Both radiographical and pathological lymph node statuses are independent predictors for survival following neoadjuvant chemotherapy and radical cystectomy for cT3/4 or cN+ bladder cancer.

INTRODUCTION: Urothelial bladder cancer (UBC) with clinical suspicion of locally advanced growth or pelvic lymphogenic spread has a high risk of progression and death. PATIENTS AND METHODS: Bladder cancer patients with locally advanced (cT3/4) tumor growth or suspected pelvic lymphogenic spread (cN+) were treated with preoperative cisplatin-containing chemotherapy and consolidative cystectomy with pelvic lymphadenectomy. We aimed to identify prognostic factors and describe the patients' oncological outcome. RESULTS: A complete dataset including follow-up data was available for 96 patients. In a univariate analysis, we identified cN stage (cN+ vs cN-, HR 2.7, 95% CI 1.3-6.0), response to chemotherapy (HR 0.2, 95% CI 0.1-0.5), ypT stage (ypT0/is/1 vs ypT2-4, HR 3.1, 95% CI 1.4-6.8), ypN stage (ypN + vs ypN-, HR 7.9, 95% CI 3.7-17.0), resection status (HR 4.4, 95% CI HR 1.5-13.0) as significantly associated with cancer-specific survival. In a multivariate regression analysis, both cN and ypN statuses were validated as independent prognostic factors for cancer-specific survival (cN: HR 2.6, 95% CI 1.1-6.1; ypN: HR 5.5, 95% CI 2.0-15.1). DISCUSSION: Lymph node status was identified as a prognostic marker in a high-risk cohort of UBC patients treated with inductive chemotherapy and cystectomy. Establishing cN status as a prognosticator underlines the necessity to aggressively treat these patients despite reported impreciseness of imaging procedures in UCB. Patients with histologically positive lymph nodes following preoperative chemotherapy have a very poor prognosis, and thus, the need for adjuvant systemic treatment is emphasized. CONCLUSION: Both clinically and pathologically affected lymph nodes convey a poor prognosis in bladder cancer and necessitate aggressive treatment.

Does experience change the role of systematic biopsy during MRI-fusion biopsy of the prostate?

PURPOSE: To determine the role of biopsy experience regarding a potential benefit of additional systematic biopsies and fusion failures during MRI-targeted biopsy of the prostate. SUBJECTS/PATIENTS AND METHODS: We retrospectively evaluated 576 men undergoing transrectal (MRI)-targeted biopsy of the prostate by seven residents in urology between November 2019 and March 2022. Benefit of systematic biopsies (detection of ISUP ≥ 2 PCa (clinically significant PCa (csPCa)) solely in systematic biopsies) and fusion failure (detection of csPCa during systematic biopsies in the area of a reported MRI-lesion and no detection of csPCa in targeted biopsy) were compared by growing biopsy experience levels. Multivariable regression analyses were calculated to investigate the association with benefit of systematic biopsies and fusion failure. RESULTS: The overall PCa detection rate was 72% (413/576). A benefit of systematic biopsies was observed in 11% (63/576); of those, fusion failure was seen in 76% (48/63). Benefit of systematic biopsies and fusion failure were more common among residents with very low experience compared to highly experienced residents (18% versus 4%, p = 0.026; 13% versus 3%, p = 0.015, respectively). Increasing biopsy experience was associated with less benefit from systematic biopsies (OR: 0.98, 95% CI 0.97-0.99) and less fusion failure (OR: 0.98, 95% CI 0.97-0.99). CONCLUSIONS: The benefit of systematic biopsies following targeted biopsy decreases with growing biopsy experience. The higher risk of fusion failure among inexperienced residents necessitates systematic biopsies to ensure the detection of csPCa. Further prospective trials are warranted before a targeted only approach can be recommended in routine clinical practice.

Sex hormones modulate pathogenic processes in experimental traumatic brain injury.

Clinical and animal studies have revealed sex-specific differences in histopathological and neurological outcome after traumatic brain injury (TBI). The impact of perioperative administration of sex steroid inhibitors on TBI is still elusive. Here, we subjected male and female C57Bl/6N mice to the controlled cortical impact (CCI) model of TBI and applied pharmacological inhibitors of steroid hormone synthesis, that is, letrozole (LET, inhibiting estradiol synthesis by aromatase) and finasteride (FIN, inhibiting dihydrotestosterone synthesis by 5α-reductase), respectively, starting 72 h prior CCI, and continuing for a further 48 h after CCI. Initial gene expression analyses showed that androgen (Ar) and estrogen receptors (Esr1) were sex-specifically altered 72 h after CCI. When examining brain lesion size, we found larger lesions in male than in female mice, but did not observe effects of FIN or LET treatment. However, LET treatment exacerbated neurological deficits 24 and 72 h after CCI. On the molecular level, FIN administration reduced calpain-dependent spectrin breakdown products, a proxy of excitotoxicity and disturbed Ca2+ homeostasis, specifically in males, whereas LET increased the reactive astrocyte marker glial fibrillary acid protein specifically in females. Examination of neurotrophins (brain-derived neurotrophic factor, neuronal growth factor, NT-3) and their receptors (p75NTR , TrkA, TrkB, TrkC) revealed CCI-induced down-regulation of TrkB and TrkC protein expression, which was reduced by LET in both sexes. Interestingly, FIN decreased neuronal growth factor mRNA expression and protein levels of its receptor TrkA only in males. Taken together, our data suggest a sex-specific impact on pathogenic processes in the injured brain after TBI. Sex hormones may thus modulate pathogenic processes in experimental TBI.

[Sequential therapy of advanced bladder cancer after prior perioperative systemic treatment : Recommendations from the Interdisciplinary Bladder Carcinoma Working Group (IABC) of the DKG e. V.] / Sequenztherapie des fortgeschrittenen Urothelkarzinoms der Harnblase nach vorheriger perioperativer Systembehandlung : Empfehlungen aus der Interdisziplinären Arbeitsgruppe BlasenCarcinom (IABC) der Deutschen Krebsgesellschaft e. V. (DKG).

Guidelines can only give treatment recommendations for defined patient groups if high quality and meaningful evidence is available. However, patients included in clinical trials for the treatment of metastatic and/or locally advanced bladder cancer (mUC) are generally not representative for the spectrum of patients encountered in daily clinical practice. In particular, patients with different systemic pretreatments, variable prestudy responses or variable time to tumor progression are not sufficiently considered in trials and guideline recommendations. Accordingly, recommendations for the treatment of mUC patients with previous perioperative systemic therapy are lacking. To provide some guidance for daily uro-oncological practice despite the limited evidence, we sought to develop expert opinion-based treatment recommendations. These recommendations focus on palliative first-line therapy of mUC. Both perioperative pretreatment with classical cisplatin-based systemic therapy and/or immunotherapy, as well as the time to tumor recurrence have been considered.

MHC I Expression Predicts Response to Checkpoint Inhibitors in Metastatic Urothelial Carcinoma but Lacks Prognostic Value in Localized Disease.

BACKGROUND: Loss of MHC I expression is a tumoral escape mechanism, part of the process of immunoediting. MHC expression patterns and their prognostic and predictive value have not been studied in urothelial carcinoma of the bladder (UC) so far. OBJECTIVE: To correlate the expression of MHC I and MHC II with prognosis after curative treatment, response to chemotherapy and checkpoint inhibition. PATIENTS AND METHODS: We analyzed different patient cohorts for their expression of MHC I(HLA-A/B/C) and II (HLA-DR/DP/DQ) and examined potential correlations with prognosis and response to cisplatin-based chemotherapy or PD-1/PD-L1 directed immunotherapy. RESULTS AND LIMITATIONS: Overall, MHC expression was analyzed in 246 patients, and complete MHC I loss was seen in 29.7% of patients. In 35% of patients aberrant tumoral expression of MHC II was observed. In a homogeneous cohort of 149 patients with cystectomy with curative intent there were no significant differences in survival between the MHC expression groups. MHC I+ and MHC II+ patients had higher infiltration densities with CD8+ T effector cells.An analysis of 77 additional patients (cohort II) with neoadjuvant chemotherapy revealed no associations of MHC status with response defined as < pT2 pN0 in the cystectomy specimen. Lastly, we analyzed 26 patients with metastatic disease treated with PD-1/PD-L1 directed immunotherapy (cohort III, best response: 11 PD, 5 SD, 10 OR) and observed responses exclusively in MHC I+ patients (10/19 patients, 52.6). All four MHC I+ /MHC II+ /PD-L1+ patients had a progression-free interval of at least 12 months. CONCLUSIONS: Tumoral MHC I expression is frequently lost in UC. We found no association with prognosis or response to cisplatin-based chemotherapy but response to checkpoint inhibitors was limited to MHC I+ patients.

[Transurethral resection of the urinary bladder : Status quo and outlook on new developments]. / Transurethrale Resektion der Harnblase : Was ist Standard, was kommt?

BACKGROUND: Transurethral resection of the urinary bladder (TURB) is the standard intervention in the diagnostic workup and treatment of non-muscle invasive bladder cancer. In order to minimize cancer recurrence and potential complications, continuous technical development of TURB is of high clinical interest. OBJECTIVES: Presentation of the current standards and discussion of technological changes. MATERIALS AND METHODS: Analysis of the current guideline recommendations and literature research. RESULTS: The limitations of classic monopolar TURB is supplemented by new resection methods (en bloc) and technologies (bipolar and laser resection). Along with improved visualization through partially established technologies of photodynamic and digital image enhancement, there is potential for optimization regarding the likelihood of recurrences and complications as well as the histological quality of the resected material. CONCLUSION: A positive impact on the oncological value and safety of TURB seems possible through the use of modern technologies. Further establishment up to evidence-based guideline recommendations are necessary.

Evaluation of Pre-operative Biopsy, Surgical Procedures and Oncologic Outcomes in Upper Tract Urothelial Carcinoma (UTUC).

Purpose: Discordance between pre-operative biopsy and final pathology for Upper Tract Urothelial Carcinoma (UTUC) is high and optimal management remains controversial. The aim of this study is to evaluate the accuracy of pre-operative biopsy, to identify prognostic factors and to evaluate the effect of adjuvant chemotherapy on survival and oncologic outcome in UTUC. Methods: We analyzed records of patients receiving surgical treatment for UTUC. Pathology of pre-operative biopsy was compared to surgical specimen. We used Kaplan-Meier method to estimate survival probabilities and Cox's proportional hazards models to estimate the association between covariates and event times. Primary endpoint was overall survival (OS). A matched-pair analysis was performed to evaluate the effect of adjuvant chemotherapy. Results: 151 patients underwent surgical treatment (28% open, 36% laparoscopic, 17% robotic radical nephroureterectomy; 14% segmental ureteral resections and 5% palliative nephrectomy) for UTUC and were included in the analysis. Upstaging from

Telephone health coaching with exercise monitoring using wearable activity trackers (TeGeCoach) for improving walking impairment in peripheral artery disease: study protocol for a randomised controlled trial and economic evaluation.

INTRODUCTION: Peripheral artery disease (PAD) is the third most prevalent cardiovascular disease worldwide, with smoking and diabetes being the strongest risk factors. The most prominent symptom is leg pain while walking, known as intermittent claudication. To improve mobility, first-line treatment for intermittent claudication is supervised exercise programmes, but these remain largely unavailable and economically impractical, which has led to the development of structured home-based exercise programmes. This trial aims to determine the effectiveness and cost advantage of TeGeCoach, a 12-month long home-based exercise programme, compared with usual care of PAD. It is hypothesised that TeGeCoach improves walking impairment and lowers the need of health care resources that are spent on patients with PAD. METHODS AND ANALYSIS: The investigators conduct a prospective, pragmatic randomised controlled clinical trial in a health insurance setting. 1760 patients diagnosed with PAD at Fontaine stage II are randomly assigned to either TeGeCoach or care-as-usual. TeGeCoach consists of telemonitored intermittent walking exercise with medical supervision by a physician and telephone health coaching. Participants allocated to the usual care group receive information leaflets and can access supervised exercise programmes, physical therapy and a variety of programmes for promoting a healthy lifestyle. The primary outcome is patient reported walking ability based on the Walking Impairment Questionnaire. Secondary outcome measures include quality of life, health literacy and health behaviour. Claims data are used to collect total health care costs, healthcare resource use and (severe) adverse events. Outcomes are measured at baseline, 12 and 24 months. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Medical Association Hamburg. Findings are disseminated through peer-reviewed journals, reports to the funding body, conference presentations and media press releases. Data from this trial are made available to the public and researchers upon reasonable request.NCT03496948 (www.clinicaltrials.gov), Pre-results.

Pelvic ring fractures in the elderly now and then - a pelvic registry study.

OBJECTIVES: To analyze the changes in demographic data stratified for age, sex and type of injury of elderly patients suffering from pelvic ring fractures over a 22-year observation period. DESIGN/SETTING: Data has been collected prospectively, multi-centrically in hospitals participating in the German Pelvic Trauma Registry. PATIENTS: We analyzed the data of 5665 patients with an age ≥60years included in the German Pelvic Trauma Registry from 1991 to 2013. KEY RESULTS: Over the 22-year study period the frequency of type A fractures decreased significantly from 84.8% to 43.9%, while type C and, in particular, type B fractures significantly increased from 7.0% and 8.2% to 14.3% and 41.8%. In patients between 60 and 70 years of age the frequency of type B and C fractures was higher compared to patients >70years. The proportion of female patients, who represent the majority of the cohort (75%), was stable over the entire observation period. Interestingly, type A fractures were found more frequently in females, while type B and C fractures were found more frequently in males. CONCLUSIONS: With the predicted demographic change and a shift toward more severe injury patterns (type B and C pelvic fractures) in the elderly population, trauma departments will need to develop specific surgical concepts for geriatric patients with pelvic ring fractures.