Commentary: the role of cytologic analysis of voided urine in the work-up of asymptomatic microhematuria

Microscopic hematuria is a common finding in patients presenting to both primary care doctors as well as urologists. Sources of microscopic hematuria include infection, stones, inflammatory disorders as well as cancer of the genitourinary tract, particularly urothelial cancer. A primary focus in the urologic workup of hematuria is to rule out cancer. This is done using radiographic studies as well as procedures such as cystoscopy and bladder biopsy. As the authors state in their article titled "The utility of serial urinary cytology in the initial evaluation of the patient with microscopic hematuria", cytologic analysis of voided urine, though attractive due to its noninvasive nature, has been found to have the neither the sensitivity, cost-effectiveness, nor the ease of administration necessary to replace more invasive diagnostics in the evaluation of microscopic hematuria

Jacobsen syndrome

Jacobsen syndrome is a MCA/MR contiguous gene syndrome caused by partial deletion of the long arm of chromosome 11. To date, over 200 cases have been reported. The prevalence has been estimated at 1/100,000 births, with a female/male ratio 2:1. The most common clinical features include pre- and postnatal physical growth retardation, psychomotor retardation, and characteristic facial dysmorphism (skull deformities, hypertelorism, ptosis, coloboma, downslanting palpebral fissures, epicanthal folds, broad nasal bridge, short nose, v-shaped mouth, small ears, low set posteriorly rotated ears). Abnormal platelet function, thrombocytopenia or pancytopenia are usually present at birth. Patients commonly have malformations of the heart, kidney, gastrointestinal tract, genitalia, central nervous system and skeleton. Ocular, hearing, immunological and hormonal problems may be also present. The deletion size ranges from ~7 to 20 Mb, with the proximal breakpoint within or telomeric to subband 11q23.3 and the deletion extending usually to the telomere. The deletion is de novo in 85% of reported cases, and in 15% of cases it results from an unbalanced segregation of a familial balanced translocation or from other chromosome rearrangements. In a minority of cases the breakpoint is at the FRA11B fragile site. Diagnosis is based on clinical findings (intellectual deficit, facial dysmorphic features and thrombocytopenia) and confirmed by cytogenetics analysis. Differential diagnoses include Turner and Noonan syndromes, and acquired thrombocytopenia due to sepsis. Prenatal diagnosis of 11q deletion is possible by amniocentesis or chorionic villus sampling and cytogenetic analysis. Management is multi-disciplinary and requires evaluation by general pediatrician, pediatric cardiologist, neurologist, ophthalmologist. Auditory tests, blood tests, endocrine and immunological assessment and follow-up should be offered to all patients. Cardiac malformations can be very severe and require heart surgery in the neonatal period. Newborns with Jacobsen syndrome may have difficulties in feeding and tube feeding may be necessary. Special attention should be devoted due to hematological problems. About 20% of children die during the first two years of life, most commonly related to complications from congenital heart disease, and less commonly from bleeding. For patients who survive the neonatal period and infancy, the life expectancy remains unknown

The example of CaPSURE: lessons learned from a national disease registry

IntroductionAlthough randomized controlled trials (RCTs) remain the gold standard for determining evidence-based clinical practices, large disease registries that enroll large numbers of patients have become paramount as a relatively cost-effective additional tool.MethodsWe highlight the advantages of disease registries focusing on the example of prostate cancer and the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE™) registry.ResultsCaPSURE collects approximately 1,000 clinical and patient-reported variables, in over 13,000 men that are enrolled. Thus far, CaPSURE has yielded over 130 peer-reviewed publications, with several others in press, in key areas of risk migration, practice patterns, outcome prediction, and quality of life outcomes.ConclusionsDisease registries, like CaPSURE complement RCTs and CaPSURE, have provided a means to better understand many aspects of prostate cancer epidemiology, practice patterns, oncologic and HRQOL outcomes, and costs of care across populations. Specialized observational disease registries such as CaPSURE provide insight and have broad implications for disease management and policy

Changes in neuronal activation patterns in response to androgen deprivation therapy: a pilot study

<p>Abstract</p> <p>Background</p> <p>A common treatment option for men with prostate cancer is androgen deprivation therapy (ADT). However, men undergoing ADT may experience physical side effects, changes in quality of life and sometimes psychiatric and cognitive side effects.</p> <p>Methods</p> <p>In this study, hormone naïve patients without evidence of metastases with a rising PSA were treated with nine months of ADT. Functional magnetic resonance imaging (fMRI) of the brain during three visuospatial tasks was performed at baseline prior to treatment and after nine months of ADT in five subjects. Seven healthy control patients, underwent neuroimaging at the same time intervals.</p> <p>Results</p> <p>ADT patients showed reduced, task-related BOLD-fMRI activation during treatment that was not observed in control subjects. Reduction in activation in right parietal-occipital regions from baseline was observed during recall of the spatial location of objects and mental rotation.</p> <p>Conclusions</p> <p>Findings, while preliminary, suggest that ADT reduces task-related neural activation in brain regions that are involved in mental rotation and accurate recall of spatial information.</p

Detrimental Effects of Non-Functional Spermatozoa on the Freezability of Functional Spermatozoa from Boar Ejaculate

In the present study, the impact of non-functional spermatozoa on the cryopreservation success of functional boar spermatozoa was evaluated. Fifteen sperm-rich ejaculate fractions collected from five fertile boars were frozen with different proportions of induced non-functional sperm (0 –native semen sample-, 25, 50 and 75% non-functional spermatozoa). After thawing, the recovery of motile and viable spermatozoa was assessed, and the functional of the spermatozoa was evaluated from plasma membrane fluidity and intracellular reactive oxygen species (ROS) generation upon exposure to capacitation conditions. In addition, the lipid peroxidation of the plasma membrane was assessed by the indirect measurement of malondialdehyde (MDA) generation. The normalized (with respect to a native semen sample) sperm motility (assessed by CASA) and viability (cytometrically assessed after staining with Hoechst 33342, propidium iodide and fluorescein-conjugated peanut agglutinin) decreased (p<0.01) as the proportion of functional spermatozoa in the semen samples before freezing decreased, irrespective of the semen donor. However, the magnitude of the effect differed (p<0.01) among boars. Moreover, semen samples with the largest non-functional sperm subpopulation before freezing showed the highest (p<0.01) levels of MDA after thawing. The thawed viable spermatozoa of semen samples with a high proportion of non-functional spermatozoa before freezing were also functionally different from those of samples with a low proportion of non-functional spermatozoa. These differences consisted of higher (p<0.01) levels of intracellular ROS generation (assessed with 5-(and-6) chloromethyl-20,70-dichlorodihydrofluorescein diacetate acetyl ester; CM-H2DCFDA) and increased (p<0.01) membrane fluidity (assessed with Merocyanine 540). These findings indicate that non-functional spermatozoa in the semen samples before freezing negatively influence the freezability of functional spermatozoa

Androgenic dependence of exophytic tumor growth in a transgenic mouse model of bladder cancer: a role for thrombospondin-1

<p>Abstract</p> <p>Background</p> <p>Steroid hormones influence mitogenic signaling pathways, apoptosis, and cell cycle checkpoints, and it has long been known that incidence of bladder cancer (BC) in men is several times greater than in women, a difference that cannot be attributed to environmental or lifestyle factors alone. Castration reduces incidence of chemically-induced BC in rodents. It is unclear if this effect is due to hormonal influences on activation/deactivation of carcinogens or a direct effect on urothelial cell proliferation or other malignant processes. We examined the effect of castration on BC growth in UPII-SV40T transgenic mice, which express SV40 T antigen specifically in urothelium and reliably develop BC. Furthermore, because BC growth in UPII-SV40T mice is exophytic, we speculated BC growth was dependent on angiogenesis and angiogenesis was, in turn, androgen responsive.</p> <p>Methods</p> <p>Flat panel detector-based cone beam computed tomography (FPDCT) was used to longitudinally measure exophytic BC growth in UPII-SV40T male mice sham-operated, castrated, or castrated and supplemented with dihydrotestosterone (DHT). Human normal bladder and BC biopsies and mouse bladder were examined quantitatively for thrombospondin-1 (TSP1) protein expression.</p> <p>Results</p> <p>Mice castrated at 24 weeks of age had decreased BC volumes at 32 weeks compared to intact mice (p = 0.0071) and castrated mice administered DHT (p = 0.0233; one-way ANOVA, JMP 6.0.3, SAS Institute, Inc.). Bladder cancer cell lines responded to DHT treatment with increased proliferation, regardless of androgen receptor expression levels. TSP1, an anti-angiogenic factor whose expression is inhibited by androgens, had decreased expression in bladders of UPII-SV40T mice compared to wild-type. Castration increased TSP1 levels in UPII-SV40T mice compared to intact mice. TSP1 protein expression was higher in 8 of 10 human bladder biopsies of normal versus malignant tissue from the same patients.</p> <p>Conclusion</p> <p>FPDCT allows longitudinal monitoring of exophytic tumor growth in the UPII-SV40T model of BC that bypasses need for chemical carcinogens, which confound analysis of androgen effects. Androgens increase tumor cell growth <it>in vitro </it>and <it>in vivo </it>and decrease TSP1 expression, possibly explaining the therapeutic effect of castration. This effect may, in part, explain gender differences in BC incidence and implies anti-androgenic therapies may be effective in preventing and treating BC.</p

Tri-Modality therapy with I-125 brachytherapy, external beam radiation therapy, and short- or long-term hormone therapy for high-risk localized prostate cancer (TRIP): study protocol for a phase III, multicenter, randomized, controlled trial

<p>Abstract</p> <p>Background</p> <p>Patients with high Gleason score, elevated prostate specific antigen (PSA) level, and advanced clinical stage are at increased risk for both local and systemic relapse. Recent data suggests higher radiation doses decrease local recurrence and may ultimately benefit biochemical, metastasis-free and disease-specific survival. No randomized data is available on the benefits of long-term hormonal therapy (HT) in these patients. A prospective study on the efficacy and safety of trimodality treatment consisting of HT, external beam radiation therapy (EBRT), and brachytherapy (BT) for high-risk prostate cancer (PCa) is strongly required.</p> <p>Methods/Design</p> <p>This is a phase III, multicenter, randomized controlled trial (RCT) of trimodality with BT, EBRT, and HT for high-risk PCa (TRIP) that will investigate the impact of adjuvant HT following BT using iodine-125 (¹²⁵I-BT) and supplemental EBRT with neoadjuvant and concurrent HT. Prior to the end of September 2012, a total of 340 patients with high-risk PCa will be enrolled and randomized to one of two treatment arms. These patients will be recruited from more than 41 institutions, all of which have broad experience with ¹²⁵I-BT. Pathological slides will be centrally reviewed to confirm patient eligibility. The patients will commonly undergo 6-month HT with combined androgen blockade (CAB) before and during ¹²⁵I-BT and supplemental EBRT. Those randomly assigned to the long-term HT group will subsequently undergo 2 years of adjuvant HT with luteinizing hormone-releasing hormone agonist. All participants will be assessed at baseline and every 3 months for the first 30 months, then every 6 months until 84 months from the beginning of CAB.</p> <p>The primary endpoint is biochemical progression-free survival. Secondary endpoints are overall survival, clinical progression-free survival, disease-specific survival, salvage therapy non-adaptive interval, and adverse events.</p> <p>Discussion</p> <p>To our knowledge, there have been no prospective studies documenting the efficacy and safety of trimodality therapy for high-risk PCa. The present RCT is expected to provide additional insight regarding the potency and limitations of the addition of 2 years of adjuvant HT to this trimodality approach, and to establish an appropriate treatment strategy for high-risk PCa.</p> <p>Trial registration</p> <p>UMIN000003992</p