Evaluation of sexual function and vaginal prolapse after radical cystectomy in women: a study to explore an under-evaluated problem.

INTRODUCTION AND HYPOTHESIS: The objective was to evaluate sexual function, vaginal prolapse, and quality of life (QoL) in women after radical cystectomy (RC) using validated questionnaires and pelvic organ prolapse quantification (POP-Q) measurement. METHODS: Female bladder cancer patients who underwent RC at our tertiary care center were included (January 2008 to March 2022). Patients received three validated questionnaires (International Consultation on Incontinence Questionnaire Vaginal Symptoms [ICIQ-VS] Part A, Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire IUGA revised [PISQ], European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC] C30/BLM30). Patients who consented were examined with vaginal POP-Q measurement. RESULTS: Out of 322 patients, 193 were still alive, 54 patients were lost to follow-up, and 43 were excluded, resulting in 96 patients who received the questionnaire. Finally, 35 patients were included, of whom 17 patients consented to vaginal examination. Complaints due to vaginal symptoms were low (ICIQ-VS 6.17 + 5.37). Sexual activity was reported by 12 patients (34.3%); 23 patients (65.71%) were not sexually active. No apical prolapse was found in POP-Q measurement; 6 patients (35.3%) had anterior, and 14 patients (82.4%) posterior prolapse; the highest prolapse stage was 2. No significant differences were found regarding POP stages, sexual function, and QoL (all p > 0.05) when comparing continent and incontinent urinary diversions. Comparing the vaginal approach (no sparing vs sparing), significant differences were found in only two PISQ subscales (significantly higher scores after vagina sparing, p = 0.01 and p = 0.02). CONCLUSIONS: The type of urinary diversion, POP-Q stages, and tumor stages did not show significant differences regarding sexual function, QoL, and prolapse complaints in women after RC, whereas a vagina- sparing approach showed significant differences only in two subscales without clinical relevance.

Impact of perioperative blood transfusions on oncologic outcomes after radical cystectomy: A systematic review and meta-analysis of comparative studies.

This study aimed at systematically analyzing and evaluating the impact of perioperative blood transfusions (PBT) on oncologic outcomes of patients undergoing radical cystectomy for bladder cancer. This systematic review follows the recommendations of the Cochrane Handbook for Systematic Reviews and Interventions and was conducted in line with the PRISMA statement and the AMSTAR II criteria. A comprehensive database search was performed based on the PICO criteria. Two independent reviewers performed all screening steps and quality assessment. Risk of bias and certainty in evidence were assessed with the Newcastle Ottawa Scale for non-randomized trials and the GRADE approach. Of 1123 identified studies 20 were eligible for qualitative analysis and 15 for quantitative analysis reporting on 21,915 patients. Receiving a PBT was associated with an increased risk of all-cause mortality (hazard ratio (HR) [95% confidence interval (CI)]: 1.29 [1.18, 1.40]; p < 0.001), cancer-specific mortality (HR [CI]: 1.27 [1.15; 1.41]; p < 0.001) and disease recurrence (HR [CI]: 1.22 [1.12; 1.34]; p < 0.001). Subgroup analysis of transfusion timing revealed a significantly increased risk of mortality with intraoperative or combined intra- and postoperative transfusions compared to postoperative transfusion only for all three outcomes (p < 0.001). Leukocyte-depletion was associated with increased all-cause mortality, but not cancer-specific mortality. The administration of PBT negatively impacts oncological outcomes after radical cystectomy. Therefore, careful treatment indication and strict adherence to transfusion guidelines is encouraged in order to avoid adverse effects during the perioperative course.

[Urological care in practices and clinics during the corona virus pandemic in Germany]. / Versorgungssituation urologischer Patienten in Praxen und Kliniken während der Coronaviruspandemie in Deutschland.

The coronavirus pandemic has had an immediate and far-reaching effect on the care of urological patients. The pandemic monitor of the German Society for Urology was able to record the restrictions on patient care in urological practices and clinics by means of regular surveys of the members. A total of 689 responses at four survey time points were included. In April there was a reduction in urological inpatients to 44% and the number of patients in practices dropped to 50%. Available operating theater capacities for urological patients were 45% in April, normalized to 90% in June and fell again to 50% in December. Elective operations could not be performed at all or only to a very limited extent in most hospitals in April and December. While urgent operations could be treated to 100% in more than 75% of the clinics in April, in December more than half of the clinics stated that they could not treat all patients with urgent indications. To some extent (8-19%) practices and clinics had to resort to a pandemic-related supraregional referral of patients. The reduction of outpatients in urological practices in April normalized to 95% in June and remained stable during the second wave of the pandemic. The increase in urological emergencies in practices observed at the beginning of the pandemic did not show up in November and December. The coronavirus pandemic has led to a significant reduction in the care of urological patients, which in particular in the second wave also affects urgent operations.

Frailty predicts outcome of partial nephrectomy and guides treatment decision towards active surveillance and tumor ablation.

PURPOSE: To examine frailty and comorbidity as predictors of outcome of nephron sparing surgery (NSS) and as decision tools for identifying candidates for active surveillance (AS) or tumor ablation (TA). METHODS: Frailty and comorbidity were assessed using the modified frailty index of the Canadian Study of Health and Aging (11-CSHA) and the age-adjusted Charlson-Comorbidity Index (aaCCI) as well as albumin and the radiological skeletal-muscle-index (SMI) in a cohort of n = 447 patients with localized renal masses. Renal tumor anatomy was classified according to the RENAL nephrometry system. Regression analyses were performed to assess predictors of surgical outcome of patients undergoing NSS as well as to identify possible influencing factors of patients undergoing alternative therapies (AS/TA). RESULTS: Overall 409 patient underwent NSS while 38 received AS or TA. Patients undergoing TA/AS were more likely to be frail or comorbid compared to patients undergoing NSS (aaCCI: p < 0.001, 11-CSHA: p < 0.001). Gender and tumor complexity did not vary between patients of different treatment approach. 11-CSHA and aaCCI were identified as independent predictors of major postoperative complications (11-CSHA ≥ 0.27: OR = 3.6, p = 0.001) and hospital re-admission (aaCCI ≥ 6: OR = 4.93, p = 0.003) in the NSS cohort. No impact was found for albumin levels and SMI. An aaCCI > 6 and/or 11-CSHA ≥ 0.27 (OR = 9.19, p < 0.001), a solitary kidney (OR = 5.43, p = 0.005) and hypoalbuminemia (OR = 4.6, p = 0.009), but not tumor complexity, were decisive factors to undergo AS or TA rather than NSS. CONCLUSION: In patients with localized renal masses, frailty and comorbidity indices can be useful to predict surgical outcome and support decision-making towards AS or TA.

B-MYB-p53-related relevant regulator for the progression of clear cell renal cell carcinoma.

PURPOSE: To investigate the mRNA expression of B-MYB and MDM2 together with their p53 relatedness in clear cell renal cell carcinoma (ccRCC). METHODS: Genes were screened for their mRNA expression from 529 patients in a publicly available ccRCC cohort (TCGA). A cohort of 101 patients with ccRCC served as validation by qRT-PCR mRNA tissue expression analysis. RESULTS: Expression: B-MYB expression was significantly higher in high-grade tumours (p < 0.0001 and p = 0.048) and in advanced stages (p = 0.005 and p = 0.037) in both cohorts. Correlation: p53-B-MYB as well as MDM2-B-MYB showed significant correlations in local and low-grade ccRCCs, but not in high grade tumours or advanced stages (r < 0.3 and/or p > 0.05). Survival: Multivariable Cox regression of the TCGA cohort revealed B-MYB upregulation and low MDM2 expression as predictors for an impaired overall survival (OS) (HR 1.97; p = 0.0003; HR 2.94, p < 0.0001) and progression-free survival (PFS) (HR 2.86; p = 0.0005; HR 1.58, p = 0.046). In the validation cohort, the results were confirmed for OS by univariable, but not multivariable regression: high B-MYB expression (HR = 3.05, p = 0.035) and low MDM2 expression (HR 3.81, p value 0.036). CONCLUSION: In ccRCC patients with high-grade tumours and advanced stages, high B-MYB expression is common and is associated with poorer OS and PFS. These patients show a loss of their physiological B-MYB-p53 network correlation, suggesting an additional, alternative regulatory, oncogenic mechanism. Assuming further characterization of its signalling pathways, B-MYB could be a potential therapy target for ccRCC.

The comprehensive complication index (CCI): proposal of a new reporting standard for complications in major urological surgery.

PURPOSE: The comprehensive complication index (CCI) is a new tool for reporting the cumulative burden of postoperative complications on a continuous scale. This study validates the CCI for urological surgery and its benefits over the Clavien-Dindo-Classification (Clavien). MATERIAL AND METHODS: Data from a prospectively maintained data base of all consecutive patients at a university care-center was analyzed. Complications after radical cystectomy (RC), radical prostatectomy (RP), and partial nephrectomy (PN) were classified using the CCI and Clavien system. Differences in complications between the CCI and the Clavien were assessed and correlation analyses performed. Sample size calculations for hypothetical clinical trials were compared between CCI and Clavien to evaluate whether the CCI would reduce the number of required patients in a clinical trial. RESULTS: 682 patients (172 RC, 297 RP, 213 PN) were analyzed. Overall, 9.4-46.6% of patients had > 1 complication cumulatively assessed with the CCI resulting in an upgrading in the Clavien classification for 2.4-32.4% of patients. Therefore, scores between the systems differed for RC: CCI (mean ± standard deviation) 26.3 ± 20.8 vs. Clavien 20.4 ± 16.7, p < 0.001; PN: CCI 8.4 ± 14.7 vs. Clavien 7.0 ± 11.8, p < 0.001 and RP: CCI 5.8 ± 11.7 vs. Clavien 5.3 ± 10.6, p = 0.102. The CCI was more accurate in predicting LOS after RC than Clavien (p < 0.001). Sample size calculations based in the CCI (for future hypothetical trials) resulted in a reduction of required patients for all procedures (- 25% RC, - 74% PN, - 80% RP). CONCLUSION: The CCI is more accurate to assess surgical complications and reduces required sample sizes that will facilitate the conduction of clinical trials.

[Enhanced imaging in urological endoscopy]. / Erweiterte Bildgebung in der urologischen Endoskopie.

White light cystoscopy and the concise documentation of pathological findings are standard diagnostic procedures in urology. Additional imaging modalities and technical innovations may support clinicians in the detection of bladder tumors. Modern endoscopy systems provide ultra-high-resolution imaging and the option of digital contrast enhancement. Photodynamic diagnostics and narrow band imaging are well-established in clinical routine and have shown significant benefits in the detection of bladder cancer. By means of multispectral imaging, different modalities can now be combined in real-time. Probe-based procedures such as optical coherence tomography (OCT) or Raman spectroscopy can further contribute to advanced imaging through an "optical biopsy" which may primarily improve diagnostics in the upper urinary tract. The aim of all techniques is to optimize the detection rate in order to achieve a more accurate diagnosis, resection and lower recurrence rates. Current research projects aim to digitalize the documentation of endoscopy and also make it more patient- and user-friendly. In the future, the use of image processing and artificial intelligence may automatically support the surgeon during endoscopy.

Prospective geriatric assessment for perioperative risk stratification in partial nephrectomy.

PURPOSE: Comorbidities and frailty are determinants of surgical outcome. The aim of the study was to examine various measures of frailty and comorbidities in predicting postoperative outcome of partial nephrectomy (PN). METHODS: We prospectively analyzed the frailty and comorbidity status of 150 patients undergoing PN between 2015 and 2018. Primary endpoint was the occurrence of major postoperative complications (MPC) and secondary endpoints were the failure of Trifecta achievement and the need for hospital readmissions. For the transfer into clinical practice the most significant frailty parameters were summarized in a multi-dimensional test. RESULTS: Median age was 67 (33-93) years, 64.7% of the patients were male. Univariable regression analysis showed, that patients with increased frailty indices (Hopkins frailty score ≥2 (OR = 3.74, p = 0.005), Groningen frailty index ≥4 (OR = 2.85, p = 0.036)) are at higher risk to develop MPC. Furthermore, poor physical performance, such as a low handgrip strength or a Full-Tandem-Stand (FTS) < 10 s were associated with MPC (OR = 4.76, p = 0.014; OR = 4.48, p = 0.018) and Trifecta failure (OR = 3.60, p = 0.037, OR = 5.50, p = 0.010). Six measures were combined to the geriatric assessment in partial nephrectomy score (GAPN). A GAPN-score ≥3 proved to be a significant predictor for MPC (OR = 4.30, p = 0.029) and for Trifecta failure (OR = 0.20, p = 0.011) in multivariable regression analysis. CONCLUSION: The frailty status and comorbidities are important determinants of the postoperative course after PN. These parameters should be assessed preoperatively and included in the treatment planning, especially in light of available alternative therapies. In this context, the GAPN-score may be a suitable tool.

[Urology in the corona-virus pandemic-a guideline 4/20]. / Urologie in der Corona-Virus-Pandemie ­ Leitfaden 4/20.

The coronavirus pandemic is a major challenge for healthcare systems worldwide. For urology, the expansion of the health-care structures for the treatment of patients suffering from COVID-19 should be supported as best as possible. At the same time, one should aim to ensure adequate care for urological emergencies and urgent urological treatments as far as possible, even during the pandemic. For this, patients must be prioritized individually, alternative therapy concepts must be considered and regional and supraregional cooperation must be used. Outpatient departments are of great importance in the care, examination and coordination of urological emergencies and urgent treatment. Urological clinics must prepare themselves to perform urgent operations and interventions on SARS-CoV­2-positive patients. Here, the creation of a separate, appropriately equipped emergency operating room to perform operations and interventions on SARS-CoV­2 patients should be considered. Furthermore strictly defined hygiene measures to protect employees in various clinical scenarios should be set up.

Early recovery after surgery for radical cystectomy: comprehensive assessment and meta-analysis of existing protocols.

PURPOSE: Different enhanced recovery after surgery (ERAS) protocols (EP) for radical cystectomy (RC) have been published. Protocols highly differ in number of included items and specific measures. MATERIALS AND METHODS: A systematic review and meta-analysis on EPs in RC were performed using the databases MedLine, Cochrane Library, Web of science, and Google Scholar. The specific ERAS measures of the protocols were extracted, analyzed, and compared. Pooling of available outcome data was performed for length of stay, complications, readmission rate, and time to defecation. RESULTS: The search yielded a total of 860 studies of which 25 studies were included in qualitative and 22 in quantitative analysis. Oral bowel preparation (BP) was omitted in 24/25 (96%) EPs, optimized fluid management was administered in 22/25 (88%) EPs and early mobilization (postoperative day 1) in 21/25 (84%). Gum chewing (n = 12, 46%), metoclopramide (n = 11, 44%), and alvimopan (n = 6, 24%) were the most common measures to prevent postoperative ileus. Our meta-analysis revealed a significant benefit in favor of EPs for the outcome parameters length of stay [mean difference (MD) - 3.46 d, 95% confidence interval (CI) - 4.94 to - 1.98, p < 0.01], complications [Odds ratio (OR) = 0.76, 95% CI 0.61-0.94, p = 0.01] and time to defecation (MD - 1.37 d, 95% CI - 2.06 to - 0.69, p < 0.01). Readmission rate did not show a significant difference (OR = 0.73, 95% CI 0.52-1.03, p = 0.07). CONCLUSION: Current EPs focus on omitting oral BP, early mobilization, and optimized fluid management while they differ in methods preventing postoperative ileus. Our meta-analysis revealed a benefit in introducing these protocols into clinical practice.

Prophylactic abdominal or retroperitoneal drain placement in major uro-oncological surgery: a systematic review and meta-analysis of comparative studies on radical prostatectomy, cystectomy and partial nephrectomy.

PURPOSE: To systematically analyze the impact of prophylactic abdominal or retroperitoneal drain placement or omission in uro-oncologic surgery. METHODS: This systematic review follows the Cochrane recommendations and was conducted in line with the PRISMA and the AMSTAR-II criteria. A comprehensive database search including Medline, Web-of-Science, and CENTRAL was performed based on the PICO criteria. All review steps were done by two independent reviewers. Risk of bias was assessed with the Cochrane tool for randomized trials and the Newcastle-Ottawa Scale. RESULTS: The search identified 3427 studies of which eleven were eligible for qualitative and ten for quantitative analysis reporting on 3664 patients. Six studies addressed radical prostatectomy (RP), four studies partial nephrectomy (PN) and one study radical cystectomy. For RP a reduction in postoperative complications was found without drainage (odds ratio (OR)[95% confidence interval (CI)]: 0.62[0.44;0.87], p = 0.006), while there were no differences for re-intervention (OR[CI]: 0.72[0.39;1.33], p = 0.300), lymphocele OR[CI]: 0.60[0.22;1.60], p = 0.310), hematoma (OR[CI]: 0.68[0.18;2.53], p = 0.570) or urinary retention (OR[CI]: 0.57[0.26;1.29], p = 0.180). For partial nephrectomy no differences were found for overall complications (OR[CI]: 0.99[0.65;1.51], p = 0.960) or re-intervention (OR[CI]: 1.16[0.31;4.38], p = 0.820). For RC, there were no differences for all parameters. The overall-quality of evidence was assessed as low. CONCLUSION: The omission of drains can be recommended for standardized RP and PN cases. However, deviations from the standard can still mandate the placement of a drain and remains surgeon preference. For RC, there is little evidence to recommend the omission of drains and future research should focus on this issue. REVIEW REGISTRATION NUMBER (PROSPERO): CRD42019122885.

[The development of real-time multispectral imaging for the diagnostics of bladder cancer]. / Entwicklung der Echtzeitmultispektralbildgebung für die Diagnostik des Harnblasenkarzinoms.

The performance of white light (WL) cystoscopy in the diagnostics of bladder cancer can be optimized by the use of modern imaging modalities, such as photodynamic diagnostics (PDD) and narrow band imaging (NBI). Real-time multispectral imaging (rMSI) enables simultaneous imaging of reflectance and fluorescence modalities in multiple spectral bands. We created a multiparametric cystoscopy image by digital overlapping of several modalities, e.g. WL, enhanced vascular contrast (EVC), raw fluorescence mode, protoporphyrin IX and autofluorescence (AF). The technical development and the subsequent clinical implementation of rMSI required a structured preclinical evaluation process, including both ex vivo and in vivo trials before the technology can be applied in patients. This review article presents the phases of testing, validation and the first clinical application of rMSI in urological endoscopy.

[Attending physicians in urology working at university centers or non-university centers-what are the differences? : Results of a web-based cross-sectional study at German hospitals]. / Urologische Oberärztinnen und Oberärzte an universitären oder nicht-universitären Kliniken ­ welche Unterschiede gibt es? : Ergebnisse einer webbasierten Querschnittstudie an deutschen Kliniken.

BACKGROUND: Attending physicians (AP) in urology represent a very heterogeneous group covering various clinical priorities and career objectives. To date, there are no reliable data on professional, personal and position-linked aspects of AP in urology working in university centers (univ-AP) opposed to those working in non-university centers (n-univ-AP). MATERIALS AND METHODS: The objective of this study was to analyze individual professional perspectives, professional and personal settings, specific job-related activities and individual professional goals of univ-AP opposed to n­univ-AP. Thus, a web-based survey containing 55 items was designed to perform a cross-sectional study that was then forwarded using a link which was sent via a mailing list of the German Society of Urology. The survey was available for completion by AP at German urological centers from February to April 2019. Group-specific differences were evaluated using bootstrap-adjusted multivariate logistic regression models. RESULTS: Of the 192 evaluable surveys, 61 (31.8%) and 131 (68.2%) were part of the univ-AP and n­univ-AP study group, respectively. Participating n­univ-AP compared to univ-AP held the position of AP (p = 0.022) significantly longer and were on call significantly more frequently (p < 0.001). AP in urology (self)-assessed themselves as autonomously confident in performing robotic, laparoscopic, open, endo-urologic, and plastic-reconstructive surgery in 12.4%, 25%, 59.6%, 92.1%, and 25.7%, respectively, with no significant differences between the two groups among all above mentioned surgical subdomains based on multivariate analysis. AP in urology were (very) content in 92% concerning the choice of their discipline, in 73.9% concerning their actual working circumstances, and in 60.2% concerning their level of surgical expertise. Only 27.1% and 19.9% were (very) content with the amount of available time for their personal professional development and for private affairs, respectively. As opposed to n­univ-AP, univ-AP would choose a career in clinical centers once again significantly more frequently (OR 2.87; p(BS) = 0.041), but assess the position of AP as their definitive career goal significantly less frequently (OR 0.42; p(BS) = 0.40). Univ-AP state significantly more frequently that they were running for the position of head of department or full professor (OR 5.64; p(BS) = 0.001). CONCLUSION: In this first survey study world-wide on AP in urology divided according to their academic background, similarities and variances were analyzed, baring the potential to further improve identification of AP for a career in clinical centers.

Radical cystectomy under continuous antiplatelet therapy with acetylsalicylic acid.

INTRODUCTION: Aim of this study was to analyse the perioperative outcome of patients undergoing radical cystectomy under continuous antiplatelet therapy with acetylsalicylic acid. MATERIALS AND METHODS: Using prospectively maintained databases of two departments of urology, we identified 461 consecutive patients who underwent radical cystectomy for bladder cancer (2011-2017). Patients were divided into three groups: 1) on-going antiplatelet therapy with acetylsalicylic acid (n = 50), 2) discontinuing antiplatelet therapy (n = 65) and 3) no antiplatelet therapy (n = 346). Perioperative outcome was compared between the three groups using ANOVA, likelihood ratio or Kruskal Wallis test with post-hoc testing. Uni- and multivariate analyses were performed to identify predictor for perioperative complications and transfusion. RESULTS: Group 1 showed an average estimated blood loss of 732 ±â€¯424, group 2 752 ±â€¯488 and group 3 810 ±â€¯544 ml (p = 0.51). There was no significant difference in transfusion rate (44% in group 1, 45% and 39% in groups 2 and 3, p = 0.63). Severe complications occurred in 26%, 15% and 15% in groups 1-3 (p = 0.19). Ischemic complications were more often observed in group 1 (n = 4, 8%) and 2 (n = 5, 8%) than group 3 (n = 7, 2%), p = 0.02. 90-day readmission (n = 99, 22%) and mortality rate (n = 10, 2.2%) were low and did not show any significant differences between the groups. In uni- and multivariate analysis ongoing therapy with acetylsalicylic acid was no independent risk factor for transfusion or severe complications. CONCLUSION: Perioperative continuation of therapy with acetylsalicylic acid in radical cystectomy is safe with no difference in intraoperative blood loss, transfusion rate, complications or mortality.

Influence of symptomatic pseudoaneurysms on postoperative renal function after partial nephrectomy: results of a matched pair analysis.

PURPOSE: A symptomatic pseudoaneurysm (SPA) is a rare but severe complication after partial nephrectomy (PN). Selective trans-arterial embolization (TAE) is the treatment of choice with high success rates. However, the influence of this intervention on postsurgical renal function has not been studied. METHODS: Between 2005 and 2016 we performed 1047 PNs at our institution. Postsurgical SPA occurred in 40 patients (3.8%). Patients with and without SPA were matched in a 1:2 ratio concerning tumor complexity (RENAL) and pre-operative renal function (CKD stage). Any CKD upstage and a relevant CKD progression (CKD ≥ III) were defined as endpoints. Furthermore, the influence of the amount of contrast agent applied during TAE was assessed. RESULTS: All patients with SPA were treated successfully with TAE. No significant difference could be detected concerning clinical, functional and surgical aspects. Median follow-up time accounted for 12.5 (6.75-27.5) months. Kaplan-Meier analyses detected an increased rate of any CKD upstage (p = 0.066) and relevant CKD progression (p = 0.01) in patients with SPA. Multivariate analysis identified post-operative SPA to be an independent predictor for a relevant CKD progression (HR 4.15, p = 0.01). The amount of contrast agents used did not have an impact on the development of a relevant CKD progression (p = 0.72). CONCLUSION: Patients treated with TAE after PN show an additional risk for an impairment of renal function over time. Hence, those patients should explicitly be informed about possible consequences and closely monitored by nephrologists.

Prognostic Value of Molecular Breast Cancer Subtypes based on Her2, ESR1, PGR and Ki67 mRNA-Expression in Muscle Invasive Bladder Cancer.

INTRODUCTION: Gene expression analyses have identified similarities between bladder and breast cancer, where clinical risk stratification is based on Her2, ESR1, PGR and Ki67 expression. The aim of the study was to assess the respective marker gene expression in patients treated with radical cystectomy for muscle-invasive bladder cancer (MIBC) and to evaluate the applicability of breast cancer subtypes for MIBC risk stratification. MATERIALS & METHODS: 102 patients treated with radical cystectomy for MIBC were assessed. Using routine FFPE tissue and an IVD validated kit, mRNA expression was measured by single step RT-qPCR. Partition test were employed to define cut-off values for high or low marker gene expression. Association of expression with outcome was assessed using Kaplan-Meier analysis and multivariate cox regression analysis. Finally, we performed validation of our results in the MD-Anderson cohort (n=57). RESULTS: Cancer specific survival (CSS) was impaired in patients with high gene expression of Her2 (P=0.0009) and ESR1 (P=0.04). In the multivariate regression model Her2 expression remained significant for the prediction of CSS (HR=2.11, CI 1.11-4.21, P=0.024). Furthermore, molecular stratification by breast cancer subgroups was significant (P=0.023) for CSS prediction. Especially the differentiation between Her2-positive and Luminal A (HR=4.41, CI 1.53-18.71, P=0.004) and Luminal B (HR=1.96, CI 0.99-4.08, P=0.053) respectively was an independent prognostic parameter for CSS. External validation resulted in comparable risk stratification with differences in fractional subgroups distribution. CONCLUSION: Gene expression of Her2, ESR1, PGR, Ki67 and corresponding breast cancer subtypes allow a risk-stratification in MIBC, whereby Her2 overexpressing tumors reveal a particularly poor prognosis.

[Ablative therapy of small renal masses]. / Ablative Therapien kleiner Nierentumoren.

Renal cell cancer is nowadays predominantly diagnosed in early stages due to the widespread use of sectional imaging for unrelated symptoms. Small renal masses (<4 cm) feature a largely indolent biology with a very low risk for metastasis or even a benign biology in up to 30% of the cases. Consequently, there is a need for less invasive therapeutic alternatives to nephron-sparing surgery. Meanwhile, there is a broad portfolio of local ablation techniques to treat small renal tumors. These include the extensively studied radiofrequency ablation and cryoablation techniques as well as newer modalities like microwave ablation and irreversible electroporation as more experimental techniques. Tumor ablation can be performed percutaneously under image guidance or laparoscopically. In particular, the percutaneous approach is a less invasive alternative to nephron-sparing surgery with lower risk for complications. Comparative studies and meta-analyses report a higher risk for local recurrence after renal tumor ablation compared to surgery. However, long-term oncological results after treatment of small renal masses are promising and do not seem to differ from partial nephrectomy. The possibility for salvage therapy in case of recurrence also accounts for this finding. Especially old patients with an increased risk of surgical and anesthesiological complications as well as patients with recurrent and multiple hereditary renal cell carcinomas may benefit from tumor ablation. Tumor biopsy prior to intervention is associated with very low morbidity rates and is oncologically safe. It can help to assess the biology of the renal mass and prevent therapy of benign lesions.

[Modern endoscopic imaging tools for urothelial carcinoma of the urinary bladder]. / Moderne endoskopische Bildgebungsverfahren für das Urothelkarzinom der Harnblase.

Cystoscopy is the gold standard for the initial diagnosis of urothelial carcinoma in the urinary bladder (UCB). White light exhibits significant limitations in its ability to detect flat lesions or carcinoma in situ. Photodynamic Diagnosis (PDD) and Narrow Band Imaging (NBI) are established techniques which may improve the detection rates of UCB and reduce the risk of recurrence. Multiple novel tools have been developed in order to improve the diagnostic accuracy of endoscopic procedures, including Digital Contrast Enhancement Technology, Confocal Laser Endomicroscopy (CLE) and Optical Coherence Tomography (OCT). In future, spectral analysis of urothelial lesions may be achieved by Raman spectroscopy, thus providing information about biological alterations in the tissue. Furthermore, molecular imaging may allow specific targeting by fluorescent antibodies or small molecule agents, thus enabling differential diagnosis of suspicious lesions. Software-based approaches have been developed to incorporate computer-aided diagnosis and improve digital documentation of endoscopic findings. This study reviews current and future developments in the field of modern endoscopy of the urinary bladder and discusses the different approaches.

Novel insights into a reputably irreversible process: combined mRNA and miRNA profiling of tissue from vesicourethral anastomotic stenosis after radical prostatectomy.

PURPOSE: Until recently, tissue fibrosis-ultimately leading to permanent scaring-has been considered an irreversible process. However, recent findings indicate that it may be reversible after all. Vesicourethral anastomotic stenosis (VUAS) as fibrous narrowing is a frequent complication after radical prostatectomy with high recurrence rates and requires invasive treatment. The pathophysiology is poorly understood. Therefore, a combined mRNA and miRNA transcription profiling in tissue from VUAS was performed using nCounter technology. METHODS: To assess tissue morphology and fiber composition, histochemical staining was performed. RNA expression of healthy and fibrotic tissue of twelve patients was analyzed using the human miRNA panel v3 and mRNA PanCancer pathway panel on the nCounter gene1 system and qRT-PCR. Differential expression data analysis was performed using the nSolver software implementing the R-based advanced pathway analysis tool. miRWalk2.0 was used for miRNA target prediction. RESULTS: More linearized tissue architecture, increased collagens, and decreased elastic fibers were observed in VUAS samples. 23 miRNAs and 118 protein coding genes were differentially expressed (p < 0.01) in fibrotic tissue. miRNA target prediction and overlap analysis indicated an interaction of the strongest deregulated miRNAs with 29 deregulated mRNAs. Pathway analysis revealed alterations in DNA repair, cell cycle regulation, and TGF-beta signaling. qRT-PCR confirmed differential expression of top deregulated miRNAs and mRNAs. CONCLUSIONS: In VUAS tissue, severe alterations on mRNA and miRNA level are found. These consistent changes give insights into the pathogenesis of VUAS after radical prostatectomy and point to future options for transcriptomics-based risk stratification and targeted therapies.