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PURPOSE: To evaluate the impact of severe acute kidney injury (AKI) on short-term mortality in patients with urosepsis. METHODS: This prospective cohort study evaluated 207 patients with urosepsis. AKI was diagnosed in accordance with the Kidney Disease Improving Global Outcomes criteria, and severe AKI was defined as stage 2 or 3 AKI. Patients were divided into two groups: patients who developed severe AKI (severe AKI group) and patients who did not (control group). The primary endpoint was all-cause mortality within 30 days. The secondary endpoints were 90-day mortality and in-hospital mortality. The exploratory outcomes were the risk factors for severe AKI development. RESULTS: The median patient age was 79 years. Of the 207 patients, 56 (27%) developed severe AKI. The 30-day mortality rate in the severe AKI group was significantly higher than that in the control group (20% vs. 2.0%, respectively; P < 0.001). In the multivariable analysis, performance status and severe AKI were significantly associated with 30-day mortality. The in-hospital mortality and 90-day mortality rates in the severe AKI group were significantly higher than those in the control group (P < 0.001 and P < 0.001, respectively). In the multivariable analysis, age, urolithiasis-related sepsis, lactate values, and disseminated intravascular coagulation were significantly associated with severe AKI development. CONCLUSIONS: Severe AKI was a common complication in patients with urosepsis and contributed to high short-term mortality rates.
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Lesión Renal Aguda , Mortalidad Hospitalaria , Sepsis , Índice de Severidad de la Enfermedad , Infecciones Urinarias , Humanos , Lesión Renal Aguda/mortalidad , Lesión Renal Aguda/etiología , Femenino , Masculino , Sepsis/complicaciones , Sepsis/mortalidad , Anciano , Estudios Prospectivos , Infecciones Urinarias/complicaciones , Infecciones Urinarias/epidemiología , Infecciones Urinarias/mortalidad , Anciano de 80 o más Años , Factores de Tiempo , Estudios de Cohortes , Persona de Mediana Edad , Causas de MuerteRESUMEN
PURPOSE: The International Bladder Cancer Group designated the subgroup that is resistant to Bacillus Calmette-Guérin (BCG) but does not meet the criteria for BCG-unresponsive NMIBC as "BCG-exposed high-risk NMIBC" to guide optimal trial design. We aimed to investigate the treatment patterns and prognoses of patients with BCG-exposed NMIBC. METHODS: We conducted a retrospective chart review of 3283 patients who received intravesical BCG therapy for NMIBC at 14 participating institutions between January 2000 and December 2019. Patients meeting the criteria for BCG-exposed and BCG-unresponsive NMIBC, as defined by the Food and Drug Administration and International Bladder Cancer Group, were selected. To compare treatment patterns and outcomes, high-risk recurrence occurring more than 24 months after the last dose of BCG was defined as "BCG-treated NMIBC." In addition, we compared prognoses between BCG rechallenge and early cystectomy in patients with BCG-exposed NMIBC. RESULTS: Of 3283 patients, 108 (3.3%), 150 (4.6%), and 391 (11.9%) were classified as having BCG-exposed, unresponsive, and treated NMIBC, respectively. BCG-exposed NMIBC demonstrated intermediate survival curves for intravesical recurrence-free and progression-free survival, falling between those of BCG-unresponsive and treated NMIBC. Among patients with BCG-exposed NMIBC, 48 (44.4%) received BCG rechallenge, which was the most commonly performed treatment, and 19 (17.6%) underwent early cystectomy. No significant differences were observed between BCG rechallenge and early cystectomy in patients with BCG-exposed NMIBC. CONCLUSIONS: The newly proposed definition of BCG-exposed NMIBC may serve as a valuable disease subgroup for distinguishing significant gray areas, except in cases of BCG-unresponsive NMIBC.
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Neoplasias Vesicales sin Invasión Muscular , Neoplasias de la Vejiga Urinaria , Humanos , Vacuna BCG/uso terapéutico , Estudios Retrospectivos , Adyuvantes Inmunológicos/uso terapéutico , Pronóstico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Análisis de Datos , Administración Intravesical , Invasividad Neoplásica , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/tratamiento farmacológicoRESUMEN
OBJECTIVE: Several guidelines recommended that second transurethral resection should be performed in patients with diagnosis of high-risk non-muscle-invasive bladder cancer. However, therapeutic benefits of second transurethral resection before bacillus Calmette-Guérin intravesical instillation were conflicting amongst previous studies. We investigated the prognostic impact of second transurethral resection before bacillus Calmette-Guérin instillation in high-risk non-muscle-invasive bladder cancer patients. METHODS: This retrospective study included 3104 non-muscle-invasive bladder cancer patients who received bacillus Calmette-Guérin instillations between 2000 and 2019 at 31 collaborative institutions. Univariate and multivariate Cox proportional hazards models were used to assess the risk factors of intravesical recurrence, disease progression, cancer-specific mortality and overall mortality. RESULTS: In the entire population, patients undergoing second transurethral resection (33%, 1026/3104) had a lower risk of intravesical recurrence on univariate analysis (hazard ratio 0.85, 95% confidence interval 0.73-0.98, P = 0.027), although it did not remain significant on multivariate analysis (hazard ratio 0.90, 95% confidence interval 0.76-1.07, P = 0.24). Subgroup analysis revealed that, in pT1 patients (n = 1487), second transurethral resection was significantly correlated with a lower risk of intravesical recurrence on multivariate analysis (hazard ratio 0.80, 95% confidence interval 0.64-1.00, P = 0.048), but lower risks of disease progression (hazard ratio 0.75, 95% confidence interval 0.56-1.00, P = 0.049), cancer-specific mortality (hazard ratio 0.54, 95% confidence interval 0.35-0.85, P = 0.007) and overall mortality (hazard ratio 0.73, 95% confidence interval 0.55-0.97, P = 0.027) on univariate analysis. CONCLUSIONS: Second transurethral resection confers accurate pathological staging and could be used to safely select good candidates for intravesical bacillus Calmette-Guérin instillation. We further confirm that second transurethral resection could confer an oncological benefit in pT1 bladder cancer patients treated by bacillus Calmette-Guérin instillation, and so strongly recommend second transurethral resection in this patient population.
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Neoplasias Vesicales sin Invasión Muscular , Neoplasias de la Vejiga Urinaria , Humanos , Vacuna BCG/uso terapéutico , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/patología , Administración Intravesical , Progresión de la Enfermedad , Recurrencia Local de Neoplasia/patología , Invasividad Neoplásica/patología , Adyuvantes Inmunológicos/uso terapéuticoRESUMEN
OBJECTIVES: Several systematic reviews and meta-analyses have reported positive relationships between erectile dysfunction (ED) and periodontal disease. However, no study has evaluated the relationships of occlusal support status and the number of remaining teeth with ED. The aim of the present study was to investigate the relationships between ED and the remaining teeth number, periodontal disease, and occlusal support status. METHODS: This study included 400 community-dwelling men. Periodontal health status and occlusal support condition were evaluated using the Community Periodontal Index (CPI) and Eichner classification. Multivariable analyses were performed to evaluate the relationships between ED and the remaining teeth number, periodontal disease, and occlusal support status. RESULTS: The median age was 53 years. Of the 400 men, 333 (83%) were classified into ED group. In univariable analyses, remaining teeth number, CPI score, and Eichner classification were significantly associated with ED. In multivariable analyses, the remaining teeth number (odds ratio [OR]: 0.907, p = 0.114) and CPI score (OR: 0.978, p = 0.864) were not significantly associated with ED, whereas the Eichner classification was independently and significantly associated with ED (OR: 3.490, p = 0.042). CONCLUSIONS: Poor occlusal support status was significantly associated with ED in community-dwelling men, as opposed to remaining teeth number and periodontal health status.
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Disfunción Eréctil , Vida Independiente , Enfermedades Periodontales , Humanos , Masculino , Disfunción Eréctil/epidemiología , Disfunción Eréctil/etiología , Persona de Mediana Edad , Enfermedades Periodontales/complicaciones , Enfermedades Periodontales/epidemiología , Adulto , Vida Independiente/estadística & datos numéricos , Anciano , Índice Periodontal , Pérdida de Diente/epidemiología , Pérdida de Diente/complicaciones , Estudios TransversalesRESUMEN
BACKGROUND: We aimed to evaluate the effects of apalutamide dose reduction on skin-related adverse events (AEs) and castration-resistant prostate cancer (CRPC)-free survival in patients with advanced prostate cancer (PC). METHODS: We retrospectively evaluated 35 patients with nonmetastatic CRPC and 72 patients with treatment-naïve metastatic castration-sensitive PC (mCSPC) who were treated with apalutamide. The primary outcome was the effect of apalutamide dose reduction on skin-related AEs. The secondary outcomes were the effect of apalutamide dose reduction on skin-related AEs in patients with small body size, postskin AE apalutamide discontinuation rate, and CRPC-free survival in patients with mCSPC treated with upfront apalutamide plus androgen deprivation therapy. RESULTS: Of the 107 patients, 65 (60.7%) and 42 (39.3%) were treated with full and reduced doses of apalutamide, respectively. The skin-related AE rate was not significantly different between the groups (55% vs. 43%, p = 0.761). In the group receiving reduced apalutamide dose, the incidence of skin-related AEs was significantly lower in patients with small body sizes (body weight <67 kg and body mass index <24 kg/m2 ) than in those with other body sizes. The postskin AE apalutamide discontinuation rate was significantly differed between patients receiving the full (50%) and reduced (16.7%) doses. In the 72 patients with mCSPC, CRPC-free survival was not significantly different between the full and reduced dose groups. CONCLUSION: Apalutamide dose reduction was not significantly associated with the incidence of skin-related AEs. However, dose reduction in patients with small body sizes may alleviate skin-related AEs without sacrificing oncological outcomes.
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Antagonistas de Receptores Androgénicos , Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Estudios Retrospectivos , Antagonistas de Receptores Androgénicos/uso terapéutico , Antagonistas de Andrógenos/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/patologíaRESUMEN
PURPOSE: We compared the real-world efficacy and medical costs for treatment with upfront docetaxel (DOC) and abiraterone acetate (ABI) up to progression-free survival 2 (PFS2) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). METHODS: This multicenter retrospective study included 340 patients with mHSPC treated with either upfront DOC or upfront ABI between October 2015 and December 2021. We compared PFS2 and medical costs between the two treatment groups. PFS2 was defined as the time from first-line therapy to progression on second-line therapy. Medical costs were estimated using the National Health Insurance drug prices in 2022 in Japan. RESULTS: The upfront DOC and ABI groups included 107 and 233 patients, respectively. The incidence of metastatic castration-resistant PC progression was significantly higher in the upfront DOC group compared with the incidence in the upfront ABI group. However, no significant differences in PFS2 were observed between the two treatment groups. Monthly medical costs per patient were significantly higher in the upfront ABI group ($3453) compared with the costs in the upfront DOC group ($1239, P < 0.001). The cost differences were significantly influenced by differences in the length of androgen deprivation therapy monotherapy (DOC group, 13.4 months vs. ABI group, 0.0 months). CONCLUSIONS: We observed a significant cost benefit in the upfront DOC group in Japanese real-world practice, while the PFS2 rates were similar between the groups. Upfront DOC was a more cost-effective option for men with mHSPC who were eligible for toxic chemotherapy.
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Neoplasias de la Próstata Resistentes a la Castración , Neoplasias de la Próstata , Masculino , Humanos , Docetaxel/uso terapéutico , Neoplasias de la Próstata/patología , Estudios Retrospectivos , Antagonistas de Andrógenos/uso terapéutico , Hormonas/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resultado del TratamientoRESUMEN
OBJECTIVES: To investigate the impact of global aging on the trends in the age of hospitalized patients with a urological cancer diagnosis. METHODS: We retrospectively evaluated a cumulative total of 10 652 cases of referred patients (n = 6637) with a urological disease who were hospitalized in our institution between January 2005 and December 2021. We compared age and the proportion of patients aged ≥80 years among patients who were hospitalized in the urological ward between the period of 2005-2013 and that of 2014-2021. RESULTS: We identified 8168 hospitalized patients with urological cancer. The median age was significantly increased in patients with urological cancer between the periods of 2005-2013 and 2014-2021. The proportion of hospitalized patients with urological cancer aged ≥80 years was significantly increased between the periods of 2005-2013 (9.3%) and 2014-2021 (13.8%). The median ages of the patients with urothelial cancer (UC) and renal cell carcinoma (RCC), but not the median age of those with prostate cancer (PC), were significantly increased between the study periods. The proportion of hospitalized patients with UC, but not the proportions of those with PC and RCC, aged ≥80 years was significantly increased between the study periods. CONCLUSIONS: The age of patients with urological cancer who were hospitalized in the urological ward and the proportion of patients with UC aged ≥80 years significantly increased over the entire study period.
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Carcinoma de Células Renales , Carcinoma de Células Transicionales , Neoplasias Renales , Neoplasias de la Próstata , Neoplasias de la Vejiga Urinaria , Neoplasias Urológicas , Masculino , Humanos , Carcinoma de Células Renales/patología , Estudios Retrospectivos , Neoplasias Urológicas/epidemiología , Neoplasias Urológicas/terapia , Neoplasias Urológicas/patología , Neoplasias Renales/epidemiología , Neoplasias Renales/patologíaRESUMEN
OBJECTIVE: To elucidate the relationship between frailty and lower urinary tract symptoms (LUTS). METHODS: We longitudinally evaluated the temporal changes and the relationships between frailty and LUTS in 247 community-dwelling adults (45 years or older) at baseline and at a 5-year follow-up. We used the Fried phenotype (phenotype-based frailty), 5-item modified frailty index (5i-mFI; comorbidity-based frailty), and frailty discriminant score (comprehensive frailty assessment) to evaluate frailty. LUTS were evaluated using the international prostate symptom score (IPSS) and overactive bladder symptom score (OABSS). RESULTS: We analyzed 247 participants with a median age of 60 years. The median IPSS and OABSS were significantly increased over the 5 years. The proportion of frail individuals did not increase significantly over the 5 years. Of the three frailty assessment tools, the 5i-mFI score significantly increased between 2014 and 2019. Multiple linear regression analyses showed that the 5i-mFI score was significantly associated with the severity of LUTS in 2014 to 5i-mFI in 2019 but not with 5i-mFI in 2014 to the severity of LUTS in 2019. CONCLUSION: The effect of LUTS on frailty might be greater than the effect of frailty on LUTS. Further large-scale studies are needed to elucidate the relationship between LUTS and frailty.
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Fragilidad , Síntomas del Sistema Urinario Inferior , Vejiga Urinaria Hiperactiva , Masculino , Humanos , Fragilidad/complicaciones , Fragilidad/epidemiología , Síntomas del Sistema Urinario Inferior/complicaciones , Síntomas del Sistema Urinario Inferior/epidemiología , Síntomas del Sistema Urinario Inferior/diagnóstico , Vejiga Urinaria Hiperactiva/complicaciones , Vejiga Urinaria Hiperactiva/epidemiología , ComorbilidadRESUMEN
OBJECTIVE: To assess the impact of radical nephroureterectomy on postoperative renal function in patients with upper tract urothelial carcinoma (UTUC). METHODS: We retrospectively evaluated 645 patients with UTUC treated with radical nephroureterectomy between January 2000 and May 2022. The primary outcome was the rate of postoperative estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 . Secondary outcomes included the rate of eGFR decline, identification of factors related to eGFR decline, and the impact of comorbidities (diabetes or cardiovascular disease) on postoperative eGFR at 1 year. RESULTS: The median preoperative and postoperative eGFR levels were 55.6 and 43.3 mL/min/1.73 m2 , respectively. The rate of patients with preoperative and postoperative eGFR ≥60 mL/min/1.73 m2 was 40.9% and 9.0%, respectively. The median decline in eGFR after surgery was 25.1%. The presence of preoperative unilateral hydronephrosis and eGFR <60 mL/min/1.73 m2 was significantly associated with a low decline of postoperative eGFR and poor survival. The impact of the presence of comorbidities on postoperative eGFR at 1 year was significant (p < 0.001). CONCLUSION: Impaired renal function is prevalent in patients with UTUC. The rate of patients with postoperative eGFR ≥60 mL/min/1.73 m2 was 9.0%. The presence of preoperative renal impairment was significantly related to a low decline in postoperative eGFR and poor survival. The presence of comorbidities had a significant effect on eGFR decline 1 year after radical nephroureterectomy.
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Carcinoma de Células Transicionales , Neoplasias Renales , Insuficiencia Renal , Neoplasias Ureterales , Neoplasias de la Vejiga Urinaria , Humanos , Nefroureterectomía , Carcinoma de Células Transicionales/cirugía , Neoplasias de la Vejiga Urinaria/cirugía , Estudios Retrospectivos , Nefrectomía/efectos adversos , Neoplasias Renales/complicaciones , Riñón/cirugía , Riñón/fisiología , Neoplasias Ureterales/cirugíaRESUMEN
Testosterone plays an important role in maintaining both physical and mental function. Age-related testosterone depletion contributes to the development of angina, arteriosclerosis, obesity, metabolic syndrome, dementia, frailty, and a range of other conditions. A condition involving age-related testosterone depletion and the associated clinical symptoms is defined as late-onset hypogonadism (LOH). LOH is treated by testosterone replacement therapy. Indications for testosterone replacement therapy are determined by evaluating symptoms and signs.
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Hipogonadismo , Síndrome Metabólico , Humanos , Hipogonadismo/diagnóstico , Hipogonadismo/tratamiento farmacológico , Testosterona/uso terapéutico , Obesidad , Síndrome Metabólico/diagnóstico , Terapia de Reemplazo de HormonasRESUMEN
Cell surface hyaluronidase transmembrane protein 2 (TMEM2), which also serves as a reportedly functions in malignancy of several solid tumors. However, TMEM2 involvement in bladder cancer (BCa) is unknown. Therefore, we investigate potential changes in expression of TMEM2 during BCa invasion and over the course of the epithelial mesenchymal transition (EMT). Immunohistochemical analysis of 127 clinical specimens revealed that TMEM2 expression changed with pathological stage (pT) and infiltration pattern (INF) and was highest in pTa-pT1 of INFa tumors and significantly lower at stages from pTa-pT1 to pT2 or 3 in INFb or INFc. E-cadherin expression was highest in INFa and lowest in INFc, a pattern comparable to TMEM2 expression. TMEM2 protein expression analysis of BCa cell lines showed that muscle-invasive T24 and YTS-1 cells with low TMEM2 expression exhibited EMT phenotypes in vitro, in contrast to high TMEM2-expressing non-muscle invasive RT4 cells. EMT-induced non-muscle invasive RT4 cells also showed significantly decreased plasma membrane expression of TMEM2. Our data suggested TMEM2 expression is higher in non-invasive cancers, whereas invasive cancer cells are less likely to express TMEM2 during muscle-invasion and "partial EMT".
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Proteínas de la Membrana , Neoplasias de la Vejiga Urinaria , Línea Celular Tumoral , Membrana Celular , Transición Epitelial-Mesenquimal , Humanos , Hialuronoglucosaminidasa/genética , Hialuronoglucosaminidasa/metabolismo , Proteínas de la Membrana/biosíntesis , Proteínas de la Membrana/genética , Músculos/metabolismo , Invasividad Neoplásica , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
OBJECTIVE: To investigate the associations of impaired muscle strength and gait function with the severity of erectile dysfunction (ED) in men undergoing dialysis. METHODS: This cross-sectional study included 63 men undergoing dialysis. ED was assessed with the Sexual Health Inventory for Men (SHIM). Patients were divided into the mild/moderate (SHIM score ≥8) and severe ED groups (SHIM score ≤7). Correlations between variables were analyzed using Spearman's rank correlation coefficient. Multivariable logistic regression analyses were performed to evaluate the impact of impaired grip strength and gait function on the severity of ED. RESULTS: The median age of the study participants was 62 years; all had ED, with 67% having severe ED. Spearman's rank correlation test demonstrated significant negative and positive correlations between gait function and SHIM score (ρ = -0.257, p = 0.042) and between grip strength and SHIM score (ρ = 0.305, p = 0.015), respectively. In the multivariable analyses, impaired grip strength was significantly associated with severe ED (odds ratio [OR]: 4.965, p = 0.017), whereas gait function was not (OR: 3.147, p = 0.064). CONCLUSION: Impaired muscle strength was significantly associated with severe ED, whereas impaired gait function had a marginal effect on this erectile condition.
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Disfunción Eréctil , Estudios Transversales , Disfunción Eréctil/etiología , Marcha , Fuerza de la Mano , Humanos , Masculino , Diálisis RenalRESUMEN
OBJECTIVES: To investigate the association between oxidative stress and erectile dysfunction (ED) in community-dwelling men and men on dialysis. METHODS: This cross-sectional study included 398 community-dwelling men and 42 men on dialysis. Oxidative stress was assessed using 8-hydroxy-2'-deoxyguanosine (8-OHdG). Univariable and multivariable logistic regression analyses were performed to evaluate the association between oxidative stress and ED. RESULTS: Spearman's rank correlation test showed no significant correlation between urine 8-OHdG levels and the 5-Item International Index of Erectile Function scores in community-dwelling men (ρ = -0.005, p = 0.917) and between plasma 8-OHdG levels and the Sexual Health Inventory for Men scores in men on dialysis (ρ = 0.166, p = 0.295). In community-dwelling men, univariable and multivariable analyses revealed that urine 8-OHdG level was not significantly associated with ED (odds ratio [OR]: 1.005, 95% confidence interval [CI]: 0.884-1.144, p = 0.934; OR: 0.930, 95% CI: 0.798-1.084, p = 0.353; respectively). In men on dialysis, univariable analyses revealed that plasma 8-OHdG level was not significantly associated with severe ED (OR: 0.967, 95% CI: 0.876-1.066, p = 0.498). CONCLUSIONS: Oxidative stress was not significantly associated with ED prevalence and severity in community-dwelling men and men on dialysis.
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Disfunción Eréctil , Estudios Transversales , Disfunción Eréctil/epidemiología , Humanos , Vida Independiente , Masculino , Estrés Oxidativo , Diálisis RenalRESUMEN
OBJECTIVES: To evaluate the serologic response to the BNT162b2 messenger ribonucleic acid vaccine in patients with urothelial carcinoma and renal cell carcinoma. METHODS: Between June 2021 and November 2021, we retrospectively evaluated blood samples from 60 healthy controls (control group), 57 patients with urothelial carcinoma, and 28 patients with renal cell carcinoma who had received two doses of the BNT162b2 vaccine at Hirosaki University Hospital. We determined the immunoglobulin G antibody titers against the severe acute respiratory syndrome coronavirus 2 spike receptor-binding domain. Seropositivity was defined as ≥15 U/mL. We investigate factors associated with antibody titers and seropositivity in the patients with urothelial carcinoma and renal cell carcinoma. RESULTS: Antibody titers in the control, urothelial carcinoma, and renal cell carcinoma groups were 813, 431, and 500 U/mL, respectively. Seropositivity was 100%, 90%, and 96% in the control, urothelial carcinoma, and renal cell carcinoma groups, respectively. Of the 85 patients, 37 of 57 (65%) and 21 of 28 (75%) were actively undergoing anticancer treatment for urothelial carcinoma and renal cell carcinoma, respectively. Anti-severe acute respiratory syndrome coronavirus 2 spike immunoglobulin G antibody titers and seropositivity was not significantly different between the patients with urothelial carcinoma and renal cell carcinoma. Anti-severe acute respiratory syndrome coronavirus 2 spike immunoglobulin G antibody titers were not significantly associated with active anticancer therapy or steroid treatment for immune-related adverse events. Univariable logistic regression analysis revealed that older age and metastatic disease were significantly and negatively associated with seropositivity. CONCLUSIONS: Patients with urothelial carcinoma or renal cell carcinoma exhibited an adequate antibody response to the BNT162b2 vaccine. Active anticancer therapy was not significantly associated with seropositivity following vaccination with severe acute respiratory syndrome coronavirus 2 BNT162b2 in patients with urothelial carcinoma and renal cell carcinoma.
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COVID-19 , Carcinoma de Células Renales , Carcinoma de Células Transicionales , Neoplasias Renales , Neoplasias de la Vejiga Urinaria , Anticuerpos Antivirales , Vacuna BNT162 , COVID-19/prevención & control , Vacunas contra la COVID-19 , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Transicionales/tratamiento farmacológico , Humanos , Inmunoglobulina G , Neoplasias Renales/tratamiento farmacológico , Estudios Retrospectivos , SARS-CoV-2 , Neoplasias de la Vejiga Urinaria/tratamiento farmacológicoRESUMEN
OBJECTIVES: To investigate whether a single intravesical instillation of chemotherapy is associated with improved oncological outcomes in patients with high-risk non-muscle-invasive bladder cancer who receive adjuvant induction bacillus Calmette-Guérin therapy. METHODS: This multi-institutional retrospective study included 205 patients with high-risk non-muscle-invasive bladder cancer who received adjuvant induction bacillus Calmette-Guérin therapy. Patients were divided into two groups: those who received the combined therapy of a single instillation of chemotherapy plus subsequent adjuvant induction bacillus Calmette-Guérin therapy (combined therapy group), and those who received adjuvant induction bacillus Calmette-Guérin therapy alone (bacillus Calmette-Guérin monotherapy group). Multivariable analyses using the inverse probability of treatment weighting method and Fine-Gray competing risk regression models were performed to evaluate the impact of a single instillation of chemotherapy on intravesical recurrence-free survival and muscle-invasive bladder cancer-free survival. RESULTS: Among the 205 patients, 130 (63%) and 75 (37%) were classified as the combined therapy and bacillus Calmette-Guérin monotherapy groups, respectively. Multivariable analyses using the inverse probability of treatment weighting method showed that a single instillation of chemotherapy was significantly associated with longer intravesical recurrence-free survival (hazard ratio 0.279; P < 0.001) and muscle-invasive bladder cancer-free survival (hazard ratio 0.078; P < 0.001). Fine-Gray competing risk regression model revealed that a single instillation of chemotherapy was associated with a significantly lower probability of intravesical recurrence and muscle-invasive bladder cancer progression, with an adjusted subdistribution hazard ratio of 0.477 (P = 0.008) and 0.261 (P = 0.043), respectively. CONCLUSION: A single intravesical instillation of chemotherapy may be a potential treatment option in patients with high-risk non-muscle-invasive bladder cancer who receive adjuvant induction bacillus Calmette-Guérin therapy.
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Mycobacterium bovis , Neoplasias de la Vejiga Urinaria , Adyuvantes Inmunológicos , Administración Intravesical , Vacuna BCG/uso terapéutico , Humanos , Invasividad Neoplásica , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/prevención & control , Estudios Retrospectivos , Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/tratamiento farmacológicoRESUMEN
OBJECTIVES: The US Food and Drug Administration recently defined the clinical term "bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer" as a disease state resistant to adequate bacillus Calmette-Guérin therapy. There is a significant lack of prognostication for this disease even in patients who have undergone early radical cystectomy. This study aimed to identify the clinical outcomes and prognostic factors in Japanese patients with bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer who underwent early radical cystectomy. METHODS: Data from a large-scale multicenter retrospective study included 2879 patients with highest-risk or high-risk non-muscle-invasive bladder cancer who received intravesical bacillus Calmette-Guérin induction therapy between January 2000 and December 2019. A total of 141 patients (4.3%) met the criteria for bacillus Calmette-Guérin-unresponsive disease, of whom 47 (33.3%) underwent early radical cystectomy. Prognostic factors for three clinical endpoints, namely, unresectable lesion-free survival, cancer-specific survival, and overall survival, were identified. RESULTS: The highest-risk status at induction bacillus Calmette-Guérin was associated with short unresectable lesion-free survival (hazard ratio 7.85; P < 0.05), cancer-specific survival (hazard ratio 12.24; P < 0.05), and overall survival (hazard ratio 9.25; P < 0.01). Moreover, extravesical tumors (pathological T3 or T4) on the radical cystectomy specimens were associated with poor prognosis and were found at a higher rate in patients with the highest-risk status at induction bacillus Calmette-Guérin than in those with high-risk status (35.7% vs 21.2%). CONCLUSIONS: The highest-risk status among the pre-bacillus Calmette-Guérin factors was associated with upstaging to extravesical tumors and poor prognosis despite early radical cystectomy procedures. Appropriate decision-making and the correct timing of radical cystectomy are vital to avoid treatment delays and improve outcomes.
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Vacuna BCG , Neoplasias de la Vejiga Urinaria , Adyuvantes Inmunológicos/uso terapéutico , Administración Intravesical , Vacuna BCG/uso terapéutico , Cistectomía/métodos , Humanos , Japón/epidemiología , Invasividad Neoplásica , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/prevención & control , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/cirugíaRESUMEN
BACKGROUND: The presence of glycosylated isoforms of prostate-specific antigen (PSA) in prostate cancer (PC) cells is a potential marker of their aggressiveness. We characterized the origin of α2,3-sialylated prostate-specific antigen (S23PSA) by tissue-based sialylation-related gene expression and studied the performance of S23PSA density (S23PSAD) alone and in combination with multiparametric magnetic resonance imaging (MRI) for the detection of clinically significant prostate cancer in men with elevated PSA. METHODS: Tissue-based quantification of S23PSA and sialyltransferase and sialidase gene expression was evaluated in 71 radical prostatectomy specimens. The diagnostic performance of S23PSAD was studied in 1099 men retrospectively enrolled in a multicenter systematic biopsy (SBx) cohort. We correlated the S23PSAD with Prostate Imaging Reporting and Data System (PI-RADS) scores in 98 men prospectively enrolled in a single-center MRI-targeted biopsy (MRI-TBx) cohort. The primary outcome was the PC-diagnostic performance of the S23PSAD, the secondary outcome was the avoidable biopsy rate of S23PSAD combined with DRE and total PSA (tPSA), and with or without PI-RADS. RESULTS: S23PSA was significantly higher in Gleason pattern 4 and 5 compared with benign prostate tissue. In the retrospective cohort, the performance of S23PSAD for detecting PC was superior to tPSA or PSA density (PSAD) (AUC: 0.7758 vs. 0.6360 and 0.7509, respectively). In the prospective cohort, S23PSAD was superior to tPSA, PSAD, and PI-RADS (AUC: 0.7725 vs. 0.5901, 0.7439 and 0.7305, respectively), and S23PSAD + PI-RADS + DRE + tPSA was superior to DRE + tPSA+PI-RADS with avoidance rate of MRI-TBx (13% vs. 1%) at 30% risk threshold. CONCLUSIONS: The diagnostic performance of S23PSAD was superior to conventional strategies but comparable to mpMRI.
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Neuraminidasa/metabolismo , Antígeno Prostático Específico , Próstata , Neoplasias de la Próstata , Isoformas de Proteínas/análisis , Sialiltransferasas/metabolismo , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Biopsia/métodos , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Imágenes de Resonancia Magnética Multiparamétrica/métodos , Clasificación del Tumor , Estadificación de Neoplasias , Próstata/diagnóstico por imagen , Próstata/metabolismo , Próstata/patología , Antígeno Prostático Específico/análisis , Antígeno Prostático Específico/metabolismo , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patologíaRESUMEN
BACKGROUND: To explore possible solutions to overcome chronic Bacillus Calmette-Guérin (BCG) shortage affecting seriously the management of non-muscle invasive bladder cancer (NMIBC) in Europe and throughout the world, we investigated whether non-maintenance eight-dose induction BCG (iBCG) was comparable to six-dose iBCG plus maintenance BCG (mBCG). METHODS: This observational study evaluated 2669 patients with high- or highest-risk NMIBC who treated with iBCG with or without mBCG during 2000-2019. The patients were classified into five groups according to treatment pattern: 874 (33%) received non-maintenance six-dose iBCG (Group A), 405 (15%) received six-dose iBCG plus mBCG (Group B), 1189 (44%) received non-maintenance seven-/eight-dose iBCG (Group C), 60 (2.2%) received seven-/eight-dose iBCG plus mBCG, and 141 (5.3%) received only ≤5-dose iBCG. Recurrence-free survival (RFS), progression-free survival, and cancer-specific survival were estimated and compared using Kaplan-Meier analysis and the log-rank test, respectively. Propensity score-based one-to-one matching was performed using a multivariable logistic regression model based on covariates to obtain balanced groups. To eliminate possible immortal bias, 6-, 12-, 18-, and 24-month conditional landmark analyses of RFS were performed. RESULTS: RFS comparison confirmed that mBCG yielded significant benefit following six-dose iBCG (Group B) in recurrence risk reduction compared to iBCG alone (groups A and C) before (P < 0.001 and P = 0.0016, respectively) and after propensity score matching (P = 0.001 and P = 0.0074, respectively). Propensity score-matched sequential landmark analyses revealed no significant differences between groups B and C at 12, 18, and 24 months, whereas landmark analyses at 6 and 12 months showed a benefit of mBCG following six-dose iBCG compared to non-maintenance six-dose iBCG (P = 0.0055 and P = 0.032, respectively). There were no significant differences in the risks of progression and cancer-specific death in all comparisons of the matched cohorts. CONCLUSIONS: Although non-maintenance eight-dose iBCG was inferior to six-dose iBCG plus mBCG, the former might be an alternative remedy in the BCG shortage era. To overcome this challenge, further investigation is warranted to confirm the real clinical value of non-maintenance eight-dose iBCG.
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Adyuvantes Inmunológicos/administración & dosificación , Vacuna BCG/administración & dosificación , Quimioterapia de Inducción/métodos , Recurrencia Local de Neoplasia/epidemiología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Administración Intravesical , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Quimioterapia de Inducción/estadística & datos numéricos , Japón/epidemiología , Estimación de Kaplan-Meier , Quimioterapia de Mantención/estadística & datos numéricos , Masculino , Recurrencia Local de Neoplasia/prevención & control , Supervivencia sin Progresión , Estudios Retrospectivos , Vejiga Urinaria/inmunología , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
OBJECTIVE: To evaluate temporal trends in neoadjuvant chemotherapy (NAC) utilisation and outcomes in patients with locally advanced upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: We included 289 patients from seven hospitals who underwent radical nephroureterectomy (RNU) for locally advanced UTUC (≥cT3 or cN+) between 2000 and 2020. These patients received RNU alone or two to four courses of NAC with either a cisplatin- or carboplatin-based regimen. We evaluated the temporal changes in NAC use and compared the visceral recurrence-free, cancer-specific, and overall survival rates. The effect of NAC on oncological outcomes was examined using multivariate Cox regression analysis with inverse probability of treatment weighting (IPTW) models. RESULTS: Of 289 patients, 144 underwent NAC followed by RNU (NAC group) and 145 underwent RNU alone (Control [Ctrl] group). NAC use increased significantly from 19% (2006-2010), 58% (2011-2015), to 79% (2016-2020). Pathological downstaging was significantly higher in the NAC group than in the Ctrl group. The IPTW-adjusted multivariable analyses showed that NAC significantly improved the oncological outcomes in the NAC group compared with the Ctrl group. Moreover, carboplatin-based NAC significantly improved the oncological outcomes in the NAC group compared with the Ctrl group among patients with chronic kidney disease Stage ≥3. There were no significant differences in oncological outcomes between the cisplatin- and carboplatin-based regimens. CONCLUSIONS: The use of NAC for high-risk UTUC increased significantly after 2010. Platinum-based short-term NAC followed by immediate RNU may not impede and potentially improves oncological outcomes.
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Carcinoma de Células Transicionales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Terapia Neoadyuvante/tendencias , Neoplasias Ureterales/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Carcinoma de Células Transicionales/cirugía , Femenino , Humanos , Neoplasias Renales/cirugía , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/estadística & datos numéricos , Nefroureterectomía , Utilización de Procedimientos y Técnicas/tendencias , Estudios Retrospectivos , Medición de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Neoplasias Ureterales/cirugíaRESUMEN
PURPOSE: To investigate the association between serum serotonin (5-HT) levels and overactive bladder (OAB) in a community-dwelling population. METHODS: This cross-sectional study analyzed 1024 subjects who participated in the Iwaki Health Promotion Project in 2015 in Hirosaki, Japan. OAB was assessed using the Overactive Bladder Symptom Score (OABSS). OAB was defined as an occurrence of urinary urgency at least once a week and an OABSS of ≥ 3. We assessed serum 5-HT levels, laboratory data, and comorbidities of each participants. Participants' mental health status was evaluated using the Center for Epidemiologic Studies Depression (CES-D) scale. The association of serum 5-HT levels and OAB was analyzed by multivariable logistic regression analysis. RESULTS: This study included 394 men and 630 women. Of those, 118 (44 male and 74 female) were OAB sufferers. There were significant group differences in age, history of cardiovascular disease, chronic kidney disease, hypertension, diabetes mellitus, and CES-D score. Participants' serum 5-HT levels in the OAB group were significantly lower than those in the non-OAB group (100 vs. 127 ng/mL, P < 0.001). Multivariable analysis showed that age (odds ratio [OR]; 1.06, 95% confidence interval [CI]; 1.04-1.08, P < 0.001) and log serum 5-HT level (OR; 0.25, 95% CI; 0.10-0.68, P = 0.006) were independently associated with OAB. CONCLUSIONS: Lower serum 5-HT levels could independently be associated with the presence of OAB. Further study is necessary to elucidate a possible causal relationship between serum 5-HT levels and OAB.