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1.
J Epidemiol ; 33(11): 582-588, 2023 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-36310059

RESUMO

BACKGROUND: Although cigarette smoking is an established risk factor for bladder cancer, assessment of smoking impact on bladder cancer in Asian populations has been hindered by few cohort studies conducted in Asian populations. Therefore, we investigated the risk of bladder cancer associated with smoking status, cumulative smoking intensity, and smoking cessation in Japan. METHODS: We analyzed data for 157,295 men and 183,202 women in 10 population-based cohort studies in Japan. The risk associated with smoking behaviors was estimated using Cox regression models within each study, and pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) for the incidence of bladder cancer were calculated. RESULTS: During 4,729,073 person-years of follow-up, 936 men and 325 women developed bladder cancer. In men, former smokers (HR 1.47; 95% CI, 1.18-1.82) and current smokers (HR 1.96; 95% CI, 1.62-2.38) had higher risk than never smokers. In women, current smokers had higher risk than never smokers (HR 2.35; 95% CI, 1.67-3.32). HRs in men linearly increased with increasing pack-years. Risk decreased with increasing years of smoking cessation in men, with a significant dose-response trend. Former smokers with a duration of more than 10 years after smoking cessation had no significantly increased risk compared with never smokers (HR 1.26; 95% CI, 0.97-1.63). CONCLUSION: Data from a pooled analysis of 10 population-based cohort studies in Japan clearly show an association between cigarette smoking and bladder cancer risk. The risk of smokers may approximate that of never smokers following cessation for many years.


Assuntos
Fumar Cigarros , Abandono do Hábito de Fumar , Neoplasias da Bexiga Urinária , Masculino , Humanos , Feminino , Japão/epidemiologia , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/etiologia , Estudos de Coortes , Fatores de Risco
2.
J Epidemiol ; 30(7): 309-313, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-31204364

RESUMO

BACKGROUND: The association of alcohol drinking with bladder cancer risk remains unclear in East Asian populations. Aldehyde dehydrogenase 2 (ALDH2) enzyme oxidizes alcohol-metabolized carcinogenic acetaldehyde into acetate. It is well known that the inactive ALDH2 carriers, specific to East Asian populations, have an increased risk of several cancer types because of increased exposure to acetaldehyde after alcohol consumption. The aim of this study was to examine the association between alcohol drinking and bladder cancer risk using data from ten population-based prospective cohort studies in Japan, where approximately 40% of the population has inactive ALDH2 enzyme. METHODS: We analyzed 340,497 Japanese participants with average follow-up of 13.4 years. The association between alcohol drinking and bladder cancer risk was evaluated using Cox regression models within each study, and random-effects models were used to estimate pooled hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). RESULTS: During 4,729,071 person-years, 936 men and 325 women were newly diagnosed with bladder cancer. Our results showed no evidence of significant association between alcohol drinking and bladder cancer risk even among men who consumed alcohol of ≥69 g/week, with HR of 1.02 (95% CI, 0.79-1.33). The null result was observed consistently among women. CONCLUSIONS: Our findings do not support an association between alcohol drinking and bladder cancer risk in the Japanese, at least without consideration of the polymorphisms of alcohol-metabolizing enzymes.


Assuntos
Álcool Desidrogenase/genética , Consumo de Bebidas Alcoólicas/efeitos adversos , Aldeído-Desidrogenase Mitocondrial/metabolismo , Neoplasias da Bexiga Urinária/etiologia , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Aldeído Desidrogenase/genética , Aldeído-Desidrogenase Mitocondrial/genética , Povo Asiático/genética , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo Genético , Estudos Prospectivos , Neoplasias da Bexiga Urinária/epidemiologia
3.
Gastric Cancer ; 21(6): 936-945, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29616362

RESUMO

BACKGROUND: Aldehyde dehydrogenase 2 (ALDH2; rs671, Glu504Lys) and alcohol dehydrogenase 1B (ADH1B; rs1229984, His47Arg) polymorphisms have a strong impact on carcinogenic acetaldehyde accumulation after alcohol drinking. To date, however, evidence for a significant ALDH2-alcohol drinking interaction and a mediation effect of ALDH2/ADH1B through alcohol drinking on gastric cancer have remained unclear. We conducted two case-control studies to validate the interaction and to estimate the mediation effect on gastric cancer. METHODS: We calculated odds ratios (OR) and 95% confidence intervals (CI) for ALDH2/ADH1B genotypes and alcohol drinking using conditional logistic regression models after adjustment for potential confounding in the HERPACC-2 (697 cases and 1372 controls) and HERPACC-3 studies (678 cases and 678 controls). We also conducted a mediation analysis of the combination of the two studies to assess whether the effects of these polymorphisms operated through alcohol drinking or through other pathways. RESULTS: ALDH2 Lys alleles had a higher risk with increased alcohol consumption compared with ALDH2 Glu/Glu (OR for heavy drinking, 3.57; 95% CI 2.04-6.27; P for trend = 0.007), indicating a significant ALDH2-alcohol drinking interaction (Pinteraction = 0.024). The mediation analysis indicated a significant positive direct effect (OR 1.67; 95% CI 1.38-2.03) and a protective indirect effect (OR 0.84; 95% CI 0.76-0.92) of the ALDH2 Lys alleles with the ALDH2-alcohol drinking interaction. No significant association of ADH1B with gastric cancer was observed. CONCLUSION: The observed ALDH2-alcohol drinking interaction and the direct effect of ALDH2 Lys alleles may suggest the involvement of acetaldehyde in the development of gastric cancer.


Assuntos
Álcool Desidrogenase/genética , Consumo de Bebidas Alcoólicas/genética , Aldeído-Desidrogenase Mitocondrial/genética , Neoplasias Gástricas/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Infecções por Helicobacter/complicações , Infecções por Helicobacter/genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fumar/genética , Neoplasias Gástricas/virologia
4.
Int J Cancer ; 141(12): 2480-2488, 2017 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-28875523

RESUMO

The association between alcohol consumption and bladder cancer risk has been insufficiently investigated in East Asian populations, who frequently have the inactive enzyme for metabolizing acetaldehyde. Given that acetaldehyde associated with alcohol consumption is assessed as a carcinogen, consideration of differences in acetaldehyde exposure would aid accuracy in assessing the bladder cancer risk associated with alcohol consumption. Here, we conducted a population-based cohort study in Japan to examine this association, including information on the flushing response as a surrogate marker of the capacity of acetaldehyde metabolism. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using multivariate Cox proportional hazard models. During follow up from 1990 through 2012 for the 95,915 subjects (45,649 men and 50,266 women, aged 40-69 years), 354 men and 110 women were newly diagnosed with bladder cancer. No significant association between alcohol consumption and bladder cancer risk was observed in the overall analysis. Among male flushers, HRs were 1.04 (95% CI 0.70-1.54), 1.67 (1.16-2.42), 1.02 (0.62-1.67) and 0.63 (0.33-1.20) for alcohol consumption of 1-150, 151-300, 301-450, >450 g/week of pure ethanol compared with non-drinkers and occasional drinkers, respectively, indicating an inverted U-shaped association between alcohol consumption and bladder cancer risk. In contrast, no significant association was identified among male non-flushers. The marginally significant interaction between alcohol consumption and the flushing response (p for interaction = 0.083) may support our hypothesis that acetaldehyde derived from alcohol consumption is associated with bladder cancer risk. A prospective study considering polymorphisms of genes involved in acetaldehyde metabolism is warranted.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Rubor/epidemiologia , Neoplasias da Bexiga Urinária/epidemiologia , Acetaldeído/metabolismo , Adulto , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Feminino , Rubor/metabolismo , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Neoplasias da Bexiga Urinária/etiologia , Neoplasias da Bexiga Urinária/metabolismo
5.
Cancer Sci ; 108(8): 1673-1680, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28594447

RESUMO

Despite treatment guidelines recommending observation for men with low-risk prostate cancer with life expectancy <10 years, a majority of elderly patients choose active treatment, which may result in overtreatment. Given the growing burden of prostate cancer among men aged ≥80 years (super-elderly men), accumulation of survival data for evaluation of overtreatment among super-elderly patients is imperative. Here, we report results of a population-based cohort study to clarify potential overtreatment of super-elderly men with localized prostate cancer. We used cancer registry data from the Monitoring of Cancer Incidence in Japan project, which covers 47% of the Japanese population. The subjects were men diagnosed with prostate cancer between 2006 and 2008. Follow-up period was 5 years. We calculated 5-year relative survival rates among the active treatment and observation groups after imputation for missing values. Of the 48 782 patients with prostate cancer included in the analysis, 15.1% were super-elderly men. The 5-year relative survival rates of super-elderly men with localized cancer were 105.9% and 104.1% among the active treatment and observation groups, respectively. This excellent relative survival rate in the observation group remained consistent even after stratification by tumor grade. Of the 2963 super-elderly men with localized cancer, 252 (8.5%) with curative treatment and 1476 (49.8%) with hormone therapy were assumed to have been overtreated. The proportion of overtreatment was estimated to reach 80% after imputation. These specific survival data in super-elderly men in the observation group can be useful in shared decision-making for these patients and may lead to a reduction in overtreatment.


Assuntos
Uso Excessivo dos Serviços de Saúde/estatística & dados numéricos , Neoplasias da Próstata/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias da Próstata/patologia , Sistema de Registros , Análise de Sobrevida
6.
Nicotine Tob Res ; 19(9): 1087-1094, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-27986911

RESUMO

INTRODUCTION: Smoking cessation has been known to be associated with drinking behaviors, which are influenced by polymorphisms in genes encoding alcohol metabolizing enzymes. The aim was to evaluate the impact of aldehyde dehydrogenase 2 (ALDH2, rs671) and alcohol dehydrogenase 1B (ADH1B, rs1229984) polymorphisms together with drinking behaviors on smoking cessation. METHODS: We conducted a cross-sectional study with 1137 former smokers and 1775 current smokers without any cancer at Aichi Cancer Center Hospital between 2001 and 2005. Unconditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for successful smoking cessation by comparing former smokers (quitters) with current smokers (non-quitters). RESULTS: Older age, lower amount of cumulative smoking exposure, lower number of cigarettes per day, younger age of smoking initiation, shorter smoking duration, longer time to first cigarette in the morning, and lower amount of drinking among ever drinkers were predictors of smoking cessation. After careful adjustment for age, sex, smoking patterns, and drinking status, the ORs for smoking cessation among subjects with ALDH2 Glu/Lys and Lys/Lys were 1.02 (95% CI 0.84-1.23) and 1.78 (95% CI 1.23-2.58) compared with those with ALDH2 Glu/Glu, respectively Mediation analyses confirmed that the effect of ALDH2 Lys/Lys on smoking cessation was independent by dinking behaviors. No statistically significant association between ADH1B polymorphism and smoking cessation was observed. CONCLUSIONS: In our Japanese population, ALDH2 polymorphism predicts smoking cessation, independent by drinking behaviors. Interventions for promoting smoking cessation by ALDH2 polymorphism may be useful in Asian populations. IMPLICATIONS: We newly show that subjects with ALDH2 Lys/Lys genotype in a functional polymorphism, rs671, are more likely to quit smoking than those with ALDH2 Glu allele in a Japanese population. Our finding suggests that ALDH2 polymorphism may be useful for promoting smoking cessation in those specific populations as East Asian ones with frequent ALDH2 Lys allele carriers.


Assuntos
Aldeído-Desidrogenase Mitocondrial/genética , Polimorfismo Genético/genética , Fumantes/estatística & dados numéricos , Abandono do Hábito de Fumar/estatística & dados numéricos , Fumar , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fumar/epidemiologia , Fumar/genética
7.
Carcinogenesis ; 37(6): 583-588, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26992901

RESUMO

Although a range of chemical exposures (cigarette smoking and occupational exposure) are recognized risk factors for the development of bladder cancer (BCa), many epidemiological studies have demonstrated that alcohol drinking is not associated with BCa risk. Aldehyde dehydrogenase 2 (ALDH2; rs671, Glu504Lys) and alcohol dehydrogenase 1B (ADH1B; rs1229984, His47Arg) polymorphisms impact the accumulation of acetaldehyde, resulting in an increased risk of various cancers. To date, however, no studies evaluating the association between BCa risk and alcohol drinking have considered these polymorphisms. Here, we conducted a matched case-control study to investigate whether ALDH2 and ADH1B polymorphisms influence BCa risk associated with alcohol drinking. Cases were 74 BCa patients and controls were 740 first-visit outpatients without cancer at Aichi Cancer Center Hospital between January 2001 and December 2005. Odds ratio (OR), 95% confidence interval (CI) and gene-environment interaction were assessed by conditional logistic regression analysis with adjustment for potential confounders. Results showed that ALDH2 Glu/Lys was associated with a significantly increased risk of BCa compared with Glu/Glu (OR 2.03, 95% CI 1.14-3.62, P = 0.017). In contrast, ALDH2 Glu/Lys showed no increase in risk among the stratum of never drinkers compared with Glu/Glu, indicating a gene-environment interaction. ADH1B His/Arg had an OR of 1.98 (1.20-3.24, P = 0.007) compared with His/His. ADH1B Arg+ showed a similar OR and 95% CI. Individuals with ALDH2 Glu/Lys and ADH1B Arg+ had the highest risk of BCa compared with ALDH2 Glu/Glu and ADH1B His/His [OR 4.00 (1.81-8.87), P = 0.001].


Assuntos
Álcool Desidrogenase/genética , Consumo de Bebidas Alcoólicas/genética , Aldeído-Desidrogenase Mitocondrial/genética , Polimorfismo de Nucleotídeo Único , Neoplasias da Bexiga Urinária/genética , Adulto , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Povo Asiático/genética , Estudos de Casos e Controles , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
8.
Jpn J Clin Oncol ; 46(3): 273-83, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26941372

RESUMO

OBJECTIVE: Although several epidemiological studies have demonstrated that cigarette smoking is an important risk factor for bladder cancer, no systematic review in the Japanese population has yet been performed. Accurate evaluation of bladder cancer risk in relation to smoking for Japanese populations can provide necessary information for Japanese policy-makers and doctors to enlighten the importance of smoking cessation. We reviewed epidemiologic data to estimate the strength of the association between cigarette smoking and bladder cancer in the Japanese population. METHODS: We identified previous cohort and case-control studies, extracting data from databases in the MEDLINE (PubMed) and Ichushi. The magnitude of association and strength of evidence were evaluated in each study, and a meta-analysis was conducted to obtain summary estimates for the overall magnitude of association. RESULTS: Three cohort and eight case-control studies were identified. Except for one case-control study, all studies showed a strong positive association between cigarette smoking and bladder cancer. The summary relative risk for ever smokers relative to never smokers was 2.14 (95% confidence interval 1.87-2.44) in a fixed-effect model. CONCLUSIONS: We conclude that cigarette smoking is a convincing risk factor for bladder cancer among Japanese.


Assuntos
Povo Asiático/estatística & dados numéricos , Fumar/efeitos adversos , Fumar/epidemiologia , Neoplasias da Bexiga Urinária/epidemiologia , Estudos de Casos e Controles , Estudos de Coortes , Fatores de Confusão Epidemiológicos , Estudos Epidemiológicos , Humanos , Japão/epidemiologia , Projetos de Pesquisa , Fatores de Risco , Abandono do Hábito de Fumar , Neoplasias da Bexiga Urinária/etiologia
9.
Low Urin Tract Symptoms ; 16(4): e12529, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38956950

RESUMO

OBJECTIVES: This study aimed to evaluate the efficacy and safety of Vibegron for the treatment of residual overactive bladder (OAB) symptoms after laser vaporization of the prostate (photo-selective vaporization of the prostate, contact laser vaporization of the prostate, and thulium laser vaporization). METHODS: This randomized, open-label, parallel-group, single-center superiority trial with a 12-week observation (jRCTs071190040) enrolled male patients with OAB aged 40 years or older who had undergone laser vaporization of the prostate for not less than 12 weeks and not more than 1 year earlier. Patients were allocated to receive Vibegron 50 mg once daily or follow-up without treatment for 12 weeks. RESULTS: Forty-seven patients were enrolled between January 2020 and March 2023. The median age (interquartile range) was 75.5 (72.5-78.5) years for the Vibegron group and 76.5 (71.0-81.0) years for the control group. The intergroup difference in the mean change (95% confidence interval) in the 24-hour urinary frequency at 12 weeks after randomization was -3.66 (-4.99, -2.33), with a significant decrease for the Vibegron group. The Overactive Bladder Symptom Score, International Prostate Symptom Score, IPSS storage score, and Overactive Bladder Questionnaire score significantly improved for the Vibegron group. Voided volume per micturition also increased for the Vibegron group. CONCLUSIONS: The administration of 50 mg of Vibegron once daily for 12 weeks showed significant improvement compared with follow-up without treatment in bladder storage (OAB) symptoms after laser vaporization of the prostate for symptomatic benign prostatic hyperplasia.


Assuntos
Terapia a Laser , Bexiga Urinária Hiperativa , Humanos , Masculino , Idoso , Bexiga Urinária Hiperativa/etiologia , Bexiga Urinária Hiperativa/tratamento farmacológico , Estudos Prospectivos , Terapia a Laser/métodos , Terapia a Laser/efeitos adversos , Hiperplasia Prostática/cirurgia , Hiperplasia Prostática/complicações , Resultado do Tratamento , Idoso de 80 Anos ou mais , Pirimidinonas , Pirrolidinas
10.
Clin Genitourin Cancer ; 22(5): 102148, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39033710

RESUMO

INTRODUCTION: To evaluate the organ-specific therapeutic effect of enfortumab vedotin (EV) after chemotherapy and immunotherapy failed for advanced urothelial carcinoma. MATERIALS METHODS: At 6 institutions between December 2021 and July 2023, we retrospectively analyzed patients with metastatic upper and lower urinary tract cancer who received EV monotherapy after platinum-based chemotherapy and immune checkpoint blockade therapy. Objective response rate (ORR) and organ-specific response rate (OSRR) were evaluated according to the Response Evaluation Criteria in Solid Tumors, version 1.1. RESULTS: This study analyzed 58 patients with 210 tumor lesions, of which 24% were females and 48% had upper urinary tract cancer. The ORR and disease control rate were 53.5% and 74.1%. Moreover, we found 15 target lesions in the primary site, 7 in local recurrence, 93 in the lymph nodes, 46 in the lung, 29 in the liver, and 20 in the bone, with OSRRs of 40%, 71.4%, 61.1%, 70.6%, 90.9%, and 18.2%, respectively. Over time from baseline, the reduction rate (median) in tumor burden was 50% or more in the lymph node, lung, and liver metastases. CONCLUSION: The organ-specific tumor response to EV in patients with metastatic urothelial carcinoma was almost favorable. The antitumor activity of EV monotherapy may be less in bone metastasis than in other organ sites. Conversely, EV showed remarkably high efficacy against liver metastasis.


Assuntos
Anticorpos Monoclonais , Humanos , Feminino , Masculino , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/administração & dosagem , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/secundário , Resultado do Tratamento , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/patologia , Adulto , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Metástase Neoplásica , Antineoplásicos Imunológicos/uso terapêutico
11.
Anticancer Res ; 44(8): 3409-3417, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39060060

RESUMO

BACKGROUND/AIM: The efficacy, safety, and liver toxicity of enfortumab vedotin (EV) for elderly advanced urothelial carcinoma (UC) patients and patients with a poor performance status (PS) are unclear. PATIENTS AND METHODS: We retrospectively analyzed the efficacy, safety, and liver toxicity of EV in elderly patients and patients with a poor PS between December 2021 and August 2023. RESULTS: Sixty-two patients (≥75 years old, n=22; PS≥2, n=10) were enrolled. Patients with PS≥2 had significantly lower albumin levels than those with PS<2 (p=0.023). The objective response and disease control rates did not differ significantly between patients <75 and ≥75 years old (p=0.598 and p=0.769, respectively) or between those with PS<2 and PS≥2 (p>0.99 and p=0.178, respectively). Progression-free survival (PFS) and overall survival (OS) were not significantly different in patients <75 years and ≥75 years (p=0984, 0.368). A significant difference in PFS (p=0.047) but not OS (p=0.086) was observed between the PS<2 and PS≥2 groups. The rates of any-grade and severe (grade ≥3) adverse events did not differ significantly between patients <75 and ≥75 years (p=0.471, p=0.136) or between PS<2 and PS≥2 groups (p>0.99, 0.99). Aspartate aminotransferase (AST) levels significantly increased, but alanine aminotransferase levels did not, following EV treatment (p<0.001). Multivariate analyses revealed that the albumin level was an independent prognostic factor (hazard ratio=0.159; p<0.001). CONCLUSION: EV demonstrated similar efficacy and safety in elderly and younger patients with advanced UC. In patients with a poor PS, although the safety was similar, survival was significantly worse in terms of PFS, while the AST levels were significantly elevated.


Assuntos
Anticorpos Monoclonais , Humanos , Idoso , Masculino , Feminino , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/patologia , Neoplasias Urológicas/mortalidade , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/mortalidade , Intervalo Livre de Progressão , Pessoa de Meia-Idade , Resultado do Tratamento
12.
Anticancer Res ; 44(8): 3419-3426, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39060065

RESUMO

BACKGROUND/AIM: This study retrospectively evaluated whether enfortumab vedotin (EV) monotherapy is effective as a late-line treatment according to prior treatment type in patients with advanced urothelial carcinoma (UC). PATIENTS AND METHODS: We assessed consecutive patients from the Uro-Oncology Group in the Kyushu study population with lower and upper urinary tract cancer treated with EV monotherapy after platinum-based chemotherapy and immune checkpoint inhibitor therapy failure between December 2021 and March 2024. In particular, patients receiving avelumab maintenance or pembrolizumab therapy before EV for advanced UC were analyzed and compared according to the response rate, progression-free survival (PFS), and overall survival (OS). RESULTS: Of the 80 enrolled patients, 31 and 49 received avelumab and pembrolizumab before EV therapy, respectively. The avelumab and pembrolizumab groups had comparable objective response rates (48.4% vs. 44.9%, p=0.820) and disease control rates (77.4% vs. 67.3%, p=0.448). These two groups showed no significant difference in PFS from the initiation of EV (median: 6.4 months vs. 4.2 months, p=0.184); meanwhile, the avelumab group had better OS from the initiation of EV than the pembrolizumab group (median: 16.0 months vs. 10.2 months, p=0.019). Moreover, the median OS after first-line chemotherapy initiation was longer in the avelumab group than in the pembrolizumab group (40.3 months vs. 24.7 months, p=0.054). On multivariate analysis, avelumab maintenance therapy before EV reduced the mortality risk by 47% (95% confidence interval=0.27-1.03; p=0.059). CONCLUSION: EV monotherapy after avelumab maintenance therapy provides favorable survival outcomes in patients with advanced UC.


Assuntos
Anticorpos Monoclonais Humanizados , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/patologia , Neoplasias Urológicas/mortalidade , Resultado do Tratamento , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Intervalo Livre de Progressão , Inibidores de Checkpoint Imunológico/uso terapêutico
13.
Curr Oncol ; 31(2): 862-871, 2024 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-38392058

RESUMO

Subtype of urothelial carcinoma (SUC), defined here as urothelial carcinoma with any histologic subtype or divergent differentiation, is a clinically aggressive disease. However, the efficacy of enfortumab vedotin (EV) against SUC remains unclear. Hence, this study aimed to assess the oncological outcomes of patients with SUC treated with EV for metastatic disease. We retrospectively evaluated consecutive patients with advanced lower and upper urinary tract cancer who received EV after platinum-based chemotherapy and immune checkpoint blockade therapy at six institutions. The objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were compared between patients with pure urothelial carcinoma (PUC) and those with SUC. We identified 44 and 18 patients with PUC and SUC, respectively. Squamous differentiation was the most common subtype element, followed by glandular differentiation and sarcomatoid subtype. Although patients with SUC had a comparable ORR to those with PUC, the duration of response for SUC was short. Patients with SUC had poorer PFS than those with PUC; however, no significant difference was observed in OS. Multivariate analysis revealed that SUC was significantly associated with shorter PFS. Although the response of metastatic SUC to EV was similar to that of PUC, SUC showed faster progression than PUC.


Assuntos
Anticorpos Monoclonais , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/patologia , Prognóstico , Estudos Retrospectivos
14.
Anticancer Res ; 44(7): 3025-3032, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38925809

RESUMO

BACKGROUND/AIM: The clinical outcomes associated with cutaneous toxicity and changes in the renal function of patients receiving enfortumab vedotin (EV) for advanced urothelial carcinoma (UC) is unclear. PATIENTS AND METHODS: We retrospectively analyzed the relationship between clinical outcomes and EV-related cutaneous toxicity, and the influence on the renal function in 58 patients with advanced UC who received EV after the failure of platinum-based chemotherapy and immune checkpoint inhibitors from December 2021 to July 2023. RESULTS: There were no differences in the overall response and disease control rates between patients with any grade of EV-related cutaneous toxicity and without (p=0.605 and p>0.99, respectively) nor of grade ≥3 (p>0.99 and p=0.173, respectively). Progression-free survival was not significantly associated with EV-related cutaneous toxicity of any grade (5.4 vs. 5.6 months, p=0.557) nor of grade ≥3 (2.7 vs. 5.6 months, p=0.053). Overall survival was not significantly associated with EV-related cutaneous toxicity of any grade (11.8 vs. 8.9 months, p=0.389), nor of grade ≥3 (4.6 vs. 11.4 months, p=0.168). The incidence of EV-related cutaneous toxicity of any grade was significantly higher in patients with any grade of ICI-related cutaneous toxicity (88.9% vs. 36.7%, p=0.008). There was no significant difference in the serum creatinine levels after EV treatment (p=0.211). Divided into two groups according to their renal function, using a serum creatinine cut-off of 2 mg/dl, there were no significant changes after EV treatment in either group (p=0.187 and p=0.938). CONCLUSION: EV-related cutaneous toxicity did not affect clinical outcomes, although it occurred in patients who experienced immune checkpoint inhibitor-related cutaneous toxicity. EV did not affect renal function.


Assuntos
Anticorpos Monoclonais , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/patologia , Rim/efeitos dos fármacos , Rim/patologia , Rim/fisiopatologia , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/patologia
15.
Acta Neurochir Suppl ; 118: 143-6, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23564121

RESUMO

Subacute subdural hematoma (SASDH) is a rare entity. We retrospectively reviewed 8 patients with SASDH. Four patients were male and 4 were female, with an age range of 45-87 years (mean, 67.8 years). The minimal level of deterioration ranged from 8 to 14 (mean, 10.5). The deterioration of neurological symptoms was confirmed 4-20 days after injury (mean, 12.9). The hematoma volume was increased in 6 patients. Seven patients underwent surgeries (burr-hole irrigation in 6, craniotomy in 1). The Glasgow Outcome Scale indicated a good recovery in 4 patients and moderate disability in 4 patients. Increased cerebral blood flow was observed just below the SDH in 1 patient. We consider that the hypoperfused tissue in the acute phase might become hyperperfused during the subacute phase owing to impaired autoregulation, and the hyperperfusion may be responsible for the development of the SASDH, leading to deterioration. Further investigations in a larger series are needed to elucidate the mechanism underlying the development of SASDH.


Assuntos
Hematoma Subdural , Idoso , Idoso de 80 Anos ou mais , Feminino , Hematoma Subdural/diagnóstico por imagem , Hematoma Subdural/fisiopatologia , Hematoma Subdural/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
16.
Acta Neurochir Suppl ; 118: 135-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23564119

RESUMO

Posterior fossa injury is rare, occurring in less than 3 % of head injuries. We retrospectively reviewed patients' clinical and radiological findings, management, and outcomes. The aim of the present study was to investigate the features of posterior fossa hematoma, including posterior fossa epidural hematoma (EDH), posterior fossa subdural hematoma (SDH), and intracerebellar hematoma. From January 1995 to January 2009, 4,315 patients with head trauma were hospitalized at our institution. The -present study focused on 41 patients (1.0 %) with traumatic hematomas of the posterior fossa. Eighteen patients had EDH, 10 patients had SDH, and 17 patients had intracerebellar hematomas. In each type of injury, occipital bone fractures were seen in many patients, and hematoma enlargement was often observed within a few days of the injury. In addition, a high frequency of associated lesions and a high poor outcome rate were features of intracerebellar hematomas and -posterior fossa SDH. The present study suggests that repeat CT imaging and careful management are necessary until the lesion is stabilized, and patients showing lesions with mass effects should therefore be immediately treated with surgery.


Assuntos
Fossa Craniana Posterior/patologia , Hematoma Epidural Craniano/patologia , Hematoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cerebelo/patologia , Pré-Escolar , Feminino , Escala de Coma de Glasgow , Hematoma Epidural Craniano/classificação , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
17.
Acta Neurochir Suppl ; 118: 139-42, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23564120

RESUMO

Twenty patients with traumatic basal ganglia hematoma (TBGH) were studied. Of the 20 patients, 16 were male and 4 were female, with an age range of 4-89 years (mean, 54.4 years). The causes of injury were traffic accidents in 12 patients and falls in 8. The mean admission GCS score was 7.5. Skull fractures were revealed in five patients (25 %). The hematoma was found in the putamen in 15 patients (80 %), the thalamus in 4, and the caudate in 1. The mean hematoma volume was 10.7 mL. The CT findings indicated focal contusions in 9 patients, subdural hematoma in 5, intraventricular hemorrhage in 4, subarachnoid hemorrhage in 10, and diffuse axonal injury in 5. Six patients (30 %) underwent surgery. The final outcomes were poor: 7 patients (35 %) died, 1 was in a vegetative state, 4 experienced severe disabilities, and 8 patients (40 %) made a favorable recovery. The statistical analysis identified the GCS score and midline shift as prognostic factors.Our study revealed interesting characteristics of TBGH, including a high frequency of putaminal involvement, a low frequency of skull fractures, a high frequency of associated intracranial lesions, and a high poor outcome and mortality rate.


Assuntos
Hemorragia dos Gânglios da Base , Gânglios da Base/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Gânglios da Base/diagnóstico por imagem , Hemorragia dos Gânglios da Base/diagnóstico , Hemorragia dos Gânglios da Base/fisiopatologia , Hemorragia dos Gânglios da Base/terapia , Criança , Pré-Escolar , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto Jovem
18.
Acta Neurochir Suppl ; 118: 235-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23564139

RESUMO

New findings (NF) on postoperative CTs are -occasionally found in patients who undergo surgery for traumatic brain injury (TBI). We conducted a retrospective -registry-based review of the care of 102 patients who underwent decompressive craniectomy (DC) for TBI to investigate the prognostic factors of new findings on CT early after -surgery. Of the 102 patients, the mean age was 50 years and 69.6 % were male. The overall survival was 72.5 %. The primary indication for DC included subdural hematoma in 72 (70.6 %), epidural hematoma in 17 (16.7 %), and intraparenchymal contusion in 13 (12.7 %). New findings on postoperative CTs were observed in 26 patients (25.5 %). The univariate analysis showed that a GCS score ≤8 (P = 0.012) and the absence of a basal cistern (P = 0.012) were significantly associated with NF on postoperative CT. The logistic regression analysis demonstrated that the GCS score ≤8 (P = 0.041; OR, 3.0; 95 % CI, 1.048-8.517) was the only significant factor. TBI patients with a low GCS score who underwent DC should undergo additional CT evaluations immediately after surgery.


Assuntos
Traumatismos Craniocerebrais/diagnóstico por imagem , Traumatismos Craniocerebrais/cirurgia , Craniectomia Descompressiva/métodos , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Traumatismos Craniocerebrais/mortalidade , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
19.
Acta Neurochir Suppl ; 118: 277-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23564148

RESUMO

Hemispheric hypertensive intracerebral hemorrhage (ICH) has a high mortality rate. Decompressive craniectomy (DC) has generally been used for the treatment of severe traumatic brain injury, aneurysmal subarachnoid hemorrhage, and hemispheric cerebral infarction. However, the effect of DC on hemispheric hypertensive ICH is not well understood. To investigate the effects of DC for treating hemispheric hypertensive ICH, we retrospectively reviewed the clinical and radiological findings of 21 patients who underwent DC for hemispheric hypertensive ICH. Eleven of the patients were male and 10 were female, with an age range of 22-75 years (mean, 56.6 years). Their preoperative Glasgow Coma Scale scores ranged from 3 to 13 (mean, 6.9). The hematoma volumes ranged from 33.4 to 98.1 mL (mean, 74.2 mL), and the hematoma locations were the basal ganglia in 10 patients and the subcortex in 11 patients. Intraventricular extensions were observed in 11 patients. With regard to the complications after DC, postoperative hydrocephalus developed in ten patients, and meningitis was observed in three patients. Six patients had favorable outcomes and 15 had poor outcomes. The mortality rate was 10 %. A statistical analysis showed that the GCS score at admission was significantly higher in the favorable outcome group than that in the poor outcome group (P = 0.029). Our results suggest that DC with hematoma evacuation might be a useful surgical procedure for selected patients with large hemispheric hypertensive ICH.


Assuntos
Craniectomia Descompressiva/métodos , Hematoma/etiologia , Hematoma/cirurgia , Hemorragia Intracraniana Hipertensiva/complicações , Hemorragia Intracraniana Hipertensiva/cirurgia , Adulto , Idoso , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
20.
Acta Neurochir Suppl ; 118: 289-91, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23564151

RESUMO

Numerous studies on hydrocephalus after decompressive craniectomy (DC) for severe traumatic brain injury have been reported, whereas there have been only two reports on DC for hemispheric cerebral infarction. Here, we present the clinical details of 23 patients who underwent DC for hemispheric cerebral infarction and the incidence of hydrocephalus following DC. Of the 23 patients, 13 were male and 10 were female, with an age range from 34 to 75 years (mean, 60.8 years). The areas of hemispheric infarctions were those of the middle cerebral arteries in 12 patients and of the internal carotid arteries in 11 patients. The mean preoperative GCS score was 6. Nineteen patients (82.6 %) underwent cranioplasty. Pre-cranioplasty hydrocephalus was observed in 11 (47.8 %) patients. Four patients who had precranioplasty hydrocephalus were transferred or died without cranioplasty, and post-cranioplasty hydrocephalus occurred in 7 (36.8 %). Only one patient underwent a shunt procedure after cranioplasty. We consider that the explanation for the discrepancies between our study and the previous studies might lie in the definition of hydrocephalus and the indications for shunting.


Assuntos
Craniectomia Descompressiva/efeitos adversos , Hidrocefalia/etiologia , Complicações Pós-Operatórias/fisiopatologia , Acidente Vascular Cerebral/cirurgia , Adulto , Idoso , Feminino , Escala de Resultado de Glasgow , Humanos , Hidrocefalia/diagnóstico , Isquemia/complicações , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/etiologia
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