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Radical cystectomy (RC) and pelvic lymph node dissection (LND) are standard treatments for muscle-invasive urothelial carcinoma of the bladder. Lymph node staging is a prerequisite for clinical decision-making regarding adjuvant chemotherapy and follow-up regimens. Recently, the clinical and pathological nodal staging scores (cNSS and pNSS) were developed. Prior to RC, cNSS determines the minimum number of lymph nodes required to be dissected; pNSS quantifies the accuracy of negative nodal staging based on pT stage and dissected LNs. cNSS and pNSS have not been externally validated, and their relevance for prediction of cancer-specific mortality (CSM) has not been assessed. In this retrospective study of 2,483 RC patients from eight German centers, we externally validated cNSS and pNSS and determined their prediction of CSM. All patients underwent RC and LND. Median follow-up was 44 months. cNSS and pNSS sensitivities were evaluated using the original beta-binominal models. Adjusted proportional hazards models were calculated for pN0 patients to assess the predictive value of cNSS and pNSS for CSM. cNSS and pNSS both pass external validation. Adjusted for other clinical parameters, cNSS can predict outcome after RC. pNSS has no independent impact on prediction of CSM. The retrospective design is the major limitation of the study. In the present external validation, we confirm the validity of both cNSS and pNSS. cNSS is an independent predictor of CSM, thus rendering it useful as a tool for planning the extent of LND.

Chronic lymphocytic leukemia (CLL) with 17p deletion or mutations of the TP53 gene has a very poor outcome. Optimal treatment of these patients remains a major clinical challenge, and disagreement on the optimal treatment approach exists. Conventional chemo-immunotherapy with rituximab in combination with purine analogues yields lower response-rates and less satisfactory results than for CLL patients with intact p53. Allogeneic stem cell transplantation may allow long-term remissions in this challenging group of patients. In this review, we will discuss current treatment options as well as experimental approaches in clinical trials for CLL patients with deleted or mutated TP53. Particular emphasis will be placed on novel agents with the potential to change clinical practice and future perspectives for the management of these "highest risk" patients.

Fragestellung: Irritative Symptome des unteren Harntrakts sind haufige Miktionsstorungen vielgestaltiger Atiologie und werden als „lower urinary tract symptoms“ (LUTS) zusammengefasst. Als Therapieoptionen stehen nach Versagen der medikamentosen Behandlung neben intravesikaler Botulinumtoxin-Applikation sowie Blasenaugmentation auch die sakrale Neuromodulation (SNM) als therapeutische Verfahren zur Verfugung. Wir prasentieren aktuelle Daten unserer prospektiven Serie zur SNM bei Patienten mit uberaktiver Harnblase. Material und Methoden: Es wurde die klinische Erfolgsrate aller Patienten untersucht, die von Mai 2007 bis Dezember 2010 an einem Einzelzentrum aufgrund LUTS mit oder ohne Dranginkontinenz idiopathischer, neurogener (Multiple Sklerose) und nicht-neurogener (chronisches Beckenschmerzsyndrom) Genese einer SNM zugefuhrt wurden. Dazu wurden die praoperativ erfassten Symptome mit den aktuellen Patientenangaben zum Follow-up-Zeitpunkt verglichen. Der Follow-up-Zeitraum betrug im Median 11 Monate (1 – 43). Ergebnisse: Im Untersuchungszeitraum wurde bei insgesamt 47 Patienten die Indikation zur SNM gestellt. 80,9 % der Patienten waren weiblich, das mediane Alter betrug 67 Jahre (19 – 84). In 38 (80,9 %) Fallen verlief die Testphase erfolgreich, bei 9 (19,1 %) Patienten wurde die Elektrode explantiert. Eine Analyse der einzelnen Indikationen zeigte statistisch signifikante Erhohung des Miktionsvolumens sowie Abnahme des Vorlagengebrauchs bei der idiopathischen Form der LUTS. Wahrend Patienten mit multipler Sklerose keine statistisch signifikanten Besserungen der Miktionsparameter zeigten, konnte bei chronischem Beckenschmerzsyndrom eine statistisch signifikante Abnahme der Miktionsfrequenz sowie eine subjektive Symptombesserung in 75 % festgestellt werden. Schlussfolgerung: Die SNM ist im selektierten Patientengut eine vielversprechende und in geubter Hand komplikationsarme Zweitlinien-Therapie bei irritativen Symptomen des unteren Harntrakts idiopathischer Atiologie. Eine generelle Empfehlung bei multipler Sklerose und chronischem Beckenschmerzsyndrom kann dagegen aufgrund der Ergebnisse auf der einen und den geringen Patientenzahlen auf der anderen Seite nicht gegeben werden. Durch prospektive, randomisierte multizentrische Studien sollte die Wertigkeit der SNM insbesondere bei neurogener und nicht-neurogener LUTS in Zukunft weiter prazisiert werden.

INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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-Guerin (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. CONCLUSION: 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.

PURPOSE: Renal cell carcinoma is the third most frequent urogenital malignancy. The increased inci-dence 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. MATERIAL AND METHODS: 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. RESULTS: 59 % of the patients were male, the median age being 64 years [range: 26-91 years]. In the study period, the number of patients ≤ 45 years and > 75 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 % (p < 0.001). -Tumours of stage pT1a increased statististically significantly to 42 %, the number of partial renal resections in the same period to 25 % (p < 0.001). There was no difference in residual tumour rate between nephron-sparing surgery and tumour nephrectomy. CONCLUSIONS: 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.

Urothelial carcinoma with plasmacytoid morphology is a rare and only recently described histological variant. To date only 22 cases have been published. We present clinical and histopathological features of 5 cases of plasmacytoid urothelial carcinoma at our institutions.From a consecutive series of 130 muscle invasive urothelial carcinoma cases 3 of plasmacytoid urothelial carcinoma (2.3%) were identified. Two additional plasmacytoid urothelial carcinoma cases, including 1 that was noninvasive, were also studied. Data were collected from clinical charts, histological review and followup.Four patients had a muscle invasive tumor at first presentation. The nonmuscle invasive plasmacytoid urothelial carcinoma represents the second published case in the literature. Conventionally differentiated urothelial carcinoma was focally present in every case. Plasmacytoid urothelial carcinoma cells were dyshesive and showed abundant eosinophilic cytoplasm, leading to a plasmacytoid appearance. Positive staining for epithelial markers confirmed the epithelial nature of the tumor. All tumors showed negative E-cadherin expression. Adjuvant or neoadjuvant chemotherapy seemed to have a beneficial effect on survival in patients with advanced tumors since they experienced prolonged survival.Plasmacytoid urothelial carcinoma is a rare variant of urothelial carcinoma with defined clinical and pathological characteristics. Diagnostic pitfalls are missing hematuria and no grossly identifiable tumor despite muscle invasive tumor stage. Cases only show mucosal induration and thickened bladder walls. Our data raise the possibility that the loss of E-cadherin expression is a prerequisite for plasmacytoid urothelial carcinoma. Awareness of these aspects should lead to earlier diagnosis and improved long-time survival in patients with plasmacytoid urothelial carcinoma.

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.

Bladder cancer represents the fifth most common malignancy in the US. In Germany we face 25,000 new incidences of urothelial cancers every year. At present a variety of different techniques is available for the diagnosis of bladder cancer. On the one hand techniques are needed that show the possible presence of a tumour and on the other hand procedures that can confirm a lesion to be a tumour, like in most cases histology does. The following article gives an overview of the currently used standards in the diagnosis of urothelial cancer. Also new techniques for diagnosis and surveillance of urothelial cancer are discussed. The combination of white light endoscopy and urine cytology is currently considered the gold standard for diagnosis. Transurethral biopsies or TUR-BT subsequently follow in the case of positive findings. To optimize the sensitivity and lower the recurrence rate as well as the residual tumour rate, fluorescence endoscopy can be used as an additional approach. Also urine-based markers play an important role in the diagnosis and surveillance of urothelial carcinomas, but cannot yet be recommended as a single procedure in the routine diagnosis of bladder tumour.

PURPOSE: 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 diameter ≥ 3 cm and associated carcinoma in situ (Cis) on the outcome of initial T1G3 bladder cancers treated in various ways. MATERIALS AND METHODS: Of 223 patients with initial T1G3 bladder cancer, 125 patients underwent transurethral resection of the tumour (TURB), second resection and adjuvant bacille Calmette-Guerin (BCG) instillations (TURB group), 98 patients chose initial radical cystectomy (CX group). RESULTS: 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 diameter ≥ 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. CONCLUSIONS: 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.

Up to 50-70 % of superficial bladder carcinomas recur. To improve the surgical results of transurethral resection the photodynamic diagnostic with 5-aminolevulinic acid is used. 5-aminolevulinic acid specifically accumulates in malignant cells leading to fluorescence under blue light cystoscopy. After intravesical instillation before transurethral resection also lesions like Carcinoma in situ, hardly to recognize in conventional cystoscopy, are noticed due to their fluorescence. Thus a significantly higher number of tumors can be diagnosed and resected. Also the recurrence rate decreases statistically significant. Long-term results with 5-aminolevulinic acid showed recurrence-free survival rates of 71 % versus 45 % after conventional transurethral resection under conventional white light. A recent cost analysis showed that photodynamic diagnostic reduces the number of stays in hospital thus also leading to cost reduction. Because of 18 000 newly diagnosed diseases in Germany per year this could result in remarkable saving possibilities of the health system.

Rectourinary fistula (RUF) is an uncommon but devastating condition that usually occurs as a complication of surgical treatment or radiotherapy of prostate cancer. Although operative fistula repair remains the most successful treatment, there still is no consensus concerning the management of RUF. We present first experiences and transanal surgical technique using biological mesh for fistula repair after urological intervention. From January 2009 to December 2013, four cases of RUF were reported at our university hospital. Fistula occurred after extraperitoneal laparoscopic radical prostatectomy, open radical prostatectomy, and high-intensity focused ultrasound, respectively. All patients were initially treated with transanal Cook Biodesign™ mesh, whereas two patients received reoperation with rectal mucosa advancement flap and gracilis muscle flap interposition, respectively. Mean follow-up was 36 months (range 9–62). Fistula diameters ranged from 0.6 to 3.0 cm and were located 5 to 6 cm of anocutaneous line. The time from diagnosis to fistula repair was 3 to 7 weeks. The median operative time for Cook Biodesing™ mesh procedure was 79 min (IQR 60, 98). The initial success rate for biological mesh was 50 % (2/4 patients). Larger fistulae were minimalized successfully and finally closed with reoperation mentioned above. No deterioration of continence was documented. Management of rectourinary fistula is still challenging. Using biomaterials for fistula closure seems to be a promising and minimally invasive transanal technique in future. Further analysis including more patients is needed to clarify its exact role in comparison to traditional surgical techniques.

Radical cystectomy (RC) can be associated with significant blood loss, whereas many patients are presenting with anemia preoperatively. To date, there is a lack of data addressing the impact of preoperative anemia (PA) on survival of patients undergoing RC for urothelial carcinoma of the bladder (UCB).This retrospective multicenter study includes 684 patients with UCB undergoing RC with pelvic lymph node dissection. The median follow-up was 50 (IQR 29,78) months. Anemia was defined in line with the WHO classification (hemoglobin (Hb): male ≤13 g/dL, female ≤12 g/dL) and based on contemporary gender- and age-adjusted classification (Hb: white male aged60 years: ≤13.7 g/dL; ≥60 years: ≤13.2 g/dL; white female of all ages ≤12.2 g/dL). Univariable and multivariable Cox regression analyses were used to assess the effects of PA on oncological outcomes.A total of 269 (39.3 %) and 302 (44.2 %) patients were anemic according to the WHO classification versus contemporary classification. Age, increased ECOG performance status, advanced tumor stages, lymph node metastasis, positive surgical margin and anemia were associated with disease recurrence (DR), cancer-specific mortality (CSM) and all-cause mortality (ACM). In multivariable analysis, anemia was an independent predictor of DR, CSM and ACM (WHO and/or contemporary classification). Blood transfusion was significantly associated with ACM in both classifications of anemia.PA is significantly associated with worse oncological outcome in patients undergoing RC. Based on the additional unfavorable influence of blood transfusion, this emphasizes the importance of early diagnosis and correction of anemia and implementation of alternative methods of blood volume management.

Incidental prostate cancer is often found in cystoprostatectomy specimens. The presence of a clinically significant tumour has an impact on follow-up strategies. In prostatectomy specimen for prostate cancer, whole-mount sections improve diagnostic accuracy. The present study compares detection of incidental prostate cancer in complete to routine processing. We included 295 consecutive patients who underwent radical cystoprostatectomy. Between 01/1995 and 12/2003 (period I), specimens of 129 patients were partially processed, whereas between 01/2004 and 03/2009 (period II), specimens of 166 patients were completely processed. Incidental prostate cancer was detected overall in 91 (30.8 %) patients. Prostate cancer was detected in 24 (18.6 %) patients in period 1 and in 67 (40.4 %) patients in period 2 (p < 0.001). Potentially clinically significant prostate cancer was detected in 12 (9.2 %) and 29 (17.5 %) patients, respectively (p = 0.044). Complete embedding and processing of cystoprostatectomy specimen yield significantly more potentially clinically relevant prostate cancers. The present data suggest that notably in younger men the specimens should be completely processed.

Somatic point mutations in the fibroblast growth factor receptor 3 (FGFR3) gene have been identified in certain types of urological cancers, especially urothelial carcinoma of the bladder and the renal pelvis, and could be correlated with a favourable outcome. However, comprehensive data on the FGFR3 mutation status in renal cell carcinoma (RCC) are still missing. In order to investigate a possible role for FGFR3 mutations in renal cell carcinogenesis, we performed a sequence-based mutational analysis of FGFR3 in 238 primary RCC. The cohort obtained the common RCC subtypes including 101 clear cell, 50 papillary and 68 chromophobe RCC specimens. The analysed regions encompassed all FGFR3 point mutations previously described in epithelial tumours and other noncutaneous epithelial malignancies. No mutations were detected in any renal tumour type examined, and all cases showed wild-type sequence. Our results argue against an involvement of mutational activation of FGFR3 in the development of RCC. A recently described cystic renal dysplasia in a patient with thanatophoric dysplasia type 1 due to a germ line FGFR3 mutation might portend to an involvement of mutational FGFR3 activation in renal cyst formation, but this speculation needs further evaluation.

e15103 Background: Bladder cancer is significantly more frequent in men than in women, which mostly is explained by greater exposure to carcinogenic influences in men. It has been repeatedly report...