[Interdisciplinary recommendations for the treatment of metastatic renal cell carcinoma]. / Interdisziplinäre Empfehlungen zur Behandlung des metastasierten Nierenzellkarzinoms.

With the introduction of targeted therapies, a paradigm shift for the treatment of metastatic renal cell cancer has taken place. New compounds like sunitinib, sorafenib, bevacizumab and temsirolimus have become established as new therapeutic standards. An interdisciplinary consensus conference was held to discuss treatment sequences and open questions. Results from the 2007 conference provided the basis for the 2008 meeting. The results of the 2008 conference are presented as short theses.

[Solitary peritoneal carcinomatosis in prostate cancer]. / Solitäre Peritonealkarzinose eines Prostatakarzinoms.

INTRODUCTION: Peritoneal carcinomatosis is a rare finding in metastatic prostate cancer. In the literature peritoneal carcinomatosis is usually reported in its final stages with multiple metastases. A single peritoneal carcinomatosis with no further metastases is a very rare finding. CASE REPORT: We report the case of a 75-year-old patient with initial ischuria. A prostate cancer could be confirmed and the further diagnostics showed no metastasis. In a transperitoneal approach for laparoscopic pelvic lymphadenectomy a peritoneal carcinomatosis from prostate cancer was proven. A complete antiandrogen therapy was started and PSA decreased for more than 14 months to a stable level of < 1 microg/L. CONCLUSION: An isolated peritoneal carcinomatosis from prostate cancer is a very rare finding. The complete antiandrogen therapy is effective.

[Neoadjuvant and adjuvant chemotherapy in patients with advanced penile cancer]. / Neoadjuvante und adjuvante Chemotherapie bei Patienten mit fortgeschrittenem Peniskarzinom.

With an incidence of 0.1-0.9/100,000 men per year penile cancer is a rare cancer of the urogenital tract in Western Europe. At the time of initial diagnosis up to 45% of the patients already demonstrate metastatic disease and need some type of systemic treatment. It is the aim of this paper to review the current concepts of adjuvant and neoadjuvant chemotherapy for locally advanced penile cancer. A curative effect of combined surgical and cytotoxic management can only be achieved in patients with locoregional spread to the lymph nodes, but not with systemic spread. Although there are prospective randomized trials available indicating the optimal cytotoxic regime, cisplatin-based protocols or combination therapies with bleomycin, vincristine, and methotrexate appear to be the most effective options. Finally, there are no data available with regard to the effect of adjuvant chemotherapy on progression-free survival. In patients with locoregional bulky disease or with fixed inguinal lymph nodes, neoadjuvant chemotherapy will result in a partial response in 20-60% of patients and enables complete resection of the mass. For the future, the use of taxane-based chemotherapy as described for squamous cell cancer of other origin might improve outcome.

[Interdisciplinary recommendations on targeted therapy in the treatment of renal cell carcinoma]. / Interdisziplinäre Therapieempfehlungen zur Behandlung des metastasierten Nierenzellkarzinoms.

Recently, new data have been published on the treatment of metastasized renal cell cancer using targeted therapies. With the approval of the tyrosine kinase inhibitors Sunitinib and Sorafenib, two of these new therapies are now available in clinical practice. This has raised both new opportunities and new questions for the health care professionals involved. Here we report on a consensus conference addressing these questions with answers based on evidence from the recent literature.

[Magnetic stimulation of the pelvic floor in older patients. Results of a prospective analysis]. / Magnetstimulation des Beckenbodens beim älteren Menschen. Ergebnisse einer prospektiven Untersuchung.

Since 2001 magnetic stimulation therapy has been available in Germany for treating urinary incontinence as an alternative to traditional electrical stimulation therapy. The results of 83 patients who underwent magnetic stimulation therapy for stress incontinence, OAB, and pelvic pain syndrome were evaluated. The results differed depending on the underlying disease. Patients with stress incontinence who could not properly contract pelvic floor muscles before could do so in 74% when clinically evaluated and patients with OAB symptoms improved in 54% as assessed by objective and subjective criteria, whereas patients with pelvic pain syndrome only benefited in 23%. Comparison of the results according to age revealed no significant difference between patients >65 years and younger patients.

[Magnet stimulation therapy: a simple solution for the treatment of stress and urge incontinence?]. / Magnetstimulationstherapie. Eine einfache Lösung für die Behandlung der Stress- und Dranginkontinenz?

AIM: Magnet stimulation therapy has been offered as a new, conservative therapy for stress and urge incontinence in Germany since 2001. Focussed, pulsating magnetic fields are used to stimulate the musculature of the floor of the pelvis. This publication describes our initial experience with this method. PATIENTS AND METHODS: We treated 27 patients with magnetic stimulation. The individual patient sits clothed on a therapy-chair and is treated for 20 min twice a week for 2 weeks. RESULTS: The best results were recorded in female patients with grades I and II stress incontinence who could not actively flex their pelvic-floor musculature during physiotherapy. A marked reduction in the frequency of micturition was obtained in 67% of patients with urge incontinence symptoms and non-responsiveness to anticholinergic therapy. Patients with a non-organically tangible pelvic-pain-syndrome did not benefit from the therapy. CONCLUSIONS: Magnet stimulation therapy can act as a useful addition to conservative therapies for stress and urge incontinence. It is free of complications and does not involve the insertion of an electrode into the patient as is the case for vaginal and anal electrostimulation. However, this method does not appear to be useful for chronic, non-specific pain in the lower pelvis.

PSCA expression is regulated by phorbol ester and cell adhesion in the bladder carcinoma cell line RT112.

The expression of the surface protein prostate stem cell antigen (PSCA) in prostate carcinoma increases in parallel with the progression of the tumor. In contrast, we have recently shown that PSCA expression is reduced or undetectable in other types of undifferentiated tumors. To elucidate the cellular mechanisms that underlie this complex pattern of expression, we studied regulatory parameters for PSCA expression in the bladder carcinoma cell line RT112 by Northern analysis. PSCA gene expression was stimulated by a culture dish surface that caused aggregation of cells, suggesting that its expression is regulated by mechanisms related to the adhesion of epithelial cells. Phorbol ester markedly stimulated PSCA gene expression in a cycloheximide- and actinomycin-inhibitable manner after a lag phase of 10 h, indicating that transcription of the PSCA gene is regulated by protein kinase C and a newly synthesized protein. In contrast, epidermal growth factor, platelet-derived growth factor (PDGF)-BB, tumor necrosis factor-alpha, interferon-gamma or a slightly lowered pH failed to increase PSCA mRNA levels. Consistent with the variable expression of PSCA in different tumors, our analysis in RT112 cells shows that its expression is controlled by a strongly inducible promoter that is specifically regulated by extracellular signals.

Altered prostate specific antigen reference range after transurethral resection of the prostate.

OBJECTIVES: We investigated how transurethral resection of the prostate (TURP) affected the serum concentration of prostate specific antigen (PSA) and whether the reference range for PSA has to be altered in these patients following TURP. METHODS: 55 patients were retrospectively analysed. All had undergone TURP for bladder outlet obstruction due to benign prostatic hyperplasia which was confirmed by histopathological amination. PSA was determined pre-operatively and postoperatively every 6 months for 48 months. These patients were compared to 12 patients who had undergone radical perineal prostatectomy (RPP) for prostate cancer (CaP). In the latter group, in all patients a TURP had been performed up to 7 years before CaP was diagnosed. RESULTS: The median PSA concentration was 4.9 ng/ml before TURP and was subsequently reduced to 0.6 ng/ml after 48 months. There was a steady decrease of the PSA concentration during the observation period. In contrast in patients who subsequently developed a CaP, the median PSA concentration before TURP was 6.8 ng/ml and was reduced to only 2.2 ng/ml after 48 months. PSA levels started to rise before CaP was diagnosed. CONCLUSION: After a TURP with a benign histopathologic specimer) PSA levels decrease steadily to values below 2 ng/ml. In case these patients demonstrate a rising PSA in the follow-up after partial prostatectomy, a CaP should be ruled out.

5-Fluorouracil versus folinic acid and 5-fluorouracil in advanced, hormone-resistant prostate cancer: a prospective randomized pilot trial.

OBJECTIVES: Results of cytotoxic chemotherapy for hormone-resistant prostate cancer are not impressive. One of the substances which seems to have a therapeutic benefit is 5-fluorouracil (5-FU). The effect of 5-FU can be modulated by addition of folinic acid (FA). We tested in a prospective, randomized phase II trial monotherapy with 5-FU versus the combination of 5-FU and high-dose FA. METHODS: 25 patients received 600 mg/m2 5-FU, and 24 patients 400 mg/m2 FA plus 600 or 400 mg/m2 5-FU. They were treated for two cycles for 5 days in a 21-day interval followed by a weekly single-day application until progression occurred. Pain remission, toxicity, time to progression and survival were evaluated. RESULTS: Both regimens led to a pain remission in nearly 70% of the patients. Mucosal side effects like diarrhea and stomatitis occurred more often in the combination arm, whereas leukopenias were more frequent in the monotherapy are. We observed no statistically significant difference between the two treatment arms regarding time to progression and survival. CONCLUSIONS: Although both regimens led to a pain remission, side effects are too severe to recommend these protocols for standard treatment of hormone-resistant prostate cancer.

Role of lasertripsy in the management of ureteral calculi: experience with alexandrite laser system in 232 patients.

In 232 patients with ureteral stones, lasertripsy was used as primary treatment or as second-line therapy after extracorporeal shockwave lithotripsy (SWL). In all patients, a semirigid 6.5F ureteroscope or a flexible 6F ureteroscope was used. Lithotripsy was performed employing an alexandrite laser with an energy of 50 to 65 mJ. The immediate success rate was 67.5% for stones in the upper ureter, 86.1% for those in the midureter, and 94.5% for those in the distal ureter. In 16.5% of the treatments, it was necessary to insert a double-J stent. A perforation of the ureter happened in two patients (0.9%), but no laser-related complications were seen. Stone fragmentation was not dependent on stone composition or size. Using small semirigid or flexible ureteroscopes, lasertripsy of ureteral stones is a minimally invasive treatment with an insignificant complication rate. In case of midureteral stones, our results revealed a higher immediate stone-free rate than is reported in the literature after treatment by SWL, and we can therefore recommend lasertripsy as primary treatment. For upper ureteral stones, lasertripsy can be recommended as a helpful auxillary procedure. Furthermore, in cases of distal ureteral stones, lasertripsy challenges SWL as the primary treatment.

Biofeedback in the treatment of voiding disorders in childhood.

Voiding disorders are a common problem in pediatric urology. Biofeedback is a non-invasive method in the treatment of voiding disorders in childhood. Biofeedback takes aim at the learning or relearning of influencing involuntary functions. We report about our preliminary results of biofeedback training in the treatment of the enuretic syndrome in children. Out of 26 children with pseudo-detrusor-sphincter-dyssynergy 17 could be completely cured and 5 improved considerably. Out of 21 children with motor urgency 9 could be completely cured and 7 children improved. Biofeedback is a successful method to treat children with the enuretic syndrome.

Measurement of BBN-induced alterations in rat urothelium by electron microscopic X-ray microanalysis.

The aim of this study was to analyse N-butyl-n-butanol-4-nitrosamine (BBN)-induced alterations of the urothelium in rats concerning its content of phosphorus, sulphur, chlorine, potassium and calcium using electron microscopic X-ray microanalysis (REM analysis). The following histopathological findings of the bladder mucosa were discovered after exposure to BBN: normal urothelium (n = 36); focal epithelial proliferations (n = 12) following 6-12 week's exposure; epithelial hyperplasia (n = 8) after urothelial carcinoma (n = 4) following 12 weeks' exposure. The observed phosphorus/sulphur and phosphorus/calcium ratios based on REM analysis did not show any statistical correlation with the morphological changes classified by light microscopy. Our data do not support the hypothesis raised by other investigators that an increase in phosphorus content or phosphorus/sulphur or phosphorus/calcium ratio could indicate early neoplastic transformations of urothelial cells as "tumor markers".

Stage T1, grade 3 transitional cell carcinoma of the bladder: an unfavorable tumor?

Transurethral resection only was performed in 172 patients with initial stage Ta, T1 transitional cell carcinoma of the bladder. Additional treatment during the course of disease was given to 9 patients with carcinoma in situ and to 8 patients with tumor progression. The mean followup was 106 months. The 10-year survival rates were 95 per cent for patients with stage Ta, grade 1 disease, 89 per cent for stage Ta, grade 2, 84 per cent for stage Ta, grade 3, 78 per cent for stage T1, grade 2 and 50 per cent for stage T1, grade 3. The percentage of first tumor recurrence at the same site increased with tumor grade (stage T1, grade 3 was 74 per cent). The recurrence rate in stage T1, grade 3 tumors (4.08) differed significantly from the other groups of superficial tumors. The tumor progression rate for stage T1, grade 3 tumors (32.5 per cent) was significantly higher as well. The characteristics of stage T1, grade 3 tumors with and without progression were different in regard to multiplicity, recurrence rate, mean interval to recurrence and type of tumor invasion. Of the 13 patients who died of progressive neoplastic disease 11 presented initially with stage T1, grade 3 tumors. When these results are considered it is obvious that a patient with a stage T1, grade 3 tumor deserves additional therapy, such as chemotherapy, immunotherapy or phototherapy.

Combined radiation and chemotherapy for locally advanced transitional cell carcinoma of the urinary bladder.

A prospective study was performed on 22 patients with locally advanced transitional cell carcinoma of the urinary bladder to evaluate the toxicity and efficacy of an integrated treatment with cis-diamminedichloroplatinum (1.6 mg/kg body weight every 3 weeks for four cycles) and 60 G cobalt 60 or 18 MEV photons. Local and systemic toxicity caused by this treatment schedule was minor. Late sequelae consisted of contracted bladder in three patients. The rate of tumor-free bladders after a mean follow-up of 14 months was 17 of 22. Distant metastases occurred in three patients. Local recurrence of superficial tumor elsewhere in the bladder was observed in two patients. Six patients died 4 to 10 months after initiation of the integrated therapy, three of these without evidence of disease.