Distinct distribution patterns of exercise-induced natural killer cell mobilization into the circulation and tumor tissue of patients with prostate cancer.

The mobilization and activation of natural killer (NK) cells have been proposed as key mechanisms promoting anti-oncogenic effects of physical exercise. Although mouse models have proven that physical exercise recruits NK cells to tumor tissue and inhibits tumor growth, this preclinical finding has not been transferred to the clinical setting yet. In this first-in-human study, we found that physical exercise mobilizes and redistributes NK cells, especially those with a cytotoxic phenotype, in line with preclinical models. However, physical exercise did not increase NK cell tumor infiltrates. Future studies should carefully distinguish between acute and chronic exercise modalities and should be encouraged to investigate more immune-responsive tumor entities.

Long-term outcomes of active surveillance for clinically localized prostate cancer in a community-based setting: results from a prospective non-interventional study.

PURPOSE: To report on long-term outcomes of patients treated with active surveillance (AS) for localized prostate cancer (PCa) in the daily routine setting. METHODS: HAROW (2008-2013) was a non-interventional, health service research study about the management of localized PCa in the community setting, with 86% of the study centers being office-based urologists. A follow-up examination of all patients who opted for AS as primary treatment was carried out. Overall, cancer-specific, and metastasis-free survival, as well as discontinuation rates, were determined. RESULTS: Of 329 patients, 62.9% had very-low- and 21.3% low-risk tumours. The median follow-up was 7.7 years (IQR 4.7-9.1). Twenty-eight patients (8.5%) died unrelated to PCa, of whom 19 were under AS or watchful waiting (WW). Additionally, seven patients (2.1%) developed metastasis. The estimated 10-year overall and metastasis-free survival was 86% (95% CI 81.7-90.3) and 97% (95% CI 94.6-99.3), respectively. One hundred eighty-seven patients (56.8%) discontinued AS changing to invasive treatment: 104 radical prostatectomies (RP), 55 radiotherapies (RT), and 28 hormonal treatments (HT). Another 50 patients switched to WW. Finally, 37.4% remained alive without invasive therapy (22.2% AS and 15.2% WW). Intervention-free survival differed between the risk groups: 47.8% in the very-low-, 33.8% in the low- and 34.6% in the intermediate-/high-risk-group (p = 0.008). On multivariable analysis, PSA-density ≥ 0.2 ng/ml2 was significantly predictive for receiving invasive treatment (HR 2.55; p = 0.001). CONCLUSION: Even in routine care, AS can be considered a safe treatment option. Our results might encourage office-based urologists regarding the implementation of AS and to counteract possible concerns against this treatment option.

Non-invasive urine markers for the differentiation between RCCs and oncocytoma.

BACKGROUND: Recently, our group showed that Vim3 is overexpressed in tissue samples of renal oncocytomas and Mxi-2 in clear cell renal carcinoma (ccRCC). The mechanism leading to the truncation of both proteins is known and involves with two miRs, both detectable in urine. Since the analysis of miRs is time-consuming, our aim was to identify the truncated proteins in urine instead. Furthermore, urine samples from small renal masses (SRMs) (n = 45, <4 cm) were analyzed to get a pre-surgical differentiation of the cancer subtypes. METHODS: Urines were accessed from the urological biobank (n = 350). Proteins were isolated from urine samples, and Western blots were performed. Each sample was analyzed with ELISA for the expression of Vim3 and Mxi-2. A lateral flow assay was established. For the detection of SRMs, the miRs were isolated and qRT-PCR was performed. RESULTS: A significant increase of Vim3 in urines from patients with oncocytoma (n = 20) was detectable with ELISA compared to all other subtypes of RCCs (chromophobe (n = 50), papillary (n = 40), ccRCC (n = 200), and controls (n = 40) (***p < 0.0001)). Mxi-2 was predominantly overexpressed in ccRCCs (***p < 0.0001). Lateral flow assay of Vim3 and Mxi-2 shows two bands in the case of oncocytoma and ccRCC indicating the specificity of this test. For SRMs, an overexpression of miR-15a/Mxi2 was detectable in urine samples from ccRCC and chromoRCC patients. In contrast to that, miR-498/Vim3 were predominantly overexpressed in oncocytoma patients. CONCLUSION: Both proteins (Vim3 and Mxi-2) were detectable in patients' urines and can be used for the non-invasive differentiation of kidney cancers.

Active Surveillance for Incidental (cT1a/b) Prostate Cancer: Long-Term Outcomes of the Prospective Noninterventional HAROW Study.

INTRODUCTION: Optimal treatment for incidental prostate cancer (IPC) after surgical treatment for benign prostate obstruction is still debatable. We report on long-term outcomes of IPC patients managed with active surveillance (AS) in a German multicenter study. METHODS: HAROW (2008-2013) was designed as a noninterventional, prospective, health-service research study for patients with localized prostate cancer (≤cT2), including patients with IPC (cT1a/b). A follow-up examination of all patients treated with AS was carried out. Overall, cancer-specific, and metastasis-free survival and discontinuation rates were determined. RESULTS: Of 210 IPC patients, 68 opted for AS and were available for evaluation. Fifty-four patients had cT1a category and 14 cT1b category. Median follow-up was 7.7 years (IQR: 5.7-9.1). Eight patients died of which 6 were still under AS or watchful waiting (WW). No PCa-specific death could be observed. One patient developed metastasis. Twenty-three patients (33.8%) discontinued AS changing to invasive treatment: 12 chose radical prostatectomy, 7 radiotherapy, and 4 hormonal treatment. Another 19 patients switched to WW. The Kaplan-Meier estimated 10-year overall, cancer-specific, metastasis-free, and intervention-free survival was 83.8% (95% CI: 72.2-95.3), 100%, 98.4% (95% CI: 95.3-99.9), and 61.0% (95% CI: 47.7-74.3), respectively. In multivariable analysis, age (RR: 0.97; p < 0.001), PSA density ≥0.2 ng/mL2 (RR: 13.23; p < 0.001), and PSA ≥1.0 ng/mL after surgery (RR: 5.19; p = 0.016) were significantly predictive for receiving an invasive treatment. CONCLUSION: In comparison with other AS series with a general low-risk prostate cancer population, our study confirmed the promising survival outcomes for IPC patients, whereas discontinuation rates seem to be lower for IPC. Thus, IPC patients at low risk of progression may be good candidates for AS.

Perioperative Outcomes of Transurethral Resection, Open Prostatectomy, and Laser Therapy in the Surgical Treatment of Benign Prostatic Obstruction: A "Real-World" Data Analysis from the URO-Cert Prostate Centers.

INTRODUCTION: The aim of the study is to compare length of hospital stay, transfusion rates, and re-intervention rates during hospitalization for transurethral resection of the prostate (TUR-P), open prostatectomy (OP), and laser therapy (LT) for surgical treatment of benign prostatic obstruction (BPO). METHODS: URO-Cert is an organization, in which clinical data of prostatic diseases from 2 university, 19 public, and 3 private hospitals and 270 office-based urologists are collected in order to document treatment quality. Data on diagnostics, therapy, and course of disease are recorded web based. The analysis includes datasets from 2005 to 2017. RESULTS: Of 10,420 patients, 8,389 were treated with TUR-P, 1,334 with OP, and 697 with LT. Median length of hospital stay was 6 days (IQR: 4-7) for TUR-P, 9 days (IQR: 7-11) for OP, and 5 days (IQR: 4-6) for LT (p < 0.001). Risk for a hospital stay ≥7 days was higher for OP versus TUR-P (OR: 7.25; 95% CI = 6.27-8.36; p < 0.001) and LT (OR: 17.89; 95% CI = 14.12-22.65; p < 0.001) and higher for TUR-P versus LT (OR: 2.47; 95% CI = 2.03-3.01; p < 0.001). OP had a significantly higher risk for transfusions than TUR-P (OR: 2.44; 95% CI = 1.74-3.41; p < 0.001) and LT (OR: 3.32; 95% CI = 1.56-7.01; p < 0.001). Transfusion rates were not significantly different between TUR-P and LT (OR: 1.36; 95% CI = 0.66-2.79; p = 0.51). Risk of re-intervention was not different between all 3 approaches. CONCLUSION: OP was associated with higher transfusion rates and longer hospital stay than TUR-P and LT. Risk of transfusion was not different between TUR-P and LT, but TUR-P was inferior to LT concerning length of hospital stay. Re-intervention rates during hospitalization did not differ between the groups.

Efficacy of the Oestrogen Antagonist Tamoxifen on Sperm Parameters in Patients with Idiopathic Oligoathenoteratozoospermia.

BACKGROUND: The oestrogen antagonist tamoxifen has been suggested as an empiric treatment option for treating idiopathic oligoathenoteratozoospermia (iOAT). OBJECTIVES: To analyse the use of tamoxifen in iOAT. METHOD: Fifty-seven men receiving tamoxifen for iOAT were recruited from 2016 to 2017 in a retrospective, single-centre setting. Hormone and semen analysis was performed before and after 3 months of treatment. RESULTS: After a 3-month treatment, serum levels of testosterone (3.4 ng/mL [2.7-4.8] vs. 5.3 [3.1-7.1]; p = 0.026), follicle stimulating hormone (FSH; 7.6 [5.9-11.5] vs. 15.9 mIU/mL [8.4-19.9]; p = 0.003) and luteinizing hormone (4.5 [3.3-6.6] vs. 7.6 mIU/mL [4.8-10.7]; p = 0.007) significantly increased. At a cut-off of >8.8 mIU/mL, serum levels of FSH were predictive for an improved sperm motility (OR 0.229 [95% CI 0.068-0.773]; p  = 0.018) and serum levels of inhibin B were predictive for an improved total sperm count at a cut-off of <82 ng/L (OR 18.0 [95% CI 1.267-255.744]; p = 0.033). During an 11 month-follow-up, patients receiving tamoxifen showed a clinical pregnancy rate of 42%, leading to a live birth rate of 56% of all pregnant women. Twenty-three per cent of all patients reported non-serious adverse events. CONCLUSIONS: Tamoxifen is effective in improving the total sperm count as well as motility and can thus be safely used as empiric medical therapy in iOAT.

Health-related quality of life in active surveillance and radical prostatectomy for low-risk prostate cancer: a prospective observational study (HAROW - Hormonal therapy, Active Surveillance, Radiation, Operation, Watchful Waiting).

OBJECTIVES: To compare health-related quality of life (HRQOL) between patients with localised prostate cancer in an active surveillance (AS) group and a radical prostatectomy (RP) group, as evidence shows that both groups have similar oncological outcomes. Thus, comparative findings on the patients' HRQOL are becoming even more important to allow for informed treatment decision-making. PATIENTS AND METHODS: The Hormonal therapy, Active Surveillance, Radiation, Operation, Watchful Waiting (HAROW) study is a prospective, observational study designed to collect data for different treatment options for newly diagnosed patients with localised prostate cancer under real-life conditions. At 6-month intervals, clinical data (D'Amico risk categories, Charlson Comorbidity Index) and HRQOL (European Organisation for Research and Treatment of Cancer quality of life questionnaire 30-item core questionnaire) were collected. Data were analysed by longitudinal multilevel analysis for patients with localised prostate cancer under AS and RP. RESULTS: Data from 961 patients (556 RP, 405 AS) were considered. The follow-up was 3.5 years (median 2 years). The results reveal significant, but not clinically relevant advantages for patients with low-risk prostate cancer managed with AS in contrast to RP concerning global HRQOL as well as role, emotional and social functioning over time, after controlling for age, comorbidities, and partnership status. In some, but not all HRQOL scales, RP patients start with a slightly lower HRQOL and recover up to the level of AS patients within 1-2 years after diagnosis. CONCLUSION: HRQOL is an important aspect in the decision-making and advising process for patients with prostate cancer. In many aspects of HRQOL, AS is associated with more favourable outcomes than RP within the first 1-2 years after diagnosis in our observational design, although the differences were not clinically significant. The result that HRQOL in AS patients is at least as high as in RP patients should be considered when advising patients about the different treatment options for low-risk localised prostate cancer.

Utilization of Active Surveillance and Watchful Waiting for localized prostate cancer in the daily practice.

PURPOSE: To analyze the utilization of Active Surveillance (AS) and Watchful Waiting (WW) in the daily routine setting, since both are non-invasive treatment options for localized prostate cancer (PCa), which are used in a curative (AS) or palliative (WW) setting. Since differentiation of both strategies is not always clear, patients were compared with respect to the inclusion criteria, frequency of follow-up examinations (Prostate Specific Antigen = PSA tests, rebiopsies), and initiation of a deferred treatment. METHODS: HAROW is a non-interventional, health-service research study on the management of localized PCa in the community setting. Of 3169 patients, prospectively enrolled from 2008 to 2013 with a mean follow-up of 28.2 months, 468 chose AS and 126 WW. Treating urologists reported clinical variables, information on therapy and clinical course of disease. RESULTS: AS patients were significantly younger and had more low-risk tumors. No differences were seen in the number of PSA tests during follow-up: mean number of PSA tests was 6.08 for AS- and 5.18 for WW patients, more than four PSA tests were reported in 63.9% AS- and 59.5% WW patients (p = 0.136). At least one re-biopsy was performed in 39.7% AS- and 9.5% WW patients (p < 0.001). Discontinuation rates were 23.9% (n = 112) for AS and 11.9% (n = 15) for WW. Most of the AS patients opted for a curative treatment (prostatectomy = 65, radiotherapy = 30), whereas 12 WW patients received a palliative hormone therapy and three patients received radiotherapy. CONCLUSIONS: Physicians seem to distinguish clearly between AS and WW in terms of inclusion criteria and deferred therapy, whereas this differentiation tends to become indistinct in terms of follow-up examinations.

Risk stratification: a tool to predict the course of active surveillance for localized prostate cancer?

OBJECTIVE: To investigate a cohort of patients undergoing active surveillance (AS) for localized prostate cancer (PCa) with regard to possible differences in discontinuation rates, subsequent therapies, reasons for intervention and pathological findings after deferred surgery after patient stratification into very-low-risk, low-risk and intermediate-/high-risk PCa groups. PATIENTS AND METHODS: The HAROW study was a non-interventional, observational, outcomes research study on the management of localized PCa in the community setting. A total of 468 patients were prospectively enrolled in the HAROW study, with a mean follow-up of 28.5 months. Treating urologists reported clinical variables, information on therapy and clinical course of disease at 6-month intervals. RESULTS: Of 468 patients under AS, 244 were stratified into very-low-risk, 142 into low-risk and 82 into intermediate-/high-risk groups. Of these patients, 112 discontinued AS. Discontinuation rates were 25.4% in the very-low-risk, 21.1% in the low-risk and 24.4% in the intermediate-/high-risk groups (P = 0.633). The main reasons for intervention were biopsy upgrade and/or prostate-specific antigen elevation in the very-low- and low-risk groups, and patient preference in the intermediate-/high-risk group (P < 0.05). No significant differences were found regarding subsequent therapies and pathological findings after deferred surgery. CONCLUSION: Our results show no differences in the outcome of risk-stratified patients in the specified risk groups managed with AS, while switching to an invasive treatment on the patient's request was more frequent in the intermediate-/high-risk group.

Patient-physician communication and health-related quality of life of patients with localised prostate cancer undergoing radical prostatectomy - a longitudinal multilevel analysis.

OBJECTIVES: To examine whether patient-physician communication is associated with health-related quality of life (HRQoL) in a sample of patients with localised prostate cancer undergoing radical prostatectomy (RP). PATIENTS AND METHODS: HAROW (Hormonal therapy, Active Surveillance, Radiation, Operation, Watchful Waiting) is a prospective, observational study designed to collect data of the different treatment options for newly diagnosed patients with localised prostate cancer under real-life conditions. At 6-months intervals, clinical data (D'Amico risk categories, Charlson comorbidity index), aspects of patient-provider communication (standardised psychosocial-care instrument for patients' assessment of communication; Cologne Patient Questionnaire), and HRQoL (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire) were assessed. Data were analysed by longitudinal multilevel analysis. RESULTS: Completed questionnaires for 1772 patients undergoing a RP were analysed over a 3-year follow-up period. Patients rated the patient-provider communication generally high with slight variations over the course of treatment (3.2-3.8). The HRQoL of the patients varied substantial over time and between the reported subscales (global HRQoL 71.1-77.2; physical functioning 89.1-92.1; role functioning 81.0-88.1; emotional functioning 74.4-84.0; cognitive functioning 84.3-87.7; social functioning (77.7-84.0). The longitudinal multilevel models showed significant associations between patient-provider communication in terms of devotion, support and shared decision-making, and functional aspects of HRQoL. CONCLUSION: Patient-provider communication is a valuable resource to support patients with prostate cancer coping with the disease and to improve their HRQoL. Future interventions should be designed especially for urologists to enhance their awareness for the importance of communication and the relationship with their patients with prostate cancer for treatment outcomes.

Patients' perceptions of mortality risk for localized prostate cancer vary markedly depending on their treatment strategy.

Treatment choice for localized prostate cancer (PCa) is a controversial issue, and mortality risk is probably the most decisive factor in this regard. The study aimed to compare prostate-cancer-specific mortality risk estimates for different treatment options assigned by patients managed with active surveillance (AS), radical prostatectomy (RP) and patients who had discontinued AS (DAS). Patients initially managed with AS or RP (N = 370) were matched according to length of therapy. All patients completed mailed questionnaires assessing their mortality risk estimates (in %) and prostate-cancer-specific anxiety. Differences in risk estimates among the three treatment groups were analyzed using ANOVA, relationships of clinical and psychosocial variables with risk estimates using standard multiple regression. In all treatment groups, the prostate- cancer-specific mortality risk was overestimated. This applied whether it was the patient's own treatment or the alternative treatment option. RP patients assigned a mortality risk to AS that was almost three times higher than that assigned to RP (50.9 ± 25.0 vs. 17.8 ± 19.7, d = 1.48; p < 0.001). Anxiety was significantly associated with risk estimates for AS (p = 0.008) and RP (p = 0.001). Compared with clinical data that suggest that the prostate-cancer-specific mortality risk for AS is low and does not significantly differ from that for RP, patients strongly overestimated the mortality risk. This was most markedly so in RP patients, who drastically overestimated the benefits of RP compared to the risk of AS. This overestimation could increase overtreatment and should therefore be corrected by better patient education.

Active surveillance in localized prostate cancer: comparison of incidental tumours (T1a/b) and tumours diagnosed by core needle biopsy (T1c/T2a): results from the HAROW study.

OBJECTIVE: To conduct a comparative prospective analysis of patients with incidental T1a/T1b prostate cancer (IPCa) and those with prostate cancer (PCa) diagnosed by core needle biopsy, treated by active surveillance (AS), with regard to inclusion criteria, progression and switch to deferred treatment. PATIENTS AND METHODS: The HAROW study is an observational outcomes research study on the management of localized PCa. Treating urologists reported clinical variables and information on therapy and clinical course of disease at 6-month intervals. With respect to therapy, only recommendations were made; the final decision on the therapeutic method rested with the treating physician. RESULTS: Out of 2 957 patients included in the HAROW study, 447 chose AS. The median follow-up was 28.3 months. T1a, T1b, T1c and T2a disease were diagnosed in 81, 18, 292 and 56 patients, respectively. Patients in the IPCa group had lower prostate-specific antigen (PSA) levels (4.2 vs 6.1 ng/mL) and more comorbidities than those diagnosed by core needle biospy. The IPCa group also had fewer re-biopsies (25.3 vs 43.2%) and fewer changes to invasive treatment (12.1 vs 25.9%). No significant differences were found with respect to the criteria for discontinuation, subsequent therapies and histological findings after radical prostatectomy. CONCLUSION: Urologists are highly inclined to use AS as a therapeutic option in IPCa. More patients with IPCa than those diagnosed after core needle biopsy continued on AS, which was also associated with the indication for a re-biopsy being less stringently observed.

Treatment of Incidental Prostate Cancer by Active Surveillance: Results of the HAROW Study.

OBJECTIVE: To report on a cohort of patients with incidental prostate cancer (IPC) that was treated by an active surveillance (AS) protocol in the HAROW study. MATERIALS AND METHODS: The HAROW study is an observational study on the management of localized prostate cancer in Germany. Treating urologists were reporting clinical parameters, information on therapy and clinical course of disease at 6-month intervals. RESULTS: In total, 3,169 patients were enrolled. In 224 patients were found an IPC and 104 (46%) of them were put on an AS protocol. The mean follow-up was 26.5 months. Tumor progression was noted in 16 patients. In 11 patients, AS was replaced by a definite intervention. In univariate and multivariate analyses, only PSA density correlated with progression. CONCLUSION: This is the first prospective description of an IPC patient cohort on AS as part of an outcomes research study. AS was selected as a therapeutic strategy in nearly half of the patients (46%). Only a minor proportion (16%) displayed progression. Of the clinical parameters, only PSA density correlated with progression.

MicroRNA 15a, inversely correlated to PKCα, is a potential marker to differentiate between benign and malignant renal tumors in biopsy and urine samples.

NF-κB signal transduction is a potential therapeutic target in many malignant tumors. We have recently shown, in malignant renal proximal tumor cells, that a transcription complex, consisting of NF-κB p65 and mitogen-activated protein kinase p38α, joined by protein kinase C (PKC) α, transmigrates into the nucleus. There, PKCα suppresses the nuclear release of primary microRNA (pri-miRNA) 15a. Induced by endothelin (ET)-1, a decrease in PKCα levels leads to increased miRNA 15a (miR-15A) expression. An identical system can be identified in renal carcinomas, in which, after nuclear transmigration, PKCα binds directly to pri-miRNA 15a in the nucleus. However, the pattern of PKC isoforms differs between malignant renal cell carcinoma (RCC) and benign oncocytoma. PKCα, a component of the transcription complex in tumors, is up-regulated in benign oncocytoma but down-regulated in RCC. Conversely, miRNA 15a is up-regulated in RCC and down-regulated in oncocytoma. A similar behavior is observed in chromophobe carcinoma, whereas differences are less pronounced in papillary RCC (type I): NF-κB target gene expression (ie, ET-1, ET-A and ET-B receptors, vascular cell adhesion molecule-1, IL-6, and fractalkine) is particularly high in malignant RCCs. Up-regulated miRNA 15a can be measured in urine from patients with RCC but is nearly undetectable in oncocytoma, other tumors, and urinary tract inflammation. Thus, the up-regulation of miRNA 15a may be an important marker to help identify malignant clear-cell RCCs in both biopsy and urine samples.

Linkage of data from diverse data sources (LDS): a data combination model provides clinical data of corresponding specimens in biobanking information system.

To provide sufficient clinical data for corresponding specimens from diverse databases established before the implementation of biobanks for research purposes with respect to data privacy regulations. For this purpose, we developed a data model called "linkage of data from diverse data sources (LDS)". The data model was developed to merge clinical data from an existing local database with biospecimen repository data in our serum bank for uro-oncology. This concept combines two data models based on XML: the first stores information required to connect multiple data sources and retrieve clinical data, and the second provides a data architecture to acquire clinical and repository data. All data were anonymized and encrypted using the Advanced Encryption Standard. X.509 certificates were applied to secure data access. Furthermore, we tested the feasibility of implementing these models in the information management system for biobanking. The data concept can provide clinical and repository data of biospecimens. Only authorized receivers can access these data. Sensitive and personal data are not accessible by the data receivers. The data receiver cannot backtrack to the individual donor using the data model. The acquired data can be converted into a text file format supported by familiar statistical software. Supplementary tools were implemented to generate and view XML documents based on these data models. This data model provides an effective approach to distribute clinical and repository data from different data sources to enable data analysis compliant with data privacy regulations.

Treatment Failure in Vertebral Osteomyelitis: Is it All About Staphylococcus aureus ?

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The aim was to compare the influence of 2 common vertebral osteomyelitis (VO) causing pathogens on treatment failure within the first year of diagnosis. SUMMARY OF BACKGROUND DATA: VO is mainly caused by Staphylococcus aureus (SA), while enterococci and streptococci (ENST) are also responsible for a significant proportion of VO, particularly in elderly patients. Data on VO caused by SA show a tendency for worse outcome, whereas data on VO caused by ENST are scarce. For this purpose, our study compares characteristics of patients with VO caused by SA or ENST in order to analyze risk factors for treatment failure. METHODS: We conducted a retrospective monocentric study including VO patients from 2008 to 2020. Primary outcome was treatment failure defined as death or relapse within 1 year (T1). We compared patients diagnosed with VO caused by Staphylococcus aureus including MRSA to patients diagnosed with VO caused by Enterococcus and Streptococcus species, which were combined into one group. Polymicrobial infections were excluded. We employed multiple logistic regression analysis to adjust for confounding. To account for moderation, the model was repeated with an included interaction term. RESULTS: Data of 130 VO patients (SA=95; ENST=35) were available at T1. Treatment failure occurred in 37% of SA patients and 23% of ENST patients. On multivariate analysis SA [odds ratio (OR): 3.12; 95% confidence interval (CI): 1.09-10.53; P =0.046], Charlson comorbidity index (OR: 1.31; 95% CI: 1.11-1.58; P =0.002) and infectious endocarditis (IE; OR: 4.29; 95% CI: 1.23-15.96; P =0.024) were identified as independent risk factors for treatment failure. CONCLUSION: In our cohort every third patient with VO caused by SA or ENST dies within 1 year. Our findings indicate that patients with VO caused by SA, concomitant IE and/or a high Charlson comorbidity index score may be at elevated risk for treatment failure. These findings can be used to individualize patient care and to direct clinical surveillance. This could include echocardiography evaluating for the presence of IE in patients with VO caused by gram-positive pathogens.

[Active surveillance-much safety, little recruitment : Is it possible to extend the indication for "intermediate-risk" prostate cancer?] / Active Surveillance ­ viel Sicherheit, wenig Rekrutierung : Ist eine Ausdehnung der Indikation auf das intermediäre Risiko möglich?

BACKGROUND: In contrast to North America or Sweden, active surveillance (AS) has not yet become established in our country for suitable prostate carcinomas (PCa). The strict entry criteria specified by the guideline are not likely to improve the acceptance in the near future. In early detection, prostate-specific antigen (PSA) testing leads to high numbers of overtreatment. There are various reasons for the continued preference for radical surgery. OBJECTIVES: The goal is to examine whether the heterogeneous group with intermediate-risk PCa contains tumors that may be eligible for AS. MATERIALS AND METHODS: In the HAROW trial, 52 AS patients with differently defined intermediate-risk PCa were followed for a median of 85.6 months. Oncologic outcomes are reported. RESULTS: Sixteen (30%) patients had a tumor of cT2b category, 21 (40%) had a Gleason score 3 + 4, 7 (14%) had ≥3 positive biopsy cores, 21 (40%) had a PSA >10 ng/ml, and 22 (42%) had a PSA density >0.2 ng/ml2. Carcinoma-specific and metastasis-free survival were 100% and 96%, respectively. Thirty four patients discontinued AS in favor of invasive treatment, and an additional eight men maintained a noninvasive approach by switching to watchful waiting. CONCLUSIONS: Efforts are under way to specify the criteria for patients with intermediate-risk PCa who may be eligible for AS. Tumors of cT2 category could be grouped together. The Gleason 4 fraction needs to be quantified because it determines the prognosis.

EBV induced loss of sperm quality.

OBJECTIVE: To analyze the presence of Epstein-Barr-virus (EBV) in sperm samples from patients diagnosed with some impairment of the fertility parameters evaluated using seminogram and to observe if there is any difference with the normozoospermic samples. We hypothesize that an EBV infection is responsible for the upregulation of the miRNA 199-3p, which binds to the 3'UTR of endothelin-1 (ET-1). ET-1 is a key factor to produce Vimentin (Vim3), and therefore, it influences the expression of Vim3. Since Vim3 is predominantly detectable in sperms without any structural defects, the newly identified regulation mechanism can be responsible for the loss of sperm quality. MATERIAL AND METHODS: This study was performed from January 2017 to December 2020 and included 27 patients who provided ejaculated samples obtained by masturbation. Ejaculates were evaluated according to the Word Health Organization's criteria. Posteriorly, the samples were sorted according to the seminogram diagnosis and further analyzed using different enzyme-linked absorbed immune assays to determine the level or concentration of Epstein-Barr nuclear antigen (EBNA), ET-1, and Vim3. RESULTS: All sperm samples with the impairment of fertility parameters contained the EBNA and presented a downregulation of ET-1 and Vim3. In addition, sperms located in the swim ups are also partially positive for the EBV virus in different clinical aspects. CONCLUSION: Based on the regulation mechanism here presented, it seems that the EBV induces changes at the miRNA level, which are responsible for the decreasing of sperm quality.

Stage and Grade Migration in Prostate Cancer Treated With Radical Prostatectomy in a Large German Multicenter Cohort.

INTRODUCTION: Overdiagnosis and overtherapy in prostate cancer (PCa) treatment should be avoided, which has led to an awareness of the need to decrease treatment in cases of low-risk PCa with radical prostatectomy (RP). Simultaneously, prostate-specific antigen testing has become less popular in the last few years, which has resulted in higher cancer grade and stage at diagnosis. We evaluated stage and grade migration in the disease of patients treated with RP in a large German cohort. PATIENTS AND METHODS: Overall, 4842 patients undergoing RP between 2000 and 2019 were included. Age, prostate-specific antigen level, biopsy, and pathologic Gleason score as well as clinical and pathologic stage were collected. D'Amico risk groups and Gleason score were evaluated over different time points. RESULTS: We detected a significant grade migration toward higher grade. The proportion of biopsy Gleason sum ≤ 6 dropped from 45.8% to 20.6% between ≤ 2010 and 2017-2019. Further, the proportion of patients with low D'Amico risk scores also decreased by almost 50% (20.8% vs 12.2%). Finally, the proportion of non-organ-confined PCa increased over time, and the proportion of postoperative Gleason sum ≤ 6 decreased from 20% to 10% over time. CONCLUSION: Taken together, data indicate a significant preoperative grade and stage migration toward disease of higher grade in RP-treated PCa. Between the years 2000 and 2019, the proportion of biopsy Gleason sum ≤ 6 and the proportions of D'Amico low risk disease decreased by approximately 50% (respectively, 45% to 20% and 20.8% to 12.2%). This might indicate better patient selection for RP, but might also be a telltale sign of the rising mortality and morbidity of PCa.

[Noninvasive treatment of organ-confined prostate cancer in elderly patients-results of the HAROW study]. / Die nichtinvasive Therapie des organbegrenzten Prostatakarzinoms im Alter ­ Ergebnisse der HAROW-Studie.

BACKGROUND: Noninvasive treatment options such as active surveillance (AS), watchful waiting (WW), and hormone deprivation therapy (HT) are particularly important in elderly patients with localized prostate cancer (PCa). OBJECTIVES: We examine the use of these noninvasive treatment options in the everyday care in a cohort of patients ≥70 years old. MATERIALS AND METHODS: In the HAROW study, the treatment of localized PCa under everyday conditions is investigated. The only inclusion criterion was newly diagnosed organ-confined PCa (≤cT2c). In AS, WW, and HT patients, we compared initial tumor and patient characteristics, follow-up examinations and changes of therapy. RESULTS: Of 457 patients ≥70 years, 210 chose AS, 160 HT, and 87 WW. Observation times were 6.3 years (AS), 7.5 years (HT), and 7.0 years (WW). AS patients (73.2 years) were younger than WW (76.0 years) and HT patients (76.9 years) and had a higher proportion of low-risk tumors (80%) versus WW (31%) and HT (19%). A change of therapy was observed in 47.1% of AS, 17.2% of WW and 13.1% of HT patients. Metastasis occurred in 1.0% of AS, 4.6% of WW, and 6.9% of HT patients. Overall survival was 94.3% for AS, 90.8% for WW and 81.9% for HT. Within the first 28.4 months, the mean number of PSA determinations did not differ between AS and WW (6.1 vs. 5.2; p = 0.09); a rebiopsy was performed in 37.6% of AS, 11.4% of WW, and 17% of HT patients. CONCLUSIONS: The allocation to curative and palliative strategies should be made according to patient and tumor characteristics by definition. Palliative procedures may represent concepts in older patients who initially chose a curative AS strategy.