Nephroureterectomy surgery in the UK in 2012: British Association of Urological Surgeons (BAUS) Registry data.

OBJECTIVE: To report registry data obtained by the British Association of Urological Surgeons (BAUS) for nephroureterectomy (NU) surgery in the UK performed between 1 January and 31 December 2012. SUBJECTS/PATIENTS AND METHODS: Registry data entered by each individual surgeon's team (self-reported) on all 6042 nephrectomy surgeries reported to BAUS during 2012 were analysed to identify all NU surgery. Parameters for analysis included demographics, indication, type of surgery, histopathology and complications (Clavien system) of surgery. Data did not include tumour location or multiplicity, preoperative diagnostic evaluation or details of minimally invasive surgery (MIS) undertaken. Before analysis for this report a central process of 'data-cleansing' was undertaken by a BAUS group to address any discrepancy between the listed surgery and the preoperative indication. RESULTS: In all, 863 NU surgeries were included, performed by 220 consultant surgeons in 119 centres, and the median (range) number of NU per surgeon and unit was 3 (1-20) and 6 (1-29), respectively. The most common age group was 71-80 years (40%), most were male (64%), and haematuria was the most common presentation (74%). The dominant pathology was upper tract urothelial cancer (89%, 735), with final stage ≥pT2 in 47% (367), and the grade was 1, 2 or 3 in 6% (38), 36% (228) and 58% (362) respectively. Operative technique included MIS in 85% (720) and total reported operative complication rate (any Clavien) was 15% (128), of which Clavien ≥3 was reported in 4% (36), and perioperative death was reported in nine patients (1%). Advantages in favour of MIS included reduced hospital stay (median 5 vs 8 days), reduced major blood loss (3% vs 14%) and reduced transfusion requirement (6% vs 24%). In all, 76 cases (8%) were excluded from analysis based on benign pathology leading to reassignment to the 'simple nephrectomy' category. CONCLUSIONS: NU is currently a low-volume operation (median 3 cases/year) within the remit of the nephrectomy surgeon, but is a safe procedure with a relatively low complication rate. Most NU surgery in the UK is now performed with laparoscopic assistance, with advantages including reduced major blood loss, reduced transfusion requirement and shorter hospital stay.

Development and validation of risk score for predicting positive repeat prostate biopsy in patients with a previous negative biopsy in a UK population.

BACKGROUND: Little evidence is available to determine which patients should undergo repeat biopsy after initial benign extended core biopsy (ECB). Attempts have been made to reduce the frequency of negative repeat biopsies using PSA kinetics, density, free-to-total ratios and Kattan's nomogram, to identify men more likely to harbour cancer but no single tool accurately predicts biopsy outcome. The objective of this study was to develop a predictive nomogram to identify men more likely to have a cancer diagnosed on repeat prostate biopsy. METHODS: Patients with previous benign ECB undergoing repeat biopsy were identified from a database. Association between age, volume, stage, previous histology, PSA kinetics and positive repeat biopsy was analysed. Variables were entered stepwise into logistic regression models. A risk score giving the probability of positive repeat biopsy was estimated. The performance of this score was assessed using receiver characteristic (ROC) analysis. RESULTS: 110 repeat biopsies were performed in this period. Cancer was detected in 31% of repeat biopsies at Hospital (1) and 30% at Hospital (2). The most accurate predictive model combined age, PSA, PSA velocity, free-to-total PSA ratio, prostate volume and digital rectal examination (DRE) findings. The risk model performed well in an independent sample, area under the curve (AUCROC) was 0.818 (95% CI 0.707 to 0.929) for the risk model and 0.696 (95% CI 0.472 to 0.921) for the validation model. It was calculated that using a threshold risk score of > 0.2 to identify high risk individuals would reduce repeat biopsies by 39% while identifying 90% of the men with prostate cancer. CONCLUSION: An accurate multi-variable predictive tool to determine the risk of positive repeat prostate biopsy is presented. This can be used by urologists in an outpatient setting to aid decision-making for men with prior benign histology for whom a repeat biopsy is being considered.

A randomised trial of conventional versus BAUS procedure-specific consent forms for transurethral resection of prostate.

INTRODUCTION: Conventional consent forms often contain incomplete information regarding risks associated with invasive procedures. BAUS has introduced procedure-specific consent forms (PSCF) documenting the risks associated with urological procedures. We compared patients' understanding of the risks and benefits of TURP after the consenting process with either conventional documentation or PSCF. PATIENTS AND METHODS: One hundred patients were randomised to be consented with either a conventional or PSCF. After 3 h, their understanding was assessed with a questionnaire asking patients to document the indication and likelihood of symptomatic improvement, estimate frequency of complications and the risk of future re-operation. Data were compared by Mann-Whitney test. RESULTS: Fifty patients were randomised to each group. There was no significant difference in mean age, grade of doctor obtaining consent or time interval from consent to questionnaire. Both groups accurately predicted the chance of improved symptoms (median, 80%). There was no significant difference in patients' median estimation of risk of complications such as incontinence, erectile dysfunction, or retrograde ejaculation. Patients consented with the PSCF predicted the risk of re-operation more accurately (median answer, 10% versus 30%; P = 0.007, Mann-Whitney test). CONCLUSIONS: Recall of data was sub-optimal in both groups. For most data points there was no significant difference in estimation of risks between groups. Those consented with a procedure-specific consent form predicted risk of re-operation at 10 years more accurately. Procedure-specific consent forms offer an advantage over conventional consent in this study. We feel that the provision of a written structured framework allows better informed consent for TURP.

The type 1 insulin-like growth factor receptor is over-expressed in bladder cancer.

OBJECTIVE: To analyse bladder cancer biopsies and investigate the pattern of expression of the type 1 insulin-like growth factor receptor (IGF1R), a receptor tyrosine kinase that mediates tumour cell proliferation, motility and protection from apoptosis. MATERIALS AND METHODS: Formalin-fixed specimens of bladder cancer (40 whole-mount, 80 cores on a tumour microarray) and normal bladder (15 samples) were stained immunohistochemically for the IGF1R. The IGF1R expression was also measured by quantitative reverse transcription-polymerase chain reaction (Q-RT-PCR) on RNA extracted from fresh frozen bladder cancers (61) and benign bladder (12). RESULTS: Of the 15 samples of normal bladder, 14 showed negligible (1+) or light (2+) IGF1R immunostaining. By contrast moderate (3+) or heavy (4+) staining for IGF1R was detected in 89 (74%) of the 120 samples of malignant urothelium. Q-RT-PCR showed significantly higher levels of steady-state IGF1R mRNA in tumours (all cases, Ta-T4) than in normal bladder (P < 0.05), indicating up-regulation at the transcriptional level. This difference was particularly evident when comparing normal urothelium with superficial (Ta-T1) or invasive (T2-4) tumours; only the latter showed significant IGF1R over-expression at the RNA level (P < 0.05 vs normal bladder). CONCLUSION: The IGF1R is up-regulated in bladder cancer compared with non-malignant bladder, and might contribute to a propensity for invasion.

A double-blind, randomized, controlled trial of topical glyceryl trinitrate for transrectal ultrasound guided prostate biopsy.

PURPOSE: We evaluated the efficacy and tolerance of topical 0.2% glyceryl trinitrate (GTN) paste vs placebo to decrease pain associated with transrectal ultrasound guided prostate biopsy. MATERIALS AND METHODS: Between October 2003 and April 2004, 134 consecutive patients referred for a first prostate biopsy were randomized to receive topical 0.2% GTN paste or placebo 30 minutes prior to biopsy. Participants completed a 10 point visual analog pain score following the procedure. RESULTS: Mean patient age was 68.5 years in the GTN group and 68.8 in the placebo group. There was a significant decrease in mean pain score in the GTN group compared with placebo (3.7 vs 4.8, p <0.05). Six patients (10%) in the GTN group complained of headache. CONCLUSIONS: Topical GTN paste is an effective and well tolerated method of decreasing pain associated with transrectal ultrasound guided prostate biopsy. It is safe and easy to use, and it should be offered to patients undergoing this procedure.

Silencing of the IGF1R gene enhances sensitivity to DNA-damaging agents in both PTEN wild-type and mutant human prostate cancer.

The type 1 insulin-like growth factor receptor (IGF1R) is overexpressed in prostate cancer, and mediates proliferation, motility, and survival. Many prostate cancers harbor inactivating PTEN mutations, enhancing Akt phosphorylation. This activates the principal antiapoptotic pathway downstream of the IGF1R, calling into question the value of IGF1R targeting in this tumor. The aim of the current study was to assess the effect of IGF1R gene silencing in prostate cancer cells that lack functional PTEN protein. In human DU145, LNCaP and PC3 prostate cancer cells, transfection with IGF1R small interfering RNA induced significant enhancement of apoptosis and inhibition of survival, not only in PTEN wild-type DU145 but also in PTEN mutant LNCaP and PC3. This was attributed to attenuation of IGF signaling via Akt, ERKs and p38. In both DU145 and PC3, IGF1R knockdown led to enhancement of sensitivity to mitoxantrone, etoposide, nitrogen mustard and ionizing radiation. There was no sensitization to paclitaxel or 5-fluorouracil, which do not damage DNA, suggesting that chemosensitization results from impairment of the DNA damage response, in addition to removal of apoptosis protection. These results support the concept of IGF1R targeting in prostate cancer, and indicate that PTEN loss does not render tumor cells refractory to this strategy.