Moore, Lee E; Sampson, Joshua; Yan, Liying; Meyer, Ann; Oler, Andrew J; Chung, Charles C; Wang, Zhaoming; Yeager, Meredith; Amundadottir, Laufey; Berndt, Sonja I

2014-12-01

Chromosome 8q24 has emerged as an important region for genetic susceptibility to various cancers, but little is known about the contribution of DNA methylation at 8q24. To evaluate variability in DNA methylation levels at 8q24 and the relationship with cancer susceptibility single nucleotide polymorphisms (SNPs) in this region, we quantified DNA methylation levels in peripheral blood at 145 CpG sites nearby 8q24 cancer susceptibility SNPs or MYC using pyrosequencing among 80 Caucasian men in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. For the 60 CpG sites meeting quality control, which also demonstrated temporal stability over a 5-year period, we calculated pairwise Spearman correlations for DNA methylation levels at each CpG site with 42 8q24 cancer susceptibility SNPs. To account for multiple testing, we adjusted P values into q values reflecting the false discovery rate (FDR). In contrast to the MYC CpG sites, most sites nearby the SNPs demonstrated good reproducibility, high methylation levels, and moderate-high between-individual variation. We observed 10 statistically significant (FDR < 0.05) CpG site-SNP correlations. These included correlations between an intergenic CpG site at Chr8:128393157 and the prostate cancer SNP rs16902094 (ρ = -0.54; P = 9.7 × 10(-7); q = 0.002), a PRNCR1 CpG site at Chr8:128167809 and the prostate cancer SNP rs1456315 (ρ = 0.52; P = 1.4 × 10(-6); q = 0.002), and two POU5F1B CpG sites and several prostate/colorectal cancer SNPs (for Chr8:128498051 and rs6983267, ρ = 0.46; P = 2.0 × 10(-5); q = 0.01). This is the first report of correlations between blood DNA methylation levels and cancer susceptibility SNPs at 8q24, suggesting that DNA methylation at this important susceptibility locus may contribute to cancer risk. ©2014 American Association for Cancer Research.

[Prostate cancer detection by assessing stiffness of different tissues using shear wave ultrasound elastog- raphy].

PubMed

Glybochko, P V; Alyaev, Yu G; Amosov, A V; Krupinov, G E; Ganzha, T M; Vorobev, A V; Lumpov, I S; Semendyaev, R I

2016-08-01

Early detection of prostate cancer (PCa) remains a challenging issue. There are studies underway aimed to develop and implement new methods for prostate cancer screening by tumor imaging and obtaining tissue samples from suspicious areas for morphological examination. One of these new methods is shear wave ultrasound elastography (SWUE). The current literature is lacking sufficient coverage of informativeness and specificity of SWUE in the prostate cancer detection, there is no clear criteria for assessing tissue stiffness at different values of PSA and tumor grade, and in prostate hyperplasia and prostatitis. To evaluate the informativeness and specificity of SWUE compared with other diagnostic methods. SWUE has been used in the Clinic of Urology of Sechenov First MSMU since October 2015. During this period, 302 patients were examined using SWUE. SWUE was performed with Aixplorer ultrasound system (Super Sonic Imagine), which provides a single-stage SWUE imaging with both B-mode and real-time mode. The first group (prospective study) included 134 men aged 47 to 81 years with suspected prostate cancer scheduled to either initial or repeat prostate biopsy. PSA levels ranged from 4 to 24 ng/ml. The second group (retrospective study) comprised 120 men with confirmed prostate cancer and PSA levels between 4 and 90 ng/ml. The third group (the control group), comprised 48 healthy men whose PSA level did not exceed 3 ng/ml. All patients of the groups 1 and 2 underwent a standard comprehensive examination. Patients in group 1 were subsequently subjected to transrectal prostate biopsy guided by localization of areas with abnormal tissue stiffness. PCa was detected in 100 of 134 patients. 217 patients of groups 1 and 2 underwent radical prostatectomy. In 28 of them, the match between the cancer location and differentiation in the removed prostate and SWUE findings before surgery was examined. Contrast-enhanced magnetic resonance imaging of pelvic organs was performed in 63 patients of groups 1 and 2. Threshold values of stiffness (Emean) were determined, which normally range from 0 to 23 kPa, from 23.4 to 50 kPa in prostatic hyperplasia and 50.5 kPa and greater in prostate cancer. A total of 220 patients in groups 1 and 2 were found to have prostate cancer. The findings showed increased stiffness of prostate tissue depending on tumor differentiation, Gleason score, and hence, cancer risk. The sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) were calculated for SWUE, biopsy based on 6 peripheral points used during SWUE, and for histologic findings from prostate cross sections. When compared to needle biopsy, Se, Sp, PPV, NPV for SWUE were 90.8, 94.6, 56.6 and 97.9%, respectively. The study findings suggest a high diagnostic performance of SWUE in detecting prostate cancer.

Heat Damage Zones Created by Different Energy Sources Used in the Treatment of Benign Prostatic Hyperplasia in a Pig Liver Model.

PubMed

Kan, Chi Fai; Chan, Alexander Chak Lam; Pun, Chung Ting; Ho, Lap Yin; Chan, Steve Wai-Hee; Au, Wing Hang

2015-06-01

There are different types of transurethral prostatic surgeries and the complication profiles are different. This study aims to compare the heat damage zones (HDZ) created by five different technologies in a pig liver model. Monopolar resection, bipolar resection, electrovaporization, and Greenlight™ lasers of 120 and 180 W were used to remove fresh pig liver tissue in a simulated model. Each procedure was repeated in five specimens. Two blocks were selected from each specimen to measure the three deepest HDZ. The mean of HDZ was 295, 234, 192, 673, and 567 μm, respectively, for monopolar resection, bipolar resection, electrovaporization, Greenlight laser 120 W, and Greenlight laser 180 W, respectively. The Greenlight laser produced one to three times deeper HDZ than the other energy sources (p=0.000). Both 120 and 180 W Greenlight lasers produced deeper HDZ than the other energy sources. Urologists need to be aware of HDZ that cause tissue damage outside the operative field.

[Real-time three-dimensional (4D) ultrasound-guided prostatic biopsies on a phantom. Comparative study versus 2D guidance].

PubMed

Long, Jean-Alexandre; Daanen, Vincent; Moreau-Gaudry, Alexandre; Troccaz, Jocelyne; Rambeaud, Jean-Jacques; Descotes, Jean-Luc

2007-11-01

The objective of this study was to determine the added value of real-time three-dimensional (4D) ultrasound guidance of prostatic biopsies on a prostate phantom in terms of the precision of guidance and distribution. A prostate phantom was constructed. A real-time 3D ultrasonograph connected to a transrectal 5.9 MHz volumic transducer was used. Fourteen operators performed 336 biopsies with 2D guidance then 4D guidance according to a 12-biopsy protocol. Biopsy tracts were modelled by segmentation in a 3D ultrasound volume. Specific software allowed visualization of biopsy tracts in the reference prostate and evaluated the zone biopsied. A comparative study was performed to determine the added value of 4D guidance compared to 2D guidance by evaluating the precision of entry points and target points. The distribution was evaluated by measuring the volume investigated and by a redundancy ratio of the biopsy points. The precision of the biopsy protocol was significantly improved by 4D guidance (p = 0.037). No increase of the biopsy volume and no improvement of the distribution of biopsies were observed with 4D compared to 2D guidance. The real-time 3D ultrasound-guided prostate biopsy technique on a phantom model appears to improve the precision and reproducibility of a biopsy protocol, but the distribution of biopsies does not appear to be improved.

Clinical utility of transperineal template-guided mapping biopsy of the prostate after negative magnetic resonance imaging-guided transrectal biopsy.

PubMed

Sivaraman, Arjun; Sanchez-Salas, Rafael; Ahmed, Hashim U; Barret, Eric; Cathala, Nathalie; Mombet, Annick; Uriburu Pizarro, Facundo; Carneiro, Arie; Doizi, Steeve; Galiano, Marc; Rozet, Francois; Prapotnich, Dominique; Cathelineau, Xavier

2015-07-01

We evaluated the prostate cancer detection with transperineal template-guided mapping biopsy in patients with elevated prostate-specific antigen and negative magnetic resonance imaging (MRI)-guided biopsy. Totally 75 patients underwent transperineal template-guided mapping biopsy for prior negative MRI-guided (cognitive registration) biopsy during April 2013 to August 2014. Primary objective was to report clinically significant cancer detection in this cohort of patients. Significant cancer was defined using varying thresholds of MCL or Gleason grade 3+4 or greater or both. Cancers with more than 80% of positive core length anterior to the level of urethra were termed anterior zone cancer. Secondary objective was to evaluate the potential clinical and radiological predictors for significant cancer detection. The mean age was 61.6 ± 6.5 years and median prostate-specific antigen was 10.4 ng/dl (7.9-18) with a mean MRI target size of 7.2mm (4-11). Transperineal template-guided mapping biopsy identified cancer in 36% (27/75) patients and 66.6% (18/27) of them were anterior zone cancers. The rates of detection of clinically significant and insignificant cancer according to the several definitions used range from 22.7% to 30.7% and 5.3% to 13.3%, respectively. Multivariate analysis did not identify any predictors for finding clinically significant and anterior cancers in this group of patients. Transperineal template-guided mapping biopsy appears to be an excellent biopsy protocol for downstream management following negative MRI-guided biopsy. Most of the cancers detected were predominantly anterior tumors. Copyright © 2015 Elsevier Inc. All rights reserved.

Connexin43high prostate cancer cells induce endothelial connexin43 up-regulation through the activation of intercellular ERK1/2-dependent signaling axis.

PubMed

Piwowarczyk, Katarzyna; Paw, Milena; Ryszawy, Damian; Rutkowska-Zapała, Magdalena; Madeja, Zbigniew; Siedlar, Maciej; Czyż, Jarosław

2017-06-01

Connexin(Cx)43 regulates the invasive potential of prostate cancer cells and participates in their extravasation. To address the role of endothelial Cx43 in this process, we analyzed Cx43 regulation in human umbilical vein endothelial cells in the proximity of Cx43 high (DU-145 and MAT-LyLu) and Cx43 low prostate cancer cells (PC-3 and AT-2). Endothelial Cx43 up-regulation was observed during the diapedesis of DU-145 and MAT-LyLu cells. This process was attenuated by transient Cx43 silencing in cancer cells and by chemical inhibition of ERK1/2-dependent signaling in endothelial cells. Cx43 expression in endothelial cells was insensitive to the inhibition of gap junctional intercellular coupling between Cx43 high prostate cancer and endothelial cells by 18α-glycyrrhetinic acid. Instead, endothelial Cx43 up-regulation was correlated with the local contraction of endothelial cells and with their activation in the proximity of Cx43 high DU-145 and MAT-LyLu cells. It was also sensitive to pro-inflammatory factors secreted by peripheral blood monocytes, such as TNFα. In contrast to Cx43 low AT-2 cells, Cx43 low PC-3 cells produced angioactive factors that locally activated the endothelial cells in the absence of endothelial Cx43 up-regulation. Collectively, these data show that Cx43 low and Cx43 high prostate cancer cells can adapt discrete, Cx43-independent and Cx43-dependent strategies of diapedesis. Our observations identify a novel strategy of prostate cancer cell diapedesis, which depends on the activation of intercellular Cx43/ERK1/2/Cx43 signaling axis at the interfaces between Cx43 high prostate cancer and endothelial cells. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

Comparison of intraoperative dosimetric implant representation with postimplant dosimetry in patients receiving prostate brachytherapy.

PubMed

Stone, Nelson N; Hong, Suzanne; Lo, Yeh-Chi; Howard, Victor; Stock, Richard G

2003-01-01

To compare the results of intraoperative dosimetry with those of CT-based postimplant dosimetry in patients undergoing prostate seed implantation. Seventy-seven patients with T1-T3 prostate cancer received an ultrasound-guided permanent seed implant (36 received (125)I, 7 (103)Pd, and 34 a partial (103)Pd implant plus external beam radiation therapy). The implantation was augmented with an intraoperative dosimetric planning system. After the peripheral needles were placed, 5-mm axial images were acquired into the treatment planning system. Soft tissue structures (prostate, urethra, and rectum) were contoured, and exact needle positions were registered. Seeds were placed with an applicator, and their positions were entered into the planning system. The dose distributions for the implant were calculated after interior needle and seed placement. Postimplant dosimetry was performed 1 month later on the basis of CT imaging. Prostate and urethral doses were compared, by using paired t tests, for the real-time dosimetry in the operating room (OR) and the postimplant dosimetry. The mean preimplant prostate volume was 39.8 cm(3), the postneedle planning volume was 41.5 cm(3) (p<0.001), and the 1-month CT volume was 43.6 cm(3) (p<0.001). The mean difference between the OR dose received by 90% of the prostate (D(90)) and the CT D(90) was 3.4% (95% confidence interval, 2.5-6.6%; p=0.034). The mean dose to 30% of the urethra was 120% of prescription in the OR and 138% on CT. The mean difference was 18% (95% confidence interval, 13-24%; p<0.001). Although small differences exist between the OR and CT dosimetry results, these data suggest that this intraoperative implant dosimetric representation system provides a close match to the actual delivered doses. These data support the use of this system to modify the implant during surgery to achieve more consistent dosimetry results.

[Prostate cancer. Epidemiology. Risk factors. Pathology].

PubMed

Fournier, G; Valeri, A; Mangin, P; Cussenot, O

2004-10-01

Prostate cancer (prostate adenocarcinoma) has become an important concern in terms of public health these past fifteen years; recent French epidemiological data revealed 10,104 deaths due to this disease in 2000. The two main factors involved are the serum prostatic specific antigen (PSA), routinely used since late 1980's and which allows early diagnosis (before symptom onset), and the lengthened duration of life. Such cancer is rare before the age of 50, but its frequency increases with age, making it the most frequent type of cancer in French men. Although the aetiology of this disease is unknown, the ethnic origin, and a familial history of prostate or breast cancer are known risk factors. Predisposing genes to such hereditary types remain to be identified. Other genetic factors (polymorphisms), combined with environmental factors such as nutrition, have been incriminated, which is likely to explain the geographical variations of this affection. At the molecular level, the mechanisms involved in the tumoral initiation and progression remain unclear. Various genetic alterations have been identified among the genome of cancerous cells, at various stages of the affection: intraepithelial neoplasia, localized, locally advanced, metastatic or hormone refractory stage -, hormonal escape). However, the precise sequence and nature of the complex molecular events remain to be determined prior to their routine utilisation in the determination of subjects at risk, or as prognostic factors, and even as therapeutic targets. The anatomopathology is a key for the diagnosis. Intraepithelial neoplasia is the pre-cancerous lesion observed in most adenocarcinomas; these are localized in the peripheral part of the prostate gland in 70% of the cases. Gleason's classification is the current gold standard for the determination of tumoral aggressiveness and categorisation of the adenocarcinomas which are basically heterogeneous (coexistence of tumors cells with different degrees of differenciation in the same tumor). This anatomopathological classification allows distinguishing the tumours in terms of potential progressiveness and prognosis, and hence, to orientate the therapeutic strategy in case of localised or locally advanced prostate cancer.

Laser Treatment of Benign Prostatic Hyperplasia: Dosimetric and Thermodynamic Considerations

NASA Astrophysics Data System (ADS)

Anvari, Bahman

1993-01-01

Benign prostatic hyperplasia (BPH) is the most commonly occurring neoplastic disease in the aging human male. Currently, surgical treatment of BPH is the primary therapeutic method. However, due to surgical complications, less invasive methods of treatment are desirable. In recent years, thermal coagulation of the hyperplastic prostate by a laser has received a considerable amount of attention. Nevertheless, the optimum laser irradiation parameters that lead to a successful and safe treatment of BPH have not been determined. This dissertation studies the physics of laser coagulation of prostate from both basic science and practical perspectives. Optical properties of prostatic tissue are determined over a spectrum of wavelengths. Knowledge of these properties allows for selection of appropriate laser wavelengths and provides a basis for performing dose equivalency studies among various types of lasers. Furthermore, knowledge of optical properties are needed for development of computer simulation models that predict the extent of thermal injury during laser irradiation of prostate. A computer model of transurethral heating of prostate that can be used to guide the clinical studies in determining an optimum dosimetry is then presented. Studies of the effects of non-laser heating devices, optical properties, blood perfusion, surface irrigation, and beam geometry are performed to examine the extent of heat propagation within the prostate. An in vitro model for transurethral laser irradiation of prostate is also presented to examine the effects of an 810 nm diode laser, thermal boundary conditions, and energy deposition rate during Nd:YAG laser irradiation. Results of these studies suggest that in the presence of laminar irrigation, the convective boundary condition is dominated by thermal diffusion as opposed to the bulk motion of the irrigation fluid. Distinct phases of thermal events are also identified during the laser irradiation. The in vivo studies of transurethral laser irradiation of prostate in canine models are also performed to search for an optimum dosimetry that will result in a maximum zone of coagulation necrosis.

17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Advanced Epithelial Cancer, Malignant Lymphoma, or Sarcoma

ClinicalTrials.gov

2013-02-06

AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Primary CNS Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Chondrosarcoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Osteosarcoma; Nodal Marginal Zone B-cell Lymphoma; Ovarian Sarcoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Osteosarcoma; Recurrent Small Lymphocytic Lymphoma; Recurrent Uterine Sarcoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small Lymphocytic Lymphoma; Stage IV Uterine Sarcoma; Unspecified Adult Solid Tumor, Protocol Specific

Highly directional transurethral ultrasound applicators with rotational control for MRI-guided prostatic thermal therapy

NASA Astrophysics Data System (ADS)

Ross, Anthony B.; Diederich, Chris J.; Nau, William H.; Gill, Harcharan; Bouley, Donna M.; Daniel, Bruce; Rieke, Viola; Butts, R. Kim; Sommer, Graham

2004-01-01

Transurethral ultrasound applicators with highly directional energy deposition and rotational control were investigated for precise treatment of benign prostatic hyperplasia (BPH) and adenocarcinoma of the prostate (CaP). Two types of catheter-based applicators were fabricated, using either 90° sectored tubular (3.5 mm OD × 10 mm) or planar transducers (3.5 mm × 10 mm). They were constructed to be MRI compatible, minimally invasive and allow for manual rotation of the transducer array within a 10 mm cooling balloon. In vivo evaluations of the applicators were performed in canine prostates (n = 3) using MRI guidance (0.5 T interventional magnet). MR temperature imaging (MRTI) utilizing the proton resonance frequency shift method was used to acquire multiple-slice temperature overlays in real time for monitoring and guiding the thermal treatments. Post-treatment T1-weighted contrast-enhanced imaging and triphenyl tetrazolium chloride stained tissue sections were used to define regions of tissue coagulation. Single sonications with the 90° tubular applicator (9-15 W, 12 min, 8 MHz) produced coagulated zones covering an 80° wedge of the prostate extending from 1-2 mm outside the urethra to the outer boundary of the gland (16 mm radial coagulation). Single sonications with the planar applicator (15-20 W, 10 min, ~8 MHz) generated thermal lesions of ~30° extending to the prostate boundary. Multiple sequential sonications (sweeping) of a planar applicator (12 W with eight rotations of 30° each) demonstrated controllable coagulation of a 270° contiguous section of the prostate extending to the capsule boundary. The feasibility of using highly directional transurethral ultrasound applicators with rotational capabilities to selectively coagulate regions of the prostate while monitoring and controlling the treatments with MRTI was demonstrated in this study.

Evolving Novel Chemical Entities for Management of Benign Prostatic Hyperplasia.

PubMed

Gupta, Sonal; Gupta, Gopal; Sharma, V L

2017-01-01

Proliferation of the smooth muscle and epithelial cells within the prostatic transition zone in older men leads to benign prostatic hyperplasia (BPH), which is hallmarked by the troublesome lower urinary tract symptoms. The affair responsible for the initiation and promotion of disease is still unresolved, though alpha-blockers and 5α-reductase inhibitors are used as management options for relief from the dynamic and static components respectively. Combination therapy including both the alpha blocker and 5α-reductase inhibitor is emerging as inclusive parcel for treatment. However, selective androgen receptor modulators (SARM) and selective estrogen receptor modulators (SERM) are the other management resources, which are in the limelight. This review gives a glimpse of BPH and the various chemical entities which have been reported in literature till date for the condition since 2005. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Multiple joint metastasis of a transitional cell carcinoma in a dog.

PubMed

Colledge, Sarah L; Raskin, Rose E; Messick, Joanne B; Tiffany Reed, L; Wigle, William L; Balog, Kelley A

2013-06-01

An 8-year-old castrated male hound mix was referred to the Purdue University Veterinary Teaching Hospital for severe lameness, pollakiuria, and dyschezia. On presentation, the dog was nonweight bearing on the right rear limb and the right carpus was diffusely swollen. Synovial fluid analysis from the right carpus revealed a population of epithelial cells displaying marked anisocytosis, anisokaryosis, multinucleation, and prominent, variably sized nucleoli. A metastatic carcinoma with presumed prostatic or urothelial origin was diagnosed based on cytomorphology. Subsequent cytologic evaluation of peripheral lymph nodes revealed the presence of a similar neoplastic population. The dog was euthanized and synovial fluid from both stifle joints, as well as impression smears of the prostate gland, were collected. Carcinoma cells were identified in each stifle joint and in the prostate gland. Immunocytochemistry was performed on synovial fluid smears from 2 of the joints (right stifle and right carpus) and on impression smears of the prostate gland. The neoplastic population in the joints and prostate gland showed strong immunoreactivity to uroplakin III, a urothelial marker, indicating metastasis of a transitional cell carcinoma to multiple joints. In addition, evidence for epithelial to mesenchymal transition was identified using cytokeratin, an epithelial marker, and vimentin, a mesenchymal marker. A necropsy was performed and histopathology confirmed the presence of metastatic transitional cell carcinoma in various tissues. This case illustrates the importance of considering metastatic disease when a patient is presented with severe lameness and joint pain, and the clinical utility of synovial fluid cytology for diagnosis of metastasis in these cases. © 2013 American Society for Veterinary Clinical Pathology.

Computed Tomography Perfusion, Magnetic Resonance Imaging, and Histopathological Findings After Laparoscopic Renal Cryoablation: An In Vivo Pig Model.

PubMed

Nielsen, Tommy Kjærgaard; Østraat, Øyvind; Graumann, Ole; Pedersen, Bodil Ginnerup; Andersen, Gratien; Høyer, Søren; Borre, Michael

2017-08-01

The present study investigates how computed tomography perfusion scans and magnetic resonance imaging correlates with the histopathological alterations in renal tissue after cryoablation. A total of 15 pigs were subjected to laparoscopic-assisted cryoablation on both kidneys. After intervention, each animal was randomized to a postoperative follow-up period of 1, 2, or 4 weeks, after which computed tomography perfusion and magnetic resonance imaging scans were performed. Immediately after imaging, open bilateral nephrectomy was performed allowing for histopathological examination of the cryolesions. On computed tomography perfusion and magnetic resonance imaging examinations, rim enhancement was observed in the transition zone of the cryolesion 1week after laparoscopic-assisted cryoablation. This rim enhancement was found to subside after 2 and 4 weeks of follow-up, which was consistent with the microscopic examinations revealing of fibrotic scar tissue formation in the peripheral zone of the cryolesion. On T2 magnetic resonance imaging sequences, a thin hypointense rim surrounded the cryolesion, separating it from the adjacent renal parenchyma. Microscopic examinations revealed hemorrhage and later hemosiderin located in the peripheral zone. No nodular or diffuse contrast enhancement was found in the central zone of the cryolesions at any follow-up stage on neither computed tomography perfusion nor magnetic resonance imaging. On microscopic examinations, the central zone was found to consist of coagulative necrosis 1 week after laparoscopic-assisted cryoablation, which was partially replaced by fibrotic scar tissue 4 weeks following laparoscopic-assisted cryoablation. Both computed tomography perfusion and magnetic resonance imaging found the renal collecting system to be involved at all 3 stages of follow-up, but on microscopic examination, the urothelium was found to be intact in all cases. In conclusion, cryoablation effectively destroyed renal parenchyma, leaving the urothelium intact. Both computed tomography perfusion and magnetic resonance imaging reflect the microscopic findings but with some differences, especially regarding the peripheral zone. Magnetic resonance imaging seems an attractive modality for early postoperative follow-up.

PSMA-targeted polyinosine/polycytosine vector induces prostate tumor regression and invokes an antitumor immune response in mice.

PubMed

Langut, Yael; Talhami, Alaa; Mamidi, Samarasimhareddy; Shir, Alexei; Zigler, Maya; Joubran, Salim; Sagalov, Anna; Flashner-Abramson, Efrat; Edinger, Nufar; Klein, Shoshana; Levitzki, Alexander

2017-12-26

There is an urgent need for an effective treatment for metastatic prostate cancer (PC). Prostate tumors invariably overexpress prostate surface membrane antigen (PSMA). We designed a nonviral vector, PEI-PEG-DUPA (PPD), comprising polyethylenimine-polyethyleneglycol (PEI-PEG) tethered to the PSMA ligand, 2-[3-(1, 3-dicarboxy propyl)ureido] pentanedioic acid (DUPA), to treat PC. The purpose of PEI is to bind polyinosinic/polycytosinic acid (polyIC) and allow endosomal release, while DUPA targets PC cells. PolyIC activates multiple pathways that lead to tumor cell death and to the activation of bystander effects that harness the immune system against the tumor, attacking nontargeted neighboring tumor cells and reducing the probability of acquired resistance and disease recurrence. Targeting polyIC directly to tumor cells avoids the toxicity associated with systemic delivery. PPD selectively delivered polyIC into PSMA-overexpressing PC cells, inducing apoptosis, cytokine secretion, and the recruitment of human peripheral blood mononuclear cells (PBMCs). PSMA-overexpressing tumors in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice with partially reconstituted immune systems were significantly shrunken following PPD/polyIC treatment, in all cases. Half of the tumors showed complete regression. PPD/polyIC invokes antitumor immunity, but unlike many immunotherapies does not need to be personalized for each patient. The potent antitumor effects of PPD/polyIC should spur its development for clinical use.

Potential role of nuclear PD-L1 expression in cell-surface vimentin positive circulating tumor cells as a prognostic marker in cancer patients.

PubMed

Satelli, Arun; Batth, Izhar Singh; Brownlee, Zachary; Rojas, Christina; Meng, Qing H; Kopetz, Scott; Li, Shulin

2016-07-01

Although circulating tumor cells (CTCs) have potential as diagnostic biomarkers for cancer, determining their prognostic role in cancer patients undergoing treatment is a challenge. We evaluated the prognostic value of programmed death-ligand 1 (PD-L1) expression in CTCs in colorectal and prostate cancer patients undergoing treatment. Peripheral blood samples were collected from 62 metastatic colorectal cancer patients and 30 metastatic prostate cancer patients. CTCs were isolated from the samples using magnetic separation with the cell-surface vimentin(CSV)-specific 84-1 monoclonal antibody that detects epithelial-mesenchymal transitioned (EMT) CTCs. CTCs were enumerated and analyzed for PD-L1 expression using confocal microscopy. PD-L1 expression was detectable in CTCs and was localized in the membrane and/or cytoplasm and nucleus. CTC detection alone was not associated with poor progression-free or overall survival in colorectal cancer or prostate cancer patients, but nuclear PD-L1 (nPD-L1) expression in these patients was significantly associated with short survival durations. These results demonstrated that nPD-L1 has potential as a clinically relevant prognostic biomarker for colorectal and prostate cancer. Our data thus suggested that use of CTC-based models of cancer for risk assessment can improve the standard cancer staging criteria and supported the incorporation of nPD-L1 expression detection in CTCs detection in such models.

PSMA-targeted polyinosine/polycytosine vector induces prostate tumor regression and invokes an antitumor immune response in mice

PubMed Central

Langut, Yael; Talhami, Alaa; Mamidi, Samarasimhareddy; Shir, Alexei; Zigler, Maya; Joubran, Salim; Sagalov, Anna; Flashner-Abramson, Efrat; Edinger, Nufar; Klein, Shoshana; Levitzki, Alexander

2017-01-01

There is an urgent need for an effective treatment for metastatic prostate cancer (PC). Prostate tumors invariably overexpress prostate surface membrane antigen (PSMA). We designed a nonviral vector, PEI-PEG-DUPA (PPD), comprising polyethylenimine–polyethyleneglycol (PEI–PEG) tethered to the PSMA ligand, 2-[3-(1, 3-dicarboxy propyl)ureido] pentanedioic acid (DUPA), to treat PC. The purpose of PEI is to bind polyinosinic/polycytosinic acid (polyIC) and allow endosomal release, while DUPA targets PC cells. PolyIC activates multiple pathways that lead to tumor cell death and to the activation of bystander effects that harness the immune system against the tumor, attacking nontargeted neighboring tumor cells and reducing the probability of acquired resistance and disease recurrence. Targeting polyIC directly to tumor cells avoids the toxicity associated with systemic delivery. PPD selectively delivered polyIC into PSMA-overexpressing PC cells, inducing apoptosis, cytokine secretion, and the recruitment of human peripheral blood mononuclear cells (PBMCs). PSMA-overexpressing tumors in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice with partially reconstituted immune systems were significantly shrunken following PPD/polyIC treatment, in all cases. Half of the tumors showed complete regression. PPD/polyIC invokes antitumor immunity, but unlike many immunotherapies does not need to be personalized for each patient. The potent antitumor effects of PPD/polyIC should spur its development for clinical use. PMID:29229829

Diode laser prostatectomy (VLAP): initial canine evaluation

NASA Astrophysics Data System (ADS)

Kopchok, George E.; Verbin, Chris; Ayres, Bruce; Peng, Shi-Kaung; White, Rodney A.

1995-05-01

This study evaluated the acute and chronic effects of diode laser (960 nm) prostatectomy using a Prolase II fiber in a canine model (n equals 5). The laser fiber consists of a 1000 um quartz fiber which reflects a cone of laser energy, at 45 degree(s) to the axis of the fiber, into the prostatic urethra (Visual Laser Ablation of Prostate). Perineal access was used to guide a 15.5 Fr cystoscope to the level of the prostate. Under visual guidance and continual saline irrigation, 60 watts of laser power was delivered for 60 seconds at 3, 9, and 12 o'clock and 30 seconds at the 6 o'clock (posterior) positions for a total energy fluence of 12,600 J. One prostate received an additional 60 second exposure at 3 and 9 o'clock for a total fluence of 19,800 J. The prostates were evaluated at one day (n equals 1) and 8 weeks (n equals 4). The histopathology of laser effects at one day show areas of necrosis with loss of glandular structures and stromal edema. Surrounding this area was a zone of degenerative glandular structures extending up to 17.5 mm (cross sectional diameter). The histopathology of the 8 week laser treated animals demonstrated dilated prostatic urethras with maximum cross- sectional diameter of 23.4 mm (mean equals 18.5 +/- 3.9 mm). This study demonstrates the effectiveness of diode laser energy for prostatic tissue coagulation and eventual sloughing. The results also demonstrate the safety of diode laser energy, with similar tissue response as seen with Nd:YAG laser, for laser prostatectomy.

Peripheral Avascular Retina in a Term Male Neonate With Microvillus Inclusion Disease and Pancreatic Insufficiency.

PubMed

Paulus, Yannis M; Alcorn, Deborah M; Gaynon, Michael; Moshfeghi, Darius M

2015-05-01

The authors present the first case of peripheral avascular retina in a term male neonate with pancreatic exocrine insufficiency, atypical microvillus inclusion disease, flat tympanograms, and recurrent urinary tract infections. Clinical examination showed avascular peripheral retina to posterior zone II temporally, with a flat stage 1-like demarcation line, and no plus disease. Genetic testing results were normal. The patient developed peripheral neovascularization and underwent panretinal photocoagulation. This case likely represents mild Norrie disease, familial exudative vitreoretinopathy, or incontinentia pigmenti due to a Wnt signaling abnormality. While these conditions are usually more severe, a variable spectrum of Wnt abnormalities exists throughout the body. Copyright 2015, SLACK Incorporated.

A novel urinary long non-coding RNA transcript improves diagnostic accuracy in patients undergoing prostate biopsy.

PubMed

Zhang, Wei; Ren, Shan-Cheng; Shi, Xiao-Lei; Liu, Ya-Wei; Zhu, Ya-Sheng; Jing, Tai-Le; Wang, Fu-Bo; Chen, Rui; Xu, Chuan-Liang; Wang, Hui-Qing; Wang, Hai-Feng; Wang, Yan; Liu, Bing; Li, Yao-Ming; Fang, Zi-Yu; Guo, Fei; Lu, Xin; Shen, Dan; Gao, Xu; Hou, Jian-Guo; Sun, Ying-Hao

2015-05-01

Long non-coding RNA (LncRNA) PCA3 has been a well-established urine biomarker for the detection of prostate cancer (PCa). Our previous study showed a novel LncRNA FR0348383 is up-regulated in over 70% of PCa compared with matched benign tissues. The aim of this study was to evaluate the diagnostic value of urinary FR0348383 for men undergoing prostate biopsy due to elevated PSA (PSA > 4.0 ng/ml) and/or abnormal digital rectal examination (DRE). Post-DRE first-catch urine specimens prior to prostate biopsies were prospectively collected. After the whole transcriptome amplification, quantitative real time polymerase chain reaction was applied to quantify urine FR0348383 and PSA levels. The FR0348383 score was calculated as the ratio of PSA and FR0348383 mRNA (PSA mRNA/FR0348383 mRNA × 1000). The diagnostic value of FR0348383 score was evaluated by logistic regression and decision curve analysis. 213 cases with urine samples containing sufficient mRNA were included, 94 cases had serum PSA level 4.0-10.0 ng/ml. PCa was identified in 72 cases. An increasing FR0348383 score was correlated with an increasing probability of a positive biopsy (P < 0.001). Multivariable logistic analysis indicated FR0348383 score (P < 0.001), PSA (P = 0.004), age (P = 0.007), prostate volume (P < 0.001) were independent predictors of PCa. ROC analysis demonstrated FR0348383 score outperformed PSA, %free PSA, and PSA Density in the prediction of PCa in the subgroup of patients with grey area PSA (AUC: 0.815 vs. 0.562 vs. 0.599 vs. 0.645). When using a probability threshold of 30% in the grey zone cohort, The FR0348383 score would save 52.0% of avoidable biopsies without missing any high grade cancers. FR0348383 transcript in post-DRE urine may be a novel biomarker for detection of PCa with great diagnostic value, especially in the grey zone cohort. The application of FR0348383 score in clinical practice might avoid unnecessary prostate biopsies and increase the specificity of PCa diagnosis. © 2015 Wiley Periodicals, Inc.

Metabolic syndrome and prostate abnormalities in male subjects of infertile couples

PubMed Central

Lotti, Francesco; Corona, Giovanni; Vignozzi, Linda; Rossi, Matteo; Maseroli, Elisa; Cipriani, Sarah; Gacci, Mauro; Forti, Gianni; Maggi, Mario

2014-01-01

No previous study has evaluated systematically the relationship between metabolic syndrome (MetS) and prostate-related symptoms and signs in young infertile men. We studied 171 (36.5 ± 8.3-years-old) males of infertile couples. MetS was defined based on the National Cholesterol Education Program Third Adult Treatment Panel. All men underwent hormonal (including total testosterone (TT) and insulin), seminal (including interleukin-8 (IL-8), seminal plasma IL-8 (sIL-8)), scrotal and transrectal ultrasound evaluations. Because we have previously assessed correlations between MetS and scrotal parameters in a larger cohort of infertile men, here, we focused on transrectal features. Prostate-related symptoms were assessed using the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and the International Prostate Symptom Score (IPSS). Twenty-two subjects fulfilled MetS criteria. In an age-adjusted logistic ordinal model, insulin levels increased as a function of MetS components (Wald = 29.5, P < 0.0001) and showed an inverse correlation with TT (adjusted r = -0.359, P< 0.0001). No association between MetS and NIH-CPSI or IPSS scores was observed. In an age-, TT-, insulin-adjusted logistic ordinal model, an increase in number of MetS components correlated negatively with normal sperm morphology (Wald = 5.59, P< 0.02) and positively with sIL-8 levels (Wald = 4.32, P < 0.05), which is a marker of prostate inflammation, with prostate total and transitional zone volume assessed using ultrasound (Wald = 17.6 and 12.5, both P < 0.0001), with arterial peak systolic velocity (Wald = 9.57, P = 0.002), with texture nonhomogeneity (hazard ratio (HR) = 1.87 (1.05–3.33), P < 0.05), with calcification size (Wald = 3.11, P < 0.05), but not with parameters of seminal vesicle size or function. In conclusion, in males of infertile couples, MetS is positively associated with prostate enlargement, biochemical (sIL8) and ultrasound-derived signs of prostate inflammation but not with prostate-related symptoms, which suggests that MetS is a trigger for a subclinical, early-onset form of benign prostatic hyperplasia. PMID:24435050

The beta-3 adrenoceptor agonist, mirabegron relaxes isolated prostate from human and rabbit: new therapeutic indication?

PubMed

Calmasini, Fabiano B; Candido, Tuany Z; Alexandre, Eduardo C; D'Ancona, Carlos A; Silva, Daniel; de Oliveira, Marco Antonio; De Nucci, Gilberto; Antunes, Edson; Mónica, Fabíola Z

2015-03-01

Alpha1 (α1)-blockers, 5-alpha reductase and phosphodiesterase type-5 inhibitors are pharmacological classes currently available for benign prostatic hyperplasia (BPH) treatment. Mirabegron, a beta-3 adrenoceptor (β3-AR) agonist has been approved for the therapy of overactive bladder and may constitute a new therapeutic option for BPH treatment. This study is aimed to evaluate the in vitro effects of mirabegron in human and rabbit prostatic smooth muscle. In rabbit prostate, electrical field stimulation (EFS)-induced contraction and concentration-response curve (CRC) to mirabegron in phenylephrine pre-contracted tissues were carried out. The potency (pEC50 ) and maximal response (Emax ) values were determined. In human prostate, CRC to phenylephrine was carried out in the absence and presence of mirabegron. Immunohistochemistry analysis for β3-AR was also carried out. In human prostate, immunohistochemistry analysis revealed the presence of β3-AR on the transition zone and mirabegron reduced by 42% the phenylephrine-induced contractions. In rabbit prostate, mirabegron produced concentration-dependent relaxations (pEC50 : 6.01 ± 0.12; Emax : 106 ± 3%), which were fully resistant to the blockade of β1-AR and β2-AR. The β3-AR blocker L748,337 caused a six-fold rightward shift in mirabegron-induced relaxations. Mirabegron (10 μM) reduced by 63% the EFS-induced contractions. Inhibitors of nitric oxide (L-NAME) and of soluble guanylate cyclase (ODQ) along with a cocktail of K+ channel blockers (apamin, charybdotoxin, glibenclamide, tetraethylammonium) all failed to significantly affect the mirabegron-induced rabbit relaxations. Mirabegron relaxes prostatic smooth muscle, providing an experimental support for the clinical investigation of its combination with an α1-blockers or PDE5 inhibitors in the treatment of BPH. Prostate 75:440-447, 2015. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

The effect of fractal contact lenses on peripheral refraction in myopic model eyes.

PubMed

Rodriguez-Vallejo, Manuel; Benlloch, Josefa; Pons, Amparo; Monsoriu, Juan A; Furlan, Walter D

2014-12-01

To test multizone contact lenses in model eyes: Fractal Contact Lenses (FCLs), designed to induce myopic peripheral refractive error (PRE). Zemax ray-tracing software was employed to simulate myopic and accommodation-dependent model eyes fitted with FCLs. PRE, defined in terms of mean sphere M and 90°-180° astigmatism J180, was computed at different peripheral positions, ranging from 0 to 35° in steps of 5°, and for different pupil diameters (PDs). Simulated visual performance and changes in the PRE were also analyzed for contact lens decentration and model eye accommodation. For comparison purposes, the same simulations were performed with another commercially available contact lens designed for the same intended use: the Dual Focus (DF). PRE was greater with FCL than with DF when both designs were tested for a 3.5 mm PD, and with and without decentration of the lenses. However, PRE depended on PD with both multizone lenses, with a remarkable reduction of the myopic relative effect for a PD of 5.5 mm. The myopic PRE with contact lenses decreased as the myopic refractive error increased, but this could be compensated by increasing the power of treatment zones. A peripheral myopic shift was also induced by the FCLs in the accommodated model eye. In regard to visual performance, a myopia under-correction with reference to the circle of least confusion was obtained in all cases for a 5.5 mm PD. The ghost images, generated by treatment zones of FCL, were dimmer than the ones produced with DF lens of the same power. FCLs produce a peripheral myopic defocus without compromising central vision in photopic conditions. FCLs have several design parameters that can be varied to obtain optimum results: lens diameter, number of zones, addition and asphericity; resulting in a very promising customized lens for the treatment of myopia progression.

Positive regulation of prostate cancer cell growth by lipid droplet forming and processing enzymes DGAT1 and ABHD5.

PubMed

Mitra, Ranjana; Le, Thuc T; Gorjala, Priyatham; Goodman, Oscar B

2017-09-06

Neoplastic cells proliferate rapidly and obtain requisite building blocks by reprogramming metabolic pathways that favor growth. Previously, we observed that prostate cancer cells uptake and store lipids in the form of lipid droplets, providing building blocks for membrane synthesis, to facilitate proliferation and growth. Mechanisms of lipid uptake, lipid droplet dynamics and their contribution to cancer growth have yet to be defined. This work is focused on elucidating the prostate cancer-specific modifications in lipid storage pathways so that these modified gene products can be identified and therapeutically targeted. To identify genes that promote lipid droplet formation and storage, the expression profiles of candidate genes were assessed and compared between peripheral blood mononuclear cells and prostate cancer cells. Subsequently, differentially expressed genes were inhibited and growth assays performed to elucidate their role in the growth of the cancer cells. Cell cycle, apoptosis and autophagy assays were performed to ascertain the mechanism of growth inhibition. Our results indicate that DGAT1, ABHD5, ACAT1 and ATGL are overexpressed in prostate cancer cells compared to PBMCs and of these overexpressed genes, DGAT1 and ABHD5 aid in the growth of the prostate cancer cells. Blocking the expression of both DGAT1 and ABHD5 results in inhibition of growth, cell cycle block and cell death. DGAT1 siRNA treatment inhibits lipid droplet formation and leads to autophagy where as ABHD5 siRNA treatment promotes accumulation of lipid droplets and leads to apoptosis. Both the siRNA treatments reduce AMPK phosphorylation, a key regulator of lipid metabolism. While DGAT1 siRNA reduces phosphorylation of ACC, the rate limiting enzyme in de novo fat synthesis and triggers phosphorylation of raptor and ULK-1 inducing autophagy and cell death, ABHD5 siRNA decreases P70S6 phosphorylation, leading to PARP cleavage, apoptosis and cell death. Interestingly, DGAT-1 is involved in the synthesis of triacylglycerol where as ABHD5 is a hydrolase and participates in the fatty acid oxidation process, yet inhibition of both enzymes similarly promotes prostate cancer cell death. Inhibition of either DGAT1 or ABHD5 leads to prostate cancer cell death. Both DGAT1 and ABHD5 can be selectively targeted to block prostate cancer cell growth.

Comparative effectiveness in urology: a state of the art review utilizing a systematic approach.

PubMed

Bandari, Jathin; Wessel, Charles B; Jacobs, Bruce L

2017-07-01

Comparative effectiveness research plays a vital role in healthcare delivery by guiding evidence-based practices. We performed a state-of-the-art review of comparative effectiveness research in the urology literature for 2016, utilizing a systematic approach. Seven high-impact papers are reviewed in detail. Across the breadth of urology, there were several important studies in comparative effectiveness research, of which we will highlight two randomized controlled trials and five observational trials: radiotherapy, prostatectomy, and active monitoring have equivalent mortality outcomes in patients with localized prostate cancer; the ideal modality of patient education is yet to be determined, and written education has minimal effect on patient perception of prostate specific antigen screening; robotic prostatectomy is associated with higher perioperative complication rates on a population basis; racial disparities exist in incontinence rates after treatment for localized prostate cancer, but not in irritative, bowel, or sexual function; androgen deprivation therapy is associated with higher fracture, peripheral artery disease, and cardiac-related complications than bilateral orchiectomy; robotic and open cystectomy offer comparable cancer-specific mortality and perioperative outcomes; and bonuses for low-cost hospitals can inadvertently reward low-quality hospitals. There have been major advancements in comparative effectiveness research in urology in 2016.

Acute myositis: an unusual and severe side effect of docetaxel: a case report and literature review.

PubMed

Rochigneux, Philippe; Schleinitz, Nicolas; Ebbo, Mikael; Aymonier, Marie; Pourroy, Bertrand; Boissier, Romain; Salas, Sébastien; Deville, Jean-Laurent

2018-06-01

Docetaxel is an antimicrotubules cytotoxic agent prescribed widely by medical oncologists in multiple tumor types (breast, lung, prostate, stomach, head, and neck). However, the side effects of docetaxel are numerous (cytopenia, peripheral edema, myalgia, arthralgia, alopecia, and sensitive neuropathy) and recent concerns have been raised about neutropenic enterocolitis in France. Here, we report the case of a 57-year-old patient with metastatic prostatic cancer, who developed a severe myositis and fasciitis grade IV 1 week after his second docetaxel infusion. We reviewed the five cases of docetaxel-related myositis described in the literature, and found that most of them occurred in patients with diabetes (n=5/5) or hypertension (n=4/5). A vascular toxicity may explain this severe complication, and patients with diabetes or hypertension should be monitored closely in the context of a docetaxel chemotherapy.

Targeting Peripheral-Derived Regulatory T Cells as a Means of Enhancing Immune Responses Directed against Prostate Cancer

DTIC Science & Technology

2016-08-01

TRAMP transgenic mice) that lack or preferentially generate pTregs (TRAMP+ mice bred onto Lck-cre; Klf2fl/fl and Smurf1-/- backgrounds, respectively...We have successfully generated TRAMP+; Lck-cre; Klf2fl/fl and TRAMP+; Smurf1-/- breeding lines, which will provide us with the necessary animals to...Aim 1: Determine how blocking pTreg production impacts PCa Major Task 1: Score tumors in TRAMP cohorts that contain or lack pTregs. The breeding

Low-Dose Total Body Irradiation and Donor Peripheral Blood Stem Cell Transplant Followed by Donor Lymphocyte Infusion in Treating Patients With Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, or Multiple Myeloma

ClinicalTrials.gov

2017-10-23

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage II Multiple Myeloma; Stage III Multiple Myeloma; Testicular Lymphoma; Waldenström Macroglobulinemia

Donor Peripheral Stem Cell Transplant in Treating Patients With Hematolymphoid Malignancies

ClinicalTrials.gov

2016-11-17

Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Relapsing Chronic Myelogenous Leukemia; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

Rare ADAR and RNASEH2B variants and a type I interferon signature in glioma and prostate carcinoma risk and tumorigenesis.

PubMed

Beyer, Ulrike; Brand, Frank; Martens, Helge; Weder, Julia; Christians, Arne; Elyan, Natalie; Hentschel, Bettina; Westphal, Manfred; Schackert, Gabriele; Pietsch, Torsten; Hong, Bujung; Krauss, Joachim K; Samii, Amir; Raab, Peter; Das, Anibh; Dumitru, Claudia A; Sandalcioglu, I Erol; Hakenberg, Oliver W; Erbersdobler, Andreas; Lehmann, Ulrich; Reifenberger, Guido; Weller, Michael; Reijns, Martin A M; Preller, Matthias; Wiese, Bettina; Hartmann, Christian; Weber, Ruthild G

2017-12-01

In search of novel germline alterations predisposing to tumors, in particular to gliomas, we studied a family with two brothers affected by anaplastic gliomas, and their father and paternal great-uncle diagnosed with prostate carcinoma. In this family, whole-exome sequencing yielded rare, simultaneously heterozygous variants in the Aicardi-Goutières syndrome (AGS) genes ADAR and RNASEH2B co-segregating with the tumor phenotype. AGS is a genetically induced inflammatory disease particularly of the brain, which has not been associated with a consistently increased cancer risk to date. By targeted sequencing, we identified novel ADAR and RNASEH2B variants, and a 3- to 17-fold frequency increase of the AGS mutations ADAR,c.577C>G;p.(P193A) and RNASEH2B,c.529G>A;p.(A177T) in the germline of familial glioma patients as well as in test and validation cohorts of glioblastomas and prostate carcinomas versus ethnicity-matched controls, whereby rare RNASEH2B variants were significantly more frequent in familial glioma patients. Tumors with ADAR or RNASEH2B variants recapitulated features of AGS, such as calcification and increased type I interferon expression. Patients carrying ADAR or RNASEH2B variants showed upregulation of interferon-stimulated gene (ISG) transcripts in peripheral blood as seen in AGS. An increased ISG expression was also induced by ADAR and RNASEH2B variants in tumor cells and was blocked by the JAK inhibitor Ruxolitinib. Our data implicate rare variants in the AGS genes ADAR and RNASEH2B and a type I interferon signature in glioma and prostate carcinoma risk and tumorigenesis, consistent with a genetic basis underlying inflammation-driven malignant transformation in glioma and prostate carcinoma development.

Expression and potential role of the peptide orexin-A in prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valiante, Salvatore; Liguori, Giovanna; Tafuri, Simona

The peptides orexin-A and orexin-B and their G protein-coupled OX1 and OX2 receptors are involved in multiple physiological processes in the central nervous system and peripheral organs. Altered expression or signaling dysregulation of orexins and their receptors have been associated with a wide range of human diseases including narcolepsy, obesity, drug addiction, and cancer. Although orexin-A, its precursor molecule prepro-orexin and OX1 receptor have been detected in the human normal and hyperplastic prostate tissues, their expression and function in the prostate cancer (PCa) remains to be addressed. Here, we demonstrate for the first time the immunohistochemical localization of orexin-A inmore » human PCa specimens, and the expression of prepro-orexin and OX1 receptor at both protein and mRNA levels in these tissues. Orexin-A administration to the human androgen-dependent prostate carcinoma cells LNCaP up-regulates OX1 receptor expression resulting in a decrease of cell survival. Noteworthy, nanomolar concentrations of the peptide counteract the testosterone-induced nuclear translocation of the androgen receptor in the cells: the orexin-A action is prevented by the addition of the OX1 receptor antagonist SB-408124 to the test system. These findings indicate that orexin-A/OX1 receptor interaction interferes with the activity of the androgen receptor which regulates PCa onset and progression, thus suggesting that orexin-A and its receptor might represent novel therapeutic targets to challenge this aggressive cancer. - Highlights: • Orexin-A and OX1 receptor are present in human cancer prostate tissues. • Orexin-A up-regulates OX1 receptor expression in LNCaP cells. • Orexin-A inhibits testosterone-induced nuclear translocation of androgen receptor.« less

Phase I/II trial of dendritic cell-based active cellular immunotherapy with DCVAC/PCa in patients with rising PSA after primary prostatectomy or salvage radiotherapy for the treatment of prostate cancer.

PubMed

Fucikova, Jitka; Podrazil, Michal; Jarolim, Ladislav; Bilkova, Pavla; Hensler, Michal; Becht, Etienne; Gasova, Zdenka; Klouckova, Jana; Kayserova, Jana; Horvath, Rudolf; Fialova, Anna; Vavrova, Katerina; Sochorova, Klara; Rozkova, Daniela; Spisek, Radek; Bartunkova, Jirina

2018-01-01

Immunotherapy of cancer has the potential to be effective mostly in patients with a low tumour burden. Rising PSA (prostate-specific antigen) levels in patients with prostate cancer represents such a situation. We performed the present clinical study with dendritic cell (DC)-based immunotherapy in this patient population. The single-arm phase I/II trial registered as EudraCT 2009-017259-91 involved 27 patients with rising PSA levels. The study medication consisted of autologous DCs pulsed with the killed LNCaP cell line (DCVAC/PCa). Twelve patients with a favourable PSA response continued with the second cycle of immunotherapy. The primary and secondary objectives of the study were to assess the safety and determine the PSA doubling time (PSADT), respectively. No significant side effects were recorded. The median PSADT in all treated patients increased from 5.67 months prior to immunotherapy to 18.85 months after 12 doses (p < 0.0018). Twelve patients who continued immunotherapy with the second cycle had a median PSADT of 58 months that remained stable after the second cycle. In the peripheral blood, specific PSA-reacting T lymphocytes were increased significantly already after the fourth dose, and a stable frequency was detected throughout the remainder of DCVAC/PCa treatment. Long-term immunotherapy of prostate cancer patients experiencing early signs of PSA recurrence using DCVAC/PCa was safe, induced an immune response and led to the significant prolongation of PSADT. Long-term follow-up may show whether the changes in PSADT might improve the clinical outcome in patients with biochemical recurrence of the prostate cancer.

EMMPRIN and ADAM12 in prostate cancer: preliminary results of a prospective study.

PubMed

Bilgin Doğru, Elif; Dizdar, Yavuz; Akşit, Ece; Ural, Feyyaz; Şanlı, Öner; Yasasever, Vildan

2014-11-01

Extracellular metalloproteinase inducer (EMMPRIN) and a disintegrin and metalloproteinase (ADAM12) play a major role in cancer invasion and metastasis owing to the fact that they are directly related to the cell microenvironment and extracellular matrix (ECM) degradation. The aim of this study was to search for an answer to the question "whether the determination of EMMPRIN and ADAM12 values especially in urine may be helpful for the early diagnosis of prostate cancer without employing invasive methods" and also to check whether they may be useful for the determination of the patients with high metastasis risk. Peripheral blood and urine from 66 prostate cancer patients (40 local, 20 locally advanced, 6 metastatic) and 14 healthy controls were evaluated by enzyme-linked immunosorbent assay (ELISA) method. Serum EMMPRIN and ADAM12 values of the patients were seen to be statistically higher than the serum EMMPRIN and ADAM12 values of the healthy controls (p=0.01 and p=0.001, respectively). The urine ADAM12 levels were significantly higher in patients (p=0.013). No significant relationships were found between urine EMMPRIN values of the patients and the healthy controls (p>0.05). Positive correlation between urine EMMPRIN-urine ADAM12 tests was found in total patients group (r=0.683, p=0.001). Our preliminary results revealed that serum EMMPRIN and ADAM12 values and urine ADAM12 values may be useful markers in prostate cancer therapy. Due to the high correlation between these two tests, we are of the opinion that the use of urine ADAM12 in clinic may be sufficient and favorable together with prostate-specific antigen (PSA) for treatment.

Retrospective evaluation of thoracic computed tomography findings in dogs naturally infected by Angiostrongylus vasorum.

PubMed

Coia, Mark E; Hammond, Gawain; Chan, Daniel; Drees, Randi; Walker, David; Murtagh, Kevin; Stone, Janine; Bexfield, Nicholas; Reeve, Lizzie; Helm, Jenny

2017-09-01

Angiostrongylus vasorum (A. vasorum) is an important emerging disease of canidae. Cardiorespiratory signs are common in affected dogs, therefore thoracic imaging is critical for diagnosing and monitoring disease. Descriptions of thoracic computed tomography (CT) findings in dogs naturally infected with A. vasorum are currently lacking. Aims of this multicenter, retrospective study were to describe thoracic CT findings in a group of dogs with confirmed disease, determine whether any changes were consistent among dogs, and propose standardized terms for describing thoracic CT findings. Nine UK-based referral centers' clinical and imaging databases were searched for dogs that had a confirmed diagnosis of A. vasorum, and had undergone thoracic CT examination. Eighteen dogs, from seven of the centers, fulfilled the inclusion criteria. The lung lobes were divided into the following three zones and the CT changes described in each: pleural (zone 1), subpleural (zone 2), and peribronchovascular (zone 3). The predominent abnormality was increased lung attenuation due to poorly defined ground-glass opacity or consolidation. There were regions of mosaic attenuation due to peripheral bronchiectasis. Nine/18 (50%) dogs showed hyperattenuating nodules of varying sizes with ill-defined margins. The distribution always affected zones 1 and 2 with varied involvement of zone 3; this resulted in clear delineation between zones 2 and 3. Tracheobronchial lymphadenomegaly was frequently noted. Findings were nonspecific and there was considerable overlap with other pulmonary conditions. However, authors recommend that A. vasorum be considered a likely differential diagnosis for dogs with a predominantly peripheral distribution of lung changes. © 2017 American College of Veterinary Radiology.

Recovery from retinal lesions: molecular plasticity mechanisms in visual cortex far beyond the deprived zone.

PubMed

Hu, Tjing-Tjing; Van den Bergh, Gert; Thorrez, Lieven; Heylen, Kevin; Eysel, Ulf T; Arckens, Lutgarde

2011-12-01

In cats with central retinal lesions, deprivation of the lesion projection zone (LPZ) in primary visual cortex (area 17) induces remapping of the cortical topography. Recovery of visually driven cortical activity in the LPZ involves distinct changes in protein expression. Recent observations, about molecular activity changes throughout area 17, challenge the view that its remote nondeprived parts would not be involved in this recovery process. We here investigated the dynamics of the protein expression pattern of remote nondeprived area 17 triggered by central retinal lesions to explore to what extent far peripheral area 17 would contribute to the topographic map reorganization inside the visual cortex. Using functional proteomics, we identified 40 proteins specifically differentially expressed between far peripheral area 17 of control and experimental animals 14 days to 8 months postlesion. Our results demonstrate that far peripheral area 17 is implicated in the functional adaptation to the visual deprivation, involving a meshwork of interacting proteins, operating in diverse pathways. In particular, endocytosis/exocytosis processes appeared to be essential via their intimate correlation with long-term potentiation and neurite outgrowth mechanisms.

Nutritional status and nutritional habits of men with benign prostatic hyperplasia or prostate cancer - preliminary investigation.

PubMed

Goluch-Koniuszy, Zuzanna; Rygielska, Magda; Nowacka, Ilona

2013-01-01

The ageing in men, the most frequent pathologic lesions affecting the prostatic gland in this period are benign prostatic hyperplasia (BPH) and prostate cancer (PC), the course of which may be influenced by the improper nutritional status of patients and their nutritional habits. The aim of this study was, therefore, to evaluate the nutritional status and eating habits of men diagnosed and treated for one of the above diseases. MATERIAL AND METODS: The nutritional status of 30 male patients with clinically confirmed and treated disease of the prostatic gland, including 15 men (aged 51-75 years) with BPH and 15 men (aged 51-73 years) with PC, was evaluated based on their BMI, WC, WHR, and WHtR parameters. In turn, the energy and nutritive value of 90 daily food rations (DFRs) was evaluated. Finally, calculations were made for the Key's index of diet atherogenicity, resultant Glycemic Index (GI) and Glycemic Load (GL). Higher values of the BMI, WC, WHR and WHtR parameters were noted in the men with PC, they were also characterized by a higher incidence of peripheral subcutaneous obesity and visceral obesity. The DFRs of the men were characterized by a low energy value and by a low intake of available carbohydrates, dietary fi ber, K, Ca, Mg, vitamins D and C, and fl uids at a simultaneously high intake of total and animal protein, cholesterol, Na, P, Fe, Cu as well as vitamins B2 and PP. The contribution of energy derived from the basic nutrients diverged from the recommended values. In addition, the DFRs were characterized by high values of Key's index and 24-h GL. Differences in meeting the RDA for selected nutrients between the analysed groups of men were statistically significant. The improper nutritional status of the men may result from their incorrect nutritional habits which fail to improve their health status, and even predispose them to the development of some diet-dependent diseases. In view of that, both correction of diets of the surveyed men, as well as their health-promoting nutritional education in the aspect of prostate diseases seem necessary.

An MRI guided system for prostate laser ablation with treatment planning and multi-planar temperature monitoring

NASA Astrophysics Data System (ADS)

Xu, Sheng; Agarwal, Harsh; Bernardo, Marcelino; Seifabadi, Reza; Turkbey, Baris; Partanen, Ari; Negussie, Ayele; Glossop, Neil; Choyke, Peter; Pinto, Peter; Wood, Bradford J.

2016-03-01

Prostate cancer is often over treated with standard treatment options which impact the patients' quality of life. Laser ablation has emerged as a new approach to treat prostate cancer while sparing the healthy tissue around the tumor. Since laser ablation has a small treatment zone with high temperature, it is necessary to use accurate image guidance and treatment planning to enable full ablation of the tumor. Intraoperative temperature monitoring is also desirable to protect critical structures from being damaged in laser ablation. In response to these problems, we developed a navigation platform and integrated it with a clinical MRI scanner and a side firing laser ablation device. The system allows imaging, image guidance, treatment planning and temperature monitoring to be carried out on the same platform. Temperature sensing phantoms were developed to demonstrate the concept of iterative treatment planning and intraoperative temperature monitoring. Retrospective patient studies were also conducted to show the clinical feasibility of the system.

Considerations for theoretical modeling of thermal ablation with catheter-based ultrasonic sources: implications for treatment planning, monitoring and control

PubMed Central

Prakash, Punit; Diederich, Chris J.

2012-01-01

Purpose To determine the impact of including dynamic changes in tissue physical properties during heating on feedback controlled thermal ablation with catheter-based ultrasound. Additionally, we compared impact several indicators of thermal damage on predicted extents of ablation zones for planning and monitoring ablations with this modality. Methods A 3D model of ultrasound ablation with interstitial and transurethral applicators incorporating temperature based feedback control was used to simulate thermal ablations in prostate and liver tissue. We investigated five coupled models of heat dependent changes in tissue acoustic attenuation/absorption and blood perfusion of varying degrees of complexity.. Dimensions of the ablation zone were computed using temperature, thermal dose, and Arrhenius thermal damage indicators of coagulative necrosis. A comparison of the predictions by each of these models was illustrated on a patient-specific anatomy in the treatment planning setting. Results Models including dynamic changes in blood perfusion and acoustic attenuation as a function of thermal dose/damage predicted near-identical ablation zone volumes (maximum variation < 2.5%). Accounting for dynamic acoustic attenuation appeared to play a critical role in estimating ablation zone size, as models using constant values for acoustic attenuation predicted ablation zone volumes up to 50% larger or 47% smaller in liver and prostate tissue, respectively. Thermal dose (t43 ≥ 240min) and thermal damage (Ω ≥ 4.6) thresholds for coagulative necrosis are in good agreement for all heating durations, temperature thresholds in the range of 54 °C for short (< 5 min) duration ablations and 50 °C for long (15 min) ablations may serve as surrogates for determination of the outer treatment boundary. Conclusions Accounting for dynamic changes in acoustic attenuation/absorption appeared to play a critical role in predicted extents of ablation zones. For typical 5—15 min ablations with this modality, thermal dose and Arrhenius damage measures of ablation zone dimensions are in good agreement, while appropriately selected temperature thresholds provide a computationally cheaper surrogate. PMID:22235787

Cardiovascular mortality in patients with prostate cancer exposed to androgen deprivation therapy.

PubMed

Monzó-Gardiner, J I; Herranz-Amo, F

2015-10-01

A relationship between the administration of GnRH agonists and the risk of acute myocardial infarction (AMC) in patients with prostate cancer has been showed in the third observational study published in April 2014. The association AMC-orchiectomy was not found in any of these studies. Define risk factors for cardiovascular disease in patients treated with GnRH agonist. Their probable underlying pathogenic mechanism in the myocardium and peripheral vascular tree was also analyzed. English articles cited in PubMed were reviewed. No time period is specified. The last search date was 11/30/14. In patients with coronary history of AMC or congestive heart failure, hormonal neoadjuvant therapy increased cardiovascular mortality rates (HR: 1.96, IC 95%: 1.04-3.71; P=.04) as well as cardiovascular-specific mortality rates (AHR: 3.28; IC 95%: 1.01-10.64; P=.048). Two possible mechanisms can be involved: a) direct mechanism through myocardial receptor for GnRH/PKA along with atherogenic plaques; and b) indirect mechanism related with metabolic disturbances. Patients with AMC or congestive heart failure history could present a higher risk of death related to the use of GnRH agonists. In these cases, should carefully consider appropriateness of such treatment. These effects can explained by a direct mechanism on myocardium and peripheral vascular tree and indirect ones related with modified metabolic syndrome. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

GE132+Natural: Novel promising dietetic supplement with antiproliferative influence on prostate, colon, and breast cancer cells.

PubMed

Okic-Djordjevic, I; Trivanovic, D; Krstic, J; Jaukovic, A; Mojsilovic, S; Santibanez, J F; Terzic, M; Vesovic, D; Bugarski, D

2013-01-01

Natural products have been investigated for promising new leads in pharmaceutical development. The purpose of this study was to analyze the biological effect of GE132+Natural, a novel supplement consisting of 5 compounds: Resveratrol, Ganoderma lucidum, Sulforaphane, Lycopene and Royal jelly. The antiproliferative activity of GE132+Natural was tested on 3 different human cancer cell lines: MCF7 (breast cancer cells), PC3 (prostate cancer cells), and SW480 (colon cancer cells), as well as on EA.hy 926 (normal human endothelial cell line). In addition, the cytotoxicity of GE132+- Natural on the proliferation of primary human mesenchymal stem cells isolated from dental pulp (DP=MSC), along with its in vitro impact on different peripheral blood parameters, was determined. The results revealed high antiproliferative activity of GE132+Natural on all tested cancer cell lines (PC3, MCF7 and SW480), as well as on the EA.hy 926 endothelial cell line in a dose-dependent manner. However, applied in a wide range of concentrations GE132+Natural did not affect both the proliferation of primary mesenchymal stem cells and the peripheral blood cells counts. The data obtained demonstrated that GE132+Natural is effective in inhibiting cancer cell proliferation, indicating its potential beneficial health effects. In addition, the results pointed that adult mesenchymal stem cells might be valuable as a test system for evaluating the toxicity and efficacy of new medicines or chemicals.

Peripheral innervation patterns of vestibular nerve afferents in the bullfrog utriculus

NASA Technical Reports Server (NTRS)

Baird, Richard A.; Schuff, N. R.

1994-01-01

Vestibular nerve afferents innervating the bullfrog utriculus differ in their response dynamics and sensitivity to natural stimulation. They also supply hair cells that differ markedly in hair bundle morphology. To examine the peripheral innervation patterns of individual utricular afferents more closely, afferent fibers were labeled by the extracellular injection of horseradish peroxidase (HRP) into the vestibular nerve after sectioning the vestibular nerve medial to Scarpa's ganglion to allow the degeneration of sympathetic and efferent fibers. The peripheral arborizations of individual afferents were then correlated with the diameters of their parent axons, the regions of the macula they innervate, and the number and type of hair cells they supply. The utriculus is divided by the striola, a narrow zone of distinctive morphology, into media and lateral parts. Utiricular afferents were classified as striolar or extrastriolar according to the epithelial entrance of their parent axons and the location of their terminal fields. In general, striolar afferents had thicker parent axons, fewer subepithelial bifurcations, larger terminal fields, and more synaptic endings than afferents in extrstriolar regions. Afferents in a juxtastriolar zone, immediately adjacent to the medial striola, had innervation patterns transitional between those in the striola and more peripheral parts of the medial extrastriola. moast afferents innervated only a single macular zone. The terminal fields of striolar afferents, with the notable exception of a few afferents with thin parent axons, were generally confined to one side of the striola. Hair cells in the bullfrog utriculus have perviously been classified into four types based on hair bundle morphology. Afferents in the extrastriolar and juxtastriolar zones largely or exclusively innervated Type B hair cells, the predominant hair cell type in the utricular macula. Striolar afferents supplied a mixture of four hair cell types, but largely contacted Type B and Type C hair cells, particularly on the outer rows of the medial striola. Afferents supplying more central striolar regions innervated fewer Type B and larger numbers of Type E and Type F hair cells. Striolar afferents with thin parent axons largely supplied Type E hair cells with bulbed kniocilia in the innermost striolar rows.

Adiponectin as a routine clinical biomarker.

PubMed

Kishida, Ken; Funahashi, Tohru; Shimomura, Iichiro

2014-01-01

Adiponectin is a protein synthesized and secreted predominantly by adipocytes into the peripheral blood. However, circulating adiponectin level is inversely related with body weight, especially visceral fat accumulation. The mechanism of this paradoxical relation remains obscure. Low circulating adiponectin concentrations (hypoadiponectinemia; <4 μg/mL) are associated with a variety of diseases, including dysmetabolism (type 2 diabetes, insulin resistance, hypertension, dyslipidemia, metabolic syndrome, hyperuricemia), atherosclerosis (coronary artery disease, stroke, peripheral artery disease), sleep apnea, non-alcoholic fatty liver disease, gastritis and gastro-esophageal reflux disease, inflammatory bowel diseases, pancreatitis, osteoporosis, and cancer (endometrial cancer, postmenopausal breast cancer, leukemia, colon cancer, gastric cancer, prostate cancer). On the other hand, hyperadiponectinemia is associated with cardiac, renal and pulmonary diseases. This review article focuses on the significance of adiponectin as a clinical biomarker of obesity-related diseases. Routine measurement of adiponectin in patients with lifestyle-related diseases is highly recommended. Copyright © 2013 Elsevier Ltd. All rights reserved.

Immune mediators of chronic pelvic pain syndrome

PubMed Central

Murphy, Stephen F.; Schaeffer, Anthony J.; Thumbikat, Praveen

2016-01-01

The cause of chronic pelvic pain syndrome (CPPS) has yet to be established. Since the late 1980s, cytokine, chemokine, and immunological classification studies using human samples have focused on identifying biomarkers for CPPS, but no diagnostically beneficial biomarkers have been identified, and these studies have done little to deepen our understanding of the mechanisms underlying chronic prostatic pain. Given the large number of men thought to be affected by this condition and the ineffective nature of current treatments, there is a pressing need to elucidate these mechanisms. Prostatitis types IIIa and IIIb are classified according to the presence of pain without concurrent presence of bacteria; however, it is becoming more evident that, although levels of bacteria are not directly associated with levels of pain, the presence of bacteria might act as the initiating factor that drives primary activation of mast-cell-mediated inflammation in the prostate. Mast cell activation is also known to suppress regulatory T cell (Treg) control of self-tolerance and also activate neural sensitization. This combination of established autoimmunity coupled with peripheral and central neural sensitization can result in the development of multiple symptoms, including pelvic pain and bladder irritation. Identifying these mechanisms as central mediators in CPPS offers new insight into the prospective treatment of the disease. PMID:24686526

Formation of various types of nanostructures on germanium surface by nanosecond laser pulses

NASA Astrophysics Data System (ADS)

Mikolutskiy, S. I.; Khasaya, R. R.; Khomich, Yu V.; Yamshchikov, V. A.

2018-03-01

The paper describes the formation of micro- and nanostructures in different parts of irradiation zone on germanium surface by multiple action of nanosecond pulses of ArF-laser. It proposes a simple method using only one laser beam without any optional devices and masks for surface treatment. Hexa- and pentagonal cells with submicron dimensions along the surface were observed in peripheral zone of irradiation spot by atomic-force microscopy. Nanostructures in the form of bulbs with rounded peaks with lateral sizes of 40-120 nm were obtained in peripheral low-intensity region of the laser spot. Considering experimental data on material processing by nanosecond laser pulses, a classification of five main types of surface reliefs formed by nanosecond laser pulses with energy density near or slightly above ablation threshold was proposed.

Deformable segmentation of 3D MR prostate images via distributed discriminative dictionary and ensemble learning

PubMed Central

Guo, Yanrong; Gao, Yaozong; Shao, Yeqin; Price, True; Oto, Aytekin; Shen, Dinggang

2014-01-01

Purpose: Automatic prostate segmentation from MR images is an important task in various clinical applications such as prostate cancer staging and MR-guided radiotherapy planning. However, the large appearance and shape variations of the prostate in MR images make the segmentation problem difficult to solve. Traditional Active Shape/Appearance Model (ASM/AAM) has limited accuracy on this problem, since its basic assumption, i.e., both shape and appearance of the targeted organ follow Gaussian distributions, is invalid in prostate MR images. To this end, the authors propose a sparse dictionary learning method to model the image appearance in a nonparametric fashion and further integrate the appearance model into a deformable segmentation framework for prostate MR segmentation. Methods: To drive the deformable model for prostate segmentation, the authors propose nonparametric appearance and shape models. The nonparametric appearance model is based on a novel dictionary learning method, namely distributed discriminative dictionary (DDD) learning, which is able to capture fine distinctions in image appearance. To increase the differential power of traditional dictionary-based classification methods, the authors' DDD learning approach takes three strategies. First, two dictionaries for prostate and nonprostate tissues are built, respectively, using the discriminative features obtained from minimum redundancy maximum relevance feature selection. Second, linear discriminant analysis is employed as a linear classifier to boost the optimal separation between prostate and nonprostate tissues, based on the representation residuals from sparse representation. Third, to enhance the robustness of the authors' classification method, multiple local dictionaries are learned for local regions along the prostate boundary (each with small appearance variations), instead of learning one global classifier for the entire prostate. These discriminative dictionaries are located on different patches of the prostate surface and trained to adaptively capture the appearance in different prostate zones, thus achieving better local tissue differentiation. For each local region, multiple classifiers are trained based on the randomly selected samples and finally assembled by a specific fusion method. In addition to this nonparametric appearance model, a prostate shape model is learned from the shape statistics using a novel approach, sparse shape composition, which can model nonGaussian distributions of shape variation and regularize the 3D mesh deformation by constraining it within the observed shape subspace. Results: The proposed method has been evaluated on two datasets consisting of T2-weighted MR prostate images. For the first (internal) dataset, the classification effectiveness of the authors' improved dictionary learning has been validated by comparing it with three other variants of traditional dictionary learning methods. The experimental results show that the authors' method yields a Dice Ratio of 89.1% compared to the manual segmentation, which is more accurate than the three state-of-the-art MR prostate segmentation methods under comparison. For the second dataset, the MICCAI 2012 challenge dataset, the authors' proposed method yields a Dice Ratio of 87.4%, which also achieves better segmentation accuracy than other methods under comparison. Conclusions: A new magnetic resonance image prostate segmentation method is proposed based on the combination of deformable model and dictionary learning methods, which achieves more accurate segmentation performance on prostate T2 MR images. PMID:24989402

Deformable segmentation of 3D MR prostate images via distributed discriminative dictionary and ensemble learning.

PubMed

Guo, Yanrong; Gao, Yaozong; Shao, Yeqin; Price, True; Oto, Aytekin; Shen, Dinggang

2014-07-01

Automatic prostate segmentation from MR images is an important task in various clinical applications such as prostate cancer staging and MR-guided radiotherapy planning. However, the large appearance and shape variations of the prostate in MR images make the segmentation problem difficult to solve. Traditional Active Shape/Appearance Model (ASM/AAM) has limited accuracy on this problem, since its basic assumption, i.e., both shape and appearance of the targeted organ follow Gaussian distributions, is invalid in prostate MR images. To this end, the authors propose a sparse dictionary learning method to model the image appearance in a nonparametric fashion and further integrate the appearance model into a deformable segmentation framework for prostate MR segmentation. To drive the deformable model for prostate segmentation, the authors propose nonparametric appearance and shape models. The nonparametric appearance model is based on a novel dictionary learning method, namely distributed discriminative dictionary (DDD) learning, which is able to capture fine distinctions in image appearance. To increase the differential power of traditional dictionary-based classification methods, the authors' DDD learning approach takes three strategies. First, two dictionaries for prostate and nonprostate tissues are built, respectively, using the discriminative features obtained from minimum redundancy maximum relevance feature selection. Second, linear discriminant analysis is employed as a linear classifier to boost the optimal separation between prostate and nonprostate tissues, based on the representation residuals from sparse representation. Third, to enhance the robustness of the authors' classification method, multiple local dictionaries are learned for local regions along the prostate boundary (each with small appearance variations), instead of learning one global classifier for the entire prostate. These discriminative dictionaries are located on different patches of the prostate surface and trained to adaptively capture the appearance in different prostate zones, thus achieving better local tissue differentiation. For each local region, multiple classifiers are trained based on the randomly selected samples and finally assembled by a specific fusion method. In addition to this nonparametric appearance model, a prostate shape model is learned from the shape statistics using a novel approach, sparse shape composition, which can model nonGaussian distributions of shape variation and regularize the 3D mesh deformation by constraining it within the observed shape subspace. The proposed method has been evaluated on two datasets consisting of T2-weighted MR prostate images. For the first (internal) dataset, the classification effectiveness of the authors' improved dictionary learning has been validated by comparing it with three other variants of traditional dictionary learning methods. The experimental results show that the authors' method yields a Dice Ratio of 89.1% compared to the manual segmentation, which is more accurate than the three state-of-the-art MR prostate segmentation methods under comparison. For the second dataset, the MICCAI 2012 challenge dataset, the authors' proposed method yields a Dice Ratio of 87.4%, which also achieves better segmentation accuracy than other methods under comparison. A new magnetic resonance image prostate segmentation method is proposed based on the combination of deformable model and dictionary learning methods, which achieves more accurate segmentation performance on prostate T2 MR images.

A Study of CDX-1127 (Varlilumab) in Patients With Select Solid Tumor Types or Hematologic Cancers

ClinicalTrials.gov

2018-01-29

CD27 Expressing B-cell Malignancies for Example Hodgkin's Lymphoma; Chronic Lymphocytic Leukemia; Mantle Cell Lymphoma; Marginal Zone B Cell Lymphoma); Any T-cell Malignancy; Solid Tumors (Metastatic Melanoma, Renal (Clear) Cell Carcinoma; Hormone-refractory Prostate Adenocarcinoma, Ovarian Cancer; Colorectal Adenocarcinoma, Non-small Cell Lung Cancer); Burkett's Lymphoma; Primary Lymphoma of the Central Nervous System

A Workflow to Improve the Alignment of Prostate Imaging with Whole-mount Histopathology.

PubMed

Yamamoto, Hidekazu; Nir, Dror; Vyas, Lona; Chang, Richard T; Popert, Rick; Cahill, Declan; Challacombe, Ben; Dasgupta, Prokar; Chandra, Ashish

2014-08-01

Evaluation of prostate imaging tests against whole-mount histology specimens requires accurate alignment between radiologic and histologic data sets. Misalignment results in false-positive and -negative zones as assessed by imaging. We describe a workflow for three-dimensional alignment of prostate imaging data against whole-mount prostatectomy reference specimens and assess its performance against a standard workflow. Ethical approval was granted. Patients underwent motorized transrectal ultrasound (Prostate Histoscanning) to generate a three-dimensional image of the prostate before radical prostatectomy. The test workflow incorporated steps for axial alignment between imaging and histology, size adjustments following formalin fixation, and use of custom-made parallel cutters and digital caliper instruments. The control workflow comprised freehand cutting and assumed homogeneous block thicknesses at the same relative angles between pathology and imaging sections. Thirty radical prostatectomy specimens were histologically and radiologically processed, either by an alignment-optimized workflow (n = 20) or a control workflow (n = 10). The optimized workflow generated tissue blocks of heterogeneous thicknesses but with no significant drifting in the cutting plane. The control workflow resulted in significantly nonparallel blocks, accurately matching only one out of four histology blocks to their respective imaging data. The image-to-histology alignment accuracy was 20% greater in the optimized workflow (P < .0001), with higher sensitivity (85% vs. 69%) and specificity (94% vs. 73%) for margin prediction in a 5 × 5-mm grid analysis. A significantly better alignment was observed in the optimized workflow. Evaluation of prostate imaging biomarkers using whole-mount histology references should include a test-to-reference spatial alignment workflow. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

Validity of Prostate Health Index and Percentage of [-2] Pro-Prostate-Specific Antigen as Novel Biomarkers in the Diagnosis of Prostate Cancer: Omani Tertiary Hospitals Experience

PubMed Central

Al Saidi, Safana S.; Al Riyami, Nafila B.; Al Marhoon, Mohammed S.; Al Saraf, Mohammed S.; Al Busaidi, Salim S.; Bayoumi, Riad; Mula-Abed, Waad-Allah S.

2017-01-01

Objectives Prostate cancer is the leading cancer in older men. The Ministry of Health Oman Cancer Incidence Registry 2013 lists cancer of the prostate as the first most common cancer in males. Therefore, early detection is important and prostate-specific antigen (PSA) is widely used as an established laboratory test. However, despite its wide use, its value in screening, particularly in asymptomatic males, is controversial when considering the risks and benefits of early detection. Methods This prospective, observational study included 136 males (67.0±8.9 years; range 45–90) who were scheduled for a prostate biopsy in two different tertiary care teaching hospitals in Oman: the Royal Hospital and Sultan Qaboos University Hospital. Blood specimens from these patients were collected at the same setting before obtaining a prostatic biopsy. Three PSA markers (total PSA (tPSA), free PSA (fPSA), and [-2]proPSA (p2PSA)) were measured and the Prostate Health Index (phi) calculated. The histopathological report of the prostatic biopsy for each patient was obtained from the histopathology laboratory of the concerned hospital along with clinical and laboratory data through the hospital information system. Results Phi has the highest validity markers compared with other prostate markers, with a sensitivity of 82.1%, specificity of 80.6%, and area under the curve (AUC) value of 0.81 at a cutoff of 41.9. The other prostatic markers showed sensitivities and specificities of 78.6% and 25.9% for tPSA; 35.7% and 92.6% for %fPSA; and 64.3% and 82.4% for %p2PSA, respectively. The AUCs at the best cutoff values were 0.67 at 10.1 µg/L for tPSA; 0.70 at 11.6% for %fPSA; and 0.55 at 1.4% for %p2PSA. An association between phi values and aggressiveness of prostate malignancy was noted. Of the 28 patients with prostate cancer, 22 patients had tPSA > 4 µg/L. However, no patient had phi in the low-risk category, and five, six, and 17 patients had phi in the moderate-, high-, and very high-risk categories, respectively. Conclusions Phi outperforms tPSA and fPSA when used alone or in combination, and appears to be more accurate than both markers in excluding prostate cancer before biopsy. Use of this biomarker helps clinicians to avoid unnecessary biopsies, particularly in patients with gray-zone tPSA level. Phi is the strongest marker that correlates proportionally with Gleason Score; therefore, it is also useful in predicting the aggressiveness of the disease. This is the first reported experience for the use of p2PSA and phi in Oman, the Middle East, and North Africa. PMID:28804579

Fresnel zone plate with apodized aperture for hard X-ray Gaussian beam optics.

PubMed

Takeuchi, Akihisa; Uesugi, Kentaro; Suzuki, Yoshio; Itabashi, Seiichi; Oda, Masatoshi

2017-05-01

Fresnel zone plates with apodized apertures [apodization FZPs (A-FZPs)] have been developed to realise Gaussian beam optics in the hard X-ray region. The designed zone depth of A-FZPs gradually decreases from the center to peripheral regions. Such a zone structure forms a Gaussian-like smooth-shouldered aperture function which optically behaves as an apodization filter and produces a Gaussian-like focusing spot profile. Optical properties of two types of A-FZP, i.e. a circular type and a one-dimensional type, have been evaluated by using a microbeam knife-edge scan test, and have been carefully compared with those of normal FZP optics. Advantages of using A-FZPs are introduced.

Heath risk among pesticide sellers in Bamenda (Cameroon) and peripheral areas.

PubMed

Sonchieu, Jean; Akono, Edouard Nantia; Ngwamitang, Cheche Tanwi; Ngassoum, Benoït Martin

2018-04-01

In Bamenda and peripheral zones, studies have been focused on the effects of pesticides on farmers (pesticide users) while nothing has been done to assess the exposure of sellers to pesticides. This study aimed at evaluating the exposure of pesticide sellers in the same area. Thirty-two questionnaires were administered to 32 pesticide sellers systematically selected, and chi-square was used for statistical analysis. From each shop, a respondent was chosen among the workers according to its daily time spent in the workplace. The results showed that there is similarity between sellers in Bamenda and peripheral area; one active ingredient (metalaxyl) and one formulation (beauchamp) sold are not registered; throat irritation, headaches, fatigue, skin irritation, eye irritation, and difficulty in breathing with more cases of nose irritation were symptoms observed; pesticides are stored either in the shops or in warehouses; safety measures generally applied are sitting outside the shop, taking medicated charcoal and the use of protective clothing; 56% have less than 5 years experience. Permanent pesticide sellers are then exposed to chronic intoxication in Bamenda and neighboring zones. Employers should make use of protective clothing in their shops when manipulating pesticides in the application of safety measures.

5α-Reductase inhibitor is less effective in men with small prostate volume and low serum prostatic specific antigen level.

PubMed

Lin, Victor C; Liao, Chun-Hou; Wang, Chung-Cheng; Kuo, Hann-Chorng

2015-09-01

Large total prostate volumes (TPVs) or high serum prostate-specific antigen (PSA) levels indicate high-risk clinical progression of benign prostatic hyperplasia. This prospective study investigated the treatment outcome of combined 5α-reductase inhibitor and α-blocker in patients with and without large TPVs or high PSA levels. Men aged ≥ 45 years with International Prostate Symptom scores (IPSS) ≥ 8, TPV ≥ 20 mL, and maximum flow rate ≤ 15 mL/s received a combination therapy (dutasteride plus doxaben) for 2 years. Patients with baseline PSA ≥ 4 ng/mL underwent prostatic biopsy for excluding malignancy. The changes in the parameters from baseline to 24 months after combination therapy were compared in those with and without TPV ≥ 40 mL or PSA levels ≥ 1.5 ng/mL. A total of 285 patients (mean age 72 ± 9 years) completed the study. Combination therapy resulted in significant continuous improvement in IPSS, quality of life index, maximum flow rate, and postvoid residual (all p < 0.0001) regardless of baseline TPV or PSA levels. However, only patients with baseline TPV ≥ 40 mL had significant improvements in IPSS-storage subscore, voided volume, reduction in TPV, transitional zone index, and PSA levels. In addition, patients with baseline TPV < 40 mL and PSA < 1.5 ng/mL had neither a reduction in TPV nor a decrease in serum PSA level. A high TPV indicates more outlet resistance, whereas elevated serum PSA level reflects glandular proliferation. Thus, patients with TPV<40 mL and low PSA levels has less benefit from 5α-reductase inhibitor therapy. The therapeutic effect of combined treatment may arise mainly from the α-blocker in these patients. Copyright © 2013. Published by Elsevier B.V.

The Prognostic Significance of Metastasis to Lymph Nodes in Aortopulmonary Zone (Stations 5 and 6) in Completely Resected Left Upper Lobe Tumors.

PubMed

Citak, Necati; Sayar, Adnan; Metin, Muzaffer; Büyükkale, Songül; Kök, Abdulaziz; Solak, Okan; Yurt, Sibel; Gürses, Atilla

2015-10-01

We investigated the prognostic effect of lymph nodes metastasis in aortopulmonary (AP) zone in resected non-small cell lung cancer of the left upper lobe (LUL). Between 1998 and 2010, 181 patients with LUL carcinoma underwent complete resection and were retrospectively analyzed. The patients were divided into four groups according to N status: N0 (n = 68, 37.6%), N1 (n = 64, 35.3%), N2(5,6+) (only metastasized to stations 5 and/or 6, n = 36, 19.9%), and N2(7+) (only metastasized to stations 7, n = 13, 7.2%). N1 were divided according to single and multiple (N1(single) n = 49, N1(multiple) n = 15) or peripheral and hilar (N1(peripheral) n = 39, N1(hilar) n = 25). Overall 5-year survival rate was 55.1%. Five-year survivals were 76.1% for N0, 54.3% for N1, and 20.7% for N2. N1(peripheral) had a better survival than N1(hilar) (60.3 vs. 29.4%, p = 0.09). Five-year survival of N1(single) was 60.1%, whereas it was 36.6% for N1(multiple) (p = 0.02). Five-year survival rate was 24.6% for N2(5,6+). Skip metastasis for lymph nodes in AP zone (n = 13) was a factor of better prognosis as compared to nonskip metastasis (n = 23) (29.9 vs. 19.2%). There was no statistically significant difference between the N2(5,6+) and N1(hilar) (p = 0.772), although N1(peripheral) had a significantly better survival than N2(5,6+) (p = 0.02). AP zone metastases alone had a significantly worse survival than N1(single) (p = 0.008), whereas there was no statistically significant difference between the N1(multiple) and N2(5,6+) (p = 0.248). N2(7+) was not expected to survive 3 years after operation. They had a significantly worse prognosis than N2(5,6+) (p = 0.02). LUL tumors with metastasis in the AP zone lymph nodes, especially skip metastasis, were associated with a more favorable prognosis than other mediastinal lymph nodes. However, the therapy of choice for lung cancer with N2(5,6+) has not been clarified yet. Georg Thieme Verlag KG Stuttgart · New York.

Performance of PI-RADS version 1 versus version 2 regarding the relation with histopathological results.

PubMed

Auer, Thomas; Edlinger, Michael; Bektic, Jasmin; Nagele, Udo; Herrmann, Thomas; Schäfer, Georg; Aigner, Friedrich; Junker, Daniel

2017-05-01

Aim of this study was to compare the diagnostic performance of PI-RADS version 1 (v1) and version 2 (v2) in the detection of prostate cancer (PCa). Multiparametric MRIs (mpMRI) of 50 consecutive patients with biopsy proven PCa, which had originally been evaluated according to PIRADS v1, were now retrospectively re-evaluated, comparing PI-RADS v1 and v2. MpMRI data were evaluated in comparison with histopathological whole-mount step-section slides. MRI examinations included T2-weighted, diffusion-weighted, and dynamic contrast-enhanced MRI. Overall PI-RADS v1 showed a significantly larger discriminative ability of tumor detection: PI-RADS v1 AUC 0.96 (95 % CI 0.94-0.98) and v2 AUC 0.90 (95 % CI 0.86-0.94). For peripheral zone lesions, PI-RADS v1 showed a significantly larger ability of PCa discrimination: v1 AUC 0.97 (95 % CI 0.95-0.99) and v2 AUC 0.92 (95 % CI 0.88-0.96). For transition zone lesions, PI-RADS v1 showed more discrimination: v1 AUC 0.96 (95 % CI 0.92-1.00) and v2 0.90 (95 % CI 0.83-0.97), but the difference was not significant. PI-RADS v2 resulted in significantly more false negative results (3 % in v1, 14 % in v2) and a comparable number of true positive results (82 % in v1, 80 % in v2). PI-RADS v2 uses a simplified approach, but shows a lower diagnostic accuracy. This could lead to a higher rate of false negative results with the risk of missing tumors within low PI-RADS score levels. Therefore, its use cannot be recommended unconditionally, and further improvement should be considered.

Everolimus and Lenalidomide in Treating Patients With Relapsed or Refractory Non-Hodgkin or Hodgkin Lymphoma

ClinicalTrials.gov

2018-02-07

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

Specific features of direct formation of graphite-like microstructures in polycarbonate samples by single femtosecond laser pulses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ganin, D V; Lapshin, K E; Obidin, A Z

2015-11-30

We present the result of the experiments on producing graphite-like cylindrical microstructures by focusing single femtosecond laser pulses into the bulk of a transparent polymer (polycarbonate). The microstructures are embedded in a cladding with a modified refractive index, possessing waveguide properties. In the experiments with nontransparent screens and diaphragms, placed in the laser beam in front of the entrance pupil of the objective with a large numerical aperture, we have found that the paraxial rays are blocked by the peripheral ones, which reduces the length of the destruction region in the pre-focal zone. In the experiments with transparent screens andmore » diaphragms, introducing optical delays τ{sub d} between the paraxial and peripheral rays, the quantitative dependence of the destruction region length in the pre-focal zone on the value of τ{sub d} is determined. (interaction of laser radiation with matter. laser plasma)« less

A parathyroid-hormone-related-protein (PTH-rP)-specific cytotoxic T cell response induced by in vitro stimulation of tumour-infiltrating lymphocytes derived from prostate cancer metastases, with epitope peptide-loaded autologous dendritic cells and low-dose IL-2

PubMed Central

Correale, P; Micheli, L; Vecchio, M T Del; Sabatino, M; Petrioli, R; Pozzessere, D; Marsili, S; Giorgi, G; Lozzi, L; Neri, P; Francini, G

2001-01-01

Bone metastases are one of the most common events in patients with prostate carcinoma. PTH-rP, a protein produced by prostate carcinoma and other epithelial cancers, is a key agent for the development of bone metastases. A PTH-rP-derived peptide, designated PTR-4 was identified, which is capable to bind HLA-A2.1 molecules and to generate PTH-rP-specific cytotoxic T cell (CTL) lines from healthy HLA-A2.1+ individual peripheral-blood-mononuclear-cells (PBMC). In this model, we investigated the in vitro possibility of generating an efficient PTH-rP specific CTL response by cyclical stimulations with IL-2 and PTR-4 peptide-pulsed autologous dendritic cells (DC), of HLA-A2.1+ tumour infiltrating lymphocytes (TIL) derived from a patient with metastatic prostate carcinoma. A T cell line generated in this way (called TM-PTR-4) had a CD3+, CD5+, CD4−, CD8+, CD45Ro+, CD56− immunophenotype and a HLA-A2.1 restricted cytotoxic activity to PTR-4-peptide pulsed CIR-A2 (HLA-A2.1+) target cells, PTH-rP+/HLA-A2.1+ CIR-A2 transfected with PTH-rP gene, prostate carcinoma LNCaP cells, and autologous metastatic prostate cancer cells (M-CaP). These lymphocytes were not cytotoxic to HLA-A2.1+ targets not producing PTH-rP, such as peptide-unpulsed CIR-A2 and colon carcinoma SW-1463, cell lines. Our results provide evidence that PTR-4 peptide-pulsed autologous DC may break the tolerance of human TIL against the autologous tumour by inducing a PTH-rP-specific CTL immune reaction. In conclusion PTR-4 peptide-pulsed autologous DC may be a promising approach for vaccine-therapy and antigen-specific CTL adoptive immunotherapy of hormone-resistant prostrate cancer. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11742494

7 to 10 years' follow-up of 573 patients with elevated prostate-specific antigen (>4 ng/mL) or/and suspected rectal examination: biopsies protocol and follow-up guides.

PubMed

Kravchick, Sergey; Cytron, Shmuel; Stepnov, Eugeny; Ben-Dor, David; Kravchenko, Yakov; Peled, Ronit

2009-06-01

In this study, we tried to design a scheme for performing transrectal ultrasonographic (TRUS)-biopsies that would be accurate and include the optimal number of cores. We included in this study 600 consecutive patients with suspicious findings on a per-rectum examination and/or an elevated prostate-specific antigen (PSA) (>4 ng/mL) level. Patients were followed for 7 to 10 years. In all patients, we took from 8 to 16 biopsy samples, according to the prostate volume, from the lateral aspects. In the second session, the biopsy samples were taken medially; in the third session, we included the transitional zone, while in consecutive sessions, we increased the number of cores from all areas. Only 573 of the patients remained in follow-up. TRUS-biopsy detected prostate cancer (PCa) in 257 patients (44.85% overall detection rate). The detection rate in the first and second sessions was 32.98% and 14.94%, respectively, reaching 13.2% and 2.17%, in the third and fourth sessions, respectively. Prostate volumes were significantly smaller (52.9 +/- 22.4 cc vs 58.9 +/- 23.8 cc, P < 0.002) and the PSA/adenoma/prostate volumes ratio (ad-pro) ratio was higher (18.3 +/- 9 vs 13.96, P < 0/001) in the patients with PCa. Patients with PCa underwent fewer biopsy procedures and biopsy sessions than patients without a diagnosis of PCa (14.9 +/- 8.9 vs 20.4 +/- 12, P < 0.001;1.3 +/- 0.6 vs 1.7 +/- 0.9, P < 0.001). Biopsy samples obtained from the base were positive for cancer only in larger prostates with a mean volume of 54.3 +/- 15.3 cc. Numbers of biopsy procedures and PSA/ad-pro ratio were the strongest predictive factors for PCa detection (P < 0.001). In patients with a prostate volume >or=53 cc and PSA/ad-pro ratio >or=18, the optimal biopsy cores should be >or=15. Using this scheme, the discontinuation of biopsy procedures might be considered after three consecutive sessions.

Association of polymorphisms in CYP19A1 and CYP3A4 genes with lower urinary tract symptoms, prostate volume, uroflow and PSA in a population-based sample.

PubMed

Berges, Richard; Gsur, Andrea; Feik, Elisabeth; Höfner, Klaus; Senge, Theodor; Pientka, Ludger; Baierl, Andreas; Michel, Martin C; Ponholzer, Anton; Madersbacher, Stephan

2011-04-01

The known importance of testosterone for the development of benign prostatic hyperplasia (BPH) prompted us to test the hypothesis whether polymorphisms of two genes (CYP19A1 and CYP3A4) involved in testosterone metabolism are associated with clinical BPH-parameters. A random sample of the population-based Herne lower urinary tract symptoms cohort was analysed. All these men underwent a detailed urological work-up. Two polymorphisms in the CYP19A1 gene [rs700518 in exon 4 (A57G); rs10046 at the 3'UTR(C268T)] and one in the 3'UTR of CYP3A4 [rs2740574 (A392G)] were determined by TaqMan assay from genomic DNA of peripheral blood. These polymorphisms were correlated to clinical and laboratory BPH-parameters. A total of 392 men (65.4 ± 7.0 years; 52-79 years) were analysed. Mean International Prostate Symptom Score (IPSS; 7.5), Q (max) (15.4 ml/s), prostate volume (31 ml) and prostate specific antigen (PSA) (1.8 ng/ml) indicated a typical elderly population. Both polymorphisms in the CYP19A1 gene were not correlated to age, IPSS, Q (max), prostate volume and post-void residual volume. Serum PSA was higher in men carrying the heterozygous rs10046 genotype (2.0 ± 0.1 ng/ml) than in those with the CC-genotype (1.7 ± 0.2 ng/ml, P = 0.012). Men carrying one a mutated allele of the CYP3A4 gene had smaller prostates (27.0 ± 2.0 vs. 32 ± 0.8 ml, P = 0.02) and lower PSA levels (1.6 ± 0.3 vs. 1.9 ± 0.1 ng/ml). The inconsistent associations observed herein and for other gene polymorphisms warrant further studies. In general, the data regarding the association of gene polymorphism to BPH-parameters suggest that this disease is caused by multiple rather than a single genetic variant. A rigorous patient selection based on anatomo-pathological and hormonal profile may possible reduce the number of confounders for future studies thus enabling a more detailed assessment of the association between genetic factors and BPH-parameters.

AR-V7 in Peripheral Whole Blood of Patients with Castration-resistant Prostate Cancer: Association with Treatment-specific Outcome Under Abiraterone and Enzalutamide.

PubMed

Seitz, Anna Katharina; Thoene, Silvia; Bietenbeck, Andreas; Nawroth, Roman; Tauber, Robert; Thalgott, Mark; Schmid, Sebastian; Secci, Ramona; Retz, Margitta; Gschwend, Jürgen E; Ruland, Jürgen; Winter, Christof; Heck, Matthias M

2017-11-01

It has been demonstrated that androgen receptor splice variant 7 (AR-V7) expression in circulating tumor cells (CTCs) predicts poor treatment response in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone or enzalutamide. To develop a practical and robust liquid profiling approach for direct quantification of AR-V7 in peripheral whole blood without the need for CTC capture and to determine its potential for predicting treatment response in mCRPC patients. Whole blood samples from a prospective biorepository of 85 mCRPC patients before treatment initiation with abiraterone (n=56) or enzalutamide (n=29) were analyzed via droplet digital polymerase chain reaction. The association of AR-V7 status with prostate-specific antigen (PSA) response defined by PSA decline ≥50% and with PSA-progression-free survival (PSA-PFS), clinical PFS, and overall survival (OS) was assessed. High AR-V7 expression levels in whole blood were detectable in 18% (15/85) of patients. No patient with high AR-V7 expression achieved a PSA response, and AR-V7 status was an independent predictor of PSA response in multivariable logistic regression analysis (p=0.03). High AR-V7 expression was associated with shorter PSA-PFS (median 2.4 vs 3.7 mo; p<0.001), shorter clinical PFS (median 2.7 vs 5.5 mo; p<0.001), and shorter OS (median 4.0 vs. 13.9 mo; p<0.001). On multivariable Cox regression analysis, high AR-V7 expression remained an independent predictor of shorter PSA-PFS (hazard ratio [HR] 7.0, 95% confidence interval [CI] 2.3-20.7; p<0.001), shorter clinical PFS (HR 2.3, 95% CI 1.1-4.9; p=0.02), and shorter OS (HR 3.0, 95% CI 1.4-6.3; p=0.005). Testing of AR-V7 mRNA levels in whole blood is a simple and promising approach to predict poor treatment outcome in mCRPC patients receiving abiraterone or enzalutamide. We established a method for determining AR-V7 status in whole blood. This test predicted treatment resistance in patients with metastatic castration-resistant prostate cancer undergoing treatment with abiraterone or enzalutamide. Prospective validation is needed before application to clinical practice. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Deformable segmentation of 3D MR prostate images via distributed discriminative dictionary and ensemble learning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo, Yanrong; Shao, Yeqin; Gao, Yaozong

Purpose: Automatic prostate segmentation from MR images is an important task in various clinical applications such as prostate cancer staging and MR-guided radiotherapy planning. However, the large appearance and shape variations of the prostate in MR images make the segmentation problem difficult to solve. Traditional Active Shape/Appearance Model (ASM/AAM) has limited accuracy on this problem, since its basic assumption, i.e., both shape and appearance of the targeted organ follow Gaussian distributions, is invalid in prostate MR images. To this end, the authors propose a sparse dictionary learning method to model the image appearance in a nonparametric fashion and further integratemore » the appearance model into a deformable segmentation framework for prostate MR segmentation. Methods: To drive the deformable model for prostate segmentation, the authors propose nonparametric appearance and shape models. The nonparametric appearance model is based on a novel dictionary learning method, namely distributed discriminative dictionary (DDD) learning, which is able to capture fine distinctions in image appearance. To increase the differential power of traditional dictionary-based classification methods, the authors' DDD learning approach takes three strategies. First, two dictionaries for prostate and nonprostate tissues are built, respectively, using the discriminative features obtained from minimum redundancy maximum relevance feature selection. Second, linear discriminant analysis is employed as a linear classifier to boost the optimal separation between prostate and nonprostate tissues, based on the representation residuals from sparse representation. Third, to enhance the robustness of the authors' classification method, multiple local dictionaries are learned for local regions along the prostate boundary (each with small appearance variations), instead of learning one global classifier for the entire prostate. These discriminative dictionaries are located on different patches of the prostate surface and trained to adaptively capture the appearance in different prostate zones, thus achieving better local tissue differentiation. For each local region, multiple classifiers are trained based on the randomly selected samples and finally assembled by a specific fusion method. In addition to this nonparametric appearance model, a prostate shape model is learned from the shape statistics using a novel approach, sparse shape composition, which can model nonGaussian distributions of shape variation and regularize the 3D mesh deformation by constraining it within the observed shape subspace. Results: The proposed method has been evaluated on two datasets consisting of T2-weighted MR prostate images. For the first (internal) dataset, the classification effectiveness of the authors' improved dictionary learning has been validated by comparing it with three other variants of traditional dictionary learning methods. The experimental results show that the authors' method yields a Dice Ratio of 89.1% compared to the manual segmentation, which is more accurate than the three state-of-the-art MR prostate segmentation methods under comparison. For the second dataset, the MICCAI 2012 challenge dataset, the authors' proposed method yields a Dice Ratio of 87.4%, which also achieves better segmentation accuracy than other methods under comparison. Conclusions: A new magnetic resonance image prostate segmentation method is proposed based on the combination of deformable model and dictionary learning methods, which achieves more accurate segmentation performance on prostate T2 MR images.« less

Biomarkers of Selenium Action in Prostate Cancer

DTIC Science & Technology

2005-01-01

secretory by conventional methods according to published literature. In addition, we have determined the similarities and differences in global gene...transition zone tissue of a 42-year-old man ac- arrays in the resulting data tables were ordered by their cording to previously described methods [4]. The pre...hundred fifteen genes identified by ELISA method . Replicating the conditions used for the SAM analysis showed significant differential expres- microarray

Moving toward focal therapy in prostate cancer: dual-isotope permanent seed implants as a possible solution.

PubMed

Todor, Dorin A; Barani, Igor J; Lin, Peck-Sun; Anscher, Mitchell S

2011-09-01

To compare the ability of single- and dual-isotope prostate seed implants to escalate biologically effective dose (BED) to foci of disease while reducing prescription dose to the prostate. Nine plans, using 125I, 103Pd, and 131Cs alone and in combination were created retrospectively for 2 patients. Ultrasound and MRI/MRS datasets were used for treatment planning. Voxel-by-voxel BED was calculated for single- and dual-isotope plans. Equivalent uniform BED (EUBED) was used to compare plans. The MRS-positive planning target volumes (PTVi) were delineated along with PTV (prostate+5 mm), rectum, and urethra. Single-isotope implants, prescribed to conventional doses, were generated to achieve good PTV coverage. The PTVi were prospectively used to generate implants using mixtures of isotopes. For mixed-radioisotope implants, we also explored the impact on EUBED of lowering prescription doses by 15%. The EUBED of PTVi in the setting of primary 125I implant increased 20-66% when 103Pd and 131Cs were used compared with 125I boost. Decreasing prescription dose by 15% in mixed-isotope implants results in a potential 10% reduction in urethral EUBED with preservation of PTV coverage while still boosting PTVi (up to 80%). When radiobiologic parameters corresponding to more-aggressive disease are assigned to foci, faster-decaying isotopes used in mixed implants have the potential to preserve the equivalent biological effect of mono-isotope implants considering less-aggressive disease distributed in the entire prostate. This is a hypothesis-generating study proposing a treatment paradigm that could be the middle ground between whole-gland irradiation and focal-only treatment. The use of two isotopes concurrent with decreasing the minimal peripheral dose is shown to increase EUBED of selected subvolumes while preserving the therapeutic effect at the level of the gland. Copyright © 2011 Elsevier Inc. All rights reserved.

Moving Toward Focal Therapy in Prostate Cancer: Dual-Isotope Permanent Seed Implants as a Possible Solution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Todor, Dorin A., E-mail: dtodor@mcvh-vcu.edu; Barani, Igor J.; Lin, Peck-Sun

2011-09-01

Purpose: To compare the ability of single- and dual-isotope prostate seed implants to escalate biologically effective dose (BED) to foci of disease while reducing prescription dose to the prostate. Methods and Materials: Nine plans, using {sup 125}I, {sup 103}Pd, and {sup 131}Cs alone and in combination were created retrospectively for 2 patients. Ultrasound and MRI/MRS datasets were used for treatment planning. Voxel-by-voxel BED was calculated for single- and dual-isotope plans. Equivalent uniform BED (EUBED) was used to compare plans. The MRS-positive planning target volumes (PTV{sub i}) were delineated along with PTV (prostate + 5 mm), rectum, and urethra. Single-isotope implants,more » prescribed to conventional doses, were generated to achieve good PTV coverage. The PTV{sub i} were prospectively used to generate implants using mixtures of isotopes. For mixed-radioisotope implants, we also explored the impact on EUBED of lowering prescription doses by 15%. Results: The EUBED of PTV{sub i} in the setting of primary {sup 125}I implant increased 20-66% when {sup 103}Pd and {sup 131}Cs were used compared with {sup 125}I boost. Decreasing prescription dose by 15% in mixed-isotope implants results in a potential 10% reduction in urethral EUBED with preservation of PTV coverage while still boosting PTV{sub i} (up to 80%). When radiobiologic parameters corresponding to more-aggressive disease are assigned to foci, faster-decaying isotopes used in mixed implants have the potential to preserve the equivalent biological effect of mono-isotope implants considering less-aggressive disease distributed in the entire prostate. Conclusions: This is a hypothesis-generating study proposing a treatment paradigm that could be the middle ground between whole-gland irradiation and focal-only treatment. The use of two isotopes concurrent with decreasing the minimal peripheral dose is shown to increase EUBED of selected subvolumes while preserving the therapeutic effect at the level of the gland.« less

Application of a quick-freezing and deep-etching method to pathological diagnosis: a case of elastofibroma.

PubMed

Hemmi, Akihiro; Tabata, Masahiko; Homma, Taku; Ohno, Nobuhiko; Terada, Nobuo; Fujii, Yasuhisa; Ohno, Shinichi; Nemoto, Norimichi

2006-04-01

A case of elastofibroma in a middle-aged Japanese woman was examined by the quick-freezing and deep-etching (QF-DE) method, as well as by immunohistochemistry and conventional electron microscopy. The slowly growing tumor developed at the right scapular region and was composed of fibrous connective tissue with unique elastic materials called elastofibroma fibers. A normal elastic fiber consists of a central core and peripheral zone, in which the latter has small aggregates of 10 nm microfibrils. By the QF-DE method, globular structures consisting of numerous fibrils (5-20 nm in width) were observed between the collagen bundles. We could confirm that they were microfibril-rich peripheral zones of elastofibroma fibers by comparing the replica membrane and conventional electron microscopy. One of the characteristics of elastofibroma fibers is that they are assumed to contain numerous microfibrils. Immunohistochemically, spindle tumor cells showed positive immunoreaction for vimentin, whereas alpha-smooth muscle actin, desmin, S-100 protein and CD34 showed negative immunoreaction. By conventional electron microscopy, the tumor cell had thin cytoplasmic processes, pinocytotic vesicles and prominent rough endoplasmic reticulum. Abundant intracytoplasmic filaments were observed in some tumor cells. Thick lamina-like structures along with their inner nuclear membrane were often observed in the tumor cell nuclei. The whole image of the tumor cell was considered to be a periosteal-derived cell, which would produce numerous microfibrils in the peripheral zone of elastofibroma fibers. This study indicated that the QF-DE method could be applied to the pathological diagnosis and analysis of pathomechanism, even for surgical specimens obtained from a patient.

Combined serum and EPS-urine proteomic analysis using iTRAQ technology for discovery of potential prostate cancer biomarkers.

PubMed

Zhang, Mo; Chen, Lizhu; Yuan, Zhengwei; Yang, Zeyu; Li, Yue; Shan, Liping; Yin, Bo; Fei, Xiang; Miao, Jianing; Song, Yongsheng

2016-11-01

Prostate cancer (PCa) is one of the most common malignant tumors and a major cause of cancer-related death for men worldwide. The aim of our study was to identify potential non-invasive serum and expressed prostatic secretion (EPS)-urine biomarkers for accurate diagnosis of PCa. Here, we performed a combined isobaric tags for relative and absolute quantification (iTRAQ) proteomic analysis to compare protein profiles using pooled serum and EPS-urine samples from 4 groups of patients: benign prostate hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN), localized PCa and metastatic PCa. The differentially expressed proteins were rigorously selected and further validated in a large and independent cohort using classical ELISA and Western blot assays. Finally, we established a multiplex biomarker panel consisting of 3 proteins (serum PF4V1, PSA, and urinary CRISP3) with an excellent diagnostic capacity to differentiate PCa from BPH [area under the receiver operating characteristic curve (AUC) of 0.941], which showed an evidently greater discriminatory ability than PSA alone (AUC, 0.757) (P<0.001). Importantly, even when PSA level was in the gray zone (4-10 ng/mL), a combination of PF4V1 and CRISP3 could achieve a relatively high diagnostic efficacy (AUC, 0.895). Furthermore, their combination also had the potential to distinguish PCa from HGPIN (AUC, 0.934). Our results demonstrated that the combined application of serum and EPS-urine biomarkers can improve the diagnosis of PCa and provide a new prospect for non-invasive PCa detection.

Transurethral ultrasound applicators with dynamic multi-sector control for prostate thermal therapy: In vivo evaluation under MR guidance

PubMed Central

Kinsey, Adam M.; Diederich, Chris J.; Rieke, Viola; Nau, William H.; Pauly, Kim Butts; Bouley, Donna; Sommer, Graham

2008-01-01

The purpose of this study was to explore the feasibility and performance of a multi-sectored tubular array transurethral ultrasound applicator for prostate thermal therapy, with potential to provide dynamic angular and length control of heating under MR guidance without mechanical movement of the applicator. Test configurations were fabricated, incorporating a linear array of two multi-sectored tubular transducers (7.8–8.4 MHz, 3 mm OD, 6 mm length), with three 120° independent active sectors per tube. A flexible delivery catheter facilitated water cooling (100 ml min−1) within an expandable urethral balloon (35 mm long×10 mm diameter). An integrated positioning hub allows for rotating and translating the transducer assembly within the urethral balloon for final targeting prior to therapy delivery. Rotational beam plots indicate ∼90°−100° acoustic output patterns from each 120° transducer sector, negligible coupling between sectors, and acoustic efficiencies between 41% and 53%. Experiments were performed within in vivo canine prostate (n=3), with real-time MR temperature monitoring in either the axial or coronal planes to facilitate control of the heating profiles and provide thermal dosimetry for performance assessment. Gross inspection of serial sections of treated prostate, exposed to TTC (triphenyl tetrazolium chloride) tissue viability stain, allowed for direct assessment of the extent of thermal coagulation. These devices created large contiguous thermal lesions (defined by 52 °C maximum temperature, t43=240 min thermal dose contours, and TTC tissue sections) that extended radially from the applicator toward the border of the prostate (∼15 mm) during a short power application (∼8−16 W per active sector, 8–15 min), with ∼200° or 360° sector coagulation demonstrated depending upon the activation scheme. Analysis of transient temperature profiles indicated progression of lethal temperature and thermal dose contours initially centered on each sector that coalesced within ∼5 min to produce uniform and contiguous zones of thermal destruction between sectors, with smooth outer boundaries and continued radial propagation in time. The dimension of the coagulation zone along the applicator was well-defined by positioning and active array length. Although not as precise as rotating planar and curvilinear devices currently under development for MR-guided procedures, advantages of these multi-sectored transurethral applicators include a flexible delivery catheter and that mechanical manipulation of the device using rotational motors is not required during therapy. This multi-sectored tubular array transurethral ultrasound technology has demonstrated potential for relatively fast and reasonably conformal targeting of prostate volumes suitable for the minimally invasive treatment of BPH and cancer under MR guidance, with further development warranted. PMID:18561684

Validation of the Dominant Sequence Paradigm and Role of Dynamic Contrast-enhanced Imaging in PI-RADS Version 2.

PubMed

Greer, Matthew D; Shih, Joanna H; Lay, Nathan; Barrett, Tristan; Kayat Bittencourt, Leonardo; Borofsky, Samuel; Kabakus, Ismail M; Law, Yan Mee; Marko, Jamie; Shebel, Haytham; Mertan, Francesca V; Merino, Maria J; Wood, Bradford J; Pinto, Peter A; Summers, Ronald M; Choyke, Peter L; Turkbey, Baris

2017-12-01

Purpose To validate the dominant pulse sequence paradigm and limited role of dynamic contrast material-enhanced magnetic resonance (MR) imaging in the Prostate Imaging Reporting and Data System (PI-RADS) version 2 for prostate multiparametric MR imaging by using data from a multireader study. Materials and Methods This HIPAA-compliant retrospective interpretation of prospectively acquired data was approved by the local ethics committee. Patients were treatment-naïve with endorectal coil 3-T multiparametric MR imaging. A total of 163 patients were evaluated, 110 with prostatectomy after multiparametric MR imaging and 53 with negative multiparametric MR imaging and systematic biopsy findings. Nine radiologists participated in this study and interpreted images in 58 patients, on average (range, 56-60 patients). Lesions were detected with PI-RADS version 2 and were compared with whole-mount prostatectomy findings. Probability of cancer detection for overall, T2-weighted, and diffusion-weighted (DW) imaging PI-RADS scores was calculated in the peripheral zone (PZ) and transition zone (TZ) by using generalized estimating equations. To determine dominant pulse sequence and benefit of dynamic contrast-enhanced (DCE) imaging, odds ratios (ORs) were calculated as the ratio of odds of cancer of two consecutive scores by logistic regression. Results A total of 654 lesions (420 in the PZ) were detected. The probability of cancer detection for PI-RADS category 2, 3, 4, and 5 lesions was 15.7%, 33.1%, 70.5%, and 90.7%, respectively. DW imaging outperformed T2-weighted imaging in the PZ (OR, 3.49 vs 2.45; P = .008). T2-weighted imaging performed better but did not clearly outperform DW imaging in the TZ (OR, 4.79 vs 3.77; P = .494). Lesions classified as PI-RADS category 3 at DW MR imaging and as positive at DCE imaging in the PZ showed a higher probability of cancer detection than did DCE-negative PI-RADS category 3 lesions (67.8% vs 40.0%, P = .02). The addition of DCE imaging to DW imaging in the PZ was beneficial (OR, 2.0; P = .027), with an increase in the probability of cancer detection of 15.7%, 16.0%, and 9.2% for PI-RADS category 2, 3, and 4 lesions, respectively. Conclusion DW imaging outperforms T2-weighted imaging in the PZ; T2-weighted imaging did not show a significant difference when compared with DW imaging in the TZ by PI-RADS version 2 criteria. The addition of DCE imaging to DW imaging scores in the PZ yields meaningful improvements in probability of cancer detection. © RSNA, 2017 An earlier incorrect version of this article appeared online. This article was corrected on July 27, 2017. Online supplemental material is available for this article.

[Prostate cancer microenvironment: Its structure, functions and therapeutic applications].

PubMed

Lorion, R; Bladou, F; Spatz, A; van Kempen, L; Irani, J

2016-06-01

In the field of prostate cancer there is a growing tendency for more and more studies to emphasise the predominant role of the zone situated between the tumour and the host: the tumour microenvironment. The aim of this article is to describe the structure and the functions of the prostate cancer microenvironment as well as the principal treatments that are being applied to it. PubMed and ScienceDirect databases have been interrogated using the association of keywords "tumour microenvironment" and "neoplasm therapy" along with "microenvironnement tumoral" and "traitements". Of the 593 articles initially found, 50 were finally included. The tumour microenvironment principally includes host elements that are diverted from their primary functions and encourage the development of the tumour. In it we find immunity cells, support tissue as well as vascular and lymphatic neovascularization. Highlighting the major role played by this microenvironment has led to the development of specific treatments, notably antiangiogenic therapy and immunotherapy. The tumour microenvironment, the tumour and the host influence themselves mutually and create a variable situation over time. Improvement of the knowledge of the prostate cancer microenvironment gradually enables us to pass from an approach centred on the tumour to a broader approach to the whole tumoral ecosystem. This enabled the emergence of new treatments whose place in the therapeutic arsenal still need to be found. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Laser Biostimulation Of Wound Healing In Arteriopatic Patients

NASA Astrophysics Data System (ADS)

Tallarida, G.; Baldoni, F.; Raimondi, G.; Massaro, M.; Peruzzi, G.; Bertolotti, M.; Ferrari, A.; Scudieri, F.

1981-05-01

Low-power laser irradiation has been employed in the attempt to accelerate the wound-healing of ischemic cutaneous ulcerations with threatening or manifest gangrene due to arteriosclerosis obliterans of the lower limbs. Irradiation was performed by using a low-power He-Ne gas laser of 6328 Å wavelength and was concentrated at the peripheral zone of the lesions. The preliminary results of the study indicate that laser stimulation might be new approach in the conservative menagement of the ischemic ulcers in patients with severe peripheral obstructive arteriopaties not suited for arterial reconstruction.

Liquid biopsy: ready to guide therapy in advanced prostate cancer?

PubMed

Hegemann, Miriam; Stenzl, Arnulf; Bedke, Jens; Chi, Kim N; Black, Peter C; Todenhöfer, Tilman

2016-12-01

The identification of molecular markers associated with response to specific therapy is a key step for the implementation of personalised treatment strategies in patients with metastatic prostate cancer. Only in a low proportion of patients biopsies of metastatic tissue are performed. Circulating tumour cells (CTC), cell-free DNA (cfDNA) and RNA offer the potential for non-invasive characterisation of disease and molecular stratification of patients. Furthermore, a 'liquid biopsy' approach permits longitudinal assessments, allowing sequential monitoring of response and progression and the potential to alter therapy based on observed molecular changes. In prostate cancer, CTC enumeration using the CellSearch© platform correlates with survival. Recent studies on the presence of androgen receptor (AR) variants in CTC have shown that such molecular characterisation of CTC provides a potential for identifying patients with resistance to agents that inhibit the androgen signalling axis, such as abiraterone and enzalutamide. New developments in CTC isolation, as well as in vitro and in vivo analysis of CTC will further promote the use of CTC as a tool for retrieving molecular information from advanced tumours in order to identify mechanisms of therapy resistance. In addition to CTC, nucleic acids such as RNA and cfDNA released by tumour cells into the peripheral blood contain important information on transcriptomic and genomic alterations in the tumours. Initial studies have shown that genomic alterations of the AR and other genes detected in CTC or cfDNA of patients with castration-resistant prostate cancer correlate with treatment outcomes to enzalutamide and abiraterone. Due to recent developments in high-throughput analysis techniques, it is likely that CTC, cfDNA and RNA will be an important component of personalised treatment strategies in the future. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

Resistance Element Welding of Magnesium Alloy/austenitic Stainless Steel

NASA Astrophysics Data System (ADS)

Manladan, S. M.; Yusof, F.; Ramesh, S.; Zhang, Y.; Luo, Z.; Ling, Z.

2017-09-01

Multi-material design is increasingly applied in the automotive and aerospace industries to reduce weight, improve crash-worthiness, and reduce environmental pollution. In the present study, a novel variant of resistance spot welding technique, known as resistance element welding was used to join AZ31 Mg alloy to 316 L austenitic stainless steel. The microstructure and mechanical properties of the joints were evaluated. It was found that the nugget consisted of two zones, including a peripheral fusion zone on the stainless steel side and the main fusion zone. The tensile shear properties of the joints are superior to those obtained by traditional resistance spot welding.

Theranostic Perspectives in Prostate Cancer with the Gastrin-Releasing Peptide Receptor Antagonist NeoBOMB1: Preclinical and First Clinical Results.

PubMed

Nock, Berthold A; Kaloudi, Aikaterini; Lymperis, Emmanouil; Giarika, Athina; Kulkarni, Harshad R; Klette, Ingo; Singh, Aviral; Krenning, Eric P; de Jong, Marion; Maina, Theodosia; Baum, Richard P

2017-01-01

We recently introduced the potent gastrin-releasing peptide receptor (GRPR) antagonist 68 Ga-SB3 ( 68 Ga-DOTA-p-aminomethylaniline-diglycolic acid-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-NHEt), showing excellent tumor localizing efficacy in animal models and in patients. By replacement of the C-terminal Leu 13 -Met 14 -NH 2 dipeptide of SB3 by Sta 13 -Leu 14 -NH 2 , the novel GRPR antagonist NeoBOMB1 was generated and labeled with different radiometals for theranostic use. We herein report on the biologic profile of resulting 67/68 Ga-, 111 In-, and 177 Lu-NeoBOMB1 radioligands in GRPR-expressing cells and mouse models. The first evidence of prostate cancer lesion visualization in men using 68 Ga-NeoBOMB1 and PET/CT is also presented. NeoBOMB1 was radiolabeled with 67/68 Ga, 111 In, and 177 Lu according to published protocols. The respective metalated species nat Ga-, nat In-, and nat Lu-NeoBOMB1 were also synthesized and used in competition binding experiments against [ 125 I-Tyr 4 ]BBN in GRPR-positive PC-3 cell membranes. Internalization of 67 Ga-, 111 In-, and 177 Lu-NeoBOMB1 radioligands was studied in PC-3 cells at 37°C, and their metabolic stability in peripheral mouse blood was determined by high-performance liquid chromatography analysis of blood samples. Biodistribution was performed by injecting a 67 Ga-, 111 In-, or 177 Lu-NeoBOMB1 bolus (74, 74, or 370 kBq, respectively, 100 μL, 10 pmol total peptide ± 40 nmol Tyr 4 -BBN: for in vivo GRPR blockade) in severe combined immunodeficiency mice bearing PC-3 xenografts. PET/CT images with 68 Ga-NeoBOMB1 were acquired in prostate cancer patients. NeoBOMB1 and nat Ga-, nat In-, and nat Lu-NeoBOMB1 bound to GRPR with high affinity (half maximal inhibitory concentration, 1-2 nM). 67 Ga-, 111 In-, and 177 Lu-NeoBOMB1 specifically and strongly bound on the cell membrane of PC-3 cells displaying low internalization, as expected for receptor antagonists. They showed excellent metabolic stability in peripheral mouse blood (>95% intact at 5 min after injection). After injection in mice, all 3 ( 67 Ga-, 111 In-, and 177 Lu-NeoBOMB1) showed comparably high and GRPR-specific uptake in the PC-3 xenografts (e.g., 30.6 ± 3.9, 28.6 ± 6.0, and >35 percentage injected dose per gram at 4 h after injection, respectively), clearing from background predominantly via the kidneys. During a translational study in prostate cancer patients, 68 Ga-NeoBOMB1 rapidly localized in pathologic lesions, achieving high-contrast imaging. The GRPR antagonist radioligands 67 Ga-, 111 In-, and 177 Lu-NeoBOMB1, independent of the radiometal applied, have shown comparable behavior in prostate cancer models, in favor of future theranostic use in GRPR-positive cancer patients. Such translational prospects were further supported by the successful visualization of prostate cancer lesions in men using 68 Ga-NeoBOMB1 and PET/CT. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Stress-strain state of a rock mass in the vicinity of the meeting point of intersecting and branching workings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Konstantinova, S.A.; Spirkov, V.L.; Sokolov, V.Yu.

1987-07-01

The results of solving the problems of the stress-strain state of peripheral rock in the vicinity of the meeting point of two workings of intersection and branching type are presented. Values of the load coefficients are obtained, as well as values of the dimensions of the zone of influence of the meeting point and the conventional zone of inelastic deformations. Intersection and branching of workings at various angles are considered.

Identification, characterization and potent antitumor activity of ECO-4601, a novel peripheral benzodiazepine receptor ligand.

PubMed

Gourdeau, Henriette; McAlpine, James B; Ranger, Maxime; Simard, Bryan; Berger, Francois; Beaudry, Francis; Farnet, Chris M; Falardeau, Pierre

2008-05-01

ECO-4601 is a structurally novel farnesylated dibenzodiazepinone discovered through DECIPHER technology, Thallion's proprietary drug discovery platform. The compound was shown to have a broad cytotoxic activity in the low micromolar range when tested in the NCI 60 cell line panel. In the work presented here, ECO-4601 was further evaluated against brain tumor cell lines. Preliminary mechanistic studies as well as in vivo antitumor evaluation were performed. Since ECO-4601 has a benzodiazepinone moiety, we first investigated if it binds the central and/or peripheral benzodiazepine receptors. ECO-4601 was tested in radioligand binding assays on benzodiazepine receptors obtained from rat hearts. The ability of ECO-4601 to inhibit the growth of CNS cancers was evaluated on a panel of mouse, rat and human glioma cell lines using a standard MTT assay. Antitumor efficacy studies were performed on gliomas (rat and human), human breast and human prostate mouse tumor xenografts. Antitumor activity and pharmacokinetic analysis of ECO-4601 was evaluated following intravenous (i.v.), subcutaneous (s.c.), and intraperitoneal (i.p.) bolus administrations. ECO-4601 was shown to bind the peripheral but not the central benzodiazepine receptor and inhibited the growth of CNS tumor cell lines. Bolus s.c. and i.p. administration gave rise to low but sustained drug exposure, and resulted in moderate to significant antitumor activity at doses that were well tolerated. In a rat glioma (C6) xenograft model, ECO-4601 produced up to 70% tumor growth inhibition (TGI) while in a human glioma (U-87MG) xenograft, TGI was 34%. Antitumor activity was highly significant in both human hormone-independent breast (MDA-MB-231) and prostate (PC-3) xenografts, resulting in TGI of 72 and 100%, respectively. On the other hand, i.v. dosing was followed by rapid elimination of the drug and was ineffective. Antitumor efficacy of ECO-4601 appears to be associated with the exposure parameter AUC and/or sustained drug levels rather than C (max). These in vivo data constitute a rationale for clinical studies testing prolonged continuous administration of ECO-4601.

On the mechanism of the ring zone effect obtained with the mixed haemadsorption technique

PubMed Central

Jonsson, J.; Fagraeus, Astrid

1969-01-01

A ring zone effect noted with the radial diffusion disc test modification of the mixed haemadsorption technique has been studied using human anti-thyroid sera reacting with thyroid monolayer cultures. Results are presented which suggest that the `empty' centre of the ring zones is due to an excess of attached antibody. Sera giving the ring zone effect contain a larger number of antibody specificities than those producing filled zones. The appearance of ring zones is favoured by a low density of antigens on the culture. These findings and a number of synergistic effects produced by mixing ring and filled zone reactions are compatible with the hypothesis that the ring zone is produced when several antibodies of different specificities react with restricted antigenic areas carrying densely located clusters of antigenic determinants representing the different specificities contained in the ring zone sera. The crowding of antibodies on the clusters in the centre of the ring zones creates a steric hindrance for the indicator cells so that they are not firmly attached in this area. The antibody zone is therefore indicated as a peripheral haemadsorption ring. ImagesFIG. 1FIG. 2FIG. 4FIG. 6FIG. 7FIG. 9 PMID:5307718

Study of ADCT-301 in Patients With Relapsed or Refractory Hodgkin and Non-Hodgkin Lymphoma

ClinicalTrials.gov

2018-05-07

Hodgkin Lymphoma; Non-Hodgkin Lymphoma; Burkitt's Lymphoma; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, Marginal Zone; Waldenstrom's Macroglobulinaemia; Lymphoma,T-cell Cutaneous; Lymphoma, T-Cell, Peripheral

Genetically Modified T-cell Infusion Following Peripheral Blood Stem Cell Transplant in Treating Patients With Recurrent or High-Risk Non-Hodgkin Lymphoma

ClinicalTrials.gov

2018-01-26

Adult Grade III Lymphomatoid Granulomatosis; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

The safety and efficacy of irreversible electroporation for the ablation of prostate cancer: a multicentre prospective human in vivo pilot study protocol.

PubMed

van den Bos, W; de Bruin, D M; Muller, B G; Varkarakis, I M; Karagiannis, A A; Zondervan, P J; Laguna Pes, M P; Veelo, D P; Savci Heijink, C D; Engelbrecht, M R W; Wijkstra, H; de Reijke, T M; de la Rosette, J J M C H

2014-10-29

Current surgical and ablative treatment options for prostate cancer have a relatively high incidence of side effects, which may diminish the quality of life. The side effects are a consequence of procedure-related damage of the blood vessels, bowel, urethra or neurovascular bundle. Ablation with irreversible electroporation (IRE) has shown to be effective in destroying tumour cells and harbours the advantage of sparing surrounding tissue and vital structures. The aim of the study is to evaluate the safety and efficacy and to acquire data on patient experience of minimally invasive, transperineally image-guided IRE for the focal ablation of prostate cancer. In this multicentre pilot study, 16 patients with prostate cancer who are scheduled for a radical prostatectomy will undergo an IRE procedure, approximately 30 days prior to the radical prostatectomy. Data as adverse events, side effects, functional outcomes, pain and quality of life will be collected and patients will be controlled at 1 and 2 weeks post-IRE, 1 day preprostatectomy and postprostatectomy. Prior to the IRE procedure and the radical prostatectomy, all patients will undergo a multiparametric MRI and contrast-enhanced ultrasound of the prostate. The efficacy of ablation will be determined by whole mount histopathological examination, which will be correlated with the imaging of the ablation zone. The protocol is approved by the ethics committee at the coordinating centre (Academic Medical Center (AMC) Amsterdam) and by the local Institutional Review Board at the participating centres. Data will be presented at international conferences and published in peer-reviewed journals. This pilot study will determine the safety and efficacy of IRE in the prostate. It will show the radiological and histopathological effects of IRE ablations and it will provide data to construct an accurate treatment planning tool for IRE in prostate tissue. Clinicaltrials.gov database: NCT01790451. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Dose-Escalated Stereotactic Body Radiation Therapy for Patients With Intermediate- and High-Risk Prostate Cancer: Initial Dosimetry Analysis and Patient Outcomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kotecha, Rupesh; Djemil, Toufik; Tendulkar, Rahul D.

Purpose: To report the short-term clinical outcomes and acute and late treatment-related genitourinary (GU) and gastrointestinal (GI) toxicities in patients with intermediate- and high-risk prostate cancer treated with dose-escalated stereotactic body radiation therapy (SBRT). Methods and Materials: Between 2011 and 2014, 24 patients with prostate cancer were treated with SBRT to the prostate gland and proximal seminal vesicles. A high-dose avoidance zone (HDAZ) was created by a 3-mm expansion around the rectum, urethra, and bladder. Patients were treated to a minimum dose of 36.25 Gy in 5 fractions, with a simultaneous dose escalation to a dose of 50 Gy to the targetmore » volume away from the HDAZ. Acute and late GU and GI toxicity outcomes were measured according to the National Cancer Institute Common Terminology Criteria for Adverse Events toxicity scale, version 4. Results: The median follow-up was 25 months (range, 18-45 months). Nine patients (38%) experienced an acute grade 2 GU toxicity, which was medically managed, and no patients experienced an acute grade 2 GI toxicity. Two patients (8%) experienced late grade 2 GU toxicity, and 2 patients (8%) experienced late grade 2 GI toxicity. No acute or late grade ≥3 GU or GI toxicities were observed. The 24-month prostate-specific antigen relapse-free survival outcome for all patients was 95.8% (95% confidence interval 75.6%-99.4%), and both biochemical failures occurred in patients with high-risk disease. All patients are currently alive at the time of this analysis and continue to be followed. Conclusions: A heterogeneous prostate SBRT planning technique with differential treatment volumes (low dose: 36.25 Gy; and high dose: 50 Gy) with an HDAZ provides a safe method of dose escalation. Favorable rates of biochemical control and acceptably low rates of acute and long-term GU and GI toxicity can be achieved in patients with intermediate- and high-risk prostate cancer treated with SBRT.« less

Phase 1 and 2 studies demonstrate the safety and efficacy of intraprostatic injection of PRX302 for the targeted treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia.

PubMed

Denmeade, Samuel R; Egerdie, Blair; Steinhoff, Gary; Merchant, Rosemina; Abi-Habib, Ralph; Pommerville, Peter

2011-05-01

PRX302 is a prostate specific antigen (PSA)-activated pore-forming protein toxin under development as a targeted approach for improving lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) without affecting sexual function. To evaluate the safety and efficacy of PRX302 in men with moderate to severe BPH. Eligible subjects were refractory, intolerant, or unwilling to undergo medical therapies for BPH and had International Prostate Symptom Score (IPSS) ≥12, a quality of life (QoL) score ≥3, and prostate volumes between 30 and 80 g. Fifteen patients were enrolled in phase 1 studies, and 18 patients entered phase 2 studies. Subjects received intraprostatic injection of PRX302 into the right and left transition zone via a transperineal approach in an office-based setting. Phase 1 subjects received increasing concentrations of PRX302 at a fixed volume; phase 2 subjects received increasing volumes per deposit at a fixed concentration. IPSS, QoL, prostate volume, maximum flow rate (Q(max)), International Index of Erectile Function, serum PSA levels, pharmacokinetics, and adverse events were recorded at 30, 60, 90, 180, 270, and 360 d after treatment with PRX302. Sixty percent of men in the phase 1 study and 64% of men in the phase 2 study treated with PRX302 had ≥30% improvement compared to baseline in IPSS out to day 360. Patients also experienced improvement in QoL and reduction in prostate volume out to day 360. Patients receiving ≥1 ml of PRX302 per deposit had the best response overall. PRX302 had no deleterious effect on erectile function. Adverse events were mild to moderate and transient in nature. The major study limitation was the small sample size. The promising safety profile and evidence of efficacy in the majority of treated subjects in these phase 1 and 2 studies supports further development of PRX302 as a minimally invasive, targeted treatment for BPH. Copyright © 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Serial Changes in Sexual Function Following Holmium Laser Enucleation of the Prostate: A Short-term Follow-up Study.

PubMed

Jeong, Min Su; Ha, Seung Beom; Lee, Chang Ju; Cho, Min Chul; Kim, Soo Woong; Paick, Jae-Seung

2012-02-01

To evaluate the serial changes in sexual function in the short-term period after holmium laser enucleation of the prostate (HoLEP) for benign prostatic hyperplasia (BPH) and to investigate whether a change in each domain of the International Index of Erectile Function (IIEF) is associated with improvement of micturition. Thirty-eight potent men who underwent HoLEP and in whom complete 12-month follow-up data on the IIEF were available were included in this retrospective study. All patients underwent a baseline evaluation for BPH. The surgical outcome was evaluated at 1, 3, 6, and 12 months postoperatively by use of the International Prostate Symptom Score, IIEF, and uroflowmetry. The mean age and body mass index of the patients was 64.5±6.2 years and 24.2±2.6 kg/m(2), respectively. Mean total prostate volume and transitional zone volume were 48.8±18.8 ml and 24.2±16.1 ml, respectively. Most IIEF domain scores showed a slight decrease at 1, 3, and 6 months after surgery but recovered to the baseline or showed a marginal but nonsignificant increase at 12 months postoperatively compared with baseline. Orgasmic function and the overall sexual satisfaction domain score remained slightly reduced up to 12 months postoperatively. There was no significant correlation between improvement of micturition and change in sexual function throughout the follow-up period after surgery. Although HoLEP achieves significant improvements in micturition, overall sexual function decreases slightly in the early postoperative period, but recovers to the baseline at 12 months postoperatively. Our data suggest that changes in sexual function after HoLEP are not associated with improvement of micturition.

Apoptotic Pathways Linked to Endocrine System as Potential Therapeutic Targets for Benign Prostatic Hyperplasia

PubMed Central

Minutoli, Letteria; Rinaldi, Mariagrazia; Marini, Herbert; Irrera, Natasha; Crea, Giovanni; Lorenzini, Cesare; Puzzolo, Domenico; Valenti, Andrea; Pisani, Antonina; Adamo, Elena B.; Altavilla, Domenica; Squadrito, Francesco; Micali, Antonio

2016-01-01

Benign prostatic hyperplasia (BPH) is a chronic condition common in older men that can result in bothersome lower urinary tract symptoms. The molecular mechanisms and networks underlying the development and the progression of the disease are still far from being fully understood. BPH results from smooth muscle cell and epithelial cell proliferation, primarily within the transition zone of the prostate. Apoptosis and inflammation play important roles in the control of cell growth and in the maintenance of tissue homeostasis. Disturbances in molecular mechanisms of apoptosis machinery have been linked to BPH. Increased levels of the glycoprotein Dickkopf-related protein 3 in BPH cause an inhibition of the apoptosis machinery through a reduction in B cell lymphoma (Bcl)-2 associated X protein (Bax) expression. Inhibitors of apoptosis proteins influence cell death by direct inhibition of caspases and modulation of the transcription factor nuclear factor-κB. Current pharmacotherapy targets either the static component of BPH, including finasteride and dutasteride, or the dynamic component of BPH, including α-adrenoceptor antagonists such as tamsulosin and alfuzosin. Both these classes of drugs significantly interfere with the apoptosis machinery. Furthermore, phytotherapic supplements and new drugs may also modulate several molecular steps of apoptosis. PMID:27529214

Apoptotic Pathways Linked to Endocrine System as Potential Therapeutic Targets for Benign Prostatic Hyperplasia.

PubMed

Minutoli, Letteria; Rinaldi, Mariagrazia; Marini, Herbert; Irrera, Natasha; Crea, Giovanni; Lorenzini, Cesare; Puzzolo, Domenico; Valenti, Andrea; Pisani, Antonina; Adamo, Elena B; Altavilla, Domenica; Squadrito, Francesco; Micali, Antonio

2016-08-11

Benign prostatic hyperplasia (BPH) is a chronic condition common in older men that can result in bothersome lower urinary tract symptoms. The molecular mechanisms and networks underlying the development and the progression of the disease are still far from being fully understood. BPH results from smooth muscle cell and epithelial cell proliferation, primarily within the transition zone of the prostate. Apoptosis and inflammation play important roles in the control of cell growth and in the maintenance of tissue homeostasis. Disturbances in molecular mechanisms of apoptosis machinery have been linked to BPH. Increased levels of the glycoprotein Dickkopf-related protein 3 in BPH cause an inhibition of the apoptosis machinery through a reduction in B cell lymphoma (Bcl)-2 associated X protein (Bax) expression. Inhibitors of apoptosis proteins influence cell death by direct inhibition of caspases and modulation of the transcription factor nuclear factor-κB. Current pharmacotherapy targets either the static component of BPH, including finasteride and dutasteride, or the dynamic component of BPH, including α-adrenoceptor antagonists such as tamsulosin and alfuzosin. Both these classes of drugs significantly interfere with the apoptosis machinery. Furthermore, phytotherapic supplements and new drugs may also modulate several molecular steps of apoptosis.

Adipose tissue-organotypic culture system as a promising model for studying adipose tissue biology and regeneration

PubMed Central

Uchihashi, Kazuyoshi; Aoki, Shigehisa; Sonoda, Emiko; Yamasaki, Fumio; Piao, Meihua; Ootani, Akifumi; Yonemitsu, Nobuhisa; Sugihara, Hajime

2009-01-01

Adipose tissue consists of mature adipocytes, preadipocytes and mesenchymal stem cells (MSCs), but a culture system for analyzing their cell types within the tissue has not been established. We have recently developed “adipose tissue-organotypic culture system” that maintains unilocular structure, proliferative ability and functions of mature adipocytes for a long term, using three-dimensional collagen gel culture of the tissue fragments. In this system, both preadipocytes and MSCs regenerate actively at the peripheral zone of the fragments. Our method will open up a new way for studying both multiple cell types within adipose tissue and the cell-based mechanisms of obesity and metabolic syndrome. Thus, it seems to be a promising model for investigating adipose tissue biology and regeneration. In this article, we introduce adipose tissue-organotypic culture, and propose two theories regarding the mechanism of tissue regeneration that occurs specifically at peripheral zone of tissue fragments in vitro. PMID:19794899

Dose escalation in permanent brachytherapy for prostate cancer: dosimetric and biological considerations

NASA Astrophysics Data System (ADS)

Li, X. Allen; Wang, Jian Z.; Stewart, Robert D.; Di Biase, Steven J.

2003-09-01

No prospective dose escalation study for prostate brachytherapy (PB) with permanent implants has been reported. In this work, we have performed a dosimetric and biological analysis to explore the implications of dose escalation in PB using 125I and 103Pd implants. The concept of equivalent uniform dose (EUD), proposed originally for external-beam radiotherapy (EBRT), is applied to low dose rate brachytherapy. For a given 125I or 103Pd PB, the EUD for tumour that corresponds to a dose distribution delivered by EBRT is calculated based on the linear quadratic model. The EUD calculation is based on the dose volume histogram (DVH) obtained retrospectively from representative actual patient data. Tumour control probabilities (TCPs) are also determined in order to compare the relative effectiveness of different dose levels. The EUD for normal tissue is computed using the Lyman model. A commercial inverse treatment planning algorithm is used to investigate the feasibility of escalating the dose to prostate with acceptable dose increases in the rectum and urethra. The dosimetric calculation is performed for five representative patients with different prostate sizes. A series of PB dose levels are considered for each patient using 125I and 103Pd seeds. It is found that the PB prescribed doses (minimum peripheral dose) that give an equivalent EBRT dose of 64.8, 70.2, 75.6 and 81 Gy with a fraction size of 1.8 Gy are 129, 139, 150 and 161 Gy for 125I and 103, 112, 122 and 132 Gy for 103Pd implants, respectively. Estimates of the EUD and TCP for a series of possible prescribed dose levels (e.g., 145, 160, 170 and 180 Gy for 125I and 125, 135, 145 and 155 for 103Pd implants) are tabulated. The EUD calculation was found to depend strongly on DVHs and radiobiological parameters. The dosimetric calculations suggest that the dose to prostate can be escalated without a substantial increase in both rectal and urethral dose. For example, increasing the PB prescribed dose from 145 to 180 Gy increases EUD for the rectum by only 3%. Our studies indicate that the dose to urethra can be kept within 100-120% of the prescription dose for all the dose levels studied. In conclusion, dose escalation in permanent implant for localized prostate cancer may be advantageous. It is dosimetrically possible to increase dose to prostate without a substantial increase in the dose to the rectum and urethra. Based on the results of our studies, a prospective dose escalation trial for prostate permanent implants has been initiated at our institution.

[The clinical investigation of peripheral retinal changes of anterior uveitis].

PubMed

Guo, Chunying; Qiao, Lijun; Yang, Liu

2015-10-01

To observe the peripheral retinal changes of anterior uveitis patients using ultra-wide field fluorescein angiography. Retrospective case series study. Thirty-three eyes of 20 patients diagnosed as anterior uveitis from September to November 2013 in the ophthalmic clinic of Peking University First Hospital was included. All the patients underwent routine ocular examination, followed by ultra-wide field Fluorescein. There were 13 male patients and 7 female patients, aged 23-66, an average of 46 years old. The anterior uveitis recurrent in both eyes in 13 patients and only one eye in 7 patients. Uveitis duration ranging from months to 30 years. Twenty eyes were at the active stage of the anterior uveitis while 13 eyes in the quiescent stage. Peripheral retinal vessels leakage was detected in 57.6% (19/33) of the eyes, among which in eyes with active disease the rate of peripheral retinal vessels leakage was 75% (15/20), and in eyes with quiescent disease the rate was 30.8% (4/13). Optic disk hyperfluorescence was found in 6 of 20 eyes with active disease. Cystoid macular edema was found in 4 eyes. In addition, peripheral retinal hyperfluorescence dot and zone were detected in 2 eyes. Peripheral retinal vessels were detected to have inflammative leakage in patients of anterior uveitis by ultra-wide field fluorescein agiography. Peripheral retinal inflammation may still exist even in the quiescent stage of the anterior uveitis.

Novel grid combined with peripheral distortion correction for ultra-widefield image grading of age-related macular degeneration

PubMed Central

Mach, Steven; Garas, Shady; Kim, Ivana K; Vavvas, Demetrios G; Miller, Joan W; Husain, Deeba; Miller, John B

2017-01-01

Purpose Eyes with age-related macular degeneration (AMD) often harbor pathological changes in the retinal periphery and perimacular region. These extramacular changes have not been well classified, but may be phenotypically and functionally relevant. The purpose of this study was to demonstrate a novel grid to systematically study peripheral retinal abnormalities in AMD using geometric distortion-corrected ultra-widefield (UWF) imaging. Methods This is a cross-sectional observational case series. Consecutive patients with AMD without any other coexisting vitreoretinal disease and control patients over age 50 without AMD or any other vitreoretinal disease were imaged using Optos 200 Tx. Captured 200° UWF images were corrected for peripheral geometric distortion using Optos transformation software. A newly developed grid to study perimacular and peripheral abnormalities in AMD was then projected onto the images. Results Peripheral and perimacular changes such as drusen, retinal pigment epithelium changes and atrophy were found in patients with AMD. The presented grid in conjunction with geometric distortion-corrected UWF images allowed for systematic study of these peripheral changes in AMD. Conclusion We present a novel grid to study peripheral and posterior pole changes in AMD. The grid is unique in that it adds a perimacular zone, which may be important in characterizing certain phenotypes in AMD. Our UWF images were corrected for geometric peripheral distortion to accurately reflect the anatomical dimensions of the retina. This grid offers a reliable and reproducible foundation for the exploration of peripheral retinal pathology associated with AMD. PMID:29184386

Tissue engineered constructs for peripheral nerve surgery

PubMed Central

Johnson, P. J.; Wood, M. D.; Moore, A. M.; Mackinnon, S. E.

2013-01-01

Summary Background Tissue engineering has been defined as “an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function or a whole organ”. Traumatic peripheral nerve injury resulting in significant tissue loss at the zone of injury necessitates the need for a bridge or scaffold for regenerating axons from the proximal stump to reach the distal stump. Methods A review of the literature was used to provide information on the components necessary for the development of a tissue engineered peripheral nerve substitute. Then, a comprehensive review of the literature is presented composed of the studies devoted to this goal. Results Extensive research has been directed toward the development of a tissue engineered peripheral nerve substitute to act as a bridge for regenerating axons from the proximal nerve stump seeking the distal nerve. Ideally this nerve substitute would consist of a scaffold component that mimics the extracellular matrix of the peripheral nerve and a cellular component that serves to stimulate and support regenerating peripheral nerve axons. Conclusions The field of tissue engineering should consider its challenge to not only meet the autograft “gold standard” but also to understand what drives and inhibits nerve regeneration in order to surpass the results of an autograft. PMID:24385980

The prevention of benign prostatic hyperplasia (bph).

PubMed

Roper, W G

2017-03-01

Barry Marshall and Robin Warren were the first to show that the chronic diseases (gastric ulcer and chronic gastritis) were caused by an infection (Helicobacter pylori). The chronic disease benign prostatic hyperplasia belongs to the same ilk, except that the infection process is much more subtle and complex. The enzyme Phospholipase D (PLD) which is attached to the outer membrane of Escherichia coli (E. coli) has now been almost completely proven to be the basic cause of BPH. The evidence for this process is now extremely strong and compelling. PLD obtained from the organism Streptomyces chromofuscus has been used in past research because of its PLD content. It is commercially available. In vitro, on a culture of prostatic smooth muscle, PLD stimulated the production of lysophosphatidic acid (LPA) which acted on and caused substantial growth of that muscle in accordance with the quantity of PLD/ LPA generated. It has been asserted that repeated colonization by E. coli of the transitional zone of the prostate gland and the release of PLD following repeated destruction of these colonized bacteria, is the basic cause of BPH. The evidence for colonizing and re-colonizing infection is now overwhelming. PLD is a simple lipid consisting of a phosphate, glycerol and a fatty acid. After absorption into the prostatic stroma (which consists of connective tissue and of smooth muscle), it stimulates the production of LPA which, in turn, apart from directly stimulating prostatic smooth muscle, also acts on the connective tissue in the prostate and induces a complex mixture of growth regulatory proteins, which include members of the fibroblast, insulin-like and growth transforming factor families and implicates autocrine hormones acting on the stroma and paracrine hormones acting on epithelium. Also involved, are a variety of interleukins and other inflammatory cell cytokines, secreted by the stroma, which may further promote autocrine/paracrine proliferation of BPH cells. Cadherins involved in cell adhesion and possibly chalone which exerts negative effects, must also be considered. Overall, the degree of BPH that any older male develops is governed largely by: Apart from providing the existing huge evidence for infection in BPH, this manuscript explains the production, release and absorption of PLD into the prostate gland where it is converted to LPA. This is a growth factor and acts within the prostate both on smooth muscle (research proof given) and on prostatic connective tissue, resulting in BPH. This manuscript indicates the vital research, including the requisite materials, which would readily provide irrefutable and final etiological proof of all of the hormones involved. It explains how, to a large extent, the use of a vaccine which is now being developed, would likely allow the ultimate prevention of this ubiquitous disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Lack of an Association between Neutrophil-to-Lymphocyte Ratio and PSA Failure of Prostate Cancer Patients Who Underwent Radical Prostatectomy.

PubMed

Maeda, Yoko; Kawahara, Takashi; Koizumi, Mitsuyuki; Ito, Hiroki; Kumano, Yohei; Ohtaka, Mari; Kondo, Takuya; Mochizuki, Taku; Hattori, Yusuke; Teranishi, Jun-Ichi; Yumura, Yasushi; Miyoshi, Yasuhide; Yao, Masahiro; Miyamoto, Hiroshi; Uemura, Hiroji

2016-01-01

Introduction. The neutrophil-to-lymphocyte ratio (NLR), which can be easily calculated from routine complete blood counts of the peripheral blood, has been suggested to serve as a prognostic factor for some solid malignancies. In the present study, we aimed to determine the relationship between NLR in prostate cancer patients undergoing radical prostatectomy (RP) and their prognosis. Materials and Methods. We assessed NLR in 73 men (patients) who received RP for their prostate cancer. We also performed immunohistochemistry for CD8 and CD66b in a separate set of RP specimens. Results. The median NLR in the 73 patients was 1.85. There were no significant correlations of NLR with tumor grade (p = 0.834), pathological T stage (p = 0.082), lymph node metastasis (p = 0.062), or resection margin status (p = 0.772). Based on the area under the receiver operator characteristic curve (AUROC) to predict biochemical recurrence after RP, potential NLR cut-off point was determined to be 2.88 or 3.88. However, both of these cut-off points did not precisely predict the prognosis. There were no statistically significant differences in the number of CD66b-positive neutrophils or CD8-positive lymphocytes between stromal tissues adjacent to cancer glands and stromal tissues away from cancer glands and between different grades or stages of tumors. Conclusions. There was no association between NLR and biochemical failure after prostatectomy.

A Case of oculocutaneous albinism in a Maltese.

PubMed

Park, Shin Ae; Yi, Na Young; Kim, Min Su; Lim, Ji Hey; Jeong, Man Bok; Nam, Tchi Chou; Seo, Kang Moon

2005-12-01

A 4-month-old female maltese dog was admitted to Veterinary Medical Teaching Hospital of Seoul National University for evaluation of abnormal color of bilateral irises. This patient had the photophobia in the light and exhibited the complete absence of pigment resulting in white hair, pink muzzle, eyelids and foot-pads. Central zone of the irises were yellow in color influenced by tapetal reflex, and peripheral zone were pale blue. The iridal capillaries were transparented on the irises. Ophthalmoscopic examination revealed a yellow tapetal fundus but no pigment in the nontapetal fundus.

Pathological characteristics of low risk prostate cancer based on totally embedded prostatectomy specimens.

PubMed

Swanson, Gregory P; Epstein, Jonathan I; Ha, Chul S; Kryvenko, Oleksandr N

2015-03-01

Surveillance and focal therapy are increasingly considered for low risk prostate cancer (PC). We describe pathological characteristics of low risk PC at radical prostatectomy in contemporary patients. Five-hundred-fifty-two men from 2008 to 2012 with low risk (stage T1c/T2a, PSA ≤ 10 ng/ml, Gleason score ≤6) PC underwent radical prostatectomy. Slides were re-reviewed to grade and stage the tumor, map separate tumor nodules, and calculate their volumes. Ninety-three (16.9%) men had prostatectomy Gleason score 3 + 4 = 7 or higher and were excluded. Five (0.9%) men had no residual carcinoma. Remaining 454 patients composed the study cohort. The median age was 57 years (36-73) and median PSA 4.4 ng/ml (0.4-9.9). Racial distribution was 77.5% Caucasian, 15.5% African American, and 7% other. The median total tumor volume was 0.38 cm(3) (0.003-7.22). Seventy percent of the patients had bilateral tumor and 34% had a tumor nodule >0.5 cm(3) . The index lesion represented 89% (median) of the total tumor volume. Extraprostatic extension and positive margin were present in 5.7% and 9% of cases, respectively. The tumor nodules measuring >0.5 cm(3) were located almost equally between the anterior (53%) and peripheral (47%) gland. The relationship between PSA and total tumor volume was weak (r = 0.13, P = 0.005). The relationship between PSA density and total tumor volume was slightly better (r = 0.26, P < 0.001). Low risk prostate cancer is generally a low volume disease. Gleason score upgrade is seen in 16.9% of cases at radical prostatectomy. While the index lesion accounts for the bulk of the disease, the cancer is usually multifocal and bilateral. Neither PSA nor PSA density correlates well with the total tumor volume. Prostate size has a significant contribution to PSA level. These factors need to be considered in treatment planning for low risk prostate cancer. © 2014 Wiley Periodicals, Inc.

The characterization of neural tissue ablation rate and corresponding heat affected zone of a 2 micron Tm3+ doped fiber laser(Conference Presentation)

NASA Astrophysics Data System (ADS)

Marques, Andrew J.; Jivraj, Jamil; Reyes, Robnier; Ramjist, Joel; Gu, Xijia J.; Yang, Victor X. D.

2017-02-01

Tissue removal using electrocautery is standard practice in neurosurgery since tissue can be cut and cauterized simultaneously. Thermally mediated tissue ablation using lasers can potentially possess the same benefits but with increased precision. However, given the critical nature of the spine, brain, and nerves, the effects of direct photo-thermal interaction on neural tissue needs to be known, yielding not only high precision of tissue removal but also increased control of peripheral heat damage. The proposed use of lasers as a neurosurgical tool requires that a common ground is found between ablation rates and resulting peripheral heat damage. Most surgical laser systems rely on the conversion of light energy into heat resulting in both desirable and undesirable thermal damage to the targeted tissue. Classifying the distribution of thermal energy in neural tissue, and thus characterizing the extent of undesirable thermal damage, can prove to be exceptionally challenging considering its highly inhomogenous composition when compared to other tissues such as muscle and bone. Here we present the characterization of neural tissue ablation rate and heat affected zone of a 1.94 micron thulium doped fiber laser for neural tissue ablation. In-Vivo ablation of porcine cerebral cortex is performed. Ablation volumes are studied in association with laser parameters. Histological samples are taken and examined to characterize the extent of peripheral heat damage.

Relationship between central and peripheral corneal astigmatism in elderly patients

NASA Astrophysics Data System (ADS)

Kawamorita, Takushi; Shimizu, Kimiya; Hoshikawa, Rie; Kamiya, Kazutaka; Shoji, Nobuyuki

2018-03-01

Abstract Purpose We investigated the relationship between central and peripheral corneal astigmatism in elderly patients. Methods Seventy-six eyes of 76 elderly subjects (mean age = 72.6 ± 3.0 years) were included in the study. Corneal shape was evaluated using the Pentacam HR (Oculus, Wetzlark, Germany), which is comprised of a rotating Scheimpflug camera and a short-wavelength slit light. The power distribution map was selected and corneal astigmatism was calculated using front K-Readings in zones centered on the pupil. Analyzed zones were 2.0-6.0 mm in diameter. Results Corneal astigmatism decreased as diameter increased, similar to what was observed in eyes with with-the-rule astigmatism and against-the-rule astigmatism (ANOVA, p < 0.01). This effect was more pronounced in eyes with a large central corneal astigmatism (Spearman's rank-correlation coefficient test, r = 0.51, p < 0.01). There was no change as to axis of corneal astigmatism (ANOVA, p = 0.98). Conclusion These results suggest that the relationship between central and peripheral corneal astigmatism should be taken into consideration to optimize vision when astigmatic correction is needed.

Renal blood flow and oxygenation drive nephron progenitor differentiation.

PubMed

Rymer, Christopher; Paredes, Jose; Halt, Kimmo; Schaefer, Caitlin; Wiersch, John; Zhang, Guangfeng; Potoka, Douglas; Vainio, Seppo; Gittes, George K; Bates, Carlton M; Sims-Lucas, Sunder

2014-08-01

During kidney development, the vasculature develops via both angiogenesis (branching from major vessels) and vasculogenesis (de novo vessel formation). The formation and perfusion of renal blood vessels are vastly understudied. In the present study, we investigated the regulatory role of renal blood flow and O2 concentration on nephron progenitor differentiation during ontogeny. To elucidate the presence of blood flow, ultrasound-guided intracardiac microinjection was performed, and FITC-tagged tomato lectin was perfused through the embryo. Kidneys were costained for the vasculature, ureteric epithelium, nephron progenitors, and nephron structures. We also analyzed nephron differentiation in normoxia compared with hypoxia. At embryonic day 13.5 (E13.5), the major vascular branches were perfused; however, smaller-caliber peripheral vessels remained unperfused. By E15.5, peripheral vessels started to be perfused as well as glomeruli. While the interior kidney vessels were perfused, the peripheral vessels (nephrogenic zone) remained unperfused. Directly adjacent and internal to the nephrogenic zone, we found differentiated nephron structures surrounded and infiltrated by perfused vessels. Furthermore, we determined that at low O2 concentration, little nephron progenitor differentiation was observed; at higher O2 concentrations, more differentiation of the nephron progenitors was induced. The formation of the developing renal vessels occurs before the onset of blood flow. Furthermore, renal blood flow and oxygenation are critical for nephron progenitor differentiation. Copyright © 2014 the American Physiological Society.

Asymmetrical bonding in cold spraying of dissimilar materials

NASA Astrophysics Data System (ADS)

Nikbakht, R.; Seyedein, S. H.; Kheirandish, S.; Assadi, H.; Jodoin, B.

2018-06-01

Characteristics of particle bonding, especially for dissimilar materials, remains a key question in cold spray deposition. There are limited reports in direct correlation to particle/substrate bonding and peripheral shear zones. Cold spraying experiments and numerical simulations are conducted to characterise and analyse the correlation between bonding and peripheral shear zones for asymmetric particle/substrate pairs of intermetallic-forming elements of nickel and titanium. The correlation between metallic bonding and highly strained areas is explored in view of the growth of the intermetallic phase at the particle/substrate interface during subsequent heat treatments. Characterisation of the as-sprayed samples reveal that for the Ni(particle)/Ti(substrate) pair, plastic deformation of the particle is dominating over substrate deformation. However, for the Ti(particle)/Ni(substrate) pair, it is observed that the substrate and particle deform to similar extents. Characterisation of the samples after a brief heat treatment at 700 °C indicate that intermetallic formation, and hence metallurgical bonding of the pairs is more likely to occur at the particle peripheries where the interface areas are highly strained, and rarely achieved at the particle base. Results also reveal that bonding extends from peripheries toward the central part of the interfaces with increasing the impact velocity. The kinetics of interfacial intermetallic formation at peripheral areas and its correlation to particle bonding is discussed in view of deformation-enhanced interdiffusion.

High-Dose Chemotherapy With or Without Total-Body Irradiation Followed by Autologous Stem Cell Transplant in Treating Patients With Hematologic Cancer or Solid Tumors

ClinicalTrials.gov

2018-04-05

Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor (PNET); Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Plasma Cell Neoplasm; Primary Systemic Amyloidosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Neuroblastoma; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Regional Neuroblastoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

Cabazitaxel Versus Docetaxel As First-Line Therapy for Patients With Metastatic Castration-Resistant Prostate Cancer: A Randomized Phase III Trial-FIRSTANA.

PubMed

Oudard, Stéphane; Fizazi, Karim; Sengeløv, Lisa; Daugaard, Gedske; Saad, Fred; Hansen, Steinbjørn; Hjälm-Eriksson, Marie; Jassem, Jacek; Thiery-Vuillemin, Antoine; Caffo, Orazio; Castellano, Daniel; Mainwaring, Paul N; Bernard, John; Shen, Liji; Chadjaa, Mustapha; Sartor, Oliver

2017-10-01

Purpose In patients with metastatic castration-resistant prostate cancer (mCRPC), overall survival (OS) is significantly improved with cabazitaxel versus mitoxantrone after prior docetaxel treatment. FIRSTANA ( ClinicalTrials.gov identifier: NCT01308567) assessed whether cabazitaxel 20 mg/m 2 (C20) or 25 mg/m 2 (C25) is superior to docetaxel 75 mg/m 2 (D75) in terms of OS in patients with chemotherapy-naïve mCRPC. Patients and Methods Patients with mCRPC and Eastern Cooperative Oncology Group performance status of 0 to 2 were randomly assigned 1:1:1 to receive C20, C25, or D75 intravenously every 3 weeks plus daily prednisone. The primary end point was OS. Secondary end points included safety; progression-free survival (PFS); tumor, prostate-specific antigen, and pain response; pharmacokinetics; and health-related quality of life. Results Between May 2011 and April 2013, 1,168 patients were randomly assigned. Baseline characteristics were similar across cohorts. Median OS was 24.5 months with C20, 25.2 months with C25, and 24.3 months with D75. Hazard ratio for C20 versus D75 was 1.01 (95% CI, 0.85 to 1.20; P = .997), and hazard ratio for C25 versus D75 was 0.97 (95% CI, 0.82 to 1.16; P = .757). Median PFS was 4.4 months with C20, 5.1 months with C25, and 5.3 months with D75, with no significant differences between treatment arms. Radiographic tumor responses were numerically higher for C25 (41.6%) versus D75 (30.9%; nominal P = .037, without multiplicity test adjustment). Rates of grade 3 or 4 treatment-emergent adverse events were 41.2%, 60.1%, and 46.0% for C20, C25, and D75, respectively. Febrile neutropenia, diarrhea, and hematuria were more frequent with C25; peripheral neuropathy, peripheral edema, alopecia, and nail disorders were more frequent with D75. Conclusion C20 and C25 did not demonstrate superiority for OS versus D75 in patients with chemotherapy-naïve mCRPC. Tumor response was numerically higher with C25 versus D75; pain PFS was numerically improved with D75 versus C25. Cabazitaxel and docetaxel demonstrated different toxicity profiles, with overall less toxicity with C20.

Clinical and Pathologic Studies in Non-Hodgkin's Lymphoma Patients Receiving Antibody Treatment

ClinicalTrials.gov

2011-05-31

Lymphoma, Non-Hodgkin; Lymphomas: Non-Hodgkin; Lymphomas: Non-Hodgkin Cutaneous Lymphoma; Lymphomas: Non-Hodgkin Diffuse Large B-Cell; Lymphomas: Non-Hodgkin Follicular / Indolent B-Cell; Lymphomas: Non-Hodgkin Mantle Cell; Lymphomas: Non-Hodgkin Marginal Zone; Lymphomas: Non-Hodgkin Peripheral T-Cell; Lymphomas: Non-Hodgkin Waldenstr Macroglobulinemia

Immunomodulation of Hyperthermia for Recurrent Prostate Cancer

DTIC Science & Technology

2006-03-01

cells treated with Hyperthermia (HT). HT was administered either as incubation in a 43.7oC water bath or by High frequency focused ultrasound ( HIFU ...immunity and improve local and distant tumor regression. B. BODY B.1. HT induced by water bath (43.7C,1hr) in vivo was compared to HIFU in vivo... HIFU induces coagulative tissue necrosis in the focal zone by rapidly elevating tissue temperature in a short exposure (seconds) while keeping the

Development of transrectal diffuse optical tomography combined with 3D-transrectal ultrasound imaging to monitor the photocoagulation front during interstitial photothermal therapy of primary focal prostate cancer

NASA Astrophysics Data System (ADS)

He, Jie; Weersink, Robert; Veilleux, Israel; Mayo, Kenwrick; Zhang, Anqi; Piao, Daqing; Alam, Adeel; Trachtenberg, John; Wilson, Brian C.

2013-03-01

Interstitial near-infrared laser thermal therapy (LITT) is currently undergoing clinical trials as an alternative to watchful waiting or radical surgery in patients with low-risk focal prostate cancer. Currently, we use magnetic resonance image (MRI)-based thermography to monitor treatment delivery and determine indirectly the completeness of the target tissue destruction while avoiding damage to adjacent normal tissues, particularly the rectal wall. However, incomplete tumor destruction has occurred in a significant fraction of patients due to premature termination of treatment, since the photocoagulation zone is not directly observed. Hence, we are developing transrectal diffuse optical tomography (TRDOT), in combination with transrectal 3D ultrasound (3D-TRUS), to address his limitation. This is based on the large changes in optical scattering expected upon tissue coagulation. Here, we present forward simulations of a growing coagulated lesion with optical scattering contrast, using an established finite element analysis software platform (NIRFAST). The simulations were validated in tissue-simulating phantoms, with measurements acquired by a state-of-the-art continuous wave (CW) TRDOT system and a recently assembled bench-top CW-DOT system, with specific source-detector configurations. Two image reconstruction schemes were investigated and evaluated, specifically for the accurate delineation of the posterior boundary of the coagulation zone as the critical parameter for treatment guidance in this clinical application.

Optimal Parameters to Determine the Apparent Diffusion Coefficient in Diffusion Weighted Imaging via Simulation

NASA Astrophysics Data System (ADS)

Perera, Dimuthu

Diffusion weighted (DW) Imaging is a non-invasive MR technique that provides information about the tissue microstructure using the diffusion of water molecules. The diffusion is generally characterized by the apparent diffusion coefficient (ADC) parametric map. The purpose of this study is to investigate in silico how the calculation of ADC is affected by image SNR, b-values, and the true tissue ADC. Also, to provide optimal parameter combination depending on the percentage accuracy and precision for prostate peripheral region cancer application. Moreover, to suggest parameter choices for any type of tissue, while providing the expected accuracy and precision. In this research DW images were generated assuming a mono-exponential signal model at two different b-values and for known true ADC values. Rician noise of different levels was added to the DWI images to adjust the image SNR. Using the two DWI images, ADC was calculated using a mono-exponential model for each set of b-values, SNR, and true ADC. 40,000 ADC data were collected for each parameter setting to determine the mean and the standard-deviation of the calculated ADC, as well as the percentage accuracy and precision with respect to the true ADC. The accuracy was calculated using the difference between known and calculated ADC. The precision was calculated using the standard-deviation of calculated ADC. The optimal parameters for a specific study was determined when both the percentage accuracy and precision were minimized. In our study, we simulated two true ADCs (ADC 0.00102 for tumor and 0.00180 mm2/s for normal prostate peripheral region tissue). Image SNR was varied from 2 to 100 and b-values were varied from 0 to 2000s/mm2. The results show that the percentage accuracy and percentage precision were minimized with image SNR. To increase SNR, 10 signal-averagings (NEX) were used considering the limitation in total scan time. The optimal NEX combination for tumor and normal tissue for prostate peripheral region was 1: 9. Also, the minimum percentage accuracy and percentage precision were obtained when low b-value is 0 and high b-value is 800 mm2/s for normal tissue and 1400 mm2/s for tumor tissue. Results also showed that for tissues with 1 x 10-3 < ADC < 2.1 x 10-3 mm 2/s the parameter combination at SNR = 20, b-value pair 0, 800 mm 2/s with NEX = 1:9 can calculate ADC with a percentage accuracy of less than 2% and percentage precision of 6-8%. Also, for tissues with 0.6 x 10-3 < ADC < 1.25 x 10-3 mm2 /s the parameter combination at SNR = 20, b-value pair 0, 1400 mm 2/s with NEX =1:9 can calculate ADC with a percentage accuracy of less than 2% and percentage precision of 6-8%.

MAPK1 is required for establishing the pattern of cell proliferation and for cell survival during lens development

PubMed Central

Upadhya, Dinesh; Ogata, Masato; Reneker, Lixing W.

2013-01-01

The mitogen-activated protein kinases (MAPKs; also known as ERKs) are key intracellular signaling molecules that are ubiquitously expressed in tissues and were assumed to be functionally equivalent. Here, we use the mouse lens as a model system to investigate whether MAPK1 plays a specific role during development. MAPK3 is known to be dispensable for lens development. We demonstrate that, although MAPK1 is uniformly expressed in the lens epithelium, its deletion significantly reduces cell proliferation in the peripheral region, an area referred to as the lens germinative zone in which most active cell division occurs during normal lens development. By contrast, cell proliferation in the central region is minimally affected by MAPK1 deletion. Cell cycle regulators, including cyclin D1 and survivin, are downregulated in the germinative zone of the MAPK1-deficient lens. Interestingly, loss of MAPK1 subsequently induces upregulation of phosphorylated MAPK3 (pMAPK3) levels in the lens epithelium; however, this increase in pMAPK3 is not sufficient to restore cell proliferation in the germinative zone. Additionally, MAPK1 plays an essential role in epithelial cell survival but is dispensable for fiber cell differentiation during lens development. Our data indicate that MAPK1/3 control cell proliferation in the lens epithelium in a spatially defined manner; MAPK1 plays a unique role in establishing the highly mitotic zone in the peripheral region, whereas the two MAPKs share a redundant role in controlling cell proliferation in the central region of the lens epithelium. PMID:23482492

Diffusion-weighted magnetic resonance imaging in cancer: Reported apparent diffusion coefficients, in-vitro and in-vivo reproducibility

PubMed Central

Jafar, Maysam M; Parsai, Arman; Miquel, Marc E

2016-01-01

There is considerable disparity in the published apparent diffusion coefficient (ADC) values across different anatomies. Institutions are increasingly assessing repeatability and reproducibility of the derived ADC to determine its variation, which could potentially be used as an indicator in determining tumour aggressiveness or assessing tumour response. In this manuscript, a review of selected articles published to date in healthy extra-cranial body diffusion-weighted magnetic resonance imaging is presented, detailing reported ADC values and discussing their variation across different studies. In total 115 studies were selected including 28 for liver parenchyma, 15 for kidney (renal parenchyma), 14 for spleen, 13 for pancreatic body, 6 for gallbladder, 13 for prostate, 13 for uterus (endometrium, myometrium, cervix) and 13 for fibroglandular breast tissue. Median ADC values in selected studies were found to be 1.28 × 10-3 mm2/s in liver, 1.94 × 10-3 mm2/s in kidney, 1.60 × 10-3 mm2/s in pancreatic body, 0.85 × 10-3 mm2/s in spleen, 2.73 × 10-3 mm2/s in gallbladder, 1.64 × 10-3 mm2/s and 1.31 × 10-3 mm2/s in prostate peripheral zone and central gland respectively (combined median value of 1.54×10-3 mm2/s), 1.44 × 10-3 mm2/s in endometrium, 1.53 × 10-3 mm2/s in myometrium, 1.71 × 10-3 mm2/s in cervix and 1.92 × 10-3 mm2/s in breast. In addition, six phantom studies and thirteen in vivo studies were summarized to compare repeatability and reproducibility of the measured ADC. All selected phantom studies demonstrated lower intra-scanner and inter-scanner variation compared to in vivo studies. Based on the findings of this manuscript, it is recommended that protocols need to be optimised for the body part studied and that system-induced variability must be established using a standardized phantom in any clinical study. Reproducibility of the measured ADC must also be assessed in a volunteer population, as variations are far more significant in vivo compared with phantom studies. PMID:26834942

Anorectal and Pelvic Pain

PubMed Central

Bharucha, Adil E.; Lee, Tae Hee

2016-01-01

Although pelvic pain is a symptom of several structural anorectal and pelvic disorders (eg, anal fissure, endometriosis, and pelvic inflammatory disease), this comprehensive review will focus on the three most common nonstructural, or functional, disorders associated with pelvic pain: functional anorectal pain (ie, levator ani syndrome, unspecified anorectal pain, and proctalgia fugax), interstitial cystitis/bladder pain syndrome, and chronic prostatitis/chronic pelvic pain syndrome. The first two conditions occur in both sexes, while the latter occurs only in men. They are defined by symptoms, supplemented with levator tenderness (levator ani syndrome) and bladder mucosal inflammation (interstitial cystitis). Although distinct, these conditions share several similarities, including associations with dysfunctional voiding or defecation, comorbid conditions (eg, fibromyalgia, depression), impaired quality of life, and increased health care utilization. Several factors, including pelvic floor muscle tension, peripheral inflammation, peripheral and central sensitization, and psychosocial factors, have been implicated in the pathogenesis. The management is tailored to symptoms, is partly supported by clinical trials, and includes multidisciplinary approaches such as lifestyle modifications and pharmacologic, behavioral, and physical therapy. Opioids should not be avoided, and surgery has a limited role, primarily in refractory interstitial cystitis. PMID:27712641

Can manipulation of orthokeratology lens parameters modify peripheral refraction?

PubMed

Kang, Pauline; Gifford, Paul; Swarbrick, Helen

2013-11-01

To investigate changes in peripheral refraction, corneal topography, and aberrations induced by changes in orthokeratology (OK) lens parameters in myopes. Subjects were fitted with standard OK lenses that were worn overnight for 2 weeks. Peripheral refraction, corneal topography, and corneal surface aberrations were measured at baseline and after 14 nights of OK lens wear. Subsequent to a 2-week washout period, subjects were refitted with another set of lenses where one eye was randomly assigned to wear an OK lens with a smaller optic zone diameter (OZD) and the other eye with a steeper peripheral tangent. Measurements were taken again at a second baseline and after 14 days of overnight wear of the second OK lens set. Standard OK lenses with a 6-mm OZD and 1/4 peripheral tangent caused significant changes in both peripheral refraction and corneal topography. Significant hyperopic shift occurred in the central visual field (VF) while a myopic shift was found at 35 degrees in the nasal VF. OK induced significant reductions in corneal power at all positions along the horizontal corneal chord except at 2.4 mm nasal where there was no significant change and at 2.8 mm nasal where there was an increase in corneal refractive power. A positive shift in spherical aberration was induced for all investigated lens designs except for the 1/2 tangent design when calculated over a 4-mm pupil. Reducing OZD and steepening the peripheral tangent did not cause significant changes in peripheral refraction or corneal topography profiles across the horizontal meridian. OK lenses caused significant changes in peripheral refraction, corneal topography, and corneal surface aberrations. Modifying OZD and peripheral tangent made no significant difference to the peripheral refraction or corneal topography profile. Attempting to customize refraction and topography changes through manipulation of OK lens parameters appears to be a difficult task.

Gemcitabine Hydrochloride, Carboplatin, Dexamethasone, and Rituximab in Treating Patients With Previously Treated Lymphoid Malignancies

ClinicalTrials.gov

2017-05-28

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

Transcontinental communication and quantitative digital histopathology via the Internet; with special reference to prostate neoplasia

PubMed Central

Montironi, R; Thompson, D; Scarpelli, M; Bartels, H G; Hamilton, P W; Da Silva, V D; Sakr, W A; Weyn, B; Van Daele, A; Bartels, P H

2002-01-01

Objective: To describe practical experiences in the sharing of very large digital data bases of histopathological imagery via the Internet, by investigators working in Europe, North America, and South America. Materials: Experiences derived from medium power (sampling density 2.4 pixels/μm) and high power (6 pixels/μm) imagery of prostatic tissues, skin shave biopsies, breast lesions, endometrial sections, and colonic lesions. Most of the data included in this paper were from prostate. In particular, 1168 histological images of normal prostate, high grade prostatic intraepithelial neoplasia (PIN), and prostate cancer (PCa) were recorded, archived in an image format developed at the Optical Sciences Center (OSC), University of Arizona, and transmitted to Ancona, Italy, as JPEG (joint photographic experts group) files. Images were downloaded for review using the Internet application FTP (file transfer protocol). The images were then sent from Ancona to other laboratories for additional histopathological review and quantitative analyses. They were viewed using Adobe Photoshop, Paint Shop Pro, and Imaging for Windows. For karyometric analysis full resolution imagery was used, whereas histometric analyses were carried out on JPEG imagery also. Results: The three applications of the telecommunication system were remote histopathological assessment, remote data acquisition, and selection of material. Typical data volumes for each project ranged from 120 megabytes to one gigabyte, and transmission times were usually less than one hour. There were only negligible transmission errors, and no problem in efficient communication, although real time communication was an exception, because of the time zone differences. As far as the remote histopathological assessment of the prostate was concerned, agreement between the pathologist's electronic diagnosis and the diagnostic label applied to the images by the recording scientist was present in 96.6% of instances. When these images were forwarded to two pathologists, the level of concordance with the reviewing pathologist who originally downloaded the files from Tucson was as high as 97.2% and 98.0%. Initial results of studies made by researchers belonging to our group but located in others laboratories showed the feasibility of making quantitative analysis on the same images. Conclusions: These experiences show that diagnostic teleconsultation and quantitative image analyses via the Internet are not only feasible, but practical, and allow a close collaboration between researchers widely separated by geographical distance and analytical resources. PMID:12037030

Urinary microRNAs for prostate cancer diagnosis, prognosis, and treatment response: are we there yet?

PubMed

Balacescu, Ovidiu; Petrut, Bogdan; Tudoran, Oana; Feflea, Dragos; Balacescu, Loredana; Anghel, Andrei; Sirbu, Ioan O; Seclaman, Edward; Marian, Catalin

2017-11-01

Prostate cancer (PCa) remains one of the leading causes of cancer-related deaths in men. Despite the tremendous progress in research over the years, a suitable minimally invasive PCa biomarker is yet to be discovered. The recent advances regarding the roles of microRNAs as biomarkers has allowed for their study in PCa as well, especially as blood-based markers. However, there are several studies that used urine as biological sample to evaluate microRNAs as biomarkers for PCa diagnosis, prognosis, and treatment response, which were reviewed herein. A high degree of inconsistency among reports has been observed, which could be due to several analytical aspects, starting with different urinary fractions used for analysis and continuing with the employment of various analytical platforms and methods of statistical analysis. However, a few microRNAs were found to be dysregulated in the urine of PCa patients, which alone or together with serum prostate-specific antigen seem to improve diagnostic power even in the gray zone of PCa. These results warrant further confirmation by larger prospective studies, preferably using a standardized protocol for analysis. WIREs RNA 2017, 8:e1438. doi: 10.1002/wrna.1438 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

Artificial ascites and pneumoperitoneum to facilitate thermal ablation of liver tumors: a pictorial essay.

PubMed

Bhagavatula, Sharath K; Chick, Jeffrey F B; Chauhan, Nikunj R; Shyn, Paul B

2017-02-01

Image-guided percutaneous thermal ablation is increasingly utilized in the treatment of hepatic malignancies. Peripherally located hepatic tumors can be difficult to access or located adjacent to critical structures that can be injured. As a result, ablation of peripheral tumors may be avoided or may be performed too cautiously, leading to inadequate ablation coverage. In these cases, separating the tumor from adjacent critical structures can increase the efficacy and safety of procedures. Artificial ascites and artificial pneumoperitoneum are techniques that utilize fluid and gas, respectively, to insulate critical structures from the thermal ablation zone. Induction of artificial ascites and artificial pneumoperitoneum can enable complete ablation of otherwise inaccessible hepatic tumors, improve tumor visualization, minimize unintended thermal injury to surrounding organs, and reduce post-procedural pain. This pictorial essay illustrates and discusses the proper technique and clinical considerations for successful artificial ascites and pneumoperitoneum creation to facilitate safe peripheral hepatic tumor ablation.

Comparison of semi-extended and standard lymph node dissection in radical prostatectomy: A single-institute experience.

PubMed

Hoshi, Senji; Hayashi, Natuho; Kurota, Yuuta; Hoshi, Kiyotsugu; Muto, Akinori; Sugano, Osamu; Numahata, Kenji; Bilim, Vladimir; Sasagawa, Isoji; Ohta, Shoichiro

2015-09-01

Standard lymphadenectomy for prostate cancer is limited to the obturator lymph nodes (LNs), although the internal and external iliac LNs represent the primary landing zone for prostatic lymphatic drainage. We performed anatomically semi-extended pelvic lymph node dissection (PLND) to assess the incidence of LN metastasis in cases of clinically localized prostate cancer. A total of 730 consecutive patients underwent radical prostatectomy with either semi-extended PLND, comprising 6 selective fields, namely the external iliac, internal iliac and obturator LNs bilaterally, or standard LND (obturator LNs alone). A total of 131 patients undergoing semi-extended PLND were compared with 599 patients undergoing standard LND. The patients were stratified into high-risk [prostate-specific antigen (PSA)>20 ng/ml, Gleason score (GS)≥8], intermediate-risk (PSA 10-20 ng/ml, GS=4+3) and low-risk (PSA<10 ng/ml, GS≤3+4) subgroups. Following semi-extended LND, positive LNs were detected in 12/61 (20%) of the high-risk, 1/30 (3%) of the intermediate-risk and 0/40 (0%) of the low-risk cases. Following standard LND, positive LNs were detected in 13/182 (7%) of the high-risk, 1/164 (0.6%) of the intermediate-risk and 0/253 (0%) of the low-risk cases. In high-risk patients, the detection rate of LN metastasis was significantly higher following extended LND compared with standard LND (P<0.01). In 9 of 13 patients (69%), metastases were identified in the internal and external iliac regions, despite negative obturator LNs. There were no significant differences regarding intraoperative and postoperative complications or blood loss in the two groups. There was no lymphocele formation in patients undergoing either standard or semi-extended LND. Extended pelvic LND (PLND) is associated with a high rate of LN metastasis detection outside the fields of standard LND in cases with clinically localized prostate cancer. Therefore, LND including the internal and external iliac LNs should be performed in all patients with high-risk prostate cancer; however, in the low-risk group, PLND may be omitted.

Development of Environmental Education Programs for Protected Areas in Madagascar

ERIC Educational Resources Information Center

Ormsby, Alison

2007-01-01

Environmental education programs for schools in the peripheral zone of protected areas in Madagascar are still needed in numerous locations. My research investigated the status of environmental education and communication (EE&C) programs at Masoala National Park, Madagascar, as well as the attitudes of local residents toward the park and park…

Lead isotopes reveal bilateral asymmetry and vertical continuity in the Hawaiian mantle plume.

PubMed

Abouchami, W; Hofmann, A W; Galer, S J G; Frey, F A; Eisele, J; Feigenson, M

2005-04-14

The two parallel chains of Hawaiian volcanoes ('Loa' and 'Kea') are known to have statistically different but overlapping radiogenic isotope characteristics. This has been explained by a model of a concentrically zoned mantle plume, where the Kea chain preferentially samples a more peripheral portion of the plume. Using high-precision lead isotope data for both centrally and peripherally located volcanoes, we show here that the two trends have very little compositional overlap and instead reveal bilateral, non-concentric plume zones, probably derived from the plume source in the mantle. On a smaller scale, along the Kea chain, there are isotopic differences between the youngest lavas from the Mauna Kea and Kilauea volcanoes, but the 550-thousand-year-old Mauna Kea lavas are isotopically identical to Kilauea lavas, consistent with Mauna Kea's position relative to the plume, which was then similar to that of present-day Kilauea. We therefore conclude that narrow (less than 50 kilometres wide) compositional streaks, as well as the larger-scale bilateral zonation, are vertically continuous over tens to hundreds of kilometres within the plume.

Morphogenesis in Plants: Modeling the Shoot Apical Meristem, and Possible Applications

NASA Technical Reports Server (NTRS)

Mjolsness, Eric; Gor, Victoria; Meyerowitz, Elliot; Mann, Tobias

1998-01-01

A key determinant of overall morphogenesis in flowering plants such as Arabidopsis thaliana is the shoot apical meristem (growing tip of a shoot). Gene regulation networks can be used to model this system. We exhibit a very preliminary two-dimensional model including gene regulation and intercellular signaling, but omitting cell division and dynamical geometry. The model can be trained to have three stable regions of gene expression corresponding to the central zone, peripheral zone, and rib meristem. We also discuss a space-engineering motivation for studying and controlling the morphogenesis of plants using such computational models.

Selective Androgen Receptor Modulator RAD140 Is Neuroprotective in Cultured Neurons and Kainate-Lesioned Male Rats

PubMed Central

Jayaraman, Anusha; Christensen, Amy; Moser, V. Alexandra; Vest, Rebekah S.; Miller, Chris P.; Hattersley, Gary

2014-01-01

The decline in testosterone levels in men during normal aging increases risks of dysfunction and disease in androgen-responsive tissues, including brain. The use of testosterone therapy has the potential to increase the risks for developing prostate cancer and or accelerating its progression. To overcome this limitation, novel compounds termed “selective androgen receptor modulators” (SARMs) have been developed that lack significant androgen action in prostate but exert agonist effects in select androgen-responsive tissues. The efficacy of SARMs in brain is largely unknown. In this study, we investigate the SARM RAD140 in cultured rat neurons and male rat brain for its ability to provide neuroprotection, an important neural action of endogenous androgens that is relevant to neural health and resilience to neurodegenerative diseases. In cultured hippocampal neurons, RAD140 was as effective as testosterone in reducing cell death induced by apoptotic insults. Mechanistically, RAD140 neuroprotection was dependent upon MAPK signaling, as evidenced by elevation of ERK phosphorylation and inhibition of protection by the MAPK kinase inhibitor U0126. Importantly, RAD140 was also neuroprotective in vivo using the rat kainate lesion model. In experiments with gonadectomized, adult male rats, RAD140 was shown to exhibit peripheral tissue-specific androgen action that largely spared prostate, neural efficacy as demonstrated by activation of androgenic gene regulation effects, and neuroprotection of hippocampal neurons against cell death caused by systemic administration of the excitotoxin kainate. These novel findings demonstrate initial preclinical efficacy of a SARM in neuroprotective actions relevant to Alzheimer's disease and related neurodegenerative diseases. PMID:24428527

A phase 3 randomized controlled trial of the efficacy and safety of atrasentan in men with metastatic hormone-refractory prostate cancer.

PubMed

Carducci, Michael A; Saad, Fred; Abrahamsson, Per-Anders; Dearnaley, David P; Schulman, Claude C; North, Scott A; Sleep, Darryl J; Isaacson, Jeffrey D; Nelson, Joel B

2007-11-01

The objective of this study was to evaluate the efficacy and safety of atrasentan (Xinlay), a selective endothelin-A receptor antagonist, in patients with metastatic hormone-refractory prostate cancer (HRPC). This multinational, double-blind, placebo-controlled trial enrolled 809 men with metastatic HRPC. Patients were randomized 1:1 to receive either atrasentan 10 mg per day or placebo. The primary endpoint was time to disease progression (TTP), which was determined according to radiographic and clinical measures. Analyses of overall survival and changes in biomarkers also were performed. Atrasentan did not reduce the risk of disease progression relative to placebo (hazards ratio, 0.89; 95% confidence interval, 0.76-1.04; P = .136). Most patients progressed radiographically at the first 12-week bone scan without concomitant clinical progression. In exploratory analyses, increases from baseline to final bone alkaline phosphatase (BAP) and prostate-specific antigen (PSA) levels were significantly lower with atrasentan treatment (P < .05 for each). The median time to BAP progression (>/=50% increase from nadir) was twice as long with atrasentan treatment (505 days vs 254 days; P < .01). The delay in time to PSA progression did not reach statistical significance. Atrasentan generally was tolerated well, and the most common adverse events associated with treatment were headache, rhinitis, and peripheral edema, reflecting the vasodilatory and fluid-retention properties of endothelin-A receptor antagonism. Atrasentan did not delay disease progression in men with metastatic HRPC despite evidence of biologic effects on PSA and BAP as markers of disease burden.

Expression of the IGF and the aromatase/estrogen receptor systems in human adrenal tissues from early infancy to late puberty: implications for the development of adrenarche.

PubMed

Belgorosky, Alicia; Baquedano, María Sonia; Guercio, Gabriela; Rivarola, Marco A

2009-03-01

Adrenarche is a process of postnatal sexual maturation occurring in higher primates, in which there is an increase in the secretion of adrenal androgens. It is the consequence of a process of postnatal organogenesis characterized by the development of a new zone in the adrenal cortex, the zona reticularis (ZR). The mechanism of this phenomenon remains poorly understood, suggesting that it might be a multifactorial event. A relationship between circulating IGF-I, insulin sensitivity, and adrenal androgens has been postulated. Boys and girls have different patterns of changes in insulin sensitivity at puberty, perhaps secondary to differences in the estrogen milieu. Estrogen effects may also play a role in premature adrenarche. Peripheral or local IGF-1 actions could regulate adrenal progenitor cell proliferation and migration. Since adrenal progenitor cells as well as IGF-I and the IGF-R1 are located in the outer zone of the adrenal cortex during childhood and adolescence, this peripheral cell layer, below the capsule, may contain undifferentiated progenitor cells. Therefore, the IGF-R1 signaling pathway might positively modulate the proliferation and migration of adrenal progenitor cell to stimulate the development of adrenal zones, including ZR. However, no evidence of a direct action of IGF-I on ZR was found. In addition, a role for estrogens in the ontogenesis of ZR is suggested by the presence of aromatase (CYP19) in the subcapsular zona glomerulosa and in the adrenal medulla. Estrogens produced locally could act on ZR by interacting with estrogen receptor beta (ERbeta), but not alpha, and membrane estrogen receptor GPR-30. An estradiol-induced increase in DHEA/cortisol ratio was indeed seen in cultures of adrenocortical cells from post-adrenarche adrenals. In summary, several lines of evidence point to the action of multiple factors, such as local adrenal maturational changes and peripheral metabolic signals, on postnatal human adrenal gland ZR formation.

Severe hypocalcaemia as a cause of seemingly idiopathic bilateral lower limb oedema.

PubMed

Hung, Aaron Karnell Dachuan

2014-01-10

The existing scientific literature has not drawn a link between severe hypocalcaemia and its role in recalcitrant peripheral oedema. This phenomenon is particularly relevant in oncological and geriatric medicine as bone strengthening but serum calcium-lowering agents such as bisphosphonates and denosumab are used for osteoporosis and/or bone metastasis. This case report, through metastatic prostate cancer in a 66-year-old man with bone metastasis being treated with a monoclonal antibody denosumab, proposes the mechanism of hypocalcaemic oedema as being akin to calcium deprivation such as those induced by calcium channel antagonism. It demonstrates the importance of calcium supplementation as a concurrent treatment while patients are on these osteoclast inhibiting agents.

Association between metabolic syndrome and intravesical prostatic protrusion in patients with benign prostatic enlargement and lower urinary tract symptoms (MIPS Study).

PubMed

Russo, Giorgio I; Regis, Federica; Spatafora, Pietro; Frizzi, Jacopo; Urzì, Daniele; Cimino, Sebastiano; Serni, Sergio; Carini, Marco; Gacci, Mauro; Morgia, Giuseppe

2018-05-01

To investigate the association between metabolic syndrome (MetS) and morphological features of benign prostatic enlargement (BPE), including total prostate volume (TPV), transitional zone volume (TZV) and intravesical prostatic protrusion (IPP). Between January 2015 and January 2017, 224 consecutive men aged >50 years presenting with lower urinary tract symptoms (LUTS) suggestive of BPE were recruited to this multicentre cross-sectional study. MetS was defined according to International Diabetes Federation criteria. Multivariate linear and logistic regression models were performed to verify factors associated with IPP, TZV and TPV. Patients with MetS were observed to have a significant increase in IPP (P < 0.01), TPV (P < 0.01) and TZV (P = 0.02). On linear regression analysis, adjusted for age and metabolic factors of MetS, we found that high-density lipoprotein (HDL) cholesterol was negatively associated with IPP (r = -0.17), TPV (r = -0.19) and TZV (r = -0.17), while hypertension was positively associated with IPP (r = 0.16), TPV (r = 0.19) and TZV (r = 0.16). On multivariate logistic regression analysis adjusted for age and factors of MetS, hypertension (categorical; odds ratio [OR] 2.95), HDL cholesterol (OR 0.94) and triglycerides (OR 1.01) were independent predictors of TPV ≥ 40 mL. We also found that HDL cholesterol (OR 0.86), hypertension (OR 2.0) and waist circumference (OR 1.09) were significantly associated with TZV ≥ 20 mL. On age-adjusted logistic regression analysis, MetS was significantly associated with IPP ≥ 10 mm (OR 34.0; P < 0.01), TZV ≥ 20 mL (OR 4.40; P < 0.01) and TPV ≥ 40 mL (OR 5.89; P = 0.03). We found an association between MetS and BPE, demonstrating a relationship with IPP. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Examining Radiation-Induced In Vivo and In Vitro Gene Expression Changes of the Peripheral Blood in Different Laboratories for Biodosimetry Purposes: First RENEB Gene Expression Study.

PubMed

Abend, M; Badie, C; Quintens, R; Kriehuber, R; Manning, G; Macaeva, E; Njima, M; Oskamp, D; Strunz, S; Moertl, S; Doucha-Senf, S; Dahlke, S; Menzel, J; Port, M

2016-02-01

The risk of a large-scale event leading to acute radiation exposure necessitates the development of high-throughput methods for providing rapid individual dose estimates. Our work addresses three goals, which align with the directive of the European Union's Realizing the European Network of Biodosimetry project (EU-RENB): 1. To examine the suitability of different gene expression platforms for biodosimetry purposes; 2. To perform this examination using blood samples collected from prostate cancer patients (in vivo) and from healthy donors (in vitro); and 3. To compare radiation-induced gene expression changes of the in vivo with in vitro blood samples. For the in vitro part of this study, EDTA-treated whole blood was irradiated immediately after venipuncture using single X-ray doses (1 Gy/min(-1) dose rate, 100 keV). Blood samples used to generate calibration curves as well as 10 coded (blinded) samples (0-4 Gy dose range) were incubated for 24 h in vitro, lysed and shipped on wet ice. For the in vivo part of the study PAXgene tubes were used and peripheral blood (2.5 ml) was collected from prostate cancer patients before and 24 h after the first fractionated 2 Gy dose of localized radiotherapy to the pelvis [linear accelerator (LINAC), 580 MU/min, exposure 1-1.5 min]. Assays were run in each laboratory according to locally established protocols using either microarray platforms (2 laboratories) or qRT-PCR (2 laboratories). Report times on dose estimates were documented. The mean absolute difference of estimated doses relative to the true doses (Gy) were calculated. Doses were also merged into binary categories reflecting aspects of clinical/diagnostic relevance. For the in vitro part of the study, the earliest report time on dose estimates was 7 h for qRT-PCR and 35 h for microarrays. Methodological variance of gene expression measurements (CV ≤10% for technical replicates) and interindividual variance (≤twofold for all genes) were low. Dose estimates based on one gene, ferredoxin reductase (FDXR), using qRT-PCR were as precise as dose estimates based on multiple genes using microarrays, but the precision decreased at doses ≥2 Gy. Binary dose categories comprising, for example, unexposed compared with exposed samples, could be completely discriminated with most of our methods. Exposed prostate cancer blood samples (n = 4) could be completely discriminated from unexposed blood samples (n = 4, P < 0.03, two-sided Fisher's exact test) without individual controls. This could be performed by introducing an in vitro-to-in vivo correction factor of FDXR, which varied among the laboratories. After that the in vitro-constructed calibration curves could be used for dose estimation of the in vivo exposed prostate cancer blood samples within an accuracy window of ±0.5 Gy in both contributing qRT-PCR laboratories. In conclusion, early and precise dose estimates can be performed, in particular at doses ≤2 Gy in vitro. Blood samples of prostate cancer patients exposed to 0.09-0.017 Gy could be completely discriminated from pre-exposure blood samples with the doses successfully estimated using adjusted in vitro-constructed calibration curves.

Region-specific ischemia, neovascularization and macular oedema in treatment-naïve proliferative diabetic retinopathy.

PubMed

Lange, Jason; Hadziahmetovic, Majda; Zhang, Jingfa; Li, Weiye

2018-02-07

Region-specific pathology in proliferative diabetic retinopathy enhances our understanding and management of this disease. To investigate non-perfusion, neovascularization and macular oedema. A cross-sectional, observational, non-randomized study. Consecutive 43 eyes of 27 treatment-naïve patients. Ultra-widefield fluorescein angiography for studying specific zones, that is, far-peripheral zone, mid-peripheral zone and central retina (cr), and spectral-domain optical coherence tomography for analysing thickness of macular layers. Non-perfusion index (NPI) and neovascularization index (NVI) in different zones, thickness of cr, retinal nerve fibre layer, ganglion cell layer (GCL), inner nuclear layer (INL) and outer plexiform layer in parafoveal regions. The NPI of far-periphery and NVI of mid-periphery were the highest by one-way analysis of variance testing. Ischemic retina defined as high NPI in far-periphery was significantly related to macular oedema via a binary classification approach (P < 0.05). The ischemic retina was correlated with a decreased thickness of both retinal nerve fibre and GCL (P < 0.05); macular oedema was correlated with increased INL thickness (P < 0.0001). The region-specific correlation of NPI of far-periphery and NVI of mid-periphery, but not with central retinal thickness, suggests different pathogeneses of neovascularization and macular oedema. Retinal nerve fibre layer and GCL, both biomarkers of diabetic retinal neuronopathy, are associated with retinal ischemia, but not with macular oedema, suggesting that diabetic microangiopathy and neuronopathy possess distinct pathogenic pathways. The strong correlation between macular oedema and INL indicates that intracellular oedema is a determining factor of diabetic macular oedema. © 2018 Royal Australian and New Zealand College of Ophthalmologists.

Three-dimensional spheroid culture promotes odonto/osteoblastic differentiation of dental pulp cells.

PubMed

Yamamoto, Mioko; Kawashima, Nobuyuki; Takashino, Nami; Koizumi, Yu; Takimoto, Koyo; Suzuki, Noriyuki; Saito, Masahiro; Suda, Hideaki

2014-03-01

Three-dimensional (3D) spheroid culture is a method for creating 3D aggregations of cells and their extracellular matrix without a scaffold mimicking the actual tissues. The aim of this study was to evaluate the effects of 3D spheroid culture on the phenotype of immortalized mouse dental papilla cells (MDPs) that have the ability to differentiate into odontoblasts. We cultured MDPs for 1, 3, 7, and 14 days in 96-well low-attachment culture plates for 3D spheroid culture or flat-bottomed plates for two-dimensional (2D) monolayer culture. Cell proliferation and apoptosis were detected by immunohistochemical staining of Ki67 and cleaved caspase-3, respectively. Hypoxia was measured by the hypoxia probe LOX-1. Odonto/osteoblastic differentiation marker gene expression was evaluated by quantitative PCR. We also determined mineralized nodule formation, alkaline phosphatase (ALP) activity, and dentine matrix protein-1 (DMP1) expression. Vinculin and integrin signalling-related proteins were detected immunohistochemically. Odonto/osteoblastic marker gene expression and mineralized nodule formation were significantly up-regulated in 3D spheroid-cultured MDPs compared with those in 2D monolayer-cultured MDPs (p<0.05). Histologically, 3D spheroid colonies consisted of two compartments: a cell-dense peripheral zone and cell-sparse core zone. Proliferating cells with high ALP activity and DMP1 expression were found mainly in the peripheral zone that also showed strong expression of vinculin and integrin signalling-related proteins. In contrast, apoptotic and hypoxic cells were detected in the core zone. 3D spheroid culture promotes odonto/osteoblastic differentiation of MDPs, which may be mediated by integrin signalling. Copyright © 2013 Elsevier Ltd. All rights reserved.

Atomic force microscopy of torus-bearing pit membranes

Treesearch

Roland R. Dute; Thomas Elder

2011-01-01

Atomic force microscopy was used to compare the structures of dried, torus-bearing pit membranes from four woody species, three angiosperms and one gymnosperm. Tori of Osmanthus armatus are bipartite consisting of a pustular zone overlying parallel sets of microfibrils that form a peripheral corona. Microfibrils of the corona form radial spokes as they traverse the...

Transurethral canine prostatectomy with a cylindrically diffusing fiber

NASA Astrophysics Data System (ADS)

Cromeens, Douglas M.; Johnson, Douglas E.; Price, Roger E.

1994-09-01

In this study, visual laser ablation of the prostate (VLAP) was performed on eight mongrel dogs utilizing a cylindrically diffusing fiber attached to a 1.06 neodymium:YAG (Nd:YAG) laser. All dogs received one continuous dose totaling 15,000 J (25 W for 10 min) applied from the vesical neck to the colliculus seminalis. There was no visible hemorrhage from the lasing intraoperatively in any dog. Postoperative recovery was uneventful with no dog experiencing urinary incontinence and only one incident of dysuria with urinary retention during their observation period. Gross and histopathologic examinations of serial sections of the prostate were performed from 2 hours to 7 weeks postoperatively and demonstrated a consistent spherical zone of destruction 2.9 cm (average) in diameter. We believe the simplified fiber placement and complete lack of postoperative complications in this small group of dogs suggest that the cylindrically diffusing fiber offers significant advantage over laterally deflecting fibers for transurethral prostatectomies in the dog.

Methylation of subtelomeric repeat D4Z4 in peripheral blood leukocytes is associated with biochemical recurrence in localized prostate cancer patients.

PubMed

Han, Yuyan; Xu, Junfeng; Kim, Jeri; Wu, Xifeng; Gu, Jian

2017-08-01

Global DNA methylation may affect chromosome structure and genomic stability and is involved in carcinogenesis. In this study, we aimed to investigate whether methylation of pericentromeric repeat NBL2 and subtelomeric repeat D4Z4 in peripheral blood was associated with the aggressiveness of prostate cancer (PCa). We measured the methylation status of different CpG sites of NBL2 and D4Z4 in 795 PCa patients and compared their methylation levels among patients with different Gleason Score at diagnosis. We then analyzed the association of the NBL2 and D4Z4 methylation with the risk of biochemical recurrence (BCR) in patients receiving radical prostatectomy or radiotherapy using a multivariate Cox proportional hazards model. In addition, we used the Kaplan-Meier survival function and log-rank tests to assess BCR-free survival associated with D4Z4 methylation. There was no significant difference in methylation level of NBL2 and D4Z4 between clinically defined aggressive and non-aggressive PCa at diagnosis. However, the methylation of D4Z4 was associated with BCR, while the methylation of NBL2 was not. In tertile analysis, patients in the highest tertile of D4Z4 methylation had an increased risk of BCR (HR = 2.17, 95% CI 1.36-3.48) compared to patients in the lower tertiles after adjustment of age, body mass index, smoking status, pack year, D'Amico risk groups and treatments. Among the four CpG sites in this region, the association was mostly attributable to the methylation of the second CpG site of D4Z4. These data suggest that higher methylation in D4Z4 was associated with worse prognosis of localized PCa patients. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Impact of extended prostate biopsy including apical anterior region for cancer detection and prediction of surgical margin status for radical prostatectomy.

PubMed

Hashimoto, Kohei; Shinkai, Nobuo; Tanaka, Toshiaki; Masumori, Naoya

2017-06-01

We investigated diagnostic yield of initial biopsy and repeated biopsy including apical cores. We investigated 573 consecutive men with PSA of ≤20 ng/ml who underwent prostate biopsy between 2004 and 2013. The initial 14-core biopsy consisted of the sextant type, lateral sites at the base and middle, lateral apices (la) at anterior horn sites, and apical anterior sites (aa). The repeated 18-core biopsy consisted of the initial 14-core biopsy with four transition zone (TZ) sites at the base (tzb) and middle (tzm). Prostate cancer was diagnosed in 178 (38.9%) of 458 men with the initial 14-core biopsy, and 44 (38.3%) of 115 men with the repeated 18-core biopsy. In the initial biopsy setting, the unique cancer detection rate was high in apical sites (apex, la, and aa: 6.2%, 6.2% and 5.1%, respectively). In the repeated setting, it was high in the TZ site in addition to the apical site (apex, la, aa, tzm, and tzb: 6.8%, 6.8%, 11.4%, 9.1% and 11.4%, respectively). The positive SM rate at the apex was higher in patients whose cancer was detected only in sites other than the sextant region than for those in the sextant region (36.4% vs. 14.8%, P = 0.037). The initial 14-core and the repeated 18-core biopsy scheme including apical anterior cores are feasible for prostate cancer detection. We propose that apical biopsy cores can be used to predict not only the existence of cancer but also surgical margin status at the apex. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Pathological examination of radical prostatectomy specimens in men with very low risk disease at biopsy reveals distinct zonal distribution of cancer in black American men.

PubMed

Sundi, Debasish; Kryvenko, Oleksandr N; Carter, H Ballentine; Ross, Ashley E; Epstein, Jonathan I; Schaeffer, Edward M

2014-01-01

Of men with very low risk prostate cancer at biopsy recent evidence shows that black American men are at greater risk for adverse oncologic outcomes after radical prostatectomy. We studied radical prostatectomy specimens from black and white men at very low risk to determine whether there are systematic pathological differences. Radical prostatectomy specimens were evaluated in men with National Comprehensive Cancer Network® (NCCN) very low risk prostate cancer. At diagnosis all men underwent extended biopsy sampling (10 or more cores) and were treated in the modern Gleason grade era. We analyzed tumor volume, grade and location in 87 black and 89 white men. For each specimen the dominant nodule was defined as the largest tumor with the highest grade. Compared to white men, black men were more likely to have significant prostate cancer (61% vs 29%), Gleason 7 or greater (37% vs 11%, each p <0.001) and a volume of greater than 0.5 cm(3) (45% vs 21%, p = 0.001). Dominant nodules in black men were larger (median 0.28 vs 0.13 cm(3), p = 0.002) and more often anterior (51% vs 29%, p = 0.003). In men who underwent pathological upgrading the dominant nodule was also more frequently anterior in black than in white men (59% vs 0%, p = 0.001). Black men with very low risk prostate cancer at diagnosis have a significantly higher prevalence of anterior cancer foci that are of higher grade and larger volume. Enhanced imaging or anterior zone sampling may detect these significant anterior tumors, improving the outcome in black men considering active surveillance. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Patterns of peripheral retinal and central macula ischemia in diabetic retinopathy as evaluated by ultra-widefield fluorescein angiography.

PubMed

Sim, Dawn A; Keane, Pearse A; Rajendram, Ranjan; Karampelas, Michael; Selvam, Senthil; Powner, Michael B; Fruttiger, Marcus; Tufail, Adnan; Egan, Catherine A

2014-07-01

To investigate the association between peripheral and central ischemia in diabetic retinopathy. Retrospective, cross-sectional. Consecutive ultra-widefield fluorescein angiography images were collected from patients with diabetes over a 12-month period. Parameters quantified include the foveal avascular zone (FAZ) area, peripheral ischemic index, peripheral leakage index, and central retinal thickness measurements, as well as visual acuity. The peripheral ischemia or leakage index was calculated as the area of capillary nonperfusion or leakage, expressed as a percentage of the total retinal area. Forty-seven eyes of 47 patients were included. A moderate correlation was observed between the peripheral ischemia index and FAZ area (r = 0.49, P = .0001). A moderate correlation was also observed between the peripheral leakage index and FAZ area, but only in eyes that were laser naïve (r = 0.44, P = .02). A thinner retina was observed in eyes with macular ischemia (217 ± 81.8 μm vs 272 ± 36.0 μm) (P = .02), but not peripheral ischemia (258 ± 76.3 μm vs 276 ± 68.0 μm) (P = .24). The relationships between different patterns of peripheral and central macular pathology and visual acuity were evaluated in a step-wise multivariable regression model, and the variables that remained independently associated were age (r = 0.33, P = .03), FAZ area (r = 0.45, P = .02), and central retinal thickness (r = 0.38, P = .01), (R(2)-adjusted = 0.36). Ultra-widefield fluorescein angiography provides an insight into the relationships between diabetic vascular complications in the retinal periphery and central macula. Although we observed relationships between ischemia and vascular leakage in the macula and periphery, it was only macular ischemia and retinal thinning that was independently associated with a reduced visual function. Copyright © 2014 Elsevier Inc. All rights reserved.

Use of the holmium:YAG laser in urology.

PubMed

Johnson, D E; Cromeens, D M; Price, R E

1992-01-01

The tissue effects of a holmium:YAG (Ho:YAG) laser operating at a wavelength of 2.1 mu with a maximum power of 15 watts (W) and 10 different energy-pulse settings was systematically evaluated on kidney, bladder, prostate, ureteral, and vasal tissue in the dog. In addition, various urologic surgical procedures (partial nephrectomy, transurethral laser incision of the prostate, and laser-assisted vasovasostomy) were performed in the dog, and a laparoscopic pelvic lymph node dissection was carried out in a pig. Although the Ho:YAG laser has a strong affinity for water, precise tissue ablation was achieved in both the contact and non-contact mode when used endoscopically in a fluid medium to ablate prostatic and vesical tissue. Using the usual parameters for tissue destruction (blanching without charring), the depth of thermal injury in the bladder and ureter was kept superficial. In performing partial nephrectomies, a 2-fold reduction in the zone of coagulative necrosis was demonstrated compared to the use of the continuous wave Neodymium:YAG laser (Nd:YAG). When used through the laparoscope, the Ho:YAG laser provided precise cutting and, combined with electrocautery, allowed the dissection to proceed quickly and smoothly. Hemostatic control was adequate in all surgical procedures. Although the results of these investigations are preliminary, our initial experience with the Ho:YAG laser has been favorable and warrants further investigations.

Conduction block in the peripheral nervous system in experimental allergic encephalomyelitis

NASA Astrophysics Data System (ADS)

Pender, M. P.; Sears, T. A.

1982-04-01

Experimental allergic encephalomyelitis (EAE) has been widely studied as a model of multiple sclerosis, a central nervous system (CNS) disease of unknown aetiology. The clinical features of both EAE and multiple sclerosis provide the only guide to the progress and severity of these diseases, and are used to assess the response to treatment. In such comparisons the clinical features of EAE are assumed to be due to lesions in the CNS, but in this disease there is also histological evidence of damage to the peripheral nervous system1-8. However, the functional consequences of such peripheral lesions have been entirely ignored. To examine this we have studied nerve conduction in rabbits with EAE. We report here that most of the large diameter afferent fibres are blocked in the region of the dorsal root ganglion and at the dorsal root entry zone, thus accounting for the loss of tendon jerks and also, through the severe loss of proprioceptive information, the ataxia of these animals. We conclude that whenever clinical comparisons are made between EAE and multiple sclerosis, the pathophysiology associated with the histological damage of the peripheral nervous system must be taken into account.

Ipilimumab and Local Radiation Therapy in Treating Patients With Recurrent Melanoma, Non-Hodgkin Lymphoma, Colon, or Rectal Cancer

ClinicalTrials.gov

2017-01-12

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Colon Cancer; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Melanoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Rectal Cancer; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

Monoclonal Antibody Therapy Before Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoid Malignancies

ClinicalTrials.gov

2017-10-10

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

Methoxyamine and Fludarabine Phosphate in Treating Patients With Relapsed or Refractory Hematologic Malignancies

ClinicalTrials.gov

2015-08-12

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Chronic Lymphocytic Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

The ciliary marginal zone of the zebrafish retina: clonal and time-lapse analysis of a continuously growing tissue.

PubMed

Wan, Yinan; Almeida, Alexandra D; Rulands, Steffen; Chalour, Naima; Muresan, Leila; Wu, Yunmin; Simons, Benjamin D; He, Jie; Harris, William A

2016-04-01

Clonal analysis is helping us understand the dynamics of cell replacement in homeostatic adult tissues (Simons and Clevers, 2011). Such an analysis, however, has not yet been achieved for continuously growing adult tissues, but is essential if we wish to understand the architecture of adult organs. The retinas of lower vertebrates grow throughout life from retinal stem cells (RSCs) and retinal progenitor cells (RPCs) at the rim of the retina, called the ciliary marginal zone (CMZ). Here, we show that RSCs reside in a niche at the extreme periphery of the CMZ and divide asymmetrically along a radial (peripheral to central) axis, leaving one daughter in the peripheral RSC niche and the other more central where it becomes an RPC. We also show that RPCs of the CMZ have clonal sizes and compositions that are statistically similar to progenitor cells of the embryonic retina and fit the same stochastic model of proliferation. These results link embryonic and postembryonic cell behaviour, and help to explain the constancy of tissue architecture that has been generated over a lifetime. © 2016. Published by The Company of Biologists Ltd.

Macrophage migration inhibitory factor in lung tissue of idiopathic pulmonary fibrosis patients.

PubMed

Olivieri, Carmela; Bargagli, Elena; Inghilleri, Simona; Campo, Ilaria; Cintorino, Marcella; Rottoli, Paola

2016-06-01

Idiopathic pulmonary fibrosis (IPF) is a severe interstitial lung disorder characterized by a pattern of Usual Interstitial Pneumonia where the presence of fibroblastic foci is the hallmark of the disease. In the present study, we analyzed the migration inhibitory factor (MIF) expression in lung tissue of IPF patients compared with healthy controls and organizing pneumonia (OP) patients focusing into MIF potential role in fibroblastic foci development. The immunohistochemical analysis was performed in 10 IPF patients (7 male), 3 OP patients (2 male), and 3 healthy controls (all male) using the streptavidin-biotin method (Dako). In IPF samples, MIF resulted overexpressed in the areas of active fibrosis and, in particular, in the alveolar epithelium, bronchiolar epithelium, and in the peripheral zones of fibroblastic foci. Bronchiolar epithelium from organizing pneumonia patients resulted only weakly positive for MIF while no evidence of MIF expression was reported for alveolar epithelium. In the control subject group, MIF was unexpressed except for a weak presence in the bronchiolar epithelium. In conclusion, MIF is a pleiotropic cytokine involved in the pathogenesis of IPF being mainly expressed in the areas of remodeling and active fibrosis, in bronchiolar and alveolar epithelium, and in the peripheral zone of fibroblastic foci.

Effects of Preprocessing on Multi-Direction Properties of Aluminum Alloy Cold-Spray Deposits

NASA Astrophysics Data System (ADS)

Rokni, M. R.; Nardi, A. T.; Champagne, V. K.; Nutt, S. R.

2018-05-01

The effects of powder preprocessing (degassing at 400 °C for 6 h) on microstructure and mechanical properties of 5056 aluminum deposits produced by high-pressure cold spray were investigated. To investigate directionality of the mechanical properties, microtensile coupons were excised from different directions of the deposit, i.e., longitudinal, short transverse, long transverse, and diagonal and then tested. The results were compared to properties of wrought 5056 and the coating deposited with as-received 5056 Al powder and correlated with the observed microstructures. Preprocessing softened the particles and eliminated the pores within them, resulting in more extensive and uniform deformation upon impact with the substrate and with underlying deposited material. Microstructural characterization and finite element simulation indicated that upon particle impact, the peripheral regions experienced more extensive deformation and higher temperatures than the central contact zone. This led to more recrystallization and stronger bonding at peripheral regions relative to the contact zone area and yielded superior properties in the longitudinal direction compared with the short transverse direction. Fractography revealed that crack propagation takes place along the particle-particle interfaces in the transverse directions (caused by insufficient bonding and recrystallization), whereas through the deposited particles, fracture is dominant in the longitudinal direction.

Anorectal and Pelvic Pain.

PubMed

Bharucha, Adil E; Lee, Tae Hee

2016-10-01

Although pelvic pain is a symptom of several structural anorectal and pelvic disorders (eg, anal fissure, endometriosis, and pelvic inflammatory disease), this comprehensive review will focus on the 3 most common nonstructural, or functional, disorders associated with pelvic pain: functional anorectal pain (ie, levator ani syndrome, unspecified anorectal pain, and proctalgia fugax), interstitial cystitis/bladder pain syndrome, and chronic prostatitis/chronic pelvic pain syndrome. The first 2 conditions occur in both sexes, while the latter occurs only in men. They are defined by symptoms, supplemented with levator tenderness (levator ani syndrome) and bladder mucosal inflammation (interstitial cystitis). Although distinct, these conditions share several similarities, including associations with dysfunctional voiding or defecation, comorbid conditions (eg, fibromyalgia, depression), impaired quality of life, and increased health care utilization. Several factors, including pelvic floor muscle tension, peripheral inflammation, peripheral and central sensitization, and psychosocial factors, have been implicated in the pathogenesis. The management is tailored to symptoms, is partly supported by clinical trials, and includes multidisciplinary approaches such as lifestyle modifications and pharmacological, behavioral, and physical therapy. Opioids should be avoided, and surgical treatment has a limited role, primarily in refractory interstitial cystitis. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Fatty Acid Amide Hydrolase Inhibitor Treatment in Men With Chronic Prostatitis/Chronic Pelvic Pain Syndrome: An Adaptive Double-blind, Randomized Controlled Trial.

PubMed

Wagenlehner, Florian M E; van Till, J W Olivier; Houbiers, Jos G A; Martina, Reynaldo V; Cerneus, Dirk P; Melis, Joost H J M; Majek, Antoni; Vjaters, Egils; Urban, Michael; Ramonas, Henrikas; Shoskes, Daniel A; Nickel, J Curtis

2017-05-01

To examine the effect of a peripherally active fatty acid amide hydrolase (FAAH) inhibitor ASP3652 on safety and efficacy outcomes in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Inhibition of FAAH is hypothesized to reduce the excitability of urinary tract afferents including nociceptors. In this adaptive, randomized, double-blind, placebo-controlled study, adult male patients with moderate to severe CP/CPPS were treated for 12 weeks with an oral dose of ASP3652 (25, 75, 150, or 300 mg twice daily, or 300 mg once daily), or placebo. A Bayesian model was used for adaptive prospective modeling of randomization, study continuation decisions, and analysis of the efficacy variables. The study was stopped for futility at preplanned interim analysis when 239 patients were randomized (226 were included in the intention-to-treat set): the 25 mg group showed the largest reduction of the primary end point National Institutes of Health Chronic Prostatitis Symptom Index total score (7.0 points), but the placebo group showed a mean reduction of 7.3 points (difference: 0.3 [95% confidence interval: -1.9, 2.6]). Micturition outcomes improved compared with placebo in all ASP3652 groups; for example, in the 300 mg twice daily group, voiding frequency decreased by -1.10 (95% CI: -2.0, -0.2) voids/24 hours vs placebo. Safety outcomes were comparable across the treatment groups. ASP3652 was generally safe and well-tolerated. It did not show efficacy on pain symptoms in patients with CP/CPPS. However, the results indicate that FAAH inhibition may attenuate lower urinary tract symptoms. Dedicated studies in patients with lower urinary tract dysfunction are needed to confirm this. Copyright © 2017 Elsevier Inc. All rights reserved.

Molecular Mechanism of Active Zone Organization at Vertebrate Neuromuscular Junctions

PubMed Central

Nishimune, Hiroshi

2013-01-01

Organization of presynaptic active zones is essential for development, plasticity, and pathology of the nervous system. Recent studies indicate a trans-synaptic molecular mechanism that organizes the active zones by connecting the pre- and the postsynaptic specialization. The presynaptic component of this trans-synaptic mechanism is comprised of cytosolic active zone proteins bound to the cytosolic domains of voltage-dependent calcium channels (P/Q-, N-, and L-type) on the presynaptic membrane. The postsynaptic component of this mechanism is the synapse organizer (laminin β2) that is expressed by the postsynaptic cell and accumulates specifically on top of the postsynaptic specialization. The pre- and the postsynaptic components interact directly between the extracellular domains of calcium channels and laminin β2 to anchor the presynaptic protein complex in front of the postsynaptic specialization. Hence, the presynaptic calcium channel functions as a scaffolding protein for active zone organization and as an ion-conducting channel for synaptic transmission. In contrast to the requirement of calcium influx for synaptic transmission, the formation of the active zone does not require the calcium influx through the calcium channels. Importantly, the active zones of adult synapses are not stable structures and require maintenance for their integrity. Furthermore, aging or diseases of the central and peripheral nervous system impair the active zones. This review will focus on the molecular mechanisms that organize the presynaptic active zones and summarize recent findings at the neuromuscular junctions and other synapses. PMID:22135013

Pilot study of a novel tool for input-free automated identification of transition zone prostate tumors using T2- and diffusion-weighted signal and textural features.

PubMed

Stember, Joseph N; Deng, Fang-Ming; Taneja, Samir S; Rosenkrantz, Andrew B

2014-08-01

To present results of a pilot study to develop software that identifies regions suspicious for prostate transition zone (TZ) tumor, free of user input. Eight patients with TZ tumors were used to develop the model by training a Naïve Bayes classifier to detect tumors based on selection of most accurate predictors among various signal and textural features on T2-weighted imaging (T2WI) and apparent diffusion coefficient (ADC) maps. Features tested as inputs were: average signal, signal standard deviation, energy, contrast, correlation, homogeneity and entropy (all defined on T2WI); and average ADC. A forward selection scheme was used on the remaining 20% of training set supervoxels to identify important inputs. The trained model was tested on a different set of ten patients, half with TZ tumors. In training cases, the software tiled the TZ with 4 × 4-voxel "supervoxels," 80% of which were used to train the classifier. Each of 100 iterations selected T2WI energy and average ADC, which therefore were deemed the optimal model input. The two-feature model was applied blindly to the separate set of test patients, again without operator input of suspicious foci. The software correctly predicted presence or absence of TZ tumor in all test patients. Furthermore, locations of predicted tumors corresponded spatially with locations of biopsies that had confirmed their presence. Preliminary findings suggest that this tool has potential to accurately predict TZ tumor presence and location, without operator input. © 2013 Wiley Periodicals, Inc.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bednarz, Natalia; Eltze, Elke; Semjonow, Axel

A recent study concluded that serum prostate specific antigen (PSA)-based screening is beneficial for reducing the lethality of PCa, but was also associated with a high risk of 'overdiagnosis'. Nevertheless, also PCa patients who suffered from organ confined tumors and had negative bone scans succumb to distant metastases after complete tumor resection. It is reasonable to assume that those tumors spread to other organs long before the overt manifestation of metastases. Our current results confirm that prostate tumors are highly heterogeneous. Even a small subpopulation of cells bearing BRCA1 losses can initiate PCa cell regional and distant dissemination indicating thosemore » patients which might be at high risk of metastasis. A preliminary study performed on a small cohort of multifocal prostate cancer (PCa) detected BRCA1 allelic imbalances (AI) among circulating tumor cells (CTCs). The present analysis was aimed to elucidate the biological and clinical role of BRCA1 losses on metastatic spread and tumor progression in prostate cancer patients. Experimental Design: To map molecular progression in PCa outgrowth we used FISH analysis of tissue microarrays (TMA), lymph node sections and CTC from peripheral blood. We found that 14% of 133 tested patients carried monoallelic BRCA1 loss in at least one tumor focus. Extended molecular analysis of chr17q revealed that this aberration was often a part of larger cytogenetic rearrangement involving chr17q21 accompanied by AI of the tumor suppressor gene PTEN and lack of the BRCA1 promoter methylation. The BRCA1 losses correlated with advanced T stage (p < 0.05), invasion to pelvic lymph nodes (LN, p < 0.05) as well as BR (p < 0.01). Their prevalence was twice as high within 62 LN metastases (LNMs) as in primary tumors (27%, p < 0.01). The analysis of 11 matched primary PCa-LNM pairs confirmed the suspected transmission of genetic abnormalities between those two sites. In 4 of 7 patients with metastatic disease, BRCA1 losses appeared in a minute fraction of cytokeratin- and vimentin-positive CTCs. Small subpopulations of PCa cells bearing BRCA1 losses might be one confounding factor initiating tumor dissemination and might provide an early indicator of shortened disease-free survival.« less

Effects of 8-Year Treatment of Long-Acting Testosterone Undecanoate on Metabolic Parameters, Urinary Symptoms, Bone Mineral Density, and Sexual Function in Men With Late-Onset Hypogonadism.

PubMed

Permpongkosol, Sompol; Khupulsup, Kalayanee; Leelaphiwat, Supatra; Pavavattananusorn, Sarawan; Thongpradit, Supranee; Petchthong, Thanom

2016-08-01

The long-term effects of long-acting testosterone undecanoate (TU) and androgen receptor CAG repeat lengths in Thai men with late-onset hypogonadism (LOH) have not been reported. To analyze the 8-year follow-up effects of intramuscular TU therapy on metabolic parameters, urinary symptoms, bone mineral density, and sexual function and investigate CAG repeat lengths in men with LOH. We reviewed the medical records of 428 men with LOH who had been treated with TU and 5 patients were diagnosed with prostate cancer during TU therapy. There were 120 patients (mean age = 65.6 ± 8.9 years) who had 5 to 8 years of continuous TU supplementation and sufficiently completed records for analysis. Genomic DNA was extracted from peripheral blood and the CAG repeat region was amplified by polymerase chain reaction. Fragment analysis, sequencing, electropherography, and chromatography were performed. The main outcome measure was dynamic parameter changes during testosterone supplementation. TU did not improve all obesity parameters. A statistically significant decrease was found in waist circumference, percentage of body fat, glycated hemoglobin, cholesterol, low-density lipoprotein, and International Prostate Symptom Score (P < .05). TU did not produce differences in body mass index, high-density lipoprotein, triglyceride, or the Aging Male Symptoms score from baseline. However, a statistically significant increase was found in the level of testosterone, prostate-specific antigen, hematocrit, International Index of Erectile Function score, and vertebral and femoral bone mineral density (P < .05). No major adverse cardiovascular events or prostate cancer occurred during this study. The CAG repeat length was 14 to 28 and the median CAG length was 22. There was no association between CAG repeat length and any of the anthropometric measurements. Long-term TU treatment in men with LOH for up to 8 years appears to be safe, tolerable, and effective in correcting obesity parameters. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Salvia Hispanica Seed in Reducing Risk of Disease Recurrence in Patients With Non-Hodgkin Lymphoma

ClinicalTrials.gov

2018-02-05

Adult Nasal Type Extranodal NK/T-Cell Lymphoma; Adult T-Cell Leukemia/Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; B Lymphoblastic Leukemia/Lymphoma; Blastic Plasmacytoid Dendritic Cell Neoplasm; Burkitt Leukemia; Central Nervous System Lymphoma; Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma; Diffuse Large B-Cell Lymphoma; Enteropathy-Associated T-Cell Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3 Follicular Lymphoma; Hepatosplenic T-Cell Lymphoma; Lymphoplasmacytic Lymphoma; Mantle Cell Lymphoma; Mediastinal (Thymic) Large B-Cell Lymphoma; Mycosis Fungoides; Nasal Type Extranodal NK/T-Cell Lymphoma; Nodal Marginal Zone Lymphoma; Peripheral T-Cell Lymphoma, Not Otherwise Specified; Post-Transplant Lymphoproliferative Disorder; Primary Cutaneous Anaplastic Large Cell Lymphoma; Primary Effusion Lymphoma; Sezary Syndrome; Splenic Marginal Zone Lymphoma; Subcutaneous Panniculitis-Like T-Cell Lymphoma; Systemic Anaplastic Large Cell Lymphoma; T Lymphoblastic Leukemia/Lymphoma; Transformed Recurrent Non-Hodgkin Lymphoma

[Radiation exposure of cultured tissue cells and animals (mice) within 10-kilometers zone of accident at Chernobyl nuclear plant. Effect on radiosensitivity to future radiation].

PubMed

Pelevina, I I; Afanasév, G G; Gotlib, V Ia; Alferovich, A A; Antoshchina, M M; Riabchenko, N I; Saenko, A S; Riabtsev, I A; Riabov, I N

1993-01-01

The effect of chronic low-level radiation exposure on radiosensitivity to posterior acute irradiation at high doses has been studied. Cells and mice were exposed within the ten-kilometer zone of Chernobyl disaster during various spaces of time (1-12 days), then over one or more days were additionally irradiated by doses of 1-4 Gy. It was shown that no adaptive response was developed under chronic exposure of cells and mice within the zone of disaster. On the contrary increased sensitivity to posterior irradiation was revealed. The number of cytogenetic damages of cultured tissue cells and marrow cells (chromosome aberrations and micronuclei) increases, the spectrum of aberrations being shifted to chromosome type, cells with multiaberration appearing. The decay of chromatine increases indicating an interphase death; the number of leucocytes in peripheral blood decreases.

Single-Cell RNA Sequencing of Lymph Node Stromal Cells Reveals Niche-Associated Heterogeneity.

PubMed

Rodda, Lauren B; Lu, Erick; Bennett, Mariko L; Sokol, Caroline L; Wang, Xiaoming; Luther, Sanjiv A; Barres, Ben A; Luster, Andrew D; Ye, Chun Jimmie; Cyster, Jason G

2018-05-15

Stromal cells (SCs) establish the compartmentalization of lymphoid tissues critical to the immune response. However, the full diversity of lymph node (LN) SCs remains undefined. Using droplet-based single-cell RNA sequencing, we identified nine peripheral LN non-endothelial SC clusters. Included are the established subsets, Ccl19 hi T-zone reticular cells (TRCs), marginal reticular cells, follicular dendritic cells (FDCs), and perivascular cells. We also identified Ccl19 lo TRCs, likely including cholesterol-25-hydroxylase + cells located at the T-zone perimeter, Cxcl9 + TRCs in the T-zone and interfollicular region, CD34 + SCs in the capsule and medullary vessel adventitia, indolethylamine N-methyltransferase + SCs in the medullary cords, and Nr4a1 + SCs in several niches. These data help define how transcriptionally distinct LN SCs support niche-restricted immune functions and provide evidence that many SCs are in an activated state. Copyright © 2018 Elsevier Inc. All rights reserved.

Urban vegetation and thermal patterns following city growth in different socio-economic contexts

NASA Astrophysics Data System (ADS)

Dronova, I.; Clinton, N.; Yang, J.; Radke, J.; Marx, S. S.; Gong, P.

2015-12-01

Urban expansion accompanied by losses of vegetated spaces and their ecological services raises significant concerns about the future of humans in metropolitan "habitats". Despite recent growth of urban studies globally, it is still not well understood how environmental effects of urbanization vary with the rate and socioeconomic context of development. Our study hypothesized that with urban development, spatial patterns of surface thermal properties and green plant cover would shift towards higher occurrence of relatively warmer and less vegetated spaces such as built-up areas, followed by losses of greener and cooler areas such as urban forests, and that these shifts would be more pronounced with higher rate of economic and/or population growth. To test these ideas, we compared 1992-2011 changes in remotely sensed patterns of green vegetation and surface temperature in three example cities that experienced peripheral growth under contrasting socio-economic context - Dallas, TX, USA, Beijing, China and Kyiv, Ukraine. To assess their transformation, we proposed a metric of thermal-vegetation angle (TVA) estimated from per-pixel proxies of vegetation greenness and surface temperature from Landsat satellite data and examined changes in TVA distributions within each city's core and two decadal zones of peripheral sprawl delineated from nighttime satellite data. We found that higher economic and population growth were coupled with more pronounced changes in TVA distributions, and more urbanized zones often exhibited higher frequencies of warmer, less green than average TVA values with novel patterns such as "cooler" clusters of building shadows. Although greener and cooler spaces generally diminished with development, they remained relatively prevalent in low-density residential areas of Dallas and peripheral zones of Kyiv with exurban subsistence farming. Overall, results indicate that the effects of modified green space and thermal patterns within growing cities highly vary depending on economy, population trends and historical legacies of planned green spaces. Remote sensing-based metrics such as TVA facilitate their comparisons and offer useful strategies to cost-effectively monitor urban transformation and inform more explicit environmental modeling of cities in the future.

Comparative Effectiveness of Targeted Prostate Biopsy Using Magnetic Resonance Imaging Ultrasound Fusion Software and Visual Targeting: a Prospective Study.

PubMed

Lee, Daniel J; Recabal, Pedro; Sjoberg, Daniel D; Thong, Alan; Lee, Justin K; Eastham, James A; Scardino, Peter T; Vargas, Hebert Alberto; Coleman, Jonathan; Ehdaie, Behfar

2016-09-01

We compared the diagnostic outcomes of magnetic resonance-ultrasound fusion and visually targeted biopsy for targeting regions of interest on prostate multiparametric magnetic resonance imaging. Patients presenting for prostate biopsy with regions of interest on multiparametric magnetic resonance imaging underwent magnetic resonance imaging targeted biopsy. For each region of interest 2 visually targeted cores were obtained, followed by 2 cores using a magnetic resonance-ultrasound fusion device. Our primary end point was the difference in the detection of high grade (Gleason 7 or greater) and any grade cancer between visually targeted and magnetic resonance-ultrasound fusion, investigated using McNemar's method. Secondary end points were the difference in detection rate by biopsy location using a logistic regression model and the difference in median cancer length using the Wilcoxon signed rank test. We identified 396 regions of interest in 286 men. The difference in the detection of high grade cancer between magnetic resonance-ultrasound fusion biopsy and visually targeted biopsy was -1.4% (95% CI -6.4 to 3.6, p=0.6) and for any grade cancer the difference was 3.5% (95% CI -1.9 to 8.9, p=0.2). Median cancer length detected by magnetic resonance-ultrasound fusion and visually targeted biopsy was 5.5 vs 5.8 mm, respectively (p=0.8). Magnetic resonance-ultrasound fusion biopsy detected 15% more cancers in the transition zone (p=0.046) and visually targeted biopsy detected 11% more high grade cancer at the prostate base (p=0.005). Only 52% of all high grade cancers were detected by both techniques. We found no evidence of a significant difference in the detection of high grade or any grade cancer between visually targeted and magnetic resonance-ultrasound fusion biopsy. However, the performance of each technique varied in specific biopsy locations and the outcomes of both techniques were complementary. Combining visually targeted biopsy and magnetic resonance-ultrasound fusion biopsy may optimize the detection of prostate cancer. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Sombrero uplift above the Altiplano-Puna Magma Body: evidence of a ballooning mid-crustal diapir.

PubMed

Fialko, Yuri; Pearse, Jill

2012-10-12

The Altiplano-Puna ultralow-velocity zone in the central Andes, South America, is the largest active magma body in Earth's continental crust. Space geodetic observations reported an uplift in the Altiplano-Puna proper at a rate of ~10 mm/year; however, the nature of the inferred inflation source has been uncertain. We present data showing that the uplift has persisted at a nearly constant rate over the past two decades, and is surrounded by a broad zone of subsidence. We show that the ongoing uplift and peripheral subsidence may result from a large mid-crustal diapir fed by partial melt from the Altiplano-Puna Magma Body.

State of some peripheral organs during laser puncture correction of ovarian functional deficiency

NASA Astrophysics Data System (ADS)

Vylegzhanina, T. A.; Kuznetsova, Tatiana I.; Maneeva, O.; Ryzhkovskaya, E. L.; Yemelianova, A.

2001-01-01

The findings from studies on structural and functional parameters of the adrenal, thyroid, and pineal glands in conditions of ovarian hypofunction and after its correction by laser puncture are presented. An experimentally induced hypofunction of the ovaries was shown to be accompanied by a decreased hormonal synthesis in the cortical fascicular zone. The epiphysis showed ultra structural signs of increased functional activity. Application of a helium-neon laser to biologically active points of the ovarian reflexogenic zone induced normalization of the ovarian cycle, potentiating of the adrenal functional state, and a decreased thyroid hormone production and abolished the activatory effect of the dark regime on the functional state of the pineal gland.

In vitro assessment of fiber sweeping angle during Q-switched 532-nm laser tissue ablation

NASA Astrophysics Data System (ADS)

Rajabhandharaks, Danop; Kang, Hyun Wook; Ko, Woo Jin; Stinson, Douglas; Choi, Benjamin

2011-03-01

Photoselective vaporization of the prostate (PVP) has been widely used to treat benign prostatic hyperplasia (BPH). It is well regarded as a safe and minimally invasive procedure and an alternative to the gold standard transurethral resection of the prostate (TURP). Despite of its greatness, as well aware of, the operative procedure time during the PVP is still prolonged. Such attempts have been tried out in order to shorten the operative time and increase its efficacy. However, scientific study to investigate techniques used during the PVP is still lacking. The objective of this study is to investigate how sweeping angle might affect the PVP performance. Porcine kidneys acquired from a local grocery store were used (N=140). A Q-switched 532-nm GreenLight XPSTM (American Medical Systems, Inc., MN, USA), together with 750- μm core MoXyTM fiber, was set to have power levels of 120 W and 180 W. Treatment speed and sweeping speed were fixed at 2 mm/s and 0.5 sweep/s, respectively. Sweeping angles were varied from 0 (no sweeping motion) to 120 degree. Ablation rate, depth, and coagulation zone were measured and quantified. Tissue ablation rate was peaked at 15 and 30 degree for both 120- and 180-W power levels and dramatically decreased beyond 60 degree. At 180 W, ablation rate increased 20% at 30 degree compared to 0 degree. This study demonstrated that ablation rate could be maximized and was contingent upon sweeping angle.

Wiskott-Aldrich syndrome protein deficiency in B cells results in impaired peripheral homeostasis

PubMed Central

Meyer-Bahlburg, Almut; Becker-Herman, Shirly; Humblet-Baron, Stephanie; Khim, Socheath; Weber, Michele; Bouma, Gerben; Thrasher, Adrian J.; Batista, Facundo D.

2008-01-01

To more precisely identify the B-cell phenotype in Wiskott-Aldrich syndrome (WAS), we used 3 distinct murine in vivo models to define the cell intrinsic requirements for WAS protein (WASp) in central versus peripheral B-cell development. Whereas WASp is dispensable for early bone marrow B-cell development, WASp deficiency results in a marked reduction in each of the major mature peripheral B-cell subsets, exerting the greatest impact on marginal zone and B1a B cells. Using in vivo bromodeoxyuridine labeling and in vitro functional assays, we show that these deficits reflect altered peripheral homeostasis, partially resulting from an impairment in integrin function, rather than a developmental defect. Consistent with these observations, we also show that: (1) WASp expression levels increase with cell maturity, peaking in those subsets exhibiting the greatest sensitivity to WASp deficiency; (2) WASp+ murine B cells exhibit a marked selective advantage beginning at the late transitional B-cell stage; and (3) a similar in vivo selective advantage is manifest by mature WASp+ human B cells. Together, our data provide a better understanding of the clinical phenotype of WAS and suggest that gene therapy might be a useful approach to rescue altered B-cell homeostasis in this disease. PMID:18687984

Dynamic impact of brief electrical nerve stimulation on the neural immune axis-polarization of macrophages toward a pro-repair phenotype in demyelinated peripheral nerve.

PubMed

McLean, Nikki A; Verge, Valerie M K

2016-09-01

Demyelinating peripheral nerves are infiltrated by cells of the monocyte lineage, including macrophages, which are highly plastic, existing on a continuum from pro-inflammatory M1 to pro-repair M2 phenotypic states. Whether one can therapeutically manipulate demyelinated peripheral nerves to promote a pro-repair M2 phenotype remains to be elucidated. We previously identified brief electrical nerve stimulation (ES) as therapeutically beneficial for remyelination, benefits which include accelerated clearance of macrophages, making us theorize that ES alters the local immune response. Thus, the impact of ES on the immune microenvironment in the zone of demyelination was examined. Adult male rat tibial nerves were focally demyelinated via 1% lysophosphatidyl choline (LPC) injection. Five days later, half underwent 1 hour 20 Hz sciatic nerve ES proximal to the LPC injection site. ES had a remarkable and significant impact, shifting the macrophage phenotype from predominantly pro-inflammatory/M1 toward a predominantly pro-repair/M2 one, as evidenced by an increased incidence of expression of M2-associated phenotypic markers in identified macrophages and a decrease in M1-associated marker expression. This was discernible at 3 days post-ES (8 days post-LPC) and continued at the 5 day post-ES (10 days post-LPC) time point examined. ES also affected chemokine (C-C motif) ligand 2 (CCL2; aka MCP-1) expression in a manner that correlated with increases and decreases in macrophage numbers observed in the demyelination zone. The data establish that briefly increasing neuronal activity favorably alters the immune microenvironment in demyelinated nerve, rapidly polarizing macrophages toward a pro-repair phenotype, a beneficial therapeutic concept that may extend to other pathologies. GLIA 2016;64:1546-1561. © 2016 Wiley Periodicals, Inc.

Multiple binding sites involved in the effect of choline esters on decarbamoylation of monomethylcarbamoyl- or dimethylcarbamoly-acetylcholinesterase.

PubMed Central

Sok, D E; Kim, Y B; Choi, S J; Jung, C H; Cha, S H

1994-01-01

Multiple binding sites for inhibitory choline esters in spontaneous decarbamoylation of dimethylcarbamoyl-acetylcholinesterase (AChE) were suggested from a wide range of IC50 values, in contrast with a limited range of AC50 values (concentration giving 50% of maximal activation) at a peripheral activatory site. Association of choline esters containing a long acyl chain (C7-C12) with the hydrophobic zone in the active site could be deduced from a linear relationship between the size of the acyl group and the inhibitory potency in either spontaneous decarbamoylation or acetylthiocholine hydrolysis. Direct support for laurylcholine binding to the active site might come from the competitive inhibition (Ki 33 microM) of choline-catalysed decarbamoylation by laurylcholine. Moreover, its inhibitory action was greater for monomethylcarbamoyl-AChE than for dimethylcarbamoyl-AChE, where there is a greater steric hindrance at the active centre. In further support, the inhibition of pentanoylthiocholine-induced decarbamoylation by laurylcholine was suggested to be due to laurylcholine binding to a central site rather than a peripheral site, similar to the inhibition of spontaneous decarbamoylation by laurylcholine. Supportive data for acetylcholine binding to the active site are provided by the results that acetylcholine is a competitive inhibitor (Ki 7.6 mM) of choline-catalysed decarbamoylation, and its inhibitory action was greater for monomethylcarbamoyl-AChE than for dimethylcarbamoyl-AChE. Meanwhile, choline esters with an acyl group of an intermediate size (C4-C6), more subject to steric exclusion at the active centre, and less associable with the hydrophobic zone, appear to bind preferentially to a peripheral activity site. Thus the multiple effects of choline esters may be governed by hydrophobicity and/or a steric effect exerted by the acyl moiety at the binding sites. PMID:8053896

Quantitative evaluation of treatment related changes on multi-parametric MRI after laser interstitial thermal therapy of prostate cancer

NASA Astrophysics Data System (ADS)

Viswanath, Satish; Toth, Robert; Rusu, Mirabela; Sperling, Dan; Lepor, Herbert; Futterer, Jurgen; Madabhushi, Anant

2013-03-01

Laser interstitial thermal therapy (LITT) has recently shown great promise as a treatment strategy for localized, focal, low-grade, organ-confined prostate cancer (CaP). Additionally, LITT is compatible with multi-parametric magnetic resonance imaging (MP-MRI) which in turn enables (1) high resolution, accurate localization of ablation zones on in vivo MP-MRI prior to LITT, and (2) real-time monitoring of temperature changes in vivo via MR thermometry during LITT. In spite of rapidly increasing interest in the use of LITT for treating low grade, focal CaP, very little is known about treatment-related changes following LITT. There is thus a clear need for studying post-LITT changes via MP-MRI and consequently to attempt to (1) quantitatively identify MP-MRI markers predictive of favorable treatment response and longer term patient outcome, and (2) identify which MP-MRI markers are most sensitive to post-LITT changes in the prostate. In this work, we present the first attempt at examining focal treatment-related changes on a per-voxel basis (high resolution) via quantitative evaluation of MR parameters pre- and post-LITT. A retrospective cohort of MP-MRI data comprising both pre- and post- LITT T2-weighted (T2w) and diffusion-weighted (DWI) acquisitions was considered, where DWI MRI yielded an Apparent Diffusion Co-efficient (ADC) map. A spatially constrained affine registration scheme was implemented to first bring T2w and ADC images into alignment within each of the pre- and post-LITT acquisitions, following which the pre- and post-LITT acquisitions were aligned. Pre- and post-LITT MR parameters (T2w intensity, ADC value) were then standardized to a uniform scale (to correct for intensity drift) and then quantified via the raw intensity values as well as via texture features derived from T2w MRI. In order to quantify imaging changes as a result of LITT, absolute differences were calculated between the normalized pre- and post-LITT MRI parameters. Quantitatively combining the ADC and T2w MRI parameters enabled construction of an integrated MP-MRI difference map that was highly indicative of changes specific to the LITT ablation zone. Preliminary quantitative comparison of the changes in different MR parameters indicated that T2w texture may be highly sensitive as well as specific in identifying changes within the ablation zone pre- and post-LITT. Visual evaluation of the differences in T2w texture features pre- and post-LITT also appeared to provide an indication of LITT-related effects such as edema. Our preliminary results thus indicate great potential for non-invasive MP-MRI imaging markers for determining focal treatment related changes, and hence long- and short-term patient outcome.

Color Fundus Photography versus Fluorescein Angiography in Identification of the Macular Center and Zone in Retinopathy of Prematurity

PubMed Central

Patel, Samir N.; Klufas, Michael A.; Ryan, Michael C.; Jonas, Karyn E.; Ostmo, Susan; Martinez-Castellanos, Maria Ana; Berrocal, Audina M.; Chiang, Michael F.; Chan, R.V. Paul

2016-01-01

Purpose To examine the utility of fluorescein angiography (FA) in identification of the macular center and the diagnosis of zone in patients with retinopathy of prematurity (ROP). Design Validity and reliability analysis of diagnostic tools Methods 32 sets (16 color fundus photographs; 16 color fundus photographs paired with the corresponding FA) of wide-angle retinal images obtained from 16 eyes of eight infants with ROP were compiled on a secure web site. 9 ROP experts (3 pediatric ophthalmologists; 6 vitreoretinal surgeons) participated in the study. For each image set, experts identified the macular center and provided a diagnosis of zone. Main Outcome Measures (1) Sensitivity and specificity of zone diagnosis (2) “Computer facilitated diagnosis of zone,” based on precise measurement of the macular center, optic disc center, and peripheral ROP. Results Computer facilitated diagnosis of zone agreed with the expert’s diagnosis of zone in 28/45 (62%) cases using color fundus photographs and in 31/45 (69%) cases using FA. Mean (95% CI) sensitivity for detection of zone I by experts as compared to a consensus reference standard diagnosis when interpreting the color fundus images alone versus interpreting the color fundus photographs and FA was 47% (35.3% – 59.3%) and 61.1% (48.9% – 72.4%), respectively, (t(9) ≥ (2.063), p = 0.073). Conclusions There is a marginally significant difference in zone diagnosis when using color fundus photographs compared to using color fundus photographs and the corresponding fluorescein angiograms. There is inconsistency between traditional zone diagnosis (based on ophthalmoscopic exam and image review) compared to a computer-facilitated diagnosis of zone. PMID:25637180

Color fundus photography versus fluorescein angiography in identification of the macular center and zone in retinopathy of prematurity.

PubMed

Patel, Samir N; Klufas, Michael A; Ryan, Michael C; Jonas, Karyn E; Ostmo, Susan; Martinez-Castellanos, Maria Ana; Berrocal, Audina M; Chiang, Michael F; Chan, R V Paul

2015-05-01

To examine the usefulness of fluorescein angiography (FA) in identifying the macular center and diagnosis of zone in patients with retinopathy of prematurity (ROP). Validity and reliability analysis of diagnostic tools. Thirty-two sets (16 color fundus photographs and 16 color fundus photographs paired with the corresponding FA images) of wide-angle retinal images obtained from 16 eyes of 8 infants with ROP were compiled on a secure web site. Nine ROP experts (3 pediatric ophthalmologists and 6 vitreoretinal surgeons) participated in the study. For each image set, experts identified the macular center and provided a diagnosis of zone. (1) Sensitivity and specificity of zone diagnosis and (2) computer-facilitated diagnosis of zone, based on precise measurement of the macular center, optic disc center, and peripheral ROP. Computer-facilitated diagnosis of zone agreed with the expert's diagnosis of zone in 28 (62%) of 45 cases using color fundus photographs and in 31 (69%) of 45 cases using FA images. Mean (95% confidence interval) sensitivity for detection of zone I by experts compared with a consensus reference standard diagnosis when interpreting the color fundus images alone versus interpreting the color fundus photographs and FA images was 47% (range, 35.3% to 59.3%) and 61.1% (range, 48.9% to 72.4%), respectively (t(9) ≥ (2.063); P = .073). There is a marginally significant difference in zone diagnosis when using color fundus photographs compared with using color fundus photographs and the corresponding FA images. There is inconsistency between traditional zone diagnosis (based on ophthalmoscopic examination and image review) compared with a computer-facilitated diagnosis of zone. Copyright © 2015 Elsevier Inc. All rights reserved.

'Presenting CXR phenotype of H1N1' flu compared with contemporaneous non-H1N1, community acquired pneumonia, during pandemic and post-pandemic outbreaks'.

PubMed

Minns, F C; Mhuineachain, A Ni; van Beek, E J R; Ritchie, G; Hill, A; Murchison, J T

2015-09-01

To review, phenotype and assess potential prognostic value of initial chest X-ray findings in patients with H1N1 influenza during seasonal outbreaks of 2009 and 2010, in comparison with non-H1N1, community acquired pneumonia (CAP). We retrospectively identified 72 patients admitted to hospital with pneumonia during the seasons of 2009 and 2010. H1N1 cases were confirmed by virology PCR. Presenting chest X-rays were jointly read by 2 radiologists, who were 'blinded' to further patient details and divided into 6 zones. Total number of opacified zones, the pattern and distribution of changes and length of hospital stay were recorded. Patients with H1N1 demonstrated more opacified zones (mean of 2.9 compared with 2.0; p=0.006), which were bilateral in two-thirds compared with a quarter of those with non-H1N1 CAP (p=0.001). H1N1 radiographs were more likely to be 'patchy' versus 'confluent' changes of non-H1N1 CAP (p=0.03) and more often demonstrated peripheral distribution (p=0.01). H1N1 patients tended to stay in hospital longer (not significant; p=0.08). A positive correlation existed between number of affected zones and length of inpatient stay, which was statistically significant for the cohorts combined (p=0.02). The findings were the same for the two evaluated seasons. H1N1 patients demonstrated more extensive disease, which was more likely bilateral, 'patchy', and peripheral in distribution. With increasing global cases of H1N1, knowledge of the typical findings of the H1N1 presenting chest X-ray may assist with early triage of patients, particularly where rapid viral testing is not available. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

SU-F-19A-07: Is a Day30 Scan Necessary to Evaluate Activity-Based Regulatory Compliance in Permanent Interstitial Brachytherapy for Prostate Cancer?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kapur, P; Ford, J; Moghanaki, D

Purpose: To evaluate the Medical Event (ME) criteria for I-125 prostate implants based on the assessment of post implant dosimetry on “Day0”/“Day30” imaging. The new ME criteria do not mandate a timeframe for this assessment. The compliance criteria are: more than 80% of the activity from the written directive for treatment site (TS) must be implanted inside TS, and doses to 1cc of either uninvolved rectum (D1-UR) or uninvolved bladder (D1-UB), or 2cc of other non-specified tissue (D2-UT) must be less than 150% of the planned dose. Methods: “Day0”/“Day30” post-implant analyses for 25 patients were evaluated. Treatment plans had amore » peripheral loading pattern with 2 core needles placed at least 10 mm away from urethra, with several seeds planned outside of the prostate for adequate target coverage. TS were a uniform 5 mm expansion of the prostate, except posteriorly (no expansion). Results: “Day0”/“Day30”analyses found no MEs. The relative changes for D1-UR, D1-UB, and D2-UT were (ranges): [−37.0, 38.2]%, [−96.5, 74.7]%, and [−41.2, 37.7]%. Furthermore, changes did not correlate with prostate volume changes of −18.7% [σ:16.0%, range:−60.5%, +6.4%]. These unfavorable changes did not lead to ME at “Day30” because these values were generally well below 150% at “Day0”. However, D2-UT dose values exceeded those for D1-UR and D1-UB at both “Day0”/“Day30”. Conclusion: The total activity was relatively insensitive to changes in target volume from “Day0” to ”Day30”. The dose metrics of interest, albeit susceptible to large, often unfavorable changes, remained less than the 150% threshold. Data from this study suggest that “Day0” can be used for the regulatory compliance evaluation. However, further evaluation at “Day30” is advisable if D2-UT is 110% or above (based on the largest D2-UT increase of 37.7% observed in this patient population). Future rigorous statistical analysis of a larger cohort will afford a refinement of this recommendation.« less

Lenalidomide With or Without Rituximab in Treating Patients With Progressive or Relapsed Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Prolymphocytic Leukemia, or Non-Hodgkin Lymphoma Previously Treated With Donor Stem Cell Transplant

ClinicalTrials.gov

2017-07-24

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Prolymphocytic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

Study of Akt Inhibitor MK2206 in Patients With Relapsed Lymphoma

ClinicalTrials.gov

2015-10-09

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

Etoposide, Filgrastim, and Plerixafor in Improving Stem Cell Mobilization in Treating Patients With Non-Hodgkin Lymphoma

ClinicalTrials.gov

2016-12-06

Adult Acute Lymphoblastic Leukemia in Remission; Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

Alisertib in Combination With Vorinostat in Treating Patients With Relapsed or Recurrent Hodgkin Lymphoma, B-Cell Non-Hodgkin Lymphoma, or Peripheral T-Cell Lymphoma

ClinicalTrials.gov

2018-04-10

Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Chronic Lymphocytic Leukemia; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Hepatosplenic T-Cell Lymphoma; Intraocular Lymphoma; Lymphomatous Involvement of Non-Cutaneous Extranodal Site; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Nodal Marginal Zone Lymphoma; Primary Cutaneous B-Cell Non-Hodgkin Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides and Sezary Syndrome; Recurrent Non-Hodgkin Lymphoma; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; T-Cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenstrom Macroglobulinemia

Density and Ultrasonic Characterization of Oil Palm Trunk Infected by Ganoderma Boninense Disease

NASA Astrophysics Data System (ADS)

Najmie, M. M. K.; Khalid, K.; Sidek, A. A.; Jusoh, M. A.

2011-01-01

Oil palm trunks infected by Ganoderma boninense disease have been studied using density and ultrasonic characterizations. The ultrasonic characterizations have been performed using a commercial ultrasonic instrument at the frequency of 54 kHz. The measurements have been done in 3 zones: inner zone, central zone and peripheral zone. It was found that the stem density of the oil palm infected by Ganoderma boninense disease was reduced by 50% in comparison to the original healthy trunk. From this effect the velocity of the ultrasonic wave propagated through the Longitudinal, Radial, and Tangential directions is lower for the trunk infected by Ganoderma boninense disease compared to a healthy trunk. For the 10 cm thickness of samples, the ultrasonic velocity for all transit directions was in range of 260 - 750 ms-1 for the infected sample, whereas for healthy samples was in the range of 460 - 900 ms-1. These results are very useful for the detection of the area which has been affected by the disease.

Chapter C: Hydrothermal Enrichment of Gallium in Zones of Advanced Argillic Alteration-Examples from the Paradise Peak and McDermitt Ore Deposits, Nevada

USGS Publications Warehouse

Rytuba, James J.; John, David A.; Foster, Andrea; Ludington, Steven D.; Kotlyar, Boris

2003-01-01

Gallium is produced as a byproduct from bauxite and zinc sulfide ores and rarely from primary Ga ores. High Ga contents (>60 ppm) can occur in zones of advanced argillic alteration consisting of alunite+kaolinite+quartz associated with quartz-alunite (high sulfidation Au-Ag) deposits. In a magmatic-hydrothermal environment, the zones of advanced argillic alteration associated with quartz-alunite (high sulfidation) Au-Ag deposits have the highest Ga contents (max 120 ppm). In these Au deposits, Ga is enriched in the zone of alunite+kaolinite alteration and depleted in the zone of quartz-rich alteration within acid-leached rocks. Peripheral zones of argillic alteration have Ga contents and Al/Ga ratios similar to those in unaltered volcanic rocks. The zones of advanced argillic alteration that formed in a steam-heated environment in association with hot-spring-type Hg-Au deposits are not Ga enriched, and residual silicified zones have very low Ga contents. The McDermitt Hg and Paradise Peak Au-Hg deposits, Nev., have zones of advanced argillic alteration that are Ga enriched. At the Paradise Peak Au-Hg deposits, Ga is enriched in the zone of alunite+jarosite alteration that formed in a magmatic-hydrothermal environment. Ga is depleted in the zone of opal+alunite alteration formed in a steam-heated environment, in residual silicified zones formed in a magmatic-hydrothermal environment, and in zones of supergene jarosite alteration. At the McDermitt Hg deposit, Ga is enriched in the zone of alunite+kaolinite alteration below the zone of adularia-quartz alteration that coincides with the Hg ore body. The spatial relation of Ga enrichment to alunite-kaolinite alteration suggests that formation in a magmatic-hydrothermal environment. X-ray-absorption spectra of Ga-enriched samples from the McDermitt Hg deposit are similar to that of gallium sulfate and support the association of Ga enrichment with alunite alteration.

DMEK lenticule preparation using an air dissection technique: central versus peripheral injection.

PubMed

Feizi, Sepehr; Javadi, Mohammad Ali

2016-01-01

To compare 2 sites of air injection to prepare donor lenticules for Descemet membrane (DM) endothelial keratoplasty. Fifty-one human corneoscleral buttons from donors aged 4 to 57 years were used. Corneoscleral buttons were placed endothelial side up and a 27-G needle was inserted just outside Schwalbe line and advanced immediately beneath the endothelium. Air was injected centrally inside the 8-mm zone (group 1) or peripherally approximately 1 mm in front of the limbus (group 2). Air injection was continued to extend the DM detachment as far as possible into the corneal periphery. Comparisons of central versus peripheral air injection were performed for reproducibility, the rate of usable tissue, and the type and diameter of the acquired bubble. The mean donor age was 30.0 ± 12.9 years. A big bubble was achieved following central or peripheral air injection in all cases. A usable donor lenticule (≥ 8.0 mm) was achieved in 95.7% of cases in group 1 and 89.3% of cases in group 2 (p>0.99). Both injection sites were comparable with regard to the diameter of the achieved bubbles (9.57 ± 2.11 mm versus 10.22 ± 2.34 mm, respectively, p = 0.32), the chance of complete DM detachment (39.1% versus 53.6%, respectively, p = 0.25), and the risk of bubble bursting (4.4% versus 7.1%, respectively, p = 0.41). The odds of a type 2 bubble increased by 11.86 for peripheral air injections compared to central injections (p = 0.01). Both injection sites exhibited comparable rates of usable donor lenticules. However, peripheral air injection was more likely to yield stroma-free grafts.

The Effect of Spectacle Lenses Containing Peripheral Defocus on Refractive Error and Horizontal Eye Shape in the Guinea Pig

PubMed Central

E. Bowrey, Hannah; Zeng, Guang; Y. Tse, Dennis; J. Leotta, Amelia; Wu, Yi; To, Chi-Ho; F. Wildsoet, Christine; McFadden, Sally A.

2017-01-01

Purpose It has been proposed that the peripheral retina, responding to local optical defocus, contributes to myopia and associated altered eye growth in humans. To test this hypothesis, we measured the changes in central (on-axis) and peripheral ocular dimensions in guinea pigs wearing a concentric bifocal spectacle lens design with power restricted to the periphery. Methods Five groups of guinea pigs (n = 83) wore either a unifocal (UF) spectacle lens (−4, 0, or +4 Diopters [D]), or a peripheral defocus (PF) spectacle lens that had a plano center (diameter of 5 mm) with either −4 or +4 D in the surround (−4/0 or +4/0 D). The overall optical diameter of all lenses was 12 mm. Lenses were worn over one eye from 8 to 18 days of age for negative and plano lenses, or from 8 to 22 days of age for positive lenses. Refractive error was measured centrally and 30° off-axis in the temporal and nasal retina. The shape of the eye was analyzed from images of sectioned eyes. Results Lenses of −4 D UF induced myopia, reflecting enhanced ocular elongation, which was centered on the optic nerve head and included the surrounding peripapillary zone (PPZ, 18° in diameter). Some ocular expansion, including within the PPZ, also was recorded with −4/0 and +4/0 D PF lenses while the +4 D UF lens inhibited rather than enhanced elongation, centrally and peripherally. Conclusions Peripheral defocus-induced ocular expansion encompasses the PPZ, irrespective of the sign of the inducing defocus. Understanding the underlying mechanism potentially has important implications for designing multifocal lenses for controlling myopia in humans and also potentially for understanding the link between myopia and glaucoma. PMID:28549092

Upregulation of autophagy and glycolysis markers in keloid hypoxic-zone fibroblasts: Morphological characteristics and implications.

PubMed

Ryoko, Okuno; Ito, Yuko; Eid, Nabil; Otsuki, Yoshinori; Kondo, Yoichi; Ueda, Koichi

2018-05-29

Keloid is a fibro-proliferative skin disorder with tumor-like behavior and dependence on anaerobic glycolysis (the Warburg effect), but its exact pathogenesis is unknown. Although autophagy is widely accepted as a lysosomal pathway for cell survival and cellular homeostasis (specifically upon exposure to stressors such as hypoxia), very few studies have investigated the involvement of autophagy and related glycolytic effectors in keloidogenesis. Here the authors examined the expression and cellular localization of autophagy proteins (LC3, pan-cathepsin), glycolytic markers (LDH, MCT1, MCT4) and the transcription factor HIF isoforms in human keloid samples using immunohistochemical analysis and double-labeling immunofluorescence methods. Based on H&E staining and expression of CD31, keloids were compartmentalized into hypoxic central and normoxic marginal zones. Vimentin-expressing fibroblasts in the central zone exhibited greater autophagy than their marginal-zone counterparts, as evidenced by increased LC3 puncta formation and co-localization with lysosomal pan-cathepsin. LDH (a lactate stimulator), MCT4 (a lactate exporter) and HIF-1 α expression levels were also higher in central-zone fibroblasts. Conversely, HIF-2 α expression was upregulated in fibroblasts and endothelial cells of the peripheral zone, while MCT1 was expressed in both zones. Taken together, these observations suggest that upregulation of autophagy and glycolysis markers in keloid hypoxic-zone fibroblasts may indicate a prosurvival mechanism allowing the extrusion of lactate to marginal-zone fibroblasts via metabolic coupling. The authors believe this is the first report on differential expression of autophagic and glycolytic markers in keloid-zone fibroblasts. The study results indicate that autophagy inhibitors and MCT4 blockers may have therapeutic implications in keloid treatment.

Label-free single-cell separation and imaging of cancer cells using an integrated microfluidic system

PubMed Central

Antfolk, Maria; Kim, Soo Hyeon; Koizumi, Saori; Fujii, Teruo; Laurell, Thomas

2017-01-01

The incidence of cancer is increasing worldwide and metastatic disease, through the spread of circulating tumor cells (CTCs), is responsible for the majority of the cancer deaths. Accurate monitoring of CTC levels in blood provides clinical information supporting therapeutic decision making, and improved methods for CTC enumeration are asked for. Microfluidics has been extensively used for this purpose but most methods require several post-separation processing steps including concentration of the sample before analysis. This induces a high risk of sample loss of the collected rare cells. Here, an integrated system is presented that efficiently eliminates this risk by integrating label-free separation with single cell arraying of the target cell population, enabling direct on-chip tumor cell identification and enumeration. Prostate cancer cells (DU145) spiked into a sample with whole blood concentration of the peripheral blood mononuclear cell (PBMC) fraction were efficiently separated and trapped at a recovery of 76.2 ± 5.9% of the cancer cells and a minute contamination of 0.12 ± 0.04% PBMCs while simultaneously enabling a 20x volumetric concentration. This constitutes a first step towards a fully integrated system for rapid label-free separation and on-chip phenotypic characterization of circulating tumor cells from peripheral venous blood in clinical practice. PMID:28425472

Label-free single-cell separation and imaging of cancer cells using an integrated microfluidic system.

PubMed

Antfolk, Maria; Kim, Soo Hyeon; Koizumi, Saori; Fujii, Teruo; Laurell, Thomas

2017-04-20

The incidence of cancer is increasing worldwide and metastatic disease, through the spread of circulating tumor cells (CTCs), is responsible for the majority of the cancer deaths. Accurate monitoring of CTC levels in blood provides clinical information supporting therapeutic decision making, and improved methods for CTC enumeration are asked for. Microfluidics has been extensively used for this purpose but most methods require several post-separation processing steps including concentration of the sample before analysis. This induces a high risk of sample loss of the collected rare cells. Here, an integrated system is presented that efficiently eliminates this risk by integrating label-free separation with single cell arraying of the target cell population, enabling direct on-chip tumor cell identification and enumeration. Prostate cancer cells (DU145) spiked into a sample with whole blood concentration of the peripheral blood mononuclear cell (PBMC) fraction were efficiently separated and trapped at a recovery of 76.2 ± 5.9% of the cancer cells and a minute contamination of 0.12 ± 0.04% PBMCs while simultaneously enabling a 20x volumetric concentration. This constitutes a first step towards a fully integrated system for rapid label-free separation and on-chip phenotypic characterization of circulating tumor cells from peripheral venous blood in clinical practice.

Radiculopathy in neuromyelitis optica. How does anti-AQP4 Ab involve PNS?

PubMed

Kim, Seungyeon; Park, Joonghyun; Kwon, Bum Sun; Park, Jin-Woo; Lee, Ho Jun; Choi, Jin-Ho; Nam, Kiyeun

2017-11-01

Until recently, the peripheral nervous system (PNS) had been known to be spared in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). However, some studies of late have reported PNS damage in demyelination diseases of the central nervous system (CNS) such as MS and NMOSD. Although multiple studies have reported characteristics reminiscent of peripheral neuropathy in MS, there have been limited reports in NMOSD. To investigate the incidence and pathology of peripheral neuropathy in NMOSD, we reviewed articles describing such cases including our own case. We performed a search of all clinical studies of peripheral neuropathy in NMOSD published up to December 17, 2016. We put no restrictions on language or year of publication in our search. The following keywords were searched: radiculopathy, peripheral nervous system diseases, neuromyelitis optica, neuromyelitis optica septrum disorder, aquaporin 4, electrodiagnosis, neural conduction and electromyography. We review ten cases (nine published reports and our own case study) of peripheral neuropathy in NMOSD. Each case could be confirmed as radiculopathy by electrodiagnostic (EDX) testing. Presently, there are two disparate viewpoints on peripheral neuropathy in NMOSD. In the first, aquaporin 4, which exists in the transitional zone of the CNS-PNS at the root level, may be the target of radiculitis in NMOSD. In the second, there may be some other unknown antibody to an axoglial antigen or something else that may play an active role in PNS damage. In our survey of ten case studies, the EDX results confirmed mixed axonal loss as well as demyelination type radiculopathy, which lends support to the first viewpoint. Pathophysiology of PNS damage in NMOSD might be due to radiculopathy. Although it seems to be rare, radiculopathy may actually be underestimated, and correspondingly underreported, due to its overlap with symptoms of myelitis. Therefore, further evaluation is needed to establish the incidence and pathophysiology of radiculopathy in NMOSD. Copyright © 2017 Elsevier B.V. All rights reserved.

Bone Marrow Biopsy: RNA Isolation with Expression Profiling in Men with Metastatic Castration-resistant Prostate Cancer—Factors Affecting Diagnostic Success

PubMed Central

Afonso, P. Diana; Vinson, Emily N.; Turnbull, James D.; Morris, Karla K.; Foye, Adam; Madden, John F.; Roy Choudhury, Kingshuk; Febbo, Phillip G.; George, Daniel J.

2013-01-01

Purpose To determine the rate at which computed tomographically guided pelvic percutaneous bone biopsy in men with metastatic castration-resistant prostate cancer (mCRPC) yields adequate tissue for genomic profiling and to identify issues likely to affect diagnostic yields. Materials and Methods This study was institutional review board approved, and written informed consent was obtained. In a phase II trial assessing response to everolimus, 31 men with mCRPC underwent 54 biopsy procedures (eight men before and 23 men both before and during treatment). Variables assessed were lesion location (iliac wing adjacent to sacroiliac joint, iliac wing anterior and/or superior to sacroiliac joint, sacrum, and remainder of pelvis), mean lesion attenuation, subjective lesion attenuation (purely sclerotic vs mixed), central versus peripheral lesion sampling, lesion size, core number, and use of zoledronic acid for more than 1 year. Results Of 54 biopsy procedures, 21 (39%) yielded adequate tissue for RNA isolation and genomic profiling. Three of four sacral biopsies were adequate. Biopsies of the ilium adjacent to the sacroiliac joints were more likely adequate than those from elsewhere in the ilium (48% vs 28%, respectively). All five biopsies performed in other pelvic locations yielded inadequate tissue for RNA isolation. Mean attenuation of lesions with inadequate tissue was 172 HU greater than those with adequate tissue (621.1 HU ± 166 vs 449 HU ± 221, respectively; P = .002). Use of zoledronic acid, peripheral sampling, core number, and lesion size affected yields, but the differences were not statistically significant. Histologic examination with hematoxylin-eosin staining showed that results of 36 (67%) biopsies were positive for cancer; only mean attenuation differences were significant (707 HU ± 144 vs 473 HU ± 191, negative vs positive, respectively; P < .001). Conclusion In men with mCRPC, percutaneous sampling of osseous metastases for genomic profiling is possible, but use of zoledronic acid for more than 1 year may reduce the yield of adequate tissue for RNA isolation. Sampling large low-attenuating lesions at their periphery maximizes yield. © RSNA, 2013 PMID:23925271

Longitude Position in a Time Zone and Cancer Risk in the United States.

PubMed

Gu, Fangyi; Xu, Shangda; Devesa, Susan S; Zhang, Fanni; Klerman, Elizabeth B; Graubard, Barry I; Caporaso, Neil E

2017-08-01

Background: Circadian disruption is a probable human carcinogen. From the eastern to western border of a time zone, social time is equal, whereas solar time is progressively delayed, producing increased discrepancies between individuals' social and biological circadian time. Accordingly, western time zone residents experience greater circadian disruption and may be at an increased risk of cancer. Methods: We examined associations between the position in a time zone and age-standardized county-level incidence rates for total cancers combined and 23 specific cancers by gender using the data of the Surveillance, Epidemiology, and End Results Program (2000-2012), including four million cancer diagnoses in white residents of 607 counties in 11 U.S. states. Log-linear regression was conducted, adjusting for latitude, poverty, cigarette smoking, and state. Bonferroni-corrected P values were used as the significance criteria. Results: Risk increased from east to west within a time zone for total and for many specific cancers, including chronic lymphocytic leukemia (both genders) and cancers of the stomach, liver, prostate, and non-Hodgkin lymphoma in men and cancers of the esophagus, colorectum, lung, breast, and corpus uteri in women. Conclusions: Risk increased from the east to the west in a time zone for total and many specific cancers, in accord with the circadian disruption hypothesis. Replications in analytic epidemiologic studies are warranted. Impact: Our findings suggest that circadian disruption may not be a rare phenomenon affecting only shift workers, but is widespread in the general population with broader implications for public health than generally appreciated. Cancer Epidemiol Biomarkers Prev; 26(8); 1306-11. ©2017 AACR . ©2017 American Association for Cancer Research.

Provenance of Mesozoic clastic rocks within the Bangong-Nujiang suture zone, central Tibet: Implications for the age of the initial Lhasa-Qiangtang collision

NASA Astrophysics Data System (ADS)

Li, Shun; Guilmette, Carl; Ding, Lin; Xu, Qiang; Fu, Jia-Jun; Yue, Ya-Hui

2017-10-01

The Bangong-Nujiang suture zone, separating the Lhasa and Qiangtang blocks of the Tibetan Plateau, is marked by remnants of the Bangong-Nujiang oceanic basin. In the Gaize area of central Tibet, Mesozoic sedimentary strata recording the evolution of the basin and subsequent collision between these two blocks include the Upper Triassic-Lower Jurassic turbidites of the Mugagangri Group, the Upper Jurassic-Lower Cretaceous sandstone-dominated Wuga and Shamuluo formations, and the Upper Cretaceous molasse deposits of the Jingzhushan Formation. The Shamuluo and Jingzhushan formations rest unconformably on the underlying Mugagangri Group and Wuga Formation, respectively. In this contribution, we analyze petrographic components of sandstones and U-Pb-Hf isotopic compositions of detrital zircons from the Wuga and Jingzhushan formations for the first time. Based on the youngest detrital zircon ages, the maximum depositional ages of the Wuga and Jingzhushan formations are suggested to be ∼147-150 Ma and ∼79-91 Ma, respectively. Petrographic and isotopic results indicate that sediments in the Wuga Formation were mainly sourced from the accretionary complex (preserved as the Mugagangri Group) in the north, while sediments in the Jingzhushan Formation have mixed sources from the Lhasa block, the Qiangtang block and the intervening suture zone. Provenance analysis, together with regional data, suggests that the Upper Jurassic-Lower Cretaceous Wuga and Shamuluo formations were deposited in a peripheral foreland basin and a residual-sea basin, respectively, in response to the Lhasa-Qiangtang collision, whereas the Upper Cretaceous Jingzhushan Formation reflects continental molasse deposition during the post-collisional stage. The development of the peripheral foreland basin evidenced by deposition of the Wuga Formation reveals that the age of the initial Lhasa-Qiangtang collision might be the latest Jurassic (∼150 Ma).

Inheritance of silicate differentiation during lunar origin by giant impact

NASA Technical Reports Server (NTRS)

Warren, Paul H.

1992-01-01

It is pointed out that the implication of the popular giant impact model of lunar origin (e.g., Hartmann and Davis, 1975; Cameron and Ward, 1976; Stevenson, 1987) is that any depth-related silicate differentiation within the impactor (and/or the earth) at the time of the impact must be partly inherited by the preferentially peripheral matter that forms the moon. This paper presents calculations of the magnitude of the net differentiation of the protolunar matter for a variety of elements and scenarios, with different assumptions regarding the geometries of the 'sampled' peripheral zones, the relative proportions of the earth-derived to impactor-derived matter in the final moon, and the degree to which the impactor mantle had crystallized prior to the giant impact. It is shown that these differention effects constrain the overall plausibility of the giant impact hypothesis.

Peripheral blood metabolic and inflammatory factors as biomarkers to ocular findings in diabetic macular edema.

PubMed

Figueras-Roca, Marc; Molins, Blanca; Sala-Puigdollers, Anna; Matas, Jessica; Vinagre, Irene; Ríos, José; Adán, Alfredo

2017-01-01

To study the association between peripheral blood metabolic and inflammatory factors and presence of diabetic macular edema (DME) and its related anatomic features in type 2 diabetic mellitus (T2DM) patients. Observational cross-sectional study on a proof of concept basis. Seventy-six T2DM included patients were divided based on the presence (n = 58) or absence of DME (n = 18) according to optical coherence tomography (OCT). Ultra-widefield fluorescein angiography (UWFA) was performed in DME patients. Fasting peripheral blood sample testing included glycemia, glycated hemoglobin, creatinin and lipid levels among others. Serum levels of a broad panel of cytokines and inflammatory mediators were also analysed. OCT findings included central subfoveal thickness, diffuse retinal thickness (DRT), cystoid macular edema (CME), serous retinal detachment and epirretinal membrane. UWFA items included pattern of DME, presence of peripheral retinal ischemia and enlarged foveal avascular zone (FAZ). Metabolic and inflammatory factors did not statistically differ between groups. However, several inflammatory mediators did associate to certain ocular items of DME cases: IL-6 was significantly higher in patients with DRT (p = 0.044), IL-10 was decreased in patients with CME (p = 0.012), and higher IL-8 (p = 0.031) and VEGF levels (p = 0.031) were observed in patients with enlarged FAZ. Inflammatory and metabolic peripheral blood factors in T2DM may not be differentially associated to DME when compared to non-DME cases. However, some OCT and UWFA features of DME such as DRT, CME and enlarged FAZ may be associated to certain systemic inflammatory mediators.

Vascular changes on fluorescein angiography of premature infants with low risk of retinopathy of prematurity after high oxygen exposure.

PubMed

Martinez-Castellanos, Maria Ana; Velez-Montoya, Raul; Price, Kenneth; Henaine-Berra, Andree; García-Aguirre, Gerardo; Morales-Canton, Virgilio; Cernichiaro-Espinosa, Linda Alejandra

2017-01-01

To describe a wide array of peripheral vascular changes using fluorescein angiography in preterm neonates, without high risk characteristics for developing retinopathy of prematurity, that were exposed to high oxygen concentration. Retrospective, two center, case series. Newborns at two different hospitals with ≥1500 g or gestational age of ≥32 weeks, fluorescein angiography performed, and with high oxygen exposure without adequate control were included. 294 infants diagnosed with ROP were analyzed. Only 28 eyes from 14 patients with peripheral vascular abnormalities in older and heavier babies were included. Two distinct type of peripheral vascular changes were observed: group 1 or non-proliferative: areas of capillary non-perfusion along with widespread arteriovenous shunting between adjacent primary vessels, tortuosity of primary vessels, abnormal budding of tertiary vessels and capillaries, abnormal capillary tufts and absence of foveal avascular zone; group 2 or proliferative: all of the characteristics of group 1 plus leakage of dye from the boundary between perfused and non-perfused retina and/or optic disc. Peripheral vascular abnormalities different from retinopathy of prematurity are observed in older than 32 weeks of gestational age, and heavier than 1500 g babies. This makes the authors classify these patients as having a disease caused solely by oxygen dysregulation at the neonatal intensive care unit similarly to the oxygen induced retinopathy in experimental studies.

CRMPs colocalize and interact with cytoskeleton in hippocampal neurons

PubMed Central

Yang, Yuhao; Zhao, Bo; Ji, Zhisheng; Zhang, Guowei; Zhang, Jifeng; Li, Sumei; Guo, Guoqing; Lin, Hongsheng

2015-01-01

CRMP family proteins (CRMPs) are widely expressed in the developing neurons, mediating a variety of fundamental functions such as growth cone guidance, neuronal polarity and axon elongation. However, whether all the CRMP proteins interact with cytoskeleton remains unknown. In this study, we found that in cultured hippocampal neurons, CRMPs mainly colocalized with tubulin and actin network in neurites. In growth cones, CRMPs colocalized with tubulinmainly in the central (C-) domain and transition zone (T-zone), less in the peripheral (P-) domain and colocalized with actin in all the C-domain, T-zone and P-domain. The correlation efficiency of CRMPs between actin was significantly higher than that between tubulin, especially in growth cones. We successfully constructed GST-CRMPs plasmids, expressed and purified the GST-CRMP proteins. By GST-pulldown assay, all the CRMP family proteins were found to beinteracted with cytoskeleton proteins. Taken together, we revealed that CRMPs were colocalized with cytoskeleton in hippocampal neurons, especially in growth cones. CRMPs can interact with both tubulin and actin, thus mediating neuronal development. PMID:26885211

An analysis of leukapheresis and central venous catheter use in the randomized, placebo controlled, phase 3 IMPACT trial of Sipuleucel-T for metastatic castrate resistant prostate cancer.

PubMed

Flanigan, Robert C; Polcari, Anthony J; Shore, Neil D; Price, Thomas H; Sims, Robert B; Maher, Johnathan C; Whitmore, James B; Corman, John M

2013-02-01

Sipuleucel-T is an autologous cellular immunotherapy. We review the safety of the leukapheresis procedure required for sipuleucel-T preparation and complications related to venous catheter use in the randomized, placebo controlled phase 3 IMPACT (IMmunotherapy for ProstAte Cancer Trial) study (NCT 00065442). A total of 512 patients with asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer were enrolled in the study. All patients were scheduled to undergo 3 standard 1.5 to 2.0 blood volume leukapheresis procedures at 2-week intervals. Leukapheresis related adverse events and those related to venous catheter use were reviewed. Immune cell counts were examined throughout the treatment course. Of 512 enrolled patients 506 underwent 1 or more leukapheresis procedures and were included in this analysis. Adverse events were comparable between the sipuleucel-T and control arms. Leukapheresis related adverse events were primarily associated with transient hypocalcemia (39.3%). Most leukapheresis related adverse events (97%) were of mild/moderate intensity. Median white blood cell count and absolute monocyte and lymphocyte counts were stable and within normal ranges throughout the treatment course. Of all patients 23.3% had a central venous catheter placed primarily for leukapheresis. Patients with vs without a central venous catheter had a higher risk of infection potentially related to catheter use (11.9% vs 1.3%, p <0.0001) and a trend toward a higher incidence of venous vascular events potentially related to catheter use, excluding the central nervous system (5.9% vs 2.1%, p = 0.06). Adverse events related to leukapheresis are manageable and quickly reversible. The majority of patients can undergo leukapheresis without a central venous catheter. Central venous catheters are associated with an increased risk of infections and venous vascular events. Peripheral intravenous access should be used when feasible. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Efficacy of cabazitaxel rechallenge in heavily treated patients with metastatic castration-resistant prostate cancer.

PubMed

Thibault, Constance; Eymard, Jean-Christophe; Birtle, Alison; Krainer, Michael; Baciarello, Giulia; Fléchon, Aude; Le Moulec, Sylvestre; Spaeth, Dominique; Laguerre, Brigitte; Caffo, Orazio; Deville, Jean-Laurent; Beuzeboc, Phillipe; Hasbini, Ali; Gross-Goupil, Marine; Helissey, Carole; Bennamoun, Mostefa; Hardy-Bessard, Anne-Claire; Oudard, Stéphane

2018-07-01

Treatment option in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel (DOC), cabazitaxel (CABA) and new hormone therapy (NHT) is limited. Rechallenge with DOC is limited because of cumulative toxicities. This study investigated the activity and safety of CABA rechallenge in mCRPC. Clinical data were collected retrospectively in 17 centres in Europe. Eligible patients had undergone rechallenge with cabazitaxel after three previous lines of treatment (DOC, NHT and CABA, in any order). Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. Data on toxicities were collected. A total of 69 of 562 patients (Eastern Cooperative Oncology Group performance status 0-1 69%) were rechallenged with CABA (25 mg/m 2 q3w, 58%; 20 mg/m 2 q3w, 27.5%; other, 14.5%) for 1-10 (median 6) cycles; 76.8% received prophylactic granulocyte colony-stimulating factor. Median radiological or clinical PFS with CABA rechallenge was 7.8 months and 11.9 months with initial CABA therapy. OS was 13.7 months (95% confidence interval [CI]: 9.3-15.7) from the first CABA rechallenge cycle, 59.9 months (47.8-67.1) from the first life-extending therapy in mCRPC and 78.3 months (66.4-90.7) from mCRPC diagnosis. Best clinical benefit was improved (34.3%) or stable (47.8%). Lack of response to rechallenge occurred in 17.9% of patients (3.1% with initial CABA). The level of prostate-specific antigen decreased by ≥ 50% in 24% of patients at rechallenge (71% with initial CABA). There was no grade ≥III peripheral neuropathy or nail disorders. CABA rechallenge may be a treatment option without cumulative toxicity in heavily pretreated patients with mCRPC who are still fit and had a progression >3 months after the last CABA injections. Copyright © 2018 Elsevier Ltd. All rights reserved.

Functional Characterization of Circulating Tumor Cells with a Prostate-Cancer-Specific Microfluidic Device

PubMed Central

Kirby, Brian J.; Jodari, Mona; Loftus, Matthew S.; Gakhar, Gunjan; Pratt, Erica D.; Chanel-Vos, Chantal; Gleghorn, Jason P.; Santana, Steven M.; Liu, He; Smith, James P.; Navarro, Vicente N.; Tagawa, Scott T.; Bander, Neil H.; Nanus, David M.; Giannakakou, Paraskevi

2012-01-01

Cancer metastasis accounts for the majority of cancer-related deaths owing to poor response to anticancer therapies. Molecular understanding of metastasis-associated drug resistance remains elusive due to the scarcity of available tumor tissue. Isolation of circulating tumor cells (CTCs) from the peripheral blood of patients has emerged as a valid alternative source of tumor tissue that can be subjected to molecular characterization. However, issues with low purity and sensitivity have impeded adoption to clinical practice. Here we report a novel method to capture and molecularly characterize CTCs isolated from castrate-resistant prostate cancer patients (CRPC) receiving taxane chemotherapy. We have developed a geometrically enhanced differential immunocapture (GEDI) microfluidic device that combines an anti-prostate specific membrane antigen (PSMA) antibody with a 3D geometry that captures CTCs while minimizing nonspecific leukocyte adhesion. Enumeration of GEDI-captured CTCs (defined as intact, nucleated PSMA+/CD45− cells) revealed a median of 54 cells per ml identified in CRPC patients versus 3 in healthy donors. Direct comparison with the commercially available CellSearch® revealed a 2–400 fold higher sensitivity achieved with the GEDI device. Confocal microscopy of patient-derived GEDI-captured CTCs identified the TMPRSS2:ERG fusion protein, while sequencing identified specific androgen receptor point mutation (T868A) in blood samples spiked with only 50 PC C4-2 cells. On-chip treatment of patient-derived CTCs with docetaxel and paclitaxel allowed monitoring of drug-target engagement by means of microtubule bundling. CTCs isolated from docetaxel-resistant CRPC patients did not show any evidence of drug activity. These measurements constitute the first functional assays of drug-target engagement in living circulating tumor cells and therefore have the potential to enable longitudinal monitoring of target response and inform the development of new anticancer agents. PMID:22558290

Superficial or deep implantation of motor nerve after denervation: an experimental study--superficial or deep implantation of motor nerve.

PubMed

Askar, Ibrahím; Sabuncuoglu, Bízden Tavíl

2002-01-01

Neurorraphy, conventional nerve grafting technique, and artificial nerve conduits are not enough for repair in severe injuries of peripheral nerves, especially when there is separation of motor nerve from muscle tissue. In these nerve injuries, reinnervation is indicated for neurotization. The distal end of a peripheral nerve is divided into fascicles and implanted into the aneural zone of target muscle tissue. It is not known how deeply fascicles should be implanted into muscle tissue. A comparative study of superficial and deep implantation of separated motor nerve into muscle tissue is presented in the gastrocnemius muscle of rabbits. In this experimental study, 30 white New Zealand rabbits were used and divided into 3 groups of 10 rabbits each. In the first group (controls, group I), only surgical exposure of the gastrocnemius muscle and motor nerve (tibial nerve) was done without any injury to nerves. In the superficial implantation group (group II), tibial nerves were separated and divided into their own fascicles. These fascicles were implanted superficially into the lateral head of gastrocnemius muscle-aneural zone. In the deep implantation group (group III), the tibial nerves were separated and divided into their own fascicles. These fascicles were implanted around the center of the muscle mass, into the lateral head of the gastrocnemius muscle-aneural zone. Six months later, histopathological changes and functional recovery of the gastrocnemius muscle were investigated. Both experimental groups had less muscular weight than in the control group. It was found that functional recovery was achieved in both experimental groups, and was better in the superficial implantation group than the deep implantation group. EMG recordings revealed that polyphasic and late potentials were frequently seen in both experimental groups. Degeneration and regeneration of myofibrils were observed in both experimental groups. New motor end-plates were formed in a scattered manner in both experimental groups. However, they were more dense in the superficial implantation group than the deep implantation group. It was concluded that superficial implantation has a more powerful contractile capacity than that of deep implantation. We believe that this might arise from the high activity of glycolytic enzymes in peripheral muscle fibers of gastrocnemius muscle, decrease in insufficient intramuscular guidance apparatus, and intramuscular microneuroma formation at the insufficient neuromuscular junction since the motor nerve had less route to muscle fibers. Copyright 2002 Wiley-Liss, Inc.

Cabazitaxel Plus Prednisone With Octreotide For Castration-Resistant Prostate Cancer (CRPC) Previously Treated With Docetaxel

ClinicalTrials.gov

2014-11-21

Diarrhea; Hormone-resistant Prostate Cancer; Recurrent Prostate Cancer; Stage I Prostate Cancer; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer; Stage III Prostate Cancer; Stage IV Prostate Cancer

Cutting Zone Temperature Identification During Machining of Nickel Alloy Inconel 718

NASA Astrophysics Data System (ADS)

Czán, Andrej; Daniš, Igor; Holubják, Jozef; Zaušková, Lucia; Czánová, Tatiana; Mikloš, Matej; Martikáň, Pavol

2017-12-01

Quality of machined surface is affected by quality of cutting process. There are many parameters, which influence on the quality of the cutting process. The cutting temperature is one of most important parameters that influence the tool life and the quality of machined surfaces. Its identification and determination is key objective in specialized machining processes such as dry machining of hard-to-machine materials. It is well known that maximum temperature is obtained in the tool rake face at the vicinity of the cutting edge. A moderate level of cutting edge temperature and a low thermal shock reduce the tool wear phenomena, and a low temperature gradient in the machined sublayer reduces the risk of high tensile residual stresses. The thermocouple method was used to measure the temperature directly in the cutting zone. An original thermocouple was specially developed for measuring of temperature in the cutting zone, surface and subsurface layers of machined surface. This paper deals with identification of temperature and temperature gradient during dry peripheral milling of Inconel 718. The measurements were used to identification the temperature gradients and to reconstruct the thermal distribution in cutting zone with various cutting conditions.

Rituximab in Treating Patients Undergoing Donor Peripheral Blood Stem Cell Transplant for Relapsed or Refractory B-cell Lymphoma

ClinicalTrials.gov

2017-12-05

B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

Persistence of Retinopathy of Prematurity in an Infant with Tetralogy of Fallot

PubMed Central

Celik, Gokhan; Uludag, Gunay

2016-01-01

We report an infant with tetralogy of fallot (TOF) who was born at 35 weeks of gestation and of 1700 g birth weight and presented with persistent retinopathy of prematurity (ROP) at 6 months of age. Follow-up ophthalmic examinations were done at 2, 3, and 4 weeks of age. A demarcation line in Zone II was noticed on the first ocular examination done at 4 weeks of postnatal age. At 6 months of postnatal age, the infant still had an avascular peripheral retina with the demarcation line in Zone II. Even though this index subject did not have any typical risk factors for ROP, TOF seems to be the probable reason for developing as well as persistence of avascular retina. PMID:27525147

Variable residence time vortex combustor

DOEpatents

Melconian, Jerry O.

1987-01-01

A variable residence time vortex combustor including a primary combustion chamber for containing a combustion vortex, and a plurality of louvres peripherally disposed about the primary combustion chamber and longitudinally distributed along its primary axis. The louvres are inclined to impel air about the primary combustion chamber to cool its interior surfaces and to impel air inwardly to assist in driving the combustion vortex in a first rotational direction and to feed combustion in the primary combustion chamber. The vortex combustor also includes a second combustion chamber having a secondary zone and a narrowed waist region in the primary combustion chamber interconnecting the output of the primary combustion chamber with the secondary zone for passing only lower density particles and trapping higher density particles in the combustion vortex in the primary combustion chamber for substantial combustion.

Corneal Epithelium Thickness Profile in 614 Normal Chinese Children Aged 7-15 Years Old.

PubMed

Ma, Yingyan; He, Xiangui; Zhu, Xiaofeng; Lu, Lina; Zhu, Jianfeng; Zou, Haidong

2016-03-23

The purpose of the study is to describe the values and distribution of corneal epithelium thickness (CET) in normal Chinese school-aged children, and to explore associated factors with CET. CET maps were measured by Fourier-domain optical coherence tomography (FD-OCT) in normal Chinese children aged 7 to 15 years old from two randomly selected schools in Shanghai, China. Children with normal intraocular pressure were further examined for cycloplegic autorefraction, corneal curvature radius (CCR) and axial length. Central (2-mm diameter area), para-central (2- to 5-mm diameter area), and peripheral (5- to 6-mm diameter area) CET in the superior, superotemporal, temporal, inferotemporal, inferior, inferonasal, nasal, superonasal cornea; minimum, maximum, range, and standard deviation of CET within the 5-mm diameter area were recorded. The CET was thinner in the superior than in the inferior and was thinner in the temporal than in the nasal. The maximum CET was located in the inferior zone, and the minimum CET was in the superior zone. A thicker central CET was associated with male gender (p = 0.009) and older age (p = 0.037) but not with CCR (p = 0.061), axial length (p = 0.253), or refraction (p = 0.351) in the multiple regression analyses. CCR, age, and gender were correlated with para-central and peripheral CET.

Geology and petroleum resources of Venezuela

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klemme, H.D.

1986-05-01

Venezuela occupies a peripheral position to the Guiana shield and craton in northern South America. The larger sedimentary basins of the Venezuelan craton zone are marginal cratonic basins (Lanos-Barinas), resulting from Tertiary Andean eastward movements, and basins formed by collisional, extensional, and transformed movement of the American portion of Tethys (eastern Venezuela-Trinidad). The smaller sedimentary basins of Venezuela are Tertiary transverse-wrench basins in the disturbed intermontane zone peripheral to the cratonic basins (Maracaibo, Falcon, parts of the Gulf of Venezuela, Carioca, and parts of Tobago-Margarita). Venezuela accounts for 75% of the recoverable oil and 55% of the gas discovered inmore » South America. These deposits occur primarily in two basins (East Venezuela and Maracaibo - where one complex, the Bolivar Coastal and lake pools, represents 40% of South American discovered oil). The East Venezuela basin contains the Orinico heavy oil belt, currently assessed at 1 to 2 trillion bbl of oil in place. Source rocks for Venezuelan hydrocarbons are middle Cretaceous calcareous bituminous shales and marls (40% of discovered hydrocarbons), lower Tertiary deltaic and transitional shales, Paleocene-Eocene (40%), and Oligocene-Miocene deltaic and coastal shales (20%). A key factor in high recovery of hydrocarbons appears to be preservation of middle Cretaceous and lower Tertiary source rocks during maturation and migration. Reservoirs are dominantly (> 90%) clastic sediments (sandstones) within, above, or updip from source sequences. Cap rocks are interbedded and overlying shale.« less

Mover Is a Homomeric Phospho-Protein Present on Synaptic Vesicles

PubMed Central

Kremer, Thomas; Hoeber, Jan; Kiran Akula, Asha; Urlaub, Henning; Islinger, Markus; Kirsch, Joachim; Dean, Camin; Dresbach, Thomas

2013-01-01

With remarkably few exceptions, the molecules mediating synaptic vesicle exocytosis at active zones are structurally and functionally conserved between vertebrates and invertebrates. Mover was found in a yeast-2-hybrid assay using the vertebrate-specific active zone scaffolding protein bassoon as a bait. Peptides of Mover have been reported in proteomics screens for self-interacting proteins, phosphorylated proteins, and synaptic vesicle proteins, respectively. Here, we tested the predictions arising from these screens. Using flotation assays, carbonate stripping of peripheral membrane proteins, mass spectrometry, immunogold labelling of purified synaptic vesicles, and immuno-organelle isolation, we found that Mover is indeed a peripheral synaptic vesicle membrane protein. In addition, by generating an antibody against phosphorylated Mover and Western blot analysis of fractionated rat brain, we found that Mover is a bona fide phospho-protein. The localization of Mover to synaptic vesicles is phosphorylation dependent; treatment with a phosphatase caused Mover to dissociate from synaptic vesicles. A yeast-2-hybrid screen, co-immunoprecipitation and cell-based optical assays of homomerization revealed that Mover undergoes homophilic interaction, and regions within both the N- and C- terminus of the protein are required for this interaction. Deleting a region required for homomeric interaction abolished presynaptic targeting of recombinant Mover in cultured neurons. Together, these data prove that Mover is associated with synaptic vesicles, and implicate phosphorylation and multimerization in targeting of Mover to synaptic vesicles and presynaptic sites. PMID:23723986

High-Intensity Focused Ultrasound in Treating Participants With Intermediate and High-risk Prostate Cancer

ClinicalTrials.gov

2018-06-13

Stage I Prostate Cancer AJCC v8; Stage II Prostate Cancer AJCC v8; Stage IIA Prostate Cancer AJCC v8; Stage IIB Prostate Cancer AJCC v8; Stage IIC Prostate Cancer AJCC v8; Stage III Prostate Cancer AJCC v8; Stage IIIA Prostate Cancer AJCC v8; Stage IIIB Prostate Cancer AJCC v8; Stage IIIC Prostate Cancer AJCC v8

Racial differences in the relationship between clinical prostatitis, presence of inflammation in benign prostate and subsequent risk of prostate cancer.

PubMed

Rybicki, B A; Kryvenko, O N; Wang, Y; Jankowski, M; Trudeau, S; Chitale, D A; Gupta, N S; Rundle, A; Tang, D

2016-06-01

Epidemiologic studies, primarily done in white men, suggest that a history of clinically-diagnosed prostatitis increases prostate cancer risk, but that histological prostate inflammation decreases risk. The relationship between a clinical history of prostatitis and histologic inflammation in terms of how these two manifestations of prostatic inflammation jointly contribute to prostate cancer risk and whether racial differences exist in this relationship is uncertain. Using a nested design within a cohort of men with benign prostate tissue specimens, we analyzed the data on both clinically-diagnosed prostatitis (NIH categories I-III) and histological inflammation in 574 prostate cancer case-control pairs (345 white, 229 African American). Clinical prostatitis was not associated with increased prostate cancer risk in the full sample, but showed a suggestive inverse association with prostate cancer in African Americans (odds ratio (OR)=0.47; 95% confidence interval (CI)=0.27-0.81). In whites, clinical prostatitis increased risk by 40%, but was only associated with a significant increased prostate cancer risk in the absence of evidence of histological inflammation (OR=3.56; 95% CI=1.15-10.99). Moreover, PSA velocity (P=0.008) and frequency of PSA testing (P=0.003) were significant modifiers of risk. Clinical prostatitis increased risk of prostate cancer almost three-fold (OR=2.97; 95% CI=1.40-6.30) in white men with low PSA velocity and about twofold in white men with more frequent PSA testing (OR=1.91; 95% CI=1.09-3.35). In our cohort of men with benign prostate specimens, race, and histological inflammation were important cofactors in the relationship between clinical prostatitis and prostate cancer. Clinical prostatitis was associated with a slightly decreased risk for prostate cancer in African American men. In white men, the relationship between clinical prostatitis and prostate cancer risk was modified by histological prostatic inflammation, PSA velocity, and frequency of PSA testing-suggesting a complex interplay between these indications of prostatic inflammation and prostate cancer detection.

Racial differences in the relationship between clinical prostatitis, presence of inflammation in benign prostate and subsequent risk of prostate cancer

PubMed Central

Rybicki, BA; Kryvenko, ON; Wang, Y; Jankowski, M; Trudeau, S; Chitale, DA; Gupta, NS; Rundle, A; Tang, D

2016-01-01

BACKGROUND Epidemiologic studies, primarily done in white men, suggest that a history of clinically-diagnosed prostatitis increases prostate cancer risk, but that histological prostate inflammation decreases risk. The relationship between a clinical history of prostatitis and histologic inflammation in terms of how these two manifestations of prostatic inflammation jointly contribute to prostate cancer risk and whether racial differences exist in this relationship is uncertain. METHODS Using a nested design within a cohort of men with benign prostate tissue specimens, we analyzed the data on both clinically-diagnosed prostatitis (NIH categories I–III) and histological inflammation in 574 prostate cancer case-control pairs (345 white, 229 African American). RESULTS Clinical prostatitis was not associated with increased prostate cancer risk in the full sample, but showed a suggestive inverse association with prostate cancer in African Americans (odds ratio (OR) = 0.47; 95% confidence interval (CI) = 0.27–0.81). In whites, clinical prostatitis increased risk by 40%, but was only associated with a significant increased prostate cancer risk in the absence of evidence of histological inflammation (OR = 3.56; 95% CI = 1.15–10.99). Moreover, PSA velocity (P = 0.008) and frequency of PSA testing (P = 0.003) were significant modifiers of risk. Clinical prostatitis increased risk of prostate cancer almost three-fold (OR = 2.97; 95% CI = 1.40–6.30) in white men with low PSA velocity and about twofold in white men with more frequent PSA testing (OR = 1.91; 95% CI = 1.09–3.35). CONCLUSIONS In our cohort of men with benign prostate specimens, race, and histological inflammation were important cofactors in the relationship between clinical prostatitis and prostate cancer. Clinical prostatitis was associated with a slightly decreased risk for prostate cancer in African American men. In white men, the relationship between clinical prostatitis and prostate cancer risk was modified by histological prostatic inflammation, PSA velocity, and frequency of PSA testing—suggesting a complex interplay between these indications of prostatic inflammation and prostate cancer detection. PMID:26620738

[Peripheral nerve repair: 30 centuries of scientific research].

PubMed

Desouches, C; Alluin, O; Mutaftschiev, N; Dousset, E; Magalon, G; Boucraut, J; Feron, F; Decherchi, P

2005-11-01

Nerve injury compromises sensory and motor functions. Techniques of peripheral nerve repair are based on our knowledge regarding regeneration. Microsurgical techniques introduced in the late 1950s and widely developed for the past 20 years have improved repairs. However, functional recovery following a peripheral mixed nerve injury is still incomplete. Good motor and sensory function after nerve injury depends on the reinnervation of the motor end plates and sensory receptors. Nerve regeneration does not begin if the cell body has not survived the initial injury or if it is unable to initiate regeneration. The regenerated axons must reach and reinnervate the appropriate target end-organs in a timely fashion. Recovery of motor function requires a critical number of motor axons reinnervating the muscle fibers. Sensory recovery is possible if the delay in reinnervation is short. Many additional factors influence the success of nerve repair or reconstruction. The timing of the repair, the level of injury, the extent of the zone of injury, the technical skill of the surgeon, and the method of repair and reconstruction contribute to the functional outcome after nerve injury. This review presents the recent advances in understanding of neural regeneration and their application to the management of primary repairs and nerve gaps.

Predictive value of different prostate-specific antigen-based markers in men with baseline total prostate-specific antigen <2.0 ng/mL.

PubMed

Fujizuka, Yuji; Ito, Kazuto; Oki, Ryo; Suzuki, Rie; Sekine, Yoshitaka; Koike, Hidekazu; Matsui, Hiroshi; Shibata, Yasuhiro; Suzuki, Kazuhiro

2017-08-01

To investigate the predictive value of various molecular forms of prostate-specific antigen in men with baseline prostate-specific antigen <2.0 ng/mL. The case cohort comprised 150 men with a baseline prostate-specific antigen level <2.0 ng/mL, and who developed prostate cancer within 10 years. The control cohort was 300 baseline prostate-specific antigen- and age-adjusted men who did not develop prostate cancer. Serum prostate-specific antigen, free prostate-specific antigen, and [-2] proenzyme prostate-specific antigen were measured at baseline and last screening visit. The predictive impact of baseline prostate-specific antigen- and [-2] proenzyme prostate-specific antigen-related indices on developing prostate cancer was investigated. The predictive impact of those indices at last screening visit and velocities from baseline to final screening on tumor aggressiveness were also investigated. The baseline free to total prostate-specific antigen ratio was a significant predictor of prostate cancer development. The odds ratio was 6.08 in the lowest quintile baseline free to total prostate-specific antigen ratio subgroup. No serum indices at diagnosis were associated with tumor aggressiveness. The Prostate Health Index velocity and [-2] proenzyme prostate-specific antigen/free prostate-specific antigen velocity significantly increased in patients with higher risk D'Amico risk groups and higher Gleason scores. Free to total prostate-specific antigen ratio in men with low baseline prostate-specific antigen levels seems to predict the risk of developing prostate cancer, and it could be useful for a more effective individualized screening system. Longitudinal changes in [-2] proenzyme prostate-specific antigen-related indices seem to correlate with tumor aggressiveness, and they could be used as prognostic tool before treatment and during active surveillance. © 2017 The Japanese Urological Association.

Genetic and Molecular Mechanisms in Assessing Response in Patients With Prostate Cancer Receiving Enzalutamide Therapy

ClinicalTrials.gov

2018-01-22

Castration Levels of Testosterone; Castration-Resistant Prostate Carcinoma; Metastatic Prostate Carcinoma in the Soft Tissue; Metastatic Prostatic Adenocarcinoma; Prostate Carcinoma Metastatic in the Bone; PSA Progression; Recurrent Prostate Carcinoma; Stage III Prostate Adenocarcinoma; Stage IV Prostate Adenocarcinoma

The effect of abdominal pressure on urinary flow rate.

PubMed

Hasegawa, N; Kitagawa, Y; Takasaki, N; Miyazaki, S

1983-07-01

We examined the effect of abdominal pressure on urinary flow rate and urethral closure pressure in 46 subjects, ranging in age from 26 to 82 years. An increase in urinary flow rate caused by abdominal straining was not found when organic obstruction was present in the prostatic urethra in men or the proximal urethra in women, or when dysuria is caused by the lowered detrusor pressure. An increase in urinary flow rate caused by straining was noted when anterior urethral stricture or stress incontinence was present. The increase in urinary flow rate owing to straining was undetermined in the control group. The urethral closure pressure on the anti-stress incontinence zone increased as a result of straining at the same time and to the same degree as did the intravesical pressure. When the anti-stress incontinence zone was subjected to transurethral resection for canal formation urination became possible as a result of straining. The patients who were able to urinate with straining sometimes suffered temporary stress incontinence. The degree of straining did not determine whether the patient could urinate with straining. Therefore, it was concluded that abdominal pressure should be excluded from intravesical pressure in performing several urodynamic studies on the lower urinary tract, such as pressure flow studies, and that it is important to have a sufficient canal formation in the anti-stress incontinence zone when urination with straining is expected when performing an operation on patients with urethral obstruction in the anti-stress incontinence zone.

Pollen record of the penultimate glacial period in Yuchi Basin, Central Taiwan

NASA Astrophysics Data System (ADS)

Lai, Hsiao-Yin; Liew, Ping-Mei

2010-05-01

Pollen records of the penultimate glacial period are scare not only in Taiwan, but also in East Asia area. Hence, this study intends to provide a new pollen record from a site, Yuchi Basin, in central Taiwan, which may improve our knowledge of the penultimate glacial period. The sediment core, CTN6, was drilled in the northern part of Yuchi Basin. The core is 29.4 m in length and the sampling interval is 10 cm. In total, 86 samples are processed for pollen analysis. Three pollen zones (I,II and III) are determined according to the ratio of arboreal pollens (AP) and non-arboreal pollens (NAP). Because of the scarcity of dating data, pollen assemblages compared with previous pollen records at peripheral areas is utilized to estimate the ages of each pollen zone. AP dominate (60%) Zone I and III, which consist mainly of Cyclobalanopsis-Castanopsis. Thus, Zone I may mark the MIS 5 because of a Cyclobalanopsis-Castanopsis dominant condition. In Zone II, the increase in NAP and pollen of Taxodiaceae and decrease in pollens of Cyclobalanopsis-Castanopsis indicates the penultimate glacial period, i.e. MIS 6. In contrast to the evergreen broadleaved forest found there today, the herbs occupied the basin in Zone II, indicating a relatively dry climate condition than present. Furthermore, during the penultimate glacial period, the climate condition of early part is wetter, evidenced by a higher AP/NAP in Zone IIb. Finally, comparing with the last glacial period in Toushe, we suggest that the penultimate glacial period is drier due to the lower AP/NAP.

HISTOPATHOLOGICAL EFFECTS IN MICE OF HETEROLOGOUS ANTILYMPHOCYTE SERUM

PubMed Central

Taub, Robert N.; Lance, Eugene M.

1968-01-01

The effects of heterologous rabbit anti-mouse lymphocyte antiserum on the morphology of lymphoid and other tissues was investigated in CBA mice. The lymphoid tissues exhibited characteristic changes specific for ALS treatment, which were an invariable accompaniment to its immunosuppressive effects. These consisted of peripheral lymphopenia occurring at some time during a course of ALS treatment and persistent depletion of small lymphocytes in lymph node paracortical areas and splenic follicular periarteriolar zones. The thymic histology was generally well preserved. It is suggested that the relevant lesions reflect a rapid depletion of the pool of recirculating lymphocytes, possibly by a primary cytotoxic effect exerted on cells peripheral to lymphoid tissue. Other histologic features attendant to the administration of ALS were accounted for as consequences of immunization of ALS recipients to rabbit serum constituents or by the deleterious effects of antibodies directed against tissues other than lymphoid cells. PMID:5688077

[Specific features of blood cell composition and structure in fishes from the pelagial and coastal zones of Lake Baikal].

PubMed

Iakhnenko, V M; Klimenkov, I V

2009-01-01

Differences in the proportions and ultrastructure of peripheral blood cells between the Baikal cisco and roach have been revealed. Both species contain all main cell types involved in the immune response in higher vertebrates. However, cells mediating the innate immune response are represented in the Baikal cisco only by monocytes and pseudogranulocytes, whereas the blood of roach additionally contains true granulocytes. Significantly greater numbers of leukocytes and thrombocytes per unit volume in the roach are evidence for mobilization of the immune system in this species. The peripheral blood of both species contains lymphocytes, which are responsible for adaptive immunity. The content of hemoglobin in erythrocytes is lower in the roach than in the Baikal cisco. The state of blood in the two species may be considered adapted to typical conditions in their habitats.

Cyclophosphamide for Prevention of Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With Hematological Malignancies

ClinicalTrials.gov

2017-05-17

Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Myeloid Leukemia in Remission; Adult Erythroleukemia (M6a); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Pure Erythroid Leukemia (M6b); Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Philadelphia Chromosome Negative Chronic Myelogenous Leukemia; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Multiple Myeloma; Testicular Lymphoma; Waldenström Macroglobulinemia

A novel approach to 32-channel peripheral nervous system myelin imaging in vivo, with single axon resolution.

PubMed

Grochmal, Joey; Teo, Wulin; Gambhir, Hardeep; Kumar, Ranjan; Stratton, Jo Anne; Dhaliwal, Raveena; Brideau, Craig; Biernaskie, Jeff; Stys, Peter K; Midha, Rajiv

2018-01-19

OBJECTIVE Intravital spectral imaging of the large, deeply situated nerves in the rat peripheral nervous system (PNS) has not been well described. Here, the authors have developed a highly stable platform for performing imaging of the tibial nerve in live rodents, thus allowing the capture of high-resolution, high-magnification spectral images requiring long acquisition times. By further exploiting the qualities of the topically applied myelin dye Nile red, this technique is capable of visualizing the detailed microenvironment of peripheral nerve demyelination injury and recovery, while allowing us to obtain images of exogenous Schwann cell myelination in a living animal. METHODS The authors caused doxorubicin-induced focal demyelination in the tibial nerves of 25 Thy-1 GFP rats, of which 2 subsets (n = 10 each) received either BFP-labeled SKP-SCs or SCs to the zone of injury. Prior to acquiring images of myelin recovery in these nerves, a tibial nerve window was constructed using a silicone hemitube, a fast drying silicone polymer, and a small coverslip. This construct was then affixed to a 3D-printed nerve stage, which in turn was affixed to an external fixation/microscope stage device. Myelin visualization was facilitated by the topical application of Nile red. RESULTS The authors reliably demonstrated intravital peripheral nerve myelin imaging with micron-level resolution and magnification, and minimal movement artifact. The detailed microenvironment of nerve remyelination can be vividly observed, while exogenously applied Schwann cells and skin-derived precursor Schwann cells can be seen myelinating axons. CONCLUSIONS Topically applied Nile red enables intravital study of myelin in the living rat PNS. Furthermore, the use of a tibial nerve window facilitates stable intravital peripheral nerve imaging, making possible high-definition spectral imaging with long acquisition times.

Peripheral blood metabolic and inflammatory factors as biomarkers to ocular findings in diabetic macular edema

PubMed Central

Sala-Puigdollers, Anna; Matas, Jessica; Vinagre, Irene; Ríos, José; Adán, Alfredo

2017-01-01

Aims To study the association between peripheral blood metabolic and inflammatory factors and presence of diabetic macular edema (DME) and its related anatomic features in type 2 diabetic mellitus (T2DM) patients. Material and methods Observational cross-sectional study on a proof of concept basis. Seventy-six T2DM included patients were divided based on the presence (n = 58) or absence of DME (n = 18) according to optical coherence tomography (OCT). Ultra-widefield fluorescein angiography (UWFA) was performed in DME patients. Fasting peripheral blood sample testing included glycemia, glycated hemoglobin, creatinin and lipid levels among others. Serum levels of a broad panel of cytokines and inflammatory mediators were also analysed. OCT findings included central subfoveal thickness, diffuse retinal thickness (DRT), cystoid macular edema (CME), serous retinal detachment and epirretinal membrane. UWFA items included pattern of DME, presence of peripheral retinal ischemia and enlarged foveal avascular zone (FAZ). Results Metabolic and inflammatory factors did not statistically differ between groups. However, several inflammatory mediators did associate to certain ocular items of DME cases: IL-6 was significantly higher in patients with DRT (p = 0.044), IL-10 was decreased in patients with CME (p = 0.012), and higher IL-8 (p = 0.031) and VEGF levels (p = 0.031) were observed in patients with enlarged FAZ. Conclusion Inflammatory and metabolic peripheral blood factors in T2DM may not be differentially associated to DME when compared to non-DME cases. However, some OCT and UWFA features of DME such as DRT, CME and enlarged FAZ may be associated to certain systemic inflammatory mediators. PMID:28328965

Correlation of central and peripheral corneal thickness in healthy corneas.

PubMed

Fares, Usama; Otri, Ahmad Muneer; Al-Aqaba, Mouhamed Ali; Dua, Harminder S

2012-02-01

To study the thickness profile of the normal cornea in order to establish any correlation between central and peripheral points. Sixty-seven eyes of 40 patients were subjected to central corneal thickness measurement (CCT) with an ultrasound pachymeter (UP) and corneal thickness mapping with the Oculus Pentacam. The corneal apex thickness (CAT), pupil centre thickness (recorded as CCT and corresponded to CCT of UP) and thickness at the thinnest location (CTL) were obtained and compared with each other. Corneal thickness data at 3 mm and 7 mm temporally, nasally, superiorly and inferiorly from the corneal apex were obtained. The mean corneal thickness values along the 2, 4, 6, 8 and 10 mm diameter concentric circles, with the CTL as the centre, were also obtained. The above data at different points were statistically correlated. There was no significant difference between CCT readings measured by UP and Pentacam (P=0.721). There was high positive correlation between the CAT values and the thickness at 3 mm (R≥0.845, P<0.001) and at 7 mm points (R≥0.654, P<0.001). A gradual increase in thickness was noted from the centre to the periphery with a high positive correlation between the CTL values and the mean thickness at the circles of 2, 4, 6, 8 and 10 mm (R≥0.635, P<0.001). The results suggest that central corneal thickness can serve as a good guide for predicting peripheral thickness. For surgical procedures specifically undertaken at mid-peripheral and peripheral zones, the actual measurements at the site of surgery may confer some advantage. Copyright © 2011 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Prostatic Lesions in Odontocete Cetaceans.

PubMed

Suárez-Santana, Cristian M; Sierra, Eva; Díaz-Delgado, Josue; Zucca, Daniele; de Quirós, Yara Bernaldo; Puig-Lozano, Raquel; Câmara, Nakita; De la Fuente, Jesús; de Los Monteros, Antonio Espinosa; Rivero, Miguel; Arbelo, Manuel; Fernández, Antonio

2018-05-01

The prostate is the only accessory male genital gland described in cetaceans. Although few studies describe the gross and histologic anatomy of the prostate in cetaceans, there is no information on pathological findings involving this organ. The prostate glands of 45 cetaceans, including 8 different odontocete species ( n = 44) and 1 mysticete, were evaluated. The main pathologic diagnoses were verminous prostatitis, septic prostatitis, viral prostatitis, benign prostatic hyperplasia, and prostatitis of unknown etiology. Verminous prostatitis ( n = 12) was caused by nematodes of the genus Crassicauda, and different presentations were observed. Septic prostatitis, identified in 2 cases, both involved nematode infestation and Clostridium spp coinfection. One case of viral prostatitis was identified and was associated with morbillivirus infection. In prostatitis of unknown cause ( n = 7), varying degrees of prostatic lesions, mostly chronic inflammation, were identified. Impacts at individual levels (eg, localized disease, loss of reproductive capacity) and population levels (eg, decreased reproductive success) are plausible. Our results indicate a high occurrence of prostatic lesions in free-ranging odontocetes. For this reason, the prostate should be routinely inspected and sampled during necropsy of odontocete cetaceans.

Prostate-specific antigen lowering effect of metabolic syndrome is influenced by prostate volume.

PubMed

Choi, Woo Suk; Heo, Nam Ju; Paick, Jae-Seung; Son, Hwancheol

2016-04-01

To investigate the influence of metabolic syndrome on prostate-specific antigen levels by considering prostate volume and plasma volume. We retrospectively analyzed 4111 men who underwent routine check-ups including prostate-specific antigen and transrectal ultrasonography. The definition of metabolic syndrome was based on the modified Adult Treatment Panel III criteria. Prostate-specific antigen mass density (prostate-specific antigen × plasma volume / prostate volume) was calculated for adjusting plasma volume and prostate volume. We compared prostate-specific antigen and prostate-specific antigen mass density levels of participants with metabolic syndrome (metabolic syndrome group, n = 1242) and without metabolic syndrome (non-prostate-specific antigen metabolic syndrome group, n = 2869). To evaluate the impact of metabolic syndrome on prostate-specific antigen, linear regression analysis for the natural logarithm of prostate-specific antigen was used. Patients in the metabolic syndrome group had significantly older age (P < 0.001), larger prostate volume (P < 0.001), higher plasma volume (P < 0.001) and lower mean serum prostate-specific antigen (non-metabolic syndrome group vs metabolic syndrome group; 1.22 ± 0.91 vs 1.15 ± 0.76 ng/mL, P = 0.006). Prostate-specific antigen mass density in the metabolic syndrome group was still significantly lower than that in the metabolic syndrome group (0.124 ± 0.084 vs 0.115 ± 0.071 μg/mL, P = 0.001). After adjusting for age, prostate volume and plasma volume using linear regression model, the presence of metabolic syndrome was a significant independent factor for lower prostate-specific antigen (prostate-specific antigen decrease by 4.1%, P = 0.046). Prostate-specific antigen levels in patients with metabolic syndrome seem to be lower, and this finding might be affected by the prostate volume. © 2016 The Japanese Urological Association.

Effectiveness of the combined evaluation of KLK3 genetics and free-to-total prostate specific antigen ratio for prostate cancer diagnosis.

PubMed

Zambon, Carlo-Federico; Prayer-Galetti, Tommaso; Basso, Daniela; Padoan, Andrea; Rossi, Elisa; Secco, Silvia; Pelloso, Michela; Fogar, Paola; Navaglia, Filippo; Moz, Stefania; Zattoni, Filiberto; Plebani, Mario

2012-10-01

Of serum prostate specific antigen variability 40% depends on inherited factors. We ascertained whether the knowledge of KLK3 genetics would enhance prostate specific antigen diagnostic performance in patients with clinical suspicion of prostate cancer. We studied 1,058 men who consecutively underwent prostate biopsy for clinical suspicion of prostate cancer. At histology prostate cancer was present in 401 cases and absent in 657. Serum total prostate specific antigen and the free-to-total prostate specific antigen ratio were determined. Four polymorphisms of the KLK3 gene (rs2569733, rs2739448, rs925013 and rs2735839) and 1 polymorphism of the SRD5A2 gene (rs523349) were studied. The influence of genetics on prostate specific antigen variability was evaluated by multivariate linear regression analysis. The performance of total prostate specific antigen and the free-to-total prostate specific antigen ratio alone or combined with a genetically based patient classification were defined by ROC curve analyses. For prostate cancer diagnosis the free-to-total prostate specific antigen ratio index alone (cutoff 11%) was superior to total prostate specific antigen (cutoff 4 ng/ml) and to free-to-total prostate specific antigen ratio reflex testing (positive predictive value 61%, 43% and 54%, respectively). Prostate specific antigen correlated with KLK3 genetics (rs2735839 polymorphism p = 0.001, and rs2569733, rs2739448 and rs925013 haplotype combination p = 0.003). In patients with different KLK3 genetics 2 optimal free-to-total prostate specific antigen ratio cutoffs (11% and 14.5%) were found. For free-to-total prostate specific antigen ratio values between 11% and 14.5% the prostate cancer probability ranged from 30.0% to 47.4% according to patient genetics. The free-to-total prostate specific antigen ratio is superior to total prostate specific antigen for prostate cancer diagnosis, independent of total prostate specific antigen results. Free-to-total prostate specific antigen ratio findings below 11% are positively associated with prostate cancer and those above 14.5% are negatively associated with prostate cancer, while the interpretation of those between 11% and 14.5% is improved by patient KLK3 genetic analysis. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.