A. Finelli

INFLUENCE OF SEMEN PROCESSING TECHNIQUE ON HUMAN SPERM DNA INTEGRITY

OBJECTIVES To compare the effects of density-gradient centrifugation and swim-up technique on sperm DNA integrity. METHODS Semen samples (n = 22) were obtained from consecutive nonazoospermic men presenting for infertility evaluation. Individual samples were divided into three aliquots (whole semen, density-gradient centrifugation, and swim-up) for subsequent analysis of sperm motility and DNA integrity. Sperm DNA integrity was evaluated by flow cytometry analysis of acridine orange-treated spermatozoa and expressed as the percentage of spermatozoa demonstrating denatured DNA. RESULTS Mean sperm motility (+/-SEM) improved significantly after processing with two-layer density-gradient and swim-up compared with whole semen (65.6% +/- 4.0% and 73.0% +/- 3.0% versus 52.0% +/- 3.6%, respectively, P <0.005), with no significant difference in motility between Percoll-treated and swim-up-treated spermatozoa. In contrast, the percentage of spermatozoa with denatured DNA was reduced significantly in swim-up-treated but not in Percoll-treated spermatozoa compared with whole semen (4.8% +/- 1. 2% and 13.6% +/- 3.6% versus 10.1% +/- 2.3%, respectively, P <0. 0001). CONCLUSIONS Although density-gradient centrifugation is comparable to swim-up technique in recovering spermatozoa with enhanced motility, spermatozoa recovered after swim-up possess higher DNA integrity. These data urge us to reexamine our current sperm processing techniques in order to minimize sperm DNA damage.

THE USE OF MAGNETIC RESONANCE IMAGING IN THE DIAGNOSIS AND FOLLOWUP OF PEDIATRIC PELVIC RHABDOMYOSARCOMA

PURPOSE Previous radiological descriptions of pelvic rhabdomyosarcoma emphasized ultrasonography and computerized tomography (CT). Few reports are available on the use of magnetic resonance imaging (MRI) for diagnosing and following pelvic rhabdomyosarcoma. We retrospectively compared MRI to CT for diagnosing and following children with pelvic rhabdomyosarcoma. MATERIALS AND METHODS We treated 4 boys and 3 girls for pelvic rhabdomyosarcoma. Initial and followup evaluations included pelvic CT and MRI at intervals determined by treatment and disease status. We retrospectively reviewed the clinical charts and imaging studies of these patients. The initial radiological report was evaluated and then 1 radiologist reviewed all studies. Attention was directed toward identifying lesions revealed by CT or MRI but not by the other modality. RESULTS MRI detected all lesions shown by CT. On the other hand, MRI detected residual disease in 1 case that was not demonstrated by CT. In 2 other patients MRI was superior to CT for delineating the local extent of disease, especially urethral involvement. CONCLUSIONS Compared with CT, MRI improves the detection of residual pelvic rhabdomyosarcoma. Tissue planes are well delineated, allowing more accurate assessment of tumor invasion into adjacent structures. MRI is the imaging modality of choice for following pediatric patients with pelvic rhabdomyosarcoma.

Should Follow-up Biopsies for Men on Active Surveillance for Prostate Cancer Be Restricted to Limited Templates?

OBJECTIVE To investigate if prostate biopsy templates with fewer cores can be used during active surveillance (AS) for prostate cancer. METHODS At present, we use an AS protocol template (ASPT) consisting of 13-17 cores. We hypothesize in the setting of known cancer, sextant (6 cores) or standard extended (10-12 cores) templates, could be used with similar effect. We identified patients in our referral institution database (1997-2009) with entry prostate-specific antigen <10 ng/mL, stage ≤cT2, Gleason sum ≤6, ≤3 cores positive for cancer, <50% of single core involved, and age ≤75 years (N = 272). Patients fulfilling standard criteria for pathologic reclassification (N = 94) at any follow-up biopsy were selected for evaluation. By mapping tumor location on the pathologic reclassification determining biopsy, hypothetical scenarios of sextant or standard extended templates (SET) were compared with our ASPT and examined for frequency of cancer detection and pathologic reclassification. RESULTS For the 94 patients analyzed, the median number of cores taken was 9.7 (6-22) at baseline and 15 (14-17) for the reclassification biopsy. The median time between baseline and the pathologic reclassification determining biopsy was 15.4 months. Analysis of subgroupings showed that sextant template would identify 84% of cancers and 47.9% of the reclassification events, whereas SET detected 99% of cancers and 81.9% of patients who pathologically reclassified. When only considering Gleason sum ≥7 related progression events, SET found 16.2% less (n = 57) compared with ASPT (n = 68). CONCLUSION When monitoring patients on AS, a 13-17 core template detects more pathologic reclassification than standard sextant (18.1%) or extended (52.1%) biopsy templates.

The treatment choice of elderly patients with erectile dysfunction

The aim of this study was to determine treatment preference, commitment to choice of therapy, and the influence of physical disability on treatment choice in a geriatric group of males with erectile dysfunction (E.D.) of various etiologies. Eighty-nine patients aged 65 to 83 years (mean 69.5 years) were assessed and followed at our erectile dysfunction clinic from July 1991 to September 1996. Etiology of ED was based on clinical assessment. Available treatment options included oral medications, vacuum devices, injection therapy, penile prostheses, sex counseling and testosterone when indicated. Median follow-up since initial consultation was 9 months (range 1 to 63 months). Data was retrieved in a retrospective fashion from chart review and selective telephone follow-up. Clinical assessment yielded the following distribution of etiologies: vasculogenic (57.2%), neurogenic (7.9%), hormonal (1.1%), psychogenic (2.2%), and multifactorial (32.6%). The most popular initial treatment choices were injection therapy (30.3%), vacuum device (27.0%), and oral medication (20.2%). Of the 84 patients who chose to be treated, 34 (40.5%) elected to switch to a different form of therapy after a median time of 7.5 months (range 1 week to 63 months). Five patients tried a third form of therapy and two proceeded to a fourth. The remaining patients have continued with their original choice for a median time of 7 months (range 1 to 63 months). A greater drop-out rate (78%) amongst those who initially chose oral medication was statistically significant when compared to drop-out rates for injection therapy (48%) and vacuum devices (29%), p = 0.044 and p = 0.005, respectively. Significant physical disabilities in eight patients did not appear to influence their treatment selection. In conclusion, the elderly are a unique group of patients who are more likely to have an organic etiology to their erectile dysfunction. When they do present with erectile dysfunction, they are inclined to pursue treatment. The choices made by this group of men did not differ from impotent men in general. When unsatisfied with one form of therapy they were inclined to pursue an alternative treatment. A significant physical disability did not preclude a therapeutic choice.

Diagnostic prostate biopsy performed in a non-academic center increases the risk of re-classification at confirmatory biopsy for men considering active surveillance for prostate cancer

Background:To examine whether diagnostic biopsy (B1), for patients on active surveillance (AS) for prostate cancer, performed at an outside referral centre (external) compared with our in-house tertiary center (internal), increased the risk of re-classification on the second (confirmatory) biopsy (B2).Methods:Patients on AS were identified from our tertiary center database (1997–2012) with PSA<10, Gleason sum (GS) ⩽6, clinical stage ⩽cT2, ⩽3 positive cores, <50% of single core involved, age ⩽75 years and having a B2. Patients who had <10 cores at B1 and delay in B2 >24 mo were excluded. Depending on center where B1 was performed, men were dichotomized to internal or external groups. All B2 were performed internally. Multivariate logistic regression examined if external B1 was a predictor of re-classification at B2.Results:A total of 375 patients were divided into external (n=71, 18.9%) and internal groups (n=304, 81.1%). At B2, more men in the external group re-classified (26.8%) compared with the internal group (13.8%)(P=0.008). On multivariate analysis, external B1 predicted grade-related re-classification (odds ratio (OR) 4.14, confidence interval (CI) 2.01–8.54, P<0.001) and volume-related re-classification (OR 3.43, CI 1.87–6.25, P<0.001). Other significant predictors for grade-related re-classification were age (OR 2.13 per decade, CI 1.32–3.57, P<0.001), PSA density (OR 2.56 per unit, CI 1.44–4.73, P<0.001), maximum % core involvement (OR 1.04 per percentage point, CI 1.01–1.09, P=0.02) and time between B1 and B2 (OR 1.43 per 6 months, CI 1.21–1.71, P<0.001).Conclusion:At our institution, patients on AS who had their initial B1 performed externally were more likely to have adverse pathological features and re-classify on internal B2.

625 A non-invasive urine-based epigenetic urinary biomarker panel for the detection of bladder cancer and the discrimination of high-grade and low-grade disease

1Princess Margaret Cancer Centre, Dept. of Surgical Oncology, Division of Urology, University of Toronto, Toronto, Canada, 2Mount Sinai Hospital, Samuel Lunenfeld Research Institute, Toronto, Canada, 3University Health Network, Dept. of Surgery, Division of Urology, University of Toronto, Toronto, Canada, 4Mount Sinai Hospital, Dept. of Surgery, Division of Urology, Toronto, Canada, 5Dalhousie University, Dept. of Urology, Halifax, Canada, 6University of Liege, Dept. of Urology, Liege, Belgium, 7University Health Network, Dept. of Pathology, University of Toronto, Toronto, Canada

1092 5-alpha reductase inhibitors diminish the rate of progression in men with low risk prostate cancer on active surveillance

INTRODUCTION AND OBJECTIVES: 5-alpha reductase inhibitors (5ARIs) have been shown to prevent prostate cancer in two large randomized controlled trials. No prior work has shown the effect of 5ARIs on those already diagnosed with low risk prostate cancer. Our goal was to determine the effect of 5ARIs on pathologic progression in men on active surveillance for prostate cancer. METHODS: This was a single institution retrospective cohort study comparing men taking a 5ARI versus no 5ARI while on active surveillance for prostate cancer. All men had at least two biopsies. Inclusion criteria for active surveillance were PSA 10 ng/ml, clinical stage T1c/T2a, Gleason score 6, and 3 cores positive with no more than 50% of a core involved at initial diagnostic biopsy. Pathologic progression was evaluated and defined as Gleason score 6, or maximum core involvement 50% or 3 cores positive on a follow-up prostate biopsy. Univariate, multivariate and Kaplan-Meir analyses were conducted. RESULTS: A total of 288 men on active surveillance met the inclusion criteria. The median follow-up was 38.5 months (IQR 23.6– 59.4) with 93 men (32%) experiencing pathologic progression and 96 men (33%) abandoning active surveillance. Men taking a 5ARI experienced a lower rate of pathologic progression (18.6% vs 36.7%, p 0.004) and were less likely to abandon active surveillance (20% vs 37.6%, p 0.006). The median time to progression was longer in the 5ARI group (42.5 months) compared to the non-5ARI group (31.5 months; p 0.026). On multivariate analysis, lack of 5ARI use was most strongly associated with pathologic progression (OR 2.98, 95% CI 1.5–5.9) followed by age and baseline maximum percentage involvement of any biopsy core. CONCLUSIONS: 5ARIs were associated with a significantly lower rate of pathologic progression and abandonment of active surveillance.