Prostate cancer screening in Switzerland: a literature review and consensus statement from the Swiss Society of Urology.

Over a decade ago, the United States Preventive Services Taskforce (USPSTF) recommended against prostate-specific antigen (PSA)-based screening for prostate cancer in all men, which considerably influenced prostate cancer screening policies worldwide after that. Consequently, the world has seen increasing numbers of advanced stages and prostate cancer deaths, which later led the USPSTF to withdraw its initial statement. Meanwhile, the European Union has elaborated a directive to address the problem of implementing prostate cancer screening in "Europe's Beating Cancer Plan". In Switzerland, concerned urologists formed an open Swiss Prostate Cancer Screening Group to improve the early detection of prostate cancer. On the 20th of September 2023, during the annual general assembly of the Swiss Society of Urology (SGU/SSU) in Lausanne, members positively voted for a stepwise approach to evaluate the feasibility of implementing organised prostate cancer screening programs in Switzerland. The following article will summarise the events and scientific advances in the last decade during which evidence and promising additional modalities to complement PSA-based prostate cancer screening have emerged. It also aims to provide an overview of contemporary strategies and their potential harms and benefits.

Comparison of ciprofloxacin versus fosfomycin versus fosfomycin plus trimethoprim/sulfamethoxazole for preventing infections after transrectal prostate biopsy.

BACKGROUND: To evaluate antibiotic prophylaxis in transrectal prostate biopsies due to the recommendation of the European Medicines Agency (EMA): We describe our single center experience switching from ciprofloxacin to fosfomycin trometamol (FMT) alone and to an augmented prophylaxis combining fosfomycin and trimethoprim/sulfamethoxazole (TMP/SMX). METHODS: Between 01/2019 and 12/2020 we compared three different regimes. The primary endpoint was the clinical diagnosis of an infection within 4 weeks after biopsy. We enrolled 822 men, 398 (48%) of whom received ciprofloxacin (group-C), 136 (16.5%) received FMT (group-F) and 288 (35%) received the combination of TMP/SMX and FMT (group-BF). RESULTS: Baseline characteristics were similar between groups. In total 37/398 (5%) postinterventional infections were detected, of which 13/398 (3%) vs 18/136 (13.2%) vs 6/288 (2.1%) were detected in group-C, group-F and group-BF respectively. The relative risk of infectious complication was 1.3 (CI 0.7-2.6) for group-C vs. group-BF and 2.8 (CI 1.4-5.7) for group-F vs. group-BF respectively. CONCLUSION: The replacement of ciprofloxacin by fosfomycin alone resulted in a significant increase of postinterventional infections, while the combination of FMT and TMP/SMX had a comparable infection rate to FQ without apparent adverse events. Therefore, this combined regimen of FMT and TMP/SMX is recommended.

Overexpression of cyclin F/CCNF as an independent prognostic factor for poor survival in clear cell renal cell carcinoma.

Cyclin F (encoded by CCNF gene) has been reported to be implicated in the pathobiology of several human cancers. However, its potential clinical significance in clear cell renal cell carcinoma (ccRCC) remains unknown. The present study aimed to evaluate the potential significance of cyclin F, assessed by immunohistochemical (IHC) staining and molecular (bioinformatics) techniques, as a prognostic marker in ccRCC in relation to clinicopathological features and outcomes. IHC staining was performed using two independent ccRCC tissue array cohorts, herein called tissue macroarray (TMA)_1 and tissue microarray (TMA)_2, composed of 108 ccRCCs and 37 histologically normal tissues adjacent to the tumor (NAT) and 192 ccRCCs and 16 normal kidney samples, respectively. The mRNA expression data were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) public datasets, followed by bioinformatics analysis of biological mechanisms underlying prognosis. The relationship between immune cell infiltration level and CCNF expression in ccRCC was investigated using the Tumor Immune Estimation Resource 2.0 (TIMER2) and Gene Expression Profiling Interactive Analysis 2 (GEPIA2). Cyclin F expression was significantly elevated in ccRCC lesions compared to both NAT and normal renal tissues. Likewise, CCNF mRNA was markedly increased in ccRCCs relative to non-cancerous tissues. In all analyzed cohorts, tumors with features of more aggressive behavior were more likely to display cyclin F/CCNF-high expression than low. Furthermore, patients with high cyclin F/CCNF expression had shorter overall survival (OS) times than those with low expression. In addition, multivariable analysis revealed that cyclin F/CCNF-high expression was an independent prognostic factor for poor OS in ccRCC. Enrichment analysis for mechanistically relevant processes showed that CCNF and its highly correlated genes initiate the signaling pathways that eventually result in uncontrolled cell proliferation. CCNF expression was also correlated with immune cell infiltration and caused poor outcomes depending on the abundance of tumor-infiltrating immune cells in ccRCC. Our findings suggest that cyclin F/CCNF expression is likely to have an essential role in ccRCC pathobiology through regulating multiple oncogenic signaling pathways and affecting the tumor immune microenvironment and may serve as prognostic biomarker and promising therapeutic target in ccRCC.

Acute effects of angler's groundbaits: nutrient flux to water column.

Although ground-baiting related nutrient loading has been widely studied, we do not know what proportion of these nutrients release into the water column, affecting primary production directly. We conducted short-term (24-h, 5-day) experiments at wide temperature range, in presence and absence of fish using fish meal-based (FM-GB) and plant-based groundbait (PB-GB), to assess the nitrogen (N) and phosphorus (P) fluxes from GB into the water column. Nitrogen release from unconsumed FM-GB was negligible in the first 3 days, then increased abruptly, releasing 32% of its total N content by the fifth day. In contrast, PB-GB acted as temporary sink for inorganic N forms. Considerable (18-21%) inorganic P release was observed in both GB types in the first twelve hours. Consumed GBs induced considerable inorganic N release and its rate increased with temperature. Particulate forms predominated the released N in PB-GB, suggesting impaired digestion. Phosphorus-dominated by particulate forms-release was similar or lower than in unconsumed GB. Based on our results, excessive use of GB-when high amount of it remains unconsumed-can enhance eutrophication in P-limited ecosystems. Although less digestible GBs may have less abrupt effect on the primary production, undigested nutrients remain unavailable for removal through fish harvest.

Retrospective Evaluation of a Single Surgeon's Learning Curve of Robot-Assisted Radical Cystectomy with Intracorporeal Urinary Diversion via Ileal Conduit.

Robot-assisted radical cystectomy with intracorporeal urinary diversion (iRARC) is increasingly being performed instead of open surgery. A criticism of this technique is the long learning curve, but limited data are available on this topic. At our center, the transition from open radical cystectomy (ORC) to iRARC began in May 2017. A retrospective analysis was conducted on the initial 53 cases of robot-assisted cystectomy with intracorporeal urinary diversion via ileal conduit, which were performed by one single surgeon. The patients were divided into four consecutive groups according to the surgeon's increasing experience, and perioperative parameters were analyzed as a surrogate for the learning curve. Over the course of the learning curve, a decline in median operation time from 415 to 361 min (p = 0.02), blood loss from 400 to 200 mL (p = 0.01), and minor complications from 71% to 15% (p = 0.02) was observed. No significant difference in overall and major complications, length of hospital stay, and total lymph node yield was shown. During the initial period of the learning curve, only the less complex cases were operated on using robotic surgery, while the more challenging ones were handled through open surgery. After experience with 28 cases, no more cystectomies were performed through open surgery. This led to an increase in operation time and length of hospital stay, as well as a higher incidence of both minor and overall complications among cases 28-40. After 40 cases, a significant decrease in these parameters was observed again. Our analysis demonstrated that operation time, blood loss, and minor complications decrease with increasing surgical experience in iRARC, while suggesting that technically challenging cases should be operated on after experience with 40 robotic cystectomies.

Influence of Alumina Grade on Sintering Properties and Possible Application in Binder Jetting Additive Technology.

Alumina is one of the most popular ceramic materials widely used in both tooling and construction applications due to its low production cost, and high properties. However, the final properties of the product depend not only on the purity of the powder, but also, e.g., on its particle size, specific surface area, and the production technology used. These parameters are particularly important in the case of choosing additive techniques for the production of details. Therefore, the article presents the results of comparing five grades of Al2O3 ceramic powder. Their specific surface area (via Brunauer-Emmett-Teller (BET) and Barrett-Joyner-Halenda (BJH) methods), particle size distribution, and phase composition by X-ray diffraction (XRD) were determined. Moreover, the surface morphology was characterized by the scanning electron microscopy (SEM) technique. The discrepancy between generally available data and the results obtained from measurements has been indicated. Moreover, the method of spark plasma sintering (SPS), equipped with the registration system of the position of the pressing punch during the process, was used to determine the sinterability curves of each of the tested grades of Al2O3 powder. Based on the obtained results, a significant influence of the specific surface area, particle size, and the width of their distribution at the beginning of the Al2O3 powder sintering process was confirmed. Furthermore, the possibility of using the analyzed variants of powders for binder jetting technology was assessed. The dependence of the particle size of the powder used on the quality of the printed parts was demonstrated. The procedure presented in this paper, which involves analyzing the properties of alumina varieties, was used to optimize the Al2O3 powder material for binder jetting printing. The selection of the best powder in terms of technological properties and good sinterability makes it possible to reduce the number of 3D printing processes, which makes it more economical and less time-consuming.

Relationship Between Baseline Prostate-specific Antigen on Cancer Detection and Prostate Cancer Death: Long-term Follow-up from the European Randomized Study of Screening for Prostate Cancer.

BACKGROUND: The European Association of Urology guidelines recommend a risk-based strategy for prostate cancer screening based on the first prostate-specific antigen (PSA) level and age. OBJECTIVE: To analyze the impact of the first PSA level on prostate cancer (PCa) detection and PCa-specific mortality (PCSM) in a population-based screening trial (repeat screening every 2-4 yr). DESIGN, SETTING, AND PARTICIPANTS: We evaluated 25589 men aged 55-59 yr, 16898 men aged 60-64 yr, and 12936 men aged 65-69 yr who attended at least one screening visit in the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial (screening arm: repeat PSA testing every 2-4 yr and biopsy in cases with elevated PSA; control arm: no active screening offered) during 16-yr follow-up (FU). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We assessed the actuarial probability for any PCa and for clinically significant (cs)PCa (Gleason ≥7). Cox proportional-hazards regression was performed to assess whether the association between baseline PSA and PCSM was comparable for all age groups. A Lorenz curve was computed to assess the association between baseline PSA and PCSM for men aged 60-61 yr. RESULTS AND LIMITATIONS: The overall actuarial probability at 16 yr ranged from 12% to 16% for any PCa and from 3.7% to 5.7% for csPCa across the age groups. The actuarial probability of csPCa at 16 yr ranged from 1.2-1.5% for men with PSA <1.0 ng/ml to 13.3-13.8% for men with PSA ≥3.0 ng/ml. The association between baseline PSA and PCSM differed marginally among the three age groups. A Lorenz curve for men aged 60-61 yr showed that 92% of lethal PCa cases occurred among those with PSA above the median (1.21 ng/ml). In addition, for men initially screened at age 60-61 yr with baseline PSA <2 ng/ml, further continuation of screening is unlikely to be beneficial after the age of 68-70 yr if PSA is still <2 ng/ml. No case of PCSM emerged in the subsequent 8 yr (up to age 76-78 yr). A limitation is that these results may not be generalizable to an opportunistic screening setting or to contemporary clinical practice. CONCLUSIONS: In all age groups, baseline PSA can guide decisions on the repeat screening interval. Baseline PSA of <1.0 ng/ml for men aged 55-69 yr is a strong indicator to delay or stop further screening. PATIENT SUMMARY: In prostate cancer screening, the patient's baseline PSA (prostate-specific antigen) level can be used to guide decisions on when to repeat screening. The PSA test when used according to current knowledge is valuable in helping to reduce the burden of prostate cancer.

Variation across operating sites in urinary and sexual outcomes after radical prostatectomy in localized and locally advanced prostate cancer.

PURPOSE: The extent of variation in urinary and sexual functional outcomes after radical prostatectomy (RPE) between prostate cancer (PC) operating sites remains unknown. Therefore, this analysis aims to compare casemix-adjusted functional outcomes (EPIC-26 scores incontinence, irritative/obstructive function and sexual function) between operating sites 12 months after RPE. MATERIALS AND METHODS: Analysis of a cohort of 7065 men treated with RPE at 88 operating sites (prostate cancer centers, "PCCs") between 2016 and 2019. Patients completed EPIC-26 and sociodemographic information surveys at baseline and 12 months after RPE. Survey data were linked to clinical data. EPIC-26 domain scores at 12 months after RPE were adjusted for relevant confounders (including baseline domain score, clinical and sociodemographic information) using regression analysis. Differences between sites were described using minimal important differences (MIDs) and interquartile ranges (IQR). The effects of casemix adjustment on the score results were described using Cohen's d and MIDs. RESULTS: Adjusted domain scores at 12 months varied between sites, with IQRs of 66-78 (incontinence), 89-92 (irritative/obstructive function), and 20-29 (sexual function). Changes in domain scores after casemix adjustment for sites ≥ 1 MID were noted for the incontinence domain (six sites). Cohen's d ranged between - 0.07 (incontinence) and - 0.2 (sexual function), indicating a small to medium effect of casemix adjustment. CONCLUSIONS: Variation between sites was greatest in the incontinence and sexual function domains for RPE patients. Future research will need to identify the factors contributing to this variation. TRIAL REGISTRY: The study is registered at the German Clinical Trial Registry ( https://www.drks.de/drks_web/ ) with the following ID: DRKS00010774.

A Phase 1/2 Single-arm Clinical Trial of Recombinant Bacillus Calmette-Guérin (BCG) VPM1002BC Immunotherapy in Non-muscle-invasive Bladder Cancer Recurrence After Conventional BCG Therapy: SAKK 06/14.

BACKGROUND: VPM1002BC is a genetically modified Mycobacterium bovis bacillus Calmette-Guérin (BCG) strain with potentially improved immunogenicity and attenuation. OBJECTIVE: To report on the efficacy, safety, tolerability and quality of life of intravesical VPM1002BC for the treatment of non-muscle-invasive bladder cancer (NMIBC) recurrence after conventional BCG therapy. DESIGN, SETTING, AND PARTICIPANTS: We designed a phase 1/2 single-arm trial (NCT02371447). Patients with recurrent NMIBC after BCG induction ± BCG maintenance therapy and intermediate to high risk for cancer progression were eligible. INTERVENTION: Patients were scheduled for standard treatment of six weekly instillations with VPM1002BC followed by maintenance for 1 yr. Treatment was stopped in cases of recurrence. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was defined as the recurrence-free rate (RFR) in the bladder 60 wk after trial registration. The sample size was calculated based on the assumption that ≥30% of the patients would be without recurrence at 60 wk after registration. RESULTS AND LIMITATIONS: After exclusion of two ineligible patients, 40 patients remained in the full analysis set. All treated tumours were of high grade and 27 patients (67.5%) presented with carcinoma in situ. The recurrence-free rate in the bladder at 60 wk after trial registration was 49.3% (95% confidence interval [CI] 32.1-64.4%) and remained at 47.4% (95% CI 30.4-62.6%] at 2 yr and 43.7% (95% CI 26.9-59.4%) at 3 yr after trial registration. At the same time, progression to muscle-invasive disease had occurred in three patients and metastatic disease in four patients. Treatment-related grade 1, 2, and 3 adverse events (AEs) were observed in 14.3%, 54.8%, and 4.8% of the patients, respectively. No grade ≥4 AEs occurred. Two of the 42 patients did not tolerate five or more instillations during induction. Limitations include the single-arm trial design and the low number of patients for subgroup analysis. CONCLUSIONS: At 1 yr after treatment start, almost half of the patients remained recurrence-free after therapy with VPM100BC. The primary endpoint of the study was met and the therapy is safe and well tolerated. PATIENT SUMMARY: We conducted a trial of VPM100BC, a genetically modified bacillus Calmette-Guérin (BCG) strain for treatment of bladder cancer not invading the bladder muscle. At 1 year after the start of treatment, almost half of the patients with a recurrence after previous conventional BCG were free from non-muscle-invasive bladder cancer (NMIBC). The results are encouraging and VPM1002BC merits further evaluation in randomised studies for patients with NMIBC.

Indication for Active Surveillance in the Era of MRI-Targeted Prostate Biopsies.

INTRODUCTION: Active surveillance (AS) strategies were established to avoid overtreatment of low-risk prostate cancer (PCa) patients. Low tumor volume represents one indication criteria; however, applying this criterion after MRI-targeted prostate biopsies may lead to overestimation of tumor volume; wherefore, patients suitable for AS would be exposed to the risk of overtreatment. METHODS: This retrospective analysis included 318 patients in which PCa was detected by MRI-TRUS fusion prostate biopsy. Classic and extended indication for AS included Gleason 6 and Gleason 3 + 4 cancer, respectively. We assessed the effect of targeted biopsies and temporary rating strategies on eligibility for AS and developed new "composite" algorithms to more accurately assess eligibility for AS. RESULTS: Forty-four (13.8%) and 60 (18.9%) of the 318 patients qualified for AS according to "classic" and "extended" criteria, respectively. Application of the "composite 1" definition led to AS eligibility of 52 of 248 patients (20.97%) in the classic and of 77 of 248 patients (31.05%) in the "extended" group. CONCLUSIONS: We could demonstrate that classic algorithms led to ineligibility of patients for AS. We propose a new rating algorithm to improve tumor assessment for a more accurate indication for AS.

Intervention-related Deaths in the European Randomized Study of Screening for Prostate Cancer.

BACKGROUND: Identification of intervention-related deaths is important for an accurate assessment of the ratio of benefit to harm in screening trials. OBJECTIVE: To investigate intervention-related deaths by study arm in the European Randomized Study of Prostate Cancer Screening (ERSPC). DESIGN SETTING AND PARTICIPANTS: ERSPC is a multicenter trial initiated in the 1990s to investigate whether screening on the basis of prostate-specific antigen (PSA) can decrease prostate cancer mortality. The present study included men in the core age group (55-69 yr: screening group n = 112 553, control group n = 128 681) with 16-yr follow-up. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Causes of death among men with prostate cancer in ERSPC were predominantly evaluated by independent national committees via review of medical records according to a predefined algorithm. Intervention-related deaths were defined as deaths caused by complications during the screening procedure, treatment, or follow-up. Descriptive statistics were used for the results. RESULTS AND LIMITATIONS: In total, 34 deaths were determined to be intervention-related, of which 21 were in the screening arm and 13 in the control arm. The overall risk of intervention-related death was 1.41 (95% confidence interval 0.99-1.99) per 10 000 randomized men for both arms combined and varied among centers from 0 to 7.0 per 10 000 randomized men. A limitation of this study is that differences in procedures among centers decreased the comparability of the results. CONCLUSIONS: Intervention-related deaths were rare in ERSPC. Monitoring of intervention-related deaths in screening trials is important for assessment of harms. PATIENT SUMMARY: We investigated deaths due to screening or treatment to assess harm in a trial of prostate cancer screening. Few such deaths were identified.

Diagnostic accuracy and clinical implications of robotic assisted MRI-US fusion guided target saturation biopsy of the prostate.

MRI-targeted prostate biopsy improves detection of clinically significant prostate cancer (PCa). However, up to 70% of PCa lesions display intralesional tumor heterogeneity. Current target sampling strategies do not yet adequately account for this finding. This prospective study included 118 patients who underwent transperineal robotic assisted biopsy of the prostate. We identified a total of 58 PCa-positive PI-RADS lesions. We compared diagnostic accuracy of a target-saturation biopsy strategy to accuracy of single, two, or three randomly selected targeted biopsy cores and analysed potential clinical implications. Intralesional detection of clinically significant cancer (ISUP ≥ 2) was 78.3% for target-saturation biopsy and 39.1%, 52.2%, and 67.4% for one, two, and three targeted cores, respectively. Target-saturation biopsies led to a more accurate characterization of PCa in terms of Gleason score and reduced rates of significant cancer missed. Compared to one, two, and three targeted biopsy cores, target-saturation biopsies led to intensified staging procedures in 21.7%, 10.9, and 8.7% of patients, and ultimately to a potential change in therapy in 39.1%, 26.1%, and 10.9% of patients. This work presents the concept of robotic-assisted target saturation biopsy. This technique has the potential to improve diagnostic accuracy and thus individual staging procedures and treatment decisions.

Effects of hormonal treatment before water warming on synchronisation of spawning time, oocyte size, and egg quality in pikeperch (Sander lucioperca).

Inducing reproduction during periods of the year when spawning typically does not occur is an important goal for the feasibility of commercial fish farming. Pre-seasonal propagation of pikeperch generally occurs about 3 months before the natural spawning season. The objective of this study was to assess effects of imposing a thermal schedule for control of water temperature and differing salmon gonadotropin releasing hormone analogue (sGnRHa) dosages on final stages of oocyte growth, and egg quality by optimizing protocol duration and synchronizing spawning time. In Experiment 1, there was analysis of thermal schedule effects for water temperature control when hormonal administrations occurred before or after water warming (WARMING and STABLE, respectively). In Experiment 2, there was assessment of the sGnRHa dosage effects during the warming schedule. In both experiments there was analysis of oocyte diameter from time of sGnRHa administration until the late stages of maturation. There was greater synchrony in time of spawning in specimens of the WARMING group with lesser variability in time from sGnRHa administration to spawning. In Experiment 2, values for reproductive variables were variable among the different groups, without any differences between treatments. Oocyte diameter at the time of sGnRHa administration was correlated with embryo survival. For effective pre-seasonal pikeperch propagation, the selection of breeders based on oocyte diameter, and administration of 5 µg/kg sGnRHa immediately upon transport to hatchery, followed by a 1 °C/d temperature increase to 10 °C, are effective methods for induction of spawning during periods when spawning does not naturally occur.

Impact of cancer screening on metastasis: A prostate cancer case study.

BACKGROUND: Trials of cancer screening present results in terms of deaths prevented, but metastasis is also a key endpoint that screening seeks to prevent. We developed a framework for projecting overall (de novo and progressive) metastases prevented in a screening trial using prostate cancer screening as a case study. METHODS: Mechanistic simulation model in which screening shifts a fraction of cases that would be metastatic at diagnosis to being non-metastatic. This shift increases the incidence of non-overdiagnosed, organ-confined cases. We use estimates of the risk of metastatic progression for these cases to project how many progress to metastasis after diagnosis and tally the projected de novo and progressive metastatic cases with and without screening. We use data on stage shift from the European Randomized Study of Screening for Prostate Cancer (ERSPC) and data on the risk of metastatic progression from the Scandinavian Prostate Cancer Group-4 trial. We estimate the relative risk and absolute risk reductions in metastatic disease at diagnosis and compare these with reductions in overall metastases. RESULTS: Assuming no effect of screening beyond initial stage shift at diagnosis, the model projects a 43% reduction in metastasis at diagnosis but a 22% reduction in the cumulative probability of metastasis over 12 years in favor of screening. These results are consistent with the empirical findings from the ERSPC. CONCLUSION: Any reduction in metastatic disease at diagnosis under screening is likely to be an overly optimistic predictor of the impact of screening on overall metastasis and disease-specific mortality.

Efficacy, safety, and perioperative outcomes of holmium laser enucleation of the prostate-a comparison of patients with lower urinary tract symptoms and urinary retention.

Holmium laser enucleation of the prostate (HoLEP) is a valid treatment option to relieve bladder outlet obstruction in patients with large prostate volumes (PV). Its efficacy, tolerability, and safety are comparable to the ones of other laser treatments of the prostate and resection techniques. However, safety and efficacy of HoLEP have not been compared between patients with and without preoperative urinary retention. We included 350 patients (mean age 71.2 years) who had undergone HoLEP due to lower urinary tract symptoms (LUTS) or urinary retention caused by prostatic hyperplasia. We evaluated the differences in peri- and postoperative outcomes and complications between patients with and patients without preoperative urinary retention. The mean PV was 115 cm3. PV was > 100 cm3 in 61.9% and < 100 cm3 in 38.1% of the patients. Perioperative complications occurred in 23 patients (6.6%), 15 of which (4.3%) required operative revision. We found no significant differences in terms of complication rates between patients with PV > 100 cm3 and patients with PV < 100 cm3. Mean catheterization-duration was 3.3 days. Preoperatively, 140 patients (40%) had a suprapubic or transurethral indwelling catheter; they did not differ from patients without preoperative catheter regarding postoperative catheter removal success rate, early postoperative complications, and functional outcomes. Prostate cancer was diagnosed in 43 patients (12.3%). Median postoperative PSA-decline was 6.1 ug/l (89.8% drop). HoLEP is a safe and effective treatment for patients with LUTS or urinary retention and large PV. PV > 100 cm3 was not associated with higher complication rates or successful catheter-removal. Furthermore, functional outcomes were independent of preoperative catheterization.

Feasibility of freehand MRI/US cognitive fusion transperineal biopsy of the prostate in local anaesthesia as in-office procedure-experience with 400 patients.

BACKGROUND: Transrectal (TR) ultrasound-guided prostate biopsy is one of the most commonly performed urologic procedures worldwide. The major drawback of this approach is the associated risk for infectious complications. Sepsis rates are increasing due to rising antibiotic resistance, representing a global issue. The transperineal (TP) approach for prostate biopsy has recently been adopted at many centres as an alternative to the TR biopsy, and it was shown to be associated with a lower risk for sepsis. The aim of this study was to assess safety and tolerability of TP prostate biopsy performed in local anaesthesia. METHODS: We retrospectively analysed data of patients who had undergone office-based TP prostate biopsy in local anaesthesia, performed by a single surgeon between January 2015 and May 2019. We evaluated the patients' acceptance of the procedure by a pain score, as well as its safety and diagnostic performance. RESULTS: Four hundred patients were included. Median age was 66 years [range, 49-86]. Median prostate-specific antigen (PSA) concentration was 6.4 ng/ml [range, 0.3-1400], median PSA density was 0.15 ng/ml2 [range, 0-31.1] and median prostate volume was 40 ml [range, 6-150]. A total of 118 (29.5%) and 105 (26.2%) patients had orally received two and one doses of 500 mg fluoroquinolone, respectively, and 177 (44.3%) patients did not receive any antibiotic prophylaxis. No infectious complications occurred. Median pain score was 2.0 (range, 0-8). Overall cancer detection rate was 64.5% (258/400). CONCLUSIONS: Freehand TP prostate biopsy in local anaesthesia is a safe, effective and well-tolerated outpatient procedure with a high cancer detection rate. The elimination of infectious complications and its high accuracy make this technique a feasible alternative to the TR approach for the urological office. We assume that the single puncture and our trocar-like access sheath introduction technique diminish tissue trauma and bacterial exposition, and thus contribute to these promising results.

Influence of regular aspirin intake on PSA values, prostate cancer incidence and overall survival in a prospective screening trial (ERSPC Aarau).

OBJECTIVES: To analyze the influence of aspirin (ASA) intake on PSA values and prostate cancer (PCa) development in a prospective screening study cohort. METHODS: 4314 men from the Swiss section of the European Randomized Study of Screening for Prostate Cancer (ERSPC) were included. A transrectal prostate biopsy was performed in men with a PSA level ≥ 3 ng/ml. Mortality data were obtained through registry linkages. PCa incidence and grade, total PSA, free-to-total PSA and overall survival were compared between ASA users and non-users. RESULTS: Median follow-up time was 9.6 years. In 789 men (18.3%) using aspirin [ASA +], the overall PCa incidence was significantly lower (6.8% vs. 9.6%, p = 0.015), but the multivariate Cox regression analysis showed no significant decrease in risk of PCa diagnosis (HR 0.84, p = 0.297). Total PSA values were significantly lower in ASA users for both baseline (1.6 vs. 1.8 ng/ml, p = 0.007) and follow-up visits (1.75 vs. 2.1 ng/ml, p < 0.001). Multivariate Cox regression analysis predicted significantly higher overall mortality risk among ASA users (HR 1.46, p = 0.009). CONCLUSIONS: In our study population, PCa incidence was significantly reduced among patients on aspirin. While we did not observe a statistically significant PCa risk reduction during the follow-up period, we found lower PSA values among ASA users compared to non-users, with a more distinct difference after 4 years of ASA intake, suggesting a cumulative effect and a potential protective association between regular ASA intake and PCa development. As for clinical practice, lowering PSA cutoff values by 0.4 ng/ml could be considered in long-term ASA users to avoid a potential bias towards delayed PCa detection.

Exactly solvable model of gene expression in a proliferating bacterial cell population with stochastic protein bursts and protein partitioning.

Many of the existing stochastic models of gene expression contain the first-order decay reaction term that may describe active protein degradation or dilution. If the model variable is interpreted as the molecule number, and not concentration, the decay term may also approximate the loss of protein molecules due to cell division as a continuous degradation process. The seminal model of that kind leads to gamma distributions of protein levels, whose parameters are defined by the mean frequency of protein bursts and mean burst size. However, such models (whether interpreted in terms of molecule numbers or concentrations) do not correctly account for the noise due to protein partitioning between daughter cells. We present an exactly solvable stochastic model of gene expression in cells dividing at random times, where we assume description in terms of molecule numbers with a constant mean protein burst size. The model is based on a population balance equation supplemented with protein production in random bursts. If protein molecules are partitioned equally between daughter cells, we obtain at steady state the analytical expressions for probability distributions similar in shape to gamma distributions, yet with quite different values of mean burst size and mean burst frequency than would result from fitting of the classical continuous-decay model to these distributions. For random partitioning of protein molecules between daughter cells, we obtain the moment equations for the protein number distribution and thus the analytical formulas for the squared coefficient of variation.

Could Differences in Treatment Between Trial Arms Explain the Reduction in Prostate Cancer Mortality in the European Randomized Study of Screening for Prostate Cancer?

BACKGROUND: Differential treatment between trial arms has been suggested to bias prostate cancer (PC) mortality in the European Randomized Study of Screening for Prostate Cancer (ERSPC). OBJECTIVE: To quantify the contribution of treatment differences to the observed PC mortality reduction between the screening arm (SA) and the control arm (CA). DESIGN, SETTING, AND PARTICIPANTS: A total of 14 136 men with PC (SA: 7310; CA: 6826) in the core age group (55-69yr) at 16yr of follow-up. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The outcomes measurements were observed and estimated numbers of PC deaths by treatment allocation in the SA and CA, respectively. Primary treatment allocation was modeled using multinomial logistic regression adjusting for center, age, year, prostate-specific antigen, grade group, and tumor-node-metastasis stage. For each treatment, logistic regression models were fitted for risk of PC death, separately for the SA and CA, and using the same covariates as for the treatment allocation model. Treatment probabilities were multiplied by estimated PC death risks for each treatment based on one arm, and then summed and compared with the observed number of deaths. RESULTS AND LIMITATIONS: The difference between the observed and estimated treatment distributions (hormonal therapy, radical prostatectomy, radiotherapy, and active surveillance/watchful waiting) in the two arms ranged from -3.3% to 3.3%. These figures, which represent the part of the treatment differences between arms that cannot be explained by clinicopathological differences, are small compared with the observed differences between arms that ranged between 7.2% and 10.1%. The difference between the observed and estimated numbers of PC deaths among men with PC was 0.05% (95% confidence interval [CI] -0.1%, 0.2%) when applying the CA model to the SA, had the two groups received identical primary treatment, given their clinical characteristics. When instead applying the SA model to the CA, the difference was, as expected, very similar-0.01% (95% CI -0.3%, 0.2%). Consistency of the results of the models demonstrates the robustness of the modeling approach. As the observed difference between trial arms was 4.2%, our findings suggest that differential treatment explains only a trivial proportion of the main findings of ERSPC. A limitation of the study is that only data on primary treatment were available. CONCLUSIONS: Use of prostate-specific antigen remains the predominant explanation for the reduction in PC mortality seen in the ERSPC trial and is not attributable to differential treatment between trial arms. PATIENT SUMMARY: This study shows that prostate cancer deaths in the European screening trial (European Randomized Study of Screening for Prostate Cancer) were prevented because men were diagnosed and treated earlier through prostate-specific antigen screening, and not because of different, or better, treatment in the screening arm compared with the control arm.

Renal pseudoaneuryms and pulmonary embolism: A unique manifestation of complications following blunt renal trauma.

This case report presents a unique manifestation of complications in a 71-year-old man following blunt renal trauma. Initially, computed tomography (CT) revealed a traumatic left kidney laceration. Hematuria ceased quickly after ureteral stent placement. One week later, hematuria reoccurred while the patient was treated for pulmonary embolism. Multiphase CT revealed two renal pseudoaneurysms as the underlying cause. Renal pseudoaneurysms are commonly associated with surgery or inflammation and rarely seen after trauma. Selective angiographic embolization successfully stopped hematuria. Thereafter, the patient was hemodynamically stable to continue therapeutic thrombolysis. After discharge, the patient remained symptom-free and had an unremarkable follow up assessment.