Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 91
Filtrar
1.
Int J Clin Oncol ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919691

RESUMO

PURPOSE: Clinical outcomes of patients with newly diagnosed metastatic hormone-naïve prostate cancer (mHNPC) and initially treated with androgen deprivation therapy (ADT) were evaluated. METHODS: The medical records of 605 consecutive mHNPC patients with initial ADT or combined androgen blockade (CAB) at nine study centers between 2008 and 2016 were retrospectively reviewed. Castration-resistant prostate cancer (CRPC)-free and overall survival (OS) were estimated by the Kaplan-Meier method. The association of pretreatment risk factors with CRPC-free survival and OS was evaluated by Cox proportional hazard models and differences in survival were classified by the number of risk factors. RESULTS: Median follow-up was 2.95 years, median CRPC-free survival was 21.9 months and median OS was 5.37 years. Multivariable analysis found that four risk factors, a Gleason score ≥ 9, lymph node metastasis, an extent of disease score ≥ 2, and serum LDH of > 220 IU were independently associated with both CRPC-free survival and OS. Median CRPC-free survival of low-risk patients with no or one factor was 86.5 months, 17.9 months in intermediate-risk patients with two or three factors, and 11.0 months in high-risk patients with four factors. Median OS was 4.72 years in intermediate- and 2.44 years in high-risk patients. It was not reached in low-risk patients. CONCLUSION: In this series, CRPC-free and OS of a subset of mHNPC patients in Japan who were treated with ADT or CAB had better CRPC-free and overall survivals in Japan. Risk-adapted treatment based on the presence of novel prognostic factors may be beneficial for selected mHNPC patients.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31810867

RESUMO

INTRODUCTION: We aimed to evaluate the treatment sequence for patients with metastatic castration-resistant prostate cancer (mCRPC) in real-world practice and compare overall survival in each sequential therapy. PATIENTS AND METHODS: We retrospectively evaluated 146 patients with mCRPC who were initially treated with androgen deprivation therapy as metastatic hormone-naive prostate cancer in 14 hospitals between January 2010 and March 2019. The agents for the sequential therapy included new androgen receptor-targeted agents (ART: abiraterone acetate or enzalutamide), docetaxel, and/or cabazitaxel. We evaluated the treatment sequence for mCRPC and the effect of sequence patterns on overall survival. RESULTS: The median age was 71 years. A total of 35 patients received ART-ART, 33 received ART-docetaxel, 68 received docetaxel-ART, and 10 received docetaxel-cabazitaxel sequences. The most prescribed treatment sequence was docetaxel-ART (47%), followed by ART-ART (24%). Overall survival calculated from the initial diagnosis reached 83, 57, 79, and 37 months in the ART-ART, ART-docetaxel, docetaxel-ART, and docetaxel-cabazitaxel, respectively. Multivariate Cox regression analyses showed no significant difference in overall survival between the first-line ART (n = 68) and first-line docetaxel (n = 78) therapies (hazard ratio [HR], 0.84; P = .530), between the ART-ART (n = 35) and docetaxel-mixed (n = 111) sequences (HR, 0.82; P = .650), and between the first-line abiraterone (n = 32) and first-line enzalutamide (n = 36) sequences (HR, 1.58; P = .384). CONCLUSION: The most prescribed treatment sequence was docetaxel followed by ART. No significant difference was observed in overall survival among the treatment sequences in real-world practice.

3.
Clin Genitourin Cancer ; 17(6): e1091-e1098, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31575477

RESUMO

INTRODUCTION: This study aimed to investigate the effect of low prostate-specific antigen (PSA) on prognosis, as the association of initial PSA level with prognosis in patients with metastatic castration-naive prostate cancer (mCNPC) remains unclear. PATIENTS AND METHODS: We evaluated 575 patients with mCNPC from 10 hospitals. Patients were stratified into 2 groups according to their initial PSA: PSA < 100 and PSA ≥ 100 groups. We compared castration-resistant prostate cancer (CRPC)-free survival, overall survival (OS), and OS from the CRPC diagnosis between the groups. Multivariate Cox regression analysis was performed to evaluate the effect of initial PSA level on prognosis. RESULTS: Of the 575 patients, 196 (34%) patients belonged to the PSA < 100 group. No significant difference was found in patients' backgrounds except for PSA, the extent of disease, and high tumor burden between the groups. CRPC-free survival was significantly shorter in the PSA ≥ 100 group than in the PSA < 100 group. However, the OS after CRPC diagnosis was significantly shorter in the PSA < 100 group than that of the PSA ≥ 100 group. Multivariate analyses showed that PSA < 100 ng/mL was an independent factor for OS after CRPC, whereas no significant association was observed in the CRPC-free survival and OS. CONCLUSIONS: A significant effect of initial PSA < 100 ng/mL on OS after CRPC was observed. PSA < 100 ng/mL might be a poor prognostic factor in patients with mCNPC after CRPC.

4.
Cancer Med ; 8(15): 6566-6577, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31508900

RESUMO

BACKGROUND: The purpose of this study was to identify predictive factors associated with conditional net survival in patients with metastatic hormone-naive prostate cancer (mHNPC) initially treated with androgen deprivation therapy (ADT). METHODS: At nine hospitals in Tohoku, Japan, the medical records of 605 consecutive patients with mHNPC who initially received ADT were retrospectively reviewed. The Pohar Perme estimator was used to calculate conditional net cancer-specific survival (CSS) and overall survival (OS) for up to 5 years subsequent to the diagnosis. Using multiple imputation, proportional hazard ratios for conditional CSS and OS were calculated with adjusted Cox regression models. RESULTS: During a median follow up of 2.95 years, 208 patients died, of which 169 died due to progressive prostate cancer. At baseline, the 5-year CSS and OS rates were 65.5% and 58.2%, respectively. Conditional 5-year net CSS and OS survival gradually increased for all the patients. In patients given a 5-year survivorship, the conditional 5-year net CSS and OS rates improved to 0.906 and 0.811, respectively. Only the extent of disease score (EOD) ≥2 remained a prognostic factor for CSS and OS up to 5 years; as survival time increased, other variables were no longer independent prognostic factors. CONCLUSIONS: The conditional 5-year net CSS and OS in patients with mHNPC gradually increased; thus, the risk of mortality decreased with increasing survival. The patient's risk profile changed over time. EOD remained an independent prognostic factor for CSS and OS after 5-year follow-up. Conditional net survival can play a role in clinical decision-making, providing intriguing information for cancer survivors.

5.
PLoS One ; 14(8): e0220173, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31369573

RESUMO

OBJECTIVE: TP53, a well-known tumor-suppressor gene in bladder carcinogenesis, has a functional single-nucleotide polymorphism on codon 72. The aim of this study was to elucidate the association between TP53 codon 72 polymorphism and somatic mutations in bladder cancer. MATERIAL AND METHODS: Germline TP53 codon 72 polymorphism and somatic mutations of 50 cancer-associated genes were analyzed in 103 bladder cancer patients (59 non-muscle-invasive and 44 muscle-invasive), using Taqman genotyping assay and target sequencing, respectively. The expression of FGF-FGFR signaling pathway genes was analyzed by RNA sequencing of frozen tissue. RESULTS: The allele frequency of TP53 codon 72 in our cohort was 37, 42, and 21% for Arg/Arg, Arg/Pro, and Pro/Pro, respectively. Interestingly, the prevalence of FGFR3 mutation was higher in patients with the Arg allele, whereas that of the RAS mutation was higher in patients without the Arg allele. The same association was seen in non-muscle-invasive bladder cancer (NMIBC) patients and no differences were observed in muscle-invasive bladder cancer patients. In NMIBC, FGFR1 expression was higher in patients without the Arg allele and FGFR3 expression was higher in patients with the Arg allele. CONCLUSION: The germline TP53 codon 72 polymorphism was associated with mutations of FGFR3 or RAS and expression of FGFR1 and FGFR3 in NMIBC. These findings provide new insight into the molecular mechanisms underlying the influence of the genetic background on carcinogenesis in bladder cancer.

6.
Sci Rep ; 9(1): 12071, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31427687

RESUMO

We evaluated the impact of early changes in serum biomarker levels on the survival of patients with metastatic hormone-sensitive prostate cancer (mHSPC) who were initially treated with androgen deprivation therapy (ADT). We retrospectively investigated 330 patients with mHSPC whose serum maker levels were at baseline and at 2-4 months. An optimal Cox regression model was established with the highest optimism-corrected concordance index based on 10-fold cross-validation. The median cancer-specific survival (CSS) and overall survival (OS) were 7.08 and 6.47 years (median follow-up, 2.53 years), respectively. In the final optimal Cox model with serum biomarker levels treated as time-varying covariates, prostate-specific antigen (PSA), hemoglobin (Hb), and alkaline phosphatase (ALP) significantly increased the risk of poor survival in the context of both CSS and OS. Kaplan-Meier curves stratified by the three risk factors of high PSA, low Hb and high ALP desmondtated that median OS were not reached with none of these factors, 6.47 years with one or two factors, and 1.76 years with all three factors.Early changes in serum biomarker levels after ADT may be good prognostic markers for the survival of patients with mHSPC.

7.
Eur Urol Oncol ; 2(3): 320-328, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31200847

RESUMO

BACKGROUND: There has been growth in the treatment options for castration-sensitive metastatic prostate cancer (mPCa), but without clear guidance for risk stratification. OBJECTIVE: To identify clinical parameters associated with overall survival (OS) and establish a prognostic model for use with treatment-naïve castration-sensitive mPCa. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of 304 patients treated at Kyoto University Hospital was performed. A prognostic model was created using clinical parameters associated with OS. The model was externally validated in an independent cohort of 520 patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable analysis was performed to identify the clinical parameters associated with OS. Risk scores were calculated using Cox proportional hazards analysis for each combination of risk factors, and patients were grouped into categories based on those scores. RESULTS AND LIMITATIONS: Over 80% of the cohort had a Gleason sum score ≥8. The median OS was 53mo among patients with CHAARTED high-volume PCa (n=172) and 131mo among those with low-volume PCa (n=100). Independent factors associated with OS were extent of disease score ≥2 or the presence of liver metastasis; lactate dehydrogenase >250U/L; and a primary Gleason score of 5. The median OS for the high-, intermediate-, and low-risk groups according to the new model were 28mo, 59mo, and not reached, respectively; the corresponding values in the validation cohort were 41mo, 63mo, and not reached. Harrell's C-index was 0.649. CONCLUSIONS: Our simple and reproducible prognostic model for treatment-naïve castration-sensitive mPCa could aid in risk stratification and treatment selection. PATIENT SUMMARY: We identified clinical parameters associated with prognosis in castration-sensitive metastatic prostate cancer and established a reproducible prognostic model that could be used to guide treatment decisions.

8.
Cancer Sci ; 110(8): 2573-2589, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31145522

RESUMO

To reduce unnecessary prostate biopsies (Pbx), better discrimination is needed. To identify clinically significant prostate cancer (CSPC) we determined the performance of LacdiNAc-glycosylated prostate-specific antigen (LDN-PSA) and LDN-PSA normalized by prostate volume (LDN-PSAD). We retrospectively measured LDN-PSA, total PSA (tPSA), and free PSA/tPSA (F/T PSA) values in 718 men who underwent a Pbx in 3 academic urology clinics in Japan and Canada (Pbx cohort) and in 174 PC patients who subsequently underwent radical prostatectomy in Australia (preop-PSA cohort). The assays were evaluated using the area under the receiver operating characteristics curve (AUC) and decision curve analyses to discriminate CSPC. In the Pbx cohort, LDN-PSAD (AUC 0.860) provided significantly better clinical performance for discriminating CSPC compared with LDN-PSA (AUC 0.827, P = 0.0024), PSAD (AUC 0.809, P < 0.0001), tPSA (AUC 0.712, P < 0.0001), and F/T PSA (AUC 0.661, P < 0.0001). The decision curve analysis showed that using a risk threshold of 20% and adding LDN-PSA and LDN-PSAD to the base model (age, digital rectal examination status, tPSA, and F/T PSA) permitted avoidance of even more biopsies without missing CSPC (9.89% and 18.11%, respectively vs 2.23% [base model]). In the preop-PSA cohort, LDN-PSA values positively correlated with tumor volume and tPSA and were significantly higher in pT3, pathological Gleason score ≥ 7. Limitations include limited sample size, retrospective nature, and no family history information prior to biopsy. LacdiNAc-glycosylated PSA is significantly better than the conventional PSA test in identifying patients with CSPC. This study was approved by the ethics committee of each institution ("The Study about Carbohydrate Structure Change in Urological Disease"; approval no. 2014-195).


Assuntos
Lactose/análogos & derivados , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Idoso , Glicosilação , Humanos , Lactose/metabolismo , Masculino , Pessoa de Meia-Idade , Gradação de Tumores/métodos , Antígeno Prostático Específico , Curva ROC , Estudos Retrospectivos , Carga Tumoral/fisiologia
9.
Tohoku J Exp Med ; 248(1): 31-36, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31092738

RESUMO

Aldosterone affects various systems and organs, including the cardiovascular system, through mineralocorticoid receptors. We here report a primary aldosteronism patient with severe cardiac dysfunction who showed dramatic improvement after laparoscopic adrenalectomy. The 57-year-old man presented with acute heart failure exacerbation. Performance status was 4, and New York Heart Association classification was 4. Echocardiography showed diffuse hypokinetic wall motion with an ejection fraction of 20%. The patient was found to have a high plasma level of brain natriuretic peptide (4,935 pg/mL), hypokalemia (2.7 mEq/L), an extremely elevated plasma aldosterone concentration (1,804 pg/mL), and high aldosterone-to-renin ratio [plasma aldosterone concentration (pg/mL)/plasma renin activity (ng/mL/hr)] (9,002). Computed tomography revealed a tumor 42 mm in diameter in the right adrenal gland. Primary aldosteronism was diagnosed with adrenal venous sampling. Medical treatment for heart failure was continued for several months, but the cardiac function was not sufficiently improved, suggesting the indication of heart transplantation. However, the patient could not be considered a candidate because of the adrenal tumor. Laparoscopic adrenalectomy was therefore performed. Immediately after surgery, echocardiography showed improved wall motion with an ejection fraction of 36%. Performance status and New York Heart Association classification were improved to 0 and 2, respectively. The present case has shown the efficacy of laparoscopic adrenalectomy for primary aldosteronism patients with severe heart failure.


Assuntos
Adrenalectomia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/cirurgia , Testes de Função Cardíaca , Hiperaldosteronismo/fisiopatologia , Hiperaldosteronismo/cirurgia , Laparoscopia , Biópsia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico por imagem , Hormônios/metabolismo , Humanos , Hiperaldosteronismo/complicações , Hiperaldosteronismo/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Radiografia Torácica , Fatores de Tempo
10.
Hypertension ; 73(6): 1283-1290, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31006333

RESUMO

Peripheral 18-oxocortisol (18oxoF) level could contribute to the detection of aldosterone-producing adenoma (APA) in patients with primary aldosteronism. However, peripheral 18oxoF varies among such patients, which is a big drawback concerning its clinical application. We studied 48 cases of APA, 35 harboring KCNJ5 mutation, to clarify the significance of clinical and pathological parameters about peripheral 18oxoF. Peripheral 18oxoF concentration ranged widely from 0.50 to 183.13 ng/dL and correlated positively with intratumoral areas stained positively for steroidogenic enzymes ( P<0.0001). The peripheral 18oxoF level also correlated significantly with that of circulating aldosterone ( P<0.0001) but not with that of cortisol, a precursor of 18oxoF. However, a significant correlation was detected between peripheral 18oxoF and intratumoral glucocorticoids ( P<0.05). In addition, peripheral 18oxoF correlated positively with the number of hybrid cells double positive for 11ß-hydroxylase and aldosterone synthase ( P<0.0001). Comparing between the cases with and those without KCNJ5 mutation, the KCNJ5-mutated group demonstrated a significantly higher concentration of peripheral 18oxoF (28.4±5.6 versus 3.0±0.9 ng/dL, P<0.0001) and a larger intratumoral environment including the hybrid cells ( P<0.001), possibly representing a deviation from normal aldosterone biosynthesis. After multivariate analysis, KCNJ5 mutation status turned out to be the most associated factor involved in 18oxoF synthesis in APA ( P<0.0001). Results of our present study first revealed that enhanced 18oxoF synthesis in APA could come from a functional deviation of aldosterone biosynthesis from the normal zona glomerulosa and the utility of peripheral 18oxoF measurement could be influenced by the prevalence of KCNJ5 mutation in an APA.


Assuntos
Neoplasias do Córtex Suprarrenal/genética , Adenoma Adrenocortical/genética , Aldosterona/metabolismo , DNA de Neoplasias/genética , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G/genética , Hidrocortisona/análogos & derivados , Mutação/genética , Neoplasias do Córtex Suprarrenal/metabolismo , Adenoma Adrenocortical/metabolismo , Análise Mutacional de DNA , Feminino , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G/metabolismo , Humanos , Hidrocortisona/biossíntese , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
BMC Cancer ; 19(1): 156, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30770773

RESUMO

BACKGROUND: We analyzed the efficacy and toxicity of cabazitaxel (CBZ) at high and low initial doses in Japanese patients with docetaxel-resistant castration-resistant prostate cancer (CRPC). METHODS: We retrospectively evaluated 118 patients who received CBZ for docetaxel-resistant CRPC in 10 university hospitals in Japan between 2014 and 2016. The rate of decrease of prostate-specific antigen (PSA), adverse events, progression-free survival (PFS), and overall survival (OS) were compared between patients receiving initially high (≥22.5 mg/m2, n = 36) and low (≤20 mg/m2, n = 80) CBZ doses. Factors associated with survival and grade 4 neutropenia were evaluated. RESULTS: PSA values decreased by > 50% in 22 patients (19%), with a higher frequency in the high-dose group than in the low-dose group (29 and 14%, P = 0.073). The median PFS time for the all-patient, high- and low-dose groups was 2.8 months (95% confidence interval [CI] 1.9-4.4), 2.1 months (1.2-5.5), and 3.0 months (2.0-4.4), respectively (P = 0.904). The median OS times were 16.3 months (95% CI 9.7-30.9), 30.9 months (11.8-47.4), and 10.2 months (8.6-20), respectively (P = 0.020). In multivariate analyses, PFS was significantly associated with existing bone metastasis at diagnosis (P = 0.005) and OS with PSA > 100 ng/ml (P = 0.007), hemoglobin < 12 g/dl (P = 0.030), and low initial CBZ dose (P = 0.030). Grade 4 neutropenia occurred in 53 patients (45%) and was associated with a low CBZ dose (hazard ratio 0.21, 95% CI 0.08-0.59, P = 0.002). CONCLUSIONS: CBZ at a higher initial dose may have similar response rate and response duration, but longer survival duration after treatment with higher toxicity than a lower initial dose for docetaxel-resistant CRPC in Japanese patients.


Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/efeitos adversos , Taxoides/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Docetaxel/uso terapêutico , Humanos , Japão , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Antígeno Prostático Específico/análise , Neoplasias de Próstata Resistentes à Castração/mortalidade , Estudos Retrospectivos , Taxoides/administração & dosagem , Resultado do Tratamento
12.
World J Urol ; 37(11): 2365-2373, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30729312

RESUMO

PURPOSE: We determine whether the nadir prostate-specific antigen level (PSA nadir) and time to nadir (TTN) during initial androgen deprivation therapy (ADT) are prognostic factors in metastatic castration-resistant prostate cancer (mCRPC) patients. METHODS: We reviewed the Michinoku Japan Urological Cancer Study Group database, including 321 mCRPC patients. Optimal cutoff values for PSA nadir and TTN on survival were calculated with the receiver operating characteristic (ROC) curve. Patients were stratified into unfavorable (higher PSA nadir and/or shorter TTN) and favorable (lower PSA nadir and longer TTN) groups. The inversed probability of treatment weighing (IPTW)-adjusted Cox proportional hazard model was performed to evaluate the impact of the unfavorable group on overall survival (OS) after CRPC diagnosis. RESULTS: Median age and follow-up period were 71 years and 35 months, respectively. ROC curve analysis demonstrated cutoffs of PSA nadir > 0.64 ng/mL and TTN < 7 months. The unfavorable group included 248 patients who had significantly shorter OS after mCRPC. The IPTW-adjusted multivariate model revealed that the unfavorable group had a negative impact on OS in mCRPC patients [hazards ratio (HR) 2.98, P < 0.001]. CONCLUSIONS: Higher PSA nadir and shorter TTN during the initial ADT are poor prognostic factors in patients with mCRPC.

13.
Int J Cancer ; 145(2): 484-493, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-30628065

RESUMO

Renal cell carcinoma (RCC) is a malignant tumor that currently lacks clinically useful biomarkers indicative of early diagnosis or disease status. RCC has commonly been diagnosed based on imaging results. Metabolomics offers a potential technology for discovering biomarkers and therapeutic targets by comprehensive screening of metabolites from patients with various cancers. We aimed to identify metabolites associated with early diagnosis and clinicopathological factors in RCC using global metabolomics (G-Met). Tumor and nontumor tissues were sampled from 20 cases of surgically resected clear cell RCC. G-Met was performed by liquid chromatography mass spectrometry and important metabolites specific to RCC were analyzed by multivariate statistical analysis for cancer diagnostic ability based on area under the curve (AUC) and clinicopathological factors (tumor volume, pathological T stage, Fuhrman grade, presence of coagulation necrosis and distant metastasis). We identified 58 metabolites showing significantly increased levels in tumor tissues, 34 of which showed potential early diagnostic ability (AUC >0.8), but 24 did not discriminate between tumor and nontumor tissues (AUC ≤0.8). We recognized 6 pathways from 9 metabolites with AUC >0.8 and 7 pathways from 10 metabolites with AUC ≤0.8 about malignant status. Clinicopathological factors involving malignant status correlated significantly with metabolites showing AUC ≤0.8 (p = 0.0279). The tricarboxylic acid cycle (TCA) cycle, TCA cycle intermediates, nucleotide sugar pathway and inositol pathway were characteristic pathways for the malignant status of RCC. In conclusion, our study found that metabolites and their pathways allowed discrimination between early diagnosis and malignant status in RCC according to our G-Met protocol.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/diagnóstico , Neoplasias Renais/diagnóstico , Metabolômica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Estudos de Casos e Controles , Cromatografia Líquida , Ciclo do Ácido Cítrico , Detecção Precoce de Câncer , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nefrectomia , Transdução de Sinais , Espectrometria de Massas em Tandem
14.
Medicine (Baltimore) ; 98(2): e13962, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30633177

RESUMO

The objective of this study was to evaluate intraoperative hypothermia as a predictor of complication and prognosis in patients with muscle-invasive bladder cancer treated with radical cystectomy.The data of 124 patients treated with radical cystectomy for muscle-invasive bladder cancer in our department, from 2003 to 2016, were retrospectively collected. The patients were divided into 2 groups according to the lowest intraoperative deep body temperature, that is, the hypothermia group (<96.8°F) and the normothermia group (≥96.8°F). Preoperative and intraoperative variables were compared among the 2 groups, and factors associated with complications, recurrences, and survivals were analyzed.Sixty-eight (54.8%) of the 124 patients presented intraoperative hypothermia. There was no significant difference in the patient's characteristics between the 2 groups. Postoperative complications (Clavien-Dindo ≤III) of any types occurred in 15 patients (22.1%) in the hypothermia group, as compared with 8 patients (14.3%) in the normothermia group (P = .27). The hypothermia group had a higher pathologic stage (P = .029) and a higher recurrence rate within 12 months (P = .013), as compared with the normothermia group. Intraoperative hypothermia was an independent prognostic factor for overall survival in all patients (hazard ratio [HR] 2.47; 95% confidence interval [CI], 1.01-2.85; P = .047). When stratified by disease stage, stage II intraoperative hypothermia was an independent prognostic factor for disease-free survival (HR 3.35; 95% CI, 1.27-8.83; P = .015) and overall survival (HR 4.24; 95% CI, 1.38-12.9; P = .011).This study suggests that intraoperative hypothermia could be a significant predictor for recurrence and survival in muscle-invasive bladder cancer treated with radical cystectomy.


Assuntos
Cistectomia/efeitos adversos , Cistectomia/métodos , Hipotermia Induzida/métodos , Neoplasias da Bexiga Urinária/cirurgia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante/métodos , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Hipotermia Induzida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Músculos/patologia , Invasividade Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Prognóstico , Estudos Retrospectivos , Fatores Sexuais , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia
15.
Urology ; 123: 265-272, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30359707

RESUMO

OBJECTIVE: To evaluate renal damage after off-clamp partial nephrectomy (PN) using a novel surgical device, piezo actuator-driven pulsed water jet (ADPJ) system. METHODS: Sprague-Dawley rats were divided into 4 groups and subjected to sham operation, off-clamp PN by the piezo ADPJ system, radio knife, and soft coagulation, which have been used as thermal coagulation devices. Urine and blood samples were collected, and residual kidneys were harvested at 1, 7, 14, 30, and 90 days after PN. Serum blood urea nitrogen, creatinine, and urinary and serum kidney injury molecule-1 KIM-1 levels were measured. Morphological features and the extent of renal ischemia of resection surfaces were evaluated by hematoxylin-eosin staining and immunostaining using antibodies to 1-methyladenosine, respectively. In addition, the expression levels of KIM-1 mRNA extracted from each resection surface were analyzed by quantitative real-time reverse transcription polymerase chain reaction. RESULTS: Serum blood urea nitrogen and creatinine were significantly lower with the piezo ADPJ system than with soft coagulation. Urinary and serum KIM-1 levels were also significantly decreased with the ADPJ. The extent of 1-methyladenosine immunostaining was significantly less with the ADPJ than with thermal coagulation devices. The expression levels of KIM-1 mRNA were also lower in the ADPJ system group. CONCLUSION: The piezo ADPJ system might attenuate renal damage after off-clamp PN.


Assuntos
Complicações Intraoperatórias/prevenção & controle , Rim/lesões , Nefrectomia/instrumentação , Animais , Desenho de Equipamento , Rim/fisiologia , Testes de Função Renal , Masculino , Modelos Animais , Nefrectomia/métodos , Ratos , Ratos Sprague-Dawley , Água
16.
Hum Pathol ; 84: 124-132, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30290162

RESUMO

The expression statuses of sex steroid receptors and sex steroid-synthesizing/metabolizing enzymes have been reported in primary prostate cancer lesions, but that in metastatic lymph nodes has remained unknown. Therefore, in this study, we immunolocalized these proteins in primary tumors and paired metastatic lymph nodes of prostate cancer and correlated the findings with clinicopathological factors of individual patients. The expression statuses of AR and ER ß was significantly increased in metastatic lymph nodes compared with primary lesions, whereas that of 17ßHSD1, 17ßHSD2, 17ßHSD5, and STS immunoreactivity was decreased in metastatic lymph nodes. In metastatic lymph nodes, the status of 5α2 was significantly correlated with that of AR. In addition, 17ßHSD5-, 5α1-, STS-, and EST-positive cases were significantly associated with Gleason score (GS) status (GS > 8 versus GS < 7) in metastatic lymph nodes. Results of our present study did demonstrate that in situ androgen and estrogen metabolism and action play roles in pathophysiology of prostate cancer in metastatic lymph nodes, but these steroidogenic effects could be different from those in primary lesions.


Assuntos
Linfonodos/metabolismo , Neoplasias da Próstata/metabolismo , Aromatase/metabolismo , Estradiol Desidrogenases/metabolismo , Receptor beta de Estrogênio/metabolismo , Humanos , Linfonodos/patologia , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/patologia , Receptores Androgênicos/metabolismo , Esteril-Sulfatase/metabolismo , Sulfotransferases/metabolismo
17.
Urol Int ; 102(1): 118-121, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-28427078

RESUMO

A 32-year-old man visited our hospital due to urinary retention. Prostate-specific antigen was 13.7 ng/mL. Imaging examinations showed a large prostatic tumor and lung and internal iliac lymph node metastases. Transrectal biopsy confirmed embryonal rhabdomyosarcoma of the prostate classified as cT2bN1M1 (stage IV) by the International Rhabdomyosarcoma Study (IRS) Group staging system. Systemic chemotherapy was started according to the IRS III regimen 36, which consisted of 16 weeks of induction chemotherapy with radiation. After 20 weeks, magnetic resonance imaging showed the disappearance of metastases, and the prostate tumor shrunk markedly. Moreover, prostatic re-biopsy showed no viable tumor cells. Maintenance chemotherapy, excluding vincristine because of severe peripheral nerve disorder, was performed for 2 years. There has been no recurrence for 49 months after the termination of maintenance chemotherapy. To the best of our knowledge, this is the longest surviving case of adult-onset metastatic rhabdomyosarcoma of the prostate reported in the literature.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Rabdomiossarcoma/tratamento farmacológico , Rabdomiossarcoma/radioterapia , Adulto , Terapia Combinada , Ciclofosfamida/administração & dosagem , Dactinomicina/administração & dosagem , Doxorrubicina/administração & dosagem , Humanos , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Próstata/patologia , Neoplasias da Próstata/patologia , Rabdomiossarcoma/patologia , Vincristina/administração & dosagem
18.
Prostate ; 79(5): 536-543, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30593704

RESUMO

BACKGROUND: Many elderly men suffer from benign prostatic hyperplasia (BPH). Recently, chronic ischemia in the prostate has been suggested to be related to BPH. Thus, the impact of chronic ischemia on the development of prostatic hyperplasia and the efficacy of phosphodiesterase type 5 (PDE5) inhibitor for hyperplasia were evaluated in a rat model with chronic ischemia induced by local atherosclerosis. METHODS: Eighteen male Sprague-Dawley rats were divided into three groups: sham operation, regular diet, placebo (SRP); arterial endothelial injury, high cholesterol diet, placebo (AHP); or arterial endothelial injury, high cholesterol diet, and tadalafil as a PDE5 inhibitor (AHT). The endothelial injury in the common iliac arteries was performed using a 2-Fr Fogarty arterial embolectomy catheter through an incision in the femoral artery into the common iliac artery. Diet and oral drugs were administrated for 8 weeks after surgery. At 8 weeks, blood flow to the ventral prostate (VP) was measured using laser speckle blood flow analysis, and the VP was histologically evaluated. RESULTS: In the AHP group, prostatic blood flow was reduced, and mean VP weight and the interstitial area were significantly enlarged compared with the SRP group. In the AHT group, tadalafil administration obviously ameliorated the reduction of prostatic blood flow relative to the AHP group. Importantly, mean VP weight and the morphological changes in the AHT group were significantly smaller than those in the AHP group. CONCLUSIONS: Enlargement of the VP resulted from chronic ischemia induced by local arteriosclerosis. Also, administration of tadalafil attenuated VP enlargement. Chronic ischemia in the prostate might thus contribute to the development of BPH, and PDE5 inhibitors might provide an innovative approach to preventing BPH.


Assuntos
Isquemia/complicações , Inibidores da Fosfodiesterase 5/farmacologia , Próstata/irrigação sanguínea , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/etiologia , Animais , Modelos Animais de Doenças , Isquemia/tratamento farmacológico , Isquemia/patologia , Masculino , Próstata/patologia , Hiperplasia Prostática/patologia , Ratos , Ratos Sprague-Dawley , Tadalafila/farmacologia
19.
Clin Genitourin Cancer ; 17(1): e113-e122, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30391137

RESUMO

BACKGROUND: To investigate the clinical outcomes in patients with high-risk prostate cancer (PCa) treated with neoadjuvant chemohormonal therapy (NCHT) before radical prostatectomy (RP). PATIENTS AND METHODS: Our NCHT protocol involved complete androgen blockade followed by 6 cycles of docetaxel (30 mg/m2) plus estramustine phosphate (560 mg). NCHT was provided to 60 patients with PCa before RP, and we compared the clinical and pathologic outcomes with those of 349 patients with high-risk PCa who underwent RP alone using propensity score matching. The data for those who underwent RP alone were obtained from the Michinoku Japan Urological Cancer Study Group database. RESULTS: In the NCHT group, 10.0% experienced pathologic complete response, 3.3% had positive surgical margins, and 13.3% developed severe complications (Clavien-Dindo grade III or higher) after RP. The median follow-up duration was 42.5 months, and the 5-year biochemical recurrence (BCR)-free survival was 60.1%. In multivariate analysis, pN+ was an independent prognostic factor for BCR (hazard ratio = 5.251, 95%CI 1.300-21.201; P = .020). In propensity score matching, the BCR rate in the NCHT group was significantly lower than that in the RP alone group (P = .021). In subgroup analyses, the BCR rate in patients with a single high-risk factor was significantly lower in the NCHT group than in the RP-alone group (P = .027). CONCLUSION: NCHT before RP can reduce the risk of BCR in patients with high-risk PCa, particularly if a single high-risk factor is present. However, the potential for perioperative complications should be considered.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Neoadjuvante/mortalidade , Pontuação de Propensão , Prostatectomia/mortalidade , Neoplasias da Próstata/terapia , Idoso , Estudos de Coortes , Terapia Combinada , Docetaxel/administração & dosagem , Estramustina/administração & dosagem , Seguimentos , Humanos , Masculino , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia , Taxa de Sobrevida , Resultado do Tratamento
20.
World J Urol ; 37(9): 1827-1835, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30511214

RESUMO

PURPOSE: To investigate the association between the Geriatric Nutritional Risk Index (GNRI) and prognosis of patients with metastatic hormone-naïve prostate cancer (mHNPC) and to design the optimal risk score predicting for prognosis. METHODS: We retrospectively reviewed data from the Michinoku Japan Urological Cancer Study Group database, containing information about 656 patients with mHNPC who initially received androgen-deprivation therapy between 2005 and 2017. The baseline GNRI was calculated using serum albumin level and body mass index. Poor nutrition was defined as GNRI < 92.0. The impact of GNRI, CHAARTED criteria, and laboratory parameters on oncological outcomes was investigated using the multivariable Cox regression models. We developed the risk comprising GNRI and laboratory parameters and compared its prognostic performance with the CHAARTED criteria using the receiver operating characteristic curve with the DeLong method. RESULTS: Of 339 patients with sufficient data, 66 (19%) were diagnosed with poor nutrition. Multivariate analyses showed that GNRI < 92.0 was an independent prognostic factor of cancer-specific survival [hazard ratio (HR) 1.76; 95% confidence interval (CI) 1.04-2.98, P = 0.035] and overall survival (HR 1.80; 95% CI 1.13-2.89, P = 0.013), in addition to hemoglobin (Hb) and lactic dehydrogenase (LDH) levels. We designed the risk score comprising GNRI < 92.0, Hb < 13.0 g/dL, and LDH > 222 IU/L. The predictive value of the risk score was significantly superior to that of the CHAARTED criteria. CONCLUSIONS: Poor nutrition may predict mortality in patients with mHNPC. Risk factors, such as nutritional status and laboratory parameters, may be useful in decision-making regarding aggressive treatments for patients with mHNPC.


Assuntos
Estado Nutricional , Neoplasias da Próstata , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Estudos Retrospectivos , Medição de Risco
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA