Search

Background: Evidence-practice gaps exist in urology. We previously surveyed European Association of Urology (EAU) guidelines for strong recommendations underpinned by high-certainty evidence that impact patient experience for which practice variations were suspected. The recommendation “Do not offer neoadjuvant androgen deprivation therapy (ADT) before surgery for patients with prostate cancer” was prioritised for further investigation. ADT before surgery is neither clinically effective nor cost effective and has serious side effects. The first step in improving implementation problems is to understand their extent. A clear picture of practice regarding ADT before surgery across Europe is not available. Objective: To assess current ADT use before prostate cancer surgery in Europe. Design, setting, and participants: This was an observational cross-sectional study. We retrospectively audited recent ADT practices in a multicentre international setting. We used nonprobability purposive sampling, aiming for breadth in terms of low- versus high-volume, academic, versus community and public versus private centres. Outcome measurements and statistical analysis: Our primary outcome was adherence to the ADT recommendation. Descriptive statistics and a multilevel model were used to investigate differences between countries across different factors (volume, centre type, and funding type). Subgroup analyses were performed for patients with low, intermediate, and high risk, and for those with locally advanced prostate cancer. We also collected reasons for nonadherence. Results and limitations: We included 6598 patients with prostate cancer from 187 hospitals in 31 countries from January 1, 2017 to May 1, 2020. Overall, nonadherence was 2%, (range 0–32%). Most of the variability was found in the high-risk subgroup, for which nonadherence was 4% (range 0–43%). Reasons for nonadherence included attempts to improve oncological outcomes or preoperative tumour parameters; attempts to control the cancer because of long waiting lists; and patient preference (changing one's mind from radiotherapy to surgery after neoadjuvant ADT had commenced or feeling that the side effects were intolerable). Although we purposively sampled for variety within countries (public/private, academic/community, high/low-volume), a selection bias toward centres with awareness of guidelines is possible, so adherence rates may be overestimated. Conclusions: EAU guidelines recommend against ADT use before prostate cancer surgery, yet some guideline-discordant ADT use remains at the cost of patient experience and an additional payer and provider burden. Strategies towards discontinuation of inappropriate preoperative ADT use should be pursued. Patient summary: Androgen deprivation therapy (ADT) is sometimes used in men with prostate cancer who will not benefit from it. ADT causes side effects such as weight gain and emotional changes and increases the risk of cardiovascular disease, diabetes, and osteoporosis. Guidelines strongly recommend that men opting for surgery should not receive ADT, but it is unclear how well the guidance is followed. We asked urologists across Europe how patients in their institutions were treated over the past few years. Most do not use ADT before surgery, but this still happens in some places. More research is needed to help doctors to stop using ADT in patients who will not benefit from it.

Urothelial cancer (UC) is most commonly found in the urinary bladder, but can also appear in the upper urinary tract, where it is associated with several disease-specific challenges affecting its diagnosis, clinical staging, surgical management, and systemic therapy. A significant number of patients experience extra-vesical disease recurrence despite radical nephroureterectomy (RNU), leading to inevitable demise. Over the last years, the therapeutic armamentarium of UC has expanded with several systemic treatment options entering clinical care and deliver the potential to support a more individualized treatment in the near future. Currently, novel targeted therapies are emerging, accompanied with extensive biomarker research, which leads to a better understanding of the disease and therefore, reshaping the treatment landscape continuously and decisively. Though, systemic treatment of UTUC comes along with certain challenges that are specific to the disease, e.g., loss of renal function after RNU, which might result in ineligibility for a cisplatin-based chemotherapy. In this narrative review, the current standard of systemic treatment of UC in the perioperative and metastatic treatment setting are reported, with focus on UTUC. In addition, molecular aspects of UTUC, as well as future directions and specific implications for treatment of patients diagnosed with UTUC are discussed.

Purpose of review To discuss treatment decisions in the first-line setting of metastatic renal cell carcinoma (mRCC). Recent findings Immune check point inhibitor (ICI) combinations have replaced sunitinib as the standard of care in the first-line treatment of mRCC. Dual ICI treatment with nivolumab and ipilimumab was shown to significantly improve overall survival and objective response rates. Similarly, the ICI-tyrosine kinase inhibitor combinations pembrolizumab and axitinib and nivolumab and cabozantinib have demonstrated superiority in terms of overall survival, objective response rates and progression-free survival versus sunitinib. The lack of both comparative trials and predictive markers impedes individualized treatment decisions. Clinicians are left to make treatment choices based on clinical and biological factors. These factors may include differences in toxicity profiles, the rate of complete remission, a clinical situation that requires urgent tumor shrinkage, the presence of inflammation, histological or immune-histochemical features and others. Summary In the absence of comparative trials, clinical and biological factors may facilitate the choice between various treatment options in the first-line setting of mRCC. In addition, both the experience of the physician with a specific treatment together with patient's preferences and expectations of systemic therapy may be part of the decision-making process.

Contains fulltext : 237261.pdf (Publisher’s version ) (Closed access) Adherence to national and international clinical practice guidelines is suboptimal throughout Europe. The European Association of Urology Guidelines Office project "IMAGINE" (IMpact Assessment of Guidelines Implementation and Education) has been developed to measure baseline adherence to urological guideline recommendations across Europe and to identify issues that drive nonadherence.

Objectives To assess the visibility of clinically significant prostate cancer (PCA) lesions on the sequences multiparametric MRI of the prostate (mpMRI) and to evaluate whether the addition of dynamic contrast–enhanced imaging (DCE) improves the overall visibility. Methods We retrospectively evaluated multiparametric MRI images of 119 lesions in 111 patients with biopsy-proven clinically significant PCA. Three readers assigned visual grading scores for visibility on each sequence, and a visual grading characteristic analysis was performed. Linear regression was used to explore which factors contributed to visibility in individual sequences. Results The visibility of lesions was significantly better with mpMRI when compared to biparametric MRI in visual grading characteristic (VGC) analysis, with an AUCVGC of 0.62 (95% CI 0.55–0.69; p < 0.001). This benefit was seen across all readers. Multivariable linear regression revealed that a location in the peripheral zone was associated with better visibility on T2-weighted imaging (T2w). A higher Prostate Imaging-Reporting and Data System (PI-RADS) score was associated with better visibility on both diffusion-weighted imaging (DWI) and DCE. Increased lesion size was associated with better visibility on all sequences. Conclusions Visibility of clinically significant PCA is improved by using mpMRI. DCE and DWI images independently improve lesion visibility compared to T2w images alone. Further research into the potential of DCE to impact on clinical decision-making is suggested. Key Points • DCE and DWI images independently improve clinically significant prostate cancer lesion visibility compared to T2w images alone. • Multiparametric MRI (DCE, DWI, T2w) achieved significantly higher visibility scores than biparametric MRI (DWI, T2w). • Location in the transition zone is associated with poor visibility on T2w, while it did not affect visibility on DWI or DCE.

Purpose of review Indications for chemotherapy have increased in prostate cancer (PCA), many of which are shared with new hormonal agents (NHA). With no head to head comparison available, defining the optimal sequence and identifying biomarkers to predict response, has been a focus of intense research in PCA. We aim to summarize the best currently available evidence in all stages of disease to help guide therapy. Recent findings In metastatic castration-resistant prostate cancer, Cabazitaxel has shown improved radiographic progression-free survival over another NHA after Docetaxel and one NHA. For hormone sensitive PCA (mHSPC) multiple meta-analyses have shown combination therapy with Docetaxel or an NHA to be superior to androgen deprivation therapy alone, yet no clear benefit over each other. For peri-interventional chemotherapy with local therapy, there is currently only one positive prospective trial, for very high-risk disease. Summary Cabazitaxel is underutilized and should be used earlier. NHAs should not be used in succession as there is significant cross resistance. Combination therapy should be used in mHSPC, yet there is no clear benefit for any combination. Peri-interventional chemotherapy might have a benefit for a small group of patients with very high-risk disease, yet this must be carefully evaluated, and side effects must be taken into account.

Angiogenesis-related marker vascular cell adhesion molecule-1 (VCAM-1) has been shown to be elevated in urothelial carcinoma of the bladder (UCB), but its predictive/prognostic role has not been determined. Thus, this study aimed to investigate the predictive/prognostic role of VCAM-1 for patients who have UCB treated with radical cystectomy (RC).The study enrolled 1036 patients with clinically non-metastatic advanced UCB who underwent RC, and plasma VCAM-1 was evaluated preoperatively. The correlation of plasma VCAM-1 with pathologic and survival outcomes was assessed using binominal logistic regression and multivariable Cox regression analyses. Discrimination was assessed using the area under the curve and concordance indices. The clinical net benefit was evaluated using decision curve analysis (DCA).Preoperative VCAM-1 was significantly elevated in patients with adverse pathologic features. Higher VCAM-1 levels were independently associated with increased risk of lymph-node-metastasis (LNM), ≥pT3 disease, and non-organ-confined disease (NOCD (p0.001 for each). Preoperative plasma VCAM-1 was independently associated with recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) in pre- and postoperative multivariable models. Adding VCAM-1 to these predictive models improved their discriminatory ability to predict all outcomes by a significant margin. In the DCA, VCAM-1 addition to the reference models for prediction of LNM, NOCD, RFS, and CSS resulted in relevant improvement.Elevated plasma VCAM-1 was associated with biologically and clinically aggressive UCB disease features. After validation, preoperative VCAM-1 may serve as a biomarker to help identify patients likely to benefit from intensified/multimodal therapy. In addition, VCAM-1 improved the discriminatory power of predictive/prognostic models and can be used to refine personalized clinical decision-making.

To determine the oncologic and toxicity outcomes of adjuvant immunotherapy with immune checkpoint inhibitors (ICIs) compared to adjuvant chemotherapy in patients treated with radical surgery for urothelial carcinoma (UC).We used the Bayesian approach in the network meta-analysis of different therapy regimens compared to observation or placebo.Nine studies comprised of 2,444 patients met the eligibility criteria. In bladder UC, chemotherapy, atezolizumab, and nivolumab did not improve disease progression compared to observation/placebo. In upper tract UC (UTUC), chemotherapy was significantly associated with a lower likelihood of disease progression compared to observation/placebo, while atezolizumab and nivolumab were not. Based on the analysis of the treatment ranking, adjuvant chemotherapy appeared as the best treatment approach in both bladder UC and UTUC. The risk of adverse events with ICIs was comparable to that of observation/placebo.Our analysis suggests a superior oncologic benefit to adjuvant chemotherapy over ICIs in patients treated with radical surgery for both bladder UC and UTUC.

Purpose: To evaluate overactive bladder (OAB) symptoms in patients undergoing diagnostic cystoscopy. Overall changes in the entire study population were assessed, as well as broken down by various subgroups. Methods: A prospective multi-center study among consecutive 450 adults undergoing diagnostic cystoscopy was conducted. OAB-symptoms were evaluated with the validated eight-item OAB Screening Awareness Tool (OAB-V8) immediately before and on days 1, 4, and 7 after cystoscopy. Patients were distinguished between being OAB-negative and OAB-positive (< 8 and ≥ 8 sum-score, respectively). Average sum-scores and subdomains were evaluated. Results: Before cystoscopy, 44.7% of patients were screened OAB-positive and 55.3% OAB- negative. Out of those being screened negative, development of de-novo OAB was noticed in 16.8%, declining to 8.1% on day 7 (p < 0.001). In patients being OAB-positive before cystoscopy, a decline of OAB-positivity was noted during follow-up (p < 0.001). No statistically significant differences were noted when broken down by gender (p = 0.92), age (p = 0.82) and type cystoscope (rigid vs. flexible, p = 0.38). Average sum-scores declined from 8.68 before cystoscopy to 6.9 during follow-up. Flexible cystoscopy was superior over rigid in four subdomains: uncomfortable urge to urinate (p = 0.04), sudden urge to urinate with little or no warning (p = 0.02), uncontrollable urge to urinate (p = 0.03), and urine loss associated with a strong desire to void (p = 0.009). Conclusion: OAB-symptoms are common in patients undergoing cystoscopy. Cystoscopy itself can cause de-novo OAB-symptoms. Controversially, a decline of OAB-symptoms was noted after cystoscopy when patients were screened OAB- positive before cystoscopy. Flexible scopes were superior in some subdomains.

Context There have been substantial changes in the management of patients with metastatic renal cell carcinoma (mRCC) over the past decade, with upfront immunotherapy-based combinations replacing targeted therapies. A broad range of combinations have been approved, and comparisons of their efficacy and safety are needed to guide the optimal choice of first-line therapy. Objective To perform indirect comparisons of efficacy and safety of first-line immune checkpoint inhibitor (ICI)-based combination therapies for mRCC. Evidence acquisition We searched multiple databases and abstracts of major scientific meetings up to February 2021 to identify phase III randomized controlled trials of patients receiving first-line ICI-based combination therapies for mRCC. Progression-free survival (PFS) and overall survival (OS) were the primary endpoints. The secondary endpoints included complete response rates (CRRs), objective response rates (ORRs), grade ≥3 treatment-related adverse events (TRAEs), and rates of treatment discontinuation due to adverse events (AEs). Subgroup network meta-analyses were performed based on patients’ risk group categories and programmed death ligand 1 (PD-L1) expression status. Evidence synthesis Six trials were included in our network meta-analyses comprising 5121 patients. Nivolumab plus cabozantinib had the highest likelihood of providing the maximal OS (P score: 0.7573). Lenvatinib plus pembrolizumab demonstrated the highest likelihood of PFS (P score: 0.9906) and ORR (P score: 0.9564). CRRs were more likely to be associated with nivolumab plus ipilimumab (P score: 0.8682). In patients with ≥1% PD-L1 expression, the highest likelihood of better PFS was associated with lenvatinib plus pembrolizumab and nivolumab plus ipilimumab. Nivolumab plus ipilimumab was also associated with the lowest rates of grade ≥3 TRAEs; while the highest likelihood of AE-related treatment discontinuation was associated with lenvatinib plus pembrolizumab and nivolumab plus ipilimumab. Conclusions Our network meta-analysis suggests that combinations of ICIs and tyrosine kinase inhibitors (TKIs) provide superior PFS, ORR, and OS to ICI-ICI combinations, regardless of the on International mRCC Database Consortium risk group. However, an ICI-ICI combination could be the optimal treatment for tumors with increased PD-L1 expression. The newly introduced ICI-TKI combinations, nivolumab plus cabozantinib and lenvatinib plus pembrolizumab, showed promising activity and are likely to have an important role in the mRCC treatment strategy. Patient summary The use of immune checkpoint inhibitor (ICI)-based combinations (ICI plus tyrosine kinase inhibitor and ICI-ICI) improved oncological outcomes of metastatic renal cell carcinoma. Programmed death ligand 1 (PD-L1) expression status could help guide physicians and patients to select the appropriate treatment strategy.

Purpose To investigate the prognostic role of the preoperative systemic immune–inflammation index (SII) in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). Materials and methods We retrospectively analyzed our multi-institutional database to identify 2492 patients. SII was calculated as platelet count × neutrophil/lymphocyte count and evaluated at a cutoff of 485. Logistic regression analyses were performed to investigate the association of SII with muscle-invasive and non-organ-confined (NOC) disease. Cox regression analyses were performed to investigate the association of SII with recurrence-free, cancer-specific, and overall survival (RFS/CSS/OS). Results Overall, 986 (41.6%) patients had an SII > 485. On univariable logistic regression analyses, SII > 485 was associated with a higher risk of muscle-invasive (P = 0.004) and NOC (P = 0.03) disease at RNU. On multivariable logistic regression, SII remained independently associated with muscle-invasive disease (P = 0.01). On univariable Cox regression analyses, SII > 485 was associated with shorter RFS (P = 0.002), CSS (P = 0.002) and OS (P = 0.004). On multivariable Cox regression analyses SII remained independently associated with survival outcomes (all P P = 0.02). However, all area under the curve and C-indexes increased by Conclusions Preoperative altered SII is significantly associated with higher pathologic stages and worse survival outcomes in patients treated with RNU for UTUC. However, the SII appears to have relatively limited incremental additive value in clinical use. Further study of SII in prognosticating UTUC is warranted before routine use in clinical algorithms.

Das UTUC („upper tract urothelial carcinoma“) ist eine seltene Erkrankung, die sich bei der Erstdiagnose in vielen Fallen als bereits invasiv wachsender Tumor prasentiert. In dieser Situation gilt nach wie vor die radikale Nephroureterektomie als Goldstandard. In ungefahr 20 bis 40 % der Falle besteht jedoch bei der Erstdiagnose ein nichtinvasiver Tumor (pTa) mit guter Differenzierung („low grade“). Bei diesen Patienten stellt die Standardtherapie potenziell eine Ubertherapie dar, sodass bei betreffenden Patienten in ausgewahlten Fallen eine nierenerhaltende Therapie in Erwagung gezogen werden kann. Eine organerhaltende Strategie kann auch im Fall aggressiverer Tumoren bei Einzelniere oder eingeschrankter Nierenfunktion diskutiert werden. Das onkologische Ergebnis bei niedriggradigen Tumoren war in einigen Studien ahnlich dem einer radikalen Nephroureterektomie und ermoglichte, einen Grosteil der Nierenfunktion zu erhalten. Im Fall eines Nierenerhalts wird der Tumor meist mittels Ureterrenoskopie oder immer seltener uber einen perkutanen Zugang mittels Laser abgetragen. Aufgrund der hohen Rezidivrate ist ein genaues Follow-up der Patienten mit regelmasigen Zystoskopien, Zytologien und CT sowie invasiven Kontrollureterrenoskopien notwendig. Um die Rezidivrate zu verringern, werden oft auch topische Therapien verwendet. Diese konnen intravesikal verabreicht werden, um ein Blasenrezidiv zu verhindern, aber auch uber einen Ureterkatheter oder eine perkutane Nephrostomie in den oberen Harntrakt instilliert werden, um die Gefahr eines Lokalrezidivs zu verringern. Ein klarer Nutzen fur eine Instillationstherapie ist noch nicht ganzlich geklart.

Summary Until recently, there were no true innovations in the management of locally advanced (aUC) and metastatic urothelial cancer (mUC) in the last three decades. Vinflunine has been approved by the EMA (European Medicines Agency) with only limited improvement compared to best supportive care in second line treatment. In addition, gemcitabine/cisplatin has been established as an alternative to methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). The advent of checkpoint inhibitors (CPI) revolutionized the care of these patients, transforming a unanimously deadly disease into one with hope through sustained disease control. Five immune CPI have recently been approved for aUC/mUC by the US Food and Drug Administration (FDA) including atezolizumab, nivolumab, pembrolizumab, durvalumab and avelumab. All five CPI are FDA-approved as second-line therapy with atezolizumab and pembrolizumab also being approved for first-line therapy in cisplatin-ineligible patients. The rapid acceptance in the treatment algorithm of UC is based on the impressive clinical efficacy of these agents in some patients, combined with their excellent safety profile. These new agents are indeed the most important advancement in UC care. However, the challenge in the age of precision medicine is to identify the patients who are most likely to benefit from CPIs, as the majority of patients do not respond to CPI. Toward this goal, validation of clinical, molecular and imaging biomarkers that serve for prediction and monitoring of treatment response are of central necessity.

Purpose of review Immunotherapies for urological malignancies have made tremendous progress by targeting immune checkpoints and have been implemented in clinical practice nowadays. Though siginifcant number of patients does not respond to immunotherapy. Biomarkers could help to predict response to treatment, but are still under investigation. We reviewed the literature to identify relevant biomarkers in patient treated with immunotherapy. Recent findings A comprehensive search of PubMed through has been performed to identify important relevant publications from 2016 to 2017 on biomarkers for immunotherapies in urological cancers including reported clinical trials. In addition, abstracts of relevant oncological scientific meetings from 2017 have been implemented. Summary Checkpoint inhibitors have shown substantial improvement in the treatment of metastatic RCC and metastatic and locally advanced urothelial cancer. There is an unmet need for the development of predictive biomarkers in order to identify patients who are more likely to respond to therapy.

Background Immune checkpoint inhibitors (ICIs) have led to a paradigm change in the management of metastatic renal cell carcinoma (mRCC). Prospective trials have focused on ICI treatment in the first or second line. The aim of this analysis is to evaluate the benefit of ICI across different treatment lines. Patients and methods This is a single-center retrospective study that included mRCC patients who received ICIs in various treatment lines. Objective response rates (ORR), progression-free survival (PFS) and overall survival (OS) were evaluated. Results Ninety-four patients were eligible for full evaluation. Patients were classified as International mRCC Database Consortium (IMDC) risk group categorization as good, intermediate and poor risk in 26.8%, 61.6% and 14.8% of cases, respectively. They were treated with ICI monotherapy, dual ICI therapy and ICI + tyrosine kinase inhibitor in 59%, 20% and 21% of cases, respectively. ORR, median PFS and OS for the entire cohort was 39.4%, 9.67 months [95% confidence interval (CI) 6.9-12.4 months] and 23.6 months (95% CI 13.3-33.9 months), respectively. The ORR by treatment line was 33% in first, 40.4% in the second, 35% in the third and 43.5% in the fourth line and beyond. Median PFS by treatment line was 8.6, 10.3, 7.9 and 7.23 months, respectively. The median OS was not reached in first-line treatment and was 26.2, 18.1 and 20.7 months in the second, third and fourth line and beyond, respectively. Conclusions ICIs or ICI combinations are active in all treatment lines and should also be offered in heavily pretreated patients. Patient selection based on tumor and patient factors allows for maximal benefit from ICI-based therapies., Highlights • Single-agent or combinations of ICI have become the standard of care in the first- and second-line treatment of mRCC. • The post-immunotherapy landscape is less well described. • We found that ICIs are active across different treatment lines. • Objective responses and PFS may not differ between first and later treatment lines.

Purpose of review Immune-checkpoint inhibitors (CPIs) have been implemented in the treatment algorithm of metastatic urothelial cancer as they have shown higher and more sustained responses compared with conventional second-line chemotherapy. Recently, several clinical trials have reported on CPIs in earlier disease stages such as muscle-invasive bladder cancer (MIBC). This review summarizes ongoing clinical trials and results from early phase clinical trials in muscle invasive and locally advanced bladder cancer. Recent findings In phase II clinical trials, neoadjuvant use of CPIs as mono and combination therapy, in patients with MIBC planned for radical cystectomy, has shown promising pathological complete response rates. Whether this will translate in survival benefit remains to be assessed. Combination of CPIs and conventional chemotherapy or other targeted agents promises to increase the efficacy of perioperative systemic therapy with potentially additive toxicities. Recently, preclinical models of combined trimodal therapy with CPIs delivered the proof of principle leading to several ongoing trials in this setting. Summary First results of clinical trials evaluating CPIs in MIBC demonstrate very promising results that warrant further investigation as they could revolutionize management of MIBC in the near future. The trend and hope are toward higher rates of safe and sustained bladder preservation.

Background Urologists’ adherence to European Association of Urology and National Comprehensive Cancer Network guideline recommendations to perform inguinal (ILND) and pelvic (PLND) lymph node dissection in penile cancer (PC) patients is not known. Objective To assess a German-speaking European cohort of urologists based on their criteria to perform ILND and PLND in PC patients. Design, setting, and participants A 14-item survey addressing general issues of PC treatment was developed and sent to 45 clinical centers in Germany (n = 34), Austria (n = 8), Switzerland (n = 2), and Italy (n = 1). Intervention Two of the 14 questions assessed the criteria to perform ILND and ipsilateral PLND. Outcome measurements and statistical analysis Correct responses for ILND and PLND criteria were assessed. Based on a multivariate logistic-regression-model, criteria independently predicting guideline adherence were identified. Results and limitations In total, 557 urologists participated in the survey, of whom 43.5%, 19.3%, and 37.2% were residents in training, certified, and in leading positions, respectively. ILND and PLND criteria were correctly identified by 35.2% and 23.9%, respectively. Of the participants, 23.3% used external sources for survey completion. The use of auxiliary tools (odds ratio [OR] 1.57; p[bootstrapped] = 0.028) and participants outside of Germany (OR 0.56; p[bootstrapped] = 0.006) were predictors of ILND guideline adherence. The number of PC patients treated yearly (p = 0.012; OR 1.06) and the use of auxiliary tools (p Conclusions Our results demonstrate overall suboptimal knowledge of the correct indications to perform ILND and PLND in PC patients among the surveyed urologists. We propose that governments and healthcare providers should be encouraged to centralize PC management. Patient summary The management of inguinal and pelvic lymph nodes is crucial for the survival of penile cancer patients. Disease rarity mandates referral to clinical practice guidelines for appropriate treatment selection.

Purpose: We hypothesized sarcopenia as predictive factor as a response to upfront chemotherapy of muscle-invasive urothelial bladder cancer (MIBC). Methods: We retrospectively studied 30 patients who received upfront cisplatin-based chemotherapy for MIBC (pT2–4 N0/+ M0) before planned radical cystectomy. Skeletal muscle index (SMI) was calculated by CT at study baseline and following completion of chemotherapy. Patients were stratified according to the presence of sarcopenia. Endpoints included clinical and pathological response. Results: Sixteen of the 30 patients (53.3%) had sarcopenia at baseline. The median SMI was 51.2 cm2/m2 (IQR 45.6–57.9). Throughout the course of chemotherapy, 22 patients (73.3%) experienced a decline in SMI, which ranged from 1 to 20% (median decline 3%, p < 0.01). All 16 patients with baseline sarcopenia persisted, while 5 of 14 patients (35.7%) without baseline sarcopenia became sarcopenic (p = 0.06). None of the clinical variables were predictive of clinical or pathological response, including SMI (p = 0.78 and p = 0.59), sarcopenia (p = 0.65 and p = 0.16) and SMI kinetics (p = 0.54 and p = 0.77). Conclusion: Sarcopenia is present in a considerable proportion of patients with MIBC undergoing upfront cisplatin-based chemotherapy before planned RC. SMI decreases during treatment, but neither baseline SMI nor its kinetics is associated with response to chemotherapy.

Objectives A small subset of patients treated with immune checkpoint inhibitors manifest atypical patterns of response, the so-called pseudoprogression (PP) and hyperprogression (HP). Their prevalence in urothelial (UC) and renal cancer (RCC) remains, to date, mostly uninvestigated. Therefore, we aimed to provide a summary of the current knowledge about PP and HP during immune checkpoint inhibitor therapy in UC and RCC patients. Methods and materials A systematic medline/pubmed© literature search was performed. The atypical patterns of response to systemic immunotherapy were reviewed. Endpoints were PP and HP in UC and RCC. Results Tumors respond differently to immunotherapy compared to systemic chemotherapy. To evaluate response to immunotherapy, new guidelines (iRECIST) have been developed. To date, no studies focused on PP in UC and RCC, and the only way to evaluate its role is to take patients who respond to treatment beyond progression as surrogate for pseudoprogressors. PP seems to occur in a non-negligible rate of UC and RCC (from 1.5 to 17% and from 5 to 15%, respectively). The concept of HP, defined as a rapid progression after treatment, just took the first steps, and therefore, data from ongoing trials are awaited to elucidate its impact in genitourinary cancers. Conclusions PP and HP are not uncommon entities in UC and RCC patients, treated with PD-1/PD-L1 inhibitors. Further investigation is warranted to define which patients are likely to experience PP and could benefit from treatment beyond progression and which ones will instead rapidly experience progression despite treatment and should, therefore, avoid systemic immunotherapy.

Purpose To prospectively assess anxiety and depression in patients undergoing diagnostic cystoscopy. Methods Patients presenting for outpatient diagnostic cystoscopy were recruited from four European urological departments. Anxiety and depression were assessed with the 'Hospital Anxiety and Depression Scale' (HADS) before cystoscopy and after 1 week. Statistical analyses, including the Chi-square test, univariate, and multivariate logistic regression analyses, were carried out with SPSS v. 21 (IBM Corp., Armonk, NY). Results Prior to cystoscopy, 30.2 % of patients were anxious and 24.8 % depressive (n = 442). In the post-examination period, anxiety declined to 24.5 %, while depression was unchanged (24.4 %). Pre-cystoscopy anxiety was significantly more common in women (41.8 vs. 24.5 %, p < 0.0001), patients aged < 65 years (34.9 vs. 25.9 %, p = 0.04), and in those being examined with rigid cystoscopes (35.7 vs. 23.9 %, p = 0.007). In multivariate regression analyses, female gender (OR 2.6, p < 0.0001)

Objective To investigate women's expectations regarding cesarean and to assess the subjective experience of birth of these women. Because the birth experience is a multidimensional phenomenon, qualitative as well as quantitative approaches were used to investigate women's expectations and experiences with cesarean. Design Descriptive cohort study. Setting The Division of Obstetrics and Feto‐Maternal Medicine of the Department of Obstetrics and Gynecology of an Austrian medical university. Participants Forty‐eight women with a planned cesarean birth. Methods Semistructured interviews were conducted with the 48 women before (36th week of gestation) the planned cesarean and shortly thereafter. Data were analyzed by means of a qualitative content analysis. Anxiety, depression, and psychological distress were assessed using standardized questionnaires. Results More than three fourths (81.3%) of the women were satisfied with the cesarean. Nevertheless, 83.3% of the women expressed anxiety about cesarean, including fears about the health of the infant, the epidural anesthesia, and possible complications. Before the cesarean, only one half of the women (54.2%) felt that they had been sufficiently informed about the planned cesarean, and only 25% had detailed knowledge about the specific course of events of the cesarean. Quantitative assessment showed low depression levels and overall psychological distress before and after the cesarean. State anxiety levels were high before the cesarean and moderate afterwards. Conclusion Although the overall satisfaction and psychological tolerability of a planned cesarean is high, improvement is possible by providing more detailed information to the prospective mothers and by specifically addressing prevalent anxieties.

The aim of this study was to prospectively assess women's pain during rigid and flexible diagnostic cystoscopy and afterwards during a one-week follow-up.Prospective, multi-institutional trial analyzing numeric rating scales (NRS) of women undergoing diagnostic cystoscopy. Pain categories: no (0 points), mild (1-3), moderate (4-6) and severe pain (7-10). Assessing of pain before, during cystoscopy, and at day 1, 4 and 7 of follow-up.A total of 150 women undergoing rigid (N.=85) or flexible (N.=65) diagnostic cystoscopy were analyzed. Women undergoing flexible cystoscopy were more frequently pain-free (64.6% vs. 40%, P=0.003) and experienced mild pain less frequently (27.7% vs. 52.9% vs. P=0.002). No significant differences were noted among moderate (6.2% vs. 5.9%, P=0.95) and severe pain (1.5% vs. 1.2%, P=0.85). Patients undergoing their first (P=0.14) and repeat cystoscopy (P=0.08) had similar pain perception. In multivariate logistic regression analyses, women undergoing flexible cystoscopy had a 2.6 increased chance of being pain-free (OR=2.6, CI: 1.28-5.11, P=0.08) and their odds of experiencing mild pain were significantly lower (OR=0.34, CI: 0.17-0.71, P=0.004). The likelihood of experiencing moderate (OR=1.1, CI: 0.28- 4.4, P=0.83) or severe pain (OR=2.42, CI: 0.11-51.79, P=0.57) differed insignificantly.Rigid and flexible cystoscopies were well-tolerated by most women. However, flexible cystoscopy was associated with a higher likelihood of being pain-free and lower chances of experiencing mild pain. Patients' previous experience with cystoscopy did not influence pain perception.

Objective To evaluate pain perception in men undergoing flexible or rigid diagnostic cystoscopy. Methods This is a prospective multi-institutional analysis of men undergoing cystoscopy in 4 European departments of urology. Pain perception was assessed with an 11-point numeric rating scale. Pain categories were as follows: no (0 points), mild (1-3), moderate (4-6), and severe pain (7-10). Assessment of pain was before, during cystoscopy, and at days 1, 4, and 7 of follow-up. Results A total of 300 cystoscopies were analyzed (150 rigid and 150 flexible). Men undergoing flexible cystoscopy were more frequently free of pain (58.7% vs 24%; P

Objectives We wanted to test whether there is a difference between the total number and duration of malfunctions and a correlation between the oxygen saturation and pulse rate values of two new generation pulse oximeters (Masimo 'Radical 7' and Nellcor 'N 600') during emergency ambulance transportation. Methods Patients were monitored with two pulse oximeters ('Radical 7' and 'N 600') on different randomly selected fingers of the same hand during transportation. Data of both devices were recorded continuously by a laptop computer. Results Fifty-two patients with signs of peripheral vasoconstriction (including 22 patients with a blood pressure ≤100/60) were included. There were 0.21 ± 0.72 (0-4) malfunctions per patient lasting for a mean 113.55 ± 272.55 s in the 'Radical 7' and 0.13 ± 0.49 (0-3) malfunctions per patient with a mean duration of 301.0 ± 426.58 s in the 'N 600'. Oxygen saturation and pulse rate values correlated significantly [r² = 0.9608 (SpO₂), r² = 0.9608 (pulse rate)] between the devices and showed a bias of -0.177770 (SpO₂) and 0.310883 (pulse rate) with a standard deviation of 1.68367 (SpO₂) and 4.46532 (pulse rate) in a Bland-Altman test. Conclusion Although number and duration of malfunctions did not differ significantly between the devices, they showed a very low number of malfunctions even in hypotensive patients with peripheral vasoconstriction. Oxygen saturation correlated significantly in the two devices investigated at 49.409 time points. In addition, pulse rate also correlated significantly.

SummaryIncreased plasma levels of plasminogen activator inhibitor-1 (PAI-1) have been shown to exist in 40 to 60% of patients with stable coronary artery disease and have been suggested to be responsible for the development of coronary thrombotic complications. However, it is also discussed whether PAI-1 elevation might mainly be due to variables like increased age or to reactive mechanisms caused e.g. by the chest pain itself. To exclude age dependent ui pain related influences, age-matched patients with stable angina pectoris (NHYA II) and angiographically proven coronary artery disease (CAD, n = 16) or without evidence for coronary sclerosis (variant angina, n = 10; angina-like syndrome with normal coronary angiogram, n = 5; non-CAD, n = 15) have been investigated for their plasma PAI-1 activity and t-PA antigen levels. The mean PAI activity in CAD patients (17.5 U/ml) was significantly higher than in non-CAD patients (9.6 U/ml) (p

SummaryA decrease in the fibrinolytic potential, mainly due to an elevation of plasminogen activator inhibitor (PAI), has been described in patients with stable coronary artery disease and a previous myocardial infarction. We investigated plasma levels of PAI and tissue plasminogen activator (t-PA) and their possible circadian variations in patients with unstable coronary artery disease (CAD). Sixty-three patients were studied for at least 2 consecutive days during their stay at the coronary care unit (CCU). Diurnal plasma fluctuations in PAI and t-PA and onset of further myocardial ischemic episodes were monitored. As controls we used 22 age-matched patients submitted to the clinic because of non cardiac chest pain or valvular disease who revealed no evidence of CAD. PAI levels were significantly elevated in patients with unstable CAD (p < 0.0001) but were not influenced by the extent of underlying CAD, history of previous myocardial infarction, known risk factors for CAD, or by extent of myocardial damage. The circadian variation of PAI levels with peak values between midnight and 6 A. M. found in controls was still present in patients but at a higher level. Preservation of circadian pattern in PAI plasma levels despite myocardial ischemic attacks indicates that elevation of PAI is rather not caused by a reactive phenomenon. On the other hand, elevated PAI levels and episodes of severe myocardial ischemia exhibiting a median time of onset at 10 A. M. seem to be closely related.

Activation of Glu-plasminogen by single-chain urokinase-type plasminogen activator (sc-uPA), isolated from human urine, was studied in a purified system in the absence and presence of the cyanogen bromide fibrinogen fragment, FCB 2, and compared to plasminogen activation by two-chain high-Mr urokinase. Plasminogen activation by sc-uPA was significantly increased by the FCB-2 fibrinogen fragment, an effect brought about by decrease of apparent Km and increase of apparent kcat. During the course of plasminogen activation by scu-PA, two-chain urokinase was formed from 125I-sc-uPA to a significant degree only when a concentration of 30 nM plasmin was reached in the incubation mixture; this was only the case in the system stimulated by FCB-2 fibrinogen fragment and only after 30 min. Formation of two-chain urokinase was not, however, related to the increase in the rate of plasmin formation induced by the FCB-2 fibrinogen fragment.

Patients with unstable coronary artery disease were randomly treated either with a combination therapy consisting of nitrates and calcium-channel blockers without or with addition of clinical grade heparin administered subcutaneously; in order to evaluate the effect of heparin treatment on the fibrinolytic system, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) plasma levels were related to the clinical course of the disease. In heparinized patients thrombin time was prolonged more than 3-fold the normal range indicating effective heparin treatment. Heparinization led to a significant increase in t-PA antigen plasma levels (p less than 0.0001) within approximately four hours while PAI-1 activities remained unaltered. However, the measurable increase of the anticoagulant and pro-fibrinolytic activities of heparin did not result in a short-term benefit for the heparinized patients because the number of further ischemic attacks per patient during the observation period of three days was not different between the two study groups.

Recent studies have shown a high incidence for the onset of acute myocardial infarction (AMI) in the morning and a possible role of high plasma levels of plasminogen activator inhibitor for the risk of reinfarction. We therefore investigated the diurnal course of PAI and the incidence of severe ischemic attacks in patients with CAD. Blood was drawn from 64 patients at the coronary care unit with angiographically proven CAD (group A = unstable angina, n=37; age = 60.7 ± 10.1 years; group B = stable angina, n=27, age = 58.2 ± 10.9 years) at 4 different time points (6 a.m., noon, 6 p.m., midnight) for at least 3 consecutive days. PAI (functional titration assay; IU t-PA inhibited/ml) and time of onset of severe ischemic attacks including AMI were determined. 50 healthy volunteers (age = 39 ± 17 years) served as controls. We found a significant diurnal variation (paired t-test, p