Jean de la Rosette

EAU Guidelines on the Treatment and Follow-up of Non-neurogenic Male Lower Urinary Tract Symptoms Including Benign Prostatic Obstruction

OBJECTIVE To present a summary of the 2013 version of the European Association of Urology guidelines on the treatment and follow-up of male lower urinary tract symptoms (LUTS). EVIDENCE ACQUISITION We conducted a literature search in computer databases for relevant articles published between 1966 and 31 October 2012. The Oxford classification system (2001) was used to determine the level of evidence for each article and to assign the grade of recommendation for each treatment modality. EVIDENCE SYNTHESIS Men with mild symptoms are suitable for watchful waiting. All men with bothersome LUTS should be offered lifestyle advice prior to or concurrent with any treatment. Men with bothersome moderate-to-severe LUTS quickly benefit from α1-blockers. Men with enlarged prostates, especially those >40ml, profit from 5α-reductase inhibitors (5-ARIs) that slowly reduce LUTS and the probability of urinary retention or the need for surgery. Antimuscarinics might be considered for patients who have predominant bladder storage symptoms. The phosphodiesterase type 5 inhibitor tadalafil can quickly reduce LUTS to a similar extent as α1-blockers, and it also improves erectile dysfunction. Desmopressin can be used in men with nocturia due to nocturnal polyuria. Treatment with an α1-blocker and 5-ARI (in men with enlarged prostates) or antimuscarinics (with persistent storage symptoms) combines the positive effects of either drug class to achieve greater efficacy. Prostate surgery is indicated in men with absolute indications or drug treatment-resistant LUTS due to benign prostatic obstruction. Transurethral resection of the prostate (TURP) is the current standard operation for men with prostates 30-80ml, whereas open surgery or transurethral holmium laser enucleation is appropriate for men with prostates >80ml. Alternatives for monopolar TURP include bipolar TURP and transurethral incision of the prostate (for glands <30ml) and laser treatments. Transurethral microwave therapy and transurethral needle ablation are effective minimally invasive treatments with higher retreatment rates compared with TURP. Prostate stents are an alternative to catheterisation for men unfit for surgery. Ethanol or botulinum toxin injections into the prostate are still experimental. CONCLUSIONS These symptom-oriented guidelines provide practical guidance for the management of men experiencing LUTS. The full version is available online (www.uroweb.org/gls/pdf/12_Male_LUTS.pdf).

The Clinical Research Office of the Endourological Society Percutaneous Nephrolithotomy Global Study: Indications, Complications, and Outcomes in 5803 Patients

PURPOSE To assess the current indications, perioperative morbidity, and stone-free outcomes for percutaneous nephrolithotomy (PCNL) worldwide. PATIENTS AND METHODS The Clinical Research Office of the Endourological Society (CROES) collected prospective data for consecutive patients who were treated with PCNL at centers around the world for 1 year. PCNL was performed according to study protocol and local clinical practice guidelines. Stone load and location were recorded, and postoperative complications were graded according to the modified Clavien grading system. RESULTS Between November 2007 and December 2009, 5803 patients were treated at 96 centers in Europe, Asia, North America, South America, and Australia. Staghorn calculus was present in 1466 (27.5%) patients, and 940, 956, and 2603 patients had stones in the upper, interpolar, and lower pole calices, respectively. The majority of procedures (85.5%) were uneventful. Major procedure-related complications included significant bleeding (7.8%), renal pelvis perforation (3.4%), and hydrothorax (1.8%). Blood transfusion was administered in 328 (5.7%) patients, and fever >38.5°C occurred in 10.5% of patients. The distribution of scores in modified Clavien grades was: No complication (79.5%), I (11.1%), II (5.3%), IIIa (2.3%), IIIb (1.3%), IVa (0.3%), IVb (0.2%), or V (0.03%). At follow-up. the 30-day stone-free rate was 75.7%, and 84.5% of patients did not need additional treatment. CONCLUSION With a high success rate and a low major complication rate, PCNL is an effective and safe technique overall for minimally invasive removal of kidney stones.

Propagation of human spermatogonial stem cells in vitro.

CONTEXT Young boys treated with high-dose chemotherapy are often confronted with infertility once they reach adulthood. Cryopreserving testicular tissue before chemotherapy and autotransplantation of spermatogonial stem cells at a later stage could theoretically allow for restoration of fertility. OBJECTIVE To establish in vitro propagation of human spermatogonial stem cells from small testicular biopsies to obtain an adequate number of cells for successful transplantation. DESIGN, SETTING, AND PARTICIPANTS Study performed from April 2007 to July 2009 using testis material donated by 6 adult men who underwent orchidectomy as part of prostate cancer treatment. Testicular cells were isolated and cultured in supplemented StemPro medium; germline stem cell clusters that arose were subcultured on human placental laminin-coated dishes in the same medium. Presence of spermatogonia was determined by reverse transcriptase polymerase chain reaction and immunofluorescence for spermatogonial markers. To test for the presence of functional spermatogonial stem cells in culture, xenotransplantation to testes of immunodeficient mice was performed, and migrated human spermatogonial stem cells after transplantation were detected by COT-1 fluorescence in situ hybridization. The number of colonized spermatogonial stem cells transplanted at early and later points during culture were counted to determine propagation. MAIN OUTCOME MEASURES Propagation of spermatogonial stem cells over time. RESULTS Testicular cells could be cultured and propagated up to 15 weeks. Germline stem cell clusters arose in the testicular cell cultures from all 6 men and could be subcultured and propagated up to 28 weeks. Expression of spermatogonial markers on both the RNA and protein level was maintained throughout the entire culture period. In 4 of 6 men, xenotransplantation to mice demonstrated the presence of functional spermatogonial stem cells, even after prolonged in vitro culture. Spermatogonial stem cell numbers increased 53-fold within 19 days in the testicular cell culture and increased 18,450-fold within 64 days in the germline stem cell subculture. CONCLUSION Long-term culture and propagation of human spermatogonial stem cells in vitro is achievable.

A Systematic Review and Meta-analysis of Functional Outcomes and Complications Following Transurethral Procedures for Lower Urinary Tract Symptoms Resulting from Benign Prostatic Obstruction: An Update

CONTEXT A number of transurethral ablative techniques based on the use of innovative medical devices have been introduced in the recent past for the surgical treatment of benign prostatic obstruction (BPO). OBJECTIVE To conduct a systematic review of the literature and a meta-analysis of available randomized controlled trials (RCTs), and to evaluate the efficacy and safety of transurethral ablative procedures for BPO. EVIDENCE ACQUISITION A systematic literature search was performed for all RCTs comparing any transurethral surgical technique for BPO to another between 1992 and 2013. Efficacy was evaluated after a minimum follow-up of 1 yr based on International Prostate Symptom Score, maximum flow rate, and postvoid residual volume. Efficacy at midterm follow-up, prostate volume, perioperative data, and short-term and long-term complications were also assessed. Data were analyzed using RevMan software. EVIDENCE SYNTHESIS A total of 69 RCTs (8517 enrolled patients) were included. No significant difference was found in terms of short-term efficacy between bipolar transurethral resection of the prostate (B-TURP) and monopolar transurethral resection of the prostate (M-TURP). However, B-TURP was associated with a lower rate of perioperative complications. Better short-term efficacy outcomes, fewer immediate complications, and a shorter hospital stay were found after holmium laser enucleation of the prostate (HoLEP) compared with M-TURP. Compared with M-TURP, GreenLight photoselective vaporization of the prostate (PVP) was associated with a shorter hospital stay and fewer complications but no different short-term efficacy outcomes. CONCLUSIONS This meta-analysis shows that HoLEP is associated with more favorable outcomes than M-TURP in published RCTs. B-TURP and PVP have resulted in better perioperative outcomes without significant differences regarding efficacy parameters after short-term follow-up compared with M-TURP. Further studies are needed to provide long-term comparative data and head-to head comparisons of emerging techniques. PATIENT SUMMARY Bipolar transurethral resection of the prostate, photovaporization of the prostate, and holmium laser enucleation of the prostate have shown efficacy outcomes comparable with conventional techniques yet reduce the complication rate. The respective role of these new options in the surgical armamentarium needs to be refined to propose tailored surgical treatment for benign prostatic obstruction relief.

Bipolar versus Monopolar Transurethral Resection of the Prostate: A Systematic Review and Meta-analysis of Randomized Controlled Trials

CONTEXT Incorporation of bipolar technology in transurethral resection (TUR) of the prostate (TURP) potentially offers advantages over monopolar TURP (M-TURP). OBJECTIVE To evaluate the evidence by a meta-analysis, based on randomized controlled trials (RCTs) comparing bipolar TURP (B-TURP) with M-TURP for benign prostatic obstruction. Primary end points included efficacy (maximum flow rate [Q(max)], International Prostate Symptom Score) and safety (adverse events). Secondary end points included operation time and duration of irrigation, catheterization, and hospitalization. EVIDENCE ACQUISITION Based on a detailed, unrestricted strategy, the literature was searched up to February 19, 2009, using Medline, Embase, Science Citation Index, and the Cochrane Library to detect all relevant RCTs. Methodological quality assessment of the trials was based on the Dutch Cochrane Collaboration checklist. Meta-analysis was performed using Review Manager 5.0. EVIDENCE SYNTHESIS Sixteen RCTs (1406 patients) were included. Overall trial quality was low (eg, allocation concealment and blinding of outcome assessors were poorly reported). No clinically relevant differences in short-term (12-mo) efficacy were detected (Q(max): weighted mean difference [WMD]: 0.72 ml/s; 95% confidence interval [CI], 0.08-1.35; p=0.03). Data on follow-up of >12 mo are scarce for B-TURP, precluding long-term efficacy evaluation. Treating 50 patients (95% CI, 33-111) and 20 patients (95% CI, 10-100) with B-TURP results in one fewer case of TUR syndrome (risk difference [RD]: 2.0%; 95% CI, 0.9-3.0%; p=0.01) and one fewer case of clot retention (RD: 5.0%; 95% CI, 1.0-10%; p=0.03), respectively. Operation times, transfusion rates, retention rates after catheter removal, and urethral complications did not differ significantly. Irrigation and catheterization duration was significantly longer with M-TURP (WMD: 8.75 h; 95% CI, 6.8-10.7 and WMD: 21.77 h; 95% CI, 19.22-24.32; p<0.00001, respectively). Inferences for hospitalization duration could not be made. PlasmaKinetic TURP showed an improved safety profile. Data on TUR in saline (TURis) are not yet mature to permit safe conclusions. CONCLUSIONS No clinically relevant differences in short-term efficacy exist between the two techniques, but B-TURP is preferable due to a more favorable safety profile (lower TUR syndrome and clot retention rates) and shorter irrigation and catheterization duration. Well-designed multicentric/international RCTs with long-term follow-up and cost analysis are still needed.

Combined quantitative dynamic contrast-enhanced MR imaging and (1)H MR spectroscopic imaging of human prostate cancer.

To differentiate prostate carcinoma from healthy peripheral zone and central gland using quantitative dynamic contrast‐enhanced (DCE) magnetic resonance (MR) imaging and two‐dimensional 1H MR spectroscopic imaging (MRSI) combined into one clinical protocol.

The clinical research office of the endourological society ureteroscopy global study: indications, complications, and outcomes in 11,885 patients.

PURPOSE To assess the current indications for ureteroscopy (URS) treatment, outcome in terms of stone-free rate, and intra- and postoperative complications using the modified Clavien grading system. PATIENTS AND METHODS The Clinical Research Office of the Endourological Society collected prospective data as part of the URS Global Study for consecutive patients treated with URS at centers around the world for 1 year. URS was performed according to study protocol and local clinical practice guidelines. The stone size and location were recorded and postoperative outcome and complications, graded according to the modified Clavien grading system, reported. RESULTS Between January 2010 and October 2012, 11,885 patients received URS at 114 centers in 32 countries; 1852 had only renal stones, 8676 had only ureteral stones, and 1145 patients had both types of stone. Fragmentation was performed principally using a laser device (49.0%) or a pneumatic device (30.3%); no device was used in 17.9% of the patients. A high stone-free rate (85.6%) was achieved. The large majority of patients did not receive any further treatment for renal or ureter stones (89.4%). The postoperative complication rate was low (3.5%). The most frequent complication was fever (1.8%); a blood transfusion was required in 0.2% of patients. The majority of complications were Clavien grade I or II (2.8% of patients). CONCLUSION URS is an established minimal invasive treatment for urinary stones with a high success rate and low morbidity. Recent advances have expanded the indication for urinary stones, which now ranges from treatment of smaller sized distal ureter stones by semirigid URS to larger sized renal pelvis stones treated by flexible URS.

Contrast-enhanced three-dimensional power doppler angiography of the human prostate: correlation with biopsy outcome

OBJECTIVES To determine the feasibility of contrast-enhanced three-dimensional (3D) imaging of the prostatic vasculature using power Doppler imaging and to analyze whether semiquantitative judgments of 3D images with respect to symmetry and distribution of vascular structures correlated with biopsy outcome. METHODS 3D power Doppler images were obtained before and after intravenous administration of 2.5 g Levovist. Subsequently, random and/or directed transrectal ultrasound (TRUS)-guided biopsies were performed. Vascular images were analyzed by two experts. Prostate vasculature was judged with respect to symmetry and vessel distribution using a (scale) grading system. RESULTS Eighteen patients with a suspicion of prostate cancer either because of an elevated prostate-specific antigen (greater than 4.0 ng/mL; Tandem-R-assay) or an abnormal digital rectal examination were included in the study. Prostate cancer was detected in 13 patients. Vascular anatomy was judged abnormal in unenhanced images in 6 cases, of which 5 proved malignant. Enhanced images were considered suspicious for malignancy in 12 cases, including 1 benign and 11 malignant biopsy results. Sensitivity of enhanced images was 85% (specificity 80%) compared with 38% for unenhanced images (specificity 80%) and 77% for conventional gray-scale TRUS (specificity 60%). Of 6 patients who showed no B-mode abnormalities, vascular patterns were judged abnormal in 4 cases, of which 3 were malignant. CONCLUSIONS Contrast-enhanced 3D power Doppler angiography is feasible in patients with suspicion of prostate cancer who are scheduled for prostate biopsies. The sensitivity of power Doppler 3D imaging for the detection of prostate malignancy increased from 38% (5 of 13) to 85% (11 of 13) after administration of intravascular microbubble contrast (Levovist), and specificity was found to be 80% (4 of 5) for both imaging modalities. Thus, the use of Levovist when combined with the power Doppler display mode and 3D image reconstruction offers a promising new research area that might prove useful in prostate cancer detection in the future.

Age and Bladder Outlet Obstruction Are Independently Associated with Detrusor Overactivity in Patients with Benign Prostatic Hyperplasia

BACKGROUND Detrusor overactivity is one known cause of lower urinary tract symptoms and has been linked to bladder storage symptoms (urgency, frequency, or urge incontinence). OBJECTIVE To determine clinical and urodynamic parameters associated with detrusor overactivity in patients with suspected benign prostatic hyperplasia. DESIGN, SETTING, AND PARTICIPANTS During 1993-2003, urodynamic investigations were performed in patients aged 40 yr or older and with lower urinary tract symptoms, benign prostatic enlargement, and/or suspicion of bladder outlet obstruction (maximum flow rate < 15 ml/s or postvoid residual urine > 50 ml). MEASUREMENTS Detrusor overactivity was defined according to the new International Continence Society classification (2002) as involuntary detrusor contractions during cystometry, which may be spontaneous or provoked, regardless of amplitude. The Schäfer algorithm was used to determine bladder outlet obstruction. RESULTS In total, 1418 men were investigated (median age: 63 yr) of whom 864 men (60.9%) had detrusor overactivity. In univariate analysis, men with detrusor overactivity were significantly older, more obstructed, had larger prostates, higher irritative International Prostate Symptoms Score subscores, a lower voiding volume at free uroflowmetry, and a lower bladder capacity at cystometry. The prevalence of detrusor overactivity rose continuously with increasing bladder outlet obstruction grade. Multivariate analysis showed that only age and bladder outlet obstruction grade were independently associated with detrusor overactivity. After age adjustment, the odds ratios of detrusor overactivity compared to Schäfer class 0 were 1.2 for class I, 1.4 for class II, 1.9 for class III, 2.5 for class IV, 3.4 for class V, and 4.7 for class VI. CONCLUSIONS In patients with clinical benign prostatic hyperplasia, detrusor overactivity is independently associated with age and bladder outlet obstruction. The probability of detrusor overactivity rises with increasing age and bladder outlet obstruction grade.

A critical analysis of the actual role of minimally invasive surgery and active surveillance for kidney cancer.

CONTEXT The incidence of renal cell carcinomas (RCCs) has increased steadily-most rapidly for small renal masses (SRMs). Paralleling the changing face of RCC in the past 2 decades, new, less invasive surgical options have been developed. Laparoscopic radical nephrectomy (LRN) is an established procedure for the treatment of RCC. Treatment of SRMs includes open partial nephrectomy (OPN), laparoscopic partial nephrectomy (LPN), thermal ablation, and active surveillance. OBJECTIVE To present an overview of minimally invasive treatment options and data on surveillance for kidney cancer. EVIDENCE ACQUISITION Literature and meeting abstracts were searched using the terms renal cell carcinoma, minimally invasive surgery, laparoscopic surgery, thermal ablation, surveillance, and robotic surgery. The articles with the highest level of evidence were identified with the consensus of all the collaborative authors and reviewed. EVIDENCE SYNTHESIS Renal insufficiency, as measured by the glomerular filtration rate, occurs more often after radical nephrectomy than partial nephrectomy (PN). OPN and LPN show comparable results in long-term oncologic outcomes. The treatment modality for SRMs should therefore be nephron-sparing surgery (NSS). In select patients, thermal ablation or active surveillance of SRMs is an alternative. CONCLUSIONS LRN has become the standard of care for most organ-confined tumours not amenable to NSS. Amongst NSS options, PN is the treatment of choice, yet remains underutilised in the community. Initial data during its learning curve revealed that LPN had higher urologic morbidity. However, current emerging data indicate that in experienced hands, LPN has shorter ischaemia times, a lower complication rate, and equivalent long-term oncologic and renal functional outcomes, yet with decreased patient morbidity compared to OPN. Robotic partial nephrectomy is being explored at select centres, and cryotherapy and radiofrequency ablation are options for carefully selected tumours. Active surveillance is an option for selected high-risk patients. Percutaneous needle biopsy is likely to gain increasing relevance in the management of small renal tumours.