The HELENA study: Hexvix®-TURB vs. white-light TURB followed by intravesical adjuvant chemotherapy-a prospective randomized controlled open-label multicenter non-inferiority study.

PURPOSE: Photodynamic diagnosis and white-light TURB with adjuvant intravesical chemotherapy (ICT) is widely used in treatment of bladder cancer. This non-inferiority trial is designed to demonstrate non-inferiority regarding recurrence-free survival (RFS) of Hexvix® TURB followed by immediate instillation compared to white-light TURB with immediate instillation followed by maintenance ICT. METHODS: Between 07/2010 and 12/2016, 129 patients with EORTC intermediate risk non-muscle invasive bladder cancer treated with TURB were included in this multicentre phase III study. Patients were randomized and received either white-light TURB with immediate ICT followed by maintenance ICT (n = 62, 20 mg Mitomycin weekly for 6 weeks as induction phase, afterwards 20 mg/month for 6 months) or Hexvix® TURB with immediate ICT only (n = 67, 40 mg Mitomycin). Primary study endpoint was RFS after 12 months. Hexvix® TURB was counted as non-inferior to white light alone if the upper limit of the one-sided 95% confidence interval of hazard ratio was lower than 1.676. Due to the non-inferiority design, the per-protocol population was used as the primary analysis population (n = 113) RESULTS: Median follow-up was 1.81 years. Hexvix® group showed more events (recurrence or death) than white-light group (19 vs. 10) resulting in a HR of 1.29 (upper limit of one-sided 95%-CI = 2.45; pnon-inferiority = 0.249). The ITT population yielded similar results (HR = 1.67); 3.18], pnon-inferiority = 0.493). There was no significant difference in overall survival between both groups (p = 0.257). CONCLUSION: Non-inferiority of Hexvix® TURB relative to white-light TURB with maintenance Mitomycin instillation in intermediate risk urothelial carcinoma of the bladder was not proven. Hence a higher effect of maintenance ICT is to assume compared to a Hexvix®-improved TURB only, confirming its important role in patient treatment.

Bicentric prospective evaluation of corporoplasty with porcine small intestinal submucosa (SIS) in patients with severe Peyronie's disease.

INTRODUCTION: Advanced Peyronie's disease (PD) with severe penile deviation demands grafting procedures following plaque incision or partial plaque excision in order to avoid penile shortening and to improve quality of life of affected patients. Small intestinal submucosa (SIS) is an established xenograft. The objective of the present study was to validate external results in a bicentric prospective manner. METHODS: Patient selection criteria, surgical technique and standards for pre- and postoperative care were defined. Consecutively, patients with severe penile deviation in stable disease and sufficient erectile function were included between 2007 and 2015. After plaque incision, grafting was performed using SIS in a standardized manner. The postoperative evaluation using a non-validated questionnaire included complications, correction of curvature, pre- and postoperative erectile function, change in penile length and general satisfaction with the procedure. RESULTS: Forty-three patients underwent surgery between 2007 and 2015. The mean degree of preoperative curvature was 73.8° (range 60-90°). No intraoperative or major postoperative complications were reported. After a mean follow-up of 33.0 months (range 10-59), complete straightening of the penis was achieved in 74.4%. 88.4% of all patients were able to achieve satisfying sexual intercourse (67.4% unaided, 21.0% with assistance). The IIEF-5 score was improved in 69.8% (mean improvement 4.0 points). Overall 86.0% were satisfied with the surgical treatment. CONCLUSION: Corporoplasty with SIS in patients with PD and severe penile curvature is a safe approach and shows good long-term results. A thorough patient selection and a standardized pre-, intra- and postoperative procedure are decisive for a satisfying outcome.

Impact of perioperative chemotherapy on survival in patients with advanced primary urethral cancer: results of the international collaboration on primary urethral carcinoma.

BACKGROUND: To investigate the impact of perioperative chemo(radio)therapy in advanced primary urethral carcinoma (PUC). PATIENTS AND METHODS: A series of 124 patients (86 men, 38 women) were diagnosed with and underwent surgery for PUC in 10 referral centers between 1993 and 2012. Kaplan-Meier analysis with log-rank testing was used to investigate the impact of perioperative chemo(radio)therapy on overall survival (OS). The median follow-up was 21 months (mean: 32 months; interquartile range: 5-48). RESULTS: Neoadjuvant chemotherapy (NAC), neoadjuvant chemoradiotherapy (N-CRT) plus adjuvant chemotherapy (ACH), and ACH was delivered in 12 (31%), 6 (15%) and 21 (54%) of these patients, respectively. Receipt of NAC/N-CRT was associated with clinically node-positive disease (cN+; P = 0.033) and lower utilization of cystectomy at surgery (P = 0.015). The objective response rate to NAC and N-CRT was 25% and 33%, respectively. The 3-year OS for patients with objective response to neoadjuvant treatment (complete/partial response) was 100% and 58.3% for those with stable or progressive disease (P = 0.30). Of the 26 patients staged ≥cT3 and/or cN+ disease, 16 (62%) received perioperative chemo(radio)therapy and 10 upfront surgery without perioperative chemotherapy (38%). The 3-year OS for this locally advanced subset of patients (≥cT3 and/or cN+) who received NAC (N = 5), N-CRT (N = 3), surgery-only (N = 10) and surgery plus ACH (N = 8) was 100%, 100%, 50% and 20%, respectively (P = 0.016). Among these 26 patients, receipt of neoadjuvant treatment was significantly associated with improved 3-year relapse-free survival (RFS) (P = 0.022) and OS (P = 0.022). Proximal tumor location correlated with inferior 3-year RFS and OS (P = 0.056/0.005). CONCLUSION: In this series, patients who received NAC/N-CRT for cT3 and/or cN+ PUC appeared to demonstrate improved survival compared with those who underwent upfront surgery with or without ACH.

The effect of intra- and postoperative allogenic blood transfusion on patients' survival undergoing radical cystectomy for urothelial carcinoma of the bladder.

PURPOSE: Radical cystectomy (RC) can be associated with significant blood loss. Allogenic blood transfusion (ABT) may alter disease outcome because of a theoretical immunomodulatory effect. We evaluated the effects of ABT on overall survival (OS) and progression-free survival (PFS) of patients undergoing RC for urothelial carcinoma of the bladder (UCB). MATERIALS AND METHODS: This is a retrospective single-center study of 350 consecutive patients of a university health center with a median follow-up of 70.1 month. All patients underwent RC and pelvic lymph node dissection. The effect of ABT on OS and PFS was analyzed using univariable and multivariable Cox proportional hazards models. RESULTS: The overall ABT rate was 63 % (n = 219), with intraoperative blood transfusion and postoperative blood transfusion being performed in 183 patients (52 %) and 99 patients (28 %), respectively. Preoperative anemia was detected in 156 patients (45 %) with median estimated blood loss of 800 ml (IQR: 500-1,200). ABT was associated with significant decrease of OS and PFS in multivariable analyses (p < 0.001), whereas patients' prognosis worsened the more packed red blood cells (PRBC) were transfused (p < 0.001). The study is limited in part due to its retrospective design. CONCLUSIONS: We found that ABT and the number of PRBC transfused are associated with poor prognosis for UCB patients undergoing RC, whereas preoperative anemia had no influence on survival. This emphasizes the importance of surgeon's awareness for a strict indication for ABT. A prospective study will be necessary to evaluate the independent risks associated with ABT during surgical treatments.

Clinical and pathological nodal staging score for urothelial carcinoma of the bladder: an external validation.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Body mass index has no impact on sperm quality but on reproductive hormones levels.

The influence of overweight and obesity on sperm quality and reproductive hormone levels is under discussion. The aim of the present retrospective study was to evaluate the influence of body mass index (BMI) on sperm quality and reproductive hormones. We analysed semen samples and serum levels of FSH, LH, T and PRL of a total of 2110 men attending our andrology unit from 1994 to 2010 due to infertility work-up. Patients were stratified according to their BMI in four groups. Main outcome measures were sperm motility, morphology and concentration. Serum levels of FSH, LH, T and PRL were evaluated as well. No statistically significant difference was found for sperm quality and BMI between patients categorised according to the four BMI levels. T (P < 0.001) and LH (P = 0.006) significantly differed between the four groups. In multivariable analysis, BMI did not have significantly independent influence on all assessed sperm quality parameters, whereas BMI significantly influenced hormone values for LH (P = 0.001), T (P = <0.001) and PRL (P = 0.044). We therefore conclude that BMI has no significant impact on sperm quality parameters. However, serum levels of LH, T and PRL were significantly influenced by BMI.

Oncological outcome of primary versus secondary muscle-invasive bladder cancer is comparable after radical cystectomy.

BACKGROUND: High-risk non-muscle-invasive bladder cancer (NMIBC) progressing to muscle-invasive bladder cancer (MIBC) is associated with adverse tumour biology. It is unclear, however, whether outcome of NMIBC progressing to MIBC is adverse compared to primary MIBC and whether NMIBC of higher risk of progression to MIBC is adverse compared to NMIBC of lower risk. OBJECTIVE: Our objective was to assess cancer-specific survival (CSS) following radical cystectomy (RC) for primary MIBC and for NMIBC progressing to MIBC in dependence of EORTC risk score. MATERIALS AND METHODS: Clinical and histopathological characteristics and CSS of 150 patients were assessed. Secondary MIBCs were stratified by EORTC risk score at the last transurethral resection of bladder tumour for NMIBC. RESULTS: CSS did not differ significantly between primary and secondary MIBC (p = 0.521). Secondary MIBC with high EORTC score had significantly shorter CSS compared to secondary MIBC with intermediate EORTC score (p = 0.029). In multivariable analysis, pathological tumour stage (HR = 3.77; p = 0.020) and lymph node stage (HR = 2.34; p = 0.022) were significantly correlated with CSS. CONCLUSION: While the outcome of secondary MIBC is not generally adverse compared to primary MIBC, the EORTC risk score not only reflects high risk of progression of NMIBC to MIBC, but also worse outcome following RC for secondary MIBC. Timely RC should thus be debated in high-risk NMIBC.

Comparison of assay methods for detection of circulating tumor cells in metastatic breast cancer: AdnaGen AdnaTest BreastCancer Select/Detect™ versus Veridex CellSearch™ system.

The detection of CTCs prior to and during therapy is an independent and strong prognostic marker, and it is predictive of poor treatment outcome. A major challenge is that different technologies are available for isolation and characterization of CTCs in peripheral blood (PB). We compare the CellSearch system and AdnaTest BreastCancer Select/Detect, to evaluate the extent that these assays differ in their ability to detect CTCs in the PB of MBC patients. CTCs in 7.5 ml of PB were isolated and enumerated using the CellSearch, before new treatment. Two cutoff values of ≥2 and ≥5 CTCs/7.5 ml were used. AdnaTest requires 5 ml of PB to detect gene transcripts of tumor markers (GA733-2, MUC-1, and HER2) by RT-PCR. AdnaTest was scored positive if ≥1 of the transcript PCR products for the 3 markers were detected at a concentration ≥0.15 ng/µl. A total of 55 MBC patients were enrolled. 26 (47%) patients were positive for CTCs by the CellSearch (≥2 cutoff), while 20 (36%) were positive (≥5 cutoff). AdnaTest was positive in 29 (53%) with the individual markers being positive in 18% (GA733-2), 44% (MUC-1), and 35% (HER2). Overall positive agreement was 73% for CTC≥2 and 69% for CTC≥5. These preliminary data suggest that the AdnaTest has equivalent sensitivity to that of the CellSearch system in detecting 2 or more CTCs. While there is concordance between these 2 methods, the AdnaTest complements the CellSearch system by improving the overall CTC detection rate and permitting the assessment of genomic markers in CTCs.

Risk stratification of pT1-3N0 patients after radical cystectomy for adjuvant chemotherapy counselling.

BACKGROUND: In pT1-T3N0 urothelial carcinoma of the bladder (UCB) patients, multi-modal therapy is inconsistently recommended. The aim of the study was to develop a prognostic tool to help decision-making regarding adjuvant therapy. METHODS: We included 2145 patients with pT1-3N0 UCB after radical cystectomy (RC), naive of neoadjuvant or adjuvant therapy. The cohort was randomly split into development cohort based on the US patients (n=1067) and validation cohort based on the Europe patients (n=1078). Predictive accuracy was quantified using the concordance index. RESULTS: With a median follow-up of 45 months, 5-year recurrence-free and cancer-specific survival estimates were 68% and 73%, respectively. pT-stage, ge, lymphovascular invasion, and positive margin were significantly associated with both disease recurrence and cancer-specific mortality (P-values ≤ 0.005). The accuracies of the multivariable models at 2, 5, and 7 years for predicting disease recurrence were 67.4%, 65%, and 64.4%, respectively. Accuracies at 2, 5, and 7 years for predicting cancer-specific mortality were 69.3%, 66.4%, and 65.5%, respectively. We developed competing-risk, conditional probability nomograms. External validation revealed minor overestimation. CONCLUSION: Despite RC, a significant number of patients with pT1-3N0 UCB experience disease recurrence and ultimately die of UCB. We developed and externally validated competing-risk, conditional probability post-RC nomograms for prediction of disease recurrence and cancer-specific mortality.

Positive urine cytology and carcinoma in situ prior to second transurethral resection of the bladder correlate with positive second resection histology and the need for subsequent cystectomy.

OBJECTIVE: A second transurethral resection of the bladder (TURB) is recommended for high-grade bladder cancer (BC) yet yields negative results in over half of the cases. Aim of this study was to identify prognostic indicators of a positive second TURB or the need for a subsequent cystectomy. MATERIALS AND METHODS: The study cohort consisted of 101 patients with high-risk BC (T1G2-3, TaG3, Carcinoma in situ) who underwent second TURB after complete first resection. Age, gender, stage, grade, carcinoma in situ (Cis), tumour number, size, localization, surgeon experience and bladder wash cytology before the second TURB were considered as potential prognostic factors of positive histology at second TURB or the need for subsequent cystectomy. RESULTS: The mean follow-up period was 23.8 months. The study cohort was comprised of 82 males and 17 females. Cytology on bladder wash urine was performed in 85/101 patients and in 39 was negative; 55.5 % of second TURB specimens were negative. The rate of upstaging to ≥T2 was 4.9 %. Cis (OR 8.4; 95 % CI 1.3-54.2; p = 0.03) and positive cytology (OR 6.8; 95 % CI 2.3-19.9; p = <0.01) were independent prognostic factors of a residual tumour in the second TURB. Cytology also correlated with clinical need for cystectomy in the follow-up (HR 6.5; 95 % CI 1.3-30.5; p = 0.02). CONCLUSIONS: CIS and positive cytology prior to second TURB increased the risk of a positive second TURB specimen. A positive cytology also increases the risk of the subsequent need for cystectomy.

Miniaturized percutaneous Nephrolithotomy without antibiotic prophylaxis: a single institution experience.

PURPOSE: To assess the feasibility of sparing routine antibiotic prophylaxis in patients without preoperative urinary tract infection (UTI) undergoing a miniaturized percutaneous nephrolithotomy (mPCNL). PATIENTS AND METHODS: A retrospective, monocentric study was conducted to evaluate the outcome of a modified perioperative antibiotic management strategy according to the principles of antibiotic stewardship (ABS). From December 2015 patients undergoing mPCNL for kidney stone with preoperative unremarkable urine culture no longer received an antibiotic prophylaxis (NoPAP). The NoPAP group was compared to mPCNL patients who received standard antibiotic prophylaxis (PAP) in the two years before. Analysis focused on postoperative complications. Logistic regression analysis was performed to identify potential risk factors. RESULTS: Postoperative fever occurred in 8% of the NoPAP and 9% of the PAP patients (p = 0.764). Clavien 1-3 complications did not differ between groups with 33% in the NoPAP and 41% in the PAP (p = 0.511). No Clavien 4-5 complications were seen. A (partial) staghorn stone (HR 5.587; p = 0.019) and an infectious stone component (HR 6.313; p = 0.003) were identified as significant risk factors for postoperative fever. By sparing routine antibiotic prophylaxis the overall antibiotic usage was reduced from 100% (PAP) to 9% (NoPAP). CONCLUSION: Patients with negative preoperative UC, a none-staghorn stone and no history of recurrent UTI or infectious stones may not need routine antibiotic prophylaxis prior to mPCNL. A prospective validation is warranted.

Technical validation of an autoantibody test for lung cancer.

BACKGROUND: Publications on autoantibodies to tumour-associated antigens (TAAs) have failed to show either calibration or reproducibility data. The validation of a panel of six TAAs to which autoantibodies have been described is reported here. MATERIALS AND METHODS: Three separate groups of patients with newly diagnosed lung cancer were identified, along with control individuals, and their samples used to validate an enzyme-linked immunosorbant assay. Precision, linearity, assay reproducibility and antigen batch reproducibility were all assessed. RESULTS: For between-replicate error, samples with higher signals gave coefficients of variation (CVs) in the range 7%-15%. CVs for between-plate variation were only 1%-2% higher. For between-run error, CVs were in the range 15%-28%. In linearity studies, the slope was close to 1.0 and correlation coefficient values were generally >0.8. The sensitivity and specificity of individual batches of antigen varied slightly between groups of patients; however, the sensitivity and specificity of the panel of antigens as a whole remained constant. The validity of the calibration system was demonstrated. CONCLUSIONS: A calibrated six-panel assay of TAAs has been validated for identifying nearly 40% of primary lung cancers via a peripheral blood test. Levels of reproducibility, precision and linearity would be acceptable for an assay used in a regulated clinical setting.

Long-term outcome after grafting with small intestinal submucosa and collagen fleece in patients with Peyronie's disease: a matched pair analysis.

Advanced Peyronie's disease (PD) with severe penile curvature requires grafting following plaque incision or partial plaque excision. So far, the ideal graft material has not been identified although various grafts have been studied. In this first matched pair analysis we compared the outcome after grafting with small intestinal submucosa (SIS) and self-adhesive collagen fleece (CF). We retrospectively identified 43 patients after SIS grafting with complete follow-up data sets to be eligible for the present study. A total of 43 patients after CF grafting were matched case by case to the SIS group using the degree of preoperative penile curvature as the primary matching factor. Postoperative outcome was compared with the focus on penile straightening, penile length, potency, relapse rates and long-term complications. Median degree of curvature was 80° in each group. Mean follow-up periods were 31 months after SIS and 39 months after CF grafting. The CF grafting procedure was significantly faster than SIS grafting (80 vs. 104 min, p < 0.001). No major short-term complications were observed. Both techniques gained good long-term penile straightening rates. Relapse of penile curvature was observed after SIS grafting only. Postoperative penile shortening occurred more often after SIS grafting (28% vs. 5%, p = 0.007). With a mean preoperative IIEF-5 score of 16, the SIS cohort significantly differed from the CF cohort with a mean IIEF-5 score of 19 (p = 0.016). The median IIEF-5 score improvement was higher after SIS grafting (+4.5 vs. +1, p = 0.002). Diminished penile sensation was the main long-term side effect with low rates after both procedures (9% and 7% in the SIS and CF group respectively, p = 0.100). In this first matched pair analysis both techniques showed promising long-term results. CF seems to have advantages regarding duration of surgery and preserving penile length. More comparative studies with larger collectives are desirable.

Plasmacytoid urothelial carcinoma of the bladder: histological and clinical features of 5 cases.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Management of early-invasive high-grade transitional cell carcinoma of the bladder.

The decision in favor or against an early cystectomy in patients with initial pT1G3 urothelial carcinoma of the bladder (UCBC) is challenging. In the present review the authors dwell on the key issues in the controversial discussion about optimal management of so called ''early invasive'' UCBC. The quality of transurethral resection of the bladder tumor (TURBT) as diagnostic and therapeutic method plays an important role. Histopathological assessment delivers crucial risk factors for stratification. Last but not least life quality under different therapeutic regimes should be comprised in the decision process.

[Plasmacytoid carcinoma. Five case reports of a rare variant of urothelial carcinoma]. / Das plasmazytoide Urothelkarzinom. 5 Fallberichte einer seltenen Variante des konventionellen Urothelkarzinoms.

Plasmacytoid carcinoma is a rare variant of urothelial carcinoma and is characterised by distinct histopathological and clinical characteristics. The incidence varies between 2.7% and 3.1% of all muscle-invasive urothelial carcinoma. It is an aggressive, high-grade tumor with poor prognosis. Negative E-cadherin expression seems to be important for exact diagnosis. Systemic chemotherapy of plasmacytoid carcinoma could lead to prolonged patient survival.

[Bladder preservation or initial cystectomy in T1G3 bladder cancer: which parameters help in therapeutic decision-making?]. / Organ erhaltende Therapie oder initiale Zystektomie beim T1G3-Harnblasenkarzinom: Welche Faktoren helfen bei der Therapieentscheidung?

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 >or= 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-Guérin (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 >or= 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.

[Impact of comorbidity on perioperative mortality after radical cystectomy]. / Auswirkung der Komorbidität auf die perioperative Mortalität nach radikaler Zystektomie.

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.

[Interrater reliability and clinical impact of the Post-Ureteroscopic Lesion Scale (PULS) grading system for ureteral lesions after ureteroscopy : Results of the German prospective multicenter BUSTER project]. / Interrater-Übereinstimmung und klinischer Nutzen der "Post-Ureteroscopic Lesion Scale" (PULS) zur Graduierung von intraoperativen Harnleiterverletzungen einer Ureterorenoskopie : Ergebnisse der deutschen prospektiv-multizentrischen BUSTER-Studie.

BACKGROUND: The Post-ureteroscopic Lesion Scale (PULS) was designed as a standardized classification system for ureteral lesions after uretero(reno)scopy (URS). This study evaluates its routine use and a possible clinical impact based on a representative patient cohort. MATERIALS AND METHODS: Data of 307 patients in 14 German centers within the BUSTER project were used to test 3 hypotheses (H): PULS score shows a high interrater reliability (IRR) after independent assessment by urologic surgeon and assistance personnel (H1); PULS score is correlated with the frequency of postoperative complications during hospital stay (H2); post-URS stenting of the ureter is associated with higher PULS scores (H3). RESULTS: Median age of patients was 54.4 years (interquartile range [IQR] 44.4-65.8; 65.5% male). Median diameter of index stones was 6 mm (IQR 4-8) with 117 (38.4%) pyelo-caliceal and 188 (61.6%) ureteral stones. Overall, 70 and 82.4% of patients had pre-stenting and post-URS stenting, respectively. Stone-free status was achieved in 68.7% after one URS procedure with a complication rate of 10.8% (mostly grade 1-2 according to Clavien-Dindo). PULS scores 0, 1, 2 and 3 were assessed in 40%, 52.1%, 6.9% and 1% of patients, respectively, when estimated by urologic surgeons. PULS score showed a high IRR between the urologic surgeon and assistance personnel (κ = 0.883, p < 0.001), but was not significantly correlated with complications (ρ = 0.09, p = 0.881). In contrast, a significant positive correlation was found between PULS score and post-URS stenting (ρ = 0.287, p < 0.001). A PULS score of 1 multiplied the likelihood of post-URS stenting by 3.24 (95% confidence interval 1.43-7.34; p = 0.005) as opposed to PULS score 0. CONCLUSIONS: Removal of upper urinary tract stones using URS is safe and efficacious. Real-world data provided by this study confirm a high IRR of the PULS score and its clinical impact on the indication for post-URS stenting. A future prospective randomized trial should evaluate a possible standardization of post-URS stenting based on PULS score assessment.