Adenovirus vector vaccination reprograms pulmonary fibroblastic niches to support protective inflating memory CD8+ T cells.

Pathogens and vaccines that produce persisting antigens can generate expanded pools of effector memory CD8+ T cells, described as memory inflation. While properties of inflating memory CD8+ T cells have been characterized, the specific cell types and tissue factors responsible for their maintenance remain elusive. Here, we show that clinically applied adenovirus vectors preferentially target fibroblastic stromal cells in cultured human tissues. Moreover, we used cell-type-specific antigen targeting to define critical cells and molecules that sustain long-term antigen presentation and T cell activity after adenovirus vector immunization in mice. While antigen targeting to myeloid cells was insufficient to activate antigen-specific CD8+ T cells, genetic activation of antigen expression in Ccl19-cre-expressing fibroblastic stromal cells induced inflating CD8+ T cells. Local ablation of vector-targeted cells revealed that lung fibroblasts support the protective function and metabolic fitness of inflating memory CD8+ T cells in an interleukin (IL)-33-dependent manner. Collectively, these data define a critical fibroblastic niche that underpins robust protective immunity operating in a clinically important vaccine platform.

Carfilzomib, thalidomide, and dexamethasone are safe and effective in relapsed and/or refractory multiple myeloma: final report of the single-arm, multicenter, phase II ALLG MM018/AMN002 study.

This multicenter, phase II study of the Australasian Lymphoma and Leukemia Group and the Asian Myeloma Network investigated fixed-duration (18-month) treatment with carfilzomib (K), thalidomide (T), and dexamethasone (d) (KTd) in patients with relapsed and/or refractory multiple myeloma who had received one to three prior lines of therapy. Patients received induction with up to 12 28-day cycles of carfilzomib (20 mg/m2 intravenously in cycle 1 on days 1 and 2, then 56 mg/m2 [36 mg/m2 for patients ≥75 years] from day 8 onwards), thalidomide 100 mg orally in the evening and weekly dexamethasone 40 mg (20 mg for patients ≥75 years). During maintenance, thalidomide was omitted, while carfilzomib was continued on days 1, 2, 15, and 16 with fortnightly dexamethasone. The primary endpoint was progression-free survival. Secondary endpoints were overall response rate, overall survival, duration of response, safety, and tolerability. Ninety-three patients (median age 66.3 years [range, 41.9-84.5]) were enrolled and followed up for a median of 26.4 months (range, 1.6-54.6). The median progression-free survival was 22.3 months (95% confidence interval: 15.7-25.6) and the 2-year progression-free survival was 46.3% (95% confidence interval: 35.1-52.8). The median overall survival was not reached and the 2-year overall survival was 73.8% (95% confidence interval: 62.9-81.9). The overall response rate was 88% (73% had a very good partial response or better). There was no difference in the depth of response, progression-free survival or overall survival comparing Asian and non-Asian cohorts (P=0.61). The safety profile of KTd was consistent with that of each individual drug. KTd is well tolerated and effective in patients with relapsed and/or refractory multiple myeloma irrespective of Asian or non-Asian ethnicity and provides an alternative treatment option, particularly in circumstances in which the use of carfilzomib, lenalidomide, and dexamethasone (KRd) is limited by access, cost, or renal impairment.

Safety and quality of cystectomy and pelvic lymph node dissection after neoadjuvant durvalumab and cisplatin/gemcitabine.

OBJECTIVE: To report on the surgical safety and quality of pelvic lymph node dissection (PLND) in patients treated with radical cystectomy (RC) and PLND for muscle-invasive bladder cancer (MIBC) after neoadjuvant chemo-immunotherapy. PATIENTS AND METHODS: The Swiss Group for Clinical Cancer Research (SAKK) 06/17 was an open-label single-arm phase II trial including 61 cisplatin-fit patients with clinical stage (c)T2-T4a cN0-1 operable urothelial MIBC or upper urinary tract cancer. Patients received neoadjuvant cisplatin/gemcitabine and durvalumab followed by surgery. Prospective quality assessment of surgeries was performed via central review of intraoperative photographs. Postoperative complications were assessed using the Clavien-Dindo Classification. Data were analysed descriptively. RESULTS: A total of 50 patients received RC and PLND. All patients received neoadjuvant chemo-immunotherapy. The median (interquartile range) number of lymph nodes removed was 29 (23-38). No intraoperative complications were registered. Grade ≥III postoperative complications were reported in 12 patients (24%). Complete nodal dissection (100%) was performed at the level of the obturator fossa (bilaterally) and of the left external iliac region; in 49 patients (98%) at the internal iliac region and at the right external iliac region; in 39 (78%) and 38 (76%) patients at the right and left presacral level, respectively. CONCLUSION: This study supports the surgical safety of RC and PLND following neoadjuvant chemo-immunotherapy in patients with MIBC. The extent and completeness of protocol-defined PLND varies between patients, highlighting the need to communicate and monitor the surgical template.

Latest insights into the pathophysiology of bladder pain syndrome/interstitial cystitis.

PURPOSE OF REVIEW: Bladder pain syndrome/interstitial cystitis (BPS/IC) is a common medical problem in both sexes affecting people of all ages. Patients might report overactive bladder symptoms with additional bladder pain at maximum bladder filling, during and after micturition. This review aims to highlight pathophysiological mechanisms associated with this disease. RECENT FINDINGS: Latest literature exposes different pathophysiological mechanisms such as impaired urothelial barrier function, alteration of urothelial factors and cytokines, chronic inflammation, vascular lesions, neurogenic inflammation and processes in the central nervous system leading to central sensitization. According to the involved mechanisms, BPS/IC may be arranged in clusters according to the clinical phenotype thus helping in clinical decision-making and treatment. Moreover, patients with BPS/IC suffer from other comorbidities such as fibromyalgia, irritable bowel syndrome, chronic pain and functional syndromes and psychosomatic diseases making the management challenging for medical professionals. SUMMARY: Bladder pain syndrome/interstitial cystitis is a complex heterogeneous medical condition involving different pathomechanisms leading to bladder pain and dysfunction, consequently, impairing quality-of-life in affected individuals. However, these mechanisms are still not fully understood, so that patient treatments often remain unsatisfactory. For this reason, continuing research is important to understand the underlying pathomechanisms to discover biomarkers and treatment targets eventually improving diagnostic and therapeutic measures of BPS/IC.

bTUNED: transcutaneous tibial nerve stimulation for neurogenic lower urinary tract dysfunction.

OBJECTIVE: To present the protocol for a randomized controlled trial (RCT) evaluating the efficacy and safety of transcutaneous tibial nerve stimulation (TTNS) for refractory neurogenic lower urinary tract dysfunction (NLUTD). STUDY DESIGN AND RESULTS: bTUNED (bladder and TranscUtaneous tibial Nerve stimulation for nEurogenic lower urinary tract Dysfunction) is an international multicentre, sham-controlled, double-blind RCT investigating the efficacy and safety of TTNS. The primary outcome is success of TTNS, defined as improvements in key bladder diary variables at study end compared to baseline values. The focus of the treatment is defined by the Self-Assessment Goal Achievement (SAGA) questionnaire. Secondary outcomes are the effect of TTNS on urodynamic, neurophysiological, and bowel function outcome measures, as well as the safety of TTNS. CONCLUSIONS: A total of 240 patients with refractory NLUTD will be included and randomized 1:1 into the verum or sham TTNS group from March 2020 until August 2026. TTNS will be performed twice a week for 30 min during 6 weeks. The patients will attend baseline assessments, 12 treatment visits and follow-up assessments at the study end.

Comparison of traditional outcome measures and self-assessed goal achievement in patients treated surgically for benign prostatic hyperplasia.

PURPOSE: To determine self-assessed goal achievement (SAGA) outcomes in men treated surgically for lower urinary tract symptoms (LUTS) due to benign prostatic obstruction (BPO) and compare them to the traditional outcome measures. METHODS: Single-center analysis of prospective database of men undergoing surgical treatment of LUTS/BPO at a single institution between July 2019 and March 2021. We assessed individual goals, traditional questionnaires, and functional outcomes prior to treatment, and at first follow-up after 6-12 weeks. We compared SAGA outcomes 'overall goal achievement' and 'satisfaction with treatment' to subjective and objective outcomes using Spearman's rank correlations (rho). RESULTS: A total of sixty-eight patients completed the individual goal formulation prior to surgery. Preoperative goals varied between different treatments and individuals. IPSS correlated with 'overall goal achievement' (rho = - 0.78, p < 0.001) and 'satisfaction with treatment' (rho = - 0.59, p < 0.001). Similarly, the IPSS-QoL was correlated with overall goal achievement (rho = - 0.79, p < 0.001) and satisfaction with treatment (rho = - 0.65, p < 0.001). No correlation was seen between SAGA outcomes and functional outcomes Qmax and PVR. CONCLUSIONS: SAGA represents a uniquely patient-specific outcome measure. Our study is, to our knowledge, the first to assess patient-specific goals prior to surgery and examine SAGA outcomes following treatment in men suffering from LUTS/BPO. The correlation of SAGA outcomes with IPSS and IPSS-QoL highlight the importance of this well-established questionnaire. Functional outcomes do not necessarily reflect patient's goals and may rather be considered physician-directed outcomes.

Management of chronic primary pelvic pain syndromes.

Management of chronic pelvic pain (CPP) remains a huge challenge for care providers and a major burden for healthcare systems. Treating chronic pain that has no obvious cause warrants an understanding of the difficulties in managing these conditions. Chronic pain has recently been accepted as a disease in its own right by the World Health Organization, with chronic pain without obvious cause being classified as chronic primary pain. Despite innumerable treatments that have been proposed and tried to date for CPP, unimodal therapeutic options are mostly unsuccessful, especially in unselected individuals. In contrast, individualised multimodal management of CPP seems the most promising approach and may lead to an acceptable situation for a large proportion of patients. In the present review, the interdisciplinary and interprofessional European Association of Urology Chronic Pelvic Pain Guideline Group gives a contemporary overview of the most important concepts to successfully diagnose and treat this challenging disease.

Localized and Locally Advanced Prostate Cancer: Treatment Options.

BACKGROUND: There are many treatment options for localized and locally advanced prostate cancer with radiotherapy and surgery representing the main local therapeutic strategies. SUMMARY: Depending on the risk of disease recurrence, we can stratify patients into low-, intermediate- and high-risk groups, which will guide patients' treatment. For low-risk patients, active surveillance is an option. Brachytherapy is also an option for low- and intermediate-risk patients and can be used as a boost following external beam radiotherapy for high-risk patients. For intermediate- and high-risk patients, radical prostatectomy and radiotherapy should be considered. Moreover, in addition to radiotherapy, concomitant androgen deprivation therapy may be needed. Finally, after radical prostatectomy and depending on pathological, biological and clinical factors, radiotherapy ± androgen deprivation therapy can be proposed as an adjuvant or salvage treatment. Key Messages: With radiotherapy and surgery being well-established treatment options for localized prostate cancer patients with equally good overall survival rates, priority must be given to patients' choice concerning the logistics and the toxicity profile of each option.

Reduction of stent-associated morbidity by minimizing stent material: a prospective, randomized, single-blind superiority trial assessing a customized 'suture stent'.

OBJECTIVES: To compare a customized 'suture stent' with a standard ureteric stent regarding stent-related symptoms, safety and efficacy. MATERIALS AND METHODS: Patients with urolithiasis located proximal to the iliac vessel crossing, requiring stenting in preparation for secondary ureterorenoscopy (URS) were randomized to standard ureteric stenting or a suture stent. Secondary ureterorenoscopy was performed 2-6 weeks later. The Ureteral Stent Symptoms Questionnaire (USSQ) was completed after 1 week, on the day before URS and 2-6 weeks after stent removal. Stent efficacy and safety were systematically assessed. RESULTS: A total of 88 patients were included in the analysis. The median (range) suture stent length was 10 (5-25) cm vs 26 cm for standard stents. Operation time was longer for insertion of the suture stent (24.0 vs 14.5 min; P < 0.001). Patients with a suture stent had a significantly lower USSQ urinary symptoms score 1 week after stent insertion, adjusted for baseline symptoms by subtracting scores from the final visit without indwelling stent (mean 7.1 vs 13.7, difference -6.6, 95% confidence interval [CI] -3.4 to -9.8; P < 0.001). Prior to secondary URS (after 2-6 weeks), baseline-adjusted urinary symptoms (mean 4.7 vs 12.2, difference -7.5, 95% CI -4.5 to -10.4; P < 0.001) and pain subscores (11.5 vs 17.6, difference -6.1, 95% CI -0.7 to -11.6; P = 0.004) were significantly lower in the suture stent group. All other USSQ subscores showed no significant differences. Adverse events occurred in 15 patients and were similarly frequent in the two groups. No significant differences were found between the groups regarding ureteric access during secondary URS. CONCLUSION: Replacement of the distal part of ureteric stents by a suture can reduce stent-associated symptoms without restrictions regarding secondary stone removal or safety.

Considering non-bladder aetiologies of overactive bladder: a functional neuroimaging study.

OBJECTIVES: To better understand the neuropathophysiology of overactive bladder (OAB) in women by characterising supraspinal activity in response to bladder distention and cold stimulation. SUBJECTS/PATIENTS AND METHODS: We recruited 24 female participants, 12 with OAB (median [interquartile range, IQR] age 40 [32-42] years) and 12 healthy controls (HCs) without lower urinary tract (LUT) symptoms (median [IQR] age 34 [28-44] years), and assessed LUT and cognitive function through neuro-urological examination, 3-day bladder diary, urodynamic investigation, and questionnaires. Functional magnetic resonance (MR) imaging using a 3-T scanner was performed in all participants during automated, repetitive bladder filling and draining (block design) with 100 mL body temperature (37 °C) saline using a MR-compatible and MR-synchronised infusion-drainage device until strong desire to void (HIGH-FILLING/DRAINING) and bladder filling with cold saline (4 °C, i.e. COLD). Whole-brain and region-of-interest analyses were conducted using Statistical Parametric Mapping, version 12. RESULTS: Significant between-group differences were found for 3-day bladder diary variables (i.e. voiding frequency/24 h, P < 0.001; voided volume/void, P = 0.04; and urinary incontinence [UI] episodes/24 h, P = 0.007), questionnaire scores (International Consultation on Incontinence Questionnaire-Female LUT symptoms [overall, filling, and UI scores, all P < 0.001]; the Overactive Bladder Questionnaire short form [symptoms and quality-of-life scores, both P < 0.001]; the Hospital Anxiety and Depression Scale [anxiety P = 0.004 and depression P = 0.003 scores]), as well as urodynamic variables (strong desire to void, P = 0.02; maximum cystometric capacity, P = 0.007; and presence of detrusor overactivity, P = 0.002). Age, weight and cognitive function (i.e. Mini-Mental State Examination, P = 1.0) were similar between groups (P > 0.05). In patients with OAB, the HIGH task elicited activity in the superior temporal gyrus, ventrolateral prefrontal cortex (VLPFC), and mid-cingulate cortex; and the COLD task elicited activity in the VLPFC, cerebellum, and basal ganglia. Compared to HCs, patients with OAB showed significantly stronger cerebellar activity during HIGH-FILLING and significantly less activity in the insula and VLPFC during HIGH-DRAINING. CONCLUSIONS: The present findings suggest a sensory processing and modulation deficiency in our OAB group, probably as part of their underlying pathophysiology, as they lacked activity in essential sensory processing areas, such as the insula. Instead, accessory areas, such as the cerebellum, showed significantly stronger activation compared to HCs, presumably supporting pelvic-floor motor activity to prevent UI. The novel findings of the present study provide physiological evidence of the necessity to consider non-bladder aetiologies of bladder symptoms.

Investigating the response scale of the EORTC QLQ-C30 in German cancer patients and a population survey.

BACKGROUND: The European Organization for research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) scales are scored on a 4-point response scale, ranging from not at all to very much. Previous studies have shown that the German translation of the response option quite a bit as mäßig violates interval scale assumptions, and that ziemlich is a more appropriate translation. The present studies investigated differences between the two questionnaire versions. METHODS: The first study employed a balanced cross-over design and included 450 patients with different types of cancer from three German-speaking countries. The second study was a representative survey in Germany including 2033 respondents. The main analyses included compared the ziemlich and mäßig version of the questionnaire using analyses of covariance adjusted for sex, age, and health burden. RESULTS: In accordance with our hypothesis, the adjusted summary score was lower in the mäßig than in the ziemlich version; Study 1: - 4.5 (95% CI - 7.8 to - 1.3), p = 0.006, Study 2: - 3.1 (95% CI - 4.6 to - 1.5), p < 0.001. In both studies, this effect was pronounced in respondents with a higher health burden; Study 1: - 6.8 (95% CI - 12.2 to - 1.4), p = 0.013; Study 2: - 4.5 (95% CI - 7.3 to - 1.7), p = 0.002. CONCLUSIONS: We found subtle but consistent differences between the two questionnaire versions. We recommend to use the optimized response option for the EORTC QLQ-C30 as well as for all other German modules. TRIAL REGISTRATION: The study was retrospectively registered on the German Registry for Clinical Studies (reference number DRKS00012759, 04th August 2017, https://www.drks.de/DRKS00012759 ).

Long-term oncological and functional follow-up in low-dose-rate brachytherapy for prostate cancer: results from the prospective nationwide Swiss registry.

OBJECTIVE: To evaluate the long-term oncological, functional and toxicity outcomes of low-dose-rate brachytherapy (LDR-BT) in relation to risk factors and radiation dose in a prospective multicentre cohort. PATIENTS AND METHODS: Data of patients from 12 Swiss centres undergoing LDR-BT from September 2004 to March 2018 were prospectively collected. Patients with a follow-up of ≥3 months were analysed. Functional and oncological outcomes were assessed at ~6 weeks, 6 and 12 months after implantation and annually thereafter. LDR-BT was performed with 125 I seeds. Dosimetry was done 6 weeks after implantation based on the European Society for Radiotherapy and Oncology recommendations. The Kaplan-Meier method was used for biochemical recurrence-free survival (BRFS). A prostate-specific antigen (PSA) rise above the PSA nadir + 2 was defined as biochemical failure. Functional outcomes were assessed by urodynamic measurement parameters and questionnaires. RESULTS: Of 1580 patients in the database, 1291 (81.7%) were evaluable for therapy outcome. The median (range) follow-up was 37.1 (3.0-141.6) months. Better BRFS was found for Gleason score ≤3+4 (P = 0.03, log-rank test) and initial PSA level of <10 ng/mL (P < 0.001). D'Amico Risk groups were significantly associated with BRFS (P < 0.001), with a hazard ratio of 2.38 for intermediate- and high-risk patients vs low-risk patients. The radiation dose covering 90% of the prostate volume (D90) after 6 weeks was significantly lower in patients with recurrence. Functional outcomes returned close to baseline levels after 2-3 years. A major limitation of these findings is a substantial loss to follow-up. CONCLUSION: Our results are in line with other studies showing that LDR-BT is associated with good oncological outcomes together with good functional results.

Ejaculatory disorders after prostatic artery embolization: a reassessment of two prospective clinical trials.

PURPOSE: This study aims to specify and explain the previous findings of unexpectedly high rates of ejaculatory disorders, i.e. 56%, found after prostatic artery embolization (PAE) in a randomized controlled trial comparing safety and efficacy of PAE and transurethral resection of the prostate (TURP). PATIENTS AND METHODS: Case report forms of the randomized controlled trial were analyzed to specify the grade of postoperative ejaculatory dysfunction 3 months postoperatively. In addition, study participants with assessable ejaculation were asked to complete the four-item Male Sexual Health Questionnaire-Ejaculation Dysfunction Short Form (MSHQ-EjD) referring to their ejaculatory function at present, as well as before treatment and 3 months after. Potential explanations for ejaculatory disorders after PAE were derived from histological examination of five radical prostatectomy specimens of patients that underwent PAE 6 weeks before radical prostatectomy within a proof-of-concept trial at the study site, St. Gallen Cantonal Hospital. An experienced uropathologist systematically examined the whole-gland embedded tissue with focus on structures that are involved into ejaculation. RESULTS: While patients after TURP predominantly suffered from anejaculation (52%), diminished ejaculation was found more often after PAE (40%). Significantly higher MSHQ-EjD scores were found 3 months after PAE and at a median follow-up of 31 months. Histological examination showed marked changes of structures involved into ejaculation (e.g., prostatic glands, seminal vesicles, ejaculatory ducts) after PAE. CONCLUSION: Although anejaculation occurs less frequently after PAE (16%) compared to TURP (52%), patients have to be informed about the relevant risk of ejaculatory disorders, especially diminished ejaculation.

Core Outcome Measures for Research in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation for Acute Respiratory or Cardiac Failure: An International, Multidisciplinary, Modified Delphi Consensus Study.

OBJECTIVES: Research evaluating outcomes in critically ill patients with acute respiratory and cardiac failure supported with extracorporeal membrane oxygenation has increased significantly. The objective was to identify a core set of outcomes that are essential to include in all clinical research evaluating the use of either venoarterial or venovenous extracorporeal membrane oxygenation in critically ill patients, particularly regarding safety and adverse events. DESIGN: A three-round modified Delphi process. SUBJECTS: Patients, caregivers, multidisciplinary clinicians, researchers, industry partners, and research funders were included. SETTING: Participants represented key extracorporeal membrane oxygenation organizations, including the Extracorporeal Life Support Organization, the International Extracorporeal Membrane Oxygenation Network, clinicians from high volume extracorporeal membrane oxygenation centers, and extracorporeal membrane oxygenation researchers or former extracorporeal membrane oxygenation patients from five continents. INTERVENTIONS: We used recommended standards for the development of a core outcome set. Outcome measures identified from systematic reviews of the literature and from qualitative studies of survivors were mapped to the domains identified by the Core Outcome Measures in Effectiveness Trials initiative separately for venovenous extracorporeal membrane oxygenation and venoarterial extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: Participant response rates were 40 of 47 (85%), 35 of 37 (95%), and 64 of 69 (93%) for survey rounds 1, 2, and 3, respectively, with participants representing 10 different countries on five continents. After the third round survey, 8 outcome measures met consensus for both venovenous extracorporeal membrane oxygenation and venoarterial extracorporeal membrane oxygenation. CONCLUSIONS: This study identified core outcomes to assess in all research evaluating the use of extracorporeal membrane oxygenation, including adverse events specific to this intervention, permitting standardization of outcome reporting for the first time. Identifying appropriate measurement instruments to evaluate these outcomes is an important next step to enable synthesis of extracorporeal membrane oxygenation research.

Outcome prediction of prostatic artery embolization: post hoc analysis of a randomized, open-label, non-inferiority trial.

OBJECTIVES: To identify predictors for different treatment outcomes after prostatic artery embolization (PAE) in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. PATIENTS AND METHODS: A post hoc analysis of data derived from the 48 patients undergoing PAE in a randomized, open-label, non-inferiority trial was performed. Relative changes in the International Prostate Symptoms Score (IPSS), absolute changes in maximum urinary flow rate (Qmax ), and relative changes in magnetic resonance imaging-assessed prostate volume from baseline to 12 weeks were defined as the outcomes measures of interest. Their association with various baseline characteristics and measures, technical details of PAE, and early postoperative measures were analysed using Spearman rank correlations and Wilcoxon rank-sum tests. The most promising predictors were further evaluated in receiver-operating characteristic (ROC) curve analyses. RESULTS: Higher total prostate and central gland (i.e. central plus transitional zone) volumes were associated with more pronounced improvements in the IPSS (Spearman rank correlation [rs]: -0.35 and -0.34; P = 0.01 and P = 0.02, respectively) and the Qmax (rs: 0.31 and 0.39; P = 0.05 and P = 0.01, respectively). ROC curve analyses suggested that volumes of 39 and 38 mL for total prostate and central gland volume, respectively, would be the optimal thresholds with which to predict PAE success as measured by the IPSS. Other anatomical characteristics of the prostate, such as the central gland index, also showed an even more distinct correlation to the improvement in Qmax (rs: 0.46, P = 0.003). The relative changes in prostate volume were clearly dependent on the technical performance of PAE. Occurrence of postoperative pain and blood levels of prostate-specific antigen and C-reactive protein emerged as potential early-stage outcome predictors after PAE. CONCLUSION: Baseline and peri-operative findings might help to guide patient selection and outcome prediction for PAE. Patients with larger prostates have a higher chance of success with PAE. Larger-scale clinical trials including a longer follow-up are warranted to further elucidate the most suitable patients for PAE.

In-hospital cost analysis of prostatic artery embolization compared with transurethral resection of the prostate: post hoc analysis of a randomized controlled trial.

OBJECTIVES: To perform a post hoc analysis of in-hospital costs incurred in a randomized controlled trial comparing prostatic artery embolization (PAE) and transurethral resection of the prostate (TURP). PATIENTS AND METHODS: In-hospital costs arising from PAE and TURP were calculated using detailed expenditure reports provided by the hospital accounts department. Total costs, including those arising from surgical and interventional procedures, consumables, personnel and accommodation, were analysed for all of the study participants and compared between PAE and TURP using descriptive analysis and two-sided t-tests, adjusted for unequal variance within groups (Welch t-test). RESULTS: The mean total costs per patient (±sd) were higher for TURP, at €9137 ± 3301, than for PAE, at €8185 ± 1630. The mean difference of €952 was not statistically significant (P = 0.07). While the mean procedural costs were significantly higher for PAE (mean difference €623 [P = 0.009]), costs apart from the procedure were significantly lower for PAE, with a mean difference of €1627 (P < 0.001). Procedural costs of €1433 ± 552 for TURP were mainly incurred by anaesthesia, whereas €2590 ± 628 for medical supplies were the main cost factor for PAE. CONCLUSIONS: Since in-hospital costs are similar but PAE and TURP have different efficacy and safety profiles, the patient's clinical condition and expectations - rather than finances - should be taken into account when deciding between PAE and TURP.

Predictability and Inducibility of Detachment of Prostatic Central Gland Tissue after Prostatic Artery Embolization: Post Hoc Analysis of a Randomized Controlled Trial.

PURPOSE: To assess the frequency and potential predictors of prostatic central gland tissue detachment (CGD), an enucleation-like reaction that sporadically occurred in a randomized controlled trial assessing efficacy and safety of prostatic artery embolization (PAE). MATERIALS AND METHODS: Trial data were analyzed to identify patients with CGD after PAE. Clinical parameters, MR imaging findings, technical details of PAE, and periinterventional data were compared between patients with and without CGD to identify parameters for prediction, induction, or early detection of CGD after PAE. RESULTS: CGD occurred after PAE in 3 of 48 patients (6.3%); these cases had good functional outcomes, but CGD was associated with increased risk of ejaculatory dysfunction and occurrence of complications. Frequency of preoperative transurethral bladder catheterization (100% vs 13.3%; P = .005), central gland index (mean ± standard deviation, 0.86 ± 0.02 vs 0.69 ± 0.14; P < .001), amount of particles applied (1.93 mL ± 0.12 vs 0.96 mL ± 0.36; P < .001), maximum early postoperative pain score (7.33 ± 2.08 vs 1.89 ± 2.40; P = .009), and blood C-reactive protein (CRP) levels after 48 hours (69.0 vs 18.58 mg/dL; P = .045) and 1 week (113.50 vs 5.16 mg/dL; P = .004) were significantly higher in cases of CGD. CONCLUSIONS: CGD is a rare reaction that might be triggered by prostatic zonal anatomy, embolization technique, and mechanical or inflammatory processes. It should be considered in patients with severe postoperative pain and high CRP levels who experience voiding dysfunction after PAE to avoid complications. Investigation of larger cohorts might further elucidate this tissue response.

Detection of microbial colonization of the urinary tract of patients prior to secondary ureterorenoscopy is highly variable between different types of assessment: results of a prospective observational study.

This study compares the findings of different detection methods for microorganisms in patients with ureteral stents undergoing secondary ureterorenoscopy including the use of a novel validated examination pipeline for biofilms on ureteral stents. Of the included 94 patients, 21.3% showed bacteriuria in preoperative urine cultures. Intraoperative urine culture showed bacteriuria in four (4.3%) of the patients. Stent biofilm cultures were positive in 12.9% and qPCR detected bacterial DNA in 18.1%. The findings of the different examinations were poorly correlated with each other. Detection of microorganisms in the urinary tract of patients with indwelling ureteral stents is highly dependent on timing (i.e. pre- vs intraoperative) and method of assessment. Preoperative routine urine cultures are not predictive for intraoperative urine- and stent culture. These results cast doubt on the clinical relevance of enterococcal species, staphylococci, and streptococci if identified preoperatively prior to stent removal. The timing of oral preoperative antibiotic prophylaxis might need to be reconsidered.

Spoilt for Choice: A Survey of Current Practices of Surgical Urinary Stone Treatment and Adherence to Evidence-Based Guidelines among Swiss Urologists.

INTRODUCTION: Urologists have to master a variety of techniques to be able to offer the most appropriate surgical stone treatment for each individual patient. Therefore, we performed a survey among board-certified Swiss urologists to assess the availability of the different surgical methods, the current practices of surgical treatment of urolithiasis and the adherence to evidence-based guideline recommendations in Switzerland. METHODS: A 14-question survey assessed the working environment, equipment, perioperative settings and decision trees for specific stone scenarios. Data was analyzed using descriptive statistics and chi-square tests to determine differences between frequencies of answers. RESULTS: Hundred and five members of Swiss Urology (38%) completed the survey. All treatment modalities are available for the majority of respondents. Ureterorenoscopy was found to have the highest availability (100%) and was the preferred choice in the majority of stone scenarios. A high adherence to the guidelines was found for the treatment of ureteral stones <10 mm (100% proximal and distal), and >10 mm (69% proximal, 94% distal). All respondents answered in accordance with the guidelines regarding the treatment of middle and upper pole stones <10 mm, 10-20 mm and lower pole stones 10-20 mm. Guideline adherence was 99% for lower pole stones <10 mm, 78% for lower pole stones >20 mm, and 63% for middle/upper pole stones >20 mm. CONCLUSION: This survey provides a detailed insight into current stone treatment practices in Switzerland. The full spectrum of urinary stone treatment options is available for the majority of Swiss urologists. The choice of treatment shows a high accordance with evidence-based guidelines and a preference for retrograde endoscopic surgery in the majority of stone scenarios.

Salvage radiotherapy for macroscopic local recurrences after radical prostatectomy : A national survey on patterns of practice.

INTRODUCTION: Although salvage radiotherapy (SRT) for PSA recurrence after radical prostatectomy provides better oncological outcomes when delivered early, in the absence of detectable disease many patients are treated for macroscopic locally recurrent tumors. Due to limited data from prospective studies, we hypothesized an important variability in the SRT management of these patients. Our aim was to investigate current practice patterns of SRT for local macroscopic recurrence after radical prostatectomy. MATERIAL AND METHODS: A total of 14 Swiss radiation oncology centers were asked to complete a survey on treatment specifications for macroscopic locally recurrent disease including information on pretherapeutic diagnostic procedures, dose prescription, radiation delivery techniques and androgen deprivation therapy (ADT). Treatment recommendations on ADT were analyzed using the objective consensus methodology. RESULTS: The majority of centers recommended pretreatment magnetic resonance imaging (MRI) of the pelvis and choline positron emission tomography (PET). The median prescribed dose to the prostate bed was 66 Gy (range 65-72 Gy) with a boost to the macroscopic lesion used by 79% of the centers with a median total dose of 72 Gy (range 70-80 Gy). Intensity-modulated rotational techniques were used by all centers and daily cone beam computed tomography (CT) was recommended by 43%. The use of concomitant ADT for any macroscopic recurrence was recommended by 43% of the centers while the remaining centers recommended it only for high-risk disease, which was not consistently defined. CONCLUSION: We observed a high variability of treatment paradigms when SRT is indicated for macroscopic local recurrences after prostatectomy. These data reflect the need for more standardized approaches and ultimately further research in this field.