Does the sonic hedgehog signaling pathway play a role in anti-reflux mechanism of bladder in children?

OBJECTIVE: A hedgehog family ligand, namely, sonic hedgehog (SHH), was reported to be important in the development of bladder and ureter smooth muscle. In this prospective study, we aimed to determine protein expression of SHH in resected ureterovesical junction (UVJ) segments of children with vesicoureteral reflux (VUR). MATERIALS AND METHODS: The study group included 19 children; 12 (63%) girls, 7 (37%) boys, who had ureteroneocystostomy operation; 3 (15.7%) right sided, 7 (36.8%) left sided, 9 (47.3%) bilateral, due to primary VUR between years 2015 and 2018. Totally, 28 UVJ segments were examined for Western Blot analysis to determine related protein expression levels. RESULTS: The mean Western blot band area of SHH gene pathway related protein was 3880.69 (2059.55-13941.61) while the mean area of ß-Actin, the house-keeping gene, was 20180.25 (9530.39-26709.75) (p = 0.001). Correlation analyses between grade of reflux and protein expression of SHH gene pathways revealed no significant relation (p = 0.300). When the UV samples were grouped as low- and high-grade reflux and compared in terms of SHH protein expression levels, no statistically significant difference was found between groups (p = 0.818). CONCLUSION: We concluded that SHH signaling molecule which is effective in development of bladder and ureter smooth musculature might also be effective in etiopathology of reflux.

OBJETIVO: Se ha informado que el ligando sonic hedgehog (SHH) es importante en el desarrollo de los músculos lisos de la vejiga y el uréter. Nuestro objetivo fue determinar la expresión proteica de SHH en los segmentos de la unión ureterovesical de niños con reflujo vesicoureteral (RVU). MATERIALES Y MÉTODOS: El grupo de estudio incluyó a 19 niños; 12 (63%) niñas, 7 (37%) niños, que tuvieron operación de ureteroneocistostomía (UNC); 3 (15.7%) derecho, 7 (36.8%) izquierdo, 9 (47.3%) bilateral, por RVU primario entre los años 2015-2018. Se examinaron un total de 28 segmentos de la unión ureterovesical para análisis de transferencia Western para determinar los niveles de expresión de proteínas relacionadas en las muestras. RESULTADOS: El área media de la banda de transferencia Western de la proteína relacionada con la vía del gen SHH fue de 3880.69 (2059.55-13941.61), mientras que el área media de la ß-actina, el gen de limpieza, fue de 20180.25 (9530.39-26709.75) (p = 0.001). Los análisis de correlación entre el grado de reflujo y la expresión de proteínas de las vías del gen SHH no revelaron una relación significativa (p = 0.300). CONCLUSIÓN: Concluimos que la molécula de señalización SHH también podría ser efectiva en la etiopatología del reflujo vesicoureteral.

UNAM-HIMFG Bacterial Lysate Activates the Immune Response and Inhibits Colonization of Bladder of Balb/c Mice Infected with the Uropathogenic CFT073 Escherichia coli Strain.

Urinary tract infections (UTIs) represent a clinical and epidemiological problem of worldwide impact that affects the economy and the emotional state of the patient. Control of the condition is complicated due to multidrug resistance of pathogens associated with the disease. Considering the difficulty in carrying out effective treatment with antimicrobials, it is necessary to propose alternatives that improve the clinical status of the patients. With this purpose, in a previous study, the safety and immunostimulant capacity of a polyvalent lysate designated UNAM-HIMFG prepared with different bacteria isolated during a prospective study of chronic urinary tract infection (CUTI) was evaluated. In this work, using an animal model, results are presented on the immunostimulant and protective activity of the polyvalent UNAM-HIMFG lysate to define its potential use in the control and treatment of CUTI. Female Balb/c mice were infected through the urethra with Escherichia coli CFT073 (UPEC O6:K2:H1) strain; urine samples were collected before the infection and every week for up to 60 days. Once the animals were colonized, sublingual doses of UNAM-HIMFG lysate were administrated. The colonization of the bladder and kidneys was evaluated by culture, and their alterations were assessed using histopathological analysis. On the other hand, the immunostimulant activity of the compound was analyzed by qPCR of spleen mRNA. Uninfected animals receiving UNAM-HIMFG lysate and infected animals administered with the physiological saline solution were used as controls. During this study, the clinical status and evolution of the animals were evaluated. At ninety-six hours after infection, the presence of CFT073 was identified in the urine of infected animals, and then, sublingual administration of UNAM-HIMFG lysate was started every week for 60 days. The urine culture of mice treated with UNAM-HIMFG lysate showed the presence of bacteria for three weeks post-treatment; in contrast, in the untreated animals, positive cultures were observed until the 60th day of this study. The histological analysis of bladder samples from untreated animals showed the presence of chronic inflammation and bacteria in the submucosa, while tissues from mice treated with UNAM-HIMFG lysate did not show alterations. The same analysis of kidney samples of the two groups (treated and untreated) did not present alterations. Immunostimulant activity assays of UNAM-HIMFG lysate showed overexpression of TNF-α and IL-10. Results suggest that the lysate activates the expression of cytokines that inhibit the growth of inoculated bacteria and control the inflammation responsible for tissue damage. In conclusion, UNAM-HIMFG lysate is effective for the treatment and control of CUTIs without the use of antimicrobials.

Effects of Hibiscus sabdariffa supplementation on metabolism and bladder in obese rats.

PURPOSE: Hibiscus sabdariffa (HS) extract has several health benefits and anti-obesogenic effects. The aim of the present study was to assess whether the medicinal properties attributable to HS would prevent or mitigate bladder changes induced by obesity in an experimental model. METHODS: Forty-eight male Wistar rats were submitted to one of four different dietary interventions (12 animals each): G1, standard diet and water (controls); G2, standard diet and HS tea; G3, a palatable high-fat diet and water; and G4, high-fat diet diet and HS tea. The animals were monitored for body weight, feed, and water and tea intake, according to the allocated group. After 16 weeks, the animals were euthanized, and the levels of creatinine, inflammatory cytokines, testosterone, cholesterol, triglycerides, and electrolytes were evaluated. In addition, histopathological analysis of the animals' bladder was performed. RESULTS: Groups receiving HS (G2 and G4) showed decreased levels of the pro-inflammatory cytokine interleukin-1α. HS tea was able to reduce low-density lipoprotein and triglyceride levels in the G2 group compared to other groups. Only in the G3 there was a significant increase in the body weight when it was compared the 12th and 16th weeks. Leptin was shown to be elevated in the groups that received a high-fat diet. There was a significant decrease in the muscle fibers thickness and in the total collagen count in G4 bladder when compared with G1 and G3. CONCLUSIONS: HS has an anti-inflammatory role, can reverse hyperlipidemia in rats, and reduced deleterious effects of obesity on these animals' bladder.

A new nomogram for the evaluation of detrusor underactivity and bladder outlet obstruction in nonneurogenic female patients with lower urinary tract symptoms who undergo urodynamic studies.

INTRODUCTION: Micturition physiology differs in men and women. However, the results in standard urodynamic studies in women with lower urinary tract symptoms (LUTS) were extrapolated from studies in men. Nowadays, the only validated nomogram for females is Solomon-Greenwell's. However, it only evaluated bladder outlet obstruction (BOO) without considering detrusor underactivity (DU). This study aims to create a nomogram that includes an evaluation of DU and BOO in nonneurogenic women and validate it against videourodynamic studies along with other nomograms. MATERIALS AND METHODS: For the first analysis (creation cohort), we included 183 women with LUTS who underwent videourodynamic study between 2022 and 2023. Exclusion criteria were females with neurologic diseases, renal transplantation, and trouble performing the flow-pressure study. Baseline characteristics of the patients, urodynamic parameters, and classifications on different nomograms and indexes were evaluated. A logistic regression found Qmax and PdetQmax as predictors for DU and BOO. The Barco-Castillo nomogram was created by clustering analysis and adjusted by the results of the logistic regression. A second (test) cohort was evaluated from 2023 to 2024, including 142 patients for the validation of the nomogram. A p < 0.05 was considered significant. RESULTS: All urodynamic parameters were compared between both cohorts, with no significant differences. The median age of the creation cohort was 50 years old (interquartile range [IQR] 39-63). All patients had LUTS and a previous standard urodynamic study without a clear diagnosis. The cluster analysis had a p < 0.05 for two groups of BOO (yes/no) and two of DU (yes/no). We created the graph based on the logistic regression results and adjusted it according to the data. The median age of the test cohort was 44 years old (IQR 33.75-59) and had the same indication for the videourodynamic study. The receiver operating characteristic (ROC) curve for BOO showed an accuracy of 85.4% for Barco-Castillo nomogram, 68.5% for Blaivas-Groutz, 58.1% for Solomon-Greenwell, 57.1% for BOOI, and 50% for LinPURR. For DU, accuracy was 80.5% for PIP-1, 80.2% for Barco-Castillo, 76.6% for BCI, and 70.1% for LinPURR. CONCLUSIONS: When evaluating women's urodynamic studies, it is important to focus on female physiology and discourage the use of parameters previously standardized in men. We encourage using the new Barco-Castillo nomogram to determine BOO and DU in women as the currently easiest and more accurate tool.

Isolated bladder training or in combination with other therapies to improve overactive bladder symptoms: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Bladder training (BT), the maintenance of a scheduled voiding regime at gradually adjusted intervals, is a common treatment for overactive bladder (OAB). OBJECTIVES: To assess the effects of isolated BT and/or in combination with other therapies on OAB symptoms. METHODS: A systematic review of eight databases was conducted. After screening titles and abstracts, full texts were retrieved. Cochrane RoB 2 and the GRADE approach were used. RESULTS: Fourteen RCTs were included: they studied isolated BT (n = 11), BT plus drug treatment (DT; n = 5), BT plus intravaginal electrical stimulation (IVES; n = 2), BT plus biofeedback and IVES (n = 1), BT plus pelvic floor muscle training and behavioral therapy (n = 2), BT plus percutaneous tibial nerve stimulation, and BT plus transcutaneous tibial nerve stimulation (n = 1). In a meta-analysis of short-term follow-up data, BT plus IVES resulted in greater improvement in nocturia (mean difference [MD]: 0.89, 95% CI: 0.5, 1.20), urinary incontinence (UI; MD: 1.93, 95% CI: 1.32, 2.55), and quality of life (QoL; MD: 4.87, 95% CI: 2.24, 7.50) than isolated BT, while DT and BT improved UI (MD: 0.58, 95% CI: 0.23, 0.92) more than isolated BT. CONCLUSION: In the short term, BT plus IVES improves the OAB symptoms of nocturia and UI while improving QoL. The limited number of RCTs and heterogeneity among them provide a low level of evidence, making the effect of BT on OAB inconclusive, which suggests that new RCTs should be performed.

An Accessible Nephrectomy and Cystotomy Simulator for Use in Teaching Small Animal Surgery.

The use of simulators in veterinary education has been increasing over the last few years. This is fundamental for surgical classes, as simulators can provide a better learning environment for the students. Two procedures commonly taught in veterinary surgical practical classes are nephrectomy and cystotomy. However, the lack of simulators for use in these classes limits the training options to the use of cadavers, which have a number of associated disadvantages, including the potential for autolysis. The aim of this study was to develop and assess the value of a simple nephrectomy and cystotomy simulator that could replace the use of cadavers in surgical practical classes. The simulator, which represented the abdominal cavity, bladder, kidneys, ureter, vessels and adipose tissue, was constructed by using synthetic materials. To evaluate its usefulness and acceptance by the students, the learning outcomes and student satisfaction, for both the simulator and an ethically sourced dog cadaver, were compared. The students completed a Likert scale questionnaire, and the answers were evaluated by using the Diagnostic Content Validation (DCV) model. The simulator was well accepted by the students, with the best scores achieved for the ureter divulsion and ligation procedures; good results were also recorded for the kidney vessel ligature and urinary bladder suture practice. The scores showed that the simulator provided an acceptable experience during the training process and increased the confidence of the students in performing the procedure.

New species of Myxobolus in potamodromous catfish from the eastern Amazon, Brazil.

The mapará (Hypophthalmus marginatus) is a commercially important fish in the Brazilian Amazon and has been described as a host for numerous myxosporid species. The integrated taxonomy of a new species, Myxobolus mickeyii n. sp., discovered in the urinary bladder of H. marginatus, is undertaken in this study. In 105 specimens of H. marginatus, plasmodia and myxospores were observed in the urinary bladder fluid, the myxospores measuring 20.5 (19.6-21.3) µm in length and 14.0 (13.2-14.9) µm in width. The posterior valves of the spore body were thick, with valvulogenic nuclei, endoplasmic reticulum, and the presence of secretory vesicles. Two elliptical, rounded appendages attached to the valve, containing tubular filaments. The two polar capsules, symmetry, measuring 6.1 (5.9-6.3) µm in length and 4.4 (3.6-6.2) µm in width, with polar tubules of 3 to 5 turns. Phylogenetic analyses of the small subunit ribosomal RNA gene (SSU rDNA) sequencing revealed that M. mickeyii n. sp. is part of a Myxobolidae family clade with freshwater fish of the Siluriformes order, with a genetic distance of 19% to the nearest species. This work contributes to the wide diversity of myxozoans in this host, as other taxa have previously been reported infecting different tissues.

The osmoregulated metabolism of trehalose contributes to production of type 1 fimbriae and bladder colonization by extraintestinal Escherichia coli strain BEN2908.

In Escherichia coli, the disaccharide trehalose can be metabolized as a carbon source or be accumulated as an osmoprotectant under osmotic stress. In hypertonic environments, E. coli accumulates trehalose in the cell by synthesis from glucose mediated by the cytosolic enzymes OtsA and OtsB. Trehalose in the periplasm can be hydrolyzed into glucose by the periplasmic trehalase TreA. We have previously shown that a treA mutant of extraintestinal E. coli strain BEN2908 displayed increased resistance to osmotic stress by 0.6 M urea, and reduced production of type 1 fimbriae, reduced invasion of avian fibroblasts, and decreased bladder colonization in a murine model of urinary tract infection. Since loss of TreA likely results in higher periplasmic trehalose concentrations, we wondered if deletion of otsA and otsB genes, which would lead to decreased internal trehalose concentrations, would reduce resistance to stress by 0.6 M urea and promote type 1 fimbriae production. The BEN2908ΔotsBA mutant was sensitive to osmotic stress by urea, but displayed an even more pronounced reduction in production of type 1 fimbriae, with the consequent reduction in adhesion/invasion of avian fibroblasts and reduced bladder colonization in the murine urinary tract. The BEN2908ΔtreAotsBA mutant also showed a reduction in production of type 1 fimbriae, but in contrast to the ΔotsBA mutant, resisted better than the wild type in the presence of urea. We hypothesize that, in BEN2908, resistance to stress by urea would depend on the levels of periplasmic trehalose, but type 1 fimbriae production would be influenced by the levels of cytosolic trehalose.

BLADDER TRANSPLANTATION: THE NEW FRONTIER IN ABDOMINAL ORGAN TRANSPLANTATION.

Lower urinary tract abnormalities are directly implicated in the etiology of renal dysfunction in 6 to 24% of dialytic patients. These patients require bladder capacity and compliance readjustment before being considered viable candidates for renal transplantation. Vesical augmentation surgeries often involve the use of intestinal segments. Although these procedures can effectively restore bladder capacity and compliance, they present various issues related to maintaining mucous absorption and secretion capacity. Acidosis, recurrent urinary tract infections, and stone formation are extremely common, leading to frequent hospitalizations and graft function loss. Urinary tissue is certainly ideal for these reconstructions; however, bladder augmentation using ureter and renal pelvis are feasible only in a minority of cases. Experimental studies have been conducted to establish the groundwork for vascularized bladder transplantation. Last year, for the first time, this procedure was performed on a brain-dead patient. During this intervention, cystectomy was performed with preservation the vascular pedicle, followed by organ reimplantation. The graft remained viable for a period of 12 hours post-transplant. However, this intervention utilized a robotic platform, making it less reproducible in a multi-organ procurement setting as well as for most transplant centers. Moreover, it is debatable whether the benefits of exclusive bladder transplantation outweigh the risks associated with immunosuppression. For patients needing renal transplantation and requiring lower urinary tract reconstruction, however, utilizing the donor's bladder may offer an attractive alternative, avoiding the inherent complications of enterocystoplasty without increasing immunological risk. Combined kidney and bladder transplantation has the potential to emerge as the next frontier in abdominal organ transplants.

The multidrug resistance protein 4 is expressed and functionally active in isolated bladder from pig.

Multidrug resistance proteins type 4 (MRP4) and 5 (MRP5) play pivotal roles in the transport of cyclic nucleotides in various tissues. However, their specific functions within the lower urinary tract remain relatively unexplored. This study aimed to investigate the effect of pharmacological inhibition of MRPs on cyclic nucleotide signaling in isolated pig bladder. The relaxation responses of the bladder were assessed in the presence of the MRP inhibitor, MK571. The temporal changes in intra- and extracellular levels of cAMP and cGMP in stimulated tissues were determined by mass spectrometry. The gene (ABCC4) and protein (MRP4) expression were also determined. MK571 administration resulted in a modest relaxation effect of approximately 26% in carbachol-precontracted bladders. The relaxation induced by phosphodiesterase inhibitors such as cilostazol, tadalafil, and sildenafil was significantly potentiated in the presence of MK571. In contrast, no significant potentiation was observed in the relaxation induced by substances elevating cAMP levels or stimulators of soluble guanylate cyclase. Following forskolin stimulation, both intracellular and extracellular cAMP concentrations increased by approximately 15.8-fold and 12-fold, respectively. Similarly, stimulation with tadalafil + BAY 41-2272 resulted in roughly 8.2-fold and 3.4-fold increases in intracellular and extracellular cGMP concentrations, respectively. The presence of MK571 reduced only the extracellular levels of cGMP. This study reveals the presence and function of MRP4 transporters within the porcine bladder and paves the way for future research exploring the role of this transporter in both underactive and overactive bladder disorders.NEW & NOTEWORTHY This study investigates the impact of pharmacological inhibition of MRP4 and MRP5 transporters on cyclic nucleotide signaling in isolated pig bladders. MK571 administration led to modest relaxation, with enhanced effects observed in the presence of phosphodiesterase inhibitors. However, substances elevating cAMP levels remained unaffected. MK571 selectively reduced extracellular cGMP levels. These findings shed light on the role of MRP4 transporters in the porcine bladder, opening avenues for further research into bladder disorders.

Step-by-step Peritoneal Bladder Flap Bunching (PBFB) technique: an innovative approach following lymph node dissection in robotic radical prostatectomy.

INTRODUCTION: Robot-assisted radical prostatectomy (RARP) has become a popular surgical approach for localized prostate cancer due to its favorable oncological and functional outcomes, as well as lower morbidity. In cases of intermediate- and high-risk prostate cancer, bilateral pelvic lymphadenectomy (PLND) is recommended as an adjunct to RARP (1-3). Despite its benefits, PLND can lead to surgical complications, with postoperative lymphocele formation being the most common. Most postoperative lymphoceles are clinically insignificant with variable incidence, reaching up to 60% of cases 4. However, a small percentage of patients 2-8% may experience symptomatic lymphoceles (SL), which can cause significant morbidity (4, 5). SURGICAL TECHNIQUE: We perform our RARP technique with our standard approach in all patients (6). After vesicourethral anastomosis a modified PF created to prevent symptomatic lymphocele. We start by suturing the peritoneal fold on the right side, medially to the vas deferens, followed by a similar stitch on the left side to approximate the edges in the midline. A running suture bunches the bladder peritoneum from both sides, passing through the pubic bone periosteum to secure it in place (7). This approach keeps the lateral pelvic gutters open for lymphatic drainage, while allowing fluid drainage from the true pelvis into the abdomen. A pelvic ultrasound was done for all patients at 6 weeks post operative, and additional clinical follow-up was carried out at 3 months following surgery. CONSIDERATIONS: We have demonstrated a modified technique of peritoneal flap (PBFB) with an initial decrease in postoperative symptomatic lymphoceles, the technique is feasible, safe, does not add significant morbidity, and does not require a learning curve.

Changes in lower urinary tract function after minimally invasive nerve-sparing for complete excision of endometriosis: An observational study.

OBJECTIVES: The objective of this paper is to evaluate changes in lower urinary tract symptoms (LUTS), severity of pain and urodynamic parameters after minimally invasive nerve-sparing surgery for patients with endometriosis. METHODS: We analyzed 143 patients undergoing minimally invasive nerve-sparing surgery for endometriosis excision (laparoscopy/robot-assisted). The endometriosis was confirmed by preoperative clinical evaluation, magnetic resonance imaging (MRI) showing at least one lesion deeper than 5 mm, and histological confirmation after laparoscopy. We evaluated three points prior and after surgery: LUTS parameters according to the International Urogynecological Association; urodynamic measures of storage and voiding and the severity of the dyspareunia, dyschezia and dysmenorrhea assessed on a self-reported 11-point numeric rating scale. The Wilcoxon signed rank and McNemar tests were used for statistical analyses (p < 0.05). RESULTS: We observed significant improvements in LUTS after the surgery with postoperative symptom-free probabilities in urgency (64.5%), daytime frequency (38.5%), and dysuria (87.1%). However, slow stream prevalence increased significantly postsurgery (p = 0.022), with a 20.5% risk of asymptomatic patients developing this symptom. Urodynamic responses varied; for instance, maximum cystometric capacity improved significantly (p = 0.004), while postvoiding residual worsened (p = 0.006). Significant worsening in postvoiding residual occurred in women with normal preoperative values (p = 0.002), with a 17.7% risk of normal values becoming abnormal. Compliance or maximum cystometric capacity not considered normal preoperatively showed significant improvements (p < 0.001), but the risk of normal values becoming abnormal after surgery was 14.5%. CONCLUSION: The minimally invasive nerve-sparing surgery for endometriosis excision shows improvement in lower urinary tract symptoms, urodynamics parameters and severity of pain. The majority of patients became asymptomatic in the postoperative period. When compared to the benefits of the patients' surgical treatment, particularly when considering the reduction of pain, the risks of the lower urinary tract treatment seem to be acceptable. The surgical intervention seems to be a safe alternative in patients with endometriosis, although studies with larger samples are needed to confirm these findings.

Clinical and urodynamics outcomes in pediatric primary bladder diverticula: a comparative study.

OBJECTIVE: This study aimed to compare the effects of bladder diverticula smaller than 30 (SD) mm and larger than 30 mm (LD) on bladder functions and urodynamics. MATERIALS AND METHODS: Our retrospective analysis involved a cohort of 40 pediatric patients diagnosed with primary bladder diverticula. RESULTS: The predicted mean bladder capacity (MBC) was 197.7 ± 95.8 mL, whereas the observed MBC was lower at an average of 170.1 ± 79.6 mL. This indicates that the observed MBC was 88.2 ± 12.9% of the predicted value (percentage). The mean diverticula diameter recorded was 33 ± 19.5 mm, and the diverticula to MBC ratio were calculated to be 0.25 ± 0.18. The distribution of urinary tract infections (UTIs) differed significantly between the groups (p < 0.001). Upper UT dilatation was significantly more common in the LD group (60%, n = 12) than in the SD group (15%, n = 3) (p = 0.003). The mean detrusor pressure (P[detrusor]) was significantly higher in the LD group (137.2 ± 24.1 cm H2O) than in the SD group (63.9 ± 5.8 cm H2O) (p = 0.001). In addition, the mean peak flow rate (Qmax) was significantly higher in the SD group (20.7 ± 7.9 mL/s) compared to the LD group (12.7 ± 3.8 mL/s) (p < 0.001). CONCLUSION: Bladder diverticula size is a significant factor in the clinical presentation and management of primary bladder diverticula in pediatric patients.

OBJETIVO: Este estudio tuvo como objetivo comparar los efectos de los divertículos vesicales menores 30 mm (SD), mayores 30 mm (LD) en las funciones y urodinámica de vejiga. MATERIALES Y MÉTODOS: Nuestro análisis retrospectivo involucró una cohorte de 40 pacientes pediátricos diagnosticados con divertículos vesicales primarios. RESULTADOS: Capacidad vesical media predicha (MBC) fue de 197.7 ± 95.8 mL, mientras que MBC observada fue menor con promedio de 170.1 ± 79.6 mL. Esto indica que MBC observada fue del 88.2 ± 12.9% del valor predicho (porcentaje). Diámetro medio de divertículos registrados fue de 33 ± 19.5 mm, y se calculó que relación entre los divertículos y la MBC era de 0.25 ± 0.18. Distribución de infecciones del tracto urinario (ITU) difirió significativamente entre grupos (p < 0.001). Dilatación del tracto urinario superior (UT) fue significativamente más común en grupo LD (60%, n = 12) que en grupo SD (15%, n = 3) (p = 0.003). Presión media del detrusor (P[detrusor]) fue significativamente mayor en grupo LD (137.2 ± 24.1 cm H2O) que en grupo SD (63.9 ± 5.8 cm H2O) (p = 0.001). Además, tasa de flujo máximo promedio (Qmax) fue significativamente mayor en grupo SD (20.7 ± 7.9 mL/seg) en comparación con grupo LD (12.7±3.8 mL/seg) (p < 0.001). CONCLUSIONES: Tamaño de divertículos vesicales es factor significativo en presentación clínica, manejo de divertículos vesicales primarios en pacientes pediátricos.

Macedo ileal catheterizable reservoir adding the scissors maneuver of channel continence: Long term follow-up.

INTRODUCTION: The Macedo ileal catheterizable channel was published in 2000 and consists of an enterocystoplasty with a catheterizable channel that precludes the need of the appendix for the efferent channel. After 25 years of experience with this technique, we decided to review our experience in a select subgroup of cases performed and followed exclusively by the author in a non-teaching hospital facility after the latest modifications of the procedure. MATERIALS AND METHODS: Since 2008, we have refined our technique with the following modifications: small skin transverse incision instead of longitudinal one, with a semicircular flap for further stoma creation in the midline and importantly the scissors maneuver. This maneuver consists of crossing two 2 cm rectus abdominis muscle flaps in the midline to create a neosphincter over the catheterizable channel. Follow-up was defined as the interval between the date of surgery and last visit to the clinic. We defined stoma continence if the dry interval between catheterization was 4hs. Early and late complications were reported as well as the reintervention rate. Additional procedures in association with bladder augmentation were also appointed. RESULTS: We have treated 49 patients. Indications were spinal dysraphism (71.4%), mainly myelomeningocele (65.3%), and others (PUV, exstrophy, anorectal anomalies). Urodynamic evaluation showed bladder pressure of high risk for upper urinary tract involvement (66%), urinary incontinence (24.5%), conversion of incontinent urinary diversion (3.8%), one exstrophy patient not considered (1.9%). Mean age at surgery was 88 months (7.3 years), 21 patients had additional surgeries in addition to Macedo ileal catheterizable channel: Macedo-Malone LACE procedure in 21 patients and bladder neck surgery to improve continence in 5 patients. Urinary stoma continence was 93.9% (46/49) after first surgery, one patient had a serous line valve revised, two patients still leak after 2 h and await revision. Overall enterocystoplasty complications rate was 12.24% and consisted of urinary leakage in 3 cases and channel/stoma stricture in 3 cases. All patients treated for sphincteric deficiency associated with bladder reconstruction are continent per urethra. Urinary stoma revision for stricture was done in 2 cases and consisted on suprafascial approach and reanastomosis, one patient resolved with dilatation of the channel to the stoma. Mean follow up is 100 months (8.3 years). CONCLUSION: We confirmed in a long term follow-up based on face-to-face visits with 8.3 years mean follow-up that the Macedo procedure associated with the scissors maneuver is associated with 93.9% continence of the stoma. Overall complications rate was 12.24%. The cosmetic aspect with a small transverse incision and a midline stoma is another strength of the technique.

Predictors of trimodality therapy in patients with muscle-invasive bladder cancer and effect on survival.

BACKGROUND: Due to its unique advantages over radical cystectomy (RC), trimodality therapy (TMT) is increasingly being utilized by patients diagnosed with muscle-invasive bladder cancer (MIBC) who are not suitable for or refuse RC. However, achieving a satisfactory oncological outcome with TMT requires strict patient selection criteria, and the comparative oncological outcomes of TMT versus RC remain controversial. METHODS: Patients diagnosed with non-metastatic MIBC who underwent TMT or RC were identified from the SEER database during 2004-2015. Before one-to-one propensity score matching (PSM), logistic regression was utilized to identify predictors of TMT. After matching, K-M curves were generated to estimate cancer-specific survival (CSS) and overall survival (OS) with log-rank to test the significance. Finally, we conducted univariate and multivariate Cox analyses to identify independent prognostic factors for CSS and OS. RESULTS: The RC and TMT groups included 5812 and 1260 patients, respectively, and the TMT patients were significantly older than the RC patients. Patients with advanced age, separated, divorced, or widowed (SDW) or unmarried marital status (married as reference), and larger tumor size (< 40 mm as reference) were more likely to be treated with TMT. After PSM, TMT was found to be associated with worse CSS and OS, and it was identified as an independent risk factor for both CSS and OS. CONCLUSION: MIBC patients may not be carefully evaluated prior to TMT, and some non-ideal candidates underwent TMT. TMT resulted in worse CSS and OS in the contemporary era, but these results may be biased. Strict TMT candidate criteria and TMT treatment modality should be required.

Redefining bladder neck dose in low-dose-rate prostate brachytherapy-Can we improve urinary toxicity without impacting disease control?

BACKGROUND: We sought to assess the impact of bladder neck dose (BND) on patient reported urinary toxicity, and feasibility of relative urethral sparing technique in prostate brachytherapy (PB). METHODS AND MATERIALS: We retrospectively identified bladder neck as a point dose on post-implant CT scans in patients treated with 131Cs PB. Urinary symptoms were assessed through EPIC questionnaires. Patient cohorts were identified based on mean BND as a percentage of prescription dose with toxicity assessment at each time point. RESULTS: In our cohort of 542 patients, BND was associated with clinically significant acute urinary symptoms and chronic symptoms, as patients receiving >70% of the prescription dose had significantly worse overall EPIC scores than patients receiving ≤70% of prescription dose. There was no difference in bDFS between patients receiving BND ≤70% (96% bDFS) and >70% (94% bDFS) at a median follow up of 57 months. CONCLUSIONS: BND has a significant impact on both acute and chronic urinary symptoms, with reduced symptoms reported with BND <70% of prescription dose. With a median follow up of 4.7 years, excellent bDFS has thus far been achieved with relative urethral and bladder neck sparing. Utilizing this constraint should improve urinary symptoms without impacting disease control.

The bladder microbiota is not significantly altered by intravesical BCG therapy.

INTRODUCTION: Bladder microbiota dysbiosis has been associated with several urological disorders. However, dysbiosis markers in bladder cancer have not been identified and little is known about the effect of Bacillus Calmette-Guérin (BCG) intravesical therapy on the bladder microbiota. In this study, we compared the bladder microbiota of patients with non-muscle-invasive bladder cancer (NMIBC) undergoing BCG therapy to nononcological controls. We also longitudinally analyzed the impact of BCG therapy on the bladder microbiota of NMIBC patients and addressed whether bladder microbiota is associated with BCG efficacy. METHODS: We collected catheterized urine samples from males with intermediate/high-risk NMIBC (cancer group, n = 32) or benign prostatic hyperplasia (control group, n = 41). The cancer group also provided urine samples during and after BCG induction. We used 16S rRNA gene sequencing to characterize the bladder microbiota. Bladder microbiota parameters, such as diversity and taxonomic composition, were compared between groups and associated with clinicopathological data and BCG efficacy. RESULTS: We observed no significant differences between the bladder microbiota of NMIBC patients and controls. BCG intravesical instillations did not significantly alter the bladder microbiota of NMIBC patients, and BCG was rarely detected in the bladder during and after BCG therapy. Microbiota diversity and overall composition before BCG induction did not influence disease persistence at 3 months. However, higher abundance of Lactobacillus, Streptococcus, and Cutibacterium in the pre-BCG bladder microbiota was associated with BCG effectiveness. CONCLUSION: We were unable to identify markers of bladder microbiota dysbiosis among male NMIBC patients. Moreover, we demonstrated for the first time using longitudinally collected samples that BCG cannot persist in the bladder microbiota nor significantly alter its diversity and composition. The associations found between bladder microbes and BCG efficacy highlight the potential of microbial-based therapeutic and risk-stratification strategies in the intermediate/high-risk NMIBC setting.

International Society of Urological Pathology Consensus Conference on Current Issues in Bladder Cancer. Working Group 4: Molecular Subtypes of Bladder Cancer-Principles of Classification and Emerging Clinical Utility.

Molecular subtyping has been a major focus of bladder cancer research over the past decade. Despite many promising associations with clinical outcomes and treatment response, its clinical impact has yet to be defined. As part of the 2022 International Society of Urological Pathology Conference on Bladder Cancer, we reviewed the current state of the science for bladder cancer molecular subtyping. Our review included several different subtyping systems. We derived the following 7 principles, which summarize progress and challenges of molecular subtyping: (1) bladder cancer has 3 major molecular subtypes: luminal, basal-squamous, and neuroendocrine; (2) signatures of the tumor microenvironment differ greatly among bladder cancers, particularly among luminal tumors; (3) luminal bladder cancers are biologically diverse, and much of this diversity results from differences in features unrelated to the tumor microenvironment, such as FGFR3 signaling and RB1 inactivation; (4) molecular subtype of bladder cancer associates with tumor stage and histomorphology; (5) many subtyping systems include idiosyncrasies, such as subtypes recognized by no other system; (6) there are broad fuzzy borders between molecular subtypes, and cases that fall on these fuzzy borders are often classified differently by different subtyping systems; and (7) when there are histomorphologically distinct regions within a single tumor, the molecular subtypes of these regions are often discordant. We reviewed several use cases for molecular subtyping, highlighting their promise as clinical biomarkers. Finally, we conclude that data are currently insufficient to support the routine use of molecular subtyping to guide bladder cancer management, an opinion shared with the majority of conference attendees. We also conclude that molecular subtype should not be considered an "intrinsic" property of a tumor but should instead be considered the result of a specific laboratory test, performed using a specific testing platform and classification algorithm, validated for a specific clinical application.

COVID-19 impact on bladder cancer treatment / Impacto de COVID-19 en el tratamiento del cáncer de vejiga

Objective: The proposed study aims to present the experience with radical cystectomy from a urology service in a public teaching, non-profit hospital with a medical residency service, during the COVID-19 pandemic period in 2020. Materials and methods: We led a prospective study from February 2020 to October 2020, in which three 2nd-year urology residents, guided by one particular attending physician, performed 20 radical cystectomies in an acute public hospital. Results: Most patients were male, with Muscle-invasive bladder cancer being the major indication in our sample. There was a meaningful and direct correlation between surgical time and length of stay in the Intensive Care Unit. Conclusion: Despite the complexity of the surgery, the execution of radical cystectomies during a pandemic period is feasible, with positive surgical results and complication rates compatible with the current literature

Objetivo: El estudio propuesto tiene como objetivo presentar la experiencia con cistectomía radical desde un servicio de urología en un hospital público docente, sin fines de lucro con el servicio de residencia médica, durante el período de pandemia de COVID-19 en 2020. Materiales y métodos: Realizamos un estudio prospectivo estudio de febrero de 2020 a octubre de 2020, en el que tres residentes de urología de segundo año, guiados por un médico tratante en particular, realizaron 20 cistectomías radicales en un hospital público de agudos. Resultados: La mayoría de los pacientes eran varones, siendo MIBC la principal indicación en nuestra muestra. Hubo una correlación significativa y directa entre el tiempo quirúrgico y la estancia en la Unidad de Cuidados Intensivos. Conclusión: A pesar de la complejidad de la cirugía, la realización de cistectomías radicales en período de pandemia es factible, con resultados quirúrgicos positivos y tasas de complicaciones compatibles con la literatura actua