Immunohistochemical ERG positivity is associated with decreased PSMA expression and lower visibility in corresponding [68Ga]Ga-PSMA-11 PET scans of primary prostate cancer.

PURPOSE: TMPRSS2:ERG gene fusion negatively regulates PSMA expression in prostate adenocarcinoma (PCa) cell lines. Therefore, immunohistochemical (IHC) ERG expression, a surrogate for an underlying ERG rearrangement, and PSMA expression patterns in radical prostatectomy (RPE) specimens of primary PCa, including corresponding PSMA-PET scans were investigated. METHODS: Two cohorts of RPE samples (total n=148): In cohort #1 (n=62 patients) with available RPE and preoperative [68Ga]Ga-PSMA-11 PET, WHO/ISUP grade groups, IHC-ERG (positive vs. negative) and IHC-PSMA expression (% PSMA-negative tumour area, PSMA%neg) were correlated with the corresponding SUVmax. In the second cohort #2 (n=86 patients) including RPE only, same histopathological parameters were evaluated. RESULTS: Cohort #1: PCa with IHC-ERG expression (35.5%) showed significantly lower IHC-PSMA expression and lower SUVmax values on the corresponding PET scans. Eight of 9 PCa with negative PSMA-PET scans had IHC-ERG positivity, and confirmed TMPRSS2::ERG rearrangement. In IHC-PSMA positive PCa, IHC-ERG positivity was significantly associated with lower SUVmax values. In cohort #2, findings of higher IHC-PSMA%neg and IHC-ERG expression was confirmed with only 0-10% PSMA%neg tumour areas in IHC-ERG-negative PCa. CONCLUSION: IHC-ERG expression is significantly associated with more heterogeneous and lower IHC-PSMA tissue expression in two independent RPE cohorts. There is a strong association of ERG positivity in RPE tissue with lower [68Ga]Ga-PSMA-11 uptake on corresponding PET scans. Results may serve as a base for future biomarker development to enable tumour-tailored, individualized imaging approaches.

Focal therapy with high-intensity focused ultrasound for prostate cancer: 3-year outcomes from a prospective trial.

OBJECTIVE: To assess the oncological and functional outcomes of focal high-intensity focused ultrasound (HIFU) in treating localised prostate cancer (PCa), a 3-year prospective study was undertaken using periodic post-ablation saturation biopsies. PATIENTS AND METHODS: Men with two or fewer lesions of grade group (GG) ≤3 PCa were eligible for participation. Additional criteria included a prostate-specific antigen (PSA) level of ≤15 ng/mL, clinical T1c-T2, and a life expectancy of ≥10 years. The primary endpoint was failure-free survival (FFS), defined as absence of clinically significant PCa (csPCa) in- or out-of-field on protocol-mandated saturation biopsy, no whole-gland or systemic salvage treatment, PCa metastasis, or PCa-related death. Results are reported using two distinct definitions of csPCa: (i) the presence of any GG ≥2 and (ii) any GG ≥3 or core involvement of ≥6 mm. Secondary endpoints were functional patient-reported outcome measures addressing urinary, sexual, and bowel function. RESULTS: A total of 91 patients were included: six (7%) with GG1 and 85 (93%) with GG ≥2. In all, 83 (91%) underwent at least one follow-up biopsy. Biopsy attendance at 6, 12, and 36 months was 84%, 67%, and 51%, respectively. The FFS at these time points for any GG ≥2 PCa was 79% (95% confidence interval [CI] 80-88%), 57% (95% CI 48-69%) and 44% (95% CI 34-56%), respectively. Using the second definition, FFS were 88% (95% CI 81-95%), 70% (95% CI 61-81%) and 65% (95% CI 55-77%), respectively. The 3-year cancer-specific survival was 100%, and freedom from metastasis was 99%. Magnetic resonance imaging (MRI) (negative predictive value of up to 89%, 95% CI 84-93%) and relative decrease of PSA values (P = 0.4) performed poorly in detecting residual disease. Urinary and bowel assessment returned to baseline questionnaire scores within 3 months. In all, 17 (21%) patients reported meaningful worsening in erectile function. A significant decrease of PCa related anxiety was observed. CONCLUSIONS: Focal HIFU treatment for localised PCa shows excellent functional outcomes with half of the patients remaining cancer-free after 3 years. Whole-gland treatment was avoided in 81%. Early follow-up biopsies are crucial to change or continue the treatment modality at the right time, while the use of MRI and PSA in detecting PCa recurrence is uncertain.

Illumination matters part I: comparative analysis of light sources and illumination in flexible ureteroscopy-fundamental findings from a PEARLS analysis.

PURPOSE: Illumination characteristics of flexible ureteroscopes have been evaluated in air, but not in saline, the native operative medium for endourology. The aim was to evaluate light properties of contemporary ureteroscopes in air versus saline, light distribution analysis, and color temperature. METHODS: We evaluated the Storz Flex-Xc and Flex-X2s, Olympus V3 and P7, Pusen 7.5F and 9.2F, and OTU WiScope using a 3D printed black target board in-vitro model submerged in saline. A spectrometer was used for lux and color temperature measurements at different opening locations. RESULTS: Illuminance was higher in saline compared to air (5679 vs. 5205 lx with Flex-Xc, p = 0.02). Illuminance in saline differed between ureteroscopes (ANOVA p < 0.001), with highest for the Flex-Xc at 100% brightness setting (5679 lx), followed by Pusen 9.2F (5280 lx), Flex-X2s (4613 lx), P7 (4371 lx), V3 (2374 lx), WiScope (582 lx) and finally Pusen 7.5F (255 lx). The same ranking was found at 50% brightness setting, with the highest ureteroscope illuminance value 34 times that of the scope with lowest illuminance. Most scopes had maximum illuminance off center, with skewness. Three scopes had two light sources, with one light source for all other scopes. Inter-scope comparisons revealed significant differences of color temperature (ANOVA p < 0.001). CONCLUSION: The study demonstrates the presence of inhomogeneous light spread as well as large differences in illumination properties of ureteroscopes, possibly impacting on the performance of individual scopes in vivo. Additionally, the study suggests that future studies on illumination characteristics of flexible ureteroscopes should ideally be done in saline, and no longer in air.

Illumination matters Part III: Impact of light obstruction on illuminance from flexible ureteroscopes - a comparative PEARLS analysis.

PURPOSE: Artifacts from poor ureteroscopes' light design with shadowing and dark areas in the field of view have been reported. The aim was to quantify effects of light obstruction in a kidney calyx model. METHODS: We evaluated a series of contemporary flexible ureteroscopes including the Storz Flex-Xc and Flex-X2s, Olympus V3 and P7, Pusen 7.5F and 9.2F, as well as OTU Wiscope using an enclosed 3D-printed pink in vitro kidney calyx model submerged in saline, where the field of light was intentionally partially obstructed alternatively at 12, 3, 6, and 9 o'clock. A color spectrometer was used for illuminance measurements at a 45° opening position in the background of the model. RESULTS: Overall and mean background illuminance for each obstructive situation were significantly different between scopes for both 50% and 100% brightness settings (ANOVA p < 0.001). At 50% brightness setting, almost all scopes had their highest and lowest background illuminance with the 6 o'clock and 3 o'clock obstructive situation, respectively. At 100% brightness setting, these became 6 o'clock and 12 o'clock obstructive situations. Considering each obstructive situation individually, the Flex-Xc was consistently the scope with highest background illuminance and the Pusen 7.5F the lowest. Background illuminance for each obstructive situation varied significantly for each scope individually, with the greatest range of variability for Pusen 7.5F and V3. CONCLUSIONS: Illuminance performance of ureteroscopes within an obstructed calyx model differ significantly for various obstructive situations. Urologists should be aware of this to help guide their choice of ureteroscope.

Illumination matters part IV: blackout and whiteout in flexible ureteroscopy - first report on a phenomenon observed by PEARLS.

PURPOSE: To date, no study has evaluated effects of varying brightness settings on image quality from flexible ureteroscopes submerged in saline. The aim was to evaluate blackout and whiteout occurrences in an in-vitro kidney calyx model. MATERIAL AND METHODS: We evaluated a series of contemporary flexible ureteroscopes including the Storz Flex-Xc and Flex-X2s, Olympus V3 and P7, Pusen 7.5F and 9.2F, as well as OTU WiScope using a 3D-printed enclosed pink in-vitro kidney calyx model submerged in saline. Endoscopic images were captured with ureteroscope tip placed at 5 mm,10 mm and 20 mm distances. The complete range of brightness settings and video capture modes were evaluated for each scope. Distribution of brightness on a grayscale histogram of images was analyzed (scale range 0 to 255). Blackout and whiteout were defined as median histogram ranges from 0 to 35 and 220 to 255, respectively (monitor image too dark or too bright for the human eye, respectively). RESULTS: Blackout occurred with the P7, Pusen 7.5F, 9.2F and WiScope at all distances, and V3 at 20 mm - with lowest brightness settings. Whiteout occurred with Flex-X2s, V3 and P7 at 5 mm and 10 mm, as well as with V3 and P7 at 20 mm - mostly with highest brightness settings. The Flex-Xc had neither blackout nor whiteout at all settings and distances. CONCLUSION: Blackout or whiteout of images is an undesirable property that was found for several scopes, possibly impacting diagnostic and therapeutic purposes during ureteroscopy. These observations form a guide to impact a urologist's choice of instruments and settings.

Illumination matters Part II: advanced comparative analysis of flexible ureteroscopes in a kidney model by PEARLS.

PURPOSE: The aim of the study was to evaluate illumination properties in an in-vitro kidney calyx model in saline. DESIGN AND METHODS: We evaluated a series of contemporary flexible ureteroscopes including the Storz Flex-Xc and Flex-X2s, Olympus V3 and P7, Pusen 7.5F and 9.2F, as well as OTU WiScope using a 3D-printed closed pink kidney calyx model, submerged in saline. A spectrometer was used for illuminance and color temperature measurements at different openings located at center (direct light), 45° (direct and indirect light) and 90°(indirect light) to the axis of the scope. RESULTS: Maximum illuminance was at the center opening for all scopes (range: 284 to 12,058 lx at 50% brightness and 454 to 11,871 lx at 100% brightness settings). The scope with the highest center illuminance (Flex-Xc) was 26 times superior to the scope with the lowest illuminance (Pusen 7.5Fr) at 100% brightness setting. For each scope, there was a peripheral illuminance drop ranging from - 43 to - 92% at 50% brightness and - 43% to - 88% at 100% brightness settings, respectively (all p < 0.01). Highest drop was for the P7 and the Pusen 9.2F. All scopes had illuminance skew, except the V3. All scopes had a warm color temperature. CONCLUSION: Illumination properties vary between ureteroscopes in an enclosed cavity in saline, and differs at center vs 45° and 90° positions within scopes. Peripheral illuminance drop can be as high as - 92%, which is undesirable. This may affect the choice of ureteroscope and light brightness settings used in surgery by urologists.

Outcomes of robot-assisted laparoscopic extended pelvic lymph node dissection for prostate Cancer.

INTRODUCTION: Extended pelvic lymph node dissection (ePLND) in men undergoing robot-assisted laparoscopic radical prostatectomy (RARP) is a widely used procedure. However, little is known about anatomical site-specific yields and subsequent metastatic patterns in these patients. PATIENTS AND METHODS: Data on a consecutive series of 1107 patients undergoing RARP at our centre between 2004 and 2018 were analysed. In men undergoing LN dissection, the internal, external and obturator nodes were removed and sent in separately. We performed an analysis of LN yields in total and for each anatomical zone, patterns of LN metastases and complications. Oncological outcome in pN+ disease was assessed including postoperative PSA persistence and survival. RESULTS: A total of 823 ePLNDs were performed in the investigated cohort resulting in 98 men being diagnosed as pN+ (8.9%). The median (IQR) LN yield was 19 (14-25), 10 (7-13) on the right and 9 (6-12) on the left side (P < 0.001). A median of six (4-8) LNs were retrieved from the external, three (1-6) from the internal iliac artery, and eight (6-12) from the obturator fossa. More men had metastatic LNs on the right side compared to the left (41 vs. 19). Symptomatic lymphoceles occurred exclusively in the ePLND group (2.3% vs. 0%, p = 0.04). Postoperatively, 47 (47.9%) of men with pN+ reached a PSA of < 0.1µg/ml. There was no association between a certain pN+ region and postoperative PSA persistence or BCRFS. The estimated cancer specific survival rate at 5 years was 98.5% for pN+ disease. CONCLUSION: Robot-assisted laparoscopic ePLND with a high LN yield and low complication rate is feasible. However, we observed an imbalance in more removed and positive LNs on the right side compared to the left. A high rate of postoperative PSA persistence and early recurrence in pN+ patients might indicate a possibly limited therapeutical value of the procedure in already spread disease. Yet, these men demonstrated an excellent survival.

PSMA-positive prostatic volume prediction with deep learning based on T2-weighted MRI.

PURPOSE: High PSMA expression might be correlated with structural characteristics such as growth patterns on histopathology, not recognized by the human eye on MRI images. Deep structural image analysis might be able to detect such differences and therefore predict if a lesion would be PSMA positive. Therefore, we aimed to train a neural network based on PSMA PET/MRI scans to predict increased prostatic PSMA uptake based on the axial T2-weighted sequence alone. MATERIAL AND METHODS: All patients undergoing simultaneous PSMA PET/MRI for PCa staging or biopsy guidance between April 2016 and December 2020 at our institution were selected. To increase the specificity of our model, the prostatic beds on PSMA PET scans were dichotomized in positive and negative regions using an SUV threshold greater than 4 to generate a PSMA PET map. Then, a C-ENet was trained on the T2 images of the training cohort to generate a predictive prostatic PSMA PET map. RESULTS: One hundred and fifty-four PSMA PET/MRI scans were available (133 [68Ga]Ga-PSMA-11 and 21 [18F]PSMA-1007). Significant cancer was present in 127 of them. The whole dataset was divided into a training cohort (n = 124) and a test cohort (n = 30). The C-ENet was able to predict the PSMA PET map with a dice similarity coefficient of 69.5 ± 15.6%. CONCLUSION: Increased prostatic PSMA uptake on PET might be estimated based on T2 MRI alone. Further investigation with larger cohorts and external validation is needed to assess whether PSMA uptake can be predicted accurately enough to help in the interpretation of mpMRI.

Mitochondrial Elongation and ROS-Mediated Apoptosis in Prostate Cancer Cells under Therapy with Apalutamide and Complex I Inhibitor.

Metabolic reprogramming and mitochondrial dynamics are pivotal in prostate cancer (PCa) progression and treatment resistance, making them essential targets for therapeutic intervention. In this study, we investigated the effects of the androgen receptor antagonist apalutamide (ARN) and the mitochondrial electron transport chain complex I inhibitor IACS-010759 (IACS) on the mitochondrial network architecture and dynamics in PCa cells. Treatment with ARN and/or IACS induced significant changes in mitochondrial morphology, particularly elongation, in androgen-sensitive PCa cells. Additionally, ARN and IACS modulated the mitochondrial fission and fusion processes, indicating a convergence of metabolic and androgen-signaling pathways in shaping mitochondrial function. Notably, the combination treatment with ARN and IACS resulted in increased apoptotic cell death and mitochondrial oxidative stress selectively in the androgen-sensitive PCa cells. Our findings highlight the therapeutic potential of targeting mitochondrial metabolism in prostate cancer and emphasize the need for further mechanistic understanding to optimize treatment strategies and improve patient outcomes.

Therapy decisions after diagnosis of prostate cancer in men with negative prostate MRI.

BACKGROUND: To investigate the clinical implications of magnetic resonance imaging (MRI) negative prostate cancer (PCa) in a cohort of men undergoing transperineal prostate biopsy. METHODS: We included all men without prior diagnosis of PCa undergoing transperineal template saturation ± fusion-guided targeted biopsy of the prostate between November 2014 and March 2018. Before biopsy, all patients underwent MRI and biopsies were performed irrespective of imaging results. Baseline characteristics, imaging, biopsy results, and follow-up information were retrieved from the patient charts. Patients were classified as either MRI negative (Prostate Imaging Reporting and Data System [PIRADS] ≤ 2) or positive (PIRADS ≥ 3). ISUP grade group 1 was defined as clinically nonsignificant (nsPCa) and ≥2 as clinically significant PCa (csPCa). Primary outcome was the individual therapeutic decision after diagnosis of PCa stratified according to MRI visibility. Secondary outcomes were the sensitivity and specificity of MRI, and the urooncological outcomes after radical prostatectomy (RP). RESULTS: From 515 patients undergoing prostate biopsy, 171 (33.2%) patients had a negative and 344 (66.8%) a positive MRI. Pathology review stratified for MRI negative and positive cases revealed nsPCa in 27 (15.8%) and 32 (9.3%) and csPCa in 26 (15.2%) and 194 (56.4%) of the patients, respectively. The rate of active treatment in the MRI negative was lower compared with the MRI positive cohort (12.3% vs. 53.2%; odd ratio [OR] = 0.12; p < 0.001). While men with negative MRI were more likely to undergo active surveillance (AS) than MRI positive patients (18.1% vs. 10.8%; OR = 1.84; p = 0.027), they rarely underwent RP (6.4% vs. 40.7%, OR = 0.10; p < 0.001). Logistic regression revealed that a negative MRI was independently protective for active treatment (OR = 0.32, p = 0.014). The specificity, sensitivity, negative, and positive predictive value of MRI for detection of csPCa were 49.2%, 88.2%, 56.4%, and 84.8%, respectively. The rate of adverse clinicopathological outcome features (pT3/4, ISUP ≥4, or prostate-specific antigen [PSA]-persistence) following RP was 4.7% for men with MRI negative compared to 17.4% for men with MRI positive PCa (OR = 3.1, p = 0.19). CONCLUSION: Only few men with MRI negative PCa need active cancer treatment at the time of diagnosis, while the majority opts for AS. Omitting prostate biopsies and performing a follow-up MRI may be a safe alternative to reduce the number of unnecessary interventions.

Transperineal template saturation and conventional biopsy for stage prediction in prostate cancer.

OBJECTIVE: To evaluate the performance of risk calculators (RCs) predicting lymph node invasion (LNI) and extraprostatic extension (EPE) in men undergoing transperineal magnetic resonance imaging/transrectal ultrasound (TRUS)-fusion template saturation biopsy (TTSB) and conventional systematic TRUS-guided biopsy (SB). PATIENTS AND METHODS: The RCs were tested in a consecutive cohort of 645 men undergoing radical prostatectomy with extended pelvic LN dissection between 2005 and 2019. TTSB was performed in 230 (35.7%) and SB in 415 (64.3%) men. Risk of LNI and EPE was calculated using the available RCs. Discrimination, calibration, and clinical usefulness stratified by different biopsy techniques were assessed. RESULTS: Lymph node invasion was observed in 23 (10%) and EPE in 73 (31.8%) of cases with TTSB and 53 (12.8%) and 158 (38%) with SB, respectively. RCs showed an excellent discrimination and acceptable calibration for prediction of LNI based on TTSB (area under the curve [AUC]/risk estimation: Memorial Sloan Kettering Cancer Center [MSKCC]-RC 0.79/-4%, Briganti (2012)-RC 0.82/-4%, Gandaglia-RC 0.81/+6%). These were comparable in SB (MSKCC-RC 0.78/+2%; Briganti (2012)-RC 0.77/-3%). Decision curve analysis (DCA) revealed a net benefit at threshold probabilities between 3% and 6% when TTSB was used. For prediction of EPE based on TTSB an inferior discrimination and variable calibration were observed (AUC/risk estimation: MSKCC-RC 0.71/+8% and Martini (2018)-RC 0.69/+2%) achieving a net benefit on DCA only at risk thresholds of >17%. Performance of RCs for prediction of LNI and EPE based on SB showed comparable results with a better performance in the DCA for LNI (risk thresholds 1-2%) and poorer performance for EPE (risk threshold >20%). This study is limited by its retrospective single-institution design. CONCLUSIONS: The potentially more accurate grading ability of TTSB did not result in improved performance of preoperative RCs. Prediction tools for LNI proved clinical usefulness while RCs for EPE did not.

Prognostic value of pretreatment inflammatory markers in localised prostate cancer before radical prostatectomy.

PURPOSE: There is growing evidence of an association between inflammatory processes and cancer development and progression. In different solid tumor entities, a pronounced inflammatory response is associated with worse oncological outcome. In this study, we aim to evaluate the prognostic role of clinically established pretreatment inflammatory markers in patients with localised prostate cancer (PCa) before radical prostatectomy (RP). METHODS: A total of 641 men met our inclusion criteria and were followed prospectively for a median of 2.85 years. Univariable logistic and Cox regression analysis were performed to analyse associations between preoperative inflammatory markers and tumor characteristics, and biochemical recurrence free survival (BRFS). RESULTS: Median age at RP was 64 years. Gleason Score (GS) 7a (263, 41%) was the most prevalent histology, whereas high-risk PCa (≥ GS 8) was present in 156 (24%) patients. Lympho-nodal metastasis and positive surgical margin (PSM) were detected in 69 (11%) and 180 (28%) patients, respectively. No statistically relevant association could be shown between pretreatment inflammatory markers with worse pathological features like higher tumor stage or grade, nodal positive disease or PSM (for all p > 0.05). Additionally, pretreatment inflammatory markers were not associated with a shorter BRFS (p > 0.05). Known risk factors (tumor grade, tumor stage, nodal positivity and positive surgical margins) were all associated with a shorter BRFS (for all p < 0.0001). CONCLUSION: In this large prospective cohort, preoperative inflammatory markers were not associated with worse outcome.

Pulsed thulium:YAG laser-ready to dust all urinary stone composition types? Results from a PEARLS analysis.

PURPOSE: To evaluate whether stone dust can be obtained from all prevailing stone composition types using the novel pulsed thulium:YAG (p-Tm:YAG), including analysis of stone particle size after lithotripsy. METHODS: Human urinary stones of 7 different compositions were subjected to in vitro lithotripsy using a p-Tm:YAG laser with 270 µm silica core fibers (Thulio®, Dornier MedTech GmbH®, Wessling, Germany). A cumulative energy of 1000 J was applied to each stone using one of three laser settings: 0.1 J × 100 Hz, 0.4 J × 25 Hz and 2.0 J × 5 Hz (average power 10 W). After lithotripsy, larger remnant fragments were separated from stone dust using a previously described method depending on the floating ability of dust particles. Fragments and dust samples were then passed through laboratory sieves to evaluate stone particle count according to a semiquantitative analysis relying on a previous definition of stone dust (i.e., stone particles ≤ 250 µm). RESULTS: The p-Tm:YAG laser was able to produce stone dust from lithotripsy up to measured smallest mesh size of 63 µm in all seven stone composition types. Notably, all dust samples from all seven stone types and with all three laser settings had high counts of particles in the size range agreeing with the definition stone dust, i.e., ≤ 250 µm. CONCLUSION: This is the first study in the literature proving the p-Tm:YAG laser capable of dusting all prevailing human urinary stone compositions, with production of dust particles ≤ 250 µm. These findings are pivotal for the broader future implementation of the p-Tm:YAG in clinical routine.

Pulsed Thulium:YAG laser - What is the lithotripsy ablation efficiency for stone dust from human urinary stones? Results from an in vitro PEARLS study.

BACKGROUND: The novel pulsed thulium:yttrium-aluminum-garnet (p-Tm:YAG) laser was recently introduced. Current studies present promising p-Tm:YAG ablation efficiency, although all are based on non-human stone models or with unknown stone composition. The present study aimed to evaluate p-Tm:YAG ablation efficiency for stone dust from human urinary stones of known compositions. METHODS: Calcium oxalate monohydrate (COM) and uric acid (UA) stones were subjected to lithotripsy in vitro using a p-Tm:YAG laser generator (Thulio®, Dornier MedTech GmbH, Germany). 200 J was applied at 0.1 J × 100 Hz, 0.4 J × 25 Hz or 2.0 J × 5 Hz (average 10W). Ablated stone dust mass was calculated from weight difference between pre-lithotripsy stone and post-lithotripsy fragments > 250 µm. Estimated ablated volume was calculated using prior known stone densities (COM: 2.04 mg/mm3, UA: 1.55 mg/mm3). RESULTS: Mean ablation mass efficiency was 0.04, 0.06, 0.07 mg/J (COM) and 0.04, 0.05, 0.06 mg/J (UA) for each laser setting, respectively. This translated to 0.021, 0.029, 0.034 mm3/J (COM) and 0.026, 0.030, 0.039 mm3/J (UA). Mean energy consumption was 26, 18, 17 J/mg (COM) and 32, 23, 17 J/mg (UA). This translated to 53, 37, 34 J/mm3 (COM) and 50, 36, 26 J/mm3 (UA). There were no statistically significant differences for laser settings or stone types (all p > 0.05). CONCLUSION: To our knowledge, this is the first study showing ablation efficiency of the p-Tm:YAG laser for stone dust from human urinary stones of known compositions. The p-Tm:YAG seems to ablate COM and UA equally well, with no statistically significant differences between differing laser settings.

Transurethral injection of autologous muscle precursor cells for treatment of female stress urinary incontinence: a prospective phase I clinical trial.

INTRODUCTION AND HYPOTHESIS: The purpose was to investigate the safety and feasibility of transurethral injections of autologous muscle precursor cells (MPCs) into the external urinary sphincter (EUS) to treat stress urinary incontinence (SUI) in female patients. METHODS: Prospective and randomised phase I clinical trial. Standardised 1-h pad test, International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF), urodynamic study, and MRI of the pelvis were performed at baseline and 6 months after treatment. MPCs gained through open muscle biopsy were transported to a GMP facility for processing and cell expansion. The final product was injected into the EUS via a transurethral ultrasound-guided route. Primary outcomes were defined as any adverse events (AEs) during follow-up. Secondary outcomes were functional, questionnaire, and radiological results. RESULTS: Ten female patients with SUI grades I-II were included in the study and 9 received treatment. Out of 8 AEs, 3 (37.5%) were potentially related to treatment and treated conservatively: 1 urinary tract infection healed with antibiotics treatment, 1 dysuria and 1 discomfort at biopsy site. Functional urethral length under stress was 25 mm at baseline compared with 30 mm at 6 months' follow-up (p=0.009). ICIQ-UI-SF scores improved from 7 points at baseline to 4 points at follow-up (p=0.035). MRI of the pelvis revealed no evidence of tumour or necrosis, whereas the diameter of the EUS muscle increased from 1.8 mm at baseline to 1.9 mm at follow-up (p=0.009). CONCLUSION: Transurethral injections of autologous MPCs into the EUS for treatment of SUI in female patients can be regarded as safe and feasible. Only a minimal number of expected and easily treatable AEs were documented.

Atherosclerosis of the iliac arteries for the prediction of erectile dysfunction and epistaxis in men undergoing abdominal CT scan.

BACKGROUND: To investigate the association between erectile dysfunction (ED) as well as epistaxis (ES) in relation to the extent of iliac atherosclerosis. METHODS: In this retrospective cross-sectional study, all consecutive male patients treated at our institution from 01/2016 to 12/2020 undergoing abdominal CT scan were evaluated. Patients (n = 1272) were invited by mail to participate in the study in returning two questionnaires for the evaluation of ED (IIEF-5) and ES. Patients who returned filled-in questionnaires within a 3-month deadline were included in the study. The extent of atherosclerosis in the common iliac artery (CIA) and the internal iliac artery (IIA) was assessed by calcium scoring on unenhanced CT. Stratification of results was performed according to reported IIEF-5 scores and consequential ED groups. RESULTS: In total, 437 patients (34.4% of contacted) met the inclusion criteria. Forty-two patients did not fulfill predefined age requirements (< 75 years) and 120 patients had to be excluded as calcium scoring on nonenhanced CT was not feasible. Finally, 275 patients were included in the analysis and stratified into groups of "no-mild" (n = 146) and "moderate-severe" (n = 129) ED. The calcium score (r=-0.28, p < 0.001) and the number of atherosclerotic lesions (r=-0.32, p < 0.001) in the CIA + IIA showed a significant negative correlation to the IIEF-5 score, respectively. Patients differed significantly in CIA + IIA calcium score (difference: 167.4, p < 0.001) and number of atherosclerotic lesions (difference: 5.00, p < 0.001) when belonging to the "no-mild" vs. "moderate-severe" ED group, respectively. A multivariable regression model, after adjusting for relevant baseline characteristics, showed that the number of atherosclerotic CIA + IIA lesions was an independent predictor of ED (OR = 1.05, p = 0.036), whereas CIA + IIA calcium score was not (OR = 1.00031, p = 0.20). No relevant correlation was found between ES episodes and IIEF-5 scores (r=-0.069, p = 0.25), CIA + IIA calcium score (r=-0.10, p = 0.87) or number of atherosclerotic CIA + IIA lesions (r=-0.032, p = 0.60), respectively. CONCLUSIONS: The number of atherosclerotic lesions in the iliac arteries on nonenhanced abdominal CT scans is associated with the severity of ED. This may be used to identify subclinical cardiovascular disease and to quantify the risk for cardiovascular hazards in the future. TRIAL REGISTRATION: BASEC-Nr. 2020 - 01637.

The Role of Additional Epididymis Resection during Hydrocelectomy: Is It of Any Benefit in Comparison to Simple Hydrocelectomy?

INTRODUCTION: Open hydrocelectomy via scrotal incision is the standard approach for secondary hydroceles. Traditionally, the Swiss urologic community offer hydrocelectomy with additional resection of the epididymis in elderly men with completed family planning. It is believed that the additional resection of the epididymis reduces the postoperative recurrence rate of hydroceles. However, there is no evidence supporting this theory. Therefore, the aim of this study was to compare the recurrence and complication rates for patients with secondary hydroceles undergoing either pure hydrocelectomy (puH) or hydrocelectomy with additional resection of the epididymis (HRE). MATERIALS AND METHODS: We reviewed all male patients who underwent surgical therapy for secondary hydroceles between May 2003 and February 2019 at our institution. Patient's baseline and perioperative characteristics as well as postoperative characteristics including complications and recurrence rates were gathered and compared between different surgical techniques. RESULTS: A total of 234 patients were identified. puH was performed in 93 (40%) cases and HRE in 141 (60%) patients. Patients in the HRE group were older (median age: 62 vs. 38 years, p < 0.001), had a higher ASA-Score (p < 0.001), were more often on platelet aggregation inhibitors (19% vs. 7.5%, p = 0.01), and had a longer median operative time (75 vs. 64 min, p < 0.001). During a median follow-up of 46 months, a similar number of recurrent hydroceles were found for puH (7 [7.5%]) and HRE (6 [4.5%]) (p = 0.3). Complications were observed in 19 (20%) cases after puH compared to 25 (18%) cases after HRE (p = 0.6). Patients after puH experienced more often severe complications (Clavien-Dindo Grade 3b) compared to the HRE group (5 vs. 12%, p = 0.046). CONCLUSION: puH and HRE showed similar results in terms of overall low recurrence rates and also in terms of postoperative complications, even though patients who underwent puH experienced slightly higher severe complications. Both procedures are safe and effective, but it seems that HRE does not provide a relevant clinical benefit in comparison to puH for the management of men with secondary hydroceles.

Myostatin Overexpression and Smad Pathway in Detrusor Derived from Pediatric Patients with End-Stage Lower Urinary Tract Dysfunction.

Cell therapies and tissue engineering approaches using smooth muscle cells (SMCs) may provide treatment alternatives for end-stage lower urinary tract dysfunction (ESLUTD). Myostatin, a negative regulator of muscle mass, is a promising target to improve muscle function through tissue engineering. The ultimate goal of our project was to investigate the expression of myostatin and its potential impact in SMCs derived from healthy pediatric bladders and pediatric ESLUTD patients. Human bladder tissue samples were evaluated histologically, and SMCs were isolated and characterized. The proliferation of SMCs was assessed by WST-1 assay. The expression pattern of myostatin, its pathway and the contractile phenotype of the cells were investigated at gene and protein levels by real-time PCR, flow cytometry, immunofluorescence, WES and gel contraction assay. Our results show that myostatin is expressed in human bladder smooth muscle tissue and in isolated SMCs at gene and protein levels. A higher expression of myostatin was detected in ESLUTD-derived compared to control SMCs. Histological assessment of bladder tissue confirmed structural changes and decreased muscle-to-collagen ratios in ESLUTD bladders. A decrease in cell proliferation and in the expression of key contractile genes and proteins, α-SMA, calponin, smoothelin and MyH11, as well as a lower degree of in vitro contractility was observed in ESLUTD-derived compared to control SMCs. A reduction in the myostatin-related proteins Smad 2 and follistatin, and an upregulation in the proteins p-Smad 2 and Smad 7 were observed in ESLUTD SMC samples. This is the first demonstration of myostatin expression in bladder tissue and cells. The increased expression of myostatin and the changes in the Smad pathways were observed in ESLUTD patients. Therefore, myostatin inhibitors could be considered for the enhancement of SMCs for tissue engineering applications and as a therapeutic option for patients with ESLUTD and other smooth muscle disorders.

Improved Prostate-Specific Membrane Antigen (PSMA) Stimulation Using a Super Additive Effect of Dutasteride and Lovastatin In Vitro.

Prostate-specific membrane antigen (PSMA)-based imaging improved the detection of primary, recurrent and metastatic prostate cancer. However, in certain patients, a low PSMA surface expression can be a limitation for this promising diagnostic tool. Pharmacological induction of PSMA might be useful to further improve the detection rate of PSMA-based imaging. To achieve this, we tested dutasteride (Duta)-generally used for treatment of benign prostatic enlargement-and lovastatin (Lova)-a compound used to reduce blood lipid concentrations. We aimed to compare the individual effects of Duta and Lova on cell proliferation as well as PSMA expression. In addition, we tested if a combination treatment using lower concentrations of Duta and Lova can further induce PSMA expression. Our results show that a treatment with ≤1 µM Duta and ≥1 µM Lova lead to a significant upregulation of whole and cell surface PSMA expression in LNCaP, C4-2 and VCaP cells. Lower concentrations of Duta and Lova in combination (0.5 µM Duta + 0.5 µM Lova or 0.5 µM Duta + 1 µM Lova) were further capable of enhancing PSMA protein expression compared to a single compound treatment using higher concentrations in all tested cell lines (LNCaP, C4-2 and VCaP).

Prostate cancer detection rate in men undergoing transperineal template-guided saturation and targeted prostate biopsy.

OBJECTIVES: To compare prostate cancer (PCa) detection rate of transperineal template-guided saturation prostate biopsy (SBx) and multiparametric magnetic resonance imaging (mpMRI)/transrectal ultrasound fusion guided targeted biopsy (TBx). MATERIALS AND METHODS: We prospectively enrolled 392 men who underwent SBx and TBx in case of suspicious lesions from November 2016 to October 2019. Triggers for a biopsy were an elevated prostate-specific antigen (PSA) and/or positive digital rectal examination and only treatment naïve patients without a previous diagnosis of PCa were included. Study inclusion occurred before biopsy and a prebiopsy mpMRI was available in all men. SBx were taken from 20 different locations according to the modified Barzell zones. The primary endpoint was the detection rate of clinically significant PCa (csPCa) and insignificant PCa (ciPCa) by SBx and/or TBx by comparing the two methods alone and in combination. Additional TBx were taken for any prostate imaging-reporting and data system (PI-RADS) lesion ≥3 seen on the mpMRI. csPCa was defined as any Gleason score ≥7 and ciPCa as Gleason score 6. RESULTS: A total of 392 men with a median age of 64 years (interquartile range [IQR]: 58-69), a median PSA of 7.0 ng/ml (IQR: 4.8-10.1) were enrolled. Overall, PCa was found in 200 (51%) of all biopsied men, with 158 (79%) being csPCa and 42 (21%) ciPCa. A total of 268 (68%) men with a suspicious mpMRI and underwent a combined TBx and SBx, of whom csPCa was found in 139 (52%). In this subgroup, 116/139 (83%) csPCa would have been detected by TBx alone, and an additional 23 (17%) were found by SBx. Men with a negative mpMRI (PI-RADS < 3, n = 124, 32%) were found to have csPCa in 19 (15%) cases. In patients with a negative mpMRI in combination with a PSA density <0.1 ng/ml2 , only 8% (3/36) had csPCa. If only TBx would have been performed and all men with a negative mpMRI would not have been biopsed, 42/158 (27%) of csPCa would have been missed, and 38/42 (90%) ciPCa would have not been detected. On multivariable analysis, significant predictors of csPCa were increasing PSA (odds ratio, OR: 1.07 [95% confidence interval, CI: 1.03-1.11]), increasing age (OR: 1.07 [95% CI: 1.03-1.11]), PI-RADS score ≥ 3 (OR: 6.49 [95% CI: 3.55-11.89]), and smaller prostate volume (OR: 0.96 [95% CI: 0.95 -0.97] (p < 0.05 for all parameters). CONCLUSION: In comparison to SBx, TBx alone detects csPCa in only ¾ of all men with a positive mpMRI lesion. Thus, systematic biopsies in addition to TBx have to be considered at least in some who undergo a prostate biopsy. In men with a negative mpMRI, SBx still detects 15% csPCa, but similarly overdetecting ciPCa. According to our results, low PSA density and negative mpMRI findings could be used to decide which men can safely avoid biopsy.