CEA (CEACAM5) expression is common in muscle-invasive urothelial carcinoma of the bladder but unrelated to the disease course.

Objectives: Carcinoembryonic antigen (CEA) is a cell surface glycoprotein that represents a promising therapeutic target. Serum measurement of shedded CEA can be utilized for monitoring of cancer patients. Material and Methods: To evaluate the potential clinical significance of CEA expression in urothelial bladder neoplasms, CEA was analysed by immunohistochemistry in more than 2500 urothelial bladder carcinomas in a tissue microarray format. Results: CEA staining was largely absent in normal urothelial cells but was observed in 30.4% of urothelial bladder carcinomas including 406 (16.7%) with weak, 140 (5.8%) with moderate, and 192 (7.9%) with strong staining. CEA positivity occurred in 10.9% of 411 pTaG2 low-grade, 32.0% of 178 pTaG2 high-grade, and 43.0% of 93 pTaG3 tumours (p < 0.0001). In 1335 pT2-4 carcinomas, CEA positivity (34.1%) was lower than in pTaG3 tumours. Within pT2-4 carcinomas, CEA staining was unrelated to pT, pN, grade, L-status, V-status, overall survival, recurrence free survival, and cancer specific survival (p > 0.25). Conclusion: CEA increases markedly with grade progression in pTa tumours, and expression occurs in a significant fraction of pT2-4 urothelial bladder carcinomas. The high rate of CEA positivity in pT2-4 carcinomas offers the opportunity of using CEA serum measurement for monitoring the clinical course of these cancers. Moreover, CEA positive urothelial carcinomas are candidates for a treatment by targeted anti-CEA drugs.

PD-L1 expression in tumor and inflammatory cells is associated with favorable tumor features and favorable prognosis in muscle-invasive urothelial carcinoma of the bladder not treated by immune checkpoint inhibitors.

BACKGROUND: A high level of PD-L1 expression is the most relevant predictive parameter for response to immune checkpoint inhibitor (CPI) therapy in urinary bladder cancer. Existing data on the relationship between PD-L1 expression and the natural course of disease are controversial and sparse. METHODS: To expand our understanding of the relationship between PD-L1 expression and parameters of cancer aggressiveness, PD-L1 was analyzed on tissue microarrays containing 2710 urothelial bladder carcinomas including 512 patients with follow-up data who underwent radical cystectomy and follow-up therapies in the pre-immune checkpoint inhibitor therapy era. RESULTS: Tumor cell positivity in ≥10% of cells were seen in 513 (20%) and an immune cell positivity occurred in 872 (34%) of 2566 interpretable cancers. PD-L1 positivity in tumor cells increased from pTaG2 low grade (0.9% positive) to pTaG3 high grade (4.1%; p = 0.0255) and was even higher in muscle-invasive (pT2-4) carcinomas (29.3%; p < 0.0001). However, within pT2-4 carcinomas, PD-L1 positivity was linked to low pT stage (p = 0.0028), pN0 (p < 0.0001), L0 status (p = 0.0005), and a better prognosis within 512 patients with cystectomy who never received CPIs (p = 0.0073 for tumor cells and p = 0.0086 for inflammatory cells). PD-L1 staining in inflammatory cells was significantly linked to PD-L1 staining in tumor cells (p < 0.0001) and both were linked to a positive p53 immunostaining (p < 0.0001). CONCLUSION: It cannot be fully excluded that the strong statistical link between PD-L1 status and favorable histological tumor features as well as better prognosis could influence the outcome of studies evaluating CPIs in muscle-invasive urothelial carcinoma.

Transplant nephrectomy: indication, surgical approach and complications-experiences from a single transplantation center.

PURPOSE: Management of a failed kidney allograft, and the question whether it should be removed is a challenging task for clinicians. The reported risks for transplant nephrectomy (TN) vary, and there is no clear recommendation on indications or surgical approach that should be used. This study gives an overview of indications, compares surgical techniques, and identifies risk factors for higher morbidity. METHODS: Retrospective analysis was conducted on all transplant nephrectomies performed between 2005 and 2020 at Charité Hospital Berlin, Department of Urology. Patient demographics, laboratory parameters, graft survival data, indication for TN, and surgical complications were extracted from medical reports. RESULTS: A total of 195 TN were performed, with graft intolerance syndrome being the most common indication in 52 patients (26.7%), acute rejection in 36 (18.5%), acute infection in 30 (15.4%), and other reasons to stop immunosuppression in 26 patients (13.3%). Rare indications were vascular complications in 16 (8.2%) and malignancies in the allograft in six (3.1%) cases. Extracapsular surgical approach was significantly more often used in cases of vascular complications and earlier allograft removal, but there was no difference in complication rates between extra- and intracapsular approach. Acute infection was identified as an independent risk factor for a complication grade IIIb or higher according to Clavien-Dindo classification, with a HR of 12.3 (CI 2.2-67.7; p = 0.004). CONCLUSION: Transplant nephrectomy should only be performed when there is a good indication, and non-elective surgery should be avoided, when possible, as it increases morbidity.

Prognostic Impact and Spatial Interplay of Immune Cells in Urothelial Cancer.

BACKGROUND AND OBJECTIVE: Quantity and the spatial relationship of specific immune cell types can provide prognostic information in bladder cancer. The objective of the study was to characterize the spatial interplay and prognostic role of different immune cell subpopulations in bladder cancer. METHODS: A total of 2463 urothelial bladder carcinomas were immunostained with 21 antibodies using BLEACH&STAIN multiplex fluorescence immunohistochemistry in a tissue microarray format and analyzed using a framework of neuronal networks for an image analysis. Spatial immune parameters were compared with histopathological parameters and overall survival data. KEY FINDINGS AND LIMITATIONS: The identification of > 300 different immune cell subpopulations and the characterization of their spatial relationship resulted in numerous spatial interaction patterns. Thirty-nine immune parameters showed prognostic significance in univariate analyses, of which 16 were independent from pT, pN, and histological grade in muscle-invasive bladder cancer. Among all these parameters, the strongest association with prolonged overall survival was identified for intraepithelial CD8+ cytotoxic T cells (time-dependent area under receiver operating characteristic curve [AUC]: 0.70), while stromal CD8+ T cells were less relevant (AUC: 0.65). A favorable prognosis of inflamed cancers with high levels of "exhaustion markers" suggests that TIM3, PD-L1, PD-1, and CTLA-4 on immune cells do not hinder antitumoral immune response in tumors rich of tumor infiltrating immune cells. CONCLUSIONS AND CLINICAL IMPLICATIONS: The density of intraepithelial CD8+ T cells was the strongest prognostic feature in muscle-invasive bladder cancer. Given that tumor cell killing by CD8+ cytotoxic T lymphocytes through direct cell-to-cell-contacts represents the "terminal end route" of antitumor immunity, the quantity of "tumor cell adjacent CD8+ T cells" may constitute a surrogate for the efficiency of cancer recognition by the immune system that can be measured straightaway in routine pathology as the CD8 labeling index. PATIENT SUMMARY: Quantification of intraepithelial CD8+ T cells, the strongest prognosticfeature identified in muscle-invasive bladder cancer, can easily be assessed by brightfield immunohistochemistry and is therefore "ready to use" for routine pathology.

Loss of Upk1a and Upk1b expression is linked to stage progression in urothelial carcinoma of the bladder.

BACKGROUND: Uroplakin-1a (Upk1a) and uroplakin-1b (Upk1b) have recently been identified as diagnostic markers for the distinction of urothelial carcinomas from other solid tumor entities. Both proteins play an important role in the stabilization and strengthening of epithelial cells that line the bladder. METHODS: To evaluate the prognostic role of uroplakin expression in urothelial carcinomas, more than 2700 urothelial neoplasms were analyzed in a tissue microarray format by immunohistochemistry. To further assess the diagnostic role of uroplakin immunohistochemistry, results were compared with preexisting GATA3 data. RESULT: The fraction of Upk1a/Upk1b positive cases decreased slightly from pTaG2 low-grade (88% positive for Upk1a/87% positive for Upk1b) and pTaG2 high-grade (92%/89%) to pTaG3 (83%/88%; p > 0.05) and was lower in muscle-invasive (pT2-4) carcinomas (42%/64%; p < 0.0001/p < 0.0001 for pTa vs. pT2-4). Within pT2-4 carcinomas, high expression of Upk1a and Upk1b was linked to nodal metastasis and lymphatic vessel infiltration (p < 0.05) but unrelated to patient outcome. There were significant associations between Upk1a, Upk1b and GATA3 immunostaining (p < 0.0001 each), but 11% of GATA3 negative cancers were Upk1a/b positive and 8% of Upk1a/b negative cancers were GATA3 positive. Absence of GATA3/Upk1a/b staining was significantly linked to poor patient survival in the subgroup of 126 pT4 carcinomas (p = 0.0004) but not in pT2 and pT3 cancers. CONCLUSIONS: In summary, the results of our study demonstrate that Upk1a and/or Upk1b immunohistochemistry can complement GATA3 for the distinction of urothelial carcinomas. Furthermore, a progressive loss of Upk1a/b expression during stage progression and a prognostic role of the combination GATA3/Upk1a/Upk1b in pT4 carcinomas is evident.

Altered p53/p16 expression is linked to urothelial carcinoma progression but largely unrelated to prognosis in muscle-invasive tumors.

BACKGROUND: Most inactivating p53 mutations result in a nuclear p53 accumulation - detectable by immunohistochemistry (IHC). p53 alterations leading to a complete lack of p53 protein and absence of immunostaining do also occur - not easily detectable by IHC. p16 is upregulated in p53 inactivated cells. We hypothesized that a positive p16 IHC may help to distinguish p53 inactivation in IHC negative cases. MATERIAL AND METHODS: We investigated p53 and p16 immunostaining on 2710 urothelial bladder carcinomas in a tissue microarray format to understand their impact in relation to clinicopathological parameters of disease progression and patient outcome. RESULTS: p16 immunostaining was absent in normal urothelium but occurred in 63.5% (30.4% strong) of cancers. p16 strongly positive cases increased from pTaG2 low-grade (9.6%) to pTaG3 high-grade tumors (46.5%, p < .0001) but decreased from pTaG3 to pT4 (33.3%; p = .0030). Among pT2-4 carcinomas, p16 positivity was linked to high-grade (p = .0005) but unrelated to overall survival. p53 staining was negative in 8.4%, very weak in 15.4%, weak in 55.3%, strong in 4.7%, and very strong in 16.2% cancers. p53 negative (potentially p53 null phenotype), strong, and very strong p53 positivity increased from pTaG2 low-grade to pTaG3 high-grade tumors (p < .0001) and from pTaG3 to pT2-4 cancers (p = .0007). p53 staining was largely unrelated to histopathological parameters or patient prognosis among pT2-4 carcinomas, except of p53 strong/very strong immunostaining. p16 expression predominated in tumors with very strong, strong, and negative p53 staining and the combination of p53 negative/p16 strongly positive cancers was linked to features of tumor aggressiveness. CONCLUSION: Aberrant p53 and p16 immunostaining increases during grade and stage progression although p53 negative and p16 positive immunostaining lack prognostic significance in pT2-4 carcinomas. Potential diagnostic features are that high level p16 expression is limited to neoplastic urothelium and p53 null phenotype to aggressive cancers (grade 3 and invasive).

SARS-CoV-2 mRNA vaccination-induced immunological memory in human nonlymphoid and lymphoid tissues.

Tissue-resident lymphocytes provide organ-adapted protection against invading pathogens. Whereas their biology has been examined in great detail in various infection models, their generation and functionality in response to vaccination have not been comprehensively analyzed in humans. We therefore studied SARS-CoV-2 mRNA vaccine-specific T cells in surgery specimens of kidney, liver, lung, bone marrow, and spleen compared with paired blood samples from largely virus-naive individuals. As opposed to lymphoid tissues, nonlymphoid organs harbored significantly elevated frequencies of spike-specific CD4+ T cells compared with blood showing hallmarks of tissue residency and an expanded memory pool. Organ-derived CD4+ T cells further exhibited increased polyfunctionality over those detected in blood. Single-cell RNA-Seq together with T cell receptor repertoire analysis indicated that the clonotype rather than organ origin is a major determinant of transcriptomic state in vaccine-specific CD4+ T cells. In summary, our data demonstrate that SARS-CoV-2 vaccination entails acquisition of tissue memory and residency features in organs distant from the inoculation site, thereby contributing to our understanding of how local tissue protection might be accomplished.

Current perceptions and working time models of female urologists in Germany: results of a large-scale survey.

PURPOSE: Female urologists are distinctly underrepresented in leading positions. The reasons behind this inequity remain unclear, with some suggesting factors such as family responsibilities, part-time work and insufficient mentorship. This study aimed to explore and characterize the working conditions of female urologists in Germany, with a focus on factors influencing the working time model. METHODS: A questionnaire was developed and distributed to 1343 female members of the German Society of Urology between February and March 2022. The survey consisted of 43 questions covering the categories demographics, occupation situation, satisfaction at work, family situation, career aspects and research activity. RESULTS: Of the 487 female German urologists who participated in the survey, 167 (34.3%) worked part-time. Doctors in training were significantly less likely to work part-time than colleagues who had completed their specialist training (p < 0.001). Only 10% of female doctors in training reported working part-time. Similarly, having children (p < 0.001) and engaging in scientific activities (p = 0.03) were independent factors influencing part-time work, with children increasing the likelihood of working part-time as expected, while scientifically active female urologists were more likely to work full-time. CONCLUSION: This study provides the largest survey on the situation of female urologists in German-speaking countries to date. Part-time work during specialist training is rare, while more than 50% of female urologists with children work part-time. With the projected decline in the number of practicing physicians and the increasing demand for medical attention, it is crucial to find ways to retain and support healthcare professionals, particularly female urologists.

[Factors influencing job satisfaction of female urologists-results of a survey by the German Society of Urology (DGU)]. / Einflussfaktoren für die Berufszufriedenheit von Urologinnen ­ Ergebnisse einer Befragung der Deutschen Gesellschaft für Urologie e. V. (DGU).

INTRODUCTION: Job satisfaction is a valuable good. However, literature on job satisfaction of female and male physicians, especially in the field of urology, is scarce. Therefore, the aim of this study was to evaluate job satisfaction among female members of the German Society of Urology (DGU). MATERIALS AND METHODS: An online questionnaire was sent to 1343 female members of the DGU in Germany, Austria, and Switzerland. The responses of 521 female physicians were statistically analyzed regarding baseline characteristics and in relation to job satisfaction and satisfaction with the choice of specialty. RESULTS: The median age of the participants was 37 (IQR 33; 45) years. While 91% of the respondents were rather or very satisfied with their choice of specialty-urology-only about 54% of the female urologists were satisfied with their job situation. Of the female urologists satisfied (vs. not satisfied) with their professional situation, 95% (vs. 87%) were also satisfied with their choice of urology as their specialty. Satisfaction with the working time model (odds ratio [OR] 9.61) and feeling unequal treatment (OR: 0.18) were independent predictors of satisfaction with the professional situation. CONCLUSION: Considering the increasing proportion of women in the health sector, it is important to identify factors influencing decisions on career and choice of specialty as well as career progression. Achieving career goals, increasing satisfaction with the working time model, and reducing unequal treatment or discrimination are central arguments for sustainably increasing the job satisfaction of female urologists.

Use of the Allium Round Posterior Stent for the Treatment of Recurrent Vesicourethral Anastomosis Stricture.

OBJECTIVE: To compare outcomes of monopolar incision and Allium Round Posterior Stent (RPS) insertion for the treatment of recurrent vesicourethral anastomosis stricture. METHODS: Having a suprapubic catheter and an obstructed pattern with a peak flow rate (PFR) ≤12 mL/s on uroflowmetry were the indications for the surgery. Once the fibrotic vesicourethral anastomosis was incised, RPS was inserted at the level of vesicourethral anastomosis under fluoroscopic guidance. All the stents were removed at postoperative first year. Patients were evaluated 3months after stent removal. Objective cure was defined as no need to further treatments and PFR ≥12 mL/s while subjective cure was defined as having points <4 on Patient Global Impression of Improvements scale. RESULTS: Of the 30 patients with a median age 66 (52-74) enrolled in the study, 18 had a suprapubic catheter, remaining 12 had median PFR 5.2 (2-10) mL/s. Stent migration was noted in two patients, these stents were replaced by new ones. Stone formation was diagnosed in one patient, a pneumatic-lithotripsy was performed. The median follow-up time was 28 (4-60) months following stent removal. Six cases needed further treatment after removal. The median PFR of remaining 24 patients was 20 (16-30) mL/s (P = .001). The objective cure rate was 24/30(80%), the Patient Global Impression of Improvements scores varied from 1 to 2, meaning subjective cure rate was 24/30(80%). For the six failed cases, according to patient preferences a lifetime RPS insertion was planned. CONCLUSION: With its minimally invasive nature, reversibility, and acceptable success and complication rates, incision of anastomosis and insertion of the RPS for a 1-year duration is a promising option for the treatment of recurrent vesicourethral anastomosis stricture.

Robot-Assisted Laparoscopic Prostatectomy Experience and Pathological Quality: Are They Always Linked?

Objective: We investigated whether pathological outcomes improved with experience and surgeon generation after robot-assisted laparoscopic prostatectomy (RALP). Materials and Methods: The study included 1338 patients who underwent RALP between February 2010 and April 2020. We created learning curves for pelvic lymph node dissection (PLND), number of lymph nodes (LNs) removed, and positive surgical margin (PSM) after adjustment for confounders. We compared the outcomes between the first and second generation of surgeons in regression models. Results: The learning curve regarding PLND indications showed a significant increase with experience for the first generation, whereas the second generation had a learning curve that remained flat at a higher level (92.3%) and significantly better than the first generation (p < 0.001). Similarly, the number of LN removed showed a significant increase with experience in both generations, but the overall median number of LN removed was significantly higher in the second generation compared with the first generation (12 vs 10, p < 0.001). However, the learning curve for PSM remained flat at ∼20% after adjustment and did not show improvement with experience in both generations of surgeons (p = 0.794). Conclusions: Surgeons showed improvement with experience and education with RALP with respect to the indications for PLND and number of LNs removed. However, there was no improvement over time and generations for PSM. Experience based solely on the number of patients operated on is not an intrinsic factor in the pathological quality of RALP. Factors other than experience may also play a role in oncologic improvement.

The Allium Ureteral Stent for the Treatment of Ureteral Complications Following Renal Transplantation-A Single-Center, Single-Surgeon Series.

Ureteral complications such as urinary leak, ureteral necrosis or ureteral stenosis are common complications after renal transplantation with major short- and long-term issues, including graft impairment and graft loss. At present, there is no agreement on the optimal management of ureteral complications. The aim of the current study was to evaluate the safety and efficacy of the self-expanding, large-caliber Allium ureteral stent in patients with ureteral complications following renal transplantation. In this retrospective study, the electronic database of Charité University Hospital was screened for patients receiving the self-expandable Allium ureteral stent in the transplant ureter after kidney transplantation between January 2016 and March 2022. Descriptive statistics were used to describe the outcomes. There were six men and four women with a median age of 61 years (interquartile range, 55 to 68 years). Nine out of 10 patients had ureteric stenosis, which was diagnosed at a median of two years (interquartile range 10 months to 9 years) following renal transplantation. The median operating time was 49 min (interquartile range, 30 to 60 min). Endoscopic Allium stent placement was successful in all patients with ureteric stenosis. The median length of stay in the hospital was four days (interquartile range 2 to 7 days). Only one patient (#5) had a postoperative grade IIIb Clavien-Dindo complication. Patients had follow-ups every 3 months with ultrasound and serum creatinine. Dislocation of the Allium stent was seen in four patients; all occurred within three months. Ultimately, three patients required ureteric re-implantation, two of which had early dislocation of the stent. Six patients are managed with a permanent Allium stent. The median dwell time was 11 months (interquartile range 3 to 20 months) and maximum dwell time was 23 months. The overall success rate was 60% (6 out of 10). According to our data, the Allium stent represents a safe and minimally invasive option with a success rate of 60%. It might, therefore, represent an alternative to DJ stents, nephrostomies or immediate re-implantation. As all dislocations occurred within three months, frequent early postoperative follow-up is required.

Cytokeratin 20 expression is linked to stage progression and to poor prognosis in advanced (pT4) urothelial carcinoma of the bladder.

Cytokeratin 20 (CK20) expression is limited to umbrella cells in the normal urothelium. Since CK20 is often upregulated in neoplastic urothelial cells including dysplasia and carcinoma in situ, immunohistochemical CK20 analysis is often used for the assessment of bladder biopsies. CK20 expression is a feature of luminal bladder cancer subtype, but its prognostic relevance is disputed. In this study, we investigated CK20 on >2700 urothelial bladder carcinomas in a tissue microarray format by immunohistochemistry. Cytoplasmic and membranous CK20 staining was seen in 1319 (51.8%) cancers. The fraction of CK20 positive and especially strongly positive cases increased from pTaG2 low grade (44.5% strongly positive) and pTaG2 high grade (57.7%) to pTaG3 high grade (62.3%; p = 0.0006) but was lower in muscle-invasive (pT2-4) carcinomas (51.1% in all pTa vs. 29.6% in pT2-4; p < 0.0001). Within pT2-4 carcinomas, CK20 positivity was linked to nodal metastasis and lymphatic vessel invasion (p < 0.0001 each) and to venous invasion (p = 0.0177). CK20 staining was unrelated to overall patient survival if all 605 pT2-4 carcinomas were jointly analyzed but subgroup analyses revealed a significant association of CK20 positivity with favorable prognosis in 129 pT4 carcinomas (p = 0.0005). CK20 positivity was strongly linked to the expression of GATA3 (p < 0.0001), another feature of luminal bladder cancer. The combined analysis of both parameters showed best prognosis for luminal A (CK20+/GATA3+, CK20+/GATA3-) and worst outcome for luminal B (CK20-/GATA3+) and basal/squamous (CK20-/GATA3-) in pT4 urothelial carcinomas (p = 0.0005). In summary, the results of our study demonstrate a complex role of CK20 expression in urothelial neoplasms including neoexpression in pTa tumors, a subsequent loss of CK20 expression in a subset of tumors progressing to muscle-invasion, and a stage dependent prognostic role in muscle-invasive cancers.

Subjective Outcome after Discontinuation of Botulinum Toxin-A Detrusor Injection for Lower Urinary Tract Disorders: The Majority Suffers!

INTRODUCTION: According to the EAU guidelines, botulinum toxin type A (BoNT-A) detrusor injections are one of the last options in the management of overactive bladder before opting for invasive surgery. So far, there have been no studies dedicated exclusively to such patients who have undergone this treatment and in whom this treatment has presumably failed. From the patient's point of view, there are questions regarding what reasons led to discontinuation, how patients perceive their BoNT-A treatment in hindsight, what further treatment do these patients receive, and how satisfied such patients are with their current situation. METHODS: A database of clinical and inpatient records was searched, and 695 records from 406 patients were identified in a 6-year period, who had received BoNT-A detrusor injections. There were 255 cases that were treated with BoNT-A injections into the detrusor muscle where the therapy was not repeated for at least 12 months (= suspected treatment failures). Interviews with these patients were conducted by mail and phone, and 115 questionnaires could be included in the analysis. RESULTS: From the subjective and prospective points of view of the patients, the most common reason for stopping the therapy was a lack of efficacy of BoNT-A injections (39.1%). For 26.1% of all patients, side effects were a reason for dissatisfaction but never a reason for discontinuation. For 10.4%, the reason for stopping the therapy was spontaneous improvement. 35.6% of the respondents had no follow-up therapy. Those with a follow-up therapy mostly returned to anticholinergic treatment (33%). Operations were carried out on 13%, of which about half were highly invasive. For 71.3% of those patients, who were under any current therapy, this therapy led to no improvement or only some improvement of the symptoms. Surprisingly, 50.4% of the respondents would choose to undergo BoNT-A injection therapy again. DISCUSSION/CONCLUSION: The majority of patients who did not continue BoNT-A therapy are still suffering from lower urinary tract symptoms. The lack of efficacy was the reason for stopping the BoNT-A injection therapy for less than half of the patients. From the patient's point of view, reasons other than the effectiveness also seem to be relevant in the choice of the treatment. When changing therapy, most returned to drug treatment. However, for the majority of patients with any follow-up therapy, this therapy could not improve the symptoms.

[Onabotulium toxin A detrusor injection: The "real world" of users, the "real world" of patients - Update BOTUROLOGY 2022]. / OnabotuliumtoxinA Detrusorinjektion: Die "Real World" der Anwender, die "Real World" der Patienten ­ Update BOTUROLOGY 2022.

BACKGROUND: OnabotulinumtoxinA (Botox) has been approved in Germany since 2013 for the second-line treatment of idiopathic overactive bladder in the form of a detrusor injection (OnabotA DI) after failure of anticholinergic therapy. Until 2018, however, its application lagged far behind the demand due to billing hurdles. Since the beginning of 2018, there has been an EBM (German Uniform Evaluation Standard) approval number in Germany for the transurethral application of Botox in urology. QUESTION: The aim of a survey performed in 2019 among course participants of regular injection workshops (WS-P) in our institution was to evaluate whether billability has changed user behaviour in Germany in line with the demand. A similar survey was carried out in 2021 to show the developments over the past two years. MATERIAL AND METHODS: In 2019, 88 consecutive participants in a user workshop that had been held regularly since 2013 were asked about their OnabotA DI practice anonymously via questionnaire. The survey was repeated in 2021 in an anonymous online survey of 55 course participants in order to evaluate changes in user behaviour over the past two years. RESULTS: Evaluation 2019: Response rate 35/88 of the questionnaires (39.8%); a large majority (82%) of the WS-P attended the workshop AFTER the establishment of the EBM code. Only 54.5% of the WS-P performed two or more (12% more than 10) OnabotA DIs per quarter after the workshop. Most users (85%) always or predominantly performed the procedure on an outpatient basis, 63% always or predominantly under local anesthesia. The majority (84%) administered no or only a perioperative antibiotic treatment, 13% for one week. 89% stated that at least 70% of their patients had no or only mild symptoms under the LA. In the 2021 evaluation, the users tended to perform the procedure more often on an outpatient basis and in LA, and more often without any antibiotics. CONCLUSIONS: The results of our user survey indicate that the implementation of the OnabotA DI has gained significant impetus since the EBM approval in Germany in January 2018. In most cases, the procedure can be performed easily on an outpatient basis under local anesthesia.

Loss of TROP2 and epithelial cell adhesion molecule expression is linked to grade progression in pTa but unrelated to disease outcome in pT2-4 urothelial bladder carcinomas.

Introduction: Trophoblast cell surface antigen 2 (TROP2; EpCAM2) is a transmembrane glycoprotein which is closely related to EpCAM (EpCAM; EpCAM1). Both proteins share partial overlapping functions in epithelial development and EpCAM expression but have not been comparatively analyzed together in bladder carcinomas. TROP2 constitutes the target for the antibody-drug conjugate Sacituzumab govitecan (SG; TrodelvyTM) which has been approved for treatment of metastatic urothelial carcinoma by the United States Food and Drug administration (FDA) irrespective of its TROP2 expression status. Methods: To evaluate the potential clinical significance of subtle differences in TROP2 and EpCAM expression in urothelial bladder cancer, both proteins were analyzed by multiplex fluorescence immunohistochemistry in combination with a deep-learning based algorithm for automated cell detection on more than 2,700 urothelial bladder carcinomas in a tissue microarray (TMA) format. Results: The staining pattern of TROP2 and EpCAM were highly similar. For both proteins, the staining intensity gradually decreased from pTa G2 low grade (TROP2: 68.8±36.1; EpCAM: 21.5±11.7) to pTa G2 high grade (64.6±38.0; 19.3±12.2) and pTa G3 (52.1±38.7; 16.0±13.0, p<0.001 each). In pT2-4 carcinomas, the average TROP2 and EpCAM staining intensity was intermediate (61.8±40.9; 18.3±12.3). For both proteins, this was significantly lower than in pTa G2 low grade (p<0.001 each) but also higher than in pTa G3 tumors (p=0.022 for TROP2, p=0.071 for EpCAM). Within pT2-4 carcinomas, the TROP2 and EpCAM staining level was unrelated to pT, grade, UICC-category, and overall or tumor-specific patient survival. The ratio TROP2/EpCAM was unrelated to malignant phenotype and patient prognosis. Conclusion: Our data show that TROP2 and EpCAM expression is common and highly interrelated in urothelial neoplasms. Despite of a progressive loss of TROP2/EpCAM during tumor cell dedifferentiation in pTa tumors, the lack of associations with clinicopathological parameters in pT2-4 cancer argues against a major cancer driving role of both proteins for the progression of urothelial neoplasms.

GATA3 expression loss is linked to stage progression but is unrelated to prognosis in muscle-invasive urothelial carcinoma of the bladder.

The transcription factor GATA binding protein 3 (GATA3) is commonly used in surgical pathology as a diagnostic marker to distinguish urothelial carcinomas from other cancer entities. However, the clinical relevance of GATA3 expression in urothelial bladder cancer is not completely clarified. In this study, we investigated GATA3 immunostaining on 2710 urothelial bladder carcinomas on a tissue microarray platform by using two different antibodies to better understand its impact in relation to pathological parameters of disease progression and patient outcome. Nuclear GATA3 immunostaining was regularly seen in normal urothelium and found in 74%/82% of interpretable urothelial neoplasms depending on the antibody used. Within pTa tumors, the rate of GATA3 positive tumors decreased with advancing grade. GATA3 positivity was seen in 98.6%/99.8% of pTaG2 low-grade, 98.6%/100% of pTaG2 high-grade, and 94.9%/99.2% of pTaG3 high-grade tumors (P = .0002). As compared to pTa tumors, GATA3 positivity was markedly less common in muscle-invasive urothelial carcinoma (59.9%/71.6%; P < .0001). Within pT2-4 cancers, high-level GATA3 immunostaining was associated with the presence of lymph node metastasis (P = .0034), and blood vessel (P = .0290) or lymphatic invasion (P = .0005) but unrelated to pT stage. GATA3 immunostaining results for both antibodies were not associated with overall survival in 586 patients treated by cystectomy for pT2-4 urothelial carcinoma. The results of our study identify GATA3 expression as a frequent event in noninvasive urothelial carcinomas with favorable tumor features. Loss of GATA3 immunostaining is linked with muscle-invasive disease but is largely unrelated to pathological parameters and patient prognosis.

[Promoting women in urology using the example of habilitation]. / Frauenförderung in der Urologie am Beispiel der Habilitation.

BACKGROUND: The proportion of female urologists is steadily increasing, yet they continue to be underrepresented in academic leadership positions. A postdoctoral lecture qualification (habilitation), which is mandatory for a successful scientific career, is achieved significantly less often by female urologists in Germany than by their male colleagues. OBJECTIVE: To identify factors to effectively promote female urologists into academic leadership positions, the current situation, as well as factors influencing successful habilitation of women who are members of the German Society of Urology (Deutsche Gesellschaft für Urologie [DGU]) were investigated. METHODS: An online questionnaire was distributed to 1343 female members of the DGU in Germany, Austria, and Switzerland. The responses of 521 women were statistically analyzed with respect to baseline characteristics and in relation to research funding. The primary endpoint of our study was the habilitation rate. RESULTS: The average age of the 521 participating female urologists who completed the questionnaire was 37 years (range 21-67 years). Of these, most female physicians were in postgraduate training (n = 168, 32%), worked full-time (n = 324, 62%), and had children (n = 277, 53%). Overall, 359 (69%) of the participants had a PhD and 63 (12%) were still working on their PhD. Thirty (5.8%) female urologists had a habilitation. In univariable logistic regression models, age (odds ratio [OR] 1.06), working time model (part-time OR 0.19), a research fellowship (OR 21.4), release from clinical work for research purposes (OR 13.7), and participation in a funding program (OR 6.9) or mentoring program (OR 7.0) were independent predictors of achieving habilitation. Whether a urologist had children was not an independent predictor of achieving habilitation. In multivariable logistic regression models, age (OR 1.08), and a research fellowship (OR 9.04) were independent predictors of achieving habilitation. CONCLUSIONS: Promoting habilitation among female urologists is required in order to increase the proportion of women in leading academic positions. The results of the data analysis show that the promotion of research fellowships explicitly for women could be a promising approach.

Real-Time Documentation of the Effect of Onabotulinumtoxin A Detrusor Injection in OAB Patients-Preliminary Results.

Introduction: Detrusor injection with onabotulinumtoxin A (OnabotA-DI) is an established therapy for overactive bladder (OAB). Little is known about the exact onset and course of the effect in the days after the injection therapy. By using a new type of app-controlled automated diary pod, for the first time, the precise onset of the effect of OnabotA-DI can be documented in real time. Materials and methods: Patients due for OnabotA-DI were asked to document voiding 3 days before and up to 3 weeks after therapy using the Diary Pod app. The detrusor injection was performed with onabotulinumtoxin A (Botox®), 100 units, at 20 sites of the detrusor muscle in a standardized manner. Voiding on the injection day itself was not documented. Results: A total of 17 patients (15 women, 2 men; aged 33−83 (mean 64.6; median 70) years) were included in the study. The handling of the Diary Pod app was user-friendly, and elderly patients did not encounter technical problems. The results of patients with reliably documented micturitions showed a continuous reduction in micturition frequency every day from the first day and significantly from day 5. For 24 h voiding, from 12.83 ± 5.54 in the 3 days before injection, the following mean values were found with significant (p < 0.05) changes after the intervention: 9.17 ± 3.19 on day 5, 8.75 ± 3.69 on day 10, 7.17 ± 2.04 on day 15, and 5.75 ± 0.5 on day 20. These changes were in similar proportions during the daytime and nighttime. Conclusions: Contrary to previous knowledge, the effect of the OnabotA-DI set in from the first postoperative days and was reflected a similar extent in day and night micturition. This study is the first to document the onset of action of OnabotA-DI in real time.

Nephron Sparing Surgery in Renal Allograft in Recipients with de novo Renal Cell Carcinoma: Two Case Reports and Review of the Literature.

We report 2 cases of de novo renal cell carcinoma (RCC) in renal grafts after transplantation. Both patients underwent nephron sparing surgery (NSS) 211 and 167 months after transplantation, revealing papillary RCC with a tumour size >4 cm (pT1a). Within a follow-up of 25 and 32 months after NSS, a stable renal function without indication for dialysis was present. No recurrence of RCC in both cases was reported within the yearly routine examinations. NSS in kidney allografts is a safe procedure with preservation of renal function.