[Intelligent early prostate cancer detection in 2021: more benefit than harm]. / Intelligente Prostatakarzinomfrüherkennung 2021 ­ mehr Nutzen als Schaden.

Prostate-specific antigen (PSA) is used for early detection of prostate cancer which represents the most frequent cancer diagnosed in men in Germany and Europe. Results of the largest screening trials revealed that PSA testing reduces the incidence of locally advanced and metastatic prostate cancer and shows an effect on cancer-specific mortality. However, since early diagnosis also results in overdiagnosis and overtreatment of insignificant cancers with associated morbidities, there is a need for a more individualized and risk-tailored modern strategy. The PSA at baseline is an important part of this strategy although the German Federal Joint Committee declined its financial coverage by health insurances. Available validated instruments should accompany the baseline PSA to optimize detection of clinically significant prostate cancer.

Peritoneal flap for lymphocele prophylaxis following robotic-assisted laparoscopic radical prostatectomy with pelvic lymph node dissection: study protocol and trial update for the randomized controlled PELYCAN study.

BACKGROUND: Data from interventional studies suggest that a peritoneal flap after pelvic lymph node dissection (LND) during laparoscopic, robotic-assisted radical prostatectomy (RARP) may reduce the rate of symptomatic lymphoceles in transperitoneal approach. However, most of these studies are not conducted in a randomized controlled fashion, thus limiting their scientific value. A recent prospective, randomized, controlled trial (RCT) did not show superiority of a peritoneal flap while further trials are lacking. Therefore, the aim of the presented RCT will be to show that creating a peritoneal flap decreases the rate of symptomatic lymphoceles compared to the current standard procedure without creation of a flap. METHODS/DESIGN: PELYCAN is a parallel-group, patient- and assessor-blinded, phase III, adaptive randomized controlled superiority trial. Men with histologically confirmed prostate cancer who undergo transperitoneal RARP with pelvic LND will be randomly assigned in a 1:1 ratio to two groups-either with creating a peritoneal flap (PELYCAN) or without creating a peritoneal flap (control). Sample size calculation yielded a sample size of 300 with a planned interim analysis after 120 patients, which will be performed by an independent statistician. This provides a possibility for early stopping or sample size recalculation. Patients will be stratified for contributing factors for the development of postoperative lymphoceles. The primary outcome measure will be the rate of symptomatic lymphoceles in both groups within 6 months postoperatively. Patients and assessors will be blinded for the intervention until the end of the follow-up period of 6 months. The surgeon will be informed about the randomization result after performance of vesicourethral anastomosis. Secondary outcome measures include asymptomatic lymphoceles at the time of discharge and within 6 months of follow-up, postoperative complications, mortality, re-admission rate, and quality of life assessed by the EORTC QLQ-C30 questionnaire. DISCUSSION: The PELYCAN study is designed to assess whether the application of a peritoneal flap during RARP reduces the rate of symptomatic lymphoceles, as compared with the standard operation technique. In case of superiority of the intervention, this peritoneal flap may be suggested as a new standard of care. TRIAL REGISTRATION: German Clinical Trials Register DRKS00016794 . Registered on 14 May 2019.

The comprehensive complication index (CCI): proposal of a new reporting standard for complications in major urological surgery.

PURPOSE: The comprehensive complication index (CCI) is a new tool for reporting the cumulative burden of postoperative complications on a continuous scale. This study validates the CCI for urological surgery and its benefits over the Clavien-Dindo-Classification (Clavien). MATERIAL AND METHODS: Data from a prospectively maintained data base of all consecutive patients at a university care-center was analyzed. Complications after radical cystectomy (RC), radical prostatectomy (RP), and partial nephrectomy (PN) were classified using the CCI and Clavien system. Differences in complications between the CCI and the Clavien were assessed and correlation analyses performed. Sample size calculations for hypothetical clinical trials were compared between CCI and Clavien to evaluate whether the CCI would reduce the number of required patients in a clinical trial. RESULTS: 682 patients (172 RC, 297 RP, 213 PN) were analyzed. Overall, 9.4-46.6% of patients had > 1 complication cumulatively assessed with the CCI resulting in an upgrading in the Clavien classification for 2.4-32.4% of patients. Therefore, scores between the systems differed for RC: CCI (mean ± standard deviation) 26.3 ± 20.8 vs. Clavien 20.4 ± 16.7, p < 0.001; PN: CCI 8.4 ± 14.7 vs. Clavien 7.0 ± 11.8, p < 0.001 and RP: CCI 5.8 ± 11.7 vs. Clavien 5.3 ± 10.6, p = 0.102. The CCI was more accurate in predicting LOS after RC than Clavien (p < 0.001). Sample size calculations based in the CCI (for future hypothetical trials) resulted in a reduction of required patients for all procedures (- 25% RC, - 74% PN, - 80% RP). CONCLUSION: The CCI is more accurate to assess surgical complications and reduces required sample sizes that will facilitate the conduction of clinical trials.

[Urological research in Germany : A retrospective, longitudinal observational study]. / Urologische Forschung in Deutschland : Eine retrospektive, longitudinale Beobachtungsstudie.

BACKGROUND AND OBJECTIVES: The congress of the German Society of Urology reflects urologic research in German-speaking countries. The objective was to identify trends by analyzing the congress' abstracts and following full publications longitudinally. MATERIALS AND METHODS: The abstracts of the 2016 congress were systematically analyzed regarding content, study design, cooperation, following full publications and journals which they were published in. Thereafter, the 2016 congress was compared to the 2002 and 2009 congresses. Statistical analysis included χ2-, Mann-Whitney U-, Cochran-Armitage-, and Kruskal-Wallis test. RESULTS: A total of 1073 abstracts were presented at the 2002, 2009, and 2016 congresses. We found an increase in abstracts regarding prostate disease (24.2%, 29.7%, and 34.0%; p = 0.0043), oncological abstracts (50.6%, 57.9%, and 61.7%; p = 0.003), multicenter studies (18.3, 28.6, and 34.3%; p < 0.0001) and cooperation (55.6%, 62.9%, and 70.5%, p < 0.0001). Experimental (29.0%, 33.2%, and 22.8%; p = 0.009) and prospective studies (62.1%, 42.0%, and 36.0%; p < 0.0001) declined. Abstracts including statistical analysis (18.4%, 14.7%, and 41.2%; p < 0.0001) and the impact factor of following full publications (2.08, 3.42, 4.42; p < 0.0001) rose. In 2016, 11.2% of those full publications were published Open Access. The publication rates of the presented abstracts were 49.1%, 56.3%, and 52.3%, respectively (p = 0.15). CONCLUSIONS: National and international networking of the urological research community has increased. Presentation of prospective studies has declined. The rate of peer-reviewed full publications following the DGU abstracts remains at a stable high level over the three congresses. The publication rate in Open Access journals is low.

Clinical relevance of gene expression in localized and metastatic prostate cancer exemplified by FABP5.

PURPOSE: Fatty acid-binding protein 5 (FABP5), a transport protein for lipophilic molecules, has been proposed as protein marker in prostate cancer (PCa). The role of FABP5 gene expression is merely unknown. METHODS: In two cohorts of PCa patients who underwent radical prostatectomy (n = 40 and n = 57) and one cohort of patients treated with palliative transurethral resection of the prostate (pTUR-P; n = 50) FABP5 mRNA expression was analyzed with qRT-PCR. Expression was correlated with clinical parameters. BPH tissue samples served as control. To independently validate findings on FABP5 expression, three microarray and sequencing datasets were reanalyzed (MSKCC 2010 n = 216; TCGA 2015 n = 333; mCRPC, Nature Medicine 2016 n = 114). FABP5 expression was correlated with ERG-fusion status, TCGA subtypes, cancer driver mutations and the expression of druggable downstream pathway components. RESULTS: FABP5 was overexpressed in PCa compared to BPH in the cohorts analyzed by qRT-PCR (radical prostatectomy p = 0.003, p = 0.010; pTUR-P p = 0.002). FABP5 expression was independent of T stage, Gleason Score, nodal status and PSA level. FABP5 overexpression was associated with the absence of TMPRSS2:ERG fusion (p < 0.001 in TCGA and MSKCC). Correlation with TCGA subtypes revealed FABP5 overexpression to be associated with SPOP and FOXA1 mutations. FABP5 was positively correlated with potential drug targets located downstream of FABP5 in the PPAR-signaling pathway. CONCLUSION: FABP5 overexpression is frequent in PCa, but seems to be restricted to TMPRESS2:ERG fusion-negative tumors and is associated with SPOP and FOXA1 mutations. FABP5 overexpression appears to be indicative for increased activity in PPAR signaling, which is potentially druggable.

Prophylactic abdominal or retroperitoneal drain placement in major uro-oncological surgery: a systematic review and meta-analysis of comparative studies on radical prostatectomy, cystectomy and partial nephrectomy.

PURPOSE: To systematically analyze the impact of prophylactic abdominal or retroperitoneal drain placement or omission in uro-oncologic surgery. METHODS: This systematic review follows the Cochrane recommendations and was conducted in line with the PRISMA and the AMSTAR-II criteria. A comprehensive database search including Medline, Web-of-Science, and CENTRAL was performed based on the PICO criteria. All review steps were done by two independent reviewers. Risk of bias was assessed with the Cochrane tool for randomized trials and the Newcastle-Ottawa Scale. RESULTS: The search identified 3427 studies of which eleven were eligible for qualitative and ten for quantitative analysis reporting on 3664 patients. Six studies addressed radical prostatectomy (RP), four studies partial nephrectomy (PN) and one study radical cystectomy. For RP a reduction in postoperative complications was found without drainage (odds ratio (OR)[95% confidence interval (CI)]: 0.62[0.44;0.87], p = 0.006), while there were no differences for re-intervention (OR[CI]: 0.72[0.39;1.33], p = 0.300), lymphocele OR[CI]: 0.60[0.22;1.60], p = 0.310), hematoma (OR[CI]: 0.68[0.18;2.53], p = 0.570) or urinary retention (OR[CI]: 0.57[0.26;1.29], p = 0.180). For partial nephrectomy no differences were found for overall complications (OR[CI]: 0.99[0.65;1.51], p = 0.960) or re-intervention (OR[CI]: 1.16[0.31;4.38], p = 0.820). For RC, there were no differences for all parameters. The overall-quality of evidence was assessed as low. CONCLUSION: The omission of drains can be recommended for standardized RP and PN cases. However, deviations from the standard can still mandate the placement of a drain and remains surgeon preference. For RC, there is little evidence to recommend the omission of drains and future research should focus on this issue. REVIEW REGISTRATION NUMBER (PROSPERO): CRD42019122885.

The Sensitivity of Euro-Atlantic Regimes to Model Horizontal Resolution.

There is growing evidence that the atmospheric dynamics of the Euro-Atlantic sector during winter is driven in part by the presence of quasi-persistent regimes. However, general circulation models typically struggle to simulate these with, for example, an overly weakly persistent blocking regime. Previous studies have showed that increased horizontal resolution can improve the regime structure of a model but have so far only considered a single model with only one ensemble member at each resolution, leaving open the possibility that this may be either coincidental or model dependent. We show that the improvement in regime structure due to increased resolution is robust across multiple models with multiple ensemble members. However, while the high-resolution models have notably more tightly clustered data, other aspects of the regimes may not necessarily improve and are also subject to a large amount of sampling variability that typically requires at least three ensemble members to surmount.

Rapidly rotating Rayleigh-Bénard convection with a tilted axis.

We numerically explore the dynamics of an incompressible fluid heated from below, bounded by free-slip horizontal plates and periodic lateral boundary conditions, subject to rapid rotation about a distant axis that is tilted with respect to the gravity vector. The angle ϕ between the rotation axis and the horizontal plane measures the tilting of the rotation axis; it can be taken as a proxy for latitude if we think of a local Cartesian representation of the convective dynamics in a rotating fluid shell. The results of the simulations indicate the existence of three different convective regimes, depending on the value of ϕ: (1) sheared, intermittent large-scale winds in the direction perpendicular to the plane defined by the gravity and rotation vectors, when rotation is "horizontal" (ϕ=0^{∘}); (2) a large-scale cyclonic vortex tilted along the rotation axis, when the angle between the rotation axis and the gravity vector is relatively small (ϕ between about 45^{∘} and 90^{∘}); and (3) a new intermediate regime characterized by vertically sheared large-scale winds perpendicular to both gravity and rotation. In this regime, the winds are organized in bands that are tilted along the rotation axis, with unit horizontal wave number in the plane defined by gravity and rotation at values of ϕ less than about 60^{∘}. This intermediate solution, studied for the first time in this work, is characterized by weaker vertical heat transport than the cases with large-scale vortices. For intermediate values of ϕ (between about 45^{∘} and 60^{∘}), the banded, sheared solution coexists with the large-scale vortex solution, with different initial conditions leading to one or the other dynamical behavior. A discussion of the possible implications of these results for the dynamics of rapidly rotating planetary atmospheres is provided.

[The role of PSMA PET-CT in patients with metastatic prostate cancer]. / Die Rolle des PSMA-PET/CT bei Patienten mit metastasiertem Prostatakarzinom.

Prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET-CT) imaging for the localization of prostate cancer is increasingly available in Germany. The advances and limitations in different disease stages are reviewed. As the clinical relevance of oligometastatic disease in primary cancer detected by PSMA PET-CT imaging is not yet completely understood, it should only be used in clinical trials. In recurrent prostate cancer after therapy with curative intent, PSMA PET-CT shows encouraging potential for the planning of salvage therapy. In metastatic castration-resistant prostate cancer evidence for its use is not available.

Prostate cancer detection among readers with different degree of experience using ultra-high b-value diffusion-weighted Imaging: Is a non-contrast protocol sufficient to detect significant cancer?

AIM: To evaluate the accuracy of a T2-weighted (T2w) - and a parallel transmit zoomed b = 2000 s/mm2 (b2000) - diffusion-weighted imaging sequence among three readers with different degrees of experience for prostate cancer (Pca) detection. METHODS: Ninety-three patients with suspected Pca were enrolled. For b2000 a two-dimensional spatially-selective RF pulse using an echo-planar transmit trajectory was applied, and the field of view (FOV) was reduced to one-third. All three readers (Reader A: 7, B 4 and C <1 years of experience in prostate MRI) independently evaluated b2000 with regard to the presence of suspicious lesions that displayed increased signal. The results were compared to histopathology obtained by real-time MR/ultrasound fusion and systematic biopsy. RESULTS: In 62 patients Pca was confirmed. One significant Pca (Gleason score (GS) 7b) was missed by Reader C. Overall, sensitivity/specificity/positive predictive value/negative predictive value were 90/71/86/79% for Reader A, 87/84/92/76% for Reader B and 85/74/87/72% for Reader C, respectively. Detection rates for significant Pca (GS >7a) were 100/100/94% for Readers A/B/C, respectively. Inter-reader agreement was generally good (Kappa A/B: 0.8; A/C: 0.82; B/C: 0.74). CONCLUSION: B2000 in combination with a T2w could be useful to detect clinically significant Pca. KEY POINTS: • Significant prostate cancer using zoomed ultra-high b-value DWI was detected. • Diagnostic performance among readers with different degrees of experience was good. • mp- MRI of the prostate using a comprehensive non-contrast protocol is clinically feasible.

[The role of PSMA PET-CT in patients with metastatic prostate cancer]. / Die Rolle des PSMA-PET/CT bei Patienten mit metastasiertem Prostatakarzinom.

Prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET-CT) imaging for the localization of prostate cancer is increasingly available in Germany. The advances and limitations in different disease stages are reviewed. As the clinical relevance of oligometastatic disease in primary cancer detected by PSMA PET-CT imaging is not yet completely understood, it should only be used in clinical trials. In recurrent prostate cancer after therapy with curative intent, PSMA PET-CT shows encouraging potential for the planning of salvage therapy. In metastatic castration-resistant prostate cancer evidence for its use is not available.

[Focal therapy of prostate cancer]. / Fokale Therapie des Prostatakarzinoms.

The target of focal therapy (FT) in prostate cancer (PC) is partial treatment of the prostate aiming at preserving surrounding anatomical structures. The intention is to minimize typical side effects of radical treatment options combined with local tumor control. Numerous established and new technologies are used. Results of published studies showed a good safety profile, few side effects and good preservation of functional results. Oncologic long-term data are lacking so far. Photodynamic therapy (PDT) is the only technology that has been studied in a published prospective randomized trial. The FT is challenged by the multifocality of PC; therefore, the quality of prostate biopsy, histopathological assessment as well as imaging are of paramount importance. Multiparametric magnetic resonance imaging (MRI) has gained increasing importance. The FT is experimental and should only be offered within clinical trials.

[MRI/TRUS fusion-guided prostate biopsy : Value in the context of focal therapy]. / MRT/TRUS-fusionierte Biopsiesysteme : Stellenwert bei der fokalen Therapie des Prostatakarzinoms.

BACKGROUND: Several systems for MRI/TRUS fusion-guided biopsy of the prostate are commercially available. Many studies have shown superiority of fusion systems for tumor detection and diagnostic quality compared to random biopsy. The benefit of fusion systems in focal therapy of prostate cancer (PC) is less clear. OBJECTIVES: Critical considerations of fusion systems for planning and monitoring of focal therapy of PC were investigated. MATERIALS AND METHODS: A systematic literature review of available fusion systems for the period 2013-5/2016 was performed. A checklist of technical details, suitability for special anatomic situations and suitability for focal therapy was established by the German working group for focal therapy (Arbeitskreis fokale und Mikrotherapie). RESULTS: Eight fusion systems were considered (Artemis™, BioJet, BiopSee®, iSR´obot™ Mona Lisa, Hitachi HI-RVS, UroNav and Urostation®). Differences were found for biopsy mode (transrectal, perineal, both), fusion mode (elastic or rigid), navigation (image-based, electromagnetic sensor-based or mechanical sensor-based) and space requirements. DISCUSSION: Several consensus groups recommend fusion systems for focal therapy. Useful features are "needle tracking" and compatibility between fusion system and treatment device (available for Artemis™, BiopSee® and Urostation® with Focal One®; BiopSee®, Hitachi HI-RVS with NanoKnife®; BioJet, BiopSee® with cryoablation, brachytherapy). CONCLUSIONS: There are a few studies for treatment planning. However, studies on treatment monitoring after focal therapy are missing.

Precision of MRI/ultrasound-fusion biopsy in prostate cancer diagnosis: an ex vivo comparison of alternative biopsy techniques on prostate phantoms.

PURPOSE: Comparing the accuracy of MRI/ultrasound-guided target-biopsy by transrectal biopsy (TRB) with elastic versus rigid image fusion versus transperineal biopsy (TPB) with rigid image fusion in a standardized setting. METHODS: Target-biopsy of six differently sized and located lesions was performed on customized CIRS 070L prostate phantoms. Lesions were only MRI-visible. After prior MRI for lesion location, one targeted biopsy per lesion was obtained by TRB with elastic image fusion with Artemis™ (Eigen, USA), TRB with rigid image fusion with real-time virtual sonography (Hitachi, Japan) and TPB with rigid image fusion with a brachytherapy approach (Elekta, Sweden), each on a phantom of 50, 100 and 150 ml prostate volume. The needle trajectories were marked by contrast agent and detected in a postinterventional MRI. RESULTS: Overall target detection rate was 79.6% with a slight superiority for the TPB (83.3 vs. 77.8 vs. 77.8%). TRB with elastic image fusion showed the highest overall precision [median distance to lesion center 2.37 mm (0.14-4.18 mm)], independent of prostate volume. Anterior lesions were significantly more precisely hit than transitional and basal lesions (p = 0.034; p = 0.015) with comparable accuracy for TRB with elastic image fusion and TPB. In general, TRB with rigid image fusion was inferior [median 3.15 mm (0.37-10.62 mm)], particularly in small lesions. CONCLUSION: All biopsy techniques allow detection of clinically significant tumors with a median error of 2-3 mm. Elastic image fusion appears to be the most precise technique, independent of prostate volume, target size or location.

Generation of Large-Scale Winds in Horizontally Anisotropic Convection.

We simulate three-dimensional, horizontally periodic Rayleigh-Bénard convection, confined between free-slip horizontal plates and rotating about a distant horizontal axis. When both the temperature difference between the plates and the rotation rate are sufficiently large, a strong horizontal wind is generated that is perpendicular to both the rotation vector and the gravity vector. The wind is turbulent, large-scale, and vertically sheared. Horizontal anisotropy, engendered here by rotation, appears necessary for such wind generation. Most of the kinetic energy of the flow resides in the wind, and the vertical turbulent heat flux is much lower on average than when there is no wind.

[Abstracts at congresses of the German Society of Urology. Trends and quality]. / Beiträge des Kongresses der Deutschen Gesellschaft für Urologie. Trends und Qualität.

BACKGROUND: The congress of the German Society of Urology is the third biggest urology congress worldwide and reflects the scientific landscape of urology in Germany. In the congress abstracts, detailed data regarding study design, current trends in urologic research and the cooperation of authors are lacking. We wanted to identify factors contributing to the likelihood of an abstract being followed by a publication in a peer-reviewed journal. MATERIAL AND METHODS: The two congresses of the years 2002 and 2009 were exemplarily analyzed. Various aspects regarding study design and cooperations were retrieved from the abstracts and trends were determined. Subsequent publications in peer-reviewed journals were searched for in MEDLINE and potential factors influencing publication success were identified. Significance was tested for using the χ (2) and Mann-Whitney-U statistical tests. RESULTS: A total of 732 abstracts (2002: 352, 2009: 380) were analyzed, one third of which contained prospective, retrospective or preclinical/experimental studies. Internal (28.7 %) and national (27.6 %) cooperations were most frequent. Significant trends towards more retrospective studies (p=0.008) and national cooperations (p=0.019) were found. Of the abstracts 49.2 % (2002) and 56.3% (2009) were followed by publication in peer-reviewed journals (median 15.1 months) with a significantly higher mean impact factor in 2009 (3.4 vs. 2.1, respectively p>0.0001). Therapeutic studies and those including statistics or national cooperations were significantly more likely to be published. CONCLUSION: In the future urologic research should focus on prospective studies. Many abstracts are not followed by a publication in a peer-reviewed journal. This is especially true for abstracts containing no statistics. As national collaborations are correlated with successful publication, an early national networking of young researching urologists should be promoted.

Patterned vegetation and rainfall intermittency.

We study a mathematical model for the dynamics of patterned dryland vegetation in the presence of rainfall intermittency, adopting a spatially explicit approach. We find that most results found for constant precipitation carry over to the case of intermittent rainfall, with a few important novelties. For intermittent precipitation, the functional forms of the water uptake and consequently of the vegetation growth rate play an important role. Nonlinear, concave-up forms of water uptake as a function of soil moisture lead to a beneficial effect of rainfall intermittency, with a stronger effect when vegetation feedbacks are absent. The results obtained with the explicit-space model employed here are in keeping with those provided by simpler, implicit-space approaches, and provide a more complete view of vegetation dynamics in arid ecosystems.

A mathematical model of plants as ecosystem engineers.

Understanding the structure and dynamics of plant communities in water-limited systems often calls for the identification of ecosystem engineers--key species that modify the landscape, redistribute resources and facilitate the growth of other species. Shrubs are excellent examples; they self-organize to form patterns of mesic patches which provide habitats for herbaceous species. In this paper we present a mathematical model for studying ecosystem engineering by woody plant species in drylands. The model captures various feedbacks between biomass and water including water uptake by plants' roots and increased water infiltration at vegetation patches. Both the uptake and the infiltration feedbacks act as mechanisms for vegetation pattern formation, but have opposite effects on the water resource; the former depletes the soil-water content under a vegetation patch, whereas the latter acts to increase it. Varying the relative strength of the two feedbacks we find a trade-off between the engineering capacity of a plant species and its resilience to disturbances. We further identify two basic soil-water distributions associated with engineering at the single patch level, hump-shaped and ring-shaped, and discuss the niches they form for herbaceous species. Finally, we study how pattern transitions at the landscape level feedback to the single patch level by affecting engineering strength.

Ecosystem engineers: from pattern formation to habitat creation.

Habitat and species richness in drylands are affected by the dynamics of a few key species, termed "ecosystem engineers." These species modulate the landscape and redistribute the water resources so as to allow the introduction of other species. A mathematical model is developed for a pair of ecosystem engineers commonly found in drylands: plants forming vegetation patterns and cyanobacteria forming soil crusts. The model highlights conditions for habitat creation and for high habitat richness, and suggests a novel mechanism for species loss events as a result of environmental changes.