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1.
Eur Rev Med Pharmacol Sci ; 28(18): 4290-4297, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39359200

RESUMEN

BACKGROUND: Intravesical bacillus Calmette-Guerin (IVBCG) is considered the most optimal follow-up therapy for high-risk urothelial cancers. Although side effects such as cystitis, hematuria, and low-grade fever are common, they are generally mild. Severe reactions involving the kidneys are extremely rare. Here, we present the case of a 64-year-old male who developed acute renal failure due to acute tubulointerstitial nephritis (ATIN) following the first IVBCG administration. We have also conducted a literature review concerning IVBCG-induced nephritis. CASE REPORT: A 64-year-old male presented to the Nephrology Department with acute kidney injury indicators and hematuria. The patient was suffering from high-grade papillary urothelial carcinoma. Transurethral resection of the bladder tumor was performed twice and followed by one IVBCG administration - two days before the symptoms occurred. The latest follow-up cystoscopy excluded the recurrence of the cancer. Laboratory tests displayed hyperkalemia, decreased glomerular filtration rate (GFR = 4 ml/min/1.73 m2), elevated C-reactive protein, and acute metabolic acidosis. Urinalysis showed proteinuria (900 mg/24 h), leukocyturia, and erythrocyturia (20,402.7 per microliter). Renal ultrasound demonstrated slight bilateral renal enlargement. The patient was identified with acute tubulointerstitial nephritis (ATIN). The treatment involved intravenous methylprednisolone (250 mg three times every two days and then 125 mg four times every two days), fol-lowed by oral methylprednisolone (24 mg and 12 mg daily alternately for a week). Piperacillin and tazobactam, probiotics, and proton pump inhibitors were also administered. Hemodialysis was conducted three times. Two weeks after the admission, a significant improvement was observed: creatinine decreased to 2.04 mg/dl, and GFR increased to 33 ml/min/1.73 m2. The patient was discharged with a recommendation to reduce the dose of glucocorticosteroids and continued in the outpatient clinic. CONCLUSIONS: IVBCG may lead to acute kidney injury due to ATIN. Symptoms may occur as early as after the first IVBCG, contrary to previous reports. Patients should be regularly assessed for potential complications, including creatine level measurement, after each IVBCG treatment.


Asunto(s)
Lesión Renal Aguda , Vacuna BCG , Nefritis Intersticial , Humanos , Masculino , Nefritis Intersticial/inducido químicamente , Nefritis Intersticial/diagnóstico , Persona de Mediana Edad , Vacuna BCG/efectos adversos , Vacuna BCG/administración & dosificación , Lesión Renal Aguda/inducido químicamente , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Administración Intravesical
2.
Investig Clin Urol ; 65(5): 435-441, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39249915

RESUMEN

PURPOSE: In high-risk non-muscle-invasive bladder cancer (NMIBC), intravesical Bacillus Calmette-Guérin (BCG) is the standard adjuvant therapy post-transurethral resection of bladder tumor (TURBT). Intravesical gemcitabine, used as an alternative or second-line therapy amid BCG shortages, lacks outcome studies in the Korean population. MATERIALS AND METHODS: Patients who received weekly intravesical gemcitabine for 6 weeks after TURBT from 2019 to 2022 were retrospectively investigated. Based on the American Urological Association risk classification, patients with high- or very high-risk NMIBC who refused cystectomy were included. Maintenance treatment was performed depending on their risk. Recurrence was defined as histologic confirmation on subsequent cystoscopic biopsies or TURBT. Disease free survival (DFS) was evaluated by the Kaplan-Meier method. RESULTS: The study included 60 patients, comprising 45 high-risk (group 1) patients with a median age of 76 years and 15 very high-risk (group 2) patients with a median age of 68 years. Among them, 28 patients had previously received intravesical BCG. Over a median follow-up of 22 months, recurrence occurred in 31 patients in group 1 and 11 in group 2. The DFS rates of the high-risk group and the very high-risk group were 57.8% versus 40% at 1 year, 20.7% versus 21.3% at 2 years and 20.7% versus 21.3% at 3 years, respectively (p=0.831). Tis stage (p=0.042) and prostatic urethra invasion (p=0.028) were significant predictors of DFS. Cancer-specific mortality rates were 2.2% in group 1 and 6.7% in group 2 (p=0.441). CONCLUSIONS: Similar DFS outcome between high-risk and very high-risk patients were observed based on short-term results in Korea. This finding is crucial for clinical practice; however, studies analyzing more patients and long-term outcomes are needed.


Asunto(s)
Antimetabolitos Antineoplásicos , Desoxicitidina , Gemcitabina , Invasividad Neoplásica , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/cirugía , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Masculino , Administración Intravesical , Anciano , Femenino , República de Corea/epidemiología , Estudios Retrospectivos , Persona de Mediana Edad , Antimetabolitos Antineoplásicos/administración & dosificación , Resultado del Tratamiento , Factores de Tiempo , Anciano de 80 o más Años , Neoplasias Vesicales sin Invasión Muscular
3.
Asian Pac J Cancer Prev ; 25(9): 3173-3177, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39342596

RESUMEN

Backgroundsː The objective of this study was to assess the efficacy of gemcitabine as a treatment option for patients diagnosed with non-muscle invasive bladder cancer (NMIBC) who had previously experienced failure with Bacillus Calmette-Guerin (BCG) therapy in the last year. METHODS: We prospectively enrolled 28 patients with recurrent NMIBC after previous intravesical treatment in the last year who declined or were unsuitable for cystectomy between 2021 and 2023. Gemcitabine at 2,000 mg/100 mL was instilled weekly for 6 weeks. Patients were assessed for response after 8 weeks, with subsequent evaluations scheduled every three months to one year. RESULTS: The findings demonstrated that out of the 28 patients, 20 (71.4%) exhibited a complete response to intravesical gemcitabine treatment, and 8 (28.6%) had no complete response. The average age of the participants was 60.25 years. The study identified significant differences in treatment response based on age but without significant differences based on gender. Furthermore, there was no noteworthy association between tumor stage and grade and treatment response. Moreover, among patients with low-grade tumors, 66.7% achieved a complete response, while 72.7% reached a complete response among those with high-grade tumors. Of the patients who reached a complete response, 28.6% experienced no recurrence during one year of follow-up, and 42.9% developed recurrent disease within one year of treatment initiation. Ten months following treatment, a patient developed muscle-invasive bladder cancer and went on to cystectomy. CONCLUSION: In conclusion, the results suggest that intravesical gemcitabine could represent a feasible choice for NMIBC patients unresponsive to BCG therapy and ineligible for or unwilling to undergo cystectomy.


Asunto(s)
Antimetabolitos Antineoplásicos , Vacuna BCG , Desoxicitidina , Gemcitabina , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Desoxicitidina/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Administración Intravesical , Vacuna BCG/administración & dosificación , Vacuna BCG/uso terapéutico , Anciano , Antimetabolitos Antineoplásicos/uso terapéutico , Antimetabolitos Antineoplásicos/administración & dosificación , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Estudios de Seguimiento , Insuficiencia del Tratamiento , Adyuvantes Inmunológicos/administración & dosificación , Invasividad Neoplásica , Pronóstico , Adulto , Neoplasias Vesicales sin Invasión Muscular
4.
World J Urol ; 42(1): 547, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39331198

RESUMEN

OBJECTIVE: To investigate the impact of ageing on survival outcomes in Bacillus Calmette-Guérin (BCG) treated non-muscle invasive bladder cancer (NMIBC) patients and its synergy with adequate BCG treatment. METHOD: Patients with NMIBC who received BCG treatment from 2001 to 2020 were divided into group 1 (< = 70 years) and group 2 (> 70 years). Overall Survival (OS), Cancer-Specific Survival (CSS), Recurrence-Free Survival (RFS), and Progression-Free Survival (PFS) were analyzed using the Kaplan-Meier method. Multivariable Cox regression analysis was used to adjust potential confounding factors and to estimate Hazard Ratio (HR) and 95% Confidence Interval (CI). Subgroup analysis was performed according to adequate versus inadequate BCG treatment. RESULTS: Overall, 2602 NMIBC patients were included: 1051 (40.4%) and 1551 (59.6%) in groups 1 and 2, respectively. At median follow-up of 11.0 years, group 1 (< = 70 years) was associated with better OS, CSS, and RFS, but not PFS as compared to group 2 (> 70 years). At subgroup analysis, patients in group 1 treated with adequate BCG showed better OS, CSS, RFS, and PFS as compared with inadequate BCG treatment in group 2, while patients in group 2 receiving adequate BCG treatment had 41% less progression than those treated with inadequate BCG from the same group. CONCLUSIONS: Being younger (< = 70 years) was associated with better OS, CSS, and RFS, but not PFS. Older patients (> 70 years) who received adequate BCG treatment had similar PFS as those younger with adequate BCG treatment.


Asunto(s)
Adyuvantes Inmunológicos , Vacuna BCG , Invasividad Neoplásica , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/terapia , Neoplasias de la Vejiga Urinaria/mortalidad , Vacuna BCG/uso terapéutico , Masculino , Anciano , Femenino , Persona de Mediana Edad , Factores de Edad , Resultado del Tratamiento , Estudios Retrospectivos , Adyuvantes Inmunológicos/uso terapéutico , Tasa de Supervivencia , Anciano de 80 o más Años , Administración Intravesical , Neoplasias Vesicales sin Invasión Muscular
5.
BMC Urol ; 24(1): 210, 2024 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-39342212

RESUMEN

BACKGROUND: Bladder cancer continues to be a significant health issue, leading to ongoing research into novel biomarkers and treatment strategies. This study aims to evaluate the potential of serum fibronectin levels and fibronectin gene polymorphisms as biomarkers for predicting the recurrence and treatment response in patients with NMIBC undergoing intravesical BCG therapy. METHODS: Between June 2022 and December 2022, data of 73 patients who applied to the Mersin University Urology Clinic due to NMIBC and were followed and treated in our clinic, receiving intravesical BCG treatment, when necessary, as well as 56 individuals without any malignancy, were prospectively examined. Serum fibronectin levels were measured using the enzyme-linked immunosorbent assay method. PCR testing was applied for the fibronectin gene RS10202709 and RS 35,343,655 gene polymorphisms by using Real-Time PCR. RESULTS: The mean serum fibronectin level in the patient group was 76.794 ± 66.998ng/ml. Simultaneously, it was 50.486 ± 25.156ng/ml in the control group, and these differences in serum fibronectin levels were statistically significant(p = 0.003). Out of the 73 patients included in the study, recurrence of bladder cancer was observed in 53 of them. They were divided into two groups based on the recurrence times: early recurrence and late recurrence. The mean fibronectin level in the early recurrence group was 102 ± 86.1 ng/ml, while it was 44.7 ± 11.8 ng/ml in the late recurrence group. Emphasize the significance of the higher fibronectin levels in the early recurrence group by stating, patients with early recurrence exhibited significantly higher serum fibronectin levels compared to those with late recurrence (p < 0.001), suggesting a potential role for fibronectin as a prognostic biomarker. CONCLUSIONS: The statistically higher concentrations of serum fibronectin levels in patients with bladder cancer observed in our study are a noteworthy finding. These findings suggest that serum fibronectin levels could serve as a valuable prognostic biomarker for early recurrence in NMIBC patients, although their predictive value for BCG treatment response remains limited.


Asunto(s)
Adyuvantes Inmunológicos , Vacuna BCG , Fibronectinas , Invasividad Neoplásica , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/sangre , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genética , Fibronectinas/sangre , Vacuna BCG/uso terapéutico , Vacuna BCG/administración & dosificación , Masculino , Femenino , Administración Intravesical , Persona de Mediana Edad , Anciano , Pronóstico , Adyuvantes Inmunológicos/uso terapéutico , Adyuvantes Inmunológicos/administración & dosificación , Polimorfismo Genético , Estudios Prospectivos , Recurrencia Local de Neoplasia/sangre , Biomarcadores de Tumor/sangre , Neoplasias Vesicales sin Invasión Muscular
6.
Cancer Med ; 13(17): e70149, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39254154

RESUMEN

BACKGROUND: The tumoricidal complex alpha1-oleate targets bladder cancer cells, triggering rapid, apoptosis-like tumor cell death. Clinical effects of alpha1-oleate were recently observed in patients with non-muscle invasive bladder cancer (NMIBC), using a randomized, placebo-controlled study protocol. AIMS: To investigate if there are dose-dependent effects of alpha1-oleate. MATERIALS AND METHODS: Here, patients with NMIBC were treated by intravesical instillation of increasing concentrations of alpha1-oleate (1.7, 8.5, or 17 mM) and the treatment response was defined relative to a placebo group. RESULTS: Strong, dose-dependent anti-tumor effects were detected in alpha1-oleate treated patients for a combination of molecular and clinical indicators; a complete or partial response was detected in 88% of tumors treated with 8.5 mM compared to 47% of tumors treated with 1.7 mM of alpha1-oleate. Uptake of alpha1-oleate by the tumor triggered rapid shedding of tumor cells into the urine and cell death by an apoptosis-like mechanism. RNA sequencing of tissue biopsies confirmed the activation of apoptotic cell death and strong inhibition of cancer gene networks, including bladder cancer related genes. Drug-related side effects were not recorded, except for local irritation at the site of instillation. DISCUSSION AND CONCLUSIONS: These dose-dependent anti-tumor effects of alpha1-oleate are promising and support the potential of alpha1-oleate treatment in patients with NMIBC.


Asunto(s)
Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/genética , Masculino , Femenino , Anciano , Persona de Mediana Edad , Apoptosis/efectos de los fármacos , Resultado del Tratamiento , Relación Dosis-Respuesta a Droga , Administración Intravesical , Antineoplásicos/uso terapéutico , Anciano de 80 o más Años
8.
Can Vet J ; 65(9): 886-893, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39219609

RESUMEN

A 15-month-old spayed female greater Swiss mountain dog was brought to our clinic because of relapsing episodes of urinary tract infection, present since her adoption at 2 mo of age. A diagnosis of chronic bacterial cystitis associated with an invasive, biofilm-forming uropathogenic Escherichia coli was made with bladder-wall histology and fluorescent in situ hybridization analysis. Local treatment with EDTA-tromethamine (EDTA-Tris) infusions along with parenteral cefquinome and prophylactic measures (Type-A proanthocyanidins and probiotics) coincided with clinical and bacterial remission. The dog has been free of clinical signs of urinary tract infection for >4 y. Biofilm-forming uropathogenic E. coli can cause chronic, recurrent cystitis due to low antibiotic efficacy and should be considered in cases of recurrent cystitis in dogs, especially in the absence of identified predisposing factors. This case report describes the diagnostic and therapeutic options that were used to manage a case of this type. Key clinical message: Fluorescent in situ hybridization analysis may be considered in the diagnosis of chronic bacterial cystitis in dogs, and intravesical instillations of EDTA-Tris may be helpful in managing such cases.


Traitement adjuvant intravésical avec de l'EDTA-trométhamine chez un chien présentant une cystite récurrente à Escherichia coli formant des biofilmsUne chienne grand bouvier suisse stérilisée de 15 mois nous a été présentée pour des épisodes d'infection du tractus urinaire récidivants depuis son adoption à l'âge de 2 mois. Une cystite bactérienne chronique associée à un Escherichia coli uropathogène formant des biofilms a été identifiée par l'examen histologique de la paroi vésicale et par hybridation in situ fluorescente. Des instillations intravésicales d'EDTA et trométhamine (EDTA-Tris) en complément d'une antibiothérapie parentérale de courte durée (cefquinome) et de mesures prophylactiques (proanthocyanidines de type A et probiotiques) ont permis une guérison clinique et bactériologique de la cystite pendant plus de 4 ans. Les infections par Escherichia coli formant des biofilms peuvent causer des cystites chroniques récurrentes dues à une faible efficacité des antibiotiques et doivent être incluses dans le diagnostic différentiel des cystites récurrentes chez le chien, particulièrement en l'absence d'autre facteur prédisposant. Ce rapport propose des stratégies diagnostiques et thérapeutiques ayant permis la prise en charge d'un de ces cas.Message clinique clé :L'analyse par hybridation in situ fluorescente peut être envisagé dans le diagnostic de cystite bactérienne chronique chez les chiens, et l'instillation intravésicale d'EDTA-Tris peut être utile dans la gestion de tels cas.(Traduit par les auteurs).


Asunto(s)
Antibacterianos , Biopelículas , Cistitis , Enfermedades de los Perros , Ácido Edético , Infecciones por Escherichia coli , Perros , Animales , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/microbiología , Femenino , Cistitis/veterinaria , Cistitis/tratamiento farmacológico , Cistitis/microbiología , Ácido Edético/uso terapéutico , Ácido Edético/administración & dosificación , Biopelículas/efectos de los fármacos , Infecciones por Escherichia coli/veterinaria , Infecciones por Escherichia coli/tratamiento farmacológico , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Administración Intravesical , Escherichia coli/efectos de los fármacos , Recurrencia
9.
J Nanobiotechnology ; 22(1): 560, 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39272197

RESUMEN

Intravesical therapy (IT) is widely used to tackle various urological diseases. However, its clinical efficacy is decreased by the impermeability of various barriers presented on the bladder luminal surface, including the urinary mucus layer and the densely packed tissue barrier. In this study, we report a mucoadhesive-to-penetrating nanomotors-in-hydrogel system for urothelium-oriented intravesical drug delivery. Upon intravesical instillation, its poloxamer 407 (PLX) hydrogel gelated and adhered to the urothelium to prolong its intravesical retention. The urea afterwards diffused into the hydrogel, thus generating a concentration gradient. Urease-powered membrane nanomotors (UMN) without asymmetric surface engineering could catalyze the urea and migrate down this concentration gradient to deeply and unidirectionally penetrate the urothelial barrier. Moreover, the intravesical hybrid system-delivered gemcitabine could effectively inhibit the bladder tumor growth without inducing any side effect. Therefore, our mucoadhesive-to-penetrating nanomotors-in-hydrogel system could serve as an alternative to IT to meet the clinical need for more efficacious therapeutics for urological diseases.


Asunto(s)
Sistemas de Liberación de Medicamentos , Hidrogeles , Poloxámero , Neoplasias de la Vejiga Urinaria , Urotelio , Urotelio/metabolismo , Animales , Hidrogeles/química , Sistemas de Liberación de Medicamentos/métodos , Administración Intravesical , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/metabolismo , Ratones , Poloxámero/química , Desoxicitidina/análogos & derivados , Desoxicitidina/química , Desoxicitidina/administración & dosificación , Gemcitabina , Vejiga Urinaria/metabolismo , Humanos , Femenino , Línea Celular Tumoral , Adhesividad
10.
World J Urol ; 42(1): 516, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39259376

RESUMEN

PURPOSE: To report the oncological outcomes and the tolerance between 6 instillations and more than 6 cycles of hyperthermic intravesical chemotherapy(HIVEC) in patients with non-muscle invasive bladder cancer(NMIBC). METHODS: This is a multicenter retrospective study from a national database including 9 expert centers. All patients treated with HIVEC between 2016 and 2023 for NMIBC were included. Patients were classified into two groups according to the total number of HIVEC instillations, including induction plus maintenance. Kaplan-Meier curves were computed to present survival outcomes. RESULTS: 261 patients with a median follow-up of 25.5 months were included. 199(76.2%) and 62(23.8%) were treated by 6 and more than 6 cycles of HIVEC, respectively. The 2-years RFS(40.2% vs. 34.4%,p = 0.3) and the 2-years PFS(86% vs. 87%,p = 0.85) were similar between group treated with 6 and more than 6 instillations. 2-years CSS and OS were also similar between both groups. Univariate Cox regression showed no association between the number of bladder instillation and RFS (HR = 1.2 95%CI[0.8-1.84], p = 0.3) or PFS (HR = 0.8 95%CI[0.29-2.02], p = 0.2). In the group treated with more than 6 cycles, 2-years RFS and 2-years PFS were similar between patients who received induction plus maintenance compared to those treated with induction only. Finally, hematuria and urinary burning were significantly higher in the group treated by more than 6 cycles (21% vs. 8.5%(p < 0.01),and 29% vs. 17% (p = 0.03), respectively). Serious side effects(grade ≥ 3) are rare(3.1%) and similar in both groups. CONCLUSIONS: Results show no significant difference in two years RFS, PFS, CSS and OS according to number of instillations received, while toxicity profile seems better in the group receiving six instillations only.


Asunto(s)
Hipertermia Inducida , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Estudios Retrospectivos , Femenino , Masculino , Administración Intravesical , Anciano , Persona de Mediana Edad , Hipertermia Inducida/métodos , Resultado del Tratamiento
12.
Urologie ; 63(10): 977-984, 2024 Oct.
Artículo en Alemán | MEDLINE | ID: mdl-39177781

RESUMEN

Bacillus Calmette-Guérin (BCG) therapy is the standard of care in the treatment of high-risk non-muscle invasive bladder cancer (NMIBC). In the absence of a response to BCG and persistent high-grade disease, cystectomy is recommended depending on the clinical risk. A variety of targeted therapy approaches, which aim at immune- and gene-based molecular targets, such as PD-(L)1 and FGFR, are currently being investigated in randomized studies for BCG-unresponsive NMIBC. Furthermore, novel forms of application for instillation therapy, such as the TAR device, in combination with gemcitabine or erdafitinib are being investigated in clinical trials in order to extend the duration of action of the active substance on the urothelium. Thus, there are now many developments that could make bladder-preserving therapy with comparable survival data possible as an alternative to BCG or in the event of BCG failure. In the future, it will be necessary to clarify how BCG response can be predicted by using molecular markers and how to define risk groups that should primarily be given an alternative therapy to BCG.


Asunto(s)
Adyuvantes Inmunológicos , Vacuna BCG , Invasividad Neoplásica , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Humanos , Vacuna BCG/uso terapéutico , Vacuna BCG/administración & dosificación , Adyuvantes Inmunológicos/uso terapéutico , Adyuvantes Inmunológicos/administración & dosificación , Tratamientos Conservadores del Órgano/métodos , Administración Intravesical , Cistectomía , Neoplasias Vesicales sin Invasión Muscular
13.
Toxins (Basel) ; 16(8)2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39195749

RESUMEN

Neurogenic bladder dysfunction (NB) represents a challenge in pediatric urology. Intravesical botulin toxin-A (BTX-A) bladder injection is part of the armamentarium for the treatment of this condition, usually after failed first-line medical strategies and before the escalation to more invasive options such as neuromodulation or augmented cystoplasty in severe cases. However, there is still a lack of consensus about the appropriate treatment modality for the pediatric population. A review of the last 10 years' research was performed on the PubMed database by two authors. Articles doubly selected and meeting the inclusion criteria were collected and analyzed for their study type, demographics, neurological disease(s) at diagnosis, BTX-A treatment modality and duration, previous treatment, clinical and urodynamic parameters, adverse events, outcomes, and follow-ups. A total of 285 studies were initially selected, 16 of which matched the inclusion criteria. A cohort of 630 patients was treated with BTX-A at a median age of 9.7 years, 40% of which had a diagnosis of myelomeningocele. The results of the selected publications show the overall efficacy and safety of BTX-A injections in children and confirmed BTX-A as a valuable strategy for NB treatment in pediatric population. Nevertheless, up to now, the literature on this topic offers scarce uniformity among the published series and poor protocol standardization.


Asunto(s)
Toxinas Botulínicas Tipo A , Vejiga Urinaria Neurogénica , Humanos , Vejiga Urinaria Neurogénica/tratamiento farmacológico , Toxinas Botulínicas Tipo A/administración & dosificación , Toxinas Botulínicas Tipo A/uso terapéutico , Toxinas Botulínicas Tipo A/efectos adversos , Administración Intravesical , Niño , Fármacos Neuromusculares/administración & dosificación , Fármacos Neuromusculares/uso terapéutico , Resultado del Tratamiento , Adolescente , Vejiga Urinaria/efectos de los fármacos , Vejiga Urinaria/fisiopatología , Preescolar
14.
Expert Opin Pharmacother ; 25(10): 1335-1348, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39104019

RESUMEN

INTRODUCTION: To reduce the risk of disease recurrence and progression of intermediate and high-risk Non-Muscle Invasive Bladder Cancers (NMIBCs), intravesical adjuvant treatment with Bacillus Calmette-Guerin (BCG) represents the standard of care, although up to 50% of patients will eventually recur and up to 20% of them will progress to Muscle Invasive Bladder Cancer (MIBC). Radical Cystectomy (RC) is the treatment of choice in this setting; however, this represents a major and morbid surgery, thus meaning that not all NMIBCs patient could undergo or may refuse this procedure or may refuse. The search for effective bladder sparing strategies in NMIBCs BCG-unresponsive patients is a hot topic in the urologic field. AREAS COVERED: We aimed to review the most important bladder-preserving strategies for BCG unresponsive disease, from those used in the past, even though rarely used nowadays (intravesical chemotherapy with single agents), to current available therapies (e.g. intravesical instillation with Gemcitabine-Docetaxel), and to future upcoming treatments (Oportuzumab Monatox). EXPERT OPINION: At present, bladder-preserving treatments in BCG-unresponsive patients are represented by the use of intravesical instillations, systemic immunotherapies, both with good short-term and modest mid-term efficacy, and numerous clinical trials ongoing, with encouraging initial results, in which patients could be recruited.


Asunto(s)
Vacuna BCG , Invasividad Neoplásica , Neoplasias Vesicales sin Invasión Muscular , Humanos , Adyuvantes Inmunológicos/uso terapéutico , Adyuvantes Inmunológicos/administración & dosificación , Administración Intravesical , Vacuna BCG/uso terapéutico , Tratamiento Conservador , Cistectomía , Progresión de la Enfermedad , Recurrencia Local de Neoplasia/prevención & control , Neoplasias Vesicales sin Invasión Muscular/patología , Neoplasias Vesicales sin Invasión Muscular/terapia
15.
J Exp Clin Cancer Res ; 43(1): 223, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39128990

RESUMEN

BACKGROUND: CRISPR-Cas13a is renowned for its precise and potent RNA editing capabilities in cancer therapy. While various material systems have demonstrated efficacy in supporting CRISPR-Cas13a to execute cellular functions in vitro efficiently and specifically, the development of CRISPR-Cas13a-based therapeutic agents for intravesical instillation in bladder cancer (BCa) remains unexplored. METHODS: In this study, we introduce a CRISPR-Cas13a nanoplatform, which effectively inhibits PDL1 expression following intravesical instillation. This system utilizes a fusion protein CAST, created through the genetic fusion of CRISPR-Cas13 and the transmembrane peptide TAT. CAST acts as a potent transmembrane RNA editor and is assembled with the transepithelial delivery carrier fluorinated chitosan (FCS). Upon intravesical administration into the bladder, the CAST-crRNAa/FCS nanoparticles (NPs) exhibit remarkable transepithelial capabilities, significantly suppressing PDL1 expression in tumor tissues.To augment immune activation within the tumor microenvironment, we integrated a fenbendazole (FBZ) intravesical system (FBZ@BSA/FCS NPs). This system is formulated through BSA encapsulation followed by FCS coating, positioning FBZ as a powerful chemo-immunological agent. RESULTS: In an orthotropic BCa model, the FBZ@BSA/FCS NPs demonstrated pronounced tumor cell apoptosis, synergistically reduced PDL1 expression, and restructured the immune microenvironment. This culminated in an enhanced synergistic intravesical instillation approach for BCa. Consequently, our study unveils a novel RNA editor nanoagent formulation and proposes a potential synergistic therapeutic strategy. This approach significantly bolsters therapeutic efficacy, holding promise for the clinical translation of CRISPR-Cas13-based cancer perfusion treatments.


Asunto(s)
Sistemas CRISPR-Cas , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/terapia , Humanos , Animales , Administración Intravesical , Ratones , Línea Celular Tumoral , Femenino
16.
Front Biosci (Landmark Ed) ; 29(8): 295, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39206898

RESUMEN

While more than four decades have elapsed since intravesical Bacillus Calmette-Guérin (BCG) was first used to manage non-muscle invasive bladder cancer (NMIBC), its precise mechanism of anti-tumor action remains incompletely understood. Besides the classic theory that BCG induces local (within the bladder) innate and adaptive immunity through interaction with multiple immune cells, three new concepts have emerged in the past few years that help explain the variable response to BCG therapy between patients. First, BCG has been found to directly interact and become internalized within cancer cells, inducing them to act as antigen-presenting cells (APCs) for T-cells while releasing multiple cytokines. Second, BCG has a direct cytotoxic effect on cancer cells by inducing apoptosis through caspase-dependent pathways, causing cell cycle arrest, releasing proteases from mitochondria, and inducing reactive oxygen species-mediated cell injury. Third, BCG can increase the expression of programmed death ligand 1 (PD-L1) on both cancer and infiltrating inflammatory cells to impair the cell-mediated immune response. Current data has shown that high-grade recurrence after BCG therapy is related to CD8+ T-cell anergy or 'exhaustion'. High-field cancerization and subsequently higher neoantigen presentation to T-cells are also associated with this anergy. This may explain why BCG therapy stops working after a certain time in many patients. This review summarizes the detailed immunologic reactions associated with BCG therapy and the role of immune cell subsets in this process. Moreover, this improved mechanistic understanding suggests new strategies for enhancing the anti-tumor efficacy of BCG for future clinical benefit.


Asunto(s)
Vacuna BCG , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/inmunología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/terapia , Neoplasias de la Vejiga Urinaria/patología , Humanos , Vacuna BCG/inmunología , Vacuna BCG/uso terapéutico , Vacuna BCG/administración & dosificación , Administración Intravesical , Antígeno B7-H1/inmunología , Antígeno B7-H1/metabolismo , Neoplasias Vesicales sin Invasión Muscular
18.
World J Urol ; 42(1): 405, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38990380

RESUMEN

PURPOSE: To investigate the protective effect of intravesical glucosamine in treating overactive bladder (OAB). METHODS: Ninety-two female Sprague-Dawley (SD) rats were divided into 4 groups i.e. protamine sulfate (PS), N-acetylcysteine (NAC), and glucosamine-treated PS (GPS), and normal saline control (NC) were used. We induced hyperactivity in rats via intravesical infusion of PS and potassium chloride (KCl), whereas the NC group underwent a sustained intravesical saline infusion for 1 h. N-acetylcysteine (NAC), a potential antioxidant as well as anti-inflammatory agent was employed as positive control. Cystometrography (CMG) was then conducted to determine urodynamic parameters, i.e., leak point pressure (LPP, n = 48) and inter-contractile interval, the duration between two voids (ICI, n = 32). RESULTS: LPP was significantly elevated in the GPS group (mean ± SD: 110.9 ± 6.2 mmHg) compared to the NC (81.0 ± 32.5 mmHg), PS (40.3 ± 10.9 mmHg), and NAC group (70.3 ± 19.4 mmHg). The cystometrogram data also reveals a prolonged ICI in the GPS group (241.3 ± 40.2 s) compared to the NC group (216.0 ± 41.7 s), PS group (128.8 ± 23.6 s), and NAC group (193.8 ± 28.3 s). CONCLUSION: This preliminary study implies the ameliorative impact of GPS treatment on OAB in terms of improved urodynamic parameters, including LPP and ICI.


Asunto(s)
Modelos Animales de Enfermedad , Glucosamina , Cloruro de Potasio , Protaminas , Ratas Sprague-Dawley , Vejiga Urinaria Hiperactiva , Animales , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Femenino , Ratas , Administración Intravesical , Glucosamina/farmacología , Glucosamina/uso terapéutico , Glucosamina/administración & dosificación
19.
Int Urogynecol J ; 35(9): 1735-1743, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38958727

RESUMEN

INTRODUCTION AND HYPOTHESIS: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a condition characterized by chronic inflammation that affects the bladder. The study was aimed at evaluating the effectiveness of intravesical platelet-rich plasma (PRP) injections in patients with IC/BPS. METHODS: We conducted a comprehensive search strategy to involve studies that investigate the efficacy of intravesical PRP injections or instillations over different time intervals. Various outcome measures were assessed, including pain scores, functional outcomes, urodynamic parameters, and surface expressions on the urothelium. RESULTS: Our search strategy revealed 1,125 studies. After screening, ten articles met the inclusion criteria. Intravesical PRP significantly reduced the visual analog scale (VAS) compared with baseline scores. Several clinical trials reported significant improvements in the global response rate (GRA), O'Leary-Sant Symptom (OSS) questionnaire, Interstitial Cystitis Symptom Index (ICSI), and Interstitial Cystitis Problem Index (ICPI). Urodynamic parameters such as maximum flow rate (Qmax) and post-voiding residual (PVR) showed significant improvements in some studies. CONCLUSION: The study concluded that intravesical PRP injections could be a promising effective treatment option for IC/BPS patients by their significant ability to reduce pain. However, improvement of urodynamic and functional outcomes is still not clear. Further large comparative trials are still warranted to assess the efficacy of PRP instillation.


Asunto(s)
Cistitis Intersticial , Plasma Rico en Plaquetas , Humanos , Cistitis Intersticial/terapia , Administración Intravesical , Femenino , Resultado del Tratamiento , Dimensión del Dolor
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