PROState Pathway Embedded Comparative Trial: The IP3-PROSPECT study.

INTRODUCTION: The traditional double blind RCT is the 'gold standard' trial design. For a variety of reasons, these designs often fail to accrue enough participants to conclude. This is particularly challenging in localized prostate cancer. The cohort multiple randomised controlled trial (cmRCT) trial design may represent an alternative approach to delivering robust comparative data in prostate cancer. PATIENTS AND METHODS: IP3-PROSPECT is a cmRCT designed to test multiple prostate cancer interventions from eligible men in one cohort. Key to the design is two points of consent. First, at point of consent one, men referred for prostate cancer investigations are invited to join the cohort. They may then be randomly invited at a later date to consider an intervention at point of consent two. In the pilot phase we will test the acceptability and feasibility of developing the cohort. RESULTS: Acceptability and feasibility of the study will be measured by a combination of quantitative and qualitative methods. The primary outcome measure is the rate of consent to inclusion to the IP3-PROSPECT cohort. Secondary outcome measures include the completeness of data collection at sites and return rates of patient questionnaires. We will also interview patients and healthcare professionals to explore their thoughts on the implementation, practicality and efficiency of IP3-PROSPECT. CONCLUSION: The IP3-PROSPECT study will evaluate the cmRCT design in prostate cancer. Initially we will pilot the design, assessing for acceptability and feasibility. The cmRCT is an innovative design that offers potential for building a modern comparative evidence base for prostate cancer.

Diagnosis of prostate cancer by detection of minichromosome maintenance 5 protein in urine sediments.

BACKGROUND: The accuracy of prostate-specific antigen (PSA) testing in prostate cancer detection is constrained by low sensitivity and specificity. Dysregulated expression of minichromosome maintenance (Mcm) 2-7 proteins is an early event in epithelial multistep carcinogenesis and thus MCM proteins represent powerful cancer diagnostic markers. In this study we investigate Mcm5 as a urinary biomarker for prostate cancer detection. METHODS: Urine was obtained from 88 men with prostate cancer and from two control groups negative for malignancy. A strictly normal cohort included 28 men with complete, normal investigations, no urinary calculi and serum PSA <2 ng ml(-1). An expanded control cohort comprised 331 men with a benign final diagnosis, regardless of PSA level. Urine was collected before and after prostate massage in the cancer patient cohort. An immunofluorometric assay was used to measure Mcm5 levels in urine sediments. RESULTS: The Mcm5 test detected prostate cancer with 82% sensitivity (confidence interval (CI)= 72-89%) and with a specificity ranging from 73 (CI=68-78%) to 93% (CI=76-99%). Prostate massage led to increased Mcm5 signals compared with pre-massage samples (median 3440 (interquartile range (IQR) 2280 to 5220) vs 2360 (IQR <1800 to 4360); P=0.009), and was associated with significantly increased diagnostic sensitivity (82 vs 60%; P=0.012). CONCLUSIONS: Urinary Mcm5 detection seems to be a simple, accurate and noninvasive method for identifying patients with prostate cancer. Large-scale prospective trials are now required to evaluate this test in diagnosis and screening.

High-intensity-focused ultrasound in the treatment of primary prostate cancer: the first UK series.

BACKGROUND: The use of minimally invasive ablative therapies in localised prostate cancer offer potential for a middle ground between active surveillance and radical therapy. METHODS: An analysis of men with organ-confined prostate cancer treated with transrectal whole-gland HIFU (Sonablate 500) between 1 February 2005 and 15 May 2007 was carried out in two centres. Outcome data (side-effects using validated patient questionnaires, biochemical, histology) were evaluated. RESULTS: A total of 172 men were treated under general anaesthetic as day-case procedures with 78% discharged a mean 5 h after treatment. Mean follow-up was 346 days (range 135-759 days). Urethral stricture was significantly lower in those with suprapubic catheter compared with urethral catheters (19.4 vs 40.4%, P=0.005). Antibiotics were given to 23.8% of patients for presumed urinary tract infection and the rate of epididymitis was 7.6%. Potency was maintained in 70% by 12 months, whereas mild stress urinary incontinence (no pads) was reported in 7.0% (12 out of 172) with a further 0.6% (1 out of 172) requiring pads. There was no rectal toxicity and no recto-urethral fistulae. In all, 78.3% achieved a PSA nadir < or =0.5 microg ml(-1) at 12 months, with 57.8% achieving < or =0.2 microg ml(-1). Then, 8 out of 13 were retreated with HIFU, one had salvage external beam radiotherapy and four chose active surveillance for small-volume low-risk disease. Overall, there was no evidence of disease (PSA <0.5 microg ml(-1) or negative biopsy if nadir not achieved) after one HIFU session in 92.4% (159 out of 172) of patients. CONCLUSION: HIFU is a minimally invasive, day-case ablative technique that can achieve good biochemical outcomes in the short term with minimal urinary incontinence and acceptable levels of erectile dysfunction. Long-term outcome needs further evaluation and the inception of an international registry for cases treated using HIFU will significantly aid this health technology assessment.

Donor-derived human herpes virus 8-related Kaposi's sarcoma in renal allograft ureter.

We present a case of human herpes virus 8 (HHV8)-associated Kaposi sarcoma (KS) occurring in a renal allograft ureter from a male donor. The female patient presented with a rising creatinine due to ureteric obstruction, and subsequent histological examination of the excised tumor revealed a KS. The tumor tested positive for HHV8 antigen and, using in situ hybridization to identify X and Y chromosomes, we were able to demonstrate that the tumor was of male origin. In the absence of any other KS lesions, this suggested that the tumor arose due to reactivation of latent HHV8 in the donor tissue, permitted by the recipient's immunosuppression. The patient was managed by a gradual reduction in immunosuppression and there has been no subsequent recurrence of the tumor. KS in renal transplantation is discussed in detail including the possible utility of pre-transplant HHV8 screening.

Evaluation of ideal irrigation fluid in 'Greenlight' photoselective vapourization of the prostate.

Although many anecdotal opinions are available that water gives a better visual quality, no studies have analysed the differences in the visual quality of the operative field with the use of either saline or sterile water. As part of a prospective audit we wished to assess the effect of differing irrigant fluids on intraoperative visibility during Greenlight photoselective vapourization of prostate (PVP). Twenty-nine consecutive patients with prostates less than 100 cm(3) who underwent PVP were studied. The irrigation fluid used was randomly connected on a bag-by-bag basis, with the surgeon blinded to the bag's contents. Towards the end of each bag the surgeon gave a score to the quality of vision. All surgeons were familiarized with the vision scoring system in advance. The scores were analysed in two ways. The mean scores for water and saline were compared. In addition, a mean score for each fluid in each patient where both fluids were used (n=24) was separately calculated and the means for each fluid compared. One hundred and twenty-four bags of fluid in 29 operative cases were analysed. The mean overall vision scores were 3.94% for saline and 4.01% for water (P=0.62). The paired data were analysed using the Student's t-test and there was no statistically significant difference (P=0.34). We showed no significant difference in visual quality between water and saline during PVP. Although fluid absorption is almost unknown with PVP, there seems to be no justification for using water irrigation if saline is available, particularly with a theoretical risk of absorption.

Misplaced Macroplastique injection presenting as a vaginal nodule and a bladder mass.

We describe a very unusual presentation of misplaced Macroplastique injection. This incidentally showed up as bladder lesion and vaginal nodule during a tension-free vaginal tape surgery.

Health related quality of life (HRQoL) after cystectomy: comparison between orthotopic neobladder and ileal conduit diversion.

INTRODUCTION: Radical cystectomy and urinary diversion carries a high morbidity. Quality of life and body image are important considerations for urinary diversion (UD). We wanted to conduct a systematic review of literature to see which form UD offers a better quality of life (QoL). METHODS: We searched MEDLINE, Pubmed, EMBASE, CINAHL and the Cochrane library for studies using the following key words: 'quality of life' and 'ileal conduit', 'orthotopic neobladder', 'continent diversion' and 'urinary diversion'. All English language articles on UD surgery were included in the original search from 1990 to 2014. To improve the quality of evidence, we stratified our inclusion criteria into studies that report on QoL in both forms of UD using at least one validated questionnaire. RESULTS: Twenty-one studies (2285 patients) were included in our study all of which used at least one validated tool. The most frequently used tools were the SF-36, EORTC QLQ-C30 and FACT BL (10, 8, 5 studies respectively). None of the studies were randomised and only 4 studies were prospectively designed. Sixteen studies reported no difference in QoL between the two types of urinary diversion and four studies reported a better QoL with orthotopic neobladder of which 2 studies had younger and fitter patients. On the other hand, one study reported a better QoL in ileal conduit patients. CONCLUSION: Orthotopic neobladder urinary diversion shows a marginally better quality of life scores compared to ileal conduit diversion especially when considering younger and fitter patients.

Robot-assisted management of Zinner's syndrome: report of seminal vesicle sparing technique and review of literature.

The range of urological procedures performed with robotic assistance has widened with increasing experience with the da Vinci robotic system. We describe the use of the da Vinci SI Surgical System for excision of a seminal vesicle cyst in a patient who had associated ipsilateral renal agenesis (Zinner's syndrome). The robotic platform afforded a minimally invasive procedure with precise dissection and no collateral damage to neighbouring vital anatomy.

Mitogenic growth signalling, DNA replication licensing, and survival are linked in prostate cancer.

Activation of mitogen/extracellular-signal-regulated kinase kinase 5/extracellular signal-regulated kinase-5 (MEK5/ERK5) growth signalling is coupled to increased cell proliferation in prostate cancer (PCa). Dysregulation of the DNA replication licensing pathway, a critical step in growth control downstream of transduction signalling pathways, is associated with development of PCa. In this study we have investigated linkages between the MEK5/ERK5 pathway and DNA replication licensing during prostate carcinogenesis. The effects of increased MEK5/ERK5 signalling on the expression of replication licensing factors Mcm2 and geminin and the proliferation marker Ki67 were studied in an ecdysone-inducible system expressing a constitutively activated mutant of MEK5 in EcR293 cells and in stable ERK5 over-expressing PC3 clones. In parallel, expression of these biomarkers in PCa biopsy specimens (n=58) was studied and compared to clinicopathological parameters. In both in vitro systems induction of MEK5 expression resulted in increased levels of phosphorylated ERK5 and Mcm2, geminin and Ki67 proteins. In PCa specimens average Mcm2 expression was greater than Ki67 and geminin expression (median labelling index (LI) 36.7, 18.1, and 3.4% respectively), consistent with their differential expression according to growth status (P<0.0001). Mcm2, geminin and Ki67 expression were significantly associated with Gleason grade (P=0.0002, P=0.0003, P=0.004); however there was no link with T or M stage. There was a significant relationship between increasing ERK5 expression and increasing Mcm2 (P=0.003) and Ki67 (P=0.009) expression, with non-significant trends seen with increasing MEK5 expression. There were significant associations between Gleason grade and the number of cells traversing G1 phase (Ki67(LI)-geminin(LI); (P=0.001)), with high ERK5 levels associated with both an increase in replication licensed but non-cycling cells (Mcm2(LI)-Ki67(LI); (P=0.01)) and accelerated cell cycle progression (geminin(LI)/Ki67(LI); (P= 0.005)), all indicative of a shift towards increasing proliferative potential. While Mcm2 and Ki67 were both prognostic factors on univariate analysis, only Mcm2 remained an independent prognostic marker on multivariate analysis. Taken together, our data show that induction of MEK5/ERK5 signalling is linked to activation of the DNA replication licensing pathway in PCa, and that the strong prognostic value of MCM proteins may result from their function as relay stations coupling growth regulatory pathways to genome duplication.

Rare case of primary lymphoma of the prostate: giving the patient the benefit of the doubt.

One third of non-Hodgkin lymphomas are extranodal, however it is uncommon for the lower urinary tract to be involved. We present an unusual case of a low-grade primary lymphoma affecting the prostate, which responded well to radical radiotherapy.