Protocol for the TRANSLATE prospective, multicentre, randomised clinical trial of prostate biopsy technique.

OBJECTIVES: Primary objectives: to determine whether local anaesthetic transperineal prostate (LATP) biopsy improves the detection of clinically significant prostate cancer (csPCa), defined as International Society of Urological Pathology (ISUP) Grade Group ≥2 disease (i.e., any Gleason pattern 4 disease), compared to transrectal ultrasound-guided (TRUS) prostate biopsy, in biopsy-naïve men undergoing biopsy based on suspicion of csPCa. SECONDARY OBJECTIVES: to compare (i) infection rates, (ii) health-related quality of life, (iii) patient-reported procedure tolerability, (iv) patient-reported biopsy-related complications (including bleeding, bruising, pain, loss of erectile function), (v) number of subsequent prostate biopsy procedures required, (vi) cost-effectiveness, (vii) other histological parameters, and (viii) burden and rate of detection of clinically insignificant PCa (ISUP Grade Group 1 disease) in men undergoing these two types of prostate biopsy. PATIENTS AND METHODS: The TRANSLATE trial is a UK-wide, multicentre, randomised clinical trial that meets the criteria for level-one evidence in diagnostic test evaluation. TRANSLATE is investigating whether LATP biopsy leads to a higher rate of detection of csPCa compared to TRUS prostate biopsy. Both biopsies are being performed with an average of 12 systematic cores in six sectors (depending on prostate size), plus three to five target cores per multiparametric/bi-parametric magnetic resonance imaging lesion. LATP biopsy is performed using an ultrasound probe-mounted needle-guidance device (either the 'Precision-Point' or BK UA1232 system). TRUS biopsy is performed according to each hospital's standard practice. The study is 90% powered to detect a 10% difference (LATP biopsy hypothesised at 55% detection rate for csPCa vs 45% for TRUS biopsy). A total of 1042 biopsy-naïve men referred with suspected PCa need to be recruited. CONCLUSIONS: This trial will provide robust prospective data to determine the diagnostic ability of LATP biopsy vs TRUS biopsy in the primary diagnostic setting.

Robot-assisted partial nephrectomy vs laparoscopic cryoablation for the small renal mass: redefining the minimally invasive 'gold standard'.

OBJECTIVE: To identify differences between the ablative and extirpative minimally invasive techniques of laparoscopic cryoablation (LC) and robot-assisted laparoscopic partial nephrectomy (RPN), respectively, in treating small renal tumours in terms of safety, peri-operative morbidity and early oncological outcomes. PATIENTS AND METHODS: Between June 2008 and April 2012 56 patients underwent LC and from October 2010 to April 2012, 47 patients underwent RPN using the Da Vinci robotic platform (Intuitive Surgical, Sunnyvale, CA, USA). Data on intra-operative, postoperative and oncological outcomes were collected prospectively, and were analysed and compared for both groups. RESULTS: The median patient ages were 69 and 60 for the LC and RPN groups, respectively (P < 0.05). There was no significant difference in disease stage, but there was a significant difference in tumour size, with patients in the RPN group having larger tumours. The mean operating times were 146 and 159 min for the LC and RPN groups, respectively (P = 0.094) and the mean blood loss was 47 and 94 mL for the LC and the RPN groups, respectively (P = 0.251). The median length of hospital stay (1 day) was the same for both groups and the mean warm ischaemia time was 23 min in the RPN group. The marginal change in preoperative and 6-week postoperative renal function was recorded: the mean postoperative increase in serum creatinine was 5.4 mmol/L in the LC group and 9.2 mmol/L in the RPN group. Of the 47 patients in the RPN group, two (4.3%) were converted to laparoscopic radical nephrectomy because of difficulty in controlling bleeding during hilar dissection. Only two patients (3.6%) had recurrence in the LC group, both of whom were treated with re-cryoablation. A total of 5.4% of patients in the LC and 4.3% in the RPN group had Clavien grade I postoperative complications, one patient in the LC group had a Clavien grade II complication, while 1.8 and 4.3% of patients had Clavien IIIb in the LC and RPN groups, respectively. CONCLUSION: Our data confirm that LC is a successful, minimally invasive and safe treatment option for the management of small renal tumours, but the apparently similar characteristics of RPN suggest that an increasing proportion of patients, whatever their age or medical comorbidities, may be reasonably offered a robot-assisted extirpative procedure with the likely benefit of lower risk of local recurrence and need for retreatment.

Internist's tumour into thyroid: A case report.

Renal cell carcinoma (RCC) is well known for its unpredictable and diverse behaviour, with tendency to cause synchronous or metachronous metastasis to unusual site, which is why it is called the "internist's tumour."Although thyroid gland is an infrequent site for metastasis of different primary malignancies, metastatic RCC is one of the most common secondary thyroid malignancies. Diagnosis relies on a high index of suspicion in patients with prior RCC, combined with cross-sectional imaging and biopsy. A case of secondary thyroid neoplasm from RCC after 13 years of radical nephrectomy is described with clinicopathological features and literature review.

Initial treatment costs of organ-confined prostate cancer: a general perspective.

With the increasing prevalence of prostate cancer and evolving methods for the definitive treatment of OCPCa, health economic analyses will be critically important, albeit difficult to carry out. Preliminary studies point to RPP as the most cost-effective treatment for OCPCa. The quickest postoperative recovery, in experienced hands, occurs in RARP and RPP, with ORPP having a slightly, but statistically in significant, shorter hospital stay. It should be stressed that initial treatment costs are not the only important factor in healthcare costs. Readmission for early and late complications and the loss of productivity resulting from variation in time to return to work, need also to be considered. Loss of productivity may also vary in cost between different institutions and countries depending upon the proportion of patients employed. Further large-scale multicentre studies are necessary to assess this.

Laparo-endoscopic single-site surgery: preliminary advances in renal surgery.

We reviewed the preliminary advances in laparo-endoscopic single-site surgery (LESS) as applied to renal surgery, and analyzed current publications based on animal models and human patients. We searched published reports in major urological meeting abstracts, Embase and Medline (1966 to 25 August 2008), with no language restrictions. Keyword searches included: 'scarless', 'scar free', 'single port/trocar/incision', 'intraumbilical', and 'transumbilical', 'natural orifice transluminal endoscopic surgery' (NOTES), 'SILS', 'OPUS' and 'LESS'. The lessons learnt from the studies using the porcine model are that further advances in instrumentation are essential to achieve optimum results, and that testing survival in animals is also necessary to further expand the NOTES and LESS techniques. Further advances in instrument technology together with increasing experience in NOTES and LESS approaches have driven the transition from porcine models to human patients. In the latter, studies show that the techniques are feasible provided that both optimal surgical technical expertise with advanced skills, and optimal instrumentation, are available. The next step towards minimal access/minimally invasive urological surgery is NOTES and LESS. It is inevitable that LESS will be extended to involve more complex and technically demanding procedures such as laparoscopic radical prostatectomy and partial nephrectomy.

Single-port 'scarless' laparoscopic nephrectomies: the United Kingdom experience.

OBJECTIVE: To present the UK experience to date with laparoendoscopic single-site surgery (LESS) simple nephrectomy. PATIENTS AND METHODS: Five female patients underwent LESS nephrectomy; three procedures were carried out with the umbilicus as the port of entry (U-LESS). RESULTS: All cases were completed uneventfully. The operative duration was 45-150 min and blood loss was negligible. There were no conversions to conventional multi-port laparoscopy or open surgery. Recovery was uneventful with only minor complications in two patients; convalescence was rapid. CONCLUSION: LESS nephrectomy offers a safe, cosmetic alternative to conventional multi-port laparoscopy, with younger female patients being especially happier with the 'scarless' outcome of U-LESS. LESS certainly appears to be more in these situations.

Evaluation of a commercial vascular clip: risk factors and predictors of failure from in vitro studies.

OBJECTIVE: To assess risk factors and predictors of failure of the Hem-o-lok(TM) vascular clip (Weck Closure Systems, Research Triangle Park, NC, USA) using vessels harvested from a porcine model. MATERIALS AND METHODS: Vessels of various diameters were harvested from a porcine model, clipped at 90 degrees or 45 degrees using the Hem-o-lok clip and then cut either flush or with a 1-mm cuff. The vessels were then connected to a burst-pressure device and pressures required to burst the clip or to cause it to leak were measured. RESULTS: The Hem-o-lok clip leaked or burst when the vessel to which it was applied was cut flush. The clip became even more likely to fail if the angle of application of the clip was not at 90 degrees to the vessel surface. CONCLUSION: The Hem-o-lok vascular clip is safe if it is applied at 90 degrees to the vessel surface and, more importantly, if a 1-mm cuff is left between the clip and the point at which the vessel is divided. We would therefore discourage the practice of not leaving this cuff of tissue, in an attempt to maximize vessel length during laparoscopic donor nephrectomy.

Optimizing outcomes in laparoscopic urologic training: toward a standardized global consensus.

BACKGROUND AND PURPOSE: Laparoscopic urologic surgery (LUS) is one of the fastest growing subspecialties in the surgical world. The procedures require technical expertise and finesse; unlike their open counterparts, there is significant limitation in the margin for error. Various ethical, medicolegal, and health economy demands have made training in laparoscopic urologic surgery challenging. Whereas several groups have sought solutions through models, there remains a lack of consensus on the optimal training program. We review the current LUS programs with a conscious effort to decipher the basic tenets of an optimal training program and propose training models based on published evidence, in conjunction with current trends in LUS. METHODS: A literature search of MEDLINE, Pubmed, CINAHL, EMBASE, the Cochrane Database of Systematic Reviews, and Google Scholar was performed, seeking publications from January 1970 to July 2006 on laparoscopic surgical training pertaining to urology. Additionally, we looked at pertinent abstracts of the annual meetings of the American Urological Association, the European Association of Urology, and the World Congress of Endourology for the period January 1996 to and inclusive of August 2006. RESULTS AND CONCLUSIONS: To date, no study has documented a global consensus on optimal LUS training programs. Our search identified several models, some of which were applied successfully in the form of minifellowships. There remain no clear guidelines on the optimum LUS training program. The optimal program may need to be tailored to individual units, based on resources (this includes country-specific health economics, mentor availability, and caseload). Further studies are needed to help elucidate how individual programs can be initiated with a global minimum standard applicable to all training programs.

Gene therapy and erectile dysfunction: the current status.

Current available treatment options for erectile dysfunction (ED) are effective but not without failure and/or side effects. Although the development of phosphodiesterase type 5 (PDE5) inhibitors (i.e. sildenafil, tadalafil and vardenafil) has revolutionized the treatment of ED, these oral medications require on-demand access and are not as effective in treating ED related to diabetic, post-prostatectomy and severe veno-occlusive disease states. Improvement in the treatment of ED is dependent on understanding the regulation of human corporal smooth muscle tone and on the identification of relevant molecular targets. Future ED therapies might consider the application of molecular technologies such as gene therapy. As a potential therapeutic tool, gene therapy might provide an effective and specific means for altering intracavernous pressure "on demand" without affecting resting penile function. However, the safety of gene therapy remains a major hurdle to overcome before being accepted as a mainstream treatment for ED. Gene therapy aims to cure the underlying conditions in ED, including fibrosis. Furthermore, gene therapy might help prolong the efficacy of the PDE5 inhibitors by improving penile nitric oxide bioactivity. It is feasible to apply gene therapy to the penis because of its location and accessibility, low penile circulatory flow in the flaccid state and the presence of endothelial lined (lacunar) spaces. This review provides a brief insight of the current role of gene therapy in the management of ED.

The management of phosphodiesterase-5 (PDE5) inhibitor failure.

The oral phosphodiesterase type 5 (PDE5) inhibitors have made a valuable contribution to the treatment of erectile dysfunction (ED). PDE5 inhibitors enhance cavernosal smooth muscle relaxation, vasodilatation and penile erection. However, PDE5 inhibitors are not always effective. Decreased efficacy, cost, incorrect administration, lack of sexual stimulation, vascular risk factors associated with ED and vascular or neurogenic diseases are causes of PDE5 inhibitor failure. Tachyphylaxis may also occur. This is defined as reduced tissue responsiveness to a drug in the presence of a constant concentration of this drug. Treatment failure may cause considerable distress. If dose titration, more attempts and continuous dosing of PDE5 inhibitors (taken on a daily basis) fail to resolve the initial PDE5 inhibitor failure, clinicians need to consider alternative treatments. These include sublingual apomorphine, intracavernosal/intraurethral pharmacotherapy, vacuum devices, the insertion of a prosthesis and penile vascular surgery. Combination therapy like prostaglandin E(1) (PGE(1)) with doxazosin (dox; an alpha-1-blocker) or ketanserin (ketan; a 5-HT(2) antagonist) as well as other pro-erection agents, like Endothelin-1 antagonists, angiotensin II antagonists (valsartan/losartan), adrenomedullin, Rho kinase inhibitors and nitric oxide (NO) donors may be beneficial in the treatment of ED. However, these combination therapies need to be validated. Adding an androgen to a PDE5 inhibitor may help when circulatory testosterone levels are low. The early use of PDE5 inhibitors in patients with hypertension, hyperlipidaemia or diabetes with concomitant ED and treating these risk factors may improve corporeal blood flow and lead to long-term preservation of cavernosal function. Therefore, the efficacy of PDE5 inhibitors may be maintained. Targeting the risk factors of ED (similar to those for arteriosclerosis) in the early stages of the disease may prevent the development or decrease the severity of ED.

Minimally invasive treatment of ureteropelvic junction obstruction: optimizing outcomes with concomitant cost reduction.

With the seemingly exponential increase in the use of minimally invasive techniques in urology, cost-benefit comparisons will continue to play a major part in establishing services and in improving those that already exist. The management of ureteropelvic junction obstruction is a focus of significant attention. An effective way of optimizing the economy of management is to understand the implications in terms of the success of each mode of treatment. Subsequently, costing models should be developed and applied in large-scale multicenter studies with the aid of health economists. The long-term benefits can then be assessed by also including patient's perceived quality of life. Economic assessment will not be enough to promote cost-effective practices. The take-up of any techniques will always be influenced not only by patient preference and surgeon expertise but also, perhaps ironically, by the way hospitals and surgeons are remunerated. In addition, the impact of the time taken to train a surgeon to carry out laparoscopic dismembered pyeloplasty competently may play a significant role. Until these issues are resolved, definitive recommendation for the treatment of ureteropelvic junction obstruction will continue to be made on an individual basis.

Presentation of case: Bladder cancer in an 18 year old female patient.

INTRODUCTION: Bladder cancers are not very common in the young population below 20 years of age, especially in those who have not been exposed to chemotherapy, bladder augmentation surgery and other known risk factors. By highlighting this case we hope to raise awareness in the medical community, that the symptom of visible haematuria can potentially be due to a bladder malignancy and therefore this should be thoroughly investigated. PRESENTATION OF CASE: An 18-year-old female presented with intermittent macroscopic haematuria and non-specific abdominal pain. Physical examination and routine blood tests were normal. An ultrasound scan initially showed a bladder wall lesion, which a flexible cystoscopy confirmed. Histology revealed grade 2 papillary transitional cell carcinoma of the bladder with no invasion into the lamina propria (G2pTa TCCB). DISCUSSION: We recognise through our literature review that paediatric bladder cancers are not commonly reported in the UK. In our paper we highlight the relevant major studies that have been carried out world-wide, the reported incidence so far and gaps in the evidence base. CONCLUSION: Despite the dearth of data about paediatric bladder malignancies there is enough case-based evidence, from world-wide sources, to support that bladder cancer must be suspected in the event of macroscopic haematuria. Ultrasound and cystoscopy are the standard diagnostic tools for bladder tumours. Endoscopic resection of the tumour followed up by interval ultrasound scans and flexible cystoscopy checks remain the mainstay of treatment hitherto.

Current Status of Hemostatic Agents and Sealants in Urologic Surgical Practice.

There has been a recent and near exponential increase in the use of hemostatic agents and sealants to supplement the rapidly evolving methods in the surgical management of urologic patients. This article reviews the use of hemostatic agents and sealants in current urologic practice.