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We enrolled 45 patients with metastatic renal cell carcinoma (RCC) at a progressive disease between March 2003 and April 2008 to assess the impact of an anti-inflammatory treatment regime in combination with metronomic low-dose chemotherapy. 42% of the patients had been systemically pre-treated. Therapy consisted of etoricoxib 60 mg daily plus pioglitazone 60 mg daily, day 1+, low-dose interferon-α 4.5 MU sc three times a week, week 1+ and low-dose capecitabine 1 g/m(2) twice daily orally for 14 days, every 3 weeks, day 1+, until disease progression. Objective response was observed in 35% of the patients (PR 27, CR 9%), which was paralleled by strong CRP decline for all patients with initially elevated CRP levels (n = 32). CRP values decreased from mean 42.3 mg/L (range 9.1-236), to 11.1 mg/L, (range 1.1-35.6), P = 0.006. Median overall survival and progression-free survival for the total cohort were 26.9 and 7.2 months for patients with elevated CRP 24.4 and 11.3 months (95% CI, 22.8-31.0/5.7-16.9) and 13.8-2.6 months (95% CI, 6.5-21.1/0.4-4.8) for the non-elevated CRP group, respectively (P = 0.082/0.017). Median observation time: 26.1 months; Overall survival at 5 years: 18%. Toxicity>WHO grade 3 was reported: Hand-foot syndrome in 16 patients (36%), diarrhea in 4, and pneumonia in 2 patients. Our data allow us to conclude that the control of tumor-associated inflammation is an important therapeutic principle in patients with metastatic RCC.

The present multi-center phase II study was designed to support the hypothesis that networking agents which bind to ubiquitous accessible targets in metastatic castration-resistent prostate cancer (CRPC) may counteract neoplasia-specific aberrant cellular functions, thereby mediating PSA response. Patients with metastatic CRPC received low-dose chemotherapy with capecitabine 1 g twice daily plus dexamethasone 1 mg daily for 14 days every 3 weeks, COX-2 blockade with rofecoxib 25 mg (or etoricoxib 60 mg) daily combined with pioglitazone 60 mg daily, starting with day 1 + until disease progression. Thirty six patients with metastatic CRPC were enrolled; n = 18 (50%) had been extensively pretreated with radio- or radionuclide therapy, n = 16 (44%) with chemotherapies; and n = 8 patients (22%) were medically non-fit, having an ECOG-score of 0–2. Nine out of fifteen patients with PSA response >50% showed objective response. Median time to PSA response was 2.4 months (range 1.0–7.3 months). Two out of nine patients responding with PSA

Therapeutic options for patients with castration-resistant prostate cancer (CRPC) remain limited. In a multicenter, Phase II study, 65 patients with histologically confirmed CRPC received a biomodulatory regimen during the six-month core study. Treatment comprised daily doses of imatinib mesylate, pioglitazone, etoricoxib, treosulfan and dexamethasone. The primary endpoint was prostate-specific antigen (PSA) response. Responders could enter an extension phase until disease progression or intolerable toxicity occurred. Mean PSA was 45.3 ng/mL at baseline, and 77 % of patients had a PSA doubling time

Objectives. A prospective investigation was carried out to evaluate the use of 5-aminolevulinic acid (5-ALA)-induced fluorescence diagnosis with secondary transurethral resection (TUR). Methods. Fifty patients underwent secondary TUR of the former resection area 6 weeks after conventional TUR for superficial bladder carcinoma. 5-ALA-induced fluorescence diagnosis was used in addition to standard white light endoscopy. All former resection areas were biopsied regardless of fluorescence findings. In addition, specific red fluorescent areas were resected, as were suspicious areas seen at white light endoscopy. Results. One hundred thirty areas or tumors were resected. The sensitivity of fluorescence cystoscopy was 77.8% (95% confidence interval 52.4% to 93.6%). Residual tumors were found in the area of the former resection in 7 (14%) of 50 patients; 4 of these 7 were fluorescence negative and 3 were fluorescence positive. In an additional 7 patients (14%), exclusively fluorescing tumors not visible under white light could be detected outside the areas of former resection (n = 5, Stage pTaG1/2; n = 1, Stage pT1G1/2; n = 1, carcinoma in situ). Conclusions. Despite high sensitivity, fluorescence diagnosis at this early stage of control does not allow us to evaluate sufficiently the granulation tissue of necrotic areas after TUR without biopsy. The main advantage of the 5-ALA-induced fluorescence endoscopy is in the evaluation of untreated urothelium because of the easier detection of tumors not visible by conventional endoscopy.

With a median survival period of approximately 19 months, therapeutic options for patients with castration-resistant prostate cancer (CRPC) remain limited. In a multicenter phase II trial, 65 patients with histologically confirmed CRPC continuously received a biomodulatory regimen during the 6-month core period for redirecting tumor-promoting normative notions, i.e. angiogenesis, inflammation, immune response and the osteoplastic process. Treatment comprised daily doses of imatinib mesylate, pioglitazone, etoricoxib, treosulfan, and dexamethasone. The primary endpoint was prostate-specific antigen (PSA) response, defined as a confirmed reduction in serum PSA of ≥ 50 % in patients with a baseline value of ≥ 5 ng/mL. Responders could enter an extension phase until disease progression or presence of intolerable toxicity. Mean PSA was 45.3 ng/mL at baseline, and 77 % of the patients had a PSA doubling time of < 3 months. Twenty three (37.7 %) out of the 61 evaluable patients were PSA responders, who showed a mean PSA decrease from 278.9 ± 784.1 ng/mL at baseline to 8.8 ± 11.6 ng/mL at the final visit (24 weeks or LOCF). The remaining 38 non-responders included 14 patients (23.0 %) with stable disease. In one center, 6 out of 16 patients showed nearly complete resolution of bone metastases. Out of the 947 adverse events observed, 57.6 % were suspected to be drug-related, 13.8 % led to dose adjustment or permanent discontinuation of the study medication, and 40.2 % required concomitant medication. Twenty seven patients experienced serious adverse events. This novel multi-targeted approach led to an impressive PSA response rate of 37.7 % in CRPC patients despite the fact that individual components had shown limited efficacy when applied on their own. The good PSA response rate and the manageable toxicity profile suggest that this combination may offer an alternative treatment option to present therapeutic regimens.

Lower urinary tract symptoms (LUTS) are a common and multiform micturition disorder of various possible origins. Several second-line techniques are available in the event of first-line medicinal treatment failure. These include the intravesical injection of Botulinum toxin, bladder augmentation and sacral neuromodulation (SNM). This study presents current data and results from a prospective study of patients with LUTS of various aetiologies.Clinical success was investigated for all patients who underwent SNM for LUTS with or without urge incontinence caused by chronic pelvic pain syndrome, multiple sclerosis and idiopathic disease between May 2007 and December 2010. The preoperatively determined symptoms were compared with current follow-up data. Median follow-up time was 11 months (1 - 43).A total of 47 patients were indicated for SNM over the investigated period. 80.9 % were female, median patient age was 67 years (19 - 84). The testing phase was successful in 38 cases (80.9 %) with 9 electrodes being explanted (19.1 %). In the case of idiopathic LUTS we could show a statistically significant increase of micturition volume and reduction of incontinence pad use. There was no statistically significant improvement of any micturition parameter for patients with multiple sclerosis, patients with chronic pelvic pain syndrome showed a statistically significant reduction of micturition frequency and a subjective improvement of symptoms in 75 %.In the selected patient groups SNM is a promising and, in experienced hands, a low-complication second-line therapy for the treatment of LUTS of idiopathic aetiology. However, the general recommendation of SNM for multiple sclerosis and chronic pelvic pain syndrome patients cannot be given on the basis of our results. Further prospective, randomised multicentre studies are need to further refine the indications for SNM in LUTS of neurogenic and non-neurogenic origins.

Introduction: The aim of our study was to evaluate the significance of transurethral resection of the prostate (TURP) to detect prostate cancer (PCa). A comparison was performed of the TURP specimens of patients undergoing high-intensity focused ultrasound (HIFU) with the core biopsies. Materials and Methods: TURP before undergoing HIFU therapy was performed in 106 patients without neoadjuvant treatment. The resected tissue was subjected to histopathological evaluation and compared to the histological results of transrectal prostate biopsy. Results: Cancer was detected in the resected tissue of 69 patients (65%). A positive correlation of the amount of resected tissue and detection of PCa could be demonstrated in a multivariate analysis. Conclusions: With a rate of 65% PCa detected by TURP, our data provide evidence that TURP might be suitable to detect PCa in a small group of selected patients with continuously rising PSA levels and several negative biopsies. On the other hand, these data underline/reinforce the necessity to treat the whole gland using modern treatment modalities such as HIFU and cryotherapy., OA-Komponente aus Allianzlizenz

Pre-cystectomy nomograms with a high predictive ability for locally advanced urothelial carcinomas of the bladder would enhance individual treatment tailoring and patient counselling. To date, there are two currently not externally validated nomograms for prediction of the tumour stages pT3-4 or lymph node involvement.Data from a German multicentre cystectomy series comprising 2,477 patients with urothelial carcinoma of the bladder were applied for the validation of two US nomograms, which were originally based on the data of 726 patients (nomogram 1: prediction of pT3-4 tumours, nomogram 2: prediction of lymph node involvement). Multivariate regression models assessed the value of clinical parameters integrated in both nomograms, i.e. age, gender, cT stage, TURB grade and associated Tis. Discriminative abilities of both nomograms were assessed by ROC analyses; calibration facilitated a comparison of the predicted probability and the actual incidence of locally advanced tumour stages.Of the patients, 44.5 and 25.8% demonstrated tumour stages pT3-4 and pN+, respectively. If only one case of a previously not known locally advanced carcinoma (pT3-4 and/or pN+) is considered as a staging error, the rate of understaging was 48.9% (n=1211). The predictive accuracies of the validated nomograms were 67.5 and 54.5%, respectively. The mean probabilities of pT3-4 tumours and lymph node involvement predicted by application of these nomograms were 36.7% (actual frequency 44.5%) and 20.2% (actual frequency 25.8%), respectively. Both nomograms underestimated the real incidence of locally advanced tumours.The present study demonstrates that prediction of locally advanced urothelial carcinomas of the bladder by both validated nomograms is not conferrable to patients of the present German cystectomy series. Hence, there is still a need for statistical models with enhanced predictive accuracy.

The therapeutic gold standard of muscle-invasive tumour stages is radical cystectomy (RC), but there are still conflicting reports about associated morbidity and mortality and the oncologic benefit of RC in elderly patients. The aim of the present study was the comparison of overall (OS) and cancer-specific survival (CSS) in patients75 and75 years of age (median follow-up was 42 months).Clinical and histopathological data of 2,483 patients with urothelial carcinoma and consecutive RC were collated. The study group was dichotomized by the age of 75 years at RC. Statistical analyses comprising an assessment of postoperative mortality within 90 days, OS and CSS were assessed. Multivariate logistic regression and survival analyses were performed.The 402 patients (16.2%) with an age of ≥75 years at RC showed a significantly higher local tumour stage (pT3/4 and/or pN+) (58 vs 51%; p=0.01), higher tumour grade (73 vs 65%; p=0.003) and higher rates of upstaging in the RC specimen (55 vs 48%; p=0.032). Elderly patients received significantly less often adjuvant chemotherapy (8 vs 15%; p0.001). The 90-day mortality was significantly higher in patients ≥75 years (6.2 vs 3.7%; p=0.026). When adjusted for different variables (gender, tumour stage, adjuvant chemotherapy, time period of RC), only in male patients and locally advanced tumour stages was an association with 90-day mortality noticed. The multivariate analysis showed that patients ≥75 years of age have a significantly worse OS (HR=1.42; p0.001) and CSS (HR=1.27; p=0.018).An age of ≥75 years at RC is associated with a worse outcome. Prospective analyses including an assessment of the role of comorbidity and possibly age-dependent tumour biology are warranted.

Few and partially contradictory data are available regarding the prognostic signature of downstaging of muscle-invasive clinical tumour stages in patients treated with radical cystectomy.Clinicopathological parameters of 1,643 patients (study group, SG) treated with radical cystectomy due to muscle-invasive urothelial bladder cancer were summarized in a multi-institutional database. Patients of the SG fulfilled the following conditions: clinical tumour stage T2 N0 M0 and no administration of neoadjuvant radiation or chemotherapy. Cancer-specific survival (CSS) rates were calculated referring to pathological tumour stages in cystectomy specimens (pT2, pT2,pT2) (mean follow-up: 51 months). Furthermore, a multivariable model integrating clinical information was developed in order to predict the probability of downstaging.A total of 173 patients (10.5%) of the SG presented with downstaging in pathological tumour stages (pT0: 4.8%, pTa: 0.4%, pTis: 1.3%, pT1: 4.1%); 12 of these patients had positive lymph nodes (7%, in comparison with 21% pN+ of pT2 tumours and 43% ofpT2 tumours). Patients with tumour stagespT2, pT2 andpT2 had CSS rates after 5 years of 89, 69 and 46%, respectively (p0.001). In a multivariable Cox model the presence of pathological downstaging resulted in a significant reduction of cancer-specific mortality (HR 0.30; 95% CI 0.18-0.50). By logistic regression analysis the date of TURB (benefit for more recent operations) was identified as the only independent predictor for downstaging of muscle-invasive clinical tumour stages. Age, gender, grading and associated Tis in the TURB did not reveal any significant influence.Patients with muscle-invasive clinical tumour stages and downstaging in cystectomy specimens represent a subgroup with significantly enhanced CSS rates. Further trials that integrate the parameters tumour size, stages cT2a vs cT2b and focality are required in order to define the independent prognostic signature of downstaging of tumour stages more precisely.

Urinary tract infections can result from bladder outlet obstruction and consecutive post-void residual urine. In a recent publication, a cutoff for post-void residual urine of 180 ml was calculated, revealing sensitivity and specificity of 87 and 98.5%, respectively, regarding occurrence of significant bacteriuria in asymptomatic men. In the present study the association between post-void residual urine volume and urinary tract infection was evaluated, and different cutoff values were validated.A total of 225 asymptomatic patients (median age 66 years) were prospectively evaluated regarding the following criteria: prostate-specific antigen, prostate volume, International Prostate Symptom Score, peak urinary flow rate, urine culture results, urinary test strip, and post-void residual urine volume. By ROC analysis a cutoff predicting significant bacteriuria was calculated, and different cutoff values were validated. The independent influence of several parameters on the incidence of urinary tract infection was measured using multivariate regression analyses.Of the patients, 60% were able to completely empty the bladder (post-void residual urine volume/=10 ml); 31% (n=69) had significant bacteriuria in the urine culture. Escherichia coli was identified in 59 of 69 patients (86%) with positive urine culture. Patients presenting with urinary tract infection had significantly higher mean post-void residual urine volumes than patients with negative urine culture (113 vs 41 ml, p0.001). In 29 men (13%) residual volume was 180 ml or greater. Regarding the coincidence of urinary tract infection, this cutoff value showed sensitivity and specificity of 28 and 94%, respectively (AUC: 0.606, p=0.012). By ROC analysis a cutoff value of 150 ml revealed the highest AUC value (0.617). Post-void residual volume had an independent significant influence on detection of urinary tract infection in multivariate regression analysis (urine culture: p=0.006; urinary test strip: p0.001).No cutoff value could be determined to predict positive urine culture with sufficient sensitivity and specificity. Based on the results of the present study and currently available data from the literature we are not able to recommend a cutoff value leading to therapeutic consequences. Hence, to establish the indication for treatment further criteria should be taken into consideration.

Transurethral resection of the bladder (TURB) is one of the most common surgical treatments in urology. We examined the TURBs that had been carried out during one year for suspected bladder cancer (first findings and recurrence) and then analysed the further clinical courses of these patients within the first twelve months after TURB.We recorded retrospectively the course of 160 patients in whom altogether 210 elective TURBs had been performed in our clinic between April 2007 and March 2008 (observation period). In addition, the patients' further clinical course within the first twelve months after TURB was recorded (follow-up period). All initial and recurrence TURB were carried out with photodynamic diagnosis; the histological evaluation was performed at a university centre.71 % of the 118 initial resections performed during the observation period showed urothelial cell carcinoma of the bladder - pTa (61 %), pT1 (20 %), pT2-4 (17 %), Cis (2 %) while 60 re-TURBs in the whole period detected 17 % residual tumours. According to the guidelines, 18 patients (14 %) received instillation therapy with mitomycin C, 32 patients (25 %) with Bacillus Calmette-Guérin (BCG). Cystectomies were performed on 23 patients (18 %). 18 TURBs after suspected recurrence in the follow-up period confirmed recurrence in 28 %, which represents a recurrence rate of 4 %. In the same period 5 patients (4 %) developed distant metastases, two patients (2 %) died. Two patients (7 %) with initially benign findings developed bladder cancer in the follow-up period.We present an analysis of TURBs performed at a university centre. When bladder cancer is diagnosed in 7 % within one year after urocystitis has been detected in the initial TURB findings, regular follow-up examination of these patients, especially with certain risk profiles, has to be discussed.

The interaction among signaling networks of tumor and neighboring stroma cells in complex disease traits is poorly understood, and read-out parameters reflecting tumor-associated functional stages are scarce. A multi-centre phase II trial was designed to prove the hypothesis whether activation of presumably complementary receptor-triggered transcriptional cascades (via pioglitazone and interferon-a) could result in synergistic clinical effects. Therapy consisted of low-dose capecitabine 1 g/m2twice daily po for 14 days, every 3 weeks, day 1+, and etoricoxib 60 mg daily plus pioglitazone 60 mg daily, day 1+, and low-dose interferon-a 4.5 MU sc three times a week, week 1+, until disease progression. Fourty-five patients with renal clear cell carcinoma at a progressive disease stage and ECOG 0–2 were enrolled between March 2003 and April 2008. Forty-two percent of the patients had been systemically pretreated. Objective response was observed in 35% of the patients (PR 27%, CR 9%), which was paralleled by strong CRP decline after 4–6 weeks’ treatment. CRP values decreased from mean 42.3 mg/L, range 9.1–236, to 11.1 mg/L, range 1.1–35.6, P = 0.006. Stable disease >3 months occurred in 40%. Median overall survival and progression-free survival for the total cohort were 26.9 and 7.2 months, for CRP non-responder 13.8 and 2.6 months (95% CI, 6.5–21.1 / 0.4–4.8), and 24.4 and 11.3 months (95% CI, 22.8–31.0 / 5.7–16.9) for CRP responder, P = 0.082 / 0.017 (median observation time 26.1 months). Overall survival at 5 years was 18%. Toxicity >WHO grade 3 was reported: Hand-foot syndrome in 16 patients (36%), diarrhea in 4 patients (9%), depression in 1 patient, and pneumonia in 2 patients. (1) Clinical results of combined anti-inflammatory and angiostatic therapy were comparable with available standard therapies, although 50% of the patients had been systemically pretreated. (2) Control of tumor-associated inflammation is an important therapeutic principle in metastatic renal clear cell carcinoma.

Renal cell carcinoma is the third most frequent urogenital malignancy. The increased incidence in the past few years can be attributed in particular to increased incidental findings since the introduction of routine ultrasound and radiological imaging. In the current contribution we analyse in a long-term approach the actual impact of these advances on indications for surgical management.From January 1992 until December 2007, 1,113 renal cell carcinoma patients underwent a total of 1,129 surgical interventions in our department. Retrospectively, we collected the clinical and histopathological data of these patients, comparing them in terms of the entire study period and the four 4-year time spans 1992-1995, 1996-1999, 2000-2003 and 2004-2007.59 % of the patients were male, the median age being 64 years [range: 26-91 years]. In the study period, the number of patientsor= 45 years and75 years increased statistically significantly (p = 0.012). The number of incidental findings -remained constant at approximately 72 %, while that of patients who had received preoperative cross-sectional imaging diagnostics rose statistically significantly from 88 % to 98 % (p0.001). Tumours of stage pT1a increased statististically significantly to 42 %, the number of partial renal resections in the same period to 25 % (p0.001). There was no difference in residual tumour rate between nephron-sparing surgery and tumour nephrectomy.We were able to confirm that the major developments in the diagnostic and surgical approaches to renal cell carcinoma over the past few years do translate into clinical benefits for patients who are increasingly being subjected to partial renal resection.

The TNM classification integrates the currently valid prognostic factors for tumour-specific survival after radical cystectomy due to bladder cancer. But it does not contain the most important criteria for general survival. We assessed the preoperative and operative aspects of our patients between 1992 and 2007 concerning the early mortality within the hospital stay or within 30 days after surgery. 3% of our 404 patients died within these periods, which is equivalent to the results of other contemporary publications. Except for the comorbidity of the patients, none of the included parameters (initial symptoms, histology, indication for cystectomy, AJCC stadium, year of surgery, durance of surgery, surgeon, concomitant interventions, type of urinary diversion, blood loss and number of transfusions) showed a significant correlation to cause or postoperative time of death. For the preoperative assessment of the health of the patient a multidisciplinary cooperation of urology, anaesthesia and general and/or internal medicine is necessary. In the era of evidence-based medicine the personal judgement of the evaluating physician is not sufficient. Instead a validated index should be used to help one to obtain an objective evaluation of the risks. The ACE-27 (Adult Comorbidity Evaluation-27) provides such a validated assistance in the assessment of the comorbidity of patients and therefore possible mortality after radical cystectomy.

T1G3 bladder cancers show the clinical and biological behaviour of muscle invasive tumours with progression rates of about 30%. While radical cystectomy in some cases is indicated, other patients can achieve healing with organ preservation. We present a study analysing the influence of the risk factors multifocality, tumour diameteror= 3 cm and associated carcinoma in situ (Cis) on the outcome of initial T1G3 bladder cancers treated in various ways.Of 223 patients with initial T1G3 bladder cancer, 125 patients underwent transurethral resection of the tumour (TURB), second resection and adjuvant bacille Calmette-Guérin (BCG) instillations (TURB group), 98 patients chose initial radical cystectomy (CX group).Median follow-up times were 56 months (TURB group) and 51 months (CX group). 5- and 10-year survival rates (82% and 65% in TURB group vs. 75% and 48% in CX group) did not show statistically significant differences. In Cox regression analysis no single risk factor showed a prognostic value. While in TURB group the combination of all risk factors (multifocality, tumour diameteror= 3 cm and associated carcinoma in situ) was associated with a statistically significantly lower survival rate, the same combination in the CX group was not oncologically relevant.While initial T1G3 bladder cancer with up to two risk factors after organ-preserving therapy is not associated with a lower tumour specific survival rate in comparison to radical cystectomy, patients with a combination of the three analysed risk factors would profit by an early radical cystectomy.

A prospective monocentre randomized parallel-group Phase III trial was performed to investigate whether primary transurethral resection (TUR) with 5-aminolevulinic acid induced Fluorescence diagnosis (FD) allows for a more thorough TUR of superficial Bladder Carcinoma compared to conventional white light (WL). Evaluation of residual tumor rate and recurrence free survival were defined as the two primary study endpoints. The residual tumor rate was 25.2% in the WL arm (n=103) vs. 4.5% in the (n=88) FD arm (p0.0001). Median follow up of the patients in the WL arm was 42 months (range 25-61) compared to 43 (range 24-61) in the FD arm. Recurrence free survival in the fluorescence diagnosis group was 90.9%, 90.9% und 85 % after 12, 24 and 48 months compared with 78.6%, 69.9% und 60.7 %, respectively, in the white light group (p=0.0005). This superiority proved to be independent of risk group. The adjusted hazard ratio of fluorescence diagnosis versus white light transurethral resection was 0.29 (95% CI: [0.15; 0.56]). ALA induced FD is statistically significantly superior to conventional WL TUR with respect to both residual tumor rate and recurrence-free survival. The differences in RFS imply that FD offers a clinically relevant procedure to reduce the number of tumor recurrences.

Objectives To evaluate in a prospective study the influence of fluorescence diagnosis (FD) controlled transurethral resection of bladder tumors on therapeutic consequences. The aim was to determine in how many patients FD led to a change in treatment strategy compared with conventional white light (WL) cystoscopy. Methods A total of 279 patients with suspected bladder tumors underwent transurethral resection using FD in addition to WL cystoscopy. The number of additional tumor-positive patients, staging change, number of multilocular tumors exclusively detected by FD, and resulting therapeutic consequences compared with the results after WL cystoscopy were investigated. In addition a biopsy-based evaluation was performed. Results Tumor or dysplasia II° (moderate dysplasia) was detected in 177 patients. In 168 patients, tumor was detected by WL cystoscopy, and in 9 (5.1%) of the patients, tumor was completely overlooked by WL cystoscopy and diagnosed exclusively by FD (n = 3 TaG1-G2, n = 2 carcinoma in situ, n = 1 greater than T1, and n = 3 dysplasia II°). Multilocular tumor involvement was detected in 10 cases using FD, and a change in the stage by detection of coexisting dysplasia II° and carcinoma in situ occurred in 8 patients. In 27 patients (15.3%), additional information was obtained by exclusive detection of tumors by FD. This resulted in a change in the treatment strategy for 16 patients (9%). Conclusions FD leads to an improvement in the diagnosis of bladder carcinoma. It allows the early selection of the best treatment option and thus has a potentially positive effect on the prognosis of the affected patients.

Transrectal high intensity focused ultrasound (HIFU) as a minimal invasive treatment approach of localized prostate cancer was evaluated concerning its efficacy and security. Post-operative monitoring included PSA-levels and histological results of control random biopsies. Seventy-three HIFU sessions were performed on 62 patients during the period from November 1997 to April 2000. Patients were classified in 4 indication groups: 1) localized prostate cancer, T1-T2, initial PSA15 ng/ml, Gleason score7, volume30 cc, no more than 4 of 6 random biopsies affected by cancer, not suitable for radical prostatectomy; 2) localized prostate cancer, T1-T3, no PSA or Gleason score limitation; 3) local recurrence after first line therapy (RPE, radiation, hormonal ablation); 4) for local debulking. Mean plus or minus standard deviation for patient age was 67.5 +/- 7.48 years, for PSA was 7.64 +/- 5.26 ng/ml and for prostate volume was 21.3 +/- 7.9 cc. Median follow up was 15 months (range 5-29) and included PSA development, control sextant biopsies and transrectal color coded duplex sonography (TCCDS) at 1, 3, 6, 12 and 24 months. At least 1 control biopsy result was available in 48 patients. We evaluated the therapy in 3 categories: 1) group 1 (complete response) included 33/48 patients (68.7%) with no residual cancer and PSA4 ng/ml; 2) group 2 (biochemical control) 8/48 patients (16.7%) with small residual cancer and PSA4 ng/ml; 3) group 3 (failure) 7/48 patients (14.6%) with residual cancer and PSA4 ng/ml (4 of them received hormone therapy). As major complications 2 urethrorectal fistulas occurred, both in post-radiation patients, 3 stress-incontinences II-III after TUR post HIFU. In 20 patients (32.3%) transurethral manoeuvres were necessary to remove obstructive necrotic tissue or because of bladderneck or urethral strictures. 11 of these patients were among the first 20 treated patients. Regarding the individual learning curve about technique, indication and the technical developments HIFU treatment can currently be considered as a valid alternative treatment strategy for patients with localized prostate cancer, who are not suitable for radical surgery. HIFU treatment can be repeated depending on biopsy result and PSA development. Local control of the localized prostate cancer was observed in group 1 and 2 (85%).

The diagnosis of benign ureteral polyps should be considered especially in patients younger than 40 years with filling defects of the proximal ureter on the intravenous pyelogram (IVP). The excellent results of conservative organ-saving surgery (open resection, ureteroscopic resection, laser coagulation) require precise diagnostic management preoperatively in these patients.

Bei Harnrohrenstrikturen jeglicher Lokalisation und Auspragung ist die Hamrohrenschlitzung mit dem kalten Messer, z. B. die Sichturethrotomie nach Sachse wegen der technischen und apparativen Einfachheit, der geringen Belastung fur den Patienten, der niedrigen Komplikationsrate und der geringen Morbiditat des Eingriffs, meist der erste Schritt der Behandlung und die Therapie der Wahl.

15636 Background: The present multi-centre phase II study was designed to support the hypothesis that networking agents binding to ubiquitous accessible targets in metastatic hormone-refractory prostate cancer (HRPC) may counteract neoplasia-specific aberrant cellular functions, thereby mediating objective response (primary endpoint). Method: Patients with metastatic HRPC, received both an anti- inflammatory and angiostatic therapy consisting of low-dose chemotherapy with capecitabine 1 g twice daily for 14 days every 3 weeks, day 15+, COX-2 blockade with etoricoxib 60 mg daily, day 1+, combined with two transcription modulators, pioglitazone 60 mg daily, day 1+, plus dexamethason 1 mg daily for 14 days, every 3 weeks, day 15+, until disease progression. The study was planned using the Simon optimal design. Results: Thirty-six consecutive patients (N= 22 (61%) chemo-naive, n= 14 (39%) with preceding chemotherapies, mean 2.1 regimen) with metastatic HRPC, confirmed PSA increase, assessable response, and ECOG 0–2 were enrolled between 1/03 to 5/06. Objective response occurred in 10 of 13 cases (N/n: 41%/7%) with PSA (and C-reactive protein) response >50% (N/n: 45%/21%). Median time to PSA response was 2.4 months (range 1.0 to 7.3 months). Two of three patients responding with PSA WHO grade II were reported: Hand-foot syndrome (n=1), anemia (n=6), edema (n=1), cushing syndrome (n=1), hydronephrosis (n=1). Conclusions: This is the first study reporting continuous complete remissions in HRPC with a biomodulatory therapy approach. Further, the study may clinically support the upper mentioned hypothesis. No significant financial relationships to disclose.

14500 Background: Interaction among signalling networks from tumor and neighbouring stroma cells in complex disease traits is poorly understood. Methods: Two consecutive multi-centre phase II trials were designed (case calculation according response rate, T. Chen two stage design) to prove the hypothesis, whether the activation of presumably complementary receptor-triggered transcriptional cascades (via pioglitazone, and interferon alpha, IFNa) could result in synergistic clinical effects. Therapy in both trials consisted of low-dose capecitabine 1 g/m2 twice daily po for 14 days, every 3 weeks, day 1+, and rofecoxib 25 mg daily, day 1+ (from 11/04 etoricoxib 60 mg daily instead) plus pioglitazone 60 mg daily, day 1+. In study II low-dose IFNa 4.5 MU sc three times a week, week 1+, was added until disease progression. Results: Eighteen, and 33 patients (pts, 31 eligible for analysis), respectively, with clear cell carcinoma, progressive disease, and ECOG 0–2 were enrolled between 2/02 to 2/03 and 4/03 to 4/05, respectively. Mean Bradley score in both trials was not significantly different, 4.1(I)/4.9(II), however, the rate of previous systemic treatments 33%/19%. Objective response (48%) was exclusively observed in study II (PR 35%, CR 13%), and paralleled by a strong CRP response (after 4 weeks on treatment) in all 29 pts with elevated CRP levels (93%) (study I: no significant CRP response): CRP values decreased from mean 41.3 mg/l, range 8.1 to 221, to 5.1 mg/l, range 2.1 to 15.6, p = 0.005. Stable disease > 2 months (mos) occurred in 50%/48%. Median progression-free survival could be more than doubled from a median of 4.7 mos (95% CI, 1.0 to 10.4) to 11.5 mos (6.8 to 16.2) in study II, p = 0.0000. Median overall survival of population II has not been reached, yet. Toxicities > WHO grade II were reported (study I/II): Hand-foot syndrome (3/3), diarrhoea (2/2), depression (0/1), pneumonia (0/1). Conclusions: (1) Clinical results of anti-inflammatory/angiostatic therapy compare with available immuno-therapies. (2) Improved outcome with additive IFNa argues for a synergistic drug interaction. (3) Control of tumor-associated inflammation is an important therapeutic principle in metastatic clear cell carcinoma. No significant financial relationships to disclose.

Die Rezidivrate bis zu 80%, die Tendenz zur Tumorprogression in bezug auf Stadium als auch Malignitatsgrad beim Tumorrezidiv, sowie das Vorhandensein von cystoskopisch nicht sichtbaren Tumorvorstufen lassen eine Tumornachbehandlung nach transurethraler Elektroresektion als unbedingt erforderlich erscheinen. Thio-Tepa seit uber 20 Jahren als lokale Chemotherapie nach TUER in Verwendung, wird jetzt durch mindestens ebenso effektive Medikamente wie Adriamycin, Mitomycin oder VM-26 ersetzt, die eine geringere lokale und fehlende systemische Toxizitat aufweisen.