Wednesday, June 26, 2013

Formalin on Needle Curbs Prostate Biopsy Infections

Tuesday, June 25, 2013

Overactive bladder and its effects on sexual dysfunction among women

OAB is a common problem among sexually active young women and significantly affects their quality of life. However, OAB-related sexual dysfunction plays a limited role among sexually active nurses.

Wednesday, June 19, 2013

Tuesday, June 18, 2013

Friday, June 14, 2013

Factors associated with persistent urinary incontinence

Older age, white race, and obesity were particularly strongly related to persistent UI

Prolaris® Combined Score

Thursday, June 13, 2013

Prolaris® Technical Specifications Myriad Genetic Laboratories, Inc. 2012

Clinically Reportable Ranges
Based on observed scores in the 779 FFPE postprostatectomy tumor samples from the two patient cohorts, a clinically reportable Prolaris Score range of -1.6 to 3.7 was established. Based on analysis of the 413 samples in the more contemporary validation cohort, individuals with a Prolaris Score of 1.2 or higher have a predicted probability of biochemical recurrence by 10 years of greater than 50% (95% CI: 37-65%). Prolaris Scores outside the range of -1.6 to 3.7 will be reported but will be qualified with the information that they lie outside the range of the prediction model  Similarly, based on observed scores in 766 out of
779 FFPE post-prostatectomy tumor samples from the two patient cohorts, a clinically reportable Prolaris Combined Score range of –0.9 to 4.5 was established. Based on analysis of the 413 samples in the more contemporary validation cohort, individuals with a Prolaris Combined Score of 2.0 or higher have a predicted probability of biochemical recurrence by 10 years of greater than 50% (95% CI: 40-61%). Prolaris Combined Scores outside of this range will be reported, but a biochemical recurrence risk estimate will not provided as these scores lie outside of the range of the prediction model.

Detection Limit/Linearity
Prolaris Scores between -8 and 8 are technically  detectable by this assay. Linearity was established within this range as follows: The 31 cell cycle genes were preamplified, diluted to different concentrations and spiked into a cDNA sample of known concentration. Each spiked sample was assayed in triplicate, and the resulting 3 data points were averaged for each concentration to generate a Recurrence score. Linearity was established for Prolaris Scores ranging from 0 to 8 using this method. Linearity for Prolaris Scores ranging from -8 to 0 was similarly  established. The 15 housekeeping genes were pre-amplified,  diluted to different concentrations and spiked into a cDNA  sample of known concentration. Each spiked sample was  assayed in triplicate, and the resulting 3 data points were averaged for each concentration to generate a ProlarisScore.

The cost for PROLARIS is $3,400.

In the United States, 192,000 men are diagnosed with prostate cancer each year and 80,000 men will undergo a radical prostatectomy, a surgical procedure that removes the prostate gland and some surrounding tissue. Approximately 35% of these men will eventually have a biochemical recurrence indicating the return of their prostate cancer. Current models based on clinical variables cannot effectively predict in which of these men the disease will recur.
PROLARIS is a molecular diagnostic assay that offers urologists a more accurate way of determining a prostate cancer patient's risk of recurrence. The new molecular diagnostic test is based on cell growth and tumor biology and provides rigorous دقيق, quantitative measures of the expression levels of multiple genes related to progression of the cell cycle.

Prognostic value of a cell cycle progression signature for prostate cancer death in a conservatively managed needle biopsy cohort



The natural history of prostate cancer is highly variable and it is difficult to predict. We showed previously that a cell cycle progression (CCP) score was a robust predictor of outcome in a conservatively managed cohort diagnosed by transurethral resection of the prostate. A greater need is to predict outcome in patients diagnosed by needle biopsy.


Total RNA was extracted from paraffin specimens. A CCP score was calculated from expression levels of 31 genes. Clinical variables consisted of centrally re-reviewed Gleason score, baseline prostate-specific antigen level, age, clinical stage, and extent of disease. The primary endpoint was death from prostate cancer.


In univariate analysis (n=349), the hazard ratio (HR) for death from prostate cancer was 2.02 (95% CI (1.62, 2.53), P<10(-9)) for a one-unit increase in CCP score. The CCP score was only weakly correlated with standard prognostic factors and in a multivariate analysis, CCP score dominated (HR for one-unit increase=1.65, 95% CI (1.31, 2.09), P=3 × 10(-5)), with Gleason score (P=5 × 10(-4)) and prostate-specific antigen (PSA) (P=0.017) providing significant additional contributions.


For conservatively managed patients, the CCP score is the strongest independent predictor of cancer death outcome yet described and may prove valuable in managing clinically localized prostate cancer.

Tuesday, June 11, 2013

Friday, June 7, 2013

Hounsfield Units for stones

Uric acid 540 ± 107
Struvite 651 ± 108
Cystine 703 ± 69
Calcium oxalate/phospate > 1,023

Thursday, June 6, 2013

Prolaris: A novel genetic test for prostate cancer prognosis

Michael K. Brawer, Jack M. Cuzick, Matthew R. Cooperberg, Gregory P. Swanson, Stephen J. Freedland, Julia E. Reid, Gabrielle Fisher, Jerry S. Lanchbury, Alexander Gutin, Steven Stone, Peter Carroll
Transatlantic Prostate Group; Myriad Genetics and Laboratories, Inc., Salt Lake City, UT; Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, London, United Kingdom; University of California, San Francisco, San Francisco, CA; University of Texas Health Science Center at San Antonio, San Antonio, TX; Duke University Medical Center and Durham VA Medical Center, Durham, NC
Background: The natural history of prostate cancer is highly variable and difficult to predict. Improved tools are needed to match treatment more appropriately to a patient’s risk of progression. Therefore, we developed an expression signature composed of genes involved in cell cycle progression (Prolaris) and tested its utility in prostate cancer.
Methods: We developed an expression signature composed of 31 cell cycle progression and 15 housekeeper genes. An expression score (Prolaris score) was derived as the mean of all cell cycle progression genes. The signature was tested at disease diagnosis in two conservatively managed cohorts from the UK (N5337 and 349), after radical prostatectomy in two cohorts from the U.S. (N5366 Scott & White Hospital, TX and 413 USCF, CA), and after external beam radiation therapy (N5141) in a cohort from Durham VA Medical Center. All studies were retrospective.
Results: The cell cycle progression signature was a highly significant predictor of outcome in all five studies. In conservatively managed patients, the Prolaris score was the dominant variable for predicting death from prostate cancer in univariate analysis (p 5 6.1 x 10-22 after diagnosis by TURP, and p 5 8.6 x 10-10 after diagnosis by needle biopsy). In both studies, the Prolaris score remained highly significant in multivariate analysis making it a stronger predictor of disease-specific mortality than other prognostic variables. After prostatectomy, Prolaris predicted biochemical recurrence (BCR) in univariate analysis (S&W p 5 5.6 x 10-9; UCSF p5 2.23 x 10-6) and provided additional prognostic information in multivariate analysis (S&W p 5 3.3 x10-6; UCSF 9.5 x10-5). After radiation therapy, Prolaris predicted BCR (Phoenix) in univariate (p50.0017) and multivariate analysis (p50.034). In all five studies the HR per unit change in the Prolaris score was remarkably similar, ranging from 1.89 to 2.92, indicating that the effect size for the Prolaris score is robust to clinical setting and patient composition.
Conclusions: The Prolaris test predicts prostate cancer outcome in multiple patient cohorts and diverse clinical settings. In all cases, it provides information beyond clinicopathologic variables to help differentiate aggressive from indolent disease. 
The ASCO Annual Meeting brings together more than 25,000 oncology professionals from a broad range of specialties, making it an excellent venue for exploring the theme of the Meeting — "Building Bridges to Conquer Cancer."

Genome-wide methylation analysis of prostate tissues reveals global methylation patterns of prostate cancer - Abstract

Altered genome methylation is a hallmark of human malignancies.
In this study, high-throughput analyses of concordant gene methylation and expression events were performed for 91 human prostate specimens, including prostate tumor (T), matched normal adjacent to tumor (AT), and organ donor (OD). Methylated DNA in genomic DNA was immunoprecipitated with anti-methylcytidine antibodies and detected by Affymetrix human whole genome SNP 6.0 chips. Among the methylated CpG islands, 11,481 islands were found located in the promoter and exon 1 regions of 9295 genes. Genes (7641) were methylated frequently across OD, AT, and T samples, whereas 239 genes were differentially methylated in only T and 785 genes in both AT and T but not OD. Genes with promoter methylation and concordantly suppressed expression were identified. Pathway analysis suggested that many of the methylated genes in T and AT are involved in cell growth and mitogenesis. Classification analysis of the differentially methylated genes in T or OD produced a specificity of 89.4% and a sensitivity of 85.7%. The T and AT groups, however, were only slightly separated by the prediction analysis, indicating a strong field effect. A gene methylation prediction model was shown to predict prostate cancer relapse with sensitivity of 80.0% and specificity of 85.0%. These results suggest methylation patterns useful in predicting clinical outcomes of prostate cancer.
Written by: 
Luo JH, Ding Y, Chen R, Michalopoulos G, Nelson J, Tseng G, Yu YP.  
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Reference: Am J Pathol. 2013 Jun;182(6):2028-36. 
doi: 10.1016/j.ajpath.2013.02.040

Wednesday, June 5, 2013

AUA 2013 - Session Highlights: AUA Guideline Presentation: Follow-up care for renal cancer

SAN DIEGO, CA USA ( - Dr. Sherri Donat presented the new AUA guideline for the follow-up of clinically localized renal neoplasms during a much-anticipated plenary session. The goal of the panel was to create evidence-based guidelines for the follow-up and surveillance of clinically localized renal cancers treated with surgery or renal ablative procedures, biopsy-proven untreated clinically localized renal cancers followed on surveillance, and radiographically suspicious but biopsy-unproven renal neoplasms. An extensive literature review from January 1999 to 2011 was performed, and statements were presented as standards, recommendations, or options, with evidence rated as A (high), B (moderate), or C (low).
Notably, only one of the 27 statements in the guideline was considered a standard. Patients with a history of renal neoplasm presenting with acute neurological signs or symptoms must undergo prompt neurologic cross-sectional CT or MRI scanning of the head or spine based on localization of symptomatology (Standard; Grade A). Bone scan can be performed in patients with an elevated alkaline phosphatase or clinical symptoms such as bone pain and/or radiographic findings suggestive of a bony neoplasm (Recommendation; Grade C).
For patients with a history of low risk (pT1, N0, Mx) RCC managed surgically, chest X-ray (CXR) should be performed annually for 3 years and then only as clinically indicated to assess for pulmonary metastases (Recommendation; Grade C). A baseline abdominal CT or MRI should be performed within 3 to 12 months following renal surgery (Expert Opinion), and if the baseline image is negative, abdominal imaging (US, CT, or MRI) may be performed yearly for 3 years following partial nephrectomy (Option; Grade C).
For moderate- to high-risk patients managed surgically (pT2-4, N0, Nx or any N+), the panel recommends baseline abdominal imaging (CT or MRI) within 3 to 6 months following surgery, with continued imaging every 6 months for at least 3 years and annually thereafter to year 5 (Recommendation; Grade C). Site- specific imaging should be performed as warranted by clinical symptoms suggestive of recurrence or metastatic spread (Recommendation; Grade C), while the routine use of FDG-PET for follow-up is not indicated (Expert Opinion).
For patients on active surveillance (AS), the panel recommends that patients undergo abdominal imaging (CT or MRI) within 6 months of AS initiation to establish a growth rate, and then annually thereafter (Recommendation; Grade C). Percutaneous biopsy may be considered prior to initiating AS (Option; Grade C), and for those patients with biopsy proven RCC on AS, annual CXR should be performed to assess for pulmonary metastases (Recommendation; Grade C). The panel recommends urologist involvement in all patients undergoing ablative procedures (Expert Opinion), and pretreatment diagnostic biopsy (Recommendation; Grade C). Following ablation, cross-sectional CT or MRI, with and without IV contrast, should be performed at 3 and 6 months to assess treatment success, and annually thereafter for 5 years (Recommendation; Grade C). Patients with biopsy proven RCC, non-diagnostic biopsies, or no prior biopsies should undergo annual CXR for 5 years (Expert Opinion) following ablation, whereas patients with pathological confirmation of benign histology and radiographic confirmation of treatment success require no further radiologic scanning (Recommendation; Grade C). If there is radiographic evidence of ablation failure within 6 months, observation, repeat treatment, and surgical intervention should be discussed (Expert Opinion).
Finally, the panel recommends against the routine use of molecular markers (Ki-67, p-53, and VEGF), as “benefits remain unproven at this time” (Recommendation; Grade C). While the guidelines present an excellent step forward in standardizing follow-up of clinically localized RCC, they also highlight the lack of available high-quality evidence to guide clinicians in the appropriate follow-up of clinically localized renal cell carcinoma.
Presented by Sherri Machele Donat, MD at the American Urological Association (AUA) Annual Meeting - May 4 - 8, 2013 - San Diego Convention Center - San Diego, California USA
Memorial Sloan-Kettering Cancer Center, New York, NY USA

Reported for by Jeffrey J. Tomaszewski, MD

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