Monitoring brain activation changes in the early postoperative period after radical prostatectomy using fMRI.

Urinary incontinence is a major concern following radical prostatectomy. The etiology is multifactorial involving intrinsic sphincter deficiency and/or detrusor hyperactivity and/or decreased bladder compliance. Recent studies employing functional imaging methodology nicely demonstrated the reference regions of the micturition circuit. Based on these landmarks this work complements this field of research by studying patients with bladder dysfunction. Our aim was to evaluate, whether iatrogenic impairment of the pelvic floor muscles after retropubic radical prostatectomy (RRP) causes detectable changes in fMRI in the early postoperative period. fMRI was performed at 3T in 22 patients before and after RRP with urge to void due to a filled bladder. In a non-voiding model they were instructed to contract or to relax the pelvic floor muscles repetitively. As previously reported in healthy men, contraction and relaxation of pelvic floor muscles induced strong activations in the brainstem and more rostral areas in our group of patients before and after RRP. In general, all of them had stronger activations during contraction than during relaxation in all regions before and after the operation. Even though there was no difference in the activation level when relaxing the pelvic floor before and after the operation, we found stronger activation during contraction when comparing the preoperative with the postoperative level in some of the regions. The results suggest that the same cortical and subcortical networks can be demonstrated for micturition control in patients with prostate cancer as in healthy subjects. However, impaired pelvic floor muscle function after RRP seems to induce different activation intensities.

Impact of ureteral stenting prior to ureterorenoscopy on stone-free rates and complications.

OBJECTIVE: To date, only few studies have evaluated the impact of ureteral stenting prior to ureterorenoscopy. This study is to clarify the role of preoperative ureteral stenting in the treatment for ureteral stones. METHODS: We retrospectively reviewed 550 ureterorenoscopies from 1998 to 2008. Patients were classified into two groups depending on whether they had a stent placed before URS. Baseline characteristics of patients and stone properties, stone-free rates, complications, and operation times were compared between both groups. Subanalysis was performed regarding stone localization. We retrospectively reviewed data from patient documentation, X-ray imagery, intravenous urography, and operation reports. RESULTS: Baseline characteristics of patients were similar in both groups. The majority of patients underwent stent placement before the ureteroscopic stone treatment (88.4%). The mean operation time in the prestented group was longer (43.3 vs. 38.4 min). Stone-free rate of patients with stent was 72.2%, compared to 59.4% without preoperative stenting. The rate of minor complications was 4.7% with stent versus 9.4% without stent, major complications 0.6% versus 1.6%, respectively. Patients with distal ureter stones had similar stone-free rates regardless of a stent placement (90.1% with stent vs. 87.6% without), and no difference in complication rates was observed (3.5% with stent vs. 3.1% without), respectively. CONCLUSIONS: Stent placement prior to ureteroscopic stone treatment in distal ureter is not reasonable and does not considerably improve stone-free rates.

[Prolapse surgery. With abdominal or vaginal meshes?]. / Prolapschirurgie. Mit abdominal oder vaginal eingesetzten Netzen?

In prolapse surgery several surgical techniques are available. The different open, laparoscopic and vaginal approaches are distinguished by distinct success and relapse rates and operation-specific complications. A safe and optimal therapeutic pelvic floor surgery should be based on the three support levels according to DeLancy and be individually adjusted for every patient. The vaginal approach may be used for all kinds of female genital prolapse and is a comparatively less invasive technique with a short time of convalescence. Apart from stress incontinence there is no need for synthetic meshes in primary approaches and excellent results with low complication and relapse rates can be achieved. An uncritical application of synthetic material is to be avoided in vaginal repair at all times. Abdominal surgical techniques, both open and laparoscopic, present their strengths in the therapeutic approach to level 1 defects or stress incontinence. They provide excellent functional and anatomical corrections and low relapse rates. Abdominally inserted meshes have lower complication rates than vaginal ones.

[Intermittent androgen deprivation as therapy for androgen-sensitive prostate cancer. Sense or nonsense?]. / Intermittierende Hormontherapie beim androgensensiblen Prostatakarzinom. Sinn oder Unsinn?

Androgen deprivation is the predominant therapy for advanced prostate cancer. There is accumulating evidence that phases of intermission in androgen deprivation may have benefits regarding side effects, albeit there is as yet no general recommendation for intermittent androgen deprivation therapy. Recent systematic reviews at least substantiate a benefit from such regimens for general quality of life without therapy compromisation. In addition, preclinical data revealed further potential strategies for intermittent androgen deprivation therapy. Future studies must prove, however, that such approaches can be implemented in the clinical situation.

[Laser now also to be used in organ-preserving kidney surgery?]. / Laser nun auch in der organerhaltenden Nierenchirurgie?

Kidney surgery is subject to continuous change. Partial nephrectomy is the prevailing method for small and medium-sized tumours and proven to be superior to radical nephrectomy. The conventional technique usually includes clamping the renal vessels. The duration of the ischaemia caused determines the outcome of the remaining renal function. The shorter the ischaemic time the more likely the renal function will be preserved. Thus, new techniques are needed to abandon renal vessel clamping. Essential is a combination of good cutting abilities and assured haemostasis. To date, the commonly used techniques for cutting in partial nephrectomy only partially fulfil these requirements. Establishment of laser in urology offers a new surgical technique that combines both. In spite of the still limited data on laser use in kidney surgery, this method can be assessed favourably. Laser offers a possibility of both open and laparoscopic partial nephrectomy avoiding renal vessel clamping without additional risks or complications.

[Antiandrogen strategies in prostate cancer: reconstitution of oestrogen receptor beta]. / Antiandrogene Strategien im Prostatakarzinom : Rekonstitution des beta-Ostrogenrezeptors.

In advanced prostate cancer, albeit castration resistant, an active androgen receptor is still pivotal for growth and cell survival. Recent therapies involving more effective antiandrogens such as MDV3100 proved to be successful. Furthermore, blocking de novo intracrine androgen synthesis, e.g. with abiraterone acetate, provides additional benefit. Besides these antiandrogen measures, compounds which enable the reconstitution of the oestrogen receptor beta as a tumour suppressor restrain aberrant androgen receptor signalling.

[Vaginal pelvic repair. Always with mesh or not?]. / Vaginaler Beckenbodenrepair. Immer mit Netz?

Several surgical methods are possible when aiming at reconstruction of pelvic organ prolapse in women, and the experienced surgeon implements the knowledge gained from open, laparoscopic, and vaginal techniques. These feature different rates of success and relapse as well as different complication risks. Because of the accumulating morbidity of aging patients, there is a search for a safe minimally invasive technique. With the advent of synthetic meshes, surgeons have used them frequently and often uncritically for reconstruction of the female pelvic floor. In these cases the vaginal approach is preferred as opposed to alternative techniques, as it is less invasive and allows for better convalescence. Furthermore, this approach leads to low complication and relapse rates even when synthetic meshes are omitted.

Gender differences in voluntary micturition control: an fMRI study.

In the last decade functional imaging has gained substantial importance for identifying cortical and subcortical brain regions being involved in the micturition circuit. However, possible gender differences are still a matter of debate. In the present study we used functional magnetic resonance imaging (fMRI) to determine micturition related brain regions in healthy men and compared them with those in women to elucidate gender-related differences. fMRI was performed at 3 T in 12 healthy men with urge to void due to a filled bladder. In a non-voiding model they were instructed to contract or to relax the pelvic floor muscles repetitively. As previously reported in women, contraction and relaxation of pelvic floor muscles induced strong activations in the brainstem and more rostral areas in our group of healthy men. In general, men had stronger activations during contraction than women in nearly all identified areas. In contrast, results for the relaxation condition were similar. Some of the differences between contraction and relaxation, formerly detected in females, could be found in our group of males as well. The results suggest that in women and men the same cortical and subcortical networks exist for micturition control. Especially, the well located activations in the putative pontine micturition centre and the periaqueductal grey could be identified in both sexes. However, pelvic floor muscle control seems to induce different activation intensities in men and women.

[Forms of urinary diversion--methods and imaging findings]. / Formen der operativen Harnableitung: Methoden und bildgebende Diagnostik.

After cystectomy two principal types of urinary diversion are used for the surgical reconstruction of the urinary tract: incontinent and continent. In the continent type of urinary diversion, a differentiation must be made between those with and without catheterization for voiding. Besides urothelial cancer other reasons for urinary diversion include neurogenic bladder palsy (connatal or acquired) due to meningomyelocele or connatal diseases like bladder exstrophy. The main objective of the clinical urologist when selecting urinary diversion are to achieve continence and to preserve upper urinary tract function. Knowledge of the different forms of urinary diversion is critical for the exact interpretation of the images. This review presents the typical imaging techniques after a description of the basic surgical features of urinary diversion. CT urography and MR urography are becoming increasingly important as further imaging tools for controlling urinary diversions.

[Molecular principles of alternative treatment approaches for hormone-refractory prostate cancer]. / Molekulare Grundlagen alternativer Therapieansätze für das hormonrefraktäre Prostatakarzinom.

Prostate cancer is more frequently diagnosed in men from Western countries than from Asian societies. Therefore, nutritional factors such as phyto-oestrogens from soya are considered to cause this prostate cancer prevention effect. As there is no curative therapy for hormone-refractory prostate cancer, new strategies are in demand which might include phyto-oestrogens or inhibitors of histone deacetylases. Both approaches have in common the potential to reduce the aberrant androgen receptor and IGF receptor signalling. Furthermore, invasiveness and acquired survival strategies of tumours can be diminished. Reduced tumour cell proliferation and PSA secretion coincide with altered gene expression in the aforementioned processes. In addition, selective knock-down of genes by RNA interference afforded functional analyses regarding impact and succession of expression events involved in the beneficial effects caused by phyto-oestrogens and histone deacetylase inhibitors.

[Risk factors for perioperative complications in renal surgery for Wilms' tumor]. / Risikofaktoren perioperativer Komplikationen in der Chirurgie des Wilms-Tumors.

BACKGROUND: There is controversy about preoperative chemotherapy in the treatment of Wilms' tumor. The perioperative morbidity plays a key role in this discussion. Therefore, risk factors of perioperative complications were analysed in our series of patients with Wilms' tumor with a special focus on the effects of preoperative chemotherapy. PATIENTS AND METHODS: Case histories of 37 patients [mean age 3.9 (range: 0.6 - 14) years] were retrospectively analysed concerning follow-up, clinical and histopathological stage, size of the primary tumor, as well as duration and extent of preoperative chemotherapy. RESULTS: 35 patients underwent radical nephrectomy, 2 patients had organ-sparing surgery because of bilateral involvement. The mean maximal tumor diameter was 9.5 cm (range: 4 - 24 cm). 11/37 patients had no or shortened preoperative chemotherapy. 6/37 patients (16.2 %) had perioperative complications. There was one intraoperative tumor rupture, 4 small bowel obstructions, 1 pancreatitis. All complications occurred in patients of clinical stages III and IV, maximal tumor diameter > 10 cm after unusually extended operative procedures. 4 patients showed only poor response to preoperative chemotherapy. Patients with doxorubicin pre-treatment showed a higher risk of postoperative small bowel obstruction. CONCLUSIONS: The risk of perioperative complications was correlated with the local extent of the primary tumor and was higher with those requiring more extensive surgical interventions. The influence of preoperative chemotherapy on the complications rate is inconstant. Considering a good response of the primary tumor, the complication rate will be decreased. However, the comorbidity of more intense preoperative chemotherapy in patients of stage IV may contribute to a higher risk of surgical complications.

[Obstructive nephropathy]. / Obstruktive Nephropathie.

Congenital anomalies of the kidney and urinary tract (CAKUT) are regarded as a single entity. The degree of obstruction may have an additional influence on the parenchymal malfunction. Congenital dilatation of the upper urinary tract associated with symptomatic urinary tract infection must be treated early with intensive antibiotic therapy. In some cases temporary urinary diversion is also required. Further diagnostic procedures are then postponed in such cases. In all other cases of dilatation of the upper urinary tract diagnosed prenatally or early in the postnatal period, diuresis renography is still the cornerstone of diagnosis, even though it has definite limitations in young infants and in babies with poor kidney function. Functional gadolinum MR-urography will become the method of choice in the near future, since it combines good functional and excellent morphological presentation. When an obstruction hampering function is definitely present surgical correction is indicated: open and endoscopic surgery yield similarly good results. Molecular markers in CAKUT may soon be used as prognostic indicators. Examination of the molecular alterations that occur in renal and urinary tract anomalies may also lead to medicamentous protection of renal function.

[Long-term experience with Cohen ureteral reimplantation in bilateral vesicoureteral reflux in childhood]. / Langzeiterfahrungen mit der Ureterozystoneostomie nach Cohen beim bilateralen vesikoureterorenalen Reflux im Kindesalter.

INTRODUCTION: In bilateral VUR, Cohen cross-trigonal ureteric reimplantation is a popular but also controversial surgical approach. We present our own experience in a retrospective analysis. PATIENTS AND METHODS: Between 1990 and 2005, 41 children (26 girls, 15 boys) with bilateral reflux [92 renal units (RU)] underwent ureteric reimplantation. The mean age was 4.5 (0.3-12) years. Eight patients had ureteral duplication (six unilateral, two bilateral); 12 of 41 patients had no intraoperative ureteral stenting. Seven patients had prior surgery for VUR. A successful result was defined as absence of VUR, significant UVJ obstruction, or voiding dysfunction throughout the follow-up. RESULTS: The mean follow-up was 7.8 (0.5-15) years. Eight patients (19.5%) had 13 complications. One patient had an intraoperative small bowel lesion (2%). Six patients (14.6%) had UTI. Four patients (9.8%) showed transient UVJ obstruction. Three required a temporary percutaneous nephrostomy. Two of these patients had no intraoperative ureteral stenting. Recurrence of VUR was found in 2 patients (4.8%) and 2/92 RU (2.2%), respectively. Complications were more frequent in high-grade VUR, ureter duplex, or unstented ureteral reimplantation. Prior surgery for VUR did not influence the postoperative outcome. Postoperative voiding disorders were not observed. CONCLUSIONS: Two unilateral recurrences of VUR were observed, requiring a reoperation in one patient. A reoperation for UVJ obstruction was not necessary. Related to 92 RU the surgical success rate was 97.8%. Intraoperative ureteral stenting has to be considered with respect to the current discussion of shortening inpatient procedures. In our experience, the perioperative risk was elevated in patients with high-grade VUR or ureteral duplication.

Voluntary pelvic floor muscle control--an fMRI study.

Storage and periodic expulsion of urine by the bladder are controlled by central pathways and organized as simple on-off switching circuits. Several reports concerning aspects of micturition control have identified distinct regions in the brainstem, like the pontine micturition center (PMC) and the periaqueductal gray (PAG), as well as the cerebellum, basal ganglia, limbic system, and cortical areas that are organized in a widespread network. The present study focused on the involvement of these specific brain regions in pelvic floor muscle control. Functional magnetic resonance imaging (fMRI) was performed at 3T in 11 healthy women with urge to void due to a filled bladder, who were instructed to either imitate voiding by releasing or to imitate interruption of voiding by contracting pelvic floor muscles. None of the subjects was able to start voiding during the experiments, presumably due to subconscious restraint resulting from the inconvenient situation. Relaxation and contraction of pelvic floor muscles induced strong and similar activation patterns including frontal cortex, sensory-motor cortex, cerebellum, and basal ganglia. Furthermore, well-localized activations in the PMC and the PAG were identified. To our knowledge, this is the first study using fMRI to demonstrate micturition-related activity in these brainstem structures. The presented approach proved to characterize the widespread central network in pelvic floor muscle control. Thus, in patients with voiding dysfunction, fMRI will be useful to elucidate the individual disturbance level.

[Pharmacological potential of phytoestrogens in the treatment of prostate cancer]. / Das pharmakologische Potential von Phytoöstrogenen in der Therapie des Prostatakarzinoms.

INTRODUCTION: Phytoestrogenes are plant-derived compounds that have been shown to exert an antiproliferative potential on prostate cancer cells, although the exact mechanisms are still unclear. In prostate cancer cells proliferation is regulated by modulation of the IGF-1 receptor (IGF-R-1) by the androgen receptor (AR) and its co-activator prostate derived Ets factor (PDEF). Phytooestrogenes interact with these mechanisms as demonstrated exemplarily in the presented study with the isoflavone tectorigenin derived from Belamcanda chinensis. MATERIAL AND METHODS: Cultured androgen-sensitive LNCaP prostate cancer cells were treated with tectorigenin of 100 microM for 24 hours. The mRNA-expression of AR, PSA, PDEF, hTERT, TIMP-3 and IGF-R-1 were quantified by real-time RT-PCR. Furthermore, the expression or activity of PSA, telomerase and IGF-R-1 was measured on the protein level. In addition, we investigated in nude mice the influence of a diet of extracts of Belamcanda chinensis on the growth of subcutaneously injected LNCaP cells versus a control group of animals fed with a soy-free diet. RESULTS: In cultured LNCaP cells treatment with tectorigenin resulted in a significant down-regulation of the gene expression of AR, PDEF, PSA, IGF-R-1 and hTERT. On the protein level PSA secretion and the activity of telomerase and IGF-R-1 expression was also decreased. The gene expression of TIMP-3 was distinctly up-regulated by tectorigenin. Nude mice fed with Belamcanda chinensis extract showed a significantly decreased incidence and tumor growth compared to controls. CONCLUSIONS: Tectorigenin shows an inhibition of the IGF-1-R modulated cell proliferation of PCa-Cells, due to modulation of the activity the co-activator PDEF independently from the AR. Furthermore, tectorigenin has pro-apoptotic effects and decreases tissue invasion by up-regulation of TIMP-3. Therefore, phytooestrogenes are an interesting option in the therapy of prostate especially advanced prostate cancer.

Inhibition of telomerase activity and secretion of prostate specific antigen by silibinin in prostate cancer cells.

PURPOSE: The androgen sensitive prostate cancer cell line LNCaP is strongly positive for dihydrotestosterone (DHT) dependent telomerase activity, which is an important factor in cellular immortality and carcinogenesis. In this study we determined the potential of silibinin as an anticancer drug that down-regulates telomerase activity and prostate specific antigen (PSA) together with the co-activator of the androgen receptor prostate epithelium specific Ets transcription factor. MATERIALS AND METHODS: LNCaP cells were treated with various concentrations of silibinin in the presence or absence of 5alpha-DHT. We used real-time reverse transcriptase-polymerase chain reaction to quantify mRNA expression of PSA, prostate epithelium specific Ets transcription factor and the catalytic subunit of telomerase vs the housekeeping gene porphobilinogen deaminase with gene specific, dual labeled fluorescence probes. PSA secretion from LNCaP cells in conditioned medium was measured with an Elecsys System 2010 (Roche Diagnostics, Mannheim, Germany) and telomerase activity in extracts from LNCaP cells was measured with a TRAP (telomeric repeat amplification protocol) assay. RESULTS: Silibinin down-regulated PSA mRNA expression and PSA secretion in conditioned medium. Simultaneous stimulation with silibinin and 10(-8) M DHT also resulted in PSA down-regulation, whereas DHT alone increased PSA secretion. Telomerase catalytic subunit mRNA decreased significantly after silibinin stimulation. Telomerase activity was down-regulated by silibinin and stimulated by DHT. The 2 agents in combination resulted in telomerase down-regulation. CONCLUSIONS: The down-regulation of PSA by silibinin and its counteraction on DHT effects indicate that this compound can interact with the expression of genes that are regulated through the androgen receptor. Silibinin can also inhibit the telomerase activity that mediates cell immortality and carcinogenesis. The 2 effects underline the possible therapeutic use of silibinin as an antiproliferative agent in intervention for prostate cancer.

Bladder dysfunction in children with bilateral single ectopic ureters.

BACKGROUND: Single ectopic ureters are a rare malformation in children. Therapy consists of ureteral reimplantation. However, in case of bilateral single ectopic ureters, subsequent malformation of the bladder trigone and bladder neck may result in additional voiding dysfunction, and ureteral reimplantation alone may not solve the urologic problems. METHODS: The authors report their experience with 2 girls, in whom bilateral single ectopic ureters were treated by ureteral reimplantation in early childhood and who did not gain adequate bladder control during following years. RESULTS: Videourodynamic evaluation was done in both girls. No bladder overactivity was found during the urodynamic studies. However, cystography showed a widely open bladder neck during filling with no sufficient bladder neck closure shown by urethral pressure profile studies. When blocking the bladder outlet by balloon catheters, adequate bladder filling volume was achieved. Incontinence was cured by implantation of an AMS 800 artificial sphincter system in a 10-year-old girl. A 7-year-old girl was regarded to be too young for sphincter implantation and is waiting for surgery within the next years. CONCLUSION: Insufficient development of trigone and bladder neck with subsequent urinary incontinence has to be kept in mind when deciding on surgical procedures in children with bilateral single ectopic ureters.

[Ektopic ureter - a not considered cause of persisting enuresis in girls]. / Ektoper Ureter - eine verkannte Ursache des Einnässens bei Mädchen.

BACKGROUND: Ectopic ureter - especially in a duplicated collecting renal system - is a specific cause of incontinence in young girls. Although the symptom of continuous dribbling of urine is characteristic for this malformation, diagnosis is often delayed, as the possibility of ectopic ureters is not considered in treating girls with delayed toilet training. CASE REPORT: We present the case of a young girl with a variety of unnecessary invasive diagnostic and therapeutic procedures due to a misunderstood "enuresis", before incontinence was cured by upper pole heminephrectomy. CONCLUSIONS: Girls, who never have been dry and who loose urine all the time do have an ectopic ureter, unless evidence to the contrary has been put forward. Only considering the possibility of ectopic ureters will avoid unnecessary diagnostic and therapeutic procedures in these girls.

Prognostic impacts of cytogenetic findings in clear cell renal cell carcinoma: gain of 5q31-qter predicts a distinct clinical phenotype with favorable prognosis.

To evaluate the prognostic significance of cytogenetic findings in clear cell renal cell carcinoma (RCC), cytogenetic results of 118 primary RCCs were evaluated in relation to classical indicators of prognosis and overall survival. Losses in 3p (98.3%) were most prevalent and included 32 (27.6%) monosomies of chromosome 3 and 84 (72.4%) structural aberrations involving 3p, of which 36 were unbalanced translocations, der(3)t(3;5)(p11-p22;q13-q31), resulting in duplication of 5q sequences. Patients with gain of 5q31-qter resulting from either polysomies or structural rearrangements of 5q, the most frequent of which was der(3)t(3;5), had a significantly better outcome than those without this aberration (P = 0.001). There was no association between gain of 5q or der(3)t(3;5) and any of the well-known variables for prognosis, including low versus high clinical stage and grade of malignancy. Among additional chromosomal aberrations, loss of chromosome 9/9p was associated with distant metastasis at diagnosis (P = 0.006). The data indicate that gain of 5q identifies a clinically favorable cytogenetic variant of clear cell RCC and demonstrate the impact of specific chromosome aberrations as additional prognostic indicators in clear cell RCC.