[Prostate cancer screening-current overview]. / Das Prostatakarzinom-Screening ­ aktueller Überblick.

BACKGROUND: The harm-to-benefit ratio of prostate cancer (PCa) screening remains controversial mainly due to the unfavorable test characteristics of prostate-specific antigen (PSA) as a screening test. METHODS: In this nonsystematic review, we present a current overview of the body of evidence on prostate cancer screening with a focus on the role of magnetic resonance imaging (MRI) of the prostate. RESULTS: Evidence generated in large randomized controlled trials showed that PSA-based screening significantly decreases cancer-specific mortality. The main obstacle in developing and implementing PCa screening strategies is the resulting overdiagnosis and as a consequence overtreatment of indolent cancers. Opportunistic screening is characterized by an adverse benefit-to-harm ratio and should, therefore, not be recommended. The German Statutory Early Detection Program for prostate cancer, which consists of a digital rectal examination (DRE) as a stand-alone screening test, is not evidence-based, neither specific nor sensitive enough and results in unnecessary diagnostics. The European Commission recently urged member states to develop population-based and organized risk-adapted PSA-based screening programs, which are currently tested in the ongoing German PROBASE trial. Finetuning of the diagnostic pathway following PSA-testing seems key to improve its positive and negative predictive value and thereby making PCa screening more accurate. Incorporation of prostatic MRI into screening strategies leads to more accurate diagnosis of clinically significant prostate cancer, while diagnosis of indolent cancers is reduced. In the future, molecular liquid-based biomarkers have the potential to complement or even replace PSA in PCa screening and further personalize screening strategies. Active surveillance as an alternative to immediate radical therapy of demographically increasing PCa diagnoses can potentially further improve the benefit-to-harm ratio of organized screening. CONCLUSION: Early detection of PCa should be organized on a population level into personalized and evidence-based screening strategies. Multiparametric MRI of the prostate may play a key role in this setting.

Value of magnetic resonance angiography before prostatic artery embolization for intervention planning.

Knowledge about anatomical details seems to facilitate the procedure and planning of prostatic artery embolization (PAE) in patients with symptomatic benign prostatic hyperplasia (BPS). The aim of our study was the pre-interventional visualization of the prostatic artery (PA) with MRA and the correlation of iliac elongation and bifurcation angles with technical success of PAE and technical parameters. MRA data of patients with PAE were analysed retrospectively regarding PA visibility, PA type, vessel elongation, and defined angles were correlated with intervention time, fluoroscopy time, dose area product (DAP), cumulative air kerma (CAK), contrast media (CM) dose and technical success of embolization. T-test, ANOVA, Pearson correlation, and Kruskal-Wallis test was applied for statistical analysis. Between April 2018 and March 2021, a total of 78 patients were included. MRA identified the PA origin in 126 of 147 cases (accuracy 86%). Vessel elongation affected time for catheterization of right PA (p = 0.02), fluoroscopy time (p = 0.05), and CM dose (p = 0.02) significantly. Moderate correlation was observed for iliac bifurcation angles with DAP (r = 0.30 left; r = 0.34 right; p = 0.01) and CAK (r = 0.32 left; r = 0.36 right; p = 0.01) on both sides. Comparing the first half and second half of patients, median intervention time (125 vs. 105 min.) and number of iliac CBCT could be reduced (p < 0.001). We conclude that MRA could depict exact pelvic artery configuration, identify PA origin, and might obviate iliac CBCT. Vessel elongation of pelvic arteries increased intervention time and contrast media dose while the PA origin had no significant influence on intervention time and/or technical success.

Magnetic Resonance Imaging-guided Active Surveillance Without Annual Rebiopsy in Patients with Grade Group 1 or 2 Prostate Cancer: The Prospective PROMM-AS Study.

Background: Multiparametric magnetic resonance imaging (mpMRI) may allow patients with prostate cancer (PC) on active surveillance (AS) to avoid repeat prostate biopsies during monitoring. Objective: To assess the ability of mpMRI to reduce guideline-mandated biopsy and to predict grade group upgrading in patients with International Society of Urological Pathology grade group (GG) 1 or GG 2 PC using Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) scores. The hypothesis was that the AS disqualification rate (ASDQ) rate could be reduced to 15%. Design setting and participants: PROMM-AS was a prospective study assessing 2-yr outcomes for an mpMRI-guided AS protocol. A 12 mo after AS inclusion on the basis of MRI/transrectal ultrasound fusion-guided biopsy (FBx), all patients underwent mpMRI. For patients with stable mpMRI (PRECISE 1-3), repeat biopsy was deferred and follow-up mpMRI was scheduled for 12 mo later. Patients with mpMRI progression (PRECISE 4-5) underwent FBx. At the end of the study, follow-up FBx was indicated for all patients. Outcome measurements and statistical analysis: We calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for upgrading to GG 2 in the GG 1 group, and to GG 3 in the GG 2 group on MRI. We performed regression analyses that included clinical variables. Results and limitations: The study included 101 patients with PC (60 GG 1 and 41 GG 2). Histopathological progression occurred in 31 patients, 18 in the GG 1 group and 13 in the GG 2 group. Thus, the aim of reducing the ASDQ rate to 15% was not achieved. The sensitivity, specificity, PPV, and NPV for PRECISE scoring of MRI were 94%, 64%, 81%, and 88% in the GG 1 group, and 92%, 50%, 92%, and 50%, respectively, in the GG 2 group. On regression analysis, initial prostate-specific antigen (p < 0.001) and higher PRECISE score (4-5; p = 0.005) were significant predictors of histological progression of GG 1 PC. Higher PRECISE score (p = 0.009), initial Prostate Imaging-Reporting and Data System score (p = 0.009), previous negative biopsy (p = 0.02), and percentage Gleason pattern 4 (p = 0.04) were significant predictors of histological progression of GG 2 PC. Limitations include extensive MRI reading experience, the small sample size, and limited follow-up. Conclusions: MRI-guided monitoring of patients on AS using PRECISE scores avoided unnecessary follow-up biopsies in 88% of patients with GG 1 PC and predicted upgrading during 2-yr follow-up in both GG 1 and GG 2 PC. Patient summary: We investigated whether MRI (magnetic resonance imaging) scores can be used to guide whether patients with lower-risk prostate cancer who are on active surveillance (AS) need to undergo repeat biopsies. Follow-up biopsy was deferred for 1 year for patients with a stable score and performed for patients whose score progressed. After 24 months on AS, all men underwent MRI and biopsy. Among patients with grade group 1 cancer and a stable MRI score, 88% avoided biopsy. For patients with MRI score progression, AS termination was correctly recommended in 81% of grade group 1 and 92% of grade group 2 cases.

Influence of benign prostatic hyperplasia patterns detected with MRI on the clinical outcome after prostatic artery embolization.

BACKGROUND: To investigate the influence of benign prostatic hyperplasia (BPH) patterns detected with MRI on clinical outcomes after prostatic artery embolization (PAE). MATERIALS & METHODS: This retrospective study included 71 consecutive patients with lower urinary tract symptoms (LUTS), who underwent magnetic resonance imaging (MRI) of the prostate followed by PAE at a single centre. MRI scans were evaluated and BPH patterns were determined according to Wasserman type and a modified BPH classification. Additionally, scans were evaluated regarding the presence of adenomatous-dominant benign prostatic hyperplasia (AdBPH). LUTS were assessed using the International Prostate Symptom Score (IPSS) and urinary flow rate (Qmax). Follow-up examination included MRI and clinical outcome. RESULTS: For clinical outcome at follow-up, IPSS showed median reduction of 54% (IQR 41-75%) and Qmax improved by 4.1 ml/s. We noted significant reduction in volume, intraprostatic protrusion, and prostatic urethral angle in our collective (p < 0.01). Median volume reduction was 25% (IQR 15%-34%). Bilateral embolization was a significant predictor for volume reduction at follow-up. Multiple linear regression analysis showed significant effect of high initial volume on reduction in IPSS after treatment (p < 0.01). Presence of AdBPH was significantly associated with both, volume loss and clinical improvement in terms of IPSS reduction (p < 0.01). Neither BPH pattern based on the Wassermann type nor modified BPH classification were significantly related with postinterventional IPSS and volume loss. CONCLUSIONS: Men benefit from PAE regardless the macroscopic BPH MRI pattern. Preinterventional prostate volume and presence of AdBPH on MRI should be considered for outcome prognosis after PAE.

Harmonized procedure coding system for surgical procedures and analysis of surgical site infections (SSI) of five European countries.

BACKGROUND: The use of routine data will be essential in future healthcare research. Therefore, harmonizing procedure codes is a first step to facilitate this approach as international research endeavour. An example for the use of routine data on a large scope is the investigation of surgical site infections (SSI). Ongoing surveillance programs evaluate the incidence of SSI on a national or regional basis in a limited number of procedures. For example, analyses by the European Centre for Disease Prevention (ECDC) nine procedures and provides a mapping table for two coding systems (ICD9, National Healthcare Safety Network [NHSN]). However, indicator procedures do not reliably depict overall SSI epidemiology. Thus, a broader analysis of all surgical procedures is desirable. The need for manual translation of country specific procedures codes, however, impedes the use of routine data for such an analysis on an international level. This project aimed to create an international surgical procedure coding systems allowing for automatic translation and categorization of procedures documented in country-specific codes. METHODS: We included the existing surgical procedure coding systems of five European countries (France, Germany, Italy, Spain, and the United Kingdom [UK]). In an iterative process, country specific codes were grouped in ever more categories until each group represented a coherent unit based on method of surgery, interventions performed, extent and site of the surgical procedure. Next two ID specialist (arbitrated by a third in case of disagreement) independently assigned country-specific codes to the resulting categories. Finally, specialist from each surgical discipline reviewed these assignments for their respective field. RESULTS: A total number of 153 SALT (Staphylococcus aureus Surgical Site Infection Multinational Epidemiology in Europe) codes from 10 specialties were assigned to 15,432 surgical procedures. Almost 4000 (26%) procedure codes from the SALT coding system were classified as orthopaedic and trauma surgeries, thus this medical field represents the most diverse group within the SALT coding system, followed by abdominal surgical procedures with 2390 (15%) procedure codes. CONCLUSION: Mapping country-specific codes procedure codes onto to a limited number of coherent, internally and externally validated codes proofed feasible. The resultant SALT procedure code gives the opportunity to harmonize big data sets containing surgical procedures from international centres, and may simplify comparability of future international trial findings. TRIAL REGISTRATION: The study was registered at clinicaltrials.gov under NCT03353532 on November 27th, 2017.

[Prostate cancer: surgical complications]. / Prostatakarzinom ­ chirurgische Komplikationen.

Radical prostatectomy (RP), performed as an open, laparoscopic or robotic procedure, remains the "gold standard" for patients with localised prostate cancer who can be cured with surgery and have a life expectancy of at least 10 years. Today, RP is also used as a first-line treatment for locally advanced prostate cancer, possibly in a multimodal setting with adjuvant radiation/hormonal therapy. The increasing experience of surgeons, better knowledge of anatomy and refinements of surgical techniques have greatly improved oncological and functional outcomes. In our article we would like to give an overview of the complications associated with this surgical procedure.

[Prostate cancer screening: controversies and suggested solutions]. / Prostatakrebsscreening: Kontroversen und mögliche Lösungen.

Prostate cancer is the most common cancer among men in industrialized countries. The annual incidence rate in Germany is about 60,000. Every year, 13,000 men die of this disease. Nevertheless, the 10-year survival rate is relatively favorable compared to other carcinomas.Prostate cancer screening is discussed controversially both nationally and internationally. This is due to the fact that the determination of the prostate-specific antigen (PSA) for tumor detection beginning in the 1980s led to over-diagnosis of clinically insignificant prostate cancer and consequently to over-therapy-usually by radical prostatectomy or radiotherapy.This review article will discuss the largest randomized controlled trials of PSA-based prostate cancer screening to date. It will highlight the advantages and disadvantages of this screening and give an outlook on the development of future strategies for prostate cancer screening.For PSA screening, the European Randomized Study for Screening of Prostate Cancer (ERSPC) study showed a relative reduction in prostate cancer-specific mortality of approximately 21% after a median follow-up period of 13 years. However, in absolute figures, relatively few men will benefit from population-based screening and the rate of over-diagnosed men remains high.The procedure in a Swedish long-term study, in which risk-adapted screening intervals were applied on the basis of the assessment of a baseline PSA level at a young age (40-50) showed promising results and may provide a solution to this dilemma. This strategy is the basis for the currently largest study on risk-adapted prostate cancer screening ( www.PROBASE.de ), which evaluates this concept for the first time with a randomized design.

The organic cation transporter 3 (OCT3) as molecular target of psychotropic drugs: transport characteristics and acute regulation of cloned murine OCT3.

The organic cation transporter 3 (OCT3) is a widely expressed transporter for endogenous and exogenous organic cations. Of particular interest is OCT3 expression and function in the brain, where it plays a role in serotonin clearance and influences mood and behavior. Protein kinase signaling mediates rapid modulation of cerebral processes, but little is known about acute regulation of OCT3 by protein kinases. Therefore, we cloned mouse OCT3 (mOCT3) and generated a human embryonic kidney cell line stably expressing the transporter to study transport characteristics, acute regulation by protein kinases, and interaction with psychotropic drugs. Uptake measurement was performed using the fluorescent cation 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide (ASP(+), 1 µM) as a substrate. The translational value of these findings was determined by comparing results obtained with cloned mouse and human OCT3. mOCT3-mediated transport is membrane potential dependent and pH independent. ASP(+) uptake by mOCT3 and human OCT3 (hOCT3) was efficiently inhibited by 1-methyl-4-phenylpyridinium, tetrapentylammonium (TPA(+)), corticosterone, serotonin, and histamine and by the drugs ketamine, fluoxetine, and diazepam. The half maximal inhibitory concentrations of mOCT3 and hOCT3 for TPA(+), serotonin, diazepam, and ketamine are significantly different. Diazepam is a non-transported inhibitor. Furthermore, the activities of mOCT3 and hOCT3 are acutely regulated by the p56 (lck) tyrosine kinase by decreasing their V max. Studies with freshly isolated renal proximal tubules from mOCT1/2(-/-) mice, in which mOCT3 is the only OCT present, confirmed this regulation pathway. Only the activity of hOCT3 is regulated by calmodulin. These findings suggest that even though many transport properties of mOCT3 and hOCT3 are similar, there are also species-specific aspects of OCT3 function.

Substrate- and cell contact-dependent inhibitor affinity of human organic cation transporter 2: studies with two classical organic cation substrates and the novel substrate cd2+.

Polyspecific organic cation transporter Oct2 from rat (gene Slc22A2) has been previously shown to transport Cs(+). Here we report that human OCT2 (hOCT2) is able to transport Cd(2+) showing substrate saturation with a Michaelis-Menten constant (Km) of 54 ± 5.8 µM. Uptake of Cd(2+) by hOCT2 was inhibited by typical hOCT2 ligands (unlabeled substrates and inhibitors), and the rate of uptake was decreased by a point mutation in a substrate binding domain of hOCT2. Incubation of hOCT2 overexpressing human embryonic kidney 293 cells (HEK-hOCT2-C) or rat renal proximal tubule cells expressing rOct2 (NRK-52E-C) with Cd(2+) resulted in an increased level of apoptosis that was reduced by OCT2 inhibitory ligand cimetidine(+). HEK-hOCT2-C exhibited different functional properties when they were confluent or had been dissociated by removal of Ca(2+) and Mg(2+). Only confluent HEK-hOCT2-C transported Cd(2+), and confluent and dissociated cells exhibited different potencies for inhibition of uptake of 1-methyl-4-phenylpyridinium(+) (MPP(+)) by Cd(2+), MPP(+), tetraethylammonium(+), cimetidine(+), and corticosterone. In confluent HEK-hOCT2-C, largely different inhibitor potencies were obtained upon comparison of inhibition of Cd(2+) uptake, 4-[4-(dimethylamino)styryl]-N-methylpyridinium(+) (ASP(+)) uptake, and MPP(+) uptake using substrate concentrations far below the respective Km values. Employing a point mutation in the previously identified substrate binding site of rat Oct1 produced evidence that short distance allosteric effects between binding sites for substrates and inhibitors are involved in substrate-dependent inhibitor potency. Substrate-dependent inhibitor affinity is probably a common property of OCTs. To predict interactions between drugs that are transported by OCTs and inhibitory drugs, it is necessary to employ the specific transported drug rather than a model substrate for in vitro measurements.