Explore the vast range of titles available.

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.

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.

Inflammation has been suggested to play an important role in onset and progression of prostate cancer (PCa). Histological analysis of prostatectomy specimens has revealed focal inflammation in early stage lesions of this malignancy. We addressed the role of inflammatory stimuli in the release of PCa-specific, tumor-derived soluble factors (PCa-TDSFs) already reported to be mediators of PCa morbidity, such as indoleamine 2,3-dioxygenase (IDO) and interleukin (IL)-6. Inflammation-driven production and functions of PCa-TDFSs were tested \" \" by stimulating established cell lines (CA-HPV-10 and PC3) with IFN-γ or TNF-α. Expression of genes encoding IDO, IL-6, IFN-γ, TNF-α, and their receptors was investigated in tumor tissues of PCa patients undergoing radical prostatectomy, in comparison with benign prostatic hyperplasia (BPH) specimens. IFN-γ and TNF-α-treatment resulted in the induction of IDO and IL-6 gene expression and release in established cell lines, suggesting that the elicitation of PCa-TDSFs by these cytokines might contribute to progression of cancer into an untreatable phenotype. An analysis based on timing of biochemical recurrence revealed the prognostic value of IDO but not IL-6 gene expression in predicting recurrence-free survival in patients (RFS) with PCa. In addition, a urine-based mRNA biomarker study revealed the diagnostic potential of IDO gene expression in urines of men at risk of PCa development.

Objective While statins have demonstrated a variety of antineoplastic effects in preclinical studies, several retrospective clinical studies and observational studies have not shown a consistent chemopreventive benefit against prostate cancer (PCa). Therefore, in this population‐based cohort study, we examined the association of statin intake on prostate specific antigen (PSA) values and risk of development of PCa. Method N = 4,314 men from the Swiss section of the European Randomized Study of Screening for Prostate Cancer (ERSPC) were evaluated. N = 761 men were statin users [Stat+]. The median follow‐up was 9.6 years. A transrectal prostate biopsy was performed in men with a PSA‐level ≥ 3 ng/mL. Mortality and incidence data was obtained through registry linkages. PCa incidence, total serum PSA level, free‐to‐total PSA level, and overall survival were compared between [Stat+] and [Stat−] patients. Results Total PSA values were significantly lower in [Stat+] patients at baseline (1.5 vs. 1.8 ng/mL, p < 0.001) and at last follow‐up (1.8 vs. 2.1 ng/mL, p < 0.001). PCa detection during the follow‐up period was significantly associated with baseline PSA. The overall incidence of PCa showed no statistical difference among [Stat+] and [Stat−] groups (7.4% vs. 9.5%, p = 0.08), indicating that statin use had no effect on the risk of developing PCa during follow‐up. [Stat+] patients had a significantly higher overall mortality risk compared to [Stat−] patients (HR 2.04, p < 0.001). Discussion A significant risk reduction in the development of PCa in [Stat+] patients was not found. We did observe lower PSA values among [Stat+] patients, compared to [Stat−] patients, with an increasing difference during follow‐up. Lower prostate‐specific antigen (PSA) values were found among statin users, compared to statin non‐users. A significant prostate cancer (PCa) risk reduction in statin users was not observed. Statin users had a significantly higher overall mortality risk than statin non‐users.

A key barrier to the realization of personalized medicine for cancer is the identification of biomarkers. Here we describe a two-stage strategy for the discovery of serum biomarker signatures corresponding to specific cancer-causing mutations and its application to prostate cancer (PCa) in the context of the commonly occurring phosphatase and tensin homolog (PTEN) tumor-suppressor gene inactivation. In the first stage of our approach, we identified 775 N-linked glycoproteins from sera and prostate tissue of wild-type and Pten-null mice. Using label-free quantitative proteomics, we showed that Pten inactivation leads to measurable perturbations in the murine prostate and serum glycoproteome. Following bioinformatic prioritization, in a second stage we applied targeted proteomics to detect and quantify 39 human ortholog candidate biomarkers in the sera of PCa patients and control individuals. The resulting proteomic profiles were analyzed by machine learning to build predictive regression models for tissue PTEN status and diagnosis and grading of PCa. Our approach suggests a general path to rational cancer biomarker discovery and initial validation guided by cancer genetics and based on the integration of experimental mouse models, proteomics-based technologies, and computational modeling.

In this work, several machine learning (ML) algorithms, both classical ML and modern deep learning, were investigated for their ability to improve the performance of a pipeline for the segmentation and classification of prostate lesions using MRI data. The algorithms were used to perform a binary classification of benign and malignant tissue visible in MRI sequences. The model choices include support vector machines (SVMs), random decision forests (RDFs), and multi-layer perceptrons (MLPs), along with radiomic features that are reduced by applying PCA or mRMR feature selection. Modern CNN-based architectures, such as ConvNeXt, ConvNet, and ResNet, were also evaluated in various setups, including transfer learning. To optimize the performance, different approaches were compared and applied to whole images, as well as gland, peripheral zone (PZ), and lesion segmentations. The contribution of this study is an investigation of several ML approaches regarding their performance in prostate cancer (PCa) diagnosis algorithms. This work delivers insights into the applicability of different approaches for this context based on an exhaustive examination. The outcome is a recommendation or preference for which machine learning model or family of models is best suited to optimize an existing pipeline when the model is applied as an upstream filter.

ObjectivesTo analyze the influence of aspirin (ASA) intake on PSA values and prostate cancer (PCa) development in a prospective screening study cohort.Methods4314 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.ResultsMedian 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).ConclusionsIn 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.

Introduction Laser techniques for the treatment of bladder outlet obstruction (BOO) due to benign prostate enlargement (BPE) have emerged as an alternative to transurethral resection of the prostate (TURP) and open prostatectomy (OP). Materials and methods A Medline search over the past 4 years was performed to assess the safety, intra- and postoperative morbidity of various laser techniques. Results Data on holmium laser enucleation of the prostate (HoLEP) show the highest grade of evidence with two meta-analyses available and prove the low intra- and postoperative morbidity with reproducible long-term results. Photoselective vaporization of the prostate (PVP) with the Greenlightlaser (potassium titanyl phosphate, KTP or lithium borate, LBO) is characterized by excellent haemostatic properties in patients with or without oral anticoagulation. Long-term results show a reoperation rate comparable with TURP; however, there is a lack of randomized trials. Various types of diode lasers with different wavelengths are available for laser vaporization; despite their favourable haemostatic properties, a higher invasion depth seems to result in necrosis of the tissue leading to a higher rate of reoperation. Thulium-laser resection of the prostate shows promising intra- and postoperative morbidity, but data are limited and initial results need to be confirmed in large-scale trials. Conclusion In summary, HoLEP- and KTP-, or LBO-laser vaporization of the prostate are the most mature techniques of laser prostatectomy and treatment alternatives to TURP and OP, whereas the clinical value and durability of procedures with diode laser systems and the thulium laser need to be confirmed in high-quality prospective RCTs.

Purpose To analyze the effect of the oral antidiabetic drug metformin on PSA level, free-to-total PSA ratio (f/t-ratio), PCa incidence and grade as well as mortality in men participating in a population-based screening trial. Methods Data from 4,314 men aged 55–70 years from a population-based PSA-screening trial (ERSPC Aarau) were analyzed. Information on metformin exposure was obtained by a self-administered questionnaire. Serum PSA threshold at ≥3 ng/ml triggered prostate biopsy. Data on PCa incidence and mortality were obtained through registry linkages. Results Median follow-up time was 7.6 years. Mean age at baseline was 65.5 years (±SD 4.4). In all, n  = 150 (3.5 %) men used metformin [metf+]. Mean baseline PSA levels were comparable between both groups ([metf+] 1.6 ng/ml ± 2.4 vs. [metf−] 1.8ug/l ± 2.2, p  = 0.4) while f/t-ratio was slightly higher in metformin users ([metf+] 30.7 % ± 10.9 vs. [metf−] 27.3 % ± 10.9, p  = 0.01). Overall, n  = 372 (8.6 %) PCa cases were detected. Neither cumulative PCa incidence ( n  = 11; 7.3 % [metf+] vs. n  = 361 8.7 % [metf−]; p  = 0.5) nor d`Amico risk groups were significantly different between both groups. One man in each group (metf+ 0.7 % and metf− 0.02 %) died from PCa ( p  < 0.0001), respectively. All-cause mortality was significantly higher among met + compared to met- (adjusted OR 2.50, 95 %CI 1.59–3.82; p  = 0.0001). Conclusion No significant differences in PSA levels or PCa incidence and grade were observed. The slightly higher f/t-ratio did not result in lower PCa detection rate. Metformin users were at significantly higher risk of all-cause mortality. The relatively small number of men on metformin is a main limitation of the study.

Background Chronic inflammation has been suggested to favour prostate cancer (PCA) development. Interleukins (IL) represent essential inflammation mediators. IL-2, IL-7, IL-15 and IL-21, sharing a common receptor γ chain (c-γ), control T lymphocyte homeostasis and proliferation and play major roles in regulating cancer-immune system interactions. We evaluated local IL-2, IL-7, IL-15 and IL-21 gene expression in prostate tissues from patients with early stage PCA or benign prostatic hyperplasia (BPH). As control, we used IL-6 gene, encoding an IL involved in PCA progression. IL-6, IL-7 and IL-15 titres were also measured in patients' sera. Methods Eighty patients with BPH and 79 with early (1 to 2c) stage PCA were enrolled. Gene expression in prostate tissues was analyzed by quantitative real-time PCR (qRT-PCR). Serum IL concentrations and acute phase protein titres were evaluated by ELISA. Mann-Whitney, Wilcoxon and χ 2 tests were used to compare IL gene expression and serum titers in the two groups of patients. Receiver operating characteristic (ROC) curves were constructed to evaluate the possibility to distinguish sera from different groups of patients based on IL titers. Results IL-2 and IL-21 gene expression was comparably detectable, with low frequency and at low extents, in PCA and BPH tissues. In contrast, IL-6, IL-7 and IL-15 genes were expressed more frequently (p < 0.0001, p = 0.0047 and p = 0.0085, respectively) and to significantly higher extents (p = 0.0051, p = 0.0310 and p = 0.0205, respectively) in early stage PCA than in BPH tissues. Corresponding proteins could be detected to significantly higher amounts in sera from patients with localized PCA, than in those from patients with BPH (p = 0.0153, p = 0.0174 and p = 0.0064, respectively). Analysis of ROC curves indicates that IL-7 (p = 0.0039), but not IL-6 (p = 0.2938) or IL-15 (p = 0.1804) titres were able to distinguish sera from patients with malignancy from those from patients with benign disease. Serum titres of C reactive (CRP), high mobility group B1 (HMGB1) and serum amyloid A (SAA) acute phase proteins were similar in both groups of patients. Conclusions Expression IL-7 and IL-15 genes in prostate tissues and corresponding serum titres are significantly increased in patients with early stage PCA as compared with patients with BPH.