Prognostic importance of Gleason 7 disease among patients treated with external beam radiation therapy for prostate cancer: results of a detailed biopsy core analysis.

PubMed

Spratt, Daniel E; Zumsteg, Zach; Ghadjar, Pirus; Pangasa, Misha; Pei, Xin; Fine, Samson W; Yamada, Yoshiya; Kollmeier, Marisa; Zelefsky, Michael J

2013-04-01

To analyze the effect of primary Gleason (pG) grade among a large cohort of Gleason 7 prostate cancer patients treated with external beam radiation therapy (EBRT). From May 1989 to January 2011, 1190 Gleason 7 patients with localized prostate cancer were treated with EBRT at a single institution. Of these patients, 613 had a Gleason 7 with a minimum of a sextant biopsy with nonfragmented cores and full biopsy core details available, including number of cores of cancer involved, percentage individual core involvement, location of disease, bilaterality, and presence of perineural invasion. Median follow-up was 6 years (range, 1-16 years). The prognostic implication for the following outcomes was analyzed: biochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific mortality (PCSM). The 8-year bRFS rate for pG3 versus pG4 was 77.6% versus 61.3% (P<.0001), DMFS was 96.8% versus 84.3% (P<.0001), and PCSM was 3.7% versus 8.1% (P=.002). On multivariate analysis, pG4 predicted for significantly worse outcome in all parameters. Location of disease (apex, base, mid-gland), perineural involvement, maximum individual core involvement, and the number of Gleason 3+3, 3+4, or 4+3 cores did not predict for distant metastases. Primary Gleason grade 4 independently predicts for worse bRFS, DMFS, and PCSM among Gleason 7 patients. Using complete core information can allow clinicians to utilize pG grade as a prognostic factor, despite not having the full pathologic details from a prostatectomy specimen. Future staging and risk grouping should investigate the incorporation of primary Gleason grade when complete biopsy core information is used. Copyright © 2013 Elsevier Inc. All rights reserved.

Prognostic Importance of Gleason 7 Disease Among Patients Treated With External Beam Radiation Therapy for Prostate Cancer: Results of a Detailed Biopsy Core Analysis

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

Spratt, Daniel E.; Zumsteg, Zach; Ghadjar, Pirus

2013-04-01

Purpose: To analyze the effect of primary Gleason (pG) grade among a large cohort of Gleason 7 prostate cancer patients treated with external beam radiation therapy (EBRT). Methods and Materials: From May 1989 to January 2011, 1190 Gleason 7 patients with localized prostate cancer were treated with EBRT at a single institution. Of these patients, 613 had a Gleason 7 with a minimum of a sextant biopsy with nonfragmented cores and full biopsy core details available, including number of cores of cancer involved, percentage individual core involvement, location of disease, bilaterality, and presence of perineural invasion. Median follow-up was 6more » years (range, 1-16 years). The prognostic implication for the following outcomes was analyzed: biochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific mortality (PCSM). Results: The 8-year bRFS rate for pG3 versus pG4 was 77.6% versus 61.3% (P<.0001), DMFS was 96.8% versus 84.3% (P<.0001), and PCSM was 3.7% versus 8.1% (P=.002). On multivariate analysis, pG4 predicted for significantly worse outcome in all parameters. Location of disease (apex, base, mid-gland), perineural involvement, maximum individual core involvement, and the number of Gleason 3+3, 3+4, or 4+3 cores did not predict for distant metastases. Conclusions: Primary Gleason grade 4 independently predicts for worse bRFS, DMFS, and PCSM among Gleason 7 patients. Using complete core information can allow clinicians to utilize pG grade as a prognostic factor, despite not having the full pathologic details from a prostatectomy specimen. Future staging and risk grouping should investigate the incorporation of primary Gleason grade when complete biopsy core information is used.« less

Primary Gleason Grade 4 Impact on Biochemical Recurrence After Permanent Interstitial Brachytherapy in Japanese Patients With Low- or Intermediate-Risk Prostate Cancer

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

Uesugi, Tatsuya; Saika, Takashi, E-mail: saika@cc.okayama-u.ac.jp; Edamura, Kohei

2012-02-01

Purpose: To reveal a predictive factor for biochemical recurrence (BCR) after permanent prostate brachytherapy (PPB) using iodine-125 seed implantation in patients with localized prostate cancer classified as low or intermediate risk based on National Comprehensive Cancer Network (NCCN) guidelines. Methods and Materials: From January 2004 to December 2009, 414 consecutive Japanese patients with clinically localized prostate cancer classified as low or intermediate risk based on the NCCN guidelines were treated with PPB. The clinical factors including pathological data reviewed by a central pathologist and follow-up data were prospectively collected. Kaplan-Meier and Cox regression analyses were used to assess the factorsmore » associated with BCR. Results: Median follow-up was 36.5 months. The 2-, 3-, 4-, and 5-year BCR-free rates using the Phoenix definition were 98.3%, 96.0%, 91.6%, and 87.0%, respectively. On univariate analysis, the Gleason score, especially primary Gleason grade 4 in biopsy specimens, was a strong predicting factor (p < 0.0001), while age, initial prostate-specific antigen (PSA) level, T stage, and minimal dose delivered to 90% of the prostate volume (D90) were insignificant. Multivariate analysis indicated that a primary Gleason grade 4 was the most powerful prognostic factor associated with BCR (hazard ratio = 6.576, 95% confidence interval, 2.597-16.468, p < 0.0001). Conclusions: A primary Gleason grade 4 carried a worse BCR prognosis than the primary grade 3 in patients treated with PPB. Therefore, the indication for PPB in patients with a Gleason sum of 4 + 3 deserves careful and thoughtful consideration.« less

Impact of Primary Gleason Grade on Risk Stratification for Gleason Score 7 Prostate Cancers

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

Koontz, Bridget F., E-mail: bridget.koontz@duke.edu; Tsivian, Matvey; Mouraviev, Vladimir

Purpose: To evaluate the primary Gleason grade (GG) in Gleason score (GS) 7 prostate cancers for risk of non-organ-confined disease with the goal of optimizing radiotherapy treatment option counseling. Methods: One thousand three hundred thirty-three patients with pathologic GS7 were identified in the Duke Prostate Center research database. Clinical factors including age, race, clinical stage, prostate-specific antigen at diagnosis, and pathologic stage were obtained. Data were stratified by prostate-specific antigen and clinical stage at diagnosis into adapted D'Amico risk groups. Univariate and multivariate analyses were performed evaluating for association of primary GG with pathologic outcome. Results: Nine hundred seventy-nine patientsmore » had primary GG3 and 354 had GG4. On univariate analyses, GG4 was associated with an increased risk of non-organ-confined disease. On multivariate analysis, GG4 was independently associated with seminal vesicle invasion (SVI) but not extracapsular extension. Patients with otherwise low-risk disease and primary GG3 had a very low risk of SVI (4%). Conclusions: Primary GG4 in GS7 cancers is associated with increased risk of SVI compared with primary GG3. Otherwise low-risk patients with GS 3+4 have a very low risk of SVI and may be candidates for prostate-only radiotherapy modalities.« less

Impact of primary Gleason grade on risk stratification for Gleason score 7 prostate cancers.

PubMed

Koontz, Bridget F; Tsivian, Matvey; Mouraviev, Vladimir; Sun, Leon; Vujaskovic, Zeljko; Moul, Judd; Lee, W Robert

2012-01-01

To evaluate the primary Gleason grade (GG) in Gleason score (GS) 7 prostate cancers for risk of non-organ-confined disease with the goal of optimizing radiotherapy treatment option counseling. One thousand three hundred thirty-three patients with pathologic GS7 were identified in the Duke Prostate Center research database. Clinical factors including age, race, clinical stage, prostate-specific antigen at diagnosis, and pathologic stage were obtained. Data were stratified by prostate-specific antigen and clinical stage at diagnosis into adapted D'Amico risk groups. Univariate and multivariate analyses were performed evaluating for association of primary GG with pathologic outcome. Nine hundred seventy-nine patients had primary GG3 and 354 had GG4. On univariate analyses, GG4 was associated with an increased risk of non-organ-confined disease. On multivariate analysis, GG4 was independently associated with seminal vesicle invasion (SVI) but not extracapsular extension. Patients with otherwise low-risk disease and primary GG3 had a very low risk of SVI (4%). Primary GG4 in GS7 cancers is associated with increased risk of SVI compared with primary GG3. Otherwise low-risk patients with GS 3+4 have a very low risk of SVI and may be candidates for prostate-only radiotherapy modalities. Copyright © 2012 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.

Prostate cancer: from Gleason scoring to prognostic grade grouping.

PubMed

Montironi, Rodolfo; Santoni, Matteo; Mazzucchelli, Roberta; Burattini, Luciano; Berardi, Rossana; Galosi, Andrea B; Cheng, Liang; Lopez-Beltran, Antonio; Briganti, Alberto; Montorsi, Francesco; Scarpelli, Marina

2016-01-01

The Gleason grading system was developed in the late 1960s by Dr. Donald F. Gleason. Due to changes in prostatic adenocarcinoma (PAC) detection and treatment, newer technologies to better characterize prostatic pathology, subsequently described variants of PAC and further data relating various morphologic patterns to prognosis, the application of the Gleason grading system changed substantially in surgical pathology. First in 2005 and more recently in 2014, consensus conferences were held to update PAC grading. Here, we review of the successive changes in the grading of PAC from the original system, with emphasis on the newest prognostic grade grouping.

Gleason Score Determination with Transrectal Ultrasound-Magnetic Resonance Imaging Fusion Guided Prostate Biopsies--Are We Gaining in Accuracy?

PubMed

Lanz, Camille; Cornud, François; Beuvon, Frédéric; Lefèvre, Arnaud; Legmann, Paul; Zerbib, Marc; Delongchamps, Nicolas Barry

2016-01-01

We evaluated the accuracy of prostate magnetic resonance imaging- transrectal ultrasound targeted biopsy for Gleason score determination. We selected 125 consecutive patients treated with radical prostatectomy for a clinically localized prostate cancer diagnosed on magnetic resonance imaging-transrectal ultrasound targeted biopsy and/or systematic biopsy. On multiparametric magnetic resonance imaging each suspicious area was graded according to PI-RADS™ score. A correlation analysis between multiparametric magnetic resonance imaging and pathological findings was performed. Factors associated with determining the accuracy of Gleason score on targeted biopsy were statistically assessed. Pathological analysis of radical prostatectomy specimens detected 230 tumor foci. Multiparametric magnetic resonance imaging detected 151 suspicious areas. Of these areas targeted biopsy showed 126 cancer foci in 115 patients, and detected the index lesion in all of them. The primary Gleason grade, secondary Gleason grade and Gleason score of the 126 individual tumors were determined accurately in 114 (90%), 75 (59%) and 85 (67%) cases, respectively. Maximal Gleason score was determined accurately in 80 (70%) patients. Gleason score determination accuracy on targeted biopsy was significantly higher for low Gleason and high PI-RADS score tumors. Magnetic resonance imaging-transrectal ultrasound targeted biopsy allowed for an accurate estimation of Gleason score in more than two-thirds of patients. Gleason score misclassification was mostly due to a lack of accuracy in the determination of the secondary Gleason grade. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

RANKL/RANK/OPG cytokine receptor system: mRNA expression pattern in BPH, primary and metastatic prostate cancer disease.

PubMed

Christoph, Frank; König, Frank; Lebentrau, Steffen; Jandrig, Burkhard; Krause, Hans; Strenziok, Romy; Schostak, Martin

2018-02-01

The cytokine system RANKL (receptor activator of NF-κB ligand), its receptor RANK and the antagonist OPG (osteoprotegerin) play a critical role in bone turnover. Our investigation was conducted to describe the gene expression at primary tumour site in prostate cancer patients and correlate the results with Gleason Score and PSA level. Seventy-one samples were obtained from prostate cancer patients at the time of radical prostatectomy and palliative prostate resection (n = 71). Patients with benign prostate hyperplasia served as controls (n = 60). We performed real-time RT-PCR after microdissection of the samples. The mRNA expression of RANK was highest in tumour tissue from patients with bone metastases (p < 0.001) as compared to BPH or locally confined tumours, also shown in clinical subgroups distinguished by Gleason Score (< 7 or ≥ 7, p = 0.028) or PSA level (< 10 or ≥ 10 µg/l, p = 0.004). RANKL and OPG mRNA expression was higher in tumour tissue from patients with metastatic compared to local disease. The RANKL/OPG ratio was low in normal prostate tissue and high tumours with bone metastases (p < 0.05). Expression of all three cytokines was high in BPH tissue but did not exceed as much as in the tumour tissue. We demonstrated that RANK, RANKL and OPG are directly expressed by prostate cancer cells at the primary tumour site and showed a clear correlation with Gleason Score, serum PSA level and advanced disease. In BPH, mRNA expression is also detectable, but RANK expression does not exceed as much as compared to tumour tissue.

The Relationship Between Prostate Cancer Aggressiveness and Glycemic Levels in Patients Submitted to Radical Prostatectomy

PubMed Central

Goncalves, Suzana Cristina; de Moraes Siqueira, Rafael; Nogueira, Marcus Vinicius F; Pereira-Correia, Joao Antonio; Vaz, Fernando Pires; Peres, Wilza Arantes Ferreira

2013-01-01

Background The relationship between hyperglycemia and prostate cancer remains controversial. According to current hypotheses, elevated serum glucose levels may lead to disease development or disease prevention. Our study examined the potential correlation between pre-operative glycemic levels of patients with prostate cancer and the grade of tumor aggressiveness. Method We studied the case files of patients with a diagnosis of prostate cancer who had received putatively curative cancer surgery at the Urology Department of the Servidores do Estado Federal Hospital (RJ/Brazil). We transcribed information related to glycemia - collected up to 3 months before the surgery - and the histopathological grade of tumor aggressiveness (Gleason score) of the surgically removed prostates. Results We analyzed 42 people who met the inclusion criteria. Based on Gleason scores, among the normoglycemic patients, we detected low, moderate, and highly aggressive neoplasias in 13%, 53%, and 36% of the cases, respectively. For the hyperglycemic group, these rates were 30%, 60%, and 10%, respectively. Normoglycemic patients had primary Gleason grade 3 in 40% of the cases and grade 4 in 60% of the cases. For the hyperglycemic patients, these rates were 90% and 10%, respectively (P < 0.05 vs. grade 3 group). Conclusion Both Gleason score and primary Gleason grade were lower in hyperglycemic patients with prostate cancer than in normoglycemic patients, suggesting a “protective action” of hyperglycemic states. PMID:29147337

Contemporary management of men with high-risk localized prostate cancer in the United States.

PubMed

Weiner, A B; Matulewicz, R S; Schaeffer, E M; Liauw, S L; Feinglass, J M; Eggener, S E

2017-09-01

Surgery and radiation-based therapies are standard management options for men with clinically localized high-risk prostate cancer (PCa). Contemporary patterns of care are unknown. We hypothesize the use of surgery has steadily increased in more recent years. Using the National Cancer Data Base for 2004-2013, all men diagnosed with high-risk localized PCa were identified using National Comprehensive Cancer Network criteria. Temporal trends in initial management were assessed. Multivariable logistic regression was used to evaluate demographic and clinical factors associated with undergoing radical prostatectomy (RP). In total, 127 391 men were identified. Use of RP increased from 26% in 2004 to 42% in 2013 (adjusted risk ratio (RR) 1.51, 95% CI 1.42-1.60, P<0.001), while external beam radiation therapy (EBRT) decreased from 49% to 42% (P<0.001). African American men had lower odds of undergoing RP (unadjusted rate of 28%, adjusted RR 0.69, 95% CI 0.66-0.72, <0.001) compared to White men (37%). Age was inversely associated with likelihood of receiving RP. Having private insurance was significantly associated with the increased use of RP (vs Medicare, adjusted odds ratio 1.04, 95% CI 1.01-1.08, P=0.015). Biopsy Gleason scores 8-10 with and without any primary Gleason 5 pattern were associated with decreased odds of RP (vs Gleason score ⩽6, both P<0.001). Academic and comprehensive cancer centers were more likely to perform RP compared to community hospitals (both P<0.001). The likelihood of receiving RP for high-risk PCa dramatically increased from 2004 to 2013. By 2013, the use of RP and EBRT were similar. African American men, elderly men and those without private insurance were less likely to receive RP.

Magnetic resonance imaging-transectal ultrasound image-fusion biopsies accurately characterize the index tumor: correlation with step-sectioned radical prostatectomy specimens in 135 patients.

PubMed

Baco, Eduard; Ukimura, Osamu; Rud, Erik; Vlatkovic, Ljiljana; Svindland, Aud; Aron, Manju; Palmer, Suzanne; Matsugasumi, Toru; Marien, Arnaud; Bernhard, Jean-Christophe; Rewcastle, John C; Eggesbø, Heidi B; Gill, Inderbir S

2015-04-01

Prostate biopsies targeted by elastic fusion of magnetic resonance (MR) and three-dimensional (3D) transrectal ultrasound (TRUS) images may allow accurate identification of the index tumor (IT), defined as the lesion with the highest Gleason score or the largest volume or extraprostatic extension. To determine the accuracy of MR-TRUS image-fusion biopsy in characterizing ITs, as confirmed by correlation with step-sectioned radical prostatectomy (RP) specimens. Retrospective analysis of 135 consecutive patients who sequentially underwent pre-biopsy MR, MR-TRUS image-fusion biopsy, and robotic RP at two centers between January 2010 and September 2013. Image-guided biopsies of MR-suspected IT lesions were performed with tracking via real-time 3D TRUS. The largest geographically distinct cancer focus (IT lesion) was independently registered on step-sectioned RP specimens. A validated schema comprising 27 regions of interest was used to identify the IT center location on MR images and in RP specimens, as well as the location of the midpoint of the biopsy trajectory, and variables were correlated. The concordance between IT location on biopsy and RP specimens was 95% (128/135). The coefficient for correlation between IT volume on MRI and histology was r=0.663 (p<0.001). The maximum cancer core length on biopsy was weakly correlated with RP tumor volume (r=0.466, p<0.001). The concordance of primary Gleason pattern between targeted biopsy and RP specimens was 90% (115/128; κ=0.76). The study limitations include retrospective evaluation of a selected patient population, which limits the generalizability of the results. Use of MR-TRUS image fusion to guide prostate biopsies reliably identified the location and primary Gleason pattern of the IT lesion in >90% of patients, but showed limited ability to predict cancer volume, as confirmed by step-sectioned RP specimens. Biopsies targeted using magnetic resonance images combined with real-time three-dimensional transrectal ultrasound allowed us to reliably identify the spatial location of the most important tumor in prostate cancer and characterize its aggressiveness. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Grade-specific prostate cancer associations of IGF1 (CA)19 repeats and IGFBP3-202A/C in blacks and whites.

PubMed

Hoyo, Cathrine; Grubber, Janet; Demark-Wahnefried, Wendy; Marks, Jeffrey R; Freedland, Stephen J; Jeffreys, Amy S; Grambow, Steven C; Wenham, Robert M; Walther, Philip J; Schildkraut, Joellen M

2007-07-01

Carrying the cytosine-adenosine (CA)19 repeat polymorphism in insulin-like growth factor-1 (IGF1) is associated with lower serum proteins and decreased prostate cancer risk. Carrying the -202A/C genotype in insulin-like growth factor binding protein-3 (IGFBP3) also has been associated with lower serum levels of the binding protein. However, the association between this variant and prostate cancer is inconsistent. To test the hypothesis that inconsistencies are partly due to cancer grade-specific differences in strength and direction of associations, we reanalyzed data from our previous Durham Veterans Administration Hospital study of blacks and whites comprising 47 cases (19 African Americans) with Gleason sum > or = 7, 50 cases (30 African Americans) with Gleason sum < 7 and 93 controls (49 African Americans). Compared to controls, the association between carrying the IGFBP3 C allele and prostate cancer risk was in OR(Low-Gleason) = 4.0; 95% CI: 1.4-12.3 compared to OR(High-Gleason) = 1.0; 95% CI: 0.4-2.2. Association patterns were similar in African Americans (OR(Low-Gleason) = 3.6; 95% CI: 1.0-13.2 vs. OR(High-Gleason) = 1.4; 95% CI: 0.4-2.3) and whites (OR(Low-Gleason) = 5.6; 95% CI: 0.6-49.0 vs. OR(High-Gleason) = 0.6; 95% CI: 0.2-2.2). The inverse association between carrying the IGF1 (CA)19 repeat variant did not vary by grade or ethnicity. If confirmed in larger studies, these findings support the hypothesis that the association between IGFBP3 C allele and prostate cancer is grade specific in both ethnic groups.

Grade-specific prostate cancer associations of IGF1 (CA)19 repeats and IGFBP3-202A/C in blacks and whites.

PubMed Central

Hoyo, Cathrine; Grubber, Janet; Demark-Wahnefried, Wendy; Marks, Jeffrey R.; Freedland, Stephen J.; Jeffreys, Amy S.; Grambow, Steven C.; Wenham, Robert M.; Walther, Philip J.; Schildkraut, Joellen M.

2007-01-01

Carrying the cytosine-adenosine (CA)19 repeat polymorphism in insulin-like growth factor-1 (IGF1) is associated with lower serum proteins and decreased prostate cancer risk. Carrying the -202A/C genotype in insulin-like growth factor binding protein-3 (IGFBP3) also has been associated with lower serum levels of the binding protein. However, the association between this variant and prostate cancer is inconsistent. To test the hypothesis that inconsistencies are partly due to cancer grade-specific differences in strength and direction of associations, we reanalyzed data from our previous Durham Veterans Administration Hospital study of blacks and whites comprising 47 cases (19 African Americans) with Gleason sum > or = 7, 50 cases (30 African Americans) with Gleason sum < 7 and 93 controls (49 African Americans). Compared to controls, the association between carrying the IGFBP3 C allele and prostate cancer risk was in OR(Low-Gleason) = 4.0; 95% CI: 1.4-12.3 compared to OR(High-Gleason) = 1.0; 95% CI: 0.4-2.2. Association patterns were similar in African Americans (OR(Low-Gleason) = 3.6; 95% CI: 1.0-13.2 vs. OR(High-Gleason) = 1.4; 95% CI: 0.4-2.3) and whites (OR(Low-Gleason) = 5.6; 95% CI: 0.6-49.0 vs. OR(High-Gleason) = 0.6; 95% CI: 0.2-2.2). The inverse association between carrying the IGF1 (CA)19 repeat variant did not vary by grade or ethnicity. If confirmed in larger studies, these findings support the hypothesis that the association between IGFBP3 C allele and prostate cancer is grade specific in both ethnic groups. PMID:17668637

Distinct DNA methylation alterations are associated with cribriform architecture and intraductal carcinoma in Gleason pattern 4 prostate tumors.

PubMed

Olkhov-Mitsel, Ekaterina; Siadat, Farshid; Kron, Ken; Liu, Liyang; Savio, Andrea J; Trachtenberg, John; Fleshner, Neil; van der Kwast, Theodorus; Bapat, Bharati

2017-07-01

The aim of the present study was to explore DNA methylation aberrations in association with cribriform architecture and intraductal carcinoma (IDC) of the prostate, as there is robust evidence that these morphological features are associated with aggressive disease and have significant clinical implications. Herein, the associations of a panel of seven known prognostic DNA methylation biomarkers with cribriform and IDC features were examined in a series of 91 Gleason pattern (GP) 4 tumors derived from Gleason score 7 radical prostatectomies. Gene specific DNA methylation was compared between cribriform and/or IDC positive vs. negative cases, and in association with clinicopathological features, using Chi square and Mann-Whitney U tests. DNA methylation of the adenomatous polyposis coli, Ras association domain family member 1 and T-box 15 genes was significantly elevated in GP4 tumors with cribriform and/or IDC features compared with negative cases (P=0.045, P=0.007 and P=0.013, respectively). To the best of our knowledge, this provides the first evidence for an association between cribriform and/or IDC and methylation biomarkers, and warrants further investigation of additional DNA methylation events in association with various architectural patterns in prostate cancer.

Prostate Biopsy Specimens With Gleason 3+3=6 and Intraductal Carcinoma: Radical Prostatectomy Findings and Clinical Outcomes.

PubMed

Khani, Francesca; Epstein, Jonathan I

2015-10-01

Although intraductal carcinoma of the prostate (IDC-P) is typically present on biopsies in which there is also invasive prostate carcinoma of Gleason pattern 4 or 5 and an associated unfavorable outcome, there are limited studies on IDC-P in needle core biopsies or transurethral resections (TURP) with only a concomitant low-grade invasive component. There are differing opinions on incorporating IDC-P into the Gleason score in such cases. The aim of this study was to investigate clinical outcomes and radical prostatectomy (RP) findings in patients with Gleason 3+3=6 and IDC-P on biopsy or TURP. We identified 73 patients in our consult files (2001 to 2014) who had IDC-P and Gleason score 6 carcinoma on biopsy or TURP with no invasive higher Gleason grade component. Clinical follow-up information was available in 62 patients. Treatment was RP in 14 patients, radiation therapy in 31 patients, androgen deprivation therapy in 1 patient, and cryotherapy in 1 patient. Four patients were found to have metastatic disease at the time of diagnosis and were treated with chemotherapy. Eleven patients underwent active surveillance after diagnosis, of which 6 were eventually treated for progressive disease. The 14 RP specimens were centrally reviewed, and 86% had extensive IDC-P present. The Gleason grades in these 14 RP cases were 3+3=6 in 21%, 3+4=7 in 36%, 4+3=7 in 29%, and 4+4=8 in 14%. Pathologic stage was pT2 in 36%, pT3a in 36%, and pT3b in 28%. After 3 years, there was a 20% actuarial rate of disease progression in men who underwent either RP or radiation therapy. In summary, most men with IDC-P on biopsy/TURP have aggressive tumors, even when the invasive tumor on biopsy is Gleason score 6. As a minority of men may only have Gleason 6 invasive cancer at RP and a favorable prognosis, we recommend that IDC-P on biopsy/TURP be reported separately and not assigned a Gleason score.

Magnetic resonance imaging-ultrasound fusion biopsy for prediction of final prostate pathology.

PubMed

Le, Jesse D; Stephenson, Samuel; Brugger, Michelle; Lu, David Y; Lieu, Patricia; Sonn, Geoffrey A; Natarajan, Shyam; Dorey, Frederick J; Huang, Jiaoti; Margolis, Daniel J A; Reiter, Robert E; Marks, Leonard S

2014-11-01

We explored the impact of magnetic resonance imaging-ultrasound fusion prostate biopsy on the prediction of final surgical pathology. A total of 54 consecutive men undergoing radical prostatectomy at UCLA after fusion biopsy were included in this prospective, institutional review board approved pilot study. Using magnetic resonance imaging-ultrasound fusion, tissue was obtained from a 12-point systematic grid (mapping biopsy) and from regions of interest detected by multiparametric magnetic resonance imaging (targeted biopsy). A single radiologist read all magnetic resonance imaging, and a single pathologist independently rereviewed all biopsy and whole mount pathology, blinded to prior interpretation and matched specimen. Gleason score concordance between biopsy and prostatectomy was the primary end point. Mean patient age was 62 years and median prostate specific antigen was 6.2 ng/ml. Final Gleason score at prostatectomy was 6 (13%), 7 (70%) and 8-9 (17%). A tertiary pattern was detected in 17 (31%) men. Of 45 high suspicion (image grade 4-5) magnetic resonance imaging targets 32 (71%) contained prostate cancer. The per core cancer detection rate was 20% by systematic mapping biopsy and 42% by targeted biopsy. The highest Gleason pattern at prostatectomy was detected by systematic mapping biopsy in 54%, targeted biopsy in 54% and a combination in 81% of cases. Overall 17% of cases were upgraded from fusion biopsy to final pathology and 1 (2%) was downgraded. The combination of targeted biopsy and systematic mapping biopsy was needed to obtain the best predictive accuracy. In this pilot study magnetic resonance imaging-ultrasound fusion biopsy allowed for the prediction of final prostate pathology with greater accuracy than that reported previously using conventional methods (81% vs 40% to 65%). If confirmed, these results will have important clinical implications. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Methylation profiling identified novel differentially methylated markers including OPCML and FLRT2 in prostate cancer.

PubMed

Wu, Yu; Davison, Jerry; Qu, Xiaoyu; Morrissey, Colm; Storer, Barry; Brown, Lisha; Vessella, Robert; Nelson, Peter; Fang, Min

2016-04-02

To develop new methods to distinguish indolent from aggressive prostate cancers (PCa), we utilized comprehensive high-throughput array-based relative methylation (CHARM) assay to identify differentially methylated regions (DMRs) throughout the genome, including both CpG island (CGI) and non-CGI regions in PCa patients based on Gleason grade. Initially, 26 samples, including 8 each of low [Gleason score (GS) 6] and high (GS ≥7) grade PCa samples and 10 matched normal prostate tissues, were analyzed as a discovery cohort. We identified 3,567 DMRs between normal and cancer tissues, and 913 DMRs distinguishing low from high-grade cancers. Most of these DMRs were located at CGI shores. The top 5 candidate DMRs from the low vs. high Gleason comparison, including OPCML, ELAVL2, EXT1, IRX5, and FLRT2, were validated by pyrosequencing using the discovery cohort. OPCML and FLRT2 were further validated in an independent cohort consisting of 20 low-Gleason and 33 high-Gleason tissues. We then compared patients with biochemical recurrence (n=70) vs. those without (n=86) in a third cohort, and they showed no difference in methylation at these DMR loci. When GS 3+4 cases and GS 4+3 cases were compared, OPCML-DMR methylation showed a trend of lower methylation in the recurrence group (n=30) than in the no-recurrence (n=52) group. We conclude that whole-genome methylation profiling with CHARM revealed distinct patterns of differential DNA methylation between normal prostate and PCa tissues, as well as between different risk groups of PCa as defined by Gleason scores. A panel of selected DMRs may serve as novel surrogate biomarkers for Gleason score in PCa.

Prognostic Value of the New Prostate Cancer International Society of Urological Pathology Grade Groups.

PubMed

Offermann, Anne; Hohensteiner, Silke; Kuempers, Christiane; Ribbat-Idel, Julika; Schneider, Felix; Becker, Finn; Hupe, Marie Christine; Duensing, Stefan; Merseburger, Axel S; Kirfel, Jutta; Reischl, Markus; Lubczyk, Verena; Kuefer, Rainer; Perner, Sven

2017-01-01

Gleason grading is the best independent predictor for prostate cancer (PCa) progression. Recently, a new PCa grading system has been introduced by the International Society of Urological Pathology (ISUP) and is recommended by the World Health Organization (WHO). Following studies observed more accurate and simplified grade stratification of the new system. Aim of this study was to compare the prognostic value of the new grade groups compared to the former Gleason Grading and to determine whether re-definition of Gleason Pattern 4 might reduce upgrading from prostate biopsy to radical prostatectomy (RP) specimen. A cohort of men undergoing RP from 2002 to 2015 at the Hospital of Goeppingen (Goeppingen, Germany) was used for this study. In total, 339 pre-operative prostatic biopsies and corresponding RP specimens, as well as additional 203 RP specimens were re-reviewed for Grade Groups according to the ISUP. Biochemical recurrence-free survival (BFS) after surgery was used as endpoint to analyze prognostic significance. Other clinicopathological data included TNM-stage and pre-operative PSA level. Kaplan-Meier analysis revealed risk stratification of patients based on both former Gleason Grading and ISUP Grade Groups, and was statistically significant using the log-rank test ( p  < 0.001). Both grading systems significantly correlated with TNM-stage and pre-operative PSA level ( p  < 0.001). Higher tumor grade in RP specimen compared to corresponding pre-operative biopsy was observed in 44 and 34.5% of cases considering former Gleason Grading and ISUP Grade Groups, respectively. Both, former Gleason Grading and ISUP Grade Groups predict survival when applied on tumors in prostatic biopsies as well as RP specimens. This is the first validation study on a large representative German community-based cohort to compare the former Gleason Grading with the recently introduced ISUP Grade Groups. Our data indicate that the ISUP Grade Groups do not improve predictive value of PCa grading and might be less sensitive in deciphering tumors with 3 + 4 and 4 + 3 pattern on RP specimen. However, the Grade Group system results less frequently in an upgrading from biopsy to the corresponding RP specimens, indicating a lower risk to miss potentially aggressive tumors not represented on biopsies.

Increased Expression of ALDH1A1 in Prostate Cancer is Correlated With Tumor Aggressiveness: A Tissue Microarray Study of Iranian Patients.

PubMed

Kalantari, Elham; Saadi, Faezeh H; Asgari, Mojgan; Shariftabrizi, Ahmad; Roudi, Raheleh; Madjd, Zahra

2017-09-01

Subpopulations of prostate cancer (PCa) cells expressing putative stem cell markers possess the ability to promote tumor growth, maintenance, and progression. This study aimed to evaluate the expression patterns and clinical significance of putative stem cell marker aldehyde dehydrogenase 1 A1 (ALDH1A1) in prostate tumor tissues. ALDH1A1 expression was examined in a well-defined series of prostate tissues, including 105 (68%) samples of PCa, 21 (13%) samples of high-grade prostatic intraepithelial neoplasia, and 31 (19%) samples of benign prostate hyperplasia, which were embedded in tissue microarray blocks. The correlation of ALDH1A1 expression with clinicopathologic parameters was also assessed. There was a significant difference between the expression level of ALDH1A1 in PCa compared with the high-grade prostatic intraepithelial neoplasia and benign prostate hyperplasia samples (P<0.001). PCa cells expressing ALDH1A1 were more often seen in samples with advanced Gleason score (P=0.05) and high serum prostate specific antigen level (P=0.02). In addition, a positive correlation was found between ALDH1A1 expression and primary tumor stage and regional lymph node involvement (P=0.04 and 0.03, respectively). The significant association between ALDH1A1 expressions with Gleason score indicates the potential role of this protein in PCa tumorigenesis and aggressive behavior; therefore, this cancer stem cell marker can be used as a promising candidate for targeted therapy of PCa, especially those with high Gleason score.

Immunohistochemical analysis of bcl-2, bax, bcl-X, and mcl-1 expression in prostate cancers.

PubMed Central

Krajewska, M.; Krajewski, S.; Epstein, J. I.; Shabaik, A.; Sauvageot, J.; Song, K.; Kitada, S.; Reed, J. C.

1996-01-01

Proteins encoded by bcl-2 family genes are important regulators of programmed cell death and apoptosis. Alterations in the expression of these apoptosis-regulating genes can contribute to the origins of cancer, as well as adversely influence tumor responses to chemo- and radiotherapy. Using antibodies specific for the Bcl-2, Bax, Bcl-X, and Mcl-1 proteins in combination with immunohistochemical methods, we examined for the first time the expression of these bcl-2 family genes in 64 cases of adenocarcinoma of the prostate, including 10 Gleason grade 2 to 4 tumors, 21 grade 5 to 7 tumors, 17 grade 8 to 10 tumors, 8 lymph node metastases, and 8 bone metastases. In addition, 24 cases of prostatic intraepithelial neoplasia (PIN) or PIN coexisting with carcinoma were also evaluated. All immunostaining results were scored with regard to approximate percentage of positive tumor cells and relative immunostaining intensity. Expression of the anti-apoptotic protein Bcl-2 was present in 16 of 64 (25%) adenocarcinomas and tended to be more frequent in high grade tumors (Gleason grade 8 to 10; 41%) and nodal metastases (38%) than in lower grade (Gleason 2 to 7) primary tumors (16%; P < 0.05). Bcl-X was expressed in all 64 (100%) tumors evaluated. Bcl-X immunointensity was generally stronger in high grade primary tumors (grade 8 to 10) and metastases compared with PIN and low grade neoplasms (P < 0.0001). In addition, the proportion of specimens with > 50% Bcl-X-immunopositive tumor cells also was higher in advanced grade primary tumors (Gleason 8 to 10) and metastases than in PIN and low grade tumors (Gleason 2 to 7; P < 0.005). The anti-apoptotic protein Mcl-1 was expressed in 52 of 64 (81%) tumors, compared with only 9 of 24 (38%) cases of PIN (P < 0.001). In addition, the percentage of Mcl-1-positive cells was typically higher in Gleason grade 8 to 10 tumors and metastases than in PIN or lower grade tumors (P = 0.025). In contrast, the pro-apoptotic protein Bax was expressed in all prostate cancers evaluated, with high percentages of immunopositive cells and strong immunointensity typically occurring regardless of tumor grade. The findings suggest that expression of several anti-apoptotic members of the bcl-2 gene family, including bcl-2, bcl-X, and mcl-1 increases during progression of prostate cancers, a finding that may be relevant to the hormone-insensitive, metastatic phenotype of most advanced adenocarcinomas of the prostate. Images Figure 2 PMID:8623925

A new set of wavelet- and fractals-based features for Gleason grading of prostate cancer histopathology images

NASA Astrophysics Data System (ADS)

Mosquera Lopez, Clara; Agaian, Sos

2013-02-01

Prostate cancer detection and staging is an important step towards patient treatment selection. Advancements in digital pathology allow the application of new quantitative image analysis algorithms for computer-assisted diagnosis (CAD) on digitized histopathology images. In this paper, we introduce a new set of features to automatically grade pathological images using the well-known Gleason grading system. The goal of this study is to classify biopsy images belonging to Gleason patterns 3, 4, and 5 by using a combination of wavelet and fractal features. For image classification we use pairwise coupling Support Vector Machine (SVM) classifiers. The accuracy of the system, which is close to 97%, is estimated through three different cross-validation schemes. The proposed system offers the potential for automating classification of histological images and supporting prostate cancer diagnosis.

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.

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.

Predictors of Gleason Score (GS) upgrading on subsequent prostatectomy: a single Institution study in a cohort of patients with GS 6

PubMed Central

Mehta, Vikas; Rycyna, Kevin; Baesens, Bart MM; Barkan, Güliz A; Paner, Gladell P; Flanigan, Robert C; Wojcik, Eva M; Venkataraman, Girish

2012-01-01

Background Biopsy Gleason score (bGS) remains an important prognostic indicator for adverse outcomes in Prostate Cancer (PCA). In the light of recent studies purporting difference in prognostic outcomes for the subgroups of GS7 group (primary Gleason pattern 4 vs. 3), upgrading of a bGS of 6 to a GS≥7 has serious implications. We sought to identify pre-operative factors associated with upgrading in a cohort of GS6 patients who underwent prostatectomy. Design We identified 281 cases of GS6 PCA on biopsy with subsequent prostatectomies. Using data on pre-operative variables (age, PSA, biopsy pathology parameters), logistic regression models (LRM) were developed to identify factors that could be used to predict upgrading to GS≥7 on subsequent prostatectomy. A decision tree (DT) was constructed. Results 92 of 281 cases (32.7%) were upgraded on subsequent prostatectomy. LRM identified a model with two variables with statistically significant ability to predict upgrading, including pre-biopsy PSA (Odds Ratio 8.66; 2.03-37.49, 95% CI) and highest percentage of cancer at any single biopsy site (Odds Ratio 1.03, 1.01-1.05, 95% CI). This two-parameter model yielded an area under curve of 0.67. The decision tree was constructed using only 3 leave nodes; with a test set classification accuracy of 70%. Conclusions A simplistic model using clinical and biopsy data is able to predict the likelihood of upgrading of GS with an acceptable level of certainty. External validation of these findings along with development of a nomogram will aid in better stratifying the cohort of low risk patients as based on the GS. PMID:22949931

Contemporary Population-Based Comparison of Localized Ductal Adenocarcinoma and High-Risk Acinar Adenocarcinoma of the Prostate.

PubMed

Packiam, Vignesh T; Patel, Sanjay G; Pariser, Joseph J; Richards, Kyle A; Weiner, Adam B; Paner, Gladell P; VanderWeele, David J; Zagaja, Gregory P; Eggener, Scott E

2015-10-01

To compare pathological characteristics, treatment patterns, and survival in patients with ductal adenocarcinoma (DC) compared to those with acinar adenocarcinoma (AC). Using the National Cancer Database, we identified patients diagnosed with clinically localized (cN0, cM0) pure DC (n = 1328) and AC (n = 751,635) between 1998 and 2011. High-risk AC was defined as Gleason 8-10. Demographic, treatment, pathological, and survival characteristics of patients were compared. Compared to patients with Gleason 8-10 AC, those with DC presented with lower mean prostate-specific antigen (10.3 vs 16.2 ng/mL, P <.001), had similar rates (11.7% vs 11.5%, P = .8) of clinical extra-capsular extension (stage ≥ cT3), and were more likely to undergo prostatectomy (54% vs 36%, P <.001). Compared to patients with Gleason 8-10 AC undergoing prostatectomy, those with DC had more favorable pathology: stage ≥ T3 (39% vs 52%, P <.001), fewer positive lymph nodes (4% vs 11%, P <.001), and fewer positive margins (25% vs 33%, P <.001). On Kaplan-Meier analysis, patients with DC had similar 5-year survival (75.0%, 95% confidence interval [CI] [71.7-78.9]) compared to those with Gleason 8-10 AC (77.1%, 95% CI [76.6%-77.6%], P = .2). On Cox multivariable analysis, patients with Gleason 8-10 AC had a similar risk of death compared to those with DC (hazards ratio = 0.92, 95% CI [0.69-1.23], P = 6). In this large contemporary population-based series, patients with DC of the prostate presented with lower prostate-specific antigen, had more favorable pathological features, and similar overall survival compared to men with Gleason 8-10 AC. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparison of Biochemical Relapse-Free Survival Between Primary Gleason Score 3 and Primary Gleason Score 4 for Biopsy Gleason Score 7 Prostate Cancer

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

Burdick, Michael J.; Reddy, Chandana A.; Ulchaker, James

2009-04-01

Purpose: To determine whether the primary grade (PG) of biopsy Gleason score (GS) 7 prostate cancer (CaP) was predictive for biochemical relapse-free survival (bRFS). Most of the present data regarding the PG of GS7 CaP refer to surgical specimens. Our goal was to determine whether the biopsy GS used at the time of medical decision making predicted for the biochemical outcome. Methods and Materials: We reviewed the data from 705 patients with biopsy GS7 CaP, from a prospectively maintained database, who had been treated at our institution between September 1996 and March 2005 with radical prostatectomy (n = 310), externalmore » beam radiotherapy (n = 268), or prostate radioactive seed implantation (n = 127). The bRFS rates were estimated using the Kaplan-Meier method. Cox proportional hazards regression analysis was used for univariate and multivariate analyses examining these factors in relation to bRFS: PG of biopsy GS, initial prostate-specific antigen level, clinical T stage, use of androgen deprivation, risk group (high or intermediate), and treatment modality. Results: The 5-year bRFS rate was 78% and 71% (p = 0.0108) for biopsy GS7 PG3 CaP and biopsy GS7 PG4 CaP, respectively. Comparing PG3 and PG4 within treatment modalities, only prostate implantation patients had a significant difference in the 5-year bRFS rate, 88% vs. 76%, respectively (p = 0.0231). On multivariate analysis, the PG of biopsy GS remained an independent predictor of bRFS, with PG3 having better bRFS than PG4 (relative risk, 0.655; 95% confidence interval, 0.472-0.909; p = 0.0113). Conclusion: Biopsy GS7 PG4 CaP carries a worse bRFS than biopsy GS7 PG3 CaP.« less

Upgrading and Downgrading of Prostate Cancer from Biopsy to Radical Prostatectomy: Incidence and Predictive Factors Using the Modified Gleason Grading System and Factoring in Tertiary Grades

PubMed Central

Epstein, Jonathan I.; Feng, Zhaoyong; Trock, Bruce J.; Pierorazio, Phillip M.

2015-01-01

Background Prior studies assessing the correlation of Gleason score (GS) at needle biopsy and corresponding radical prostatectomy (RP) predated the use of the modified Gleason scoring system and did not factor in tertiary grade patterns. Objective To assess the relation of biopsy and RP grade in the largest study to date. Design, setting, and participants A total of 7643 totally embedded RP and corresponding needle biopsies (2004–2010) were analyzed according to the updated Gleason system. Interventions All patients underwent prostate biopsy prior to RP. Measurements The relation of upgrading or downgrading to patient and cancer characteristics was compared using the chi-square test, Student t test, and multivariable logistic regression. Results and limitations A total of 36.3% of cases were upgraded from a needle biopsy GS 5–6 to a higher grade at RP (11.2% with GS 6 plus tertiary). Half of the cases had matching GS 3 + 4 = 7 at biopsy and RP with an approximately equal number of cases downgraded and upgraded at RP. With biopsy GS 4 + 3 = 7, RP GS was almost equally 3 + 4 = 7 and 4 + 3 = 7. Biopsy GS 8 led to an almost equal distribution between RP GS 4 + 3 = 7, 8, and 9–10. A total of 58% of the cases had matching GS 9–10 at biopsy and RP. In multivariable analysis, increasing age (p < 0.0001), increasing serum prostate-specific antigen level (p < 0.0001), decreasing RP weight (p < 0.0001), and increasing maximum percentage cancer/core (p < 0.0001) predicted the upgrade from biopsy GS 5–6 to higher at RP. Despite factoring in multiple variables including the number of positive cores and the maximum percentage of cancer per core, the concordance indexes were not sufficiently high to justify the use of nomograms for predicting upgrading and downgrading for the individual patient. Conclusions Almost 20% of RP cases have tertiary patterns. A needle biopsy can sample a tertiary higher Gleason pattern in the RP, which is then not recorded in the standard GS reporting, resulting in an apparent overgrading on the needle biopsy. PMID:22336380

Upgrading and downgrading of prostate cancer from biopsy to radical prostatectomy: incidence and predictive factors using the modified Gleason grading system and factoring in tertiary grades.

PubMed

Epstein, Jonathan I; Feng, Zhaoyong; Trock, Bruce J; Pierorazio, Phillip M

2012-05-01

Prior studies assessing the correlation of Gleason score (GS) at needle biopsy and corresponding radical prostatectomy (RP) predated the use of the modified Gleason scoring system and did not factor in tertiary grade patterns. To assess the relation of biopsy and RP grade in the largest study to date. A total of 7643 totally embedded RP and corresponding needle biopsies (2004-2010) were analyzed according to the updated Gleason system. All patients underwent prostate biopsy prior to RP. The relation of upgrading or downgrading to patient and cancer characteristics was compared using the chi-square test, Student t test, and multivariable logistic regression. A total of 36.3% of cases were upgraded from a needle biopsy GS 5-6 to a higher grade at RP (11.2% with GS 6 plus tertiary). Half of the cases had matching GS 3+4=7 at biopsy and RP with an approximately equal number of cases downgraded and upgraded at RP. With biopsy GS 4+3=7, RP GS was almost equally 3+4=7 and 4+3=7. Biopsy GS 8 led to an almost equal distribution between RP GS 4+3=7, 8, and 9-10. A total of 58% of the cases had matching GS 9-10 at biopsy and RP. In multivariable analysis, increasing age (p<0.0001), increasing serum prostate-specific antigen level (p<0.0001), decreasing RP weight (p<0.0001), and increasing maximum percentage cancer/core (p<0.0001) predicted the upgrade from biopsy GS 5-6 to higher at RP. Despite factoring in multiple variables including the number of positive cores and the maximum percentage of cancer per core, the concordance indexes were not sufficiently high to justify the use of nomograms for predicting upgrading and downgrading for the individual patient. Almost 20% of RP cases have tertiary patterns. A needle biopsy can sample a tertiary higher Gleason pattern in the RP, which is then not recorded in the standard GS reporting, resulting in an apparent overgrading on the needle biopsy. Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Gleason Score 7 Prostate Cancers Emerge through Branched Evolution of Clonal Gleason Pattern 3 and 4.

PubMed

Sowalsky, Adam G; Kissick, Haydn T; Gerrin, Sean J; Schaefer, Rachel J; Xia, Zheng; Russo, Joshua W; Arredouani, M Simo; Bubley, Glenn J; Sanda, Martin G; Li, Wei; Ye, Huihui; Balk, Steven P

2017-07-15

Purpose: The molecular features that account for the distinct histology and aggressive biological behavior of Gleason pattern 4 (Gp4) versus Gp3 prostate cancer, and whether Gp3 tumors progress directly to Gp4, remain to be established. Experimental Design: Whole-exome sequencing and transcriptome profiling of laser capture-microdissected adjacent Gp3 and cribiform Gp4 were used to determine the relationship between these entities. Results: Sequencing confirmed that adjacent Gp3 and Gp4 were clonal based on multiple shared genomic alterations. However, large numbers of unique mutations in the Gp3 and Gp4 tumors showed that the Gp4 were not derived directly from the Gp3. Remarkably, the Gp3 tumors retain their indolent-appearing morphology despite acquisition of multiple genomic alterations, including tumor suppressor losses. Although there were no consistent genomic alterations that distinguished Gp3 from Gp4, pairwise transcriptome analyses identified increased c-Myc and decreased p53 activity in Gp4 versus adjacent clonal Gp3 foci. Conclusions: These findings establish that at least a subset of Gp3 and aggressive Gp4 tumors have a common origin, and support a branched evolution model wherein the Gp3 and Gp4 tumors emerge early from a common precursor and subsequently undergo substantial divergence. Genomic alterations detectable in the Gp3 may distinguish these tumors from truly indolent Gp3. Screening for a panel of these genomic alterations in men who have prostate biopsies showing only Gp3 (Gleason score 6, Gs6) may allow for more precise selection of men who can be safely managed by active surveillance versus those who may benefit from further intervention. Clin Cancer Res; 23(14); 3823-33. ©2017 AACR . ©2017 American Association for Cancer Research.

A natural language processing program effectively extracts key pathologic findings from radical prostatectomy reports.

PubMed

Kim, Brian J; Merchant, Madhur; Zheng, Chengyi; Thomas, Anil A; Contreras, Richard; Jacobsen, Steven J; Chien, Gary W

2014-12-01

Natural language processing (NLP) software programs have been widely developed to transform complex free text into simplified organized data. Potential applications in the field of medicine include automated report summaries, physician alerts, patient repositories, electronic medical record (EMR) billing, and quality metric reports. Despite these prospects and the recent widespread adoption of EMR, NLP has been relatively underutilized. The objective of this study was to evaluate the performance of an internally developed NLP program in extracting select pathologic findings from radical prostatectomy specimen reports in the EMR. An NLP program was generated by a software engineer to extract key variables from prostatectomy reports in the EMR within our healthcare system, which included the TNM stage, Gleason grade, presence of a tertiary Gleason pattern, histologic subtype, size of dominant tumor nodule, seminal vesicle invasion (SVI), perineural invasion (PNI), angiolymphatic invasion (ALI), extracapsular extension (ECE), and surgical margin status (SMS). The program was validated by comparing NLP results to a gold standard compiled by two blinded manual reviewers for 100 random pathology reports. NLP demonstrated 100% accuracy for identifying the Gleason grade, presence of a tertiary Gleason pattern, SVI, ALI, and ECE. It also demonstrated near-perfect accuracy for extracting histologic subtype (99.0%), PNI (98.9%), TNM stage (98.0%), SMS (97.0%), and dominant tumor size (95.7%). The overall accuracy of NLP was 98.7%. NLP generated a result in <1 second, whereas the manual reviewers averaged 3.2 minutes per report. This novel program demonstrated high accuracy and efficiency identifying key pathologic details from the prostatectomy report within an EMR system. NLP has the potential to assist urologists by summarizing and highlighting relevant information from verbose pathology reports. It may also facilitate future urologic research through the rapid and automated creation of large databases.

Characteristics of PI-RADS 4 lesions within the prostatic peripheral zone: a retrospective diagnostic accuracy study evaluating 170 lesions.

PubMed

Shankar, Prasad R; Curci, Nicole E; Davenport, Matthew S

2017-12-02

To determine whether peripheral zone PI-RADS 4 observations can be further risk-stratified. This was an IRB-approved HIPAA-compliant retrospective diagnostic accuracy study. Peripheral zone PI-RADS 4 observations prospectively identified at the study institution from 8/1/2015 to 12/31/2016 (n = 170 in 149 mpMRIs) were reviewed independently by two blinded genitourinary radiologists on the basis of (a) PI-RADS v2 shape, (b) pattern of peripheral zone sparing, and (c) rationale for PI-RADS 4 designation. Reference standard was targeted MR-ultrasound fusion biopsy and detection of Gleason 7+ prostate cancer. Positive predictive values (PPVs) were calculated. Predictors were assessed with binary logistic regression. PI-RADS 4 lesions with a DWI score of 4 were more likely to represent Gleason 7+ prostate cancer (p = 0.008-0.01; Reader 1 PPV: 53%; Reader 2 PPV: 48%). Pattern of peripheral zone sparing and most lesion shapes were not predictive (p > 0.05); however, oval lesions were predictive for Reader 1 (PPV = 59%, p = 0.03) and lentiform lesions were predictive for Reader 2 (PPV = 74%, p = 0.01). Lesions scored as "not meeting PI-RADS 4 criteria" had significantly lower PPV (p = 0.016-0.003; Reader 1 PPV: 14%, Reader 2 PPV: 16%). Peripheral zone PI-RADS 4 lesions with a DWI score of 4 are more likely Gleason 7+ cancer than those with a DWI score of 3. Lesions overcalled as PI-RADS 4 have PPV similar to published PI-RADS 3 data. Lesion shape and peripheral zone sparing in general do not predict Gleason 7+ cancer within PI-RADS 4 observations.

Optimized color decomposition of localized whole slide images and convolutional neural network for intermediate prostate cancer classification

NASA Astrophysics Data System (ADS)

Zhou, Naiyun; Gao, Yi

2017-03-01

This paper presents a fully automatic approach to grade intermediate prostate malignancy with hematoxylin and eosin-stained whole slide images. Deep learning architectures such as convolutional neural networks have been utilized in the domain of histopathology for automated carcinoma detection and classification. However, few work show its power in discriminating intermediate Gleason patterns, due to sporadic distribution of prostate glands on stained surgical section samples. We propose optimized hematoxylin decomposition on localized images, followed by convolutional neural network to classify Gleason patterns 3+4 and 4+3 without handcrafted features or gland segmentation. Crucial glands morphology and structural relationship of nuclei are extracted twice in different color space by the multi-scale strategy to mimic pathologists' visual examination. Our novel classification scheme evaluated on 169 whole slide images yielded a 70.41% accuracy and corresponding area under the receiver operating characteristic curve of 0.7247.

Prostate extracellular vesicles in patient plasma as a liquid biopsy platform for prostate cancer using nanoscale flow cytometry.

PubMed

Biggs, Colleen N; Siddiqui, Khurram M; Al-Zahrani, Ali A; Pardhan, Siddika; Brett, Sabine I; Guo, Qiu Q; Yang, Jun; Wolf, Philipp; Power, Nicholas E; Durfee, Paul N; MacMillan, Connor D; Townson, Jason L; Brinker, Jeffrey C; Fleshner, Neil E; Izawa, Jonathan I; Chambers, Ann F; Chin, Joseph L; Leong, Hon S

2016-02-23

Extracellular vesicles released by prostate cancer present in seminal fluid, urine, and blood may represent a non-invasive means to identify and prioritize patients with intermediate risk and high risk of prostate cancer. We hypothesize that enumeration of circulating prostate microparticles (PMPs), a type of extracellular vesicle (EV), can identify patients with Gleason Score≥4+4 prostate cancer (PCa) in a manner independent of PSA. Plasmas from healthy volunteers, benign prostatic hyperplasia patients, and PCa patients with various Gleason score patterns were analyzed for PMPs. We used nanoscale flow cytometry to enumerate PMPs which were defined as submicron events (100-1000nm) immunoreactive to anti-PSMA mAb when compared to isotype control labeled samples. Levels of PMPs (counts/µL of plasma) were also compared to CellSearch CTC Subclasses in various PCa metastatic disease subtypes (treatment naïve, castration resistant prostate cancer) and in serially collected plasma sets from patients undergoing radical prostatectomy. PMP levels in plasma as enumerated by nanoscale flow cytometry are effective in distinguishing PCa patients with Gleason Score≥8 disease, a high-risk prognostic factor, from patients with Gleason Score≤7 PCa, which carries an intermediate risk of PCa recurrence. PMP levels were independent of PSA and significantly decreased after surgical resection of the prostate, demonstrating its prognostic potential for clinical follow-up. CTC subclasses did not decrease after prostatectomy and were not effective in distinguishing localized PCa patients from metastatic PCa patients. PMP enumeration was able to identify patients with Gleason Score ≥8 PCa but not patients with Gleason Score 4+3 PCa, but offers greater confidence than CTC counts in identifying patients with metastatic prostate cancer. CTC Subclass analysis was also not effective for post-prostatectomy follow up and for distinguishing metastatic PCa and localized PCa patients. Nanoscale flow cytometry of PMPs presents an emerging biomarker platform for various stages of prostate cancer.

Prostate extracellular vesicles in patient plasma as a liquid biopsy platform for prostate cancer using nanoscale flow cytometry

PubMed Central

Al-Zahrani, Ali A.; Pardhan, Siddika; Brett, Sabine I.; Guo, Qiu Q.; Yang, Jun; Wolf, Philipp; Power, Nicholas E.; Durfee, Paul N.; MacMillan, Connor D.; Townson, Jason L.; Brinker, Jeffrey C.; Fleshner, Neil E.; Izawa, Jonathan I.; Chambers, Ann F.; Chin, Joseph L.; Leong, Hon S.

2016-01-01

Background Extracellular vesicles released by prostate cancer present in seminal fluid, urine, and blood may represent a non-invasive means to identify and prioritize patients with intermediate risk and high risk of prostate cancer. We hypothesize that enumeration of circulating prostate microparticles (PMPs), a type of extracellular vesicle (EV), can identify patients with Gleason Score≥4+4 prostate cancer (PCa) in a manner independent of PSA. Patients and Methods Plasmas from healthy volunteers, benign prostatic hyperplasia patients, and PCa patients with various Gleason score patterns were analyzed for PMPs. We used nanoscale flow cytometry to enumerate PMPs which were defined as submicron events (100-1000nm) immunoreactive to anti-PSMA mAb when compared to isotype control labeled samples. Levels of PMPs (counts/μL of plasma) were also compared to CellSearch CTC Subclasses in various PCa metastatic disease subtypes (treatment naïve, castration resistant prostate cancer) and in serially collected plasma sets from patients undergoing radical prostatectomy. Results PMP levels in plasma as enumerated by nanoscale flow cytometry are effective in distinguishing PCa patients with Gleason Score≥8 disease, a high-risk prognostic factor, from patients with Gleason Score≤7 PCa, which carries an intermediate risk of PCa recurrence. PMP levels were independent of PSA and significantly decreased after surgical resection of the prostate, demonstrating its prognostic potential for clinical follow-up. CTC subclasses did not decrease after prostatectomy and were not effective in distinguishing localized PCa patients from metastatic PCa patients. Conclusions PMP enumeration was able to identify patients with Gleason Score ≥8 PCa but not patients with Gleason Score 4+3 PCa, but offers greater confidence than CTC counts in identifying patients with metastatic prostate cancer. CTC Subclass analysis was also not effective for post-prostatectomy follow up and for distinguishing metastatic PCa and localized PCa patients. Nanoscale flow cytometry of PMPs presents an emerging biomarker platform for various stages of prostate cancer. PMID:26814433

Validation of the prognostic grouping of the seventh edition of the tumor-nodes-metastasis classification using a large-scale prospective cohort study database of prostate cancer treated with primary androgen deprivation therapy.

PubMed

Kimura, Tomokazu; Onozawa, Mizuki; Miyazaki, Jun; Kawai, Koji; Nishiyama, Hiroyuki; Hinotsu, Shiro; Akaza, Hideyuki

2013-09-01

In the TNM seventh edition, a prognostic grouping for prostate cancer incorporating prostate-specific antigen and Gleason score was advocated. The present study was carried out to evaluate and validate prognostic grouping in prostate cancer patients. The 15 259 study patients treated with primary androgen deprivation therapy were enrolled in the Japan Study Group of Prostate Cancer. Overall survival was stratified by tumor-nodes-metastasis, Gleason score and prostate-specific antigen, and extensively analyzed. The accuracy of grouping systems was evaluated by the concordance index. The 5-year overall survival in prognostic grouping-I, IIA, IIB, III and IV was 90.0%, 88.3%, 84.8%, 80.6% and 57.1%, respectively. When considering subgroup stratification, the 5-year overall survival of subgroups prognostic grouping-IIA, IIB, III and IV was 80.9∼90.5%, 75.4∼91.8%, 75.7∼89.0% and 46.9∼86.2%, respectively. When prognostic grouping-IIB was subclassified into IIB1 (except IIB2) and IIB2 (T1-2b, prostate-specific antigen >20, Gleason score ≥8, and T2c, Gleason score ≥8), the 5-year overall survival of IIB2 was significantly lower than that of IIB1 (79.4% and 87.3%, P < 0.0001). Also, when prognostic grouping-IV was subclassified into IV1 (except IV2) and IV2 (M1, prostate-specific antigen >100 or Gleason score ≥8), the 5-year overall survival of prognostic grouping-IV1 was superior to that of IV2 (72.9% and 49.5%, P < 0.0001). Prognostic groupings were reclassified into modified prognostic groupings, divided into modified prognostic grouping-A (prognostic grouping-I, IIA, and IIB1), modified prognostic grouping-B (prognostic grouping-IIB2 and III), modified prognostic grouping-C (prognostic grouping-IV1) and modified prognostic grouping-D (prognostic grouping-IV2). The concordance index of prognostic grouping and modified prognostic grouping for overall survival was 0.670 and 0.685, respectively. Prognostic grouping could stratify the prognosis of prostate cancer patients. However, there is considerable variation among the prognostic grouping subgroups. Thus, the use of a modified prognostic grouping for patients treated with primary androgen deprivation therapy is advisable. © 2013 The Japanese Urological Association.

Body mass index was associated with upstaging and upgrading in patients with low-risk prostate cancer who met the inclusion criteria for active surveillance.

PubMed

de Cobelli, Ottavio; Terracciano, Daniela; Tagliabue, Elena; Raimondi, Sara; Galasso, Giacomo; Cioffi, Antonio; Cordima, Giovanni; Musi, Gennaro; Damiano, Rocco; Cantiello, Francesco; Detti, Serena; Victor Matei, Deliu; Bottero, Danilo; Renne, Giuseppe; Ferro, Matteo

2015-05-01

Obesity is associated with an increased risk of high-grade prostate cancer (PCa). The effect of body mass index (BMI) as a predictor of progression in men with low-risk PCa has been only poorly assessed. In this study, we evaluated the association of BMI with progression in patients with low-risk PCa who met the inclusion criteria for the active surveillance (AS) protocol. We assessed 311 patients who underwent radical prostatectomy and were eligible for AS according to the following criteria: clinical stage T2a or less, prostate-specific antigen level < 10 ng/ml, 2 or fewer cores involved with cancer, Gleason score ≤ 6 grade, and prostate-specific antigen density < 0.2 ng/ml/cc. Reclassification was defined as upstaged (pathological stage > pT2) and upgraded (Gleason score ≥ 7; primary Gleason pattern 4) disease. Seminal vesicle invasion, positive lymph nodes, and tumor volume ≥ 0.5 ml were also recorded. We found that high BMI was significantly associated with upgrading, upstaging, and seminal vesicle invasion, whereas it was not associated with positive lymph nodes or large tumor volume. At multivariate analysis, 1 unit increase of BMI significantly increased the risk of upgrading, upstaging, seminal vesicle invasion, and any outcome by 21%, 23%, 27%, and 20%, respectively. The differences between areas under the receiver operating characteristics curves comparing models with and without BMI were statistically significant for upgrading (P = 0.0002), upstaging (P = 0.0007), and any outcome (P = 0.0001). BMI should be a selection criterion for inclusion of patients with low-risk PCa in AS programs. Our results support the idea that obesity is associated with worse prognosis and suggest that a close AS program is an appropriate treatment option for obese subjects. Copyright © 2015 Elsevier Inc. All rights reserved.

Prostatic needle biopsies following primary high intensity focused ultrasound (HIFU) therapy for prostatic adenocarcinoma: histopathological features in tumour and non-tumour tissue.

PubMed

Ryan, Paul; Finelli, Antonio; Lawrentschuk, Nathan; Fleshner, Neil; Sweet, Joan; Cheung, Carol; van der Kwast, Theodorus; Evans, Andrew

2012-08-01

High intensity focused ultrasound (HIFU) is currently offered as primary treatment for patients with clinically localised prostate cancer. Data on histopathological features of post-treatment biopsies are limited. Pretreatment biopsies were identified in 45 men (age range 41-85) who received primary HIFU therapy. Post-HIFU biopsies were performed in 30 of these patients (67%) at mean 14.1 months (95% CI 11.7 to 16.5) follow-up, 22 due to rising PSA and eight as part of routine follow-up. Biopsies were examined for presence, distribution and extent of adenocarcinoma, Gleason scores, use of standard immunohistochemistry and ablative tissue changes were attributable to HIFU. In post-HIFU biopsies performed for biochemical failure, 17/22 (77%) contained adenocarcinoma; 4/22 (18%) had higher post-HIFU Gleason score; 3/22 (14%) had newly recognised bilateral involvement; and 4/22 (18%) had higher percentage tissue involvement compared with pre-HIFU biopsies. Of cases without rising post-HIFU PSA, 2/8 (25%) routine follow-up biopsies contained adenocarcinoma. Stromal fibrosis was the commonest finding in non-tumour post-HIFU biopsy tissue (17/30, 57%) with coagulative necrosis occurring in fewer cases (4/30, 13%) and over a shorter follow-up interval than cases showing fibrosis (8.5 (0.2-16.8) vs 15.3 (11.5-19.1) months). Treatment effects in tumour cells precluding the assignment of Gleason scores or use of immunohistochemistry in post-HIFU biopsies were not identified. Post-HIFU biopsies are positive in more than 75% of patients with elevated or rising PSA. Stromal fibrosis is common but the tissue effects of this modality do not appear to impair pathologists' ability to detect and grade adenocarcinoma in follow-up biopsies.

Patterns and Predictors of Early Biochemical Recurrence After Radical Prostatectomy and Adjuvant Radiation Therapy in Men With pT{sub 3}N{sub 0} Prostate Cancer: Implications for Multimodal Therapies

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

Briganti, Alberto, E-mail: briganti.alberto@hsr.it; Joniau, Steven; Gandaglia, Giorgio

Purpose: The aim of our study was to evaluate patterns and predictors of early biochemical recurrence (eBCR) after radical prostatectomy (RP) and adjuvant radiation therapy (aRT) in order to identify which individuals might benefit from additional treatments. Methods and Materials: We evaluated 390 patients with pT{sub 3}N{sub 0} prostate cancer (PCa) receiving RP and aRT at 6 European centers between 1993 and 2006. Patients who were free from BCR at <2 years' follow-up were excluded. This resulted in 374 assessable patients. Early BCR was defined as 2 consecutive prostate-specific antigen (PSA) test values >0.2 ng/mL within 2 or 3 yearsmore » after aRT. Uni- and multivariable Cox regression analyses predicting overall and eBCR after aRT were fitted. Covariates consisted of preoperative PSA results, surgical margins, pathological stage, Gleason score, and aRT dose. Results: Overall, 5- and 8-year BCR-free survival rates were 77.1% and 70.8%, respectively. At a median follow-up of 86 months after aRT, 33 (8.8%) and 55 (14.6%) men experienced BCR within 2 or 3 years after aRT, respectively. In multivariable analyses, Gleason scores of 8 to 10 represented the only independent predictor of eBCR after aRT (all, P≤.01). The risk of BCR was significantly higher in patients with a Gleason score of 8 to 10 disease than in those with Gleason 2 to 6 within 24 months after treatment, after adjusting for all covariates (all, P≤.04). However, given a 24-month BCR free period, the risk of subsequent BCR for men with poorly differentiated disease was equal to that of men with less aggressive disease (all, P≥.3). Conclusions: High Gleason score represents the only predictor of eBCR after RP and aRT in patients affected by pT{sub 3}N{sub 0} PCa. Given the association between early PSA recurrence, clinical progression, and mortality, these patients might be considered candidates for adjuvant medical therapy and/or prophylactic whole-pelvis radiation therapy in addition to aRT, delivered to the prostatic bed.« less

Unification of favourable intermediate-, unfavourable intermediate-, and very high-risk stratification criteria for prostate cancer.

PubMed

Zumsteg, Zachary S; Zelefsky, Michael J; Woo, Kaitlin M; Spratt, Daniel E; Kollmeier, Marisa A; McBride, Sean; Pei, Xin; Sandler, Howard M; Zhang, Zhigang

2017-11-01

To improve on the existing risk-stratification systems for prostate cancer. This was a retrospective investigation including 2 248 patients undergoing dose-escalated external beam radiotherapy (EBRT) at a single institution. We separated National Comprehensive Cancer Network (NCCN) intermediate-risk prostate cancer into 'favourable' and 'unfavourable' groups based on primary Gleason pattern, percentage of positive biopsy cores (PPBC), and number of NCCN intermediate-risk factors. Similarly, NCCN high-risk prostate cancer was stratified into 'standard' and 'very high-risk' groups based on primary Gleason pattern, PPBC, number of NCCN high-risk factors, and stage T3b-T4 disease. Patients with unfavourable-intermediate-risk (UIR) prostate cancer had significantly inferior prostate-specific antigen relapse-free survival (PSA-RFS, P < 0.001), distant metastasis-free survival (DMFS, P < 0.001), prostate cancer-specific mortality (PCSM, P < 0.001), and overall survival (OS, P < 0.001) compared with patients with favourable-intermediate-risk (FIR) prostate cancer. Similarly, patients with very high-risk (VHR) prostate cancer had significantly worse PSA-RFS (P < 0.001), DMFS (P < 0.001), and PCSM (P = 0.001) compared with patients with standard high-risk (SHR) prostate cancer. Moreover, patients with FIR and low-risk prostate cancer had similar outcomes, as did patients with UIR and SHR prostate cancer. Consequently, we propose the following risk-stratification system: Group 1, low risk and FIR; Group 2, UIR and SHR; and Group 3, VHR. These groups have markedly different outcomes, with 8-year distant metastasis rates of 3%, 9%, and 29% (P < 0.001) for Groups 1, 2, and 3, respectively, and 8-year PCSM of 1%, 4%, and 13% (P < 0.001) after EBRT. This modified stratification system was significantly more accurate than the three-tiered NCCN system currently in clinical use for all outcomes. Modifying the NCCN risk-stratification system to group FIR with low-risk patients and UIR with SHR patients, results in modestly improved prediction of outcomes, potentially allowing better personalisation of therapeutic recommendations. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Risk of Pathologic Upgrading or Locally Advanced Disease in Early Prostate Cancer Patients Based on Biopsy Gleason Score and PSA: A Population-Based Study of Modern Patients

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

Caster, Joseph M.; Falchook, Aaron D.; Hendrix, Laura H.

Purpose: Radiation oncologists rely on available clinical information (biopsy Gleason score and prostate-specific antigen [PSA]) to determine the optimal treatment regimen for each prostate cancer patient. Existing published nomograms correlating clinical to pathologic extent of disease were based on patients treated in the 1980s and 1990s at select academic institutions. We used the Surveillance, Epidemiology, and End Results (SEER) database to examine pathologic outcomes (Gleason score and cancer stage) in early prostate cancer patients based on biopsy Gleason score and PSA concentration. Methods and Materials: This analysis included 25,858 patients whose cancer was diagnosed between 2010 and 2011, with biopsymore » Gleason scores of 6 to 7 and clinical stage T1 to T2 disease, who underwent radical prostatectomy. In subgroups based on biopsy Gleason score and PSA level, we report the proportion of patients with pathologically advanced disease (positive surgical margin or pT3-T4 disease) or whose Gleason score was upgraded. Logistic regression was used to examine factors associated with pathologic outcomes. Results: For patients with biopsy Gleason score 6 cancers, 84% of those with PSA <10 ng/mL had surgical T2 disease with negative margins; this decreased to 61% in patients with PSA of 20 to 29.9 ng/mL. Gleason score upgrading was seen in 43% (PSA: <10 ng/mL) to 61% (PSA: 20-29.9 ng/mL) of biopsy Gleason 6 patients. Patients with biopsy Gleason 7 cancers had a one-third (Gleason 3 + 4; PSA: <10 ng/mL) to two-thirds (Gleason 4 + 3; PSA: 20-29.9 ng/mL) probability of having pathologically advanced disease. Gleason score upgrading was seen in 11% to 19% of patients with biopsy Gleason 4 + 3 cancers. Multivariable analysis showed that higher PSA and older age were associated with Gleason score upgrading and pathologically advanced disease. Conclusions: This is the first population-based study to examine pathologic extent of disease and pathologic Gleason score upgrading based on clinically available information in modern patients. These data inform the selection of radiation therapy strategies and an understanding of whether prostatectomy alone is likely to be curative for patients with early prostate cancers.« less

Multicentre evaluation of targeted and systematic biopsies using magnetic resonance and ultrasound image-fusion guided transperineal prostate biopsy in patients with a previous negative biopsy.

PubMed

Hansen, Nienke L; Kesch, Claudia; Barrett, Tristan; Koo, Brendan; Radtke, Jan P; Bonekamp, David; Schlemmer, Heinz-Peter; Warren, Anne Y; Wieczorek, Kathrin; Hohenfellner, Markus; Kastner, Christof; Hadaschik, Boris

2017-11-01

To evaluate the detection rates of targeted and systematic biopsies in magnetic resonance imaging (MRI) and ultrasound (US) image-fusion transperineal prostate biopsy for patients with previous benign transrectal biopsies in two high-volume centres. A two centre prospective outcome study of 487 patients with previous benign biopsies that underwent transperineal MRI/US fusion-guided targeted and systematic saturation biopsy from 2012 to 2015. Multiparametric MRI (mpMRI) was reported according to Prostate Imaging Reporting and Data System (PI-RADS) Version 1. Detection of Gleason score 7-10 prostate cancer on biopsy was the primary outcome. Positive (PPV) and negative (NPV) predictive values including 95% confidence intervals (95% CIs) were calculated. Detection rates of targeted and systematic biopsies were compared using McNemar's test. The median (interquartile range) PSA level was 9.0 (6.7-13.4) ng/mL. PI-RADS 3-5 mpMRI lesions were reported in 343 (70%) patients and Gleason score 7-10 prostate cancer was detected in 149 (31%). The PPV (95% CI) for detecting Gleason score 7-10 prostate cancer was 0.20 (±0.07) for PI-RADS 3, 0.32 (±0.09) for PI-RADS 4, and 0.70 (±0.08) for PI-RADS 5. The NPV (95% CI) of PI-RADS 1-2 was 0.92 (±0.04) for Gleason score 7-10 and 0.99 (±0.02) for Gleason score ≥4 + 3 cancer. Systematic biopsies alone found 125/138 (91%) Gleason score 7-10 cancers. In patients with suspicious lesions (PI-RADS 4-5) on mpMRI, systematic biopsies would not have detected 12/113 significant prostate cancers (11%), while targeted biopsies alone would have failed to diagnose 10/113 (9%). In equivocal lesions (PI-RADS 3), targeted biopsy alone would not have diagnosed 14/25 (56%) of Gleason score 7-10 cancers, whereas systematic biopsies alone would have missed 1/25 (4%). Combination with PSA density improved the area under the curve of PI-RADS from 0.822 to 0.846. In patients with high probability mpMRI lesions, the highest detection rates of Gleason score 7-10 cancer still required combined targeted and systematic MRI/US image-fusion; however, systematic biopsy alone may be sufficient in patients with equivocal lesions. Repeated prostate biopsies may not be needed at all for patients with a low PSA density and a negative mpMRI read by experienced radiologists. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

3+4 = 6? Implications of the stratification of localised Gleason 7 prostate cancer by number and percentage of positive biopsy cores in selecting patients for active surveillance.

PubMed

Ruiz-Cerdá, J L; Lorenzo Soriano, L; Ramos-Soler, D; Marzullo-Zucchet, L; Loras Monfort, A; Boronat Tormo, F

2018-03-01

To determine whether the number and percentage of positive biopsy cores identify a Gleason 3+4 prostate cancer (PC) subgroup of similar biologic behaviour to Gleason 3+3. An observational post-radical prostatectomy study was conducted of a cohort of 799 patients with localised low-risk (n=582, Gleason 6, PSA <10ng/ml and cT1c-2a) and favourable intermediate PC (n=217, Gleason 3+4, PSA ≤10 ng/ml and pT2abc). The Gleason 3+4 tumours were stratified by number (≤3 vs.>3) and by percentage of positive cores (≤33% vs. >33%). We analysed the tumours' association with the biochemical recurrence risk (BRR) and cancer-specific mortality (CSM). We conducted various predictive models using Cox regression and estimated (C-index) and compared their predictive capacity. With a median follow-up of 71 months, the BRR and CSM of the patient group with Gleason 3+4 tumours and a low number (≤3) and percentage (≤33%) of positive cores were not significantly different from those of the patients with Gleason 6 tumours. At 5 and 10 years, there were no significant differences in the number of biochemical recurrences, the probability of remaining free of biochemical recurrences, the number of deaths by PC or the probability of death by PC between the 2 groups. In contrast, the patients with Gleason 3+4 tumours and more than 33% of positive cores presented more deaths by PC than the patients with Gleason 6 tumours. At 10 years, the probability of CSM was significantly greater. This subgroup of tumours showed a significantly greater BRR (RR, 1.6; P=.02) and CSM (RR, 5.8, P≤.01) compared with the Gleason 6 tumours. The model with Gleason 3+4 stratified by the percentage of positive cores significantly improved the predictive capacity of BRR and CSM. Fewer than 3 cores and a percentage <33% of positive cores identifies a subgroup of Gleason 3+4 tumours with biological behaviour similar to Gleason 6 tumours. At 10 years, there were no differences in BRR and CSM between the 2 groups. These results provide evidence supporting active surveillance as an alternative for Gleason 3+4 tumours and low tumour extension in biopsy. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

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.

Site Characterization for Remote Minefield Detection Scanner (REMIDS) system Data Acquisition

DTIC Science & Technology

1991-04-01

pattern - Standard A ) (US Army Engineer School 1988 ). This pattern dictates two straight rows of mines at each end of the area located 100 m apart...Westpoint, NY. Cespedes, E. R., Goodson, R. A ., and Ginsberg, I. W. 1988 (April). "Multi- sensor Image Processing Techniques for Real-Time Standoff...Monterey, CA. Gleason, H. A ., and Cronquist , A . 1963. Manual of Vascular Plants, D. Van Nostrand Co., New York. Goodson, R. A ., Cress, D. H., and

Gleason grading system

MedlinePlus

... medlineplus.gov/ency/patientinstructions/000920.htm Gleason grading system To use the sharing features on this page, ... score of between 5 and 7. Gleason Grading System Sometimes, it can be hard to predict how ...

Pathological Gleason prediction through gland ring morphometry in immunofluorescent prostate cancer images

NASA Astrophysics Data System (ADS)

Scott, Richard; Khan, Faisal M.; Zeineh, Jack; Donovan, Michael; Fernandez, Gerardo

2016-03-01

The Gleason score is the most common architectural and morphological assessment of prostate cancer severity and prognosis. There have been numerous quantitative techniques developed to approximate and duplicate the Gleason scoring system. Most of these approaches have been developed in standard H and E brightfield microscopy. Immunofluorescence (IF) image analysis of tissue pathology has recently been proven to be extremely valuable and robust in developing prognostic assessments of disease, particularly in prostate cancer. There have been significant advances in the literature in quantitative biomarker expression as well as characterization of glandular architectures in discrete gland rings. In this work we leverage a new method of segmenting gland rings in IF images for predicting the pathological Gleason; both the clinical and the image specific grade, which may not necessarily be the same. We combine these measures with nuclear specific characteristics as assessed by the MST algorithm. Our individual features correlate well univariately with the Gleason grades, and in a multivariate setting have an accuracy of 85% in predicting the Gleason grade. Additionally, these features correlate strongly with clinical progression outcomes (CI of 0.89), significantly outperforming the clinical Gleason grades (CI of 0.78). This work presents the first assessment of morphological gland unit features from IF images for predicting the Gleason grade.

Immunohistochemical expression of Ets-related gene-transcriptional factor in adenocarcinoma prostate and its correlation with Gleason score.

PubMed

Mannan, Rahul; Bhasin, Tejinder Singh; Manjari, Mridu; Singh, Gagandeep; Bhatia, Puneet Kaur; Sharma, Sonam

2016-01-01

Prostate carcinoma is the second leading cause of cancer-related deaths in males worldwide. The burden is expected to grow 1.7 million new cases and 499,000 new deaths by 2030. In developing countries such as India, prostate carcinoma will show an increase by 140% in the next few years. Although the diagnosis of prostate carcinoma can usually be made on histological features, now a days many immunohistochemical (IHC) markers are used to distinguish it from benign mimickers as well as in predicting prognosis and treatment. Out of these markers, Ets-related gene (ERG product) is a proto-oncogene which participates in chromosomal translocations and is frequently over expressed in prostate carcinoma which harbors ERG-transmembrane protease, serine 2 fusion. Fifty cases of carcinoma prostate diagnosed in needle biopsies and prostatic chips, in the Department of Pathology of a tertiary care teaching hospital in Punjab, India, were included in the present study. The slides were observed under the light microscope, and Gleason scoring was done using the 2005 International Society of Urological Pathology modified Gleason system. IHC study for ERG expression was done on all the cases, for which anti-ERG monoclonal rabbit clone antibody EP111 (Dako, Denmark) was used. Lymphocytes and endothelial cells were taken as in built positive controls for staining. The intensity of ERG positivity was scored as no staining (0), weak staining (+1), moderate staining (+2) and intense staining (+3). The H score was then calculated by multiplying the intensity of the stain with the percentage (0-100) of the cells showing that staining intensity. The H-score has a range of 0-300. The relationship between IHC expression and clinico-pathological parameters was compared and analyzed using Chi-square test. P < 0.05 was considered statistically significant. Majority of patients included in the study were in the age group of 61-80 (84% of the total). When ERG expression was studied with age-specific rates, it was not found to be statistically significant. The most common pattern noted in the present study was 4 + 3, constituting 36% of total, followed by 3 + 4 constituting 32%. Calculating the score, the majority of patients had a Gleason score of 5-8, constituting 76% of total. Out of the total fifty cases of prostate carcinoma, ERG was positive in 29 cases (58%) and negative in 21 cases (42%). Fourteen out of 21 (48%) of the ERG positive cases had an intensity score of 3. When the ERG intensity was correlated with the Gleason score group, it was seen that patients having Gleason score 7-8 showed ERG positivity in 19 out of 38 cases (50%), with 11/19 (57%) cases showing an ERG intensity score of 3. The Gleason score group 9-10 showed ERG positivity in 83% (10/12) cases, 20% (2/10) cases showing intensity score of 3. This correlation was found to be statistically significant. ERG immunostaining was performed in a small Indian cohort of prostate cancer patients, diagnosed in trucut biopsy specimens and prostatic chips. ERG expression was found in 58% patients. An increase in the ERG expression was observed with an increase in Gleason score. The intensity of ERG expression, however, decreased with an increasing Gleason score.

QPI for prostate cancer diagnosis: quantitative separation of Gleason grades 3 and 4

NASA Astrophysics Data System (ADS)

Sridharan, Shamira; Macias, Virgilia; Tangella, Krishnarao; Kajdacsy-Balla, Andre; Popescu, Gabriel

2015-03-01

1 in 7 men receive a diagnosis of prostate cancer in their lifetime. The aggressiveness of the treatment plan adopted by the patient is strongly influenced by Gleason grade. Gleason grade is determined by the pathologist based on the level of glandular formation and complexity seen in the patient's biopsy. However, studies have shown that the disagreement rate between pathologists on Gleason grades 3 and 4 is high and this affects treatment options. We used quantitative phase imaging to develop an objective method for Gleason grading. Using the glandular solidity, which is the ratio of the area of the gland to a convex hull fit around it, and anisotropy of light scattered from the stroma immediately adjoining the gland, we were able to quantitatively separate Gleason grades 3 and 4 with 81% accuracy in 43 cases marked as difficult by pathologists.

Extreme Gleason Upgrading From Biopsy to Radical Prostatectomy: A Population-based Analysis.

PubMed

Winters, Brian R; Wright, Jonathan L; Holt, Sarah K; Lin, Daniel W; Ellis, William J; Dalkin, Bruce L; Schade, George R

2016-10-01

To examine the risk factors associated with the odds of extreme Gleason upgrading at radical prostatectomy (RP) (defined as a Gleason prognostic group score increase of ≥2), we utilized a large, population-based cancer registry. The Surveillance, Epidemiologic, and End Results database was queried (2010-2011) for all patients diagnosed with Gleason 3 + 3 or 3 + 4 on prostate needle biopsy. Available clinicopathologic factors and the odds of upgrading and extreme upgrading at RP were evaluated using multivariate logistic regression. A total of 12,459 patients were identified, with a median age of 61 (interquartile range: 56-65) and a diagnostic prostate-specific antigen (PSA) of 5.5 ng/mL (interquartile range: 4.3-7.5). Upgrading was observed in 34% of men, including 44% of 7402 patients with Gleason 3 + 3 and 19% of 5057 patients with Gleason 3 + 4 disease. Age, clinical stage, diagnostic PSA, and % prostate needle biopsy cores positive were independently associated with odds of any upgrading at RP. In baseline Gleason 3 + 3 disease, extreme upgrading was observed in 6%, with increasing age, diagnostic PSA, and >50% core positivity associated with increased odds. In baseline Gleason 3 + 4 disease, extreme upgrading was observed in 4%, with diagnostic PSA and palpable disease remaining predictive. Positive surgical margins were significantly higher in patients with extreme upgrading at RP (P < .001). Gleason upgrading at RP is common in this large population-based cohort, including extreme upgrading in a clinically significant portion. Copyright © 2016 Elsevier Inc. All rights reserved.

PTEN loss and chromosome 8 alterations in Gleason grade 3 prostate cancer cores predicts the presence of un-sampled grade 4 tumor: implications for active surveillance.

PubMed

Trock, Bruce J; Fedor, Helen; Gurel, Bora; Jenkins, Robert B; Knudsen, B S; Fine, Samson W; Said, Jonathan W; Carter, H Ballentine; Lotan, Tamara L; De Marzo, Angelo M

2016-07-01

Men who enter active surveillance because their biopsy exhibits only Gleason grade 3 (G3) frequently have higher grade tumor missed by biopsy. Thus, biomarkers are needed that, when measured on G3 tissue, can predict the presence of higher grade tumor in the whole prostate. We evaluated whether PTEN loss, chromosome 8q gain (MYC) and/or 8p loss (LPL) measured only on G3 cores is associated with un-sampled G4 tumor. A tissue microarray was constructed of prostatectomy tissue from patients whose prostates exhibited only Gleason score 3+3, only 3+4 or only 4+3 tumor (n=50 per group). Cores sampled only from areas of G3 were evaluated for PTEN loss by immunohistochemistry, and PTEN deletion, LPL/8p loss and MYC/8q gain by fluorescence in situ hybridization. Biomarker results were compared between Gleason score 6 vs 7 tumors using conditional logistic regression. PTEN protein loss, odds ratio=4.99, P=0.033; MYC/8q gain, odds ratio=5.36, P=0.010; and LPL/8p loss, odds ratio=3.96, P=0.003 were significantly more common in G3 cores derived from Gleason 7 vs Gleason 6 tumors. PTEN gene deletion was not statistically significant. Associations were stronger comparing Gleason 4+3 vs 6 than for Gleason 3+4 vs 6. MYC/8q gain, LPL/8p loss and PTEN protein loss measured in G3 tissue microarray cores strongly differentiate whether the core comes from a Gleason 6 or Gleason 7 tumor. If validated to predict upgrading from G3 biopsy to prostatectomy these biomarkers could reduce the likelihood of enrolling high-risk men and facilitate safe patient selection for active surveillance.

Oncological Outcomes After Radical Prostatectomy for High-Risk Prostate Cancer Based on New Gleason Grouping System: A Validation Study From University of Southern California With 3,755 Cases.

PubMed

Djaladat, Hooman; Amini, Erfan; Xu, Weichen; Cai, Jie; Daneshmand, Siamak; Lieskovsky, Gary

2017-05-01

To assess the prognostic value of new Gleason grade grouping system in high-risk prostate cancer patients, we compared oncological outcomes after radical prostatectomy for patients with Gleason score 8 versus 9-10. Between 1987 and 2008, 3,755 men underwent radical prostatectomy with curative intent at University of Southern California. Patients who had Gleason score 8-10 at final histopathological evaluation (pT2-4N0) were included in this study. Eligible patients were divided into two groups; 226 with Gleason score 8 and 132 with Gleason score 9-10. Various patient and disease characteristics as well as oncological outcomes (biochemical recurrence, clinical recurrence, and overall survival) were compared between the groups. Impact of Gleason score on outcomes was controlled for preoperative prostate specific antigen, pathological stage, use of adjuvant radiotherapy, and neoadjuvant/adjuvant hormone therapy in multivariable analyses. A total of 358 patients (mean age: 65 years) were included in the analysis. Mean age and median duration of follow-up (9.6 years) were comparable between the study groups. Gleason 9-10 prostate cancer was associated with worse biochemical (HR 1.6; 95%CI [1.1-2.3]) and clinical recurrence free survival (HR = 1.9; 95%CI [1.1-3.3]); however, overall survival did not differ significantly between the groups. In addition, more patients with Gleason score 9-10 received adjuvant hormone therapy in the course of disease. Long-term follow-up after radical prostatectomy revealed significant differences in disease-specific outcomes between patients with Gleason score 8 versus 9-10. This sub-classification of high-risk patients might be helpful for patient counseling and determining therapeutic strategies. Prostate 77:743-748, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Active Surveillance for Low and Intermediate Risk Prostate Cancer: Opinions of North American Genitourinary Oncology Expert Radiation Oncologists.

PubMed

McClelland, Shearwood; Sandler, Kiri A; Degnin, Catherine; Chen, Yiyi; Mitin, Timur

2018-04-01

The ProtecT trial has provided level 1 evidence supporting active surveillance for prostate cancer patients with low-risk and intermediate-risk disease. The effect of these findings on the opinions of North American genitourinary (GU) experts regarding the role of active surveillance for these patients has not been previously examined. A survey was distributed to 88 practicing North American GU physicians serving on decision-making committees of cooperative group research organizations. Questions pertained to appropriateness of active surveillance in patients with low-risk and intermediate-risk (Gleason 3+4) disease. Opinions regarding active surveillance were correlated with practice patterns using Fisher exact test. Forty-two radiation oncologists completed the survey. Forty percent had been in practice for more than 20 years; 90% practice at an academic center. Forty-five percent see ≥ 20 patients per month in consultation. More than 95% (40 of 42) recommended active surveillance for Gleason 6 disease, whereas only 17% recommended active surveillance for Gleason 3+4 disease. There were no demographic differences between supporters or opponents regarding active surveillance with regard to monthly patient volume, practice type, likelihood of self-identifying as an expert brachytherapist, belief in advanced imaging techniques, or preferred default external beam radiation therapy dose/fractionation for either low-risk or intermediate-risk disease. However, there was a trend toward greater support of active surveillance for Gleason 3+4 disease among experts having practiced < 10 years versus ≥ 10 years (P = .085). Active surveillance is almost universally supported by North American GU expert radiation oncologists for low-risk prostate cancer. However, there is very weak support for this strategy in Gleason 3+4 disease despite the ProtecT trial providing level 1 evidentiary support in both risk groups. There were no significant differences between experts supporting versus opposing active surveillance for either low-risk or intermediate-risk disease. These preferences might affect the design of future clinical studies, influencing the adoption of active surveillance in North American clinical practice. Copyright © 2017 Elsevier Inc. All rights reserved.

Correlation between apparent diffusion coefficient value on diffusion-weighted MR imaging and Gleason score in prostate cancer.

PubMed

Wu, X; Reinikainen, P; Vanhanen, A; Kapanen, M; Vierikko, T; Ryymin, P; Hyödynmaa, S; Kellokumpu-Lehtinen, P-L

2017-01-01

To investigate whether diffusion-weighted imaging (DWI) apparent diffusion coefficient (ADC) correlates with prostate cancer aggressiveness and further to compare the diagnostic performance of ADC and normalized ADC (nADC: normalized to non-tumor tissue). Thirty pre-treatment patients (mean age, 69years; range: 59-78years) with prostate cancer underwent magnetic resonance imaging (MRI) examination, including DWI with three b values: 50, 400, and 800s/mm 2 . Both ADC and nADC were correlated with the Gleason score obtained through transrectal ultrasound-guided biopsy. The tumor minimum ADC (ADC min : the lowest ADC value within tumor) had an inverse correlation with the Gleason score (r=-0.43, P<0.05), and it was lower in patients with Gleason score 3+4 than in those with Gleason score 3+3 (0.54±0.11×10 3 mm 2 /s vs. 0.64±0.12×10 -3 mm 2 /s, P<0.05). Both the nADC min and nADC mean correlated with the Gleason score (r=-0.52 and r=-0.55, P<0.01; respectively), and they were lower in patients with Gleason score 3+4 than those with Gleason score 3+3 (P<0.01; respectively). Receiver operating characteristic (ROC) analysis showed that the area under the ROC curve was 0.765, 0.818, or 0.833 for the ADC min , nADC min , or nADC mean ; respectively, in differentiating between Gleason score 3+4 and 3+3 tumors. Tumor ADC min , nADC min , and nADC mean are useful markers to predict the aggressiveness of prostate cancer. Copyright © 2016 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

Gleason grade remains an important prognostic predictor in men diagnosed with prostate cancer while on finasteride therapy

PubMed Central

CARVER, BRETT S.; KATTAN, MICHAEL W.; SCARDINO, PETER T.; EASTHAM, JAMES A.

2007-01-01

OBJECTIVE To evaluate men treated with finasteride for lower urinary tract symptoms, who subsequently were diagnosed with prostate cancer and had a radical prostatectomy (RP) at our institution, to determine if finasteride therapy prevented accurate Gleason grade assignment and prediction of biochemical recurrence. PATIENTS AND METHODS Between May 1996 and July 2003, 45 men were identified who had RP and had previously been treated with finasteride for ≥6 months before the diagnosis of prostate cancer. Clinical and pathological information was gathered from a RP database. Serum prostate-specific antigen (PSA) level, duration of finasteride therapy, biopsy Gleason grade, clinical stage, RP Gleason grade and pathological stage were reviewed. Freedom from recurrence was predicted using validated nomograms before and after RP, and compared against actuarial 5-year freedom from recurrence using the Kaplan-Meier method. RESULTS The mean duration of finasteride therapy before diagnosis was 23.6 months, the mean serum PSA (doubled to account for finasteride use) 11.02 ng/mL and mean biopsy Gleason score 6. When comparing the biopsy and RP specimen Gleason score, it was downgraded by 1 point in six men, upgraded by 1 point in eight, and upgraded by 2 points in one. The Gleason score was constant in 30 patients. The nomograms predicted freedom from recurrence in 83% and 85%, respectively; the 5-year actuarial freedom from recurrence was 86%. CONCLUSION Finasteride does not appear to compromise the assignment of Gleason grade for use in prediction tools before or after RP in men undergoing prostate biopsy or RP. The actuarial 5-year freedom from recurrence was similar to that predicted by the validated nomograms. Gleason grade remains an important prognostic predictor in men treated with finasteride and undergoing RP for clinically localized prostate cancer. PMID:15705069

8q24 allelic imbalance and MYC gene copy number in primary prostate cancer.

PubMed

Chen, H; Liu, W; Roberts, W; Hooker, S; Fedor, H; DeMarzo, A; Isaacs, W; Kittles, R A

2010-09-01

Four independent regions within 8q24 near the MYC gene are associated with risk for prostate cancer (Pca). Here, we investigated allelic imbalance (AI) at 8q24 risk variants and MYC gene DNA copy number (CN) in 27 primary Pcas. Heterozygotes were observed in 24 of 27 patients at one or more 8q24 markers and 27% of the loci exhibited AI in tumor DNA. The 8q24 risk alleles were preferentially favored in the tumors. Increased MYC gene CN was observed in 33% of tumors, and the co-existence of increased MYC gene CN with AI at risk loci was observed in 86% (P<0.004 exact binomial test) of the informative tumors. No AI was observed in tumors, which did not reveal increased MYC gene CN. Higher Gleason score was associated with tumors exhibiting AI (P=0.04) and also with increased MYC gene CN (P=0.02). Our results suggest that AI at 8q24 and increased MYC gene CN may both be related to high Gleason score in Pca. Our findings also suggest that these two somatic alterations may be due to the same preferential chromosomal duplication event during prostate tumorigenesis.

Oncologic control obtained after radical prostatectomy in men with a pathological Gleason score ≥ 8: a single-center experience.

PubMed

Audenet, François; Comperat, Eva; Seringe, Elise; Drouin, Sarah J; Richard, François; Cussenot, Olivier; Bitker, Marc-Olivier; Rouprêt, Morgan

2011-01-01

To assess the oncologic control afforded by radical prostatectomy (RP) in high-risk prostate cancers with a Gleason score ≥ 8. We performed a retrospective review of prostate cancer patients who underwent RP between 1995 and 2005 for prostate cancer and who had a pathologic Gleason score ≥ 8. Biochemical recurrence was defined as a single rise in PSA levels over 0.2 ng/ml after surgery. Overall, 64 patients were included and followed for a median time of 84.3 months. The mean age was 63 ± 5.2 years. The mean preoperative PSA was 11.9 ± 7.3 ng/ml (1.9-31), and 29 patients (46%) had a PSA > 10 ng/ml. The biopsy Gleason score was ≤ 7 for 49 patients (76.6%). After pathologic analysis, there were 25 (39%) stage pT2, 37 (58%) stage pT3, and 2 (3%) stage pT4 patients. Nine patients had lymph node involvement (14%). The surgical margins were positive in 25 patients (39%). In 51 patients, (80%) the Gleason score was underestimated by biopsies: 40 patients with a definitive score of Gleason 8 had a Gleason score of 6 or 7 on biopsies, while 11 patients with a Gleason score of 9 initially, had a Gleason score of 7 or 8. Twenty-seven patients underwent adjuvant treatment: external radiation therapy (n = 19), HRT (n = 3), or both (n = 5). During follow-up, 41 patients (64%) presented with a biochemical recurrence, and 11 (17%) died. The PSA-free survival rate at five year was 44%. RP remains a possible therapeutic option in certain cases of the high-risk cohort of patients with a Gleason score ≥ 8. However, patients should be warned that surgery might only be the first step of a multi-modal treatment approach. The modalities of adjuvant treatments and the right schedule to deliver it following RP still need to be defined. Copyright © 2011 Elsevier Inc. All rights reserved.

Automatic Gleason grading of H and E stained microscopic prostate images using deep convolutional neural networks

NASA Astrophysics Data System (ADS)

Gummeson, Anna; Arvidsson, Ida; Ohlsson, Mattias; Overgaard, Niels C.; Krzyzanowska, Agnieszka; Heyden, Anders; Bjartell, Anders; Aström, Kalle

2017-03-01

Prostate cancer is the most diagnosed cancer in men. The diagnosis is confirmed by pathologists based on ocular inspection of prostate biopsies in order to classify them according to Gleason score. The main goal of this paper is to automate the classification using convolutional neural networks (CNNs). The introduction of CNNs has broadened the field of pattern recognition. It replaces the classical way of designing and extracting hand-made features used for classification with the substantially different strategy of letting the computer itself decide which features are of importance. For automated prostate cancer classification into the classes: Benign, Gleason grade 3, 4 and 5 we propose a CNN with small convolutional filters that has been trained from scratch using stochastic gradient descent with momentum. The input consists of microscopic images of haematoxylin and eosin stained tissue, the output is a coarse segmentation into regions of the four different classes. The dataset used consists of 213 images, each considered to be of one class only. Using four-fold cross-validation we obtained an error rate of 7.3%, which is significantly better than previous state of the art using the same dataset. Although the dataset was rather small, good results were obtained. From this we conclude that CNN is a promising method for this problem. Future work includes obtaining a larger dataset, which potentially could diminish the error margin.

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.

Gleason-Busch theorem for sequential measurements

NASA Astrophysics Data System (ADS)

Flatt, Kieran; Barnett, Stephen M.; Croke, Sarah

2017-12-01

Gleason's theorem is a statement that, given some reasonable assumptions, the Born rule used to calculate probabilities in quantum mechanics is essentially unique [A. M. Gleason, Indiana Univ. Math. J. 6, 885 (1957), 10.1512/iumj.1957.6.56050]. We show that Gleason's theorem contains within it also the structure of sequential measurements, and along with this the state update rule. We give a small set of axioms, which are physically motivated and analogous to those in Busch's proof of Gleason's theorem [P. Busch, Phys. Rev. Lett. 91, 120403 (2003), 10.1103/PhysRevLett.91.120403], from which the familiar Kraus operator form follows. An axiomatic approach has practical relevance as well as fundamental interest, in making clear those assumptions which underlie the security of quantum communication protocols. Interestingly, the two-time formalism is seen to arise naturally in this approach.

Predicting the risk of patients with biopsy Gleason score 6 to harbor a higher grade cancer.

PubMed

Gofrit, Ofer N; Zorn, Kevin C; Taxy, Jerome B; Lin, Shang; Zagaja, Gregory P; Steinberg, Gary D; Shalhav, Arieh L

2007-11-01

Prostate cancer Gleason score 3 + 3 = 6 is currently the most common score assigned on prostatic biopsies. We analyzed the clinical variables that predict the likelihood of a patient with biopsy Gleason score 6 to harbor a higher grade tumor. The study population consisted of 448 patients with a mean age of 59.1 years who underwent radical prostatectomy between February 2003 to October 2006 for Gleason score 6 adenocarcinoma. The effect of preoperative variables on the probability of a Gleason score upgrade on final pathological evaluation was evaluated using logistic regression, and classification and regression tree analysis. Gleason score upgrade was found in 91 of 448 patients (20.3%). Logistic regression showed that only serum prostate specific antigen and the greatest percent of cancer in a core were significantly associated with a score upgrade (p = 0.0014 and 0.023, respectively). Classification and regression tree analysis showed that the risk of a Gleason score upgrade was 62% when serum prostate specific antigen was higher than 12 ng/ml and 18% when serum prostate specific antigen was 12 ng/ml or less. In patients with serum prostate specific antigen lower than 12 ng/ml the risk of a score upgrade could be dichotomized at a greatest percent of cancer in a core of 5%. The risk was 22.6% and 10.5% when the greatest percent of cancer in a core was higher than 5% and 5% or lower, respectively. The probability of patients with a prostate biopsy Gleason score of 6 to conceal a Gleason score of 7 or higher can be predicted using serum prostate specific antigen and the greatest percent of cancer in a core. With these parameters it is possible to predict upgrade rates as high as 62% and as low as 10.5%.

Very-high-risk localized prostate cancer: definition and outcomes.

PubMed

Sundi, D; Wang, V M; Pierorazio, P M; Han, M; Bivalacqua, T J; Ball, M W; Antonarakis, E S; Partin, A W; Schaeffer, E M; Ross, A E

2014-03-01

Outcomes in men with National Comprehensive Cancer Network (NCCN) high-risk prostate cancer (PCa) can vary substantially-some will have excellent cancer-specific survival, whereas others will experience early metastasis even after aggressive local treatments. Current nomograms, which yield continuous risk probabilities, do not separate high-risk PCa into distinct sub-strata. Here, we derive a binary definition of very-high-risk (VHR) localized PCa to aid in risk stratification at diagnosis and selection of therapy. We queried the Johns Hopkins radical prostatectomy database to identify 753 men with NCCN high-risk localized PCa (Gleason sum 8-10, PSA >20 ng ml(-1), or clinical stage ≥T3). Twenty-eight alternate permutations of adverse grade, stage and cancer volume were compared by their hazard ratios for metastasis and cancer-specific mortality. VHR criteria with top-ranking hazard ratios were further evaluated by multivariable analyses and inclusion of a clinically meaningful proportion of the high-risk cohort. The VHR cohort was best defined by primary pattern 5 present on biopsy, or ≥5 cores with Gleason sum 8-10, or multiple NCCN high-risk features. These criteria encompassed 15.1% of the NCCN high-risk cohort. Compared with other high-risk men, VHR men were at significantly higher risk for metastasis (hazard ratio 2.75) and cancer-specific mortality (hazard ratio 3.44) (P<0.001 for both). Among high-risk men, VHR men also had significantly worse 10-year metastasis-free survival (37% vs 78%) and cancer-specific survival (62% vs 90%). Men who meet VHR criteria form a subgroup within the current NCCN high-risk classification who have particularly poor oncological outcomes. Use of these characteristics to distinguish VHR localized PCa may help in counseling and selection optimal candidates for multimodal treatments or clinical trials.

Regarding the Focal Treatment of Prostate Cancer: Inference of the Gleason Grade From Magnetic Resonance Spectroscopic Imaging

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

Brame, Ryan S.; Zaider, Marco; Zakian, Kristen L.

2009-05-01

Purpose: To quantify, as a function of average magnetic resonance spectroscopy (MRS) score and tumor volume, the probability that a cancer-suspected lesion has an elevated Gleason grade. Methods and Materials: The data consist of MRS imaging ratios R stratified by patient, lesion (contiguous abnormal voxels), voxels, biopsy and pathologic Gleason grade, and lesion volume. The data were analyzed using a logistic model. Results: For both low and high Gleason score biopsy lesions, the probability of pathologic Gleason score {>=}4+3 increases with lesion volume. At low values of R a lesion volume of at least 15-20 voxels is needed to reachmore » a probability of success of 80%; the biopsy result helps reduce the prediction uncertainty. At larger MRS ratios (R > 6) the biopsy result becomes essentially uninformative once the lesion volume is >12 voxels. With the exception of low values of R, for lesions with low Gleason score at biopsy, the MRS ratios serve primarily as a selection tool for assessing lesion volumes. Conclusions: In patients with biopsy Gleason score {>=}4+3, high MRS imaging tumor volume and (creatine + choline)/citrate ratio may justify the initiation of voxel-specific dose escalation. This is an example of biologically motivated focal treatment for which intensity-modulated radiotherapy and especially brachytherapy are ideally suited.« less

Do Maori and Pacific Islander men present with more advanced prostate cancer than European New Zealand men? An analysis of 486 men undergoing biopsy in Auckland.

PubMed

Pokorny, Morgan R; Scott, David J

2011-04-01

• To address the question of whether Maori and Pacific Islander men in Auckland present with more advanced prostate cancer at diagnosis than New Zealand European or European men. • A retrospective database audit was undertaken of all men presenting for a first prostate biopsy under the Auckland Hospital Urology Service in 2005 and 2006. • Ethnicity was coded from self-identification codes on hospital databases. • Population numbers were obtained from the 2006 Census figures from Statistics New Zealand. • Primary outcome measures used as surrogates for advanced disease were PSA level at biopsy, Gleason Score and palpable abnormality on digital rectal examination and rates of metastatic disease as determined by nuclear medicine bone scan. • There was no appreciable difference when Maori and Pacific Islander men were compared with European men for median PSA level (13.30 vs 12.55 ng/mL, P = 0.264); median Gleason score (7 and 7), mean Gleason score (7.0 vs 6.9, P = 0.196) or the proportion of Gleason Score 7 or 8-10 (P = 0.431) • There was no difference between the rates of metastatic disease at presentation (11.5% vs 7.8%, P = 0.376). • There appeared to be a significant difference in the proportion of Maori and Pacific Islanders presenting with palpable disease (67.2%) compared with European men (53.3%, P = 0.042). • The crude population biopsy rate per 100,000 was similar for Maori and Pacific Islander and European men (560 vs 547). • Maori and Pacific Islander men present with similar prostate cancer characteristics to European men at diagnosis but there appears to be a real discrepancy in the rates of palpable disease. © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

Contemporary referral pattern for robotic prostatectomy.

PubMed

Dangle, Pankaj P; Abaza, Ronney

2010-01-01

In spite of the current widespread application of robotic surgery in the treatment of prostate cancer, it remains unclear whether current patterns of use are based on patient benefit or driven by marketing. We sought to investigate this possibility by analyzing the source of our patient population for robot-assisted laparoscopic prostatectomy (RALP). We reviewed 200 consecutive patients who underwent robotic prostatectomy by a single surgeon (RA) at our institution. The source of referral for each patient was analyzed along with individual patient characteristics to identify whether only low-risk or unusually ideal candidates were referred. Of the 200 patients, 90.5% were referred by a urologist with only 5.5% being referred by another urologist at our institution. Only <10 patients cited media or marketing sources as the reason for self-referral, and 10 were referred by primary care physicians or other acquaintances. This referral pattern did not change between the first and second 100 patients. Referred patients included those up to 80 years of age, up to 51 kg/m(2) in body mass index, and up to Gleason 9 on biopsy, with 36% of those referred by urologists having some history of previous abdominal or prostate surgery. The referral pattern for RALP at our institution may reflect a growing acceptance of robotic surgery among urologists in our region and is unlikely driven by patient-directed marketing. Additionally, urologists may also be more confident in the role of RALP as evidenced by their referral of even complex and higher-risk patients.

Mediterranean Dietary Pattern is Associated with Low Risk of Aggressive Prostate Cancer: MCC-Spain Study.

PubMed

Castelló, Adela; Boldo, Elena; Amiano, Pilar; Castaño-Vinyals, Gemma; Aragonés, Nuria; Gómez-Acebo, Inés; Peiró, Rosana; Jimenez-Moleón, Jose Juan; Alguacil, Juan; Tardón, Adonina; Cecchini, Lluís; Lope, Virginia; Dierssen-Sotos, Trinidad; Mengual, Lourdes; Kogevinas, Manolis; Pollán, Marina; Pérez-Gómez, Beatriz

2018-02-01

We explored the association of the previously described Western, prudent and Mediterranean dietary patterns with prostate cancer risk by tumor aggressiveness and extension. MCC-Spain (Multicase-Control Study on Common Tumors in Spain) is a population based, multicase-control study that was done in 7 Spanish provinces between September 2008 and December 2013. It collected anthropometric, epidemiological and dietary information on 754 histologically confirmed incident cases of prostate cancer and 1,277 controls 38 to 85 years old. Three previously identified dietary patterns, including Western, prudent and Mediterranean, were reconstructed using MCC-Spain data. The association of each pattern with prostate cancer risk was assessed by logistic regression models with random, province specific intercepts. Risk according to tumor aggressiveness (Gleason score 6 vs greater than 6) and extension (cT1-cT2a vs cT2b-cT4) was evaluated by multinomial regression models. High adherence to a Mediterranean dietary pattern rich not only in fruits and vegetables but also in fish, legumes and olive oil was specifically associated with a lower risk of Gleason score greater than 6 prostate cancer (quartile 3 vs 1 relative RR 0.66, 95% CI 0.46-0.96 and quartile 4 vs 1 relative RR 0.68, 95% CI 0.46-1.01, p-trend = 0.023) or with higher clinical stage (cT2b-T4 quartile 4 vs 1 relative RR 0.49, 95% CI 0.25-0.96, p-trend = 0.024). This association was not observed with the prudent pattern, which combines vegetables and fruits with low fat dairy products, whole grains and juices. The Western pattern did not show any association with prostate cancer risk. Nutritional recommendations for prostate cancer prevention should consider whole dietary patterns instead of individual foods. We found important differences between the Mediterranean dietary pattern, which was associated with a lower risk of aggressive prostate cancer, and Western and prudent dietary patterns, which had no relationship with prostate cancer risk. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Prostate specific antigen density to predict prostate cancer upgrading in a contemporary radical prostatectomy series: a single center experience.

PubMed

Magheli, Ahmed; Hinz, Stefan; Hege, Claudia; Stephan, Carsten; Jung, Klaus; Miller, Kurt; Lein, Michael

2010-01-01

We investigated the value of pretreatment prostate specific antigen density to predict Gleason score upgrading in light of significant changes in grading routine in the last 2 decades. Of 1,061 consecutive men who underwent radical prostatectomy between 1999 and 2004, 843 were eligible for study. Prostate specific antigen density was calculated and a cutoff for highest accuracy to predict Gleason upgrading was determined using ROC curve analysis. The predictive accuracy of prostate specific antigen and prostate specific antigen density to predict Gleason upgrading was evaluated using ROC curve analysis based on predicted probabilities from logistic regression models. Prostate specific antigen and prostate specific antigen density predicted Gleason upgrading on univariate analysis (as continuous variables OR 1.07 and 7.21, each p <0.001) and on multivariate analysis (as continuous variables with prostate specific antigen density adjusted for prostate specific antigen OR 1.07, p <0.001 and OR 4.89, p = 0.037, respectively). When prostate specific antigen density was added to the model including prostate specific antigen and other Gleason upgrading predictors, prostate specific antigen lost its predictive value (OR 1.02, p = 0.423), while prostate specific antigen density remained an independent predictor (OR 4.89, p = 0.037). Prostate specific antigen density was more accurate than prostate specific antigen to predict Gleason upgrading (AUC 0.61 vs 0.57, p = 0.030). Prostate specific antigen density is a significant independent predictor of Gleason upgrading even when accounting for prostate specific antigen. This could be especially important in patients with low risk prostate cancer who seek less invasive therapy such as active surveillance since potentially life threatening disease may be underestimated. Further studies are warranted to help evaluate the role of prostate specific antigen density in Gleason upgrading and its significance for biochemical outcome.

Multiple Time-Point 68Ga-PSMA I&T PET/CT for Characterization of Primary Prostate Cancer: Value of Early Dynamic and Delayed Imaging.

PubMed

Schmuck, Sebastian; Mamach, Martin; Wilke, Florian; von Klot, Christoph A; Henkenberens, Christoph; Thackeray, James T; Sohns, Jan M; Geworski, Lilli; Ross, Tobias L; Wester, Hans-Juergen; Christiansen, Hans; Bengel, Frank M; Derlin, Thorsten

2017-06-01

The aims of this study were to gain mechanistic insights into prostate cancer biology using dynamic imaging and to evaluate the usefulness of multiple time-point Ga-prostate-specific membrane antigen (PSMA) I&T PET/CT for the assessment of primary prostate cancer before prostatectomy. Twenty patients with prostate cancer underwent Ga-PSMA I&T PET/CT before prostatectomy. The PET protocol consisted of early dynamic pelvic imaging, followed by static scans at 60 and 180 minutes postinjection (p.i.). SUVs, time-activity curves, quantitative analysis based on a 2-tissue compartment model, Patlak analysis, histopathology, and Gleason grading were compared between prostate cancer and benign prostate gland. Primary tumors were identified on both early dynamic and delayed imaging in 95% of patients. Tracer uptake was significantly higher in prostate cancer compared with benign prostate tissue at any time point (P ≤ 0.0003) and increased over time. Consequently, the tumor-to-nontumor ratio within the prostate gland improved over time (2.8 at 10 minutes vs 17.1 at 180 minutes p.i.). Tracer uptake at both 60 and 180 minutes p.i. was significantly higher in patients with higher Gleason scores (P < 0.01). The influx rate (Ki) was higher in prostate cancer than in reference prostate gland (0.055 [r = 0.998] vs 0.017 [r = 0.996]). Primary prostate cancer is readily identified on early dynamic and static delayed Ga-PSMA ligand PET images. The tumor-to-nontumor ratio in the prostate gland improves over time, supporting a role of delayed imaging for optimal visualization of prostate cancer.

Primary Cryotherapy for High-Grade Clinically Localized Prostate Cancer: Oncologic and Functional Outcomes from the COLD Registry.

PubMed

Tay, Kae Jack; Polascik, Thomas J; Elshafei, Ahmed; Cher, Michael L; Given, Robert W; Mouraviev, Vladimir; Ross, Ashley E; Jones, J Stephen

2016-01-01

To evaluate the oncological and functional outcomes of primary cryotherapy in men with clinically localized, high-grade prostate cancer. We included all men with biopsy Gleason score ≥8, localized (cT1-2) disease with a serum prostate-specific antigen (PSA) ≤50 ng/mL from the Cryo On-Line Data (COLD) registry. The primary outcome was biochemical progression free survival (BPFS) as defined by the Phoenix criteria (nadir PSA +2 ng/mL). Secondary outcomes of continence (defined as strictly no leak) and potency (able to have intercourse) were patient reported. Factors influencing BPFS were evaluated individually using Kaplan Meier and in a multivariate model using Cox regression. Altogether, 300 men were included for analysis. The median follow-up was 18.2 months (mean 28.4) and median BPFS was 69.8 months. Based on Kaplan-Meier analysis, the estimated 2- and 5-year BPFS rate was 77.2% and 59.1%, respectively. Neoadjuvant hormonal therapy was administered to 41% of men and this tended to occur in men with larger prostates, likely as a technical consideration for downsizing before cryosurgery. At multivariate analysis, the presence of Gleason score 9 or 10 (Hazard Ratio [HR] 1.9) and a posttreatment PSA nadir of ≥0.4 ng/mL (HR 5.7) were the only significant variables associated with biochemical progression using Cox regression. Complete continence was noted in 90.5% of men and potency in 17% of men at the 12-month follow-up. The incidence of rectourethral fistulae and urinary retention requiring intervention beyond temporary catheterization was 1.3% and 3.3%, respectively. Primary cryotherapy appears to be effective and safe in the community setting for high-grade, clinically localized prostate cancer in the short term.

Effect of pathologic revision and Ki67 and ERG immunohistochemistry on predicting radical prostatectomy outcome in men initially on active surveillance.

PubMed

Bokhorst, Leonard P; Roobol, Monique J; Bangma, Chris H; van Leenders, Geert J

2017-07-01

To investigate if pathologic biopsy reevaluation and implementation of immunohistochemical biomarkers could improve prediction of radical prostatectomy outcome in men initially on active surveillance. Biopsy specimens from diagnosis until switching to radical prostatectomy in men initially on active surveillance in the Dutch part of the Prostate cancer Research International Active Surveillance (PRIAS) study were collected and revised by a single pathologist. Original and revised biopsy Gleason score were compared and correlated with radical prostatectomy Gleason score. Biopsy specimens were immunohistochemically stained for Ki67 and ERG. Predictive ability of clinical characteristics and biomarkers on Gleason ≥7 or ≥pT3 on radical prostatectomy was tested using logistic regression and ROC curve analysis. A total of 150 biopsies in 95 men were revised. In 13% of diagnostic or second-to-last biopsies and 20% of the last biopsies on active surveillance revision of Gleason score resulted in change of recommendation (ie, active treatment or active surveillance). Concordance with Gleason score on radical prostatectomy was however similar for both the revised and original Gleason on biopsy. Ki67 and ERG were not statistically significant predictors of Gleason ≥7 or ≥pT3 on radical prostatectomy. Although interobserver differences in pathology reporting on biopsy could result in a change of management strategy in approximately 13-20% of men on active surveillance, both pathological revision and tested biomarkers (Ki67 and ERG) did not improve prediction of outcome on radical prostatectomy. Undersampling of most aggressive tumor remains the main focus in order to increase accurate grading at time of treatment decision making. © 2017 Wiley Periodicals, Inc.

Decreased fucosylated PSA as a urinary marker for high Gleason score prostate cancer.

PubMed

Fujita, Kazutoshi; Hayashi, Takuji; Matsuzaki, Kyosuke; Nakata, Wataru; Masuda, Mika; Kawashima, Atsunari; Ujike, Takeshi; Nagahara, Akira; Tsuchiya, Mutsumi; Kobayashi, Yuka; Nojima, Satoshi; Uemura, Motohide; Morii, Eiichi; Miyoshi, Eiji; Nonomura, Norio

2016-08-30

Fucosylation is an important oligosaccharide modification associated with cancer and inflammation. We investigated whether urinary fucosylated PSA (Fuc-PSA) levels could be used for the detection of high Gleason score prostate cancer. Urine samples were collected from men with abnormal digital rectal examination findings or elevated serum PSA levels, before prostate biopsy. Lectin-antibody ELISA was used to quantify the Lewis-type or core-type fucosylated PSA (PSA-AAL) and core-type fucosylated PSA (PSA-PhoSL) in the urine samples. Both types of urinary Fuc-PSA were significantly decreased in the men with prostate cancer compared with the men whose biopsies were negative for cancer (P = 0.026 and P < 0.001, respectively). Both were also significantly associated with the Gleason scores of the biopsy specimens (P = 0.001 and P < 0.001, respectively). Multivariate analysis showed that PSA density, urinary PSA-AAL, and urinary PSA-PhoSL were independent predictors of high Gleason score prostate cancer. The area under the receiver-operator characteristic curve (AUC) value for the prediction of cancers of Gleason score ≥ 7 was 0.69 for urinary PSA-AAL and 0.72 for urinary PSA-PhoSL. In contrast, the AUC value was 0.59 for serum PSA, 0.63 for PSA density, and 0.58 for urinary PSA. In conclusion, a decreased urinary Fuc-PSA level is a potential marker for the detection of high Gleason score prostate cancer.

Decreased fucosylated PSA as a urinary marker for high Gleason score prostate cancer

PubMed Central

Fujita, Kazutoshi; Hayashi, Takuji; Matsuzaki, Kyosuke; Nakata, Wataru; Masuda, Mika; Kawashima, Atsunari; Ujike, Takeshi; Nagahara, Akira; Tsuchiya, Mutsumi; Kobayashi, Yuka; Nojima, Satoshi; Uemura, Motohide; Morii, Eiichi; Miyoshi, Eiji; Nonomura, Norio

2016-01-01

Fucosylation is an important oligosaccharide modification associated with cancer and inflammation. We investigated whether urinary fucosylated PSA (Fuc-PSA) levels could be used for the detection of high Gleason score prostate cancer. Urine samples were collected from men with abnormal digital rectal examination findings or elevated serum PSA levels, before prostate biopsy. Lectin-antibody ELISA was used to quantify the Lewis-type or core-type fucosylated PSA (PSA-AAL) and core-type fucosylated PSA (PSA-PhoSL) in the urine samples. Both types of urinary Fuc-PSA were significantly decreased in the men with prostate cancer compared with the men whose biopsies were negative for cancer (P = 0.026 and P < 0.001, respectively). Both were also significantly associated with the Gleason scores of the biopsy specimens (P = 0.001 and P < 0.001, respectively). Multivariate analysis showed that PSA density, urinary PSA-AAL, and urinary PSA-PhoSL were independent predictors of high Gleason score prostate cancer. The area under the receiver-operator characteristic curve (AUC) value for the prediction of cancers of Gleason score ≥ 7 was 0.69 for urinary PSA-AAL and 0.72 for urinary PSA-PhoSL. In contrast, the AUC value was 0.59 for serum PSA, 0.63 for PSA density, and 0.58 for urinary PSA. In conclusion, a decreased urinary Fuc-PSA level is a potential marker for the detection of high Gleason score prostate cancer. PMID:27494861

2. Historic American Buildings Survey Gleason Collection S.F. College ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

2. Historic American Buildings Survey Gleason Collection - S.F. College for Women Taken about: 1870 TOWER RESTORED AFTER EARTHQUAKE OF 1868 - John Marsh House, Marsh Creek Road, Brentwood, Contra Costa County, CA

Spectral grading and Gleason grading of malignant prostate tissue using Stokes shift spectra

NASA Astrophysics Data System (ADS)

Al Salhi, M.; Masilamani, V.; Rabah, D.; Farhat, K.; Liu, C. H.; Pu, Y.; Alfano, R. R.

2012-01-01

Gleason score is the most common method of grading the virulence of prostate malignancy and is based on the pathological assessment of morphology of cellular matrix. Since this involves the excision of the tissue, we are working on a new, minimally invasive, non contact, procedure of spectral diagnosis of prostate malignancy. In this preliminary in vitro study reported here, we have analyzed 27 tissue samples (normal control =7: benign=8: malignant =12) by Stokes' shift spectra (SSS) to establish a one- to- one correlation between spectral grading and Gleason grading.

Declining Use of Radiotherapy for Adverse Features After Radical Prostatectomy: Results From the National Cancer Data Base.

PubMed

Sineshaw, Helmneh M; Gray, Phillip J; Efstathiou, Jason A; Jemal, Ahmedin

2015-11-01

Patterns of postoperative radiotherapy (RT) use in prostate cancer (PCa) after the publication of major randomized trials have not been well characterized. To describe patterns of postoperative RT use after radical prostatectomy (RP) in patients with adverse pathologic features in the United States. Retrospective analysis of 97 270 patients with PCa diagnosed between 2005 and 2011 whose presentation and outcomes were recorded in the National Cancer Data Base. Temporal changes in receipt of postoperative RT and factors associated with receipt of this treatment using the Cochran-Armitage trend test and multiple logistic regression, respectively. Between 2005 and 2011, receipt of postoperative RT decreased steadily from 9.1% to 7.3% (ptrend<0.001). Use of RT with or without androgen deprivation therapy monotonically decreased with advancing age from 8.5% in patients aged 18-59 yr to 6.8% in patients aged 70-79 yr (ptrend<0.001). Receipt of RT was higher at community cancer programs compared with teaching/research centers (14% vs 7.3%; odds ratio [OR]: 2.16; p<0.001), in those with pT3-4 disease and positive margins compared with those with pT3-4 and negative margins (17% vs 5.9%; OR: 2.89; p<0.001), and in patients with a Gleason score of 8-10 compared with those with a Gleason score of 2-6 (17% vs 4.2%; OR: 3.50; p<0.001). Limitations include lack of postprostatectomy prostate-specific antigen level. Postoperative RT use for localized PCa in patients with adverse pathologic features is declining in the United States. In this report, we show that use of postoperative radiotherapy in patients with prostate cancer with adverse pathologic features is declining. Patients treated at community cancer programs, those with locally advanced disease and positive margins, and those with a high Gleason score were more likely to receive postoperative radiotherapy. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

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

Ability of sextant biopsies to predict radical prostatectomy stage.

PubMed

Wills, M L; Sauvageot, J; Partin, A W; Gurganus, R; Epstein, J I

1998-05-01

There are few studies evaluating multiple variables on sextant biopsies with the intent to predict stage in radical prostatectomy specimens. We studied 113 sextant biopsies with corresponding totally submitted radical prostatectomy specimens. Variables evaluated on sextant biopsies included total length and percent of cancer; maximum length and percent of cancer on one core; location (apex, mid, base); bilaterality; Gleason grade; number of cores involved; serum prostate-specific antigen (PSA) level; and serum PSA density (PSAD). Radical prostatectomy stage was classified as organ versus non-organ confined. The following variables individually correlated with radical prostatectomy stage: total cancer measured in millimeters (P <0.0001) or percent (P <0.0005); biopsy Gleason score (P <0.0001); number of involved cores (P <0.0001); maximum cancer on one core measured in millimeters (P = 0.0001); maximum percent of cancer on one core (P = 0.01); bilaterality (P = 0.01); PSA level (P = 0.03), and PSAD (P = 0.001). The most predictive sets of two variables that correlated with stage included high Gleason score (P <0.0001) combined with numbers of cores involved (P = 0.002). When biopsies had Gleason scores of 6 or less, two or fewer positive cores, and serum PSA of 0 to 4 ng/mL, 89% were organ confined. When biopsies had Gleason scores of 6 or less with two unilaterally positive cores, 87% were organ confined. In biopsies with Gleason scores of 7 or more and more than one positive core, only 10% were organ confined. The most important predictors of stage by sextant needle biopsy evaluation are numbers of cores involved with carcinoma and high Gleason score. Bilaterality and serum PSA values improved prediction in two small subgroups. In 37% of our population we were able to predict with a greater than 87% probability the organ-confined versus non-organ-confined status.

Characterization of 1,577 Primary Prostate Cancers Reveals Novel Biological and Clinicopathological Insights into Molecular Subtypes

PubMed Central

Tomlins, Scott A.; Alshalalfa, Mohammed; Davicioni, Elai; Erho, Nicholas; Yousefi, Kasra; Zhao, Shuang; Haddad, Zaid; Den, Robert B.; Dicker, Adam P.; Trock, Bruce; DeMarzo, Angelo; Ross, Ashley; Schaeffer, Edward M.; Klein, Eric A.; Magi-Galluzzi, Cristina; Karnes, Jeffery R.; Jenkins, Robert B.; Feng, Felix Y.

2015-01-01

Background Prostate cancer (PCa) molecular subtypes have been defined by essentially mutually exclusive events, including ETS gene fusions (most commonly involving ERG) and SPINK1 over-expression. Clinical assessment may aid in disease stratification, complementing available prognostic tests. Objective To determine the analytical validity and clinicopatholgical associations of microarray-based molecular subtyping. Design, Setting and Participants We analyzed Affymetrix GeneChip expression profiles for 1,577 patients from eight radical prostatectomy (RP) cohorts, including 1,351 cases assessed using the Decipher prognostic assay (performed in a CLIA-certified laboratory). A microarray-based (m-) random forest ERG classification model was trained and validated. Outlier expression analysis was used to predict other mutually exclusive non-ERG ETS gene rearrangements (ETS+) or SPINK1 over-expression (SPINK1+). Outcome Measurements Associations with clinical features and outcomes by multivariable logistic regression analysis and receiver operating curves. Results and Limitations The m-ERG classifier showed 95% accuracy in an independent validation subset (n=155 samples). Across cohorts, 45%, 9%, 8% and 38% of PCa were classified as m-ERG+, m-ETS+, m-SPINK1+, and triple negative (m-ERG−/m-ETS−/m-SPINK1−), respectively. Gene expression profiling supports three underlying molecularly defined groups (m-ERG+, m-ETS+ and m-SPINK1+/triple negative). On multivariable analysis, m-ERG+ tumors were associated with lower preoperative serum PSA and Gleason scores, but enriched for extraprostatic extension (p<0.001). m-ETS+ tumors were associated with seminal vesicle invasion (p=0.01), while m-SPINK1+/triple negative tumors had higher Gleason scores and were more frequent in Black/African American patients (p<0.001). Clinical outcomes were not significantly different between subtypes. Conclusions A clinically available prognostic test (Decipher) can also assess PCa molecular subtypes, obviating the need for additional testing. Clinicopathological differences were found among subtypes based on global expression patterns. PMID:25964175

7. Historic American Buildings Survey Gleason Collection, S.F. College for ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

7. Historic American Buildings Survey Gleason Collection, S.F. College for Women San Francisco, California Original: 1850's Re-photo: March 1940 VIEW FROM SOUTHEAST - Mission San Antonio de Padua, Hunter Liggett Military Reservation, Jolon, Monterey County, CA

Concordance of Gleason grading with three-dimensional ultrasound systematic biopsy and biopsy core pre-embedding.

PubMed

van der Aa, Anouk A M A; Mannaerts, Christophe K; van der Linden, Hans; Gayet, Maudy; Schrier, Bart Ph; Mischi, Massimo; Beerlage, Harrie P; Wijkstra, Hessel

2018-02-01

To determine the value of a three-dimensional (3D) greyscale transrectal ultrasound (TRUS)-guided prostate biopsy system and biopsy core pre-embedding method on concordance between Gleason scores of needle biopsies and radical prostatectomy (RP) specimens. Retrospective analysis of prostate biopsies and subsequent RP for PCa in the Jeroen Bosch Hospital, the Netherlands, from 2007 to 2016. Two cohorts were analysed: conventional 2D TRUS-guided biopsies and RP (2007-2013, n = 266) versus 3D TRUS-guided biopsies with pre-embedding (2013-2016, n = 129). The impact of 3D TRUS-guidance with pre-embedding on Gleason score (GS) concordance between biopsy and RP was evaluated using the κ-coefficient. Predictors of biopsy GS 6 upgrading were assessed using logistic regression models. Gleason concordance was comparable between the two cohorts with a κ = 0.44 for the 3D cohort, compared to κ = 0.42 for the 2D cohort. 3D TRUS-guidance with pre-embedding, did not significantly affect the risk of biopsy GS 6 upgrading in univariate and multivariate analysis. 3D TRUS-guidance with biopsy core pre-embedding did not improve Gleason concordance. Improved detection techniques are needed for recognition of low-grade disease upgrading.

The efficacy and utilisation of preoperative multiparametric magnetic resonance imaging in robot-assisted radical prostatectomy: does it change the surgical dissection plan?

PubMed

Tavukçu, Hasan Hüseyin; Aytaç, Ömer; Balcı, Numan Cem; Kulaksızoğlu, Haluk; Atuğ, Fatih

2017-12-01

We investigated the effect of the use of multiparametric prostate magnetic resonance imaging (mp-MRI) on the dissection plan of the neurovascular bundle and the oncological results of our patients who underwent robot-assisted radical prostatectomy. We prospectively evaluated 60 consecutive patients, including 30 patients who had (Group 1), and 30 patients who had not (Group 2) mp-MRI before robot-assisted radical prostatectomy. Based on the findings of mp-MRI, the dissection plan was changed as intrafascial, interfascial, and extrafascial in the mp-MRI group. Two groups were compared in terms of age, prostate-specific antigen (PSA), Gleason sum scores and surgical margin positivity. There was no statistically significant difference between the two groups in terms of age, PSA, biopsy Gleason score, final pathological Gleason score and surgical margin positivity. mp-MRI changed the initial surgical plan in 18 of 30 patients (60%) in Group 1. In seventeen of these patients (56%) surgical plan was changed from non-nerve sparing to interfascial nerve sparing plan. In one patient dissection plan was changed to non-nerve sparing technique which had extraprostatic extension on final pathology. Surgical margin positivity was similar in Groups 1, and 2 (16% and 13%, respectively) although, Group 1 had higher number of high- risk patients. mp-MRI confirmed the primary tumour localisation in the final pathology in 27 of of 30 patients (90%). Preoperative mp-MRI effected the decision to perform a nerve-sparing technique in 56% of the patients in our study; moreover, changing the dissection plan from non-nerve-sparing technique to a nerve sparing technique did not increase the rate of surgical margin positivity.

Clinical significance of prospectively assigned Gleason tertiary pattern 4 in contemporary Gleason score 3+3=6 prostate cancer.

PubMed

Doshi, Chirag; Vacchio, Michael; Attwood, Kristopher; Murekeyisoni, Christine; Mehedint, Diana C; Badkhshan, Shervin; Azabdaftari, Gissou; Sule, Norbert; Guru, Khurshid A; Mohler, James L; Kauffman, Eric C

2016-06-01

To determine the oncologic impact of prospectively assigned tertiary pattern 4 in contemporary Gleason score (GS) 3 + 3 = 6 radical prostatectomy (RP) specimens. Oncologic outcomes were retrospectively reviewed for 720 consecutive patients from a single National Comprehensive Cancer Network (NCCN) center with at least 6 months follow-up after RP for GS3 + 3 = 6 (GS6, N = 222), GS6 with tertiary pattern 4 (GS6t4, N = 62), or GS3 + 4 = 7 (N = 436) prostate cancer, as prospectively graded since 2006 using the 2005 International Society of Urologic Pathologists criteria. Preoperative NCCN risk category, RP pathology, progression-free survival (PFS) and metastasis-free survival (MFS) were compared among the GS6, GS6t4, and GS3 + 4 = 7 groups using χ(2) , Kaplan-Meier, and log-rank analyses. The incidence of low NCCN preoperative risk classification for GS6t4 patients (63%) was less than that for GS6 patients (77%) while greater than that for GS3 + 4 = 7 patients (30%, P < 0.001). GS6t4 patients had RP pathologic features which were intermediate in risk between that of GS6 and GS3 + 4 = 7 based on extraprostatic extension (27% vs. 6% vs. 31%, respectively, P < 0.001) and mean percentage of prostate gland involvement (13% vs. 10% vs. 16%, respectively, P < 0.001). With a mean overall follow-up of 42 months, PFS for GS6t4 patients (5-year 85%) was intermediate between that of GS6 (5-year 93%) and GS3 + 4 = 7 (5-year 76%) patients (P < 0.001). The 5-year MFS rate was 100% for GS6 and GS6t4 patients compared to 97% for GS3 + 4 = 7 patients (P = 0.07). This study provides the longest follow-up to date for RP patients with prospectively assigned GS6t4 and supports a risk for adverse RP pathology and postoperative disease progression that is intermediate between GS6 and GS3 + 4 = 7. Whether a tertiary pattern 4 in GS6 disease increases the risk of metastasis is uncertain and requires longer term study. Given favorable oncologic outcomes, less stringent postoperative surveillance for both GS6 and GS6t4 patients may be warranted. © 2016 Wiley Periodicals, Inc.

Adverse pathology and undetectable ultrasensitive prostate-specific antigen after radical prostatectomy: is adjuvant radiation warranted?

PubMed

Simon, Ross M; Howard, Lauren E; Freedland, Stephen J; Aronson, William J; Terris, Martha K; Kane, Christopher J; Amling, Christopher L; Cooperberg, Matthew R; Vidal, Adriana C

2016-06-01

To determine if men with adverse pathology but undetectable ultrasensitive (<0.01 ng/mL) PSA are at high-risk for biochemical recurrence (BCR), or if there is a subset of patients at low-risk for whom the benefit of adjuvant radiation therapy might be limited. We evaluated 411 patients treated with RP from 2001 to 2013 without adjuvant radiation who had an undetectable (<0.01 ng/mL) PSA level after RP but with adverse pathology [positive surgical margins (PSMs), extraprostatic extension (EPE), and/or seminal vesicle invasion (SVI)]. Multivariable Cox regression analyses tested the relationship between pathological characteristics and BCR to identify groups of men at highest risk of early BCR. On multivariable analysis, only pathological Gleason 7 (4 + 3), Gleason ≥8, and SVI independently predicted BCR (P = 0.019, P < 0.001, and P = 0.001, respectively), although on two-way analysis men with Gleason 7 (4 + 3) did not have significantly higher rates of BCR compared with patients with Gleason ≤6 (log-rank, P = 0.074). Men with either Gleason ≥8 (with PSMs or EPE) or SVI (15% of the cohort) defined a high-risk group vs men without these characteristics (3-year BCR risk of 50.4% vs 11.9%, log-rank, P < 0.001). Among men with adverse pathology but an undetectable (<0.01 ng/mL) PSA level after RP, the benefits of adjuvant radiation are probably limited except for men with Gleason 8-10 (with PSMs or EPE) or SVI who are at high-risk of early BCR. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

Prostate-specific antigen velocity is not better than total prostate-specific antigen in predicting prostate biopsy diagnosis.

PubMed

Gorday, William; Sadrzadeh, Hossein; de Koning, Lawrence; Naugler, Christopher T

2015-12-01

1.) Identify whether prostate-specific antigen velocity improves the ability to predict prostate biopsy diagnosis. 2.) Test whether there is an increase in the predictive capability of models when Gleason 7 prostate cancers are separated into a 3+4 and a 4+3 group. Calgary Laboratory Services' Clinical Laboratory Information System was searched for prostate biopsies reported between January 1, 2009 and December 31, 2013. Total prostate-specific antigen tests were recorded for each patient from January 1, 2007 to the most recent test before their recorded prostate biopsy. The data set was divided into the following three groups for comparison; benign, all prostate cancer and Gleason 7-10. The Gleason grade 7-10 group was further divided into 4+3 and 3+4 Gleason 7 prostate cancers. Prostate-specific antigen velocity was calculated using four different methods found in the literature. Receiver operator curves were used to assess operational characteristics of the tests. 4622 men between the ages of 40-89 with a prostate biopsy were included for analysis. Combining prostate-specific antigen velocity with total prostate-specific antigen (AUC=0.570-0.712) resulted in small non-statistically significant changes to the area under the curve compared to the area under the curve of total prostate-specific antigen alone (AUC=0.572-0.699). There were marked increases in the area under curves when 3+4 and 4+3 Gleason 7 cancers were separated. Prostate-specific antigen velocity does not add predictive value for prostate biopsy diagnosis. The clinical significance of the prostate specific antigen test can be improved by separating Gleason 7 prostate cancers into a 3+4 and 4+3 group. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Prostate cancer in the Baby Boomer generation: results from CaPSURE.

PubMed

Scales, Charles D; Moul, Judd W; Curtis, Lesley H; Elkin, Eric P; Hughes, M E; Carroll, Peter R

2007-12-01

Baby Boomers (those born in 1946 to 1964) are thought to place a high value on quality of life, and have a higher propensity to consume healthcare services than previous generations. We sought to characterize prostate cancer (CaP) presentation among this group, and determine whether treatment patterns differ between Baby Boomers and the preceding generation. We defined two birth cohorts: men born in 1927 to 1945 (pre-Boomers) and Baby Boomers. Our study cohort included men less than 65 years old, diagnosed with CaP between 1999 and 2003 (Baby Boomers, n = 812; pre-Boomers, n = 1843). We compared the two groups for clinical presentation, sociodemographics, and primary treatment, controlling for age effects. The primary endpoint was selection of radical prostatectomy as primary treatment. Most Baby Boomers were diagnosed with stage T1 disease (466, 61%), biopsy Gleason sums less than 7 (572, 73%), and prostate-specific antigen levels of 4.1 to 10.0 (509, 66%). This presentation was not clinically different from pre-Boomers. Baby Boomers had higher socioeconomic status than pre-Boomers. On multivariate analysis, Baby Boomers were more likely to undergo radical prostatectomy as primary therapy (odds ratio [OR] 1.63, 95% confidence interval [CI] 1.13 to 2.35). Controlling for age effects, however, there were no significant differences in treatment choice (OR 0.86, 95% CI 0.40 to 1.87) or sociodemographics between these groups. Differences in CaP presentation and treatment between Baby Boomers and pre-Boomers may be related to age at diagnosis rather than innate differences in behavior. As more Baby Boomers are diagnosed with CaP, further research will be required to characterize this generation's impact on CaP care.

Ectonucleotide pyrophosphatase/phosphodiesterase (E-NPP) and adenosine deaminase (ADA) activities in prostate cancer patients: influence of Gleason score, treatment and bone metastasis.

PubMed

Battisti, Vanessa; Maders, Liési D K; Bagatini, Margarete D; Battisti, Iara E; Bellé, Luziane P; Santos, Karen F; Maldonado, Paula A; Thomé, Gustavo R; Schetinger, Maria R C; Morsch, Vera M

2013-04-01

The relation between adenine nucleotides and cancer has already been described in literature. Considering that the enzymes ectonucleotide pyrophosphatase/phosphodiesterase (E-NPP) and adenosine deaminase (ADA) act together to control nucleotide levels, we aimed to investigate the role of these enzymes in prostate cancer (PCa). E-NPP and ADA activities were determined in serum and platelets of PCa patients and controls. We also verified the influence of the Gleason score, bone metastasis and treatment in the enzyme activities. Platelets and serum E-NPP activity increased, whereas ADA activity in serum decreased in PCa patients. In addition, Gleason score, metastasis and treatment influenced E-NPP and ADA activities. We may propose that E-NPP and ADA are involved in the development of PCa. Moreover, E-NPP and ADA activities are modified in PCa patients with distinct Gleason score, with bone metastasis, as well as in patients under treatment. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Analysis of histological findings obtained combining US/mp-MRI fusion-guided biopsies with systematic US biopsies: mp-MRI role in prostate cancer detection and false negative.

PubMed

Faiella, Eliodoro; Santucci, Domiziana; Greco, Federico; Frauenfelder, Giulia; Giacobbe, Viola; Muto, Giovanni; Zobel, Bruno Beomonte; Grasso, Rosario Francesco

2018-02-01

To evaluate the diagnostic accuracy of mp-MRI correlating US/mp-MRI fusion-guided biopsy with systematic random US-guided biopsy in prostate cancer diagnosis. 137 suspected prostatic abnormalities were identified on mp-MRI (1.5T) in 96 patients and classified according to PI-RADS score v2. All target lesions underwent US/mp-MRI fusion biopsy and prostatic sampling was completed by US-guided systematic random 12-core biopsies. Histological analysis and Gleason score were established for all the samples, both target lesions defined by mp-MRI, and random biopsies. PI-RADS score was correlated with the histological results, divided in three groups (benign tissue, atypia and carcinoma) and with Gleason groups, divided in four categories considering the new Grading system of the ISUP 2014, using t test. Multivariate analysis was used to correlate PI-RADS and Gleason categories to PSA level and abnormalities axial diameter. When the random core biopsies showed carcinoma (mp-MRI false-negatives), PSA value and lesions Gleason median value were compared with those of carcinomas identified by mp-MRI (true-positives), using t test. There was statistically significant difference between PI-RADS score in carcinoma, atypia and benign lesions groups (4.41, 3.61 and 3.24, respectively) and between PI-RADS score in Gleason < 7 group and Gleason > 7 group (4.14 and 4.79, respectively). mp-MRI performance was more accurate for lesions > 15 mm and in patients with PSA > 6 ng/ml. In systematic sampling, 130 (11.25%) mp-MRI false-negative were identified. There was no statistic difference in Gleason median value (7.0 vs 7.06) between this group and the mp-MRI true-positives, but a significant lower PSA median value was demonstrated (7.08 vs 7.53 ng/ml). mp-MRI remains the imaging modality of choice to identify PCa lesions. Integrating US-guided random sampling with US/mp-MRI fusion target lesions sampling, 3.49% of false-negative were identified.

[Impact of Gleason score on biochemical recurrence free survival after radical prostatectomy with positive surgical margins].

PubMed

Roux, V; Eyraud, R; Brureau, L; Gourtaud, G; Senechal, C; Fofana, M; Blanchet, P

Research of predictive factors of biochemical recurrence to guide the establishment of an adjuvant treatment after radical prostatectomy for cancer with positive surgical margins. A retrospective cohort of 1577 afro-caribbean patients undergoing radical prostatectomy operated between 1st January 2000 and 1st July 2013 was analyzed. In this cohort, 406 patients had positive surgical margin, we excluded 11 patients who received adjuvant therapy (radiotherapy, hormonotherapy, radio-hormonotherapy) and 2 patients for whom histological analysis of the surgical specimen was for a pT4 pathological stage. After a descriptive analysis, we used a Cox model to look for predictors of survival without biochemical recurrence then, depending on the significant variables, we separated our population into six groups: stage pT2 with Gleason score≤3+4 (group 1), stage pT2 with a score of Gleason≥4+3 (group 2), stage pT3a with a Gleason core≤3+4 (group 3), pT3a stage with a score of Gleason≥4+3 (group 4), stage pT3b with a Gleason score≤3+4 (group 5) and stage pT3b Gleason≥with a score of 4+3 (group 6) and compared survival without biochemical recurrence using a log rank test. After radical prostatectomy with surgical margins with an anatomopathological stage≤pT3b, a Gleason score≥4+3 had a pejorative survival without biochemical recurrence than pathological stage (P<0.001). In multivariate analysis, predictors of survival without biochemical recurrence after radical prostatectomy with positive surgical margins were the majority Gleason postoperative (P<0.0001), pathological stage (P=0.049) adjusted preoperative PSA (P=0.826), with the body mass index (BMI) (P=0.59) and tumor volume (P=0.95). A high postoperatively Gleason score (≥4+3) has a better predictive value of biochemical recurrence than pathological stage pT2 or pT3 at the patients having been treated for prostate cancer by radical prostatectomy with positive surgical margins. 4. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Dominant intraprostatic cancer confirmed by direct MRI-guided biopsy: Concordance with histopathological findings.

PubMed

Meermeier, Nicholas P; Turner, Kevin R; Foster, Bryan R; Várallyay, Csanád; Liu, Jen-Jane; Coakley, Fergus V

2018-06-09

To investigate the concordance between dominant intraprostatic cancer seen on endorectal multiparametric MRI and confirmed by MRI-targeted biopsy with histopathological findings at radical prostatectomy, since existing literature has emphasized the miss rather than the concordance rate of MRI. We retrospectively identified 20 patients who underwent radical prostatectomy after a dominant intraprostatic cancer focus was identified at endorectal multiparametric MRI and confirmed by MRI-targeted biopsy. Concordance was determined by comparing the location and Gleason grade group of dominant tumor at MRI with the location and Gleason grade group determined at histopathological review. Mean patient age was 65 years (range, 48 to 76) and median serum prostatic specific antigen level was 9.4 ng/mL (range, 4.6 to 58.0). In all 20 patients, the location of dominant tumor based on MRI and targeted biopsy corresponded with the dominant tumor location at histopathology. In 9 patients, Gleason grade group was the same at targeted biopsy and final histopathology. In 9 patients, final Gleason grade group was higher and in two patients it was lower. Our preliminary results suggest dominant tumor as determined by endorectal multiparametric MRI and confirmed by a positive MRI-targeted biopsy has high concordance with histopathological findings at radical prostatectomy for location, and reasonable concordance for Gleason grade group. Copyright © 2018 Elsevier Inc. All rights reserved.

Can Prostate-Specific Antigen Kinetics before Prostate Biopsy Predict the Malignant Potential of Prostate Cancer?

PubMed

Kim, Sang Jin; Jeong, Tae Yoong; Yoo, Dae Seon; Park, Jinsung; Cho, Seok; Kang, Seok Ho; Lee, Sang Hyub; Jeon, Seung Hyun; Lee, Tchun Yong; Park, Sung Yul

2015-11-01

To predict the malignant potential of prostate cancer (PCa) according to prostate-specific antigen velocity (PSAV), PSA density (PSAD), free/total PSA ratio (%fPSA), and digital rectal examination (DRE). From January 2009 to December 2012, 548 adult male patients were diagnosed with PCa by prostate biopsy at four hospitals in Korea. We retrospectively analyzed 155 adult male patients with an initial PSA level≤10 ng/mL and whose PSA levels had been checked more than two times at least 6 months before they had been diagnosed with PCa, with test intervals of more than 3 months. Patients with a urinary tract infection, and patients who had previously undergone cystoscopy or surgery of the prostate were excluded. We separated patients into two groups according to Gleason sum [Gleason sum≤7 (n=134) or Gleason sum≥8 (n=21)] and the presence of extracapsular invasion [organ confined (n=129) or extracapsular invasion (n=26)]. Differences between the groups were compared. The group with a Gleason sum≥8 or extracapsular invasion of PCa showed high PSAV and significantly lower %fPSA. There were no significant differences in PSAD and the presence of an abnormality on DRE between two groups. In PCa patients treated with other therapies besides prostatectomy, a high PSA velocity and a low %fPSA may predict high grade PCa with a Gleason sum≥8 or the presence of extracapsular invasion.

Is Primary Prostate Cancer Treatment Influenced by Likelihood of Extraprostatic Disease? A Surveillance, Epidemiology and End Results Patterns of Care Study

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

Holmes, Jordan A.; Wang, Andrew Z.; University of North Carolina-Lineberger Comprehensive Cancer Center, Chapel Hill, NC

2012-09-01

Purpose: To examine the patterns of primary treatment in a recent population-based cohort of prostate cancer patients, stratified by the likelihood of extraprostatic cancer as predicted by disease characteristics available at diagnosis. Methods and Materials: A total of 157,371 patients diagnosed from 2004 to 2008 with clinically localized and potentially curable (node-negative, nonmetastatic) prostate cancer, who have complete information on prostate-specific antigen, Gleason score, and clinical stage, were included. Patients with clinical T1/T2 disease were grouped into categories of <25%, 25%-50%, and >50% likelihood of having extraprostatic disease using the Partin nomogram. Clinical T3/T4 patients were examined separately as themore » highest-risk group. Logistic regression was used to examine the association between patient group and receipt of each primary treatment, adjusting for age, race, year of diagnosis, marital status, Surveillance, Epidemiology and End Results database region, and county-level education. Separate models were constructed for primary surgery, external-beam radiotherapy (RT), and conservative management. Results: On multivariable analysis, increasing likelihood of extraprostatic disease was significantly associated with increasing use of RT and decreased conservative management. Use of surgery also increased. Patients with >50% likelihood of extraprostatic cancer had almost twice the odds of receiving prostatectomy as those with <25% likelihood, and T3-T4 patients had 18% higher odds. Prostatectomy use increased in recent years. Patients aged 76-80 years were likely to be managed conservatively, even those with a >50% likelihood of extraprostatic cancer (34%) and clinical T3-T4 disease (24%). The proportion of patients who received prostatectomy or conservative management was approximately 50% or slightly higher in all groups. Conclusions: There may be underutilization of RT in older prostate cancer patients and those with likely extraprostatic disease. Because more than half of prostate cancer patients do not consult with a radiation oncologist, a multidisciplinary consultation may affect the treatment decision-making process.« less

Prostate cancer and polymorphism D85Y in gene for dihydrotestosterone degrading enzyme UGT2B15: Frequency of DD homozygotes increases with Gleason Score.

PubMed

Hajdinjak, Tine; Zagradisnik, Boris

2004-06-01

Although, a functional rationale for influence of polymorphism D85Y in gene UGT2B15 on prostate cancer (PCa) exists (different V(max) of enzyme), conflicting results have been reported. DNA from 178 controls and 206 PCa patients with known Gleason score were genotyped using a newly developed RFLP assay, which allowed the detection of both alleles in an individual after single PCR amplification. 16% DD, 52% DY; PCa patients: 23% DD, 49% DY. Subgroups of PCa: well differentiated: 11% DD, 37% DY; moderately differentiated: 22% DD, 50% DY; poorly differentiated: 34% DD, 50% DY. Correlation was confirmed between Gleason score and number of D alleles (P = 0.018) and persisted after age adjustment. When comparing controls to patients with a Gleason score of 7 or more, difference for the frequency of homozygosity DD was significant between the groups (P = 0.032, OR = 2.04). Polymorphism D85Y in gene UGT2B15 correlates with differentiation of PCa. Copyright 2004 Wiley-Liss, Inc.

Method and metaphysics in Clements's and Gleason's ecological explanations.

PubMed

Eliot, Christopher

2007-03-01

To generate explanatory theory, ecologists must wrestle with how to represent the extremely many, diverse causes behind phenomena in their domain. Early twentieth-century plant ecologists Frederic E. Clements and Henry A. Gleason provide a textbook example of different approaches to explaining vegetation, with Clements allegedly committed, despite abundant exceptions, to a law of vegetation, and Gleason denying the law in favor of less organized phenomena. However, examining Clements's approach to explanation reveals him not to be expressing a law, and instead to be developing an explanatory structure without laws, capable of progressively integrating causal complexity. Moreover, Clements and Gleason largely agree on the causes of vegetation; but, since causal understanding here underdetermines representation, they differ on how to integrate recognized causes into general theory--that is, in their methodologies. Observers of the case may have mistakenly assumed that scientific representation across the disciplines typically aims at laws like Newton's, and that representations always reveal scientists' metaphysical commitments. Ironically, in the present case, this assumption seems to have been made even by observers who regard Clements as nai ve for his alleged commitment to an ecological law.

Identification of the G protein-coupled estrogen receptor (GPER) in human prostate: expression site of the estrogen receptor in the benign and neoplastic gland.

PubMed

Rago, V; Romeo, F; Giordano, F; Ferraro, A; Carpino, A

2016-01-01

Estrogens are involved in growth, differentiation and pathogenesis of human prostate through the mediation of the classical estrogen receptors ERα and ERβ. The G protein-coupled estrogen receptor (GPER) is a 'novel' mediator of estrogen signaling which has been recently recognized in some human reproductive tissues, but its expression in the prostate gland is still unknown. Here, we investigated GPER in benign (from 5 patients) and neoplastic prostatic tissues (from 50 patients) by immunohistochemical analysis and Western blotting. Normal areas of benign prostates revealed a strong GPER immunoreactivity in the basal epithelial cells while luminal epithelial cells were unreactive and stromal cells were weakly immunostained. GPER was also immunolocalized in adenocarcinoma samples but the immunoreactivity of tumoral areas decreased from Gleason pattern 2 to Gleason pattern 4. Furthermore, a strong GPER immunostaining was also revealed in cells of pre-neoplastic lesions (high-grade prostatic intra-epithelial neoplasia). Western blot analysis of benign and tumor protein extracts showed the presence of a ~42 kDa band, consistent with the GPER molecular weight. An increase in both pAkt and p cAMP-response-binding protein (pCREB) levels was also observed in poorly differentiated PCa samples. Finally, this work identified GPER in the epithelial basal cells of benign human prostate, with a different localization with respect to the classical estrogen receptors. Furthermore, the expression of GPER in prostatic adenocarcinoma cells was also observed but with a modulation of the immunoreactivity according to tumor cell arrangements. © 2015 American Society of Andrology and European Academy of Andrology.

A single microfocus (5% or less) of Gleason 6 prostate cancer at biopsy--can we predict adverse pathological outcomes?

PubMed

Thong, Alan E; Shikanov, Sergey; Katz, Mark H; Gofrit, Ofer N; Eggener, Scott; Zagaja, Gregory P; Shalhav, Arieh L; Zorn, Kevin C

2008-12-01

Patients with Gleason score 6 microfocal prostate cancer, defined as 5% or less in 1 biopsy core, are often considered to have favorable disease. Few studies have addressed clinical parameters that predict pathological upgrading or up staging at radical prostatectomy. From a prospective database of 1,271 consecutive robot assisted laparoscopic prostatectomies performed from 2003 to 2008 patients with Gleason score 6 microfocal prostate cancer were identified. Adverse pathological outcome was defined as any upgrading and/or up staging on prostatectomy pathological findings. Multivariate logistic regression was used to evaluate the ability of patient age, clinical stage, the total number of biopsy cores, preoperative prostate specific antigen, prostate volume and pathological prostate specific antigen density to predict adverse pathological outcomes. A total of 192 patients with a median age of 59 years (range 42 to 73) were identified with Gleason score 6 prostate cancer involving 5% or less of 1 biopsy core, including 177 (92%) with clinical T1c disease. Mean +/- SD preoperative prostate specific antigen was 6.0 +/- 3.9 ng/ml (range 0.8 to 35). Overall 42 patients (22%) had adverse pathological outcomes, including upgrading in 35 (18%) and up staging in 16 (8%). Multivariate logistic regression revealed that age more than 65 years and pathological prostate specific antigen density greater than 0.20 ng/ml/gm were predictive of an increased risk of adverse pathological results (p = 0.0081 and 0.0169, respectively). While a microfocus of Gleason score 6 prostate cancer on biopsy is commonly considered low risk disease, there was a greater than 1/5 risk of pathological upgrading and/or up staging. Patients with Gleason score 6 microfocal prostate cancer should be counseled that they may harbor more aggressive disease, especially when pretreatment clinical risk factors are present, such as advanced age or high clinical prostate specific antigen density.

How accurate is our clinical prediction of "minimal prostate cancer"?

PubMed

Leibovici, Dan; Shikanov, Sergey; Gofrit, Ofer N; Zagaja, Gregory P; Shilo, Yaniv; Shalhav, Arieh L

2013-07-01

Recommendations for active surveillance versus immediate treatment for low risk prostate cancer are based on biopsy and clinical data, assuming that a low volume of well-differentiated carcinoma will be associated with a low progression risk. However, the accuracy of clinical prediction of minimal prostate cancer (MPC) is unclear. To define preoperative predictors for MPC in prostatectomy specimens and to examine the accuracy of such prediction. Data collected on 1526 consecutive radical prostatectomy patients operated in a single center between 2003 and 2008 included: age, body mass index, preoperative prostate-specific antigen level, biopsy Gleason score, clinical stage, percentage of positive biopsy cores, and maximal core length (MCL) involvement. MPC was defined as < 5% of prostate volume involvement with organ-confined Gleason score < or = 6. Univariate and multivariate logistic regression analyses were used to define independent predictors of minimal disease. Classification and Regression Tree (CART) analysis was used to define cutoff values for the predictors and measure the accuracy of prediction. MPC was found in 241 patients (15.8%). Clinical stage, biopsy Gleason's score, percent of positive biopsy cores, and maximal involved core length were associated with minimal disease (OR 0.42, 0.1, 0.92, and 0.9, respectively). Independent predictors of MPC included: biopsy Gleason score, percent of positive cores and MCL (OR 0.21, 095 and 0.95, respectively). CART showed that when the MCL exceeded 11.5%, the likelihood of MPC was 3.8%. Conversely, when applying the most favorable preoperative conditions (Gleason < or = 6, < 20% positive cores, MCL < or = 11.5%) the chance of minimal disease was 41%. Biopsy Gleason score, the percent of positive cores and MCL are independently associated with MPC. While preoperative prediction of significant prostate cancer was accurate, clinical prediction of MPC was incorrect 59% of the time. Caution is necessary when implementing clinical data as selection criteria for active surveillance.

Fifteen-year Outcomes Following Conservative Management Among Men Aged 65 Years or Older with Localized Prostate Cancer.

PubMed

Lu-Yao, Grace L; Albertsen, Peter C; Moore, Dirk F; Lin, Yong; DiPaola, Robert S; Yao, Siu-Long

2015-11-01

To understand the threat posed by localized prostate cancer and the potential impact of surgery or radiation, patients and healthcare providers require information on long-term outcomes following conservative management. To describe 15-yr survival outcomes and cancer therapy utilization among men 65 years and older managed conservatively for newly diagnosed localized prostate cancer. This is a population-based cohort study with participants living in predefined geographic areas covered by the Surveillance, Epidemiology, and End Results program. The study includes 31 137 Medicare patients aged ≥65 yr diagnosed with localized prostate cancer in 1992-2009 who initially received conservative management (no surgery, radiotherapy, cryotherapy, or androgen deprivation therapy [ADT]). All patients were followed until death or December 31, 2009 (for prostate cancer-specific mortality [PCSM]) and December 31, 2011 (for overall mortality). Competing-risk analyses were used to examine PCSM, overall mortality, and utilization of cancer therapies. The 15-yr risk of PCSM for men aged 65-74 yr diagnosed with screening-detected prostate cancer was 5.7% (95% confidence interval [CI] 3.7-8.0%) for T1c Gleason 5-7 and 22% (95% CI 16-35%) for Gleason 8-10 disease. After 15 yr of follow-up, 24% (95% CI 21-27%) of men aged 65-74 yr with screening-detected Gleason 5-7 cancer received ADT. The corresponding result for men with Gleason 8-10 cancer was 38% (95% CI 32-44%). The major study limitations are the lack of data for men aged <65 yr and detailed clinical information associated with secondary cancer therapy. The 15-yr outcomes following conservative management of newly diagnosed Gleason 5-7 prostate cancer among men aged ≥65 yr are excellent. Men with Gleason 8-10 disease managed conservatively face a significant risk of PCSM. We examined the long-term survival outcomes for a large group of patients diagnosed with localized prostate cancer who did not have surgery, radiotherapy, cryotherapy, or androgen deprivation therapy in the first 6 mo after cancer diagnosis. We found that the 15-yr disease-specific survival is excellent for men diagnosed with Gleason 5-7 disease. The data support conservative management as a reasonable choice for elderly patients with low-grade localized prostate cancer. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Development of ProCaRS Clinical Nomograms for Biochemical Failure-free Survival Following Either Low-Dose Rate Brachytherapy or Conventionally Fractionated External Beam Radiation Therapy for Localized Prostate Cancer

PubMed Central

Warner, Andrew; Pickles, Tom; Crook, Juanita; Martin, Andre-Guy; Souhami, Luis; Catton, Charles; Lukka, Himu

2015-01-01

Purpose: Although several clinical nomograms predictive of biochemical failure-free survival (BFFS) for localized prostate cancer exist in the medical literature, making valid comparisons can be challenging due to variable definitions of biochemical failure, the disparate distribution of prognostic factors, and received treatments in patient populations. The aim of this investigation was to develop and validate clinically-based nomograms for 5-year BFFS using the ASTRO II “Phoenix” definition for two patient cohorts receiving low-dose rate (LDR) brachytherapy or conventionally fractionated external beam radiation therapy (EBRT) from a large Canadian multi-institutional database. Methods and Materials: Patients were selected from the GUROC (Genitourinary Radiation Oncologists of Canada) Prostate Cancer Risk Stratification (ProCaRS) database if they received (1) LDR brachytherapy ≥ 144 Gy (n=4208) or (2) EBRT ≥ 70 Gy  (n=822). Multivariable Cox regression analysis for BFFS was performed separately for each cohort and used to generate clinical nomograms predictive of 5-year BFFS. Nomograms were validated using calibration plots of nomogram predicted probability versus observed probability via Kaplan-Meier estimates. Results: Patients receiving LDR brachytherapy had a mean age of 64 ± 7 years, a mean baseline PSA of 6.3 ± 3.0 ng/mL, 75% had a Gleason 6, and 15% had a Gleason 7, whereas patients receiving EBRT had a mean age of 70 ± 6 years, a mean baseline PSA of 11.6 ± 10.7 ng/mL, 30% had a Gleason 6, 55% had a Gleason 7, and 14% had a Gleason 8-10. Nomograms for 5-year BFFS included age, use and duration of androgen deprivation therapy (ADT), baseline PSA, T stage, and Gleason score for LDR brachytherapy and an ADT (months), baseline PSA, Gleason score, and biological effective dose (Gy) for EBRT. Conclusions: Clinical nomograms examining 5-year BFFS were developed for patients receiving either LDR brachytherapy or conventionally fractionated EBRT and may assist clinicians in predicting an outcome. Future work should be directed at examining the role of additional prognostic factors, comorbidities, and toxicity in predicting survival outcomes. PMID:26180700

68Ga-PSMA-11 PET/CT in primary staging of prostate cancer: PSA and Gleason score predict the intensity of tracer accumulation in the primary tumour.

PubMed

Uprimny, Christian; Kroiss, Alexander Stephan; Decristoforo, Clemens; Fritz, Josef; von Guggenberg, Elisabeth; Kendler, Dorota; Scarpa, Lorenza; di Santo, Gianpaolo; Roig, Llanos Geraldo; Maffey-Steffan, Johanna; Horninger, Wolfgang; Virgolini, Irene Johanna

2017-06-01

Prostate cancer (PC) cells typically show increased expression of prostate-specific membrane antigen (PSMA), which can be visualized by 68 Ga-PSMA-11 PET/CT. The aim of this study was to assess the intensity of 68 Ga-PSMA-11 uptake in the primary tumour and metastases in patients with biopsy-proven PC prior to therapy, and to determine whether a correlation exists between the primary tumour-related 68 Ga-PSMA-11 accumulation and the Gleason score (GS) or prostate-specific antigen (PSA) level. Ninety patients with transrectal ultrasound biopsy-proven PC (GS 6-10; median PSA: 9.7 ng/ml) referred for 68 Ga-PSMA-11 PET/CT were retrospectively analysed. PET images were analysed visually and semiquantitatively by measuring the maximum standardized uptake value (SUV max ). The SUV max of the primary tumour and pathologic lesions suspicious for lymphatic or distant metastases were then compared to the physiologic background activity of normal prostate tissue and gluteal muscle. The SUV max of the primary tumour was assessed in relation to both PSA level and GS. Eighty-two patients (91.1%) demonstrated pathologic tracer accumulation in the primary tumour that exceeded physiologic tracer uptake in normal prostate tissue (median SUV max : 12.5 vs. 3.9). Tumours with GS of 6, 7a (3+4) and 7b (4+3) showed significantly lower 68 Ga-PSMA-11 uptake, with median SUV max of 5.9, 8.3 and 8.2, respectively, compared to patients with GS >7 (median SUV max : 21.2; p < 0.001). PC patients with PSA ≥10.0 ng/ml exhibited significantly higher uptake than those with PSA levels <10.0 ng/ml (median SUV max : 17.6 versus 7.7; p < 0.001). In 24 patients (26.7%), 82 lymph nodes with pathologic tracer accumulation consistent with metastases were detected (median SUV max : 10.6). Eleven patients (12.2%) revealed 55 pathologic osseous lesions suspicious for bone metastases (median SUV max : 11.6). The GS and PSA level correlated with the intensity of tracer accumulation in the primary tumours of PC patients on 68 Ga-PSMA-11 PET/CT. As PC tumours with GS 6+7 and patients with PSA values ≤10 ng/ml showed significantly lower 68 Ga-PSMA-11 uptake, 68 Ga-PSMA-11 PET/CT should be preferentially applied for primary staging of PC in patients with GS >7 or PSA levels ≥10 ng/ml.

Exploiting a Molecular Gleason Grade for Prostate Cancer Therapy

DTIC Science & Technology

2010-03-01

clinical effectiveness of chemotherapy. MAOA influences chemotherapy resistance 3 INTRODUCTION Despite numerous clinical trials conducted...therapy resistance. Although residual viable tumor cells were identified in each case, chemotherapy effects were evident. We previously reported the...found that MAOA expression was upregulated in prostate cancers in association with higher Gleason grades (11), but effects on modulating cytotoxic drug

Label free aggressive prostate cancer identification with ultraviolet photoacoustic spectral analysis (Conference Presentation)

NASA Astrophysics Data System (ADS)

Xu, Guan; Davis, Mandy A.; Siddiqui, Javed; Chao, Wan-yu; Tomlins, Scott A.; Wei, John T.; Wang, Xueding

2017-03-01

Prostate cancer (PCa) is the most commonly diagnosed cancer in American men for the past decades. PCa has a relatively low progression rate but the 5 year survival rate decreases dramatically once the cancer has metastasized. Differentiating aggressive from indolent PCa is critical for improving PCa patient outcomes and preventing metastasis and death. Prostate biopsy is the standard procedure for evaluating the presence and aggressiveness of PCa. The microarchitecture of the biopsied tissues visualized by histology process is evaluated by pathologists and assigned a Gleason score as a quantification of the aggressiveness. In our previous study, we have shown that photoacoustic spectral analysis (PASA) is capable of quantifying the Gleason scores of the H&E stained human prostate tissues. In this study, we attempt to assess the Gleason scores without any staining by taking advantage of the strong optical absorption of nucleic acid at ultraviolet wavelengths. PA signals were generated by wide field illumination at 266 nm and received by a hydrophone with a bandwidth of 0-20 MHz. DU145 prostate cancer cells at the concentrations of 0.8, 0.4, 0.05, 0.025 and 0.0125 million per cm3 simulating those in cancerous and normal tissues were first attempted. The measurements were repeated for 10 times at each concentration. A correlation of 0.86 was observed between the PA signal intensities and the cell concentrations. Human PCa tissues with Gleason score 6, 7 and 8 and normal tissues were assessed. With 11 samples, a correlation of 0.89 was found between the Gleason scores and PASA slopes.

Expression and role of the angiotensin II AT2 receptor in human prostate tissue: in search of a new therapeutic option for prostate cancer.

PubMed

Guimond, Marie-Odile; Battista, Marie-Claude; Nikjouitavabi, Fatemeh; Carmel, Maude; Barres, Véronique; Doueik, Alexandre A; Fazli, Ladan; Gleave, Martin; Sabbagh, Robert; Gallo-Payet, Nicole

2013-07-01

Evidence shows that angiotensin II type 1 receptor (AT1R) blockers may be associated with improved outcome in prostate cancer patients. It has been proposed that part of this effect could be due to angiotensin II type 2 receptor (AT2R) activation, the only active angiotensin II receptor in this situation. This study aimed to characterize the localization and expression of AT2R in prostate tissues and to assess its role on cell morphology and number in prostatic epithelial cells in primary culture. AT2R and its AT2R-interacting protein (ATIP) expression were assessed on non-tumoral and tumoral human prostate using tissue microarray immunohistochemistry, binding assay, and Western blotting. AT2R effect on cell number was measured in primary cultures of epithelial cells from non-tumoral human prostate. AT2R was localized at the level of the acinar epithelial layer and its expression decreased in cancers with a Gleason score 6 or higher. In contrast, ATIP expression increased with cancer progression. Treatment of primary cell cultures from non-tumoral prostate tissues with C21/M024, a selective AT2R agonist, alone or in co-incubation with losartan, an AT1R antagonist, significantly decreased cell number compared to untreated cells. AT2R and ATIP are present in non-tumoral human prostate tissues and differentially regulated according to Gleason score. The decrease in non-tumoral prostate cell number upon selective AT2R stimulation suggests that AT2R may have a protective role against prostate cancer development. Treatment with a selective AT2R agonist could represent a new approach for prostate cancer prevention or for patients on active surveillance. Copyright © 2013 Wiley Periodicals, Inc.

Very High-Risk Localized Prostate Cancer: Outcomes Following Definitive Radiation

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

Narang, Amol K.; Gergis, Carol; Robertson, Scott P.

Purpose: Existing definitions of high-risk prostate cancer consist of men who experience significant heterogeneity in outcomes. As such, criteria that identify a subpopulation of National Comprehensive Cancer Network (NCCN) high-risk prostate cancer patients who are at very high risk (VHR) for poor survival outcomes following prostatectomy were recently developed at our institution and include the presence of any of the following disease characteristics: multiple NCCN high-risk factors, primary Gleason pattern 5 disease and/or ≥5 biopsy cores with Gleason sums of 8 to 10. Whether these criteria also apply to men undergoing definitive radiation is unclear, as is the optimal treatment regimenmore » in these patients. Methods and Materials: All men consecutively treated with definitive radiation by a single provider from 1993 to 2006 and who fulfilled criteria for NCCN high-risk disease were identified (n=288), including 99 patients (34%) with VHR disease. Multivariate-adjusted competing risk regression models were constructed to assess associations between the VHR definition and biochemical failure (BF), distant metastasis (DM), and prostate cancer–specific mortality (PCSM). Multivariate-adjusted Cox regression analysis assessed the association of the VHR definition with overall mortality (OM). Cumulative incidences of failure endpoints were compared between VHR men and other NCCN high-risk men. Results: Men with VHR disease compared to other NCCN high-risk men experienced a higher 10-year incidence of BF (54.0% vs 35.4%, respectively, P<.001), DM (34.9% vs 13.4%, respectively, P<.001), PCSM (18.5% vs 5.9%, respectively, P<.001), and OM (36.4% vs 27.0%, respectively, P=.04). VHR men with a detectable prostate-specific antigen (PSA) concentration at the end of radiation (EOR) remained at high risk of 10-year PCSM compared to VHR men with an undetectable EOR PSA (31.0% vs 13.7%, respectively, P=.05). Conclusions: NCCN high-risk prostate cancer patients who meet VHR criteria experience distinctly worse outcomes following definitive radiation and long-term androgen deprivation therapy, particularly if an EOR PSA is detectable. Optimal use of local therapies for VHR patients should be explored further, as should novel agents.« less

Comptonia peregrina

Treesearch

Paula M. Pijut

2004-01-01

Sweet fern is a densely branched, deciduous, rhizomatous shrub that grows 0.5 to 1.5 m tall and 1.2 to 2.5 m wide or more (Dirr 1998, Gleason and Cronquist 1991). Sweet fern is a dioecious or seldom monoecious (Gleason and Cronquist 1991), actinorhizal nitrogen-fixing shrub (Del Tredici 1996, Ziegler and Huser 1963) with fern-like leaves and stems that are aromatic...

Epigenome-Wide Tumor DNA Methylation Profiling Identifies Novel Prognostic Biomarkers of Metastatic-Lethal Progression in Men Diagnosed with Clinically Localized Prostate Cancer.

PubMed

Zhao, Shanshan; Geybels, Milan S; Leonardson, Amy; Rubicz, Rohina; Kolb, Suzanne; Yan, Qingxiang; Klotzle, Brandy; Bibikova, Marina; Hurtado-Coll, Antonio; Troyer, Dean; Lance, Raymond; Lin, Daniel W; Wright, Jonathan L; Ostrander, Elaine A; Fan, Jian-Bing; Feng, Ziding; Stanford, Janet L

2017-01-01

Aside from Gleason sum, few factors accurately identify the subset of prostate cancer patients at high risk for metastatic progression. We hypothesized that epigenetic alterations could distinguish prostate tumors with life-threatening potential. Epigenome-wide DNA methylation profiling was performed in surgically resected primary tumor tissues from a population-based (n = 430) and a replication (n = 80) cohort of prostate cancer patients followed prospectively for at least 5 years. Metastasis was confirmed by positive bone scan, MRI, CT, or biopsy, and death certificates confirmed cause of death. AUC, partial AUC (pAUC, 95% specificity), and P value criteria were used to select differentially methylated CpG sites that robustly stratify patients with metastatic-lethal from nonrecurrent tumors, and which were complementary to Gleason sum. Forty-two CpG biomarkers stratified patients with metastatic-lethal versus nonrecurrent prostate cancer in the discovery cohort, and eight of these CpGs replicated in the validation cohort based on a significant (P < 0.05) AUC (range, 0.66-0.75) or pAUC (range, 0.007-0.009). The biomarkers that improved discrimination of patients with metastatic-lethal prostate cancer include CpGs in five genes (ALKBH5, ATP11A, FHAD1, KLHL8, and PI15) and three intergenic regions. In the validation dataset, the AUC for Gleason sum alone (0.82) significantly increased with the addition of four individual CpGs (range, 0.86-0.89; all P <0.05). Eight differentially methylated CpGs that distinguish patients with metastatic-lethal from nonrecurrent tumors were validated. These novel epigenetic biomarkers warrant further investigation as they may improve prognostic classification of patients with clinically localized prostate cancer and provide new insights on tumor aggressiveness. Clin Cancer Res; 23(1); 311-9. ©2016 AACR. ©2016 American Association for Cancer Research.

Automatic Gleason grading of prostate cancer using quantitative phase imaging and machine learning

NASA Astrophysics Data System (ADS)

Nguyen, Tan H.; Sridharan, Shamira; Macias, Virgilia; Kajdacsy-Balla, Andre; Melamed, Jonathan; Do, Minh N.; Popescu, Gabriel

2017-03-01

We present an approach for automatic diagnosis of tissue biopsies. Our methodology consists of a quantitative phase imaging tissue scanner and machine learning algorithms to process these data. We illustrate the performance by automatic Gleason grading of prostate specimens. The imaging system operates on the principle of interferometry and, as a result, reports on the nanoscale architecture of the unlabeled specimen. We use these data to train a random forest classifier to learn textural behaviors of prostate samples and classify each pixel in the image into different classes. Automatic diagnosis results were computed from the segmented regions. By combining morphological features with quantitative information from the glands and stroma, logistic regression was used to discriminate regions with Gleason grade 3 versus grade 4 cancer in prostatectomy tissue. The overall accuracy of this classification derived from a receiver operating curve was 82%, which is in the range of human error when interobserver variability is considered. We anticipate that our approach will provide a clinically objective and quantitative metric for Gleason grading, allowing us to corroborate results across instruments and laboratories and feed the computer algorithms for improved accuracy.

Circulating and intraprostatic sex steroid hormonal profiles in relation to male pattern baldness and chest hair density among men diagnosed with localized prostate cancers.

PubMed

Zhou, Cindy Ke; Stanczyk, Frank Z; Hafi, Muhannad; Veneroso, Carmela C; Lynch, Barlow; Falk, Roni T; Niwa, Shelley; Emanuel, Eric; Gao, Yu-Tang; Hemstreet, George P; Zolfghari, Ladan; Carroll, Peter R; Manyak, Michael J; Sesterhenn, Isabell A; Levine, Paul H; Hsing, Ann W; Cook, Michael B

2017-12-01

Prospective cohort studies of circulating sex steroid hormones and prostate cancer risk have not provided a consistent association, despite evidence from animal and clinical studies. However, studies using male pattern baldness as a proxy of early-life or cumulative androgen exposure have reported significant associations with aggressive and fatal prostate cancer risk. Given that androgens underlie the development of patterned hair loss and chest hair, we assessed whether these two dermatological characteristics were associated with circulating and intraprostatic concentrations of sex steroid hormones among men diagnosed with localized prostate cancer. We included 248 prostate cancer patients from the NCI Prostate Tissue Study, who answered surveys and provided a pre-treatment blood sample as well as fresh frozen adjacent normal prostate tissue. Male pattern baldness and chest hair density were assessed by trained nurses before surgery. General linear models estimated geometric means and 95% confidence intervals (95%CIs) of each hormone variable by dermatological phenotype with adjustment for potential confounding variables. Subgroup analyses were performed by Gleason score (<7 vs ≥7) and race (European American vs. African American). We found strong positive associations of balding status with serum testosterone, dihydrotestosterone (DHT), estradiol, and sex hormone-binding globulin (SHBG), and a weak association with elevated intraprostatic testosterone. Conversely, neither circulating nor intraprostatic sex hormones were statistically significantly associated with chest hair density. Age-adjusted correlation between binary balding status and three-level chest hair density was weak (r = 0.05). There was little evidence to suggest that Gleason score or race modified these associations. This study provides evidence that balding status assessed at a mean age of 60 years may serve as a clinical marker for circulating sex hormone concentrations. The weak-to-null associations between balding status and intraprostatic sex hormones reaffirm differences in organ-specific sex hormone metabolism, implying that other sex steroid hormone-related factors (eg, androgen receptor) play important roles in organ-specific androgenic actions, and that other overlapping pathways may be involved in associations between the two complex conditions. © 2017 Wiley Periodicals, Inc.

Magnetic Resonance and Ultrasound Image Fusion Supported Transperineal Prostate Biopsy Using the Ginsburg Protocol: Technique, Learning Points, and Biopsy Results.

PubMed

Hansen, Nienke; Patruno, Giulio; Wadhwa, Karan; Gaziev, Gabriele; Miano, Roberto; Barrett, Tristan; Gnanapragasam, Vincent; Doble, Andrew; Warren, Anne; Bratt, Ola; Kastner, Christof

2016-08-01

Prostate biopsy supported by transperineal image fusion has recently been developed as a new method to the improve accuracy of prostate cancer detection. To describe the Ginsburg protocol for transperineal prostate biopsy supported by multiparametric magnetic resonance imaging (mpMRI) and transrectal ultrasound (TRUS) image fusion, provide learning points for its application, and report biopsy results. The article is supplemented by a Surgery in Motion video. This single-centre retrospective outcome study included 534 patients from March 2012 to October 2015. A total of 107 had no previous prostate biopsy, 295 had benign TRUS-guided biopsies, and 159 were on active surveillance for low-risk cancer. A Likert scale reported mpMRI for suspicion of cancer from 1 (no suspicion) to 5 (cancer highly likely). Transperineal biopsies were obtained under general anaesthesia using BiopSee fusion software (Medcom, Darmstadt, Germany). All patients had systematic biopsies, two cores from each of 12 anatomic sectors. Likert 3-5 lesions were targeted with a further two cores per lesion. Any cancer and Gleason score 7-10 cancer on biopsy were noted. Descriptive statistics and positive predictive values (PPVs) and negative predictive values (NPVs) were calculated. The detection rate of Gleason score 7-10 cancer was similar across clinical groups. Likert scale 3-5 MRI lesions were reported in 378 (71%) of the patients. Cancer was detected in 249 (66%) and Gleason score 7-10 cancer was noted in 157 (42%) of these patients. PPV for detecting 7-10 cancer was 0.15 for Likert score 3, 0.43 for score 4, and 0.63 for score 5. NPV of Likert 1-2 findings was 0.87 for Gleason score 7-10 and 0.97 for Gleason score ≥4+3=7 cancer. Limitations include lack of data on complications. Transperineal prostate biopsy supported by MRI/TRUS image fusion using the Ginsburg protocol yielded high detection rates of Gleason score 7-10 cancer. Because the NPV for excluding Gleason score 7-10 cancer was very high, prostate biopsies may not be needed for all men with elevated prostate-specific antigen values and nonsuspicious mpMRI. We present our technique to sample (biopsy) the prostate by the transperineal route (the area between the scrotum and the anus) to detect prostate cancer using a fusion of magnetic resonance and ultrasound images to guide the sampling. Copyright © 2016 European Association of Urology. All rights reserved.

Ability of preoperative 3.0-Tesla magnetic resonance imaging to predict the absence of side-specific extracapsular extension of prostate cancer.

PubMed

Hara, Tomohiko; Nakanishi, Hiroyuki; Nakagawa, Tohru; Komiyama, Motokiyo; Kawahara, Takashi; Manabe, Tomoko; Miyake, Mototaka; Arai, Eri; Kanai, Yae; Fujimoto, Hiroyuki

2013-10-01

Recent studies have shown an improvement in prostate cancer diagnosis with the use of 3.0-Tesla magnetic resonance imaging. We retrospectively assessed the ability of this imaging technique to predict side-specific extracapsular extension of prostate cancer. From October 2007 to August 2011, prostatectomy was carried out in 396 patients after preoperative 3.0-Tesla magnetic resonance imaging. Among these, 132 (primary sample) and 134 patients (validation sample) underwent 12-core prostate biopsy at the National Cancer Center Hospital of Tokyo, Japan, and at other institutions, respectively. In the primary dataset, univariate and multivariate analyses were carried out to predict side-specific extracapsular extension using variables determined preoperatively, including 3.0-Tesla magnetic resonance imaging findings (T2-weighted and diffusion-weighted imaging). A prediction model was then constructed and applied to the validation study sample. Multivariate analysis identified four significant independent predictors (P < 0.05), including a biopsy Gleason score of ≥8, positive 3.0-Tesla diffusion-weighted magnetic resonance imaging findings, ≥2 positive biopsy cores on each side and a maximum percentage of positive cores ≥31% on each side. The negative predictive value was 93.9% in the combination model with these four predictors, meanwhile the positive predictive value was 33.8%. Good reproducibility of these four significant predictors and the combination model was observed in the validation study sample. The side-specific extracapsular extension prediction by the biopsy Gleason score and factors associated with tumor location, including a positive 3.0-Tesla diffusion-weighted magnetic resonance imaging finding, have a high negative predictive value, but a low positive predictive value. © 2013 The Japanese Urological Association.

Initial brazilian experience in the treatment of localized prostate cancer using a new generation cryotechnology: feasibility study.

PubMed

Kim, Fernando J; Cerqueira, Michael A; Almeida, Jose C; Pompeo, Alexandre; Sehrt, David; Calheiros, Jose M; Martins, Fernando A; Molina, Wilson R

2012-01-01

The objective of our study is to present the first Brazilian cryoablation experience in the treatment of low and intermediate risk localized prostate cancer using 3rd generation cryoablation and real-time biplanar transrectal ultrasonography. Ten Brazilian patients underwent primary cryoablation for localized prostate cancer between October 2010 and June 2011. All patients consented for whole gland primary cryotherapy. The procedures were performed by 3rd generation cryoablation with the Cryocare System ® (Endocare, Irvine, California). Preoperative data collection included patient demographics along with prostate gland size, Gleason score, serum prostate specific antigen, and erectile function status. Operative and post--operative assessment involved estimated blood loss, operative time, complications, serum PSA level, erectile function status, urinary incontinence, biochemical disease free survival (BDFS), and follow-up time. All patients in the study successfully underwent whole gland cryoablation. The mean of: age, prostate size, PSA level, and Gleason score, was 66.2 years old; 40.7 g; 7.8 ng/mL; and 6 respectively. All patients were classified as low or moderate D' Amico risk (5 low and 5 moderate). Erectile dysfunction was present in 50% of patients. The estimated blood loss was minimal, operative time was 46.1 minutes. All patients that developed erectile dysfunction post-treatment responded to oral or intracavernosal medications with early penile rehabilitation. All patients maintained urinary continence by the end of a 10 months evaluation period and none had biochemical relapse within the mean follow-up of 13 months (7-15 months). Our initial experience shows that cryoablation is a minimally invasive option for the treatment of localized prostate cancer. Short term data seems to be promising but longer follow-up is necessary to verify oncological and functional results.

Markers of epithelial-to-mesenchymal transition reflect tumor biology according to patient age and Gleason score in prostate cancer

PubMed Central

Jędroszka, Dorota; Hamouz, Raneem; Górniak, Karolina; Bednarek, Andrzej K.

2017-01-01

Introduction Prostate carcinoma (PRAD) is one of the most frequently diagnosed malignancies amongst men worldwide. It is well-known that androgen receptor (AR) plays a pivotal role in a vast majority of prostate tumors. However, recent evidence emerged stating that estrogen receptors (ERs) may also contribute to prostate tumor development. Moreover, progression and aggressiveness of prostate cancer may be associated with differential expression genes of epithelial-to-mesenchymal transition (EMT). Therefore we aimed to assess the significance of receptors status as well as EMT marker genes expression among PRAD patients in accordance to their age and Gleason score. Materials and methods We analyzed TCGA gene expression profiles of 497 prostate tumor samples according to 43 genes involved in EMT and 3 hormone receptor genes (AR, ESR1, ESR2) as well as clinical characteristic of cancer patients. Then patients were divided into four groups according to their age and 5 groups according to Gleason score. Next, we evaluated PRAD samples according to relationship between the set of variables in different combinations and compared differential expression in subsequent groups of patients. The analysis was applied using R packages: FactoMineR, gplots, RColorBrewer and NMF. Results MFA analysis resulted in distinct grouping of PRAD patients into four age categories according to expression level of AR, ESR1 and ESR2 with the most distinct group of age less than 50 years old. Further investigations indicated opposite expression profiles of EMT markers between different age groups as well as strong association of EMT gene expression with Gleason score. We found that depending on age of prostate cancer patients and Gleason score EMT genes with distinctly altered expression are: KRT18, KRT19, MUC1 and COL4A1, CTNNB1, SNAI2, ZEB1 and MMP3. Conclusions Our major observation is that prostate cancer from patients under 50 years old compared to older ones has entirely different EMT gene expression profiles showing potentially more aggressive invasive phenotype, despite Gleason score classification. PMID:29206234

Markers of epithelial-to-mesenchymal transition reflect tumor biology according to patient age and Gleason score in prostate cancer.

PubMed

Jędroszka, Dorota; Orzechowska, Magdalena; Hamouz, Raneem; Górniak, Karolina; Bednarek, Andrzej K

2017-01-01

Prostate carcinoma (PRAD) is one of the most frequently diagnosed malignancies amongst men worldwide. It is well-known that androgen receptor (AR) plays a pivotal role in a vast majority of prostate tumors. However, recent evidence emerged stating that estrogen receptors (ERs) may also contribute to prostate tumor development. Moreover, progression and aggressiveness of prostate cancer may be associated with differential expression genes of epithelial-to-mesenchymal transition (EMT). Therefore we aimed to assess the significance of receptors status as well as EMT marker genes expression among PRAD patients in accordance to their age and Gleason score. We analyzed TCGA gene expression profiles of 497 prostate tumor samples according to 43 genes involved in EMT and 3 hormone receptor genes (AR, ESR1, ESR2) as well as clinical characteristic of cancer patients. Then patients were divided into four groups according to their age and 5 groups according to Gleason score. Next, we evaluated PRAD samples according to relationship between the set of variables in different combinations and compared differential expression in subsequent groups of patients. The analysis was applied using R packages: FactoMineR, gplots, RColorBrewer and NMF. MFA analysis resulted in distinct grouping of PRAD patients into four age categories according to expression level of AR, ESR1 and ESR2 with the most distinct group of age less than 50 years old. Further investigations indicated opposite expression profiles of EMT markers between different age groups as well as strong association of EMT gene expression with Gleason score. We found that depending on age of prostate cancer patients and Gleason score EMT genes with distinctly altered expression are: KRT18, KRT19, MUC1 and COL4A1, CTNNB1, SNAI2, ZEB1 and MMP3. Our major observation is that prostate cancer from patients under 50 years old compared to older ones has entirely different EMT gene expression profiles showing potentially more aggressive invasive phenotype, despite Gleason score classification.

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.

Expanding indication of padeliporfin (WST11) vascular-targeted photodynamic therapy: results of prostate cancer Latin-American multicenter study.

PubMed

Rodriguez-Rivera, J A; Rodriguez-Lay, R; Zegarra-Montes, L; Benzaghou, F; Gaillac, B; Azzouzi, A R; Reis, L O; Palma, P

2018-04-23

To explore the proportion of patients with higher risk localized prostate cancer (PCa) that would become safely biopsy negative 12 months after non-thermal focal therapy with padeliporfin vascular-targeted photodynamic therapy (VTP). Multicenter study in a scenario of prostate-specific antigen (PSA) ≤20ng/ml and variable PCa target volumes Gleason pattern 3 or low-volume secondary Gleason pattern 4, all patients received VTP, consisting of intravenous 4mg/kg padeliporfin activated by light-diffusing fibers in the prostate. The prostate was biopsied at baseline, months 6 and 12, PSA, patient-reported functional outcomes and quality of life (QoL) questionnaires were recorded at baseline, months 3, 6, and 12 and adverse events (AE) throughout the study. In the intention-to-treat population (n=81), the proportion of patients with negative biopsies at month 12 was 74% (60/81 patients; 95% CI: 63.1%,83.2%). In the per-protocol population, the proportion was 79% (58/73 patients; 95% CI: 68.4%,88.0%). Questionnaire results indicated a slight improvement in urinary function and limited deterioration in sexual function. No difference in QoL was observed over time. A total of 42/81 (52%) patients reported mild or moderate and 4 of 81 (4.9%) experienced serious AE, all resolved without sequelae. No phototoxicity, cardiovascular event, fistula or prolonged urinary incontinence, secondary cancer or death was reported. Results support the efficacy, safety, and QoL associated with padeliporfin focal treatment for low/intermediate risk localized PCa. Copyright © 2018 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Predictive value of [-2]propsa (p2psa) and its derivatives for the prostate cancer detection in the 2.0 to 10.0ng/mL PSA range.

PubMed

Vukovic, I; Djordjevic, D; Bojanic, N; Babic, U; Soldatovic, I

2017-01-01

To assess predictive value of new tumor markers, precursor of prostate specific antigen (p2PSA) and its derivates-%p2PSA and prostate health index (PHI) in detection of patients with indolent and aggressive prostate cancer (PC) in a subcohort of man whose total PSA ranged from 2 to 10ng/mL. This cross-sectional study included 129 consecutive male patients aged over 50 years, with no previous history of PC and with normal digital rectal examination findings, but with serum PSA in interval between 2 and 10ng/mL. All patients underwent standard transrectal ultrasonography guided prostate biopsy for the first time. For all patients, serum PSA, free PSA (fPSA) and p2PSA were measured and PHI and %p2PSA were calculated. PHI and %p2PSA levels were significanlty higher in patients with PC compared to those without this malignancy. The same findings have been observed in group of patients with Gleason score ≥7 compared to those with Gleason score <7. ROC analysis reveled the highest area under the curve with these two markers. Multivariate logistic regression showed significant improvement in PC detection and its agressive form (assumed as Gleason score ≥7). New markers, derivates of p2PSA (especially %p2PSA and PHI), represente potentially very important clinical tool for predicting presence of PC, and even more important, to discriminate patients with Gleason score <7 from those with Gleason score ≥7 with total PSA in range from 2 to 10ng/mL. Copyright® by the International Brazilian Journal of Urology.

The new Epstein gleason score classification significantly reduces upgrading in prostate cancer patients.

PubMed

De Nunzio, Cosimo; Pastore, Antonio Luigi; Lombardo, Riccardo; Simone, Giuseppe; Leonardo, Costantino; Mastroianni, Riccardo; Collura, Devis; Muto, Giovanni; Gallucci, Michele; Carbone, Antonio; Fuschi, Andrea; Dutto, Lorenzo; Witt, Joern Heinrich; De Dominicis, Carlo; Tubaro, Andrea

2018-06-01

To evaluate the differences between the old and the new Gleason score classification systems in upgrading and downgrading rates. Between 2012 and 2015, we identified 9703 patients treated with retropubic radical prostatectomy (RP) in four tertiary centers. Biopsy specimens as well as radical prostatectomy specimens were graded according to both 2005 Gleason and 2014 ISUP five-tier Gleason grading system (five-tier GG system). Upgrading and downgrading rates on radical prostatectomy were first recorded for both classifications and then compared. The accuracy of the biopsy for each histological classification was determined by using the kappa coefficient of agreement and by assessing sensitivity, specificity, positive and negative predictive value. The five-tier GG system presented a lower clinically significant upgrading rate (1895/9703: 19,5% vs 2332/9703:24.0%; p = .001) and a similar clinically significant downgrading rate (756/9703: 7,7% vs 779/9703: 8%; p = .267) when compared to the 2005 ISUP classification. When evaluating their accuracy, the new five-tier GG system presented a better specificity (91% vs 83%) and a better negative predictive value (78% vs 60%). The kappa-statistics measures of agreement between needle biopsy and radical prostatectomy specimens were poor and good respectively for the five-tier GG system and for the 2005 Gleason score (k = 0.360 ± 0.007 vs k = 0.426 ± 0.007). The new Epstein classification significantly reduces upgrading events. The implementation of this new classification could better define prostate cancer aggressiveness with important clinical implications, particularly in prostate cancer management. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Prostate Cancer Patients' Understanding of the Gleason Scoring System: Implications for Shared Decision-Making.

PubMed

Tagai, Erin K; Miller, Suzanne M; Kutikov, Alexander; Diefenbach, Michael A; Gor, Ronak A; Al-Saleem, Tahseen; Chen, David Y T; Fleszar, Sara; Roy, Gem

2018-01-15

The Gleason scoring system is a key component of a prostate cancer diagnosis, since it indicates disease aggressiveness. It also serves as a risk communication tool that facilitates shared treatment decision-making. However, the system is highly complex and therefore difficult to communicate: factors which have been shown to undermine well-informed and high-quality shared treatment decision-making. To systematically explore prostate cancer patients' understanding of the Gleason scoring system (GSS), we assessed knowledge and perceived importance among men who had completed treatment (N = 50). Patients were administered a survey that assessed patient knowledge and patients' perceived importance of the GSS, as well as demographics, medical factors (e.g., Gleason score at diagnosis), and health literacy. Bivariate analyses were conducted to identify associations with patient knowledge and perceived importance of the GSS. The sample was generally well-educated (48% with a bachelor's degree or higher) and health literate (M = 12.9, SD = 2.2, range = 3-15). Despite this, patient knowledge of the GSS was low (M = 1.8, SD = 1.4, range = 1-4). Patients' understanding of the importance of the GSS was moderate (M = 2.8, SD = 1.0, range = 0-4) and was positively associated with GSS knowledge (p < .01). Additionally, GSS knowledge was negatively associated with years since biopsy (p < .05). Age and health literacy were positively associated with patients' perceived importance of the GSS (p < .05), but not with GSS knowledge. Patient knowledge is thus less than optimal and would benefit from enhanced communication to maximize shared treatment decision-making. Future studies are needed to explore the potential utility of a simplified Gleason grading system and improved patient-provider communication.

Upgrading Reference Set — EDRN Public Portal

Cancer.gov

We are proposing a multi-institutional study to identify molecular biomarkers and clinical measures that will predict presence of Gleason 7 or higher cancer (as evidence in the radical prostatectomy specimen) among patients with a biopsy diagnosis of Gleason score ≤ 6 prostate cancer. This proposal will be conducted in two phases. The first phase will assemble an “Upgrading Reference Set” that will include clinical information as well as biologics on a cohort of 600 men. The first phase will also assess the clinical parameters associated with upgrading, as well as, perform a central pathology review of both biopsies and prostatectomy specimens to confirm tumor grade. The second phase will use the biologics collected in phase 1 to evaluate a series of biomarkers to further refine the prediction of Gleason 7-10 cancer at radical prostatectomy.

Molecular Profiling of Intraductal Carcinoma of the Prostate

DTIC Science & Technology

2016-12-01

carcinoma of the prostate (IDC-P) occurs almost exclusively in high Gleason grade and stage tumors and is a consistent independent risk factor for tumor...malignant cells spreading within intact prostatic ducts and acini, IDC-P occurs almost exclusively in high Gleason grade and stage tumors and is a...consistent independent risk factor for tumor progression and death in cohorts treated with surgery or radiotherapy. Importantly, however, IDC-P is currently

Thioredoxin 1 in Prostate Tissue Is Associated with Gleason Score, Erythrocyte Antioxidant Enzyme Activity, and Dietary Antioxidants.

PubMed

Vance, Terrence M; Azabdaftari, Gissou; Pop, Elena A; Lee, Sang Gil; Su, L Joseph; Fontham, Elizabeth T H; Bensen, Jeannette T; Steck, Susan E; Arab, Lenore; Mohler, James L; Chen, Ming-Hui; Koo, Sung I; Chun, Ock K

2015-01-01

Background. Prostate cancer is the most common noncutaneous cancer and second leading cause of cancer-related mortality in men in the US. Growing evidence suggests that oxidative stress is involved in prostate cancer. Methods. In this study, thioredoxin 1 (Trx 1), an enzyme and subcellular indicator of redox status, was measured in prostate biopsy tissue from 55 men from the North Carolina-Louisiana Prostate Cancer Project. A pathologist blindly scored levels of Trx 1. The association between Trx 1 and the Gleason score, erythrocyte antioxidant enzyme activity, and dietary antioxidant intake was determined using Fisher's exact test. Results. Trx 1 levels in benign prostate tissue in men with incident prostate cancer were positively associated with the Gleason score (P = 0.01) and inversely associated with dietary antioxidant intake (P = 0.03). In prostate cancer tissue, Trx 1 levels were associated with erythrocyte glutathione peroxidase activity (P = 0.01). No association was found for other erythrocyte enzymes. Greater Gleason score of malignant tissue corresponds to a greater difference in Trx 1 levels between malignant and benign tissue (P = 0.04). Conclusion. These results suggest that the redox status of prostate tissue is associated with prostate cancer grade and both endogenous and exogenous antioxidants.

Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error.

PubMed

Shipitsin, M; Small, C; Choudhury, S; Giladi, E; Friedlander, S; Nardone, J; Hussain, S; Hurley, A D; Ernst, C; Huang, Y E; Chang, H; Nifong, T P; Rimm, D L; Dunyak, J; Loda, M; Berman, D M; Blume-Jensen, P

2014-09-09

Key challenges of biopsy-based determination of prostate cancer aggressiveness include tumour heterogeneity, biopsy-sampling error, and variations in biopsy interpretation. The resulting uncertainty in risk assessment leads to significant overtreatment, with associated costs and morbidity. We developed a performance-based strategy to identify protein biomarkers predictive of prostate cancer aggressiveness and lethality regardless of biopsy-sampling variation. Prostatectomy samples from a large patient cohort with long follow-up were blindly assessed by expert pathologists who identified the tissue regions with the highest and lowest Gleason grade from each patient. To simulate biopsy-sampling error, a core from a high- and a low-Gleason area from each patient sample was used to generate a 'high' and a 'low' tumour microarray, respectively. Using a quantitative proteomics approach, we identified from 160 candidates 12 biomarkers that predicted prostate cancer aggressiveness (surgical Gleason and TNM stage) and lethal outcome robustly in both high- and low-Gleason areas. Conversely, a previously reported lethal outcome-predictive marker signature for prostatectomy tissue was unable to perform under circumstances of maximal sampling error. Our results have important implications for cancer biomarker discovery in general and development of a sampling error-resistant clinical biopsy test for prediction of prostate cancer aggressiveness.

Influence of age on the pattern and outcome of external beam radiotherapy for clinically localized prostate cancer.

PubMed

Ogawa, Kazuhiko; Nakamura, Katsumasa; Onishi, Hiroshi; Koizumi, Masahiko; Sasaki, Tomonari; Araya, Masayuki; Miyabe, Yuuki; Otani, Yuuki; Teshima, Teruki

2006-01-01

The influence of age on the patterns and outcomes of external beam radiotherapy for clinically localized prostate cancer patients was examined. The Japanese Patterns of Care Study surveys were used to compare the processes and outcomes of radical external beam radiotherapy in 140 elderly patients (>75 years old) and 304 younger patients (<75 years old). Although the Karnofsky performance status was significantly different between elderly and younger patients, there were no significant differences in disease characteristics such as pretreatment PSA level, differentiation, Gleason combined score and clinical T stage. There were also no significant differences in the treatment characteristics such as CT-based treatment planning, conformal therapy, total radiation doses (both a median of 66.0 Gy) and hormonal therapy usage. Moreover, no significant differences in overall survival, biochemical relapse-free survival and late toxicity rates were observed between elderly and younger patients. Age did not influence the disease characteristics, patterns of external beam radiotherapy, survival and late toxicities for clinically localized prostate cancer patients. Therefore, radiotherapy could represent an important treatment modality for elderly patients as well as for younger ones.

Biomarkers for Early Detection of Clinically Relevant Prostate Cancer. A Multi-Institutional Validation Trial

DTIC Science & Technology

2016-10-01

Study (PASS). We are in the process of evaluating these three biomarker panels in tissue, blood, and urine samples with well annotated clinical and...impacting both the initial choice of therapy and decision-making during AS. The objective of the study is to utilize analytically validated assays that...predict reclassification from Gleason 6 cancer to Gleason 7 or greater. The analysis plan was determined before specimens were selected for the study

Biomarkers for Early Detection of Clinically Relevant Prostate Cancer. A Multi-Institutional Validation Trial

DTIC Science & Technology

2016-10-01

Study (PASS). We are in the process of evaluating these three biomarker panels in tissue, blood, and urine samples with well annotated clinical and...choice of therapy and decision-making during AS. The objective of the study is to utilize analytically validated assays that take into account tumor...Gleason 6 cancer to Gleason 7 or greater. The analysis plan was determined before specimens were selected for the study , and included 7 breaking

Convolutional neural networks for an automatic classification of prostate tissue slides with high-grade Gleason score

NASA Astrophysics Data System (ADS)

Jiménez del Toro, Oscar; Atzori, Manfredo; Otálora, Sebastian; Andersson, Mats; Eurén, Kristian; Hedlund, Martin; Rönnquist, Peter; Müller, Henning

2017-03-01

The Gleason grading system was developed for assessing prostate histopathology slides. It is correlated to the outcome and incidence of relapse in prostate cancer. Although this grading is part of a standard protocol performed by pathologists, visual inspection of whole slide images (WSIs) has an inherent subjectivity when evaluated by different pathologists. Computer aided pathology has been proposed to generate an objective and reproducible assessment that can help pathologists in their evaluation of new tissue samples. Deep convolutional neural networks are a promising approach for the automatic classification of histopathology images and can hierarchically learn subtle visual features from the data. However, a large number of manual annotations from pathologists are commonly required to obtain sufficient statistical generalization when training new models that can evaluate the daily generated large amounts of pathology data. A fully automatic approach that detects prostatectomy WSIs with high-grade Gleason score is proposed. We evaluate the performance of various deep learning architectures training them with patches extracted from automatically generated regions-of-interest rather than from manually segmented ones. Relevant parameters for training the deep learning model such as size and number of patches as well as the inclusion or not of data augmentation are compared between the tested deep learning architectures. 235 prostate tissue WSIs with their pathology report from the publicly available TCGA data set were used. An accuracy of 78% was obtained in a balanced set of 46 unseen test images with different Gleason grades in a 2-class decision: high vs. low Gleason grade. Grades 7-8, which represent the boundary decision of the proposed task, were particularly well classified. The method is scalable to larger data sets with straightforward re-training of the model to include data from multiple sources, scanners and acquisition techniques. Automatically generated heatmaps for theWSIs could be useful for improving the selection of patches when training networks for big data sets and to guide the visual inspection of these images.

Texture analysis of tissues in Gleason grading of prostate cancer

NASA Astrophysics Data System (ADS)

Alexandratou, Eleni; Yova, Dido; Gorpas, Dimitris; Maragos, Petros; Agrogiannis, George; Kavantzas, Nikolaos

2008-02-01

Prostate cancer is a common malignancy among maturing men and the second leading cause of cancer death in USA. Histopathological grading of prostate cancer is based on tissue structural abnormalities. Gleason grading system is the gold standard and is based on the organization features of prostatic glands. Although Gleason score has contributed on cancer prognosis and on treatment planning, its accuracy is about 58%, with this percentage to be lower in GG2, GG3 and GG5 grading. On the other hand it is strongly affected by "inter- and intra observer variations", making the whole process very subjective. Therefore, there is need for the development of grading tools based on imaging and computer vision techniques for a more accurate prostate cancer prognosis. The aim of this paper is the development of a novel method for objective grading of biopsy specimen in order to support histopathological prognosis of the tumor. This new method is based on texture analysis techniques, and particularly on Gray Level Co-occurrence Matrix (GLCM) that estimates image properties related to second order statistics. Histopathological images of prostate cancer, from Gleason grade2 to Gleason grade 5, were acquired and subjected to image texture analysis. Thirteen texture characteristics were calculated from this matrix as they were proposed by Haralick. Using stepwise variable selection, a subset of four characteristics were selected and used for the description and classification of each image field. The selected characteristics profile was used for grading the specimen with the multiparameter statistical method of multiple logistic discrimination analysis. The subset of these characteristics provided 87% correct grading of the specimens. The addition of any of the remaining characteristics did not improve significantly the diagnostic ability of the method. This study demonstrated that texture analysis techniques could provide valuable grading decision support to the pathologists, concerning prostate cancer prognosis.

An analysis of microvessel density, androgen receptor, p53 and HER-2/neu expression and Gleason score in prostate cancer . preliminary results and therapeutic implications.

PubMed

Mydlo, J H; Kral, J G; Volpe, M; Axotis, C; Macchia, R J; Pertschuk, L P

1998-01-01

To investigate relationships between microvessel density (MVD), androgen receptors (AR), mutant p53 and HER-2/neu expression and Gleason score (GS) to further understand the tumor biology of prostate cancer (CAP). Slides of CAP from patients who underwent radical prostatectomy or channel transurethral resection of the prostate (TURP) were tested for androgen receptors by immunocytochemical assay and MVD was analyzed by staining with antibodies to the endothelial cell membrane molecule PECAM-1/CD-31. The p53 monoclonal antibody D07 and HER-2 9G6 mouse monoclonal antibody were used to assess p53 and HER-2/neu expression, respectively. The results were correlated with GS and clinical stage by multivariate analysis. We found a fourfold greater expression of MVD in prostate cancer specimens compared to neighboring normal prostate tissue. We observed a greater concentration of MVD in the higher Gleason scores (r = 0.40, p = 0. 06), and a correlation of Gleason score with mutant p53 expression (r = 0.57, p <0.05). We did not observe any associations between AR or HER-2/neu to Gleason score. More than half of the patients with specimens with 50% or greater expression of mutant p53 were in stage D2 (T4NxM1b) at the time of biopsy. We observed a correlation between mutant p53 and GS, and a greater concentration of MVD in the higher GS. Since the neovascularity of prostate tumors can be attenuated by radiation and hormones, while mutant p53 may confer resistance to such treatment, it appears that p53 expression may also play an important role in addition to angiogenesis in the virulence of prostate cancer. These data may aid in allocating patients to different treatment modalities.

Detection of prostate cancer index lesions with multiparametric magnetic resonance imaging (mp-MRI) using whole-mount histological sections as the reference standard.

PubMed

Russo, Filippo; Regge, Daniele; Armando, Enrico; Giannini, Valentina; Vignati, Anna; Mazzetti, Simone; Manfredi, Matteo; Bollito, Enrico; Correale, Loredana; Porpiglia, Francesco

2016-07-01

To evaluate the sensitivity of multiparametric magnetic resonance imaging (mp-MRI) for detecting prostate cancer foci, including the largest (index) lesions. In all, 115 patients with biopsy confirmed prostate cancer underwent mp-MRI before radical prostatectomy. A single expert radiologist recorded all prostate cancer foci including the index lesion 'blinded' to the pathologist's biopsy report. Stained whole-mount histological sections were used as the reference standard. All lesions were contoured by an experienced uropathologist who assessed their volume and pathological Gleason score. All lesions with a volume of >0.5 mL and/or pathological Gleason score of >6 were defined as clinically significant prostate cancer. Multivariate analysis was used to ascertain the characteristics of lesions identified by MRI. In all, 104 of 115 index lesions were correctly diagnosed by mp-MRI (sensitivity 90.4%; 95% confidence interval [CI] 83.5-95.1%), including 98/105 clinically significant index lesions (93.3%; 95% CI 86.8-97.3%), among which three of three lesions had a volume of <0.5 mL and Gleason score of >6. Overall, mp-MRI detected 131/206 lesions including 13 of 68 'insignificant' prostate cancers. The multivariate logistic regression modelling showed that pathological Gleason score (odds ratio [OR] 11.7, 95% CI 2.3-59.8; P = 0.003) and lesion volume (OR 4.24, 95% CI 1.3-14.7; P = 0.022) were independently associated with the detection of index lesions at MRI. This study shows that mp-MRI has a high sensitivity for detecting clinically significant prostate cancer index lesions, while having disappointing results for the detection of small-volume, low Gleason score prostate cancer foci. Thus, mp-MRI could be used to stratify patients according to risk, allowing better treatment selection. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

A subset of high Gleason grade prostate carcinomas contain a large burden of prostate cancer syndecan-1 positive stromal cells.

PubMed

Sharpe, Benjamin; Alghezi, Dhafer A; Cattermole, Claire; Beresford, Mark; Bowen, Rebecca; Mitchard, John; Chalmers, Andrew D

2017-05-01

There is a pressing need to identify prognostic and predictive biomarkers for prostate cancer to aid treatment decisions in both early and advanced disease settings. Syndecan-1, a heparan sulfate proteoglycan, has been previously identified as a potential prognostic biomarker by multiple studies at the tissue and serum level. However, other studies have questioned its utility. Anti-Syndecan-1 immunohistochemistry was carried out on 157 prostate tissue samples (including cancerous, adjacent normal tissue, and non-diseased prostate) from three independent cohorts of patients. A population of Syndecan-1 positive stromal cells was identified and the number and morphological parameters of these cells quantified. The identity of the Syndecan-1-positive stromal cells was assessed by multiplex immunofluorescence using a range of common cell lineage markers. Finally, the burden of Syndecan-1 positive stromal cells was tested for association with clinical parameters. We identified a previously unreported cell type which is marked by Syndecan-1 expression and is found in the stroma of prostate tumors and adjacent normal tissue but not in non-diseased prostate. We call these cells Prostate Cancer Syndecan-1 Positive (PCSP) cells. Immunofluorescence analysis revealed that the PCSP cell population did not co-stain with markers of common prostate epithelial, stromal, or immune cell populations. However, morphological analysis revealed that PCSP cells are often elongated and displayed prominent lamellipodia, suggesting they are an unidentified migratory cell population. Analysis of clinical parameters showed that PCSP cells were found with a frequency of 20-35% of all tumors evaluated, but were not present in non-diseased normal tissue. Interestingly, a subset of primary Gleason 5 prostate tumors had a high burden of PCSP cells. The current study identifies PCSP cells as a novel, potentially migratory cell type, which is marked by Syndecan-1 expression and is found in the stroma of prostate carcinomas, adjacent normal tissue, but not in non-diseased prostate. A subset of poor prognosis high Gleason grade 5 tumors had a particularly high PCSP cell burden, suggesting an association between this unidentified cell type and tumor aggressiveness. © 2017 Wiley Periodicals, Inc.

SBRT for the Primary Treatment of Localized Prostate Cancer: The Effect of Gleason Score, Dose and Heterogeneity of Intermediate Risk on Outcome Utilizing 2.2014 NCCN Risk Stratification Guidelines.

PubMed

Bernetich, Matthew; Oliai, Caspian; Lanciano, Rachelle; Hanlon, Alexandra; Lamond, John; Arrigo, Stephen; Yang, Jun; Good, Michael; Feng, Jing; Brown, Royce; Garber, Bruce; Mooreville, Michael; Brady, Luther W

2014-01-01

To report an update of our previous experience using stereotactic body radiation therapy (SBRT) for the primary treatment of prostate cancer, risk stratified by the updated National Comprehensive Cancer Network (NCCN) version 2.2014, reporting efficacy and toxicity in a community hospital setting. From 2007 to 2012, 142 localized prostate cancer patients were treated with SBRT using CyberKnife. NCCN guidelines Version 2.2014 risk groups analyzed included very low (20%), low (23%), intermediate (35%), and high (22%) risk. To further explore group heterogeneity and to comply with new guidelines, we separated our prior intermediate risk group into favorable intermediate and unfavorable intermediate groups depending on how many intermediate risk factors were present (one vs. > one). The unfavorable intermediate group was further analyzed in combination with the high risk group as per NCCN guidelines Version 2.2014. Various dose levels were used over the years of treatment, and have been categorized into low dose (35 Gy, n = 5 or 36.25 Gy, n = 107) and high dose (37.5 Gy, n = 30). All treatments were delivered in five fractions. Toxicity was assessed using radiation therapy oncology group criteria. Five-year actuarial freedom from biochemical failure (FFBF) was 100, 91.7, 95.2, 90.0, and 86.7% for very low, low, intermediate and high risk patients, respectively. A significant difference in 5 year FFBF was noted for patients with Gleason score (GS) ≥8 vs. 7 vs. 5/6 (p = 0.03) and low vs. high dose (p = 0.05). T-stage, pretreatment PSA, age, risk stratification group, and use of ADT did not affect 5-year FFBF. Multivariate analysis revealed GS and dose to be the most predictive factors for 5-year FFBF. Our experience with SBRT for the primary treatment of localized prostate cancer demonstrates favorable efficacy and toxicity comparable to the results reported for IMRT in literature. GS remains the single most important pretreatment predictor of outcome.

Continued Benefit to Androgen Deprivation Therapy for Prostate Cancer Patients Treated With Dose-Escalated Radiation Therapy Across Multiple Definitions of High-Risk Disease

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

Stenmark, Matthew H.; Blas, Kevin; Halverson, Schuyler

2011-11-15

Purpose: To analyze prognostic factors in patients with high-risk prostate cancer treated with dose-escalated external-beam radiation therapy (EBRT) and androgen deprivation (ADT). Methods and Materials: Between 1998 and 2008 at University of Michigan Medical Center, 718 men were consecutively treated with EBRT to at least 75 Gy. Seven definitions of high-risk prostate cancer, applying to 11-33% of patients, were evaluated. Biochemical failure (BF), salvage ADT use, metastatic progression, and prostate cancer-specific mortality (PCSM) were estimated by the Kaplan-Meier method and Cox proportional hazards regression. Results: Each high-risk definition was associated with increased BF (hazard ratio [HR] 2.8-3.9, p < 0.0001),more » salvage ADT use (HR 3.9-6.3, p < 0.0001), metastasis (HR 3.7-6.6, p < 0.0001), and PCSM (HR 3.7-16.2, p < 0.0001). Furthermore, an increasing number of high-risk features predicted worse outcome. Adjuvant ADT yielded significant reductions in both metastases (HR 0.19-0.38, p < 0.001) and PCSM (HR 0.38-0.50, p < 0.05) for all high-risk definitions (with the exception of clinical Stage T3-4 disease) but improved BF only for those with elevated Gleason scores (p < 0.03, HR 0.25-0.48). When treated with ADT and dose-escalated EBRT, patients with Gleason scores 8 to 10, without other high-risk features, had 8-year freedom from BF of 74%, freedom from distant metastases of 93%, and cause-specific survival of 92%, with salvage ADT used in 16% of patients. Conclusion: Adjuvant ADT results in a significant improvement in clinical progression and PCSM across multiple definitions of high-risk disease even with dose-escalated EBRT. There is a subset of patients, characterized by multiple high-risk features or the presence of Gleason Pattern 5, who remain at significant risk for metastasis and PCSM despite current treatment.« less

Prostate Cancer Prognostic Factors Among Asian Patients Born in the US Compared to Those Born Abroad.

PubMed

Xu, Junjun; Goodman, Michael; Jemal, Ahemdin; Fedewa, Stacey A

2015-06-01

US surveillance data indicate that incidence of prostate cancer differs by place of birth among Asian men. However, it is less clear if the prognostic factors for prostate cancer also differ by place of birth. The study included 7,824 Asian prostate cancer patients diagnosed between 2004 and 2009 and reported to the Surveillance Epidemiology and End Results (SEER) program. Logistic regression models were used to evaluate the relation of place of birth (foreign born vs. US born) to three outcomes: prostate specific antigen (PSA) level, Gleason score, and T classification, adjusting for age, marital status, Rural-Urban Continuum Code, and SEER registry. All outcome variables were binary using different cutoffs: ≥ 4, ≥ 10 and ≥ 20 ng/ml for PSA; ≥ 7 and ≥ 8 for Gleason score; and ≥ T2 and ≥ T3 for T classification. Elevated PSA was more common among foreign born Asian men regardless of the cut point used. In the analysis comparing foreign born versus US born patients by ethnic group, the association with PSA was most pronounced at cut point of ≥ 20 ng/ml for Chinese men (OR 1.68, 95% CI 1.02-2.75), and at cut point of ≥ 4 ng/ml for Japanese men (OR 2.73, 95% CI 1.20-6.21). A statistically significant association with Gleason score was only found for Japanese men and only for the cutoff ≥ 7 (OR 1.71, 95% CI 1.12-2.61). There was no difference in clinical T classification between foreign-born and US-born Asian men. Inclusion of cases with missing place of birth or restriction of data to those who underwent radical prostatectomy did not substantially change the results. The data suggest that foreign-born Asian prostate cancer patients may have moderately elevated PSA levels at diagnosis compared with their US born counterparts. For the other prognostic markers, the associations were less consistent and did not form a discernible pattern.

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.

[Prostate cancer. Part 2: Review of the various tumor grading systems over the years 1966-2015 and future perspectives of the new grading of the International Society of Urological Pathology (ISUP)].

PubMed

Helpap, B; Bubendorf, L; Kristiansen, G

2016-02-01

The continued development of methods in needle biopsies and radical prostatectomy for treatment of prostate cancer has given special emphasis to the question of the prognostic relevance of the various systems of grading. The classical purely histological grading system of Gleason has been modified several times in the past decades and cleared the way for a new grading system by the prognostic grading of Epstein. Assessment of the old and also modified combined histological and cytological grading of Mostofi, the World health Organization (WHO) and the urologic-pathological working group of prostate cancer in connection with the Gleason grading (combined Gleason-Helpap grading), has led to considerably improved rates of concordance between biopsy and radical prostatectomy and to improved estimations of prognosis beside its contribution to the development of a more practicable grading system for clinical use.

Characterization of 1577 primary prostate cancers reveals novel biological and clinicopathologic insights into molecular subtypes.

PubMed

Tomlins, Scott A; Alshalalfa, Mohammed; Davicioni, Elai; Erho, Nicholas; Yousefi, Kasra; Zhao, Shuang; Haddad, Zaid; Den, Robert B; Dicker, Adam P; Trock, Bruce J; DeMarzo, Angelo M; Ross, Ashley E; Schaeffer, Edward M; Klein, Eric A; Magi-Galluzzi, Cristina; Karnes, R Jeffrey; Jenkins, Robert B; Feng, Felix Y

2015-10-01

Prostate cancer (PCa) molecular subtypes have been defined by essentially mutually exclusive events, including ETS gene fusions (most commonly involving ERG) and SPINK1 overexpression. Clinical assessment may aid in disease stratification, complementing available prognostic tests. To determine the analytical validity and clinicopatholgic associations of microarray-based molecular subtyping. We analyzed Affymetrix GeneChip expression profiles for 1577 patients from eight radical prostatectomy cohorts, including 1351 cases assessed using the Decipher prognostic assay (GenomeDx Biosciences, San Diego, CA, USA) performed in a laboratory with Clinical Laboratory Improvements Amendment certification. A microarray-based (m-) random forest ERG classification model was trained and validated. Outlier expression analysis was used to predict other mutually exclusive non-ERG ETS gene rearrangements (ETS(+)) or SPINK1 overexpression (SPINK1(+)). Associations with clinical features and outcomes by multivariate logistic regression analysis and receiver operating curves. The m-ERG classifier showed 95% accuracy in an independent validation subset (155 samples). Across cohorts, 45% of PCas were classified as m-ERG(+), 9% as m-ETS(+), 8% as m-SPINK1(+), and 38% as triple negative (m-ERG(-)/m-ETS(-)/m-SPINK1(-)). Gene expression profiling supports three underlying molecularly defined groups: m-ERG(+), m-ETS(+), and m-SPINK1(+)/triple negative. On multivariate analysis, m-ERG(+) tumors were associated with lower preoperative serum prostate-specific antigen and Gleason scores, but greater extraprostatic extension (p<0.001). m-ETS(+) tumors were associated with seminal vesicle invasion (p=0.01), while m-SPINK1(+)/triple negative tumors had higher Gleason scores and were more frequent in Black/African American patients (p<0.001). Clinical outcomes were not significantly different among subtypes. A clinically available prognostic test (Decipher) can also assess PCa molecular subtypes, obviating the need for additional testing. Clinicopathologic differences were found among subtypes based on global expression patterns. Molecular subtyping of prostate cancer can be achieved using extra data generated from a clinical-grade, genome-wide expression-profiling prognostic assay (Decipher). Transcriptomic and clinical analysis support three distinct molecular subtypes: (1) m-ERG(+), (2) m-ETS(+), and (3) m-SPINK1(+)/triple negative (m-ERG(-)/m-ETS(-)/m-SPINK1(-)). Incorporation of subtyping into a clinically available assay may facilitate additional applications beyond routine prognosis. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

The correlation between biological activity and diffusion-weighted MR imaging and ADC value in cases with prostate cancer.

PubMed

Sokmen, Bedriye Koyuncu; Sokmen, Dogukan; Ucar, Nese; Ozkurt, Huseyin; Simsek, Abdulmuttalip

2017-12-31

Firstly, we aimed to investigate the correlation among dynamic contrasted magnetic resonance (MR) images, diffusion-weighted MR images, and apparent diffusion coefficent (ADC) values in patients with prostate cancer. Secondly, we aimed to investigate the roles of these variables on clinical risk classification and the biological behavior of the prostate cancer. A total of sixty with prostatic adenocarcinoma patients diagnosed between January 2011 and May 2013 were retrospectively included in the study. Risk classification of patients were evaluated as low-risk (Group 1) (n = 20) (Stage T1c-T2a, PSA < 10 ng/ml, Gleason Score < 7), moderate-risk (Group 2) (n = 18) (Stage T1b-T2c, PSA = 10-20 ng/ml, Gleason Score = 7) and high-risk (Group 3) (n = 22) (Stage > T3a, PSA > 20 ng/ml, Gleason Score > 7). Diffusion-weighted MR images, dynamic contrasted MR images, and ADC values of the prostates were correlated. ADC values of the cases in Group 3 were lower than those of the other groups (p < 0.001). ADC values of the areas without malignancy did not differ significantly between groups (p > 0.05). Biological activity of the tumor tissue was determined by GS, while a negative correlation was observed between GSs and ADC values of the patients, (p < 0.001). In tumors with higher Gleason scores, lower ADC values were obtained. These measured values can play a role in the noninvasive determination of the cellularity of the tumoral mass.

Significance and outcome of nuclear anaplasia and mitotic index in prostatic adenocarcinomas.

PubMed

Kır, Gozde; Sarbay, Billur Cosan; Gumus, Eyup

2016-10-01

The Gleason grading system measures architectural differentiation and disregards nuclear atypia and the cell proliferation index. Several studies have reported that nuclear grade and mitotic index (MI) are prognostically useful. This study included 232 radical prostatectomy specimens. Nuclear anaplasia (NA) was determined on the basis of nucleomegali (at least 20µm); vesicular chromatin; eosinophilic macronucleoli, nuclear lobulation, and irregular thickened nuclear membranei. The proportion of area of NA was recorded in each tumor in 10% increments. The MI was defined as the number of mitotic figures in 10 consecutive high-power fields (HPF). In univariate analysis, significant differences included associations between biochemical prostate-specific antigen recurrence (BCR) and Gleason score, extraprostatic extension, positive surgical margin, the presence of high-pathologic stage, NA≥10% of tumor area, MI≥3/10 HPF, and preoperative prostate-specific antigen. In a stepwise Cox regression model, a positive surgical margin, the presence of a NA≥10% of tumor area, and a MI of≥3/10 HPF were independent predictors of BCR after radical prostatectomy. NA≥10% of tumor area appeared to have a stronger association with outcome than MI≥3/10 HPF, as still associated with BCR when Gleason score was in the model. The results of our study showed that, in addition to the conventional Gleason grading system, NA, and MI are useful prognostic parameters while evaluating long-term prognosis in prostatic adenocarcinoma. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Nuclear morphometry in histological specimens of canine prostate cancer: Correlation with histological subtypes, Gleason score, methods of collection and survival time.

PubMed

Di Donato, Guido; Laufer-Amorim, Renée; Palmieri, Chiara

2017-10-01

Ten normal prostates, 22 benign prostatic hyperplasia (BPH) and 29 prostate cancer (PC) were morphometrically analyzed with regard to mean nuclear area (MNA), mean nuclear perimeter (MNP), mean nuclear diameter (MND), coefficient of variation of the nuclear area (NACV), mean nuclear diameter maximum (MDx), mean nuclear diameter minimum (MDm), mean nuclear form ellipse (MNFe) and form factor (FF). The relationship between nuclear morphometric parameters and histological type, Gleason score, methods of sample collection, presence of metastases and survival time of canine PC were also investigated. Overall, nuclei from neoplastic cells were larger, with greater variation in nuclear size and shape compared to normal and hyperplastic cells. Significant differences were found between more (small acinar/ductal) and less (cribriform, solid) differentiated PCs with regard to FF (p<0.05). MNA, MNP, MND, MDx, and MDm were significantly correlated with the Gleason score of PC (p<0.05). MNA, MNP, MDx and MNFe may also have important prognostic implications in canine prostatic cancer since negatively correlated with the survival time. Biopsy specimens contained nuclei that were smaller and more irregular in comparison to those in prostatectomy and necropsy specimens and therefore factors associated with tissue sampling and processing may influence the overall morphometric evaluation. The results indicate that nuclear morphometric analysis in combination with Gleason score can help in canine prostate cancer grading, thus contributing to the establishment of a more precise prognosis and patient's management. Copyright © 2017 Elsevier Ltd. All rights reserved.

The novel nomogram of Gleason sum upgrade: possible application for the eligible criteria of low dose rate brachytherapy.

PubMed

Budäus, Lars; Graefen, Markus; Salomon, Georg; Isbarn, Hendrik; Lughezzani, Giovanni; Sun, Maxine; Chun, Felix K H; Schlomm, Thorsten; Steuber, Thomas; Haese, Alexander; Koellermann, Jens; Sauter, Guido; Fisch, Margit; Heinzer, Hans; Huland, Hartwig; Karakiewicz, Pierre I

2010-10-01

To examine the rate of Gleason sum upgrading (GSU) from a sum of 6 to a Gleason sum of ≥7 in patients undergoing radical prostatectomy (RP), who fulfilled the recommendations for low dose rate brachytherapy (Gleason sum 6, prostate-specific antigen ≤10 ng/mL, clinical stage ≤T2a and prostate volume ≤50 mL), and to test the performance of an existing nomogram for prediction of GSU in this specific cohort of patients. The analysis focused on 414 patients, who fulfilled the European Society for Therapeutic Radiation and Oncology and American Brachytherapy Society criteria for low dose rate brachytherapy (LD-BT) and underwent a 10-core prostate biopsy followed by RP. The rate of GSU was tabulated and the ability of available clinical and pathological parameters for predicting GSU was tested. Finally, the performance of an existing GSU nomogram was explored. The overall rate of GSU was 35.5%. When applied to LD-BT candidates, the existing nomogram was 65.8% accurate versus 70.8% for the new nomogram. In decision curve analysis tests, the new nomogram fared substantially better than the assumption that no patient is upgraded and better than the existing nomogram. GSU represents an important issue in LD-BT candidates. The new nomogram might improve patient selection for LD-BT and cancer control outcome by excluding patients with an elevated probability of GSU. © 2010 The Japanese Urological Association.

Apparent diffusion coefficient value is a strong predictor of unsuspected aggressiveness of prostate cancer before radical prostatectomy.

PubMed

Renard Penna, Raphaele; Cancel-Tassin, Geraldine; Comperat, Eva; Mozer, Pierre; Léon, Priscilla; Varinot, Justine; Roupret, Morgan; Bitker, Marc-Olivier; Lucidarme, Olivier; Cussenot, Olivier

2016-10-01

To evaluate the use of multiparametric MRI (mp MRI) parameters in order to predict prostate cancer aggressiveness as defined by pathological Gleason score or molecular markers in a cohort of patients defined with a Gleason score of 6 at biopsy. Sixty-seven men treated by radical prostatectomy (RP) for a low grade (Gleason 6) on biopsy and mp MRI before biopsy were selected. The cycle cell proliferation (CCP) score assessed by the Prolaris test and Ki-67/PTEN expression assessed by immunohistochemistry were quantified on the RP specimens. 49.25 % of the cancers were undergraded on biopsy compared to the RP specimens. Apparent diffusion coefficient (ADC) < 0.80 × 10(-3) mm(2)/s (P value 0.003), Likert score >4 (P value 0.003) and PSA density >0.15 ng/ml/cc (P value 0.035) were significantly associated with a higher RP Gleason score. Regarding molecular markers of aggressiveness, ADC < 0.80 × 10(-3) mm(2)/s and Likert score >4 were also significantly associated with a positive staining for Ki-67 (P value 0.039 and 0.01, respectively). No association was found between any analyzed MRI or clinical parameter and the CCP score. Decreasing ADC value is a stronger indicator of aggressive prostate cancer as defined by molecular markers or postsurgical histology than biopsy characteristics.

The influence of prostate-specific antigen density on positive and negative predictive values of multiparametric magnetic resonance imaging to detect Gleason score 7-10 prostate cancer in a repeat biopsy setting.

PubMed

Hansen, Nienke L; Barrett, Tristan; Koo, Brendan; Doble, Andrew; Gnanapragasam, Vincent; Warren, Anne; Kastner, Christof; Bratt, Ola

2017-05-01

To evaluate the influence of prostate-specific antigen density (PSAD) on positive (PPV) and negative (NPV) predictive values of multiparametric magnetic resonance imaging (mpMRI) to detect Gleason score ≥7 cancer in a repeat biopsy setting. Retrospective study of 514 men with previous prostate biopsy showing no or Gleason score 6 cancer. All had mpMRI, graded 1-5 on a Likert scale for cancer suspicion, and subsequent targeted and 24-core systematic image-fusion guided transperineal biopsy in 2013-2015. The NPVs and PPVs of mpMRIs for detecting Gleason score ≥7 cancer were calculated (±95% confidence intervals) for PSAD ≤0.1, 0.1-0.2, ≤0.2 and >0.2 ng/mL/mL, and compared by chi-square test for linear trend. Gleason score ≥7 cancer was detected in 31% of the men. The NPV of Likert 1-2 mpMRI was 0.91 (±0.04) with a PSAD of ≤0.2 ng/mL/mL and 0.71 (±0.16) with a PSAD of >0.2 ng/mL/mL (P = 0.003). For Likert 3 mpMRI, PPV was 0.09 (±0.06) with a PSAD of ≤0.2 ng/mL/mL and 0.44 (±0.19) with a PSAD of >0.2 ng/mL/mL (P = 0.002). PSAD also significantly affected the PPV of Likert 4-5 mpMRI lesions: the PPV was 0.47 (±0.08) with a PSAD of ≤0.2 ng/mL/mL and 0.66 (±0.10) with a PSAD of >0.2 ng/mL/mL (P < 0.001). In a repeat biopsy setting, a PSAD of ≤0.2 ng/mL/mL is associated with low detection of Gleason score ≥7 prostate cancer, not only in men with negative mpMRI, but also in men with equivocal imaging. Surveillance, rather than repeat biopsy, may be appropriate for these men. Conversely, biopsies are indicated in men with a high PSAD, even if an mpMRI shows no suspicious lesion, and in men with an mpMRI suspicious for cancer, even if the PSAD is low. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

Association of a Controlled Substance Scoring Algorithm with Health Care Costs and Hospitalizations: A Cohort Study.

PubMed

Starner, Catherine I; Qiu, Yang; Karaca-Mandic, Pinar; Gleason, Patrick P

2016-12-01

Patients often misuse a combination of prescription drugs including opioids; however, the relationship between a controlled substance (CS) score and health outcomes is unknown. To examine the association between a CS scoring algorithm and health care use, specifically total cost of care, hospitalizations, and emergency room (ER) visits. This analysis was a retrospective cohort study using administrative claims data from a large U.S. health insurer. Included in the analysis were 999,852 members with a minimum CS score of 2.5 in the fourth quarter (4Q) of 2012, who were continuously enrolled from January 1, 2012, to December 31, 2013, and who were aged 18 years or older. A CS score was calculated using 4Q 2012 (3 months) prescription claims data and divided into 3 components: (1) number of CS claims, (2) number of unique pharmacies and unique prescribers, and (3) evidence of increasing CS use. The primary outcomes were total cost of care (pharmacy and medical costs), all-cause hospitalizations, and ER visits in 2013. We also quantified what a 1-point change in CS score meant for the primary outcomes. 47% of members had a CS score of 2.5, indicating a single CS claim, and 51% of members had a score between 3 and less than 12. The remaining 2% (20,858 members) had a score of 12 or more. There was a statistically significant and consistently increasing association between the 4Q 2012 CS score and hospitalizations, ER visits, and total costs of care in 2013. A 1-point change in CS score was associated with a $1,488 change in total cost of care, 0.9% change in the hospitalization rate, and 1.5% change in the ER visit rate. There is a linear association between increasing CS score and negative health outcomes. Insurers should consider interventions to lower member CS scores. This study was funded internally by Prime Therapeutics. Starner, Qiu, and Gleason are employees of Prime Therapeutics, a pharmacy benefits management company. Karaca-Mandic is an employee of the University of Minnesota and did not receive any compensation related to this work. The results of this study were presented as a poster at the Academy of Managed Care Pharmacy's 27th Annual Meeting and Expo; San Diego, California; April 7-10, 2015. Study concept and design were contributed by Starner, Gleason, and Qiu. Qiu took the lead in data collection, assisted by Starner and Gleason. Data interpretation was performed by all the authors. Starner primarily wrote and revised the manuscript, along with the other authors.

A Phase I Trial of Samarium-153-Lexidronam Complex for Treatment of Clinically Nonmetastatic High-Risk Prostate Cancer: First Report of a Completed Study

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

Valicenti, Richard K., E-mail: richard.valicenti@ucdmc.ucdavis.ed; Trabulsi, Edouard; Intenzo, Charles

Purpose: We completed a Phase I trial to determine the maximum tolerated dose of samarium-153 EDTMP ({sup 153}Sm) with hormonal therapy (HT) and radiation therapy (RT) in high-risk clinically nonmetastatic prostate cancer. Methods and Materials: High-risk M0 prostate cancer patients (prostate-specific antigen >20 ng/mL, Gleason score >7, or >T3) were eligible for this prospective trial of dose-escalated radioactive {sup 153}Sm-EDTMP (.25-2.0 mCi/kg) as primary or postoperative therapy. After 1 month of HT, we administered {sup 153}Sm-EDTMP followed by 4 more months of HT, 46.8 Gy to the pelvic region and 23.4 Gy to the prostate target (TD = 70.2 Gy).more » The primary endpoint was Grade III toxicity or higher by the National Cancer Institute Common Toxicity Criteria. Results: Twenty-nine patients enrolled (median prostate-specific antigen = 8.2 ng/mL, 27/29 (93%) T stage {>=}T2b, 24/29 (83%) had Gleason >7) and received {sup 153}Sm-EDTMP (.25 mCi/kg, 4 patients; 0.5 mCi/kg, 4 patients; 0.75 mCi/kg, 6 patients; 1.0 mCi/kg, 6 patients; 1.5 mCi/kg, 5 patients; 2.0mCi/kg, 4 patients). Twenty-eight patients underwent all planned therapy without delays (1 patient required surgery before the start of RT). With a median follow-up time of 23 months, there were 2 patients (7 %) experiencing Grade III hematologic toxicity. There were no other Grade III or IV side effects. Conclusions: Our trial demonstrates that 2 mCi/kg {sup 153}Sm -EDTMP with HT and RT was safe and feasible in men with high-risk M0 prostate cancer. A Phase II study to test this treatment is currently underway by the Radiation Therapy Oncology Group.« less

PD-1/PD-L1 pathway inhibitors in advanced prostate cancer.

PubMed

Isaacsson Velho, Pedro; Antonarakis, Emmanuel S

2018-05-01

Pharmacological inhibition of immune checkpoint receptors or their ligands represents a transformative breakthrough in the management of multiple cancers. However, immune checkpoint inhibitors have yet to be FDA-approved for the management of metastatic prostate cancer (PCa), the commonest non-cutaneous malignancy in men. Areas covered: We review our current understanding of the PD-1/PD-L1 pathway in cancer, the use of anti-PD-1/PD-L1 therapeutics in PCa, and potential subgroups of PCa patients who may derive the greatest benefit from these agents (such as men with tumors that have expression of PD-L1 and/or high mutational load). We also review the prior and current clinical trials evaluating the blockade of PD-1/PD-L1 in PCa, highlighting some of the key ongoing studies of greatest relevance to the field. Expert commentary: Clinical trials investigating PD-1/PD-L1 inhibitors should be encouraged in patients with PCa. While it is unlikely that immune checkpoint monotherapies will produce long-lasting responses in a substantial proportion of patients, there is early evidence of activity in some patient subsets. These subgroups may include those with high PD-L1 expression, those with hypermutated or microsatellite-unstable tumors, and those enriched for germline and/or somatic DNA-repair gene mutations (e.g. intraductal/ductal histology, primary Gleason pattern 5, and perhaps AR-V7-positive tumors).

Measurement of cellular proliferation in human prostate by AgNOR, PCNA, and SPF.

PubMed

Sakr, W A; Sarkar, F H; Sreepathi, P; Drozdowicz, S; Crissman, J D

1993-01-01

Tumor differentiation and proliferative activity are important predictors of biological behavior. While routine histological evaluation is fairly adequate to assess differentiation, tumor proliferative activity is difficult to measure. Silver staining for nucleolar organizer regions (AgNORs) is reported to be helpful for assessing tumor proliferation. We investigated the AgNOR counts in 20 formalin fixed, paraffin embedded human prostate tissues in three microscopic fields of 330X, using an image analysis system. A total of 200-700 nuclei were evaluated on histologically controlled areas of nonneoplastic prostate tissue, prostatic intraepithelial neoplasia (PIN), and invasive carcinoma. The values were compared to flow cytometrically obtained synthesis phase fractions (SPF) and immunohistochemically semi-quantitated, proliferative cell nuclear antigen (PCNA) patterns. AgNOR counts were also compared to tumor stage and Gleason's score. The pattern of PCNA staining in formalin fixed specimens was widely variable, probably due to differences in preservation of antigen. The positive counts varied from 0 to 55%, with a mean value of 8.55 +/- 15.9. The SPF values ranged from 5 to 13% with a mean value of 8.50 +/- 2.37. Two of 20 tumors were aneuploid and 18 were of diploid range. The mean AgNOR values in nonneoplastic nuclei (1.836 +/- 0.299), PIN (3.129 +/- 0.295), and invasive tumor cell nuclei (4.737 +/- 0.369) were highly significant (P < 0.0001) when paired differences were compared. AgNOR counts correlated significantly with tumor Gleason's score (P < 0.0145). However, the correlation coefficient for SPF and AgNOR values was not significant (P > 0.24), possibly because of the small number of samples examined. The highest AgNOR counts were found in the two aneuploid tumors. We conclude that AgNOR count may be a potential indicator of cellular proliferation, and possibly a marker of tumor differentiation.

A Gleason-Type Theorem for Any Dimension Based on a Gambling Formulation of Quantum Mechanics

NASA Astrophysics Data System (ADS)

Benavoli, Alessio; Facchini, Alessandro; Zaffalon, Marco

2017-07-01

Based on a gambling formulation of quantum mechanics, we derive a Gleason-type theorem that holds for any dimension n of a quantum system, and in particular for n=2. The theorem states that the only logically consistent probability assignments are exactly the ones that are definable as the trace of the product of a projector and a density matrix operator. In addition, we detail the reason why dispersion-free probabilities are actually not valid, or rational, probabilities for quantum mechanics, and hence should be excluded from consideration.

Evaluation of various active surveillance protocols in prostate cancer.

PubMed

Yılmaz, Kayhan; Karadeniz, Tahir; Ozkaptan, Orkunt; Yilanoglu, Oguz

2014-06-30

This study aims to investigate whether pathology results obtained by radical retropubic prostatectomy (RRP) were correlated with active surveillance (AS) criteria defined by Klotz, Soloway and D'Amico. In our clinic we evaluated 211 patients with diagnosis of localized prostate cancer who underwent RRP between 2007 and 2012. AS criteria defined by Soloway (cT ≤ T2, PSA ≤ 15 ng/dl, Gleason ≤ 6), Klotz (cT1c-T2a; if age ≥ 70 PSA ≤ 15 ng/dl, if age < 70 PSA ≤ 10 ng/dl; if age ≥ 70 Gleason ≤ 7(3+4), if age < 70 Gleason ≤ 6) and D'Amico (cT1c-T2a, PSA ≤ 10 ng/dl, Gleason ≤ 6) were used in our study. Pathological stages and Gleason scores were evaluated with coherence to AS protocols, mis-staging rates, biochemical recurrence (BC) of the mis-staged patients and death due to prostate cancer Data was analyzed using NCSS 2007 & PASS 2008 Statistical Software (Utah, USA). Chi square test and Mann-Whitney U test were applied for analyzing qualitative data. Significance was determined as p < 0.05. 137 (64.9%) patients were coherent with Soloway AS criteria, 118 (55.9%) with Klotz AS criteria and 108 (51.1%) with D'Amico AS criteria. Histopathological results of the patients grouped according to Soloway, Klotz and D'Amico AS protocols showed high stage prostate cancer in 40 (29.2%), 32 (27%) and 27 (24.9%) patients, respectively. High grade prostate cancer rates in Soloway, Klotz, D'Amico groups were 55 (40.2%), 46 (38%) and 39 (36.1%); respectively. Misstaging rates of Soloway, Klotz and D'Amico AS protocols were determined as 65 (47.4%), 54 (45.5%) and 46 (42.5%), respectively. In the Soloway group BC rate was 21.9% in those with high stages. Relation between BC and high stage was found to be statistically significant (p < 0.05). Misstaging rates were relatively high in the three groups and there was no difference between the three groups in BC rates. Randomized studies with adequate follow up are needed.

Pathological upgrading in prostate cancer patients eligible for active surveillance: Does prostate-specific antigen density matter?

PubMed

Jin, Byung-Soo; Kang, Seok-Hyun; Kim, Duk-Yoon; Oh, Hoon-Gyu; Kim, Chun-Il; Moon, Gi-Hak; Kwon, Tae-Gyun; Park, Jae-Shin

2015-09-01

To evaluate prospectively the role of prostate-specific antigen (PSA) density in predicting Gleason score upgrading in prostate cancer patients eligible for active surveillance (T1/T2, biopsy Gleason score≤6, PSA≤10 ng/mL, and ≤2 positive biopsy cores). Between January 2010 and November 2013, among patients who underwent greater than 10-core transrectal ultrasound-guided biopsy, 60 patients eligible for active surveillance underwent radical prostatectomy. By use of the modified Gleason criteria, the tumor grade of the surgical specimens was examined and compared with the biopsy results. Tumor upgrading occurred in 24 patients (40.0%). Extracapsular disease and positive surgical margins were found in 6 patients (10.0%) and 8 patients (17.30%), respectively. A statistically significant correlation between PSA density and postoperative upgrading was found (p=0.030); this was in contrast with the other studied parameters, which failed to reach significance, including PSA, prostate volume, number of biopsy cores, and number of positive cores. Tumor upgrading was also highly associated with extracapsular cancer extension (p=0.000). The estimated optimal cutoff value of PSA density was 0.13 ng/mL(2), obtained by receiver operating characteristic analysis (area under the curve=0.66; p=0.020; 95% confidence interval, 0.53-0.78). PSA density is a strong predictor of Gleason score upgrading after radical prostatectomy in patients eligible for active surveillance. Because tumor upgrading increases the potential for postoperative pathological adverse findings and prognosis, PSA density should be considered when treating and consulting patients eligible for active surveillance.

Automatic Gleason grading of prostate cancer using SLIM and machine learning

NASA Astrophysics Data System (ADS)

Nguyen, Tan H.; Sridharan, Shamira; Marcias, Virgilia; Balla, Andre K.; Do, Minh N.; Popescu, Gabriel

2016-03-01

In this paper, we present an updated automatic diagnostic procedure for prostate cancer using quantitative phase imaging (QPI). In a recent report [1], we demonstrated the use of Random Forest for image segmentation on prostate cores imaged using QPI. Based on these label maps, we developed an algorithm to discriminate between regions with Gleason grade 3 and 4 prostate cancer in prostatectomy tissue. The Area-Under-Curve (AUC) of 0.79 for the Receiver Operating Curve (ROC) can be obtained for Gleason grade 4 detection in a binary classification between Grade 3 and Grade 4. Our dataset includes 280 benign cases and 141 malignant cases. We show that textural features in phase maps have strong diagnostic values since they can be used in combination with the label map to detect presence or absence of basal cells, which is a strong indicator for prostate carcinoma. A support vector machine (SVM) classifier trained on this new feature vector can classify cancer/non-cancer with an error rate of 0.23 and an AUC value of 0.83.

Prostate malignancy grading using gland-related shape descriptors

NASA Astrophysics Data System (ADS)

Braumann, Ulf-Dietrich; Scheibe, Patrick; Loeffler, Markus; Kristiansen, Glen; Wernert, Nicolas

2014-03-01

A proof-of-principle study was accomplished assessing the descriptive potential of two simple geometric measures (shape descriptors) applied to sets of segmented glands within images of 125 prostate cancer tissue sections. Respective measures addressing glandular shapes were (i) inverse solidity and (ii) inverse compactness. Using a classifier based on logistic regression, Gleason grades 3 and 4/5 could be differentiated with an accuracy of approx. 95%. Results suggest not only good discriminatory properties, but also robustness against gland segmentation variations. False classifications in part were caused by inadvertent Gleason grade assignments, as a-posteriori re-inspections had turned out.

The New Prostate Cancer Grading System Does Not Improve Prediction of Clinical Recurrence After Radical Prostatectomy: Results of a Large, Two-Center Validation Study.

PubMed

Dell'Oglio, Paolo; Karnes, Robert Jeffrey; Gandaglia, Giorgio; Fossati, Nicola; Stabile, Armando; Moschini, Marco; Cucchiara, Vito; Zaffuto, Emanuele; Karakiewicz, Pierre I; Suardi, Nazareno; Montorsi, Francesco; Briganti, Alberto

2017-02-01

A new prostate cancer (PCa) grading system (namely, Gleason score-GS- ≤6 vs. 3 + 4 vs. 4 + 3 vs. 8 vs. ≥9) was recently proposed and assessed on biochemical recurrence (BCR) showing improved predictive abilities compared to the commonly used three-tier system (GS ≤6 vs. 7 vs. ≥8). We assessed the predictive ability of the five-tier grade group (GG) system on harder clinical endpoint, namely clinical recurrence (CR). Between 2005 and 2014, 9,728 clinically localized PCa patients were treated with radical prostatectomy (RP) at two tertiary referral centers. Kaplan-Meier curves, multivariable Cox regression analyses, and concordance index (C-index) were used to assess CR after treatment according to four Gleason grade classifications at biopsy and RP: Group 1: ≤6 versus 7 versus ≥8; Group 2: ≤6 versus 3 + 4 vs. 4 + 3 versus ≥8; Group 3: ≤6 versus 7 versus 8 versus ≥9; Group 4: ≤6 versus 3 + 4 versus 4 + 3 versus 8 versus ≥9. Same analyses were repeated in patients who had BCR (n = 1,624). Decision curve analyses were performed to evaluate and compare the net benefit associated with the use of the four Gleason grade classifications. Overall, 443 (4.6%) patients had CR. The hazard ratio of the GS 3 + 4, 4 + 3, 8, and ≥9 relative to GS ≤6 were 3.63, 5.93, 11.44, 18.08 and 4.93, 9.99, 15.31 and 25.12 in the pre- and post-treatment models, respectively. The C-index of the five-tier GG system was slightly higher relative to the other 3 Gleason grade classifications both in the pre- (range: 0.001-0.006) and post-treatment models (range: 0-0.008). Similar findings were observed when we focused our analyses in patients with BCR after RP. The use of the five-tier GG system did not result into higher net-benefit relative to the other three Gleason grade classifications. The difference in accuracy between the five-tier GG system and the other Gleason grade classifications, using CR as an endpoint, is clinically negligible. Current evidence suggests that the five-tier GG system represents a simplified user-friendly scheme available for patient counseling rather than a new histopathological diagnostic system that improves the prediction of CR. Prostate 77:263-273, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A Positive Family History as risk factor for Prostate Cancer in a Population-based Study with organized PSA-Screening: Results of the Swiss ERSPC (Aarau)

PubMed Central

Randazzo, Marco; Müller, Alexander; Carlsson, Sigrid; Eberli, Daniel; Huber, Andreas; Grobholz, Rainer; Manka, Lukas; Mortezavi, Ashkan; Sulser, Tullio; Recker, Franz; Kwiatkowski, Maciej

2016-01-01

Objective To assess the value of positive family history (FH) as a risk factor for prostate cancer (PCa) incidence and grade among men undergoing organized PSA-screening in a population-based study. Patients and Methods The study cohort comprised all attendees of the Swiss arm of the European Randomized Study of Screening for Prostate Cancer (ERSPC) with systematic PSA-tests every 4 years. Men reporting first-degree relative(s) diagnosed with PCa were considered to have a positive FH. Biopsy was exclusively PSA-triggered with a threshold of 3 ng/ml. Primary endpoint was PCa diagnosis. Kaplan-Meier and Cox regression analyses were used. Results Of 4,932 attendees with a median age of 60.9 (IQR 57.6–65.1) years, 334 (6.8%) reported a positive FH. Median follow-up duration was 11.6 years (IQR 10.3–13.3). Cumulative PCa incidence was 60/334 (18%, positive FH) and 550/4,598 (12%, negative FH) (OR 1.6, 95% CI 1.2–2.2, p=0.001), respectively. In both groups, most PCa diagnosed had a low grade. There were no significant differences in PSA at diagnosis, biopsy Gleason score or Gleason score on pathologic specimen among men who underwent radical prostatectomy between both groups, respectively. On multivariable analysis, age (HR 1.04, 95% CI 1.02–1.06), baseline PSA (HR 1.13 95% CI 1.12–1.14), and FH (HR 1.6, CI 1.24–2.14) were independent predictors for overall PCa incidence (p<0.0001 each). Only baseline PSA (HR 1.14, 95% CI 1.12–1.16, p<0.0001) was an independent predictor of Gleason score ≥7 PCa on prostate biopsy. The proportion of interval PCa diagnosed in between the screening rounds was non-significantly different. Conclusion Irrespective of the FH status, the current PSA-based screening setting detects the majority of aggressive PCa and missed only a minority of interval cancers with a 4-year screening algorithm. Our results suggest that men with a positive FH are at increased risk for low grade but not aggressive PCa. PMID:26332304

H. A. Gleason's 'individualistic concept' and theory of animal communities: a continuing controversy.

PubMed

McIntosh, R P

1995-05-01

A tradition of natural history and of the lore of early twentieth-century ecology was that organisms lived together and interacted to form natural entities or communities. Before there was a recognizable science of ecology, Mobius (1877) had provided a name 'biocoenosis' for such entities. This concept persisted in the early decades of ecological science; at an extreme it was maintained that the community had integrating capabilities and organization like those of an individual organism, hence the term organismic community. In the 1950s-1970s an alternative individualist concept, derived from the ideas of H. A. Gleason (1939), gained credence which held that communities were largely a coincidence of individualistic species characteristics, continuously varying environments and different probabilities of a species arriving on a given site. During the same period, however, a body of population based theory of animal communities became dominant which perpetuated the idea of patterns in nature based on biotic interactions among species resulting in integrated communities. This theory introduced an extended terminology and mathematical models to explain the organization of species into groups of compatible species governed by rules. In the late 1970s the premises and methods of the theory came under attack and a vigorous debate ensued. The alternatives proposed were, at an extreme, null models of random aggregations of species or stochastic, individualistic aggregations of species, sensu Gleason. Extended research and debate ensued during the 1980s resulting in an explosion of studies of animal communities and a plethora of symposia and volumes of collected works concerning the nature of animal communities. The inherent complexity of communities and the traditional differences among animal ecologists about how they should be defined and delimited, at what scale of taxa, space and time to study them, and appropriate methods of study and analysis have resulted in extended and as yet inconclusive discussions. Recent differences and discussions are considered under five general categories, evolution and community theory, individualistic concept, community definition, questions from community ecology and empirical studies. Communities are seen by some ecologists as entities of coevolving species and, in any case, it is necessary to integrate evolutionary ideas with the varied concepts of community.(ABSTRACT TRUNCATED AT 400 WORDS)

Lack of Benefit for the Addition of Androgen Deprivation Therapy to Dose-Escalated Radiotherapy in the Treatment of Intermediate- and High-Risk Prostate Cancer

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

Krauss, Daniel, E-mail: dkrauss@beaumont.edu; Kestin, Larry; Ye, Hong

2011-07-15

Purpose: Assessment of androgen deprivation therapy (ADT) benefits for prostate cancer treated with dose-escalated radiotherapy (RT). Methods and Materials: From 1991 to 2004, 1,044 patients with intermediate- (n = 782) or high-risk (n = 262) prostate cancer were treated with dose-escalated RT at William Beaumont Hospital. Patients received external-beam RT (EBRT) alone, brachytherapy (high or low dose rate), or high dose rate brachytherapy plus pelvic EBRT. Intermediate-risk patients had Gleason score 7, prostate-specific antigen (PSA) 10.0-19.9 ng/mL, or Stage T2b-T2c. High-risk patients had Gleason score 8-10, PSA {>=}20, or Stage T3. Patients were additionally divided specifically by Gleason score, presencemore » of palpable disease, and PSA level to further define subgroups benefitting from ADT. Results: Median follow-up was 5 years; 420 patients received ADT + dose-escalated RT, and 624 received dose-escalated RT alone. For all patients, no advantages in any clinical endpoints at 8 years were associated with ADT administration. No differences in any endpoints were associated with ADT administration based on intermediate- vs. high-risk group or RT modality when analyzed separately. Patients with palpable disease plus Gleason {>=}8 demonstrated improved clinical failure rates and a trend toward improved survival with ADT. Intermediate-risk patients treated with brachytherapy alone had improved biochemical control when ADT was given. Conclusion: Benefits of ADT in the setting of dose-escalated RT remain poorly defined. This question must continue to be addressed in prospective study.« less

Surgery confounds biology: the predictive value of stage-, grade- and prostate-specific antigen for recurrence after radical prostatectomy as a function of surgeon experience.

PubMed

Vickers, Andrew J; Savage, Caroline J; Bianco, Fernando J; Klein, Eric A; Kattan, Michael W; Secin, Fernando P; Guilloneau, Bertrand D; Scardino, Peter T

2011-04-01

Statistical models predicting cancer recurrence after surgery are based on biologic variables. We have shown previously that prostate cancer recurrence is related to both tumor biology and to surgical technique. Here, we evaluate the association between several biological predictors and biochemical recurrence across varying surgical experience. The study included two separate cohorts: 6,091 patients treated by open radical prostatectomy and an independent replication set of 2,298 patients treated laparoscopically. We calculated the odds ratios for biological predictors of biochemical recurrence-stage, Gleason grade and prostate-specific antigen (PSA)-and also the predictive accuracy (area under the curve, AUC) of a multivariable model, for subgroups of patients defined by the experience of their surgeon. In the open cohort, the odds ratio for Gleason score 8+ and advanced pathologic stage, though not PSA or Gleason score 7, increased dramatically when patients treated by surgeons with lower levels of experience were excluded (Gleason 8+: odds ratios 5.6 overall vs. 13.0 for patients treated by surgeons with 1,000+ prior cases; locally advanced disease: odds ratios of 6.6 vs. 12.2, respectively). The AUC of the multivariable model was 0.750 for patients treated by surgeons with 50 or fewer cases compared to 0.849 for patients treated by surgeons with 500 or more. Although predictiveness was lower overall for the independent replication set cohort, the main findings were replicated. Surgery confounds biology. Although our findings have no direct clinical implications, studies investigating biological variables as predictors of outcome after curative resection of cancer should consider the impact of surgeon-specific factors. Copyright © 2010 UICC.

Hyperspectral-stimulated Raman scattering imaging of cholesteryl ester accumulation: new avenue to diagnosis of human prostate cancer

NASA Astrophysics Data System (ADS)

Du, Jun; Wang, Ping; Yue, Shuhua

2016-10-01

Most prostate cancers (PCa) are slowly growing, and only the aggressive ones require early diagnosis and effective treatment. The current standard for PCa diagnosis remains histopathology. Nonetheless, for the differentiation between Gleason score 6 (low-risk PCa), which can be left without treatment, and Gleason score 7 (high-risk PCa), which requires active treatment, the inter-observer discordance can be up to 40%. Our previous study reveals that cholesteryl ester (CE) accumulation induced by PI3K/AKT activation underlies human PCa aggressiveness. However, Raman spectromicroscopy used in this study could only provide compositional information of certain lipid droplets (LDs) selected by the observer, which overlooked cell-to-cell variation and hindered translation to accurate automated diagnosis. Here, we demonstrated quantitative mapping of CE level in human prostate tissues using hyperspectral stimulated Raman scattering (SRS) microscopy that renders compositional information for every pixel in the image. Specifically, hundreds of SRS images at Raman shift between 1620-1800 cm-1 were taken, and multivariate curve resolution algorism was used to retrieve concentration images of acyl C=C bond, sterol C=C bond, and ester C=O bond. Given that the ratio between images of sterol C=C and ester C=O (sterol C=C/C=O) is nonlinearly proportional to CE percentage out of total lipid, we were able to quantitatively map CE level. Our data showed that CE level was significantly greater in high Gleason grade compared to low Gleason grade, and could be a factor that significantly contributed to cancer recurrence. Our study provides an opportunity towards more accurate PCa diagnosis and prediction of aggressiveness.

No Detrimental Effect of a Positive Family History on Long-Term Outcomes Following Radical Prostatectomy.

PubMed

Brath, Johannes M S; Grill, Sonja; Ankerst, Donna P; Thompson, Ian M; Gschwend, Juergen E; Herkommer, Kathleen

2016-02-01

Overall 1 in 5 patients with prostate cancer has a positive family history. In this report we evaluated the association between family history and long-term outcomes following radical prostatectomy. Patients treated with radical prostatectomy were identified from a German registry, and separated into positive first-degree family history vs negative family history (strictly negative, requiring at least 1 male first-degree relative older than 60 years and no prostate cancer in the family). Kaplan-Meier curves and Cox proportional hazards models were used for association analyses with biochemical recurrence-free and prostate cancer specific survival. Median followup for 7,690 men included in the study was 8.4 years. Of the 754 younger patients less than 55 years old 50.9% (384) had a family history compared to 40.4% of the older patients (2,803; p <0.001). The 10-year biochemical recurrence-free (62.5%) and prostate cancer specific survival (96.1%) rates did not differ between patients with vs without a family history, nor between the younger vs older patient groups (all p >0.05). Prostate specific antigen, pathological stage, node stage and Gleason score were the only significant predictors for biochemical recurrence-free survival, while pathological stage, node stage (all p <0.005) and Gleason score (Gleason 7 vs 6 or less-HR 1.711, 95% CI 1.056-2.774, p = 0.03; Gleason 8 or greater vs 6 or less-HR 4.516, 95% CI 2.776-7.347, p <0.0001) were the only predictors for prostate cancer specific survival. A family history of prostate cancer has no bearing on long-term outcomes after radical prostatectomy. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Diagnostic performance of 68Gallium-PSMA-11 PET/CT to detect significant prostate cancer and comparison with 18FEC PET/CT.

PubMed

Hoffmann, Manuela A; Miederer, Matthias; Wieler, Helmut J; Ruf, Christian; Jakobs, Frank M; Schreckenberger, Mathias

2017-12-19

Radiolabeled prostate-specific membrane antigen (PSMA) has proven to be a highly accurate method to detect recurrence and metastases of prostate cancer, but only sparse data is available about its performance in the diagnosis of clinically significant primary prostate cancer. We compared 68 Ga-PSMA-11 PET/CT in 25 patients with 18 FEC PET/CT in 40 patients with suspected prostate carcinoma based on an increased PSA level.The PET/CT results were compared with the histopathologic Gleason Score (GS) of biopsies. The 68 Ga-PSMA-11 PET/CT revealed highly suspect prostatic lesions (maximum standardized uptake value/SUV max >2.5) in 21/25 patients (84%), associated with GS≥6 (low-grade/high-grade carcinoma). Two histopathologic non-malignancy-relevant cases (GS<6) had PSMA-SUV max ≤2.5; all histopathologic high-grade cases (GS≥7b) showed PSMA-SUV max >12.0 which further increased with rising GS. There were 2 false positives and no false negative findings for high-grade prostate cancer using a cut off-level for SUV max of 2.5.In contrast, the 18 FEC PET/CT showed suspected malignant lesions in 38/40 patients (95%), which included 3 lesions with GS<6. The mean SUV max values did not differ with different GS. There were 11 false positives and 1 false negative for detection of high-grade prostate cancer (cut off 2.5).By means of ROC analysis a SUV max of 5.4 was found to be an optimal cut off-level to distinguish between low- and high-grade carcinoma in 68 Ga-PSMA-11 PET/CT (AUC=0.9692; 95% CI 0.9086;1.0000;SD(AUC)=0.0309)). Choosing a cut off-level of SUV max 5.4, 68 Ga-PSMA-11 PET/CT was able to distinguish between GS ≤7a/≥7b with a sensitivity of 84%, a specificity of 100%, a negative predictive value (NPV) of 67%, and an efficiency of 88% ( p <0.001).The ROC analysis revealed a SUV max 6.5 as an optimal cut off-level to distinguish between low- and high-grade carcinoma in 18 FEC PET/CT (AUC=0.7470; 95% CI 0.5919;0.9020;SD(AUC)=0.0791) with a sensitivity of 61% and a specificity of 92%; but the efficiency was only 70% and the NPV 50% ( p =0.01). 68 Ga-PSMA-11 PET/CT guided biopsy of the prostate increases diagnostic precision and is likely to help to reduce overtreatment of low-grade malignant disease as well as detect the foci of the highest Gleason pattern. Both methods ( 68 Ga-PSMA-11, 18 FEC) were suitable to detect primary prostate cancer, but the excellent image quality, the higher specificity and the good correlation of positive scans with GS are advantages of 68 Ga-PSMA-11.

68Ga-PSMA-11 PET/CT in primary staging of prostate carcinoma: preliminary results on differences between black and white South-Africans.

PubMed

Sathekge, Mike; Lengana, Thabo; Maes, Alex; Vorster, Mariza; Zeevaart, JanRijn; Lawal, Ismaheel; Ebenhan, Thomas; Van de Wiele, Christophe

2018-02-01

The incidence of prostate cancer is 60% higher and the mortality rate is two- to three-times greater in black versus white men. We report on differences in 68 Ga-PSMA-11 PET/CT imaging findings in 77 black South-African (BSAs) and 18 white South-African (WSAs) treatment-naïve primary prostate carcinoma (PPC) patients. 68 Ga-PSMA-11 PET/CT imaging findings were compared to histological, biochemical and morphological imaging data. Patients were grouped into three Gleason grade groups (GG), GG 1 (scores 3 + 3 and 3 + 4), GG2 (scores 4 + 3 and 4 + 4) and GG3 (scores 9 and 10), and the PSA difference among the groups was determined. Inter-racial difference in SUVmax of the primary tumor as well as its correlation with serum PSA were also determined. Ninety-three out of 95 PPC where readily identified on 68 Ga-PSMA-11 PET/CT imaging. Median PPC SUVmax and serum PSA values proved significantly higher (p = 0.033 and p = 0.003) in GG3 patients (median 16.4 and 180 ng/ml) when compared to GG1 patients (median 9.6 and 25.1 ng/ml) or GG2 patients (median 8.8 and 46.2 ng/ml). SUVmax significantly correlated with serum PSA-values (r = 0.377 (p = 0.0001)). Age, frequency of lymph node involvement and distant metastases, and GGs (p ≥ 0.153) were similar in BSAs and WSAs, both median serum PSA-values as well as SUVmax values proved significantly higher in BSAs when compared to WSAs, respectively, 81.6 ng/ml versus 14.5 ng/ml (p = 0.0001) and 11.9 versus 4.38 (p = 0.004). Moreover, Gleason-score normalized median SUVmax values proved 2.5 times higher in BSAs when compared to WSAs (p = 0.005). SUVmax values proved significantly related to GG and to be significantly higher in BSAs when compared to WSAs. Also, SUVmax significantly correlated with serum PSA values, which was significantly higher in BSAs when compared with WSAs.

Outcome According to Elective Pelvic Radiation Therapy in Patients With High-Risk Localized Prostate Cancer: A Secondary Analysis of the GETUG 12 Phase 3 Randomized Trial.

PubMed

Blanchard, Pierre; Faivre, Laura; Lesaunier, François; Salem, Naji; Mesgouez-Nebout, Nathalie; Deniau-Alexandre, Elisabeth; Rolland, Frédéric; Ferrero, Jean-Marc; Houédé, Nadine; Mourey, Loïc; Théodore, Christine; Krakowski, Ivan; Berdah, Jean-François; Baciuchka, Marjorie; Laguerre, Brigitte; Davin, Jean-Louis; Habibian, Muriel; Culine, Stéphane; Laplanche, Agnès; Fizazi, Karim

2016-01-01

The role of pelvic elective nodal irradiation (ENI) in the management of prostate cancer is controversial. This study analyzed the role of pelvic radiation therapy (RT) on the outcome in high-risk localized prostate cancer patients included in the Groupe d'Etude des Tumeurs Uro-Genitales (GETUG) 12 trial. Patients with a nonpretreated high-risk localized prostate cancer and a staging lymphadenectomy were randomly assigned to receive either goserelin every 3 months for 3 years and 4 cycles of docetaxel plus estramustine or goserelin alone. Local therapy was administered 3 months after the start of systemic treatment. Performance of pelvic ENI was left to the treating physician. Only patients treated with primary RT were included in this analysis. The primary endpoint was biochemical progression-free survival (bPFS). A total of 413 patients treated from 2002 to 2006 were included, of whom 358 were treated using primary RT. A total of 208 patients received pelvic RT and 150 prostate-only RT. Prostate-specific antigen (PSA) concentration, Gleason score, or T stage did not differ according to performance of pelvic RT; pN+ patients more frequently received pelvic RT than pN0 patients (P<.0001). Median follow-up was 8.8 years. In multivariate analysis, bPFS was negatively impacted by pN stage (hazard ratio [HR]: 2.52 [95% confidence interval [CI]: 1.78-3.54], P<.0001), Gleason score 8 or higher (HR: 1.41 [95% CI: 1.03-1.93], P=.033) and PSA higher than 20 ng/mL (HR: 1.41 [95% CI: 1.02-1.96], P=.038), and positively impacted by the use of chemotherapy (HR: 0.66 [95% CI: 0.48-0.9], P=.009). There was no association between bPFS and use of pelvic ENI in multivariate analysis (HR: 1.10 [95% CI: 0.78-1.55], P=.60), even when analysis was restricted to pN0 patients (HR: 0.88 [95% CI: 0.59-1.31], P=.53). Pelvic ENI was not associated with increased acute or late patient reported toxicity. This unplanned analysis of a randomized trial failed to demonstrate a benefit of pelvic ENI on bPFS in high-risk localized prostate cancer patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Phase II trial of short-term neoadjuvant docetaxel and complete androgen blockade in high-risk prostate cancer

PubMed Central

Mellado, B; Font, A; Alcaraz, A; Aparicio, L A; Veiga, F J G; Areal, J; Gallardo, E; Hannaoui, N; Lorenzo, J R M; Sousa, A; Fernandez, P L; Gascon, P

2009-01-01

Background: The low probability of curing high-risk prostate cancer (PC) with local therapy suggests the need to study modality of therapeutic approaches. To this end, a prospective phase II trial of neoadjuvant docetaxel (D) and complete androgen blockade (CAB) was carried out in high-risk PC patients. The primary end point was to detect at least 10% of pCRs after chemohormonal treatment. Methods: Patients with T1c–T2 clinical stage with prostate-specific antigen (PSA) >20 ng ml−1 and/or Gleason score ⩾7 (4+3) and T3 were included. Treatment consisted of three cycles of D 36 mg m−2 on days 1, 8 and 15 every 28 days concomitant with CAB, followed by radical prostatectomy (RP). Results: A total of 57 patients were included. Clinical stage was T1c, 11 patients (19.3%); T2, 30 (52.6%) and T3, 16 (28%) patients. Gleason score was ⩾7 (4+3) in 44 (77%) patients and PSA >20 ng ml−1 in 15 (26%) patients. Treatment was well tolerated with 51 (89.9%) patients completing neoadjuvant therapy together with RP. The rate of pCR was 6% (three patients). Three (6%) additional patients had microscopic residual tumour (near pCR) in prostate specimen. With a median follow-up of 35 months, 18 (31.6%) patients presented PSA relapse. Conclusion: Short-term neoadjuvant D and CAB induced a 6% pCR rate, which is close to what would be expected with ADT alone. The combination was generally well tolerated. PMID:19755998

Robotic-assisted pelvic lymph node dissection for prostate cancer: frequency of nodal metastases and oncological outcomes.

PubMed

Ledezma, Rodrigo A; Negron, Edris; Razmaria, Aria A; Dangle, Pankaj; Eggener, Scott E; Shalhav, Arieh L; Zagaja, Gregory P

2015-11-01

Limited data are available regarding the oncologic efficacy of pelvic lymph node dissection (PLND) performed during robotic-assisted laparoscopic prostatectomy (RALP) for prostate cancer. We aimed to determine the frequency of pelvic lymph node metastasis and oncological outcomes following RALP with PLND in patients who did not receive adjuvant androgen deprivation therapy (ADT). We retrospectively reviewed the records of 1740 consecutive patients who underwent RALP and extended PLND. The primary endpoint was biochemical recurrence (BCR). The estimated BCR probability was obtained using the Kaplan-Meier method. Cox proportional hazard regression models were used to assess for predictors of BCR. One hundred and eight patients (6 %) with positive LNs were identified. The median number of LNs removed was 17 (IQR 11-24), and median follow-up was 26 months (IQR 14-43). Ninety-one (84 %) patients did not receive adjuvant ADT of whom 60 % had BCR with a median time to recurrence of 8 months. The 1- and 3-year BCR-free probability was 42 and 28 %, respectively. Patients with ≤2 LN+ had significantly better biochemical-free estimated probability compared to those with >2 LN+ (p = 0.002). The total number of LN+ (HR = 1.1; 95 % CI 1.01-1.2, p = 0.04) and Gleason 8-10 (HR = 1.96; 95 % CI 1.1-3.4, p = 0.02) were predictors of BCR on multivariate analysis. Among men with positive lymph nodes at time of robotic prostatectomy, those with two or fewer positive nodes and Gleason <8 exhibited favorable biochemical-free survival without adjuvant therapy.

Tumor and Plasma Met Levels in Non-Metastatic Prostate Cancer.

PubMed

Kaye, Deborah R; Pinto, Peter A; Cecchi, Fabiola; Reilly, Joseph; Semerjian, Alice; Rabe, Daniel C; Gupta, Gopal; Choyke, Peter L; Bottaro, Donald P

2016-01-01

To measure Met protein content in prostate biopsies guided by fused magnetic resonance and ultrasound imaging, and to measure soluble Met (sMet) protein concentration in plasma samples from patients presenting evidence of prostate cancer. 345 patients had plasma samples drawn prior to image-guided biopsy of the prostate. Of these, 32% had benign biopsies. Of the 236 that were positive for prostate adenocarcinoma (PCa), 132 treated by total prostatectomy had Gleason scores of 6 (17%), 7, (55%), 8 (16%), or 9-10 (12%). 23% had evidence of local invasion. Plasma samples were also obtained from 80 healthy volunteers. Tissue Met and plasma sMet were measured by two-site immunoassay; values were compared among clinically defined groups using non-parametric statistical tests to determine significant differences or correlations. PCa tumor Met correlated significantly with plasma sMet, but median values were similar among benign and malignant groups. Median plasma sMet values were also similar among those groups, although both medians were significantly above normal. Median Met content in primary PCa tumors and sMet concentrations were independent of Gleason score, final pathologic stage and age. Plasma sMet is not predictive of PCa or its severity in patients with organ-confined or locally invasive disease. Quantitative analysis of Met protein content and activation state in PCa tumor biopsy samples was highly feasible and may have value in follow-up to genomic and/or transcriptomic-based screens that show evidence of oncogenically relevant MET gene features that occur at relatively low frequency in non-metastatic PCa.

Performance assessment of automated tissue characterization for prostate H and E stained histopathology

NASA Astrophysics Data System (ADS)

DiFranco, Matthew D.; Reynolds, Hayley M.; Mitchell, Catherine; Williams, Scott; Allan, Prue; Haworth, Annette

2015-03-01

Reliable automated prostate tumor detection and characterization in whole-mount histology images is sought in many applications, including post-resection tumor staging and as ground-truth data for multi-parametric MRI interpretation. In this study, an ensemble-based supervised classification algorithm for high-resolution histology images was trained on tile-based image features including histogram and gray-level co-occurrence statistics. The algorithm was assessed using different combinations of H and E prostate slides from two separate medical centers and at two different magnifications (400x and 200x), with the aim of applying tumor classification models to new data. Slides from both datasets were annotated by expert pathologists in order to identify homogeneous cancerous and non-cancerous tissue regions of interest, which were then categorized as (1) low-grade tumor (LG-PCa), including Gleason 3 and high-grade prostatic intraepithelial neoplasia (HG-PIN), (2) high-grade tumor (HG-PCa), including various Gleason 4 and 5 patterns, or (3) non-cancerous, including benign stroma and benign prostatic hyperplasia (BPH). Classification models for both LG-PCa and HG-PCa were separately trained using a support vector machine (SVM) approach, and per-tile tumor prediction maps were generated from the resulting ensembles. Results showed high sensitivity for predicting HG-PCa with an AUC up to 0.822 using training data from both medical centres, while LG-PCa showed a lower sensitivity of 0.763 with the same training data. Visual inspection of cancer probability heatmaps from 9 patients showed that 17/19 tumors were detected, and HG-PCa generally reported less false positives than LG-PCa.

Multiparametric MRI Apparent Diffusion Coefficient (ADC) Accuracy in Diagnosing Clinically Significant Prostate Cancer.

PubMed

Pepe, Pietro; D'Urso, Davide; Garufi, Antonio; Priolo, Giandomenico; Pennisi, Michele; Russo, Giorgio; Sabini, Maria Gabriella; Valastro, Lucia Maria; Galia, Antonio; Fraggetta, Filippo

2017-01-01

To evaluate the accuracy of multiparametric magnetic resonance imaging apparent diffusion coefficient (mpMRI ADC) in the diagnosis of clinically significant prostate cancer (PCa). From January 2016 to December 2016, 44 patients who underwent radical prostatectomy for PCa and mpMRI lesions suggestive of cancer were retrospectively evaluated at definitive specimen. The accuracy of suspicious mpMRI prostate imaging reporting and data system (PI-RADS ≥3) vs. ADC values in the diagnosis of Gleason score ≥7 was evaluated. Receiver operating characteristics (ROC) curve analysis gave back an ADC threshold of 0.747×10 -3 mm 2 /s to separate between Gleason Score 6 and ≥7. The diagnostic accuracy of ADC value (cut-off 0.747×10 -3 mm 2 /s) vs. PI-RADS score ≥3 in diagnosing PCa with Gleason score ≥7 was equal to 84% vs. 63.6% with an area under the curve (AUC) ROC of 0.81 vs. 0.71, respectively. ADC evaluation could support clinicians in decision making of patients with PI-RADS score <3 at risk for PCa. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Gland segmentation in prostate histopathological images

PubMed Central

Singh, Malay; Kalaw, Emarene Mationg; Giron, Danilo Medina; Chong, Kian-Tai; Tan, Chew Lim; Lee, Hwee Kuan

2017-01-01

Abstract. Glandular structural features are important for the tumor pathologist in the assessment of cancer malignancy of prostate tissue slides. The varying shapes and sizes of glands combined with the tedious manual observation task can result in inaccurate assessment. There are also discrepancies and low-level agreement among pathologists, especially in cases of Gleason pattern 3 and pattern 4 prostate adenocarcinoma. An automated gland segmentation system can highlight various glandular shapes and structures for further analysis by the pathologist. These objective highlighted patterns can help reduce the assessment variability. We propose an automated gland segmentation system. Forty-three hematoxylin and eosin-stained images were acquired from prostate cancer tissue slides and were manually annotated for gland, lumen, periacinar retraction clefting, and stroma regions. Our automated gland segmentation system was trained using these manual annotations. It identifies these regions using a combination of pixel and object-level classifiers by incorporating local and spatial information for consolidating pixel-level classification results into object-level segmentation. Experimental results show that our method outperforms various texture and gland structure-based gland segmentation algorithms in the literature. Our method has good performance and can be a promising tool to help decrease interobserver variability among pathologists. PMID:28653016

Radical Prostatectomy, External Beam Radiotherapy, or External Beam Radiotherapy With Brachytherapy Boost and Disease Progression and Mortality in Patients With Gleason Score 9-10 Prostate Cancer.

PubMed

Kishan, Amar U; Cook, Ryan R; Ciezki, Jay P; Ross, Ashley E; Pomerantz, Mark M; Nguyen, Paul L; Shaikh, Talha; Tran, Phuoc T; Sandler, Kiri A; Stock, Richard G; Merrick, Gregory S; Demanes, D Jeffrey; Spratt, Daniel E; Abu-Isa, Eyad I; Wedde, Trude B; Lilleby, Wolfgang; Krauss, Daniel J; Shaw, Grace K; Alam, Ridwan; Reddy, Chandana A; Stephenson, Andrew J; Klein, Eric A; Song, Daniel Y; Tosoian, Jeffrey J; Hegde, John V; Yoo, Sun Mi; Fiano, Ryan; D'Amico, Anthony V; Nickols, Nicholas G; Aronson, William J; Sadeghi, Ahmad; Greco, Stephen; Deville, Curtiland; McNutt, Todd; DeWeese, Theodore L; Reiter, Robert E; Said, Johnathan W; Steinberg, Michael L; Horwitz, Eric M; Kupelian, Patrick A; King, Christopher R

2018-03-06

The optimal treatment for Gleason score 9-10 prostate cancer is unknown. To compare clinical outcomes of patients with Gleason score 9-10 prostate cancer after definitive treatment. Retrospective cohort study in 12 tertiary centers (11 in the United States, 1 in Norway), with 1809 patients treated between 2000 and 2013. Radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy, or EBRT plus brachytherapy boost (EBRT+BT) with androgen deprivation therapy. The primary outcome was prostate cancer-specific mortality; distant metastasis-free survival and overall survival were secondary outcomes. Of 1809 men, 639 underwent RP, 734 EBRT, and 436 EBRT+BT. Median ages were 61, 67.7, and 67.5 years; median follow-up was 4.2, 5.1, and 6.3 years, respectively. By 10 years, 91 RP, 186 EBRT, and 90 EBRT+BT patients had died. Adjusted 5-year prostate cancer-specific mortality rates were RP, 12% (95% CI, 8%-17%); EBRT, 13% (95% CI, 8%-19%); and EBRT+BT, 3% (95% CI, 1%-5%). EBRT+BT was associated with significantly lower prostate cancer-specific mortality than either RP or EBRT (cause-specific HRs of 0.38 [95% CI, 0.21-0.68] and 0.41 [95% CI, 0.24-0.71]). Adjusted 5-year incidence rates of distant metastasis were RP, 24% (95% CI, 19%-30%); EBRT, 24% (95% CI, 20%-28%); and EBRT+BT, 8% (95% CI, 5%-11%). EBRT+BT was associated with a significantly lower rate of distant metastasis (propensity-score-adjusted cause-specific HRs of 0.27 [95% CI, 0.17-0.43] for RP and 0.30 [95% CI, 0.19-0.47] for EBRT). Adjusted 7.5-year all-cause mortality rates were RP, 17% (95% CI, 11%-23%); EBRT, 18% (95% CI, 14%-24%); and EBRT+BT, 10% (95% CI, 7%-13%). Within the first 7.5 years of follow-up, EBRT+BT was associated with significantly lower all-cause mortality (cause-specific HRs of 0.66 [95% CI, 0.46-0.96] for RP and 0.61 [95% CI, 0.45-0.84] for EBRT). After the first 7.5 years, the corresponding HRs were 1.16 (95% CI, 0.70-1.92) and 0.87 (95% CI, 0.57-1.32). No significant differences in prostate cancer-specific mortality, distant metastasis, or all-cause mortality (≤7.5 and >7.5 years) were found between men treated with EBRT or RP (cause-specific HRs of 0.92 [95% CI, 0.67-1.26], 0.90 [95% CI, 0.70-1.14], 1.07 [95% CI, 0.80-1.44], and 1.34 [95% CI, 0.85-2.11]). Among patients with Gleason score 9-10 prostate cancer, treatment with EBRT+BT with androgen deprivation therapy was associated with significantly better prostate cancer-specific mortality and longer time to distant metastasis compared with EBRT with androgen deprivation therapy or with RP.

Identifying molecular features for prostate cancer with Gleason 7 based on microarray gene expression profiles.

PubMed

Bălăcescu, Loredana; Bălăcescu, O; Crişan, N; Fetica, B; Petruţ, B; Bungărdean, Cătălina; Rus, Meda; Tudoran, Oana; Meurice, G; Irimie, Al; Dragoş, N; Berindan-Neagoe, Ioana

2011-01-01

Prostate cancer represents the first leading cause of cancer among western male population, with different clinical behavior ranging from indolent to metastatic disease. Although many molecules and deregulated pathways are known, the molecular mechanisms involved in the development of prostate cancer are not fully understood. The aim of this study was to explore the molecular variation underlying the prostate cancer, based on microarray analysis and bioinformatics approaches. Normal and prostate cancer tissues were collected by macrodissection from prostatectomy pieces. All prostate cancer specimens used in our study were Gleason score 7. Gene expression microarray (Agilent Technologies) was used for Whole Human Genome evaluation. The bioinformatics and functional analysis were based on Limma and Ingenuity software. The microarray analysis identified 1119 differentially expressed genes between prostate cancer and normal prostate, which were up- or down-regulated at least 2-fold. P-values were adjusted for multiple testing using Benjamini-Hochberg method with a false discovery rate of 0.01. These genes were analyzed with Ingenuity Pathway Analysis software and were established 23 genetic networks. Our microarray results provide new information regarding the molecular networks in prostate cancer stratified as Gleason 7. These data highlighted gene expression profiles for better understanding of prostate cancer progression.

Is seminal vesiculectomy necessary in all patients with biopsy Gleason score 6?

PubMed

Gofrit, Ofer N; Zorn, Kevin C; Shikanov, Sergey A; Zagaja, Gregory P; Shalhav, Arieh L

2009-04-01

Radiotherapists are excluding the seminal vesicles (SVs) from their target volume in cases of low-risk prostate cancer. However, these glands are routinely removed in every radical prostatectomy. Dissection of the SVs can damage the pelvic plexus, compromise trigonal, bladder neck, and cavernosal innervation, and contribute to delayed gain of continence and erectile function. In this study we evaluated the oncological benefit of routine removal of the SVs in currently operated patients. A total of 1003 patients (mean age, 59.7 years) with prostate cancer underwent robot-assisted radical prostatectomy between February 2003 and July 2007. Seminal vesicle invasion (SVI) was found in 46 of the operated patients (4.6%). Biopsy Gleason score (BGS), preoperative serum PSA, clinical tumor stage, percent of positive cores, and maximal percentage of cancer in a core had all a significant impact on the risk of SVI. Only 4/634 patients (0.6%) with BGS < or =6 suffered from SVI, as opposed to 42/369 (11.4%) with higher Gleason scores. Seminal vesiculectomy does not benefit more than 99% of the patients with BGS < or =6. Considering the potential neural and vascular damage associated with seminal vesiculectomy, we suggest that routine removal of these glands during radical prostatectomy in these cases is not necessary.

Angiotensin Receptor Blockers and Risk of Prostate Cancer among United States Veterans

PubMed Central

Rao, Gowtham A; Mann, Joshua R.; Bottai, Matteo; Uemura, Hiroji; Burch, James B; Bennett, Charles Lee; Haddock, Kathlyn Sue; Hébert, James R

2013-01-01

Objectives To address concerns regarding increased risk of prostate cancer (PrCA) among Angiotensin Receptor Blocker users, we used national retrospective data from the Department of Veterans Affairs (VA) through the Veterans Affairs Informatics and Computing Infrastructure (VINCI). Methods We identified a total of 543,824 unique Veterans who were classified into either ARB treated or not-treated in 1:15 ratio. The two groups were balanced using inverse probability of treatment weights. A double-robust cox-proportional hazards model was used to estimate the hazard ratio for PrCA incidence. To evaluate for a potential Gleason score stage migration we conducted weighted Cochrane-Armitage test. Results Post weighting, the rates of PrCA in treated and not-treated groups were 506 (1.5%) and 8,269 (1.6%), respectively; representing a hazard ratio of (0.91, p-value 0.049). There was no significant difference in Gleason scores between the two groups. Conclusions We found a small, but statistically significant, reduction in the incidence of clinically detected PrCA among patients assigned to receive ARB with no countervailing effect on degree of differentiation (as indicated by Gleason score). Findings from this study support FDA’s recent conclusion that ARB use does not increase risk of incident PrCA. PMID:23686462

Gleason drift in the NIHR ProtecT study.

PubMed

Oxley, Jon; Simpkin, Andrew; Goepel, John; Varma, Murali; Griffiths, David; Grigor, Ken; Mayer, Nick; Warren, Anne; Deshmukh, Nayneeta; Bhattarai, Selina; Dormer, John; Hounsome, Luke; Adamczyk, Lukasz A; Metcalfe, Christopher; Lane, J Athene; Davis, Michael; Donovan, Jenny L; Neal, David E; Hamdy, Freddy C; Robinson, Mary C

2015-02-01

There is increasing evidence of Gleason score (GS) drift in prostatic core biopsies during the last two decades. The ProtecT study is a randomized controlled study and provides an excellent cohort to study the effect of time, prostate-specific antigen (PSA) level, perineural invasion, tumour length and age on GS. The ProtecT study recruited men in the United Kingdom between 1999 and 2010. The Gleason scores were grouped into four categories ≤ 3 + 3, 3 + 4, 4 + 3 and ≥ 4 + 4 for analysis. Data from England between 2000 and 2012 were also available. A total of 3282 biopsies containing cancer were analysed. For each year of the ProtecT study, the odds of being diagnosed with a higher GS category increased by 4.9%. Higher GS was also associated with perineural invasion, increasing tumour length, age and PSA level. While biopsy GS from England was incomplete, it also showed a marked decrease in GS five and six tumours during the same period. There was GS drift from 3 + 3 to 3 + 4 with time in the ProtecT study, but there appeared to be no significant change in percentage of GS 4 + 3 or higher. This drift was less dramatic when compared to GS in the rest of England. © 2014 John Wiley & Sons Ltd.

Prostatectomy-based validation of combined urine and plasma test for predicting high grade prostate cancer.

PubMed

Albitar, Maher; Ma, Wanlong; Lund, Lars; Shahbaba, Babak; Uchio, Edward; Feddersen, Søren; Moylan, Donald; Wojno, Kirk; Shore, Neal

2018-03-01

Distinguishing between low- and high-grade prostate cancers (PCa) is important, but biopsy may underestimate the actual grade of cancer. We have previously shown that urine/plasma-based prostate-specific biomarkers can predict high grade PCa. Our objective was to determine the accuracy of a test using cell-free RNA levels of biomarkers in predicting prostatectomy results. This multicenter community-based prospective study was conducted using urine/blood samples collected from 306 patients. All recruited patients were treatment-naïve, without metastases, and had been biopsied, designated a Gleason Score (GS) based on biopsy, and assigned to prostatectomy prior to participation in the study. The primary outcome measure was the urine/plasma test accuracy in predicting high grade PCa on prostatectomy compared with biopsy findings. Sensitivity and specificity were calculated using standard formulas, while comparisons between groups were performed using the Wilcoxon Rank Sum, Kruskal-Wallis, Chi-Square, and Fisher's exact test. GS as assigned by standard 10-12 core biopsies was 3 + 3 in 90 (29.4%), 3 + 4 in 122 (39.8%), 4 + 3 in 50 (16.3%), and > 4 + 3 in 44 (14.4%) patients. The urine/plasma assay confirmed a previous validation and was highly accurate in predicting the presence of high-grade PCa (Gleason ≥3 + 4) with sensitivity between 88% and 95% as verified by prostatectomy findings. GS was upgraded after prostatectomy in 27% of patients and downgraded in 12% of patients. This plasma/urine biomarker test accurately predicts high grade cancer as determined by prostatectomy with a sensitivity at 92-97%, while the sensitivity of core biopsies was 78%. © 2018 Wiley Periodicals, Inc.

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.

18F-choline PET/MRI in suspected recurrence of prostate carcinoma.

PubMed

Riola-Parada, C; Carreras-Delgado, J L; Pérez-Dueñas, V; Garcerant-Tafur, M; García-Cañamaque, L

2018-05-21

To evaluate the usefulness of simultaneous 18 F-choline PET/MRI in the suspicion of prostate cancer recurrence and to relate 18 F-choline PET/MRI detection rate with analytical and pathological variables. 27 patients with prostate cancer who received local therapy as primary treatment underwent a 18 F-choline PET/MRI due to suspicion of recurrence (persistently rising serum PSA level). 18 F-choline PET/MRI findings were validated by anatomopathological analysis, other imaging tests or by biochemical response to oncological treatment. 18 F-choline PET/MRI detected disease in 15 of 27 patients (detection rate 55.56%). 4 (15%) presented exclusively local recurrence, 5 (18%) lymph node metastases and 7 (26%) bone metastases. Mean PSA (PSA med ) at study time was 2.94ng/mL (range 0.18-10ng/mL). PSA med in patients with positive PET/MRI was 3.70ng/mL (range 0.24-10ng/mL), higher than in patients with negative PET/MRI, PSA med 1.97ng/mL (range 0.18-4.38ng/mL), although without statistically significant differences. Gleason score at diagnosis in patients with a positive study was 7.33 (range 6-9) and in patients with a negative study was 7 (range 6-9), without statistically significant differences. 18 F-choline PET/MRI detection rate was considerable despite the relatively low PSA values in our sample. The influence of Gleason score and PSA level on 18 F-choline PET/MRI detection rate was not statistically significant. Copyright © 2018 Sociedad Española de Medicina Nuclear e Imagen Molecular. Publicado por Elsevier España, S.L.U. All rights reserved.

Temporarily deferred therapy (watchful waiting) for men younger than 70 years and with low-risk localized prostate cancer in the prostate-specific antigen era.

PubMed

Carter, Corey A; Donahue, Timothy; Sun, Leon; Wu, Hongyu; McLeod, David G; Amling, Christopher; Lance, Raymond; Foley, John; Sexton, Wade; Kusuda, Leo; Chung, Andrew; Soderdahl, Douglas; Jackmaan, Stephen; Moul, Judd W

2003-11-01

Watchful waiting (WW) is an acceptable strategy for managing prostate cancer (PC) in older men. Prostate-specific antigen (PSA) testing has resulted in a stage migration, with diagnoses made in younger men. An analysis of the Department of Defense Center for Prostate Disease Research Database was undertaken to document younger men with low- or intermediate-grade PC who initially chose WW. We identified men choosing WW who were diagnosed between January 1991 and January 2002, were 70 years or younger, had a Gleason score < or = 6 with no Gleason pattern 4, had no more than three positive cores on biopsy, and whose clinical stage was < or = T2 and PSA level was < or = 20. We analyzed their likelihood of remaining on WW, the factors associated with secondary treatment, and the influence of comorbidities. Three hundred thirteen men were identified. Median follow-up time was 3.8 years. Median age was 65.4 years (range, 41 to 70 years). Ninety-eight patients remained on WW; 215 proceeded to treatment. A total of 57.3% and 73.2% chose treatment within the first 2 and 4 years, respectively. Median PSA doubling time (DT) was 2.5 years for those who underwent therapy; those remaining on WW had a median DT of 25.8 years. The type of secondary treatment was associated with the number of patient's comorbidities (P =.012). Younger patients who choose WW seemed more likely to receive secondary treatment than older patients. PSA DTs often predict the use of secondary treatment. The number of comorbidities a patient has influences the type of secondary therapy chosen. The WW strategy may better be termed temporarily deferred therapy.

Relevance of prostate cancer in patients with synchronous invasive bladder urothelial carcinoma: a monocentric retrospective analysis.

PubMed

Dell'Atti, Lucio

2015-03-31

We retrospectively reviewed data of patients with incidental prostate cancer (PCa) who underwent radical cystoprostatectomy (RCP) for invasive bladder cancer and we analyzed their features with regard to incidence, pathologic characteristics, clinical significance, and implications for management. Clinical data and pathological features of 64 patients who underwent standard RCP for bladder cancer were included in this study. Besides the urothelial carcinoma of the urinary bladder, the location and tumor volume of the PCa, prostate apex involvement, Gleason score, pathological staging and surgical margins were evaluated. Clinically significant PCa was defined as a tumor with a Gleason 4 or 5 pattern, stage ≥ pT3, lymph node involvement, positive surgical margin or multifocality of three or more lesions. Postoperative follow-up was scheduled every 3 months in the first year, every 6 months in the second and third year, annually thereafter. 11 out of 64 patients (17.2%) who underwent RCP had incidentally diagnosed PCa. 3 cases (27.3%) were diagnosed as significant PCa, while 8 cases (72.7%) were clinically insignificant. The positive surgical margin of PCa was detected in 1 patient with significant disease. The prostate apex involvement was present in 1 patient of the significant PCa group. Median follow-up period was 47.8 ± 29.2 (range 4-79). During the follow-up, biochemical recurrence occurred in 1 patient (9%). Concerning the cancer specific survival there was no statistical significance (P = 0.326) between the clinically significant and clinical insignificant cancer group. In line with published studies, incidental PCa does not impact on the prognosis of bladder cancer of patients undergoing RCP.

Extraprostatic Extension Is Extremely Rare for Contemporary Gleason Score 6 Prostate Cancer.

PubMed

Anderson, Blake B; Oberlin, Daniel T; Razmaria, Aria A; Choy, Bonnie; Zagaja, Gregory P; Shalhav, Arieh L; Meeks, Joshua J; Yang, Ximing J; Paner, Gladell P; Eggener, Scott E

2017-09-01

A significant proportion of men with Gleason score 6 (GS6) prostate cancer undergo treatment with radiation or surgery. To assess pathologic stage of pure GS6 at radical prostatectomy (RP). In the period 2003-2014, 7817 patients underwent RP at two institutions. Of 2502 patients with GS6 at surgery, 60 were identified as stage pT3a-b on initial pathologic review, 55 with pT3a (extraprostatic extension, EPE), and five with pT3b (seminal vesicle invasion; SVI). All cases of GS6 with pT3 disease underwent contemporary pathologic evaluation for Gleason grade, stage, and extent of EPE. At one institution, all GS≥7 pT3b cases were re-reviewed for downgrading. The 2014 International Society of Urological Pathology (ISUP) Gleason grading criteria and 2009 ISUP recommendations on pT3 staging were applied. Calculated incidence (%) of pT3a, pT3b, pT4, and lymph node-positive disease. Of the 60 GS6 pT3a-b cases identified in the period 2003-2014, seven (0.28% of entire GS6 cohort) with GS6 and pT3a were identified after re-review, all focal EPE. Among the re-examined cohort, no cases of GS6 with pT3b were observed. None of the 132 GS≥7 pT3b cases were downgraded to GS6. Limitations include partial embedding of specimens and separate pathologic review at each institution. In a large prostatectomy cohort, GS6 never had seminal vesicle invasion (0%) and was very rarely (0.28%) associated with extraprostatic extension. GS6 prostate cancer rarely spreads outside the prostate. A new finding in this study was that GS6 prostate cancer never spread to the seminal vesicles. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

CT-guided transgluteal biopsy for systematic sampling of the prostate in patients without rectal access: a 13-year single-center experience.

PubMed

Olson, Michael C; Atwell, Thomas D; Mynderse, Lance A; King, Bernard F; Welch, Timothy; Goenka, Ajit H

2017-08-01

The purpose of our study was to examine the safety and diagnostic utility of transgluteal CT-guided prostate biopsy for prostate sampling in patients without rectal access. Seventy-three biopsies were performed in 65 patients over a 13-year period (2002-2015). Mean prostate-specific antigen (PSA) at biopsy was 7.8 ng/mL (range 0.37-31.5). Electronic medical records were reviewed for procedural details and complications. Mean PSA and number of cores in malignant and benign cohorts were compared with Student's t test. Technical success rate was 97.3% (71/73; mean cores 8, range 3-28). Of these, 43.6% (31/71) yielded malignancy (mean Gleason score 7, range 6-10) and 56.3% (40/71) yielded benign tissue. The only complication was an asymptomatic periprostatic hematoma (1/73; 1.4%). In 14 patients who underwent surgery, Gleason scores were concordant in 71.4% (10/14) and discordant in 28.6% (4/14; Gleason 6 on biopsy but Gleason 7 on surgical specimen). Mean effective radiation dose was 18.5 mSv (median 15.0, range 4.4-86.2). There was no significant difference in either mean PSA (p = 0.06) or number of core specimens (p = 0.33) between malignant and benign cohorts. CT-guided transgluteal prostate biopsy is highly safe and reliable for the detection of prostate cancer in men without rectal access. • Prostate cancer detection in men without rectal access is challenging. • CT-guided transgluteal prostate biopsy is safe and effective in these patients. • CT-guided biopsy may be particularly effective in diagnosing high-grade prostate cancer. • Unilateral CT-guided biopsy may be effective in patients with focal lesions. • The radiation exposure with this technique is acceptable.

CD147 expression predicts biochemical recurrence after prostatectomy independent of histologic and pathologic features.

PubMed

Bauman, Tyler M; Ewald, Jonathan A; Huang, Wei; Ricke, William A

2015-07-25

CD147 is an MMP-inducing protein often implicated in cancer progression. The purpose of this study was to investigate the expression of CD147 in prostate cancer (PCa) progression and the prognostic ability of CD147 in predicting biochemical recurrence after prostatectomy. Plasma membrane-localized CD147 protein expression was quantified in patient samples using immunohistochemistry and multispectral imaging, and expression was compared to clinico-pathological features (pathologic stage, Gleason score, tumor volume, preoperative PSA, lymph node status, surgical margins, biochemical recurrence status). CD147 specificity and expression were confirmed with immunoblotting of prostate cell lines, and CD147 mRNA expression was evaluated in public expression microarray datasets of patient prostate tumors. Expression of CD147 protein was significantly decreased in localized tumors (pT2; p = 0.02) and aggressive PCa (≥pT3; p = 0.004), and metastases (p = 0.001) compared to benign prostatic tissue. Decreased CD147 was associated with advanced pathologic stage (p = 0.009) and high Gleason score (p = 0.02), and low CD147 expression predicted biochemical recurrence (HR 0.55; 95 % CI 0.31-0.97; p = 0.04) independent of clinico-pathologic features. Immunoblot bands were detected at 44 kDa and 66 kDa, representing non-glycosylated and glycosylated forms of CD147 protein, and CD147 expression was lower in tumorigenic T10 cells than non-tumorigenic BPH-1 cells (p = 0.02). Decreased CD147 mRNA expression was associated with increased Gleason score and pathologic stage in patient tumors but is not associated with recurrence status. Membrane-associated CD147 expression is significantly decreased in PCa compared to non-malignant prostate tissue and is associated with tumor progression, and low CD147 expression predicts biochemical recurrence after prostatectomy independent of pathologic stage, Gleason score, lymph node status, surgical margins, and tumor volume in multivariable analysis.

Effect of Prostate Magnetic Resonance Imaging/Ultrasound Fusion-guided Biopsy on Radiation Treatment Recommendations

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

Reed, Aaron; Valle, Luca F.; Shankavaram, Uma

Purpose: Targeted magnetic resonance imaging (MRI)/ultrasound fusion prostate biopsy (MRI-Bx) has recently been compared with the standard of care extended sextant ultrasound-guided prostate biopsy (SOC-Bx), with the former associated with an increased rate of detection of clinically significant prostate cancer. The present study sought to determine the influence of MRI-Bx on radiation therapy and androgen deprivation therapy (ADT) recommendations. Methods and Materials: All patients who had received radiation treatment and had undergone SOC-Bx and MRI-Bx at our institution were included. Using the clinical T stage, pretreatment prostate-specific antigen, and Gleason score, patients were categorized into National Comprehensive Cancer Network riskmore » groups and radiation treatment or ADT recommendations assigned. Intensification of the recommended treatment after multiparametric MRI, SOC-Bx, and MRI-Bx was evaluated. Results: From January 2008 to January 2016, 73 patients received radiation therapy at our institution after undergoing a simultaneous SOC-Bx and MRI-Bx (n=47 with previous SOC-Bx). Repeat SOC-Bx and MRI-Bx resulted in frequent upgrading compared with previous SOC-Bx (Gleason score 7, 6.7% vs 44.6%; P<.001; Gleason score 8-10, 2.1% vs 38%; P<.001). MRI-Bx increased the proportion of patients classified as very high risk from 24.7% to 41.1% (P=.027). Compared with SOC-Bx alone, including the MRI-Bx findings resulted in a greater percentage of pathologically positive cores (mean 37% vs 44%). Incorporation of multiparametric MRI and MRI-Bx results increased the recommended use and duration of ADT (duration increased in 28 of 73 patients and ADT was added for 8 of 73 patients). Conclusions: In patients referred for radiation treatment, MRI-Bx resulted in an increase in the percentage of positive cores, Gleason score, and risk grouping. The benefit of treatment intensification in accordance with the MRI-Bx findings is unknown.« less

BPH: a tell-tale sign of prostate cancer? Results from the Prostate Cancer and Environment Study (PROtEuS).

PubMed

Boehm, Katharina; Valdivieso, Roger; Meskawi, Malek; Larcher, Alessandro; Sun, Maxine; Sosa, José; Blanc-Lapierre, Audrey; Weiss, Deborah; Graefen, Markus; Saad, Fred; Parent, Marie-Élise; Karakiewicz, Pierre I

2015-12-01

In a population-based case-control study (PROtEuS), we examined the association between prostate cancer (PCa) and (1) benign prostatic hypertrophy (BPH) history at any time prior to PCa diagnosis, (2) BPH-history reported at least 1 year prior to interview/diagnosis (index date) and (3) exposure to BPH-medications. Cases were 1933 men with incident prostate cancer diagnosed across Montreal French hospitals between 2005 and 2009. Population controls were 1994 men from the same age distribution and residential area. In-person interviews collected socio-demographic characteristics and medical history, e.g., BPH diagnosis, duration and treatment, as well as on PCa screening. Logistic regression analyses tested overall and grade-specific associations, including subgroup analyses with frequent PSA testing. A BPH-history was associated with an increased risk of PCa (OR 1.37 [95 % CI 1.16-2.61]), more pronounced for low-grade PCa (Gleason ≤6: OR 1.54 [1.26-1.87]; Gleason ≥7: OR 1.05 [0.86-1.27]). The association was not significant when BPH-history diagnosis was more than 1 year prior to index date, except for low-grade PCa (OR 1.29 [1.05-1.60]). Exposure to 5α reductase inhibitors (5α-RI) resulted in a decreased risk of overall PCa (OR 0.62 [0.42-0.92]), particularly for intermediate- to high-grade PCa (Gleason ≤6: OR 0.70 [0.43-1.14]; Gleason ≥7: OR 0.43 [0.26-0.72]). Adjusting for PSA testing frequency or restricting analyses to frequently screened subjects did not affect these results. BPH-history was associated with an increased PCa risk, which disappeared, when BPH-history did not include BPH diagnosis within the previous year. Our results also suggest that 5α-RI exposure exerts a protective effect on intermediate and high-grade PCa.

Association between late-onset hypogonadism syndrome plus metabolic syndrome and prostate cancer and its aggressiveness.

PubMed

Fuentes-Pastor, J; Pellejero, P; Ortiz, I; Ramírez-Backhaus, M; de Gracia, A; Marrugo, C; Gomez-Ferrer, A; Calatrava, A; Rubio-Briones, J; Rodriguez-Torreblanca, C; Solsona-Narbón, E

2016-09-01

To assess the relationship between prostate cancer (PC) and the presence of metabolic syndrome and late-onset hypogonadism (LOH) syndrome. A retrospective study was conducted on 686 patients who underwent prostate biopsy. We analysed the demographic variables, clinical data and biopsy results. To diagnose metabolic syndrome, we employed the criteria of the American Heart Association. For the diagnosis of LOH syndrome, we employed the Androgen Deficiency in the Aging Male questionnaire and testosterone levels (TT). We evaluated the relationship between free testosterone (FT) and bioavailable testosterone (BT) on one hand and PC and its aggressiveness on the other, as well as the usefulness of the TT to prostate specific antigen (TT/PSA) ratio in the PC diagnosis. The patient's median age was 65 years. Metabolic syndrome is not associated with PC (39.4% vs. 35%; P=.1) but is associated with a PC Gleason score >7 (50.4% vs. 29.44%; P=.002). LOH, low FT and low BT are associated with an increased presence of PC (51% vs. 35%, P=.02; 44.86% vs. 33.33%, P=.03; and 46.46% vs. 33.08%, P=.01, respectively) and with an increased probability of a PC Gleason score >7 (61.54% vs. 37.5%, P=.02; 54.17% vs. 34.12%, P=.02; 54.35% vs. 34.48%, P=.02, respectively). Additionally, the median TT/PSA ratio was significantly lower in patients with positive biopsies (P=.022). Metabolic syndrome was not associated with the probability of having PC but was associated with a PC Gleason score >7. Moreover, LOH syndrome had a higher percentage of PC and a greater presence of PC Gleason scores >7, as did low levels of FT and low levels of BT. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Perineural invasion is associated with increased relapse after external beam radiotherapy for men with low-risk prostate cancer and may be a marker for occult, high-grade cancer.

PubMed

Beard, C J; Chen, M H; Cote, K; Loffredo, M; Renshaw, A A; Hurwitz, M; D'Amico, A V

2004-01-01

To investigate the risk of postradiotherapy prostate-specific antigen (PSA) failure on the basis of pretreatment risk factors in prostate cancer patients with and without perineural invasion (PNI) in prostate biopsy specimens and to explain the observation that otherwise low-risk patients with PNI experience decreased freedom from PSA failure after external beam radiotherapy (RT). The study cohort consisted of 381 patients who underwent RT between 1989 and 2000 for clinically localized prostate cancer. A single genitourinary pathologist scored the absence or presence of PNI on all prostate biopsy specimens. Patients were divided into low-, intermediate- and high-risk subgroups on the basis of their 1992 American Joint Committee on Cancer T-stage, pretreatment PSA level, and Gleason score. Cox regression uni- and multivariate analyses were performed to evaluate whether the presence or absence of PNI in the biopsy specimen was a predictor of the time to post-RT PSA failure for patients in each pretreatment risk group. PSA failure was defined using the American Society for Therapeutic Radiology and Oncology consensus definition. Actuarial PSA failure-free survival was estimated using the Kaplan-Meier method, and comparisons were performed using the log-rank test. Cox regression univariate analysis revealed that PNI was a significant predictor of the time to PSA failure in the low-risk (p = 0.04) and high-risk (p = 0.03) cohorts. The 5-year PSA failure-free survival rate was 50% vs. 80% (p = 0.04) in low-risk patients, 70% vs. 75% (p = 0.72) in intermediate-risk patients, and 29% vs. 53% (p = 0.03) in high-risk patients with and without PNI, respectively. Cox regression multivariate analysis within the high-risk group revealed that a PSA level > or =20 ng/mL (p = 0.01) and Gleason score > or =8 (p = 0.02), but not PNI, were the only significant predictors of the time to PSA failure after RT. However, an association was found between the presence of PNI in the needle biopsy specimen and a biopsy Gleason score of 8-10 (p = 0.06). The association was stronger between the presence of PNI in the needle biopsy specimen and a biopsy Gleason score of 7-10 (p = 0. 033). A decrement in PSA outcome after RT for low-risk patients with PNI-positive biopsy specimens was found. The association between PNI and high Gleason score provides a possible explanation for the loss of statistical significance of PNI in the Cox regression multivariate analysis of the high-risk cohort. The data suggest that PNI found in the biopsy specimen of an otherwise low-risk patient predicts for occult high-grade disease that is missed owing to the sampling error associated with prostate biopsy. The association between PNI and a high Gleason score argues for the use of more aggressive therapy, such as hormonal therapy with RT and/or dose escalation, in these select patients.

A prospective randomized multicentre study of the impact of gallium-68 prostate-specific membrane antigen (PSMA) PET/CT imaging for staging high-risk prostate cancer prior to curative-intent surgery or radiotherapy (proPSMA study): clinical trial protocol.

PubMed

Hofman, Michael S; Murphy, Declan G; Williams, Scott G; Nzenza, Tatenda; Herschtal, Alan; Lourenco, Richard De Abreu; Bailey, Dale L; Budd, Ray; Hicks, Rodney J; Francis, Roslyn J; Lawrentschuk, Nathan

2018-05-03

Accurate staging of patients with prostate cancer (PCa) is important for therapeutic decision-making. Relapse after surgery or radiotherapy of curative intent is not uncommon and, in part, represents a failure of staging with current diagnostic imaging techniques to detect disease spread. Prostate-specific membrane antigen (PSMA) positron-emission tomography (PET)/computed tomography (CT) is a new whole-body scanning technique that enables visualization of PCa with high contrast. The hypotheses of this study are that: (i) PSMA-PET/CT has improved diagnostic performance compared with conventional imaging; (ii) PSMA-PET/CT should be used as a first-line diagnostic test for staging; (iii) the improved diagnostic performance of PSMA-PET/CT will result in significant management impact; and (iv) there are economic benefits if PSMA-PET/CT is incorporated into the management algorithm. The proPSMA trial is a prospective, multicentre study in which patients with untreated high-risk PCa will be randomized to gallium-68-PSMA-11 PET/CT or conventional imaging, consisting of CT of the abdomen/pelvis and bone scintigraphy with single-photon emission CT/CT. Patients eligible for inclusion are those with newly diagnosed PCa with select high-risk features, defined as International Society of Urological Pathology grade group ≥3 (primary Gleason grade 4, or any Gleason grade 5), prostate-specific antigen level ≥20 ng/mL or clinical stage ≥T3. Patients with negative, equivocal or oligometastatic disease on first line-imaging will cross over to receive the other imaging arm. The primary objective is to compare the accuracy of PSMA-PET/CT with that of conventional imaging for detecting nodal or distant metastatic disease. Histopathological, imaging and clinical follow-up at 6 months will define the primary endpoint according to a predefined scoring system. Secondary objectives include comparing management impact, the number of equivocal studies, the incremental value of second-line imaging in patients who cross over, the cost of each imaging strategy, radiation exposure, inter-observer agreement and safety of PSMA-PET/CT. Longer-term follow-up will also assess the prognostic value of a negative PSMA-PET/CT. This trial will provide data to establish whether PSMA-PET/CT should replace conventional imaging in the primary staging of select high-risk localized PCa, or whether it should be used to provide incremental diagnostic information in selected cases. © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.

The relationship of TMPRSS2-ERG gene fusion between primary and metastatic prostate cancers.

PubMed

Guo, Charles C; Wang, Yan; Xiao, Li; Troncoso, Patricia; Czerniak, Bogdan A

2012-05-01

Recent studies have revealed the presence of TMPRSS2-ERG gene fusion in both primary and metastatic prostate cancers. However, the relationship between primary and corresponding metastatic prostate cancers with respect to the status of this gene fusion remains unclear. Using fluorescence in situ hybridization, we evaluated the rearrangement of the ERG gene in the radical prostatectomy specimens and corresponding lymph node metastases from 19 patients with prostate cancer. The mean age of the patients was 61 years, and the median Gleason score in the radical prostatectomy specimens was 7 (4 + 3). Prostate cancer was unifocal in 6 cases and multifocal in 13 cases, including 10 with 2 foci and 3 with 3 foci. In the primary prostate cancers, rearrangement of the ERG gene was observed in 13 cases and associated with deletion of the 5' ERG gene in 8 cases. In the metastases, the ERG rearrangement was present in 10 cases and associated with deletion of the 5' ERG gene in 6 cases. In unifocal prostate cancers, the status of the ERG rearrangement was concordant between the primary prostate cancer and metastasis in 5 of 6 cases. In multifocal prostate cancer, despite a significant interfocal discordance, the status of the ERG rearrangement was concordant between the index (largest) primary tumor focus and metastasis in all 13 cases. Our study demonstrates a close relationship of the TMPRSS2-ERG gene fusion status between primary and metastatic prostate cancer. The concordance of the ERG gene rearrangement status between the index primary tumor focus and metastasis suggests that metastasis most likely arises from the index tumor focus in multifocal prostate cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

Immunohistochemical differentiation of high-grade prostate carcinoma from urothelial carcinoma.

PubMed

Chuang, Ai-Ying; DeMarzo, Angelo M; Veltri, Robert W; Sharma, Rajni B; Bieberich, Charles J; Epstein, Jonathan I

2007-08-01

The histologic distinction between high-grade prostate cancer and infiltrating high-grade urothelial cancer may be difficult, and has significant implications because each disease may be treated very differently (ie, hormone therapy for prostate cancer and chemotherapy for urothelial cancer). Immunohistochemistry of novel and established prostatic and urothelial markers using tissue microarrays (TMAs) were studied. Prostatic markers studied included: prostate-specific antigen (PSA), prostein (P501s), prostate-specific membrane antigen (PSMA), NKX3.1 (an androgen-related tumor suppressor gene), and proPSA (pPSA) (precursor form of PSA). "Urothelial markers" included high molecular weight cytokeratin (HMWCK), p63, thrombomodulin, and S100P (placental S100). TMAs contained 38 poorly differentiated prostate cancers [Gleason score 8 (n=2), Gleason score 9 (n=18), Gleason score 10 (n=18)] and 35 high-grade invasive urothelial carcinomas from radical prostatectomy and cystectomy specimens, respectively. Each case had 2 to 8 tissue spots (0.6-mm diameter). If all spots for a case showed negative staining, the case was called negative. The sensitivities for labeling prostate cancers were PSA (97.4%), P501S (100%), PSMA (92.1%), NKX3.1 (94.7%), and pPSA (94.7%). Because of PSA's high sensitivity on the TMA, we chose 41 additional poorly differentiated primary (N=36) and metastatic (N=5) prostate carcinomas which showed variable PSA staining at the time of diagnosis and performed immunohistochemistry on routine tissue sections. Compared to PSA, which on average showed 18.8% of cells with moderate to strong positivity, cases stained for P501S, PSMA, and NKX3.1 had on average 42.5%, 53.7%, 52.9% immunoreactivity, respectively. All prostatic markers showed excellent specificity. HMWCK, p63, thrombomodulin, and S100P showed lower sensitivities in labeling high-grade invasive urothelial cancer in the TMAs with 91.4%, 82.9%, 68.6%, and 71.4% staining, respectively. These urothelial markers were relatively specific with only a few prostate cancers showing scattered (

Quantum probability rule: a generalization of the theorems of Gleason and Busch

NASA Astrophysics Data System (ADS)

Barnett, Stephen M.; Cresser, James D.; Jeffers, John; Pegg, David T.

2014-04-01

Busch's theorem deriving the standard quantum probability rule can be regarded as a more general form of Gleason's theorem. Here we show that a further generalization is possible by reducing the number of quantum postulates used by Busch. We do not assume that the positive measurement outcome operators are effects or that they form a probability operator measure. We derive a more general probability rule from which the standard rule can be obtained from the normal laws of probability when there is no measurement outcome information available, without the need for further quantum postulates. Our general probability rule has prediction-retrodiction symmetry and we show how it may be applied in quantum communications and in retrodictive quantum theory.

Concepts of epigenetics in prostate cancer development.

PubMed

Cooper, C S; Foster, C S

2009-01-27

Substantial evidence now supports the view that epigenetic changes have a role in the development of human prostate cancer. Analyses of the patterns of epigenetic alteration are providing important insights into the origin of this disease and have identified specific alterations that may serve as useful diagnostic and prognostic biomarkers. Examination of cancer methylation patterns supports a stem cell origin of prostate cancer. It is well established that methylation of GSTpi is a marker of prostate cancer, and global patterns of histone marking appear to be linked to cancer prognosis with levels of acetylated histones H3K9, H3K18, and H4K12, and of dimethylated H4R3 and H3K4, dividing low-grade prostate cancer (Gleason 6 or less) into two prognostically separate groups. Elevated levels of several components of the polycomb group protein complex, EZH2, BMI1, and RING1, can also act as biomarkers of poor clinical outcome. Many components of the epigenetic machinery, including histone deacetylase (whose expression level is linked to the TMPRSS2:ERG translocation) and the histone methylase EZH2, are potential therapeutic targets. The recent discovery of the role of small RNAs in governing the epigenetic status of individual genes offers exciting new possibilities in therapeutics and chemoprevention.

Outcome According to Elective Pelvic Radiation Therapy in Patients With High-Risk Localized Prostate Cancer: A Secondary Analysis of the GETUG 12 Phase 3 Randomized Trial

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

Blanchard, Pierre, E-mail: pierre.blanchard@gustaveroussy.fr; University of Paris-Sud, Cancer Campus, Villejuif; Faivre, Laura

Purpose: The role of pelvic elective nodal irradiation (ENI) in the management of prostate cancer is controversial. This study analyzed the role of pelvic radiation therapy (RT) on the outcome in high-risk localized prostate cancer patients included in the Groupe d'Etude des Tumeurs Uro-Genitales (GETUG) 12 trial. Methods and Materials: Patients with a nonpretreated high-risk localized prostate cancer and a staging lymphadenectomy were randomly assigned to receive either goserelin every 3 months for 3 years and 4 cycles of docetaxel plus estramustine or goserelin alone. Local therapy was administered 3 months after the start of systemic treatment. Performance of pelvic ENI was leftmore » to the treating physician. Only patients treated with primary RT were included in this analysis. The primary endpoint was biochemical progression-free survival (bPFS). Results: A total of 413 patients treated from 2002 to 2006 were included, of whom 358 were treated using primary RT. A total of 208 patients received pelvic RT and 150 prostate-only RT. Prostate-specific antigen (PSA) concentration, Gleason score, or T stage did not differ according to performance of pelvic RT; pN+ patients more frequently received pelvic RT than pN0 patients (P<.0001). Median follow-up was 8.8 years. In multivariate analysis, bPFS was negatively impacted by pN stage (hazard ratio [HR]: 2.52 [95% confidence interval [CI]: 1.78-3.54], P<.0001), Gleason score 8 or higher (HR: 1.41 [95% CI: 1.03-1.93], P=.033) and PSA higher than 20 ng/mL (HR: 1.41 [95% CI: 1.02-1.96], P=.038), and positively impacted by the use of chemotherapy (HR: 0.66 [95% CI: 0.48-0.9], P=.009). There was no association between bPFS and use of pelvic ENI in multivariate analysis (HR: 1.10 [95% CI: 0.78-1.55], P=.60), even when analysis was restricted to pN0 patients (HR: 0.88 [95% CI: 0.59-1.31], P=.53). Pelvic ENI was not associated with increased acute or late patient reported toxicity. Conclusions: This unplanned analysis of a randomized trial failed to demonstrate a benefit of pelvic ENI on bPFS in high-risk localized prostate cancer patients.« less

Evaluation of urinary prostate cancer antigen-3 (PCA3) and TMPRSS2-ERG score changes when starting androgen-deprivation therapy with triptorelin 6-month formulation in patients with locally advanced and metastatic prostate cancer.

PubMed

Martínez-Piñeiro, Luis; Schalken, Jack A; Cabri, Patrick; Maisonobe, Pascal; de la Taille, Alexandre

2014-10-01

To assess prostate cancer antigen-3 (PCA3) and TMPRSS2-ERG scores in patients with advanced and metastatic prostate cancer at baseline and after 6 months of treatment with triptorelin 22.5 mg, and analyse these scores in patient-groups defined by different disease characteristics. The Triptocare study was a prospective, open-label, multicentre, single-arm, Phase III study of triptorelin 22.5 mg in men with locally advanced or metastatic prostate cancer, who were naïve to androgen-deprivation therapy (ADT). The primary objective was to model the urinary PCA3 change at 6 months, according to baseline variables. Other outcome measures included urinary PCA3 and TMPRSS2-ERG scores and statuses, and serum testosterone and prostate-specific antigen (PSA) levels at baseline and at 1, 3 and 6 months after initiation of ADT. Safety was assessed by recording adverse events and changes in laboratory parameters. The intent-to-treat population comprised 322 patients; 39 (12.1%) had non-assessable PCA3 scores at baseline, and 109/322 (33.9%), 215/313 (68.7%) and 232/298 (77.9%) had non-assessable PCA3 scores at 1, 3 and 6 months, respectively. Baseline Gleason score was the only variable associated with non-assessability of PCA3 score at 6 months (P = 0.017) - the hazard of having a non-assessable PCA3 score at 6 months was 1.824-fold higher (95% confidence interval 1.186-2.805) in patients with a Gleason score ≥8 vs those with a Gleason score ≤6. The median PCA3 scores at baseline were significantly higher in patients aged ≥65 years vs those aged <65 years and in patients with a serum PSA level <100 ng/mL vs those with serum PSA level of >200 ng/mL. The median PCA3 score was significantly lower in patients with metastasis than in patients with no metastasis or unknown metastasis status. TMPRSS2-ERG scores ≥35 were considered positive (n = 149 [51.6%]). Age, presence of metastasis, PSA level and Gleason score at baseline were not associated with a significant difference in the proportion of TMPRSS2-ERG-positive scores. The median serum PSA levels decreased from 45.5 ng/mL at baseline to 1.2 ng/mL after 6 months, and as expected, >90% of patients achieved castrate levels of testosterone (<50 ng/dL) at 1, 3, and 6 months during triptorelin treatment. The safety profile reported from this study is consistent with the known safety profile of triptorelin. These data from the Triptocare study suggest that urinary PCA3 or TMPRSS2-ERG score are not reliable markers of cancer stage in advanced prostate cancer. Urinary PCA3 and TMPRSS2-ERG scores do not appear to be useful in assessing response to ADT in advanced prostate cancer, with most patients having non-assessable scores after 6 months of treatment. © 2013 The Authors. BJU International © 2013 BJU International.

Diagnostic Performance of Multiparametric Magnetic Resonance Imaging and Fusion Targeted Biopsy to Detect Significant Prostate Cancer.

PubMed

Hoffmann, Manuela A; Taymoorian, Kasra; Ruf, Christian; Gerhards, Arnd; Leyendecker, Karlheinz; Stein, Thomas; Jakobs, Frank M; Schreckenberger, Mathias

2017-12-01

Multiparametric magnetic resonance imaging combined with ultrasound-fusion-targeted biopsy of the prostate intends to increase diagnostic precision, which has to be clarified. We performed multiparametric magnetic resonance imaging followed by ultrasound-fusion-guided perineal biopsy in 99 male patients with elevated prostate-specific-antigen and previous negative standard biopsy-procedures. In 33/99 patients (33%) no malignancy could be confirmed by histopathology. Low-grade carcinomas (Gleason-Score 6+7a) were found in 42/66 (64%) and high-grade carcinomas (Gleason-Score ≥7b) in 24/66 (36%) men. A high-grade carcinoma corresponded to PI-RADS 4 or 5 (suspected malignancy) in 21/24 cases, which accounted for a sensitivity of 88% and negative-predictive-value of 85% (p=0.002). Differentiation between high-/low-grade carcinomas (Gleason-Score ≤7a vs. ≥7b) by means of PI-RADS related to a sensitivity of 88% and a negative-predictive-value of 70% (p=0.74). The results support the view that multiparametric magnetic resonance imaging/ultrasound-fusion-guided biopsy promotes considerably higher detection rates of clinically relevant prostate malignancies than do conventional diagnostic procedures. With regard to differentiation between high- and low-grade carcinomas, no significant difference was demonstrated. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Modulated plasma deposition of super hydrophobic fluorinated coatings

NASA Astrophysics Data System (ADS)

Favia, Pietro

2002-10-01

Modulated (pulsed) RF glow discharges fed with unsaturated fluorocarbons originate often films with superior characteristics and remarkable monomer structure retention degree. Properties such as low dielectric constant, low friction coefficient, high flexibility and high hydrophobic character can be granted by such coatings, as well as applications in textiles, packaging, biomaterials, microelectronics and other fields [1-4]. Albeit the surface chemistry of fluorinated films has been extensively analysed, very few works deal with the investigation of the plasma phase and of the material morphology and crystalline. We present our last results on the plasma deposition of coatings from modulated glow discharges fed with tetrafluoroethylene. Period and Duty Cycle (DC) have been changed in the range 20-200 ms and 2-100%, respectively. Chemical composition and structure of the coatings were determined by means of XPS, SIMS, FT-IR and XRD measurements; SEM and AFM allowed morphological investigations. The diagnostics of the gas phase was carried out by time resolved (TR) OES [5] and by IR-AS diagnostics [6]. At low DC (< 10%) a unique morphology is observed at the surface of the films, in form of ribbon-like features many microns long and hundreds of nanometers wide, whose surface density increases at lower DC values. XPS has been used to determine the surface fluorine to carbon ratio of the coatings; best-fitting procedures of the C1s signals have been also carried out. XPS and SIMS results show a high F/C ratio and a chemical structure close to conventional PTFE for samples with ribbon-like features. Due to the combined presence of structures and high fluorination degree, structured surfaces revealed very high hydrophobic character (Water Contact Angle > 150^o). XRD patterns of the structured coatings exhibited a diffraction peak at 2Θ = 18^o, characteristic of crystalline PTFE [4, 6]; this finding, and the presence of the structures, open questions about the deposition mechanism of such unique materials, which still need to be rationalized. In order to understand the deposition mechanism of unstructured and structured coatings, spectroscopic diagnostics of the plasma phase has been carried out by TR-OES and IR-AS. TR-OES results reveals only CF2 emitting radicals (A16B_1-X^1A1 230-340 nm; ^3B_1-^1A1 340-450 nm systems), whose evolution trends during time on of the discharge are clearly dependent on the DC value. TR-OES allowed to distinguish between two different deposition regimes which give origin (low DC) or not (high DC) to structured coatings, respectively. References [1] V. Panchalingam, B. Poon, H.H. Huo, C.R. Savage, R.B. Timmons, R.C. Eberhart; J. Biomat. Sci. Polym. Ed. 5, (1993) 131, [2] S.J. Limb, K.K. Gleason, D.J. Edell, E.F. Gleason; J. Vac. Sci. Tech. A 15, (1997) 1814, [3] S.R. Coulson, I.S. Woodward, S.A. Brewer, C.Willis, J.P.S. Badyal; Chem. Mater. 12, (2000) 2031, [4] S.J. Limb, K.K.S. Lau, D.J. Edell, E.F. Gleason, K.K. Gleason; Plasmas and Polymers 4, (1999) 21 [5] M. Creatore, F. Palumbo, R. d'Agostino P. Fayet - Surface & Coatings Technology 142, (2001) 163 [6] G. Cicala, A. Milella, F. Palumbo, P. Favia and R. d'Agostino Appl. Phys. Lett. (submitted)

Hepatic and skin metastases after laparoscopic radical prostatectomy for prostate cancer.

PubMed

Coman, Ioan; Crişan, Nicolae; Petrut, Bogdan; Bungărdean, Cătălina; Cristea, Tudor; Crişan, Dana

2007-09-01

Between 2004 and 2006, 50 radical prostatectomies were performed in our department, 46 of them through a laparoscopic approach addressed to early stage cancer (T1a,b,c and T2a,b,c N0 M0). We present the case of a 63 year old patient, who was initially diagnosed with prostate cancer in T1bN0M0 stage, Gleason score 8 and later presented atypical hepatic and trocar site metastases. This particular evolution of the case can be explained by the high value of the Gleason score and by the extension into microvessels observed on the sample prelevated by prostatectomy. The rarity of this atypical metastases and its association, the diagnostic and therapy problems are the reasons for the detailed presentation of this case.

How Precisely Can Prostate Cancer Be Managed?

PubMed Central

2016-01-01

Progress has been made in applying genetic information to disease management in the postgenomic era, and precision medicine is emerging in prostate cancer management. The prostate health index, the 4-kallikrein (4K) score, and the PCA3, TMPRSS2-ERG, and Prostarix tests have potential for refining prostate cancer screening in conjunction with traditional prostate-specific antigen testing. The Confirm MDx and PCA3 tests have shown promise in identifying men who need be rebiopsied after a primary negative biopsy. Oncotype DX, Prolaris, the biopsy-based Decipher prostate cancer test, and ProMark may improve predictive risk stratification in addition to the traditional Gleason score and tumor stage. Decipher and Prolaris may predict biochemical recurrence and metastasis after radical prostatectomy and possibly help identify patients who need adjuvant therapy. Androgen receptor splice variant 7 appears effective in guiding the selection of second hormonal manipulation with abiraterone or enzalutamide versus chemotherapy when treating metastatic castration-resistant prostate cancer. PMID:27915475

Fusion of multi-parametric MRI and temporal ultrasound for characterization of prostate cancer: in vivo feasibility study

NASA Astrophysics Data System (ADS)

Imani, Farhad; Ghavidel, Sahar; Abolmaesumi, Purang; Khallaghi, Siavash; Gibson, Eli; Khojaste, Amir; Gaed, Mena; Moussa, Madeleine; Gomez, Jose A.; Romagnoli, Cesare; Cool, Derek W.; Bastian-Jordan, Matthew; Kassam, Zahra; Siemens, D. Robert; Leveridge, Michael; Chang, Silvia; Fenster, Aaron; Ward, Aaron D.; Mousavi, Parvin

2016-03-01

Recently, multi-parametric Magnetic Resonance Imaging (mp-MRI) has been used to improve the sensitivity of detecting high-risk prostate cancer (PCa). Prior to biopsy, primary and secondary cancer lesions are identified on mp-MRI. The lesions are then targeted using TRUS guidance. In this paper, for the first time, we present a fused mp-MRI-temporal-ultrasound framework for characterization of PCa, in vivo. Cancer classification results obtained using temporal ultrasound are fused with those achieved using consolidated mp-MRI maps determined by multiple observers. We verify the outcome of our study using histopathology following deformable registration of ultrasound and histology images. Fusion of temporal ultrasound and mp-MRI for characterization of the PCa results in an area under the receiver operating characteristic curve (AUC) of 0.86 for cancerous regions with Gleason scores (GSs)>=3+3, and AUC of 0.89 for those with GSs>=3+4.

High concordance of findings obtained from transgluteal magnetic resonance imaging - and transrectal ultrasonography-guided biopsy as compared with prostatectomy specimens.

PubMed

Steurer, Stefan; Rico, Sebastian Dwertmann; Simon, Ronald; Minner, Sarah; Tsourlakis, Maria Christina; Krech, Till; Koop, Christina; Graefen, Markus; Heinzer, Hans; Adam, Meike; Huland, Hartwig; Schlomm, Thorsten; Sauter, Guido; Lumiani, Agron

2017-09-01

To determine the utility of our transgluteal magnetic resonance imaging (MRI)-guided prostate biopsy approach. A total of 960 biopsy series, taken within the period of 1 year, were evaluated, including 301 MRI-guided and 659 transrectal ultrasonography (TRUS)-guided biopsies. The positivity rate and proportion of high grade cancers were significantly higher in MRI-guided than in TRUS-guided biopsies. Of 301 MRI-guided biopsies, 65.4% contained cancer while 57.2% of 659 TRUS biopsies contained cancer (P = 0.016). Gleason grade 3 + 3 = 6 disease was observed in 16.8% of 197 MRI-guided and in 36.1% of 377 TRUS-guided biopsies (P < 0.001). There was also a markedly higher quantity of cancer tissue in MRI-guided biopsies. In all cancers, the mean cancer surface area was 64.8 ± 51.6 mm 2 in MRI-guided biopsies as compared with 23.0 ± 31.4 mm 2 in non-MRI-guided biopsies (P < 0.001). With respect to the tissue quantity, superiority of MRI-guided biopsy was highest in Gleason grade 3 + 3 = 6 cancers (20.9 ± 27.9 vs 5.1 ± 10.2 mm 2 ; P < 0.001) and in Gleason grade 3 + 4 = 7 cancers (59.7 ± 38.0 vs 17.7 ± 18.4 mm 2 ; P < 0.001). Comparison of biopsy Gleason grades with findings in prostatectomy specimens was possible in 80 patients with MRI-guided and in 170 patients with non-MRI-guided biopsies. This comparison showed a very high but almost identical concordance of TRUS- and MRI-guided biopsies with the prostatectomy specimen findings. With both approaches, undetected high-risk cancers were present in ~10% of patients with low-risk biopsy results. A significant difference was observed, however, in the proportion of patients who had clinically insignificant cancers and who underwent surgery. The proportion of patients with Gleason grade 3 + 3 = 6 carcinoma in their prostatectomy specimen was 11.2% in the post-TRUS biopsy cohort, but only 2.5% in the post-MRI biopsy cohort (P = 0.021). MRI-guided transgluteal prostate biopsy has a high detection rate for high-risk carcinomas, while the risk of detecting clinically insignificant carcinomas appears to be reduced. This may by itself lead to a reduction of unnecessary prostatectomies. Overtreatment may be further avoided by better applicability of molecular testing to MRI-guided biopsies because of the excessive amount of tissue available for analysis, especially in patients with potential low-risk carcinomas. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Reconstructing air temperature and permafrost attributes associated with past periglacial structures: a case study for sorted nets from the Krkonoše Mts., Czech Republic

NASA Astrophysics Data System (ADS)

Uxa, Tomáš; Křížek, Marek; Krause, David

2017-04-01

Many regions of the world host a number relict periglacial landforms that have been inherited from colder periods of the Quaternary. So far, these assemblages have been used to reconstruct former environmental conditions particularly in two basic manners. One is to search for a representative analogue in present-day periglacial environments. Second is based on present climatic context of active landforms (Ballantyne and Harris, 1994). Unfortunately, numerous problems arise with both approaches and therefore, the reconstructions are frequently considered as unreliable. Consequently, most periglacial phenomena have been widely accepted only as indicators of seasonally freezing or permafrost conditions and ground-ice presence, but this may also be dubious and rather tentative in some cases. On the other hand, many theoretical, physically-based studies have emerged in the last few decades that aimed to explain the formation of some periglacial landforms, such as patterned ground. The investigations focused on patterned-ground formation have shown that the length scale of the patterns is more-or-less of the same size as the length scale that initiates the patterns, i.e. the frost depth in seasonally frozen regions and the thaw depth in permafrost areas, respectively. Importantly, the diameter-to-sorting depth ratio of the resulting patterns is constant, of c. 3.1 to 3.8 under subaerial conditions (Ray et al., 1983; Gleason et al., 1986; Hallet and Prestrud, 1986), and of the same value regardless of the formation mechanism as well. These findings clearly indicate direct coupling between patterned-ground geometry and both ground and air temperature conditions at the time when the pattern first developed (Peterson and Krantz, 2008). Hence, if these genetic rules are adopted then the temperature attributes during the pattern initiation can be inferred via the sorting depth, which closely approximates former frost or thaw depth, respectively. In this contribution, we aim to infer the palaeo-temperature and palaeo-permafrost conditions associated with relict large-scale sorted nets in the Krkonoše Mts., Czech Republic. To achieve this, we employ a multi-disciplinary approach consisting of the Monte Carlo simulation based on a simple equilibrium thermal model, the Stefan equation, in an inverse form, driven by data obtained from remote sensing, geophysical soundings, and modern analogues from elsewhere. The results are subjected to a comprehensive uncertainty and sensitivity analysis. We introduce a robust, yet straightforward and easy-to-follow procedure to utilize these periglacial phenomena and other structures indicative of the base of palaeo-active layer to reconstruct former climate. Acknowledgement The research is supported by the Czech Science Foundation, project number 17-21612S. References Ballantyne, C. K., and Harris, C.: The Periglaciation of Great Britain, Cambridge University Press, Cambridge, UK, 1994. Gleason, K. J., Krantz, W. B., Caine, N., George, J. H., and Gunn, R. D.: Geometrical Aspects of Sorted Patterned Ground in Recurrently Frozen Soil, Science, 232, 216-220, doi: 10.1126/science.232.4747.216, 1986. Hallet, B., and Prestrud, S.: Dynamics of periglacial sorted circles in Western Spitsbergen, Quaternary Res., 26, 81-99, doi: 10.1016/0033-5894(86)90085-2, 1986. Ray, R. J., Krantz, W. B., Caine, T. N., and Gunn, R. D.: A model for sorted patterned-ground regularity, J. Glaciol., 29, 317-337, doi: 10.3198/1983JoG29-102-317-337, 1983. Peterson, R. A., and Krantz, W. B.: Differential frost heave model for patterned ground formation: Corroboration with observations along a North American arctic transect, J. Geophys. Res., 113, G03S04, doi: 10.1029/2007JG000559, 2008.

High-intensity focused ultrasound (HIFU) in prostate cancer: a single centre experience in patients with low, intermediate or high-risk of progression.

PubMed

Callea, Andrea; Piccinni, Roberto; Zizzi, Vito; Sblendorio, Domenico; Berardi, Bartolomeo; Tempesta, Antonio; Gala, Francesco Giuseppe; Traficante, Antonio

2010-12-01

High-intensity focused ultrasound (HIFU) is a minimally invasive treatment based on thermal ablation of tissues which are warmed up to 85 degrees C in the focal area. Clinical studies have shown such treatment modality to be safe and effective in the management of localised prostate cancer as well as of local recurrences after radical prostatectomy or radiotherapy. From May 2002 to June 2010, 171 patients with no previous treatment for prostate cancer, aged 44 to 86 years (mean 74.7) underwent 197 HIFU treatments; 22 patients needed a second treatment as the first was incomplete (4 patients) or because of recurrence (18 patients). The prognosis subgroups were defined as low-risk in 29 patients (clinical stage T1-T2a, PSA < or = 10 ng/mL and Gleason score lower than 7), intermediate-risk in 47 patients (clinical stage T2b or PSA 10 - 20 ng/mL or Gleason score of 7), and high-risk in 95 patients (clinical stage > or = T2c or PSA > 20 ng/mL or Gleason score higher than 7). At a mean follow-up of 67.9 months, biochemical success rate (PSA constantly < 0.5 ng/ml) was obtained in 84.2% of low and intermediate risk patients and in 43.1% of high risk patients; post-treatment biopsies (6 months after treatment) revealed no residual tumour in 93.4% of low or intermediate risk patients and in 63.1% of high risk patients. Radical prostatectomy remains the "gold standard" for localised prostate cancer. However, HIFU seems to be a promising alternative and less invasive treatment modality with an encouraging success rate, at least in the short-term, in patients with low and medium risk of progression, not candidates for radical surgery; in cancers with clinical stage > or = T2c, or PSA > 20 ng/mL, or Gleason score higher than 7 seems to get good results in about half of patients.

Pathological and 3 Tesla Volumetric Magnetic Resonance Imaging Predictors of Biochemical Recurrence after Robotic Assisted Radical Prostatectomy: Correlation with Whole Mount Histopathology.

PubMed

Tan, Nelly; Shen, Luyao; Khoshnoodi, Pooria; Alcalá, Héctor E; Yu, Weixia; Hsu, William; Reiter, Robert E; Lu, David Y; Raman, Steven S

2018-05-01

We sought to identify the clinical and magnetic resonance imaging variables predictive of biochemical recurrence after robotic assisted radical prostatectomy in patients who underwent multiparametric 3 Tesla prostate magnetic resonance imaging. We performed an institutional review board approved, HIPAA (Health Insurance Portability and Accountability Act) compliant, single arm observational study of 3 Tesla multiparametric magnetic resonance imaging prior to robotic assisted radical prostatectomy from December 2009 to March 2016. Clinical, magnetic resonance imaging and pathological information, and clinical outcomes were compiled. Biochemical recurrence was defined as prostate specific antigen 0.2 ng/cc or greater. Univariate and multivariate regression analysis was performed. Biochemical recurrence had developed in 62 of the 255 men (24.3%) included in the study at a median followup of 23.5 months. Compared to the subcohort without biochemical recurrence the subcohort with biochemical recurrence had a greater proportion of patients with a high grade biopsy Gleason score, higher preoperative prostate specific antigen (7.4 vs 5.6 ng/ml), intermediate and high D'Amico classifications, larger tumor volume on magnetic resonance imaging (0.66 vs 0.30 ml), higher PI-RADS® (Prostate Imaging-Reporting and Data System) version 2 category lesions, a greater proportion of intermediate and high grade radical prostatectomy Gleason score lesions, higher pathological T3 stage (all p <0.01) and a higher positive surgical margin rate (19.3% vs 7.8%, p = 0.016). On multivariable analysis only tumor volume on magnetic resonance imaging (adjusted OR 1.57, p = 0.016), pathological T stage (adjusted OR 2.26, p = 0.02), positive surgical margin (adjusted OR 5.0, p = 0.004) and radical prostatectomy Gleason score (adjusted OR 2.29, p = 0.004) predicted biochemical recurrence. In this cohort tumor volume on magnetic resonance imaging and pathological variables, including Gleason score, staging and positive surgical margins, significantly predicted biochemical recurrence. This suggests an important new imaging biomarker. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Treatment of prostate cancer cell lines and primary cells using low temperature plasma

NASA Astrophysics Data System (ADS)

O'Connell, Deborah; Hirst, Adam; Frame, Fiona F.; Maitland, Norman J.

2014-10-01

The mechanisms of cell death after plasma treatment of both benign and cancerous prostate epithelial cells are investigated. Prostate cancer tissue was obtained with patient consent from targeted needle core biopsies following radical prostatectomy. Primary cells were cultured from cancer tissue and plated onto a chamber slide at a density of 10,000 cells per well in 200 microliter of stem cell media (SCM). The treated sample was previously identified as Gleason grade 7 cancer through tissue histo-pathology. A dielectric barrier discharge (DBD) jet configuration, with helium as a carrier gas, and 0.3% O2 admixture was used for treating the cells. Reactive oxygen and nitrogen species (RONS) produced by the plasma are believed to be the main mediators of the plasma-cell interaction and response. We found the concentration of reactive oxygen species (ROS) induced inside the cells increased with plasma exposure. Exposure to the plasma for >3 minutes showed high levels of DNA damage compared to untreated and hydrogen peroxide controls. Cell viability and cellular recovery are also investigated and will be presented. All findings were common to both cell lines, suggesting the potential of LTP therapy for both benign and malignant disease.

Pieter Gagnon | NREL

Science.gov Websites

. Improving our understanding of how retail electricity tariffs may evolve, as the bulk power system changes Mike Gleason. 2017. The Impacts of Changes to Nevada's Net Metering Policy on the Financial Performance

Understanding Prostate Changes

Cancer.gov

Prostate changes and symptoms that are not cancer. Learn about symptoms, risk factors, and treatment for prostatitis, enlarged prostate (BPH), prostate cancer. Talk with doctor about prostate cancer screening tests (DRE, PSA), biopsy, and Gleason score.

Metabolic syndrome is not associated with greater evidences of proliferative inflammatory atrophy and inflammation in patients with suspected prostate cancer.

PubMed

Russo, Giorgio I; Cimino, Sebastiano; Giranio, Giorgia; Regis, Federica; Favilla, Vincenzo; Privitera, Salvatore; Motta, Fabio; Caltabiano, Rosario; Stenzl, Arnulf; Todenhöfer, Tilman; Morgia, Giuseppe

2018-05-01

To evaluate the association between metabolic syndrome (MetS) and proliferative inflammatory atrophy (PIA) in patients with suspected prostate cancer (PCa). From June 2015 to July 2016, we conducted the FIERY (Flogosis Increased Events of pRostatic biopsY) study at the Urology section, Department of Surgery of the University of Catania (Local registration number: #131/2015). A total of 205 patients with elevated prostate-specific antigen (≥ 4 ng/ml) or clinical suspicion of PCa who underwent primary transperineal prostate biopsy were included in this cross-sectional study. The assessment of PIA, HGPIN, and PCa were performed by 2 experienced pathologists and samples were investigated for the presence of an inflammatory infiltrate, according to the Irani score. Primary and secondary Gleason grade of tumor in positive biopsies were evaluated according to the 2016 ISUP Modified Gleason System. In the entire cohort, median age was 68.0 (interquartile range: 62.0-74.5), median prostate-specific antigen was 6.5 (interquartile range: 5.51-9.57). The prevalence of MetS was 34.1%, the detection rate of PCa was 32.7%, the rate of PIA was 28.3%, the rate of HGPIN was 32.2%, whereas the rate of severe intraprostatic inflammation (Irani-score ≥4) was 28.8%. When comparing clinical and histological variables in patients without and with PIA, metabolic aberrations where not significantly different in both groups. We did not find statistical association in detection rate of PCa (29.3% vs. 34.0%; P = 0.07) and HGPIN (27.6% vs. 34.0%; P = 0.37) in patients with and without PIA, respectively. When considering metabolic aberrations, MetS was not associated with Irani-score ≥4 (28.6% vs. 28.4%; P = 0.96) and none of each component was statistically predictive of severe inflammation. At the multivariable logistic regression analysis, PIA, HGPIN, and MetS were not associated with greater risk of PCa. In this study, we did not show an association between MetS and PIA and PCa. Although the small sample size and the cross-sectional nature of the study, we do not suppose that MetS could be associated with greater evidence of PIA. Further studies should be conducted to evaluate the exact nature of this pathological lesion. Copyright © 2018 Elsevier Inc. All rights reserved.

25. VIEW SHOWING ENTRANCE TO SILO 'ALFA,' LOOKING WEST Everett ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

25. VIEW SHOWING ENTRANCE TO SILO 'ALFA,' LOOKING WEST Everett Weinreb, photographer, March 1988 - Mount Gleason Nike Missile Site, Angeles National Forest, South of Soledad Canyon, Sylmar, Los Angeles County, CA

Racial differences in clinically localized prostate cancers of black and white men.

PubMed

deVere White, R W; Deitch, A D; Jackson, A G; Gandour-Edwards, R; Marshalleck, J; Soares, S E; Toscano, S N; Lunetta, J M; Stewart, S L

1998-06-01

Tumor grade, deoxyribonucleic acid (DNA) ploidy, proliferation, p53 and bcl-2 expression were examined in clinically localized prostate cancers of black and white American men to learn whether these features showed racial differences. A total of 117 prostate cancers (43 black and 74 white patients) obtained at radical prostatectomy for clinically localized disease were assigned Gleason scores by a single pathologist. Enzymatically dissociated nuclei from archival prostate cancers were examined by DNA flow cytometry using propidium iodide staining and the multicycle program to remove debris and sliced nuclei and to perform cell cycle analysis. For immunostaining after microwave antigen retrieval we used a DO-1/DO-7 monoclonal antibody cocktail for p53 and the clone 124 antibody for bcl-2. Significantly more black than white men had Gleason score 7 tumors. The DNA ploidy distribution of Gleason 6 or less tumors was similar for both races. As anticipated, the ploidy distribution of higher grade prostate cancer in white men was more abnormal but, unexpectedly, this was not found for higher grade prostate cancer in black men. No significant racial differences were found in S phase fractions, p53 or bcl-2 immunopositivity. However, for prostate cancer in black men there was a significant association between bcl-2 immunopositivity and higher S-phase fractions. The aggressive prostate cancers of black men may be characterized by the 2 features of high proliferation and a block to programmed cell death.

Trichomonas vaginalis infection and risk of prostate cancer: associations by disease aggressiveness and race/ethnicity in the PLCO Trial.

PubMed

Marous, Miguelle; Huang, Wen-Yi; Rabkin, Charles S; Hayes, Richard B; Alderete, John F; Rosner, Bernard; Grubb, Robert L; Winter, Anke C; Sutcliffe, Siobhan

2017-08-01

Results from previous sero-epidemiologic studies of Trichomonas vaginalis infection and prostate cancer (PCa) support a positive association between this sexually transmitted infection and aggressive PCa. However, findings from previous studies are not entirely consistent, and only one has investigated the possible relation between T. vaginalis seropositivity and PCa in African-American men who are at highest risk of both infection and PCa. Therefore, we examined this possible relation in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, including separate analyses for aggressive PCa and African-American men. We included a sample of participants from a previous nested case-control study of PCa, as well as all additional Caucasian, aggressive, and African-American cases diagnosed since the previous study (total n = 438 Gleason 7 Caucasian cases, 487 more advanced Caucasian cases (≥Gleason 8 or stage III/IV), 201 African-American cases, and 1216 controls). We tested baseline sera for T. vaginalis antibodies. No associations were observed for risk of Gleason 7 (odds ratio (OR) = 0.87, 95% confidence interval (CI) 0.55-1.37) or more advanced (OR = 0.90, 95% CI 0.58-1.38) PCa in Caucasian men, or for risk of any PCa (OR = 1.06, 95% CI 0.67-1.68) in African-American men. Our findings do not support an association between T. vaginalis infection and PCa.

Prognostic Significance of Percentage and Architectural Types of Contemporary Gleason Pattern 4 Prostate Cancer in Radical Prostatectomy.

PubMed

Choy, Bonnie; Pearce, Shane M; Anderson, Blake B; Shalhav, Arieh L; Zagaja, Gregory; Eggener, Scott E; Paner, Gladell P

2016-10-01

The International Society of Urological Pathology (ISUP) 2014 consensus meeting recommended a novel grade grouping for prostate cancer that included dividing Gleason score (GS) 7 into grade groups 2 (GS 3+4) and 3 (GS 4+3). This division of GS 7, essentially determined by the percent of Gleason pattern (GP) 4 (< or >50%), raises the question of whether a more exact quantification of the percent GP 4 within GS 7 will yield additional prognostic information. Modifications were also made by ISUP regarding the definition of GP 4, now including 4 main architectural types: cribriform, glomeruloid, poorly formed, and fused glands. This study was conducted to analyze the prognostic significance of the percent GP 4 and main architectural types of GP 4 according to the 2014 ISUP grading criteria in radical prostatectomies (RPs). The cohort included 585 RP cases of GS 6 (40.2%), 3+4 (49.0%), and 4+3 (10.8%) prostate cancers. Significantly different 5-year biochemical recurrence (BCR)-free survival rates were observed among GS 6 (99%, 95% confidence interval [CI]: 97%-100%), 3+4 (81%, 95% CI: 76%-86%), and 4+3 (60%, 95% CI: 45%-71%) cancers (P<0.01). Dividing the GP 4 percent into quartiles showed a 5-year BCR-free survival of 84% (95% CI: 78%-89%) for 1% to 20%, 74% (95% CI: 62%-83%) for 21% to 50%, 66% (95% CI: 50%-78%) for 51% to 70%, and 32% (95% CI: 9%-59%) for >70% (P<0.001). Among the GP 4 architectures, cribriform was the most prevalent (43.7%), and combination of architectures with cribriform present was more frequently observed in GS 4+3 (60.3%). Glomeruloid was mostly (67.1%) seen combined with other GP 4 architectures. Unlike the other GP 4 architectures, glomeruloid as the sole GP 4 was observed only as a secondary pattern (ie, 3+4). Among patients with GS 7 cancer, the presence of cribriform architecture was associated with decreased 5-year BCR-free survival when compared with GS 7 cancers without this architecture (68% vs. 85%, P<0.01), whereas the presence of glomeruloid architecture was associated with improved 5-year BCR-free survival when compared with GS 7 cancers without this architecture (87% vs. 75%, P=0.01). However, GS 7 disease having only the glomeruloid architecture had significantly lower 5-year BCR-free survival than GS 6 cancers (86% vs. 99%, P<0.01). Multivariable Cox proportional hazards regression model for factors associated with BCR among GS 7 cancers identified age (hazard ratio [HR] 0.95, P<0.01), preoperative prostate-specific antigen (HR 1.07, P<0.01), positive surgical margin (HR 2.70, P<0.01), percent of GP 4 (21% to 50% [HR 2.21], 51% to 70% [HR 2.59], >70% [HR 6.57], all P<0.01), presence of cribriform glands (HR 1.78, P=0.02), and presence of glomeruloid glands (HR 0.43, P=0.03) as independent predictors. In conclusion, our study shows that increments in percent of GP 4 correlate with increased risk for BCR supporting the ISUP recommendation of recording the percent of GP 4 in GS 7 prostate cancers at RP. However, additional larger studies are needed to establish the optimal interval for reporting percent GP 4 in GS 7 cancers. Among the GP 4 architectures, cribriform independently predicts BCR, whereas glomeruloid reduces the risk of BCR. Distinction should be made between cribriform and glomeruloid architectures, despite glomeruloid being considered as an early stage of cribriform, as cribriform confers a higher risk for poorer outcome.

23. VIEW OF DOG KENNELS LOCATED AT LAUNCH SITE, LOOKING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

23. VIEW OF DOG KENNELS LOCATED AT LAUNCH SITE, LOOKING NORTH Marilyn Ziemer, photographer, March 1988 - Mount Gleason Nike Missile Site, Angeles National Forest, South of Soledad Canyon, Sylmar, Los Angeles County, CA

24. OVERALL VIEW OF LOWEST LEVEL SILO ('ALFA'), LOOKING NORTHWEST ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

24. OVERALL VIEW OF LOWEST LEVEL SILO ('ALFA'), LOOKING NORTHWEST Everett Weinreb, photographer, March 1988 - Mount Gleason Nike Missile Site, Angeles National Forest, South of Soledad Canyon, Sylmar, Los Angeles County, CA

Is it necessary to cure prostate cancer when it is possible? (Understanding the role of prostate inflammation resolution to prostate cancer evolution)

PubMed Central

Wheeler, Ronald E

2007-01-01

Objective: Definitive therapy with radical prostatectomy, cryotherapy, or radiation therapy generally follows the initial diagnosis of prostate cancer, particularly when men have at least 10 additional years of life expectancy. There is growing concern regarding the optimal conservative treatment for patients who decline or do not otherwise qualify for such definitive curative treatment. For those patients who choose a watchful waiting approach, it would be beneficial to know what specific dietary and nutritional methods could potentially slow the progression of their disease. In this prospective study, it was our goal to analyze the efficacy and safety of treating prostate cancer conservatively using the principles of a Mediterranean diet in association with a specific prostate nutritional supplement. Method: Twenty-three men aged 43–74 (median age: 64) with biopsy proven, organ-confined prostate cancer who had already declined immediate hormonal therapy and attempts at a curative cancer treatment agreed to participate in a Chronic Disease Management (CDM) protocol highlighted by diet with a specific prostate nutritional supplement. The diet recommended was a modified Mediterranean diet while a patented nutritional prostatitis formula (Peenuts®) was the supplement common to all patients. Prostate specific antigen (PSA), a recognized marker of prostate disease and prostate cancer activity, was the primary indicator to validate exacerbation or suppression of disease. All men were followed with serial PSA testing, a digital rectal exam, an International Prostate Symptom Score index (IPSS-Index) and an expressed prostatic secretion (EPS) examination. The primary Gleason sum/score represented in this study was 6 (n = 11), while Gleason sum patterns 5, 5/6, 6/7, and 7 were also evaluated. Referencing the Partin Tables, organ confinement was predicted to be 66%. Results: Eighty-seven percent of men (n = 20) noted a 58% reduction (range of improvement: 13%–90%) in PSA over an average of 38.5 months (range: 13–84 months). The remaining 13% of men included three men who experienced a mild elevation in PSA of 0.3 ng/ml, 0.7 ng/ml, and 0.9 ng/ml over 14 months, 42 months, and 34 months, respectively. Fifteen men had completed an initial and secondary IPSS-Index while 14 men had undergone an initial and secondary EPS. The mean percentage reduction in IPSS-Index was 61% (range: 20%–100% with a median of 55%), while men evaluated with EPS examinations noted a mean percentage reduction in white blood cells of 77.5% (range: 33%–99% with a median of 82%). These results were evaluated using the t-test, Wilcoxon Analysis and the Null Hypothesis and found to be statistically significant. Conclusion: Clearly there is a need to develop effective alternative conservative therapies for the increasing numbers of prostate cancer patients who will not tolerate definitive curative measures or simply choose a conservative approach. Although this prospective study had no control arm, was of limited duration and included only 23 participants, it did appear to show significant benefit to the majority of prostate cancer patients treated with selective nutritional and dietary therapy alone. Such treatments may provide a safe and effective long-term treatment alternative for some patients. Further study is encouraged. PMID:18044088

Preoperative Staging With 11C-Choline PET/CT Is Adequately Accurate in Patients With Very High-Risk Prostate Cancer.

PubMed

Schiavina, Riccardo; Bianchi, Lorenzo; Mineo Bianchi, Federico; Borghesi, Marco; Pultrone, Cristian Vincenzo; Dababneh, Hussam; Castellucci, Paolo; Ceci, Francesco; Nanni, Cristina; Gaudiano, Caterina; Fiorentino, Michelangelo; Porreca, Angelo; Chessa, Francesco; Minervini, Andrea; Fanti, Stefano; Brunocilla, Eugenio

2018-05-30

To evaluate the accuracy of 11 C-choline positron emission tomography (PET)/computed tomography (CT) for nodal staging of prostate cancer (PCa) in different populations of high-risk patients. We evaluated 262 individuals with intermediate- or high-risk PCa submitted to radical prostatectomy and extended pelvic lymph node dissection. Within men with high-risk disease, we identified a subgroup of individuals harboring very high-risk (VHR, n = 28) disease: clinical stage ≥ T2c and more than 5 cores with Gleason score 8-10; primary biopsy Gleason score of 5; 3 high-risk features; or prostate-specific antigen ≥ 30 ng/mL. The diagnostic accuracy of PET/CT and contrast-enhanced CT (CECT) was assessed after stratifying patients according to risk group classification on a patient- and anatomic region-based analysis. On patient-based analysis, considering high-risk patients (n = 155), 11 C-choline PET/CT versus CECT had sensitivity and specificity of 50% and 76% versus 21% and 92%, respectively. Considering VHR men as separate subgroups (n = 28), 11 C-choline PET/CT versus CECT had sensitivity and specificity of 71% and 93% versus 25% and 79%, respectively. Accordingly, in the VHR category, the area under the curve of 11 C-choline PET/CT versus CECT was 0.86 (95% confidence interval, 0.71-1.0) versus 0.69 (95% confidence interval, 0.52-0.86), respectively. On anatomic region-based analysis, considering the VHR group, 11 C-choline PET/CT versus CECT had sensitivity and specificity of 70.6% and 95.5% versus 35.3% and 98.5%, respectively. Patients with VHR characteristics could represent the ideal candidate to undergo disease staging with PET/CT before surgery with the highest cost efficacy. Copyright © 2018 Elsevier Inc. All rights reserved.

Time from first detectable PSA following radical prostatectomy to biochemical recurrence: A competing risk analysis.

PubMed

de Boo, Leonora; Pintilie, Melania; Yip, Paul; Baniel, Jack; Fleshner, Neil; Margel, David

2015-01-01

In this study, we estimated the time from first detectable prostate-specific antigen (PSA) following radical prostatectomy (RP) to commonly used definitions of biochemical recurrence (BCR). We also identified the predictors of time to BCR. We identified subjects who underwent a RP and had an undetectable PSA after surgery followed by at least 1 detectable PSA between 2000 and 2011. The primary outcome was time to BCR (PSA ≥0.2 and successive PSA ≥0.2) and prediction of the rate of PSA rise. Outcomes were calculated using a competing risk analysis, with univariable and multivariable Fine and Grey models. We employed a mixed effect model to test clinical predictors that are associated with the rate of PSA rise. The cohort included 376 patients. The median follow-up from surgery was 60.5 months (interquartile range [IQR] 40.8-91.5) and from detectable PSA was 18 months (IQR 11-32). Only 45.74% (n = 172) had PSA values ≥0.2 ng/mL, while 15.16% (n = 57) reached the PSA level of ≥0.4 ng/mL and rising. On multivariable analysis, the values of the first detectable PSA and pathologic Gleason grade 8 or higher were consistently independent predictors of time to BCR. In the mixed effect model rate, the PSA rise was associated with time from surgery to first detectable PSA, Gleason score, and prostate volume. The main limitation of this study is the large proportion of patients that received treatment without reaching BCR. It is plausible that shorter estimated median times would occur at a centre that does not use salvage therapy at such an early state. The time from first detectable PSA to BCR may be lengthy. Our analyses of the predictors of the rate of PSA rise can help determine a personalized approach for patients with a detectable PSA after surgery.

Time from first detectable PSA following radical prostatectomy to biochemical recurrence: A competing risk analysis

PubMed Central

de Boo, Leonora; Pintilie, Melania; Yip, Paul; Baniel, Jack; Fleshner, Neil; Margel, David

2015-01-01

Introduction: In this study, we estimated the time from first detectable prostate-specific antigen (PSA) following radical prostatectomy (RP) to commonly used definitions of biochemical recurrence (BCR). We also identified the predictors of time to BCR. Methods: We identified subjects who underwent a RP and had an undetectable PSA after surgery followed by at least 1 detectable PSA between 2000 and 2011. The primary outcome was time to BCR (PSA ≥0.2 and successive PSA ≥0.2) and prediction of the rate of PSA rise. Outcomes were calculated using a competing risk analysis, with univariable and multivariable Fine and Grey models. We employed a mixed effect model to test clinical predictors that are associated with the rate of PSA rise. Results: The cohort included 376 patients. The median follow-up from surgery was 60.5 months (interquartile range [IQR] 40.8–91.5) and from detectable PSA was 18 months (IQR 11–32). Only 45.74% (n = 172) had PSA values ≥0.2 ng/mL, while 15.16% (n = 57) reached the PSA level of ≥0.4 ng/mL and rising. On multivariable analysis, the values of the first detectable PSA and pathologic Gleason grade 8 or higher were consistently independent predictors of time to BCR. In the mixed effect model rate, the PSA rise was associated with time from surgery to first detectable PSA, Gleason score, and prostate volume. The main limitation of this study is the large proportion of patients that received treatment without reaching BCR. It is plausible that shorter estimated median times would occur at a centre that does not use salvage therapy at such an early state. Conclusion: The time from first detectable PSA to BCR may be lengthy. Our analyses of the predictors of the rate of PSA rise can help determine a personalized approach for patients with a detectable PSA after surgery. PMID:25624961

Novel biparametric MRI and targeted biopsy improves risk stratification in men with a clinical suspicion of prostate cancer (IMPROD Trial).

PubMed

Jambor, Ivan; Boström, Peter J; Taimen, Pekka; Syvänen, Kari; Kähkönen, Esa; Kallajoki, Markku; Perez, Ileana Montoya; Kauko, Tommi; Matomäki, Jaakko; Ettala, Otto; Merisaari, Harri; Kiviniemi, Aida; Dean, Peter B; Aronen, Hannu J

2017-10-01

To evaluate the role of a 3T biparametric magnetic resonance imaging (bpMRI), T 2 -weighted imaging, and three separate diffusion-weighted imaging acquisitions combined with targeted biopsy (TB) for improving risk stratification of men with elevated prostate-specific antigen (PSA). Between March 2013 and February 2015, 175 men with a clinical suspicion of prostate cancer (PCa) were offered bpMRI (NCT01864135) based on a suspicion of PCa (two repeated PSA measurements in the range 2.5-20.0 ng/ml and/or abnormal digital rectal examination). Men with an equivocal to high suspicion of PCa had two TBs of the dominant lesion using cognitive ultrasound guidance, followed by systematic biopsy (SB). Men with a low to very low suspicion had only SB. In total, 161 (161/175, 92%) prospectively enrolled men completed the trial and were included in the final analyses. The primary endpoint of the trial was the cancer detection rate (CDR) of TB and SB. Clinically significant cancer (SPCa) was defined as Gleason score ≥3 + 4. TB compared with SB had higher CDR for SPCa (45%, 72/161 vs. 39%, 63/161, respectively; P > 0.05) and a lower CDR for Gleason score 3 + 3 (8%, 15/161 vs. 16%, 30/161; P < 0.05). Restricting biopsy to men with equivocal to highly suspicious bpMRI findings would have resulted in a 24% (38/161) reduction in the number of men undergoing biopsy, while missing 4 (2%) with SPCa. All anonymized datasets, including bpMRI reports and follow up information, are freely available on the trial server. Prebiopsy bpMRI and TB in men with a clinical suspicion of PCa improved risk stratification. 1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2017;46:1089-1095. © 2017 International Society for Magnetic Resonance in Medicine.

Outcomes of active surveillance for the management of clinically localized prostate cancer in the prospective, multi-institutional Canary PASS cohort

PubMed Central

Newcomb, Lisa F.; Thompson, Ian M.; Boyer, Hilary D.; Brooks, James D.; Carroll, Peter R.; Cooperberg, Matthew R.; Dash, Atreya; Ellis, William J.; Fazli, Ladan; Feng, Ziding; Gleave, Martin E.; Kunju, Priya; Lance, Raymond S.; McKenney, Jesse K.; Meng, Maxwell V.; Nicolas, Marlo M.; Sanda, Martin G.; Simko, Jeffry; So, Alan; Tretiakova, Maria S.; Troyer, Dean A.; True, Lawrence D.; Vakar-Lopez, Funda; Virgin, Jeff; Wagner, Andrew A.; Wei, John T.; Zheng, Yingye; Nelson, Peter S.; Lin, Daniel W.

2016-01-01

Purpose Active surveillance represents a strategy to address the overtreatment of prostate cancer, yet uncertainty regarding individual patient outcomes remains a concern. We evaluated outcomes in a prospective multi-center study of active surveillance. Methods We studied 905 men in the prospective Canary Prostate cancer Active Surveillance Study (PASS) enrolled between 2008 to 2013. We collected clinical data at study entry and at pre-specified intervals and determined associations with adverse reclassification defined as increased Gleason grade or greater cancer volume on follow-up biopsy. We also evaluated the relationships of clinical parameters with pathology findings in participants who underwent surgery after a period of active surveillance. Results During a median follow-up of 28 months, 24% of participants experienced adverse reclassification, of whom 53% underwent treatment while 31% continued active surveillance. Overall, 19% of participants received treatment, 68% with adverse reclassification while 32% opted for treatment without disease reclassification. In multivariate Cox proportional hazards modeling, percent of biopsy cores with cancer, BMI, and PSA density were associated with adverse reclassification (P = 0.01, 0.04, 0.04). Of 103 participants subsequently treated by radical prostatectomy, 34% had adverse pathology, defined as primary pattern 4–5 or non-organ confined disease, including two with positive lymph nodes, with no significant relationship between risk category at diagnosis and findings at surgery (P = 0.76). Conclusion Most men remain on active surveillance at five years without adverse reclassification or adverse pathology at surgery. However, clinical factors had only modest association with disease reclassification, supporting the need for approaches that improve prediction of this outcome. PMID:26327354

Intake of Meat Mutagens and Risk of Prostate Cancer in a Cohort of U.S. Health Professionals.

PubMed

Rohrmann, Sabine; Nimptsch, Katharina; Sinha, Rashmi; Willett, Walter C; Giovannucci, Edward L; Platz, Elizabeth A; Wu, Kana

2015-10-01

Evidence relating heterocyclic aromatic amines (HCA), associated with high-temperature cooking methods, to prostate cancer risk is inconsistent. In a large U.S. cohort study, intakes of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and a meat-derived mutagenicity (MDM) index were assessed using a cooking method questionnaire administered in 1996. Until 2010, 2,770 prostate cancer cases were observed among 26,030 participants. Intake of PhIP from red meat was statistically significantly associated with total prostate cancer risk (top vs. bottom quintile HR, 1.18; 95% confidence intervals; CI, 1.03-1.35), but not other HCAs (MeIQx, 1.12; 0.98-1.27, PhIP from white meat, 1.08; 0.95-1.22, DiMeIQx, 1.09; 0.97-1.21) or MDM (1.13; 1.00-1.28). For high-grade (Gleason sum 7 with pattern 4+3 and Gleason sum 8-10, n = 483 cases) and advanced cancers (n = 281), we only observed positive associations for PhIP from red meat (top vs. bottom quintile: high grade: HR, 1.44; 95% CI, 1.04-1.98, Ptrend = 0.03; advanced: HR, 1.50; 95% CI, 0.99-2.26; Ptrend = 0.12), but associations for advanced cancers did not reach statistical significance. Observed associations remained similar after adjustment for total, unprocessed, or processed red meat intake. Observed positive associations between PhIP intake from red meat and prostate cancer, particularly high-grade and possibly also advanced prostate cancer, need to be confirmed in other studies. Results do not provide strong evidence that HCAs increase risk of prostate cancers. ©2015 American Association for Cancer Research.

Intake of meat mutagens and risk of prostate cancer in a cohort of U.S. health professionals

PubMed Central

Rohrmann, Sabine; Nimptsch, Katharina; Sinha, Rashmi; Willett, Walter C; Giovannucci, Edward L.; Platz, Elizabeth A; Wu, Kana

2015-01-01

Background Evidence relating heterocyclic aromatic amines (HCA), associated with high-temperature cooking methods, to prostate cancer risk is inconsistent Methods In a large US cohort study, intakes of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and a meat-derived mutagenicity index (MDM) were assessed using a cooking method questionnaire administered in 1996. Until 2010, 2,770 prostate cancer cases were observed among 26,030 participants. Results Intake of PhIP from red meat was statistically significantly associated with total prostate cancer risk (top vs. bottom quintile HR=1.18, 95% CI 1.03–1.35), but not other HCAs (MeIQx, 1.12, 0.98–1.27, PhIP from white meat, 1.08, 0.95–1.22, DiMeIQx, 1.09, 0.97–1.21) or MDM (1.13, 1.00–1.28). For high grade (Gleason sum 7 with pattern 4+3 and Gleason sum 8–10, n=483 cases) and advanced cancers (n=281), we only observed positive associations for PhIP from red meat (top vs. bottom quintile: high grade: HR=1.44, 95% CI 1.04–1.98, p-trend=0.03; advanced: HR=1.50, 95% 0.99–2.26; p-trend=0.12), but associations for advanced cancers did not reach statistical significance. Observed associations remained similar after adjustment for total, unprocessed or processed red meat intake. Conclusion Observed positive associations between PhIP intake from red meat and prostate cancer, particularly high-grade and possibly also advanced prostate cancer need to be confirmed in other studies. Impact Results do not provide strong evidence that HCAs increase risk of prostate cancers. PMID:26224797

Development of Castration Resistant Prostate Cancer can be Predicted by a DNA Hypermethylation Profile.

PubMed

Angulo, Javier C; Andrés, Guillermo; Ashour, Nadia; Sánchez-Chapado, Manuel; López, Jose I; Ropero, Santiago

2016-03-01

Detection of DNA hypermethylation has emerged as a novel molecular biomarker for prostate cancer diagnosis and evaluation of prognosis. We sought to define whether a hypermethylation profile of patients with prostate cancer on androgen deprivation would predict castrate resistant prostate cancer. Genome-wide methylation analysis was performed using a methylation cancer panel in 10 normal prostates and 45 tumor samples from patients placed on androgen deprivation who were followed until castrate resistant disease developed. Castrate resistant disease was defined according to EAU (European Association of Urology) guideline criteria. Two pathologists reviewed the Gleason score, Ki-67 index and neuroendocrine differentiation. Hierarchical clustering analysis was performed and relationships with outcome were investigated by Cox regression and log rank analysis. We found 61 genes that were significantly hypermethylated in greater than 20% of tumors analyzed. Three clusters of patients were characterized by a DNA methylation profile, including 1 at risk for earlier castrate resistant disease (log rank p = 0.019) and specific mortality (log rank p = 0.002). Hypermethylation of ETV1 (HR 3.75) and ZNF215 (HR 2.89) predicted disease progression despite androgen deprivation. Hypermethylation of IRAK3 (HR 13.72), ZNF215 (HR 4.81) and SEPT9 (HR 7.64) were independent markers of prognosis. Prostate specific antigen greater than 25 ng/ml, Gleason pattern 5, Ki-67 index greater than 12% and metastasis at diagnosis also predicted a negative response to androgen deprivation. Study limitations included the retrospective design and limited number of cases. Epigenetic silencing of the mentioned genes could be novel molecular markers for the prognosis of advanced prostate cancer. It might predict castrate resistance during hormone deprivation and, thus, disease specific mortality. Gene hypermethylation is associated with disease progression in patients who receive hormone therapy. It could serve as a marker of the treatment response. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

26. VIEW SHOWING ENTRANCE TO SILO 'ALFA,' LOOKING NORTH Marilyn ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

26. VIEW SHOWING ENTRANCE TO SILO 'ALFA,' LOOKING NORTH Marilyn Ziemer and Everett Weinreb, photographers, March 1988 - Mount Gleason Nike Missile Site, Angeles National Forest, South of Soledad Canyon, Sylmar, Los Angeles County, CA

Watershed Restoration Project

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

Julie Thompson; Betsy Macfarlan

2007-09-27

In 2003, the U.S. Department of Energy issued the Eastern Nevada Landscape Coalition (ENLC) funding to implement ecological restoration in Gleason Creek and Smith Valley Watersheds. This project was made possible by congressionally directed funding that was provided through the US Department of Energy, Energy Efficiency and Renewable Energy, Office of the Biomass Program. The Ely District Bureau of Land Management (Ely BLM) manages these watersheds and considers them priority areas within the Ely BLM district. These three entities collaborated to address the issues and concerns of Gleason Creek and Smith Valley and prepared a restoration plan to improve themore » watersheds’ ecological health and resiliency. The restoration process began with watershed-scale vegetation assessments and state and transition models to focus on restoration sites. Design and implementation of restoration treatments ensued and were completed in January 2007. This report describes the restoration process ENLC undertook from planning to implementation of two watersheds in semi-arid Eastern Nevada.« less

A pretreatment nomogram for prediction of biochemical failure after primary cryoablation of the prostate.

PubMed

Elshafei, Ahmed; Kovac, Evan; Dhar, Nivedita; Levy, David; Polascik, Thomas; Mouraviev, Vladimir; Yu, Changhong; Jones, J Stephen

2015-09-01

To create a predictive nomogram for biochemical failure following primary whole-gland cryoablation of the prostate for localized prostate cancer (LPCa). We retrospectively analyzed 2,242 patients from the Cryo On-Line Database (COLD) who were treatment naive and had undergone primary whole gland cryoablation of the prostate for biopsy-confirmed LPCa. Kaplan-Meier (KM) curves estimating 5 year biochemical progression-free survival (bPFS) were generated. Multivariable Cox proportional hazards analysis (CoxPH) was performed in order to construct the nomogram. The nomogram was internally validated using the bootstrap technique. Overall, the KM estimated 5 year bPFS was 72.8%. Stratified by D'Amico risk, The KM estimated 5 year bPFS was 82.6%, 71.1%, and 57.8% for low-, intermediate-, and high-risk groups, respectively. Statistically significant predictors of biochemical outcomes from CoxPH analysis were pre-treatment prostate specific antigen (PTPSA) (P < 0.001), total prostate volume (P = 0.004), clinical stage (P = 0.034), and Gleason score (0.004). A nomogram for predicted 5 year biochemical progression free probability was constructed with a concordance index of 0.652. An online risk calculator was also generated. To the best of our knowledge, this is the first predictive nomogram for biochemical outcomes after primary whole gland cryoablation of the prostate using socio-demographic, pretreatment, clinical, and prostate biopsy data. Our nomogram and online risk calculator can guide both patients and urologists for shared decision making regarding definitive treatment options. © 2015 Wiley Periodicals, Inc.

Serum ferritin in combination with prostate-specific antigen improves predictive accuracy for prostate cancer.

PubMed

Wang, Xijuan; An, Peng; Zeng, Jiling; Liu, Xiaoyan; Wang, Bo; Fang, Xuexian; Wang, Fudi; Ren, Guoping; Min, Junxia

2017-03-14

Ferritin is highly expressed in many cancer types. Although a few studies have reported an association between high serum ferritin levels and an increased risk of prostate cancer, the results are inconsistent. Therefore, we performed a large case-control study consisting of 2002 prostate cancer patients and 951 control patients with benign prostatic hyperplasia (BPH). We found that high ferritin levels were positively associated with increased serum prostate-specific antigen (PSA) levels and prostate cancer risk; each 100 ng/ml increase in serum ferritin increased the odds ratio (OR) by 1.20 (95% CI: 1.13-1.36). In the prostate cancer group, increased serum ferritin levels were significantly correlated with higher Gleason scores (p < 0.001). Notably, serum PSA values had even higher predictive accuracy among prostate cancer patients with serum ferritin levels > 400 ng/ml (Gleason score + total PSA correlation: r = 0.38; Gleason score + free PSA correlation: r = 0.49). Moreover, using immunohistochemistry, we found that prostate tissue ferritin levels were significantly higher (p < 0.001) in prostate cancer patients (n = 129) compared to BPH controls (n = 31). Prostate tissue ferritin levels were also highly correlated with serum ferritin when patients were classified by cancer severity (r = 0.81). Importantly, we found no correlation between serum ferritin levels and the inflammation marker C-reactive protein (CRP) in prostate cancer patients. In conclusion, serum ferritin is significantly associated with prostate cancer and may serve as a non-invasive biomarker to complement the PSA test in the diagnosis and prognostic evaluation of prostate cancer.

[High-intensity focused ultrasound (HIFU): our experience in the treatment of prostate cancer relapsing after radiotherapy].

PubMed

Giovanessi, Luca; Peroni, Angelo; Mirabella, Giuseppe; Fugini, Andrea Vismara; Zani, Danilo; Cunico, Sergio Cosciani; Simeone, Claudio

2011-01-01

The aim of the study is to evaluate the safety and efficacy of high-intensity focused ultrasound (HIFU) treatment in patients with local prostate cancer recurrence after radiotherapy. From February 2009 to June 2010, 14 patients with prostate cancer recurrence after radiotherapy were selected for HIFU treatment; all patients had a positive TRUS-guided biopsy and the absence of distant metastases was confirmed by computer tomography, PET choline or bone scintigraphy. We classified all patients in 3 groups using D'Amico's classification: 4 patients high risk (PSA >20 ng/ml - 8≤ Gleason Score≤ 10 - clinical stage≥T2c), 8 patients intermediate risk (10 PSAnadir+1.2ng/ml) or after adjuvant therapy introduction. All complications were recorded. Of the 14 patients selected, 12 patients underwent HIFU treatments; 2 patients were excluded because of rectal strictures induced by radiotherapy. At a mean 13 months' follow-up, biochemical success rate was obtained in 1 of the high risk patients and in 5 of the low and intermediate risk patients; 1 man died for a disease not correlated with prostate cancer recurrence. Complications included urinary tract infection, acute urinary retentions, urethral strictures and light stress incontinence. In our experience salvage HIFU is a safe treatment option for local relapse after radiotherapy; its efficacy depends on a careful patient selection.

Estrogen receptor alpha polymorphisms and the risk of prostate cancer development.

PubMed

Jurečeková, Jana; Babušíková, Eva; Kmeťová, Monika; Kliment, Ján; Dobrota, Dušan

2015-11-01

The main purpose of the study was to evaluate the effect of two polymorphisms in the estrogen receptor alpha, rs2077647 and rs3798577, on the development of prostate cancer, their correlation with selected clinical characteristics, as well as consideration of potential interactions between four estrogen receptor alpha polymorphisms (rs2077647, rs3798577, PvuII, XbaI). The study was performed using 395 patients with histologically verified prostate cancer and 253 healthy male controls. The CC genotype of rs2077647 was significantly associated with prostate cancer (OR = 1.61). No association was found between rs3798577 polymorphism and prostate cancer. After stratification of patients according to the age at diagnosis and Gleason score, we observed significant correlation between rs2077647 polymorphism and prostate cancer risk in patients diagnosed before the age of 60 as well as patients with Gleason score <7, while rs3798577 was significantly associated with prostate cancer risk development in patients older than 60 and with Gleason score ≥7. Double analysis of each combination of four studied polymorphisms showed that presence of at least three variant alleles was associated with prostate cancer risk in all combinations, while each containing rs3798577 was significantly associated with development of high-grade carcinomas. The present study suggests that rs2077647 polymorphism may be a risk factor for prostate cancer especially in patients diagnosed before the age of 60, while rs3798577 polymorphism could probably serve rather as promoting factor in combination with other polymorphisms in estrogen receptor alpha contributing preferably to development of high-grade carcinomas.

Upgrading the Gleason Score in Extended Prostate Biopsy: Implications for Treatment Choice

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

Moreira Leite, Katia Ramos; Laboratory of Surgical and Molecular Pathology - Hospital Sirio Libanes, Sao Paulo; Camara-Lopes, Luiz H.A.

2009-02-01

Purpose: To determine the incidence of overestimation of Gleason score (GS) in extended prostate biopsy, and consequently circumventing unnecessary aggressive treatment. Methods and Materials: This is a retrospective study of 464 patients who underwent prostate biopsy and radical prostatectomy between January 2001 and November 2007. The GS from biopsy and radical prostatectomy were compared. The incidence of overestimation of GS in biopsies and tumor volume were studied. Multivariate analysis was applied to find parameters that predict upgrading the GS in prostate biopsy. Results: The exact agreement of GS between prostate biopsy and radical prostatectomy occurred in 56.9% of cases. Inmore » 29.1% cases it was underestimated, and it was overestimated in 14%. One hundred and six (22.8%) patients received a diagnosis of high GS (8, 9, or 10) in a prostate biopsy. In 29.2% of cases, the definitive Gleason Score was 7 or lower. In cases in which GS was overestimated in the biopsy, tumors were significantly smaller. In multivariate analysis, the total percentage of tumor was the only independent factor in overestimation of GS. Tumors occupying less than 33% of cores had a 5.6-fold greater chance of being overestimated. Conclusion: In the extended biopsy era and after the International Society of Urological Pathology consensus on GS, almost one third of tumors considered to have high GS at the biopsy may be intermediate-risk cancers. In that condition, tumors are smaller in biopsy. This should be remembered by professionals involved with prostate cancer to avoid overtreatment and undesirable side effects.« less

PSA and Prostate Health Index based prostate cancer screening in a hereditary migration complicated population: implications in precision diagnosis.

PubMed

Akizhanova, Mariyam; Iskakova, Elzira E; Kim, Valdemir; Wang, Xiao; Kogay, Roman; Turebayeva, Aiym; Sun, Qinglei; Zheng, Ting; Wu, Shenghui; Miao, Lixia; Xie, Yingqiu

2017-01-01

Precision diagnosis requires specific markers for differential ethnic populations. Prostate-Specific Antigen (PSA) level (threshold of 4ng/ml) has been widely used to screen prostate cancer and as reference of pro-biopsy but false diagnosis frequently occurs. Prostate health Index (PHI) is a new diagnosis marker which combines PSA, free PSA and p2PSA4. Overall the PCa screening database is lacking in Kazakhstani patients. We analyzed the PSA levels and Gleason scores of 222 biopsies collected in 2015 in Almaty area, Kazakhstan approved by institutional ethics board. We found using PSA of 4ng/ml as threshold, only 25.68% of patients have cancer with Gleason score ranged 6-8 and 65.77% of patients have no character of cancer. Moreover, there is no significant correlation between PSA and cancerous (P=0.266) or Gleason grade (P=0.3046) based on pathological biopsy. In addition, PHI is not correlated to prostate cancer (P=0.4301). Our data suggest that false-positive rate is much higher than the correct-positive diagnosis when using PSA as the first screening. Thus in this cohort study, most patients can not get benefit from the PSA screening for precision PCa diagnosis. As Kazakhstani family trees are unique and complicated because of history and migration, the high rate of over diagnosis might be due to the hyperexpression of PSA via heterosis in Eurasian men. Therefore we should be cautious when using pro-biopsy in precision diagnosis for Eurasian prostate cancer patients.

The detection and upgrade rates of prostate adenocarcinoma following transperineal template-guided prostate biopsy – a tertiary referral centre experience

PubMed Central

Telford, Robert; Viney, Richard; Patel, Prashant

2016-01-01

Introduction We aim to present transperineal template-guided prostate biopsy (template biopsy) outcomes at a tertiary referral centre. Furthermore, to identify the detection rate of prostate cancer in those with a previous negative transrectal ultrasound guided prostate biopsy and the upgrade rate of those on active surveillance for Gleason 3 + 3 = 6 prostate adenocarcinoma. Material and methods We conducted a prospective study of 200 consecutive men who underwent template biopsy over a 22-month period in a tertiary referral centre, using a standard 24 region template prostate biopsy technique. Indications and histology results, as well as complications, were recorded. Results Median age was 67 years and median PSA was 10 ng/mL. Overall detection rate was 47%. 39.5% of cases with previous negative transrectal biopsies were found to have prostate adenocarcinoma. 47.5% of cases on active surveillance for Gleason 3 + 3 = 6 prostate adenocarcinoma were upgraded. The most frequent complication was acute urinary retention at a rate of 12.5%, however, the use of a single prophylactic dose of tamsulosin was found to be beneficial, with 13 cases needed to treat to prevent one episode. Conclusions Template biopsies are safe and efficacious with an overall detection rate of 47% in the present series. Due to the high detection rate, one must consider template biopsy following one negative transrectal biopsy where there is persistent clinical suspicion. Furthermore, those considering active surveillance for Gleason 3 + 3 = 6 disease should be offered template biopsy to confirm the grade of their disease. PMID:27123325

T2-weighted MRI-derived textural features reflect prostate cancer aggressiveness: preliminary results.

PubMed

Nketiah, Gabriel; Elschot, Mattijs; Kim, Eugene; Teruel, Jose R; Scheenen, Tom W; Bathen, Tone F; Selnæs, Kirsten M

2017-07-01

To evaluate the diagnostic relevance of T2-weighted (T2W) MRI-derived textural features relative to quantitative physiological parameters derived from diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) MRI in Gleason score (GS) 3+4 and 4+3 prostate cancers. 3T multiparametric-MRI was performed on 23 prostate cancer patients prior to prostatectomy. Textural features [angular second moment (ASM), contrast, correlation, entropy], apparent diffusion coefficient (ADC), and DCE pharmacokinetic parameters (K trans and V e ) were calculated from index tumours delineated on the T2W, DW, and DCE images, respectively. The association between the textural features and prostatectomy GS and the MRI-derived parameters, and the utility of the parameters in differentiating between GS 3+4 and 4+3 prostate cancers were assessed statistically. ASM and entropy correlated significantly (p < 0.05) with both GS and median ADC. Contrast correlated moderately with median ADC. The textural features correlated insignificantly with K trans and V e . GS 4+3 cancers had significantly lower ASM and higher entropy than 3+4 cancers, but insignificant differences in median ADC, K trans , and V e . The combined texture-MRI parameters yielded higher classification accuracy (91%) than the individual parameter sets. T2W MRI-derived textural features could serve as potential diagnostic markers, sensitive to the pathological differences in prostate cancers. • T2W MRI-derived textural features correlate significantly with Gleason score and ADC. • T2W MRI-derived textural features differentiate Gleason score 3+4 from 4+3 cancers. • T2W image textural features could augment tumour characterization.

28. VIEW OF ELECTRICAL HOLE INTO 'ALFA' SILO, LOOKING FROM ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

28. VIEW OF ELECTRICAL HOLE INTO 'ALFA' SILO, LOOKING FROM TOP Marily Ziemer and Everett Weinreb, photographers, March 1988 - Mount Gleason Nike Missile Site, Angeles National Forest, South of Soledad Canyon, Sylmar, Los Angeles County, CA

32. VIEW LOOKING INSIDE 'BRAVO' SILO. GRAFFITI IS YELLOWCOLORED LION, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

32. VIEW LOOKING INSIDE 'BRAVO' SILO. GRAFFITI IS YELLOW-COLORED LION, SAME AS IN 'ALFA' Marilyn Ziemer, photographer, March 1988 - Mount Gleason Nike Missile Site, Angeles National Forest, South of Soledad Canyon, Sylmar, Los Angeles County, CA

Effects of groundwater withdrawals associated with combined-cycle combustion turbine plants in west Tennessee and northern Mississippi

USGS Publications Warehouse

Haugh, Connor J.

2012-01-01

The Mississippi Embayment Regional Aquifer Study groundwater-flow model was used to simulate the potential effects on future groundwater withdrawals at five powerplant sites-Gleason, Weakley County, Tennessee; Tenaska, Haywood County, Tennessee; Jackson, Madison County, Tennessee; Southaven, DeSoto County, Mississippi; and Magnolia, Benton County, Mississippi. The scenario used in the simulation consisted of a 30-year average water-use period followed by a 30-day peak water-demand period. Effects of the powerplants on the aquifer system were evaluated by comparing the difference in simulated water levels in the aquifers at the end of the scenario (30 years plus 30 days) with and without the combined-cycle-plant withdrawals. Simulated potentiometric surface declines in source aquifers at potential combined-cycle-plant sites ranged from 56 feet in the upper Wilcox aquifer at the Magnolia site to 20 feet in the Memphis aquifer at the Tenaska site. The affected areas in the source aquifers at the sites delineated by the 4-foot potentiometric surface-decline contour ranged from 11,362 acres at Jackson to 535,143 acres at Southaven. The extent of areas affected by potentiometric surface declines was similar at the Gleason and Magnolia sites. The affected area at the Tenaska site was smaller than the affected areas at the other sites, most likely as a result of lower withdrawal rates and greater aquifer thickness. The extent of effect was smallest at the Jackson site, where the nearby Middle Fork Forked Deer River may act as a recharge boundary. Additionally, the Jackson site lies in the Memphis aquifer outcrop area where model-simulated recharge rates are higher than in areas where the Memphis aquifer underlies less permeable deposits. The potentiometric surface decline in aquifers overlying or underlying a source aquifer was generally 2 feet or less at all the sites except Gleason. At the Gleason site, withdrawals from the Memphis aquifer resulted in declines of as much as 9 feet in the underlying Fort Pillow aquifer. The simulated potentiometric surface change occurring in the Fort Pillow aquifer appears to be the result of leakage through the Flour Island Formation separating the Memphis and Fort Pillow aquifers where this confining unit is thin, sandy, or absent.

Use of individual containers for prostate biopsy samples: Do we gain diagnostic performance?

PubMed

Panach-Navarrete, J; García-Morata, F; Valls-González, L; Martínez-Jabaloyas, J M

2016-05-01

Prostate cores from transrectal biopsies are usually sent in separate vials for pathological processing. Although this is a common practice, there are controversial studies on its usefulness. We wanted to compare the rate of prostate cancer diagnosis between processing samples in 2 containers and processing them in individual containers to see if there are differences. Our secondary objective was to check the rate of diagnosis of various tumour subtypes in each of the 2 groups. A retrospective observational study was conducted of 2,601 cases of prostate biopsies. Ten cores were extracted in each biopsy. We divided the sample into 2 groups: biopsies sent in 2 containers to the department of pathology (left and right lobes) or sent in 10 (one for each cylinder), according to the different criteria used in our centre in the past. We then classified the cases according to the absence of neoplasia, insignificant tumour (involvement of just 1 cylinder, <5%, Gleason score<7), Gleason 6 or Gleason≥7. A bivariate statistical analysis was performed using the chi-squared test. A total of 1,777 participants were included in the 2-container group, and 824 were included in the 10-container group. We diagnosed a rate of 32.4% of cancers in the 2-container group and 40% in the 10-container group, a difference that was statistically significant (P<.001). The insignificant carcinomas were diagnosed more often in the 2-container group than in the 10-container group (6.4% vs. 4.3%, respectively; P=.03). Samples with a Gleason score of 6 were diagnosed more often in the 10-container group than in the 2-container group (11.9% vs. 8.1%, respectively; P=.002). The same occurred with the Gleason score≥7 (23.8% in the 10-container group vs. 17.9% in the 2-container group; P<.001). We diagnosed more prostate cancers when sending biopsied cores in individual containers. Once the procedure was conducted, we also observed in our series a reduction in the diagnoses of insignificant carcinoma to the detriment of an increased diagnosis of not insignificant carcinomas. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

African-American Men with Gleason Score 3+3=6 Prostate Cancer Produce Less Prostate Specific Antigen than Caucasian Men: A Potential Impact on Active Surveillance.

PubMed

Kryvenko, Oleksandr N; Balise, Raymond; Soodana Prakash, Nachiketh; Epstein, Jonathan I

2016-02-01

We assess the difference in prostate specific antigen production between African-American and Caucasian men with Gleason score 3+3=6 prostate cancer. We measured tumor volume in 414 consecutive radical prostatectomies from men with National Comprehensive Cancer Network(®) low risk prostate cancer (348 Caucasian, 66 African-American) who had Gleason score 3+3=6 disease at radical prostatectomy. We then compared clinical presentation, pathological findings, prostate specific antigen, prostate specific antigen density and prostate specific antigen mass (an absolute amount of prostate specific antigen in patient's circulation) between African-American and Caucasian men. The t-test and Wilcoxon rank sum were used for comparison of means. African-American and Caucasian men had similar clinical findings based on age, body mass index and prostate specific antigen. There were no statistically significant differences between the dominant tumor nodule volume and total tumor volume (mean 0.712 vs 0.665 cm(3), p=0.695) between African-American and Caucasian men. Prostates were heavier in African-American men (mean 55.4 vs 46.3 gm, p <0.03). Despite the significantly greater weight of benign prostate tissue contributing to prostate specific antigen in African-American men, prostate specific antigen mass was not different from that of Caucasian men (mean 0.55 vs 0.558 μg, p=0.95). Prostate specific antigen density was significantly less in African-American men due to larger prostates (mean 0.09 vs 0.105, p <0.02). African-American men with Gleason score 3+3=6 prostate cancer produce less prostate specific antigen than Caucasian men. African-American and Caucasian men had equal serum prostate specific antigen and prostate specific antigen mass despite significantly larger prostates in African-American men with all other parameters, particularly total tumor volume, being the same. This finding has practical implications in T1c cases diagnosed with prostate cancer due to prostate specific antigen screening. Lowering the prostate specific antigen density threshold in African-American men may account for this disparity, particularly in selecting patients for active surveillance programs. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

A multicenter study shows PTEN deletion is strongly associated with seminal vesicle involvement and extracapsular extension in localized prostate cancer.

PubMed

Troyer, Dean A; Jamaspishvili, Tamara; Wei, Wei; Feng, Ziding; Good, Jennifer; Hawley, Sarah; Fazli, Ladan; McKenney, Jesse K; Simko, Jeff; Hurtado-Coll, Antonio; Carroll, Peter R; Gleave, Martin; Lance, Raymond; Lin, Daniel W; Nelson, Peter S; Thompson, Ian M; True, Lawrence D; Brooks, James D; Squire, Jeremy A

2015-08-01

Loss of the phosphatase and tensin homolog (PTEN) tumor suppressor gene is a promising marker of aggressive prostate cancer. Active surveillance and watchful waiting are increasingly recommended to patients with small tumors felt to be low risk, highlighting the difficulties of Gleason scoring in this setting. There is an urgent need for predictive biomarkers that can be rapidly deployed to aid in clinical decision-making. Our objectives were to assess the incidence and ability of PTEN alterations to predict aggressive disease in a multicenter study. We used recently developed probes optimized for sensitivity and specificity in a four-color FISH deletion assay to study the Canary Retrospective multicenter Prostate Cancer Tissue Microarray (TMA). This TMA was constructed specifically for biomarker validation from radical prostatectomy specimens, and is accompanied by detailed clinical information with long-term follow-up. In 612 prostate cancers, the overall rate of PTEN deletion was 112 (18.3%). Hemizygous PTEN losses were present in 55/612 (9.0%) of cancers, whereas homozygous PTEN deletion was observed in 57/612 (9.3%) of tumors. Significant associations were found between PTEN status and pathologic stage (P < 0.0001), seminal vesicle invasion (P = 0.0008), extracapsular extension (P < 0.0001), and Gleason score (P = 0.0002). In logistic regression analysis of clinical and pathological variables, PTEN deletion was significantly associated with extracapsular extension, seminal vesicle involvement, and higher Gleason score. In the 406 patients in which clinical information was available, PTEN homozygous (P = 0.009) deletion was associated with worse post-operative recurrence-free survival (number of events = 189), pre-operative prostate specific antigen (PSA) (P < 0.001), and pathologic stage (P = 0.03). PTEN status assessed by FISH is an independent predictor for recurrence-free survival in multivariate models, as were seminal vesicle invasion, extracapsular extension, and Gleason score, and preoperative PSA. Furthermore, these data demonstrate that the assay can be readily introduced at first diagnosis in a cost effective manner analogous to the use of FISH for analysis of HER2/neu status in breast cancer. Combined with published research beginning 17 years ago, both the data and tools now exist to implement a PTEN assay in the clinic. © 2015 The Authors. The Prostate, published by Wiley Periodicals, Inc.

Roles of Distal and Genic Methylation in the Development of Prostate Tumorigenesis Revealed by Genome-wide DNA Methylation Analysis.

PubMed

Wang, Yao; Jadhav, Rohit Ramakant; Liu, Joseph; Wilson, Desiree; Chen, Yidong; Thompson, Ian M; Troyer, Dean A; Hernandez, Javier; Shi, Huidong; Leach, Robin J; Huang, Tim H-M; Jin, Victor X

2016-02-29

Aberrant DNA methylation at promoters is often linked to tumorigenesis. But many aspects of DNA methylation remain unexplored, including the individual roles of distal and gene body methylation, as well as their collaborative roles with promoter methylation. Here we performed a MBD-seq analysis on prostate specimens classified into low, high, and very high risk group based on Gleason score and TNM stages. We identified gene sets with differential methylation regions (DMRs) in Distal, TSS, gene body and TES. To understand the collaborative roles, TSS was compared with the other three DMRs, resulted in 12 groups of genes with collaborative differential methylation patterns (CDMPs). We found several groups of genes that show opposite methylation patterns in Distal and Genic regions compared to TSS region, and in general they are differentially expressed genes (DEGs) in tumors in TCGA RNA-seq data. IPA (Ingenuity Pathway Analysis) reveals AR/TP53 signaling network to be a major signaling pathway, and survival analysis indicates genes subsets significantly associated with prostate cancer recurrence. Our results suggest that DNA methylation in Distal and Genic regions also plays critical roles in contributing to prostate tumorigenesis, and may act either positively or negatively with TSSs to alter gene regulation in tumors.

Optimizing D'Amico risk groups in radical prostatectomy through the addition of magnetic resonance imaging data.

PubMed

Algarra, R; Zudaire, B; Tienza, A; Velis, J M; Rincón, A; Pascual, I; Zudaire, J

2014-11-01

To improve the predictive efficacy of the D'Amico risk classification system with magnetic resonance imaging (MRI) of the pelvis. We studied 729 patients from a series of 1310 radical prostatectomies for T1-T2 prostate cancer who underwent staging pelvic MRI. Each patient was classified with T2, T3a or T3b MRI, and N (+) patients were excluded. We identified the therapeutic factors that affected the biochemical progression-free survival (BPFS) time (prostate specific antigen [PSA] levels>0.4ng/mL) using a univariate and multivariate study with Cox models. We attempted to improve the predictive power of the D'Amico model (low risk: T1; Gleason 2-6; PSA levels<10ng/mL; intermediate risk: T2 or Gleason 7 or PSA levels 10-20ng/mL; high risk: T3 or Gleason 8-10 or PSA levels>20ng/mL). In the univariate study, the clinical factors that influenced BPFS were the following: Gleason 7 (HR: 1.7); Gleason 8-10 (HR: 2.9); T2 (HR: 1.6); PSA levels 10-20 (HR: 2); PSA levels>20 (HR: 4.3); D'Amico intermediate (HR: 2.1) and high (HR: 4.8) risk; T3a MRI (HR: 2.3) and T3b MRI (HR: 4.5). In the multivariate study, the only variables that affected BPFS were the following: D'Amico intermediate risk (HR: 2; 95% CI 1.2-3.3); D'Amico high risk (HR: 4.1; 95% CI 2.4-6.8); T3a MRI (HR: 1.9; 95% CI 1.2-2.9) and T3b MRI (HR: 3.9; 95% CI 2.5-6.1). Predictive model: Using the multivariate Cox models, we assessed the weight of each variable. A value of 1 was given to D'Amico low risk and T2 MRI; a value of 2 was given to D'Amico intermediate risk and T3a MRI and a value 3 was given to D'Amico high risk and T3b MRI. Each patient had a marker that varied between 2 and 6. The best model included 3 groups, as follows: 494 (67.7%) patients in group 1, with a score of 2-3 points (HR, 1), a BPFS of 86%±2% and 79%±2% at 5 and 10 years, respectively; 179 (24.6%) patients in group 2, with a score of 4 points (HR, 3), a BPFS of 60%±4% and 54%±5% at 5 and 10 years, respectively; and 56 (7.7%) patients in group 3, with a score of 5-6 points (HR, 9.3), a BPFS of 29%±8% and 19%±7% at 5 and 10 years, respectively. The median BPFS time was 1.5 years. MRI data significantly improves the predictive capacity of BPFS when using the D'Amico model data. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

Gigabit Nectar: Architecture and Performance.

DTIC Science & Technology

1995-09-01

proposed American National Standard for Information Systems, 1992. [3] Jose Arabe, Adam Beguelin, Bruce Lowekamp, Eric Seligman , Mike Starkey, and Peter...Shekhar Borkar, Robert Cohn, George Cox, Sha Gleason, Thomas Gross, H. T. Kung, Monica Lam, Brian Moore, Craig Peterson, John Pieper, Linda Rankin, P

Graphic Organizers for Secondary Students with Learning Disabilities

ERIC Educational Resources Information Center

Singleton, Sabrina M.; Filce, Hollie Gabler

2015-01-01

Research suggests students with learning disabilities often have trouble connecting new and prior knowledge, distinguishing essential and nonessential information, and applying comprehension strategies (DiCecco & Gleason, 2002; Vaughn & Edmonds, 2006). Graphic organizers have been suggested as tools educators can use to facilitate critical…

Monitoring Soil Erosion of a Burn Site in the Central Basin and Range Ecoregion: Final Report on Measurements at the Gleason Fire Site, Nevada

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

Miller, Julianne; Etyemezian, Vicken; Shillito, Rose

The increase in wildfires in arid and semi-arid parts of Nevada and elsewhere in the southwestern United States has implications for post-closure management and long-term stewardship for Soil Corrective Action Units (CAUs) on the Nevada National Security Site (NNSS) for which the Nevada Field Office of the United States Department of Energy, National Nuclear Security Administration has responsibility. For many CAUs and Corrective Action Sites, where closure-in-place alternatives are now being implemented or considered, there is a chance that these sites could burn over at some time while they still pose a risk to the environment or human health, givenmore » the long half lives of some of the radionuclide contaminants. This study was initiated to examine the effects and duration of wildfire on wind and water erodibility on sites analogous to those that exist on the NNSS. The data analyzed herein were gathered at the prescribed Gleason Fire site near Ely, Nevada, a site comparable to the northern portion of the NNSS. Quantification of wind erosion was conducted with a Portable In-Situ Wind ERosion Lab (PI-SWERL) on unburned soils, and on interspace and plant understory soils within the burned area. The PI-SWERL was used to estimate emissions of suspendible particles (particulate matter with aerodynamic diameters less than or equal to 10 micrometers) at different wind speeds. Filter samples, collected from the exhaust of the PI-SWERL during measurements, were analyzed for chemical composition. Based on nearly three years of data, the Gleason Fire site does not appear to have returned to pre burn wind erosion levels. Chemical composition data of suspendible particles are variable and show a trend toward pre-burn levels, but provide little insight into how the composition has been changing over time since the fire. Soil, runoff, and sediment data were collected from the Gleason Fire site to monitor the water erosion potential over the nearly three-year period. Soil hydrophobicity (water repellency) was noted on burned understory soils up to 12 months after the fire, as was the presence of ash on the soil surface. Soil deteriorated from a strong, definable pre-fire structure to a weakly cohesive mass (unstructured soil) immediately after the fire. Surface soil structure was evident 34 months after the fire at both burned and unburned sites, but was rare and weaker at burned sites. The amount of runoff and sediment was highly variable, but runoff occurred more frequently at burned interspace sites compared to burned understory and unburned interspace sites up to 34 months after the burn. No discernible pattern was evident on the amount of sediment transported, but the size of sediment from burned understory sites was almost double that of burned and unburned interspace soils after the fire, and decreased over the monitoring period. Curve numbers, a measure of the runoff potential, did not indicate any obvious runoff response to the fire. However, slight seasonal changes in curve numbers and runoff potential and, therefore, post-fire runoff response may be a function of fire impacts as well as the time of year that precipitation occurs. Site (interspace or understory) differences in soil properties and runoff persisted even after the fire. Vegetation data showed the presence of invasive grasses after the fire. Results from analysis of wind and water coupled with the spatial analysis of vegetation suggest that wind erosion may continue to occur due to the additional exposed soil surface (burned understory sites) until vegetation becomes re-established, and runoff may occur more frequently in interspace sites. The potential for fire-related wind erosion and water erosion may persist beyond three years in this system.« less

Heterogeneity of PTEN and ERG expression in prostate cancer on core needle biopsies: implications for cancer risk stratification and biomarker sampling.

PubMed

Shah, Rajal B; Bentley, James; Jeffery, Zach; DeMarzo, Angelo M

2015-05-01

ERG and PTEN biomarkers are increasingly being analyzed on prostate core biopsies (NBXs); ERG as a marker of clonality and number of separately arising tumor foci and PTEN for prognostic information. Yet, in patients with multiple biopsy cores positive for cancer (PCa), there is no standardized approach for interrogation of these biomarkers in terms of the number of positive cores to evaluate. A total of 194 NBX cases containing more than one positive core with cancer were evaluated for ERG overexpression and PTEN loss by immunostaining (immunohistochemistry) of all positive cores. ERG overexpression or PTEN loss in at least one cancer core was present in 111 (57%) and 69 (36%) cases respectively. ERG overexpression was significantly associated with PTEN loss (P < .0001), and PTEN loss was associated with a high Gleason score (P < .0001). Inter- and intra-tumor core staining heterogeneity for ERG overexpression occurred in 42% and 5% cases and for PTEN loss both intra- and inter-tumor core heterogeneity was 68%. PTEN staining was highly discordant between PCa sites regardless of laterality. When the Gleason score was non-uniform across PCa sites, the combination of cores showing the highest Gleason score and largest tumor volume provided the best representation of ERG overexpression (92%) and PTEN loss (98%). When grades were uniform across cancer sites, the highest tumor volume core was generally representative of ERG overexpression (90%) but was less representative for PTEN loss (76%). Our results suggest that knowledge of this heterogeneity is critical for developing optimal yet cost-effective strategies to identify these underlying molecular abnormalities. Copyright © 2015 Elsevier Inc. All rights reserved.

The use of artificial intelligence technology to predict lymph node spread in men with clinically localized prostate carcinoma.

PubMed

Crawford, E D; Batuello, J T; Snow, P; Gamito, E J; McLeod, D G; Partin, A W; Stone, N; Montie, J; Stock, R; Lynch, J; Brandt, J

2000-05-01

The current study assesses artificial intelligence methods to identify prostate carcinoma patients at low risk for lymph node spread. If patients can be assigned accurately to a low risk group, unnecessary lymph node dissections can be avoided, thereby reducing morbidity and costs. A rule-derivation technology for simple decision-tree analysis was trained and validated using patient data from a large database (4,133 patients) to derive low risk cutoff values for Gleason sum and prostate specific antigen (PSA) level. An empiric analysis was used to derive a low risk cutoff value for clinical TNM stage. These cutoff values then were applied to 2 additional, smaller databases (227 and 330 patients, respectively) from separate institutions. The decision-tree protocol derived cutoff values of < or = 6 for Gleason sum and < or = 10.6 ng/mL for PSA. The empiric analysis yielded a clinical TNM stage low risk cutoff value of < or = T2a. When these cutoff values were applied to the larger database, 44% of patients were classified as being at low risk for lymph node metastases (0.8% false-negative rate). When the same cutoff values were applied to the smaller databases, between 11 and 43% of patients were classified as low risk with a false-negative rate of between 0.0 and 0.7%. The results of the current study indicate that a population of prostate carcinoma patients at low risk for lymph node metastases can be identified accurately using a simple decision algorithm that considers preoperative PSA, Gleason sum, and clinical TNM stage. The risk of lymph node metastases in these patients is < or = 1%; therefore, pelvic lymph node dissection may be avoided safely. The implications of these findings in surgical and nonsurgical treatment are significant.

The role of imaging based prostate biopsy morphology in a data fusion paradigm for transducing prognostic predictions

NASA Astrophysics Data System (ADS)

Khan, Faisal M.; Kulikowski, Casimir A.

2016-03-01

A major focus area for precision medicine is in managing the treatment of newly diagnosed prostate cancer patients. For patients with a positive biopsy, clinicians aim to develop an individualized treatment plan based on a mechanistic understanding of the disease factors unique to each patient. Recently, there has been a movement towards a multi-modal view of the cancer through the fusion of quantitative information from multiple sources, imaging and otherwise. Simultaneously, there have been significant advances in machine learning methods for medical prognostics which integrate a multitude of predictive factors to develop an individualized risk assessment and prognosis for patients. An emerging area of research is in semi-supervised approaches which transduce the appropriate survival time for censored patients. In this work, we apply a novel semi-supervised approach for support vector regression to predict the prognosis for newly diagnosed prostate cancer patients. We integrate clinical characteristics of a patient's disease with imaging derived metrics for biomarker expression as well as glandular and nuclear morphology. In particular, our goal was to explore the performance of nuclear and glandular architecture within the transduction algorithm and assess their predictive power when compared with the Gleason score manually assigned by a pathologist. Our analysis in a multi-institutional cohort of 1027 patients indicates that not only do glandular and morphometric characteristics improve the predictive power of the semi-supervised transduction algorithm; they perform better when the pathological Gleason is absent. This work represents one of the first assessments of quantitative prostate biopsy architecture versus the Gleason grade in the context of a data fusion paradigm which leverages a semi-supervised approach for risk prognosis.

The histogram analysis of diffusion-weighted intravoxel incoherent motion (IVIM) imaging for differentiating the gleason grade of prostate cancer.

PubMed

Zhang, Yu-Dong; Wang, Qing; Wu, Chen-Jiang; Wang, Xiao-Ning; Zhang, Jing; Liu, Hui; Liu, Xi-Sheng; Shi, Hai-Bin

2015-04-01

To evaluate histogram analysis of intravoxel incoherent motion (IVIM) for discriminating the Gleason grade of prostate cancer (PCa). A total of 48 patients pathologically confirmed as having clinically significant PCa (size > 0.5 cm) underwent preoperative DW-MRI (b of 0-900 s/mm(2)). Data was post-processed by monoexponential and IVIM model for quantitation of apparent diffusion coefficients (ADCs), perfusion fraction f, diffusivity D and pseudo-diffusivity D*. Histogram analysis was performed by outlining entire-tumour regions of interest (ROIs) from histological-radiological correlation. The ability of imaging indices to differentiate low-grade (LG, Gleason score (GS) ≤6) from intermediate/high-grade (HG, GS > 6) PCa was analysed by ROC regression. Eleven patients had LG tumours (18 foci) and 37 patients had HG tumours (42 foci) on pathology examination. HG tumours had significantly lower ADCs and D in terms of mean, median, 10th and 75th percentiles, combined with higher histogram kurtosis and skewness for ADCs, D and f, than LG PCa (p < 0.05). Histogram D showed relatively higher correlations (ñ = 0.641-0.668 vs. ADCs: 0.544-0.574) with ordinal GS of PCa; and its mean, median and 10th percentile performed better than ADCs did in distinguishing LG from HG PCa. It is feasible to stratify the pathological grade of PCa by IVIM with histogram metrics. D performed better in distinguishing LG from HG tumour than conventional ADCs. • GS had relatively higher correlation with tumour D than ADCs. • Difference of histogram D among two-grade tumours was statistically significant. • D yielded better individual features in demonstrating tumour grade than ADC. • D* and f failed to determine tumour grade of PCa.

Planned nerve preservation to reduce positive surgical margins during robot-assisted laparoscopic radical prostatectomy.

PubMed

Zorn, Kevin C; Gofrit, Ofer N; Steinberg, Gary P; Taxy, Jerome B; Zagaja, Gregory P; Shalhav, Arieh L

2008-06-01

The main objective of radical prostatectomy (RP) is optimal oncologic resection with preservation of sexual function (SF). During our initial experience with robot-assisted laparoscopic radical prostatectomy (RLRP), we noted a high rate of posterolateral location of positive surgical margins (PSM) with nerve preservation (NP). With its magnified view of the surgical field and improved instrument precision, one potential advantage of RLRP is the ability to tailor the degree of NP. We evaluated the effect of a protocol for side-specific NP based on preoperative variables on PSM rates and SF outcomes. Between June and November 2006, 150 consecutive RLRPs were performed using a surgical protocol to select side-specific NP techniques (interfascial [IF], partial extrafascial [pEF], and wide extrafascial resection [WEFR]) based on preoperative risk factors (clinical stage, biopsy Gleason score, percentage of positive cores and maximal core cancer percentage, and preoperative PSA). Pathologic and SF outcomes in these patients were compared with those of a control group of 245 consecutive RLRPs in whom non-selective IF dissection was performed. All data were prospectively collected. Mean patient age, PSA, clinical stage, biopsy Gleason score and positive core involvement, pathologic Gleason score, and stage were comparable among the two groups. The overall PSM rate (12.6% nu 20.4%; P = 0.04) and posterolateral location of PSMs (37% nu 70%; P = 0.04) were significantly lower in the study group. At 12 months, potency was reported in 80%, 67%, and 11% of men undergoing bilateral IFNP, partial extrafascial nerve preservation (pEFNP), and WEFR, respectively (P = 0.27). Planning side-specific NP during RLRP, according to selected preoperative variables, can significantly reduce overall and posterolateral PSM rates. Furthermore, partial nerve sparing (pEFNP) also appears to confer favorable early SF outcomes.

Prostate weight: an independent predictor for positive surgical margins during robotic-assisted laparoscopic radical prostatectomy.

PubMed

Msezane, Lambda P; Gofrit, Ofer N; Lin, Shang; Shalhav, Arieh L; Zagaja, Gregory P; Zorn, Kevin C

2007-10-01

Pre-operative prediction of pathological stage represents the cornerstone of prostate cancer management. Patient counseling is routinely based on pre-operative PSA, Gleason score and clinical stage. In this study, we evaluated whether prostate weight (PW) is an independent predictor of extracapsular extension (ECE) and positive surgical margin (PSM). Between February 2003 and November 2006, 709 men underwent robotic-assisted laparoscopic radical prostatectomy (RLRP). Pre-operative parameters (patient age, pre-operative PSA, biopsy Gleason score, clinical stage) as well as pathological data (prostate weight, pathological stage) were prospectively gathered after internal-review board (IRB) approval. Evaluation of the influence of these variables on ECE and PSM outcomes were assessed using both univariate and multivariate logistic regression analysis. Mean overall patient age, pre-operative PSA and PW were 59.6 years, 6.5 ng/ml and 52.9 g (range 5.5 g-198.7 g), respectively. Of the 393, 209 and 107 men with PW < 50 g, 50 g-< 70 g and < 70 g, ECE was observed in 20.1%, 15.3% and 9.3%, respectively (p = 0.015). In the same patient cohorts, PSM was observed in 25.4%, 14.4% and 7.5%, respectively (p < 0.001). In a multivariate logistic regression analysis, PW, in addition to pre-operative PSA, biopsy Gleason score and clinical stage, was an independent risk factor for ECE (p < 0.001). Similarly, in multi-variate analysis, PW was observed to be a risk factor for PSM (p < 0.001). PW is an independent predictor of both ECE and PSM, with an inverse relationship having been demonstrated between both variables. PW should be considered when counseling patients with prostate cancer treatment.

Impact of prostate weight on probability of positive surgical margins in patients with low-risk prostate cancer after robotic-assisted laparoscopic radical prostatectomy.

PubMed

Marchetti, Pablo E; Shikanov, Sergey; Razmaria, Aria A; Zagaja, Gregory P; Shalhav, Arieh L

2011-03-01

To evaluate the impact of prostate weight (PW) on probability of positive surgical margin (PSM) in patients undergoing robotic-assisted radical prostatectomy (RARP) for low-risk prostate cancer. The cohort consisted of 690 men with low-risk prostate cancer (clinical stage T1c, prostate-specific antigen <10 ng/mL, biopsy Gleason score ≤6) who underwent RARP with bilateral nerve-sparing at our institution by 1 of 2 surgeons from 2003 to 2009. PW was obtained from the pathologic specimen. The association between probability of PSM and PW was assessed with univariate and multivariate logistic regression analysis. A PSM was identified in 105 patients (15.2%). Patients with PSM had significant higher prostate-specific antigen (P = .04), smaller prostates (P = .0001), higher Gleason score (P = .004), and higher pathologic stage (P < .0001). After logistic regression, we found a significant inverse relation between PSM and PW (OR 0.97%; 95% confidence interval [CI] 0.96, 0.99; P = .0003) in univariate analysis. This remained significant in the multivariate model (OR 0.98%; 95% CI 0.96, 0.99; P = .006) adjusting for age, body mass index, surgeon experience, pathologic Gleason score, and pathologic stage. In this multivariate model, the predicted probability of PSM for 25-, 50-, 100-, and 150-g prostates were 22% (95% CI 16%, 30%), 13% (95% CI 11%, 16%), 5% (95% CI 1%, 8%), and 1% (95% CI 0%, 3%), respectively. Lower PW is independently associated with higher probability of PSM in low-risk patients undergoing RARP with bilateral nerve-sparing. Copyright © 2011 Elsevier Inc. All rights reserved.

A four-kallikrein panel for the prediction of repeat prostate biopsy: data from the European Randomized Study of Prostate Cancer screening in Rotterdam, Netherlands.

PubMed

Gupta, A; Roobol, M J; Savage, C J; Peltola, M; Pettersson, K; Scardino, P T; Vickers, A J; Schröder, F H; Lilja, H

2010-08-24

Most men with elevated levels of prostate-specific antigen (PSA) do not have prostate cancer, leading to a large number of unnecessary biopsies. A statistical model based on a panel of four kallikreins has been shown to predict the outcome of a first prostate biopsy. In this study, we apply the model to an independent data set of men with previous negative biopsy but persistently elevated PSA. The study cohort consisted of 925 men with a previous negative prostate biopsy and elevated PSA (>or=3 ng ml(-1)), with 110 prostate cancers detected (12%). A previously published statistical model was applied, with recalibration to reflect the lower positive biopsy rates on rebiopsy. The full-kallikrein panel had higher discriminative accuracy than PSA and DRE alone, with area under the curve (AUC) improving from 0.58 (95% confidence interval (CI): 0.52, 0.64) to 0.68 (95% CI: 0.62, 0.74), P<0.001, and high-grade cancer (Gleason >or=7) at biopsy with AUC improving from 0.76 (95% CI: 0.64, 0.89) to 0.87 (95% CI: 0.81, 0.94), P=0.003). Application of the panel to 1000 men with persistently elevated PSA after initial negative biopsy, at a 15% risk threshold would reduce the number of biopsies by 712; would miss (or delay) the diagnosis of 53 cancers, of which only 3 would be Gleason 7 and the rest Gleason 6 or less. Our data constitute an external validation of a previously published model. The four-kallikrein panel predicts the result of repeat prostate biopsy in men with elevated PSA while dramatically decreasing unnecessary biopsies.

Socioeconomic disadvantage but not remoteness affects short-term survival in prostate cancer: A population-based study using competing risks.

PubMed

Thomas, Audrey A; Pearce, Alison; Sharp, Linda; Gardiner, Robert Alexander; Chambers, Suzanne; Aitken, Joanne; Molcho, Michal; Baade, Peter

2017-04-01

We examined how sociodemographic, clinical and area-level factors are related to short-term prostate cancer mortality versus mortality from other causes, a crucial distinction for this disease that disproportionately affects men older than 60 years. We applied competing risk survival models to administrative data from the Queensland Cancer Registry (Australia) for men diagnosed with prostate cancer between January 2005 and July 2007, including stratification by Gleason score. The men (n = 7393) in the study cohort had a median follow-up of 5 years 3 months. After adjustment, remoteness and area-level disadvantage were not significantly associated with prostate cancer mortality. However, area-level disadvantage had a significant negative relationship with hazard of death from a cause other than prostate cancer within 7 years; compared with those living in the most advantaged areas, the likelihood of mortality was higher for those in the most disadvantaged (subhazard ratio [SHR] = 1.39; 95% CI, 1.01-1.90; P = 0.041), disadvantaged (SHR = 1.51; 95% CI, 1.14-2.00; P = 0.004), middle (SHR = 1.34; 95% CI, 1.02-1.75; P = 0.034) and advantaged areas (SHR = 1.44; 95% CI, 1.09-1.89; P = 0.009). Those with Gleason score of 7 and higher had a lower hazard of prostate cancer mortality if they were living with a partner, whereas those with lower Gleason scores and living a partner had lower hazards of other-cause mortality. Understanding why men living in more disadvantaged areas have higher risk of non-prostate cancer mortality should be a priority. © 2016 John Wiley & Sons Australia, Ltd.

Informed Decision Making: Assessment of the Quality of Physician Communication about Prostate Cancer Diagnosis and Treatment.

PubMed

Holmes-Rovner, Margaret; Montgomery, Jeffrey S; Rovner, David R; Scherer, Laura D; Whitfield, Jesse; Kahn, Valerie C; Merkle, Edgar C; Ubel, Peter A; Fagerlin, Angela

2015-11-01

Little is known about how physicians present diagnosis and treatment planning in routine practice in preference-sensitive treatment decisions. We evaluated completeness and quality of informed decision making in localized prostate cancer post biopsy encounters. We analyzed audio-recorded office visits of 252 men with presumed localized prostate cancer (Gleason 6 and Gleason 7 scores) who were seeing 45 physicians at 4 Veterans Affairs Medical Centers. Data were collected between September 2008 and May 2012 in a trial of 2 decision aids (DAs). Braddock's previously validated Informed Decision Making (IDM) system was used to measure quality. Latent variable models for ordinal data examined the relationship of IDM score to treatment received. Mean IDM score showed modest quality (7.61±2.45 out of 18) and high variability. Treatment choice and risks and benefits were discussed in approximately 95% of encounters. However, in more than one-third of encounters, physicians provided a partial set of treatment options and omitted surveillance as a choice. Informing quality was greater in patients treated with surveillance (β = 1.1, p = .04). Gleason score (7 vs 6) and lower age were often cited as reasons to exclude surveillance. Patient preferences were elicited in the majority of cases, but not used to guide treatment planning. Encounter time was modestly correlated with IDM score (r = 0.237, p = .01). DA type was not associated with IDM score. Physicians informed patients of options and risks and benefits, but infrequently engaged patients in core shared decision-making processes. Despite patients having received DAs, physicians rarely provided an opportunity for preference-driven decision making. More attention to the underused patient decision-making and engagement elements could result in improved shared decision making. © The Author(s) 2015.

Prostate cancer: role of pretreatment multiparametric 3-T MRI in predicting biochemical recurrence after radical prostatectomy.

PubMed

Park, Jung Jae; Kim, Chan Kyo; Park, Sung Yoon; Park, Byung Kwan; Lee, Hyun Moo; Cho, Seong Whi

2014-05-01

The purpose of this study is to retrospectively investigate whether pretreatment multiparametric MRI findings can predict biochemical recurrence in patients who underwent radical prostatectomy (RP) for localized prostate cancer. In this study, 282 patients with biopsy-proven prostate cancer who received RP underwent pretreatment MRI using a phased-array coil at 3 T, including T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and dynamic contrast-enhanced MRI (DCE-MRI). MRI variables included apparent tumor presence on combined imaging sequences, extracapsular extension, and tumor size on DWI or DCE-MRI. Clinical variables included baseline prostate-specific antigen (PSA) level, clinical stage, and Gleason score at biopsy. The relationship between clinical and imaging variables and biochemical recurrence was evaluated using Cox regression analysis. After a median follow-up of 26 months, biochemical recurrence developed in 61 patients (22%). Univariate analysis revealed that all the imaging and clinical variables were significantly associated with biochemical recurrence (p < 0.01). On multivariate analysis, however, baseline PSA level (p = 0.002), Gleason score at biopsy (p = 0.024), and apparent tumor presence on combined T2WI, DWI, and DCE-MRI (p = 0.047) were the only significant independent predictors of biochemical recurrence. Of the independent predictors, apparent tumor presence on combined T2WI, DWI, and DCE-MRI showed the highest hazard ratio (2.38) compared with baseline PSA level (hazard ratio, 1.05) and Gleason score at biopsy (hazard ratio, 1.34). The apparent tumor presence on combined T2WI, DWI, and DCE-MRI of pretreatment MRI is an independent predictor of biochemical recurrence after RP. This finding may be used to construct a predictive model for biochemical recurrence after surgery.

Role of serial multiparametric magnetic resonance imaging in prostate cancer active surveillance

PubMed Central

Vos, Larissa J; Janoski, Michele; Wachowicz, Keith; Yahya, Atiyah; Boychak, Oleksandr; Amanie, John; Pervez, Nadeem; Parliament, Matthew B; Pituskin, Edith; Fallone, B Gino; Usmani, Nawaid

2016-01-01

AIM: To examine whether addition of 3T multiparametric magnetic resonance imaging (mpMRI) to an active surveillance protocol could detect aggressive or progressive prostate cancer. METHODS: Twenty-three patients with low risk disease were enrolled on this active surveillance study, all of which had Gleason score 6 or less disease. All patients had clinical assessments, including digital rectal examination and prostate specific antigen (PSA) testing, every 6 mo with annual 3T mpMRI scans with gadolinium contrast and minimum sextant prostate biopsies. The MRI images were anonymized of patient identifiers and clinical information and each scan underwent radiological review without the other results known. Descriptive statistics for demographics and follow-up as well as the sensitivity and specificity of mpMRI to identify prostate cancer and progressive disease were calculated. RESULTS: During follow-up (median 24.8 mo) 11 of 23 patients with low-risk prostate cancer had disease progression and were taken off study to receive definitive treatment. Disease progression was identified through upstaging of Gleason score on subsequent biopsies for all 11 patients with only 2 patients also having a PSA doubling time of less than 2 years. All 23 patients had biopsy confirmed prostate cancer but only 10 had a positive index of suspicion on mpMRI scans at baseline (43.5% sensitivity). Aggressive disease prediction from baseline mpMRI scans had satisfactory specificity (81.8%) but low sensitivity (58.3%). Twenty-two patients had serial mpMRI scans and evidence of disease progression was seen for 3 patients all of whom had upstaging of Gleason score on biopsy (30% specificity and 100% sensitivity). CONCLUSION: Addition of mpMRI imaging in active surveillance decision making may help in identifying aggressive disease amongst men with indolent prostate cancer earlier than traditional methods. PMID:27158428

Telecommunications in Education (T.I.E.) News. 1996-1997.

ERIC Educational Resources Information Center

Owen, Trevor, Ed.

1997-01-01

This document consists of one volume year (four quarterly issues) of the journal "Telecommunications in Education News." Each issue contains a call for articles and three regular columns: "Editor's Message" (Trevor Owen), "President's Message" (Chuck Lynd), and "NewsBits" (Gleason Sackman, Ed.). Article…

Regular Gleason Measures and Generalized Effect Algebras

NASA Astrophysics Data System (ADS)

Dvurečenskij, Anatolij; Janda, Jiří

2015-12-01

We study measures, finitely additive measures, regular measures, and σ-additive measures that can attain even infinite values on the quantum logic of a Hilbert space. We show when particular classes of non-negative measures can be studied in the frame of generalized effect algebras.

Role of endorectal magnetic resonance spectroscopic imaging in two different Gleason scores in prostate cancer.

PubMed

Nagarajan, Rajakumar; Margolis, Daniel; McClure, Tim; Raman, Steve; Thomas, M Albert

2011-01-01

The major goal of the work was to record three-dimensional magnetic resonance spectroscopic imaging (MRSI) and to compare metabolite ratios between different Gleason scores (GS). MRSI localized by endorectal coil-acquired point-resolved spectroscopy was performed in 14 men with prostate cancer of GS 6 (n = 7) and 7 (n = 7) using a 1.5-tesla MRI scanner. The ratio of (choline + creatine)/citrate was increased with an increase of GS, i.e. 0.590 ± 0.171 in the target lesion and 0.321 ± 0.157 in the contralateral region of patients with a GS of 6 as opposed to 1.082 ± 0.432 in the target lesion and 0.360 ± 0.243 in the contralateral region of patients with a GS of 7. Our pilot results demonstrated that MRSI was an additional biochemical tool which is complementary to the current imaging modalities for early diagnosis and therapeutic management of prostate cancer. Copyright © 2011 S. Karger AG, Basel.

68Ga-PSMA-11 Dynamic PET/CT Imaging in Primary Prostate Cancer.

PubMed

Sachpekidis, Christos; Kopka, Klaus; Eder, Matthias; Hadaschik, Boris A; Freitag, Martin T; Pan, Leyun; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

2016-11-01

The aim of our study is to assess the pharmacokinetics and biodistribution of Ga-PSMA-11 in patients suffering from primary prostate cancer (PC) by means of dynamic and whole-body PET/CT. Twenty-four patients with primary, previously untreated PC were enrolled in the study. All patients underwent dynamic PET/CT (dPET/CT) scanning of the pelvis and whole-body PET/CT studies with Ga-PSMA-11. The evaluation of dPET/CT studies was based on qualitative evaluation, SUV calculation, and quantitative analysis based on two-tissue compartment modeling and a noncompartmental approach leading to the extraction of fractal dimension (FD). A total of 23/24 patients (95.8%) were Ga-PSMA-11 positive. In 9/24 patients (37.5%), metastatic lesions were detected. PC-associated lesions demonstrated the following mean values: SUVaverage = 14.3, SUVmax = 23.4, K1 = 0.24 (1/min), k3 = 0.34 (1/min), influx = 0.15 (1/min), and FD = 1.27. The parameters SUVaverage, SUVmax, k3, influx, and FD derived from PC-associated lesions were significantly higher than respective values derived from reference prostate tissue. Time-activity curves derived from PC-associated lesions revealed an increasing Ga-PSMA-11 accumulation during dynamic PET acquisition. Correlation analysis revealed a moderate but significant correlation between PSA levels and SUVaverage (r = 0.60) and SUVmax (r = 0.57), and a weak but significant correlation between Gleason score and SUVaverage (r = 0.33) and SUVmax (r = 0.28). Ga-PSMA-11 PET/CT confirmed its capacity in detecting primary PC with a detection rate of 95.8%. Dynamic PET/CT studies of the pelvis revealed an increase in tracer uptake in PC-associated lesions during the 60 minutes of dynamic PET acquisition, a finding with potential applications in anti-PSMA approaches.

Trends in Radical Prostatectomy Risk Group Distribution in a European Multicenter Analysis of 28 572 Patients: Towards Tailored Treatment.

PubMed

van den Bergh, Roderick; Gandaglia, Giorgio; Tilki, Derya; Borgmann, Hendrik; Ost, Piet; Surcel, Christian; Valerio, Massimo; Sooriakumaran, Prasanna; Salomon, Laurent; Briganti, Alberto; Graefen, Markus; van der Poel, Henk; de la Taille, Alexandre; Montorsi, Francesco; Ploussard, Guillaume

2017-08-08

Active surveillance (AS) has been increasingly proposed as the preferential initial management strategy for low-risk prostate cancer (PC), while in high-risk PC the indication for surgery has widened. To evaluate the development of risk group distribution of patients undergoing radical prostatectomy (RP). Retrospective database review of combined RP databases (2000-2015) of four large European centers (Créteil, Paris; San Rafaele, Milan; Martini Klinik, Hamburg; NKI, AvL, Amsterdam). Clinical and pathological characteristics per year of surgery. Eligibility for AS was defined according to Prostate Cancer Research International Active Surveillance criteria: cT≤2c, cN0/X, cM0/X, PSA ≤10ng/ml, prostate-specific antigen density <0.2ng/ml/ml, one to two positive biopsies, and Gleason score ≤6, high-risk disease as: cT≥3, c N1, cM1, PSA >20ng/ml, and/or Gleason ≥8. In total, 28572 patients had complete clinical and 24790 complete pathological data available. The absolute number of RPs increased: 401, 975, 2344, and 2504 in 2000, 2005, 2010, and 2015, respectively. The proportion of cases considered suitable for AS decreased: 31%, 32%, 18%, and 5%, while the cases considered high risk increased: 10%, 8%, 16%, and 30%. The percentage of patients having only localized Gleason 6 disease after RP decreased: 46%, 34%, 14%, and 8% for all patients (p<0.01), as well as for AS-suitable patients: 70%, 54%, 41%, and 38% (p<0.01). Comparisons between centers were outside the scope of this article. Developments in diagnostics may have impacted on results. This European analysis confirmed the risk profile of patients undergoing RP shifting away of the most favorable disease spectrum. Patients with PC clinically considered suitable for AS and men having only localized Gleason 6 disease pathologically comprised a decreasing share of all RP performed. High-risk disease comprised an increasing share of all RPs. The databases of four large European centers of prostate cancer surgery were analyzed. In recent years, the risk profile of patients shifted away of low-risk cancer, while high-risk cancer comprised a larger part of cases. This confirms the introduction of active surveillance for low-risk prostate cancer and increase in potentially curative options for high-risk disease. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Men presenting with prostate-specific antigen (PSA) values of over 100 ng/mL.

PubMed

Ang, Mann; Rajcic, Branimir; Foreman, Darren; Moretti, Kim; O'Callaghan, Michael E

2016-04-01

To investigate overall survival and prostate cancer-specific mortality in men with prostate cancer presenting with a PSA level <100 ng/mL at the time of diagnosis. Five-thousand seven hundred and sixteen patients with prostate cancer and a recorded diagnostic PSA level extracted from the South Australian Prostate Cancer Clinical Outcomes Collaborative (SA-PCCOC) database. Men included were diagnosed between January 1998 and August 2013. Patients were divided into groups according to diagnostic PSA level: <20, 20-≤100, 100-≤200 ng/mL, 200-≤500 ng/mL, and >500 ng/mL. Outcomes measured include overall survival and prostate cancer-specific mortality. Clinical stage, Gleason score and the presence of bony metastasis was evaluated to determine if they were prognostic factors in patients with PSA over 100 at diagnosis. Cox proportional hazards and competing risks regression were used to model overall survival and prostate cancer-specific mortality outcomes respectively. Of this cohort, 241 patients (4.2%) had a diagnostic PSA level >100 ng/mL. Patients with PSA >100 ng/mL have a significant reduction in five (29.1% vs 62.5% vs 87%) and ten-year (18.2% vs 36.7% vs 70.7%) overall survival when compared to men with diagnostic PSA 20-100 and <20 ng/mL respectively. In this group, prostate cancer-specific mortality was associated with Gleason score and metastases, but not PSA level at diagnosis. Overall survival was associated with PSA level, Gleason score and age. There was a linear increase in risk (overall survival) as PSA increased until 200 and no association thereafter. Models of overall survival and prostate cancer-specific mortality incorporating a risk stratification developed by Izumi et al. predicted overall survival but not prostate cancer-specific mortality. The use of this stratification did not improve model accuracy. Only a small number of men (4.2%) with prostate cancer present with PSA >100 ng/mL at diagnosis. Overall survival at five and ten years was significantly poorer in patients with PSA >100 ng/mL. In this cohort of men presenting with PSA >100 at diagnosis, PSA level was not associated with prostate cancer-specific mortality. Gleason score and metastases are significant prognostic factors in this group of men. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

A multicenter study shows PTEN deletion is strongly associated with seminal vesicle involvement and extracapsular extension in localized prostate cancer

PubMed Central

Troyer, Dean A; Jamaspishvili, Tamara; Wei, Wei; Feng, Ziding; Good, Jennifer; Hawley, Sarah; Fazli, Ladan; McKenney, Jesse K; Simko, Jeff; Hurtado-Coll, Antonio; Carroll, Peter R; Gleave, Martin; Lance, Raymond; Lin, Daniel W; Nelson, Peter S; Thompson, Ian M; True, Lawrence D; Brooks, James D; Squire, Jeremy A

2015-01-01

BACKGROUND Loss of the phosphatase and tensin homolog (PTEN) tumor suppressor gene is a promising marker of aggressive prostate cancer. Active surveillance and watchful waiting are increasingly recommended to patients with small tumors felt to be low risk, highlighting the difficulties of Gleason scoring in this setting. There is an urgent need for predictive biomarkers that can be rapidly deployed to aid in clinical decision-making. Our objectives were to assess the incidence and ability of PTEN alterations to predict aggressive disease in a multicenter study. METHODS We used recently developed probes optimized for sensitivity and specificity in a four-color FISH deletion assay to study the Canary Retrospective multicenter Prostate Cancer Tissue Microarray (TMA). This TMA was constructed specifically for biomarker validation from radical prostatectomy specimens, and is accompanied by detailed clinical information with long-term follow-up. RESULTS In 612 prostate cancers, the overall rate of PTEN deletion was 112 (18.3%). Hemizygous PTEN losses were present in 55/612 (9.0%) of cancers, whereas homozygous PTEN deletion was observed in 57/612 (9.3%) of tumors. Significant associations were found between PTEN status and pathologic stage (P < 0.0001), seminal vesicle invasion (P = 0.0008), extracapsular extension (P < 0.0001), and Gleason score (P = 0.0002). In logistic regression analysis of clinical and pathological variables, PTEN deletion was significantly associated with extracapsular extension, seminal vesicle involvement, and higher Gleason score. In the 406 patients in which clinical information was available, PTEN homozygous (P = 0.009) deletion was associated with worse post-operative recurrence-free survival (number of events = 189), pre-operative prostate specific antigen (PSA) (P < 0.001), and pathologic stage (P = 0.03). CONCLUSION PTEN status assessed by FISH is an independent predictor for recurrence-free survival in multivariate models, as were seminal vesicle invasion, extracapsular extension, and Gleason score, and preoperative PSA. Furthermore, these data demonstrate that the assay can be readily introduced at first diagnosis in a cost effective manner analogous to the use of FISH for analysis of HER2/neu status in breast cancer. Combined with published research beginning 17 years ago, both the data and tools now exist to implement a PTEN assay in the clinic. Prostate 75: 1206–1215, 2015. © 2015 The Authors. The Prostate, published by Wiley Periodicals, Inc. PMID:25939393

Information Technology: Making It All Fit. Track II: Managing Technologies Integration.

ERIC Educational Resources Information Center

CAUSE, Boulder, CO.

Nine papers from the 1988 CAUSE conference's Track II, Managing Technologies Integration, are presented. They include: "Computing in the '90s--Will We Be Ready for the Applications Needed?" (Stephen Patrick); "Glasnost, The Era of 'Openness'" (Bernard W. Gleason); "Academic and Administrative Computing: Are They Really…

Publications | Distributed Generation Market Demand Model | NREL

Science.gov Websites

, Changgui, Benjamin Sigrin, and Gregory Brinkman The Impacts of Changes to Nevada's Net Metering Policy on Business Model Reforms for Addressing the Financial Impacts of Distributed Solar on Utilities, NREL Authors: Lantz, Eric, Benjamin Sigrin, Michael Gleason, Robert Preus, and Ian Baring-Gould Impacts of

JPSS-1 Mission Science Briefing

NASA Image and Video Library

2017-11-12

JPSS-1 Mission Science Briefing hosted by Steve Cole, NASA Communications, with Mitch Goldberg, Chief Program Scientist, NOAA Joint Polar Satellite System, Joe Pica, Director, NOAA National Weather Service Office of Observations, James Gleason, Senior Project Scientist, NASA Joint Polar Satellite System, and Jana Luis, Division Chief, CAL FIRE Predictive Services.

College, Country, Church. 1789-1989.

ERIC Educational Resources Information Center

Current Issues in Catholic Higher Education, 1989

1989-01-01

A collection of papers on current issues in Catholic higher education is presented. Papers are as follows: "Introduction" (Alice Gallin); "Changing and Remaining the Same: A Look at the Record" (Philip Gleason); "Catholic Women's Colleges: A Review of the Record" (Karen M. Kennelly); "A Weight to Our Establishment: Georgetown University and the…

Predictive factors and oncological outcomes of persistently elevated prostate-specific antigen in patients following robot-assisted radical prostatectomy.

PubMed

Kumar, Anup; Samavedi, Srinivas; Mouraviev, Vladimir; Bates, Anthony S; Coelho, Rafael F; Rocco, Bernardo; Patel, Vipul R

2017-03-01

Our aim was to evaluate factors associated with persistently elevated prostate-specific antigen (PSA) and biochemical recurrence following robotic-assisted radical prostatectomy (RARP). The study population (N = 5300) consisted of consecutive patients who underwent RARP for localized prostate cancer by a single surgeon (VP) from January 2008 through July 2013. A query of our Institutional Review Board-approved registry identified 162 men with persistently elevated PSA (group A), defined as PSA level ≥0.1 ng/ml at 6 weeks after surgery, who were compared with rest of the cohort group having undetectable PSA, group B (<0.1 ng/ml). A univariate and multivariate logistic regression analysis was used to evaluate the significant association between various variables and the following: (1) persistently elevated PSA, (2) BCR (PSA value ≥0.2 ng/ml) on follow-up in the persistent PSA group. On multivariate analysis, only the following parameters were significantly associated with persistent PSA after RARP-preoperative [PSA >10 ng/ml (p = 0.01), Gleason Score ≥8 (p = 0.001) and clinical stage(p = 0.001)]; postoperative [pathologic stage (p = 0.001), extraprostatic extension (EPE, p = 0.01), lymph node positivity (p = 0.001), positive surgical margin (PSM, p = 0.02), Gleason score (p = 0.01) and tumor volume percent (p < 0.001)]. The mean follow-up was 38.1 months. The BCR was significantly higher in group A as compared to group B(52.47 vs 7.9 %) respectively; p = 0.01). The mean time to BCR was significantly lesser in group A as compared to group B(8.9 vs 21.1 months respectively; p = 0.01). The BCR-free survival rates at 1 year and 3 years were significantly lower statistically in the persistent PSA group in comparison to other groups (69.7 vs 97.3 % and 48.5 vs 92.1 %, respectively; p = 0.01). On multivariate logistic regression analysis in patients with persistent PSA on follow-up, preoperative PSA >10 ng/ml, postoperative Gleason score ≥8, postoperative stage ≥pT3, positive pelvic lymph nodes, PSM >3 mm and post-RARP PSA doubling time (DT) <10 months (p < 0.001) were significantly associated with BCR. In patients after RARP, factors associated with aggressive disease (high preoperative PSA, Gleason score ≥8, stage ≥T3, PSM, high tumor volume percent and EPE) predict PSA persistence. Although these patients with persistent PSA after RARP are more likely to have BCR and that too earlier than those patients with undetectable PSA after RARP, a significant proportion of these patients (47.53 %) remain free of BCR. This subset of patients is associated with these favorable parameters (preoperative PSA <10 ng/ml, post-RARP PSA DT ≥10 months, postoperative Gleason score <8, pathologic stage 

Proteomic Profiling of Exosomes Leads to the Identification of Novel Biomarkers for Prostate Cancer

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

Duijvesz, Diederick; Burnum-Johnson, Kristin E.; Gritsenko, Marina A.

Introduction: Current markers for prostate cancer, such as PSA lack specificity. Therefore, novel biomarkers are needed. Unfortunately, biomarker discovery from body fluids is often hampered by the high abundance of many proteins unrelated to disease. An attractive alternative biomarker discovery approach is the isolation of small vesicles (exosomes, ~100 nm). They contain proteins that are specific to the tissue from which they are derived and therefore can be considered as treasure chests for disease-specific marker discovery. Profiling prostate cancer-derived exosomes could reveal new markers for this malignancy. Materials and Methods: Exosomes were isolated from 2 immortalized primary prostate epithelial cellsmore » (PNT2C2 and RWPE-1) and 2 PCa cell lines (PC346C and VCaP) by ultracentrifugation. Proteomic analyses utilized a nanoLC coupled with an LTQ-Orbitrap operated in tandem MS (MS/MS) mode, followed by the Accurate Mass and Time (AMT) tag approach. Exosomal proteins were validated by Western blotting. A Tissue Micro Array, containing 481 different PCa samples (radical prostatectomy), was used to correlate candidate markers with several clinical-pathological parameters such as PSA, Gleason score, biochemical recurrence, and (PCa-related) death. Results: Proteomic characterization resulted in the identification of 263 proteins by at least 2 peptides. Specifically analysis of exosomes from PNT2C2, RWPE-1, PC346C, and VCaP identified 248, 233, 169, and 216 proteins, respectively. Statistical analyses revealed 52 proteins differently expressed between PCa and control cells, 9 of which were more abundant in PCa. Validation by Western blotting confirmed a higher abundance of FASN, XPO1 and PDCD6IP (ALIX) in PCa exosomes. The Tissue Micro 4 Array showed strong correlation of higher Gleason scores and local recurrence with increased cytoplasmic XPO1 (P<0.001). Conclusions: Differentially abundant proteins of cell line-derived exosomes make a clear subdivision between benign and malignant origin. Validation showed a preferential abundance of PDCD6IP, FASN and XPO1. Cytoplasmic XPO1 is the most promising candidate biomarker.« less

Comparison of the epidemiologic features and patterns of initial care for prostate cancer between public and private institutions: a survey by the Brazilian Society of Urology.

PubMed

Nardi, Aguinaldo Cesar; Reis, Rodolfo Borges dos; Zequi, Stenio de Cassio; Nardozza, Archimedes

2012-01-01

To describe the epidemiological features and patterns of initial care for prostate cancer at public and private institutions in the State of Sao Paulo, Brazil. A total of 1,082 physicians affiliated to the Sao Paulo Section of the Brazilian Society of Urology were invited to participate in this cross-sectional, web-based survey. Between September 2004 and September 2005, participating urologists entered data on demographic, clinical and pathological characteristics of patients diagnosed with prostate cancer in their practice. Data on patients attended at public institutions were analyzed and compared with those patients attended at private practice. One hundred and ten society members contributed with data from 1915 patients, 1026 (53.6%) of whom from public institutions. When compared with patients attended at private institutions, those attended at public institutions were older and more likely to be black, had higher serum prostate specific antigen (PSA) levels, had a higher probability of being diagnosed with metastatic disease, but were less likely to undergo prostatectomy (all P < 0.001). In multivariate analysis, age, biopsy Gleason score, and being attended at a public institution were independently associated with metastatic disease upon diagnosis. The significant predictors of nonsurgical treatment were age, black race, and higher serum levels of PSA. A statewide registry provides valuable information regarding patient demographics, clinical features, and patterns of care. The results of this study suggest that significant disparities exist for patients with prostate cancer attended at different health-care systems. The relative contribution of biological versus socioeconomic features remains uncertain.

Focus on Technology: Enhancing Instruction and Communication with Twitter

ERIC Educational Resources Information Center

Morgan, Hani

2014-01-01

The growth of Twitter and similar sites has influenced many institutions. Many employers, for example, currently value digital literacy and look to hire employees who are skilled in social media. Since corporations increasingly value this type of literacy, researchers such as Greenhow and Gleason (2012) argue that educators need to respond by…

DEVELOP students attend conference

NASA Image and Video Library

2009-06-08

Last month, Madeline Brozen and Jason Jones of the DEVELOP Program at John C. Stennis Space Center joined members from the program's national office at Langley Research Center to attend the Southern Growth Policies Board annual conference in Biloxi. Pictured are (l to r): Karen Allsbrook, Jonathan Gleason, Gov. Haley Barbour, Madeline Brozen, Lindsay Rogers and Tracey Silcox.

Prunus pumila L.

Treesearch

Don C. Bragg

2002-01-01

Sand cherry, also called beach plum, "cerise de sable" (Fernald 1923), or dwarf American cherry, is a diffusely branched, low growing (0.5 to 3 m tall, depending on variety and habitat) to sometimes decumbent or prostrate shrub (Fernald 1923, Gleason 1952, Lamson-Scribner 1891). Older stems develop a grayish, glabrous bark, while younger twigs are often...

USING MODELS TO EXTRAPOLATE POPULATION-LEVEL EFFECTS FROM LABORATORY TOXICITY TESTS IN SUPPORT OF POPULATION RISK ASSESSMENTS

EPA Science Inventory

Using models to extrapolate population-level effects from laboratory toxicity tests in support of population risk assessments. Munns, W.R., Jr.*, Anne Kuhn, Matt G. Mitro, and Timothy R. Gleason, U.S. EPA ORD NHEERL, Narragansett, RI, USA. Driven in large part by management goa...

Growing into Equity: Professional Learning and Personalization in High-Achieving Schools

ERIC Educational Resources Information Center

Gleason, Sonia Caus; Gerzon, Nancy

2013-01-01

What makes a Title I school high-achieving, and what can we all learn from that experience? Professional learning and leadership that supports personalized instruction makes the difference, as captured in the ground-breaking research of authors Sonia Caus Gleason and Nancy Gerzon. This illuminating book shows how four outstanding schools are…

Inverse association between gluthathione peroxidase activity and both selenium-binding protein 1 levels and gleason score in human prostate tissue

USDA-ARS?s Scientific Manuscript database

BACKGROUND. Data from human epidemiological studies, cultured mammalian cells, and animal models have supported a potentially beneficial role of selenium (Se) in prostate cancer prevention. In addition, Se-containing proteins including members of the gutathione peroxidase (GPx) family and Selenium-B...

Biases in the subjective timing of perceptual events: Libet et al. (1983) revisited.

PubMed

Danquah, Adam N; Farrell, Martin J; O'Boyle, Donald J

2008-09-01

We report two experiments in which participants had to judge the time of occurrence of a stimulus relative to a clock. The experiments were based on the control condition used by Libet, Gleason, Wright, and Pearl [Libet, B., Gleason, C. A., Wright, E. W., & Pearl, D. K. (1983). Time of conscious intention to act in relation to onset of cerebral activities (readiness-potential): The unconscious initiation of a freely voluntary act. Brain 106, 623-642] to correct for any bias in the estimation of the time at which an endogenous event, the conscious intention to perform a movement, occurred. Participants' responses were affected systematically by the sensory modality of the stimulus and by the speed of the clock. Such findings demonstrate the variability in judging the time at which an exogenous event occurs and, by extension, suggest that such variability may also apply to the judging the time of occurrence of endogenous events. The reliability of participants' estimations of when they formed the conscious intention to perform a movement in Libet et al.'s (1983) study is therefore questionable.

External validation and comparison of two nomograms predicting the probability of Gleason sum upgrading between biopsy and radical prostatectomy pathology in two patient populations: a retrospective cohort study.

PubMed

Utsumi, Takanobu; Oka, Ryo; Endo, Takumi; Yano, Masashi; Kamijima, Shuichi; Kamiya, Naoto; Fujimura, Masaaki; Sekita, Nobuyuki; Mikami, Kazuo; Hiruta, Nobuyuki; Suzuki, Hiroyoshi

2015-11-01

The aim of this study is to validate and compare the predictive accuracy of two nomograms predicting the probability of Gleason sum upgrading between biopsy and radical prostatectomy pathology among representative patients with prostate cancer. We previously developed a nomogram, as did Chun et al. In this validation study, patients originated from two centers: Toho University Sakura Medical Center (n = 214) and Chibaken Saiseikai Narashino Hospital (n = 216). We assessed predictive accuracy using area under the curve values and constructed calibration plots to grasp the tendency for each institution. Both nomograms showed a high predictive accuracy in each institution, although the constructed calibration plots of the two nomograms underestimated the actual probability in Toho University Sakura Medical Center. Clinicians need to use calibration plots for each institution to correctly understand the tendency of each nomogram for their patients, even if each nomogram has a good predictive accuracy. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Incidence and clinicopathological characteristics of incidental prostatic adenocarcinoma in radical cystoprostatectomy specimens].

PubMed

Shen, Qi; Hu, Shuai; Li, Jun; Wang, Jing-hua; He, Qun

2014-08-18

To analyze the incidence and clinicopathological features of incidental prostate cancer (IPCa) in specimens from radical cystoprostatectomy (RCP) for bladder cancer. We retrospectively reviewed the histopathological features of 865 male patients who underwent an RCP between January 2005 and March 2014. No patients had preoperative clinical or biological suspicion of prostate cancer (PCa). Among the 865 specimens, IPCa was diagnosed in 235 patients (27.2%). Most tumors (228/235, 97.0%) were organ-confined (pT2); And 7 cases (3.0 %) of them were diagnosed at T3. Gleason score was < 6 in 84 cases (35.7 %), 6 in 77 cases (32.8%), 7 in 64 cases (27.2 %), and > 7 in 10 cases (4.3 %). The rate of incidentally diagnosed IPCa was 8.5%, and that in RCP and TURP specimens was 19.5% and 4.4% respectively. The majority of these IPCas were organ-confined. Gleason score in most of these specimens was ≤ 7. Moreover, prostate examination in the RCP specimen should be careful and sufficient, whole-amount prostate sections improve diagnostic accuracy.

LINE-1 methylation status in prostate cancer and non-neoplastic tissue adjacent to tumor in association with mortality.

PubMed

Fiano, Valentina; Zugna, Daniela; Grasso, Chiara; Trevisan, Morena; Delsedime, Luisa; Molinaro, Luca; Gillio-Tos, Anna; Merletti, Franco; Richiardi, Lorenzo

2017-01-02

Aberrant DNA methylation seems to be associated with prostate cancer behavior. We investigated LINE-1 methylation in prostate cancer and non-neoplastic tissue adjacent to tumor (NTAT) in association with mortality from prostate cancer. We selected 157 prostate cancer patients with available NTAT from 2 cohorts of patients diagnosed between 1982-1988 and 1993-1996, followed up until 2010. An association between LINE-1 hypomethylation and prostate cancer mortality in tumor was suggested [hazard ratio per 5% decrease in LINE-1 methylation levels: 1.40, 95% confidence interval (CI): 0.95-2.01]. After stratification of the patients for Gleason score, the association was present only for those with a Gleason score of at least 8. Among these, low (<75%) vs. high (>80%) LINE-1 methylation was associated with a hazard ratio of 4.68 (95% CI: 1.03-21.34). LINE-1 methylation in the NTAT was not associated with prostate cancer mortality. Our results are consistent with the hypothesis that tumor tissue global hypomethylation may be a late event in prostate cancerogenesis and is associated with tumor progression.

Retrospective Evaluation Reveals That Long-term Androgen Deprivation Therapy Improves Cause-Specific and Overall Survival in the Setting of Dose-Escalated Radiation for High-Risk Prostate Cancer

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

Feng, Felix Y., E-mail: ffeng@med.umich.edu; Department of Radiation Oncology, Veterans Affairs Medical Center, Ann Arbor, Michigan; Blas, Kevin

2013-05-01

Purpose: To evaluate the role of androgen deprivation therapy (ADT) and duration for high-risk prostate cancer patients treated with dose-escalated radiation therapy (RT). Methods and Materials: A retrospective analysis of high-risk prostate cancer patients treated with dose-escalated RT (minimum 75 Gy) with or without ADT was performed. The relationship between ADT use and duration with biochemical failure (BF), metastatic failure (MF), prostate cancer-specific mortality (PCSM), non-prostate cancer death (NPCD), and overall survival (OS) was assessed as a function of pretreatment characteristics, comorbid medical illness, and treatment using Fine and Gray's cumulative incidence methodology. Results: The median follow-up time was 64more » months. In men with National Comprehensive Cancer Network defined high-risk prostate cancer treated with dose-escalated RT, on univariate analysis, both metastasis (P<.0001; hazard ratio 0.34; 95% confidence interval 0.18-0.67; cumulative incidence at 60 months 13% vs 35%) and PCSM (P=.015; hazard ratio 0.41; 95% confidence interval 0.2-1.0; cumulative incidence at 60 months 6% vs 11%) were improved with the use of ADT. On multivariate analysis for all high-risk patients, Gleason score was the strongest negative prognostic factor, and long-term ADT (LTAD) improved MF (P=.002), PCSM (P=.034), and OS (P=.001). In men with prostate cancer and Gleason scores 8 to 10, on multivariate analysis after adjustment for other risk features, there was a duration-dependent improvement in BF, metastasis, PCSM, and OS, all favoring LTAD in comparison with STAD or RT alone. Conclusion: For men with high-risk prostate cancer treated with dose-escalated EBRT, this retrospective study suggests that the combination of LTAD and RT provided a significant improvement in clinical outcome, which was especially true for those with Gleason scores of 8 to 10.« less

The Efficacy of Multiparametric Magnetic Resonance Imaging and Magnetic Resonance Imaging Targeted Biopsy in Risk Classification for Patients with Prostate Cancer on Active Surveillance.

PubMed

Recabal, Pedro; Assel, Melissa; Sjoberg, Daniel D; Lee, Daniel; Laudone, Vincent P; Touijer, Karim; Eastham, James A; Vargas, Hebert A; Coleman, Jonathan; Ehdaie, Behfar

2016-08-01

We determined whether multiparametric magnetic resonance imaging targeted biopsies may replace systematic biopsies to detect higher grade prostate cancer (Gleason score 7 or greater) and whether biopsy may be avoided based on multiparametric magnetic resonance imaging among men with Gleason 3+3 prostate cancer on active surveillance. We identified men with previously diagnosed Gleason score 3+3 prostate cancer on active surveillance who underwent multiparametric magnetic resonance imaging and a followup prostate biopsy. Suspicion for higher grade cancer was scored on a standardized 5-point scale. All patients underwent a systematic biopsy. Patients with multiparametric magnetic resonance imaging regions of interest also underwent magnetic resonance imaging targeted biopsy. The detection rate of higher grade cancer was estimated for different multiparametric magnetic resonance imaging scores with the 3 biopsy strategies of systematic, magnetic resonance imaging targeted and combined. Of 206 consecutive men on active surveillance 135 (66%) had a multiparametric magnetic resonance imaging region of interest. Overall, higher grade cancer was detected in 72 (35%) men. A higher multiparametric magnetic resonance imaging score was associated with an increased probability of detecting higher grade cancer (Wilcoxon-type trend test p <0.0001). Magnetic resonance imaging targeted biopsy detected higher grade cancer in 23% of men. Magnetic resonance imaging targeted biopsy alone missed higher grade cancers in 17%, 12% and 10% of patients with multiparametric magnetic resonance imaging scores of 3, 4 and 5, respectively. Magnetic resonance imaging targeted biopsies increased the detection of higher grade cancer among men on active surveillance compared to systematic biopsy alone. However, a clinically relevant proportion of higher grade cancer was detected using only systematic biopsy. Despite the improved detection of disease progression using magnetic resonance imaging targeted biopsy, systematic biopsy cannot be excluded as part of surveillance for men with low risk prostate cancer. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Serial Magnetic Resonance Imaging in Active Surveillance of Prostate Cancer: Incremental Value.

PubMed

Felker, Ely R; Wu, Jason; Natarajan, Shyam; Margolis, Daniel J; Raman, Steven S; Huang, Jiaoti; Dorey, Fred; Marks, Leonard S

2016-05-01

We assessed whether changes in serial multiparametric magnetic resonance imaging can help predict the pathological progression of prostate cancer in men on active surveillance. A retrospective cohort study was conducted of 49 consecutive men with Gleason 6 prostate cancer who underwent multiparametric magnetic resonance imaging at baseline and again more than 6 months later, each followed by a targeted prostate biopsy, between January 2011 and May 2015. We evaluated whether progression on multiparametric magnetic resonance imaging (an increase in index lesion suspicion score, increase in index lesion volume or decrease in index lesion apparent diffusion coefficient) could predict pathological progression (Gleason 3 + 4 or greater on subsequent biopsy, in systematic or targeted cores). Diagnostic performance of multiparametric magnetic resonance imaging was determined with and without clinical data using a binary logistic regression model. The mean interval between baseline and followup multiparametric magnetic resonance imaging was 28.3 months (range 11 to 43). Pathological progression occurred in 19 patients (39%). The sensitivity, specificity, positive predictive value and negative predictive value of multiparametric magnetic resonance imaging was 37%, 90%, 69% and 70%, respectively. Area under the receiver operating characteristic curve was 0.63. A logistic regression model using clinical information (maximum cancer core length greater than 3 mm on baseline biopsy or a prostate specific antigen density greater than 0.15 ng/ml(2) at followup biopsy) had an AUC of 0.87 for predicting pathological progression. The addition of serial multiparametric magnetic resonance imaging data significantly improved the AUC to 0.91 (p=0.044). Serial multiparametric magnetic resonance imaging adds incremental value to prostate specific antigen density and baseline cancer core length for predicting Gleason 6 upgrading in men on active surveillance. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Multiple cores of Gleason score 6 correlate with favourable findings at radical prostatectomy

PubMed Central

Ellis, Carla L.; Walsh, Patrick C.; Partin, Alan W.; Epstein, Jonathan I.

2014-01-01

Objective To establish whether the good prognosis of Gleason score 6 (GS6) is maintained in the setting of multiple involved cores. Patients and Methods In total, 6156 men (from 1 April 2000 to 30 April 2007) with GS6 on biopsy underwent radical prostatectomy (RP) at our institution. The number of positive cores was correlated with the outcome at RP. Results More positive cores correlated with less organ-confined disease (P < 0.001), positive margins (P < 0.012), increasing RP grade (P < 0.001) and increased seminal vesicles/lymph node involvement (P = 0.012). For men with data available, the actuarial risk of being biochemically free of disease at 5 years was 93.2% when ≤6 cores were positive (812 men followed to 5 years) vs 89.1% if >6 cores were positive (41 men followed to 2 years) (P = 0.6). Although the predicted ‘cure rate’ of >75% probability of a tumour showing no evidence of biochemical recurrence at 10 years after RP was statistically different between cases with ≤6 vs >6 positive cores (P < 0.0001), the outcome in both groups was still favourable (90.5% vs 84%). Partin-like tables were generated factoring in the number of positive cores to predict organ-confined disease as a guide for urologists to perform nerve-sparing surgery. For example, with T1c disease, there was a ≥75% probability of organ-confined disease with one to three positive cores regardless of prostate-specific antigen (PSA) level, and the same probability was present with four to six positive cores and a PSA level of 0–4 ng/mL. Conclusion A low Gleason score on biopsy is a powerful prognostic finding, such that this favourable outcome is maintained even in the setting of multiple positive cores with GS6. PMID:23350787

Multiple cores of Gleason score 6 correlate with favourable findings at radical prostatectomy.

PubMed

Ellis, Carla L; Walsh, Patrick C; Partin, Alan W; Epstein, Jonathan I

2013-06-01

To establish whether the good prognosis of Gleason score 6 (GS6) is maintained in the setting of multiple involved cores. In total, 6156 men (from 1 April 2000 to 30 April 2007) with GS6 on biopsy underwent radical prostatectomy (RP) at our institution. The number of positive cores was correlated with the outcome at RP. More positive cores correlated with less organ-confined disease (P < 0.001), positive margins (P < 0.012), increasing RP grade (P < 0.001) and increased seminal vesicles/lymph node involvement (P = 0.012). For men with data available, the actuarial risk of being biochemically free of disease at 5 years was 93.2% when ≤6 cores were positive (812 men followed to 5 years) vs 89.1% if >6 cores were positive (41 men followed to 2 years) (P = 0.6). Although the predicted 'cure rate' of >75% probability of a tumour showing no evidence of biochemical recurrence at 10 years after RP was statistically different between cases with ≤6 vs >6 positive cores (P < 0.0001), the outcome in both groups was still favourable (90.5% vs 84%). Partin-like tables were generated factoring in the number of positive cores to predict organ-confined disease as a guide for urologists to perform nerve-sparing surgery. For example, with T1c disease, there was a ≥75% probability of organ-confined disease with one to three positive cores regardless of prostate-specific antigen (PSA) level, and the same probability was present with four to six positive cores and a PSA level of 0-4 ng/mL. A low Gleason score on biopsy is a powerful prognostic finding, such that this favourable outcome is maintained even in the setting of multiple positive cores with GS6. © 2013 BJU International.

Phase II Trial of Combined High-Dose-Rate Brachytherapy and External Beam Radiotherapy for Adenocarcinoma of the Prostate: Preliminary Results of RTOG 0321

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

Hsu, I-Chow, E-mail: ihsu@radonc.ucsf.ed; Bae, Kyounghwa; Shinohara, Katsuto

2010-11-01

Purpose: To estimate the rate of late Grade 3 or greater genitourinary (GU) and gastrointestinal (GI) adverse events (AEs) after treatment with external beam radiotherapy and prostate high-dose-rate (HDR) brachytherapy. Methods and Materials: Each participating institution submitted computed tomography-based HDR brachytherapy dosimetry data electronically for credentialing and for each study patient. Patients with locally confined Stage T1c-T3b prostate cancer were eligible for the present study. All patients were treated with 45 Gy in 25 fractions using external beam radiotherapy and one HDR implant delivering 19 Gy in two fractions. All AEs were graded according to the Common Terminology Criteria formore » Adverse Events, version 3.0. Late GU/GI AEs were defined as those occurring >9 months from the start of the protocol treatment, in patients with {>=}18 months of potential follow-up. Results: A total of 129 patients from 14 institutions were enrolled in the present study. Of the 129 patients, 125 were eligible, and AE data were available for 112 patients at analysis. The pretreatment characteristics of the patients were as follows: Stage T1c-T2c, 91%; Stage T3a-T3b, 9%; prostate-specific antigen level {<=}10 ng/mL, 70%; prostate-specific antigen level >10 but {<=}20 ng/mL, 30%; and Gleason score 2-6, 10%; Gleason score 7, 72%; and Gleason score 8-10, 18%. At a median follow-up of 29.6 months, three acute and four late Grade 3 GU/GI AEs were reported. The estimated rate of late Grade 3-5 GU and GI AEs at 18 months was 2.56%. Conclusion: This is the first prospective, multi-institutional trial of computed tomography-based HDR brachytherapy and external beam radiotherapy. The technique and doses used in the present study resulted in acceptable levels of AEs.« less

IMPACT OF STAGE MIGRATION AND PRACTICE CHANGES ON HIGH RISK PROSTATE CANCER: RESULTS FROM PATIENTS TREATED WITH RADICAL PROSTATECTOMY OVER THE LAST TWO DECADES

PubMed Central

Fossati, N.; Passoni, N. M.; Moschini, M.; Gandaglia, G.; Larcher, A.; Freschi, M.; Guazzoni, G.; Sjoberg, D. D.; Vickers, A. J.; Montorsi, F.; Briganti, A.

2016-01-01

Background Phenotype of prostate cancer at diagnosis has changed through the years. We aim to evaluate the impact of year of surgery on clinical, pathologic and oncologic outcomes of high-risk prostate cancer patients. Patients and methods We evaluated 1,033 clinically high-risk patients, defined as the presence of at least one of the following risk factors: pre-operative prostate specific antigen (PSA) level >20 ng/ml, and/or clinical stage ≥T3, and/or biopsy Gleason score ≥8. Patients were treated between 1990 and 2013 at a single Institution. Year-per-year trends of clinical and pathologic characteristics were examined. Multivariable Cox regression analysis was used to test the relationship between year of surgery and oncologic outcomes. Results We observed a decrease over time in the proportion of high-risk patients with a pre-operative PSA level >20 ng/ml or clinical stage cT3. An opposite trend was seen for biopsy Gleason score ≥8. We observed a considerable increase in the median number of lymph nodes removed that was associated with an increased rate of LNI. At multivariable Cox regression analysis, year of surgery was associated with a reduced risk of biochemical recurrence (HR per 5-year: 0.90; 95% CI: 0.84–0.96; p=0.01) and distant metastasis (HR per 5-year: 0.91; 95% CI: 0.83–0.99; p=0.039), after adjusting for age, pre-operative PSA, pathologic stage, lymph node invasion, surgical margin status, and pathological Gleason score. Conclusions In this single center study, an increased diagnosis of localized and less extensive high-grade prostate cancer was observed over the last two decades. High-risk patients selected for radical prostatectomy showed better cancer control over time. Better definitions of what constitutes high-risk prostate cancer among contemporary patients are needed. PMID:25787671

MRI Fusion-Targeted Transrectal Prostate Biopsy and the Role of Prostate-Specific Antigen Density and Prostate Health Index for the Detection of Clinically Significant Prostate Cancer in Southeast Asian Men.

PubMed

Tan, Teck Wei; Png, Keng Siang; Lee, Chau Hung; Yuwono, Arianto; Yeow, Yuyi; Chong, Kian Tai; Lee, Yee Mun; Tan, Cher Heng; Tan, Yung Khan

2017-11-01

To test the hypothesis that targeted biopsy has a higher detection rate for clinically significant prostate cancer (csPCa) than systematic biopsy. We defined csPCa as any Gleason sum ≥7 cancer. In patients with Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions, to determine if factors, such as prostate-specific antigen density (PSAD) and prostate health index (PHI), can predict csPCa and help select patients for biopsy. We report the first series of targeted biopsies in Southeast Asian men, with comparison against systematic biopsy. Consecutive patients were registered into a prospective institutional review board-approved database in our institution. We reviewed patients who underwent biopsy from May 2016 to June 2017. Inclusion criteria for our study were patients with at least one PI-RADS ≥3, and who underwent both targeted and systematic biopsies in the same sitting. There were 115 patients in the study, of whom 74 (64.3%) had a previous negative systematic biopsy. Targeted biopsies detected significantly less Gleason 6 cancers than systematic biopsies (p < 0.01), and demonstrated significantly higher sensitivity, specificity, positive predictive value, and negative predictive value (NPV) for the detection of csPCa. For patients with PI-RADS 3 lesions, PHI and PSAD were found to be the best predictors for csPCa. PSAD <0.10 ng/mL/mL had an NPV of 93% and sensitivity of 92%, while allowing 20% of patients to avoid biopsy. PHI cutoff of <27 would allow 34% of patients to avoid biopsy, with both sensitivity and NPV of 100%. Targeted prostate biopsies were found to be significantly superior to systematic biopsies for the detection of csPCa, while detecting less Gleason 6 cancer. Usage of PSAD and PHI cutoff levels in patients with PI-RADS 3 lesions may enable a number of patients to avoid unnecessary biopsy.

Differential expression of CD10 in prostate cancer and its clinical implication

PubMed Central

Dall'Era, Marc A; True, Lawrence D; Siegel, Andrew F; Porter, Michael P; Sherertz, Tracy M; Liu, Alvin Y

2007-01-01

Background CD10 is a transmembrane metallo-endopeptidase that cleaves and inactivates a variety of peptide growth factors. Loss of CD10 expression is a common, early event in human prostate cancer; however, CD10 positive cancer cells frequently appear in lymph node metastasis. We hypothesize that prostate tumors expressing high levels of CD10 have a more aggressive biology with an early propensity towards lymph node metastasis. Methods Eighty-seven patients, 53 with and 34 without pathologically organ confined prostate cancer at the time of radical prostatectomy (RP), were used for the study. Fourteen patients with lymph node metastasis found at the time of surgery were identified and included in this study. Serial sections from available frozen tumor specimens in OCT were processed for CD10 immunohistochemistry. Cancer glands were graded for the presence and intensity of CD10 staining, and overall percentage of glands staining positive was estimated. Clinical characteristics including pre- and post-operative PSA and Gleason score were obtained. A similar study as a control for the statistical analysis was performed with CD13 staining. For statistical analysis, strong staining was defined as > 20% positivity based on the observed maximum separation of the cumulative distributions. Results CD10 expression significantly correlated with Gleason grade, tumor stage, and with pre-operative serum PSA. Seventy percent of RP specimens from patients with node metastasis showed strong staining for CD10, compared to 30% in the entire cohort (OR = 3.4, 95% CI: 1.08–10.75, P = 0.019). Increased staining for CD10 was associated with PSA recurrence after RP. CD13 staining did not correlate significantly with any of these same clinical parameters. Conclusion These results suggest that the expression of CD10 by prostate cancer corresponds to a more aggressive phenotype with a higher malignant potential, described histologically by the Gleason score. CD10 offers potential clinical utility for stratifying prostate cancer to predict biological behavior of the tumor. PMID:17335564

High b Value (2,000 s/mm2) Diffusion-Weighted Magnetic Resonance Imaging in Prostate Cancer at 3 Tesla: Comparison with 1,000 s/mm2 for Tumor Conspicuity and Discrimination of Aggressiveness

PubMed Central

Tamada, Tsutomu; Kanomata, Naoki; Sone, Teruki; Jo, Yoshimasa; Miyaji, Yoshiyuki; Higashi, Hiroki; Yamamoto, Akira; Ito, Katsuyoshi

2014-01-01

Objective The objective of our study was to investigate tumor conspicuity and the discrimination potential for tumor aggressiveness on diffusion-weighted magnetic resonance imaging (DW-MRI) with high b value at 3-T. Materials and Methods The institutional review board approved this study and waived the requirement for informed consent. A total of 50 patients with prostate cancer (69 cancer foci; 48 in the PZ, 20 in the TZ, and one in whole prostate) who underwent multiparametric prostate MRI including DW-MRI (b values: 0, 1000 s/mm2 and 0, 2000 s/mm2) on a 3-T system were included. Lesion conspicuity score (LCS) using visual assessment (1 = invisible for surrounding normal site; 2 = slightly high intensity; 3 = moderately high; and 4 = very high) and tumor-normal signal intensity ratio (TNR) were assessed, and apparent diffusion coefficient (ADC, ×10−3 mm2/s) of the tumor regions and normal regions were measured. Results Mean LCS and TNR at 0, 2000 s/mm2 was significantly higher than those at 0, 1000 s/mm2 (p<0.001 for both). In addition, ADC at both 0, 1000 and 0, 2000 s/mm2 was found to distinguish intermediate or high risk cancer with Gleason score ≥7 from low risk cancer with Gleason score ≤6 (p<0.001 for both). Furthermore, ADC of tumor regions correlated with Gleason score at both 0, 1000 s/mm2 (ρ = −0.602; p<0.001) and 0, 2000 s/mm2 (ρ = −0.645; p<0.001). Conclusions For tumor conspicuity and characterization of prostate cancer on DW-MRI of 3-T MRI, b = 0, 2000 s/mm2 is more useful than b = 0, 1000 s/mm2. PMID:24802652

High b value (2,000 s/mm2) diffusion-weighted magnetic resonance imaging in prostate cancer at 3 Tesla: comparison with 1,000 s/mm2 for tumor conspicuity and discrimination of aggressiveness.

PubMed

Tamada, Tsutomu; Kanomata, Naoki; Sone, Teruki; Jo, Yoshimasa; Miyaji, Yoshiyuki; Higashi, Hiroki; Yamamoto, Akira; Ito, Katsuyoshi

2014-01-01

The objective of our study was to investigate tumor conspicuity and the discrimination potential for tumor aggressiveness on diffusion-weighted magnetic resonance imaging (DW-MRI) with high b value at 3-T. The institutional review board approved this study and waived the requirement for informed consent. A total of 50 patients with prostate cancer (69 cancer foci; 48 in the PZ, 20 in the TZ, and one in whole prostate) who underwent multiparametric prostate MRI including DW-MRI (b values: 0, 1000 s/mm2 and 0, 2000 s/mm2) on a 3-T system were included. Lesion conspicuity score (LCS) using visual assessment (1 = invisible for surrounding normal site; 2 = slightly high intensity; 3 = moderately high; and 4 = very high) and tumor-normal signal intensity ratio (TNR) were assessed, and apparent diffusion coefficient (ADC, ×10-3 mm2/s) of the tumor regions and normal regions were measured. Mean LCS and TNR at 0, 2000 s/mm2 was significantly higher than those at 0, 1000 s/mm2 (p<0.001 for both). In addition, ADC at both 0, 1000 and 0, 2000 s/mm2 was found to distinguish intermediate or high risk cancer with Gleason score ≥7 from low risk cancer with Gleason score ≤6 (p<0.001 for both). Furthermore, ADC of tumor regions correlated with Gleason score at both 0, 1000 s/mm2 (ρ = -0.602; p<0.001) and 0, 2000 s/mm2 (ρ = -0.645; p<0.001). For tumor conspicuity and characterization of prostate cancer on DW-MRI of 3-T MRI, b = 0, 2000 s/mm2 is more useful than b = 0, 1000 s/mm2.

Computer aided detection in prostate cancer diagnostics: A promising alternative to biopsy? A retrospective study from 104 lesions with histological ground truth.

PubMed

Thon, Anika; Teichgräber, Ulf; Tennstedt-Schenk, Cornelia; Hadjidemetriou, Stathis; Winzler, Sven; Malich, Ansgar; Papageorgiou, Ismini

2017-01-01

Prostate cancer (PCa) diagnosis by means of multiparametric magnetic resonance imaging (mpMRI) is a current challenge for the development of computer-aided detection (CAD) tools. An innovative CAD-software (Watson Elementary™) was proposed to achieve high sensitivity and specificity, as well as to allege a correlate to Gleason grade. To assess the performance of Watson Elementary™ in automated PCa diagnosis in our hospital´s database of MRI-guided prostate biopsies. The evaluation was retrospective for 104 lesions (47 PCa, 57 benign) from 79, 64.61±6.64 year old patients using 3T T2-weighted imaging, Apparent Diffusion Coefficient (ADC) maps and dynamic contrast enhancement series. Watson Elementary™ utilizes signal intensity, diffusion properties and kinetic profile to compute a proportional Gleason grade predictor, termed Malignancy Attention Index (MAI). The analysis focused on (i) the CAD sensitivity and specificity to classify suspect lesions and (ii) the MAI correlation with the histopathological ground truth. The software revealed a sensitivity of 46.80% for PCa classification. The specificity for PCa was found to be 75.43% with a positive predictive value of 61.11%, a negative predictive value of 63.23% and a false discovery rate of 38.89%. CAD classified PCa and benign lesions with equal probability (P 0.06, χ2 test). Accordingly, receiver operating characteristic analysis suggests a poor predictive value for MAI with an area under curve of 0.65 (P 0.02), which is not superior to the performance of board certified observers. Moreover, MAI revealed no significant correlation with Gleason grade (P 0.60, Pearson´s correlation). The tested CAD software for mpMRI analysis was a weak PCa biomarker in this dataset. Targeted prostate biopsy and histology remains the gold standard for prostate cancer diagnosis.

Relationships between serum PSA levels, Gleason scores and results of 68Ga-PSMAPET/CT in patients with recurrent prostate cancer.

PubMed

Sanli, Yasemin; Kuyumcu, Serkan; Sanli, Oner; Buyukkaya, Fikret; İribaş, Ayça; Alcin, Goksel; Darendeliler, Emin; Ozluk, Yasemin; Yildiz, Sevda Ozel; Turkmen, Cüneyt

2017-11-01

To investigate the relationship between serum PSA level, Gleason score of PCa and the outcomes of Ga 68 -PSMA PET/CT in patients with recurrent PCa. A total of 109 consecutive patients (median age 71 years; range 48-89 years) who had PSA recurrence after RP and/or hormonotherapy and/or radiotherapy were included in this study. Local recurrences, lymph node metastasis (pelvic, abdominal and/or supradiaphragmatic), bone metastases (oligometastatic/multimetastatic) and other metastatic sites (lung, liver, brain, etc) were documented. In 91(83.4%) patients at least one lesion characteristic for PCa was detected by 68 Ga-PSMA PET/CT. The median serum total PSA (tPSA) was 6.5 (0.2-640) ng/ml.There was a significant difference between 68 Ga-PSMA PET/CT positive and negative patients in terms of serum total PSA value. No statistical significance was found between positive and negative 68 Ga-PSMA PET/CT findings in terms of Gleason score. Local recurrence was detected in 56 patients. whereas lymph node metastases were demonstrated in 46 patients. Pelvic nodal disease was the most frequent presentation followed by abdominal and supradiaphragmaticnodal involvement. Bone metastases [oligometastasis, (n = 20); multimetastasis, (n = 35)⦌ were also detected in 55 patients. In the ROC analysis for the study cohort, the optimal cut-off value of total serum PSA was determined as 0.67 ng/ml for distinguishing between positive and negative 68 Ga-PSMA PET/CT images, with an area under curve of 0.952 (95% CI 0.911-0.993). 68 Ga-PSMA PET/CT was found to be an effective tool for the detection of recurrent PCa. Even though no relationship was detected between the GS and 68 Ga-PSMA PET/CT findings, serum total PSA values may be used for estimating the likelihood of positive 68 Ga-PSMA PET/CT results.

Extent of disease in recurrent prostate cancer determined by [(68)Ga]PSMA-HBED-CC PET/CT in relation to PSA levels, PSA doubling time and Gleason score.

PubMed

Verburg, Frederik A; Pfister, David; Heidenreich, Axel; Vogg, Andreas; Drude, Natascha I; Vöö, Stefan; Mottaghy, Felix M; Behrendt, Florian F

2016-03-01

To examine the relationship between the extent of disease determined by [(68)Ga]PSMA-HBED-CC-PET/CT and the important clinical measures prostate-specific antigen (PSA), PSA doubling time (PSAdt) and Gleason score. We retrospectively studied the first 155 patients with recurrent prostate cancer (PCA) referred to our university hospital for [(68)Ga]PSMA-HBED-CC PET/CT. PET/CT was positive in 44%, 79% and 89% of patients with PSA levels of ≤1, 1-2 and ≥2 ng/ml, respectively. Patients with high PSA levels showed higher rates of local prostate tumours (p < 0.001), and extrapelvic lymph node (p = 0.037) and bone metastases (p = 0.013). A shorter PSAdt was significantly associated with pelvic lymph node (p = 0.026), extrapelvic lymph node (p = 0.001), bone (p < 0.001) and visceral (p = 0.041) metastases. A high Gleason score was associated with more frequent pelvic lymph node metastases (p = 0.039). In multivariate analysis, both PSA and PSAdt were independent determinants of scan positivity and of extrapelvic lymph node metastases. PSAdt was the only independent marker of bone metastases (p = 0.001). Of 20 patients with a PSAdt <6 months and a PSA ≥2 ng/ml, 19 (95%) had a positive scan and 12 (60%) had M1a disease. Of 14 patients with PSA <1 ng/ml and PSAdt >6 months, only 5 (36%) had a positive scan and 1 (7%) had M1a disease. [(68)Ga]PSMA-HBED-CC PET/CT will identify PCA lesions even in patients with very low PSA levels. Higher PSA levels and shorter PSAdt are independently associated with scan positivity and extrapelvic metastases, and can be used for patient selection for [(68)Ga]PSMA-HBED-CC PET/CT.

Prostate-specific antigen (PSA) density in the diagnostic algorithm of prostate cancer.

PubMed

Nordström, Tobias; Akre, Olof; Aly, Markus; Grönberg, Henrik; Eklund, Martin

2018-04-01

Screening for prostate cancer using prostate-specific antigen (PSA) alone leads to un-necessary biopsying and overdiagnosis. PSA density is easily accessible, but early evidence on its use for biopsy decisions was conflicting and use of PSA density is not commonly recommended in guidelines. We analyzed biopsy outcomes in 5291 men in the population-based STHLM3 study with PSA ≥ 3 ng/ml and ultrasound-guided prostate volume measurements by using percentages and regression models. PSA density was calculated as total PSA (ng/ml) divided by prostate volume (ml). Main endpoint was clinically significant cancer (csPCa) defined as Gleason Score ≥ 7. The median PSA-density was 0.10 ng/ml 2 (IQR 0.075-0.14). PSA-density was associated with the risk of finding csPCa both with and without adjusting for the additional clinical information age, family history, previous biopsies, total PSA and free/total PSA (OR 1.06; 95% CI:1.05-1.07 and OR 1.07, 95% CI 1.06-1.08). Discrimination for csPCa was better when PSA density was added to a model with additional clinical information (AUC 0.75 vs. 0.73, P < 0.05). The proportion of men with Gleason Score 6 (ISUP 1) was similar across stratas of PSA-density. Omitting prostate biopsy for men with PSA-density ≤0.07 ng/ml 2 would save 19.7% of biopsy procedures, while missing 6.9% of csPCa. PSA-density cutoffs of 0.10 ng/ml 2 and 0.15 ng/ml 2 resulted in detection of 77% (729/947) and 49% (461/947) of Gleason Score ≥7 tumors. PSA-density might inform biopsy decisions, and spare some men from the morbidity associated with a prostate biopsy and diagnosis of low-grade prostate cancer.

Clinical outcomes of prostate cancer patients in Yokosuka City, Japan: A comparative study between cases detected by prostate-specific antigen-based screening in Yokosuka and those detected by other means.

PubMed

Sakai, Naoki; Taguri, Masataka; Kobayashi, Kazuki; Noguchi, Sumio; Ikeda, Shigeru; Koh, Hideshige; Satomi, Yoshiaki; Furuhata, Akihiko

2015-08-01

To investigate whether prostate-specific antigen-based screening reduced the prostate cancer mortality rate in Yokosuka, Japan. We carried out a cohort study, in which we compared clinical outcomes between patients detected by prostate-specific antigen-based screening (S group n = 524) versus those detected by other means (NS group n = 1044). Clinical and pathological factors were evaluated using Cox regression analyses and the Kaplan-Meier method. A total of 1.5% (8/524) of patients in the S group and 6.7% (70/1044) of those in the NS group died from prostate cancer during follow up. A total of 8.0% (42/524) of patients in the S group and 11.4% (119/1044) in the NS group died from other causes. The 10-year cancer specific survival rates of the S and NS groups were 97% and 86%, respectively (P < 0.001). The median age was significantly lower in the S group than the NS group: 71 and 73 years, respectively (P < 0.001). The rate of Gleason score 8-10 was significantly lower in the S group than the NS group: 9.7% and 16.7%, respectively (P < 0.001). The rate of patients with metastasis or prostate-specific antigen 100 ng/mL or more was significantly lower in the S group than the NS group: 7.8% and 23.0%, respectively (P < 0.001). On multivariate analysis, Gleason score 8-10 compared with Gleason score 6 was independently associated with cancer-specific survival (hazard ratio 4.808, 95% confidence interval 1.044-22.14, P = 0.044). Prostate-specific antigen-based population screening in Yokosuka City might help to reduce the prostate cancer mortality rate. © 2015 The Japanese Urological Association.

Computer aided detection in prostate cancer diagnostics: A promising alternative to biopsy? A retrospective study from 104 lesions with histological ground truth

PubMed Central

Thon, Anika; Teichgräber, Ulf; Tennstedt-Schenk, Cornelia; Hadjidemetriou, Stathis; Winzler, Sven; Malich, Ansgar

2017-01-01

Background Prostate cancer (PCa) diagnosis by means of multiparametric magnetic resonance imaging (mpMRI) is a current challenge for the development of computer-aided detection (CAD) tools. An innovative CAD-software (Watson Elementary™) was proposed to achieve high sensitivity and specificity, as well as to allege a correlate to Gleason grade. Aim/Objective To assess the performance of Watson Elementary™ in automated PCa diagnosis in our hospital´s database of MRI-guided prostate biopsies. Methods The evaluation was retrospective for 104 lesions (47 PCa, 57 benign) from 79, 64.61±6.64 year old patients using 3T T2-weighted imaging, Apparent Diffusion Coefficient (ADC) maps and dynamic contrast enhancement series. Watson Elementary™ utilizes signal intensity, diffusion properties and kinetic profile to compute a proportional Gleason grade predictor, termed Malignancy Attention Index (MAI). The analysis focused on (i) the CAD sensitivity and specificity to classify suspect lesions and (ii) the MAI correlation with the histopathological ground truth. Results The software revealed a sensitivity of 46.80% for PCa classification. The specificity for PCa was found to be 75.43% with a positive predictive value of 61.11%, a negative predictive value of 63.23% and a false discovery rate of 38.89%. CAD classified PCa and benign lesions with equal probability (P 0.06, χ2 test). Accordingly, receiver operating characteristic analysis suggests a poor predictive value for MAI with an area under curve of 0.65 (P 0.02), which is not superior to the performance of board certified observers. Moreover, MAI revealed no significant correlation with Gleason grade (P 0.60, Pearson´s correlation). Conclusion The tested CAD software for mpMRI analysis was a weak PCa biomarker in this dataset. Targeted prostate biopsy and histology remains the gold standard for prostate cancer diagnosis. PMID:29023572

Pretreatment Endorectal Coil Magnetic Resonance Imaging Findings Predict Biochemical Tumor Control in Prostate Cancer Patients Treated With Combination Brachytherapy and External-Beam Radiotherapy

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

Riaz, Nadeem; Afaq, Asim; Akin, Oguz

Purpose: To investigate the utility of endorectal coil magenetic resonance imaging (eMRI) in predicting biochemical relapse in prostate cancer patients treated with combination brachytherapy and external-beam radiotherapy. Methods and Materials: Between 2000 and 2008, 279 men with intermediate- or high-risk prostate cancer underwent eMRI of their prostate before receiving brachytherapy and supplemental intensity-modulated radiotherapy. Endorectal coil MRI was performed before treatment and retrospectively reviewed by two radiologists experienced in genitourinary MRI. Image-based variables, including tumor diameter, location, number of sextants involved, and the presence of extracapsular extension (ECE), were incorporated with other established clinical variables to predict biochemical control outcomes.more » The median follow-up was 49 months (range, 1-13 years). Results: The 5-year biochemical relapse-free survival for the cohort was 92%. Clinical findings predicting recurrence on univariate analysis included Gleason score (hazard ratio [HR] 3.6, p = 0.001), PSA (HR 1.04, p = 0.005), and National Comprehensive Cancer Network risk group (HR 4.1, p = 0.002). Clinical T stage and the use of androgen deprivation therapy were not correlated with biochemical failure. Imaging findings on univariate analysis associated with relapse included ECE on MRI (HR 3.79, p = 0.003), tumor size (HR 2.58, p = 0.04), and T stage (HR 1.71, p = 0.004). On multivariate analysis incorporating both clinical and imaging findings, only ECE on MRI and Gleason score were independent predictors of recurrence. Conclusions: Pretreatment eMRI findings predict for biochemical recurrence in intermediate- and high-risk prostate cancer patients treated with combination brachytherapy and external-beam radiotherapy. Gleason score and the presence of ECE on MRI were the only significant predictors of biochemical relapse in this group of patients.« less

Are 10-, 10-12-, or > 12-mm prostate biopsy core quality control cutoffs reasonable?

PubMed

Sanches, Brunno C F; Lalli, Ana Luiza; Azal Neto, Wilmar; Billis, Athanase; Reis, Leonardo Oliveira

2018-07-01

To explore the role of prostate biopsy core length on prediction of index tumor clinical significance and localization on radical prostatectomy (RP) and time to recurrence, hypothesizing 10-, 10-12-, or > 12-mm minimum core as potential biopsy quality control. Assessed 2424 prostate biopsy cores and corresponding RP of 202 patients submitted to the first set of 12 cores prostate biopsy between 2010 and 2015. Analyzed biopsy core length, age, prostate volume (PV), free and total PSA ratio, PSA density, RP index tumor clinical significance, extension, localization, surgical margins, and cancer control. Prostate biopsy confronted to surgical specimens defined Gleason grade-grouping system (1-5) agreement. Median age was 63.7 years, PSA 10.1 ng/dl, PSA density 28%, and mean follow-up 5 years. Recurrence was identified in 64 (31.7%) patients and predicted by PSA > 10 at time of diagnosis (p = 0.008), seminal vesicle invasion (p = 0.0019), core tumor percentage (p = 0.033), and tumor localization predominantly in the prostate base (p = 0017). The mean core length was longer in index tumor positive cores (p = 0.043) and in tumors classified as clinically insignificant (p = 0.011), without impact on tumor localization (basal vs apical p = 0.592; left vs. right p = 0.320). Biopsy core length categories (≤ 10, 10-12 and > 12 mm) did not significantly impact Gleason grade-grouping agreement or time to recurrence (p > 0.05). Core length was not significantly different in all Gleason grade-groupings 1-5 (p = 0.312). Prostate biopsy core length impacts tumor characterization; however, 10 mm minimum core length and even 10-12- and > 12-mm categories failed as a biopsy quality control in our data.

Favorable Preliminary Outcomes for Men With Low- and Intermediate-risk Prostate Cancer Treated With 19-Gy Single-fraction High-dose-rate Brachytherapy

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

Krauss, Daniel J., E-mail: dkrauss@beaumont.edu; Ye, Hong; Martinez, Alvaro A.

Purpose: To report the toxicity and preliminary clinical outcomes of a prospective trial evaluating 19-Gy, single-fraction high-dose-rate (HDR) brachytherapy for men with low- and intermediate-risk prostate cancer. Methods and Materials: A total of 63 patients were treated according to an institutional review board-approved prospective study of single-fraction HDR brachytherapy. Eligible patients had tumor stage ≤T2a, prostate-specific antigen level ≤15 ng/mL, and Gleason score ≤7. Patients with a prostate gland volume >50 cm{sup 3} and baseline American Urologic Association symptom score >12 were ineligible. Patients underwent transrectal ultrasound-guided transperineal implantation of the prostate, followed by single-fraction HDR brachytherapy. Treatment was delivered using {sup 192}Irmore » to a dose of 19 Gy prescribed to the prostate, with no additional margin applied. Results: Of the 63 patients, 58 had data available for analysis. Five patients had withdrawn consent during the follow-up period. The median follow-up period was 2.9 years (range 0.3-5.2). The median age was 61.4 years. The median gland volume at treatment was 34.8 cm{sup 3}. Of the 58 patients, 91% had T1 disease, 71% had Gleason score ≤6 (29% with Gleason score 7), and the median pretreatment prostate-specific antigen level was 5.1 ng/mL. The acute and chronic grade 2 genitourinary toxicity incidence was 12.1% and 10.3%, respectively. No grade 3 urinary toxicity occurred. No patients experienced acute rectal toxicity grade ≥2, and 2 experienced grade ≥2 chronic gastrointestinal toxicity. Three patients experienced biochemical failure, yielding a 3-year cumulative incidence estimate of 6.8%. Conclusions: Single-fraction HDR brachytherapy is well-tolerated, with favorable preliminary biochemical and clinical disease control rates.« less

Expression of Ki-67 (MIB-1) and GLUT-1 proteins in non-advanced prostatic cancer.

PubMed

Luczynska, Elzbieta; Gasinska, Anna; Wilk, Waclaw

2012-12-01

The expression of Ki-67 (MIB-1) and glucose transporter-1 (GLUT-1) were evaluated in patients with clinically localized prostate cancer (PC) who had undergone radical prostatectomy with curative intent. 140 low advanced PC specimens were studied. Protein expression was assessed immunohistochemically on tumour sections and expressed as a labelling index, i.e. the percentage of positively stained cells. In the case of Ki-67 nuclear staining and in the case of GLUT-1 membrane and cytoplasmic staining was considered as positive. The patients' mean age was 62.9 ±6.2 years. There were 13 (9.3%) at pTNM stage 1, 78 (55.7%) at stage 2, 40 (28.6%) at stage 3 and 9 (6.4%) at stage 4, respectively. 75 (53.6%) tumours were well differentiated (Gleason score ≤6), 52 (37.1%) moderately differentiated (Gleason score of 7) and 13 (9.3%) poorly differentiated (Gleason score 8-10). The mean pre-operative serum PSA was 9.9 ± SE 0.5 ng/ml, and the mean LI was equal to 8.1 ±0.6% and 29.7 ±2.0%, for MIB-1 and GLUT-1, respectively. Increase of pathological tumor volume and tumor grade was associated with statistically significant growth of PSA (p < 0.011) and MIB-1LI (p < 0.003), however, for GLUT-1 LI the relation was not significant. Ki-67 expression was correlated with PSA levels (p = 0.013) and GLUT-1 scores (p = 0.04). In PC, an increase in the proliferation rate (higher MIB-1LI) in higher pTNM stages and tumour grades may point to Ki-67 as a good marker of biological aggressiveness useful in selecting patients for more aggressive treatment. A correlation between proliferation and GLUT-1 score may be the evidence of active glycolytic metabolism in hypoxic regions.

Gleason grade grouping of prostate cancer is of prognostic value in Asian men.

PubMed

Yeong, Joe; Sultana, Rehena; Teo, Jonathan; Huang, Hong Hong; Yuen, John; Tan, Puay Hoon; Khor, Li Yan

2017-09-01

The International Society of Urological Pathology made recommendations for the use of Grade Groups (GG) originally described by Epstein and colleagues over Gleason score (GS) alone in 2014, which was subsequently adopted by the WHO classification in 2016. The majority of studies validating this revision have been in Caucasian populations. We therefore asked whether the new GG system was retrospectively associated with biochemical disease-free survival in a mixed-ethnicity cohort of Asian men. A total of 680 radical prostatectomies (RPs) from 2005 to 2014 were included. GS from initial biopsy and RP were compared and used to allocate cases to GG, defined as: 1 (GS≤6); 2 (GS 3+4=7); 3 (GS 4+3=7); 4 (GS 4+4=8/5+3=8/3+5=8) and 5 (GS 9-10). Biochemical recurrence was defined as two consecutive post-RP prostate-specific antigen (PSA) levels of >0.2 ng/mL after post-RP PSA reaching the nadir of <0.1 ng/mL. Our data showed that Kaplan-Meier analysis revealed significant differences in biochemical recurrence within Gleason GG based on either biopsy or prostatectomy scoring. Multivariate analysis further confirmed that a higher GG was significantly associated with risk of biochemical recurrence. This GG system had a higher prognostic discrimination for both initial biopsy and RP than GS. Our study validates the use of the revised and updated GG system in a mixed-ethnicity population of Asian men. Higher GG was significantly associated with increased risk of biochemical recurrence. We therefore recommend its use to inform clinical management for patients with prostate cancer. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

18F-Fluorocholine PET/CT Complementing the Role of Dynamic Contrast-Enhanced MRI for Providing Comprehensive Diagnostic Workup in Prostate Cancer Patients With Suspected Relapse Following Radical Prostatectomy.

PubMed

Vadi, Shelvin Kumar; Singh, Baljinder; Basher, Rajender K; Watts, Ankit; Sood, Ashwani K; Lal, Anupam; Kakkar, Nandita; Singh, S K

2017-08-01

The aim of this study was to compare the diagnostic performance of F-fluorocholine (FCH) PET/CT and dynamic contrast-enhanced MRI (DCE-MRI) of pelvis in restaging prostate cancer (PC) patients with biochemical recurrence (BCR) following radical prostatectomy (RP). Twenty PC patients who had undergone RP and had BCR were recruited in this study. All the patients underwent whole-body FCH PET/CT and DCE-MRI of the pelvis. An overall pattern of recurrent disease was analyzed, and diagnostic accuracy for the detection of pelvic disease recurrence by the 2 modalities was evaluated by taking histopathologic analysis as the criterion standard. The whole-body FCH PET/CT images were also analyzed separately for the presence of any extra lesion(s). The initial mean Gleason score was 6.3 ± 1.53 (range, 4-9). The mean prostate-specific antigen levels at the time of relapse were 1.9 ± 2.87 ng/mL (range, 0.24-13.2 ng/mL). MRI findings were positive for primary tumor recurrence in the prostate bed in 6 patients (6/20 [30.0%]), pelvic lymph node metastases in 4 patients (4/20 [20.0%]), and for pelvic skeletal metastases in 2 patients (2/20 [10.0%]), respectively. On the other hand, FCH PET/CT results were positive in the corresponding sites in 7 (7/20 [35.0%]), 9 (9/20 [45.0%]), and 2 patients (2/20 [10.0%]), respectively. F-fluorocholine PET/CT and MRI showed comparable results in terms of sensitivity, specificity, and positive and negative predictive values for PC characterization. The whole-body FCH PET/CT was found to be useful in identifying unknown distant metastases in a significant proportion of patients. The correlative whole-body FCH PET/CT and pelvic DCE-MRI offer a complementary and comprehensive diagnostic workup for better management of PC patients with BCR following RP.

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.

Development of a Biological Control Program for Eurasian Watermilfoil (Myriophyllum Spicatum)

DTIC Science & Technology

2006-12-22

spicatum). Pakistan Station Commonwealth Institute of Biological Control, Rawalpindi. 16 Gleason, H.A., Cronquist , A . 1991. Manual of Vascular Plants of...Development of a biological control program for Eurasian watermilfoil (Myriophyllum spicatum...control agents have not considered potential impact on non target indigenous species. A phased programme to address these gaps is put forward. List of

De La Salle Christian Brothers' Experiences of Catholic Identity in Higher Education in the United States

ERIC Educational Resources Information Center

Kier, Scott A.

2012-01-01

Catholic identity is considered to be the single most important issue facing Catholic higher education in the United States. Scholars (Burtchaell, 1998; Gallin, 1999; Gleason, 1995; Heft, 2003; Marsden, 1994; O'Brien, 1994) have suggested that sustaining Catholic identity and preventing secularization depends on the integration of the…

Acer spicatum

Treesearch

Paula M. Pijut

2004-01-01

Mountain maple is a tall, deciduous shrub or clumped small tree that grows 3 to 10 m tall and can spread to form dense thickets (Dirr 1998; Gleason and Cronquist 1991; van Gelderen and others 1994). In the northern part of its native range mountain maple reaches a maximum height of 6 m (Sullivan 1993). Leaves are opposite, simple, threelobed or obscurely five-lobed,...

Psychiatric Consultation at Your Fingertips: Descriptive Analysis of Electronic Consultation From Primary Care to Psychiatry.

PubMed

Lowenstein, Margaret; Bamgbose, Olusinmi; Gleason, Nathaniel; Feldman, Mitchell D

2017-08-04

Mental health problems are commonly encountered in primary care, with primary care providers (PCPs) experiencing challenges referring patients to specialty mental health care. Electronic consultation (eConsult) is one model that has been shown to improve timely access to subspecialty care in a number of medical subspecialties. eConsults generally involve a PCP-initiated referral for specialty consultation for a clinical question that is outside their expertise but may not require an in-person evaluation. Our aim was to describe the implementation of eConsults for psychiatry in a large academic health system. We performed a content analysis of the first 50 eConsults to psychiatry after program implementation. For each question and response, we coded consults as pertaining to diagnosis and/or management as well as categories of medication choice, drug side effects or interactions, and queries about referrals and navigating the health care system. We also performed a chart review to evaluate the timeliness of psychiatrist responses and PCP implementation of recommendations. Depression was the most common consult template selected by PCPs (20/50, 40%), followed by the generic template (12/50, 24%) and anxiety (8/50, 16%). Most questions (49/50, 98%) pertained primarily to management, particularly for medications. Psychiatrists commented on both diagnosis (28/50, 56%) and management (50/50, 100%), responded in an average of 1.4 days, and recommended in-person consultation for 26% (13/50) of patients. PCPs implemented psychiatrist recommendations 76% (38/50) of the time. For the majority of patients, psychiatrists provided strategies for ongoing management in primary care without an in-person evaluation, and PCPs implemented most psychiatrist recommendations. eConsults show promise as one means of supporting PCPs to deliver mental health care to patients with common psychiatric disorders. ©Margaret Lowenstein, Olusinmi Bamgbose, Nathaniel Gleason, Mitchell D Feldman. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 04.08.2017.

Cornus sericea

Treesearch

Paula M. Pijut

2004-01-01

Redosier dogwood is a multistemmed, deciduous, stoloniferous shrub that grows 1 to 3 m tall and 3 m wide or more, often forming dense thickets. Leaves are opposite, simple, ovate to oblonglanceolate, acuminate, rounded at the base, 5 to 12 cm long, 2.5 to 6.4 cm wide, with petioles 1.3 to 2.5 cm long (Dirr 1998, Gleason and Cronquist 1991). Leaves are medium to dark...

[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.

Dual tracer 11C-choline and FDG-PET in the diagnosis of biochemical prostate cancer relapse after radical treatment.

PubMed

Richter, José A; Rodríguez, Macarena; Rioja, Jorge; Peñuelas, Iván; Martí-Climent, Josep; Garrastachu, Puy; Quincoces, Gemma; Zudaire, Javier; García-Velloso, María J

2010-04-01

The purpose of this study was to evaluate a dual tracer 2-deoxy-2-[F-18]fluoro-D: -glucose (FDG) and (11)C-choline positron emission tomography (PET) protocol in the detection of biochemical prostate cancer relapse. Seventy-three patients (median Prostate Specific Antigen (PSA) Test value 2.7 ng/ml (1.1-5.4)) after radical treatment. PET scans were performed by means of a ECAT-Exact HR+ in the first 18 patients and in a PET/computed tomography Biograph II in the remaining 55 patients. The sensitivity of (11)C-choline and FDG was 60.6% and 31%. In PSA levels over 1.9 ng/ml, sensitivity increased to 80% and 40%, respectively. In the group receiving adjuvant hormone therapy, the diagnostic yields were 71.2% and 43%, respectively. While (11)C-choline-PET could not differentiate well and poorly differentiated Gleason score patients, FDG-PET results were almost significant (p = 0.058). A PSA value higher than 1.9 ng/ml determines a significant increase in the diagnostic yield. Adjuvant hormonotherapy has no influence on the PET results. FDG has a better correlation with the Gleason score than (11)C-choline.

Comparative evaluation of urinary PCA3 and TMPRSS2: ERG scores and serum PHI in predicting prostate cancer aggressiveness.

PubMed

Tallon, Lucile; Luangphakdy, Devillier; Ruffion, Alain; Colombel, Marc; Devonec, Marian; Champetier, Denis; Paparel, Philippe; Decaussin-Petrucci, Myriam; Perrin, Paul; Vlaeminck-Guillem, Virginie

2014-07-30

It has been suggested that urinary PCA3 and TMPRSS2:ERG fusion tests and serum PHI correlate to cancer aggressiveness-related pathological criteria at prostatectomy. To evaluate and compare their ability in predicting prostate cancer aggressiveness, PHI and urinary PCA3 and TMPRSS2:ERG (T2) scores were assessed in 154 patients who underwent radical prostatectomy for biopsy-proven prostate cancer. Univariate and multivariate analyses using logistic regression and decision curve analyses were performed. All three markers were predictors of a tumor volume≥0.5 mL. Only PHI predicted Gleason score≥7. T2 score and PHI were both independent predictors of extracapsular extension(≥pT3), while multifocality was only predicted by PCA3 score. Moreover, when compared to a base model (age, digital rectal examination, serum PSA, and Gleason sum at biopsy), the addition of both PCA3 score and PHI to the base model induced a significant increase (+12%) when predicting tumor volume>0.5 mL. PHI and urinary PCA3 and T2 scores can be considered as complementary predictors of cancer aggressiveness at prostatectomy.

Incidental Prostate Cancer in Transurethral Resection of the Prostate Specimens in the Modern Era

PubMed Central

Barbieri, Christopher; Te, Alexis E.; Kaplan, Steven A.

2014-01-01

Objectives. To identify rates of incidentally detected prostate cancer in patients undergoing surgical management of benign prostatic hyperplasia (BPH). Materials and Methods. A retrospective review was performed on all transurethral resections of the prostate (TURP) regardless of technique from 2006 to 2011 at a single tertiary care institution. 793 men (ages 45–90) were identified by pathology specimen. Those with a known diagnosis of prostate cancer prior to TURP were excluded (n = 22) from the analysis. Results. 760 patients had benign pathology; eleven (1.4%) patients were found to have prostate cancer. Grade of disease ranged from Gleason 3 + 3 = 6 to Gleason 3 + 4 = 7. Nine patients had cT1a disease and two had cT1b disease. Seven patients were managed by active surveillance with no further events, one patient underwent radiation, and three patients underwent radical prostatectomy. Conclusions. Our series demonstrates that 1.4% of patients were found to have prostate cancer, of these 0.5% required treatment. Given the low incidental prostate cancer detection rate, the value of pathologic review of TURP specimens may be limited depending on the patient population. PMID:24876835

Incidental prostate cancer in transurethral resection of the prostate specimens in the modern era.

PubMed

Otto, Brandon; Barbieri, Christopher; Lee, Richard; Te, Alexis E; Kaplan, Steven A; Robinson, Brian; Chughtai, Bilal

2014-01-01

Objectives. To identify rates of incidentally detected prostate cancer in patients undergoing surgical management of benign prostatic hyperplasia (BPH). Materials and Methods. A retrospective review was performed on all transurethral resections of the prostate (TURP) regardless of technique from 2006 to 2011 at a single tertiary care institution. 793 men (ages 45-90) were identified by pathology specimen. Those with a known diagnosis of prostate cancer prior to TURP were excluded (n = 22) from the analysis. Results. 760 patients had benign pathology; eleven (1.4%) patients were found to have prostate cancer. Grade of disease ranged from Gleason 3 + 3 = 6 to Gleason 3 + 4 = 7. Nine patients had cT1a disease and two had cT1b disease. Seven patients were managed by active surveillance with no further events, one patient underwent radiation, and three patients underwent radical prostatectomy. Conclusions. Our series demonstrates that 1.4% of patients were found to have prostate cancer, of these 0.5% required treatment. Given the low incidental prostate cancer detection rate, the value of pathologic review of TURP specimens may be limited depending on the patient population.

Ratio of prostate specific antigen to the outer gland volume of prostrate as a predictor for prostate cancer.

PubMed

Zhang, Hai-Min; Yan, Yang; Wang, Fang; Gu, Wen-Yu; Hu, Guang-Hui; Zheng, Jun-Hua

2014-01-01

As a definite diagnosis of prostate cancer, puncture biopsy of the prostate is invasive method. The aim of this study was to evaluate the value of OPSAD (the ratio of PSA to the outer gland volume of prostate) as a non-invasive screening and diagnosis method for prostate cancer in a select population. The diagnosis data of 490 subjects undergoing ultrasound-guided biopsy of the prostate were retrospectively analyzed. This included 133 patients with prostate cancer, and 357 patients with benign prostate hyperplasia (BPH). The OPSAD was significantly greater in patients with prostate cancer (1.87 ± 1.26 ng/ml(2)) than those with BPH (0.44 ± 0.21 ng/ml(2)) (P < 0.05). Receiver operating characteristic (ROC) curve analysis revealed that the performance of OPSAD as a diagnostic tool is superior to PSA and PSAD for the diagnosis of prostate cancer. In the different groups divided according to the Gleason score of prostate cancer, OPSAD is elevated with the rise of the Gleason score. OPSAD may be used as a new indicator for the diagnosis and prognosis of prostate cancer, and it can reduce the use of unnecessary puncture biopsy of the prostate.

Sampling of radical prostatectomy specimens. How much is adequate?

PubMed

Cohen, M B; Soloway, M S; Murphy, W M

1994-03-01

Prostate glands from 52 patients with clinical stage B carcinoma were examined using two sampling techniques. After fixation and conization of the apical portions, each gland was serially sectioned with sections mounted whole on oversized glass slides and examined for pathologic features of prognostic importance. A second examination was subsequently conducted on the same tissue using only alternate sections. No differences in tumor type, grade, Gleason score, multiplicity, or capsular penetration were detected in 75% of cases. The discrepancies that did occur were most often minor variations in multiplicity and Gleason score. Of the 20 glands with capsular penetration observed with the serial sectioning method, 17 (85%) were detected using alternate sectioning. The surgical margin was involved in two of the three invasive foci that would have been missed. Although the topography is better displayed, the authors' examinations indicated no significant advantage to whole mount sections compared with sections mounted on standard-sized glass slides. Considering the most effective use of resources, as well as the current modalities available for patient monitoring, the results support the use of an alternate sectioning method for pathologic examination of specimens removed for clinically localized prostate cancer.

LINE-1 methylation status in prostate cancer and non-neoplastic tissue adjacent to tumor in association with mortality

PubMed Central

Delsedime, Luisa; Molinaro, Luca; Gillio-Tos, Anna

2017-01-01

ABSTRACT Aberrant DNA methylation seems to be associated with prostate cancer behavior. We investigated LINE-1 methylation in prostate cancer and non-neoplastic tissue adjacent to tumor (NTAT) in association with mortality from prostate cancer. We selected 157 prostate cancer patients with available NTAT from 2 cohorts of patients diagnosed between 1982–1988 and 1993–1996, followed up until 2010. An association between LINE-1 hypomethylation and prostate cancer mortality in tumor was suggested [hazard ratio per 5% decrease in LINE-1 methylation levels: 1.40, 95% confidence interval (CI): 0.95–2.01]. After stratification of the patients for Gleason score, the association was present only for those with a Gleason score of at least 8. Among these, low (<75%) vs. high (>80%) LINE-1 methylation was associated with a hazard ratio of 4.68 (95% CI: 1.03–21.34). LINE-1 methylation in the NTAT was not associated with prostate cancer mortality. Our results are consistent with the hypothesis that tumor tissue global hypomethylation may be a late event in prostate cancerogenesis and is associated with tumor progression. PMID:27892790

Phase II Study of Long-Term Androgen Suppression With Bevacizumab and Intensity-Modulated Radiation Therapy (IMRT) in High-Risk Prostate Cancer

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

Vuky, Jacqueline, E-mail: vukyja@ohsu.edu; Pham, Huong T.; Warren, Sarah

Purpose: We report a Phase II trial assessing the acute and late toxicities of intensity-modulated radiation therapy (IMRT), long-term androgen suppression (LTAS), and bevacizumab in patients with high-risk localized prostate cancer. Methods and Materials: We treated 18 patients with LTAS with bicalutamide and goserelin in combination with bevacizumab and IMRT. Bevacizumab (10 mg/kg every 2 weeks) was administered for the first 16 weeks, and 15 mg/kg was then given every 3 weeks for 12 additional weeks, with an IMRT dose of 77.9 Gy to the prostate, 64.6 Gy to the seminal vesicles, and 57 Gy to the pelvic lymph nodes.more » Patients were eligible if they had clinical stage T2b to T4, a Gleason sum score of 8 to 10, or a prostate- specific antigen level of 20ng/mL or greater. The primary endpoint of the study was evaluation of acute and late toxicities. Results: The median age was 69 years, with a median pretreatment prostate-specific antigen level of 12.5 ng/mL and Gleason score of 8. The pretreatment clinical stage was T1c in 4 patients, T2 in 11, and T3 in 3. All patients completed IMRT with median follow-up of 34 months (range, 28-40 months) The most common Grade 2 or higher toxicities were hypertension (61% of patients with Grade 2 and 11% with Grade 3), proteinuria (28% with Grade 2 and 6% with Grade 3), and leucopenia (28% with Grade 2). No Grade 4 or higher acute toxicities were reported. Late toxicities included proctitis (6% of patients with Grade 2 and 11% with Grade 3), rectal bleeding (6% with Grade 2 and 11% with Grade 3), hematuria (6% with Grade 2), proteinuria (17% with Grade 2), hyponatremia (6% with Grade 3), cystitis (6% with Grade 3), and urinary retention (6% with Grade 2 and 11% with Grade 3). Grade 4 prostatitis occurred in 1 patient (6%). Conclusions: Bevacizumab does not appear to exacerbate the acute effects of IMRT. Late toxicities may have been worsened with this regimen. Further investigations of bevacizumab with LTAS and IMRT should be performed cautiously.« less

The effect of process parameters on Twin Wire Arc spray pattern shape

DOE PAGES

Hall, Aaron Christopher; McCloskey, James Francis; Horner, Allison Lynne

2015-04-20

A design of experiments approach was used to describe process parameter—spray pattern relationships in the Twin Wire Arc process using zinc feed stock in a TAFA 8835 (Praxair, Concord, NH, USA) spray torch. Specifically, the effects of arc current, primary atomizing gas pressure, and secondary atomizing gas pressure on spray pattern size, spray pattern flatness, spray pattern eccentricity, and coating deposition rate were investigated. Process relationships were investigated with the intent of maximizing or minimizing each coating property. It was determined that spray pattern area was most affected by primary gas pressure and secondary gas pressure. Pattern eccentricity was mostmore » affected by secondary gas pressure. Pattern flatness was most affected by primary gas pressure. Lastly, coating deposition rate was most affected by arc current.« less

The effect of process parameters on Twin Wire Arc spray pattern shape

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

Hall, Aaron Christopher; McCloskey, James Francis; Horner, Allison Lynne

A design of experiments approach was used to describe process parameter—spray pattern relationships in the Twin Wire Arc process using zinc feed stock in a TAFA 8835 (Praxair, Concord, NH, USA) spray torch. Specifically, the effects of arc current, primary atomizing gas pressure, and secondary atomizing gas pressure on spray pattern size, spray pattern flatness, spray pattern eccentricity, and coating deposition rate were investigated. Process relationships were investigated with the intent of maximizing or minimizing each coating property. It was determined that spray pattern area was most affected by primary gas pressure and secondary gas pressure. Pattern eccentricity was mostmore » affected by secondary gas pressure. Pattern flatness was most affected by primary gas pressure. Lastly, coating deposition rate was most affected by arc current.« less

Radical Prostatectomy Findings in White Hispanic/Latino Men With NCCN Very Low-risk Prostate Cancer Detected by Template Biopsy.

PubMed

Kryvenko, Oleksandr N; Lyapichev, Kirill; Chinea, Felix M; Prakash, Nachiketh Soodana; Pollack, Alan; Gonzalgo, Mark L; Punnen, Sanoj; Jorda, Merce

2016-08-01

Radical prostatectomy (RP) outcomes have been studied in White and Black non-Hispanic men qualifying for Epstein active surveillance criteria (EASC). Herein, we first analyzed such outcomes in White Hispanic men. We studied 70 men with nonpalpable Gleason score 3+3=6 (Grade Group [GG] 1) prostate cancer (PCa) with ≤2 positive cores on biopsy who underwent RP. In 18 men, prostate-specific antigen (PSA) density (PSAD) was >0.15 ng/mL/g. Three of these had insignificant and 15 had significant PCa. The remaining 52 men qualified for EASC. One patient had no PCa identified at RP. Nineteen (37%) had significant PCa defined by volume (n=7), grade (n=7), and volume and grade (n=5). Nine cases were 3+4=7 (GG 2) (5/9 [56%] with pattern 4 <5%), 2 were 3+5=8 (GG 4), and 1 was 4+5=9 (GG 5). Patients with significant PCa more commonly had anterior dominant disease (11/19, 58%) versus patients with insignificant cancer (7/33, 21%) (P=0.01). In 12 cases with higher grade at RP, the dominant tumor nodule was anterior in 6 (50%) and posterior in 6 (median volumes: 1.1 vs. 0.17 cm, respectively; P=0.01). PSA correlated poorly with tumor volume (r=0.28, P=0.049). Gland weight significantly correlated with PSA (r=0.54, P<0.001). While PSAD and PSA mass density correlated with tumor volume, only PSA mass density distinguished cases with significant disease (median, 0.008 vs. 0.012 μg/g; P=0.03). In summary, a PSAD threshold of 0.15 works well in predicting significant tumor volume in Hispanic men. EASC appear to perform better in White Hispanic men than previously reported outcomes for Black non-Hispanic and worse than in White non-Hispanic men. Significant disease is often Gleason score 3+3=6 (GG 1) PCa >0.5 cm. Significant PCa is either a larger-volume anterior disease that may be detected by multiparametric magnetic resonance imaging-targeted biopsy or anterior sampling of the prostate or higher-grade smaller-volume posterior disease that in most cases should not pose immediate harm and may be detected by repeat template biopsies.

Prognostic parameter for high risk prostate cancer patients at initial presentation.

PubMed

Kato, Masashi; Kimura, Kyosuke; Hirakawa, Akihiro; Kobayashi, Yumiko; Ishida, Ryo; Kamihira, Osamu; Majima, Tsuyoshi; Funahashi, Yasuhito; Sassa, Naoto; Matsukawa, Yoshihisa; Hattori, Ryohei; Gotoh, Momokazu; Tsuzuki, Toyonori

2018-01-01

High-risk prostate cancer can be defined by a patient's Gleason score (GS), prostate-specific antigen (PSA) level, and clinical T (cT) stage, but a novel marker is needed due to heterogeneity of the disease. In this study, we evaluated whether intraductal carcinoma of the prostate (IDC-P) confirmed by needle biopsy is an adverse prognostic parameter for progression-free survival (PFS) and cancer-specific survival (CSS) in patients with high-risk prostate cancer. We retrospectively evaluated 204 patients with high-risk prostate cancer treated by radical prostatectomy from 1991 to 2005 at Nagoya University and its affiliated hospitals. Data on each patient's PSA level, biopsy GS, cT stage, presence of Gleason pattern 5, presence of IDC-P, percentage of the core involved with cancer, and maximum percentage of the core involved with cancer were analyzed. The median follow-up period was 108 months (range, 11-257 months). Forty-eight patients (24%) showed disease progression. Thirty-four patients (17%) died of the disease during follow-up. The IDC-P component was detected in 74 (36%) needle biopsy samples. The 5-, 10-, and 15-year CSS rates of the IDC-P-negative cases were 3.2%, 9.0%, and 23.7%; the corresponding rates of the IDC-P-positive cases were 23.9%, 33.7%, and 52.7%, respectively (P = 0.0001). In the Fine and Gray's model for PFS, IDC-P, maximum percentage of the core involved with cancer, and cT stage were significantly associated (P = 0.013, P = 0.003, P = 0.007). In the Fine and Gray's model for CSS, only IDC-P was significant (P = 0.027). In a multivariate Cox regression analysis, IDC-P (P = 0.04; hazard ratio [HR], 1.95) and maximum percentage of the core involved with cancer (P = 0.021; HR, 0.43) were significant factors in predicting overall survival (OS). The presence of IDC-P in a needle biopsy was a prognostic factor for PFS, CSS, and OS in patients with high-risk prostate cancer who underwent radical prostatectomy. Multimodal pre-and/or post- surgical therapy may be needed when IDC-P is found in a needle biopsy specimen. © 2017 Wiley Periodicals, Inc.

Global transcriptome analysis of formalin-fixed prostate cancer specimens identifies biomarkers of disease recurrence.

PubMed

Long, Qi; Xu, Jianpeng; Osunkoya, Adeboye O; Sannigrahi, Soma; Johnson, Brent A; Zhou, Wei; Gillespie, Theresa; Park, Jong Y; Nam, Robert K; Sugar, Linda; Stanimirovic, Aleksandra; Seth, Arun K; Petros, John A; Moreno, Carlos S

2014-06-15

Prostate cancer remains the second leading cause of cancer death in American men and there is an unmet need for biomarkers to identify patients with aggressive disease. In an effort to identify biomarkers of recurrence, we performed global RNA sequencing on 106 formalin-fixed, paraffin-embedded prostatectomy samples from 100 patients at three independent sites, defining a 24-gene signature panel. The 24 genes in this panel function in cell-cycle progression, angiogenesis, hypoxia, apoptosis, PI3K signaling, steroid metabolism, translation, chromatin modification, and transcription. Sixteen genes have been associated with cancer, with five specifically associated with prostate cancer (BTG2, IGFBP3, SIRT1, MXI1, and FDPS). Validation was performed on an independent publicly available dataset of 140 patients, where the new signature panel outperformed markers published previously in terms of predicting biochemical recurrence. Our work also identified differences in gene expression between Gleason pattern 4 + 3 and 3 + 4 tumors, including several genes involved in the epithelial-to-mesenchymal transition and developmental pathways. Overall, this study defines a novel biomarker panel that has the potential to improve the clinical management of prostate cancer. ©2014 American Association for Cancer Research.

Alterations in expressed prostate secretion-urine PSA N-glycosylation discriminate prostate cancer from benign prostate hyperplasia

PubMed Central

Sun, Chenxia; Wen, Fuping; Wang, Haifeng; Guo, Huaizu; Gao, Xu; Xu, Chuanliang; Xu, Chuanliang; Yang, Chenghua; Sun, Yinghao

2017-01-01

The prostate specific antigen (PSA) test is widely used for early diagnosis of prostate cancer (PCa). However, its limited sensitivity has led to over-diagnosis and over-treatment of PCa. Glycosylation alteration is a common phenomenon in cancer development. Different PSA glycan subforms have been proposed as diagnostic markers to better differentiate PCa from benign prostate hyperplasia (BPH). In this study, we purified PSA from expressed prostate secretions (EPS)-urine samples from 32 BPH and 30 PCa patients and provided detailed PSA glycan profiles in Chinese population. We found that most of the PSA glycans from EPS-urine were complex type biantennary glycans. We observed two major patterns in PSA glycan profiles. Overall there was no distinct separation of PSA glycan profiles between BPH and PCa patients. However, we detected a significant increase of glycan FA2 and FM5A2G2S1 in PCa when compared with BPH patients. Furthermore, we observed that the composition of FA2 glycan increased significantly in advanced PCa with Gleason score ≥8, which potentially could be translated to clinic as a marker for aggressive PCa. PMID:29100363

Alterations in expressed prostate secretion-urine PSA N-glycosylation discriminate prostate cancer from benign prostate hyperplasia.

PubMed

Jia, Gaozhen; Dong, Zhenyang; Sun, Chenxia; Wen, Fuping; Wang, Haifeng; Guo, Huaizu; Gao, Xu; Xu, Chuanliang; Xu, Chuanliang; Yang, Chenghua; Sun, Yinghao

2017-09-29

The prostate specific antigen (PSA) test is widely used for early diagnosis of prostate cancer (PCa). However, its limited sensitivity has led to over-diagnosis and over-treatment of PCa. Glycosylation alteration is a common phenomenon in cancer development. Different PSA glycan subforms have been proposed as diagnostic markers to better differentiate PCa from benign prostate hyperplasia (BPH). In this study, we purified PSA from expressed prostate secretions (EPS)-urine samples from 32 BPH and 30 PCa patients and provided detailed PSA glycan profiles in Chinese population. We found that most of the PSA glycans from EPS-urine were complex type biantennary glycans. We observed two major patterns in PSA glycan profiles. Overall there was no distinct separation of PSA glycan profiles between BPH and PCa patients. However, we detected a significant increase of glycan FA2 and FM5A2G2S1 in PCa when compared with BPH patients. Furthermore, we observed that the composition of FA2 glycan increased significantly in advanced PCa with Gleason score ≥8, which potentially could be translated to clinic as a marker for aggressive PCa.

Process for Making Ceramic Mold

NASA Technical Reports Server (NTRS)

Buck, Gregory M. (Inventor); Vasquez, Peter (Inventor)

2001-01-01

An improved process for slip casting molds that can be more economically automated and that also exhibits greater dimensional stability is disclosed. The process involves subjecting an investment pattern, preferably made from wax, to successive cycles of wet-dipping in a slurry of colloidal, silica-based binder and dry powder-coating, or stuccoing with plaster of Paris or calcium sulfate mixtures to produce a multi-layer shell over the pattern. The invention as claimed entails applying a primary and a secondary coating to the investment pattern. At least two wet-dipping on in a primary slurry and dry-stuccoing cycles provide the primary coating, and an additional two wet-dippings and dry-stuccoing cycles provide the secondary, or back-up, coating. The primary and secondary coatings produce a multi-layered shell pattern. The multi-layered shell pattern is placed in a furnace first to cure and harden, and then to vaporize the investment pattern, leaving a detailed, high precision shell mold.

The (virtual) conceptual necessity of quantum probabilities in cognitive psychology.

PubMed

Blutner, Reinhard; beim Graben, Peter

2013-06-01

We propose a way in which Pothos & Busemeyer (P&B) could strengthen their position. Taking a dynamic stance, we consider cognitive tests as functions that transfer a given input state into the state after testing. Under very general conditions, it can be shown that testable properties in cognition form an orthomodular lattice. Gleason's theorem then yields the conceptual necessity of quantum probabilities (QP).

Development of a Biological Control Program for Eurasian Watermilfoil (Myriophyllum spicatum)

DTIC Science & Technology

2008-08-01

spicatum). Rawalpindi: Pakistan Station Commonwealth Institute of Biological Control. Gleason, H. A ., and A . Cronquist . 1991. Manual of vascular plants...ER D C/ EL T R- 08 -2 2 Aquatic Plant Control Research Program Development of a Biological Control Program for Eurasian Watermilfoil... a Biological Control Program for Eurasian Watermilfoil (Myriophyllum spicatum) Matthew J. W. Cock, Hariet L. Hinz, Gitta Grosskopf, and Patrick

Exploiting a Molecular Gleason Grade for Prostate Cancer Therapy

DTIC Science & Technology

2009-03-01

P. (2008) The an- drogen-regulated type II serine protease TMPRSS2 is differentially expressed and mislocal- ized in prostate adenocarcinoma . J...program associated with key points of murine prostate organogenesis spanning the initial in utero induction of prostate budding through maturity. We...studies, we found no significant associations with stages of lung morphogenesis. Genes altered in murine prostate adenocarcinoma map to the branching

Increasing Rates of School Completion: Moving from Policy and Research to Practice. A Manual for Policymakers, Administrators, and Educators. Essential Tools.

ERIC Educational Resources Information Center

Lehr, Camilla A.; Johnson, David R.; Bremer, Christine D.; Cosio, Anna; Thompson, Megan

2004-01-01

This manual provides a synthesis of research-based dropout prevention and intervention and offers examples of interventions that show evidence of effectiveness. This has proven to be a difficult task because the intervention research on dropout and school completion that can be used to inform practice is incomplete (Dynarski & Gleason, 2002;…

Use of Synthetic Nerve Grafts to Restore Cavernous Nerve Function Following Prostate Cancer Surgery: In Vitro and In Vivo Studies

DTIC Science & Technology

2007-09-01

Certain factors such as a serum PSA>10ng/ml, biopsy tumor Gleason >7, clinical stage T2a or higher, and a high number and percentage of biopsy ...Solution supplemented with 6.5 mg/ml glucose. The epineurium, connective tissue, and blood vessels were removed using fine forceps and the nerve was

Validation and Interrogation of Differentially Expressed and Alternately Spliced Genes in African American Prostate Cancer

DTIC Science & Technology

2017-10-01

aggressive disease. 15. SUBJECT TERMS Prostate cancer, health disparities among racial groups, molecular mechanisms, differential gene expression...identify molecular mechanisms of tumor aggressiveness. The studies proposed here address the urgent need to elucidate the molecular mechanisms underlying... genetic /epigenetic/post-transcriptional factors in AA prostate cancer and Gleason grade and 2) manipulate splicing using novel splice-switching

Imaging Prostatic Lipids to Distinguish Aggressive Prostate Cancer

DTIC Science & Technology

2015-10-01

this application, we propose to build upon our current work to determine the association between fatty acid synthase ( FAS ) overexpression and...cancer (as determined by Gleason scoring) we propose to: 1) Determine the correlation between FAS expression in prostatectomy samples and the amount... FAS expression and FAS activity in prostatectomy samples, intraprostatic lipid as measured by MRSI and prostate tumor aggressiveness. 3) To quantify

Terrorism: A Selective Bibliography.

DTIC Science & Technology

1984-04-01

P623 Alexander, Yonah, and Gleason, John M., eds. BEHAVIORAL AND QUANTITATIVE PERSPECTIVES ON TERRORISM. New York, NY: Pergamon Press, 1981. 396 p. HV...CONTROL AND PROSOCIAL ALTERNATIVES. New York, NY: Pergamon Press, 1981. 560 p. RC 569.5 .V55 I5 1981 Gurr, Ted Robert. HANDBOOK OF POLITICAL CONFLICT...Rapoport, David C., and Alexander, Yonah, eds. THE RATIONALIZATION OF TERRORISM. Frederick, MD: Aletheia Books, University Publications of America

Competing risk analysis of mortality in prostate cancer treated with radical prostatectomy.

PubMed

Ruiz-Cerdá, J L; Soto-Poveda, A; Luján-Marco, S; Loras-Monfort, A; Trassierra-Villa, M; Rogel-Bertó, R; Boronat-Tormo, F

To determine the risk of cancer-specific mortality (CSM) versus the competing risk of mortality by other causes (MOC) in patients with localised prostate cancer (LPC) treated with radical prostatectomy (RP). An observational cohort study of 982 patients with LPC treated with RP selected from our department's PC registry database. A competing risk analysis was performed, calculating the probability of CSM in the presence of the competing risk of MOC. Cumulative incidence curves were constructed, and point estimates were performed at 5, 10 and 15 years. The analysis was stratified by age (≤65 vs. >65 years) and risk group: low (Gleason score ≤6 and pT2abc); intermediate (Gleason score of 7 and pT2abc) and high (Gleason score of 8-10 or pT3ab). With a median follow-up of 60 months, the overall probability of dying from PC was 3.5%, and the probability of dying from other causes was 9%. A competing effect for MOC was observed. The risk of MOC was almost 3 times greater than that of CSM. This effect remained for all risk groups, although its magnitude decreased progressively according to the risk group level. At 10 years, CSM was only 0%, 1% and 2% for the low, intermediate and high-risk groups, respectively, while the likelihood of MOC was 4%, 4% and 10%, respectively. The mortality risk was shown after 10years of follow-up and was higher for other causes not attributable to PC and for patients older than 65years. The benefit of RP might be overestimated, given that the risk of MOC is greater than that of CSM, regardless of the age group and risk group, especially after 10years of follow-up. The only parameter that varied was the magnitude of the CSM/MOC ratio. This information could help in choosing the active treatment for patients with LPC and short life expectancies. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Implementation of High-Dose-Rate Brachytherapy and Androgen Deprivation in Patients With Prostate Cancer

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

Lilleby, Wolfgang, E-mail: wolfgang.lilleby@ous-hf.no; Tafjord, Gunnar; Raabe, Nils K.

2012-07-01

Purpose: To evaluate outcome (overall survival [OS], the actuarial 5-year cancer-specific survival [CSS], disease-free survival [DFS], biochemical failure-free survival [BFS]), complications and morbidity in patients treated with high-dose-rate brachytherapy (HDR-BT) boost and hormonal treatment with curative aims. Methods: Between 2004 and 2009, 275 prospectively followed pN0/N0M0 patients were included: 19 patients (7%) with T2, Gleason score 7 and prostate-specific antigen (PSA) <10 and 256 patients (93%) with T3 or Gleason score 8-10 or PSA >20 received multimodal treatment with conformal four-field radiotherapy (prostate/vesiculae 2 Gy Multiplication-Sign 25) combined with HDR-BT (iridium 192; prostate 10 Gy Multiplication-Sign 2) with long-term androgenmore » deprivation therapy (ADT). Results: After a median observation time of 44.2 months (range, 10.4-90.5 months) 12 patients had relapsed clinically and/or biochemically and 10 patients were dead, of which 2 patients died from prostate cancer. Five-year estimates of BFS, CSS, DFS, and OS rates were 98.5%, 99.3%, 95.6%, and 96.3%, respectively. None of the patients with either Gleason score <8 or with intermediate risk profile had relapsed. The number of HDR-BT treatments was not related to outcome. Despite of age (median, 65.7 years; range, 45.7-77 years) and considerable pretreatment comorbidity in 39 of 275 patients, Genitourinary treatment-related morbidity was moderate with long-lasting Radiation Therapy Oncology Group Grade 2 voiding problems in 26 patients (9.5%) and occasionally mucous discharge in 20 patients (7%), none with Grade >2 for gastrointestinal at follow-up. Complications during implantations were related to pubic arch interference (4 patients) and lithotomy time, causing 2 patients to develop compartment syndrome. Conclusion: Despite still preliminary observations, our 5-year outcome estimates favor the implementation of high-dose-rate brachytherapy in high-risk patients combined with conformal external radiotherapy and long-term ADT. High-quality implants can be achieved by a trained specialized team at a high-turnover center using transrectal ultrasound-based treatment plans with acceptable morbidity and complication rates.« less

Phase 3 study of adjuvant radiotherapy versus wait and see in pT3 prostate cancer: impact of pathology review on analysis.

PubMed

Bottke, Dirk; Golz, Reinhard; Störkel, Stephan; Hinke, Axel; Siegmann, Alessandra; Hertle, Lothar; Miller, Kurt; Hinkelbein, Wolfgang; Wiegel, Thomas

2013-08-01

In a randomised trial, radical prostatectomy (RP) followed by adjuvant radiotherapy (aRT) was compared with RP alone in patients with pT3 pN0 prostate cancer with or without positive margin at local pathology (German Cancer Society trial numbers ARO 96-02/AUO AP 09/95). A pathology review was performed on 85% of RP specimens of patients to investigate the influence of pathology review on the analysis. Patients post-RP (n=385) were randomised before achieving an undetectable prostate-specific antigen (PSA) level to either wait and see (n=192) or 60Gy aRT (n=193). Of 307 patients with undetectable PSA after RP, 262 had pathology review. These results were included prospectively into the analysis. Agreement between local and review pathology was measured by the total percentage of agreement and by simple kappa statistics. The prognostic reliability for the different parameters was analysed by Cox regression model. Event-free rates were determined by Kaplan-Meier analysis with a median follow-up of 40 mo for the wait-and-see arm and 38.5 mo for the aRT arm. There was fair concordance between pathology review and local pathologists for seminal vesicle invasion (pT3c: 91%; κ=0.76), surgical margin status (84%; κ=0.65), and for extraprostatic extension (pT3a/b: 75%; κ=0.74). Agreement was much less for Gleason score (47%; κ=0.42), whereby the review pathology resulted in a shift to Gleason score 7. In contrast to the analysis of progression-free survival with local pathology, the multivariate analysis including review pathology revealed PSMs and Gleason score >6 as significant prognostic factors. Phase 3 studies of postoperative treatment of prostate cancer should be accomplished in the future with a pathology review. In daily practice, a second opinion by a pathologist experienced in urogenital pathology would be desirable, in particular, for high-risk patients after RP. Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.

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.

[Propensity score comparison of the various radical surgical techniques for high-risk prostate cancer].

PubMed

Busch, J; Gonzalgo, M; Leva, N; Ferrari, M; Friedersdorff, F; Hinz, S; Kempkensteffen, C; Miller, K; Magheli, A

2015-01-01

The optimal surgical treatment of patients with a high risk prostate cancer (PCa) in terms of radical prostatectomy (RP) is still controversial: open retropubic RP (RRP), laparoscopic RP (LRP), or robot-assisted (RARP). We aimed to investigate the influence of the different surgical techniques on pathologic outcome and biochemical recurrence. A total of 805 patients with a high risk PCa (PSA >20 ng/mL, Gleason Score ≥8, or clinical stage ≥cT2c) were included. A comparison of 407 RRP patients with 398 minimally invasive cases (LRP+RARP) revealed significant confounders. Therefore all 110 RARP cases were propensity score (PS) matched 1:1 with LRP and RRP patients. PS included age, clinical stage, preoperative PSA, biopsy Gleason score, surgeon's experience and application of a nerve sparing technique. Comparison of overall survival (OS) and recurrence-free survival (RFS) was done with the log rank test. Predictors of RFS were analyzed by means of Cox regression models. Within the post-matching cohort of 330 patients a pathologic Gleason score < 7, = 7 and > 7 was found in 1.8, 55.5 and 42.7% for RARP, in 8.2, 36.4, 55.5% for LRP and in 0, 60.9 and 39.1% for RRP (p=0.004 for RARP vs. LRP and p=0.398 for RARP vs. RRP). Differences in histopathologic stages were not statistically significant. The overall positive surgical margin rate (PSM) as well as PSM for ≥ pT3 were not different. PSM among patients with pT2 was found in 15.7, 14.0 and 20.0% for RARP, LRP and RRP (statistically not significant). The respective mean 3-year RFS rates were 41.4, 77.9, 54.1% (p<0.0001 for RARP vs. LRP and p=0.686 for RARP vs. RRP). The mean 3-year OS was calculated as 95.4, 98.1 and 100% respectively (statistically not significant). RARP for patients with a high risk PCa reveals similar pathologic and oncologic outcomes compared with LRP and RRP. © Georg Thieme Verlag KG Stuttgart · New York.

Automatic registration of multi-modal microscopy images for integrative analysis of prostate tissue sections.

PubMed

Lippolis, Giuseppe; Edsjö, Anders; Helczynski, Leszek; Bjartell, Anders; Overgaard, Niels Chr

2013-09-05

Prostate cancer is one of the leading causes of cancer related deaths. For diagnosis, predicting the outcome of the disease, and for assessing potential new biomarkers, pathologists and researchers routinely analyze histological samples. Morphological and molecular information may be integrated by aligning microscopic histological images in a multiplex fashion. This process is usually time-consuming and results in intra- and inter-user variability. The aim of this study is to investigate the feasibility of using modern image analysis methods for automated alignment of microscopic images from differently stained adjacent paraffin sections from prostatic tissue specimens. Tissue samples, obtained from biopsy or radical prostatectomy, were sectioned and stained with either hematoxylin & eosin (H&E), immunohistochemistry for p63 and AMACR or Time Resolved Fluorescence (TRF) for androgen receptor (AR). Image pairs were aligned allowing for translation, rotation and scaling. The registration was performed automatically by first detecting landmarks in both images, using the scale invariant image transform (SIFT), followed by the well-known RANSAC protocol for finding point correspondences and finally aligned by Procrustes fit. The Registration results were evaluated using both visual and quantitative criteria as defined in the text. Three experiments were carried out. First, images of consecutive tissue sections stained with H&E and p63/AMACR were successfully aligned in 85 of 88 cases (96.6%). The failures occurred in 3 out of 13 cores with highly aggressive cancer (Gleason score ≥ 8). Second, TRF and H&E image pairs were aligned correctly in 103 out of 106 cases (97%).The third experiment considered the alignment of image pairs with the same staining (H&E) coming from a stack of 4 sections. The success rate for alignment dropped from 93.8% in adjacent sections to 22% for sections furthest away. The proposed method is both reliable and fast and therefore well suited for automatic segmentation and analysis of specific areas of interest, combining morphological information with protein expression data from three consecutive tissue sections. Finally, the performance of the algorithm seems to be largely unaffected by the Gleason grade of the prostate tissue samples examined, at least up to Gleason score 7.

Image Guided Focal Therapy for Magnetic Resonance Imaging Visible Prostate Cancer: Defining a 3-Dimensional Treatment Margin Based on Magnetic Resonance Imaging Histology Co-Registration Analysis.

PubMed

Le Nobin, Julien; Rosenkrantz, Andrew B; Villers, Arnauld; Orczyk, Clément; Deng, Fang-Ming; Melamed, Jonathan; Mikheev, Artem; Rusinek, Henry; Taneja, Samir S

2015-08-01

We compared prostate tumor boundaries on magnetic resonance imaging and radical prostatectomy histological assessment using detailed software assisted co-registration to define an optimal treatment margin for achieving complete tumor destruction during image guided focal ablation. Included in study were 33 patients who underwent 3 Tesla magnetic resonance imaging before radical prostatectomy. A radiologist traced lesion borders on magnetic resonance imaging and assigned a suspicion score of 2 to 5. Three-dimensional reconstructions were created from high resolution digitalized slides of radical prostatectomy specimens and co-registered to imaging using advanced software. Tumors were compared between histology and imaging by the Hausdorff distance and stratified by the magnetic resonance imaging suspicion score, Gleason score and lesion diameter. Cylindrical volume estimates of treatment effects were used to define the optimal treatment margin. Three-dimensional software based registration with magnetic resonance imaging was done in 46 histologically confirmed cancers. Imaging underestimated tumor size with a maximal discrepancy between imaging and histological boundaries for a given tumor of an average ± SD of 1.99 ± 3.1 mm, representing 18.5% of the diameter on imaging. Boundary underestimation was larger for lesions with an imaging suspicion score 4 or greater (mean 3.49 ± 2.1 mm, p <0.001) and a Gleason score of 7 or greater (mean 2.48 ± 2.8 mm, p = 0.035). A simulated cylindrical treatment volume based on the imaging boundary missed an average 14.8% of tumor volume compared to that based on the histological boundary. A simulated treatment volume based on a 9 mm treatment margin achieved complete histological tumor destruction in 100% of patients. Magnetic resonance imaging underestimates histologically determined tumor boundaries, especially for lesions with a high imaging suspicion score and a high Gleason score. A 9 mm treatment margin around a lesion visible on magnetic resonance imaging would consistently ensure treatment of the entire histological tumor volume during focal ablative therapy. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Magnetic Resonance Imaging Targeted Biopsy Improves Selection of Patients Considered for Active Surveillance for Clinically Low Risk Prostate Cancer Based on Systematic Biopsies.

PubMed

Ouzzane, Adil; Renard-Penna, Raphaele; Marliere, François; Mozer, Pierre; Olivier, Jonathan; Barkatz, Johann; Puech, Philippe; Villers, Arnauld

2015-08-01

Current selection criteria for active surveillance based on systematic biopsy underestimate prostate cancer volume and grade. We investigated the role of additional magnetic resonance imaging targeted biopsy in reclassifying patients eligible for active surveillance based on systematic biopsy. We performed a study at 2 institutions in a total of 281 men with increased prostate specific antigen. All men met certain criteria, including 1) prebiopsy magnetic resonance imaging, 12-core transrectal systematic biopsy and 2 additional magnetic resonance imaging targeted biopsies of lesions suspicious for cancer during the same sequence as systematic biopsy, and 2) eligibility for active surveillance based on systematic biopsy results. Criteria for active surveillance were prostate specific antigen less than 10 ng/ml, no Gleason grade 4/5, 5 mm or less involvement of any biopsy core and 2 or fewer positive systematic biopsy cores. Patient characteristics were compared between reclassified and nonreclassified groups based on magnetic resonance imaging targeted biopsy results. On magnetic resonance imaging 58% of the 281 patients had suspicious lesions. Magnetic resonance imaging targeted biopsy was positive for cancer in 81 of 163 patients (50%). Of 281 patients 28 (10%) were reclassified by magnetic resonance imaging targeted biopsy as ineligible for active surveillance based on Gleason score in 8, cancer length in 20 and Gleason score plus cancer length in 9. Suspicious areas on magnetic resonance imaging were in the anterior part of the prostate in 15 of the 28 men (54%). Reclassified patients had a smaller prostate volume (37 vs 52 cc) and were older (66.5 vs 63 years) than those who were not reclassified (p < 0.05). Magnetic resonance imaging targeted biopsy reclassified 10% of patients who were eligible for active surveillance based on systematic biopsy. Its incorporation into the active surveillance eligibility criteria may decrease the risk of reclassification to higher stages during followup. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

[Salvage cryotherapy of prostate cancer after failed external radiotherapy and brachytherapy: Morbidity and mid-term oncological results].

PubMed

Gevorgyan, A; Hétet, J-F; Robert, M; Duchattelle-Dussaule, V; Corno, L; Boulay, I; Baumert, H

2018-04-01

To study the oncologic and functional results of salvage cryotherapy after failure of external radiotherapy and brachytherapy. Patients treated by total salvage cryotherapy (3rd generation) in 2 centers (Groupe Hospitalier Saint-Joseph in Paris and Clinique Jule-Verne Nantes) in between January 2008 and April 2016 were included. The biochemical recurrence-free survival (BRFS) was calculated using the Phoenix criteria (PSA>nadir+2ng/mL). The functional results were assessed clinically. Ninety-seven patients with an average follow up of 39.4months were evaluated retrospectively. The 5-year biochemical recurrence-free survival (5y-BRFS) among all patients was 58.1% (IC à 95% [45.9-68.5]). Low and intermediate risk patients (d'Amico classification) were less prone to biochemical recurrence than high risk (81.05% (IC à 95% [64.1-90.5]) 5y-BRFS as opposed to 35.09% (IC à 95% [20.1-50.4]) respectively) (P<0.0001). As were patients with a Gleason score≤7 75.35% (IC à 95% [59.7-85.6]) compared to 32.31% (IC à 95% [16.5-49.2]) for higher Gleason (>7 scores [P=0.0002]). A Gleason score>7 (OR=6.9; P=0.002), PSA nadir>1ng/mL (OR=25.8; P=0.0026) and peri-urethral invasion (OR=35.8; P<0.001) were major risk factors for local recurrence in univariate analysis. In multivariate analysis, only PSA nadir>1ng/mL (OR=12.9; P=0.042) and peri-urethral invasion (OR=21.6; P=0.0003) remain major risk factors for recurrence. About 13 (16.46%) patients were incontinent of which 3 (3.79%) required placement of an artificial urinary sphincter. Erectile dysfunction was present in 66 (83.5%) patients. Recto-urethral fistula was uncommon in 1 patient (1.27%). Salvage cryotherapy after failure of external radiotherapy and brachytherapy is a reliable and reproducible technique with promising oncological and functional results. Study of prognostic factors will help better select eligible patients in the future. 4. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Development and External Validation of the Korean Prostate Cancer Risk Calculator for High-Grade Prostate Cancer: Comparison with Two Western Risk Calculators in an Asian Cohort

PubMed Central

Yoon, Sungroh; Park, Man Sik; Choi, Hoon; Bae, Jae Hyun; Moon, Du Geon; Hong, Sung Kyu; Lee, Sang Eun; Park, Chanwang

2017-01-01

Purpose We developed the Korean Prostate Cancer Risk Calculator for High-Grade Prostate Cancer (KPCRC-HG) that predicts the probability of prostate cancer (PC) of Gleason score 7 or higher at the initial prostate biopsy in a Korean cohort (http://acl.snu.ac.kr/PCRC/RISC/). In addition, KPCRC-HG was validated and compared with internet-based Western risk calculators in a validation cohort. Materials and Methods Using a logistic regression model, KPCRC-HG was developed based on the data from 602 previously unscreened Korean men who underwent initial prostate biopsies. Using 2,313 cases in a validation cohort, KPCRC-HG was compared with the European Randomized Study of Screening for PC Risk Calculator for high-grade cancer (ERSPCRC-HG) and the Prostate Cancer Prevention Trial Risk Calculator 2.0 for high-grade cancer (PCPTRC-HG). The predictive accuracy was assessed using the area under the receiver operating characteristic curve (AUC) and calibration plots. Results PC was detected in 172 (28.6%) men, 120 (19.9%) of whom had PC of Gleason score 7 or higher. Independent predictors included prostate-specific antigen levels, digital rectal examination findings, transrectal ultrasound findings, and prostate volume. The AUC of the KPCRC-HG (0.84) was higher than that of the PCPTRC-HG (0.79, p<0.001) but not different from that of the ERSPCRC-HG (0.83) on external validation. Calibration plots also revealed better performance of KPCRC-HG and ERSPCRC-HG than that of PCPTRC-HG on external validation. At a cut-off of 5% for KPCRC-HG, 253 of the 2,313 men (11%) would not have been biopsied, and 14 of the 614 PC cases with Gleason score 7 or higher (2%) would not have been diagnosed. Conclusions KPCRC-HG is the first web-based high-grade prostate cancer prediction model in Korea. It had higher predictive accuracy than PCPTRC-HG in a Korean population and showed similar performance with ERSPCRC-HG in a Korean population. This prediction model could help avoid unnecessary biopsy and reduce overdiagnosis and overtreatment in clinical settings. PMID:28046017

Development and External Validation of the Korean Prostate Cancer Risk Calculator for High-Grade Prostate Cancer: Comparison with Two Western Risk Calculators in an Asian Cohort.

PubMed

Park, Jae Young; Yoon, Sungroh; Park, Man Sik; Choi, Hoon; Bae, Jae Hyun; Moon, Du Geon; Hong, Sung Kyu; Lee, Sang Eun; Park, Chanwang; Byun, Seok-Soo

2017-01-01

We developed the Korean Prostate Cancer Risk Calculator for High-Grade Prostate Cancer (KPCRC-HG) that predicts the probability of prostate cancer (PC) of Gleason score 7 or higher at the initial prostate biopsy in a Korean cohort (http://acl.snu.ac.kr/PCRC/RISC/). In addition, KPCRC-HG was validated and compared with internet-based Western risk calculators in a validation cohort. Using a logistic regression model, KPCRC-HG was developed based on the data from 602 previously unscreened Korean men who underwent initial prostate biopsies. Using 2,313 cases in a validation cohort, KPCRC-HG was compared with the European Randomized Study of Screening for PC Risk Calculator for high-grade cancer (ERSPCRC-HG) and the Prostate Cancer Prevention Trial Risk Calculator 2.0 for high-grade cancer (PCPTRC-HG). The predictive accuracy was assessed using the area under the receiver operating characteristic curve (AUC) and calibration plots. PC was detected in 172 (28.6%) men, 120 (19.9%) of whom had PC of Gleason score 7 or higher. Independent predictors included prostate-specific antigen levels, digital rectal examination findings, transrectal ultrasound findings, and prostate volume. The AUC of the KPCRC-HG (0.84) was higher than that of the PCPTRC-HG (0.79, p<0.001) but not different from that of the ERSPCRC-HG (0.83) on external validation. Calibration plots also revealed better performance of KPCRC-HG and ERSPCRC-HG than that of PCPTRC-HG on external validation. At a cut-off of 5% for KPCRC-HG, 253 of the 2,313 men (11%) would not have been biopsied, and 14 of the 614 PC cases with Gleason score 7 or higher (2%) would not have been diagnosed. KPCRC-HG is the first web-based high-grade prostate cancer prediction model in Korea. It had higher predictive accuracy than PCPTRC-HG in a Korean population and showed similar performance with ERSPCRC-HG in a Korean population. This prediction model could help avoid unnecessary biopsy and reduce overdiagnosis and overtreatment in clinical settings.

Time to PSA rise differentiates the PSA bounce after HDR and LDR brachytherapy of prostate cancer

PubMed Central

Skowronek, Janusz

2018-01-01

Purpose To investigate the differences in prostate-specific antigen (PSA) bounce (PB) after high-dose-rate (HDR-BT) or low-dose-rate (LDR-BT) brachytherapy alone in prostate cancer patients. Materials and methods Ninety-four patients with localized prostate cancer (T1-T2cN0), age ranged 50-81 years, were treated with brachytherapy alone between 2008 and 2010. Patients were diagnosed with adenocarcinoma, Gleason score ≤ 7. The LDR-BT total dose was 144-145 Gy, in HDR-BT – 3 fractions of 10.5 or 15 Gy. The initial PSA level (iPSA) was assessed before treatment, then PSA was rated every 3 months over the first 2 years, and every 6 months during the next 3 years. Median follow-up was 3.0 years. Results Mean iPSA was 7.8 ng/ml. In 58 cases, PSA decreased gradually without PB or biochemical failure (BF). In 24% of patients, PB was observed. In 23 cases (24%), PB was observed using 0.2 ng/ml definition; in 10 cases (11%), BF was diagnosed using nadir + 2 ng/ml definition. The HDR-BT and LDR-BT techniques were not associated with higher level of PB (26 vs. 22%, p = 0.497). Time to the first PSA rise finished with PB was significantly shorter after HDR-BT then after LDR-BT (median, 10.5 vs. 18.0 months) during follow-up. Predictors for PB were observed only after HDR-BT. Androgen deprivation therapy (ADT) and higher Gleason score decreased the risk of PB (HR = 0.11, p = 0.03; HR = 0.51, p = 0.01). The higher PSA nadir and longer time to PSA nadir increased the risk of PB (HR 3.46, p = 0.02; HR 1.04, p = 0.04). There was no predictors for PB after LDR-BT. Conclusions HDR-BT and LDR-BT for low and intermediate risk prostate cancer had similar PB rate. The PB occurred earlier after HDR-BT than after LDR-BT. ADT and higher Gleason score decreased, and higher PSA nadir and longer time to PSA nadir increased the risk of PB after HDR-BT. PMID:29619050

Time to PSA rise differentiates the PSA bounce after HDR and LDR brachytherapy of prostate cancer.

PubMed

Burchardt, Wojciech; Skowronek, Janusz

2018-02-01

To investigate the differences in prostate-specific antigen (PSA) bounce (PB) after high-dose-rate (HDR-BT) or low-dose-rate (LDR-BT) brachytherapy alone in prostate cancer patients. Ninety-four patients with localized prostate cancer (T1-T2cN0), age ranged 50-81 years, were treated with brachytherapy alone between 2008 and 2010. Patients were diagnosed with adenocarcinoma, Gleason score ≤ 7. The LDR-BT total dose was 144-145 Gy, in HDR-BT - 3 fractions of 10.5 or 15 Gy. The initial PSA level (iPSA) was assessed before treatment, then PSA was rated every 3 months over the first 2 years, and every 6 months during the next 3 years. Median follow-up was 3.0 years. Mean iPSA was 7.8 ng/ml. In 58 cases, PSA decreased gradually without PB or biochemical failure (BF). In 24% of patients, PB was observed. In 23 cases (24%), PB was observed using 0.2 ng/ml definition; in 10 cases (11%), BF was diagnosed using nadir + 2 ng/ml definition. The HDR-BT and LDR-BT techniques were not associated with higher level of PB (26 vs. 22%, p = 0.497). Time to the first PSA rise finished with PB was significantly shorter after HDR-BT then after LDR-BT (median, 10.5 vs. 18.0 months) during follow-up. Predictors for PB were observed only after HDR-BT. Androgen deprivation therapy (ADT) and higher Gleason score decreased the risk of PB (HR = 0.11, p = 0.03; HR = 0.51, p = 0.01). The higher PSA nadir and longer time to PSA nadir increased the risk of PB (HR 3.46, p = 0.02; HR 1.04, p = 0.04). There was no predictors for PB after LDR-BT. HDR-BT and LDR-BT for low and intermediate risk prostate cancer had similar PB rate. The PB occurred earlier after HDR-BT than after LDR-BT. ADT and higher Gleason score decreased, and higher PSA nadir and longer time to PSA nadir increased the risk of PB after HDR-BT.

Associations between circulating carotenoids, genomic instability and the risk of high-grade prostate cancer.

PubMed

Nordström, Tobias; Van Blarigan, Erin L; Ngo, Vy; Roy, Ritu; Weinberg, Vivian; Song, Xiaoling; Simko, Jeffry; Carroll, Peter R; Chan, June M; Paris, Pamela L

2016-03-01

Carotenoids are a class of nutrients with antioxidant properties that have been purported to protect against cancer. However, the reported associations between carotenoids and prostate cancer have been heterogeneous and lacking data on interactions with nucleotide sequence variations and genomic biomarkers. To examine the associations between carotenoid levels and the risk of high-grade prostate cancer, also considering antioxidant-related genes and tumor instability. We measured plasma levels of carotenoids and genotyped 20 single nucleotide polymorphisms (SNP) in SOD1, SOD2, SOD3, XRCC1, and OGG1 among 559 men with non-metastatic prostate cancer undergoing radical prostatectomy. We performed copy number analysis in a subset of these men (n = 67) to study tumor instability assessed as Fraction of the Genome Altered (FGA). We examined associations between carotenoids, genotypes, tumor instability and risk of high-grade prostate cancer (Gleason grade ≥ 4 + 3) using logistic and linear regression. Circulating carotenoid levels were inversely associated with the risk of high-grade prostate cancer; odds ratios (OR) and 95% confidence intervals (CI) comparing highest versus lowest quartiles were: 0.34 (95% CI: 0.18-0.66) for α-carotene, 0.31 (95% CI: 0.15-0.63) for β-carotene, 0.55 (0.28-1.08) for lycopene and 0.37 (0.18-0.75) for total carotenoids. SNPs rs25489 in XRCC1, rs699473 in SOD3 and rs1052133 in OGG1 modified these associations for α-carotene, β-carotene and lycopene, respectively (P ≤ 0.05). The proportion of men with a high degree of FGA increased with Gleason Score (P < 0.001). Among men with Gleason score ≤ 3 + 4, higher lycopene levels were associated with lower FGA (P = 0.04). Circulating carotenoids at diagnosis, particularly among men carrying specific somatic variations, were inversely associated with risk of high-grade prostate cancer. In exploratory analyses, higher lycopene level was associated with less genomic instability among men with low-grade disease which is novel and supports the hypothesis that lycopene may inhibit progression of prostate cancer early in its natural history. © 2015 Wiley Periodicals, Inc.

Cathepsin B expression in prostate cancer of native Japanese and Japanese-American patients: an immunohistochemical study.

PubMed

Sinha, Akhouri A; Morgan, Jenifer L; Betre, Konjit; Wilson, Michael J; Le, Chap; Marks, Leonard S

2008-01-01

Japanese-American (J-A) men who have immigrated to the U.S.A. and acquired the Western lifestyle usually have more invasive prostate cancer (PCa) than native Japanese (NJ) living in Japan. The specific reasons for these differences remain unknown. The objective of this study was to examine immunostainings of cathepsin B (CB) and its endogenous inhibitor stefin A (SA) in tissue microarray (TMA) and radical prostatectomy (RP) tissue sections in the hope of obtaining insights into the invasiveness of PCa in Japanese patients. TMA and RP sections were evaluated in 50 men (25 NJ and 25 J-A) for CB and SA reaction products. The CB and SA immunostainings were imaged directly from microscope slides to a computer using a high performance charge coupled device (CCD) digital camera, quantified using Metamorph software, analyzed using the two-sample t-test, and confirmed by multiple regression analysis. The CB and SA proteins were localized in the carcinomatous glands and isolated cancer cells in the TMA and RP sections. The Gleason scores and pre-surgery serum total prostate-specific antigen (PSA) levels did not differ significantly in the NJ and J-A patients (p = 0.14, p = 0.16, respectively). The Chi-square analysis of clinical stage versus place of birth showed that the NJ patients had significantly more T2a and T2b clinical stages than the J-A patients who had more advanced T2c and T3a stages (p = 0.003). The CB and SA immunostainings and their ratios in Gleason score 6 tumors did not show any difference, but the CB:SA ratios in score > or = 7 tumors approached significance levels. The overall matching of specimens according to the Gleason grade/score, pre-RP serum total PSA levels, clinical stage and age prior to evaluation of immunostainings greatly minimizes subjectivity associated with the evaluation of markers in this ethnic sub-population of PCa patients. CB and SA immunostaining is similar in Japanese patients who have organ-confined and moderately-differentiated PCa. Analysis of the reaction product data provides indirect evidence that invasiveness of PCa is similar in the two Japanese patient populations.

Active monitoring, radical prostatectomy, or radiotherapy for localised prostate cancer: study design and diagnostic and baseline results of the ProtecT randomised phase 3 trial.

PubMed

Lane, J Athene; Donovan, Jenny L; Davis, Michael; Walsh, Eleanor; Dedman, Daniel; Down, Liz; Turner, Emma L; Mason, Malcolm D; Metcalfe, Chris; Peters, Tim J; Martin, Richard M; Neal, David E; Hamdy, Freddie C

2014-09-01

Prostate cancer is a major public health problem with considerable uncertainties about the effectiveness of population screening and treatment options. We report the study design, participant sociodemographic and clinical characteristics, and the initial results of the testing and diagnostic phase of the Prostate testing for cancer and Treatment (ProtecT) trial, which aims to investigate the effectiveness of treatments for localised prostate cancer. In this randomised phase 3 trial, men aged 50-69 years registered at 337 primary care centres in nine UK cities were invited to attend a specialist nurse appointment for a serum prostate-specific antigen (PSA) test. Prostate biopsies were offered to men with a PSA concentration of 3·0 μg/L or higher. Consenting participants with clinically localised prostate cancer were randomly assigned to active monitoring (surveillance strategy), radical prostatectomy, or three-dimensional conformal external-beam radiotherapy by a computer-generated allocation system. Randomisation was stratified by site (minimised for differences in participant age, PSA results, and Gleason score). The primary endpoint is prostate cancer mortality at a median 10-year follow-up, ascertained by an independent committee, which will be analysed by intention to treat in 2016. This trial is registered with ClinicalTrials.gov, number NCT02044172, and as an International Standard Randomised Controlled Trial, number ISRCTN20141297. Between Oct 1, 2001, and Jan 20, 2009, 228,966 men were invited to attend an appointment with a specialist nurse. Of the invited men, 100,444 (44%) attended their initial appointment and 82,429 (82%) of attenders had a PSA test. PSA concentration was below the biopsy threshold in 73,538 (89%) men. Of the 8566 men with a PSA concentration of 3·0-19·9 μg/L, 7414 (87%) underwent biopsies. 2896 men were diagnosed with prostate cancer (4% of tested men and 39% of those who had a biopsy), of whom 2417 (83%) had clinically localised disease (mostly T1c, Gleason score 6). With the addition of 247 pilot study participants recruited between 1999 and 2001, 2664 men were eligible for the treatment trial and 1643 (62%) agreed to be randomly assigned (545 to active monitoring, 545 to radiotherapy, and 553 to radical prostatectomy). Clinical and sociodemographic characteristics of randomly assigned participants were balanced across treatment groups. The ProtecT trial randomly assigned 1643 men with localised prostate cancer to active monitoring, radiotherapy, or surgery. Participant clinicopathological features are more consistent with contemporary patient characteristics than in previous prostate cancer treatment trials. UK National Institute for Health Research Health Technology Assessment Programme. Copyright © 2014 Lane et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd. All rights reserved.

Dietary patterns and the risk of rhinitis in primary school children: a prospective cohort study

PubMed Central

Liu, Xudong; Wong, Claudie Chiu-Yi; Yu, Ignatius T. S.; Zhang, Zilong; Tan, Lixing; Lau, Arthur P. S.; Lee, Albert; Yeoh, Eng Kiong; Lao, Xiang Qian

2017-01-01

This study was to investigate the association between dietary patterns and rhinitis in primary school children. 1,599 students without rhinitis at baseline survey were selected from a primary school children cohort. Information on food consumption, respiratory symptoms, and confounders was collected using questionnaires. Dietary patterns were defined using principal component analysis. Logistic regression was performed to calculate odds ratio (OR) with 95% confidence intervals (95% CI). The incidence of rhinitis during 12 months follow-up was 21.2%. Three patterns were extracted and labeled as pattern I, II and III. Dietary pattern II which had higher factor loadings of legumes, butter, nuts and potatoes was associated with an increased risk of rhinitis (OR: 1.34, 95% CI: 1.01–1.87) when the highest tertile of pattern score was compared to the lowest tertile, after adjusted for confounders. Besides, every 1-unit increase of score of pattern II was also associated with an increased risk of rhinitis (OR: 1.19, 95% CI: 1.05–1.35). Neither pattern I nor Pattern III was observed to be associated with risk of rhinitis. A diet with higher levels of consumption of legumes, butter, nuts and potatoes may increase the risk of allergic rhinitis in primary school children. PMID:28294150

Microlocalization and Quantitation of Risk Associated Elements in Gleason Graded Prostate Tissue

DTIC Science & Technology

2007-03-01

ORGANIZATION: Regents of the University of California Maya Conn Los Angeles CA 90024 REPORT DATE: March 2007 TYPE OF REPORT...California Maya Conn Los Angeles CA 90024 9. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR’S ACRONYM(S...carcinoma of different histological grading in comparison to normal prostate tissue and adenofibromyomatosis (BPH) Uro Res 10:301-303. 5. Feustel A

Elevated Prostate Health Index (phi) and Biopsy Reclassification During Active Surveillance of Prostate Cancer.

PubMed

Andreas, Darian; Tosoian, Jeffrey J; Landis, Patricia; Wolf, Sacha; Glavaris, Stephanie; Lotan, Tamara L; Schaeffer, Edward M; Sokoll, Lori J; Ross, Ashley E

2016-07-01

The Prostate Health Index (phi) has been FDA approved for decision-making regarding prostate biopsy. Phi has additionally been shown to positively correlate with tumor volume, extraprostatic disease and higher Gleason grade tumors. Here we describe a case in which an elevated phi encouraged biopsy of a gentleman undergoing active surveillance leading to reclassification of his disease as high risk prostate cancer.

Transforming Research and Clinical Knowledge in Traumatic Brain Injury

DTIC Science & Technology

2016-12-01

Szuflita, N., Orman, J., and Schwab, K. (2010). Advancing integrated research in psychological health and traumatic brain injury: common data ele- ments...Szuflita N, Orman J, et al. Advancing Integrated Research in Psychological Health and Traumatic Brain Injury: Common Data Elements. Arch Phys Med Rehabil...R, Gleason T, et al. Advancing integrated research in psychological health and traumatic brain injury: common data elements. Arch Phys Med Rehabil

Validation of Quantitative Multimodality Analysis of Telomerase Activity in Urine Cells as a Noninvasive Diagnostic and Prognostic Tool for Prostate Cancer

DTIC Science & Technology

2005-08-01

present study, who was previously misdiagnosed with BPH and inflammation, eventually has revealed the prostate cancer with the Gleason score 7. Therefore...Noninvasive Diagnostic and Prognostic Tool for Prostate Cancer ...5a. CONTRACT NUMBER Urine Cells as a Noninvasive Diagnostic and Prognostic Tool for Prostate Cancer 5b. GRANT NUMBER W81XWH-04-1-0774 5c

Genetic and Epigenetic Biomarkers for Recurrent Prostate Cancer After Radiotherapy

DTIC Science & Technology

2013-05-01

prostatectomy are urinary incontinence , erectile dysfunction, and typical post-operative complications. Radiation therapy (RT) shows several distinct...includes a low risk of urinary incontinence . Major disadvantage of external beam RT include a treatment course of 8-9 weeks. -50% of patients have some...this treatment include the risk of acute urinary retention. Currently, the level of PSA, clinical stage and the Gleason score are used to

Disease-specific survival following the brachytherapy management of prostate cancer.

PubMed

Stock, Richard G; Cesaretti, Jamie A; Stone, Nelson N

2006-03-01

To determine disease-specific survival (DSS) and associated predictive factors after prostate brachytherapy. A total of 1561 patients underwent brachytherapy for prostate cancer from 1990 to 2004 (median follow-up, 3.8 years). Treatment included brachytherapy alone (n = 634), brachytherapy and hormonal therapy (n = 420), and implant and external beam therapy (n = 507). The DSS and overall survival rates at 10 years were 96% and 74%, respectively. Gleason score significantly impacted DSS, with 10-year rates of 98%, 91%, and 92% for scores of < or = 6, 7, and > or = 8, respectively (p < 0.0001). Multivariate analysis revealed that PSA status after treatment had the most significant effect on DSS. Ten-year DSS rates were 100%, 52%, and 98%, respectively for patients without PSA failure (n = 1430), failure with a doubling time (DT) < or = 10 months (n = 64), and failure with a DT > 10 months (n = 67), respectively (p < 0.0001). In patients with PSA failure, DSS rates were 30%, 67%, and 98%, for those with DT < or = 6 months, > 6-10 months, and > 10 months, respectively (p < 0.0001). The 10-year DSS rate supports the efficacy of brachytherapy. Patients dying with disease within 10 years after treatment harbor inherently aggressive cancer with high Gleason scores and short DT.

HIFU therapy for patients with high risk prostate cancer

NASA Astrophysics Data System (ADS)

Solovov, V. A.; Vozdvizhenskiy, M. O.; Matysh, Y. S.

2017-03-01

Objectives. Patients with high-risk prostate cancer undergoing radical prostatectomy, external beam radiation therapy (EBRT) combined with androgen deprivation therapy (ADT) or ADT alone. The widely accepted definition of high-risk prostate was first proposed by D'Amico based on a pretreatment Gleason score of ≥8, clinical stage T3, PSA level ≥20 ng/mL. There is no trial that compares traditional methods of treatment of such patients with HIFU therapy. Here we explored the effectiveness of the HIFU in multimodal treatment for patients with high risk prostate cancer. Materials & Methods. 701 patients with high risk prostate cancer were treated in our center between September 2007 and December 2013. Gleason score were 8-10, stage T3N0M0, age 69 (58-86) years, mean PSA before treatment 43.3 (22.1-92.9) ng/ml, mean prostate volume - 59.3 (38-123) cc. 248 patients were treated by HIFU. We compare this group of patients with patients who undertook EBRT: number 196, and ADT: number 257. Mean follow-up time 58 months (6-72). Results. The 5-year overall survival rates in patients after HIFU were 73.8 %, after EBRT - 63.0 % and after ADT - 18.1%. Conclusions. Our experience showed that HIFU therapy in combined treatment were successful for high risk prostate cancer.

Validation of International Society of Urological Pathology (ISUP) grading for prostatic adenocarcinoma in thin core biopsies using TROG 03.04 'RADAR' trial clinical data.

PubMed

Delahunt, B; Egevad, L; Srigley, J R; Steigler, A; Murray, J D; Atkinson, C; Matthews, J; Duchesne, G; Spry, N A; Christie, D; Joseph, D; Attia, J; Denham, J W

2015-10-01

In 2014 a consensus conference convened by the International Society of Urological Pathology (ISUP) adopted amendments to the criteria for Gleason grading and scoring (GS) for prostatic adenocarcinoma. The meeting defined a modified grading system based on 5 grading categories (grade 1, GS 3+3; grade 2, GS 3+4; grade 3, GS 4+3; grade 4, GS 8; grade 5, GS 9-10). In this study we have evaluated the prognostic significance of ISUP grading in 496 patients enrolled in the TROG 03.04 RADAR Trial. There were 19 grade 1, 118 grade 2, 193 grade 3, 88 grade 4 and 79 grade 5 tumours in the series, with follow-up for a minimum of 6.5 years. On follow-up 76 patients experienced distant progression of disease, 171 prostate specific antigen (PSA) progression and 39 prostate cancer deaths. In contrast to the 2005 modified Gleason system (MGS), the hazards of the distant and PSA progression endpoints, relative to grade 2, were significantly greater for grades 3, 4 and 5 of the 2014 ISUP grading scheme. Comparison of predictive ability utilising Harrell's concordance index, showed 2014 ISUP grading to significantly out-perform 2005 MGS grading for each of the three clinical endpoints.

The HDL receptor SR-BI is associated with human prostate cancer progression and plays a possible role in establishing androgen independence.

PubMed

Schörghofer, David; Kinslechner, Katharina; Preitschopf, Andrea; Schütz, Birgit; Röhrl, Clemens; Hengstschläger, Markus; Stangl, Herbert; Mikula, Mario

2015-08-07

Human prostate cancer represents one of the most frequently diagnosed cancers in men worldwide. Currently, diagnostic methods are insufficient to identify patients at risk for aggressive prostate cancer, which is essential for early treatment. Recent data indicate that elevated cholesterol levels in the plasma are a prerequisite for the progression of prostate cancer. Here, we analyzed clinical prostate cancer samples for the expression of receptors involved in cellular cholesterol uptake. We screened mRNA microarray files of prostate cancer samples for alterations in the expression levels of cholesterol transporters. Furthermore, we performed immunohistochemistry analysis on human primary prostate cancer tissue sections derived from patients to investigate the correlation of SR-BI with clinicopathological parameters and the mTOR target pS6. In contrast to LDLR, we identified SR-BI mRNA and protein expression to be induced in high Gleason grade primary prostate cancers. Histologic analysis of prostate biopsies revealed that 53.6 % of all cancer samples and none of the non-cancer samples showed high SR-BI staining intensity. The disease-free survival time was reduced (P = 0.02) in patients expressing high intra-tumor levels of SR-BI. SR-BI mRNA correlated with HSD17B1 and HSD3B1 and SR-BI protein staining showed correlation with active ribosomal protein S6 (RS = 0.828, P < 0.00001). We identified SR-BI to indicate human prostate cancer formation, suggesting that increased levels of SR-BI may be involved in the generation of a castration-resistant phenotype.

A Comparative Evaluation between Cheiloscopic Patterns and Terminal Planes in Primary Dentition.

PubMed

Vignesh, R; Rekha, C Vishnu; Annamalai, Sankar; Norouzi, Parisa; Sharmin, Ditto

2017-01-01

To assess the correlation between different cheiloscopic patterns with the terminal planes in deciduous dentition. Three hundred children who are 3-6 years old with complete primary dentition were recruited, and the pattern of molar terminal plane was recorded in the pro forma. Lip prints of these children were recorded with lipstick-cellophane method, and the middle 10 mm of lower lip was analyzed for the lip print pattern as suggested by Sivapathasundharam et al . The pattern was classified based on Tsuchihashi and Suzuki classification. Type II (branched) pattern was the most predominant cheiloscopic pattern. The predominant patterns which related to the terminal planes were as follows: Type IV (reticular) and Type V (irregular) pattern for mesial step, Type IV (reticular) pattern for distal step, and Type I (complete vertical) pattern for flush terminal plane. No significant relationship was obtained on gender comparison. Lip prints can provide an alternative to dermatoglyphics to predict the terminal plane in primary dentition. Further studies with larger sample size are required to provide an insight into its significant correlations.

A Comparative Evaluation between Cheiloscopic Patterns and Terminal Planes in Primary Dentition

PubMed Central

Vignesh, R; Rekha, C Vishnu; Annamalai, Sankar; Norouzi, Parisa; Sharmin, Ditto

2017-01-01

Objective: To assess the correlation between different cheiloscopic patterns with the terminal planes in deciduous dentition. Materials and Methods: Three hundred children who are 3–6 years old with complete primary dentition were recruited, and the pattern of molar terminal plane was recorded in the pro forma. Lip prints of these children were recorded with lipstick-cellophane method, and the middle 10 mm of lower lip was analyzed for the lip print pattern as suggested by Sivapathasundharam et al. The pattern was classified based on Tsuchihashi and Suzuki classification. Results: Type II (branched) pattern was the most predominant cheiloscopic pattern. The predominant patterns which related to the terminal planes were as follows: Type IV (reticular) and Type V (irregular) pattern for mesial step, Type IV (reticular) pattern for distal step, and Type I (complete vertical) pattern for flush terminal plane. No significant relationship was obtained on gender comparison. Conclusion: Lip prints can provide an alternative to dermatoglyphics to predict the terminal plane in primary dentition. Further studies with larger sample size are required to provide an insight into its significant correlations. PMID:29326500

The Role of the Native Language in the Use of the English Nongeneric Definite Article by L2 Learners: A Cross-Linguistic Comparison

ERIC Educational Resources Information Center

Chrabaszcz, Anna; Jiang, Nan

2014-01-01

The study uses an elicited imitation (EI) task to examine the effect of the native language on the use of the English nongeneric definite article by highly proficient first-language (L1) Spanish and Russian speakers and to test the hierarchy of article difficulty first proposed by Liu and Gleason (2002). Our findings suggest that there is a clear…

Genetic Variations in SLCO Transporter Genes Contributing to Racial Disparity in Aggressiveness of Prostate Cancer

DTIC Science & Technology

2017-10-01

should not be construed as an official Department of the Army position, policy or decision unless so designated by other documentation. REPORT... control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE October 2017 2. REPORT TYPE Annual 3. DATES COVERED 15 Sep 2016...statistically significant difference among these three groups in either tumor characteristics including Gleason score, stage and aggressiveness, or

MRI-Derived Cellularity Index as a Potential Noninvasive Imaging Biomarker of Prostate Cancer

DTIC Science & Technology

2016-12-01

whole mount pathology sections. Analysis of these UCLA data resulted in four published manuscripts (White et al, Cancer Research 2014; Rakow-Penner...Yamin et al., Clinical Cancer Research , 2016) RSI-MRI mean z-score grouped by pathologic Gleason grade. Mean RSI-MRI cellularity index represented as...Figure 2). A quantitative validation of this approach is now provided in this study. Specifically, in a group of patients with known PCa, ROC

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

Decoding brain responses to pixelized images in the primary visual cortex: implications for visual cortical prostheses

PubMed Central

Guo, Bing-bing; Zheng, Xiao-lin; Lu, Zhen-gang; Wang, Xing; Yin, Zheng-qin; Hou, Wen-sheng; Meng, Ming

2015-01-01

Visual cortical prostheses have the potential to restore partial vision. Still limited by the low-resolution visual percepts provided by visual cortical prostheses, implant wearers can currently only “see” pixelized images, and how to obtain the specific brain responses to different pixelized images in the primary visual cortex (the implant area) is still unknown. We conducted a functional magnetic resonance imaging experiment on normal human participants to investigate the brain activation patterns in response to 18 different pixelized images. There were 100 voxels in the brain activation pattern that were selected from the primary visual cortex, and voxel size was 4 mm × 4 mm × 4 mm. Multi-voxel pattern analysis was used to test if these 18 different brain activation patterns were specific. We chose a Linear Support Vector Machine (LSVM) as the classifier in this study. The results showed that the classification accuracies of different brain activation patterns were significantly above chance level, which suggests that the classifier can successfully distinguish the brain activation patterns. Our results suggest that the specific brain activation patterns to different pixelized images can be obtained in the primary visual cortex using a 4 mm × 4 mm × 4 mm voxel size and a 100-voxel pattern. PMID:26692860

Diagnostic Accuracy of 64Copper Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography for Primary Lymph Node Staging of Intermediate- to High-risk Prostate Cancer: Our Preliminary Experience.

PubMed

Cantiello, Francesco; Gangemi, Vincenzo; Cascini, Giuseppe Lucio; Calabria, Ferdinando; Moschini, Marco; Ferro, Matteo; Musi, Gennaro; Butticè, Salvatore; Salonia, Andrea; Briganti, Alberto; Damiano, Rocco

2017-08-01

To assess the diagnostic accuracy of 64 Copper prostate-specific membrane antigen ( 64 Cu-PSMA) positron emission tomography/computed tomography (PET/CT) in the primary lymph node (LN) staging of a selected cohort of intermediate- to high-risk prostate cancer (PCa) patients. An observational prospective study was performed in 23 patients with intermediate- to high-risk PCa, who underwent 64 Cu-PSMA PET/CT for local and lymph nodal staging before laparoscopic radical prostatectomy with an extended pelvic LN dissection. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for LN status of 64 Cu-PSMA PET/CT were calculated using the final pathological findings as reference. Furthermore, we evaluated the correlation of intraprostatic tumor extent and grading with 64 Cu-PSMA intraprostatic distribution. Pathological analysis of LN involvement in 413 LNs harvested from our study cohort identified a total of 22 LN metastases in 8 (5%) of the 23 (35%) PCa patients. Imaging-based LN staging in a per-patient analysis showed that 64 Cu-PSMA PET/CT was positive in 7 of 8 LN-positive patients (22%) with a sensitivity of 87.5%, specificity of 100%, PPV of 100%, and NPV of 93.7%, considering the maximum standardized uptake value (SUV max ) at 4 hours as our reference. Receiver operating characteristic curve was characterized by an area under the curve of 0.938. A significant positive association was observed between SUV max at 4 hours with Gleason score, index, and cumulative tumor volume. In our intermediate- to high-risk PCa patients study cohort, we showed the high diagnostic accuracy of 64 Cu-PSMA PET/CT for primary LN staging before radical prostatectomy. Copyright © 2017 Elsevier Inc. All rights reserved.

Year of treatment as independent predictor of relapse-free survival in patients with localized prostate cancer treated with definitive radiotherapy in the PSA era.

PubMed

Kupelian, Patrick; Thames, Howard; Levy, Larry; Horwitz, Eric; Martinez, Alvaro; Michalski, Jeff; Pisansky, Thomas; Sandler, Howard; Shipley, William; Zelefsky, Michael; Zietman, Anthony; Kuban, Deborah

2005-11-01

To study the use of the year of therapy as an independent predictor of outcomes, serving as a proxy for time-related changes in therapy and tumor factors in the treatment of prostate cancer. Accounting for these changes would facilitate the retrospective comparison of outcomes for patients treated in different periods. Nine institutions combined data on 4,537 patients with Stages T1 and T2 adenocarcinoma of the prostate who had a pretherapy prostate-specific antigen (PSA) level and biopsy Gleason score, and who had received > or = 60 Gy external beam radiotherapy without neoadjuvant androgen deprivation or planned adjuvant androgen deprivation. All patients were treated between 1986 and 1995. Two groups were defined: those treated before 1993 (Yr < or = 92) vs. 1993 and after (Yr > or = 93). Patients treated before 1993 had their follow-up truncated to make the follow-up time similar to that for patients treated in 1993 and after. Therefore, the median follow-up time was 6.0 years for both groups (Yr < or = 92 and Yr > or = 93). Two separate biochemical failure endpoints were used. Definition A consisted of the American Society for Therapeutic Radiology Oncology endpoint (three PSA rises backdated, local failure, distant failure, or hormonal therapy). Definition B consisted of PSA level greater than the current nadir plus two, local failure, distant failure, or hormonal therapy administered. Multivariate analyses for factors affecting PSA disease-free survival (PSA-DFS) rates using both endpoints were performed for all cases using the following variables: T stage (T1b, T1c, T2a vs. T2b, T2c), pretreatment PSA (continuous variable), biopsy Gleason score (continuous variable), radiation dose (continuous variable), and year of treatment (continuous variable). The year variable (defined as the current year minus 1960) ranged from 26 to 35. To evaluate the effect of radiation dose, the multivariate analyses were repeated with the 3,897 cases who had received < 72 Gy using the same variables except for radiation dose. For all 4,537 patients, the 5- and 8-year PSA-DFS estimate using definition A (ASTRO consensus definition) was 60% and 55%, respectively. The 8-year PSA-DFS estimate for Yr < 93 vs. Yr > or = 93 was 52% vs. 57%, respectively (p < 0.001). In the subgroup of patients receiving < 72 Gy, the 8-year PSA-DFS estimate for Yr < 93 vs. Yr > or = 93 was 52% and 55%, respectively (p = 0.004). The differences in PSA-DFS rates in the different subgroups were similar when definition B was used. The multivariate analyses for all 4,537 cases with either PSA-DFS definition revealed T stage (p < 0.001), pretherapy PSA level (p < 0.001), Gleason score (p < 0.001), radiation dose (p < 0.001), and year of treatment (p < 0.001) to be independent predictors of outcomes. The multivariate analyses restricted to the 3,897 cases receiving < 72 Gy still revealed year of treatment to be an independent predictor of outcomes (p < 0.001), in addition to T stage (p < 0.001), pretherapy PSA level (p < 0.001), and Gleason score (p < 0.001). Independent of tumor stage, radiation dose, failure definition, and follow-up parameters, the year in which RT was performed was an independent predictor of outcomes. These findings indicate a more favorable presentation of localized prostate cancer in current years that is not necessarily reflected in the patients' PSA levels or Gleason scores. This phenomenon is probably related to a combination of factors, such as screening, increased patient awareness leading to earlier biopsies and earlier diagnosis, more aggressive pretherapy staging, and unrecognized improvements in therapy, but perhaps also to changing tumor biology. Outcomes predictions should be based on contemporaneous series. Alternatively, the year of therapy could be incorporated as a variable in outcomes analyses of localized prostate cancer patients treated in different periods within the PSA era.

Lymph node yield during radical prostatectomy does not impact rate of biochemical recurrence in patients with seminal vesicle invasion and node-negative disease.

PubMed

Badani, Ketan K; Reddy, Balaji N; Moskowitz, Eric J; Paulucci, David J; Beksac, Alp Tuna; Martini, Alberto; Whalen, Michael J; Skarecky, Douglas W; Huynh, Linda My; Ahlering, Thomas E

2018-06-01

Seminal vesicle invasion (SVI) is a risk factor for poor oncologic outcome in patients with prostate cancer. Modifications to the pelvic lymph node dissection (PLND) during radical prostatectomy (RP) have been reported to have a therapeutic benefit. The present study is the first to determine if lymph node yield (LNY) is associated with a lower risk of biochemical recurrence (BCR) for men with SVI. A total of 220 patients from 2 high-volume institutions who underwent RP without adjuvant treatment between 1990 and 2015 and had prostate cancer with SVI (i.e., pT3b) were identified, and 21 patients did not undergo lymph node dissection. BCR was defined as a postoperative PSA>0.2ng/mL, or use of salvage androgen deprivation therapy (ADT) or radiation. Multivariable Cox proportional hazards models were used to determine whether LNY was predictive of BCR, controlling for PSA, pathologic Gleason Score, pathologic lymph node status, NCCN risk category, etc. The Kaplan-Meier method was used to determine 3-year freedom from BCR. Median number of lymph nodes sampled were 7 (IQR: 3-12; range: 0-35) and 90.5% underwent PLND. The estimated 3-year BCR rate was 43.9%. Results from multivariable analysis demonstrated that LNY was not significantly associated with risk of BCR overall (HR = 1.00, 95% CI: 0.98-1.03; P = 0.848) for pN0 (HR = 0.99, 95% CI: 0.97-1.03; P = 0.916) or pN1 patients (HR = 0.96, 95% CI: 0.88-1.06; P = 0.468). Overall, PSA (HR = 1.02, P<0.001) and biopsy Gleason sum ≥ 8 (HR = 1.81, P = 0.001) were associated with an increased risk of BCR, and increasing LNY increased the likelihood of detecting>2 positive lymph nodes (OR = 1.27, 95% CI: 1.06-1.65, P = 0.023). Seminal vesicle invasion is associated with an increased risk of BCR at 3 years, primarily due to pathologic Gleason score and PSA. Although greater lymph node yield is diagnostic and facilitates more accurate pathologic staging, our data do not show a therapeutic benefit in reducing BCR. Copyright © 2018 Elsevier Inc. All rights reserved.

Assessment of Prospectively Assigned Likert Scores for Targeted Magnetic Resonance Imaging-Transrectal Ultrasound Fusion Biopsies in Patients with Suspected Prostate Cancer.

PubMed

Costa, Daniel N; Lotan, Yair; Rofsky, Neil M; Roehrborn, Claus; Liu, Alexander; Hornberger, Brad; Xi, Yin; Francis, Franto; Pedrosa, Ivan

2016-01-01

We assess the performance of prospectively assigned magnetic resonance imaging based Likert scale scores for the detection of clinically significant prostate cancer, and analyze the pre-biopsy imaging variables associated with increased cancer detection using targeted magnetic resonance imaging-transrectal ultrasound fusion biopsy. In this retrospective review of prospectively generated data including men with abnormal multiparametric prostate magnetic resonance imaging (at least 1 Likert score 3 or greater lesion) who underwent subsequent targeted magnetic resonance imaging-transrectal ultrasound fusion biopsy, we determined the association between different imaging variables (Likert score, lesion size, lesion location, prostate volume, radiologist experience) and targeted biopsy positivity rate. We also compared the detection of clinically significant cancer according to Likert scale scores. Tumors with high volume (50% or more of any core) Gleason score 3+4 or any tumor with greater Gleason score were considered clinically significant. Each lesion served as the elementary unit for analysis. We used logistic regression for univariate and multivariate (stepwise selection) analysis to assess for an association between targeted biopsy positivity rate and each tested variable. The relationship between Likert scale and Gleason score was evaluated using the Spearman correlation coefficient. A total of 161 men with 244 lesions met the study eligibility criteria. Targeted biopsies diagnosed cancer in 41% (66 of 161) of the men and 41% (99 of 244) of the lesions. The Likert score was the strongest predictor of targeted biopsy positivity (OR 3.7, p <0.0001). Other imaging findings associated with a higher targeted biopsy positivity rate included smaller prostate volume (OR 0.7, p <0.01), larger lesion size (OR 2.2, p <0.001) and anterior location (OR 2.0, p=0.01). On multiple logistic regression analysis Likert score, lesion size and prostate volume were significant predictors of targeted biopsy positivity. Higher Likert scores were also associated with increased detection of clinically significant tumors (p <0.0001). The Likert scale score used to convey the degree of suspicion on multiparametric magnetic resonance imaging is the strongest predictor of targeted biopsy positivity and of the presence of clinically significant tumor. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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.

Effects of increasing the PSA cutoff to perform additional biomarker tests before prostate biopsy.

PubMed

Nordström, Tobias; Adolfsson, Jan; Grönberg, Henrik; Eklund, Martin

2017-10-03

Multi-step testing might enhance performance of the prostate cancer diagnostic pipeline. Using PSA >1 ng/ml for first-line risk stratification and the Stockholm 3 Model (S3M) blood-test >10% risk of Gleason Score > 7 prostate cancer to inform biopsy decisions has been suggested. We aimed to determine the effects of changing the PSA cutoff to perform reflex testing with S3M and the subsequent S3M cutoff to recommend prostate biopsy while maintaining the sensitivity to detect Gleason Score ≥ 7 prostate cancer. We used data from the prospective, population-based, paired, diagnostic Stockholm 3 (STHLM3) study with participants invited by date of birth from the Swedish Population Register during 2012-2014. All participants underwent testing with PSA and S3M (a combination of plasma protein biomarkers [PSA, free PSA, intact PSA, hK2, MSMB, MIC1], genetic polymorphisms, and clinical variables [age, family, history, previous prostate biopsy, prostate exam]). Of 47,688 men in the STHLM3 main study, we used data from 3133 men with S3M >10% and prostate biopsy data. Logistic regression models were used to calculate prostate cancer detection rates and proportion saved biopsies. 44.2%, 62.5% and 67.9% of the participants had PSA <1, <1.5 and <1.7 ng/ml, respectively. Increasing the PSA cut-off for additional work-up from 1 ng/ml to 1.5 ng/ml would thus save 18.3% of the performed tests, 4.9% of the biopsies and 1.3% (10/765) of Gleason Grade ≥ 7 cancers would be un-detected. By lowering the S3M cutoff to recommend biopsy, sensitivity to high-grade prostate cancer can be restored, to the cost of increasing the number of performed biopsies modestly. The sensitivity to detect prostate cancer can be maintained when using different PSA cutoffs to perform additional testing. Biomarker cut-offs have implications on number of tests and prostate biopsies performed. A PSA cutoff of 1.5 ng/ml to perform additional testing such as the S3M test might be considered. ISRCTN84445406 .

Sedentarism and overweight as risk factors for the detection of prostate cancer and its aggressivenes.

PubMed

Morote, J; Celma, A; Planas, J; Placer, J; Konstantinidis, C; Iztueta, I; de Torres, I M; Oliván, M; Reventós, J; Doll, A

2014-05-01

To analyze the influence of sedentary (SE) and overweight (OW) in the risk of prostate cancer detection (CP) and aggressiveness. We performed prostate biopsy (PB) to 2,408 consecutive male, 5 ARIs untreated, because of elevated serum PSA above 4.0 ng/mL (91%) or suspicious digital rectal examination (9%). In all ultrasound guided PB, 10 cores were obtained plus 2 to 8 additionals, according to age and prostate volume. Physical activity was assessed using a survey (SE vs non-SE) and calculated body mass index (normal vs OW > 25 kg/cm(2)). The tumor aggressiveness was evaluated according to the Gleason score (high grade «HG»: Gleason > 7) and D'Amico risk (high risk «HR»: T > 3a or PSA > 20 or Gleason score > 7). We found a significant association between SE (52.5%) and OW (72.9%), P < .001. The overall PC detection rate was 35.2%. In men with SE it was 36.7% and non-SE 33.6%, P = .048. The overall rate of AG tumors was 28.3%, 29.2% in men with SE and 27.1 in non-SE, P = .261. The overall rate of AR tumors was 35%, 39.7% in men with SE and 29.4% non-SE, P < .001. CP was detected in 38.1% of men with normal BMI and 34.3% in men with OW, P = .065. HG tumor rates were 18.1% and 31.4% respectively, P < .001 and AR tumor rates were 22.6% and 39.2% respectively, P < .001. Binary logistic regression showed that SE was an independent predictor of CP, OR .791 (95% CI: .625-.989), P = .030. SE and OW were independent predictors of HG: OR .517 (95% CI: .356-.752), P = .001, and OR 1.635 (95% CI: 1070-2497), p = 0.023. SE and OW were also independent predictors of HR: OR .519 (95% CI .349-.771), P = .001, and OR 1.998 (95% CI 1.281-3.115), P = .002. In men who met criteria for prostate biopsy an association between sedentary and overweight exist. A sedentary lifestyle is associated with increased risk of PC detection while sedentary and overweight were associated with more aggressive tumors. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

Objective consensus from decision trees.

PubMed

Putora, Paul Martin; Panje, Cedric M; Papachristofilou, Alexandros; Dal Pra, Alan; Hundsberger, Thomas; Plasswilm, Ludwig

2014-12-05

Consensus-based approaches provide an alternative to evidence-based decision making, especially in situations where high-level evidence is limited. Our aim was to demonstrate a novel source of information, objective consensus based on recommendations in decision tree format from multiple sources. Based on nine sample recommendations in decision tree format a representative analysis was performed. The most common (mode) recommendations for each eventuality (each permutation of parameters) were determined. The same procedure was applied to real clinical recommendations for primary radiotherapy for prostate cancer. Data was collected from 16 radiation oncology centres, converted into decision tree format and analyzed in order to determine the objective consensus. Based on information from multiple sources in decision tree format, treatment recommendations can be assessed for every parameter combination. An objective consensus can be determined by means of mode recommendations without compromise or confrontation among the parties. In the clinical example involving prostate cancer therapy, three parameters were used with two cut-off values each (Gleason score, PSA, T-stage) resulting in a total of 27 possible combinations per decision tree. Despite significant variations among the recommendations, a mode recommendation could be found for specific combinations of parameters. Recommendations represented as decision trees can serve as a basis for objective consensus among multiple parties.

Evaluation of a deidentification (De-Id) software engine to share pathology reports and clinical documents for research.

PubMed

Gupta, Dilip; Saul, Melissa; Gilbertson, John

2004-02-01

We evaluated a comprehensive deidentification engine at the University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, that uses a complex set of rules, dictionaries, pattern-matching algorithms, and the Unified Medical Language System to identify and replace identifying text in clinical reports while preserving medical information for sharing in research. In our initial data set of 967 surgical pathology reports, the software did not suppress outside (103), UPMC (47), and non-UPMC (56) accession numbers; dates (7); names (9) or initials (25) of case pathologists; or hospital or laboratory names (46). In 150 reports, some clinical information was suppressed inadvertently (overmarking). The engine retained eponymic patient names, eg, Barrett and Gleason. In the second evaluation (1,000 reports), the software did not suppress outside (90) or UPMC (6) accession numbers or names (4) or initials (2) of case pathologists. In the third evaluation, the software removed names of patients, hospitals (297/300), pathologists (297/300), transcriptionists, residents and physicians, dates of procedures, and accession numbers (298/300). By the end of the evaluation, the system was reliably and specifically removing safe-harbor identifiers and producing highly readable deidentified text without removing important clinical information. Collaboration between pathology domain experts and system developers and continuous quality assurance are needed to optimize ongoing deidentification processes.

Exploiting a Molecular Gleason Grade for Prostate Cancer Therapy

DTIC Science & Technology

2008-03-01

influenced by epigenetic events. Through comprehensive studies of genome and gene expression alterations, it is clear that prostate cancers are...recognizing grade-determinant proteins (months 1-12). To date, we have purchased (or acquired) antibodies recognizing; TMPRSS2, MAOA , DAD1, ERG, Jagged...and neoplastic prostate cases: TMPRSS2, MAOA , DAD1, ERG, Jagged, p63, AMACR, MUC1, FLNA, ALSCR2, CCNG2, FLH2, GSTMU1, PC4, RSK2, and SMS—see reportable

Worldwide Prevalence of Human Papillomavirus and Relative Risk of Prostate Cancer: A Meta-analysis

PubMed Central

Yang, Lin; Xie, Shuanghua; Feng, Xiaoshuang; Chen, Yuheng; Zheng, Tongzhang; Dai, Min; Ke Zhou, Cindy; Hu, Zhibin; Li, Ni; Hang, Dong

2015-01-01

Despite the increasing number of studies conducted recently to evaluate the association between HPV infections and the risk of prostate cancer, the results remain inconclusive. Furthermore, the prevalence and distribution of overall and individual HPV types worldwide in prostate cancer has not been reported until now. Therefore, we estimated the prevalence of HPV in prostate cancer by pooling data of 46 studies with 4919 prostate cancer cases, taking into account the heterogeneity of major related parameters, including study region, specimen type, HPV DNA source, detection method, publication calendar period and Gleason score. Moreover, we tested the association of HPV infections with prostate cancer risks by a meta-analysis of 26 tissue-based case-control studies. We found that the prevalence of HPV infection was 18.93% (95% CI = 17.84–20.05%) in prostate cancer cases, and most of which were high-risk HPV types (17.73%, 95% CI = 16.52–18.99%). The prevalence varied by region, PCR primers used, publication calendar period and Gleason score. Our study also showed a significantly increased risk of prostate cancer with the positivity of overall HPV detected in prostate tissues (OR = 1.79, 95% CI = 1.29–2.49) and revealed the geographic variation of association strength (P < 0.001). In conclusion, HPV infections may contribute to the risk of prostate cancer. PMID:26441160

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.

[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.

[High-intensity focused ultrasound (HIFU) for the prostate cancer treatment: 5-year resuts].

PubMed

Shaplysin, L V; Solov, V A; Vosdvizhenskiĭ, M O; Khametov, R Z

2013-01-01

During 2007-2012 748 patients with prostate cancer (PCa) underwent ultrasound ablation (HIFU). Patients were divided into 3 groups according to the prevalence and risk of disease progression: low risk (localized prostate cancer, 465 (62%) of patients) stage T1-2N0M0, total Gleason score < or = 6, the level of prostate-specific antigen (PSA) less than 20 ng/ml), high risk (locally advanced prostate cancer, 251 (34%) of patients)--stage T2-3N0M0, total Gleason score < or = 9, the PSA level from 20 to 60 ng/ml, the presence of local recurrence after radical prostatectomy (RPE) and external beam radiation (EBRT)--32 (4%) patients. Median follow-up after HIFU-therapy was 36 (3-54) months. At 12 and 48 months after treatment in patients with a low risk of progression median PSA was 0.2 and 0.5 ng/ml, in the group with a high risk 0.8 and 1.2 ng/ml, in patients with local recurrence after RPE and EBRT--0.5 and 1.7 ng/ml respectively. Generally HIFU treatment was successful in 90.9% of patients. It is shown that HIFU is safe minimally invasive treatment for localizes and locally advanced prostate cancer. It can be successfully performed in patients with local recurrence after RPE and EBRT.

Incidental Prostate Adenocarcinoma in Cystoprostatectomy Specimens: Partial Versus Complete Prostate Sampling.

PubMed

Filter, Emily R; Gabril, Manal Y; Gomez, Jose A; Wang, Peter Z T; Chin, Joseph L; Izawa, Jonathan; Moussa, Madeleine

2017-08-01

The rate of incidental prostate adenocarcinoma (PCa) detection in radical cystoprostatectomy (RCP) varies widely, ranging from 15% to 54%. Such variability may be explained by institutional differences in prostate grossing protocols. Either partial or complete submission of the prostate gland in RCP may result in detection of clinically insignificant or significant incidental PCa. The aim of the study was to compare the clinical significance of PCa in RCP specimens in partial versus complete sampling. Seventy-two out of 158 RCP cases showed incidental PCa. The pathologic features, including Gleason score, margin status, extraprostatic extension (EPE), seminal vesicle invasion (SVI), PCa stage, and tumor volume, were assessed. The 72 cases were divided into partial (n = 21, 29.1%) and complete sampling (n = 51, 70.8%) groups. EPE was detected in 13/72 (18.1%) with 11/13 (84.6%) cases in the complete group. Positive margins were present in 11/72 (15.3%) with 9/11 (81.8%) in the complete group. SVI was detected in 4/72 (5.6%) with 3/4 (75.0%) in the complete group. Overall, 4/72 (5.6%) had a Gleason score >7, all of which were in the complete group. Our data suggest that complete sampling of the prostate may be the ideal approach to grossing RCP specimens, allowing for greater detection of clinically significant incidental PCa.

History of gonorrhea and prostate cancer in a population-based case-control study in Mexico.

PubMed

Vázquez-Salas, Ruth Argelia; Torres-Sánchez, Luisa; López-Carrillo, Lizbeth; Romero-Martínez, Martín; Manzanilla-García, Hugo A; Cruz-Ortíz, Carlos Humberto; Mendoza-Peña, Fernando; Jiménez-Ríos, Miguel Ángel; Rodríguez-Covarrubias, Francisco; Hernández-Toríz, Narciso; Moreno-Alcázar, Othón

2016-02-01

We evaluated the association between a history of sexually transmitted diseases (STDs) and the risk for prostate cancer (PC) among Mexican males. PC incident cases (n=402) that were identified at six public hospitals in Mexico City were matched by age (±5 years) with 805 population controls with no history of PC. By face-to-face interview, we obtained information about sexual history, previous STDs, sociodemographic characteristics, and familial history of PC. An unconditional logistic regression model was used to estimate the risk for PC. A total of 16.6% of men reported having had at least one previous STD, and the most frequently reported STD was gonorrhea (10.5%). After adjusting by PC familial history, the history of STD was associated with a two-fold greater risk of PC: odds ratio (OR)=2.67; 95% confidence interval (95% CI=1.91-3.73). When each STD was evaluated separately, only gonorrhea was associated with a significant increase in PC risk (OR=3.04; 95% CI=1.99-4.64). These associations were similar when we stratified by low-risk PC (Gleason <7) and high-risk PC (Gleason ≥7). These results confirm that STDs, and particularly gonorrhea, may play an etiological role in PC among Mexican males, which is consistent with a previous report from a multiethnic cohort. Copyright © 2015 Elsevier Ltd. All rights reserved.

Expression of matrix metalloproteinase-9 and bombesin/gastrin-releasing peptide in human prostate cancers and their lymph node metastases.

PubMed

Ishimaru, Hisashi; Kageyama, Yukio; Hayashi, Tetsuo; Nemoto, Tetsuo; Eishi, Yoshinobu; Kihara, Kazunori

2002-01-01

Neuroendocrine differentiation and subsequent excretion of neuropeptides have been demonstrated to be associated with progression of human prostate cancer. Among neuropeptides found to exist in the prostate, bombesin/gastrin-releasing peptide has been shown to upregulate matrix metalloproteinase-9 (MMP-9) in human prostate cancer cell lines. Expression levels of bombesin, MMP-9, and neuron-specific enolase were examined by immunohistochemistry in 41 cases of clinically organ-confined prostate cancers including 9 with microscopic lymph node metastases. Twenty-seven (64%) of the 41 radical prostatectomy specimens were positive for both MMP-9 and bombesin. Expression of these molecules was observed in almost the same population of the cancer cells. The remaining 14 cases were negative for both MMP-9 and bombesin. High-grade tumors (Gleason sum > or = 7) were more likely to express MMP-9 and bombesin (21/24:88%) than low-grade tumors (Gleason sum > or = 6) (7/17:41%). In eight of the nine cases with pathological lymph node metastases, expression of MMP-9 and bombesin was also noted in metastatic sites. Neuron-specific enolase was positive in 16 cases (39%) and not always associated with the expression of bombesin. Expression of bombesin and expression of MMP-9 are common in human prostate cancers and may be related to an aggressive phenotype.

The prognostic significance of the 2014 International Society of Urological Pathology (ISUP) grading system for prostate cancer.

PubMed

Samaratunga, Hemamali; Delahunt, Brett; Gianduzzo, Troy; Coughlin, Geoff; Duffy, David; LeFevre, Ian; Johannsen, Shulammite; Egevad, Lars; Yaxley, John

2015-10-01

The 2005 International Society of Urological Pathology (ISUP) modified Gleason grading system was further amended in 2014 with the establishment of grade groupings (ISUP grading). This study examined the predictive value of ISUP grading, comparing results with recognised prognostic parameters.Of 3700 men undergoing radical prostatectomy (RP) reported at Aquesta Pathology between 2008 and 2013, 2079 also had a positive needle biopsy available for review. We examined the association between needle biopsy 2014 ISUP grade and 2005 modified Gleason score, tumour volume, pathological stage of the subsequent RP tumour, as well as biochemical recurrence-free survival (BRFS). The median age was 62 (range 32-79 years). Median serum prostate specific antigen was 5.9 (range 0.4-69 ng/mL). For needle biopsies, 280 (13.5%), 1031 (49.6%), 366 (17.6%), 77 (3.7%) and 325 (15.6%) were 2014 ISUP grades 1-5, respectively. Needle biopsy 2014 ISUP grade showed a significant association with RP tumour volume (p < 0.001), TNM pT and N stage (p < 0.001) and BRFS (p < 0.001). Multivariate analysis using Cox proportional hazards regression model showed serum prostate specific antigen (PSA) at the time of diagnosis and ISUP grade >2 to be significantly associated with BRFS.This study provides evidence of the prognostic significance of ISUP grading for thin core needle biopsy of prostate.

High intensity focused ultrasound (HIFU) for treatment of T1/T2 prostate cancer

NASA Astrophysics Data System (ADS)

Sanghvi, N.; Gardner, T.; Koch, M.

2003-04-01

This FDA approved phase I/II clinical trial is to evaluate the safety and efficacy of the Sonablate device (Focus Surgery, Inc.) for the treatment of organ confined prostate cancer. 20 patients with biopsy proven prostate cancer, Gleason <=7 and PSA <=10 were treated under general anesthesia. Outcome data included serum PSA collected at day 3, 14, 30, 90, 180, PSA nadir (mean/median), and biopsy results at 6 months. Quality of life was assessed using the International Prostate Symptom Score, International Impotence and Erectile Function score, and the SF-36 health survey. The mean patient age is 62.0, Gleason score of 6.18, PSA of 5.2, and prostate size 26.0 gm. Mean PSA results were 5.62, 44, 20, 1.68, 0.87, and 0.44 ng/ml at screening, 48-72 hours, 14 days, 30 days, 90 days and 180 days, respectively. There was one patient (9%) with a positive TRUS biopsy at 6 months, which resulted in a retreatment. There were no rectal injuries. Average pre-treatment IPSS, IIEF, and SF-36 scores were 9.55, 16.1, and 103.5. At the 30 day follow-up, they were 18.3, 3, and 97.4, respectively. HIFU is a minimally invasive modality that achieves complete prostatic ablation and is efficacious in the treatment of low-stage prostate cancer.

Prospective randomized trial comparing magnetic resonance imaging (MRI)-guided in-bore biopsy to MRI-ultrasound fusion and transrectal ultrasound-guided prostate biopsy in patients with prior negative biopsies.

PubMed

Arsov, Christian; Rabenalt, Robert; Blondin, Dirk; Quentin, Michael; Hiester, Andreas; Godehardt, Erhard; Gabbert, Helmut E; Becker, Nikolaus; Antoch, Gerald; Albers, Peter; Schimmöller, Lars

2015-10-01

A significant proportion of prostate cancers (PCas) are missed by conventional transrectal ultrasound-guided biopsy (TRUS-GB). It remains unclear whether the combined approach using targeted magnetic resonance imaging (MRI)-ultrasound fusion-guided biopsy (FUS-GB) and systematic TRUS-GB is superior to targeted MRI-guided in-bore biopsy (IB-GB) for PCa detection. To compare PCa detection between IB-GB alone and FUS-GB + TRUS-GB in patients with at least one negative TRUS-GB and prostate-specific antigen ≥4 ng/ml. Patients were prospectively randomized after multiparametric prostate MRI to IB-GB (arm A) or FUS-GB + TRUS-GB (arm B) from November 2011 to July 2014. The study was powered at 80% to demonstrate an overall PCa detection rate of ≥60% in arm B compared to 40% in arm A. Secondary endpoints were the distribution of highest Gleason scores, the rate of detection of significant PCa (Gleason ≥7), the number of biopsy cores to detect one (significant) PCa, the positivity rate for biopsy cores, and tumor involvement per biopsy core. The study was halted after interim analysis because the primary endpoint was not met. The trial enrolled 267 patients, of whom 210 were analyzed (106 randomized to arm A and 104 to arm B). PCa detection was 37% in arm A and 39% in arm B (95% confidence interval for difference, -16% to 11%; p=0.7). Detection rates for significant PCa (29% vs 32%; p=0.7) and the highest percentage tumor involvement per biopsy core (48% vs 42%; p=0.4) were similar between the arms. The mean number of cores was 5.6 versus 17 (p<0.001). A limitation is the limited number of patients because of early cessation of accrual. This trial failed to identify an important improvement in detection rate for the combined biopsy approach over MRI-targeted biopsy alone. A prospective comparison between MRI-targeted biopsy alone and systematic TRUS-GB is justified. Our randomized study showed similar prostate cancer detection rates between targeted prostate biopsy guided by magnetic resonance imaging and the combination of targeted biopsy and systematic transrectal ultrasound-guided prostate biopsy. An important improvement in detection rates using the combined biopsy approach can be excluded. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Differential expression of Annexin 2, SPINK1, and Hsp60 predict progression of prostate cancer through bifurcated WHO Gleason score categories in African American men.

PubMed

Beyene, Desta A; Naab, Tammey J; Kanarek, Norma F; Apprey, Victor; Esnakula, Ashwini; Khan, Farahan A; Blackman, Marc R; Brown, Collis A; Hudson, Tamaro S

2018-08-01

Although studies have observed several markers correlate with progression of prostate cancer (PCa), no specific markers have been identified that accurately predict the progression of this disease, even in African American (AA) men who are generally at higher risk than other ethnic groups. The primary goal of this study was to explore whether three markers could predict the progression of PCa. We investigated protein expression of Annexin 2 (ANX2), serine peptidase inhibitor, kazal type 1(SPINK1)/tumor-associated trypsin inhibitor (TATI), and heat shock protein 60 (Hsp60) in 79 archival human prostate trans-rectal ultrasound (TRUS) biopsy tissues according to a modified World Health Organization (WHO) classification: normal (WHO1a), Gleason Score (GS6 (WHO1b), GS7 subgroups (WHO2 = 3 + 4, WHO3 = 4 + 3), GS8 (WHO4), and GS9-10 (WHO5). AA men aged 41-90 diagnosed from 1990 to 2013 at Howard University were included. Automated staining assessed expression of each biomarker. Spearman correlation assessed the direction and relationship between biomarkers, WHO and modified WHO GS, age, and 5-year survival. A two-tailed t-test and ANOVA evaluated biomarkers expression in relationship to WHO normal and other GS levels, and between WHO GS levels. A logistic and linear regression analysis examined the relationship between biomarker score and WHO GS categories. Kaplan-Meier curves graphed survival. ANX2 expression decreased monotonically with the progression of PCa while expression of SPINK1/TATI and Hsp60 increased but had a more WHO GS-specific effect; SPINK1/TATI differed between normal and GS 2-6 and HSP60 differed between GS 7 and GS 2-6. WHO GS was found to be significantly and negatively associated with ANX2, and positively with SPINK1/TATI and Hsp60 expression. High SPINK1/TATI expression together with the low ANX2 expression at higher GS exhibited a bi-directional relationship that is associated with PCa progression and survival. Importantly, the data reveal that ANX2, and SPINK1/TAT1 highly associate with WHO GS and with the transition from one stage of PrCa to the next in AA men. Future research is needed in biracial and larger population studies to confirm this dynamic relationship between ANX2 and SPINK1 as independent predictors of PCa progression in all men. © 2018 Wiley Periodicals, Inc.

Large institutional variations in use of androgen deprivation therapy with definitive radiotherapy in a population-based cohort of men with intermediate- and high-risk prostate cancer.

PubMed

Ong, Wee Loon; Foroudi, Farshad; Evans, Sue; Millar, Jeremy

2017-11-01

To evaluate the pattern of use of androgen deprivation therapy (ADT) with definitive radiotherapy (RT) in men with prostate cancer (PCa) in a population-based study in Australia. This is a prospective cohort of men with intermediate- and high-risk PCa, captured in the population-based Prostate Cancer Outcome Registry Victoria, who were treated with definitive prostate RT between January 2010 and December 2015. The primary outcome of interest was ADT utilization. Chi-squared test for trend was used to evaluate the temporal trend in the use of ADT over the study period. Multivariate logistic regressions were used to evaluate the effects of patient-, tumour- and treatment-related factors, and treatment institutions (public/ private and metropolitan/ regional) on the likelihood of ADT utilization. A total of 1806 men were included in the study, 199 of whom (11%) had favourable National Comprehensive Cancer Network (NCCN) intermediate-risk disease (i.e. only one intermediate-risk feature, primary Gleason grade 3, and <50% biopsy core involved), 687 (38%) had unfavourable NCCN intermediate-risk disease, and 920 (51%) had high-risk disease. Of the 1806 men, 1155 (64%) received ADT with RT. Men with NCCN high-risk PCa (84%) were more likely to have ADT than men with favourable NCCN intermediate-risk (32%) and unfavourable NCCN intermediate-risk (46%) PCa (P < 0.001). Men treated in public institutions (66%, vs 47% in private institutions; P < 0.001) and regional centres (78%, vs 59% in metropolitan institutions; P < 0.001) were more likely to receive ADT. There was a trend towards an increase in ADT utilization from 50% in 2010 to 64% in 2015 (P < 0.001). In multivariate analyses (adjusting for age, tumour-related factors, year of treatment and use of brachytherapy boost), treatment institution (public and regional) remained independently associated with increased likelihood of ADT utilization. Men with intermediate-risk PCa treated in regional and public institutions were 2.7 times (95% confidence interval [CI] 1.9-3.9; P < 0.001) and 2.8 times (95% CI 1.4-5.3; P = 0.002), more likely to receive ADT with RT, respectively, while men with high-risk PCa treated in regional and public institutions were 3.1 times (95% CI 1.7-5.7; P < 0.001) and 3.0 times (95% CI 1.7-5.4; P < 0.001), more likely to receive ADT with RT, respectively. This is the largest Australasian contemporary series reporting on the pattern of use of ADT with definitive prostate RT. While there was an increasing trend towards use of ADT over time, ADT still appeared to be underutilized in certain groups of patients who may benefit from ADT, with approximately one in five men with high-risk and one in two with unfavourable intermediate-risk PCa not receiving ADT with RT. There was notable variation in the use of ADT between public vs private and metropolitan vs regional institutions. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

68 Ga-PSMA-PET/CT staging prior to definitive radiation treatment for prostate cancer.

PubMed

Hruby, George; Eade, Thomas; Emmett, Louise; Ho, Bao; Hsiao, Ed; Schembri, Geoff; Guo, Linxin; Kwong, Carolyn; Hunter, Julia; Byrne, Keelan; Kneebone, Andrew

2018-04-16

To explore the utility of prostate specific membrane antigen (PSMA)-positron emission tomography (PET)/computed tomography (CT) in addition to conventional imaging prior to definitive external beam radiation treatment (EBRT) for prostate cancer. All men undergoing PSMA-PET/CT prior to definitive EBRT for intermediate and high-risk prostate cancer were included in our ethics approved prospective database. For each patient, clinical and pathological results, in addition to scan results including site of PSMA positive disease and number of lesions, were recorded. Results of conventional imaging (bone scan, CT and multiparametric magnetic resonance imaging [MRI]) were reviewed and included. One hundred nine men underwent staging PSMA-PET/CT between May 2015 and June 2017; all patients had national comprehensive cancer network (NCCN) intermediate or high-risk prostate cancer and 87% had Gleason score (GS) 4 + 3 or higher. There was positive uptake corresponding to the primary in 108, equivocal in one. All patients with image detected nodal or bony lesions had GS 4 + 3 or more disease. Compared to conventional imaging with bone scan, CT and multiparametric MRI, PSMA-PET/CT upstaged an additional 7 patients (6.4%) from M0 to M1, 16 from N0M0 to N1M0 (14.7%) and downstaged 3 (2.8%) from M1 to M0 disease. PSMA-PET/CT identified the primary in 99% of patients, and altered staging in 21% of men with intermediate or high-risk prostate cancer referred for definitive EBRT compared to CT, bone scan and multiparametric MRI. Following this audit, we recommend the routine use of PSMA-PET/CT prior to EBRT in this patient group. © 2018 John Wiley & Sons Australia, Ltd.

MUC1, MUC2, MUC4, MUC5AC and MUC6 expression in the progression of prostate cancer.

PubMed

Cozzi, Paul J; Wang, Jian; Delprado, Warick; Perkins, Alan C; Allen, Barry J; Russell, Pamela J; Li, Yong

2005-01-01

Molecular changes are vital for the development of prognostic markers and therapeutic modalities of prostate cancer (CaP). There is growing interest in mucins as treatment targets in human malignancies, including CaP. The role of their expression in the progression of CaP is however unclear. We examined the expressions MUC1, MUC2, MUC4, MUC5AC and MUC6 in CaP tissues using tissue microarrays (TMAs) to look for tumor-associated antigens (TAAs) for targeted therapy. In this study, 120 paraffin-embedded specimens were selected from patients who underwent radical retro-pubic prostatectomy (RRP) or trans-urethral-resection of the prostate (TURP) for primary, untreated CaP and 10 matched lymph node metastases. A series of MUC monoclonal antibodies (mAbs) was used on TMAs by standard immunohistochemistry. Our results indicate that the over-expression of MUC1 was detected in 58% of primary CaP tissues and 90% of lymph node metastases but not in normal prostate or benign tissues, while the expression of MUC2, MUC4, MUC5AC and MUC6 was found to be negative in both normal and cancer tissues. Of the MUC1 positive tumors 86% were Gleason grade 7 or higher. Over-expression of MUC1 was found in late stage CaP while MUC2, 4, 5AC and 6 were negative in CaP. MUC1 is a TAA that is highly related to tumor progression in CaP patients. This antigen is ideal for targeted therapy to control micrometastases and hormone refractory disease but additional studies are necessary to assess its usefulness in patient biopsies and CaP bone metastases before clinical trial.

Role of Magnetic Resonance Imaging Targeted Biopsy in Detection of Prostate Cancer Harboring Adverse Pathological Features of Intraductal Carcinoma and Invasive Cribriform Carcinoma.

PubMed

Prendeville, Susan; Gertner, Mark; Maganti, Manjula; Pintilie, Melania; Perlis, Nathan; Toi, Ants; Evans, Andrew J; Finelli, Antonio; van der Kwast, Theodorus H; Ghai, Sangeet

2018-07-01

The aim of this study was to compare biopsy detection of intraductal and cribriform pattern invasive prostate carcinoma in multiparametric magnetic resonance imaging positive and negative regions of the prostate. We queried a prospectively maintained, single institution database to identify patients who underwent multiparametric magnetic resonance imaging/ultrasound fusion targeted biopsy and concurrent systematic sextant biopsy of magnetic resonance imaging negative regions between January 2013 and May 2016. All multiparametric magnetic resonance imaging targets were reviewed retrospectively by 2 readers for the PI-RADS™ (Prostate Imaging-Reporting and Data System), version 2 score, the maximum dimension, the apparent diffusion coefficient parameter and whether positive or negative on dynamic contrast enhancement sequence. Biopsy slides were reviewed by 2 urological pathologists for Gleason score/Grade Group and the presence or absence of an intraductal/cribriform pattern. A total of 154 patients were included in study. Multiparametric magnetic resonance imaging/ultrasound fusion targeted biopsy and systematic sextant biopsy of magnetic resonance imaging negative regions were negative for prostate carcinoma in 51 patients, leaving 103 available for the correlation of multiparametric magnetic resonance imaging and the intraductal/cribriform pattern. Prostate carcinoma was identified by multiparametric magnetic resonance imaging/ultrasound fusion targeted biopsy in 93 cases and by systematic sextant biopsy of magnetic resonance imaging negative regions in 76 (p = 0.008). Intraductal/cribriform positive tumor was detected in 23 cases, including at the multiparametric magnetic resonance imaging/ultrasound fusion targeted biopsy site in 22 and at the systematic sextant biopsy of magnetic resonance imaging negative region site in 3 (p <0.001). The intraductal/cribriform pattern was significantly associated with a PI-RADS score of 5 and a decreasing apparent diffusion coefficient value (p = 0.008 and 0.005, respectively). In 19 of the 23 cases with the intraductal/cribriform pattern prior 12-core standard systematic biopsy was negative in 8 and showed Grade Group 1 disease in 11. Multiparametric magnetic resonance imaging/ultrasound fusion targeted biopsy was associated with significantly increased detection of intraductal/cribriform positive prostate carcinoma compared to systematic sextant biopsy of multiparametric magnetic resonance imaging negative regions. This supports the role of magnetic resonance imaging to enhance the detection of clinically aggressive intraductal/cribriform positive prostate carcinoma. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

PSA-Stratified Performance of 18F- and 68Ga-PSMA PET in Patients with Biochemical Recurrence of Prostate Cancer.

PubMed

Dietlein, Felix; Kobe, Carsten; Neubauer, Stephan; Schmidt, Matthias; Stockter, Simone; Fischer, Thomas; Schomäcker, Klaus; Heidenreich, Axel; Zlatopolskiy, Boris D; Neumaier, Bernd; Drzezga, Alexander; Dietlein, Markus

2017-06-01

Several studies outlined the sensitivity of 68 Ga-labeled PET tracers against the prostate-specific membrane antigen (PSMA) for localization of relapsed prostate cancer in patients with renewed increase in the prostate-specific antigen (PSA), commonly referred to as biochemical recurrence. Labeling of PSMA tracers with 18 F offers numerous advantages, including improved image resolution, longer half-life, and increased production yields. The aim of this study was to assess the PSA-stratified performance of the 18 F-labeled PSMA tracer 18 F-DCFPyL and the 68 Ga-labeled reference 68 Ga-PSMA-HBED-CC. Methods: We examined 191 consecutive patients with biochemical recurrence according to standard acquisition protocols using 18 F-DCFPyL ( n = 62, 269.8 MBq, PET scan at 120 min after injection) or 68 Ga-PSMA-HBED-CC ( n = 129, 158.9 MBq, 60 min after injection). We determined PSA-stratified sensitivity rates for both tracers and corrected our calculations for Gleason scores using iterative matched-pair analyses. As an orthogonal validation, we directly compared tracer distribution patterns in a separate cohort of 25 patients, sequentially examined with both tracers. Results: After prostatectomy ( n = 106), the sensitivity of both tracers was significantly associated with absolute PSA levels ( P = 4.3 × 10 -3 ). Sensitivity increased abruptly, when PSA values exceeded 0.5 μg/L ( P = 2.4 × 10 -5 ). For a PSA less than 3.5 μg/L, most relapses were diagnosed at a still limited stage ( P = 3.4 × 10 -6 ). For a PSA of 0.5-3.5 μg/L, PSA-stratified sensitivity was 88% (15/17) for 18 F-DCFPyL and 66% (23/35) for 68 Ga-PSMA-HBED-CC. This significant difference was preserved in the Gleason-matched-pair analysis. Outside of this range, sensitivity was comparably low (PSA < 0.5 μg/L) or high (PSA > 3.5 μg/L). After radiotherapy ( n = 85), tracer sensitivity was largely PSA-independent. In the 25 patients examined with both tracers, distribution patterns of 18 F-DCFPyL and 68 Ga-PSMA-HBED-CC were strongly comparable ( P = 2.71 × 10 -8 ). However, in 36% of the PSMA-positive patients we detected additional lesions on the 18 F-DCFPyL scan ( P = 3.7 × 10 -2 ). Conclusion: Our data suggest that 18 F-DCFPyL is noninferior to 68 Ga-PSMA-HBED-CC, while offering the advantages of 18 F labeling. Our results indicate that imaging with 18 F-DCFPyL may even exhibit improved sensitivity in localizing relapsed tumors after prostatectomy for moderately increased PSA levels. Although the standard acquisition protocols, used for 18 F-DCFPyL and 68 Ga-PSMA-HBED-CC in this study, stipulate different activity doses and tracer uptake times after injection, our findings provide a promising rationale for validation of 18 F-DCFPyL in future prospective trials. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Lamin A/C might be involved in the EMT signalling pathway.

PubMed

Zuo, Lingkun; Zhao, Huanying; Yang, Ronghui; Wang, Liyong; Ma, Hui; Xu, Xiaoxue; Zhou, Ping; Kong, Lu

2018-07-15

We have previously reported a heterogeneous expression pattern of the nuclear membrane protein lamin A/C in low- and high-Gleason score (GS) prostate cancer (PC) tissues, and we have now found that this change is not associated with LMNA mutations. This expression pattern appears to be similar to the process of epithelial to mesenchymal transition (EMT) or to that of mesenchymal to epithelial transition (MET). The role of lamin A/C in EMT or MET in PC remains unclear. Therefore, we first investigated the expression levels of and the associations between lamin A/C and several common EMT markers, such as E-cadherin, N-cadherin, β-catenin, snail, slug and vimentin in PC tissues with different GS values and in different cell lines with varying invasion abilities. Our results suggest that lamin A/C might constitute a type of epithelial marker that better signifies EMT and MET in PC tissue, since a decrease in lamin A/C expression in GS 4 + 5 cases is likely associated with the EMT process, while the re-expression of lamin A/C in GS 5 + 4 cases is likely linked with MET. The detailed GS better exhibited the changes in lamin A/C and the EMT markers examined. Lamin A/C overexpression or knockdown had an impact on EMT biomarkers in a cell model by direct regulation of β-catenin. Hence, we suggest that lamin A/C might serve as a reliable epithelial biomarker for the distinction of PC cell differentiation and might also be a fundamental factor in the occurrence of EMT or MET in PC. Copyright © 2018. Published by Elsevier B.V.

Moderate hypofractionated radiotherapy with volumetric modulated arc therapy and simultaneous integrated boost for pelvic irradiation in prostate cancer.

PubMed

Franzese, C; Fogliata, A; D'Agostino, G R; Di Brina, L; Comito, T; Navarria, P; Cozzi, L; Scorsetti, M

2017-07-01

The optimal treatment for unfavourable intermediate/high-risk prostate cancer is still debated. In the present study, the pattern of toxicity and early clinical outcome of patients with localized prostate cancer was analyzed. A cohort of 90 patients treated on pelvic lymph nodes from 2010 to 2015 was selected. All patients were treated with Volumetric Modulated Arc Therapy (VMAT), and Simultaneous integrated boost (SIB) in 28 fractions; the prostate, the seminal vesicle and the pelvic lymph node received total doses of 74.2, 65.5, and 51.8 Gy, respectively. End points were the detection of acute and late toxicities graded according to the Common Toxicity Criteria CTCAE version 3, evaluating the rectal, genito-urinary and gastro-intestinal toxicity. Correlation of OARs dose parameters and related toxicities was explored. Preliminary overall survival and Progression-free survival (PFS) were evaluated. With a median follow-up of 25 months, no interruptions for treatment-related toxicity were recorded. Univariate analysis among dosimetric data and acute toxicities showed no correlations. Regarding late toxicity: the dose received by a rectal volume of 90 cm 3 was found to be significant for toxicity prediction (p = 0.024). PFS was 90.6% and 60.2% at 2 and 4 years, respectively. PFS correlates with age (p = 0.011) and Gleason score (p = 0.011). Stratifying the PSA nadir in quartiles, its value was significant (p = 0.016) in predicting PFS, showing a reduction of PFS of 2 months for each PSA-nadir increase of 0.1 ng/ml. HRT with VMAT and SIB on the whole pelvis in unfavourable prostate cancer patients is effective with a mild pattern of toxicity.

fMRI-based Multivariate Pattern Analyses Reveal Imagery Modality and Imagery Content Specific Representations in Primary Somatosensory, Motor and Auditory Cortices.

PubMed

de Borst, Aline W; de Gelder, Beatrice

2017-08-01

Previous studies have shown that the early visual cortex contains content-specific representations of stimuli during visual imagery, and that these representational patterns of imagery content have a perceptual basis. To date, there is little evidence for the presence of a similar organization in the auditory and tactile domains. Using fMRI-based multivariate pattern analyses we showed that primary somatosensory, auditory, motor, and visual cortices are discriminative for imagery of touch versus sound. In the somatosensory, motor and visual cortices the imagery modality discriminative patterns were similar to perception modality discriminative patterns, suggesting that top-down modulations in these regions rely on similar neural representations as bottom-up perceptual processes. Moreover, we found evidence for content-specific representations of the stimuli during auditory imagery in the primary somatosensory and primary motor cortices. Both the imagined emotions and the imagined identities of the auditory stimuli could be successfully classified in these regions. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Different patterns of skin manifestations associated with parvovirus B19 primary infection in adults.

PubMed

Mage, Valentia; Lipsker, Dan; Barbarot, Sébastien; Bessis, Didier; Chosidow, Olivier; Del Giudice, Pascal; Aractingi, Sélim; Avouac, Jérôme; Bernier, Claire; Descamps, Vincent; Dupin, Nicolas

2014-07-01

Skin involvement is reported during primary parvovirus B19 infection in adults. We sought to describe the cutaneous presentations associated with parvovirus B19 primary infection in adults. We conducted a descriptive, retrospective, multicenter study. The patients included (>18 years old) had well-established primary infections with parvovirus B19. Twenty-nine patients were identified between 1992 and 2013 (17 women, 12 men). The elementary dermatologic lesions were mostly erythematous (86%) and often purpuric (69%). Pruritus was reported in 48% of cases. The rash predominated on the legs (93%), trunk (55%), and arms (45%), with a lower frequency of facial involvement (20%). Four different but sometimes overlapping patterns were identified (45%): exanthema, which was reticulated and annular in some cases (80%); the gloves-and-socks pattern (24%); the periflexural pattern (28%); and palpable purpura (24%). The limitations of this study were its retrospective design and possible recruitment bias in tertiary care centers. Our findings suggest that primary parvovirus B19 infection is associated with polymorphous skin manifestations with 4 predominant, sometimes overlapping, patterns. The acral or periflexural distribution of the rash and the presence of purpuric or annular/reticulate lesions are highly suggestive of parvovirus B19 infection. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Turkish Primary School Students' Strategies in Solving a Non-Routine Mathematical Problem and Some Implications for the Curriculum Design and Implementation

ERIC Educational Resources Information Center

Erdogan, Abdulkadir

2015-01-01

Turkish primary mathematics curriculum emphasizes the role of problem solving for teaching mathematics and pays particular attention to problem solving strategies. Patterns as a subject and the use of patterns as a non-routine problem solving strategy are also emphasized in the curriculum. The primary purpose of this study was to determine how…

The Pattern of Electronic Game Use and Related Bodily Discomfort in Hong Kong Primary School Children

ERIC Educational Resources Information Center

Lui, Donald P. Y.; Szeto, Grace P. Y.; Jones, Alice Y. M.

2011-01-01

The present study examined the usage pattern of electronic game devices among primary school children in Hong Kong. Commonly used types of games devices were grouped into three main categories: large-screen/TV-based games, small handheld game devices and active game devices. A survey was conducted among 476 students in a local primary school, with…

Detailed Project Report and Environmental Impact Statement, Limestone Creek Manlius, New York

DTIC Science & Technology

1990-01-01

Installations. Idano Fish and Game Department. January. Gleason, Henry A . and Arthur Cronquist , 1963. Manual of Vascular Plants of Northeastern UnitWd States...antiu§;, New York. S PERFORMING ORG. REPORT NUMBER 7. AUTNOR( a ) S. CONTRACT OR GRANT NUMBERI.) . ANIZkITN NAME AND’ AD ESS 0. PROGRAM ELEMENT...12. REPOP7I"OE 13 NUMBEF.2 J PAGES: Ř MONITORING AGENCY NAME A ADDRESSif diferent from Conr,1lint Oilrt) 15 SECURITY CLASS (of this repot

Epiphytes and the National Wetland Plant List

DTIC Science & Technology

2011-03-07

list") (Reed 1988 ). The NWPL was updated in 1996 (referred to here as the ඨ list," as posted in a USFWS draft web publication) (Reed 1998), but the...epiphytes. Ann. Missouri Bot. Gard. 74: 205–233. Gleason, H.A. and A . Cronquist . 1991. Manual of Vascular Plants of Northeastern United States and...National Wetland Plant List (NWPL) is a list of species that occur in wetlands in the United States. It is a product of a collaborative effort of

Identification of the Transformational Properties and Transcriptional Targets of the Oncogenic SRY Transcription Factor SOX4

DTIC Science & Technology

2009-01-01

has also been implicated in tumorigenesis of multiple tumor types and has been shown by our lab to be upregulated in prostate cancer. However, the...mobility group (HMG) DNA-binding domain (DBD) related to the TCF/LEF family of transcription factors. Our lab has previously shown SOX4 mRNA and...protein to be overexpressed in prostate cancer, and this expression is correlated with increasing Gleason score. Other labs have shown SOX4 mRNA to be

High-Resolution Radioluminescence Microscopy for the Study of Prostate Tissue Slice Cell Metabolism and Monitoring of Treatment Response

DTIC Science & Technology

2015-09-01

University, The Stanford CA 94305-2004 REPORT DATE : October 2015 TYPE OF REPORT: annual PREPARED FOR: U.S. Army Medical Research and Materiel... DATE (DD-MM-YYYY) October 2015 2. REPORT TYPE Annual Report 3. DATES COVERED (From - To) 30 Sep 2014 - 29 Sep 2015 4. TITLE AND SUBTITLE Monitoring...ABSTRACT Currently, prostate cancers are classified using the Gleason Grade system and immunohistochemistry. The shortcoming of this method is that

Extracontextuality and extravalence in quantum mechanics.

PubMed

Auffèves, Alexia; Grangier, Philippe

2018-07-13

We develop the point of view where quantum mechanics results from the interplay between the quantized number of 'modalities' accessible to a quantum system, and the continuum of 'contexts' that are required to define these modalities. We point out the specific roles of 'extracontextuality' and 'extravalence' of modalities, and relate them to the Kochen-Specker and Gleason theorems.This article is part of a discussion meeting issue 'Foundations of quantum mechanics and their impact on contemporary society'. © 2018 The Author(s).

Microlocalization and Quantitation of Risk Associated Elements in Gleason Graded Prostate Tissue

DTIC Science & Technology

2006-03-01

with NADC and NADH as studied by electrospray ionization mass spectrometry and 11B NMR spectroscopy , J. Mass Spectrom. 38 (2003) 632–640. [19] D.H. Kim...spectrometry and 11B NMR spectroscopy . J Mass Spectrom 38: 632 – 640 Kurz DJ, Decary S, Hong Y, Erusalimsky JD (2000) Senescence-associated (beta...232 – 235 Semmelhack MF, Campagna SR, Hwa C, Federle MJ, Bassler BL (2004) Boron binding with the quorum sensing signal AI-2 and analogues . Org Lett 6

Influence of stem design on the primary stability of megaprostheses of the proximal femur.

PubMed

Kinkel, Stefan; Graage, Jan Dennis; Kretzer, Jan Philippe; Jakubowitz, Eike; Nadorf, Jan

2013-10-01

Extended bone defects of the proximal femur can be reconstructed by megaprostheses for which aseptic loosening constitutes one of the major failure modes. The basic requirement for long-term success of endoprostheses is primary stability. We therefore assessed whether sufficient primary stability can be achieved by four different megaprostheses in a standardised bone defect of the proximal femur and whether their different design leads to different fixation patterns. Four different designs of proximal femoral replacements were implanted into 16 Sawbones® after preparing segmental bone defects (AAOS type II). Primary rotational stability was analysed by application of a cyclic torque of ±7 Nm and measuring the relative micromotions between bone and implant at different levels. The main fixation zones and differences of fixation patterns of the stem designs were determined by an analysis of variance. All four implants exhibited micromotions below 150 μm, indicating adequate primary stability. Lowest micromotions for all designs were located near the femoral isthmus. The extent of primary stability and the global implant fixation pattern differed considerably and could be related to the different design concepts. All megaprostheses studied provided sufficient primary stability if the fixation conditions of the femoral isthmus were intact. The design characteristics of the different stems largely determined the extent of primary stability and fixation pattern. Understanding these different fixation types could help the surgeon to choose the most suitable implant if the fixation conditions in the isthmus are compromised.

Patterns of new versus recycled primary production in the terrestrial biosphere

USDA-ARS?s Scientific Manuscript database

Nitrogen (N) and phosphorus (P) availability regulate plant productivity throughout the terrestrial biosphere, influencing the patterns and magnitude of net primary production (NPP) by land plants both now and into the future. These nutrients enter ecosystems via geologic and atmospheric pathways, a...

Spongiosa Primary Development: A Biochemical Hypothesis by Turing Patterns Formations

PubMed Central

López-Vaca, Oscar Rodrigo; Garzón-Alvarado, Diego Alexander

2012-01-01

We propose a biochemical model describing the formation of primary spongiosa architecture through a bioregulatory model by metalloproteinase 13 (MMP13) and vascular endothelial growth factor (VEGF). It is assumed that MMP13 regulates cartilage degradation and the VEGF allows vascularization and advances in the ossification front through the presence of osteoblasts. The coupling of this set of molecules is represented by reaction-diffusion equations with parameters in the Turing space, creating a stable spatiotemporal pattern that leads to the formation of the trabeculae present in the spongy tissue. Experimental evidence has shown that the MMP13 regulates VEGF formation, and it is assumed that VEGF negatively regulates MMP13 formation. Thus, the patterns obtained by ossification may represent the primary spongiosa formation during endochondral ossification. Moreover, for the numerical solution, we used the finite element method with the Newton-Raphson method to approximate partial differential nonlinear equations. Ossification patterns obtained may represent the primary spongiosa formation during endochondral ossification. PMID:23193429

A morphometric analysis of cellular differentiation in caps of primary and lateral roots of Helianthus annuus

NASA Technical Reports Server (NTRS)

Moore, R.

1985-01-01

In order to determine if patterns of cell differentiation are similar in primary and lateral roots, I performed a morphometric analysis of the ultrastructure of calyptrogen, columella, and peripheral cells in primary and lateral roots of Helianthus annuus. Each cell type is characterized by a unique ultrastructure, and the ultrastructural changes characteristic of cellular differentiation in root caps are organelle specific. No major structural differences exist in the structures of the composite cell types, or in patterns of cell differentiation in caps of primary vs. lateral roots.

Investigative clinical study on prostate cancer part IX and X: estradiol and the pituitary-testicular-prostate axis at the time of initial diagnosis and subsequent cluster selection of the patient population after radical prostatectomy.

PubMed

Porcaro, Antonio B; Ghimenton, Claudio; Petrozziello, Aldo; Sava, Teodoro; Migliorini, Filippo; Romano, Mario; Caruso, Beatrice; Cocco, Claudio; Antoniolli, Stefano Zecchinini; Lacola, Vincenzo; Rubilotta, Emanuele; Monaco, Carmelo

2012-10-01

To evaluate estradiol (E(2)) physiopathology along the pituitary-testicular-prostate axis at the time of initial diagnosis of prostate cancer (PC) and subsequent cluster selection of the patient population. Records of the diagnosed (n=105) and operated (n=91) patients were retrospectively reviewed. Age, percentage of positive cores at-biopsy (P+), biopsy Gleason score (bGS), E(2), prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (TT), free-testosterone (FT), prostate-specific antigen (PSA), pathology Gleason score (pGS), estimated tumor volume in relation to percentage of prostate volume (V+), overall prostate weight (Wi), clinical stage (cT), biopsy Gleason pattern (bGP) and pathology stage (pT), were the investigated variables. None of the patients had previously undergone hormonal manipulations. E(2) correlation and prediction by multiple linear regression analysis (MLRA) was performed. At diagnosis, the log E(2)/log bGS ratio clustered the population into groups A (log E(2)/log bGS ≤ 2.25), B (2.25

Fundus autofluorescence patterns in primary intraocular lymphoma.

PubMed

Casady, Megan; Faia, Lisa; Nazemzadeh, Maryam; Nussenblatt, Robert; Chan, Chi-Chao; Sen, H Nida

2014-02-01

To evaluate fundus autofluorescence (FAF) patterns in patients with primary intraocular (vitreoretinal) lymphoma. Records of all patients with primary intraocular lymphoma who underwent FAF imaging at the National Eye Institute were reviewed. Fundus autofluorescence patterns were evaluated with respect to clinical disease status and the findings on fluorescein angiography and spectral-domain optical coherence tomography. There were 18 eyes (10 patients) with primary intraocular lymphoma that underwent FAF imaging. Abnormal autofluorescence in the form of granular hyperautofluorescence and hypoautofluorescence was seen in 11 eyes (61%), and blockage by mass lesion was seen in 2 eyes (11%). All eyes with granular pattern on FAF had active primary intraocular lymphoma at the time of imaging, but there were 5 eyes with unremarkable FAF, which were found to have active lymphoma. The most common pattern on fluorescein angiography was hypofluorescent round spots with a "leopard spot" appearance (43%). These hypofluorescent spots on fluorescein angiography correlated with hyperautofluorescent spots on FAF in 5 eyes (36%) (inversion of FAF). Nodular hyperreflective spots at the level of retinal pigment epithelium on optical coherence tomography were noted in 43% of eyes. The hyperautofluorescent spots on FAF correlated with nodular hyperreflective spots on optical coherence tomography in 6 eyes (43%). Granularity on FAF was associated with active lymphoma in majority of the cases. An inversion of FAF (hyperautofluorescent spots on FAF corresponding to hypofluorescent spots on fluorescein angiography) was observed in less than half of the eyes.

Dermatoglyphics and Karyotype Analysis in Primary Amenorrhoea

PubMed Central

Sontakke, Bharat R; Waghmare, Jwalant E; Tarnekar, Aditya M; Shende, Moreshwar R; Pal, Asoke K

2014-01-01

Background: Dermatoglyphics is the scientific study of the skin ridge patterns on the fingers, toes, palms of the hands and soles of feet. Dermatoglyphics is in use as a supportive diagnostic tool in genetic or chromosomal disorders as well as in clinical conditions with genetic etiologies. Primary amenorrhoea and Dermatoglyphics, both have the suspected multifactorial (genetic and environmental) aetiologies. Objective: In the present study the finger dermatoglyphic patterns were studied in primary amenorrhoea cases and age matched fertile control females and also attention was given to find out whether a specific dermatoglyphic trait exists in primary amenorrhoea cases and whether it was statistically significant. Materials and Methods: To study the role of dermatoglyphics in primary amenorrhoea, a study was conducted on 30 subjects with primary amenorrhoea (as cases) and compared it with equal number of age matched fertile females (as controls). We studied fingertip patterns in all the subjects enrolled. Simultaneously we have assessed the Karyotype of primary amenorrhoea cases. Result and Conclusion: Two subjects in experimental group have shown abnormal Karyotypes. The most significant finding in present study was increased total finger ridge count (TFRC) in primary amenorrhoea cases which was statistically significant. We also found higher frequency of loops and arches in primary amenorrhoea with abnormal karyotypes. This type of study may be quite useful as a supportive investigation, in stating the predisposition of an individual to primary amenorrhoea and referral of an individual for karyotyping. PMID:25653930

Immunohistochemical expression of Hsp60 correlates with tumor progression and hormone resistance in prostate cancer.

PubMed

Castilla, Carolina; Congregado, Belén; Conde, José M; Medina, Rafael; Torrubia, Francisco J; Japón, Miguel A; Sáez, Carmen

2010-10-01

To investigate the expression of Hsp60 protein in prostate cancer biopsy samples, and its association with prognostic clinical parameters and hormone resistance and survival. Molecular chaperones are involved in protein folding, protein degradation, and protein trafficking among subcellular compartments. We selected 107 patients with localized and locally advanced prostate cancer at our hospital from 1999 through 2004. We performed an analysis by western blot and immunohistochemistry on paraffin-embedded tissue sections. Clinical data were used to determine associations between immunohistochemical expression of Hsp60 and tumor behavior. The expression level of Hsp60 was significantly increased in tumors with high Gleason score (P < .001). Hsp60 expression was also significantly associated with initial serum PSA levels (P < .01) and with the presence of lymph node metastasis (P < .003). In 50 locally advanced cancers treated by androgen ablation we found an association between high Hsp60-expressing tumors and an early onset of hormone refractory disease (P < .02) and reduced cancer-specific survival (P < .05). Hsp60 protein is overexpressed in poorly differentiated prostate cancers. Hsp60 expression is strongly associated with prognostic clinical parameters, such as Gleason score, initial serum PSA levels, and lymph node metastasis and with the onset of hormone-refractory disease and reduced cancer-specific survival. Identification of such markers could be of relevance in the clinical management of prostate cancer. Copyright © 2010 Elsevier Inc. All rights reserved.

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.

A comparison of radical retropubic with perineal prostatectomy for localized prostate cancer within the Uniformed Services Urology Research Group.

PubMed

Lance, R S; Freidrichs, P A; Kane, C; Powell, C R; Pulos, E; Moul, J W; McLeod, D G; Cornum, R L; Brantley Thrasher J

2001-01-01

To review and compare the outcome of patients undergoing radical retropubic prostatectomy (RRP) or radical perineal prostatectomy (RPP) for clinically localized prostate cancer. From 1988 to 1997, 1382 men who were treated by RRP and 316 by RPP were identified from databases of the Uniformed Services Urology Research Group. The following variables were assessed; age, race, prostate-specific antigen (PSA) level before surgery, clinical stage, biopsy Gleason sum, estimated blood loss (EBL), margin-positive rate, pathological stage, biochemical recurrence rate, short and long-term complication rates, impotence and incontinence rates. To eliminate selection bias, the analysis was concentrated on pairs of patients matched by race, preoperative PSA level, clinical stage and biopsy Gleason sum. In the 190 matched patients there were no significant differences between the RRP and RPP groups in either organ-confined (57% vs 55%), margin-positive (39% vs 43%), or biochemical recurrence rates (12.9% vs 17.6% at a mean follow-up of 47.1 vs 42.9 months), respectively. The mean EBL was 1575 mL in the RRP group and 802 mL in the RPP group (P < 0.001). The only significant difference in complication rates was a higher incidence of rectal injury in the RPP group (4.9%) than in the RRP group (none, P < 0.05). In similar populations of patients, RPP offers equivalent organ-confined, margin-positive and biochemical recurrence rates to RRP, while causing significantly less blood loss.

The association between metabolic syndrome and prostate cancer: Effect on its aggressiveness and progression.

PubMed

Sanchís-Bonet, A; Ortiz-Vico, F; Morales-Palacios, N; Sánchez-Chapado, M

2015-04-01

To evaluate the impact of metabolic syndrome and its individual components on prostate biopsy findings, the radical prostatectomy specimen and on biochemical recurrence. An observational study was conducted of 1319 men who underwent prostate biopsy between January 2007 and December 2011. The impact on the biopsy findings, the radical prostatectomy specimen and biochemical recurrence was evaluated using logistic regression and Cox regression. Of the 1319 patients, 275 (21%) had metabolic syndrome, and 517 prostate cancers were diagnosed. A greater percentage of metabolic syndrome was found among patients with prostate cancer than among patients without prostate cancer (25% vs. 18%; P=.002). Poorer results were found in the radical prostatectomy specimens (Gleason score ≥ 7, P<.001; stage ≥ T2c, P<.001; positive surgical margins, P<.001), and there was a greater percentage of biochemical recurrence in patients with metabolic syndrome than in those without metabolic syndrome (24% vs. 13%; P=.003). Metabolic syndrome behaved as an independent predictive factor of finding a Gleason score ≥ 7 for the specimen, as well as for finding a specimen stage ≥ T2c. Metabolic syndrome was also able to independently predict a greater rate of biochemical recurrence (OR: 3.6, P<.001; OR: 3.2, P=.03; HR: 1.7; respectively). Metabolic syndrome is associated with poorer findings in the radical prostatectomy specimens and is an independent prognostic factor of biochemical recurrence. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

TMPRSS2:ERG Gene Fusions in Prostate Cancer of West African Men and a Meta-Analysis of Racial Differences

PubMed Central

Zhou, Cindy Ke; Young, Denise; Yeboah, Edward D; Coburn, Sally B; Tettey, Yao; Biritwum, Richard B; Adjei, Andrew A; Tay, Evelyn; Niwa, Shelley; Truelove, Ann; Welsh, Judith; Mensah, James E; Hoover, Robert N; Sesterhenn, Isabell A; Hsing, Ann W; Srivastava, Shiv; Cook, Michael B

2017-01-01

Abstract The prevalence of fusions of the transmembrane protease, serine 2, gene (TMPRSS2) with the erythroblast transformation-specific–related gene (ERG), or TMPRSS2:ERG, in prostate cancer varies by race. However, such somatic aberration and its association with prognostic factors have neither been studied in a West African population nor been systematically reviewed in the context of racial differences. We used immunohistochemistry to assess oncoprotein encoded by the ERG gene as the established surrogate of ERG fusion genes among 262 prostate cancer biopsies from the Ghana Prostate Study (2004–2006). Poisson regression with robust variance estimation provided prevalence ratios and 95% confidence intervals of ERG expression in relation to patient characteristics. We found that 47 of 262 (18%) prostate cancers were ERG-positive, and being negative for ERG staining was associated with higher Gleason score. We further conducted a systematic review and meta-analysis of TMPRSS2:ERG fusions in relation to race, Gleason score, and tumor stage, combining results from Ghana with 40 additional studies. Meta-analysis showed the prevalence of TMPRSS2:ERG fusions in prostate cancer to be highest in men of European descent (49%), followed by men of Asian (27%) and then African (25%) descent. The lower prevalence of TMPRSS2:ERG fusions in men of African descent implies that alternative genomic mechanisms might explain the disproportionately high prostate cancer burden in such populations. PMID:28633309

Progesterone receptor expression during prostate cancer progression suggests a role of this receptor in stromal cell differentiation.

PubMed

Yu, Yue; Yang, Ou; Fazli, Ladan; Rennie, Paul S; Gleave, Martin E; Dong, Xuesen

2015-07-01

The progesterone receptor, like the androgen receptor, belongs to the steroid receptor superfamily. Our previous studies have reported that the PR is expressed specifically in prostate stroma. PR inhibits proliferation of, and regulates cytokine secretion by stromal cells. However, PR protein expression in cancer-associated stroma during prostate cancer progression has not been profiled. Since the phenotypes of prostate stromal cells change dynamically as tumors progress, whether the PR plays a role in regulating stromal cell differentiation needs to be investigated. Immunohistochemistry assays measured PR protein levels on human prostate tissue microarrays containing 367 tissue cores from benign prostate, prostate tumors with different Gleason scores, tumors under various durations of castration therapy, and tumors at the castration-resistant stage. Immunoblotting assays determined whether PR regulated the expression of alpha smooth muscle actin (α-SMA), vimentin, and fibroblast specific protein (FSP) in human prostate stromal cells. PR protein levels decreased in cancer-associated stroma when compared with that in benign prostate stroma. This reduction in PR expression was not correlated with Gleason scores. PR protein levels were elevated by castration therapy, but reduced to pre-castration levels when tumors progressed to the castration-resistant stage. Enhanced PR expression in human prostate stromal cells increased α-SMA, but decreased vimentin and FSP protein levels ligand-independently. These results suggest that PR plays an active role in regulating stromal cell phenotypes during prostate cancer progression. © 2015 Wiley Periodicals, Inc.

Absolute Quantitation of DNA Methylation of 28 Candidate Genes in Prostate Cancer Using Pyrosequencing

PubMed Central

Vasiljeviš, Nataڑa; Wu, Keqiang; Brentnall, Adam R.; Kim, Dae Cheol; Thorat, Mangesh A.; Kudahetti, Sakunthala C.; Mao, Xueying; Xue, Liyan; Yu, Yongwei; Shaw, Greg L.; Beltran, Luis; Lu, Yong-Jie; Berney, Daniel M.; Cuzick, Jack; Lorincz, Attila T.

2011-01-01

Aberrant DNA methylation plays a pivotal role in carcinogenesis and its mapping is likely to provide biomarkers for improved diagnostic and risk assessment in prostate cancer (PCa). We quantified and compared absolute methylation levels among 28 candidate genes in 48 PCa and 29 benign prostate hyperplasia (BPH) samples using the pyrosequencing (PSQ) method to identify genes with diagnostic and prognostic potential. RARB, HIN1, BCL2, GSTP1, CCND2, EGFR5, APC, RASSF1A, MDR1, NKX2-5, CDH13, DPYS, PTGS2, EDNRB, MAL, PDLIM4, HLAa, ESR1 and TIG1 were highly methylated in PCa compared to BPH (p < 0.001), while SERPINB5, CDH1, TWIST1, DAPK1, THRB, MCAM, SLIT2, CDKN2a and SFN were not. RARB methylation above 21% completely distinguished PCa from BPH. Separation based on methylation level of SFN, SLIT2 and SERPINB5 distinguished low and high Gleason score cancers, e.g. SFN and SERPINB5 together correctly classified 81% and 77% of high and low Gleason score cancers respectively. Several genes including CDH1 previously reported as methylation markers in PCa were not confirmed in our study. Increasing age was positively associated with gene methylation (p < 0.0001). Accurate quantitative measurement of gene methylation in PCa appears promising and further validation of genes like RARB, HIN1, BCL2, APC and GSTP1 is warranted for diagnostic potential and SFN, SLIT2 and SERPINB5 for prognostic potential. PMID:21694441

Reduced mitochondrial DNA content associates with poor prognosis of prostate cancer in African American men.

PubMed

Koochekpour, Shahriar; Marlowe, Timothy; Singh, Keshav K; Attwood, Kristopher; Chandra, Dhyan

2013-01-01

Reduction or depletion of mitochondrial DNA (mtDNA) has been associated with cancer progression. Although imbalanced mtDNA content is known to occur in prostate cancer, differences in mtDNA content between African American (AA) and Caucasian American (CA) men are not defined. We provide the first evidence that tumors in AA men possess reduced level of mtDNA compared to CA men. The median tumor mtDNA content was reduced in AA men. mtDNA content was also reduced in normal prostate tissues of AA men compared to CA men, suggesting a possible predisposition to cancer in AA men. mtDNA content was also reduced in benign prostatic hyperplasia (BPH) tissue from AA men. Tumor and BPH tissues from patients ≥ 60 years of age possess reduced mtDNA content compared to patients <60 years of age. In addition, mtDNA content was higher in normal tissues from patients with malignant T3 stage disease compared to patients with T2 stage disease. mtDNA levels in matched normal prostate tissues were nearly doubled in Gleason grade of >7 compared to ≤ 7, whereas reduced mtDNA content was observed in tumors of Gleason grade >7 compared to ≤ 7. Together, our data suggest that AA men possess lower mtDNA levels in normal and tumor tissues compared to CA men, which could contribute to higher risk and more aggressive prostate cancer in AA men.

The activation pattern of macrophages in giant cell (temporal) arteritis and primary angiitis of the central nervous system.

PubMed

Mihm, Bernhard; Bergmann, Markus; Brück, Wolfgang; Probst-Cousin, Stefan

2014-06-01

To determine if the pattern of macrophage activation reflects differences in the pathogenesis and clinical presentation of giant cell arteritis and primary angiitis of the central nervous system, specimens of 10 patients with giant cell arteritis and five with primary angiitis of the central nervous system were immunohistochemically studied and the expression of the macrophage activation markers 27E10, MRP14, MRP8 and 25F9 was determined in the vasculitic infiltrates. Thus, a partly different expression pattern of macrophage activation markers in giant cell arteritis and primary angiitis of the central nervous system was observed. The group comparison revealed that giant cell arteritis cases had significantly higher numbers of acute activated MRP14-positive macrophages, whereas primary angiitis of the central nervous system is characterized by a tendency toward more MRP8-positive intermediate/late activated macrophages. Furthermore, in giant cell arteritis comparably fewer CD8-positive lymphocytes were observed. These observations suggest, that despite their histopathological similarities, giant cell arteritis and primary angiitis of the central nervous system appear to represent either distinct entities within the spectrum of granulomatous vasculitides or different stages of similar disease processes. Their discrete clinical presentation is reflected by different activation patterns of macrophages, which may characterize giant cell arteritis as a more acute process and primary angiitis of the central nervous system as a more advanced inflammatory process. © 2013 Japanese Society of Neuropathology.

Decreased expression of serine protease inhibitor family G1 (SERPING1) in prostate cancer can help distinguish high-risk prostate cancer and predicts malignant progression.

PubMed

Peng, Shengmeng; Du, Tao; Wu, Wanhua; Chen, Xianju; Lai, Yiming; Zhu, Dingjun; Wang, Qiong; Ma, Xiaoming; Lin, Chunhao; Li, Zean; Guo, Zhenghui; Huang, Hai

2018-06-11

The aim of this study was to investigate the associations of serine proteinase inhibitor family G1 (SERPING1) down-regulation with poor prognosis in patients with prostate cancer (PCa). Furthermore, we aim to find more novel and effective PCa molecular markers to provide an early screening of PCa, distinguish patients with aggressive PCa, predict the prognosis, or reduce the economic burden of PCa. SERPING1 protein expression in both human PCa and normal prostate tissues was detected by immunohistochemical staining, which intensity was analyzed in association with clinical pathological parameters such Gleason score, pathological grade, clinical stage, tumor stage, lymph node metastasis, and distant metastasis. Moreover, we used The Cancer Genome Atlas (TCGA) Database, Taylor Database, and Oncomine dataset to validate our immunohistochemical results and investigated the value of SERPING1 in PCa at mRNA level. Kaplan-Meier analysis and Cox regression analysis were performed to evaluate the relationship between SERPING1 and prognosis of patients with PCa. The outcome showed that SERPING1 was expressed mainly in cytoplasm of grand cells of prostate tissue and was significantly expressed less in PCa (P<0.001). Furthermore, in the tissue microarray of our samples, decreasing expression of SERPING1 was correlated with the higher Gleason score (P = 0.004), the higher pathological grade (P = 0.01) and the advanced tumor stage (P = 0.005) at protein level. In TCGA dataset and Taylor Dataset, low-expressed SERPING1 was correlated with the younger patient (P = 0.02 in TCGA, P = 0.044 in Taylor) and the higher Gleason score (P = 0.019 in TCGA, P<0.001 in Taylor) at mRNA level. Kaplan-Meier analysis revealed that the lower mRNA of SERPING1 predicted lower overall survivals (P = 0.027 in TCGA), lower disease-free survival (P = 0.029) and lower biochemical recurrence-free survival (P = 0.011 in Taylor). Data from Oncomine database shown that SERPING1 low expression implying higher malignancy of prostate lesions. Using multivariate analysis, we also found that SERPING1 expression was independent prognostic marker of poor disease-free survival and biochemical recurrence-free survival. SERPING1 may play an important role in PCa and can be serve as a novel marker in diagnosis and prognostic prediction in PCa. In addition, levels of SERPING1 can help identify low-risk prostate to provide reference for patients with PCa to accept active surveillance and reduce overtreatment. Copyright © 2018 Elsevier Inc. All rights reserved.

PSA Nadir of <0.5 ng/mL Following Brachytherapy for Early-Stage Prostate Adenocarcinoma is Associated With Freedom From Prostate-Specific Antigen Failure

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

Ko, Eric C.; Stone, Nelson N.; Department of Urology, Mount Sinai Medical Center, New York, NY

2012-06-01

Purpose: Because limited information exists regarding whether the rate or magnitude of PSA decline following brachytherapy predicts long-term clinical outcomes, we evaluated whether achieving a prostate-specific antigen (PSA) nadir (nPSA) <0.5 ng/mL following brachytherapy is associated with decreased PSA failure and/or distant metastasis. Methods and Materials: We retrospectively analyzed our database of early-stage prostate adenocarcinoma patients who underwent brachytherapy, excluding those receiving androgen-deprivation therapy and those with <2 years follow-up. Median and mean pretreatment PSA were 6 ng/mL and 7.16 ng/mL, respectively. By clinical stage, 775 were low risk ({<=}T2a), 126 were intermediate risk (T2b), and 20 were high riskmore » (>T2b). By Gleason score, 840 were low risk ({<=}6), 71 were intermediate risk (7), and 10 were high risk (>7). Patients were treated with brachytherapy only (I-125, n = 779, or Pd-103, n = 47), or brachytherapy + external-beam radiation therapy (n = 95). Median follow-up was 6.3 years. We noted whether nPSA <0.5 ng/mL was achieved and the time to achieve this nadir and tested for associations with pretreatment risk factors. We also determined whether this PSA endpoint was associated with decreased PSA failure or distant metastasis. Results: Absence of high-risk factors in clinical stage ({<=}T2b), Gleason score ({<=}7), and pretreatment PSA ({<=}20 ng/mL) was significantly associated with achieving nPSA <0.5 ng/mL. By Kaplan-Meier analysis, patients achieving nPSA <0.5 ng/mL had significantly higher long-term freedom from biochemical failure (FFBF) than nonresponders (5-year FFBF: 95.2 {+-} 0.8% vs. 71.5 {+-} 6.7%; p < 0.0005). Among responders, those who achieved nPSA <0.5 ng/mL in {<=}5 years had higher FFBF than those requiring >5 years (5-year FFBF: 96.7 {+-} 0.7% vs. 80.8 {+-} 4.6%; p < 0.0005). On multivariate analysis, patients who achieved nPSA <0.5 ng/mL in {<=}5 years had significantly higher FFBF than other patients. Conclusions: Pretreatment risk factors (clinical tumor stage, Gleason score, pretreatment PSA) strongly predict for patients achieving nPSA <0.5 ng/mL following brachytherapy, and this cohort had significantly higher long-term FFBF.« less

PSA nadir of <0.5 ng/mL following brachytherapy for early-stage prostate adenocarcinoma is associated with freedom from prostate-specific antigen failure.

PubMed

Ko, Eric C; Stone, Nelson N; Stock, Richard G

2012-06-01

Because limited information exists regarding whether the rate or magnitude of PSA decline following brachytherapy predicts long-term clinical outcomes, we evaluated whether achieving a prostate-specific antigen (PSA) nadir (nPSA) <0.5 ng/mL following brachytherapy is associated with decreased PSA failure and/or distant metastasis. We retrospectively analyzed our database of early-stage prostate adenocarcinoma patients who underwent brachytherapy, excluding those receiving androgen-deprivation therapy and those with <2 years follow-up. Median and mean pretreatment PSA were 6 ng/mL and 7.16 ng/mL, respectively. By clinical stage, 775 were low risk (≤ T2a), 126 were intermediate risk (T2b), and 20 were high risk (>T2b). By Gleason score, 840 were low risk (≤ 6), 71 were intermediate risk (7), and 10 were high risk (>7). Patients were treated with brachytherapy only (I-125, n = 779, or Pd-103, n = 47), or brachytherapy + external-beam radiation therapy (n = 95). Median follow-up was 6.3 years. We noted whether nPSA <0.5 ng/mL was achieved and the time to achieve this nadir and tested for associations with pretreatment risk factors. We also determined whether this PSA endpoint was associated with decreased PSA failure or distant metastasis. Absence of high-risk factors in clinical stage (≤ T2b), Gleason score (≤ 7), and pretreatment PSA (≤ 20 ng/mL) was significantly associated with achieving nPSA <0.5 ng/mL. By Kaplan-Meier analysis, patients achieving nPSA <0.5 ng/mL had significantly higher long-term freedom from biochemical failure (FFBF) than nonresponders (5-year FFBF: 95.2 ± 0.8% vs. 71.5 ± 6.7%; p < 0.0005). Among responders, those who achieved nPSA <0.5 ng/mL in ≤ 5 years had higher FFBF than those requiring >5 years (5-year FFBF: 96.7 ± 0.7% vs. 80.8 ± 4.6%; p < 0.0005). On multivariate analysis, patients who achieved nPSA <0.5 ng/mL in ≤ 5 years had significantly higher FFBF than other patients. Pretreatment risk factors (clinical tumor stage, Gleason score, pretreatment PSA) strongly predict for patients achieving nPSA <0.5 ng/mL following brachytherapy, and this cohort had significantly higher long-term FFBF. Copyright © 2012 Elsevier Inc. All rights reserved.

Impact of Lesion Visibility on Transrectal Ultrasound on the Prediction of Clinically Significant Prostate Cancer (Gleason Score 3 + 4 or Greater) with Transrectal Ultrasound-Magnetic Resonance Imaging Fusion Biopsy.

PubMed

Garcia-Reyes, Kirema; Nguyen, Hao G; Zagoria, Ronald J; Shinohara, Katsuto; Carroll, Peter R; Behr, Spencer C; Westphalen, Antonio C

2017-09-20

The purpose of this study was to estimate the impact of lesion visibility with transrectal ultrasound on the prediction of clinically significant prostate cancer with transrectal ultrasound-magnetic resonance imaging fusion biopsy. This HIPAA (Health Insurance Portability and Accountability Act) compliant, institutional review board approved, retrospective study was performed in 178 men who were 64.7 years old with prostate specific antigen 8.9 ng/ml. They underwent transrectal ultrasound-magnetic resonance imaging fusion biopsy from January 2013 to September 2016. Visible lesions on magnetic resonance imaging were assigned a PI-RADS™ (Prostate Imaging Reporting and Data System), version 2 score of 3 or greater. Transrectal ultrasound was positive when a hypoechoic lesion was identified. We used a 3-level, mixed effects logistic regression model to determine how transrectal ultrasound-magnetic resonance imaging concordance predicted the presence of clinically significant prostate cancer. The diagnostic performance of the 2 methods was estimated using ROC curves. A total of 1,331 sextants were targeted by transrectal ultrasound-magnetic resonance imaging fusion or systematic biopsies, of which 1,037 were negative, 183 were Gleason score 3 + 3 and 111 were Gleason score 3 + 4 or greater. Clinically significant prostate cancer was diagnosed by transrectal ultrasound and magnetic resonance imaging alone at 20.5% and 19.7% of these locations, respectively. Men with positive imaging had higher odds of clinically significant prostate cancer than men without visible lesions regardless of modality (transrectal ultrasound OR 14.75, 95% CI 5.22-41.69, magnetic resonance imaging OR 12.27, 95% CI 6.39-23.58 and the 2 modalities OR 28.68, 95% CI 14.45-56.89, all p <0.001). The ROC AUC to detect clinically significant prostate cancer using the 2 methods (0.85, 95% CI 0.81-0.89) was statistically greater than that of transrectal ultrasound alone (0.80, 95% CI 0.76-0.85, p = 0.001) and magnetic resonance imaging alone (0.83, 95% CI 0.79-0.87, p = 0.04). The sensitivity and specificity of transrectal ultrasound were 42.3% and 91.6%, and the sensitivity and specificity of magnetic resonance imaging were 62.2% and 84.1%, respectively. Lesion visibility on magnetic resonance imaging or transrectal ultrasound denotes a similar probability of clinically significant prostate cancer. This probability is greater when each examination is positive. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

99m Tc-MIP-1404-SPECT/CT for the detection of PSMA-positive lesions in 225 patients with biochemical recurrence of prostate cancer.

PubMed

Schmidkonz, Christian; Hollweg, Claudia; Beck, Michael; Reinfelder, Julia; Goetz, Theresa I; Sanders, James C; Schmidt, Daniela; Prante, Olaf; Bäuerle, Tobias; Cavallaro, Alexander; Uder, Michael; Wullich, Bernd; Goebell, Peter; Kuwert, Torsten; Ritt, Philipp

2018-01-01

99m Tc-MIP-1404 (Progenics Pharmaceuticals, Inc., New York, NY) is a novel, SPECT-compatible 99m Tc-labeled PSMA inhibitor for the detection of prostate cancer. We present results of its clinical use in a cohort of 225 men with histologically confirmed prostate cancer referred for workup of biochemical relapse. From April 2013 to April 2017, 99m Tc-MIP1404-scintigraphy was performed in 225 patients for workup of PSA biochemical relapse of prostate cancer. Whole-body planar and SPECT/CT images of the lower abdomen and thorax were obtained 3-4 h p.i. of 710 ± 64 MBq 99m Tc-MIP-1404. Images were visually analyzed for presence and location of abnormal uptake. In addition, quantitative analysis of the SPECT/CT data was carried out on a subset of 125 patients. Follow-up reports of subsequent therapeutic interventions were available for 59% (139) of all patients. Tracer-positive lesions were detected in 77% (174/225) of all patients. Detections occurred at the area of local recurrence in the prostate in 25% of patients (or a total of 56), with metastases in lymph nodes in 47% (105), bone in 27% (60), lung in 5% (12), and other locations in 2% (4) of patients. Detection rates were 90% at PSA levels ≥2 ng/mL and 54% below that threshold. Lesional SUVmax values were, on average, 32.2 ± 29.6 (0.8-142.2), and tumor-to-normal ratios 146.6 ± 160.5 (1.9-1482.4). The PSA level correlated significantly with total uptake of MIP-1404 in tumors (P < 0.001). Furthermore, total tumor uptake was significantly higher in patients with Gleason scores ≥8 compared to those with Gleason scores ≤7 (P < 0.05). In patients with androgen deprivation therapy, the detection rate was significantly higher compared to patients without androgen deprivation therapy (86% vs 71%, P < 0.001). Based on 99m Tc-MIP-1404-imaging and other information, an interdisciplinary tumor board review recommended changes to treatment plans in 74% (104/139) of those patients for whom the necessary documentation was available. SPECT/CT with 99m Tc-labeled MIP-1404 has a high probability in detecting PSMA-positive lesions in patients with elevated PSA. Statistical analysis disclosed significant relationship between quantitative 99m Tc-MIP-1404 uptake, PSA level, and Gleason score. © 2017 Wiley Periodicals, Inc.

High-Intensity Focused Ultrasound (HIFU) in Localized Prostate Cancer Treatment.

PubMed

Alkhorayef, Mohammed; Mahmoud, Mustafa Z; Alzimami, Khalid S; Sulieman, Abdelmoneim; Fagiri, Maram A

2015-01-01

High-intensity focused ultrasound (HIFU) applies high-intensity focused ultrasound energy to locally heat and destroy diseased or damaged tissue through ablation. This study intended to review HIFU to explain the fundamentals of HIFU, evaluate the evidence concerning the role of HIFU in the treatment of prostate cancer (PC), review the technologies used to perform HIFU and the published clinical literature regarding the procedure as a primary treatment for PC. Studies addressing HIFU in localized PC were identified in a search of internet scientific databases. The analysis of outcomes was limited to journal articles written in English and published between 2000 and 2013. HIFU is a non-invasive approach that uses a precisely delivered ultrasound energy to achieve tumor cell necrosis without radiation or surgical excision. In current urological oncology, HIFU is used clinically in the treatment of PC. Clinical research on HIFU therapy for localized PC began in the 1990s, and the majority of PC patients were treated with the Ablatherm device. HIFU treatment for localized PC can be considered as an alternative minimally invasive therapeutic modality for patients who are not candidates for radical prostatectomy. Patients with lower pre-HIFU PSA level and favourable pathologic Gleason score seem to present better oncologic outcomes. Future advances in technology and safety will undoubtedly expand the HIFU role in this indication as more of patient series are published, with a longer follow-up period.

Prognostic Value of Protocadherin10 (PCDH10) Methylation in Serum of Prostate Cancer Patients.

PubMed

Deng, Qiu-Kui; Lei, Yong-Gang; Lin, Ying-Li; Ma, Jian-Guo; Li, Wen-Ping

2016-02-16

BACKGROUND Prostate cancer is a heterogeneous malignancy with outcome difficult to predict. Currently, there is an urgent need to identify novel biomarkers that can accurately predict patient outcome and improve the treatment strategy. The aim of this study was to investigate the methylation status of PCDH10 in serum of prostate cancer patients and its potential relevance to clinicopathological features and prognosis. MATERIAL AND METHODS The methylation status of PCDH10 in serum of 171 primary prostate cancer patients and 65 controls was evaluated by methylation-specific PCR (MSP), after which the relationship between PCDH10 methylation and clinicopathologic features was evaluated. Kaplan-Meier survival analysis and Cox analysis were used to evaluate the correlation between PCDH10 methylation and prognosis. RESULTS PCDH10 methylation occurred frequently in serum of prostate cancer patients. Moreover, PCDH10 methylation was significantly associated with higher preoperative PSA level, advanced clinical stage, higher Gleason score, lymph node metastasis, and biochemical recurrence (BCR). In addition, patients with methylated PCDH10 had shorter BCR-free survival and overall survival than patients with unmethylated PCDH10. Univariate and multivariate Cox proportional hazards model analysis indicated that PCDH10 methylation in serum is an independent predictor of worse BCR-free survival and overall survival. CONCLUSIONS PCDH10 methylation in serum is a potential prognostic biomarker for prostate cancer.

Positron emission tomography (PET) imaging of prostate cancer with a gastrin releasing peptide receptor antagonist--from mice to men.

PubMed

Wieser, Gesche; Mansi, Rosalba; Grosu, Anca L; Schultze-Seemann, Wolfgang; Dumont-Walter, Rebecca A; Meyer, Philipp T; Maecke, Helmut R; Reubi, Jean Claude; Weber, Wolfgang A

2014-01-01

Ex vivo studies have shown that the gastrin releasing peptide receptor (GRPr) is overexpressed on almost all primary prostate cancers, making it a promising target for prostate cancer imaging and targeted radiotherapy. Biodistribution, dosimetry and tumor uptake of the GRPr antagonist ⁶⁴Cu-CB-TE2A-AR06 [(⁶⁴Cu-4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo(6.6.2)hexadecane)-PEG₄-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-LeuNH₂] were studied by PET/CT in four patients with newly diagnosed prostate cancer (T1c-T2b, Gleason 6-7). No adverse events were observed after injection of ⁶⁴Cu-CB-TE2A-AR06. Three of four tumors were visualized with high contrast [tumor-to-prostate ratio > 4 at 4 hours (h) post injection (p.i.)], one small tumor (T1c, < 5% tumor on biopsy specimens) showed moderate contrast (tumor-to-prostate ratio at 4 h: 1.9). Radioactivity was cleared by the kidneys and only the pancreas demonstrated significant accumulation of radioactivity, which rapidly decreased over time. ⁶⁴Cu-CB-TE2A-AR06 shows very favorable characteristics for imaging prostate cancer. Future studies evaluating ⁶⁴Cu-CB-TE2A-AR06 PET/CT for prostate cancer detection, staging, active surveillance, and radiation treatment planning are necessary.

Automated high-grade prostate cancer detection and ranking on whole slide images

NASA Astrophysics Data System (ADS)

Huang, Chao-Hui; Racoceanu, Daniel

2017-03-01

Recently, digital pathology (DP) has been largely improved due to the development of computer vision and machine learning. Automated detection of high-grade prostate carcinoma (HG-PCa) is an impactful medical use-case showing the paradigm of collaboration between DP and computer science: given a field of view (FOV) from a whole slide image (WSI), the computer-aided system is able to determine the grade by classifying the FOV. Various approaches have been reported based on this approach. However, there are two reasons supporting us to conduct this work: first, there is still room for improvement in terms of detection accuracy of HG-PCa; second, a clinical practice is more complex than the operation of simple image classification. FOV ranking is also an essential step. E.g., in clinical practice, a pathologist usually evaluates a case based on a few FOVs from the given WSI. Then, makes decision based on the most severe FOV. This important ranking scenario is not yet being well discussed. In this work, we introduce an automated detection and ranking system for PCa based on Gleason pattern discrimination. Our experiments suggested that the proposed system is able to perform high-accuracy detection ( 95:57% +/- 2:1%) and excellent performance of ranking. Hence, the proposed system has a great potential to support the daily tasks in the medical routine of clinical pathology.

Human PIRH2 Enhances Androgen Receptor Signaling through Inhibition of Histone Deacetylase 1 and Is Overexpressed in Prostate Cancer

PubMed Central

Logan, Ian R.; Gaughan, Luke; McCracken, Stuart R. C.; Sapountzi, Vasileia; Leung, Hing Y.; Robson, Craig N.

2006-01-01

The androgen receptor (AR) is a hormone-dependent transcription factor critically involved in human prostate carcinogenesis. Optimal transcriptional control of androgen-responsive genes by AR may require complex interaction among multiple coregulatory proteins. We have previously shown that the AR coregulator TIP60 can interact with human PIRH2 (hPIRH2). In this study, we uncover important new functional role(s) for hPIRH2 in AR signaling: (i) hPIRH2 interacts with AR and enhances AR-mediated transcription with a dynamic pattern of recruitment to androgen response elements in the prostate-specific antigen (PSA) gene; (ii) hPIRH2 interacts with the AR corepressor HDAC1, leading to reduced HDAC1 protein levels and inhibition of transcriptional repression; (iii) hPIRH2 is required for optimal PSA expression; and (iv) hPIRH2 is involved in prostate cancer cell proliferation. In addition, overexpression of hPIRH2 protein was detected in 73 of 82 (89%) resected prostate cancers, with a strong correlation between increased hPIRH2 expression and aggressive disease, as signified by high Gleason sum scores and the presence of metastatic disease (P = <0.0001 and 0.0004, respectively). Collectively, our data establish hPIRH2 as a key modulator of AR function, opening a new direction for targeted therapy in aggressive human prostate cancer. PMID:16914734

Human PIRH2 enhances androgen receptor signaling through inhibition of histone deacetylase 1 and is overexpressed in prostate cancer.

PubMed

Logan, Ian R; Gaughan, Luke; McCracken, Stuart R C; Sapountzi, Vasileia; Leung, Hing Y; Robson, Craig N

2006-09-01

The androgen receptor (AR) is a hormone-dependent transcription factor critically involved in human prostate carcinogenesis. Optimal transcriptional control of androgen-responsive genes by AR may require complex interaction among multiple coregulatory proteins. We have previously shown that the AR coregulator TIP60 can interact with human PIRH2 (hPIRH2). In this study, we uncover important new functional role(s) for hPIRH2 in AR signaling: (i) hPIRH2 interacts with AR and enhances AR-mediated transcription with a dynamic pattern of recruitment to androgen response elements in the prostate-specific antigen (PSA) gene; (ii) hPIRH2 interacts with the AR corepressor HDAC1, leading to reduced HDAC1 protein levels and inhibition of transcriptional repression; (iii) hPIRH2 is required for optimal PSA expression; and (iv) hPIRH2 is involved in prostate cancer cell proliferation. In addition, overexpression of hPIRH2 protein was detected in 73 of 82 (89%) resected prostate cancers, with a strong correlation between increased hPIRH2 expression and aggressive disease, as signified by high Gleason sum scores and the presence of metastatic disease (P = <0.0001 and 0.0004, respectively). Collectively, our data establish hPIRH2 as a key modulator of AR function, opening a new direction for targeted therapy in aggressive human prostate cancer.

Sex Steroid Metabolism in Benign and Malignant Intact Prostate Biopsies: Individual Profiling of Prostate Intracrinology

PubMed Central

Gianfrilli, Daniele; Pierotti, Silvia; Leonardo, Costantino; Ciccariello, Mauro

2014-01-01

In vitro studies reveal that androgens, oestrogens, and their metabolites play a crucial role in prostate homeostasis. Most of the studies evaluated intraprostatic hormone metabolism using cell lines or preprocessed specimens. Using an ex vivo model of intact tissue cultures with preserved architecture, we characterized the enzymatic profile of biopsies from patients with benign prostatic hyperplasia (BPH) or cancer (PC), focusing on 17β-hydroxy-steroid-dehydrogenases (17β-HSDs) and aromatase activities. Samples from 26 men who underwent prostate needle core biopsies (BPH n = 14; PC n = 12) were incubated with radiolabeled 3H-testosterone or 3H-androstenedione. Conversion was evaluated by TLC separation and beta-scanning of extracted supernatants. We identified three major patterns of conversion. The majority of BPHs revealed no active testosterone/oestradiol conversion as opposed to prostate cancer. Conversion correlated with histology and PSA, but not circulating hormones. Highest Gleason scores had a higher androstenedion-to-testosterone conversion and expression of 17β-HSD-isoenzymes-3/5. Conclusions. We developed an easy tool to profile individual intraprostatic enzymatic activity by characterizing conversion pathways in an intact tissue environment. In fresh biopsies we found that 17β-HSD-isoenzymes and aromatase activities correlate with biological behaviour allowing for morphofunctional phenotyping of pathology specimens and clinical monitoring of novel enzyme-targeting drugs. PMID:25184140

Primary EFL Teachers' Technology Use in China: Patterns and Perceptions

ERIC Educational Resources Information Center

Li, Guofang; Ni, Xiaopeng

2011-01-01

Drawing on survey data, this paper examines the patterns and perceptions of technology use by primary EFL teachers in China. Findings suggest that although Chinese EFL teachers hold positive attitudes toward the value of technology for teaching and learning, they use technology mainly for teacher-centered purposes, such as teaching preparation and…

An Analysis of Primary School Dropout Patterns in Honduras

ERIC Educational Resources Information Center

Sekiya, Takeshi; Ashida, Akemi

2017-01-01

This study hypothesized that repeating a grade is one reason why Honduran primary students drop out of school but not the main reason. Using longitudinal data, we analyzed student enrollment patterns up until students left school. The results revealed that many students dropped out suddenly without having previously repeated a grade, although many…

Regulated Divergence: Textual Patterns, Creativity and Cognitive Emotion Regulation

ERIC Educational Resources Information Center

Kopcsó, Krisztina; Láng, András

2017-01-01

According to literature, several forms of creativity relate to primary process and adaptive regression. The major aim of this study was to examine whether a specific pattern of creativity and primary- and secondary-process thinking could be identified among stories while investigating some personal variables. 78 undergraduate students (41 women,…

Dune field pattern formation and recent transporting winds in the Olympia Undae Dune Field, north polar region of Mars

NASA Astrophysics Data System (ADS)

Ewing, Ryan C.; Peyret, Aymeric-Pierre B.; Kocurek, Gary; Bourke, Mary

2010-08-01

High-Resolution Imaging Science Experiment (HiRISE) imagery of the central Olympia Undae Dune Field in the north polar region of Mars shows a reticulate dune pattern consisting of two sets of nearly orthogonal dune crestlines, with apparent slipfaces on the primary crests, ubiquitous wind ripples, areas of coarse-grained wind ripples, and deflated interdune areas. Geomorphic evidence and dune field pattern analysis of dune crest length, spacing, defect density, and orientation indicates that the pattern is complex, representing two constructional generations of dunes. The oldest and best-organized generation forms the primary crestlines and is transverse to circumpolar easterly winds. Gross bed form-normal analysis of the younger pattern of crestlines indicates that it emerged with both circumpolar easterly winds and NE winds and is reworking the older pattern. Mapping of secondary flow fields over the dunes indicates that the most recent transporting winds were from the NE. The younger pattern appears to represent an influx of sediment to the dune field associated with the development of the Olympia Cavi reentrant, with NE katabatic winds channeling through the reentrant. A model of the pattern reformation based upon the reconstructed primary winds and resulting secondary flow fields shows that the development of the secondary pattern is controlled by the boundary condition of the older dune topography.

Integrated primary care, the collaboration imperative inter-organizational cooperation in the integrated primary care field: a theoretical framework

PubMed Central

Valentijn, Pim P; Bruijnzeels, Marc A; de Leeuw, Rob J; Schrijvers, Guus J.P

2012-01-01

Purpose Capacity problems and political pressures have led to a rapid change in the organization of primary care from mono disciplinary small business to complex inter-organizational relationships. It is assumed that inter-organizational collaboration is the driving force to achieve integrated (primary) care. Despite the importance of collaboration and integration of services in primary care, there is no unambiguous definition for both concepts. The purpose of this study is to examine and link the conceptualisation and validation of the terms inter-organizational collaboration and integrated primary care using a theoretical framework. Theory The theoretical framework is based on the complex collaboration process of negotiation among multiple stakeholder groups in primary care. Methods A literature review of health sciences and business databases, and targeted grey literature sources. Based on the literature review we operationalized the constructs of inter-organizational collaboration and integrated primary care in a theoretical framework. The framework is being validated in an explorative study of 80 primary care projects in the Netherlands. Results and conclusions Integrated primary care is considered as a multidimensional construct based on a continuum of integration, extending from segregation to integration. The synthesis of the current theories and concepts of inter-organizational collaboration is insufficient to deal with the complexity of collaborative issues in primary care. One coherent and integrated theoretical framework was found that could make the complex collaboration process in primary care transparent. This study presented theoretical framework is a first step to understand the patterns of successful collaboration and integration in primary care services. These patterns can give insights in the organization forms needed to create a good working integrated (primary) care system that fits the local needs of a population. Preliminary data of the patterns of collaboration and integration will be presented.

A Summary of Aquatic Vegetation Monitoring at Selected Locations in Pools 4, 8, 13, and 26 and La Grange Pool of the Upper Mississippi River System. 1993 Annual Status Report,

DTIC Science & Technology

1998-07-01

responsibility. The mode of operation and respective roles of the agencies are outlined in a 1988 Memorandum of Agreement. The UMRS encompasses the...University of Wisconsin Press, Madison. 405 pp. Gleason, H. A ., and A . Cronquist . 1991. A manual of vascular plants of northeastern United States...Long Term Resource Monitoring Program Program Report 98-P007 1993 Annual Status Report A Summary of Aquatic Vegetation Monitoring at Selected

Quantum States and Generalized Observables: A Simple Proof of Gleason's Theorem

NASA Astrophysics Data System (ADS)

Busch, P.

2003-09-01

A quantum state can be understood in a loose sense as a map that assigns a value to every observable. Formalizing this characterization of states in terms of generalized probability distributions on the set of effects, we obtain a simple proof of the result, analogous to Gleason’s theorem, that any quantum state is given by a density operator. As a corollary we obtain a vonNeumann type argument against noncontextual hidden variables. It follows that on an individual interpretation of quantum mechanics the values of effects are appropriately understood as propensities.

Identification of the Transformational Properties and Transcriptional Targets of the Oncogenic SRY Transcription Factor SOX4

DTIC Science & Technology

2008-01-01

oncogenic properties of the transcription factor SOX4 and to determine its role in murine prostate development. Our lab has previously shown SOX4...mRNA and protein to be overexpressed in prostate cancer, and this expression is correlated with increasing Gleason score. Other labs have shown SOX4...D. Lieb, Genome Biol 6, R97 (2005). 2. M. van Beest et al., J Biol Chem 275, 27266 (Sep 1, 2000). 3. M. van de Wetering, M. Oosterwegel, K. van

Determination of Selected Distillate Blending Solvents in Simple and Complex Aircraft Fuel Matrices Via Glass Capillary Gas Chromatography.

DTIC Science & Technology

1981-06-01

Division OCT 1 5 1981 June 1981 B Final Report for Period January 1979 - December 1979 j Approved for Public Release; Distribution Unlimited.-I AERO...Solvent 2040 *2040 Blending Solvent Xylene Bottoms *Xylene Bottoms Blending Solvent *Reference: Gleason, C. C., Oller , T. L. Shayeson, M. W., and Bahr...Table 4) was realistic for a 0% by volume point, 17 AFWAL- TR-80-2082 U J & J 18, AFWAL-TR-80-2082 TABLE 4 PEAK AREA PERCENTAGES FOUND IN EACH UNIQUE

Fourier Transformation Theory for Averaged Functions, with Application to Very Long Baseline Radio Interferometry.

DTIC Science & Technology

1981-02-01

primary parameters affecting the SNR. For an earth-based interferometer, the physical aperture may usually be constructed adequately large to keep the...bandwidth Av cent--.c. on vo0 by an interferometer with frequency characteristic F(v) and primary power pattern G(s-s ) (defined as the product of the...infinitely narrow beam for the primary power pattern, G(g- 0 ) = (;-S )] we have where we have assumed a flat frequency response and included as a

Effect of a Low-Intensity PSA-Based Screening Intervention on Prostate Cancer Mortality: The CAP Randomized Clinical Trial.

PubMed

Martin, Richard M; Donovan, Jenny L; Turner, Emma L; Metcalfe, Chris; Young, Grace J; Walsh, Eleanor I; Lane, J Athene; Noble, Sian; Oliver, Steven E; Evans, Simon; Sterne, Jonathan A C; Holding, Peter; Ben-Shlomo, Yoav; Brindle, Peter; Williams, Naomi J; Hill, Elizabeth M; Ng, Siaw Yein; Toole, Jessica; Tazewell, Marta K; Hughes, Laura J; Davies, Charlotte F; Thorn, Joanna C; Down, Elizabeth; Davey Smith, George; Neal, David E; Hamdy, Freddie C

2018-03-06

Prostate cancer screening remains controversial because potential mortality or quality-of-life benefits may be outweighed by harms from overdetection and overtreatment. To evaluate the effect of a single prostate-specific antigen (PSA) screening intervention and standardized diagnostic pathway on prostate cancer-specific mortality. The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) included 419 582 men aged 50 to 69 years and was conducted at 573 primary care practices across the United Kingdom. Randomization and recruitment of the practices occurred between 2001 and 2009; patient follow-up ended on March 31, 2016. An invitation to attend a PSA testing clinic and receive a single PSA test vs standard (unscreened) practice. Primary outcome: prostate cancer-specific mortality at a median follow-up of 10 years. Prespecified secondary outcomes: diagnostic cancer stage and Gleason grade (range, 2-10; higher scores indicate a poorer prognosis) of prostate cancers identified, all-cause mortality, and an instrumental variable analysis estimating the causal effect of attending the PSA screening clinic. Among 415 357 randomized men (mean [SD] age, 59.0 [5.6] years), 189 386 in the intervention group and 219 439 in the control group were included in the analysis (n = 408 825; 98%). In the intervention group, 75 707 (40%) attended the PSA testing clinic and 67 313 (36%) underwent PSA testing. Of 64 436 with a valid PSA test result, 6857 (11%) had a PSA level between 3 ng/mL and 19.9 ng/mL, of whom 5850 (85%) had a prostate biopsy. After a median follow-up of 10 years, 549 (0.30 per 1000 person-years) died of prostate cancer in the intervention group vs 647 (0.31 per 1000 person-years) in the control group (rate difference, -0.013 per 1000 person-years [95% CI, -0.047 to 0.022]; rate ratio [RR], 0.96 [95% CI, 0.85 to 1.08]; P = .50). The number diagnosed with prostate cancer was higher in the intervention group (n = 8054; 4.3%) than in the control group (n = 7853; 3.6%) (RR, 1.19 [95% CI, 1.14 to 1.25]; P < .001). More prostate cancer tumors with a Gleason grade of 6 or lower were identified in the intervention group (n = 3263/189 386 [1.7%]) than in the control group (n = 2440/219 439 [1.1%]) (difference per 1000 men, 6.11 [95% CI, 5.38 to 6.84]; P < .001). In the analysis of all-cause mortality, there were 25 459 deaths in the intervention group vs 28 306 deaths in the control group (RR, 0.99 [95% CI, 0.94 to 1.03]; P = .49). In the instrumental variable analysis for prostate cancer mortality, the adherence-adjusted causal RR was 0.93 (95% CI, 0.67 to 1.29; P = .66). Among practices randomized to a single PSA screening intervention vs standard practice without screening, there was no significant difference in prostate cancer mortality after a median follow-up of 10 years but the detection of low-risk prostate cancer cases increased. Although longer-term follow-up is under way, the findings do not support single PSA testing for population-based screening. ISRCTN Identifier: ISRCTN92187251.

Indigenous Students in Bolivian Primary Schools: Patterns and Determinants of Inequities. A World Bank Study.

ERIC Educational Resources Information Center

McEwan, Patrick J.; Jimenez, Wilson

This paper examines the patterns and determinants of inequities between indigenous and non-indigenous students in Bolivian primary (elementary) schools, using a 1997 survey of third and sixth graders. Analysis shows that, on average, indigenous students are of lower socioeconomic status, and their schools appear to have fewer instructional…

A Repeat Look at Repeating Patterns

ERIC Educational Resources Information Center

Markworth, Kimberly A.

2016-01-01

A "repeating pattern" is a cyclical repetition of an identifiable core. Children in the primary grades usually begin pattern work with fairly simple patterns, such as AB, ABC, or ABB patterns. The unique letters represent unique elements, whereas the sequence of letters represents the core that is repeated. Based on color, shape,…

Soluble syndecan-1 (SDC1) serum level as an independent pre-operative predictor of cancer-specific survival in prostate cancer.

PubMed

Szarvas, Tibor; Reis, Henning; Vom Dorp, Frank; Tschirdewahn, Stephan; Niedworok, Christian; Nyirady, Peter; Schmid, Kurt W; Rübben, Herbert; Kovalszky, Ilona

2016-08-01

PSA-screening detects many cases of clinically non-aggressive prostate cancer (PC) leading to significant overtreatment. Therefore, pre-operatively available prognostic biomarkers are needed to help therapy decisions. Syndecan-1 (SDC1) is a promising prognostic tissue marker in several cancers including PC but serum levels of shedded SDC1-ectodomain (sSDC1) have not been assessed in PC. A total of 150 patients with PC were included in this study (n = 99 serum samples, n = 103 paraffin-embedded samples (FFPE), n = 52 overlap). SDC1 protein expression and cellular localization was evaluated by immunohistochemistry (IHC), while sSDC1 serum concentrations were measured by ELISA. Serum sSDC1 levels were compared to those of MMP7, which is known to be a protease involved in SDC1 ectodomain-shedding. Clinico-pathological and follow-up data were collected and correlated with SDC1 tissue and serum levels. Disease (PC)-specific (DSS) and overall-survival (OS) were primary endpoints. Median follow-up was 167 months in the serum- and 146 months in the FFPE-group. SDC1-reactivity was higher in non-neoplastic prostate glands compared to PC. In addition, cytoplasmatic, but not membranous SDC1 expression was enhanced in PC patients with higher Gleason-score >6 PC (P = 0.016). Soluble SDC1-levels were higher in patients with Gleason-score >6 (P = 0.043) and metastatic disease (P = 0.022) as well as in patients with progressed disease treated with palliative transurethral resection (P = 0.002). In addition, sSDC1 levels were associated with higher MMP7 serum concentration (P = 0.005). In univariable analyses, only sSDC1-levels exhibited a trend to unfavorable DSS (P = 0.077). In a multivariable pre-operative model, high pre-operative sSDC1-level (>123 ng/ml) proved to be an independent marker of adverse OS (P = 0.048) and DSS (P = 0.020). The present study does not confirm the prognostic relevance of SDC1-IHC. The significant higher sSDC1 serum levels in advanced cases of PC, suggest that SDC1 shedding might be involved in PC progression. Additionally, high sSDC1-level proved to be an independent factor of adverse OS and DSS in a multivariable pre-operative model, making evaluation of sSDC1-levels a promising tool for pre-operative risk-stratification and/or therapy monitoring. Prostate 76:977-985, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Assessment of display performance for medical imaging systems: Executive summary of AAPM TG18 report

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

Samei, Ehsan; Badano, Aldo; Chakraborty, Dev

Digital imaging provides an effective means to electronically acquire, archive, distribute, and view medical images. Medical imaging display stations are an integral part of these operations. Therefore, it is vitally important to assure that electronic display devices do not compromise image quality and ultimately patient care. The AAPM Task Group 18 (TG18) recently published guidelines and acceptance criteria for acceptance testing and quality control of medical display devices. This paper is an executive summary of the TG18 report. TG18 guidelines include visual, quantitative, and advanced testing methodologies for primary and secondary class display devices. The characteristics, tested in conjunction withmore » specially designed test patterns (i.e., TG18 patterns), include reflection, geometric distortion, luminance, the spatial and angular dependencies of luminance, resolution, noise, glare, chromaticity, and display artifacts. Geometric distortions are evaluated by linear measurements of the TG18-QC test pattern, which should render distortion coefficients less than 2%/5% for primary/secondary displays, respectively. Reflection measurements include specular and diffuse reflection coefficients from which the maximum allowable ambient lighting is determined such that contrast degradation due to display reflection remains below a 20% limit and the level of ambient luminance (L{sub amb}) does not unduly compromise luminance ratio (LR) and contrast at low luminance levels. Luminance evaluation relies on visual assessment of low contrast features in the TG18-CT and TG18-MP test patterns, or quantitative measurements at 18 distinct luminance levels of the TG18-LN test patterns. The major acceptable criteria for primary/secondary displays are maximum luminance of greater than 170/100 cd/m{sup 2}, LR of greater than 250/100, and contrast conformance to that of the grayscale standard display function (GSDF) of better than 10%/20%, respectively. The angular response is tested to ascertain the viewing cone within which contrast conformance to the GSDF is better than 30%/60% and LR is greater than 175/70 for primary/secondary displays, or alternatively, within which the on-axis contrast thresholds of the TG18-CT test pattern remain discernible. The evaluation of luminance spatial uniformity at two distinct luminance levels across the display faceplate using TG18-UNL test patterns should yield nonuniformity coefficients smaller than 30%. The resolution evaluation includes the visual scoring of the CX test target in the TG18-QC or TG18-CX test patterns, which should yield scores greater than 4/6 for primary/secondary displays. Noise evaluation includes visual evaluation of the contrast threshold in the TG18-AFC test pattern, which should yield a minimum of 3/2 targets visible for primary/secondary displays. The guidelines also include methodologies for more quantitative resolution and noise measurements based on MTF and NPS analyses. The display glare test, based on the visibility of the low-contrast targets of the TG18-GV test pattern or the measurement of the glare ratio (GR), is expected to yield scores greater than 3/1 and GRs greater than 400/150 for primary/secondary displays. Chromaticity, measured across a display faceplate or between two display devices, is expected to render a u{sup '},v{sup '} color separation of less than 0.01 for primary displays. The report offers further descriptions of prior standardization efforts, current display technologies, testing prerequisites, streamlined procedures and timelines, and TG18 test patterns.« less

The Will Rogers phenomenon in urological oncology.

PubMed

Gofrit, Ofer N; Zorn, Kevin C; Steinberg, Gary D; Zagaja, Gregory P; Shalhav, Arieh L

2008-01-01

Improvement in the prognosis of patient groups due to stage or grade reclassification is called the Will Rogers phenomenon. We determined the significance of the Will Rogers phenomenon in urological oncology. Studies referring to the Will Rogers phenomenon in urological oncology were identified through a MEDLINE search. Samples of articles not referring to the phenomenon directly but likely to be biased by it, such as articles comparing contemporary data to historical controls, were also reviewed. In prostate cancer the Will Rogers phenomenon is the result of the late 1990s acceptance that Gleason scores 2 to 4 should not be assigned on prostate biopsy. Consequently grade inflation occurred and current readings are almost 1 Gleason grade higher compared to past readings of the same biopsy. The result is an illusion of improvement in grade adjusted prognosis. In bladder cancer the Will Rogers phenomenon arises from improvement in histopathological processing of cystectomy specimens enabling the identification of microscopic perivesical fat infiltration and lymph node metastases not recognized in the past. Up staging from pT2 to pT3 and N0 to N+ may partly explain the improved stage adjusted survival after radical cystectomy observed in contemporary series. The Will Rogers phenomenon may also explain the correlation between the total number of lymph nodes removed at radical cystectomy and survival. As more lymph nodes are removed the probability of identifying metastases and up staging to N+ increases. Comparison of contemporary results to historical controls may be biased by the Will Rogers phenomenon. Ignoring the possibility of stage or grade reclassification may lead to erroneous conclusions.

Expression of Voltage-Gated Sodium Channel Nav1.8 in Human Prostate Cancer is Associated with High Histological Grade

PubMed Central

Suy, Simeng; Hansen, Todd P.; Auto, Heather D.; Kallakury, Bhaskar V.S.; Dailey, Vernon; Danner, Malika; MacArthur, Linda; Zhang, Ying; Miessau, Matthew J.; Collins, Sean P.; Brown, Milton L.

2013-01-01

Voltage-gated sodium (Nav) channels are required for impulse conductance in excitable tissues. Navs have been linked to human cancers, including prostate. The expression and distribution of Nav isoforms (Nav1.1-Nav1.9) in human prostate cancer are not well established. Here, we evaluated the expression of these isoforms and investigated the expression of Nav1.8 in human prostate cancer tissues. Nav1.8 was highly expressed in all examined cells. Expression of Nav1.1, Nav1.2, and Nav1.9 were high in DU-145, PC-3 and PC-3M cells compared to LNCaP (hormone-dependent), C4-2, C4-2B, and CWR22Rv-1 cells. Nav1.5 and Nav1.6 were expressed in all cells examined. Nav1.7 expression was absent in PC-3M and CWR22Rv-1, but expressed in the other cells examined. Immunohistochemistry revealed intensive Nav1.8 staining correlated with more advanced pathologic stage of disease. Increased intensity of nuclear Nav1.8 correlated with increased Gleason grade. Our results revealed that Nav1.8 is universally expressed in human prostate cancer cells. Nav1.8 expression statistically correlated with pathologic stage (P=0.04) and Gleason score (P=0.01) of human prostate tissue specimens. The aberrant nuclear localization of Nav1.8 with advanced prostate cancer tissues warrant further investigation into use of Nav1.8 as a potential biomarker to differentiate between early and advanced disease. PMID:24163825

Decreased number of mast cells infiltrating into needle biopsy specimens leads to a better prognosis of prostate cancer

PubMed Central

Nonomura, N; Takayama, H; Nishimura, K; Oka, D; Nakai, Y; Shiba, M; Tsujimura, A; Nakayama, M; Aozasa, K; Okuyama, A

2007-01-01

Mast cell infiltration is often observed around human tumours. Inflammatory cells such as macrophages, neutrophils and mast cells infiltrating around tumours are known to contribute to tumour growth; however, the clinical significance of mast cell invasion in prostate cancer (PCa) has not been investigated. Mast cell infiltration was evaluated in 104 patients (age range, 45–88 years; median, 72 years), who underwent needle biopsy of the prostate and were confirmed to have PCa. Needle biopsy specimens of prostate were sliced into 5-μm-thick sections and immunostained for mast cells with monoclonal antibody against mast cell-specific tryptase. Mast cells were counted systematically under a microscope (× 400 magnification), and the relations between mast cell numbers and clinicopathologic findings were evaluated. The mast cell count was evaluated for prognostic value by multivariate analysis. Mast cells were immunostained around the cancer foci. The median number of mast cells in each case was 16. The mast cell count was higher around cancer foci in patients with higher Gleason scores than in those with low Gleason scores. The mast cell number correlated well with clinical stage (P<0.001). Prostate-specific antigen-free survival of patients with higher mast cell counts was better than that in patients with lower mast cell counts (P<0.001). Multivariate analysis revealed that mast cell count was a significant prognostic factor (P<0.005). The number of mast cells infiltrating around cancer foci in prostate biopsy specimens can be a significant prognostic factor of PCa. PMID:17848955

Individual and cumulative effect of prostate cancer risk-associated variants on clinicopathologic variables in 5,895 prostate cancer patients.

PubMed

Kader, A Karim; Sun, Jielin; Isaacs, Sarah D; Wiley, Kathleen E; Yan, Guifang; Kim, Seong-Tae; Fedor, Helen; DeMarzo, Angelo M; Epstein, Jonathan I; Walsh, Patrick C; Partin, Alan W; Trock, Bruce; Zheng, S Lilly; Xu, Jianfeng; Isaacs, William

2009-08-01

More than a dozen single nucleotide polymorphisms (SNPs) have been associated with prostate cancer (PCa) risk from genome-wide association studies (GWAS). Their association with PCa aggressiveness and clinicopathologic variables is inconclusive. Twenty PCa risk SNPs implicated in GWAS and fine mapping studies were evaluated in 5,895 PCa cases treated by radical prostatectomy at Johns Hopkins Hospital, where each tumor was uniformly graded and staged using the same protocol. For 18 of the 20 SNPs examined, no statistically significant differences (P > 0.05) were observed in risk allele frequencies between patients with more aggressive (Gleason scores > or =4 + 3, or stage > or =T3b, or N+) or less aggressive disease (Gleason scores < or =3 + 4, and stage < or =T2, and N0). For the two SNPs that had significant differences between more and less aggressive disease rs2735839 in KLK3 (P = 8.4 x 10(-7)) and rs10993994 in MSMB (P = 0.046), the alleles that are associated with increased risk for PCa were more frequent in patients with less aggressive disease. Since these SNPs are known to be associated with PSA levels in men without PCa diagnoses, these latter associations may reflect the enrichment of low grade, low stage cases diagnosed by contemporary disease screening with PSA. The vast majority of PCa risk-associated SNPs are not associated with aggressiveness and clinicopathologic variables of PCa. Correspondingly, they have minimal utility in predicting the risk for developing more or less aggressive forms of PCa.

The prostate health index PHI predicts oncological outcome and biochemical recurrence after radical prostatectomy - analysis in 437 patients

PubMed Central

Maxeiner, Andreas; Kilic, Ergin; Matalon, Julia; Friedersdorff, Frank; Miller, Kurt; Jung, Klaus; Stephan, Carsten; Busch, Jonas

2017-01-01

The purpose of this study was to investigate the Prostate-Health-Index (PHI) for pathological outcome prediction following radical prostatectomy and also for biochemical recurrence prediction in comparison to established parameters such as Gleason-score, pathological tumor stage, resection status (R0/1) and prostate-specific antigen (PSA). Out of a cohort of 460 cases with preoperative PHI-measurements (World Health Organization calibration: Beckman Coulter Access-2-Immunoassay) between 2001 and 2014, 437 patients with complete follow up data were included. From these 437 patients, 87 (19.9%) developed a biochemical recurrence. Patient characteristics were compared by using chi-square test. Predictors were analyzed by multivariate adjusted logistic and Cox regression. The median follow up for a biochemical recurrence was 65 (range 3-161) months. PHI, PSA, [-2]proPSA, PHI- and PSA-density performed as significant variables (p < 0.05) for cancer aggressiveness: Gleason-score <7 or ≥7 (ISUP grade 1 or ≥2) . Concerning pathological tumor stage discrimination and prediction, variables as PHI, PSA, %fPSA, [-2]proPSA, PHI- and PSA-density significantly discriminated between stages

The prostate health index PHI predicts oncological outcome and biochemical recurrence after radical prostatectomy - analysis in 437 patients.

PubMed

Maxeiner, Andreas; Kilic, Ergin; Matalon, Julia; Friedersdorff, Frank; Miller, Kurt; Jung, Klaus; Stephan, Carsten; Busch, Jonas

2017-10-03

The purpose of this study was to investigate the Prostate-Health-Index (PHI) for pathological outcome prediction following radical prostatectomy and also for biochemical recurrence prediction in comparison to established parameters such as Gleason-score, pathological tumor stage, resection status (R0/1) and prostate-specific antigen (PSA). Out of a cohort of 460 cases with preoperative PHI-measurements (World Health Organization calibration: Beckman Coulter Access-2-Immunoassay) between 2001 and 2014, 437 patients with complete follow up data were included. From these 437 patients, 87 (19.9%) developed a biochemical recurrence. Patient characteristics were compared by using chi-square test. Predictors were analyzed by multivariate adjusted logistic and Cox regression. The median follow up for a biochemical recurrence was 65 (range 3-161) months. PHI, PSA, [-2]proPSA, PHI- and PSA-density performed as significant variables (p < 0.05) for cancer aggressiveness: Gleason-score <7 or ≥7 (ISUP grade 1 or ≥2) . Concerning pathological tumor stage discrimination and prediction, variables as PHI, PSA, %fPSA, [-2]proPSA, PHI- and PSA-density significantly discriminated between stages

Race and survival following brachytherapy-based treatment for men with localized or locally advanced adenocarcinoma of the prostate.

PubMed

Winkfield, Karen M; Chen, Ming-Hui; Dosoretz, Daniel E; Salenius, Sharon A; Katin, Michael; Ross, Rudi; D'Amico, Anthony V

2011-11-15

We investigated whether race was associated with risk of death following brachytherapy-based treatment for localized prostate cancer, adjusting for age, cardiovascular comorbidity, treatment, and established prostate cancer prognostic factors. The study cohort was composed of 5,360 men with clinical stage T1-3N0M0 prostate cancer who underwent brachytherapy-based treatment at 20 centers within the 21st Century Oncology consortium. Cox regression multivariable analysis was used to evaluate the risk of death in African-American and Hispanic men compared to that in Caucasian men, adjusting for age, pretreatment prostate-specific antigen (PSA) level, Gleason score, clinical T stage, year and type of treatment, median income, and cardiovascular comorbidities. After a median follow-up of 3 years, there were 673 deaths. African-American and Hispanic races were significantly associated with an increased risk of all-cause mortality (ACM) (adjusted hazard ratio, 1.77 and 1.79; 95% confidence intervals, 1.3-2.5 and 1.2-2.7; p < 0.001 and p = 0.005, respectively). Other factors significantly associated with an increased risk of death included age (p < 0.001), Gleason score of 8 to 10 (p = 0.04), year of brachytherapy (p < 0.001), and history of myocardial infarction treated with stent or coronary artery bypass graft (p < 0.001). After adjustment for prostate cancer prognostic factors, age, income level, and revascularized cardiovascular comorbidities, African-American and Hispanic races were associated with higher ACM in men with prostate cancer. Additional causative factors need to be identified. Copyright © 2011 Elsevier Inc. All rights reserved.

Length of positive surgical margin after radical prostatectomy as a predictor of biochemical recurrence.

PubMed

Shikanov, Sergey; Song, Jie; Royce, Cassandra; Al-Ahmadie, Hikmat; Zorn, Kevin; Steinberg, Gary; Zagaja, Gregory; Shalhav, Arieh; Eggener, Scott

2009-07-01

Length and location of positive surgical margins are independent predictors of biochemical recurrence after open radical prostatectomy. We assessed their impact on biochemical recurrence in a large robotic prostatectomy series. Data were collected prospectively from 1,398 men undergoing robotic radical prostatectomy for clinically localized prostate cancer from 2003 to 2008 at a single institution. The associations of preoperative prostate specific antigen, pathological Gleason score, pathological stage and positive surgical margin parameters (location, length and focality) with biochemical recurrence rate were evaluated. Margin status and length were measured by a single uropathologist. Biochemical recurrence was defined as serum prostate specific antigen greater than 0.1 ng/ml on 2 consecutive tests. Cox regression models were constructed to evaluate predictors of biochemical recurrence. Of 1,398 consecutive patients who underwent robotic prostatectomy positive margins were present in 243 (17%) (11% of pathological T2 and 41% of T3). Preoperative prostate specific antigen, pathological stage, Gleason score, margin status, and margin length as a continuous and categorical variable (less than 1, 1 to 3, more than 3 mm) were independent predictors of biochemical recurrence. Patients with negative margins and those with a positive margin less than 1 mm had similar rates of biochemical recurrence (log rank test p = 0.18). Surgical margin location was not independently associated with biochemical recurrence. Margin status and length are independent predictors of biochemical recurrence following robotic radical prostatectomy. Although longer followup and validation studies are necessary for confirmation, patients with a positive margin less than 1 mm appear to have similar recurrence rates as those with negative margins.

External validation of a nomogram for prediction of side-specific extracapsular extension at robotic radical prostatectomy.

PubMed

Zorn, Kevin C; Gallina, Andrea; Hutterer, Georg C; Walz, Jochen; Shalhav, Arieh L; Zagaja, Gregory P; Valiquette, Luc; Gofrit, Ofer N; Orvieto, Marcelo A; Taxy, Jerome B; Karakiewicz, Pierre I

2007-11-01

Several staging tools have been developed for open radical prostatectomy (ORP) patients. However, the validity of these tools has never been formally tested in patients treated with robot-assisted laparoscopic radical prostatectomy (RALP). We tested the accuracy of an ORP-derived nomogram in predicting the rate of extracapsular extension (ECE) in a large RALP cohort. Serum prostate specific antigen (PSA) and side-specific clinical stage and biopsy Gleason sum information were used in a previously validated nomogram predicting side-specific ECE. The nomogram-derived predictions were compared with the observed rate of ECE, and the accuracy of the predictions was quantified. Each prostate lobe was analyzed independently. As complete data were available for 576 patients, the analyses targeted 1152 prostate lobes. Median age and serum PSA concentration at radical prostatectomy were 60 years and 5.4 ng/mL, respectively. The majority of side-specific clinical stages were T(1c) (993; 86.2%). Most side-specific biopsy Gleason sums were 6 (572; 49.7%). The median side-specific percentages of positive cores and of cancer were, respectively, 20.0% and 5.0%. At final pathologic review, 107 patients (18.6%) had ECE, and side-specific ECE was present in 117 patients (20.3%). The nomogram was 89% accurate in the RALP cohort v 84% in the previously reported ORP validation. The ORP side-specific ECE nomogram is highly accurate in the RALP population, suggesting that predictive and possibly prognostic tools developed in ORP patients may be equally accurate in their RALP counterparts.

Gleason 6 prostate cancer in one or two biopsy cores can harbor more aggressive disease.

PubMed

Katz, Mark H; Shikanov, Sergey; Sun, Maxine; Abdollah, Firas; Budaeus, Lars; Gong, Edward M; Eggener, Scott E; Steinberg, Gary D; Zagaja, Gregory P; Shalhav, Arieh L; Karakiewicz, Pierre I; Zorn, Kevin C

2011-04-01

Patients with Gleason (GL) 6 prostate cancer in one or two biopsy cores can be upgraded and/or upstaged at the time of surgery, which may adversely impact long-term outcome. A novel model for prediction of adverse pathologic outcomes was developed using preoperative characteristics. Between 2003 and 2007, 1159 patients underwent robot-assisted radical prostatectomy (RARP) at our institution. GL 6 prostate cancer in one or two biopsy cores was identified in 416 (36%) patients. Logistic regression analyses were used to assess the rate of GL ≥7 and/or extraprostatic extension at RARP. Covariates consisted of age, body mass index (BMI), number of positive cores, greatest percent of cancer in a core (GPC), clinical stage, and preoperative prostate-specific antigen (PSA) level. After backward variable selection, the developed model was internally validated using the area under the curve and subjected to methods of calibration. Respectively, 278 (67%) and 138 (33%) patients had one or two positive biopsy cores. At RARP, 90 (22%) patients were upgraded to GL ≥7 and 37 (9%) had extraprostatic extension. The novel model relied on age, BMI, preoperative PSA level, and GPC for prediction of adverse pathologic outcomes and was 69% accurate. Calibration plot revealed a virtually perfect relationship between predicted and observed probabilities. In patients with GL 6 prostate cancer in one or two biopsy cores, 25% have more ominous pathology at RARP. The model provides an individual assessment of adverse outcomes at surgery. Consequently, it may be considered when counseling patients regarding their management options.

Robot-assisted laparoscopic prostatectomy is not associated with early postoperative radiation therapy.

PubMed

Chino, Junzo; Schroeck, Florian R; Sun, Leon; Lee, W Robert; Albala, David M; Moul, Judd W; Koontz, Bridget F

2009-11-01

To compare open radical prostatectomy (RP) and robot-assisted laparoscopic prostatectomy (RALP), and to determine whether RALP is associated with a higher risk of features that determine recommendations for postoperative radiation therapy (RT). Patients undergoing RP from 2003 to 2007 were stratified into two groups: open RP and RALP. Preoperative (PSA level, T stage and Gleason score), pathological factors (T stage, Gleason score, extracapsular extension [ECE] and the status of surgical margins and seminal vesicle invasion [SVI]) and early treatment with RT or referral for RT within 6 months were compared between the groups. Multivariate analysis was used to control for selection bias in the RALP group. In all, 904 patients were identified; 368 underwent RALP and 536 underwent open RP (retropubic or perineal). Patients undergoing open RP had a higher pathological stage with ECE present in 24.8% vs 19.3% in RALP (P = 0.05) and SVI in 10.3% vs 3.8% (P < 0.001). In the RALP vs open RP group, there were positive surgical margins in 31.5% vs 31.9% (P = 0.9) and there were postoperative PSA levels of (3) 0.2 ng/mL in 5.7% vs 6.3% (P = 0.7), respectively. On multivariate analysis to control for selection bias, RALP was not associated with indication for RT (odds ratio (OR) 1.10, P = 0.55), or referral for RT (OR 1.04, P = 0.86). RALP was not associated with an increase in either indication or referral for early postoperative RT.

Prostatitis, other genitourinary infections and prostate cancer: results from a population-based case-control study.

PubMed

Boehm, Katharina; Valdivieso, Roger; Meskawi, Malek; Larcher, Alessandro; Schiffmann, Jonas; Sun, Maxine; Graefen, Markus; Saad, Fred; Parent, Marie-Élise; Karakiewicz, Pierre I

2016-03-01

We relied on a population-based case-control study (PROtEuS) to examine a potential association between the presence of histologically confirmed prostate cancer (PCa) and history of genitourinary infections, e.g., prostatitis, urethritis, orchitis and epididymitis. Cases were 1933 men with incident PCa, diagnosed across Montreal hospitals between 2005 and 2009. Population controls were 1994 men from the same residential area and age distribution. In-person interviews collected information about socio-demographic characteristics, lifestyle and medical history, e.g., self-reported history of several genitourinary infections, as well as on PCa screening. Logistic regression analyses tested overall and grade-specific associations, including subgroup analyses with frequent PSA testing. After multivariable adjustment, prostatitis was associated with an increased risk of any PCa (OR 1.81 [1.44-2.27]), but not urethritis (OR 1.05 [0.84-1.30]), orchitis (OR 1.28 [0.92-1.78]) or epididymitis (OR 0.98 [0.57-1.68]). The association between prostatitis and PCa was more pronounced for low-grade PCa (Gleason ≤ 6: OR 2.11 [1.61-2.77]; Gleason ≥ 7: OR 1.59 [1.22-2.07]). Adjusting for frequency of physician visits, PSA testing frequency or restricting analyses to frequently screened subjects did not affect these results. Prostatitis was associated with an increased probability for detecting PCa even after adjustment for frequency of PSA testing and physician visits, but not urethritis, orchitis or epididymitis. These considerations may be helpful in clinical risk stratification of individuals in whom the risk of PCa is pertinent.

Expression of the cancer-testis antigen BORIS correlates with prostate cancer.

PubMed

Cheema, Zubair; Hari-Gupta, Yukti; Kita, Georgia-Xanthi; Farrar, Dawn; Seddon, Ian; Corr, John; Klenova, Elena

2014-02-01

BORIS, a paralogue of the transcription factor CTCF, is a member of the cancer-testis antigen (CT) family. BORIS is normally present at high levels in the testis; however it is aberrantly expressed in various tumors and cancer cell lines. The main objectives of this study were to investigate BORIS expression together with sub-cellular localization in both prostate cell lines and tumor tissues, and assess correlations between BORIS and clinical/pathological characteristics. We examined BORIS mRNA expression, protein levels and cellular localization in a panel of human prostate tissues, cancer and benign, together with a panel prostate cell lines. We also compared BORIS levels and localization with clinical/pathological characteristics in prostate tumors. BORIS was detected in all inspected prostate cancer cell lines and tumors, but was absent in benign prostatic hyperplasia. Increased levels of BORIS protein positively correlated with Gleason score, T-stage and androgen receptor (AR) protein levels in prostate tumors. The relationship between BORIS and AR was further highlighted in prostate cell lines by the ability of ectopically expressed BORIS to activate the endogenous AR mRNA and protein. BORIS localization in the nucleus plus cytoplasm was also associated with higher BORIS levels and Gleason score. Detection of BORIS in prostate tumors suggests potential applications of BORIS as a biomarker for prostate cancer diagnosis, as an immunotherapy target and, potentially, a prognostic marker of more aggressive prostate cancer. The ability of BORIS to activate the AR gene indicates BORIS involvement in the growth and development of prostate tumors. © 2013 Wiley Periodicals, Inc.

Molecular differences in transition zone and peripheral zone prostate tumors

PubMed Central

Sinnott, Jennifer A.; Rider, Jennifer R.; Carlsson, Jessica; Gerke, Travis; Tyekucheva, Svitlana; Penney, Kathryn L.; Sesso, Howard D.; Loda, Massimo; Fall, Katja; Stampfer, Meir J.; Mucci, Lorelei A.; Pawitan, Yudi; Andersson, Sven-Olof; Andrén, Ove

2015-01-01

Prostate tumors arise primarily in the peripheral zone (PZ) of the prostate, but 20–30% arise in the transition zone (TZ). Zone of origin may have prognostic value or reflect distinct molecular subtypes; however, it can be difficult to determine in practice. Using whole-genome gene expression, we built a signature of zone using normal tissue from five individuals and found that it successfully classified nine tumors of known zone. Hypothesizing that this signature captures tumor zone of origin, we assessed its relationship with clinical factors among 369 tumors of unknown zone from radical prostatectomies (RPs) and found that tumors that molecularly resembled TZ tumors showed lower mortality (P = 0.09) that was explained by lower Gleason scores (P = 0.009). We further applied the signature to an earlier study of 88 RP and 333 transurethral resection of the prostate (TURP) tumor samples, also of unknown zone, with gene expression on ~6000 genes. We had observed previously substantial expression differences between RP and TURP specimens, and hypothesized that this might be because RPs capture primarily PZ tumors, whereas TURPs capture more TZ tumors. Our signature distinguished these two groups, with an area under the receiver operating characteristic curve of 87% (P < 0.0001). Our findings that zonal differences in normal tissue persist in tumor tissue and that these differences are associated with Gleason score and sample type suggest that subtypes potentially resulting from different etiologic pathways might arise in these zones. Zone of origin may be important to consider in prostate tumor biomarker research. PMID:25870172

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.

The pubovesical complex-sparing technique on laparoscopic radical prostatectomy.

PubMed

Rebouças, Rafael Batista; Monteiro, Rodrigo Campos; Lima, João Paulo Pereira; Almeida, Filipe Pádua B F; Britto, Cesar Araujo; Tobias-Machado, Marcos; Passerotti, Carlo

2018-03-01

Preservation of urinary continence is a great challenge in Radical Prostatectomy. In order to improve functional results, Asimakopoulos et al. (2010) described a robot-assisted surgical technique with preservation of the pubovesical complex (PVC). We present a pure laparoscopic execution. A 61-year-old male patient with a diagnosis of prostate cancer, with PSA 6.54ng/ml, DRE: T1C and Gleason 6 (3+3) 1/12 fragments. All therapeutic possibilities were discussed, including active surveillance. The patient opted for surgical treatment. A transperitoneal technique was used. We started the dissection on the left side, in the limit between the detrusor and the base of the prostate. The left seminal vesicle was dissected and left neurovascular bundle released by a high anterior dissection. We repeated the same procedure on the right side. The urethra was then divided, prostatic apex was laterally drawn and PVC was released. The bladder neck was divided and an urethrovesical anastomosis was achieved. A pelvic drain was placed. The total operative time was 150 minutes. The estimated blood loss was 300mL. The drain was removed on the 1st postoperative day and the patient was discharged. The Foley catheter was removed after 7 days and the patient remained completely dry. Hystopathology revealed adenocarcinoma Gleason 6, negative margins. PSA after 30 days was <0.04ng/mL, and the patient reported partial penile erection. The Pubovesical Complex-Sparing Technique on Laparoscopic Radical Prostatectomy was feasible and safe. Further adequately designed studies are needed to confirm whether this technique enhances early functional outcomes. Copyright® by the International Brazilian Journal of Urology.

Association of prostate cancer risk variants with clinicopathologic characteristics of the disease

PubMed Central

Xu, Jianfeng; Isaacs, Sarah D.; Sun, Jielin; Li, Ge; Wiley, Kathleen E.; Zhu, Yi; Hsu, Fang-Chi; Wiklund, Fredrik; Turner, Aubrey R.; Adams, Tamara S.; Liu, Wennuan; Trock, Bruce J.; Partin, Alan W.; Chang, Baoli; Walsh, Patrick C.; Grönberg, Henrik; Isaacs, William; Zheng, Siqun

2009-01-01

Purpose Fifteen independent genetic variants have been implicated in prostate cancer risk by recent genome-wide association studies. However, their association with clinicopathologic features of prostate cancer is uncertain. Experimental Design We systematically evaluated these 15 variants in 1,563 prostate cancer patients undergoing radical prostatectomy, taking advantage of the uniform tumor stage and grade information available for each of these cases. Associations of these variants with aggressiveness, pathologic Gleason scores, pathologic stage, age at diagnosis, or serum PSA levels were tested. Results After adjusting for multiple testing, none of the SNPs was individually or cumulatively associated with aggressiveness or individual clinicopathologic variables of prostate cancer such as Gleason scores, pathologic stage, or age at diagnosis of prostate cancer. The reported risk allele (G) for SNP rs2735839 in the KLK3 gene at 19q13 was more frequent in less aggressive prostate cancer patients (0.89) than in more aggressive prostate cancer patients (0.86), nominal P = 0.03, or in controls (0.86), nominal P = 0.04. Considering that this allele was also significantly associated with higher serum PSA levels among controls (nominal P = 0.003), the observed trend of higher frequency of this risk allele between less and more aggressive prostate cancer, or between less aggressive and controls may be due to detection bias of PSA screening. Conclusions Prostate cancer risk variants recently discovered from genome-wide case-control association studies are not associated with clinicopathologic variables in this population. Case-case studies are urgently needed in order to discover genetic variants that predict tumor aggressiveness. PMID:18794092

Individual and cumulative effect of prostate cancer risk-associated variants on clinicopathologic variables in 5,895 prostate cancer patients

PubMed Central

Kader, A. Karim; Sun, Jielin; Isaacs, Sarah D.; Wiley, Kathleen E.; Yan, Guifang; Kim, Seong-Tae; Fedor, Helen; DeMarzo, Angelo M.; Epstein, Jonathan I.; Walsh, Patrick C.; Partin, Alan W.; Trock, Bruce; Zheng, S. Lilly; Xu, Jianfeng; Isaacs, William

2009-01-01

Background More than a dozen single nucleotide polymorphisms (SNPs) have been associated with prostate cancer (PCa) risk from genome-wide association studies (GWAS). Their association with PCa aggressiveness and clinicopathologic variables is inconclusive. Methods Twenty PCa risk SNPs implicated in GWAS and fine mapping studies were evaluated in 5,895 PCa cases treated by radical prostatectomy at Johns Hopkins Hospital, where each tumor was uniformly graded and staged using the same protocol. Results For 18 of the 20 SNPs examined, no statistically significant differences (P > 0.05) were observed in risk allele frequencies between patients with more aggressive (Gleason Scores ≥ 4+3, or stage ≥ T3b, or N+) or less aggressive disease (Gleason Scores ≤ 3+4, and stage ≤ T2, and N0). For the two SNPs that had significant differences between more and less aggressive disease (rs2735839 in KLK3 (P = 8.4 × 10−7) and rs10993994 in MSMB (P = 0.046), the alleles that are associated with increased risk for PCa were more frequent in patients with less aggressive disease. Since these SNPs are known to be associated with PSA levels in men without PCa diagnoses, these latter associations may reflect the enrichment of low grade, low stage cases diagnosed by contemporary disease screening with PSA. Conclusions The vast majority of PCa risk-associated SNPs are not associated with aggressiveness and clinicopathologic variables of PCa. Correspondingly, they have minimal utility in predicting the risk for developing more or less aggressive forms of PCa. PMID:19434657

Comparison of oncological and functional outcomes of pure versus robotic-assisted laparoscopic radical prostatectomy performed by a single surgeon.

PubMed

Park, Bumsoo; Kim, Woojung; Jeong, Byong Chang; Jeon, Seong Soo; Lee, Hyun Moo; Choi, Han Yong; Seo, Seong Il

2013-02-01

The aim of this study was to compare oncological and functional outcomes of pure laparoscopic radical prostatectomy (LRP) and robotic-assisted laparoscopic radical prostatectomy (RALRP) performed by a single surgeon. In total, 327 consecutive patients with prostate cancer who underwent radical prostatectomy (144 with LRP and 183 with RALRP) were enrolled. No significant differences were found in prostate-specific antigen level, biopsy Gleason score, clinical T stage or D'Amico risk stratification between the two groups. The operating time was longer in the LRP group (p < 0.001). The RALRP group patients had significantly lower postoperative pain numerical rating scale (NRS) (p = 0.016) and catheter duration (p < 0.001). There were no differences in pathological Gleason score, pathological T stage or positive surgical margin rate. No differences were found in biochemical recurrence-free survival. Postoperative pad-free continence rates revealed a more rapid recovery in the RALRP group, but rates at 12 months were not significantly different. Multivariate analysis showed that the type of surgery was a strong independent factor to predict early postoperative pad use. Postoperative potency rates were not significantly different at 3, 6 and 12 months in patients who underwent nerve-sparing procedures. LRP and RALRP performed by a single surgeon yielded similar results in terms of safety and oncological outcomes. More favorable outcomes were noted in operating time, pain NRS and catheter duration, as well as urinary continence recovery time. Therefore, RALRP showed more favorable components in terms of postoperative quality of life than LRP.

Identifying in vivo DCE MRI markers associated with microvessel architecture and gleason grades of prostate cancer.

PubMed

Singanamalli, Asha; Rusu, Mirabela; Sparks, Rachel E; Shih, Natalie N C; Ziober, Amy; Wang, Li-Ping; Tomaszewski, John; Rosen, Mark; Feldman, Michael; Madabhushi, Anant

2016-01-01

To identify computer extracted in vivo dynamic contrast enhanced (DCE) MRI markers associated with quantitative histomorphometric (QH) characteristics of microvessels and Gleason scores (GS) in prostate cancer. This study considered retrospective data from 23 biopsy confirmed prostate cancer patients who underwent 3 Tesla multiparametric MRI before radical prostatectomy (RP). Representative slices from RP specimens were stained with vascular marker CD31. Tumor extent was mapped from RP sections onto DCE MRI using nonlinear registration methods. Seventy-seven microvessel QH features and 18 DCE MRI kinetic features were extracted and evaluated for their ability to distinguish low from intermediate and high GS. The effect of temporal sampling on kinetic features was assessed and correlations between those robust to temporal resolution and microvessel features discriminative of GS were examined. A total of 12 microvessel architectural features were discriminative of low and intermediate/high grade tumors with area under the receiver operating characteristic curve (AUC) > 0.7. These features were most highly correlated with mean washout gradient (WG) (max rho = -0.62). Independent analysis revealed WG to be moderately robust to temporal resolution (intraclass correlation coefficient [ICC] = 0.63) and WG variance, which was poorly correlated with microvessel features, to be predictive of low grade tumors (AUC = 0.77). Enhancement ratio was the most robust (ICC = 0.96) and discriminative (AUC = 0.78) kinetic feature but was moderately correlated with microvessel features (max rho = -0.52). Computer extracted features of prostate DCE MRI appear to be correlated with microvessel architecture and may be discriminative of low versus intermediate and high GS. © 2015 Wiley Periodicals, Inc.

Factors predicting biochemical recurrence after radical prostatectomy among patients with clinical T3 prostate cancer.

PubMed

Otsuka, Masafumi; Kamasako, Tomohiko; Uemura, Toshihiro; Takeshita, Nobushige; Shinozaki, Tetsuo; Kobayashi, Masayuki; Komaru, Atsushi; Fukasawa, Satoshi

2018-06-19

The effectiveness of cancer control is unclear after radical prostatectomy for patients with clinical T3 prostate cancer. We retrospectively reviewed 1409 patients who underwent radical prostatectomy between April 2007 and December 2014, including 210 patients with cT3 prostate cancer. Nine patients who received neoadjuvant hormonal therapy and three patients who were lost to follow-up were excluded from the analysis. Clinical staging was performed by an experienced radiologist using preoperative magnetic resonance imaging findings. We analyzed the predictors of biochemical recurrence using Cox proportional hazard analyses. A total of 113 patients (57%) underwent radical retropubic prostatectomy and 85 patients (43%) underwent robot-assisted radical prostatectomy. The median follow-up period was 36 months. Downstaging occurred for 60 patients (30%), positive surgical margins were identified in 117 patients (59%), and biochemical recurrence was observed for 89 patients (45%). In the multivariate analyses, the independent preoperative predictors of biochemical recurrence were ≥50% proportion of positive biopsy cores [hazard ratio (HR): 2.858, P < 0.0001] and a biopsy Gleason score of ≥8 (HR: 1.800, P = 0.0093). The independent post-operative predictors of biochemical recurrence were positive surgical margins (HR: 2.490, P = 0.0018) and seminal vesicle invasion (HR: 2.750, P < 0.0001). Among patients with cT3 prostate cancer, the percentage of positive biopsy cores and the biopsy Gleason score should be considered to select treatment. Compared with radical retropubic prostatectomy, robot-assisted radical prostatectomy may be a feasible treatment option in this setting.

In-Silico Integration Approach to Identify a Key miRNA Regulating a Gene Network in Aggressive Prostate Cancer

PubMed Central

Colaprico, Antonio; Bontempi, Gianluca; Castiglioni, Isabella

2018-01-01

Like other cancer diseases, prostate cancer (PC) is caused by the accumulation of genetic alterations in the cells that drives malignant growth. These alterations are revealed by gene profiling and copy number alteration (CNA) analysis. Moreover, recent evidence suggests that also microRNAs have an important role in PC development. Despite efforts to profile PC, the alterations (gene, CNA, and miRNA) and biological processes that correlate with disease development and progression remain partially elusive. Many gene signatures proposed as diagnostic or prognostic tools in cancer poorly overlap. The identification of co-expressed genes, that are functionally related, can identify a core network of genes associated with PC with a better reproducibility. By combining different approaches, including the integration of mRNA expression profiles, CNAs, and miRNA expression levels, we identified a gene signature of four genes overlapping with other published gene signatures and able to distinguish, in silico, high Gleason-scored PC from normal human tissue, which was further enriched to 19 genes by gene co-expression analysis. From the analysis of miRNAs possibly regulating this network, we found that hsa-miR-153 was highly connected to the genes in the network. Our results identify a four-gene signature with diagnostic and prognostic value in PC and suggest an interesting gene network that could play a key regulatory role in PC development and progression. Furthermore, hsa-miR-153, controlling this network, could be a potential biomarker for theranostics in high Gleason-scored PC. PMID:29562723

Prognostic relevance of proliferation markers (Ki-67, PHH3) within the cross-relation of ERG translocation and androgen receptor expression in prostate cancer.

PubMed

Goltz, Diane; Montani, Matteo; Braun, Martin; Perner, Sven; Wernert, Nicolas; Jung, Klaus; Dietel, Manfred; Stephan, Carsten; Kristiansen, Glen

2015-12-01

We evaluated the prognostic value of the mitosis-associated marker phosphorylated histone H3 (PHH3) and Ki-67 in prostate cancer with respect to ERG status and androgen receptor (AR) expression.PHH3 and Ki-67 expression was immunohistochemically detected and digitally quantitated in a radical prostatectomy cohort (n = 640). The results were correlated to clinicopathological parameters including biochemical recurrence times. Prognostic values of PHH3 and Ki-67 were analysed by Cox regression and Kaplan-Meier statistics.In prostate cancer, mean Ki-67 and PHH3 rates were 3.40% (95%CI 3.16-3.63%) and 0.0152% (95%CI 0.0112-0.0191%), respectively.Ki-67 showed a significant correlation with Gleason scores, pT status, margin status, and AR expression, while PHH3 showed a significant correlation with Gleason scores and pT status. Univariate analyses for biochemical recurrence times demonstrated a significant prognostic value for median Ki-67 rate and for the PHH3 rate of the 90th percentile. Of importance, in patient subgroups stratified according to AR expression and ERG translocation, the prognostic power of proliferation markers PHH3 and Ki-67 was markedly enhanced in ERG translocation negative and high-level AR expressing ERG translocation positive prostate cancers.As expected, the proliferation markers PHH3 and Ki-67 predict adverse outcome of prostate cancer and have a particularly pronounced prognostic value in specific molecular subsets of prostate cancer (ERG- or AR+).

Development of a computer aided diagnosis model for prostate cancer classification on multi-parametric MRI

NASA Astrophysics Data System (ADS)

Alfano, R.; Soetemans, D.; Bauman, G. S.; Gibson, E.; Gaed, M.; Moussa, M.; Gomez, J. A.; Chin, J. L.; Pautler, S.; Ward, A. D.

2018-02-01

Multi-parametric MRI (mp-MRI) is becoming a standard in contemporary prostate cancer screening and diagnosis, and has shown to aid physicians in cancer detection. It offers many advantages over traditional systematic biopsy, which has shown to have very high clinical false-negative rates of up to 23% at all stages of the disease. However beneficial, mp-MRI is relatively complex to interpret and suffers from inter-observer variability in lesion localization and grading. Computer-aided diagnosis (CAD) systems have been developed as a solution as they have the power to perform deterministic quantitative image analysis. We measured the accuracy of such a system validated using accurately co-registered whole-mount digitized histology. We trained a logistic linear classifier (LOGLC), support vector machine (SVC), k-nearest neighbour (KNN) and random forest classifier (RFC) in a four part ROI based experiment against: 1) cancer vs. non-cancer, 2) high-grade (Gleason score ≥4+3) vs. low-grade cancer (Gleason score <4+3), 3) high-grade vs. other tissue components and 4) high-grade vs. benign tissue by selecting the classifier with the highest AUC using 1-10 features from forward feature selection. The CAD model was able to classify malignant vs. benign tissue and detect high-grade cancer with high accuracy. Once fully validated, this work will form the basis for a tool that enhances the radiologist's ability to detect malignancies, potentially improving biopsy guidance, treatment selection, and focal therapy for prostate cancer patients, maximizing the potential for cure and increasing quality of life.

Parental Choice of Schooling, Learning Processes and Inter-Ethnic Friendship Patterns: The Case of Malay Students in Chinese Primary Schools in Malaysia

ERIC Educational Resources Information Center

Sua, Tan Yao; Ngah, Kamarudin; Darit, Sezali Md.

2013-01-01

This study surveys 200 Malay students enrolled in three Chinese primary schools in relation to three issues, i.e., parental choice of schooling, learning processes and inter-ethnic friendship patterns. The three issues are explored through a combination of quantitative and qualitative research methodologies. Parental expectations for their…

Physical Activity Patterns and Psychological Correlates of Physical Activity among Singaporean Primary, Secondary, and Junior College Students

ERIC Educational Resources Information Center

Wang, C. K. John; Koh, K. T.; Biddle, Stuart J. H.; Liu, W. C.; Chye, Stefanie

2011-01-01

The purpose of this research was to examine physical activity patterns and psychological correlates of physical activity among primary, secondary, and junior college students in Singapore. A sample of 3,333 school students aged 10 to 18 years took part in the study. Results showed that the younger students had significantly higher physical…

Patterns of Variation in Teaching the Colour of Light to Primary 3 Students

ERIC Educational Resources Information Center

Ling, Lo Mun; Chik, Pakey; Pang, Ming Fai

2006-01-01

This paper shows how the patterns of variation created in the teaching were critical in helping a class of Primary 3 students in Hong Kong to learn about the colour of light, so that the students attained conceptual rather than procedural knowledge. A "Learning Study" approach was adopted, which is a Lesson Study grounded in a particular…

Pulmonary sporotrichosis: case series and systematic analysis of literature on clinico-radiological patterns and management outcomes.

PubMed

Aung, Ar Kar; Teh, Bing Mei; McGrath, Christopher; Thompson, Philip J

2013-07-01

Pulmonary infections by Sporothrix spp. manifest radiologically as cavitary or non-cavitary disease depending on whether the infection is primary pulmonary or multifocal sporotrichosis. Despite current guidelines, the optimal management for pulmonary sporotrichosis remains unclear. In order to clarify this, we present two cases of pulmonary sporotrichosis, as well as the results of a comprehensive literature review of treatment outcomes based on clinico-radiological presentation patterns of the disease. A literature search of all case reports in English language over the last 50 years (1960-2010) was conducted. Data on patient characteristics, risk factors, clinico-radiological patterns, treatment modalities and outcomes were collected and analyzed. A total of 86 cases were identified, i.e., 64 (74.4%) primary pulmonary and 22 (25.6%) multifocal sporotrichosis. Radiologically, primary pulmonary disease was commonly characterized by cavity formation which was lacking in multifocal infections (P = 0.0001). Immunosuppressant use was more common in multifocal sporotrichosis (P = 0.0001), while hemoptysis was more common in primary pulmonary form (P = 0.01). No other differences in patient characteristics or risk factors were noted. Extra-pulmonary multifocal sporotrichosis most commonly involved skin (81.8%) and joints (45.4%). For patients with cavitary primary pulmonary sporotrichosis, outcomes from medical therapy alone were inferior to surgical intervention (P = 0.02). However, for both primary pulmonary and multifocal sporotrichosis with non-cavitary disease, medical therapy alone provided good outcomes. Only 12 (16.7%) cases were treated with itraconazole. Treatment of pulmonary sporotrichosis should be guided by the clinico-radiological patterns of presentation. Medical therapy alone is likely sufficient for non-cavitary disease while early surgery should be considered for cavitary primary pulmonary sporotrichosis. The experience in treating cavitary disease with itraconazole alone is limited and further data are required.

Utilization of health services and prescription patterns among lupus patients followed by primary care physicians and rheumatologists in Puerto Rico.

PubMed

Molina, María J; Mayor, Angel M; Franco, Alejandro E; Morell, Carlos A; López, Miguel A; Vilá, Luis M

2008-01-01

To examine the utilization of health services and prescription patterns among patients with systemic lupus erythematosus (SLE) followed by primary care physicians and rheumatologists in Puerto Rico. The insurance claims submitted by physicians to a health insurance company of Puerto Rico in 2003 were examined. The diagnosis of lupus was determined by using the International Classification of Diseases, Ninth Revision, code for SLE (710.0). Of 552,733 insured people, 665 SLE patients were seen by rheumatologists, and 92 were followed by primary care physicians. Demographic features, selected co-morbidities, healthcare utilization parameters, and prescription patterns were examined. Fisher exact test, chi2 test, and analysis of variances were used to evaluate differences between the study groups. SLE patients followed by rheumatologists had osteopenia/osteoporosis diagnosed more frequently than did patients followed by primary care physicians. The frequency of high blood pressure, diabetes mellitus, hypercholesterolemia, coronary artery disease, and renal disease was similar for both groups. Rheumatologists were more likely to order erythrocyte sedimentation rate, anti-dsDNA antibodies, and serum complements. No differences were observed for office or emergency room visits, hospitalizations, and utilization of routine laboratory tests. Rheumatologists prescribed hydroxychloroquine more frequently than did primary care physicians. The use of nonsteroidal anti-inflammatory drugs, cyclooxygenase-2 inhibitors, glucocorticoids, azathioprine, cyclophosphamide, and methotrexate was similar for both groups. Overall, the utilization of health services and prescription patterns among SLE patients followed by primary care physicians and rheumatologists in Puerto Rico are similar. However, rheumatologists ordered SLE biomarkers of disease activity and prescribed hydroxychloroquine more frequently than did primary care physicians.

Gender Differences in Patterns of Substance Use and Delinquency: A Latent Transition Analysis

PubMed Central

Bright, Charlotte Lyn; Sacco, Paul; Kolivoski, Karen M.; Stapleton, Laura M.; Jun, Hyun-Jin; Morris-Compton, Darnell

2017-01-01

This study explores gender-specific patterns and transitions of adolescent substance use and delinquency in a sample of youths at ages 12, 15, and 18 (N = 803). Latent transition analysis identified “Primary Delinquent,” “Delinquency and Substance Use,” and “Low Risk” classes. Females were less likely to be in the “Primary Delinquent” class at age 12 than males. From 15 to 18, females were approximately equally likely to transition from “Primary Delinquent” to both other classes, whereas males were more likely to transition from “Primary Delinquent” to “Delinquency and Substance Use.” These gender differences in behavior can inform services. PMID:28603406

Compression and reflection of visually evoked cortical waves

PubMed Central

Xu, Weifeng; Huang, Xiaoying; Takagaki, Kentaroh; Wu, Jian-young

2007-01-01

Summary Neuronal interactions between primary and secondary visual cortical areas are important for visual processing, but the spatiotemporal patterns of the interaction are not well understood. We used voltage-sensitive dye imaging to visualize neuronal activity in rat visual cortex and found novel visually evoked waves propagating from V1 to other visual areas. A primary wave originated in the monocular area of V1 and was “compressed” when propagating to V2. A reflected wave initiated after compression and propagated backward into V1. The compression occurred at the V1/V2 border, and local GABAA inhibition is important for the compression. The compression/reflection pattern provides a two-phase modulation: V1 is first depolarized by the primary wave and then V1 and V2 are simultaneously depolarized by the reflected and primary waves, respectively. The compression/reflection pattern only occurred for evoked but not for spontaneous waves, suggesting that it is organized by an internal mechanism associated with visual processing. PMID:17610821

Student Comprehension of Primary Literature is Aided by Companion Assignments Emphasizing Pattern Recognition and Information Literacy

ERIC Educational Resources Information Center

Shannon, Sarah; Winterman, Brian

2012-01-01

Primary literature is our main mode of communication in the sciences. As such, it is important for our undergraduates in the discipline to learn how to read primary literature. Incorporating primary literature into undergraduate science courses is often difficult because students are unprepared to comprehend primary articles. Learning to read and…

Comparative genomic hybridisation as a supportive tool in diagnostic pathology

PubMed Central

Weiss, M M; Kuipers, E J; Meuwissen, S G M; van Diest, P J; Meijer, G A

2003-01-01

Aims: Patients with multiple tumour localisations pose a particular problem to the pathologist when the traditional combination of clinical data, morphology, and immunohistochemistry does not provide conclusive evidence to differentiate between metastasis or second primary, or does not identify the primary location in cases of metastases and two primary tumours. Because this is crucial to decide on further treatment, molecular techniques are increasingly being used as ancillary tools. Methods: The value of comparative genomic hybridisation (CGH) to differentiate between metastasis and second primary, or to identify the primary location in cases of metastases and two primary tumours was studied in seven patients. CGH is a cytogenetic technique that allows the analysis of genome wide amplifications, gains, and losses (deletions) in a tumour within a single experiment. The patterns of these chromosomal aberrations at the different tumour localisations were compared. Results: In all seven cases, CGH patterns of gains and losses supported the differentiation between metastasis and second primary, or the identification of the primary location in cases of metastases and two primary tumours. Conclusion: The results illustrate the diagnostic value of CGH in patients with multiple tumours. PMID:12835298

Domain knowledge patterns in pedagogical diagnostics

NASA Astrophysics Data System (ADS)

Miarka, Rostislav

2017-07-01

This paper shows a proposal of representation of knowledge patterns in RDF(S) language. Knowledge patterns are used for reuse of knowledge. They can be divided into two groups - Top-level knowledge patterns and Domain knowledge patterns. Pedagogical diagnostics is aimed at testing of knowledge of students at primary and secondary school. An example of domain knowledge pattern from pedagogical diagnostics is part of this paper.

Evaluation of the treatment patterns and economic burden of dysmenorrhea in Japanese women, using a claims database.

PubMed

Akiyama, Sayako; Tanaka, Erika; Cristeau, Olivier; Onishi, Yoshie; Osuga, Yutaka

2017-01-01

This study aimed to describe treatment patterns and estimate health care resource utilization and associated costs among Japanese women with dysmenorrhea, using a claims database. This was a retrospective analysis using health insurance data from the Japan Medical Data Center, assessing female patients aged 18-49 years with newly diagnosed primary or secondary dysmenorrhea. Treatment pattern analyses focused on hormonal medications, analgesics, hemostatic agents, traditional Chinese medicine (TCM), and gynecological surgeries. Data were collected on health care resource utilization and costs associated with medications, imaging procedures, and inpatient and outpatient care in both patients and matched controls. The analysis included 6,315 women with dysmenorrhea (3,441 primary; 2,874 secondary). The most commonly prescribed initial therapies were low-dose estrogen progestins (LEPs, 37.7%) and TCM (30.0%), with substantial differences between primary (LEPs: 27.4%, TCM: 38.8%) and secondary (LEPs: 50.2%, TCM: 19.5%) dysmenorrhea cohorts. Surgery was conducted in <5% of all patients. Both primary and secondary cohorts of dysmenorrhea had significantly higher mean total health care costs compared to controls within the 1-year period following diagnosis (Case-primary: 191,680 JPY [1,916 USD]; secondary: 246,488 JPY [2,465 USD], Control-primary: 83,615 JPY [836 USD]; secondary: 90,711 JPY [907 USD]) ( p <0.0001). After adjusting for baseline characteristics, these costs were 2.2 and 2.9 times higher for primary and secondary dysmenorrhea cohorts, respectively, compared with matched controls, (both p <0.0001). The main driver of these excess costs was outpatient care, with eight additional physician visits per year among dysmenorrhea patients compared to controls ( p <0.0001). Considerable heterogeneity in treatment patterns was observed, with relatively low utilization of LEPs in patients with primary dysmenorrhea and those treated by internal medicine physicians. Total annual health care costs were approximately 2-3 times higher in patients with dysmenorrhea compared to women without the condition.

Evaluation of the treatment patterns and economic burden of dysmenorrhea in Japanese women, using a claims database

PubMed Central

Akiyama, Sayako; Tanaka, Erika; Cristeau, Olivier; Onishi, Yoshie; Osuga, Yutaka

2017-01-01

Purpose This study aimed to describe treatment patterns and estimate health care resource utilization and associated costs among Japanese women with dysmenorrhea, using a claims database. Methods This was a retrospective analysis using health insurance data from the Japan Medical Data Center, assessing female patients aged 18–49 years with newly diagnosed primary or secondary dysmenorrhea. Treatment pattern analyses focused on hormonal medications, analgesics, hemostatic agents, traditional Chinese medicine (TCM), and gynecological surgeries. Data were collected on health care resource utilization and costs associated with medications, imaging procedures, and inpatient and outpatient care in both patients and matched controls. Results The analysis included 6,315 women with dysmenorrhea (3,441 primary; 2,874 secondary). The most commonly prescribed initial therapies were low-dose estrogen progestins (LEPs, 37.7%) and TCM (30.0%), with substantial differences between primary (LEPs: 27.4%, TCM: 38.8%) and secondary (LEPs: 50.2%, TCM: 19.5%) dysmenorrhea cohorts. Surgery was conducted in <5% of all patients. Both primary and secondary cohorts of dysmenorrhea had significantly higher mean total health care costs compared to controls within the 1-year period following diagnosis (Case-primary: 191,680 JPY [1,916 USD]; secondary: 246,488 JPY [2,465 USD], Control-primary: 83,615 JPY [836 USD]; secondary: 90,711 JPY [907 USD]) (p<0.0001). After adjusting for baseline characteristics, these costs were 2.2 and 2.9 times higher for primary and secondary dysmenorrhea cohorts, respectively, compared with matched controls, (both p<0.0001). The main driver of these excess costs was outpatient care, with eight additional physician visits per year among dysmenorrhea patients compared to controls (p<0.0001). Conclusion Considerable heterogeneity in treatment patterns was observed, with relatively low utilization of LEPs in patients with primary dysmenorrhea and those treated by internal medicine physicians. Total annual health care costs were approximately 2–3 times higher in patients with dysmenorrhea compared to women without the condition. PMID:28579813