EAU guidelines on surgical treatment of urinary incontinence.

CONTEXT: The European Association of Urology (EAU) guidelines on urinary incontinence published in March 2012 have been rewritten based on an independent systematic review carried out by the EAU guidelines panel using a sustainable methodology. OBJECTIVE: We present a short version here of the full guidelines on the surgical treatment of patients with urinary incontinence, with the aim of dissemination to a wider audience. EVIDENCE ACQUISITION: Evidence appraisal included a pragmatic review of existing systematic reviews and independent new literature searches based on Population, Intervention, Comparator, Outcome (PICO) questions. The appraisal of papers was carried out by an international panel of experts, who also collaborated in a series of consensus discussions, to develop concise structured evidence summaries and action-based recommendations using a modified Oxford system. EVIDENCE SUMMARY: The full version of the guidance is available online (www.uroweb.org/guidelines/online-guidelines/). The guidance includes algorithms that refer the reader back to the supporting evidence and have greater accessibility in daily clinical practice. Two original meta-analyses were carried out specifically for these guidelines and are included in this report. CONCLUSIONS: These new guidelines present an up-to-date summary of the available evidence, together with clear clinical algorithms and action-based recommendations based on the best available evidence. Where high-level evidence is lacking, they present a consensus of expert panel opinion.

[European Association of Urology guidelines on assessment and nonsurgical management of urinary incontinence]. / Guía clínica de la Asociación Europea de Urología sobre la evaluación y el tratamiento no quirúrgico de la incontinencia urinaria.

CONTEXT: The previous European Association of Urology (EAU) guidelines on urinary incontinence comprised a summary of sections of the 2009 International Consultation on Incontinence. A decision was made in 2010 to rewrite these guidelines based on an independent systematic review carried out by the EAU guidelines panel, using a sustainable methodology. OBJECTIVE: We present a short version of the full guidelines on assessment, diagnosis, and nonsurgical treatment of urinary incontinence, with the aim of increasing their dissemination. EVIDENCE ACQUISITION: Evidence appraisal included a pragmatic review of existing systematic reviews and independent new literature searches, based on Population, Intervention, Comparator, Outcome questions. Appraisal of papers was carried out by an international panel of experts, who also collaborated on a series of consensus discussions, to develop concise structured evidence summaries and action-based recommendations using a modified Oxford system. EVIDENCE SUMMARY: The full version of the guidelines is available online (http://www.uroweb.org/guidelines/online-guidelines/). The guidelines include algorithms that refer the reader back to the supporting evidence, and they are more immediately useable in daily clinical practice. CONCLUSIONS: These new guidelines present an up-to-date summary of the available evidence, together with clear clinical algorithms and action-based recommendations based on the best available evidence. Where such evidence does not exist, they present a consensus of expert opinion.

The role of exenterative surgery and urinary diversion in persistent or locally recurrent gynecological malignancy: complications and survival.

OBJECTIVE: Treatment options in patients with persistent or locally recurrent cervical cancer are limited. The aim of this study was to determine the chance of cure and associated morbidity following pelvic exenteration. PATIENTS AND METHODS: Consecutive patients who underwent pelvic exenteration between January 1992 and December 2006 at the University Hospital of Bern or the Karlsruhe Medical Center were evaluated. Time to recurrence, type of exenteration and urinary diversion, pathological stage, postoperative complications and survival were assessed. RESULTS: Initial therapy prior to diagnosis of persistent or locally recurrent disease included radiation therapy in 51%. Anterior exenteration was performed in 37 (86%) and total exenteration in 6 (14%). Half of the women underwent additional procedures. A continent urinary diversion was constructed in 16 and an ileal conduit in 27 patients. Early postoperative complications were generally minor and only 2 patients required surgical intervention. Four intestinal fistulas were successfully treated conservatively. Late complications were mainly tumor-related. Complication rates associated with the urinary diversion were low and there was no difference in complications between continent and incontinent diversions. The overall disease-specific 5-year survival rate after exenteration was 36.5%. Survival correlated significantly with surgical margin status. CONCLUSION: In patients with persistent or locally recurrent gynecological malignancy of the pelvis, exenteration is a viable option with long-term survival in over one third of patients. Continent urinary diversion did not show higher complication rates than an ileal conduit and should be considered even in irradiated patients. This may be of greater significance in younger patients in whom an intact body image can play an important role in quality of life.

[Ganglion curage in prostate cancer]. / Curage ganglionnaire dans le cancer de la prostate.

In clinically Localized prostate cancers, the interest of pelvic Lymphadenectomy is debated. Nevertheless, this intervention provides important information on disease prognosis (number of positive lymph nodes, tumoural volume, and extracapsular perforation of the affected ganglions); information that previously no other technique could provide. However, no consensus exists concerning patients who should benefit from pelvic Lymphadenectomy and on the extent of this intervention. For most surgeons, decision making regarding ganglion curage is based on nomograms. According to these nomograms, patients with a level of prostate specific antigen (PSA) <10 ng/mL and a Gleason score <7 have a very low risk for ganglionic metastases; this is the reason why the benefit of pelvic Lymphadenectomy remains controversial. Besides, most of these nomograms are based upon the results of standard Lymphadenectomy (iliac vein and obturator fossa) with, subsequently, a related risk of imprecision. In addition, potential therapeutic benefit may be expected from extended ganglion curage, despite the fact that this is not clearly documented yet, due to the benign course of the disease. In other tumoural diseases (stomach cancer, breast cancer, colorectal cancer, blade cancer), on the contrary, survival and stage identification depend on the number of removed ganglions, thus on the extent of Lymphadenectomy.

[The role of pelvic lymphadenectomy in clinically localised prostate cancer]. / Stellenwert der pelvinen Lymphadenektomie beim klinisch lokalisierten Prostatakarzinom.

Lymph node dissection remains the only reliable method for exact staging to date. Extended lymphadenectomy including tissue along the external iliac vein, the obturator fossa, and along the internal iliac vessels should be performed in all patients undergoing radical prostatectomy. There is an increasing amount of data suggesting that removal of all diseased nodes, which contain minimal metastatic disease, may have a positive impact on disease-free and, perhaps, on overall survival. Due to the relatively benign course of the disease, longer follow-up periods are still necessary to make a definitive statement.

Membrane segregation and downregulation of raft markers during sarcolemmal differentiation in skeletal muscle cells.

Muscle contraction implies flexibility in combination with force resistance and requires a high degree of sarcolemmal organization. Smooth muscle cells differentiate largely from mesenchymal precursor cells and gradually assume a highly periodic sarcolemmal organization. Skeletal muscle undergoes an even more striking differentiation programme, leading to cell fusion and alignment into myofibrils. The lipid bilayer of each cell type is further segregated into raft and non-raft microdomains of distinct lipid composition. Considering the extent of developmental rearrangement in skeletal muscle, we investigated sarcolemmal microdomain organization in skeletal and smooth muscle cells. The rafts in both muscle types are characterized by marker proteins belonging to the annexin family which localize to the inner membrane leaflet, as well as glycosyl-phosphatidyl-inositol (GPI)-anchored enzymes attached to the outer leaflet. We demonstrate that the profound structural rearrangements that occur during skeletal muscle maturation coincide with a striking decrease in membrane lipid segregation, downregulation of annexins 2 and 6, and a significant decrease in raft-associated 5'-nucleotidase activity. The relative paucity of lipid rafts in mature skeletal in contrast to smooth muscle suggests that the organization of sarcolemmal microdomains contributes to the muscle-specific differences in stimulatory responses and contractile properties.

[Conservative and surgical therapy of urinary incontinence and bladder complaints in the man]. / Konservative und operative Therapie von Harninkontinenz und Blasenbeschwerden beim Mann.

Treatment of incontinence and bladder complaints in the male should be directed to the cause whenever possible. Frequently, however, only symptomatic therapy is possible. Urge incontinence or overactive bladder due to obstruction should primarily be treated by eliminating the obstruction. Medical and surgical treatment methods are available for benign prostatic hyperplasia, bladder neck hypertrophy and prostatic cancer. In contrast, bladder neck sclerosis and uretheral strictures can only be treated surgically. Anticholinergics are primarily indicated if urge symptoms/incontinence persist after obstruction has been relieved or if urge incontinence occurs without obstruction. Seldom, in special cases injection of Botulinustoxin A or augmentation of the bladder may be indicated. Another possible cause of urge symptoms is urinary tract infection. This should be adequately treated according to resistance studies and the cause of the infection determined. In cases of overflow incontinence the infravesicle obstruction must be sought and treated. If limited detrusor contractability is the cause of overflow incontinence and the bladder cannot be emptied through pressmicturition, parasympathicometics may be of help. By insufficient effect, the procedure of intermittent self-catheterization must be taught. If this is not possible, the last resort is placement of a transuretheral or percutaneous catheter for continuous drainage. Stress incontinence is a rare complication in men, usually following prostatic surgery. It can be treated conservatively with pelvic floor training and alpha-adrenergic receptor agonists and if necessary surgically with submucosal collagen or silicon injections in the sphincter area or implantation of a sphincter prosthesis. Supravesicular urinary diversion is occasionally necessary after conservative and less invasive surgical measures have been exhausted and symptomatic suffering persists. Neurogenic disturbances in bladder capacity and/or emptying can be treated conservatively, medically, surgically or a combination of these depending upon the site of the lesion and the resulting urodynamic patterns.

Noninvasive anesthesia, analgesia and radiation-free extracorporeal shock wave lithotripsy for stones in the most distal ureter: experience with 165 patients.

PURPOSE: Spontaneous ureteral stone passage often causes severe renal colic, especially when the stone passes through the narrow ureteral orifice. In these situations noninvasive anesthesia-free, analgesia-free and radiation-free extracorporeal shock wave lithotripsy (ESWL) (Dornier Medical Systems, Marietta, Georgia) is a valuable tool. It can be performed at any time without needing any further patient preparation. MATERIALS AND METHODS: A total of 165 patients underwent ESWL using the Lithostar Ultra device (Siemens, Erlangen, Germany). Only ureteral calculi within 5 cm. of the ureterovesical junction were included in this study. Patients were treated while supine and stones were localized by ultrasound through the filled bladder without x-ray exposure. Treatment was started without anesthesia or analgesia and analgesics were administered only at patient request during treatment. RESULTS: Of the patients 93% were treated without anesthesia or analgesia and 7% required a single intravenous dose of 25 mg. pethidine. Postoperatively renal colic developed in 40 patients (24%). In 4 cases (2.4%) renal drainage was required for analgesia resistant pain or obstructive pyelonephritis. On day 1 after ESWL 90% of the patients were stone-free or had fragments 2 mm. or less, while 10% had residual fragments 3 mm. or greater. Of all patients 7% were re-treated once. At 3 months postoperatively 129 of the 130 evaluable patients (99%) were stone-free. CONCLUSIONS: ESWL of stones located in the most distal ureter using the Lithostar Ultra device is effective, safe and radiation-free. It is done without anesthesia and in most cases without analgesics. This simple and noninvasive procedure is an excellent first line treatment modality for prevesical stones and it represents a valid alternative to conservative management or invasive endoscopy.

Inefficient urethral milking secondary to urethral dysfunction as an additional risk factor for incontinence after radical prostatectomy.

PURPOSE: Continence after radical prostatectomy is thought to depend completely on the striated urethral sphincter. However, some patients complain only of occasional post-void dribbling. Therefore, we determined whether urethral dysfunction may be another cause of incontinence. MATERIALS AND METHODS: The sensory threshold of electric stimulation was measured by double ring electrodes in the membranous urethra and 2.5 cm. distal in 29 men before and in 29 after radical retropubic prostatectomy. In addition, voiding cystourethrography was performed in 66 patients before and in 49 after surgery to determine complete post-void urethral emptying or milking. RESULTS: The mean sensory threshold of the membranous urethra was 15 +/- 3 mA. preoperatively versus 38 +/- 17 postoperatively (p <0.0001). The sensory threshold 2.5 cm. further distal was 12 +/- 5 mA. before and 10 +/- 4 after radical prostatectomy, which was not statistically significant. Postoperatively in completely continent patients and in those with dribbling the mean threshold was 32 +/- 12 and 43 +/- 18 mA. in the membranous urethra (p = 0.09), and 11 +/- 4 and 9 +/- 4 mA. in the bulbar urethra, respectively, which was not statistically significant. Of the 66 patients 36 (55%) showed post-void urethral milking before surgery but only 8 of 49 (16%) showed it postoperatively (chi-square test p <0.0001), including 7 who were completely continent and 1 who complained of occasional post-void dribbling. CONCLUSIONS: After radical prostatectomy sensitivity of the membranous but not of the bulbar urethra is affected, correlating with postoperative continence. In addition, post-void dribbling seems to be associated with the loss of urethral milking. We conclude that preserving urethral function is another important continence factor after radical prostatectomy.

Up-regulation of a gene homologous to the human tumor necrosis factor receptor associated factor 6 gene in the obstructed rabbit bladder determined by differential display polymerase chain reaction.

PURPOSE: We identified differentially expressed genes in the rabbit bladder after partial outlet obstruction. MATERIALS AND METHODS: Differential display polymerase chain reaction (PCR) was performed on smooth muscle tissue from normal, 2 and 6-week obstructed rabbit bladders. Semiquantitative reverse transcriptase PCR, Western and RNA blot analysis were done to confirm messenger RNA and protein up-regulation. RESULTS: A signal transducing protein human tumor necrosis factor receptor associated factor 6 (TRAF6)-like protein was identified on differential display PCR. TRAF6-like protein was up-regulated in rabbit bladders after 2 weeks of partial outlet obstruction. Reverse transcriptase PCR demonstrated TRAF6-like protein in bladder muscle tissue and semiquantitative analysis confirmed up-regulation in 2-week obstructed tissue. These findings were confirmed by RNA and Western blot analysis. CONCLUSIONS: TRAF6-like protein is up-regulated during the early phase of bladder outlet obstruction in rabbits. To our knowledge involvement of this gene in bladder outlet obstruction has not been described previously. TRAF6 may have a role in the regulation of molecular changes during the early bladder response to outlet obstruction, such as the up-regulation of growth factors and proto-oncogenes. Further understanding of this signaling pathway and its role in bladder outlet obstruction may open new avenues for treating detrusor dysfunction.

Fertility and sexual function following orchiectomy and 2 cycles of chemotherapy for stage I high risk nonseminomatous germ cell cancer.

PURPOSE: We investigate fertility and sexual function in patients following orchiectomy and adjuvant cisplatin based chemotherapy for high risk, stage I nonseminomatous germ cell tumor of the testis. MATERIALS AND METHODS: Between 1985 and 1994, 59 patients with stage I nonseminomatous germ cell tumor and poor prognostic factors were treated with 2 cycles of cisplatin, vinblastine and bleomycin, or bleomycin, etoposide and cisplatin after orchiectomy. At least 32 months following treatment all patients were contacted and asked to complete a questionnaire regarding fertility and sexual activity, and to volunteer for a semen and hormonal analysis. RESULTS: Of the 59 patients 49 (83%) completed the questionnaire. Before chemotherapy 18 (37%) patients had fathered children, 6 (12%) were involuntarily childless and none had a major sexual dysfunction. After treatment 11 (22%) patients fathered children, and 5 (10%) were involuntarily childless, with 4 involuntarily childless before chemotherapy. There were no significant alterations in sexual function. Semen analysis in 27 patients was normal in 23, and revealed mild oligospermia in 2 and azoospermia in 2. In 18 patients with hormone analysis median values for luteinizing hormone and free testosterone were normal but median value for follicle-stimulating hormone was slightly increased. CONCLUSIONS: Two cycles of cisplatin based adjuvant chemotherapy do not seem to affect adversely fertility or sexual activity.

Contractile protein expression in bladder smooth muscle is a marker of phenotypic modulation after outlet obstruction in the rabbit model.

PURPOSE: We determined changes in contractile protein expression before and after the relief of partial bladder outlet obstruction in the rabbit model and assessed their potential role as predictors of recovery. MATERIALS AND METHODS: We examined the ratio of the smooth muscle myosin heavy chain isoforms SM2-to-SM1, caldesmon isoform expression and bladder function in obstructed and unobstructed adult rabbit bladders. Cystometry, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis were done to determine changes in bladder function and contractile protein expression. RESULTS: Overall we observed significant correlation of bladder weight with the SM2-to-SM1 ratio (p <0.05). Regardless of the duration of obstruction (up to 10 weeks) the ratio appeared to stabilize around a value comparable to that in fetal rabbit smooth muscle cells, suggesting a reversal of SM2 and SM1 expression to a level similar to that at the fetal stage. The pattern of h and l-caldesmon isoform expression showed an increase in l-caldesmon expression in obstructed bladders. Except for decreased leak point pressure in the obstructed group we noted no statistically significant urodynamic changes in bladder capacity or compliance. CONCLUSIONS: There is significant correlation of bladder weight, which is the best known marker of obstruction, with the SM2-to-SM1 ratio. The myosin heavy chain isoform expression ratio appears to be an indicator of phenotypic modulation in bladder smooth muscle before and after the relief of bladder outlet obstruction. Thus, it may be useful as a marker of bladder dysfunction and predictor of functional recovery. Regression to a fetal pattern of protein expression may suggest irreversible damage to smooth muscle cells, possibly limiting recovery.

Orthotopic bladder substitution.

For a select group of patients orthotopic bladder substitution is an ideal alternative for urinary diversion after cystectomy. Initially this method was mainly applied in males, but is increasingly being used in women with good results. In general, consensus has been reached concerning patient selection criteria and surgical details, but there are some important issues of continuing debate. To achieve good long-term results meticulous postoperative patient management is of utmost importance.

Risk adapted management with adjuvant chemotherapy in patients with high risk clinical stage i nonseminomatous germ cell tumor.

PURPOSE: We propose that patients with high risk, clinical stage I nonseminomatous germ cell tumors receive 2 cycles of chemotherapy initially, instead of undergoing surgery or observation. MATERIALS AND METHODS: A total of 59 patients with high risk, clinical stage I nonseminomatous germ cell tumor received risk adapted adjuvant chemotherapy. Until June 1987, 20 patients were treated with 2 courses of adjuvant cisplatin, vinblastine and bleomycin at 3-week intervals. After June 1987 another 39 patients were treated with 2 cycles of bleomycin, etoposide and cisplatin. RESULTS: Long-term results with this treatment strategy have been excellent with limited morbidity. CONCLUSIONS: Adjuvant chemotherapy may be of particular value in patients with compromised followup.

Transurethral thermotherapy for benign prostatic hyperplasia significantly decreases infravesical obstruction: results in 134 patients after 1 year.

PURPOSE: We prospectively evaluated a decrease in outflow obstruction caused by benign prostatic hyperplasia (BPH) with second generation thermotherapy. MATERIALS AND METHODS: Transurethral microwave therapy was given with local anesthesia to 134 patients with urodynamically and cystoscopically documented obstruction by BPH and preserved detrusor function. Of 134 patients 67 (50%) had a general health score of 3 or greater. RESULTS: Urgency was the main complaint during thermotherapy. After a median followup of 24 months (minimum 12) 100 patients were evaluable at 6 and 12 months. Of the initial 134 patients 17 (13%) who required additional treatment (repeat thermotherapy, transurethral prostatic resection, permanent cystostomy), 7 who died during followup for treatment unrelated reasons and 10 who were lost to followup or refused evaluation were excluded from further analysis. Mean International Prostate Symptom Score decreased from 22.5 before to 3.6 at 6 months after treatment and remained stable at 12 months. Mean Quality of Life Index improved from 4.3 before to 1 at 12 months after treatment. Mean maximum flow increased from 7.3 ml. per second before to 14.5 at 6 months and 13.9 at 12 months after treatment. Mean post-void residual decreased from 199 to 34.8 and 37.2 ml. at 6 and 12 months, respectively. Urodynamic evaluation of 84 patients after 6 months revealed a decrease in mean detrusor opening pressure from 96.8 to 53 cm. water and mean detrusor pressure at maximum flow from 99.8 to 59.7 cm. water. Mean ultrasonographic prostate volume decreased from 57.6 to 42.4 cc and a cavity in the prostate was documented in 65 of the 84 cases (77%). All changes between the pretreatment and posttreatment values at 6 and 12 months, respectively, were statistically significant (paired t test p<0.00001). CONCLUSIONS: Targeted transurethral thermotherapy with second generation microwave equipment is minimally invasive, easy to apply and generally well tolerated with local anesthesia. Infravesical outlet obstruction and voiding pressures as assessed by pressure flow studies significantly decreased 6 months after treatment. Subjective voiding symptoms as well as post-void residual urine were significantly decreased, and urinary flow was improved 6 and 12 months after treatment of documented BPH.

The effects of transurethral needle ablation and resection of the prostate on pressure flow urodynamic parameters: analysis of the United States randomized study.

PURPOSE: We evaluated the effects of transurethral needle ablation and prostate resection on pressure flow urodynamic parameters in men with benign prostatic hyperplasia (BPH), compared symptomatic and objective parameters of efficacy 6 months after initial treatment, and determined whether urodynamic assessment may predict symptomatic improvement. MATERIALS AND METHODS: We enrolled 121 patients with clinical BPH, American Urological Association symptom index of 13 or greater and maximum urinary flow of 12 ml. per second or less in a randomized study comparing transurethral needle ablation to prostate resection at 7 institutions in the United States. Patients underwent baseline and followup assessments at 6 months, including pressure flow studies. RESULTS: Patients who underwent each procedure had statistically and clinically significant improvement in symptom index, BPH impact index and quality of life score. After needle ablation and prostate resection maximum flow improved from 8.8 to 13.5 (p<0.0001) and 8.8 to 20.8 ml. per second (p<0.0001), detrusor pressure at maximum flow decreased from 78.7 to 64.5 (p = 0.036) and 75.8 to 54.9 cm. water (p<0.001), and the Abrams-Griffiths number decreased from 61.2 to 37.2 (p<0.001) and 58.3 to 10.9 (p<0.001), respectively. At 6 months the differences in transurethral needle ablation and prostate resection were significant in terms of maximum flow (p<0.001) and the Abrams-Griffiths number (p<0.001) but not detrusor pressure at maximum flow or symptom assessment tools. The presence or absence of urinary obstruction at baseline did not predict the degree of symptomatic improvement in either treatment group. CONCLUSIONS: Transurethral needle ablation and prostate resection induce statistically and clinically significant improvement in various quantitative symptom assessment questionnaires at 6 months. The parameters of free flow rates and invasive pressure flow studies also significantly improve after each treatment. However, transurethral prostate resection induces a significantly greater decrease in the parameters of obstruction. Baseline urodynamic parameters do not predict the degree of symptomatic improvement and they may not be helpful in patient selection for transurethral needle ablation.

[Complications after bladder neck suspension by vaginal approach in the treatment of stress urinary incontinence with moderate cystocele: apropos of a case]. / Complications après colposuspension par voie vaginale pour traitement d'une incontinence urinaire d'effort avec cystocèle modérée: à propos d'une observation.

This report documents a case combining three complications after four-corner bladder neck suspension: infravesical obstruction, intravesical suture placement and de novo enterocele with vault prolapse, and discusses the prevention and management of each complication.

Immunohistochemical determination of p53 overexpression. An easy and readily available method to identify progression in superficial bladder cancer?

Overexpression of p53, as determined by immunohistochemical staining with the murine monoclonal antibody DO7, was determined in specimens of 46 primary superficial transitional cell bladder tumours (14 TaG2, 10 T1G2, 22 T1G3). A colon cancer specimen served as a positive control and normal mesenchymal cells in the specimens served as an internal negative control. An exceptionally high proportion 36/46 (78%) of the specimens were found to stain positively for p53 in over 20% of the cell nuclei. After a median follow-up of 7 years, ten patients developed progressive disease. Of these ten patients nine demonstrated p53 positivity, resulting in a sensitivity of 90%. However, 27 of the overall 36 patients (75%) with p53-positive tumours did not progress to a higher stage or metastatic disease. These findings suggest that p53 overexpression is not of predictive prognostic value in superficial transitional cell carcinoma. With 7 of 14 specimens (50%) of Ta tumours overexpressing p53, the results were suggestive of p53 mutation being an early event in carcinogenesis. When the threshold was set at 50% of the cell nuclei overexpressing p53, 16/46 (35%) classified as p53 positive. Of the 16 tumours staining positively for p53, 7 (46%) progressed and 9 (56%) did not. None of the Ta and 16 (50%) of the T1 tumours classified as positive. This more stringent definition of positivity still does not identify p53 positivity as a single prognostic factor. With 50% of T1 tumours classifying as positive, we still find that p53 mutation may be an early event in carcinogenesis of bladder cancer.