Clinical dose of enoxaparin enhances oncolytic virus M1 infection and antitumor efficacy in human bladder cancer.

Leiomyomas (LMs) represent the most frequent mesenchymal tumors of the urinary bladder. Despite their relative frequency, large clinicopathological studies are scarce, and their pathogenesis remains poorly understood. In this study, we performed a clinicopathological analysis of 35 bladder LMs and explored whether they share pathogenic mechanisms previously documented in uterine LMs. The tumors occurred in 18 women and 17 men, with a median age of 55 years (range: 20 to 78y). Clinical data were available for 30 cases (85%). Most tumors were incidentally discovered (16/30, 53%), while the remaining patients presented predominantly with lower urinary tract symptoms. Ten patients had a prior history of cancer, and 3 women had a history of uterine LM. Tumor size, available in 12 cases, ranged from 6 to 66mm (mean, 31mm). Histologically, most tumors showed a uniform morphology, consisting of well-circumscribed nodules composed of bland smooth muscle cells without mitotic activity. Rare findings included extensive necrosis (3/35, 8%) and a pseudohyperplastic appearance (1/20, 5%). On immunohistochemistry, a subset of tumors, predominantly in females, expressed estrogen receptors (7/28, 25%), progesterone receptors (5/24, 21%), and androgen receptors (10/23, 43%). HMGA2 expression was observed in one case (1/27, 4%). Fumarate hydratase (FH) expression was retained in all tested tumors (n=31); 2SC expression was detected in 4 tumors (4/32; 12%), all with preserved FH and lacking distinctive histomorphological features of FH-deficient LMs. DNA sequencing of 2SC-positive tumors identified a pathogenic FH variant in one of the 4 analyzed cases at a low variant allele frequency. No other known pathogenic variants, including MED12 commonly seen in uterine LMs, were detected. Altogether, this study characterizes the clinicopathological features of large cohort of bladder LMs, highlighting unrecognized morphologic features, including cases with massive necrosis. Our findings suggest that bladder LMs differ pathogenetically from their uterine counterparts, with a more limited role for hormone receptor signaling and distinct genetic alterations.

To evaluate the feasibility, safety, and short-term functional outcomes of adding bladder neck opening and ventral adenoma vaporization to ejaculatory hood (EH)-sparing photoselective vaporization of the prostate (PVP), aimed at preserving antegrade ejaculation in patients with benign prostatic obstruction (BPO). This retrospective, single-center pilot study included 27 patients with BPO who underwent PVP at our institution with the purpose of preserving ejaculatory function. EH was defined as the area within approximately 1 cm proximal and lateral to the verumontanum, which was preserved during bladder neck opening and ventral adenoma vaporization to create an unobstructed cavity from the prostatic apex to the bladder neck. The primary endpoint was the preservation of antegrade ejaculation at 3 months postoperatively. At 3 months postoperatively, 26 (96%) of 27 patients had preserved antegrade ejaculation, and one (4%) patient was suspected of retrograde ejaculation. The median International Prostate Symptom Score decreased from 21 to 7, and the quality-of-life score decreased from 5 to 2. Further, the maximum flow rate increased from 5.4 to 14.3 mL/s, and the postvoid residual urine volume decreased from 72.5 to 0 mL (all p < 0.001). The median prostate volume decreased from 60 to 24 mL, and Clavien-Dindo grade III or higher adverse events were not observed. EH-sparing PVP with bladder neck opening and ventral adenoma vaporization was feasible and safe in the short term and was associated with preserved antegrade ejaculation and improved urinary outcomes in patients with BPO. Further prospective studies with validated sexual function assessment and longer follow-up are necessary to confirm these findings.

Sentinel lymph node (SLN) mapping in bladder cancer has the potential to improve nodal staging while minimizing the morbidity associated with pelvic lymph node dissection (PLND). However, its feasibility, diagnostic accuracy, and influencing factors-including tumor stage, neoadjuvant chemotherapy (NAC), and imaging modality-remain under investigation. In this prospective study, 35 patients with T1-T4 urothelial carcinoma undergoing radical cystectomy and bilateral PLND were enrolled. Preoperative cystoscopic peritumoral injection of 99mTc-phytate was followed by planar lymphoscintigraphy and SPECT/CT. Intraoperative SLN detection utilized a handheld gamma probe. SLN identification was compared with standard PLND findings using patient- and hemipelvis-based analyses to determine detection rates, sensitivity, and false-negative rates. A total of 54 SLNs were identified in 24 patients (37 hemipelves). Patient-based detection rates were 68.6% for intraoperative gamma probe, 51.4% for SPECT/CT, and 45.7% for planar imaging. Hemipelvis-based detection rates were 52.9%, 40.0%, and 34.3%, respectively. Detection rates were highest in T1-T2, NAC-positive patients, with 100% intraoperative localization. Histopathological analysis identified nodal metastases in seven patients; SLNs were identified in four patients, three of whom showed concordant SLN involvement, while one showed no SLN involvement. The patient-based false-negative rate was 25%, while hemipelvis-based analysis showed no false negatives. Aberrant SLNs outside the standard PLND template were identified in 6% of patients, highlighting variable lymphatic drainage. SLN mapping in bladder cancer is technically feasible and identifies atypical drainage patterns, with performance influenced by tumor stage, NAC, and imaging modality. SLN mapping may complement PLND by improving anatomical staging and may ultimately allow more tailored or minimally invasive lymphadenectomy in selected patients.

This narrative review aims to summarize the most relevant literature published in 2024-2025 regarding the management of vesicourethral anastomotic stenosis (VUAS) and bladder neck contracture (BNC) after treatment of the prostate. We identified relevant articles focusing on novel treatment options regarding the management of VUAS and BNC, emphasizing patency rates and continence trade-offs. Vesicourethral anastomotic stenosis and bladder neck contracture represent distinct postoperative complications following radical prostatectomy and benign prostatic hyperplasia surgery, respectively. Endoscopic therapy continues to serve as first-line treatment, though reported success rates vary substantially across modalities. Emerging minimally invasive endoluminal techniques, such as transurethral incision with transverse mucosal realignment and drug-coated balloon dilation demonstrate promising early outcomes. For recalcitrant disease, reconstructive solutions including transperineal reanastomosis, buccal mucosal graft urethroplasty, and a growing spectrum of robot-assisted approaches offer encouraging patency rates with variable impacts on continence.

Exploring a critical time window for FOXM1-driven bladder injury in chronic arsenic exposure.

The aim was to investigate and clarify the cause of death of a 26-year-old male found dead in his apartment. It was known that the individual used drugs of abuse. In the apartment, the police found amongst others a "brown powder" and a glass bottle labeled with "2-methyl-2-butanol" (2m2b). Autopsy and chemical analyses were performed. The autopsy revealed unspecific morphological signs of an intoxication (cerebral swelling and cyanosis, pulmonary edema, full urine bladder). Headspace gas chromatography with flame ionization detection (HS-GC-FID) was used to determine 2m2b and ethanol. Concentrations of 245mg/L and 225mg/L 2m2b could be detected in the femoral vein blood specimen and urine, respectively. Ethanol was detected below the level of quantification (0,2g/L) in both matrices. The detected blood concentration of 2m2b was more than twice as high as the 2m2b concentration described as comatose in a previous published case report. However, in the presented case further analysis revealed toxic concentrations of methamphetamine and venlafaxine and also identified a previous intake of heroin and diazepam. Thus, a combined drug intoxication was assumed as cause of death. Little is known about the abuse of 2m2b as an alternative to ethanol. Since 2m2b is widely available, cheap, more potent than ethanol, while lacking its hangover effects and is likely not detected by routine HS-GC-FID methods for the detection of blood ethanol concentrations, it may be of forensic relevance.

Penile inversion vaginoplasty is the most commonly performed gender-affirming surgery in transgender women and results in the creation of a neovaginal canal while preserving several pelvic structures, including the urethra, prostate, and elements of erectile tissue. However, postoperative pelvic floor anatomy in transgender women has not been well characterized using functional imaging techniques. The aim of this study was to describe pelvic floor anatomy on transperineal ultrasound in transgender women after penile inversion vaginoplasty and to evaluate the feasibility and interobserver reproducibility of selected ultrasound measurements. This pilot cross-sectional study included transgender women who had undergone penile inversion vaginoplasty at least 6 months prior to evaluation. Participants underwent a standardized transperineal pelvic floor ultrasound. Anatomical landmarks, including the urethra, bladder, prostate, residual erectile tissue, neovagina, anal canal, and levator ani muscle, were identified in the midsagittal plane. Measurements included urethral length and thickness, urethral angle, bladder neck position, rectal ampulla position, detrusor thickness, postvoid residual volume and neovaginal parameters. Ultrasound volumes were analyzed offline by two independent observers blinded to clinical data. Interobserver reproducibility was assessed using intraclass correlation coefficients (ICC). Ten participants were included. Pelvic floor structures were consistently identifiable on transperineal ultrasound in all participants. The urethra, prostate, neovaginal canal, and residual erectile tissue could be reliably visualized in the midsagittal plane. Quantitative measurements demonstrated good to excellent interobserver reproducibility for most parameters (ICC: 0.72-0.99). The spatial relationship between the neovagina, urethra, and rectum could be clearly assessed, allowing characterization of the postoperative pelvic floor configuration. Pelvic floor ultrasound is a feasible and reproducible imaging modality for the evaluation of pelvic floor anatomy in transgender women after penile inversion vaginoplasty. This technique enables detailed visualization of the neovagina and adjacent pelvic structures and may represent a useful tool for postoperative anatomical assessment and for the investigation of lower urinary tract and pelvic floor symptoms in this population. Not applicable. This study is an observational pilot study and was not registered as a clinical trial.

To estimate the learning curve for thulium laser enucleation of the prostate (ThuLEP) performed by the same surgeon, appreciating the sequential progression in skill and proficiency over time. The study retrospectively enrolled 60 patients with benign prostatic hyperplasia (BPH) who underwent the ThuLEP procedure performed by a single experienced endourologist. Though not initially skilled with laser enucleation of the prostate, the surgeon had observed numerous cases before. The patients were divided into three groups, each containing 20 cases. The procedure started with inspection, followed by incision and trough creation and plane development, apicolateral dissection, sphincter release, anterior dissection, bladder neck dissection, C-shaped baso-lateral dissection, and adenoma detachment technique called veil-sparing ThuLEP using the ABCD method. Perioperative parameters, enucleation and morcellation time (min), enucleation efficiency (g/min), morcellation efficiency (g/min), enucleated tissue weight (g), hospital stay time, and catheterization time (h) were recorded. There was a statistically significant decrease in the International Prostate Symptom Score (IPSS) 6 months postoperatively (median = 3) compared with 1-day postoperatively (median = 4) and preoperatively (median = 25). Uroflowmetry parameters, IIEF-5 scores, enucleation and morcellation efficiency, hospitalization period, and catheterization time were evaluated, showing substantial improvements and stabilization over time. A highly skilled endourologist in TURP was able to master the learning curve of ThuLEP after completing the initial 40 patients. Upgrading the sequential progression in skill and proficiency over time for treating benign prostatic hyperplasia in addition to its safety, feasibility, efficacy that improve procedure outcome with fewer difficulties.

To determine the predictive value of bladder neck angle (BNA) for trial without catheter (TWOC) following acute urinary retention (AUR) due to benign prostatic obstruction (BPO), and to evaluate its role in predicting response to conservative therapy in patients with lower urinary tract symptoms (LUTS). Outpatients presenting with bothersome LUTS or acute urinary retention (AUR) due to BPO were included in the cohort. The prostate volume, intravesical prostatic protrusion, BNA, and postvoid residual volume were recorded. In patients with AUR, TWOC was performed after 2 weeks of alpha-blocker therapy; those with LUTS received alpha-blockers and 5-alpha reductase inhibitors for 12 months. Surgery was recommended for patients who experienced failure of conservative treatment. The uroflowmetry and International Prostate Symptom Score (IPSS) changes were assessed from baseline to 12 months after treatment. Among 66 patients with AUR, 32 (48.5%) experienced TWOC failure. BNA demonstrated strong discriminative ability for predicting TWOC failure (AUC 0.855, 95% CI 0.76-0.94), with an optimal cut-off of 89.94° (sensitivity 75%, specificity 84%), outperforming IPP (AUC 0.794, 95% CI 0.68-0.91). Among 335 non-AUR patients receiving combination therapy, 23 (6.8%) required surgery. BNA predicted treatment failure with an AUC of 0.87 and an optimal cut-off of 75.85° (sensitivity 78%, specificity 87%). BNA is a promising anatomical predictor of TWOC outcome in AUR and may help identify LUTS patients who are likely to experience greater benefit from conservative therapy. Incorporating BNA into clinical assessment may improve risk stratification and treatment planning in BPO management.

Hexavalent chromium (Cr(VI)) is a human carcinogen. It is unclear whether Cr(VI) can cause cancer of the small intestine, oral cavity, pancreas, prostate and urinary bladder. We performed a systematic review and meta-analyses of epidemiological studies on occupational exposure to Cr(VI) and incidence and mortality of these cancer sites.A comprehensive review of human studies on Cr(VI) and cancer was performed in Embase and Scopus. 131 potentially relevant epidemiological studies were identified. Study quality was assessed using the Newcastle-Ottawa Scale. 29 publications including 81 observations for meta-analyses were based on cohort or case-control studies with exposure assessment of sufficient quality. Site-specific random-effects meta-analyses were done separately for incidence and mortality. Sensitivity analyses focused on the studies with the highest quality scores.No indications for an association between Cr(VI) exposure and oral or small intestine cancer were found. Incidence of pancreatic cancer was not associated with Cr(VI) exposure (meta-relative risk (RR) 1.04; 95% CI 0.85 to 1.28) while for specific mortality RR was 1.41 (95% CI 0.96 to 2.08) with moderate heterogeneity (I2=41%) and an asymmetric funnel plot (Egger's test; p=0.002). For incidence of prostate cancer meta RR was 1.16 (95% CI 0.99 to 1.37) while the RR for mortality was 1.03 (95% CI 0.84 to 1.25). For bladder cancer, RR was 1.04 (95% CI 0.91 to 1.20) for incidence and 1.76 (95% CI 1.20 to 2.60) for mortality.This comprehensive meta-analysis of epidemiological studies did not provide sufficient evidence that occupational Cr(VI) exposure may cause cancer of the oral cavity, small intestine, pancreas, prostate or the urinary bladder in humans.

A Systematic Review and Meta-analysis of Surgical Reconstruction for Bladder Neck and Vesicourethral Anastomotic Stenosis: The Case for Etiology-specific Definitions and Reporting.

The Optilume® drug-coated balloon (DCB), combining mechanical dilation with localized paclitaxel delivery, is a novel minimally invasive treatment for urethral stricture disease. However, data on its effectiveness across different stricture locations are limited. This study evaluates functional outcomes following treatment for different strictures locations. This retrospective multicenter study included patients treated with Optilume® DCB for urethral strictures at five European tertiary care referral centers (June 2023 - June 2025). Stricture length was assessed by retrograde urethrography, cystoscopy, or both. Recurrence was defined as any symptomatic stricture requiring treatment. A multivariable logistic regression using preoperative data was developed to predict recurrence requiring treatment. In total 86 patients were included across four stricture locations: penile (n = 11, 13%), bulbar/penobulbar (n = 59, 68%), bulbomembranous/membranous (n = 13, 15%) and bladder neck (n = 3, 4%). Postoperative complications within 30 days occurred in 5 (5.8%) patients. Median follow-up duration ranged from 3 to 11 months. Median peak urinary flow increased from 3.5 to 8.8 mL/s preoperatively to 13.5-19 mL/s at 3 months. Stricture-free rates were highest in penile (91%) and bladder neck (100%) strictures, and lower for bulbar (74%) and bulbomembranous/membranous (69%) strictures. On multivariate logistic regression analysis, diabetes was an independent predictor of stricture recurrence (OR = 7.66, 95% CI 1.55-47.12, p = 0.01). Optilume® DCB showed encouraging efficacy and safety across different urethral stricture locations, achieving high stricture-free rates and improved urinary flow. Diabetes independently predicted recurrence, highlighting the value of optimizing modifiable risk factors.

Exercise-based heavy lifting has been suggested to challenge pelvic organ support, yet no study has investigated this in women at risk of pelvic organ prolapse. This study aimed to investigate the immediate impact of heavy weightlifting on pelvic floor morphometry in premenopausal, vaginally parous women trained in exercise-based heavy lifting. Participants without symptoms of vaginal bulge attended a heavy weightlifting session (heavy barbell back squats [5 × 5 repetitions at 80% one repetition maximum]). Pelvic floor morphometry was measured before and immediately after the session. Bladder neck and rectal ampulla positions, anorectal and levator plate angles, levator anteroposterior distance, and levator hiatal area were assessed using transperineal ultrasound at rest, during bearing down, and during pelvic floor muscle contraction, in supine and standing positions. The maximal vaginal descent was assessed using the Pelvic Organ Prolapse Quantification in supine. Thirty-seven women participated in the study. Compared to pre-lifting, immediately after lifting the anorectal angle at rest was larger in supine and standing (p ≤ 0.05); during pelvic floor muscle contraction the bladder neck was more caudal in supine (p < 0.001) and the levator hiatal area was larger in standing (p = 0.02); during bearing down the levator plate angle was smaller in standing (p = 0.002) and the levator hiatal area was larger in supine (p = 0.01). No other significant pre-post changes were found. In asymptomatic, trained, premenopausal, vaginally parous women, a single heavy lifting session may induce small immediate pelvic floor morphometric changes, with minor impact on organ support, as shown by stable bladder neck, rectal ampulla, and vaginal wall measures.

Preparation of cleared whole-mount urethra and urinary bladder from transcardially perfused mice for immunolabeling and analysis by CLSM.

BackgroundGastrin-releasing peptide receptor (GRPR) is overexpressed in several malignant tumours, while its physiological expression in major organs, except for pancreas, is low. GRPR is therefore an interesting target in nuclear medicine. The GRPR-binding ligand, [68Ga]Ga-NOTA-PEG2-RM26 has previously been proven safe in humans. This study evaluates human dosimetry of the radioligand using 12 cancer patients (6 women with breast cancer and 6 men with prostate cancer) based on PET-CT imaging at six timepoints post injection. The voided urine was also collected to serve as an input to a urinary bladder model.ResultsThe pancreas, liver, spleen, kidney parenchyma, gall bladder, urinary bladder contents and cortical bone were identified as source organs/regions. Results using OLINDA/EXM 2.3.0 dosimetry software showed that pancreas was the organ that received the highest absorbed dose, 110 ± 43 µGy/MBq, followed by the urinary bladder wall, 100 ± 36 µGy/MBq, and the kidneys, 31 ± 11 µGy/MBq. The osteogenic cells received 15 ± 7 µGy/MBq. The median (range) of the total excreted activity through urine was 56% (43–75%) of the injected activity in 4h. The effective dose (ICRP 103) from an injection of [68Ga]Ga -NOTA-PEG2-RM26 was calculated to 11 µSv/MBq, using a 1h voiding interval in the urinary bladder model.ConclusionA standard person of 70kg receiving 140MBq of [68Ga]Ga-NOTA-PEG2-RM26 will receive an effective dose of 1.5 mSv, which is lower or in accordance with other 68Ga-labelled GRPR targeted radioligands.Trial registrationClinicaltrials.gov, NCT06147362, Registered 17 November 2023 – Retrospectively registered, https://www.clinicaltrials.gov/study/NCT06147362

ObjectiveTo compare the early and long-term recovery outcomes of post-prostatectomy incontinence (PPI) among patients undergoing Retzius-sparing robotic-assisted laparoscopic prostatectomy (RS-RARP), conventional 2-layer reconstruction, and conventional 3-layer total reconstruction.MethodsWe conducted a retrospective cohort study of 79 patients who underwent RARP by at a single tertiary center. Patients were grouped as RS-RARP (n=19), 2-layer RARP (n=30), and 3-layer RARP (n=30). The primary outcome was PPI recovery, defined as “pad-free”, which was evaluated at immediate, 1, 3, and 6 months after RARP to distinguish between early (immediate/1 month) and long-term (3/6 months) outcomes. Secondary outcomes included cystographic parameters like bladder neck (BN) angle and BN downward distance. Statistical analysis utilized ANOVA and Chi-square tests, with p<0.05 considered significant.ResultsAll three groups achieved excellent long-term continence rates (≥96.7% at 6 months, p=0.723). The RS-RARP group demonstrated a borderline statistical advantage of early PPI recovery at the immediate timepoint (89.5% vs. 60.0% in the other two groups, p=0.049). A similar favorable clinical trend was observed at the 1-month follow-up, though the difference did not reach statistical significance (p=0.251). Cystographic analysis revealed a significant difference in mean BN angle (p=0.001): 128.5∘for RS-RARP, 107.7∘for 2-layer RARP, and 120.1∘for 3-layer RARP.ConclusionAll three RARP techniques yield excellent long-term continence rates. RS-RARP demonstrated a favorable advantage in immediate PPI recovery, which supports the benefit of anterior structure preservation. However, the observed significant anatomical difference in BN angle did not translate into a statistically significant functional difference in long-term PPI recovery, highlighting the multifactorial etiology of continence restoration.

Primary angiosarcoma of the urinary system is a rare, aggressive endothelial malignancy, with only 113 cases of renal angiosarcoma documented as of 2023. Angiosarcoma of the ureter is a much less common condition. Clinical manifestations commonly include flank pain, hematuria, an abdominal mass, weight loss, fatigue, and dizziness. In rare instances, spontaneous tumour rupture may result in retroperitoneal haemorrhage. Management primarily involves surgical resection, often complemented by adjuvant radiation therapy and chemotherapy. An 88-year-old patient was admitted to the hospital due to weight loss, urine retention and macroscopic hematuria. Initial evaluation with US and CT urography found a tumorous lesion in the pelvic part of the right ureter. PET/CT confirms a hypermetabolic enhancing lesion of the right ureter, with no metastatic lymph nodes or evidence of distant metastases. The patient was indicated for a laparoscopic right-sided nephroureterectomy, and the surgery was completed without complications. Histopathological evaluation confirmed the diagnosis of angiosarcoma, which was classified as grade II according to the FNCLCC classification and staged as pT3N0M0. A month after the surgery, the patient was bleeding from the right internal iliac artery. Embolisation was performed, and stent grafts were inserted. A few days later, the patient died from sepsis. Angiosarcoma within the urinary system is rare. To date, only three cases of angiosarcoma of the ureter have been reported. Cases of angiosarcoma originating in the urinary bladder, kidney or other retroperitoneal structures were reported more frequently. Surgical intervention is the principal therapeutic option, followed by adjuvant therapy. Establishing standardised diagnostic and treatment protocols is crucial to improving patient outcomes, but at this moment, case reports are the only source of information on clinical management.

Nectin4-targeted molecular imaging for precise endoscopic diagnosis and image-guided surgery in bladder cancer.

The primary goals of functional bladder reconstruction following spinal cord injury are to restore voiding power and reduce voiding resistance. The sympathetic nerve is one of the critical constraints within the reduce voiding resistance. In this paper, we sought to generate a three-dimensional (3D) reconstruction of bladder-innervating sympathetic nervous tissue, utilizing histopathological samples derived from male and female cadavers. Bladder tissue samples were collected from four formalin-fixed cadavers (two male, two female). After preparing axial cross-sections of the bladder at 4mm intervals and staining them with Tyrosine-hydroxylase, the distance between the sympathetic nerve site and lumen surface of the bladder, the number of sympathetic nerve sites, and the sympathetic nerve density were measured. The densest sympathetic innervation was observed at the bladder neck (female specimen) and the prostatic urethra (male specimen). For both sexes, nerve density at all levels of the proximal urethra and bladder neck was significantly greater in the posterior region compared to the anterior: in females, 2.51 ± 0.95 vs 1.11 ± 0.21 nerves per mm2 (p < 0.001); in males, 2.88 ± 0.81 vs 1.49 ± 0.56 nerves per mm2 (p < 0.001). The study found no statistically significant differences in nerve-to-lumen distances across multiple anatomical regions in either males or females, despite some numerical variations. In conclusion, novel 3D reconstruction of the bladder sympathetic nerve distribution is feasible, and this approach may refine our current understanding of human bladder innervation. In addition, it presents a sympathetic nerve map of the bladder, which may serve as a preliminary anatomical basis to explore the potential of nerve-targeting radiofrequency therapies for bladder dysfunction following SCI.