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Abstract The current study aimed to evaluate short‐ and long‐term complication rates and functional outcomes in a substantial cohort of patients undergoing ileal ureter interposition at two high‐volume medical centres. Materials and methods A retrospective single‐arm analysis was conducted on patients who underwent ureter reconstruction using ileum between 2003 and 2022 at the University Clinic of Cologne and the National Cancer Institute of Ukraine. Data on aetiology, surgical techniques, pre‐ and postoperative kidney function changes, readmission rates and complication management were collected. Postoperative complications were classified according to Clavien–Dindo, and estimated glomerular filtration rate (eGFR) was calculated using the CKD‐EPI formula. Results Results revealed 107 cases with consistent data. Within 90 days post‐surgery, 53% experienced complications, mainly graded as I–II. Grade III complications were seen in 13%, with two cases of grade IV complications leading to extended hospitalisation and patient death. The 90‐day mortality rate was 1.8%. Over a mean follow‐up of 52 months, clinically significant vesico‐renal refluxes occurred in 28%, with only 5.4% leading to persistent urinary tract infection. Antireflux techniques appeared to reduce urine upflow incidence compared with conventional interposition. Anastomosis stricture occurred in 15% of patients, with 63% requiring permanent re‐stenting and 37% needing re‐anastomosis. Metabolic acidosis was clinically significant in 7.5% of cases. A slight improvement in renal function was observed during the first year post‐surgery (average postoperative eGFR = 76 ± 22 ml/min; Mann–Witney U test, p = 0,0198). Affected kidney function improved in 56 (52%), was stable in 41 (38%) and deteriorated in 10 (9.3%). Loss of kidney function on the surgery side was seen in 4 (3.7%) patients and resulted in nephrectomy in 3 (2.8%) cases. Conclusion Ileal ureter interposition demonstrated a favourable safety profile and functional outcomes. This surgical intervention provides an effective tension‐free bypass, irrespective of healthy ureter length.

Background Magnetic resonance-guided transurethral ultrasound ablation (MR-TULSA) is a new focal therapy for treating localised prostate cancer that is associated with fewer adverse effects (AEs) compared with established treatments. To support large-scale clinical implementation, information about cost-effectiveness is required.Objective To evaluate the cost–utility of MR-TULSA compared with robot-assisted radical prostatectomy (RARP), external beam radiation therapy (EBRT) and active surveillance (AS) for patients with low- to favourable intermediate-risk localised prostate cancer.Design, setting and participants A Markov model was developed targeting 60-year-old men diagnosed with low- to intermediate-risk localised prostate cancer over a time horizon of 40 years from the German Statutory Health Insurance (SHI) perspective. To assess the robustness of the results, deterministic and probabilistic sensitivity analyses were performed.Intervention Four different treatment strategies were compared: minimally invasive MR-TULSA, two definitive approaches (RARP and EBRT) and one observational strategy (AS).Outcome measurements and statistical analysis Outcomes were measured in overall costs, quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER).Results AS generated the highest number of QALYs (12.67), followed by MR-TULSA (12.35), EBRT (12.35) and RARP (12.20). RARP generated the lowest costs (€ 46 997) over one patient’s lifetime, while MR-TULSA was a slightly more expensive alternative (€48 826). The incremental cost-effectiveness ratio (ICER) of AS compared with RARP was €11 600 per QALY and of MR-TULSA compared with RARP was €12 193 per QALY, while EBRT was dominated. At a willingness-to-pay of €20 000 per QALY, the probability of being cost-effective is 44% for AS, 25% for RARP, 25% for MR-TULSA and 6% for EBRT.Conclusions All treatment options for 60-year-old men diagnosed with low- to intermediate-risk localised prostate cancer are affected by considerable uncertainty. Accepting high follow-up costs by applying a higher willingness-to-pay, AS is the most favourable treatment option.

Abstract Pathologic examination of prostate biopsies is time consuming due to the large number of slides per case. In this retrospective study, we validate a deep learning-based classifier for prostate cancer (PCA) detection and Gleason grading (AI tool) in biopsy samples. Five external cohorts of patients with multifocal prostate biopsy were analyzed from high-volume pathology institutes. A total of 5922 H&E sections representing 7473 biopsy cores from 423 patient cases (digitized using three scanners) were assessed concerning tumor detection. Two tumor-bearing datasets (core n = 227 and 159) were graded by an international group of pathologists including expert urologic pathologists (n = 11) to validate the Gleason grading classifier. The sensitivity, specificity, and NPV for the detection of tumor-bearing biopsies was in a range of 0.971–1.000, 0.875–0.976, and 0.988–1.000, respectively, across the different test cohorts. In several biopsy slides tumor tissue was correctly detected by the AI tool that was initially missed by pathologists. Most false positive misclassifications represented lesions suspicious for carcinoma or cancer mimickers. The quadratically weighted kappa levels for Gleason grading agreement for single pathologists was 0.62–0.80 (0.77 for AI tool) and 0.64–0.76 (0.72 for AI tool) for the two grading datasets, respectively. In cases where consensus for grading was reached among pathologists, kappa levels for AI tool were 0.903 and 0.855. The PCA detection classifier showed high accuracy for PCA detection in biopsy cases during external validation, independent of the institute and scanner used. High levels of agreement for Gleason grading were indistinguishable between experienced genitourinary pathologists and the AI tool.

Abstract Background Metastatic germ cell tumors of the testis (GCTs) are risk‐stratified according to the International Germ Cell Cancer Collaborative Group (IGCCCG) classification system. This risk classification is based on anatomical risk factors as well as tumor marker levels of AFP, HCG, and LDH assessed pre‐chemotherapy after orchiectomy treatment. An incorrect classification is possible when pre‐orchiectomy marker levels are used, possibly resulting in over‐ or undertreatment of patients. The aim was to investigate the potential frequency and clinical relevance of incorrect risk stratification using pre‐orchiectomy tumor marker levels. Methods A multicenter registry analysis, including patients with metastasized nonseminomatous GCT (NSGCT), was conducted by investigators of the German Testicular Cancer Study Group (GTCSG). Based on the marker levels at different timepoints, IGCCCG risk groups were calculated. The agreement was tested using Cohen's kappa. Results A total of 672 of 1910 (35%) patients were diagnosed with metastatic NSGCTs, and 523 (78%) had sufficient data for 224 follow‐up data points. By using pre‐orchiectomy tumor marker levels, 106 patients (20%) would have been incorrectly classified. Seventy‐two patients (14%) were classified into a higher risk category, and 34 patients (7%) were classified into a lower risk category. Cohen's kappa was 0.69 (p

(1) Background: Local therapy is highly promising in a multimodal approach strategy for patients with low-volume metastatic prostate cancer (mPCa). We aimed to systematically assess and summarize the safety, oncologic, and functional outcomes of cytoreductive prostatectomy (cRP) in mPCa. (2) Methods: Three databases were queried in September 2022 for publications that analyzed mPCa patients treated with cytoreductive prostatectomy without restrictions. The outcomes of interest were progression-free survival (PFS), cancer-specific survival (CSS), overall survival (OS), perioperative complication rates, and functional outcomes following cRP. (3) Results: Overall, 26 studies were included in this systematic review. Among eight population-based studies, cRP was associated with a reduced risk of CSS and OS compared with no local therapy (NLT) after adjusting for the effects of possible confounders. Furthermore, one population-based study showed that cRP reduced the risk of CSS even when compared with radiotherapy (RT) of the prostate after adjusting for the effects of possible confounders. In addition, one randomized controlled trial (RCT) demonstrated that local therapy (comprising 85% of cRP) significantly improved the prostate-specific antigen (PSA)-PFS and OS. Overall, cRP had acceptable perioperative complication rates and functional outcomes. (4) Conclusions: Mounting evidence suggests that cRP offers promising oncological and functional outcomes and technical feasibility and that it is associated with limited complications. Well-designed RCTs that limit selection bias in patients treated with cRP are warranted.

Abstract Objective To evaluate the relationship between pre‐operative PSA value, 68Ga‐prostate‐specific‐membrane‐antigen (PSMA) PET performance and oncologic outcomes after salvage lymph node dissection (sLND) for biochemical recurrent prostate cancer (PCa). Patients and methods The study included 164 patients diagnosed with ≤2 pelvic lymph‐node recurrence(s) of PCa documented on 68Ga‐PSMA PET scan and treated with pelvic ± retroperitoneal sLND at 11 high‐volume centres between 2012 and 2019. Pathologic findings were correlated to PSA values at time of sLND, categorized in early (1.5 ng/ml). Clinical recurrence (CR)‐free survival after sLND was calculated using multivariable analyses and plotted over pre‐operative PSA value. Results Median [interquartile range (IQR)] PSA at sLND was 1.1 (0.6, 2.0) ng/ml, and 131 (80%) patients had one positive spot at PET scan. All patients received pelvic sLND, whereas 91 (55%) men received also retroperitoneal dissection. Median (IQR) number of node removed was 15 (6, 28). The rate of positive pathology increased as a function of pre‐operative PSA value, with highest rates for patients with pre‐operative PSA > 1.5 ng/ml (pelvic‐only sLNDs: 84%; pelvic + retroperitoneal sLNDs: 90%). After sLND, PSA ≤ 0.3 ng/ml was detected in 67 (41%) men. On multivariable analyses, pre‐operative PSA was associated with PSA response (p

Context: The aim of this review is to describe the proportion of testicular germ cell tumours (tGCTs) with recurrence, and the timing and anatomical sites of relapse across different disease stages and after different treatment options. We summarise published follow-up protocols and discuss current and future developments to personalise follow-up for patients with tGCT. Evidence acquisition: A systematic literature search was conducted and current guidelines and selected institutional follow-up protocols were reviewed. Evidence synthesis: Of 302 publications, we screened 68 full texts and included 29 studies; 22 of these were retrospective and seven were prospective in nature, contributing data for 20 570 patients. The number of patients included per study ranged from 119 to 2483. We compared the guideline follow-up protocols of the European Society for Medical Oncology, European Association of Urology, National Comprehensive Cancer Network, and American Urological Association, as well as institutional follow-up protocols. The protocols differed in terms of the number, time points, and type of follow-up investigations. Conclusions: Future research should assess how tGCT can be followed to ensure high adherence, define the role of miR-371a-3p microRNA during follow-up, and develop follow-up protocols after curative treatment in the metastatic setting. Patient summary: In this review of follow-up protocols for men with testis cancer, we observed different recommendations and discuss future research areas to improve follow-up for these patients.

Certified Cancer Centers must present all patients in multidisciplinary tumor boards (MTB), including standard cases with well-established treatment strategies. Too many standard cases can absorb much of the available time, which can be unfavorable for the discussion of complex cases. In any case, this leads to a high quantity, but not necessarily a high quality of tumor boards. Our aim was to develop a partially algorithm-driven decision support system (DSS) for smart phones to provide evidence-based recommendations for first-line therapy of common urological cancers. To assure quality, we compared each single digital decision with recommendations of an experienced MTB and obtained the concordance.1873 prostate cancer patients presented in the MTB of the urological department of the University Hospital of Cologne from 2014 to 2018 have been evaluated. Patient characteristics included age, disease stage, Gleason Score, PSA and previous therapies. The questions addressed to MTB were again answered using DSS. All blinded pairs of answers were assessed for discrepancies by independent reviewers. Overall concordance rate was 99.1% (1856/1873). Stage specific concordance rates were 97.4% (stage I), 99.2% (stage II), 100% (stage III), and 99.2% (stage IV). Quality of concordance were independent of age and risk profile. The reliability of any DSS is the key feature before implementation in clinical routine. Although our system appears to provide this safety, we are now performing cross-validation with several clinics to further increase decision quality and avoid potential clinic bias.

Background: Prostate-specific membrane antigen (PSMA) targeted molecular imaging using positron emission tomography (PET) has significantly improved the diagnosis and treatment of prostate cancer (PCA). Objective: To assess the feasibility and compare the diagnostic accuracy of [68Ga]Ga-PSMA-11 PET images taken at baseline, before the initiation of systemic treatment and preoperative images, using histopathology after cytoreductive surgery as reference. Design, setting, and participants: We identified 20 patients in our prospectively maintained database with primary oligometastatic PCA who underwent cytoreductive radical prostatectomy and superextended pelvic lymph node dissection after systemic therapy, who had baseline and preoperative [68Ga]Ga-PSMA-11 PET imaging available. Outcome measurements and statistical analysis: We performed a region-based analysis to determine the diagnostic accuracy of imaging, using pathology as a reference. Regions were predefined as prostate, internal iliac left/right, obturator left/right, external iliac left/right, common iliac left/right, and presacral. Results and limitations: Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and diagnostic effectiveness were, respectively, 95.65%, 78.22%, 98.39%, 57.89%, and 83.00% for baseline [68Ga]Ga-PSMA-11 PET, compared to 56.52%, 98.05%, 88.30%, 89.66%, and 88.50% for preoperative [68Ga]Ga-PSMA-11 PET. On a receiver operating characteristic analysis, the diagnostic accuracy of baseline [68Ga]Ga-PSMA-11 PET with an area under the curve (AUC) of 0.87 (95% confidence interval [CI] 0.83–0.92) was significantly better than that of preoperative [68Ga]Ga-PSMA-11 PET after systemic therapy with an AUC of 0.77 (95% CI 0.70–0.85, p = 0.01). Conclusions: Baseline imaging, [68Ga]Ga-PSMA-11 PET has significantly better diagnostic accuracy, sensitivity, and NPV than images obtained preoperatively, in systemically pretreated patients. If a patient is suitable for local treatment and complete resection of the residual tumor is intended, [68Ga]Ga-PSMA-11 PET images taken prior to systemic therapy are significantly more accurate in selecting the relevant lymph nodes for resection. Patient summary: We found that prostate-specific membrane antigen positron emission tomography (PSMA-PET) imaging used early, before hormonal therapy or chemotherapy, provides more accurate information about the spread of the disease, than if used immediately before surgery but after hormonal therapy or chemotherapy. Early use of PSMA-PET has the potential to improve therapy also at later stages of the disease.

Abstract Computed tomography in suspected urolithiasis provides information about the presence, location and size of stones. Particularly stone size is a key parameter in treatment decision; however, data on impact of reformatation and measurement strategies is sparse. This study aimed to investigate the influence of different image reformatations, slice thicknesses and window settings on stone size measurements. Reference stone sizes of 47 kidney stones representative for clinically encountered compositions were measured manually using a digital caliper (Man-M). Afterwards stones were placed in a 3D-printed, semi-anthropomorphic phantom, and scanned using a low dose protocol (CTDIvol 2 mGy). Images were reconstructed using hybrid-iterative and model-based iterative reconstruction algorithms (HIR, MBIR) with different slice thicknesses. Two independent readers measured largest stone diameter on axial (2 mm and 5 mm) and multiplanar reformatations (based upon 0.67 mm reconstructions) using different window settings (soft-tissue and bone). Statistics were conducted using ANOVA ± correction for multiple comparisons. Overall stone size in CT was underestimated compared to Man-M (8.8 ± 2.9 vs. 7.7 ± 2.7 mm, p 0.05), while image reformatations and window settings did (p

A valid treatment option for recurrence after definite radiotherapy (RT) for localized prostate cancer (PC) is salvage radical prostatectomy (SRP). However, data on SRP are scarce, possibly resulting in an underutilization. A systematic review was performed using MEDLINE (Pubmed), Embase, and Web of Science databases including studies published between January 1980 and April 2020. Overall, 23 English language articles including a total number of 2323 patients were selected according to PRISMA criteria. The overall median follow-up was 37.5 months (IQR 35.5–52.5). Biochemical-recurrence (BCR)-free probability ranged from 34% to 83% at five years, respectively, and from 31% to 37% at 10 years. Cancer specific survival (CSS) and overall survival (OS) ranged from 88.7% to 98% and 64% to 95% at five years and from 72% to 83% and 65% to 72% at 10 years, respectively. Positive surgical margins ranged from 14% to 45.8% and pathologic organ-confined disease was reported from 20% to 57%. The rate of pathologic > T2-disease ranged from 37% to 80% and pN1 disease differed between 0% to 78.4%. Pre-SRP PSA, pre-SRP Gleason Score (GS), pathologic stage after SRP, and pathologic lymph node involvement seemed to be the strongest prognostic factors for good outcomes. SRP provides accurate histopathological and functional outcomes, as well as durable cancer control. Careful patient counseling in a shared decision-making process is recommended.

This study aimed to compare the image quality and diagnostic accuracy of deep-learning-based image denoising reconstructions (DLIDs) to established iterative reconstructed algorithms in low-dose computed tomography (LDCT) of patients with suspected urolithiasis. LDCTs (CTDIvol, 2 mGy) of 76 patients (age: 40.3 ± 5.2 years, M/W: 51/25) with suspected urolithiasis were retrospectively included. Filtered-back projection (FBP), hybrid iterative and model-based iterative reconstruction (HIR/MBIR, respectively) were reconstructed. FBP images were processed using a Food and Drug Administration (FDA)-approved DLID. ROIs were placed in renal parenchyma, fat, muscle and urinary bladder. Signal- and contrast-to-noise ratios (SNR/CNR, respectively) were calculated. Two radiologists evaluated image quality on five-point Likert scales and urinary stones. The results showed a progressive decrease in image noise from FBP, HIR and DLID to MBIR with significant differences between each method (p < 0.05). SNR and CNR were comparable between MBIR and DLID, while it was significantly lower in HIR followed by FBP (e.g., SNR: 1.5 ± 0.3; 1.4 ± 0.4; 1.0 ± 0.3; 0.7 ± 0.2, p < 0.05). Subjective analysis confirmed best image quality in MBIR, followed by DLID and HIR, both being superior to FBP (p < 0.05). Diagnostic accuracy for urinary stone detection was best using MBIR (0.94), lowest using FBP (0.84) and comparable between DLID (0.90) and HIR (0.90). Stone size measurements were consistent between all reconstructions and showed excellent correlation (r2 = 0.958–0.975). In conclusion, MBIR yielded the highest image quality and diagnostic accuracy, with DLID producing better results than HIR and FBP in image quality and matching HIR in diagnostic precision.

ObjectivesIleal conduits (ICs) carry an additional perioperative complication risk due to the bowel procedure. This analysis compares surgical outcomes in patients ≥75 years of age with ureterocutaneostomy (UCN) and IC after cystectomy (Cx).MethodsData of 527 patients included in a retrospective cystectomy database of two high volume centers (2008–2020) were queried to identify elderly patients (≥75 years) who underwent Cx either with IC or UCN. Patient characteristics of all patients [age, BMI, Charlson Comorbidity Index (CCI)], perioperative parameters (operation time, blood loss, transfusions, tumor stage), and postoperative complications (clavien >IIIA, intensive care unit (ICU) stay) were compared. As special focus, bowel complications requiring surgical revision (rBCs) were analyzed. In patients with IC, the rate of ureteral implantation stenosis (USt) was recorded. As a population of special interest, patients ≥80 years of age were analyzed separately. Categorical data were compared using Fisher exact test, and continuous data were compared using Mann–Whitney U test.ResultsA total of 163 patients ≥75 years of age (125 IC, 38 UCN) were identified. Patients with UCN were older and presented with a higher CCI, though differences were not statistically different. Surgery with palliative intent was more frequent in patients with UCN (37 vs. 10%). Operation time in UCN was significantly shorter (233 vs. 305 min, p = 0.02), while blood loss and transfusion rate were comparable. Overall complication rate (Clavien-Dindo grade IIIA–IVB) was comparable (UCN 34% vs. IC 37%). However, rBC was a rare complication in UCN (3/38) as compared to patients with IC (15/125). Frequency of postoperative ICU stay (UCN 16% vs. IC 16%) and 90-day mortality did not differ (UCN 3/38 patients, IC 5/125 patients). Regarding long-term follow-up, USt requiring revision or permanent stenting was seen in 18/125 (14%) patients with IC. In patients >80 years of age, results were comparable to the main cohort. Low event rate regarding complications and bias inherent of a retrospective analysis (selection bias, unequal distribution in case numbers) precludes detection of statistical differences regarding patients' characteristics and overall complication rate.ConclusionUCN is an alternative to IC in elderly and/or frail patients. Severe bowel complications are numerically less frequent and operation time is minimized.

Abstract Purpose To give an overview of the multicenter Prostate Cancer Outcomes (PCO) study, involving paper-based and web-based collection of patient-reported outcome measures (PROM) in patients undergoing local treatment for prostate cancer in certified centers in Germany. The PCO study is part of the larger Movember-funded TrueNTH Global Registry. The article reports on the study’s design and provides a brief progress report after the first 2 years of data collection. Methods Prostate cancer centers (PCCs) certified according to German Cancer Society requirements were invited to participate in collecting patient-reported information on symptoms and function before and at least once (at 12 months) after treatment. The data were matched with disease and treatment information. This report describes progress in patient inclusion, response rate, and variations between centers relative to online/paper use, and also data quality, including recruitment variations relative to treatment in the first participating PCCs. Results PCC participation increased over time; 44 centers had transferred data for 3094 patients at the time of this report. Patient recruitment varied widely across centers. Recruitment was highest among patients undergoing radical prostatectomy. The completeness of the data was good, except for comorbidity information. Conclusions The PCO study benefits from a quality improvement system first established over 10 years ago, requiring collection and harmonization of a predefined clinical dataset across centers. Nevertheless, establishing a PROM routine requires substantial effort on the part of providers and constant monitoring in order to achieve high-quality data. The findings reported here may be useful for guiding implementation in similar initiatives.

Introduction: Clinical stage 1 (CS1) nonseminomatous (NS) germ cell tumors involve a 30% probability of relapse upon surveillance. Adjuvant chemotherapy with one course of bleomycin, etoposide, and cisplatin (1xBEP) can reduce this risk to pT2 was significantly associated with relapse rate. Conclusion: The relapse rate of 3.1% found in this population of NS CS1 patients treated with 1xBEP at the routine care level was not inferior to the median rate of 2.3% reported from a meta-analysis of controlled trials. Also, the cure rate of relapses of 77% is consistent with the previously reported rate of 80%. This study clearly shows that the 1xBEP regimen represents a safe treatment for NS CS1 patients.

Objective: To report the clinical outcome of urethral reconstruction by cultured urothelial or oral mucosa cells for tissue-engineered urethroplasty. Methods: We systematically searched for studies reporting the use of tissue-engineered techniques for hypospadias and urethral stricture repair in humans in PubMed and Embase (OvidSP) through January, 1990 to June, 2018. We excluded studies based on titles that clearly were not related to the subject, studies in which tissue-engineered biomaterial were used only in laboratory or experimental animals, and in the absence of autologous cultured epithelial cells. Studies were also excluded if they were not published in English, had no disease background and adequate follow-up. Finally, we search all relevant abstract presented at two of the main urological meetings in the last 10 years: European Association of Urology (EAU) and American Urological Association (AUA). Results: A total of six articles, reporting the clinical use of tissue-engineered techniques in humans, were fully reviewed in our review. The epithelial cells were harvested from the urethra (10 patients), the bladder (11 patients) and the mouth (104 patients). The tissue-engineered grafts were used in children for primary hypospadias repair in 16 cases, and in adults for posterior and anterior urethral strictures repair in 109 cases. Tissue-engineered grafts were showed working better in children for primary hypospadias repair than in adults for urethral strictures repair. Conclusion: One hundred and twenty-five patients received tissue-engineered urethroplasty using cultured epithelial cells for primary hypospadias or urethral strictures repair. The studies demonstrate a high degree of heterogeneity respect to epithelial cells (from urethra, bladder, and mouth), type of scaffold, etiology, site of urethral stricture, number of patients, follow-up and outcomes. Keywords: Urethra, Urethroplasty, Tissue engineering, Urethral mucosa, Oral mucosa, Surgical technique

ABSTRACTBackground: The COVID-19 pandemic represents an unprecedented global challenge and implicates a wide range of burden on medical professionals. Here, we evaluated the perception of the COVID-19 pandemic among medical professionals in Germany.Methods: A total of n = 2827 medical professionals participated in an online survey between 27 March and 11 April.Results: While most participants stated that Germany was well prepared and rated the measures taken by their employer as positive, subgroup analyses revealed decisive differences. The preventive measures were rated significantly worse by nurses compared to doctors (p

Abstract Aim We investigated the whole-body distribution and the radiation dosimetry of [18F]-JK-PSMA-7, a novel 18F-labeled PSMA-ligand for PET/CT imaging of prostate cancer. Methods Ten patients with prostate cancer and biochemical recurrence or radiologic evidence of metastatic diseases were examined with 329–384 MBq (mean 359 ± 17 MBq) [18F]-JK-PSMA-7. Eight sequential positron emission tomography (PET) scans were acquired from 20 min to 3 h after injection with IRB approval. The kidneys, liver, lungs, spleen, and salivary glands were segmented into volumes of interest using the QDOSE dosimetry software suite (ABX-CRO, Germany). Absorbed and effective dose were calculated using the ICRP-endorsed IDAC 1.0 package. The absorbed dose of the salivary glands was determined using the spherical model of OLINDA 1.1. PSMA-positive lesions were evaluated separately. Quantitative assessment of the uptake in suspicious lesions was performed by analysis of maximum (max) and peak SUV values. The gluteus maximus muscle (SUVmean) served as a reference region for the calculation of tumor-to-background ratios (TBR’s). Results Physiologic radiotracer accumulation was observed in the salivary and lacrimal glands, liver, spleen, and intestines, in a pattern resembling the distribution known from other PSMA-tracers with excretion via urinary and biliary pathways. The effective dose from [18F]-JK-PSMA-7 for the whole body was calculated to be 1.09E−02 mGy/MBq. The highest radiation dose was observed in the kidneys (1.76E−01 mGy/MBq), followed by liver (7.61E−02 mGy/MBq), salivary glands (4.68E−02 mGy/MBq), spleen (1.89E−02 mGy/MBq), and lungs (1.10E-2 mGy/MBq). No adverse effects of tracer injection were observed. Six out of ten patients were scored as PSMA-positive. A total of 18 suspicious lesions were analyzed, which included six bone lesions, nine lymph nodes, and three local lesions within the prostate fossa. The values for the SUVmax and SUVpeak in the PSMA-positive lesions increased until 60 min p.i. and remained at this intensity in the PET/CT scans until 140 min. In the period between 170 and 200 min after injection, a further significant increase in SUVmax and SUVpeak within the PSMA-positive lesions was observed. Conclusions The highest TBR of [18F]-JK-PSMA-7 was found 3 h after injection. From the kinetically collected data, it can be concluded that this trend may also continue in the further course. The start of the PET/CT acquisition should be chosen as late as possible. The high uptake in suspicious lesions in terms of absolute SUVmax and relative TBR values indicates potentially high sensitivity of the tracer for detection of prostate cancer manifestations.

Abstract Background Radium-223, a targeted alpha therapy, is used to treat symptomatic patients with castration-resistant prostate cancer (CRPC) and bone metastases. Data for radium-223 in asymptomatic CRPC patients with bone metastases are lacking. Methods This was a prospective, single-arm phase 3b study. Patients with metastatic CRPC (malignant lymphadenopathy not exceeding 6 cm was allowed, visceral disease was excluded) received radium-223, 55 kBq/kg intravenously, every 4 weeks for up to 6 cycles. Co-primary endpoints were safety and overall survival. Post hoc analyses were performed according to baseline asymptomatic or symptomatic disease status. Asymptomatic status was defined as no pain and no opioid use at baseline. Results Seven hundred eight patients received ≥1 radium-223 injection: 548 (77%) were symptomatic to various degrees, and 135 (19%) were asymptomatic. Asymptomatic patients had more favorable baseline disease characteristics than symptomatic. A lower proportion of asymptomatic versus symptomatic patients had received prior abiraterone (25% vs 35%) and prior docetaxel (52% vs 62%). A higher proportion of asymptomatic (71%) versus symptomatic (55%) patients completed radium-223 treatment. Overall survival (hazard ratio [HR] 0.486), time to disease progression (HR 0.722) and time to first symptomatic skeletal event (HR 0.328) were better in asymptomatic than symptomatic patients. Alkaline phosphatase (ALP) response rates were similar (46% vs 47%), and ALP normalization (44% vs 25%) and prostate-specific antigen response rates (21% vs 13%) were higher in asymptomatic than symptomatic patients. A lower proportion of asymptomatic patients reported treatment-emergent adverse events (TEAEs, 61% vs 79%), grade 3–4 TEAEs (29% vs 40%) and drug-related TEAEs (28% vs 44%). There were two treatment-related deaths, both in patients with baseline symptomatic disease. Conclusions Using radium-223 earlier in the disease course, when patients are asymptomatic or minimally symptomatic, may enable patients to complete treatment and optimize treatment outcome compared to symptomatic patients, and therefore may allow sequencing with other life-prolonging therapies. Trial registration The study was registered with ClinicalTrials.gov, number NCT01618370 on June 13, 2012 and the European Union Clinical Trials Register, EudraCT number 2012–000075-16 on April 4, 2012.

In December 2019, the first case of COVID-19 was reported and since then several groups have already published that the virus can be present in the testis. To study the influence of SARS-CoV-2 which cause a dysregulation of the androgen receptor (AR) level, thereby leading to fertility problems and inducing germ cell testicular changes in patients after the infection. Formalin-Fixed-Paraffin-Embedded (FFPE) testicular samples from patients who died with or as a result of COVID-19 (n = 32) with controls (n = 6), inflammatory changes (n = 9), seminoma with/without metastasis (n = 11) compared with healthy biopsy samples (n = 3) were analyzed and compared via qRT-PCR for the expression of miR-371a-3p. An immunohistochemical analysis (IHC) and ELISA were performed in order to highlight the miR-371a-3p targeting the AR. Serum samples of patients with mild or severe COVID-19 symptoms (n = 34) were analyzed for miR-371a-3p expression. In 70% of the analyzed postmortem testicular tissue samples, a significant upregulation of the miR-371a-3p was detected, and 75% of the samples showed a reduced spermatogenesis. In serum samples, the upregulation of the miR-371a-3p was also detectable. The upregulation of the miR-371a-3p is responsible for the downregulation of the AR in SARS-CoV-2-positive patients, resulting in decreased spermatogenesis. Since the dysregulation of the AR is associated with infertility, further studies have to confirm if the identified dysregulation is regressive after a declining infection.

Background: Harvest of oral mucosa for urethroplasty due to urethral stricture is associated with donor-site-morbidity. We assessed functionality and safety of an authorized tissue-engineered oral mucosa graft (TEOMG) under routine practice in stricture recurrences of any etiology, location, length and severity (real-world data). Methods: 99 patients from eight centers with heterogenous urethroplasty experience levels were included in this prospective, non-interventional observational study. Primary and secondary outcomes were success rate (SR) and safety at 12 and 24 months. Findings: All but one patient had ≥1, 77.1% (64 of 83) ≥ 2 and 31.3% (26 of 83) ≥ 4 previous surgical treatments. Pre- and postoperative mean ± SD peak flow rate (Qmax) were 8.3 ± 4.7 mL/s (n = 57) and 25.4 ± 14.7 mL/s (n = 51). SR was 67.3% (95% CI 57.6–77.0) at 12 and 58.2% (95% CI 47.7–68.7) at 24 months (conservative Kaplan Meier assessment). SR ranged between 85.7% and 0% in case of high and low surgical experience. Simple proportions of 12-month and 24-month SR for evaluable patients in all centers were 70.8% (46 of 65) and 76.9% (30 of 39). Except for one patient, no oral adverse event was reported. Interpretations: TEOMG is safe and efficient in urethroplasty.

The kynurenine (KYN) pathway gains growing research interest concerning the genesis, progression and therapy of solid tumors. Previous studies showed exercise-induced effects on metabolite levels along the KYN pathway. Modulations of the KYN pathway might be involved in the positive impact of exercise on prostate cancer progression and mortality. The objective of this trial was to investigate whether a single-physical exercise alters tryptophan (TRP) metabolism and related inflammatory markers in this population. We conducted a randomized controlled trial with 24 patients suffering from prostate cancer. While the control group remained inactive, the intervention group performed a 30-min aerobic exercise on a bicycle ergometer at 75% of individual VO2peak. Before (t0) and directly after the exercise intervention (t1) KYN, TRP, kynurenic acid, quinolinic acid as well as various inflammation markers (IL6, TNF-α, TGF-β) were measured in blood serum. At baseline, the present sample showed robust correlations between TRP, KYN, quinolinic acid and inflammatory markers. Regarding the exercise intervention, interaction effects for TRP, the KYN/TRP ratio and TGF-β were observed. The results show for the first time that acute physical exercise impacts TRP metabolism in prostate cancer patients. Moreover, baseline associations underline the relationship between inflammation and the KYN pathway in prostate cancer.

Perioperative preservation of renal function has a significant impact on morbidity and mortality in kidney surgery. Nephroprotective effects of the anesthetic xenon on ischemia-reperfusion injury were found in several experimental studies.We aimed to explore whether xenon anesthesia can reduce renal damage in humans undergoing partial nephrectomy and to gather pilot data of possible nephroprotection in these patients.A prospective randomized, single-blinded, controlled study.Single-center, University Hospital of Aachen, Germany between July 2013-October 2015.Forty-six patients with regular renal function undergoing partial nephrectomy.Patients were randomly assigned to receive xenon- (n = 23) or isoflurane (n = 23) anesthesia.Primary outcome was the maximum postoperative glomerular filtration rate (GFR) decline within seven days after surgery. Secondary outcomes included intraoperative and tumor-related data, assessment of further kidney injury markers, adverse events and optional determination of renal function after 3-6 months.Unexpected radical nephrectomy was performed in 5 patients, thus they were excluded from the per-protocol analysis, but included in the intention-to-treat analysis. The maximum postoperative GFR decline was attenuated by 45% in the xenon-group (10.9 ml min-1 1.73 cm-2 versus 19.7 ml min-1 1.73 cm-2 in the isoflurane group), but without significance (P = 0.084). Occurrence of adverse events was reduced (P = 0.003) in the xenon group. Renal function was similar among the groups after 3-6 months.Xenon anesthesia was feasible and safe in patients undergoing partial nephrectomy with regard to postoperative renal function. We found no significant effect on early renal function but less adverse events in the xenon group. Larger randomized controlled studies in more heterogeneous collectives are required, to confirm or refute the possible clinical benefit on renal function by xenon.ClinicalTrials.gov NCT01839084 and EudraCT 2012-005698-30.

INTRODUCTION:Twitter is a popular microblogging platform for the rapid dissemination of information and reciprocal exchange in the urological field. We aimed to assess the activity, users and content of the online discussion, #KidneyStones, on Twitter. METHODS:We investigated the Symplur Signals analytics tool for Twitter data distributed via the #KidneyStones hashtag over a one year period. Activity analysis reflected overall activity and tweet enhancements. We assessed users' geolocations and performed an influencer analysis. Content analysis included the most frequently used words, tweet sentiment and shares for top tweets. RESULTS:3,426 users generated over 10,333 tweets, which were frequently accompanied by links (49%), mentions (30%) and photos (13%). Users came from 106 countries across the globe and were most frequently from North America (63%) and Europe (16%). Individual and organisational healthcare professionals made up 56% of the influencers of the Twitter discussion on #KidneyStones. Besides the words 'kidney' (used 4,045 times) and 'stones' (3,335), 'pain' (1,233), 'urine' (1,158), and 'risk' (1,023) were the most frequently used words. 56% of tweets had a positive sentiment. The median (range) number of shares was 85 (62-587) for the top 10 links, 45.5 (17-94) for the top 10 photos, and 44 (22-95) for the top 10 retweets. CONCLUSION:The rapidly growing Twitter discussion on #KidneyStones engaged multiple stakeholders in the healthcare sector on a global scale and reached both professionals and laypeople. When used effectively and responsibly, the Twitter platform could improve prevention and medical care of kidney stone patients.

Clinical stage I testicular nonseminomatous germ cell tumours (NSGCTs) are highly curable. Following orchidectomy a risk-adapted approach using active surveillance (AS), nerve-sparing retroperitoneal lymph node dissection (nsRPLND) and primary chemotherapy is recommended by the current guidelines. Clinical stage I is defined as negative or declining tumour markers to their half-life following orchidectomy and negative imaging studies of the chest, abdomen and retroperitoneum. Active surveillance can be performed in low-risk and in high-risk NSGCTs with an anticipated relapse rate of about 15% and 50%. The majority of patients will relapse with good and intermediate prognosis tumours which have to be treated with three to four cycles chemotherapy. About 25–30% of these patients will have to undergo postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for residual masses. Primary chemotherapy with one or two cycles of cisplatin (Platinol), etoposide and bleomycin (PEB) is a therapeutic option for high-risk clinical stage I NSGCT associated with a recurrence rate of only 2–3% and a minimal acute and long-term toxicity rate. nsRPLND, if performed properly, will cure about 85% of all high-risk patients with clinical stage I NSGCT without the need for chemotherapy. PC-RPLND forms an integral part of the multimodality treatment in patients with advanced testicular germ cell tumours (TGCTs). According to current guidelines and recommendations, PC-RPLND in advanced seminomas with residual tumours is only indicated if a positron emission tomography (PET) scan performed 6–8 weeks after chemotherapy is positive. In nonseminomatous TGCT, PC-RPLND is indicated for all residual radiographic lesions with negative or plateauing markers. Loss of antegrade ejaculation represents the most common long-term complication which can be prevented by a nerve-sparing or modified template resection. The relapse rate after PC-RPLND is around 12%, however it increases significantly to about 45% in cases with redo RPLND and late relapses. Patients with increasing markers should undergo salvage chemotherapy. Only select patients with elevated markers who are thought to be chemorefractory might undergo desperation PC-RPLND if all radiographically visible lesions are completely resectable. PC-RPLND requires a complex surgical approach and should be performed in experienced, tertiary referral centres only.

Androgen deprivation therapy (ADT) is currently the standard treatment for patients with metastatic prostate cancer (mPCa) (1). Survival improvement after cytoreductive surgery is well known for kidney, breast, colon and ovarian cancers. The survival benefit of cytoreductive radical prostatectomy (CRP) for mPCa was first hypothesized in a SEER-based study (2). Heidenreich et al. recently reported survival outcomes of CRP for mPCa. In the present study, 23 mPCa patients with less than 3 bone metastases, no visceral or extensive LN metastases and PSA less than 1.0 ng /mL after ADT were included. Control group (CG) consisted of 38 mPCa patients treated with ADT alone. CRP and CG were equal with respect to patient demographics, tumor characteristics, and comorbidities. All patients had 50 mg bicalutamide with LHRH agonists at least for 6 months before surgery. Patients, who did not have PSA progression, were recommended to continue another 2 years of ADT before treatment stopped. When compared with CG, median time to castration resistance was statistically significantly longer in CRP group (40 vs 29 months, p=.014). At a median follow-up of 3 years, overall survival rates were 91.3% and 78.9% for CRP and CG, respectively (p=0.048). Cancer-specific survival rates were 95.6% and 84.2% for CRP and CG, respectively (p=0.043). Median clinical progression-free survival (PFS) (range) was 38.6 and 26.5 months in CRP and CGs, respectively (p= 0.032). This was the first case-control study that showed that CRP combined with ADT might offer better survival outcomes than ADT alone in mPCa patients. In spite of retrospective design and small cohort, the results are promising. There is an ongoing clinical trial testing the treatment efficacy of primary tumor in mPCa patients. This trial is going to compare efficacy of ADT therapy and ADT combined with either CRP or radiation (NCT01751438). SEER study was not a case-control study. This study further enhanced the hypothesis of the SEER study, and thus, these results may increase urologists’ role in multi-modal treatment approaches