Ultrasound imaging of male urethral stricture disease: a narrative review of the available evidence, focusing on selected prospective studies.

PURPOSE: To synthetize the current scientific knowledge on the use of ultrasound of the male urethra for evaluation of urethral stricture disease. This review aims to provide a detailed description of the technical aspects of ultrasonography, and provides some indications on clinical applications of it, based on the evidence available from the selected prospective studies. Advantages and limitations of the technique are also provided. METHODS: A comprehensive literature search was performed using the Medline and Cochrane databases on October 2022. The articles were searched using the keywords "sonourethrography", "urethral ultrasound", "urethral stricture" and "SUG". Only human studies and articles in English were included. Articles were screened by two reviewers (M.F. and K.M.). RESULTS: Our literature search reporting on the role of sonourethrography in evaluating urethral strictures resulted in selection of 17 studies, all prospective, even if of limited quality due to the small patients' number (varied from 28 to 113). Nine studies included patients with urethral stricture located in anterior urethra and eight studies included patients regardless of the stricture location. Final analysis was based on selected prospective studies, whose power was limited by the small patients' groups. CONCLUSION: Sonourethrography is a cost-effective and safe technique allowing for a dynamic and three-dimensional urethra assessment. Yet, because of its limited value in detecting posterior urethral strictures, the standard urethrography should remain the basic 'road-map' prior to surgery. It is an operator-dependent technique, which can provide detailed information on the length, location, and extent of spongiofibrosis without risks of exposure to ionizing radiation.

What should be next in lifelong posterior hypospadias: Conclusions from the 2023 ERN eUROGEN and EJP-RD networking meeting.

BACKGROUND: A congenital disease is for life. Posterior hypospadias, the severe form of hypospadias with a penoscrotal, scrotal, or perineal meatus, is a challenging condition with a major impact on lifelong quality of life. AIM: Our network meeting is aimed to identify what is currently missing in the lifelong treatment of posterior hypospadias, to improve care, quality of life, and awareness for these patients. METHODS: The network meeting "Lifelong Posterior Hypospadias" in Utrecht, The Netherlands was granted by the European Joint Programme on Rare Diseases-Networking Support Scheme. There was a combination of interactive sessions (hackathons) and lectures. This paper can be regarded as the last phase of the hackathon. RESULTS: Surgery for hypospadias remains challenging and complications may occur until adulthood. Posterior hypospadias affects sexual function, fertility, and hormonal status. Transitional care from childhood into adulthood is currently insufficiently established. Patients should be more involved in defining desired treatment approach and outcome measures. For optimal outcome evaluation standardization of data collection and registration at European level is necessary. Tissue engineering may provide a solution to the shortage of healthy tissue in posterior hypospadias. For optimal results, cooperation between basic researchers from different centers, as well as involving clinicians and patients is necessary. CONCLUSIONS: To improve outcomes for patients with posterior hypospadias, patient voices should be included and lifelong care by dedicated healthcare professionals guaranteed. Other requirements are joining forces at European level in uniform registration of outcome data and cooperation in basic research.

The immunoreactivity of GLI1 and VEGFA is a potential prognostic factor in kidney renal clear cell carcinoma.

Kidney renal clear cell carcinoma (KIRC) is the most common type of kidney cancer and its pathogenesis is strongly associated with VHL-HIF-VEGF signaling. SHH ligand is the upstream SHH pathway regulator, while GLI1 is its major effector that stimulates as a transcription factor, i.a. expression of VEGFA gene. The aim of present study was to assess the prognostic significance of SHH, GLI1 and VEGFA immunoreactivity in KIRC tissues. The analysis included paired tumor and normal samples from 34 patients with KIRC. The immunoreactivity of SHH, GLI1 and VEGFA proteins was determined by immunohistochemical (IHC) renal tissues staining. The IHC staining results were assessed using the immunoreactive score (IRS) method which takes into account the number of cells showing a positive reaction and the intensity of the reaction. Increased GLI1 protein immunoreactivity was observed in KIRC tissues, especially in early-stage tumors, according to the TNM classification. Elevated expression of the VEGFA protein was noted primarily in high-grade KIRC samples according to the Fuhrman/WHO/ISUP scale. Moreover, a directly proportional correlation was observed between SHH and VEGFA immunoreactivity in TNM 3 + 4 and Fuhrman/ISUP/WHO 3 + 4 tumor tissues as well as in samples of patients with shorter survival. We also observed an association between shorter patient survival as well as increased and decreased immunoreactivity, of the VEGFA and GLI1, respectively. The aforementioned findings suggest that the expression pattern of SHH, GLI1 and VEGFA demonstrates prognostic potential in KIRC.

Pro-Inflammatory Cytokine Gene Expression in Penile Cancer: Preliminary Studies.

Background and Objectives: Penile cancer is a rare neoplasm in developed countries with an incidence of 0.8/100,000 per male inhabitant. Despite the development of personalized medicine and multimodal treatment, the outcome of penile cancer treatment is insufficient. Our study aimed to assess the levels of pro-inflammatory cytokines' mRNA such as interleukin 1-A (encoded by IL1A gene, alias IL-1A), interleukin 1-B (IL1B, IL-1B), interleukin 1 receptor antagonist (IL1RN, IL-1RN), interleukin 6 (IL6, IL-6), transforming growth factor ß1 (TGFB1, TGFß-1), and Interferon-gamma (INFG, INF-γ) in penile cancer tissue and associate them with tumor progression and patient survival. Material and Methods: Skin biopsies from patients suffering from penile cancer (n = 6) and unchanged foreskin from 13 healthy adult males undergoing circumcision due to a short frenulum were obtained. Pro-inflammatory cytokine mRNA levels were quantified through qPCR. Results: We observed higher expression of pro-inflammatory cytokine genes (IL-1A, IL-1B, IL-6, INF-γ, TGF-ß) in penile cancer tissue. The average follow-up period was 48 months (range: 38-54 months), during which only one penile tumor progression was observed However, this was without association with the nature of tumor (patient refused radical treatment). Conclusions: This is the first study to show increased expression of cytokines such as IL-1A, IL-1B, IL-6, INF-γ, and TGF-ß in penile cancer with positive correlation between TNM staging and INF-γ levels in tumor samples (rs = 0.672, p = 0.045), which may be associated with the immunosuppressive role of the tumor environment.

Diverse PSMA expression in primary prostate cancer: reason for negative [68Ga]Ga-PSMA PET/CT scans? Immunohistochemical validation in 40 surgical specimens.

PURPOSE: The purpose of this study was to immunohistochemically validate the primary tumor PSMA expression in prostate cancer (PCa) patients imaged with [68Ga]Ga-PSMA PET/CT prior to surgery, with special consideration of PET-negative cases. METHODS: The study included 40 men with newly diagnosed treatment-naïve PCa imaged with [68Ga]Ga-PSMA I&T PET/CT as part of the diagnostic work-up prior to radical prostatectomy. All primary tumors were routinely stained with H&E. In addition, immunohistochemical staining of PSMA was performed and the immunoreactive score (IRS) was computed as semiquantitative measure. Subsequently, imaging findings were correlated to histopathologic results. RESULTS: Eighty-three percent (33/40) of patients presented focal uptake of [68Ga]Ga-PSMA I&T in the primary tumor in at least one prostate lobe. Among PSMA-PET positive patients, one-third had lymph node metastases (LNM) detected by post-operative histopathology, while in PET negative patients, only 1 out of 7 presented with regional LN involvement; PSMA-avid distant lesions, predominantly in bones, were observed in 15% and 0% of patients, respectively. The median IRS classification of PSMA expression in tumor tissue was 2 (range, 1-3) both in PSMA-PET positive and negative prostate lobes, with significantly different interquartile range: 2-3 vs. 2-2, respectively (p = 0.03). The median volume of PSMA-PET positive tumors was 5.4 mL (0.2-32.9) as compared to 1.6 mL (0.3-18.3) of PET-negative tumors (p < 0.001). There was a significant but weak correlation between SUVmax and percentage of PSMA-positive tumor cells (r = 0.46, p < 0.001). A total of 35/44 (~80%) lobes were positive in PSMA-PET imaging, when a cut-off percentage of PSMA-positive cells was ≥ 90%, while 19/36 (~53%) lobes with < 90% PSMA-positive cells were PSMA-PET negative. CONCLUSION: Positive [68Ga]Ga-PSMA I&T PET/CT scan of primary tumor of PCa results from a combination of factors, such as homogeneity and intensity of PSMA expression, tumor volume and grade, with a cutoff value of ≥ 90% PSMA-positive cells strongly determining PET-positivity. Focal accumulation of [68Ga]Ga-PSMA in the primary tumor may correlate positively with aggressiveness of prostate cancer, harboring higher risk of regional LN involvement and distant metastatic spread.

Comparison of retropubic tension-free vaginal tape inserted on two different height positions.

INTRODUCTION AND HYPOTHESIS: Surgical treatment using the mid-urethral tape has become a gold standard in the treatment of stress urinary incontinence in women. Many urogynecologists use ultrasound during the postoperative follow-up. The aim of this study was to investigate whether the position of the tape in the mid- or distal-urethra could influence the subjective assessment after surgery in 1-month control based on questionnaires of genitourinary symptoms, UDI6-SF and VAS scale. METHODS: A group of 76 patients using a synthetic tension-free retropubic vaginal tape after anti-incontinence surgery was retrospectively included in this study. In a postoperative follow-up, the synthetic tape detection was performed using introital ultrasound, and its position was determined as a quotient T/U (T = distance between the external urethral orifice and the lower edge of the tape, U = urethral length). The patients were divided into two groups of 38 patients: one group with the position of the tape in the distal urethra (T/U ≤ 0.24) and the other group with the tape localised in the mid-urethra (T/U = 0.25-0.37). The correlation between the height of the tape position and the subjective assessment was evaluated in both groups of patients in the 1-month control. RESULTS: No association was found between the height of the tape position in a group of patients after anti-incontinence surgery with a T/U value not exceeding 0.375 and the subjective assessment or the value of Vres. CONCLUSIONS: The height of the tape position, with the T/U not exceeding 0.375, has no impact on the subjective assessment of the surgical anti-incontinence treatment in 1-month control.

Quantitative imaging of the receptor for advanced glycation end-products in prostate cancer.

PURPOSE: Current screening and monitoring of prostate cancer (PCa) is insufficient, producing inaccurate diagnoses. Presence of the receptor for advanced glycation end-products (RAGE) is associated with signature characteristics of PCa development such as cell proliferation, anchorage-independent growth, angiogenesis, migration, invasion, and poor patient survival. Therefore, we developed a preclinical multimodal imaging strategy targeted at RAGE to diagnose and monitor PCa. METHODS: In this work, RAGE-targeted multimodal nanoparticles (64Cu-Cy5-G4-CML) were synthesized and rendered functional for nuclear and optical imaging using previously established methods. The probe's binding affinity and targeting specificity was assessed in androgen-dependent (LNCaP) and androgen-independent (DU145) prostate cancer cells using flow cytometry and confocal microscopy. In vivo PET-CT imaging was used to evaluate RAGE levels in DU145 and LNCaP xenograft models in mice. Then, tumors were excised post-imaging for histological staining and autoradiography to further assess RAGE levels and targeting efficiency of the tracer. Finally, RAGE levels from human PCa samples of varying Gleason Scores were evaluated using Western blot and immunohistochemical staining. RESULTS: PCa cell culture studies confirmed adequate RAGE-targeting with 64Cu-Cy5-G4-CML with KD between 360 and 540 nM as measured by flow cytometry. In vivo PET-CT images of PCa xenografts revealed favorable kinetics, rapid blood clearance, and a non-homogenous, enhanced uptake in tumors, which varied based on cell type and tumor size with mean uptake between 0.5 and 1.4%ID/g. RAGE quantification of human samples confirmed increased RAGE uptake corresponding to increased Gleason scoring. CONCLUSIONS: Our study has shown that RAGE-targeted cancer imaging is feasible and could significantly impact PCa management.

68Ga-PSMA I&T PET/CT for primary staging of prostate cancer.

PURPOSE: The present study is based on a retrospective analysis of Gallium-68 (68Ga)-labelled prostate-specific membrane antigen (68Ga-PSMA I&T) PET/CT performed in newly diagnosed, treatment-naïve prostate cancer (PCa) patients prior to definitive treatment. METHODS: A total of 82 men were included in the study and were imaged with 68Ga-PSMA I&T PET/CT to assess the distribution of PSMA-avid disease for staging purposes (11 with low-risk, 32 with intermediate-risk, and 39 with high-risk PCa). Forty patients (20 with intermediate- and 20 with high-risk disease) underwent subsequent radical prostatectomy with extended pelvic lymph node dissection which allowed for correlation of imaging findings with histopathologic data. RESULTS: PSMA-positive disease was detected in 83% of patients with 66/82 (80.5%) primary tumours being visualized. PSMA-avid lymph nodes were recorded in 17/82 patients (20.7%, 3 with intermediate-risk and 14 with high-risk PCa); distant disease was found in 14/82 subjects (17.1%, 2 with intermediate-risk and 12 with high-risk PCa). No extraprostatic disease was found in low-risk PCa. SUVmax of primary tumours showed a weak but significant correlation with serum PSA values (r = 0.51, p < 0.001) and Gleason scores (GSC; r = 0.35, p = 0.001), respectively. In correlation with histopathology, calculated per-region sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for detection of lymph node metastases were 35.0%, 98.4%, 63.6%, 95.0%, and 93.0%, respectively. CONCLUSIONS: In patients with initial diagnosis of intermediate- and high-risk prostate cancer, 68Ga-PSMA I&T PET/CT emerges as a relevant staging procedure by identifying nodal and/or distant metastases. Due to the low prevalence of extraprostatic disease, its value seems to be limited in low-risk disease.

Male aging as a causative factor of detrimental changes in human conventional semen parameters and sperm DNA integrity.

The effect of male aging on fertility potential is controversial and difficult to predict. The aim of our study was to determine the associations between age, basic semen parameters, and sperm DNA fragmentation (SDF). Comparison of four age-dependent groups (men ≤29 years, 30-35 years, 36-40 years, and >40 years) revealed a significant fall in the basic semen characteristics and sperm genomic integrity with age. Receiver operating characteristic (ROC) analysis confirmed that men >29 years had lower semen quality. In the group of men >29 years, the prevalence of men with abnormal semen parameters was higher, and these men had over a threefold higher odds ratio (OR) for abnormal semen parameters. Next, ROC analysis revealed that a threshold of 18% SDF was optimal for discriminating between men with normal and abnormal standard semen parameters. The prevalence of men with >18% SDF was higher in the group of men >29 years than in men ≤29 years. Older men had an almost twofold higher risk for >18% SDF than younger men. Our results suggest that age >29 years may be a causative factor of detrimental changes in semen quality, which may raise the risk for disorders of male fertility potential.

The Metastasis of Renal Cell Carcinoma to the Urethra and Local Tumor Recurrence.

We present the case of metastasis of renal cell carcinoma to the urethra in a 77-year-old woman who underwent -nephrectomy 6 years ago due to renal cell carcinoma. After 3 years, she returned to the ward due to a small, palpable nodule in the area of the urethra that turned out to be a cancer of the clear cell carcinoma. Despite the resection of the -lesion with negative margins in the pathology examination, a local regrowth in the same area was diagnosed in the MRI 8 months after the first episode of metastasis and was successfully removed. The patient keeps urine properly.

Introital ultrasound in the diagnosis of lower urinary tract symptoms following anti-incontinence surgery using a synthetic midurethral tape.

INTRODUCTION AND HYPOTHESIS: Surgical treatment of stress urinary incontinence in women using a synthetic midurethral tape has become a standard procedure. One of the complications observed postoperatively are lower urinary tract symptoms (LUTS). The aim was to analyze the role of introital ultrasound in the identification of patients at risk for developing LUTS after surgical treatment using synthetic tape. METHODS: A group of 50 patients suffering from LUTS following anti-incontinence surgery using synthetic tape was included in this study. The patients with pelvic organ prolapse and coexisting overactive bladder-wet before surgery were excluded. The control group consisted of 50 patients after the same treatment without any complications and with a good outcome. Tape visualization was performed using introital two-dimensional ultrasound. The assessment of the Tape Index (T/U) enabled us to divide the study group into the two subgroups with the tape index value of 0.375 as a borderline. The correlation between the tape position and the occurrence of LUTS was evaluated using a Chi-squared test. RESULTS: In the group of patients suffering from LUTS, the tape was found to be closer to the bladder neck (the lower edge of the tape was more than 37.5% of the urethral length) and it was statistically significant (Chi-squared = 19.87, p < 0.001). CONCLUSIONS: The tape position in the proximal urethra may have an impact on the postoperative occurrence of LUTS. The simple method of introital ultrasound could allow the identification of patients at risk for the development of LUTS after anti-incontinence surgery using synthetic tape.

Ejaculatory Disorders in Men With Urethral Stricture and Impact of Urethroplasty on the Ejaculatory Function: A Systematic Review.

BACKGROUND: Urethral stricture may disturb both micturition and semen emission. Urethroplasty, despite the restoration of a proper urethral patency, may not eliminate the accompanying ejaculatory dysfunction (EjD). AIM: To investigate the relationship among urethral stricture, urethroplasty, and ejaculatory function. METHODS: For the systematic review, the authors followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. Internet-based bibliographic databases (PubMed and Scopus) were searched to access studies that examined the influence of urethral stricture and urethroplasty on ejaculatory function. OUTCOMES: EjD accompanying urethral stricture, before and after urethroplasty, was evaluated. RESULTS: 20 Studies were included in the final analysis. In total, these studies comprised a population of 1,913 patients, aged between 11-86 years, 1,823 with an anterior urethral stricture and 90 with a posterior one. No randomized trials regarding the topic were found. Patients with urethral stricture typically report poor force of ejaculation, reduced ejaculatory volume, reduced pleasure, or complete failure to ejaculate. The prevalence of pre-operative disorders depends on patients' age and is more severe in the older population. The pre-operative stricture length, location, and type of surgery have no statistically significant influence on post-operative EjD. In some patients, despite a successful urethral reconstruction, problems with ejaculation persist. The improvement in ejaculation after urethroplasty is observed only in younger men. The available data are inconclusive whether the separation of the bulbospongiosus muscle during urethroplasty impairs its later functionality. CLINICAL IMPLICATIONS: Analyzing the available literature on the subject, this review provides knowledge about the possible influence of urethroplasty on ejaculatory function, which may be useful both in the pre-operative patient consultation and in the choice of treatment method. STRENGTHS & LIMITATIONS: The evidence is sufficient to determine effects on health outcomes. However, the strength of evidence is limited by the lack of randomized trials and differences in terms of methodology and analyzed populations, preclusive of conducting the meta-analysis. CONCLUSION: It has not been unequivocally determined which factors related to the stricture or surgery are decisive for post-operative ejaculatory function. The improvement in ejaculation after urethroplasty is observed only in younger men. Kaluzny A, Gibas A, Matuszewski M. Ejaculatory Disorders in Men With Urethral Stricture and Impact of Urethroplasty on the Ejaculatory Function: A Systematic Review. J Sex Med 2018;15:974-981.

[Practical aspects of the use of botulinum toxin in the treatment of idiopathic overactive bladder].

Idiopathic overactive bladder due to its high impact on quality of life and high prevalence is a significant problem in everyday clinical practice. Currently, we do not have medicines that allow patients to be cured completely. Therapy is focused on the elimination or reduction of symptoms. An established position in the treatment of this disease for many years has a botulinum toxin. This therapy is used in patients whose conservative methods have not improved or are not acceptable because of side effects. The therapeutic effect after the injection of bladder detrusor muscle is limited in time and does not occur in all patients. Patients who benefit from this therapy require repeated procedures to reduce the symptoms of the disease. Many authors modify the standard treatment protocol of botulinum toxin in idiopathic overactive bladder in search of better results. The main goal is to improve the efficiency and extend the duration of the drug while reducing side effects. Undoubtedly, the technique of botulinum toxin injection has an effect on the final effect of treatment. The location and depth of punctures, the dose of the drug, preparation of the drug solution, periprocedural management and prophylaxis, and observation of the patient after the procedure are some issues whose modifications in the literature have been studied in order to achieve additional benefits from this therapy. In our work, we discuss the technical and practical aspects of this procedure in the search for the most optimal treatment protocol with the use of botulinum toxin in the treatment of idiopathic overactive bladder.

Gene Expression, DNA Methylation and Prognostic Significance of DNA Repair Genes in Human Bladder Cancer.

BACKGROUND/AIMS: This study investigated the gene expression and DNA methylation of selected DNA repair genes (MBD4, TDG, MLH1, MLH3) and DNMT1 in human bladder cancer in the context of pathophysiological and prognostic significance. METHODS: To determine the relationship between the gene expression pattern, global methylation and promoter methylation status, we performed real-time PCR to quantify the mRNA of selected genes in 50 samples of bladder cancer and adjacent non-cancerous tissue. The methylation status was analyzed by methylation-specific polymerase chain reaction (MSP) or digestion of genomic DNA with a methylation-sensitive restriction enzyme and PCR with gene-specific primers (MSRE-PCR). The global DNA methylation level was measured using the antibody-based 5-mC detection method. RESULTS: The relative levels of mRNA for MBD4, MLH3, and MLH1 were decreased in 28% (14/50), 34% (17/50) and 36% (18/50) of tumor samples, respectively. The MBD4 mRNA expression was decreased in 46% of non-muscle invasive tumors (Ta/T1) compared with 11% found in muscle invasive tumors (T2-T4) (P<0.003). Analysis of mRNA expression for TDG did not show any significant differences between Ta/T1 and T2-T4 tumors. The frequency of increased DNMT1 mRNA expression was higher in T2-T4 (52%) comparing to Ta/T1 (16%). The overall methylation rates in tumor tissue were 18% for MBD4, 25% for MLH1 and there was no evidence of MLH3 promoter methylation. High grade tumors had significantly lower levels of global DNA methylation (P=0.04). There was a significant association between shorter survival and increased expression of DNMT1 mRNA (P=0.002), decreased expression of MLH1 mRNA (P=0.032) and the presence of MLH1 promoter methylation (P=0.006). CONCLUSION: This study highlights the importance of DNA repair pathways and provides the first evidence of the role of MBD4 and MLH3 in bladder cancer. In addition, our findings suggest that DNMT1 mRNA and MLH1 mRNA expression, as well as the status of MLH1 promoter methylation, are attractive prognostic markers in this pathology.

Evaluation of the Treatment of Congenital Penile Curvature Including Psychosexual Assessment.

INTRODUCTION: Penile corporoplasty is a well-established treatment method of congenital penile deviation (CPD). Anatomical results are good with only slight differences between surgical procedures used. The disease however has huge influence on young male quality of life. This issue is not well analyzed in the literature. AIM: The aim of the study was to evaluate quality of life of the patients affected with CPD before and after the surgical treatment METHODS: Study population consisted of 107 patients with CPD referred for surgical management. Patients were evaluated with not only clinical assessment, but also by four questionnaires measuring various aspects of quality of life. They were: Short-Form Medical Outcomes, Sexual Quality of Life Questionnaire for Man, Beck Depression Inventory, and International Index of Erectile Function. RESULTS: Quality of life measurements showed deep decrease in the general quality of life, sexual performance, depression scale, as well as in physical and mental health in men with CPD. All these parameters were restored to normal after the successful surgical treatment with any method. CONCLUSION: CPD deeply decreases the quality of life of the affected men in many aspects. Surgical treatment is able to repair the anatomical deformity and as well as significantly restore the patients' psychosocial well-being.

Isolated Testicular Metastasis of Prostate Cancer after Radical Prostatectomy: Case Report and Literature Review.

Clinical recurrence of prostate cancer manifested as a testicular mass is an extremely rare condition. We report a case of a 58-year-old patient with a testicular tumor who underwent orchiectomy 7 years after radical prostatectomy. The pathology analysis confirmed metastasis from prostate carcinoma. After one year, the patient had no signs of biochemical and clinical recurrence. This argues for considering metastasectomy in such patients.

The effect of sunitinib on the plasma exposure of intravenous paracetamol and its major metabolite: paracetamol glucuronide.

The study aimed to examine the effect of sunitinib on the plasma exposure of intravenous paracetamol and its major metabolite, paracetamol glucuronide. Both drugs share metabolic pathways in the liver, and the drug interactions between sunitinib and paracetamol administered in higher doses were reported. These interactions resulted in hepatotoxicity. The adult New Zealand male rabbits were divided into three groups (6 animals each): rabbits receiving sunitinib and paracetamol (SUN + PC), rabbits receiving sunitinib (SUN), and a control group receiving paracetamol (PC). Sunitinib was administered orally (25 mg) and paracetamol was administrated intravenously (35 mg/kg). Blood samples for sunitinib and SU12662 assays were collected up to 96 h after drug administration and for paracetamol and paracetamol glucuronide up to 300 min after drug administration. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin were analysed before and after drug administration. A number of pharmacokinetic parameters were analysed. There were no differences in the levels of AST, ALT, and bilirubin among the groups at either time point. Significantly higher values of AUC0-t , AUC0-∞ , and C max and lower clearance and volume of distribution of paracetamol were observed in group PC vs. group SUN + PC (p < 0.01). The maximum plasma concentration of paracetamol glucuronide tended to be higher in group PC 213.27 µg/mL (90 % CI 1.06, 1.25; p = 0.0267). Statistically significant differences were revealed for paracetamol glucuronide mean residence time (MRT); MRT was higher in group SUN + PC than in group PC (p = 0.0375). The mean t max of paracetamol glucuronide was similar in both groups: SUN + PC and group PC (15 and 20 min, respectively). The mean t max of sunitinib was different in groups SUN + PC and SUN (10.0 and 7.0, respectively; p = 0.0134). At the studied doses, neither of the drugs, whether administered alone or together, had hepatotoxic effects. The present study was not able to confirm that sunitinib, administered at low doses in conjunction with paracetamol, displays a hepatoprotective effect. Significant differences were observed in some pharmacokinetic parameters of paracetamol.

Identification of a suitable qPCR reference gene in metastatic clear cell renal cell carcinoma.

There is no data on reference gene (RG) selection in metastatic clear-cell renal cell carcinoma (mccRCC) for quantitative PCR (qPCR) data normalization. We aimed at selecting the most stable RG for further determination of new prognostic markers. Thirty-five nonmetastatic and 35 mccRCC patients undergoing radical nephrectomy were included. Paired primary tumor (T, n = 70) and normal (C, n = 70) kidney fragments were collected; from 12 out of 35 mccRCC cases, we also collected metastasized regional lymph nodes and adrenal gland tissues (M, n = 12). After RNA extraction, reverse transcription and qPCR were performed. Samples were divided into four analyzed groups. Fifteen candidate RGs were tested by RefFinder tool and manual statistics. To present the importance of RG selection, TP53 gene expression levels in samples were normalized with the use of RG data. RPL13 gene was the most stable RG in analysis of 35 primary tumor nonmetastatic versus 35 mccRCC samples and matched metastasized T/C/M samples (n = 12, each group). GUSB was the most suitable RG in total 152 samples and in paired T and C (n = 140) kidney samples. Expression of GUSB, RPL13, and the RPL13 + RPLP0 pair were independent of clinical/sample variables. Normalization of TP53 expression levels showed variability of GAPDH and ACTB assays. GUSB or RPL13 assays should be used in mccRCC for qPCR data normalization whereas GAPDH and ACTB assays should be avoided. Prior RG studies should precede each qPCR gene expression study since RG selection is associated with the origin and proportion of specimens.

Initial experience of the Versius robotic system in robot-assisted radical prostatectomy: a study of 58 cases.

Introduction: The study presents the initial outcomes of robot-assisted radical prostatectomies (RARPs) using the Versius robotic system in a urological centre with no prior robotic surgery experience. Material and methods: A retrospective analysis of 58 RARPs was conducted, including patients' parameters as well as Versius system performance. Results: The study involved 58 patients (average age 66.9 years). Median preoperative prostate specific antigen (PSA) was 9.8 ng/ml, with 48% having ISUP grade group ≥ 3 on biopsy and 25.8% showing extraprostatic extension on MRI. Median blood loss was 437 ml, with complications (10.3% Clavien-Dindo grade II and 4 grade III cases). One conversion to open surgery occurred (0.58%). Final pathology revealed 46.5% extraprostatic disease, and 25.8% had positive margins. Post-surgery, 96.5% had undetectable PSA at 6 weeks. Continence rates were 89.7% at 6 weeks, increasing to 91.3% at 12 months. Median catheter duration was 7.9 days, and the hospital stay was 4.5 days. Console time averaged 150.9 minutes, with a median operative time of 213 minutes. The Versius system reported medium priority alarms in 24.1% of operations, including 1266 alarms related to robotic arm clashes and 43 instrument swaps. One bedside unit exchange occurred with no console or robotic system failures. Conclusions: The Versius robotic system can be successfully introduced in a urological centre without prior robotic surgery experience. Our setup and operating room positioning are effective, safe, and reproducible. We encountered and resolved surgical and technical challenges. Further follow-up studies are needed to assess the system's performance.

Penile Buschke-Lowenstein tumor in HCV patient.

Buschke-Löwenstein tumor (BLT), also called giant condyloma acuminatum is a rare clinical manifestation caused by human papillomavirus (HPV), usually type 6 or 11 (90 %). The BLT is described as a tumor with localized aggressiveness, rather slow but destructive and invasive growth of surrounding tissues, benign histology, low metastatic potential, and a high tendency of recurrence. We present the case of a 55-year old non-immunocompetent man, with beige, cauliflower-like papillomae presented on glans penis and coronal sulcus which increased in size for a few weeks. The lesions were surgically removed, while maintaining negative surgical margins and good cosmetic outcomes.