Gordon Muir

Photoselective vaporization of the prostate with the potassium‐titanyl‐phosphate laser in men with prostates of >100 mL

To assess the efficacy of photoselective vaporization of the prostate (PVP) in men with prostates of >100 mL and causing bladder outlet obstruction (BOO), using the high‐power 80 W potassium‐titanyl‐phosphate laser (GreenLight PV®, Laserscope, San Jose, CA, USA), which offers rapid tissue ablation with minimal bleeding.

Identification of potential diagnostic markers of prostate cancer and prostatic intraepithelial neoplasia using cDNA microarray

The identification of novel genes or groups of genes expressed in prostate cancer may allow earlier diagnosis or more accurate staging of the disease. We describe the assembly and use of a 1877-member microarray representing cDNA clones from a range of prostate cancer stages and grades, precursor lesions and normal tissue. Using labelled cDNA from tumour samples obtained from TURP or radical prostatectomy, analysis of expression patterns identified many up-regulated transcripts. Cell lines were found to over-express fewer genes than diseased tissue samples. 17 known genes were found to over-express more than 4-fold in 4 or more cancers out of 15 cancers. Only 2 genes were over-expressed in 6 out of 15 cancers or more, whilst no genes were consistently found to be over-expressed in all cancer samples. Novel prostate cancer associations for several well characterized genes or full length cDNAs were identified, including PLRP1, JM27, human UbcM2, dynein light intermediate chain 2 and human homologue of rat sec61. Novel associations with high-grade PIN include: breast carcinoma fatty acid synthase and cDNA DKFZp434B0335. We shortlist and discuss the most significant over-expressed genes in prostate cancer and PIN, and highlight expression differences between malignant and benign samples.

180-W XPS GreenLight Laser Therapy for Benign Prostate Hyperplasia: Early Safety, Efficacy, and Perioperative Outcome After 201 Procedures

BACKGROUND Photoselective vaporisation of the prostate has evolved from the GreenLight 80-W KTP powered laser to the latest 180-W XPS laser involving a MoXy fibre. OBJECTIVE Evaluate the prevalence of perioperative complications and short-term outcome for the first time with the XPS laser in men with lower urinary tract symptoms (LUTS) due to benign prostatic enlargement (BPE). DESIGN, SETTING, AND PARTICIPANTS Prospective data were collected from consecutive patients at seven centres worldwide during June 2010 and March 2011. Indication for surgery was based on the European Association of Urology and the American Urological Association guidelines. Patients receiving anticoagulants or those with retention were included and analysed separately. INTERVENTION 180-W XPS GreenLight laser prostatectomy using the MoXy fibre. MEASUREMENTS Standard parameters associated with transurethral prostate surgery and perioperative prevalence of surgery-associated problems or complications were documented. RESULTS AND LIMITATIONS A total of 201 patients were included in the study. Mean follow-up was 5.8 mo (standard deviation [SD]: 2.8; range: 1-12 mo). A quarter of the patients had a prostate volume≥80 ml. For prostates between 51 and 60 ml, a mean of 300 kJ (SD: 112) of energy was applied (lasing time: 35.0 min; SD: 15). Statistically significant improvements were noted in all key parameters postoperatively. The prevalence of perioperative complications was low. Limitations of the study are short duration of follow-up and limited number of available patients for the functional follow-up. CONCLUSIONS The 180-W GreenLight XPS laser is a new effective treatment option with a low prevalence of perioperative complications for patients suffering from LUTS due to BPE.

180-W XPS GreenLight Laser Vaporisation Versus Transurethral Resection of the Prostate for the Treatment of Benign Prostatic Obstruction: 6-Month Safety and Efficacy Results of a European Multicentre Randomised Trial—The GOLIATH Study

BACKGROUND The comparative outcome with GreenLight (GL) photoselective vaporisation of the prostate and transurethral resection of the prostate (TURP) in men with lower urinary tract symptoms due to benign prostatic obstruction (BPO) has been questioned. OBJECTIVE The primary objective of the GOLIATH study was to evaluate the noninferiority of 180-W GL XPS (XPS) to TURP for International Prostate Symptom Score (IPSS) and maximum flow rate (Qmax) at 6 mo and the proportion of patients who were complication free. DESIGN, SETTING, AND PARTICIPANTS Prospective randomised controlled trial at 29 centres in 9 European countries involving 281 patients with BPO. INTERVENTION 180-W GL XPS system or TURP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Measurements used were IPSS, Qmax, prostate volume (PV), postvoid residual (PVR) and complications, perioperative parameters, and reintervention rates. Noninferiority was evaluated using one-sided tests at the 2.5% level of significance. The statistical significance of other comparisons was assessed at the (two-sided) 5% level. RESULTS AND LIMITATIONS The study demonstrated the noninferiority of XPS to TURP for IPSS, Qmax, and complication-free proportion. PV and PVR were comparable between groups. Time until stable health status, length of catheterisation, and length of hospital stay were superior with XPS (p<0.001). Early reintervention rate within 30 d was three times higher after TURP (p=0.025); however, the overall postoperative reintervention rates were not significantly different between treatment arms. A limitation was the short follow-up. CONCLUSIONS XPS was shown to be noninferior (comparable) to TURP in terms of IPSS, Qmax, and proportion of patients free of complications. XPS results in a lower rate of early reinterventions but has a similar rate after 6 mo. TRIAL REGISTRATION ClinicalTrials.gov, identifier NCT01218672.

TOOKAD® Soluble vascular‐targeted photodynamic (VTP) therapy: determination of optimal treatment conditions and assessment of effects in patients with localised prostate cancer

To evaluate the optimal treatment conditions and effects of TOOKAD® Soluble vascular‐targeted photodynamic (VTP) therapy in patients with localised prostate cancer. To evaluate the safety and quality of life after TOOKAD® Soluble VTP treatment in patients with localised prostate cancer.

Laparoscopic pelvic lymph node dissection allows significantly more accurate staging in “high‐risk” prostate cancer compared to MRI or CT

Objective: To compare the accuracy of lymph node staging using pelvic MRI or CT to that of laparoscopic pelvic lymph node dissection (LPLND) in prostate cancer patients prior to radical radiotherapy. Material and Methods: A total of 55 consecutive patients at high risk of locally advanced disease [prostate‐specific antigen (PSA) > 10 ng/ml, Gleason score 7 or worse on biopsy, normal 99m Tc bone scan] underwent either a pelvic MRI (n = 42) or CT (n = 13) scan and subsequent LPLND. Preoperative staging was compared to the histology of the lymph node specimens obtained. Results: A total of 20/55 (36.4%) patients had pelvic lymph node metastases confirmed by LPLND. MRI identified three patients (27.3%) with pelvic lymph node metastases and missed eight (72.7%) whilst CT identified none of nine patients with pelvic lymph node metastases. The groups with histologically‐positive and ‐negative nodes had similar mean ages (63 vs 65 years; p = 0.52), Gleason scores (6.8 vs 6.5; p = 0.41) and PSA levels (43.1 vs 31.4 ng/ml; p = 0.56). Conclusion: The presence or absence of lymph node metastases has critical implications for the prognosis and treatment of prostate cancer. In this study both MRI and CT missed many cases of lymph node metastases in “high‐risk” patients. While a positive scan seems likely to indicate nodal metastases, the low sensitivity in high‐risk patients seems unacceptable if treatment decisions are to be based on accurate staging, and LPLND offers an alternative.

Photoselective vaporization of the prostate (GreenLight PV): lessons learnt after 3500 procedures.

The technical recommendations of an international group of experts on photoselective vaporization of the prostate (PVP; GreenLight PV) for benign prostatic hyperplasia are described. Their experience stems from the treatment of over 3500 patients at five centres in Europe and the United States. The objectives of this physician-based initiative are to optimize the results achieved with PVP by standardizing the procedure, as well as to recommend training requirements.

Evaluation of P53 Protein Overexpression, Ki67 Proliferative Activity and Mitotic Index as Markers of Tumour Recurrence in Superficial Transitional Cell Carcinoma of the Bladder

Objectives: To confirm the interrelationship between p53, ki67, mitotic index with others known prognostic factors such us stage, grade, multifocality, tumour size, history of recurrence in transitional cell carcinoma (TCC) of the bladder and to determine the prognostic impact of p53, Ki67 and mitotic index in predicting recurrence in superficial bladder cancer.Methods: Two hundred and fourteen patients with apparently superficial TCC of the bladder underwent TURBT and the 192 histologically Ta–T1 were divided into 104 primary lesions (group 1, mean follow–up 26 months) and 88 recurrent tumours (group 2, mean follow–up 28 months). Data concerning focality, tumour size, number of recurrences and recurrence–free survival were considered in each patients. All samples were immunohistochemically stained with p53 and Ki67 monoclonal antibodies. Mitotic index (MI) was calculated on haematoxylin and eosin stained sections.Results: Recurrence–free survival was significantly lower in superficial recurrent tumours (group 2) compared with primary tumours (group 1). P53 staining was correlated with grade and stage for both 5 and 20% positivity thresholds. Ki67 and MI were significantly different over strata defined by stage, grade and focality in both patients groups but only Ki67 showed a correlation with p53 status. Recurrence–free survival could not be predicted either by p53 status or MI. A 20% cut–off level of Ki67 staining resulted a good predictor of recurrence in group 1 Ta–T1/G1–G2 tumours (p = 0.03). Only Ki67 and multifocality were found to be independent prognostic factors of recurrence in multivariate analysis. Stratifying Ta–T1/G1–G2 patients according to these variables, Ki67 provided a useful tool to predict early recurrence in monofocal lesions from both groups.Conclusions: P53 and MI despite a fairly good correlation with traditional prognostic factors in bladder TCC seem to play no role in the prediction of tumoural recurrence. A Ki67 index over 20% predicts those single well–differentiated (Ta–T1/G1–G2) tumours which are likely to recur within one year of treatment

A European Multicenter Randomized Noninferiority Trial Comparing 180 W GreenLight XPS Laser Vaporization and Transurethral Resection of the Prostate for the Treatment of Benign Prostatic Obstruction: 12-Month Results of the GOLIATH Study

PURPOSE We present the 1-year results of the GOLIATH prospective randomized controlled trial comparing transurethral resection of the prostate to GreenLight XPS for the treatment of men with nonneurogenic lower urinary tract symptoms due to prostate enlargement. The updated results at 1 year show that transurethral resection of the prostate and GreenLight XPS remain equivalent, and confirm the therapeutic durability of both procedures. We also report 1-year followup data from several functional questionnaires (OABq-SF, ICIQ-SF and IIEF-5) and objective assessments. MATERIALS AND METHODS A total of 291 patients were enrolled at 29 sites in 9 European countries. Patients were randomized 1:1 to undergo GreenLight XPS or transurethral resection of the prostate. The trial was designed to evaluate the hypothesis that GreenLight XPS is noninferior to transurethral resection of the prostate on the International Prostate Symptom Score at 6 months. Several objective parameters were assessed, including maximum urinary flow rate, post-void residual urine volume, prostate volume and prostate specific antigen, in addition to functional questionnaires and adverse events at each followup. RESULTS Of the 291 enrolled patients 281 were randomized and 269 received treatment. Noninferiority of GreenLight XPS was maintained at 12 months. Maximum urinary flow rate, post-void residual urine volume, prostate volume and prostate specific antigen were not statistically different between the treatment arms at 12 months. The complication-free rate at 1 year was 84.6% after GreenLight XPS vs 80.5% after transurethral resection of the prostate. At 12 months 4 patients treated with GreenLight XPS and 4 who underwent transurethral resection of the prostate had unresolved urinary incontinence. CONCLUSIONS Followup at 1 year demonstrated that photoselective vaporization of the prostate produced efficacy outcomes similar to those of transurethral resection of the prostate. The complication-free rates and overall reintervention rates were comparable between the treatment groups.

Sildenafil does not improve sexual function in men without erectile dysfunction but does reduce the postorgasmic refractory time

Sildenafil is one of two oral drugs approved for first-line treatment of erectile dysfunction (ED). Anecdotally, some young healthy men who wish to enhance their sexual performance are requesting or abusing sildenafil. In this randomized double-blind, placebo-controlled clinical study, we investigated the effect of sildenafil in young men without ED. A total of 60 young healthy men age 20–40 y with no reported ED were enrolled for this single-dose home-use study. Subjects had used no medication in the 6 months prior to the study. All had been engaged in a stable relationship for at least 3 months. After completing the IIEF-5 questionnaire, patients were randomized in a double-blind fashion to receive either one 25 mg tablet of sildenafil (group 1) taken prior to intercourse, or an identical placebo tablet (group 2). All subjects completed a questionnaire relating to their erectile quality. There were no differences between the two groups in the reported improvement of erection quality, 12/30 sildenafil vs 10/30 placebo (Fishers test, P=0.79). Sildenafil caused a significant reduction of the postejaculatory refractory time (12/30 vs 4/30) (χ2 test, P=0.04). Sildenafil does not improve erections in young healthy men. Sildenafil should not be given to young healthy men to improve their erections and patients should be advised against recreational abuse of the drug. In this limited single-dose home study, sildenafil appears to reduce the postorgasmic refractory time. Although controlled studies are needed to evaluate the efficacy of erection-enhancing drugs in premature ejaculation, it is possible that sildenafil might be useful for this indication.