Wilms’ Tumor in a 37-Year-Old

Wilms’ tumor is rare in adults. Though the approach to diagnosis and treatment of adult Wilms’ tumor (AWT) is closely modeled on recommendations for childhood Wilms’ tumor, views differ on how aggressive the treatment should be. We report a case of a 37-year-old with Stage III favorable histology AWT. A radical nephrectomy was performed and the patient was due for chemotherapy. Recent advances, controversies and current recommendations in the treatment of AWT are discussed

ФАРМАКОДИНАМИЧЕСКАЯ ЭКВИВАЛЕНТНОСТЬ ПРИМЕНЕНИЯ3-МЕСЯЧНОЙ И 28-ДНЕВНОЙ ФОРМЫ ДЕКАПЕПТИЛА ДЕПО МЕДЛЕННОГО ВЫСВОБОЖДЕНИЯ У ПАЦИЕНТОВ С РАСПРОСТРАНЕННЫМ РАКОМ ПРЕДСТАТЕЛЬНОЙ ЖЕЛЕЗЫ

Objective: to evaluate the pharmacodynamic equivalence of 3-month and 28-day formulations of tryptoreline, a sustained-release luteininghormone (LH)-releasing hormone analogue.Subjects and methods. The patients who had a verified diagnosis of locally advanced or metastatic prostate cancer were randomized intogroups to have either one injection of a 3-month dosage form (n = 63) or 3 injections of a 28-day formulation at 28-day intervals (n = 68).The onset rate of drug-induced castration, which was defined as a percentage of the patients achieving a plasma testosterone level of ≤0.5ng/ml, was compared on day 84 (i.e. thrice every 28 days). The plasma profiles of testosterone, LH, and tryptoreline, as well as the changesin the plasma concentration of prostate-specific antigen (PCA) from the baseline values were estimated within 3 months (from the initiationof therapy to day 91).Results. In the 3-month and 28-day groups, the onset rate of drug-induced castration was 98 and 96%, respectively (at confidenceintervals (94.2% bilaterally) in [-8.1%; 9.6%]. The median time for drug-induced castration was 18.8 and 18.5 days, respective-ly (p = 0.86; log-rank test). The ratios of the mean peak plasma concentrations to AUC91 of the two formulations for testosteroneand LH were within 0.80; 1.25 equivalence interval. By day 91, the mean PSA level was decreased by 91.0 and 91.7%, respec-tively (p = 0.73).Conclusion. The use of the two formulations during 3 months is pharmacologically equal.  Фармакодинамическая эквивалентность применения3-месячной и 28-дневной формы Декапептила депо медленного высвобождения у пациентов с распространенным раком предстательной железы

Contemporary update of cancer control after radical prostatectomy in the UK

Despite a significant increase of the number of radical prostatectomies (RPs) to treat organ-confined prostate cancer, there is very limited documentation of its oncological outcome in the UK. Pathological stage distribution and changes of outcome have not been audited on a consistent basis. We present the results of a multicentre review of postoperative predictive variables and prostatic-specific antigen (PSA) recurrence after RP for clinically organ-confined disease. In all, 854 patient's notes were audited for staging parameters and follow-up data obtained. Patients with neoadjuvant and adjuvant treatment as well as patients with incomplete data and follow-up were excluded. Median follow-up was 52 months for the remaining 705 patients. The median PSA was 10 ng ml−1. A large migration towards lower PSA and stage was seen. This translated into improved PSA survival rates. Overall Kaplan–Meier PSA recurrence-free survival probability at 1, 3, 5 and 8 years was 0.83, 0.69, 0.60 and 0.48, respectively. The 5-year PSA recurrence-free survival probability for PSA ranges 20 ng ml−1 was 0.82, 0.73, 0.59 and 0.20, respectively (log rank, P<0.0001). PSA recurrence-free survival probabilities for pathological Gleason grade 2–4, 5 and 6, 7 and 8–10 at 5 years were 0.84, 0.66, 0.55 and 0.21, respectively (log rank, P<0.0001). Similarly, 5-year PSA recurrence-free survival probabilities for pathological stages T2a, T2b, T3a, T3b and T4 were 0.82, 0.78, 0.48, 0.23 and 0.12, respectively (log rank, P=0.0012). Oncological outcome after RP has improved over time in the UK. PSA recurrence-free survival estimates are less optimistic compared to quoted survival figures in the literature. Survival figures based on pathological stage and Gleason grade may serve to counsel patients postoperatively and to stratify patients better for adjuvant treatment

Controversies in the management of advanced prostate cancer

For advanced prostate cancer, the main hormone treatment against which other treatments are assessed is surgical castration. It is simple, safe and effective, however it is not acceptable to all patients. Medical castration by means of luteinizing hormone-releasing hormone (LH-RH) analogues such as goserelin acetate provides an alternative to surgical castration. Diethylstilboestrol, previously the only non-surgical alternative to orchidectomy, is no longer routinely used. Castration reduces serum testosterone by around 90%, but does not affect androgen biosynthesis in the adrenal glands. Addition of an anti-androgen to medical or surgical castration blocks the effect of remaining testosterone on prostate cells and is termed combined androgen blockade (CAB). CAB has now been compared with castration alone (medical and surgical) in numerous clinical trials. Some trials show advantage of CAB over castration, whereas others report no significant difference. The author favours the view that CAB has an advantage over castration. No study has reported that CAB is less effective than castration. Of the anti-androgens which are available for use in CAB, bicalutamide may be associated with a lower incidence of side-effects compared with the other non-steroidal anti-androgens and, in common with nilutamide, has the advantage of once-daily dosing. Only one study has compared anti-androgens within CAB: bicalutamide plus LH-RH analogue and flutamide plus LH-RH analogue. At 160-week follow-up, the groups were equivalent in terms of survival and time to progression. However, bicalutamide caused significantly less diarrhoea than flutamide. Withdrawal and intermittent therapy with anti-androgens extend the range of treatment options. © 1999 Cancer Research Campaig

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio