Operative experience of urological trainees in the UK.

What's known on the subject? And what does the study add? One of the main components of surgical training is the development of operative skills which, in part, is related to the extent of the practical operative experience. The operative experience of urological trainees in the UK has not being previously published. We examine trainees' current operative experience and analyse the changes over recent years. With a notable decrease in experience of certain procedures, we highlight the possible reasons and discuss the implications for future training. We have examined the operative experience of urological trainees in the UK over a 6-year period. Between 2004 and 2009, urological trainees submitting their operative logbooks to the Specialist Advisory Committee for the award of Certificate of Completion of Training were analysed. We recorded trainees' experience in eight operative procedures; transurethral resection of the prostate (TURP, including bipolar TURP), transurethral resection of bladder tumour (TURBT), radical nephrectomy (RN, open and laparoscopic), radical cystectomy (RC), radical prostatectomy (RP), percutaneous nephrolithotomy (PCNL) and ureteroscopy (flexible and rigid). In all, 251 logbooks were identified over the 6-year period. In 2008/2009, the mean (range) number of cases 'performed' and 'supervised' were as follows; TURP 189 (41-516), TURBT 190 (50-432), open RN 21 (2-78), RC 10 (0-70), RP 13 (0-80), PCNL 19 (0-125), ureteroscopy 131 (14-465), laparoscopic RN 11 (0-97). Latterly there has been a significant reduction in the numbers of TURP, open RNs and RCs. There has been an increase in the use of trainees as assistants for RC, RP and open RN. There was a large variation in numbers of procedures performed between trainees. In summary there has been a recent decline in the numbers of TURP, open RNs and RCs performed. For all procedures, significant variability exists between trainees.

The Whitaker test: 35 years on.

OBJECTIVE: To describe a 25-year experience of using the Whitaker test in a single tertiary centre for assessing upper urinary tract dilatation, and to evaluate the role of perfusion pressure-flow studies in contemporary urological surgery for equivocal upper tract obstruction. PATIENTS AND METHODS: In all, 143 patients with suspected upper urinary tract obstruction were investigated by at least one Whitaker test. The original method was extended to include observations on high flow-rate perfusion, abnormal renal pelvic peristalsis and loin pain with no pressure increase. Data on clinical presentation, perfusion pressure-flow studies, diuresis renography and choice of initial therapy were collected prospectively, and the long-term clinical outcome was analysed retrospectively. RESULTS: In total, 145 studies were assessed; the Whitaker test showed obstructive features at conventional or higher flow rates in 61 cases and unobstructive patterns in 53. There were four equivocal results. Seventeen studies showed abnormal peristalsis within the renal pelvis and in 10 there was 'sensory' loin pain during the test. In patients with idiopathic hydronephrosis, there was agreement between the results of the pressure-flow studies and diuresis renography in 72%. The Whitaker test determined or contributed to the clinical management in 84% of the cases studied. It was accurate in its prediction of outcome in 77% of cases where obstruction was diagnosed and in 77% of unobstructive cases. CONCLUSIONS: The Whitaker test continues to have a role in modern urological surgery. It should be reserved for assessing potential upper urinary tract obstruction in the following circumstances: equivocal results from less invasive tests; suspected obstruction with poor kidney function; loin pain with a negative diuresis renogram; suspected intermittent obstruction; and gross dilatation with a positive diuresis renogram.

Characterization of benign and malignant prostate epithelial Hoechst 33342 side populations.

BACKGROUND: The prostate epithelial stem cell has been proposed as the primary origin of neoplastic change in prostate cancer. However, the isolation and characterization of unexpanded prostate epithelial stem cells have proven problematic. METHODS: A prostate epithelial side population (SP) has been isolated utilizing a modified Hoechst 33342 dye efflux assay from both benign and malignant prostate tissue. CD45(-ve), integrin alpha2(+ve) Hoechst 33342 SP and NSP cells were isolated by FACS, immunophenotyped and functionally characterized in 3D culture. RESULTS: FACS analysis revealed a verapamil sensitive SP accounting for 0.93 +/- 0.12% and 0.57 +/- 0.11% of the total epithelial population from both benign and malignant prostates. The benign SP phenotype revealed a heterogeneous cell population consisting predominantly of small basal cells containing minimal cytoplasm. Conversely, the malignant SP was of undetermined acinar origin and with a complete loss of expression of the CDK2 inhibitor p21(WAF1/Cip1). In vitro androgen-enhanced 3D culture of the benign and malignant SP cells led to the production of spheroids which had acinus like morphology and expressed primitive and basal cell markers. Incorporation of the CD133 marker isolated a further SP sub-fraction accounting for 0.037 +/- 0.01% of epithelial cells. CONCLUSIONS: Our observations are consistent with the Hoechst 33342 dye efflux assay isolating a stem cell enriched population which can be further sub-fractionated by CD133 selection. Moreover, the loss of the CDK inhibitor in malignancy is consistent with the hypothesis that neoplastic change originates in the stem cell compartment.

Differential inhibition of invasion and proliferation by bisphosphonates: anti-metastatic potential of Zoledronic acid in prostate cancer.

OBJECTIVES: To determine the mode of action of Zoledronic acid in the inhibition of metastasis in prostate cancer and the reduction of prostate cancer bone metastases. METHODS: Benign and malignant primary prostatic epithelial cells (PEC) and the PC-3 prostate cancer cell line were studied in co-culture using human bone marrow stroma in the presence of escalating doses of EDTA, Clodronate, Pamidronate and Zoledronic acid. PEC binding and colony growth in bone marrow stroma was measured using standardised quantitative techniques. PEC cellular invasion through Matrigel and an endothelial monolayer was measured either in invasion chambers or by the measurement of endothelial monolayer permeability to fluorescent dextran. Co-culture supernatants were assayed for specific cytokine levels. Bone marrow cellular toxicity was assessed using a standard Mix assay. RESULTS: Treatment of PEC with up to 100 microM bisphosphonate did not affect their ability to bind to bone marrow endothelium or stroma. Bone marrow endothelial permeability was reduced by 100 microM Zoledronic acid by 3.8% (p = 0.03856). Both Pamidronate (40% at 100 microM, p < or = 0.05) and Zoledronic acid inhibited PEC invasion, with Zoledronic acid being the most potent (40% at 10 microM, p < or = 0.05 rising to 91% at 100 microM, p < or = 0.001). Zoledronic acid inhibits malignant PEC proliferation in bone marrow stroma co-culture (26.5% at 10 microM rising to 66.5% at 40 microM). This was accompanied by changes within the cytokine milieu with a >800% rise in TIMP-2. CONCLUSION: Zoledronic acid is a potent inhibitor of PEC invasion across bone marrow endothelium and colony formation with the bone marrow stroma, affecting the MMP: TIMP-2 balance to favour MMP inhibition.

Novel method for the isolation and characterisation of the putative prostatic stem cell.

BACKGROUND: Prostate stem cells, responsible for the development, maturation, and function of the prostate, have been implicated in the aetiology of both benign prostate hyperplasia (BPH) and prostate cancer (CaP). However, research has been hampered by the lack of a definitive stem cell marker. We have adapted the protocol for differential Hoechst 33342 uptake by hemopoietic stem cells to enable isolation of putative stem cells from the prostate. METHODS: Prostate epithelial cells isolated from prostate tissue obtained from patients with BPH after transurethral resection of the prostate were stained with Hoechst 33342. The Hoechst 33342 Red/Blue flow cytometry profile was then determined. Hoechst 33342 and Pyronin Y staining was used to determined the cell cycle status. RESULTS: A verapamil-sensitive side population (SP) can be isolated from primary prostate tissue accounting for 1.38% +/- 0.07% of prostate epithelial cells. Cell cycle analysis of this SP population revealed that the majority of SP cells are in either G0 (12.38 +/- 0.31%) or G1 (63.19 +/- 2.13%). CONCLUSIONS: The Hoechst 33342 dye efflux protocol can be adapted for the isolation of a SP from primary prostate tissue.