Reliability and practicability of PSMA-RADS 1.0 for structured reporting of PSMA-PET/CT scans in prostate cancer patients.

OBJECTIVES: As structured reporting is increasingly used in the evaluation of prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) for prostate cancer, there is a need to assess the reliability of these frameworks. This study aimed to evaluate the intra- and interreader agreement among readers with varying levels of experience using PSMA-RADS 1.0 for interpreting PSMA-PET/CT scans, even when blinded to clinical data, and therefore to determine the feasibility of implementing this reporting system in clinical practice. METHODS: PSMA-PET/CT scans of 103 patients were independently evaluated by 4 readers with different levels of experience according to the reporting and data system (RADS) for PSMA-PET/CT imaging PSMA-RADS 1.0 at 2 time points within 6 weeks. For each scan, a maximum of five target lesions were freely chosen and stratified according to PSMA-RADS 1.0. Overall scan score and compartment-based scores were assessed. Intra- and interreader agreement was determined using the intraclass correlation coefficient (ICC). RESULTS: PSMA-RADS 1.0 demonstrated excellent interreader agreement for both overall scan scores (ICC ≥ 0.91) and compartment-based scores (ICC ≥ 0.93) across all four readers. The framework showed excellent intrareader agreement for overall scan scores (ICC ≥ 0.86) and compartment-based scores (ICC ≥ 0.95), even among readers with varying levels of experience. CONCLUSIONS: PSMA-RADS 1.0 is a reliable method for assessing PSMA-PET/CT with strong consistency and agreement among readers. It shows great potential for establishing a standard approach to diagnosing and planning treatment for prostate cancer patients, and can be used confidently even by readers with less experience. CLINICAL RELEVANCE STATEMENT: This study underlines that PSMA-RADS 1.0 is a valuable and highly reliable scoring system for PSMA-PET/CT scans of prostate cancer patients and can be used confidently by radiologists with different levels of experience in routine clinical practice. KEY POINTS: PSMA-RADS version 1.0 is a scoring system for PSMA-PET/CT scans. Its reproducibility needs to be analyzed in order to make it applicable to clinical practice. Excellent interreader and intrareader agreement for overall scan scores and compartment-based scores using PSMA-RADS 1.0 were seen in readers with varying levels of experience. PSMA-RADS 1.0 is a reliable tool for accurately diagnosing and planning treatment for prostate cancer patients, and can be used confidently in clinical routine.

Penile fractures: the price of a merry Christmas.

OBJECTIVES: To explore whether Christmas might be a risk factor for penile fractures due to the Christmas spirit related to the intimacy and euphoria of these holly jolly days. PATIENTS AND METHODS: We evaluated the incidence of penile fractures during Christmas and New Year's Eve through the GeRmAn Nationwide inpatient Data (GRAND) from the Research Data Center of the Federal Bureau of Statistics (Wiesbaden, Germany). Furthermore, we assessed the impact of COVID-19 on penile fractures and their seasonality. RESULTS: A total of 3,421 patients with a median, interquartile range (IQR) age of 42 (32-51) years had a penile fracture requiring a hospital stay from 2005 to 2021. In all, 40 (1.2%) penile fractures occurred in 51 days of Christmas (from 24/12 to 26/12 in each year). The daily incidence of penile fractures during Christmas was 0.78 with an incidence rate ratio (IRR) of 1.43 (95% confidence interval [CI] 1.05-1.95, P = 0.02). If every day was like Christmas, 43% more penile fractures would have occurred in Germany from 2005 on. Interestingly, only 28 (0.82%) penile fractures occurred during the New Year's Eve period (31/12 to 02/01 from 2005 to 2021). This resulted in an IRR of 0.98 (95% CI 0.69-1.5, P = 0.98) in the New Year's Eve period. Most patients with penile fractures were admitted to hospital at the weekend (n = 1,322; IRR 1.58, 95% CI 1.48-1.69; P < 0.001). Summer was also associated with more penile fractures (n = 929; IRR 1.11, 95% CI 1.03-1.19; P = 0.008). Both the COVID-19 pandemic (n = 385; IRR 1.06, 95% CI 0.95-1.18, P = 0.29) and its lockdown period (n = 93; IRR 1, 95% CI 0.82-1.23; P = 0.96) did not affect the incidence of penile fractures. CONCLUSION: The incidence of penile fractures displays a seasonality. Last Christmas penile fractures occurred more often. This year to save us from tears, we will NOT do something special (the new Christmas hit of the year).

Added value of randomised biopsy to multiparametric magnetic resonance imaging-targeted biopsy of the prostate in a contemporary cohort.

OBJECTIVE: To assess the added value of concurrent systematic randomised ultrasonography-guided biopsy (SBx) to multiparametric magnetic resonance imaging (mpMRI)-targeted biopsy and the additional rate of overdiagnosis of clinically insignificant prostate cancer (ciPCa) by SBx in a large contemporary, real-world cohort. PATIENTS AND METHODS: A total of 1552 patients with positive mpMRI and consecutive mpMRI-targeted biopsy and SBx were enrolled. Added value and the rate of overdiagnosis by SBx was evaluated. PRIMARY OUTCOME: added value of SBx, defined as detection rate of clinically significant PCa (csPCa; International Society of Urological Pathology [ISUP] Grade ≥2) by SBx, while mpMRI-targeted biopsy was negative or showed ciPCa (ISUP Grade 1). SECONDARY OUTCOME: rate of overdiagnosis by SBx, defined as detection of ciPCa in patients with negative mpMRI-targeted biopsy and PSA level of <10 ng/mL. RESULTS: Detection rate of csPCa by mpMRI-targeted biopsy and/or SBx was 753/1552 (49%). Added value of SBx was 145/944 (15%). Rate of overdiagnosis by SBx was 146/656 (22%). Added value of SBx did not change when comparing patients with previous prostate biopsy and biopsy naïve patients. In multivariable analysis, a Prostate Imaging-Reporting and Data System (PI-RADS) 4 index lesion (odds ratio [OR] 3.19, 95% confidence interval [CI] 1.66-6.78; P = 0.001), a PI-RADS 5 index lesion (OR 2.89, 95% CI 1.39-6.46; P = 0.006) and age (OR 1.05, 95% CI 1.03-1.08; P < 0.001) were independently associated with added value of SBx. CONCLUSIONS: In our real-world analysis, we saw a significant impact on added value and added rate of overdiagnosis by SBx. Subgroup analysis showed no significant decrease of added value in any evaluated risk group. Therefore, we do not endorse omitting concurrent SBx to mpMRI-guided biopsy of the prostate.

Absence of detrusor muscle in TUR-BT specimen - can we predict who is at highest risk?

INTRODUCTION: As a high-quality TUR-BT is important to ensure adequate treatment for bladder cancer patients, the aim of the current study is to investigate the impact of patient-related, surgical and tumor-specific parameters on detrusor muscle (DM) absence (primary objective) and to assess the impact of DM on the prognosis after a TUR-BT (secondary objective). PATIENTS AND METHODS: Transurethral resection of bladder tumors (TUR-BTs) between 2009 and 2021 were retrospectively screened (n = 3237). We included 2058 cases (1472 patients) for the primary and 472 patients for secondary objective. Clinicopathological variables including tumor size, localization, multifocality, configuration, operation time and skill-level of the urologist were assessed. We analyzed predictors for missing DM and prognostic factors for recurrence-free survival (RFS) for the complete cohort and subgroups. RESULTS: DM was present in 67.6% (n = 1371/2058). Surgery duration (continuous, minutes) was an independent predictor for absence of DM in the complete cohort (OR:0.98, r:0.012, 95%CI:0.98-0.99, p = 0.001). Other significant risk factors for missing DM were papillary tumors (OR:1.99, r:0.251, 95%CI:1.22-3.27, p = 0.006) in the complete cohort and bladder-roof and posterior-bladder-wall localization for re-resections. Absence of DM in high-grade BC correlated with reduced RFS (HR:1.96, 95%CI:1.0-3.79, p = 0.045). CONCLUSION: Sufficient time for a TUR-BT is mandatory to assure DM in the TUR-BT specimen. Also, cases with more difficult locations of bladder tumors should be performed with utmost surgical diligence and endourological training should incorporate how to perform such operations. Of note, DM correlates with improved oncological prognosis in high-grade BC.

Asymptomatic bacteriospermia and infertility-what is the connection?

OBJECTIVE: To determine the impact of asymptomatic bacteriospermia on semen quality in subfertile men. METHODS: We conducted a retrospective, single-centre cohort study in 1300 subfertile men. In those diagnosed with asymptomatic bacteriospermia we performed univariate and multivariate logistic regression models to evaluate the strain-specific association with semen parameters. RESULTS: Asymptomatic bacteriospermia was diagnosed in 3.2% of patients. The microbiological semen analysis revealed a poly-microbial result in 60%. The most common bacterial species were coagulase-negative Staphylococci species (71.4%), Streptococcus viridans (50.0%) and Enterococcus faecalis (26.2%). Sexually transmitted pathogens were identified in 11.9% of semen samples. The detection of Streptococcus viridians or Haemophilus parainfluenzae correlated with impaired sperm morphology (p < 0.05). The presence of coagulase-negative Staphylococci species or Enterococcus faecalis was associated with pathological low counts of live spermatozoa (p < 0.05). In multivariate analysis only Enterococcus faecalis showed a significant impact on sperm concentration (OR 4.48; 95% CI 1.06-22.10; p = 0.041). CONCLUSIONS: Asymptomatic bacteriospermia has always been a subject of great controversy. There is still an ongoing debate whether to treat or not to treat. Here, we demonstrate that asymptomatic bacteriospermia is clearly associated with impaired semen quality. Our findings speak in favour of strain-specific interactions with semen parameters. Especially Enterococcus faecalis seriously affects sperm concentration.

Prognostic Value of Pretreatment Inflammatory Markers in Patients Receiving Radical Cystectomy for Urothelial Bladder Cancer: Does Age Matter?

INTRODUCTION: Biomarkers are known predictors for survival after radical cystectomy (RC) and can improve patient stratification. Yet, it remains unclear how age influences their prognostic value. The current study aimed to assess the impact of age on standard prognostic biomarkers in different age-groups. MATERIALS AND METHODS: Overall, 1,014 patients undergoing RC for bladder cancer were included. Patients were divided into age-groups (I - <60, II - 60-69, III - 70-79, and IV - ≥80). C-reactive protein (CRP), hemoglobin (Hb), thrombocytes, and leucocytes prior to RC were used as biomarkers. The Kaplan-Meier method and log-rank test were used to compare overall survival (OS) and cancer-specific survival (CSS). For independent predictors of survival, multivariate models were applied. RESULTS: Absolute levels of biomarkers except CRP revealed a significant decrease with increasing age. We found low Hb to be associated with impaired CSS in groups II (2.05 [1.32-3.17]; p = 0.001), III (2.83 [2.01-4.00]; p < 0.001), and IV (1.79 [1.12-2.84]; p = 0.014). Thrombocytes above the cutoff were associated with impaired CSS and OS in groups II, III, and IV for CSS and OS. Leukocytes were associated with impaired CSS and OS in group II (2.11 [1.38-3.23]; p < 0.001 and 1.99 [1.36-2.90]; p < 0.001) and III (1.70 [1.08-2.67]; p = 0.021 and 1.80 [1.25-2.58]; p = 0.002). Elevated CRP was associated with impaired CSS and OS across all groups. CONCLUSION: Biomarkers are predictors for survival after RC. Yet, their impact on survival is less in the oldest patient group. Therefore, careful patient stratification and treatment administration should be considered in elderly patients. Further investigations are needed to fully understand the underlying mechanisms.

Computed-tomography based scoring system predicts outcome for clinical lymph node-positive patients undergoing radical cystectomy.

PURPOSE: Contrast-enhanced CT scan is the standard staging modality for patients with bladder cancer undergoing radical cystectomy (RC). Involvement of lymph nodes (LN) determines prognosis of patients with bladder cancer. The detection of LN metastasis by CT scan is still insufficient. Therefore, we investigated various CT scan characteristics to predict lymph node ratio (LNR) and its impact on survival. Also, pre-operative CT scan characteristics might hold potential to risk stratify cN+ patients. MATERIALS AND METHODS: We analyzed preoperative CT scans of patients undergoing RC in a tertiary high volume center. Retrospectively, local tumor stage and LN characteristics such as size, morphology (MLN) and number of loco-regional LN (NLN) were investigated and correlation to LNR and survival was analyzed. CT scan characteristics were used to develop a risk stratification using Kaplan-Maier and multivariate analysis. RESULTS: 764 cN0 and 166 cN+ patients with complete follow-up and imaging data were included in the study. Accuracy to detect LN metastasis and locally advanced tumor stage in CT scan was 72% and 62%. LN larger than 15mm in diameter were significantly associated with higher LNR (p=0.002). Increased NLN correlated with decreased CSS and OS (p=0.001: p=0.002). Furthermore, CT scan based scoring system precisely differentiates low-risk and high-risk profiles to predict oncological outcome (p < 0.001). CONCLUSION: In our study, solely LN size >15mm significantly correlated with higher LNR. Identification of increased loco-regional LN was associated with worse survival. For the first time, precise risk stratification based on computed-tomography findings was developed to predict oncological outcome for clinical lymph node-positive patients undergoing RC.

Impact of previous transurethral prostate surgery on health-related quality of life after radical prostatectomy: Does the interval between surgeries matter?

PURPOSE: To assess the impact of previous transurethral surgery for benign prostate enlargement (BPE) and time interval between procedures on functional outcomes and health-related quality of life (HRQOL) after radical prostatectomy (RP). METHODS: A propensity score-matched patient cohort [n = 685, (513 without previous BPE surgery, 172 with BPE surgery)] was created and HRQOL was pre- and postoperatively assessed using validated questionnaires (EORTC QLQ-C30). Urinary continence was measured via ICIQ-SF questionnaire and pad usage. Multivariable analysis included binary logistic and Cox regression models (p < 0.05). RESULTS: Median follow-up was 18 months. There was no significant difference in recurrence-free survival in multivariate analysis (HR 0.66, 95%CI 0.40-1.07, p = 0.093). We observe higher mean ICIQ-SF scores (5.7 vs. 8.2, p < 0.001) and daily pad usage (1.3 vs. 2.5, p < 0.001), and decreased continence recovery (OR 0.46, 95%CI 0.30-0.71, p < 0.001) for patients with BPE surgery. Postoperative general HRQOL scores were significantly lower for patients with previous BPE surgery (70.6 vs. 63.4, p = 0.003). In multivariate analysis, continence recovery (OR 5.19, 95%CI 3.10-8.68, p < 0.001) but not previous BPE surgery (0.94, 0.57-1.54, p = 0.806) could be identified as independent predictors of good general HRQOL. There was no significant correlation between time interval between both surgeries and continence (p = 0.408), and HRQOL (p = 0.386) outcomes. CONCLUSIONS: We observe favourable continence outcomes for patients without previous BPE surgery. Our results indicate that RP can be safely performed after transurethral BPE surgery, regardless of the time interval between both interventions.

Prognostic value of pretreatment inflammatory markers in variant histologies of the bladder: is inflammation linked to survival after radical cystectomy?

PURPOSE: To investigate differences in standard preoperative inflammatory markers in patients with urothelial carcinoma (UC) and variant histologies undergoing radical cystectomy (RC) and determine its impact on survival. METHODS: Patients undergoing RC at an academic high-volume center were retrospectively analyzed. Preoperatively taken CRP, leukocytes, hemoglobin (Hb), and thrombocytes were analyzed as routine inflammatory biomarkers. Log-rank tests and Kruskal-Wallis analysis were used to calculate for differences in survival and in blood levels of biomarkers. RESULTS: 886 patients with complete follow-up and UC or variant histology underwent RC at our institution between 2004 and 2019. Although variant histology presents with significantly higher t stage than UC, cancer-specific survival (CSS) of UC (1-year-CSS: 93%) is not significantly different to variant histology of UC with squamous differentiation (UCSD, 1-year-CSS: 81%), squamous cell carcinoma (SCC, 1-year-CSS: 82%), and adenocarcinoma (AC, 1-year-CSS: 81%). In UC, alterations in all biomarkers except leukocytes beyond routine cut-off values were associated with poor survival (p < 0.01), whereas Hb beyond cut-off values are associated with poor prognosis in SCC (p < 0.05). CRP levels are significantly elevated in UCSD and SCC at time of surgery compared to UC (p < 0.05). CONCLUSION: Inflammatory biomarkers reveal distinctive patterns across UC and variant histologies of bladder cancer. As inflammation might play an important role in cancer progression, further research is warranted to understand those molecular mechanisms and their potential therapeutic impact in variant histology of bladder cancer.

Salvage cystectomy and ileal conduit urinary diversion as a last-line option for benign diseases-perioperative safety and postoperative health-related quality of life.

AIMS: Radical cystectomy and urinary diversion impact various dimensions of patients' health-related-quality-of-life (HRQOL). Yet, less is known about salvage cystectomy as a last-line option for treatment-refractory benign diseases. Therefore, our aim is to provide HRQOL data from a contemporary cohort of open salvage cystectomies for benign conditions. METHODS: Fifty-four consecutive patients were enrolled in one single tertiary referral center. Analysis was limited to patients undergoing urinary diversion via ileal conduit (IC). Complications were assessed via Clavien-Dindo-scale. HRQOL was measured using the validated European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-BLM30 questionnaire. HRQOL QLQ-C30 domains were measured preoperatively and up to 3 years postoperatively. Longitudinal changes were analyzed using Friedman's rank test. Primary endpoint was good general HRQOL based on QLQ-C30 global health status (GHS). Multivariate analysis was performed using logistic regression models with a step-wise backward selection procedure. RESULTS: Longitudinal analysis of HRQOL subdomains revealed significantly improved pain (p = .005) and fatigue (p = .002) scores as well as improved social functioning (p = .038). Furthermore, general HRQOL (GHS scores) improved significantly during the follow-up period (28.0 vs. 50.6 [36 months], p = .045). In multivariate analysis, the indication for salvage cystectomy could not be identified as an independent predictor for good general HRQOL. We observed a total number of 10 (41.7%) high-grade (Clavien ≥III) 90 day-complications. Limitations include limited follow-up rates at respective time-points. CONCLUSION: Salvage cystectomy and IC can be safely performed as a last-line treatment for benign conditions and increases general HRQOL in the long-term follow-up. Thus, it can play a role in a holistic approach for a challenging clinical setting.

Listening to Music during Outpatient Cystoscopy Reduces Pain and Anxiety and Increases Satisfaction: Results from a Prospective Randomized Study.

BACKGROUND: This study investigates the effect of classical music, music of patients' own choice, or no music on pain reduction during elective cystoscopy. OBJECTIVES: The aim of the study was to describe the effect of listening to classical music, music of patients' own choice, or no music on patient's pain and satisfaction rates when carrying out an elective cystoscopy and the effect on the assessment capability of the performing urologist. DESIGN, SETTING, AND PARTICIPANTS: This randomized trial included 127 patients undergoing elective cystoscopy at the Urological Department of the University Clinic of Munich between June 2019 and March 2020. Outcome Measurements and Statistical Analysis: Patients were assigned randomly to 3 groups: group I: listening to standardized classical music (n = 35), group II: listening to music according to the patients' choice (n = 34), and control group III: no music (n = 44). Prior to cystoscopy, anxiety levels were assessed by the Beck Anxiety Inventory (BAI). The Visual Analog Scale (VAS, range 1-100) was used for a self-assessment of pain, discomfort, and satisfaction. Statistical analysis was done with Spearman's rank correlation and t-tests. RESULTS AND LIMITATIONS: The median age was 63 (range 27-91) years. The duration of cystoscopy was 5.7 (1-30) min. Patients had undergone a median of 2.3 cystoscopies in the past. Between giving informed consent and cystoscopy, patients had to wait for a median of 64 (0-260) min. The median VAS pain score was significantly lower in group I at 1.7 and group II at 2.3 versus 5.2 in the control group III (p < 0.001). The control group III had significantly worse pain and patient satisfaction rates compared with groups I and II. Group I had a significant lower VAS pain score than groups II and III (p < 0.001). Classical music also increased the assessment capability of the preforming urologist. CONCLUSIONS: Listening to music during elective cystoscopy significantly reduces pain and distress and leads to higher patient and surgeon satisfaction. We recommend listening to classical music or music chosen by the patients during outpatient flexible/rigid cystoscopy in daily clinical routine. Patient Summary: In this study, we found that patients who listened to classical music or music of their own choice while undergoing a cystoscopy showed significant reduction of pain and distress.

Is It Safe to Offer Radical Cystectomy to Patients above 85 Years of Age? A Long-Term Follow-Up in a Single-Center Institution.

PURPOSE: With a median age at diagnosis of 73 years, bladder cancer has the highest median age of all cancers. Age alone seems to be an independent risk factor for developing the disease with peak age advancing into the range of 85 years. As demographic changes will lead to an ever more aging population in western countries, incidence of advanced age malignancies will rise. We, therefore, analyzed a contemporary radical cystectomy (RC) series at a single high-volume center on patients undergoing RC for urothelial carcinoma of the bladder (UCB). We aim to evaluate the feasibility of RC in the oldest-old patient cohort by assessing perioperative complications and long-term outcome. MATERIALS AND METHODS: We retrospectively analyzed data of 1,278 consecutive patients who underwent RC for UCB at our tertiary referral center between 2004 and 2019. A total of 408 patients were aged 75-97 years at the time of RC and were further divided into 2 groups: 75-84 years of age (group 1) and ≥85 years of age (group 2). Median follow-up was 23 months. Outcome was analyzed using the χ2 test, Mann-Whitney U test, Kaplan-Meier method, and log-rank test. RESULTS: Perioperative Clavien-Dindo grade ≥III complications were seen in 25.1% (92/366) of group 1 patients and 35.7% (15/42) of group 2 patients (p = 0.073). Thirty- and 90-day mortality was 3.3 and 8.7% in group 1 and 4.8 and 14.3% in group 2 (p = 0.617 and p = 0.242, respectively). Three-year overall survival was 54.6% in group 1 and 31.3% in group 2 (p = 0.03). Three-year cancer-specific survival was 64.8% in group 1 and 38.8% in group 2 (p = 0.037). Recurrence-free survival was 105 months in group 1 and 12 months in group 2 (p = 0.039). CONCLUSION: In light of increasing life expectancy in western nations, we sought to evaluate the impact of age in a large series of elderly patients undergoing RC for UCB. We found that RC offers acceptable perioperative complication rates in the oldest-old patient cohort (≥85 years). Therefore, RC for UCB can be offered as a viable treatment option even in the oldest patients.

Early pancreatic cancer lesions suppress pain through CXCL12-mediated chemoattraction of Schwann cells.

Pancreatic ductal adenocarcinoma (PDAC) cells (PCC) have an exceptional propensity to metastasize early into intratumoral, chemokine-secreting nerves. However, we hypothesized the opposite process, that precancerous pancreatic cells secrete chemokines that chemoattract Schwann cells (SC) of nerves and thus induce ready-to-use routes of dissemination in early carcinogenesis. Here we show a peculiar role for the chemokine CXCL12 secreted in early PDAC and for its receptors CXCR4/CXCR7 on SC in the initiation of neural invasion in the cancer precursor stage and the resulting delay in the onset of PDAC-associated pain. SC exhibited cancer- or hypoxia-induced CXCR4/CXCR7 expression in vivo and in vitro and migrated toward CXCL12-expressing PCC. Glia-specific depletion of CXCR4/CXCR7 in mice abrogated the chemoattraction of SC to PCC. PDAC mice with pancreas-specific CXCL12 depletion exhibited diminished SC chemoattraction to pancreatic intraepithelial neoplasia and increased abdominal hypersensitivity caused by augmented spinal astroglial and microglial activity. In PDAC patients, reduced CXCR4/CXCR7 expression in nerves correlated with increased pain. Mechanistically, upon CXCL12 exposure, SC down-regulated the expression of several pain-associated targets. Therefore, PDAC-derived CXCL12 seems to induce tumor infiltration by SC during early carcinogenesis and to attenuate pain, possibly resulting in delayed diagnosis in PDAC.

Multiparametric magnetic resonance imaging and multiparametric magnetic resonance imaging-guided biopsy in the diagnostic pathway of prostate cancer.

Multiparametric magnetic resonance imaging (mpMRI) of the prostate and mpMRI-guided biopsy have proved to be a valuable part of the diagnostic pathway for prostate cancer. This review reports on the current results in terms of clinical performance of these diagnostic tools and their role in clinical decision-making.

Activated Schwann cells in pancreatic cancer are linked to analgesia via suppression of spinal astroglia and microglia.

OBJECTIVE: The impact of glia cells during GI carcinogenesis and in cancer pain is unknown. Here, we demonstrate a novel mechanism how Schwann cells (SCs) become activated in the pancreatic cancer (PCa) microenvironment and influence spinal activity and pain sensation. DESIGN: Human SCs were exposed to hypoxia, to pancreatic cancer cells (PCCs) and/or to T-lymphocytes. Both SC and intrapancreatic nerves of patients with PCa with known pain severity were assessed for glial intermediate filament and hypoxia marker expression, proliferation and for transcriptional alterations of pain-related targets. In conditional PCa mouse models with selective in vivo blockade of interleukin (IL)-6 signalling (Ptf1a-Cre;LSL-Kras(G12D)/KC interbred with IL6(-/-) or sgp130(tg) mice), SC reactivity, abdominal mechanosensitivity and spinal glial/neuronal activity were quantified. RESULTS: Tumour hypoxia, PCC and/or T-lymphocytes activated SC via IL-6-signalling in vitro. Blockade of the IL-6-signalling suppressed SC activation around PCa precursor lesions (pancreatic intraepithelial neoplasia (PanIN)) in KC;IL6(-/-) (32.06%±5.25% of PanINs) and KC;sgp130(tg) (55.84%±5.51%) mouse models compared with KC mice (78.27%±3.91%). Activated SCs were associated with less pain in human PCa and with decreased abdominal mechanosensitivity in KC mice (von Frey score of KC: 3.9±0.5 vs KC;IL6(-/-) mice: 5.9±0.9; and KC;sgp130(tg): 10.21±1.4) parallel to attenuation of spinal astroglial and/or microglial activity. Activated SC exhibited a transcriptomic profile with anti-inflammatory and anti-nociceptive features. CONCLUSIONS: Activated SC in PCa recapitulate the hallmarks of 'reactive gliosis' and contribute to analgesia due to suppression of spinal glia. Our findings propose a mechanism for how cancer might remain pain-free via the SC-central glia interplay during cancer progression.

mpMRI-targeted biopsy of the prostate in men ≥ 75 years. 7-year report from a high-volume referral center.

OBJECTIVE: Multiparametric magnetic resonance imaging (mpMRI) -Ultrasound- fusion guided biopsy of the prostate (FBx) is the new gold standard for the detection of prostate cancer. Hallmark studies showing superior detection rates of FBx over randomized biopsies routinely excluded patients≥75 years and information on outcome of FBx on this patient cohort is sparse. As a large referral center, we have performed FBx on a substantial number of patients this age. By evaluating outcome of FBx of patients over the age of 75 years we wanted to close the gap of knowledge on this patient cohort. MATERIALS AND METHODS: Between 2015 -2022, 1577 patients underwent FBx at our department and were considered for analysis. Clinical and histopathological parameters were recorded. Clinical data comprised age at FBx, serum level of Prostate-specific antigen (PSA), prostate volume, PSA-density, history of previous biopsies of the prostate, result of the digital rectal examination (DRE) and assessment of the indexlesion of mpMRI according to the Prostate Imaging and Reporting Data System (PI-RADS). Univariate analysis and multivariable logistic regression was used to identify age barrier of 75 years as a potential risk factor of detection of clinically significant prostate cancer by FBx. RESULTS: 379/1577 patients (24%) were≥75 years and 1198/1577 (76%) patients were < 75 years, respectively. Preoperative PSA was significantly higher in patients≥75 years compared to patients < 75 years (9.54 vs. 7.8, p < 0.001). Patients≥75 years presented significantly more often with mpMRI target lesions classified as PI-RADS 5 compared to patients < 75 years (45% vs. 29%, p < 0.001). Detection rate of clinically significant prostate cancer was significantly higher in patients≥75 years compared to patients < 75 years (63% vs. 43%, p < 0.001). Aggressive prostate cancer grade ISUP 5 was significantly more often detected in patients≥75 years compared to patients < 75 years (13% vs. 8%, p = 0.03). On multivariable logistic regression model adjusted for PSA and PI-RADS score, age barrier of 75 years was identified as a significant risk factor for the detection of clinically significant prostate cancer by FBx (OR: 1.77, 95% CI: 1.36 -2.31, p < 0.001). CONCLUSION: After evaluation of a large patient cohort, we show that age≥75 years represents a significant risk factor for the detection of clinically significant prostate cancer. Further studies on mid- and long term outcome are necessary to draw conclusions for clinical decision making in this patient cohort.

[Perineal prostate biopsy]. / Perineale Prostatabiopsie.

The prostate biopsy is an essential tool for diagnosing prostate cancer (PCa). While transrectal biopsy (TR-Bx) continues to be considered the gold standard in Germany, the European Association of Urology (EAU) guidelines increasingly recommend transperineal biopsy (TP-Bx) due to lower infection rates and higher tumor detection rates. This article provides an overview of the history and development of the perineal biopsy, compares TR-Bx and TP-Bx and discusses the need for antibiotic prophylaxis before TP-Bx. Current studies have shown that TP-Bx can be performed without antibiotic prophylaxis and new techniques such as robotic-assisted and vector biopsy show very precise results. The establishment of TP-Bx is being promoted by extrabudgetary funding and technological advancements, with the choice of biopsy method remaining an individual decision jointly made in dialogue with the patient.

Trends and outcomes of hospitalized patients with priapism in Germany: results from the GRAND study.

We aimed to provide evidence on the trends and in-hospital outcomes of patients with low- and high-flow priapism through the largest study in the field. We used the GeRmAn Nationwide inpatient Data (GRAND), provided by the Research Data Center of the Federal Bureau of Statistics (2008-2021), and performed multiple patient-level analyses. We included 6,588 men with low-flow and 729 with high-flow priapism. Among patients with low-flow priapism, 156 (2.4%) suffered from sickle cell disease, and 1,477 (22.4%) patients required shunt surgery. Of them, only 37 (2.5%) received a concomitant penile prosthesis implantation (30 inflatable and 7 semi-rigid prosthesis). In Germany, the total number of patients with low-flow priapism requiring hospital stay has steadily increased, while the number of patients with high-flow priapism requiring hospital stay has decreased in the last years. Among patients with high-flow priapism, 136 (18.7%) required selective artery embolization. In men with low-flow priapism, sickle cell disease was associated with high rates of exchange transfusion (OR: 21, 95% CI: 14-31, p < 0.001). The length of hospital stay (p = 0.06) and the intensive care unit admissions (p = 0.9) did not differ between patients with low-flow priapism due to sickle cell disease versus other causes of low-flow priapism. Accordingly, in men with high-flow priapism, embolization was not associated with worse outcomes in terms of length of hospital stay (p > 0.9), transfusion (p = 0.8), and intensive care unit admission (p = 0.5). Low-flow priapism is an absolute emergency that requires shunt surgery in more than one-fifth of all patients requiring hospital stay. On the contrary, high-flow priapism is still managed, in most cases, conservatively.

[Common errors, pitfalls, and management of complications of prostate biopsy : The most common diagnostic and procedural challenges of transrectal fusion prostate biopsy in the initial diagnosis of clinically significant prostate cancer]. / Häufige Fehler, "Pitfalls" und Komplikationsmanagement der Prostatabiopsie : Die häufigsten diagnostischen und prozeduralen Herausforderungen der transrektalen Fusionsbiopsie der Prostata bei Erstdiagnose eines klinisch signifikanten Prostatakarzinoms.

BACKGROUND: Transrectal (TR) prostate biopsy is the gold standard in diagnosis of prostate cancer (PC). It requires a precise and safe technique for sample acquisition. OBJECTIVE: Several approaches will be discussed to avoid overdiagnosis, false-negative results, and complications of the procedure. MATERIALS AND METHODS: We analyzed national and European guidelines, systematic reviews, meta-analyses, as well as prospective and retrospective studies to describe current trends in indication and performance of biopsies. RESULTS: Incorporation of risk calculators and magnetic resonance imaging (MRI) into daily routine reduces biopsy rates and results in a more precise diagnosis of clinically significant prostate cancer (csPC). Combination of random- and MRI-fusion guided biopsy-but also extending the radius of sampling by 10 mm beyond the MRI lesion and a transperineal (TP) sampling approach - lead to a higher tumor-detection rate. Bleeding is the most common complication after prostate biopsy and is usually self-limiting. Postbiopsy infection rates can be reduced through TP biopsy. CONCLUSION: TR MRI-fusion guided biopsy is a widely acknowledged tool in primary diagnostics of csPC. Higher detection rates and safety can be achieved through a TP sampling approach.