Tumor complexity and the impact on MIC and trifecta in robot-assisted partial nephrectomy: a multi-center study of over 500 cases.

PURPOSE: To demonstrate the surgical feasibility of robot-assisted partial nephrectomy for complex renal masses with comparison of low/intermediate risk versus high-risk tumors according to the PADUA score. METHODS: Since 2008, 538 robot-assisted partial nephrectomies were performed at three German robotic centers. Both the MIC (margin, ischemia, complications) criteria and trifecta were applied. RESULTS: 60.1% of the tumors were of low and intermediate complexity (PADUA score 6-9, n = 326, group A), while 39.9% were highly complex (n = 212, score ≥ 10, B). Median clinical tumor size was 28 in A versus 37 mm in B (p < 0.001). There was no significant difference in terms of operative time (160 vs. 163 min, p = 0.20); ischemia time was slightly longer for B (11 vs. 12 min, p < 0.001). There were no significant differences for intra- (3.4%, A, vs. 6.6%, B, p = 0.10) or postoperative (21.5%, A, vs. 25.5%, B, p = 0.30) complication rates. There was a median eGFR decrease of - 9.4 (A) versus - 15.1 (B) ml/min (p < 0.001) on discharge. Histopathology revealed an R1 margin rate of 3.4% for the low/intermediate versus 6.1% for the high complexity group (p = 0.14). MIC criteria were fulfilled in 81.9% (A) versus 75.5% (B, p = 0.11) and trifecta criteria in 74.2% (A) versus 68.93% (B, p = 0.26). CONCLUSIONS: Complication rates, histopathology results as well as quality criteria as indicated by MIC and trifecta were similar for high and low complexity groups. Therefore, robot-assisted partial nephrectomy is a safe and feasible option also in highly complex tumors.

Are there limits of robotic partial nephrectomy? TRIFECTA outcomes of open and robotic partial nephrectomy for completely endophytic renal tumors.

BACKGROUND: To compare the outcomes of robot-assisted (RAPN) and open partial nephrectomy (OPN) for completely endophytic renal tumors. METHODS: Consecutive patients undergoing OPN or RAPN for entirely endophytic tumors in four high-volume centers between 2008 and 2016 were identified. Endophytic masses were identified based on sectional imaging. Patient characteristics and surgical outcome were compared using Mann-Whitney-U-test and chi-squared-tests. Uni- and multivariate analyses were performed to identify predictors of TRIFECTA achievement and excisional volume loss. RESULTS: Out of 1128 patients, 10.9% (64) of RAPN and 13.9% (76) of OPN underwent surgery for entirely endophytic tumors. Operative time was longer for RAPN (169 vs 140 min, P = 0.03) while ischemia time was shorter (13 vs 18 min, P = 0.001). Complication rates were comparable (21% OPN vs 22% RAPN, P = 0.91) and TRIFECTA achievement was not different between the groups (68% OPN vs 75% RAPN, P = 0.39). In multivariate analyses type of surgery was not associated with TRIFECTA achievement or excisional volume loss. Here, only tumor complexity (OR 0.48, P = 0.001) and size (OR 1.01, P = 0.002) were independent predictors. CONCLUSION: For entirely endophytic tumors, both RAPN and OPN offer good TRIFECTA achievement. This encourages the use of NSS even for these highly complex tumors using the surgeon's preferred approach.

Adreno-muscarinic synergy in the male human urinary outflow tract.

AIM: To examine putative interaction between adrenergic and muscarinic contractile activation in the human urinary outflow tract. METHODS: Tissue from the trigone and prostatic urethra was obtained from 12 cystectomy and 16 prostatectomy specimen. Contractions were elicited by exposure to exogenous agonists before and after inhibition of Rho kinase and protein kinase c (PKC). Immunofluorescence and Western-blot studies were performed using antibodies to muscarinic M3-receptors (M3-R) and alpha1A-adrenoreceptors (alpha1A-AR). The study is registered with ClinicalTrials.gov, number NCT01227447. RESULTS: There was strong co-localization of M3-R and alpha1A-AR on trigonal and urethral myocytes. Western blot analysis revealed a significantly higher expression of alpha1A-AR in the superficial than in the deep trigone. Phenylephrine (PE, 1 µm) augmented contractions induced by carbachol (CA, 3 µm) to more than threefold control in the male superficial trigone, and to about sevenfold control in the proximal urethra. No such potentiation could be detected in female bladder outlet. Both PKC inhibitor GF 109203X and Rho kinase inhibitor Y-27632 reduced responses to 1 µM PE as well as to 3 µM CA significantly. However, the synergistic effect of the combined intervention remained proportionally unaffected. CONCLUSIONS: Muscarinic and adrenergic receptor activation exerts a strong synergistic effect in the male human bladder trigone and proximal urethra.

"Finding the needle in a haystack": oncologic evaluation of patients treated for LUTS with holmium laser enucleation of the prostate (HoLEP) versus transurethral resection of the prostate (TURP).

PURPOSE: To evaluate oncologic parameters of men with bothersome LUTS undergoing surgical treatment with HoLEP or TURP. METHODS: Five hundred and eighteen patients undergoing HoLEP (n = 289) or TURP (n = 229) were retrospectively analyzed for total PSA, prostate volume, PSA density, history of prostate biopsy, resected prostate weight, and histopathological features. Univariate and multivariate logistic regression models were used to identify independent predictors of incidental PCa (iPCa). RESULTS: Men undergoing HoLEP had a significantly higher total PSA (median 5.5 vs. 2.3 ng/mL) and prostate volume (median 80 vs. 41 cc), and displayed a greater reduction of prostate volume after surgery compared to TURP patients (median 71 vs. 50%; all p < 0.001). With a prevalence of incidental PCa (iPCa) of 15 and 17% for HoLEP and TURP, respectively, the choice of procedure had no influence on the detection of iPCa (p = 0.593). However, a higher rate of false-negative preoperative prostate biopsies was noted among iPCa patients in the HoLEP arm (40 vs. 8%, p = 0.007). In multivariate logistic regression, we identified patient age (OR 1.04; 95% CI 1.01-1.07, p = 0.013) and PSA density (OR 2.13; 95% CI 1.09-4.18, p = 0.028) as independent predictors for the detection of iPCa. CONCLUSIONS: Despite differences in oncologic parameters, the choice of technique had no influence on the detection of iPCa. Increased patient age and higher PSA density were associated with iPCa. A higher rate of false-negative preoperative prostate biopsies was noted in HoLEP patients. Therefore, diagnostic assessment of LUTS patients requires a more adapted approach to exclude malignancy, especially in those with larger prostates.

Poor standard mp-MRI and routine biopsy fail to precisely predict intraprostatic tumor localization.

PURPOSE: To evaluate the localization accuracy of routinely performed preoperative multiparametric MRI (mp-MRI), not being assessed according to PI-RADS criteria. METHODS: One hundred and six patients underwent radical retropubic prostatectomy (January 2011-June 2012) with preoperative MRI. Intraprostatic tumor localization suggested by mp-MRI was correlated to both biopsy and histopathology results. RESULTS: Sensitivity and specificity were as low as 25-62 and 60-94 %, respectively. Neither higher field force nor the use of an endorectal coil could enhance accuracy. There was no statistically significant concordance in any sextant. The mean number of correctly identified sextants was between 3.11 and 4.00 and, thus, insignificantly above the value of 3 that one would obtain by tossing the coin. For transrectal biopsies, sensitivity and specificity of tumor localization were 52-63 and 46-80 %, respectively. CONCLUSIONS: Neither routinely performed "non-PI-RADS" MRI nor transrectal biopsy can accurately localize prostate cancer. Focal therapy concepts rely on a precise intraprostatic tumor detection and therefore inevitably require PI-RADS assessment by radiologists with genitourinary specialization. Regarding patient discomfort and costs, "non-PI-RADS" MRIs of the prostate are not justified.

Single fraction radiosurgery for the treatment of renal tumors.

PURPOSE: High dose local stereotactic radiosurgery was performed in select patients to improve local tumor control and overall survival. We report on patients with renal tumors treated with single fraction robotic stereotactic radiosurgery. MATERIALS AND METHODS: A total of 40 patients with a median age of 64 years who had an indication for nephrectomy and subsequent hemodialysis were entered in a prospective case-control study of single fraction stereotactic radiosurgery. Of the patients 11 had transitional cell cancer and 29 had renal cell cancer. Tumor response, renal function, survival and adverse events were estimated every 3 months. Followup was at least 6 months. RESULTS: A total of 45 renal tumors were treated. Median followup was 28.1 months (range 6.0 to 78.3). The local tumor control rate 9 months after stereotactic radiosurgery was 98% (95% CI 89-99). There was a measurable size reduction in 38 lesions, including complete remission in 19. Renal function remained stable. Using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation median creatinine clearance was 76.8 (range 25.3 to 126.3) and 70.3 ml/minute/1.73 m(2) (range 18.6 to 127.3) at baseline and followup, respectively (p = 0.89). Grade I erythrodermia developed in 1 patient, 3 reported grade I fatigue and 2 reported grade I nausea. Nephrectomy was avoided in all cases. CONCLUSIONS: Single fraction stereotactic radiosurgery as an outpatient procedure is a treatment modality with short-term safety and efficacy. It avoids treatment related loss of renal function and hemodialysis in select patients with transitional or renal cell cancer. At short followup oncologic results were similar to those of other ablative techniques for renal tumors. To date functional results have been excellent. Further studies are needed to determine the long-term results and limits of stereotactic radiosurgery in this setting.

Preoperative mp-MRI of the prostate provides little information about staging of prostate carcinoma in daily clinical practice.

PURPOSE: To evaluate the staging accuracy of preoperative multiparametric MRI (mp-MRI), its influence on the technique of radical retropubic prostatectomy (RRP), and its value for daily clinical practice. METHODS: A total of 106 patients underwent RRP (January 2011-June 2012) and had preoperative MRI staging data available for review. Staging results acquired by mp-MRI were correlated to both biopsy and histopathology results. Surgical reports were reviewed for intraoperative aspect of tumor extension, technique of RRP (nerve sparing or extended), and extent of lymphadenectomy. RESULTS: The accuracy of diagnosing extracapsular extension (ECE) was 72.2 %, with an overall sensitivity and specificity of 30.0 and 93.3 %, respectively. The negative predictive value was 72.7 %. The sensitivity and specificity to diagnose positive seminal vesical invasion (SVI) were 63.6 and 92.9 %, respectively. Neither higher field force nor the use of an endorectal coil could enhance the accuracy of mp-MRI. In case of awareness of an existing MRI, there was a significantly higher percentage of nerve protection (left: 93 %; right: 89 % vs. left 75 %; right: 75 %). The higher percentage of nerve sparing surgery did not result in a higher level of positive resection margins. CONCLUSIONS: In routine clinical practice, mp-MRI at non-academic centers has very limited clinical value in predicting ECE and SVI. Our data support the current recommendations against the widespread preoperative use of mp-MRI because it is not adding reliable predictive information on the extent of prostate cancer.

Contraction of the anterior prostate is required for the initiation of micturition.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: In a recent rtMRI study, we were able to show that, during initiation of voiding, there was both funnelling of the bladder neck and simultaneous contraction of the ventral prostate. We presumed that the vertical contraction of the ventral prostate contributes to the initiation of successful micturition. The question remained as to whether this shortening of the ventral prostate is predominantly caused by contractile elements in the organ itself, or by surrounding contractile elements of the pelvic floor. In our study we provide insight in to anatomical changes, and biometric and functional analysis of the prostate during micturition. A sagittal contraction of the ventral prostate and the longitudinal smooth muscle elements at the onset of voiding, which can be observed on MRI, is likely to shorten and open up the prostatic urethra. OBJECTIVE: To investigate if in vitro contractile strength of the prostate and the prostatic urethra might correlate with the shortening of the ventral prostate seen on real-time magnetic resonance imaging (rtMRI). Micturition is a complex process that includes anatomical and neurological interactions for successful voiding. Recently we described on rtMRI that vertical contraction of the ventral prostate precedes initiation of male micturition and may contribute to the funnelling of the bladder neck. PATIENTS AND METHODS: In all, 10 patients undergoing radical prostatectomy (RP) were enrolled. Approval was obtained from all patients and by the local Ethics Committee. Preoperative rtMRI during voiding was performed as described before in eight patients undergoing RP, measuring the difference of the cranio-caudal distance of the ventral prostate (VP). To roughly estimate the amount of force required to deform the prostate in a vertical direction as seen on rtMRI, we uniaxially compressed the organ immediately after surgery by the same distance, assuming incompressibility and isotropy of prostatic tissue. A muscle strip (3 × 3 mm) from the ventral prostate, dorsal prostate and prostatic urethra was obtained after pathological evaluation. Contraction was elicited by electrical-field stimulation (EFS: 0.1 ms pulses at 2, 4, 8, 16, 32 and 64 Hz for 4 s). RESULTS: There was a mean cranio-caudal contraction of the ventral prostate by 7.6 mm at the onset of micturition on rtMRI (P = 0.002). The mean (sd) contractile force of strips elicited by EFS at 32 Hz was 1472.44 (706.88) mN for the ventral prostate, 1044.24 (894.66) mN for the dorsal prostate, and 639.10 (785.06) mN for the prostatic urethra (P = 0.02). Extrapolating these values to the whole organ diameter, we calculated comparable force as observed in compression experiments. CONCLUSIONS: Our functional and biometric in vitro analyses of prostate tissue showed sufficient contractile strength of the ventral prostate to induce a shortening of the organ as seen on rtMRI. There was significant higher contractile strength in the ventral prostate than in the dorsal prostate or the proximal urethra. The consistency of in vivo and in vitro results underlines the significance of the ventral prostate for the initiation of normal micturition.

Microbial colonization and ureteral stent-associated storage lower urinary tract symptoms: the forgotten piece of the puzzle?

PURPOSE: Ureteral stents are frequently associated with side effects. Most patients suffer from storage lower urinary tract symptoms (LUTS). Storage LUTS are commonly attributed to the irritation of the trigone, smooth muscle spasm or a combination of factors. The relationship between microbial ureteral stent colonization (MUSC) and de novo or worsening storage LUTS has not been investigated yet. METHODS: Five hundred ninety-one polyurethane ureteral stents from 275 male and 153 female patients were prospectively evaluated. The removed stents were sonicated to dislodge adherent microorganisms. Urine flow cytometry was performed to detect pyuria. A standardized urinary symptom questionnaire was given to all patients. RESULTS: Thirty-five per cent of male and 28% of female cases showed de novo or worsened storage LUTS. MUSC was more common in patients with storage LUTS compared to patients without storage LUTS (men: 26 vs. 13%, respectively, P < 0.05; women: 63 vs. 48%, respectively, P = 0.13). Pyuria was significantly more common in patients with storage LUTS compared to patients without storage LUTS (men: 55 vs. 40%, respectively, P < 0.05; women: 70 vs. 45%, respectively, P < 0.05). No significant correlation was observed between the detected genera of microorganisms and storage LUTS. CONCLUSIONS: Our data show a significant association between MUSC- and stent-related de novo experienced or worsened storage LUTS in men. The incidence of MUSC is most common in both female and male patients with storage LUTS and accompanying pyuria. In these patients, a combination of antibiotics and anti-inflammatory drugs may be regarded as treatment option.

Impact of the 'repositioning test' on postoperative outcome of retroluminar transobturator male sling implantation.

OBJECTIVE: To evaluate prospectively the value of the 'repositioning test' (RT) in preoperative patient selection for the efficacy of male stress urinary incontinence (SUI) treatment using a retroluminar transobturator male sling (AdVance sling). PATIENTS AND METHODS: 65 consecutive patients with SUI after radical prostatectomy were included in this single-center prospective study. Preoperatively, patients were classified into those with 'positive' and 'negative' RT. Postoperative results were analyzed and the association between the result of the RT and postoperative outcome was evaluated. RESULTS: 53 patients (81.5%) showed preoperatively a positive RT and 12 patients (18.5%) a negative RT. After a follow-up of 12 months, patients with positive RT showed a cure rate (0 pads/day) of 83% and patients with a negative RT showed only a cure rate of 25%. A positive RT significantly correlated with cure in outcome (p < 0.001). CONCLUSIONS: Patients with positive RT have a significantly better chance for successful AdVance sling implantation. The RT is minimally invasive, easy to learn and easy to perform. Therefore, the RT is a very useful tool for preoperative patient selection.

Monitoring the coupling of the lithotripter therapy head with skin during routine shock wave lithotripsy with a surveillance camera.

PURPOSE: With lithotripters today the shock waves are typically transmitted into the body via water filled bellows using coupling gel to make contact with the skin. Usually the coupling zone is not visible to the operator. We investigated coupling quality during routine clinical shock wave lithotripsy and the associated effect on shock wave disintegration efficiency. MATERIALS AND METHODS: During 30 routine shock wave lithotripsy treatments the coupling zone was continuously monitored by a video camera integrated into a DoLi SII lithotripter (Dornier MedTech, Wessling, Germany). However, it was not shown to the blinded operator to resemble the standard clinical situation. We used 3 coupling gels, including LithoClear®, Sonogel® and a custom-made gel of low viscosity. The ratio of air in the relevant coupling area was measured. Lithotripter disintegration efficiency was evaluated by in vitro model stone tests at an air ratio of 0%, 5%, 10% and 20%. RESULTS: Only in 10 of 30 treatments was good coupling achieved with an air ratio of less than 5%. In 8 treatments the ratio was greater than 20%. The best coupling conditions were achieved with low viscosity gel. The mean ± SD number of shock waves needed for complete fragmentation in the model stone tests was 100 ± 4 for bubble-free coupling, and 126 ± 3 for 5%, 151 ± 8 for 10% and 287 ± 5 for 20% air bubbles. CONCLUSIONS: At 20 of 30 shock wave lithotripsy sessions there was imperfect coupling, accompanied by significant loss of disintegration capability. A surveillance camera is useful to monitor and improve coupling.

Real-time magnetic resonance imaging (MRI): anatomical changes during physiological voiding in men.

OBJECTIVE: To investigate the interactions between the bladder, urethra, pelvic floor and the function of the prostate during 'normal' voiding. PATIENTS AND METHODS: In all, 16 men with no history of urinary incontinence, urgency or obstructive voiding dysfunction were enrolled. We analysed the interaction between the bladder, urethra, pelvic floor and changes in the prostate during the Valsalva manoeuvre and voiding using real-time magnetic resonance imaging (rtMRI). The axis through the external sphincter (AES) to pubo-coccygeal line (PC-line) and the angle between the axis of the os pubis (AOP) and ventral prostate (VP) was measured before and at the end of voiding. Additionally, the angle between the AOP and the VP was measured during the Valsalva manoeuvre. Change of position, or contraction, of the VP was measured. RESULTS: The mean age of the men was 69.8 years and mean prostate volume 33.1 mL. Before voiding, the mean AES to PC-line was 10.5 mm. At the end of voiding, the mean AES to PC-line was 20 mm. The mean angle between AOP/VP was 31.6° in the storage phase and increased to a mean of 54.5° during voiding. During the Valsalva manoeuvre, the angle between the AOP/VP remained constant. There was a mean vertical contraction of the VP of 48.25 mm before voiding and a declining of the cranio-caudal distance of the VP with a mean of 33.92 mm during voiding. CONCLUSIONS: All the men in our study showed relaxation of the pelvic floor, followed by a descent of the bladder neck. Voiding could not be initiated unless the prostate rotated around the symphysis. The study suggests that both the rotation and a vertical contraction of the prostate precede voiding. The anatomy of physiological voiding or voiding dysfunction can be investigated non-invasively using rtMRI.

Animal models in urinary diversion.

We set out to critically assess the value of animal experimentation in urinary diversion through intestinal segments, as some authors question the effectiveness of animal research, criticising the methodological quality, lack of standardization, inadequate reporting and the few systematic reviews in this field. Based on a comprehensive MEDLINE literature search (MeSH database; search terms: urinary diversion, urinary reservoirs, continent, rat, dog, animal models) we retrieved and evaluated all full-length papers published in English, German, French, and Spanish languages from 1966 to 2011 reporting the use of animal models in the setting of urinary diversion. Studies were stratified according to the addressed research question. Within each category species, gender, number of animals, age at procedure, type of diversion, mortality, length of follow-up, experimental procedure and outcome were recorded and tabulated. In all, 159 articles were judged to be relevant and while there are numerous animal models only a few have been used in more than one study. Animals were used for the systematic study of new surgical techniques (93 articles) or metabolic and functional consequences of urinary reconstruction (66 articles). For the latter purpose, the most often used animal is the rat, whereas the dog model is preferred for technical experimentation. In many studies, the validity of the model is at least questionable. Animal experiments have repeatedly been conducted addressing the same question, often with striking discrepancies in outcome. Animal studies were even performed after a surgical technique had been pioneered in humans. The use of animal models in urinary diversion is far from standardized rendering the results less than ideal for comparison across studies. Due to differences in anatomy and physiology, the applicability of findings in animal experiments to clinical urology is limited. Continued effort is needed to optimise the use of animal models in experimental urology.

Single-stage dorsal inlay for reconstruction of recurrent peno-glandular stenosis.

OBJECTIVE: To evaluate the validity of a single-stage dorsal inlay for recurrent peno-glandular stenosis following previous endourological or open urethroplastic surgery. Urethral glanular reconstruction included a deep dorsal incision followed by complete scar excision to create a deep groove presenting well-vascularized recipient bed ensuring appropriate graft healing. MATERIALS AND METHODS: Between April 2002 and January 2008, a total of 34 patients (mean age 51.5 years, 14-85 years) were enrolled in the study. Congenital anomalies included hypospadia (n = 19, 53%) and epispadia (n = 2, 6%). Condition of strictures was either iatrogenic (n = 7), due to infection (n = 5), or traumatic (n = 1). Foreskin grafts were used in 13 cases, foreskin and buccal mucosa in one case, penile skin in 6 cases, and inguinal skin/thigh (harvested by electrodermatom) in 14 cases. The combination of meticulous scar excision with a deep incision of the glans was used to provide a well-vascularized grafting bed, thus ensuring excellent graft healing. The outcome analysis included urinary flow, urethral calibration >18 ch, voiding cystometry, and patient's satisfaction in a follow-up regime every 3 months. RESULTS: The average graft length was 4.7 cm (median 8, range 1.5-14). Mean follow-up was 70 months. In 31 patients (91%), no recurrent glanular stenosis was observed resulting in a post-operative flow of average 26.2 ml/s (11-53). Three post-operative wound infections occurred resulting in stricture recurrence, which was treated with internal urethrotomy, buccal mucosa, or penile skin inlay, respectively. Cosmetic results were satisfactory in all patients. Post-operative voiding parameters were significantly improved (P < 0.001). CONCLUSION: The single-stage dorsal inlay for reconstruction of peno-glandular stenosis represents a reliable method even if the urethral plate is severely scarred or has been excised during previous surgery. The good results imply that a well-vascularized graft and the technical approach seem to be more important than the substitute material.

Volar onlay urethroplasty for reconstruction of female urethra in recurrent stricture disease.

OBJECTIVE: • To report our experience with a new and simple method of urethral repair with a volar onlay of free labium minus graft. Strictures of the female urethra are rare, and it is well accepted that the therapeutic options of dilation and urethrotomy are not lasting solutions as a result of their high recurrence rates. However, there is no consensus regarding the best way to reconstruct the female urethra in the case of stricture disease. PATIENTS AND METHODS: • Four consecutive female patients with a long lasting history of recurrent urethral strictures underwent open urethroplasty with a volar situated free split thickness epidermal graft from the labium minus. • The surgical technique is described and a short-term follow-up is presented. RESULTS: • Operating time was 40-140 min (mean 105 min), and the graft measured between 2 × 1.5 cm and 3 × 2.5 cm. Follow-up time was 11-19 months. Maximum urinary flow rate could be improved from a baseline of 9.4-11.2 mL/s (preoperatively, after intermittent use of dilation) to 19-23 mL/s. • Postvoid residual urine volume was 0-50 mL preoperatively and no postvoid residual urine volume postoperatively. • Urinary catheters were removed after 21 days. Urinary stress incontinence did not occur postoperatively. No complications related to the graft donor site were found. CONCLUSIONS: • The reported data concerning a new therapeutic approach for the treatment of recurrent female urethral stricture show that a volar onlay urethroplasty represents a feasible, safe and simple surgical method. • Larger series with long-term follow-up are needed for further evaluation.

ß-arrestin-2 is expressed in human prostate smooth muscle and a binding partner of α1A-adrenoceptors.

PURPOSE: Alpha1A-adrenoceptors are important regulators of prostatic smooth muscle tone and an important target for therapy of lower urinary tract symptoms. The function of heptahelical transmembrane receptors such as adrenoceptors can be regulated by ß-arrestin-2, which may bind to receptors besides G proteins. Here, we investigated the expression and α1A-adrenoceptor binding of ß-arrestin-2 in the human prostate. METHODS: Human prostatic tissues were obtained from patients undergoing radical prostatectomies. The expression of ß-arrestin-2 and α1A-adrenoceptors was studied by RT-PCR, Western blot analysis, and immunohistochemistry. The protein-protein interaction between α1A-adrenoceptors and ß-arrestin-2 was investigated by coimmunoprecipitation. RESULTS: RT-PCR and Western blot analysis demonstrated the expression of ß-arrestin-2 mRNA and protein in the human prostate. Immunohistochemistry demonstrated ß-arrestin-2 expression in smooth muscle and stromal cells. Coimmunoprecipitation studies demonstrated that α1A-adrenoceptors in the human prostate may interact with ß-arrestin-2. Thus, specific binding of ß-arrestin-2 to α1A-adrenoceptors was significantly higher than background during α1A-adrenoceptor detection in ß-arrestin-2 precipitates (P < 0.001) or during ß-arrestin-2 detection in α1A-adrenoceptor precipitates (P < 0.005). This interaction may be located to prostate smooth muscle cells, as expression of the α1A-adrenoceptor was exclusively found in smooth muscle cells after immunohistochemical staining. CONCLUSION: With ß-arrestin-2, we identified a new binding partner of the α1A-adrenoceptor in human prostate smooth muscle. Binding of ß-arrestin-2 may be involved in posttranslational regulation of prostate α1A-adrenoceptors.

Patient-reported side effects of intradetrusor botulinum toxin type a for idiopathic overactive bladder syndrome.

OBJECTIVE: The aim of the study was a prospective assessment of patient-reported side effects in an open-label study after intradetrusor botulinum toxin injections for idiopathic overactive bladder (OAB). PATIENTS AND METHODS: Botulinum toxin A injection was performed in 56 patients with idiopathic OAB. Patients were followed up for 6 months concerning side effects and patients' satisfaction. RESULTS: Different types of side effects were assessed such as dry mouth (19.6%), arm weakness (8.9%), eyelid weakness (8.9%), leg weakness (7.1%), torso weakness (5.4%), impaired vision (5.4%) and dysphagia (5.4%). In all cases, symptoms were mild and transient. Urological complications such as gross hematuria (17.9%), acute urinary retention (8.9%) and acute urinary tract infection (7.1%) were noticed. In all cases, acute urinary retention was transient and treated with temporary intermittent self-catheterization. There was no statistically significant correlation between dosage and observed side effects. Patients' satisfaction rate was high (71.4%). CONCLUSION: Intradetrusor injection of botulinum toxin was associated with a high rate of neurourological side effects. In general, side effects were transient, mild and did not require special treatment.

Immunohistochemical expression of muscarinic receptors in the urothelium and suburothelium of neurogenic and idiopathic overactive human bladders, and changes with botulinum neurotoxin administration.

PURPOSE: To investigate the possible associations of urothelial and suburothelial muscarinic receptors with human bladder pathophysiology we examined the immunohistochemical expression of muscarinic receptors types 1, 2 and 3 in the bladder urothelium and suburothelium of patients with neurogenic or idiopathic detrusor overactivity compared with that in controls. We also examined associations with patient quantified symptoms and the effect of intradetrusor botulinum neurotoxin type A treatment. MATERIALS AND METHODS: We obtained bladder biopsies from 36 patients with detrusor overactivity before, and 4 and 16 weeks after treatment with intradetrusor botulinum neurotoxin type A via flexible cystoscopy. Patients with neurogenic detrusor overactivity were injected with 300 U botulinum neurotoxin type A and those with idiopathic detrusor overactivity received 200 U. Control biopsies were taken from 7 patients during investigation for asymptomatic microscopic hematuria. We studied muscarinic receptor immunohistochemical expression using commercial antibodies to muscarinic receptors 1, 2 and 3 with results quantified by image analysis. RESULTS: We noted decreased suburothelial muscarinic receptor immunoreactivity in detrusor overactivity biopsies vs controls, which were significant for muscarinic receptors 1 and 3. After successful botulinum neurotoxin treatment we noted only increased muscarinic receptor 1 and 2 immunoreactivity. Urothelial muscarinic receptor 1 and 3 immunoreactivity was increased after treatment. We identified no substantial urothelial muscarinic receptor 2 immunoreactivity. Receptor levels showed inverse correlations with patient urgency and frequency. CONCLUSIONS: Decreased muscarinic receptor levels in the urothelium and suburothelium of patients with detrusor overactivity were largely restored to control levels after successful treatment with botulinum neurotoxin type A. Correlations of receptor levels with patient symptoms further support a role for urothelial and suburothelial muscarinic receptors in detrusor overactivity in humans.

Liver resection for metastatic disease prolongs survival in renal cell carcinoma: 12-year results from a retrospective comparative analysis.

UNLABELLED: The value of surgical resection of renal cell carcinoma (RCC) liver metastases still remains unclear. OBJECTIVE: Of our study was to evaluate the efficacy of liver resection by comparing patients who could have undergone metastasectomy due to limited disease, but refused surgery. MATERIALS AND METHODS: Eighty-eight patients were identified with liver metastases and indication of surgery between 1995 and 2006. In 68 patients, liver resection was performed, 20 patients denied surgery and served as comparison group. Patients were followed for survival. RESULTS: Median age was 58. Median amount of liver metastases was 2 (range 1-30). Median follow-up was 26 months (range 1-187). In both groups, 79% received systemic therapy. The 5-year overall survival rate (OSR-5) after metastasectomy was 62.2% +/- 11.4% (SEM) with a median survival (MS) of 142 (95% confidence interval (CI) 115-169) months. OSR-5 in the control group was 29.3% +/- 22.0% (SEM) with a MS of 27 (95% CI 16-38) months (P = 0.003). MS was 155 (95% CI 133-175) months with metachronous metastases compared to 29 (95% CI 25-33) months in the comparison group (P = 0.001). Low-grade primary RCC had a MS of 155 (95% CI 123-187) months compared to 29 (95% CI 8-50) months without resection (P = 0.0036). High-grade RCC as well as patients with synchronous metastases did not benefit from surgery. CONCLUSIONS: Liver metastasectomy is an independent valuable tool in the treatment of metastatic RCC and significantly prolongs patient's survival, even if further systemic treatment is necessary. With the evidence given, patients may benefit from liver metastasis resection if technically feasible.

Cadherin-11 up-regulation in overactive bladder suburothelial myofibroblasts.

PURPOSE: We investigated whether the adherens junction proteins cadherin-11 and beta-catenin can be immunohistochemically visualized in the human bladder using commercially available antibodies and, if so, whether there are differences between patients with overactive bladder and refractory detrusor overactivity, and controls without lower urinary tract symptoms. MATERIALS AND METHODS: In a prospective, nonrandomized single center study 32 patients with overactive bladder and refractory detrusor overactivity, and 8 controls without lower urinary tract symptoms underwent cystoscopic bladder biopsy. Quantitative immunohistochemistry was performed. The primary outcome was cadherin-11 and beta-catenin expression in the human bladder using commercially available antibodies. The secondary outcome was differences in cadherin-11 and beta-catenin in patients with overactive bladder and refractory detrusor overactivity, and controls. RESULTS: Double labeling experiments showed co-localization of cadherin-11 and connexin 43 in the suburothelium. There was also strong co-localization of cadherin-11 and beta-catenin in the suburothelium and detrusor. Significant 2-fold up-regulation of cadherin-11 was found in the suburothelium of patients with overactive bladder compared with that in controls (p = 0.018), whereas beta-catenin was similar in the groups (p = 0.6). In the detrusor cadherin-11 and beta-catenin expression was comparable in patients with overactive bladder and controls (each p = 0.5). No difference was observed in cadherin-11 and beta-catenin in patients with overactive bladder with idiopathic vs neurogenic detrusor overactivity in the suburothelium and the detrusor (p >0.3 and >0.2, respectively). CONCLUSIONS: Using commercially available antibodies cadherin-11 and beta-catenin expression in human bladder suburothelial myofibroblasts and detrusor smooth muscle cells was noted. Cadherin-11 up-regulation in suburothelial myofibroblasts in patients with overactive bladder may be significant in overactive bladder pathogenesis.