Botulinum neurotoxin A for overactive bladder treatment: advantages and pitfalls.

INTRODUCTION: Overactive bladder (OAB) syndrome is a special condition characterized by urgency, with or without urinary urge incontinence (UUI), associated to frequency and nocturia, with important consequences on patients' quality of life (QoL). Administered as intradetrusor injections, botulinum neurotoxin type A (BoNT/A) is a new, promising, minimally invasive treatment option for OAB patients, non-compliant to conventional antimuscarinics. The aim of our study was to perform a systematic review of the literature concerning the efficiency and safety of different BoNT/A products in the treatment of OAB. MATERIALS AND METHODS: A thorough PubMed search was performed. After having applied strict inclusion criteria, relevant articles were selected for review. Priority was given to large, multicenter, placebo-controlled trials and systematic reviews. RESULTS: Most of the eligible studies were centered around onabotulinumtoxin A (Botox), with treatment doses ranging from 50 U to 300 U. An increased efficiency of onabotulinumtoxin A was found for both OAB types, clinically resulting in a significant decrease in UUI episodes, improved urodynamic parameters and patient QoL. The most common adverse events were urinary tract infections and an increased post-void residue, with the necessity for clean intermittent self catheterization. Abobotulinumtoxin A (Dysport) obtained similar results, but with a much smaller number of trials available to date. CONCLUSION: Onabotulinumtoxin A is a promising, efficient, minimally invasive approach to OAB patients with official recommendations for both OAB types, offering large perspectives in daily urological practice. Abobotulinumtoxin A revealed similar results to onabotulinumtoxin A, making it a valid therapeutic alternative.

Finite Element Analysis of Normal and Dysplastic Hip Joints in Children.

From a surgical point of view, quantification cannot always be achieved in the developmental deformity in hip joints, but finite element analysis can be a helpful tool to compare normal joint architecture with a dysplastic counterpart. CT scans from the normal right hip of an 8-year-old boy and the dysplastic left hip of a 12-year-old girl were used to construct our geometric models. In a three-dimensional model construction, distinctions were made between the cortical bone, trabecular bone, cartilage, and contact nonlinearities of the hip joint. The mathematical model incorporated the consideration of the linear elastic and isotropic properties of bony tissue in children, separately for the cortical bone, trabecular bone, and articular cartilage. Hexahedral elements were used in Autodesk Inventor software version 2022 ("Ren") for finite element analysis of the two hips in the boundary conditions of the single-leg stance. In the normal hip joint on the cartilaginous surfaces of the acetabulum, we found a kidney-shaped stress distribution in a 471,672 mm2 area. The measured contact pressure values were between 3.0 and 4.3 MPa. In the dysplastic pediatric hip joint on a patch of 205,272 mm2 contact area, the contact pressure values reached 8.5 MPa. Furthermore, the acetabulum/femur head volume ratio was 20% higher in the dysplastic hip joint. We believe that the knowledge gained from the normal and dysplastic pediatric hip joints can be used to develop surgical treatment methods and quantify and compare the efficiency of different surgical treatments used in children with hip dysplasia.

Programmed death ligand-1 (PD-L1) immunohistochemical assessment using the QR1 clone in muscle-invasive urothelial carcinomas: a comparison with reference clones 22C3 and SP263.

Programmed death ligand-1 (PD-L1) immunohistochemical (IHC) status is used to predict which patients with metastatic urothelial carcinoma (UC) will respond to immunotherapy. We aimed to compare QR1(Quartett), 22C3 (Dako), and SP263 (Ventana) detection of PD-L1 expression in muscle-invasive UCs and determine the best scoring algorithm for assessment of PD-L1 expression when using the QR1 clone. Our study included 69 UCs. For SP263 and 22C3, PD-L1-positive tumor cell (TC) and/or immune cell (IC) percentages (TC%/IC%) and the Combined Positive Score (CPS) were assessed, respectively (positivity cut-offs of ≥ 25% and ≥ 10). For QR1, both interpretation systems were evaluated. The concordances between assays were calculated. PD-L1 IHC staining characteristics were comparable between QR1, 22C3, and SP263 in both conventional and variant histology UCs. We demonstrated strong or very strong correlations between clones; the strongest correlation for TCs was between QR1 and SP263 (r = 0.92; p = 0.001) and for ICs was between QR1 and 22C3 (r = 0.85; p = 0.001). Our comparative analysis of the scoring algorithms revealed very good concordances among the three assays (range 0.791-0.878); the highest concordance was between QR1 and SP263 when CPS was used as the scoring algorithm for QR1 (0.878; p < 0.001). Our study is the first to demonstrate that the QR1 clone can be used to evaluate PD-L1 status in UCs, with a very good agreement rate with the reference clones. QR1 appeared to be more similar to the SP263 clone. With regard to the scoring algorithm, when evaluating PD-L1 expression using QR1 clone, CPS performed better compared with the TC%/IC% score.

PD-L1 Expression in Muscle Invasive Urothelial Carcinomas as Assessed via Immunohistochemistry: Correlations with Specific Clinical and Pathological Features, with Emphasis on Prognosis after Radical Cystectomy.

In the present study, we analyzed Programmed Death Ligand-1 (PD-L1) expression in radical cystectomy (RC) specimens from patients with muscle-invasive urothelial carcinoma (UC), in order to assess any correlations with specific clinicopathological features and its potential prognostic value. A multi-institutional study was performed within the departments of urology and pathology at the Mureș County Hospital, Romania, and Centre Hospitalier Lyon Sud, France. Sixty-nine patients with MIBC were included, for whom tumor histology (conventional versus histological variant/differentiation), tumor extension (T), lymph node involvement (N), and distant metastases (M) were recorded. PD-L1 immunostaining was performed using the 22C3 clone and was interpreted using the combined positive score (CPS) as recommended (Dako Agilent, Santa Clara, CA, USA). Positive PD-L1 immunostaining was more prevalent among UCs with squamous differentiation compared to conventional UCs and trended towards an improved OS (p = 0.366). We found the T stage to be a risk factor for poor survival in PD-L1-positive patients (HR 2.9, p = 0.021), along with the N stage in PD-L1-negative patients (HR 1.98, p = 0.007). No other clinicopathological factor was found to be significantly associated with PD-L1 positivity. Thus, we confirm the need for PD-L1 immunostaining prior to initiating immune checkpoint inhibitor therapy for a more accurate assessment of the patients' chances of responding to treatment.

Histopathological and perioperative factors influencing the length of hospital stay and patients' outcome after radical cystectomy for urothelial carcinoma.

INTRODUCTION: Length of hospital stay (LOS) is considered as a key factor in estimating outcomes after radical cystectomy (RC) in urothelial carcinoma (UC) patients. We aimed to assess whether clinical perioperative (age, gender, type of urinary diversion technique) and histopathological factors [UC variant, primary tumor, node, metastasis (pTNM) staging] could be a determining factor for LOS, as well as its influence on overall survival (OS) in a single institution, retrospective cohort study. PATIENTS, MATERIALS AND METHODS: We included a total of 69 UC patients that had RC performed in our Department during November 2011 and October 2018. Regular LOS was considered arbitrarily up to 12 days. All factors were analyzed in relation to LOS, using the chi-square and the Mann-Whitney tests. Impact of LOS on survival was assessed using the Kaplan-Meier and the Cox regression methods. RESULTS: Age was associated to increased LOS (p=0.042), as well as the type of urinary diversion (p=0.003). Patients with complex diversion were found more frequently in the prolonged LOS group (ileal conduit p=0.006, Mainz pouch p=0.15, Camey neobladder p=0.517). Histopathologically, N stage had a significant association to LOS (p=0.044). Survival analysis showed decreased survival in the prolonged LOS group (p=0.653). Cox regression found no influence of LOS (p=0.653), advanced age (p=0.518) or type of urinary diversion on OS. CONCLUSIONS: Advanced age, the complexity of urinary diversion and lymph node involvement were found as associated factors for prolonged LOS in RC patients. The impact of LOS on survival is uncertain, requiring larger, in-depth studies.

Histopathological predictive factors for the overall survival rate in patients with urothelial carcinoma of the bladder treated by radical cystectomy: a Romanian cohort study.

INTRODUCTION: Urothelial carcinoma (UC) variants are considered as having a more aggressive behavior and a more advanced stage at presentation than conventional UC. However, the evidence supporting the role of UC variants on overall survival (OS) is conflicting. We aimed to assess the impact of demographic factors (age at surgery, gender) and tumor characteristics [conventional∕variant UC, associated carcinoma in situ (CIS), associated papillary component, Tumor, Node, Metastasis (TNM) staging, positive surgical margins] on OS in a series of patients treated for UC in our Department. PATIENTS, MATERIALS AND METHODS: We performed a retrospective, cohort study and included 69 UC patients treated by radical cystectomy (RC) in our Department over an eight-year period, with complete follow-up information. Associations of UC variants as well as demographic and morphological factors with OS were assessed using univariable and multivariable Cox analysis. RESULTS: Our data showed that UC variants were statistically significantly associated with the presence of distant metastases (p=0.036) and positive surgical margins (p=0.009), but had no influence on OS (p=0.504). Further on, we demonstrated that age at surgery (p=0.045), tumor stage (p=0.012), lymph node involvement (p=0.009), and presence of positive surgical margins (p=0.002) had a statistically significant influence on OS both by univariable and multivariable Cox analysis. CONCLUSIONS: Age, tumor stage and lymph node involvement, as well as positive surgical margins represent prognostic factors in RC patients. UC variants were more likely to be associated to metastases and positive surgical margins but had no influence on OS.