Decipher correlation patterns post prostatectomy: initial experience from 2 342 prospective patients.

BACKGROUND: Currently, there are multiple commercially available RNA-based biomarkers that are Medicare approved and suggested for use by the National Comprehensive Cancer Network guidelines. There is uncertainty as to which patients benefit from genomic testing and for whom these tests should be ordered. Here, we examined the correlation patterns of Decipher assay to understand the relationship between the Decipher and patient tumor characteristics. METHODS: De-identified Decipher test results (including Decipher risk scores and clinicopathologic data) from 2 342 consecutive radical prostatectomy (RP) patients tested between January and September 2015 were analyzed. For clinical testing, tumor specimen from the highest Gleason grade was sampled using a 1.5 mm tissue punch. Decipher scores were calculated based on a previously locked model. Correlations between Decipher score and clinicopathologic variables were computed using Spearman's rank correlation. Mixed-effect linear models were used to study the association of practice type and Decipher score. The significance level was 0.05 for all tests. RESULTS: Decipher score had a positive correlation with pathologic Gleason score (PGS; r=0.37, 95% confidence interval (CI) 0.34-0.41), pathologic T-stage (r=0.31, 95% CI 0.28-0.35), CAPRA-S (r=0.32, 95% CI 0.28-0.37) and patient age (r=0.09, 95% CI 0.05-0.13). Decipher reclassified 52%, 76% and 40% of patients in CAPRA-S low-, intermediate- and high-risk groups, respectively. We detected a 28% incidence of high-risk disease through the Decipher score in pT2 patients and 7% low risk in pT3b/pT4, PGS 8-10 patients. There was no significant difference in the Decipher score between patients from community centers and those from academic centers (P=0.82). CONCLUSIONS: Although Decipher correlated with baseline tumor characteristics for over 2 000 patients, there was significant reclassification of tumor aggressiveness as compared to clinical parameters alone. Utilization of the Decipher genomic classifier can have major implications in assessment of postoperative risk that may impact physician-patient decision making and ultimately patient management.

Compostos coordenados híbridos de platina no tratamento do câncer / Platinum hybrid coordinated compounds in cancertreatment

O câncer, ou neoplasia, é uma doença caracterizada pela propagação descontrolada de formas anormais das próprias células corporais e corresponde à segunda doença que mais causa mortes no mundo. A história da platina no tratamento do câncer teve início com a descoberta da sua atividade, em 1965, com a aprovação para uso clínico acontecendo apenas após 10 anos. Atualmente, os fármacos com platina estão entre os mais bem sucedidos agentes anticancerígenos, onde se destacam cisplatina (1), carboplatina (2) e oxaliplatina (3). Seus mecanismos de ação são similares: estes fármacos formam adutos com o DNA, impedindo a sua síntese e reparo, levando à morte celular. Contudo, os efeitos adversos desencadeados pelo tratamento e o desenvolvimento de resistência ao medicamento têm limitado suas aplicações. Uma das principais estratégias para a diminuição de tais efeitos consiste em alterar a estrutura destas moléculas, levando à formação de compostos híbridos, que se caracterizam pela presença de pelo menos dois fragmentos funcionais distintos em uma mesma molécula e podem apresentar maior espectro de atividade antitumoral. Dentre as alterações mais comuns encontram-se a modificação da solubilidade, através da inserção de grupos abandonadores mais ou menos hidrofóbicos e a introdução de ligantes com atividade biológica própria. Dessa forma, esta revisão visa verificar os avanços mais recentes na síntese de compostos híbridos de platina, bem como as melhorias na atividade anticâncer dos novos compostos platinados...

Cancer, or neoplasm, is a disease characterized by the uncontrolled propagation of abnormal cells of the body and is the second leading death-causing disease. The history of platinum in cancer treatment goes back to the discovery of its activity in 1965 and its approval for clinical use just 10 years later. Some of the most successful anticancer agents are Pt-based chemotherapeutics, among which cisplatin (1), carboplatin (2), and oxaliplatin (3) stand out. They have similar mechanisms of action: they form adducts with DNA, preventing its synthesis and repair and leading to cell death. However, adverse effects triggered by treatment and the development of resistance to these drugs have limited their application. One of the most important strategies to reduce such effects is to carry out structural modifications of these molecules, leading to hybrid compounds that are characterized by the presence of at least two distinct functional fragments on the same molecule and can exhibit a broader antitumor activity spectrum. Among the most typical modifications are changes to the solubility pattern, created by the insertion of leaving groups with high or low hydrophobicity, and the introduction of biologically active ligands as non-leaving groups. The purpose of these strategies is to obtain compounds capable of reducing systemic toxicity and/or overcoming acquired resistance factors to cisplatin. Therefore, the aim of this review is to discuss the most recent advances in the synthesis of hybrid platinum compounds, as well as improvements in the anticancer activity of Pt-compounds...

A new injectable bulking agent for treatment of stress urinary incontinence: results of a multicenter, randomized, controlled, double-blind study of Durasphere.

OBJECTIVES: To assess the safety and effectiveness of Durasphere compared with bovine collagen in the treatment of stress urinary incontinence (SUI) due to intrinsic sphincter deficiency (ISD). METHODS: This multicenter, randomized, controlled, double-blind trial was composed of 355 women diagnosed with SUI due to ISD and used a standardized pad test and the Stamey continence grade as the primary endpoints. The participants' ages ranged from 26 to 84 years. All patients had an abdominal leak point pressure of less than 90 cm H(2)O (average 51). RESULTS: At 12 months after the first injection, the two materials were equivalent with respect to the improvement in continence grade and pad weight testing. Less Durasphere was injected to obtain comparable clinical results (Durasphere 4.83 mL versus bovine collagen 6.23 mL, P <0.001). When examined 1 year after the date of the last treatment, 49 (80.3%) of the 61 women treated with Durasphere showed improvement of 1 continence grade or more compared with 47 (69.1%) of 68 women treated with bovine collagen (P value for difference = 0.162). Although the adverse events reported for both groups were similar, the Durasphere group had an increased short-term risk of urgency and urinary retention. CONCLUSIONS: The use of Durasphere for the treatment of SUI due to ISD was equally effective as bovine collagen and used less material. The U.S. Food and Drug Administration granted market approval for Durasphere on September 13, 1999. The product design and initial clinical data suggest the potential for greater durability of the clinical benefit, with the possibility of a permanent solution for SUI due to ISD in some patients.

Percutaneous access to a continent urinary reservoir for removal of intravesical calculi: a case report.

Stone formation within urinary reservoirs is a well recognized problem. Various endourological techniques have been used to treat these stones. We report a case in which reservoir calculi were removed via a percutaneous approach.

Use of a double cuff AMS800 urinary sphincter for severe stress incontinence.

Stress urinary incontinence in the male patient has been successfully treated with the artificial urinary sphincter. However, approximately 15% of the patients treated are still significantly wet despite some improvement with this device. These patients usually are almost totally incontinent before artificial sphincter implantation. Of 15 such patients 80% were rendered satisfactorily dry by adding a second sphincter cuff around the bulbous urethra. This double cuff technique increases the success rate with the AMS800 sphincter to greater than 95%.

Conversion of an ileal conduit to a continent catheterizable stoma.

A technique is described by which a previously constructed ileal conduit is used as an efferent limb of a continent urinary reservoir. The ileal segment is tapered; 1 end is tunneled submucosally into a reconfigured colonic reservoir and the other end is brought to the skin as a catheterizable stoma. This modification of the Mitrofanoff principle provides a highly continent stoma that is easily catheterized, and allows for preservation of the terminal ileum and ileocecal valve within the gastrointestinal tract.

The clinical implications of brushite calculi.

The clinical history of 30 patients with a total of 46 proved brushite urinary calculi was reviewed. The patients were active metabolically with 87% having a history of multiple calculi. Of the brushite stones 61% appeared hyperdense on x-ray but they had no consistent shape. Of the patients who were metabolically evaluated 82% had treatable abnormalities. Treatment with percutaneous nephrostolithotomy or ureteroscopy and ureteral lithotripsy was 92% successful in rendering the patient stone-free, whereas, extracorporeal shock wave lithotripsy monotherapy resulted in a stone-free rate of only 11%. Brushite stone patients require aggressive treatment, full metabolic evaluation and close clinical followup.

Cloacal exstrophy reconstruction for urinary continence.

From 1978 to 1989 we treated 16 patients with cloacal exstrophy, including 8 who have been treated since birth. To achieve urinary continence bladder reconstruction was required in 12 patients, including 3 ileocystoplasties, 4 gastrocystoplasties and 5 gastric continent urinary reservoirs. All 12 patients underwent simultaneous bladder neck/urethral continence procedures. Of the 12 patients with completed reconstruction 10 were evaluable for continence. All 10 patients are dry for periods of 3 or more hours, and 5 are totally dry day and night. All but 1 patient are totally dependent on clean intermittent catheterization. Followup ranges from 2 to 66 months, and all except 1 patient have stable upper tract function. Patients with cloacal exstrophy can undergo reconstruction in a fashion to maintain urinary continence, and stomach is the ideal tissue for such reconstruction.

Construction of an antirefluxing urinary conduit using a plicated ileocecal segment.

A plicated ileocecal segment was used to construct an antirefluxing urinary conduit in 3 patients. Each patient had markedly dilated or shortened ureters that prevented conventional Leadbetter ureteral reimplantation into a colon conduit. Ascending colon was brought out as a cutaneous stoma, the ureters were anastomosed to ileum, and an antireflux mechanism was created from plicated terminal ileum and the native ileocecal valve. Significant reflux was prevented in all 3 patients. This technique provides a means to prevent urinary reflux into short or dilated ureters, and increases the versatility of the ileocecal segment for use in diversion and urinary tract reconstruction.

Testicular papillary cystadenomatous tumor of low malignant potential: a case report and discussion of the literature.

We report the fifth case of a rare testicular serous papillary cystadenomatous tumor of low malignant potential. All patients presented with a testicular mass. Histologically, the tumor can be differentiated from testicular papillary cystadenocarcinoma. The natural history of this rare tumor is yet to be determined.