PURPOSE: To evaluate intravesical loss of onabolunumtoxinA (onaBTA) during endoscopic injection into the bladder wall for treatment of neurogenic detrusor overactivity (NDO). The intraluminal loss of onaBTA cannot be determined directly, therefore we added methylene blue (MB) to reconstitute onaBTA. Subsequently we used spectrophotometry to determine the total amount of MB in the irrigation fluid, which allowed us to calculate total intraluminal loss of onaBTA. METHODS: The study population was consisted of 48 patients with NDO. The mean age was 36.6±8.9 years. Forty-two patients suffered from NDO due to spinal cord injury and 6 patients suffered from multiple sclerosis. Each patient received 200 units of onaBTA administered by 30 endoscopic injections (1 mL per injection) using a 23-G needle. The entire volume of irrigation fluid was collected and spectrophotometry was used to determine the MB concentration. The total amount of injected onaBTA, total amount of irrigation solution and the known amount of MB used during reconstitution, allowed for the determination of intravesical loss of onaBTA. RESULTS: Forty-five patients were included in the final analysis. The mean volume of irrigation fluid was 603.33±400.14 mL. The mean absorbance was 0.14±0.12 with the mean MB concentration 0.19±0.18 mg/L. The mean calculated loss of onaBTA was 4.14±4.11 units. CONCLUSION: The endoscopic injection of onaBTA marked by MB into the bladder wall is associated with minimal intravesical loss of the agent, representing less than 3% of the administered dose of MB. This may reflect the amount of the onaBTA detected in the irrigation fluid.

• Klíčová slova
• Botulinum toxins, Type A, Intravesical injection, Methylene blue, Spectrophotometry, Urinary bladder, Neurogenic,
• Publikační typ
• časopisecké články MeSH

In patients with urinary bladder carcinoma, the intravesical BCG instillation is widely used. We present two cases of severe pulmonary afflictions developed during this treatment. The possible mechanisms of etiology are discussed and the classification of the intravesical BCG treatment side effects is suggested.

• MeSH
• adjuvancia imunologická aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• aplikace intravezikální MeSH
• BCG vakcína aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• granulom chemicky indukované   MeSH
• karcinom in situ farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory močovodu farmakoterapie   MeSH
• papilom farmakoterapie   MeSH
• pneumonie chemicky indukované   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• adjuvancia imunologická MeSH
• BCG vakcína MeSH

OBJECTIVE: Intravesical administration of bacillus Calmette-Guérin is standard adjuvant treatment of non-muscle invasive bladder cancer. In spite of the fact that this immunotherapy is locoregional, there are still risk of some complications. METHODS: We describe two cases of systemic BCG infection after intravesical administration of BCG vaccine in patients with early stage of bladder cancer. RESULTS: Both patients suffered from systemic BCG infection manifesting as BCG pneumonitis. After standard therapy with antituberculotic agents, both of them fully recovered. CONCLUSION: BCG infection can occur as a rare but potentially serious complication of this treatment procedure. Gravity of this side effect and its specific therapy require prompt and right diagnosis.

• Klíčová slova
• bacillus Calmette-Guérin, bladder cancer, intravesical therapy,
• MeSH
• adjuvancia imunologická škodlivé účinky   aplikace a dávkování   MeSH
• aplikace intravezikální MeSH
• BCG vakcína * škodlivé účinky   aplikace a dávkování   MeSH
• lidé MeSH
• nádory močového měchýře * farmakoterapie   MeSH
• pneumonie chemicky indukované   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• přehledy MeSH
• Názvy látek
• adjuvancia imunologická MeSH
• BCG vakcína * MeSH

OBJECTIVE: To evaluate the impact of adjuvant therapy on oncological outcomes in patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC), as due to the poorly-defined and overlapping diagnostic criteria optimal decision-making remains challenging in these patients. PATIENTS AND METHODS: In this multicentre study, patients treated with transurethral resection of bladder tumour for Ta disease were retrospectively analysed. All patients with low- or high-risk NMIBC were excluded from the analysis. Associations between adjuvant therapy administration with recurrence-free survival (RFS) and progression-free survival (PFS) rates were assessed in Cox regression models. RESULTS: A total of 2206 patients with intermediate-risk NMIBC were included in the analysis. Among them, 1427 patients underwent adjuvant therapy, such as bacille Calmette-Guérin (n = 168), or chemotherapeutic agents, such as mitomycin C or epirubicin (n = 1259), in different regimens up to 1 year. The median (interquartile range) follow-up was 73.3 (38.4-106.9) months. The RFS at 1 and 5 years in patients treated with adjuvant therapy and those without were 72.6% vs 69.5% and 50.8% vs 41.3%, respectively. Adjuvant therapy was associated with better RFS (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.70-0.89, P < 0.001), but not with PFS (P = 0.09). In the subgroup of patients aged ≤70 years with primary, single Ta Grade 2 <3 cm tumours (n = 328), adjuvant therapy was not associated with RFS (HR 0.71, 95% CI 0.50-1.02, P = 0.06). While in the subgroup of patients with at least one risk factor including patient age >70 years, tumour multiplicity, recurrent tumour and tumour size ≥3 cm (n = 1878), adjuvant intravesical therapy was associated with improved RFS (HR 0.78, 95% CI 0.68-0.88, P < 0.001). CONCLUSION: In our study, patients with intermediate-risk NMIBC benefit from adjuvant intravesical therapy in terms of RFS. However, in patients without risk factors, adjuvant intravesical therapy did not result in a clear reduction in the recurrence rate.

• Klíčová slova
• BCG, NMIBC, adjuvant, chemotherapy, intravesical,
• MeSH
• adjuvantní chemoterapie MeSH
• aplikace intravezikální MeSH
• BCG vakcína terapeutické užití   aplikace a dávkování   MeSH
• cystektomie metody   MeSH
• epirubicin aplikace a dávkování   MeSH
• invazivní růst nádoru MeSH
• lidé středního věku MeSH
• lidé MeSH
• mitomycin aplikace a dávkování   terapeutické užití   MeSH
• nádory močového měchýře neinvadující svalovinu MeSH
• nádory močového měchýře * patologie   terapie   farmakoterapie   mortalita   MeSH
• přežití bez známek nemoci MeSH
• retrospektivní studie MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Názvy látek
• BCG vakcína MeSH
• epirubicin MeSH
• mitomycin MeSH

AIM: The objectives of this study were to compare the urodynamic effects of botulinum toxin A (BoNT-A) delivered via intramural injection into the bladder wall to that of intravesical instillation in a rat model of detrusor overactivity and to evaluate the effects of intravesical instillation of BoNT-A in female patients with idiopathic overactive bladder. MATERIALS AND METHODS: Detrusor overactivity was induced in female Wistar rats using partial bladder outflow obstruction. Animals were treated with 5 units (U) of BoNT-A via intramural bladder injection (n = 6) or intravesical instillation (n = 7). Conscious cystometrograms were performed prior to BoNT-A administration and then repeated 7 days and 2 weeks following treatment. In the subsequent pilot clinical study, 16 female patients with overactive bladder refractory to antimuscarinics were treated with 200 units of BoNT-A in 50 mL of 0.9% saline instilled using a 12-F urethral catheter. Treatment outcome was evaluated immediately prior to and 1 month after BoNT-A administration. RESULTS: In the preclinical study, the average intermicturition and threshold pressures, as well as the number and amplitude of non-voiding bladder contractions, decreased significantly in both instillation and injection groups. Micturition pressure decreased significantly only in the intramural injection group. In the pilot clinical study, seven patients reported improvement in symptoms. The average number of incontinence episodes was significantly reduced, and the volume at which the first non-voiding contraction was recorded increased by 52.8%. CONCLUSION: The results of our urodynamic studies support the hypothesis that BoNT-A instilled into the urinary bladder affects bladder sensation.

• MeSH
• aplikace intravezikální MeSH
• botulotoxiny typu A aplikace a dávkování   MeSH
• hyperaktivní močový měchýř farmakoterapie   MeSH
• krysa rodu Rattus MeSH
• lidé středního věku MeSH
• lidé MeSH
• nervosvalové látky aplikace a dávkování   MeSH
• pilotní projekty MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• srovnávací studie MeSH
• Názvy látek
• botulotoxiny typu A MeSH
• nervosvalové látky MeSH

PURPOSE OF REVIEW: To critically analyze the oncological outcomes and safety profile of device-assisted intravesical chemotherapy studies reported in 2021. Studies were considered eligible if they included patients with nonmuscle invasive blood cancer (NMIBC), had a prospective or retrospective design, included at least 10 patients, were published in 2021, and assessed the oncological impact of device-assisted intravesical chemotherapy and/or reported standardized adverse effects (AEs). RECENT FINDINGS: Eight new studies reported oncological outcomes after hyperthermic intravesical chemotherapy (HIVEC). In Bacillus Calmette-Guérin (BCG) naive patients, the reported 2-yr. recurrence-free survival (RFS) ranged from 70.7% to 82.4%, with one study reporting 2 yr. progression free survival (PFS) of 92%. In both BCG naive and BCG refractory patients, the reported 1-yr. RFS ranged from 60.5% to 70% and PFS was 94% in one study. For radiofrequency-induced HIVEC, the reported 5-yr. estimates were 38%for RFS and 91.5%for PFS. Regarding AEs, 10.2% of patients had severe AEs. Six studies reported AEs after HIVEC; the majorities were grade 1-2 AEs. SUMMARY: Data coming from the studies published in the last years provides support for a consolidating role of device-assisted intravesical chemotherapy as a safe and effective alternative first- or second-line adjuvant treatment of patients with NMIBC.

• MeSH
• aplikace intravezikální MeSH
• BCG vakcína MeSH
• invazivní růst nádoru MeSH
• lidé MeSH
• lokální recidiva nádoru MeSH
• nádory močového měchýře * farmakoterapie   MeSH
• prospektivní studie MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• BCG vakcína MeSH

Despite currently used intravesical therapies in non-muscle-invasive bladder cancer (NMIBC), the rate of intravesical recurrence remains very high. We aimed to evaluate the effectiveness of adding nonintravesical interventions to standard intravesical therapies to prevent intravesical recurrence. In April 2024, 3 databases were queried for prospective studies evaluating nonintravesical interventions in addition to standard intravesical therapies for NMIBC (CRD42024490988). The primary outcome was intravesical recurrence-free survival (iRFS). Standard pairwise meta-analyses were performed using hazard ratios (HR) and 95% confidence intervals (95% CI) with a random-effects model. We identified 18 eligible studies (14 RCTs and 4 prospective trials) comprising 4,593 NMIBC patients, which investigated pharmacological interventions (eg, selenium, vitamins, Lactobacillus casei, celecoxib, metformin, mistletoe lectin) and lifestyle modifications (diet). The addition of Lactobacillus casei significantly improved iRFS (HR: 0.50; 95% CI: 0.34-0.73; P < .001). A high western diet pattern significantly worsened iRFS (HR:1.48, 95%CI:1.06-2.06, P = .03). The other nonintravesical interventions were not associated with iRFS. Our comprehensive review of the published literature highlights the need for further research into the efficacy of nonvesical interventions for NMIBC. While Lactobacillus was shown to improve iRFS in 2 RCTs, additional high-quality randomized studies are required to evaluate the effectiveness of other interventions.

• Klíčová slova
• Celecoxib, Diet, Lactobacillus casei, Non-muscle-invasive bladder cancer, Vitamins,
• MeSH
• aplikace intravezikální MeSH
• Lactobacillus casei MeSH
• lidé MeSH
• lokální recidiva nádoru * prevence a kontrola   MeSH
• nádory močového měchýře * terapie   patologie   prevence a kontrola   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• přehledy MeSH
• systematický přehled MeSH

OBJECTIVE: It was hypothesized that increasing the time for which onabotulinum toxin A (OnabotA) is exposed to the urothelium following intravesical instillation will augment its effect. TC-3 is an inert heat-sensitive hydrogel, which creates an intravesical bulk providing a slow release of the embedded drug after instillation. The aim of this study was to evaluate the effect of OnabotA, embedded in inert TC-3 hydrogel, in patients with idiopathic overactive bladder (OAB). METHODS: In total, 39 female patients (age 30-65, average 53.8 years) with OAB symptoms were randomized for the study into four groups, each receiving 50 ml of the following intravesical instillations: Group A, 0.9% NaCl (placebo, n = 11); Group B, TC-3 gel + 200 U OnabotA (n = 9); Group C, TC-3 gel + 200 U OnabotA + dimethyl sulfoxide (DMSO) (n = 10); and Group D, DMSO (n = 9). The parameters were compared before and 1 month after treatment. RESULTS: When comparing parameters using conventional statistical methods (Kruskal-Wallis test), no statistically significant changes were observed within the groups. Comparison of the medians using an analysis based on the mathematical gnostics showed the superiority of the method used in Group B over the other groups in the following parameters: number of urgency grade 3 + 4 episodes/72 h, number of leakage episodes/72 h, Overactive Bladder Questionnaire total score and Patient Perception of Bladder Condition total score. Group D showed its superiority over the other groups in respect to the number of nocturia episodes/72 h. CONCLUSIONS: The results indicate that intravesical instillation of OnabotA, embedded in TC-3 gel, could become an alternative to intramural injection for a well-selected subgroup of patients.

• Klíčová slova
• Intravesical instillation, TC-3 hydrogel, onabotulinum A, overactive bladder, urothelium,
• MeSH
• aplikace intravezikální MeSH
• botulotoxiny typu A aplikace a dávkování   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• hyperaktivní močový měchýř farmakoterapie   MeSH
• inhibitory uvolňování acetylcholinu aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nosiče léků MeSH
• PEG-DMA hydrogel MeSH
• pilotní projekty MeSH
• prospektivní studie MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Názvy látek
• botulotoxiny typu A MeSH
• inhibitory uvolňování acetylcholinu MeSH
• nosiče léků MeSH
• PEG-DMA hydrogel MeSH

CONTEXT: Patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC) may pose a clinical dilemma without an agreed evidence-based decision tree for personalized treatment. OBJECTIVE: To perform a systematic review and network meta-analysis (NMA) to summarize available evidence on the oncologic outcomes of intravesical therapy in patients with intermediate-risk NMIBC. EVIDENCE ACQUISITION: The MEDLINE, EMBASE, and ClinicalTrials.gov databases were searched in October 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Studies were deemed eligible if they reported on oncologic outcomes in patients with intermediate-risk NMIBC treated with transurethral resection of bladder tumor with and without intravesical chemotherapy or bacillus Calmette-Guérin (BCG) immunotherapy. EVIDENCE SYNTHESIS: Twelve studies were included in a qualitative synthesis (systematic review); three were deemed eligible for a quantitative synthesis (NMA). An NMA of five different regimens was conducted for the association of treatment with the 5-yr recurrence risk. Chemotherapy with maintenance was associated with a lower likelihood of 5-yr recurrence than chemotherapy without maintenance (odds ratio [OR] 0.51, 95% credible interval [CI] 0.26-1.03). Immunotherapy, regardless of whether a full- or reduced-dose regimen, was not associated with a significantly lower likelihood of 5-yr recurrence when compared with chemotherapy without maintenance (OR 0.90, 95% CI 0.39-2.11 vs OR 0.93, 95% CI 0.40-2.19). Analysis of the treatment ranking revealed that chemotherapy with maintenance had the lowest 5-yr recurrence risk (P score 0.9666). CONCLUSIONS: Our analysis indicates that chemotherapy with a maintenance regimen confers a superior oncologic benefit in terms of 5-yr recurrence risk compared to chemotherapy without maintenance in patients with intermediate-risk NMIBC. Regardless of the dose regimen, immunotherapy with BCG does not appear to be superior to chemotherapy in patients with intermediate-risk NMIBC in term of disease recurrence. However, owing to the lack of comparative studies, there is an unmet need for well-designed, large-scale trials to validate our findings and generate robust evidence on disease recurrence and progression. PATIENT SUMMARY: A maintenance schedule of chemotherapy reduces the rate of long-term recurrence of bladder cancer that has not invaded the bladder muscle. Chemotherapy inserted directly into the bladder and immunotherapy without maintenance schedules seem to have limited benefit in preventing cancer recurrence.

• Klíčová slova
• Bladder cancer, Intermediate risk, Intravesical therapy, Network meta-analysis, Non–muscle-invasive bladder cancer,
• MeSH
• aplikace intravezikální MeSH
• BCG vakcína terapeutické užití   MeSH
• lidé MeSH
• lokální recidiva nádoru prevence a kontrola   MeSH
• nádory močového měchýře * farmakoterapie   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• síťová metaanalýza MeSH
• systematický přehled MeSH
• Názvy látek
• BCG vakcína MeSH

This study aimed to assess both efficacy and safety outcomes of lowering the dose of BCG compared to intravesical chemotherapies in non-muscle-invasive bladder cancer (NMIBC) patients using a systematic review, meta-analysis, and network meta-analysis approach. A comprehensive literature search was performed through Pubmed®, Web of Science™, and Scopus® in December 2022 to identify randomized controlled trials comparing the oncologic and/or safety outcomes of reduced dose intravesical BCG and/or intravesical chemotherapies according to the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statement. The outcomes of interest were risk of recurrence, progression, treatment-related adverse events, and discontinuation. Overall, 24 studies were eligible for quantitative synthesis. Among 22 studies that adopted induction followed by maintenance intravesical therapy, with reference to the lower-dose BCG, epirubicin was associated with a significantly higher risk of recurrence (Odds ratio [OR]: 2.82, 95% CI: 1.54-5.15), but not other intravesical chemotherapies. There were no significant differences in risk of progression among the intravesical therapies. On the other hand, standard-dose BCG was associated with a higher risk of any AEs (OR: 1.91, 95% CI: 1.07-3.41) but other intravesical chemotherapies had a comparable risk of AEs compared to lower-dose BCG. The discontinuation rate did not significantly differ between lower-dose and standard-dose BCG (OR: 1.40, 95% CI: 0.81-2.43) as well as other intravesical. According to the surface under the cumulative ranking curve, gemcitabine, and standard-dose BCG were preferable to lower-dose BCG in terms of recurrence risk; gemcitabine was also preferable to lower-dose BCG in terms of risk of AEs. In patients with NMIBC, lowering the dose of BCG decreases the risks of AEs and discontinuation rate compared to standard-dose BCG, but there is no difference in these endpoints compared to other intravesical chemotherapies. Standard-dose of BCG is preferred for all intermediate and high-risk NMIBC patients based on oncologic efficacy; however, lower-dose BCG and intravesical chemotherapies, especially gemcitabine, could be considered a reasonable alternative to BCG in selected patients who suffer from significant AEs or in case standard-dose BCG is not available.

• Klíčová slova
• BCG, Instillation, Intravesical, Low dose, Non–muscle-invasive bladder cancer,
• MeSH
• adjuvancia imunologická terapeutické užití   MeSH
• aplikace intravezikální MeSH
• BCG vakcína terapeutické užití   MeSH
• gemcitabin MeSH
• invazivní růst nádoru MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   MeSH
• nádory močového měchýře neinvadující svalovinu * MeSH
• nádory močového měchýře * farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• síťová metaanalýza MeSH
• systematický přehled MeSH
• Názvy látek
• adjuvancia imunologická MeSH
• BCG vakcína MeSH
• gemcitabin MeSH