RESUMO
Immune checkpoint blockade therapies are widely used for cancer treatment, including advanced renal cell carcinoma (RCC). This study aimed to investigate the impact of zygosity in HLA genes and individual HLA genotypes on the efficacy of an anti-PD-1 Ab, nivolumab, in treating advanced RCC. Patient enrollment was conducted across 23 institutions in Japan from August 19, 2019, to September 30, 2020, with follow-up concluding on March 31, 2021. HLA genotype imputation of HLA-A, B, and C, DQB1, and DRB1 loci was performed. Among 222 patients, the presence of at least one homozygosity of the HLA-II allele significantly improved the best objective response (hazard ratio, 0.34; 95% confidence interval, 0.21-0.96; p = 0.042). The HLA evolutionary divergence (HED) of the HLA-A and HLA-B loci was higher than the HLA-C (p < 0.0001 and p < 0.0001, respectively), with high HED of the HLA-B locus correlating to clinical benefits in nivolumab treatment (hazard ratio, 0.44; 95% confidence interval, 0.21-0.90; p = 0.024) and improving cancer-specific survival compared with the low group (p = 0.0202). Additionally, high HED of the HLA-B locus was correlated with the number of infiltrated CD8+ cells in the tumor microenvironment (correlation coefficient, 0.4042). These findings indicate that the diversity of the HLA-B locus plays a significant role in the anti-tumor effect of nivolumab treatment in advanced RCC, potentially offering insights for improved risk stratification in nivolumab treatment and leading to better medical management of advanced RCC.
Assuntos
Carcinoma de Células Renais , Genótipo , Antígenos HLA , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/imunologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Neoplasias Renais/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Antígenos HLA/genética , Antígenos HLA/imunologia , Nivolumabe/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Receptor de Morte Celular Programada 1/genética , Adulto , Idoso de 80 Anos ou maisRESUMO
PURPOSE: We aimed to evaluate the therapeutic efficacy and safety of TAS-303, a highly selective noradrenaline reuptake inhibitor, in Japanese women with stress urinary incontinence (SUI). MATERIALS AND METHODS: A double-blind, placebo-controlled, phase 2 study randomized women with SUI symptoms to once-daily oral administration of TAS-303 18 mg or placebo for 12 weeks. The primary endpoint was percent change from baseline to Week 12 in mean SUI episode frequency per 24 hours (SUIEF) in the per-protocol set. The secondary endpoints were the proportion of patients with ≥ 50% reduction in mean SUIEF, incontinence episode frequency, incontinence amount, health-related quality of life, and safety in the full analysis set. RESULTS: In total, 231 patients were randomized to TAS-303 (n = 116) or placebo (n = 115). At Week 12, TAS-303 had superior efficacy to placebo, with a least squares mean percent change in mean SUIEF of -57.7% vs -46.9%, respectively, in the per-protocol set (least squares mean difference -10.8%; P = .036). TAS-303 showed some evidence of improved incontinence episode frequency, incontinence amount, and health-related quality of life (although not statistically significant) at Week 12 vs placebo in the full analysis set. The between-group difference in SUIEF improvement was more clearly confirmed in patients with ≥ 2 SUI episodes daily at baseline. All adverse events (AEs) with TAS-303 were mild or moderate; there were no serious AEs, AEs leading to discontinuation, or nervous system- or gastrointestinal-related (eg, nausea or vomiting) adverse drug reactions. CONCLUSIONS: Once-daily TAS-303 18 mg showed superior efficacy to placebo for the treatment of SUI in Japanese women, with an adequate safety profile. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04512053; Japan Registry of Clinical Trials: jRCT2080225307 (JapicCTI-205403 before site integration).
Assuntos
Incontinência Urinária por Estresse , Humanos , Método Duplo-Cego , Feminino , Incontinência Urinária por Estresse/tratamento farmacológico , Pessoa de Meia-Idade , Adulto , Resultado do Tratamento , Qualidade de Vida , Idoso , Pirrolidinas/administração & dosagem , Pirrolidinas/efeitos adversos , Pirrolidinas/uso terapêutico , PirimidinonasRESUMO
AIMS: To investigate the usefulness of novel clinical diagnostic criteria based on noninvasive examination findings to diagnose urodynamic detrusor underactivity (DU) in men. METHODS: We developed clinical diagnostic criteria to predict the presence of urodynamic DU in men as follows: (a) bladder voiding efficiency <70% on uroflowmetry, (b) existence of "sawtooth and interrupted waveforms" on uroflowmetry, and (c) ultrasonography-documented intravesical prostatic protrusion <10 mm. We analyzed the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of these clinical criteria for diagnosing urodynamic DU in men aged 50 years or above with lower urinary tract symptoms who underwent urodynamic studies. RESULTS: Of the 314 men analyzed (mean age, 72.4 years; mean detrusor contraction index [DCI], 98.8; and mean bladder outlet obstruction index [BOOI], 43.9), 89 men met this clinical DU diagnostic criteria. Of these, 79 men (88.8%) had urodynamic DU (DCI < 100 and BOOI < 40), nine (10.1%) had DU + BOO (DCI < 100 and BOOI ≥ 40), and one (1.1%) had normal voiding functions. None of the men with urodynamic BOO (DCI ≥ 100 and BOOI ≥ 40) met the clinical DU diagnostic criteria. The sensitivity, specificity, PPV, and NPV of these clinical diagnostic criteria for urodynamic DU were 69.3%, 95.0%, 88.8%, and 84.4%, respectively. CONCLUSION: The proposed clinical DU diagnostic criteria showed a high PPV (88.8%) for diagnosing urodynamic DU. None of the patients with BOO met the clinical diagnostic criteria for DU. These clinical DU diagnostic criteria may be useful in identifying men with urodynamic DU in clinical practice.
Assuntos
Sintomas do Trato Urinário Inferior , Obstrução do Colo da Bexiga Urinária , Bexiga Inativa , Masculino , Humanos , Idoso , Bexiga Inativa/diagnóstico , Urodinâmica , Bexiga Urinária/diagnóstico por imagem , Obstrução do Colo da Bexiga Urinária/diagnóstico , Micção , Sintomas do Trato Urinário Inferior/diagnósticoRESUMO
OBJECTIVES: This study evaluated patients with occult spinal dysraphism who underwent spinal cord untethering. METHODS: Twenty-four patients who visited us between 1983 and 2000 were followed-up for a mean duration of 31 years. We studied their lower urinary tract function, skin stigmata, fertility, and work participation. RESULTS: Questionnaires sent in 2022 revealed that 5 patients had normal voiding (Group A) and 19 patients had abnormal voiding (Group B). Groups A and B underwent spinal cord untethering at a mean age of 5.7 and 13.0 years, respectively, showing a significant statistical difference (p = 0.036). After spinal cord untethering, the number of patients with detrusor normoactivity increased from 0 to 5, i.e., 3 of 6 with detrusor overactivity (50%), 1 of 2 not examined, and 1 of 5 not known. Patients with detrusor underactivity also increased from 11 to 19. Severity of incontinence in the International Consultation on Incontinence Questionnaire-Short Form resulted in a mean value of 2.4 in Group A, which was significantly superior to the mean value of 9.1 in Group B (p = 0.004). Fourteen patients (58.3%) were married and had 21 healthy children. A majority of patients have had full-time jobs. A variety of skin stigmata were present in the lumbosacral region, and changes in vesico-urethral configurations were observed during a video-urodynamic study. CONCLUSIONS: Our study identified that the early timing of spinal cord untethering performed in neonates or infants and detrusor overactivity prior to untethering surgery are important factors in achieving normal bladder function.
Assuntos
Fertilidade , Humanos , Feminino , Masculino , Seguimentos , Adolescente , Criança , Adulto , Pré-Escolar , Inquéritos e Questionários , Adulto Jovem , Espinha Bífida Oculta/complicações , Lactente , Incontinência Urinária/etiologia , Incontinência Urinária/fisiopatologia , Bexiga Urinária Hiperativa/fisiopatologia , Disrafismo Espinal/complicações , Disrafismo Espinal/fisiopatologia , Disrafismo Espinal/cirurgia , Medula Espinal/fisiopatologiaRESUMO
BACKGROUND: Anti-PD-1 antibodies are widely used for cancer treatment including advanced renal cell carcinoma (RCC). However, their therapeutic and adverse effects vary among patients. This study aimed to identify genetic markers that predict outcome after nivolumab anti-PD-1 antibody treatment for advanced RCC. METHODS: This study was registered on the website of the University Hospital Medical Information Network (protocol ID, UMIN000037739). Patient enrollment was conducted at 23 institutions in Japan between August 19, 2019, and September 30, 2020. Patient follow-up ended on March 31, 2021. Patients were treated with nivolumab for advanced clear cell RCC. A genome-wide association study was performed in the development set, while genotyping of target regions in the validation set was undertaken. Single nucleotide polymorphisms (SNPs) in genes of interest CD274, PDCD1LG2 and PDCD1 were genotyped in the combined set. The primary endpoint was the association of SNPs with objective response following nivolumab treatment. As secondary endpoints, the associations of SNPs with radiographic progression-free survival (rPFS) and treatment-related grade ≥ 3 adverse events (AEs) were evaluated. RESULTS: A genome-wide association study followed by a validation study identified that SNPs in FARP1 (rs643896 and rs685736) were associated with objective response and rPFS but not AEs following nivolumab treatment. Furthermore, SNPs in PDCD1LG2 (rs822339 and rs1411262) were associated with objective response, rPFS, and AEs following nivolumab treatment. Genetic risk category determined according to the number of risk alleles in SNPs (rs643896 in FARP1 and rs4527932 in PDCD1LG2) excellently predicted objective response and rPFS in nivolumab treatment. CONCLUSION: This study revealed that SNPs in FARP1 and PDCD1LG2 were correlated with outcome in nivolumab treatment. The use of these SNPs may be beneficial in selecting appropriate treatment for individual patients and may contribute to personalized medicine.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Nivolumabe/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Estudo de Associação Genômica Ampla , Intervalo Livre de Progressão , Polimorfismo de Nucleotídeo Único , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genéticaRESUMO
PURPOSE: To investigate whether circulating adiponectin, which is considered a possible marker of anti-atherogenic effects, is a useful predictor of bladder function, especially detrusor underactivity (DU), in men with lower urinary tract symptoms (LUTS). METHODS: A total of 130 treatment-naïve men with non-neurogenic LUTS were prospectively stratified into two groups (the DU and non-DU groups) based on the presence or absence of DU, where DU is defined as a bladder contractility index < 100 and bladder outlet obstruction index (BOOI) < 40. The impact of serum adiponectin levels on urodynamic function, including DU, was assessed using univariate, binomial logistic regression, and receiver operating characteristic (ROC) curve analyses. RESULTS: In total, data from 118 men were analyzed; 39 (33.0%) had DU (DU group) and 79 (67.0%) did not have DU (non-DU group). The median serum adiponectin in the DU group was significantly lower than in the non-DU group (6.2 vs 12.6 µg/mL, p < 0.001). In the binomial logistic regression analysis, lower adiponectin, smaller intravesical prostatic protrusion, and lower bladder voiding efficiency were significant factors related to DU. In the ROC analyses, serum adiponectin had the highest area under the curve value for DU diagnosis (0.849). Additionally, a cutoff value of 7.9 µg/mL for serum adiponectin level was identified for DU, which yielded a sensitivity and specificity of 79% and 90%, respectively. CONCLUSIONS: The serum adiponectin level was significantly associated with bladder function and may be a useful marker for predicting DU in men with LUTS.
Assuntos
Sintomas do Trato Urinário Inferior , Obstrução do Colo da Bexiga Urinária , Bexiga Inativa , Masculino , Humanos , Estudos Prospectivos , Bexiga Inativa/diagnóstico , Bexiga Inativa/complicações , Adiponectina , UrodinâmicaRESUMO
AIMS: To clarify the clinical features of men with nonneurogenic detrusor underactivity (DU) by focusing on storage dysfunction (SD). METHODS: We retrospectively reviewed the clinical and urodynamic data of men with nonneurogenic DU. Patients were divided into two groups according to the presence or absence of SD, such as detrusor overactivity (DO) and reduced bladder compliance (BC). Patient characteristics, lower urinary tract symptoms (LUTS), and urodynamic parameters were compared. DU was defined as bladder contractility index (BCI) ≤ 100 and bladder outlet obstruction index (BOOI) ≤ 40. RESULTS: Of 212 men with DU, 123 (58.0%) had concomitant SD (SD + DU group), and 89 (42.0%) had only DU (DU-only group). Age, prostate volume, and severity of storage symptoms were significantly higher in the SD + DU group. Particularly, >80% of men in the SD + DU group met the diagnostic criteria for overactive bladder in Japan, which was significantly higher than the 26% of men in the DU-only group. The frequency of urinary urgency incontinence (UUI) was also significantly higher in the SD + DU group (65% vs. 12% in DU-only group). In contrast, voiding symptoms, including straining, were more severe in the DU-only group. Regarding the urodynamic parameters, compared to the DU-only group, bladder capacity was significantly smaller and BOOI and BCI were significantly higher in the SD + DU group. However, there was no significant difference in the maximum flow rate and bladder voiding efficiency. CONCLUSIONS: Approximately 60% of men with DU had SD, such as DO and/or reduced BC, whereas the remaining 40% had increased bladder capacity without an increase in detrusor pressure during the storage phase. There were significant differences in the storage and voiding symptoms between the groups. It is important to divide patients with DU based on SD to accurately clarify the clinical picture of DU.
Assuntos
Sintomas do Trato Urinário Inferior , Obstrução do Colo da Bexiga Urinária , Bexiga Inativa , Incontinência Urinária , Masculino , Humanos , Bexiga Urinária , Estudos Retrospectivos , UrodinâmicaRESUMO
BACKGROUND: This study is part of the SNPs in Nivolumab PD-1 inhibitor for RCC (SNiP-RCC). Here we aimed to reveal clinical factors for tumor response, progression, and survival in nivolumab for advanced clear cell renal cell carcinoma (RCC) in Japanese patients. METHODS: We included patients from 23 institutions in Japan. We evaluated the objective response, radiographic progression-free survival (PFS), overall survival (OS), and treatment-related grade ≥ 3 (serious adverse events [SAEs]). RESULTS: We included 222 patients. The median age was 69 years (interquartile range 62-74 years), and 71% of the patients were male. Pancreas metastasis, lung metastases, prior cytokine therapy, and SAEs, were associated with objective response. The median PFS was 18 months. Liver metastases (hazard ratio [HR], 1.61), age ≥ 75 (HR, 0.48), previous resection of primary sites (HR, 0.47), and SAEs (HR, 0.47) were independent prognostic factors for PFS. Karnofsky Performance Status <70 (HR, 2.90), high platelets (HR, 4.48), previous resection of primary sites (HR, 0.23), and pathological grade (HR, 0.19 for grade 2 and HR, 0.12 for grade 3) were independent prognostic factors for OS. SAEs were reported in 45 (20.3%) cases. In the group of patients with prior nephrectomy, SAEs were associated with objective response, PFS, and OS. CONCLUSION: The SNiP-RCC study identified clinical parameters correlated with treatment outcomes in Japanese patients with priorly treated advanced clear cell RCC undergoing nivolumab monotherapy.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Carcinoma de Células Renais/patologia , Nivolumabe/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Renais/patologia , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Tumor neoantigens derived from genetic alterations are potential T-cell targets for antitumor immunity. However, tumors develop immune escape mechanisms including loss of preexisting neoantigens and/or impairment of T-cell responses during tumor development and progression. Here, we addressed whether newly emerged immunogenic neoantigens in established tumors enabled hosts to inhibit tumor growth via controlling immune escape mechanisms. Using a doxycycline-driven gene expression system, we generated murine MC38, CT26 (colorectal cancer) and B16 (melanoma) cell lines with inducible expression of model immunogenic neoantigens such as chicken ovalbumin and human NY-ESO-1. A model neoantigen was induced by doxycycline administration in the tumors once tumors became palpable. Tumor growth was significantly inhibited upon induction of the neoantigen and this inhibition was abrogated in nude mice lacking T cells and in mice deprived of CD8+ T cells, indicating the critical role of CD8+ T cells in tumor regression. In addition, PD-1/PD-L1 blockade further augmented the antitumor immune response, resulting in a far stronger inhibition of tumor growth. Accordingly, newly emerged tumor neoantigen-specific CD8+ T cells with enhanced effector functions were significantly increased in mice treated with PD-1/PD-L1 blockade. We propose that a newly emerged neoantigen is sufficient to inhibit tumor growth via preventing immune escape in a T-cell-dependent manner. Our results imply that induction of immunogenic tumor neoantigens is a novel strategy to overcome the resistance to immune checkpoint blockade therapy.
Assuntos
Antígenos de Neoplasias/imunologia , Linfócitos T CD8-Positivos/imunologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Inibidores de Checkpoint Imunológico/farmacologia , Evasão Tumoral/imunologia , Animais , Antígeno B7-H1/antagonistas & inibidores , Linhagem Celular Tumoral , Galinhas , Neoplasias do Colo/imunologia , Doxiciclina/farmacologia , Feminino , Humanos , Melanoma Experimental/imunologia , Proteínas de Membrana/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Nus , Monitorização Imunológica , Ovalbumina/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidoresRESUMO
PURPOSE: This multicenter, randomized, double-blind, placebo-controlled phase 2 study evaluated the efficacy and safety of TAC-302, a novel drug that restores neurite outgrowth, in patients with detrusor underactivity (DU) and overactive bladder (OAB). METHODS: After 2-4 weeks of observation, patients were randomized 2:1 to receive oral TAC-302 200 mg or placebo twice daily for 12 weeks. The primary endpoint was detrusor contraction strength, estimated by bladder contractility index (BCI) for males and projected isovolumetric pressure 1 (PIP1) for females. Secondary endpoints included changes in bladder voiding efficiency (BVE) and safety. RESULTS: Seventy-six patients were included (TAC-302, n = 52; placebo, n = 24). The mean (standard deviation [SD]) BCI for males was 64.6 (16.6) at baseline and 75.2 (21.1) at week 12 (p < 0.001) with TAC-302 (n = 27), and 61.3 (16.6) and 60.5 (16.7) (p = 0.82) with placebo (n = 11). The respective mean (SD) PIP1 for females was 18.8 (6.6) and 29.4 (9.4) (p < 0.001) with TAC-302 (n = 15), and 20.6 (7.5) and 25.5 (9.6) (p = 0.14) with placebo (n = 7). TAC-302 significantly increased BCI in males and BVE in both sexes. TAC-302 efficacy on OAB was not clearly shown. The incidences of adverse events (AEs), serious AEs, and AEs leading to dose interruption were similar between groups; no adverse drug reactions occurred. CONCLUSION: Considering the significant effects on BCI in males and BVE in both sexes, TAC-302 may benefit patients with DU. REGISTRATION: ClinicalTrials.gov Identifier NCT03175029 registered 6/5/2017.
Assuntos
Bexiga Urinária Hiperativa , Bexiga Inativa , Masculino , Feminino , Humanos , Bexiga Urinária Hiperativa/tratamento farmacológico , Bexiga Urinária Hiperativa/complicações , Bexiga Inativa/complicações , Urodinâmica , Micção , Método Duplo-Cego , Resultado do TratamentoRESUMO
PURPOSE: To investigate the prevalence of asymptomatic bacteriuria (ASB) in middle-aged and older men with non-neurogenic lower urinary tract symptoms (LUTS) and clarify urodynamic factors related to the presence of ASB. METHODS: We retrospectively reviewed the clinical data of men with LUTS who underwent urine culture examination, LUTS severity assessment, and urodynamic studies. The patients were allocated into two groups (the ASB + LUTS and LUTS-only) according to presence or absence of ASB. The patients' characteristics and urodynamic factors related to the development of ASB were assessed using univariate, binomial logistic regression, and receiver-operating characteristic (ROC) curve analyses. RESULTS: Of 440 men, 93 (21.1%) had ASB. Parameters related to voiding functions, such as maximum flow rate, post-void residual urine volume, bladder voiding efficiency (BVE), and bladder contractility index (BCI), were significantly reduced in the ASB + LUTS group, while bladder outlet obstruction index was not different between the groups. Binomial logistic regression analysis showed that the presence of diabetes, lower BCI, and lower BVE were significantly associated with the presence of ASB. In addition, ROC analysis identified 55% as the optimal cutoff value of BVE for the presence of ASB, with a sensitivity of 84% and specificity of 83%. CONCLUSIONS: ASB was found in > 20% of men with non-neurogenic LUTS and was associated with decreased bladder contractility and decreased BVE. BVE could predict presence of ASB with high sensitivity and specificity.
Assuntos
Bacteriúria , Sintomas do Trato Urinário Inferior , Obstrução do Colo da Bexiga Urinária , Pessoa de Meia-Idade , Masculino , Humanos , Idoso , Urodinâmica , Estudos Retrospectivos , Bacteriúria/epidemiologia , Bacteriúria/complicações , Bexiga Urinária , Sintomas do Trato Urinário Inferior/epidemiologia , Sintomas do Trato Urinário Inferior/complicações , Obstrução do Colo da Bexiga Urinária/complicações , Fatores de RiscoRESUMO
OBJECTIVES: To investigate the complication rate of chronic prostatitis/chronic pelvic pain syndrome in men with lower urinary tract symptoms, and to clarify their clinical features and urodynamic findings. METHODS: We retrospectively reviewed the clinical data of treatment-naïve men with lower urinary tract symptoms. Patients were divided into two groups (chronic prostatitis/chronic pelvic pain syndrome + lower urinary tract symptoms and lower urinary tract symptoms only) according to the presence or absence of chronic prostatitis/chronic pelvic pain syndrome, and the patient characteristics as well as the parameters of lower urinary tract symptoms and lower urinary tract function assessed by urodynamics were compared. The diagnostic criteria for chronic prostatitis/chronic pelvic pain syndrome included a complaint of pelvic pain for ≥3 months, National Institutes of Health Chronic Prostatitis Symptom Index pain subscore ≥4, and negative culture of a urine specimen collected after prostate massage. RESULTS: Out of 386 men, 123 (31.9%) had chronic prostatitis/chronic pelvic pain syndrome. Parameters of lower urinary tract symptoms and National Institutes of Health Chronic Prostatitis Symptom Index scores were significantly higher in the chronic prostatitis/chronic pelvic pain syndrome + lower urinary tract symptoms group. Although there were no significant intergroup differences in voiding parameters such as maximum flow rate and bladder outlet obstruction index, storage functions such as the incidence of detrusor overactivity and bladder compliance were significantly reduced in the chronic prostatitis/chronic pelvic pain syndrome + lower urinary tract symptoms group. The multivariable regression analysis revealed that a low serum total testosterone level (<3.5 ng/mL), complications of hyperlipidemia, and presence of overactive bladder and detrusor overactivity were significantly associated with the development of chronic prostatitis/chronic pelvic pain syndrome. CONCLUSIONS: Chronic prostatitis causes a significant decrease in storage function, such as an increase in detrusor overactivity. Additionally, low serum testosterone levels and hyperlipidemia were found to be significantly associated with the development of chronic prostatitis/chronic pelvic pain syndrome in men with lower urinary tract symptoms.
Assuntos
Dor Crônica , Sintomas do Trato Urinário Inferior , Prostatite , Idoso , Doença Crônica , Feminino , Humanos , Sintomas do Trato Urinário Inferior/diagnóstico , Sintomas do Trato Urinário Inferior/epidemiologia , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Dor Pélvica/epidemiologia , Dor Pélvica/etiologia , Prostatite/complicações , Estudos Retrospectivos , Testosterona , Estados Unidos , UrodinâmicaRESUMO
OBJECTIVES: Many studies have shown a good prognostic association with a large number of lymph node dissections. However, most of these studies did not include patients who have received neoadjuvant chemotherapy. The purpose of this study was to verify the relationship between survival outcomes and the number of lymph nodes removed during radical cystectomy in patients with muscle-invasive bladder cancer in the era of neoadjuvant chemotherapy. METHODS: This retrospective study considered patients who were diagnosed with clinical ≥T2N0M0 muscle-invasive bladder cancer and treated with radical cystectomy at the Nagoya University Hospital and affiliated hospitals from January 2004 to December 2019. We excluded patients who had a history of upper tract urothelial cancer or non-urothelial carcinoma. The association between prognosis and the number of lymph nodes removed was investigated. RESULTS: We retrospectively enrolled a total of 477 patients. The mean number of lymph nodes dissected was 14. Two hundred and twenty-six patients (47.4%) received neoadjuvant chemotherapy. More extensive lymphadenectomy (≥15 lymph nodes) correlated with better 5-year overall survival across all patients (68% vs. 57%, p = 0.01). In patients who received neoadjuvant chemotherapy, there was no difference in overall survival according to the number of dissected lymph nodes (66% vs. 71%, p = 0.433). In patients who did not receive neoadjuvant chemotherapy, ≥15 lymph nodes dissected was associated with significantly better overall survival (70.3% vs. 46.9%, p < 0.01). CONCLUSIONS: No association between more aggressive lymph node dissection and prognosis was found in patients who underwent neoadjuvant chemotherapy. Conversely, extended lymph node dissection is desirable for patients who have not received neoadjuvant chemotherapy.
Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , Estudos Retrospectivos , Terapia Neoadjuvante , Cistectomia , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/cirurgia , Excisão de Linfonodo , Prognóstico , Linfonodos/cirurgia , Linfonodos/patologia , MúsculosRESUMO
AIMS: Recording a voiding diary can be bothersome for patients and is sometimes inaccurate and unhygienic. This study aimed to develop and assess the accuracy and convenience of a novel device that automatically records the voiding diary by measuring pre- and post-void body weight. METHODS: We used this novel device for seven healthy volunteers and ten hospitalized patients. The examinees got on the device before and after voiding and the device recorded the voiding diary automatically. The examinees also manually recorded a voiding diary by collecting their urine in a cup and measuring its volume and weight. We examined the correlation between the traditional and the automated voiding diary to confirm the accuracy of voiding measurements using this device. Additionally, we investigated which measurement method was preferred by the participants. RESULTS: In the healthy volunteers group, there was a strong correlation between the voided urine weight recorded by the device and voided urine weight measured manually by the examinee (R2 = 0.9935). In the patients group, there was a strong (R2 = 0.9117) but lower correlation than that of the volunteers group, with an error of ±25 g 62% of the time, and ±50 g 82% of the time, respectively. All of the healthy volunteers and seven of the ten patients preferred using the automated voiding diary. CONCLUSIONS: This novel device recorded a reasonably accurate voiding diary for everyday clinical practice.
Assuntos
Testes Diagnósticos de Rotina/métodos , Prontuários Médicos/normas , Micção/fisiologia , Adulto , Estudos de Viabilidade , Feminino , Voluntários Saudáveis , Humanos , Masculino , Projetos PilotoRESUMO
AIMS: To investigate factors contributing to pre and postoperative urethral function in male patients who underwent robot-assisted radical prostatectomy (RARP) using the urethral pressure profile (UPP). METHODS: Study A A total of 313 patients who underwent RARP between April 2013 and March 2015 were prospectively investigated. UPP was performed preoperatively in all patients. Correlation and multiple regression analyses were performed to investigate predictive factors for low preoperative maximum urethral closure pressure (MUCP). Study B To validate the predictive factors for low preoperative MUCP obtained in Study A, 755 patients who underwent RARP between May 2010 and October 2017 were retrospectively examined. Relationships between the time to pad-free status and the following factors were investigated: number of predictive factors, nerve-sparing surgery, and vesicourethral anastomosis (VUA) methods (barbed vs. nonbarbed suture). RESULTS: Study A A total of 187 patients were enrolled. Multivariate analysis revealed that older age, large prostate volume, low erectile function domain scores in International Index Erectile Function 15, and use of calcium channel blockers were significantly associated with low preoperative MUCP. Study B A total of 515 patients were included. Cox proportional hazard regression showed that the number of predictive factors and VUA method were significantly associated with the time to pad-free status. CONCLUSIONS: Our study demonstrated that older age, larger prostate volume, poor erectile function, and calcium channel blocker use could be predictive markers for recovery from postprostatectomy urinary incontinence.
Assuntos
Procedimentos Cirúrgicos Robóticos , Humanos , Masculino , Prostatectomia/efeitos adversos , Neoplasias da Próstata/cirurgia , Recuperação de Função Fisiológica , Estudos Retrospectivos , UrodinâmicaRESUMO
AIMS: To examine the safety and efficacy of vibegron, a new ß3-adrenoceptor agonist, in patients aged ≥65 years, with a focus on the effects on cardiovascular system and overactive bladder (OAB) symptoms. METHODS: A post-hoc subgroup analysis was performed of a randomized, placebo-controlled, double-blind comparative phase 3 study of vibegron, including those assigned to receive either vibegron 50 mg (V50), vibegron 100 mg (V100), or placebo for 12 weeks. Subjects were stratified into two subgroups based on age: a <65-year subgroup and a ≥65-year subgroup. Safety (changes in systolic and diastolic blood pressure, pulse rate, and residual urine volume) and efficacy (changes in the numbers of micturitions, urgency episodes, urgency urinary incontinence [UUI] episodes, and the voided volume/micturition) were assessed in the subgroups treated with vibegron vs. placebo. RESULTS: There were no significant differences in the cardiovascular outcomes (blood pressure and pulse rate), nor in the changes in residual urine volume, between the V50/100 and placebo groups in the <65-year or ≥65-year subgroup after 12-week treatment. Adverse events were slightly increased in the ≥65-year subgroup. In the efficacy analysis, V50/100 demonstrated similar efficacy in the <65-year and ≥65-year subgroups; an increasing trend in the voided volume/micturition was observed in subjects aged ≥65 years compared to subjects aged <65 years. CONCLUSIONS: Vibegron was suggested to be similarly effective in patients ≥65 and <65 years and to have minimal influence on cardiovascular parameters.
Assuntos
Sistema Cardiovascular , Bexiga Urinária Hiperativa , Agonistas de Receptores Adrenérgicos beta 3/efeitos adversos , Idoso , Método Duplo-Cego , Humanos , Pessoa de Meia-Idade , Antagonistas Muscarínicos , Pirimidinonas , Pirrolidinas , Receptores Adrenérgicos , Resultado do Tratamento , Bexiga Urinária Hiperativa/tratamento farmacológicoRESUMO
INTRODUCTION AND HYPOTHESIS: TAS-303, which selectively inhibits noradrenaline reuptake, was developed for treating stress urinary incontinence (SUI). The proximal urethra mainly comprises smooth muscle fibers in which α1 adrenergic receptors are abundant. This study was conducted to evaluate the effect of TAS-303 on urethral function and its safety profile in female patients with SUI. METHODS: In total, 16 women (age, 20-64 years) with SUI and > 5.0 g of leakage in the 1-h pad test at screening were randomized and administered the assigned treatment in a double-blind manner. The primary end point was change in the maximal urethral closure pressure (MUCP) at 6 h post-dose. The secondary end point was change in the urethral closure pressure of the entire urethra and each urethral region (proximal, middle, and distal) at 6 h post-dose. The results were analyzed using a t-test. RESULTS: The mean change ± standard deviation in MUCP at 6 h post-dose was 3.473 ± 12.154 cmH2O for TAS-303 and 2.615 ± 9.794 cmH2O for placebo (between-group difference: 0.858 cmH2O, P = 0.8047). The mean changes ± standard deviation in urethral closure pressure of the proximal urethra at 6 h after the administration of TAS-303 18 mg and placebo were 3.863 ± 10.941 and 1.634 ± 12.093, respectively (between-group difference: 2.229 cmH2O, P = 0.5976). CONCLUSIONS: No significant difference in MUCP and urethral closure pressure was found between TAS-303 and placebo. However, the change in the proximal urethral closure pressure with TAS-303 was larger than that with placebo. This suggests that TAS-303 has pharmacological effects on urethral sphincteric function.
Assuntos
Incontinência Urinária por Estresse , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pressão , Uretra , Urodinâmica , Adulto JovemRESUMO
BACKGROUND: Intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for urothelial carcinoma of the upper urinary tract (UCUUT) is common. One of the mechanisms driving this is the implantation of cancer cells from the UCUUT at the RNUs. Therefore, their detection after RNU can assist in predicting IVR. This study aimed to examine the utility of UroVysion® as a tool for predicting bladder recurrence after RNU for UCUUT. METHODS: We prospectively enrolled 65 patients who received RNU for high-grade UCUUT between October 2013 and April 2017. RESULTS: Of the 65 patients, 54 (83.1%) who had both bladder urine samples available immediately after RNU (0 postoperative days: POD) and 5 days after RNU (5POD) were selected. We performed UroVysion® and cytology. Twenty-two patients showed IVR with 32 foci. UroVysion® results at 0POD (26 patients, 48.1%) and/or 5POD (31 patients, 57.4%) were positive in 42 (77.8%) patients. The sensitivity, specificity, positive predictive value, and negative predictive value of UroVysion® for included cases were measured for both 0POD and 5POD samples; they were determined to be 95.5% (21/22), 34.4% (11/32), 50.0% (21/42), and 91.7% (11/12), respectively. For cytology, these values were 75.0% (15/20), 52.9% (18/34), 48.4% (15/31), and 78.3% (18/23), respectively. Forty-two (64.6%) patients who were UroVysion®-positive demonstrated IVR. The IVR rate between the group positive for either 0POD or 5POD and that negative for both significantly differed for both UroVysion® (p = 0.019) and cytology (p = 0.046). CONCLUSION: Multiple urine tests using UroVysion® after RNU could be a useful predictor for IVR.
Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Sistema Urinário , Carcinoma de Células de Transição/cirurgia , Humanos , Recidiva Local de Neoplasia/cirurgia , Nefrectomia , Nefroureterectomia , Estudos Prospectivos , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
PURPOSE: Some patients who undergo robot-assisted laparoscopic radical prostatectomy (RARP) continue to experience long-term urinary incontinence (UI). This study aimed to evaluate easily obtainable factors that can predict long-term UI following RARP. MATERIALS AND METHODS: A total of 315 patients who underwent RARP for localised prostatic cancer were analysed. We separated the patients into two groups, namely, the Continence group and the Incontinence group, according to the presence or absence of UI at 12 months after surgery, and we compared the patients' characteristics and operative data to identify clinical signs associated with long-term UI. Additionally, correlations between these factors and postoperative urethral function were evaluated. Urinary continence was defined as both the use of 0 pads/per day and <2 g of urine lost using the 24-hours pad weight test. RESULTS: Of 315 patients, 250 (79.4%) achieved urinary continence and 65 (20.6%) had long-term UI. Age, storage-related lower urinary tract symptoms before surgery, nerve-sparing surgery and the 24-hours urine loss immediately after urethral catheter removal significantly affected long-term UI after RARP. Multivariate logistic regression analyses revealed that the 24-hours urine loss after catheter removal was a significant predictor of long-term UI. Receiver operating characteristic curve analysis identified a urine loss of 330 g/d as the optimal cut-off value, which yielded 92% sensitivity and 84% specificity, and it showed significant correlations with postoperative urethral function and the time to recover urinary continence. CONCLUSION: The 24-hours urine loss immediately after urethral catheter removal may be the most reliable and useful predictor of long-term UI following RARP.
Assuntos
Laparoscopia , Neoplasias da Próstata , Robótica , Incontinência Urinária , Humanos , Laparoscopia/efeitos adversos , Masculino , Prostatectomia/efeitos adversos , Neoplasias da Próstata/cirurgia , Cateteres Urinários , Incontinência Urinária/etiologiaRESUMO
OBJECTIVE: To carry out an exploratory assessment of the efficacy and safety of TAS-303, a noradrenaline reuptake inhibitor, in women with stress urinary incontinence. METHODS: In a double-blind, placebo-controlled, early phase II study, women with stress urinary incontinence and stress urinary incontinence-predominant mixed urinary incontinence were randomized to a placebo or TAS-303 (3 or 6 mg) once daily for 8 weeks. The main efficacy end-points were mean percentage change in incontinence episode frequency per 24 h from baseline to week 8 (the primary end-point) and week 4. RESULTS: At week 8, the mean percentage change in incontinence episode frequency per 24 h was -34.73% in the TAS-303 3 mg group, -35.41% in the TAS-303 6 mg group and -28.07% in the placebo group (differences vs placebo, not significant). In patients with stress urinary incontinence, or incontinence episode frequency less than two episodes per 24 h at baseline, TAS-303 significantly reduced incontinence episode frequency versus placebo after 4 weeks; some secondary end-points also showed a tendency to improve in the same subgroups. No serious adverse events (e.g. central nervous system or cardiovascular effects) were observed; TAS-303 was well tolerated and had a favorable safety profile. CONCLUSION: These findings suggest that TAS-303 is effective for improving stress urinary incontinence symptoms in some subgroups of patients with stress urinary incontinence. Therefore, further research is warranted.