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1.
Gastroenterology ; 162(3): 799-812, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34687740

RESUMO

BACKGROUND & AIMS: A detailed understanding of antitumor immunity is essential for optimal cancer immune therapy. Although defective mutations in the B2M and HLA-ABC genes, which encode molecules essential for antigen presentation, have been reported in several studies, the effects of these defects on tumor immunity have not been quantitatively evaluated. METHODS: Mutations in HLA-ABC genes were analyzed in 114 microsatellite instability-high colorectal cancers using a long-read sequencer. The data were further analyzed in combination with whole-exome sequencing, transcriptome sequencing, DNA methylation array, and immunohistochemistry data. RESULTS: We detected 101 truncating mutations in 57 tumors (50%) and loss of 61 alleles in 21 tumors (18%). Based on the integrated analysis that enabled the immunologic subclassification of microsatellite instability-high colorectal cancers, we identified a subtype of tumors in which lymphocyte infiltration was reduced, partly due to reduced expression of HLA-ABC genes in the absence of apparent genetic alterations. Survival time of patients with such tumors was shorter than in patients with other tumor types. Paradoxically, tumor mutation burden was highest in the subtype, suggesting that the immunogenic effect of accumulating mutations was counterbalanced by mutations that weakened immunoreactivity. Various genetic and epigenetic alterations, including frameshift mutations in RFX5 and promoter methylation of PSMB8 and HLA-A, converged on reduced expression of HLA-ABC genes. CONCLUSIONS: Our detailed immunogenomic analysis provides information that will facilitate the improvement and development of cancer immunotherapy.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Genes MHC Classe I/genética , Evasão Tumoral/genética , Evasão Tumoral/imunologia , Microglobulina beta-2/genética , Alelos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Metilação de DNA , Epigênese Genética , Expressão Gênica , Antígenos HLA-A/genética , Antígenos HLA-A/metabolismo , Humanos , Imunogenética , Linfócitos do Interstício Tumoral , Instabilidade de Microssatélites , Complexo de Endopeptidases do Proteassoma/genética , Fatores de Transcrição de Fator Regulador X/genética , Taxa de Sobrevida , Microglobulina beta-2/metabolismo
2.
Int J Clin Oncol ; 24(10): 1231-1237, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31134469

RESUMO

BACKGROUND: Patients with brain metastasis from renal cell carcinoma have poor outcomes despite recent advances in diagnosis and treatment. Moreover, factors affecting such poor outcomes are unclear. This study aimed to evaluate the prognostic factors associated with overall survival in renal cell carcinoma patients with brain metastasis. METHODS: We retrospectively reviewed the data of 50 consecutive patients with brain metastasis from renal cell carcinoma at our institution between 1988 and 2017. The evaluated prognostic factors for overall survival included clinicopathological factors at diagnosis, treatment for brain metastasis, and the Graded Prognostic Assessment score of renal cell carcinoma. The associations between preoperative clinicopathological factors and overall survival were assessed using the log-rank test and Cox proportional hazards models for univariate and multivariate analyses, respectively. RESULTS: Forty-five patients were included, among whom 39 died during follow-up. The median follow-up was 8.2 months. The median survival time was 8.2 months (95% confidence interval 5.5-13.7). A Graded Prognostic Assessment score ≤ 2 (hazard ratio 1.967; 95% confidence interval 1.024-3.892; P = 0.042), the presence of sarcomatoid components (hazard ratio 3.299; 95% confidence interval 1.424-7.193; P = 0.007), and no treatment for brain metastasis (hazard ratio 2.594; 95% confidence interval 1.033-5.858; P = 0.043) were independently associated with poor prognosis in the multivariate analysis. CONCLUSIONS: Patients with renal cell carcinoma who develop brain metastasis have poor overall survival. The Graded Prognostic Assessment score, sarcomatoid components, and treatment for brain metastasis from renal cell carcinoma were independent factors associated with prognosis.


Assuntos
Neoplasias Encefálicas/mortalidade , Carcinoma de Células Renais/mortalidade , Neoplasias Renais/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/terapia , Criança , Terapia Combinada , Feminino , Humanos , Japão , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Adulto Jovem
3.
World J Urol ; 36(2): 249-256, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29185045

RESUMO

PURPOSE: To evaluate the impact of preoperative chronic kidney disease (CKD) on oncological outcomes after radical cystectomy (RC) for bladder cancer. METHODS: We reviewed the medical records of patients with urothelial bladder carcinoma who underwent RC with curative intent at seven hospitals between 1990 and 2013. After excluding patients with a history of upper urinary tract urothelial cancer or neoadjuvant chemotherapy, we analyzed 594 cases for the study. Preoperative estimated glomerular filtration rate (eGFR) was calculated using the three-variable Japanese equation for GFR estimation from serum creatinine level and age. Patients were divided into four groups of different CKD stages based on eGFR values (mL/min/1.73 m2), i.e., ≥ 60 (CKD stages G1-2), 45-60 (G3a), 30-45 (G3b), and < 30 (G4-5). Survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards regression analyses addressed survivals after RC. RESULTS: Median age of patients was 67 years. Patients were classified into CKD stages: G1-2 (n = 388; 65.3%), G3a (n = 122; 20.5%), G3b (n = 51; 8.6%), and G4-5 (n = 33; 5.6%). During a median follow-up of 4.0 years, 200 and 164 patients showed cancer progression and died of bladder cancer, with the 5-year progression-free survival (PFS) and cancer-specific survival (CSS) of 64.9 and 70.2%, respectively. On multivariate analyses, CKD stages of G3b or greater, advanced pT stage, lymph node metastasis, and positive lymphovascular invasion were independent poor prognostic factors for PFS and CSS. CONCLUSIONS: We demonstrated that the advanced preoperative CKD stage was significantly associated with poor oncological outcomes of the bladder cancer after RC.


Assuntos
Carcinoma de Células de Transição/cirurgia , Cistectomia , Insuficiência Renal Crônica/epidemiologia , Neoplasias da Bexiga Urinária/cirurgia , Idoso , Carcinoma de Células de Transição/epidemiologia , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Comorbidade , Intervalo Livre de Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Japão/epidemiologia , Estimativa de Kaplan-Meier , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Índice de Gravidade de Doença , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia
4.
Jpn J Clin Oncol ; 48(8): 760-764, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29931182

RESUMO

BACKGROUND: The effectiveness of cancer control is unclear after radical prostatectomy for patients with clinical T3 prostate cancer. METHODS: We retrospectively reviewed 1409 patients who underwent radical prostatectomy between April 2007 and December 2014, including 210 patients with cT3 prostate cancer. Nine patients who received neoadjuvant hormonal therapy and three patients who were lost to follow-up were excluded from the analysis. Clinical staging was performed by an experienced radiologist using preoperative magnetic resonance imaging findings. We analyzed the predictors of biochemical recurrence using Cox proportional hazard analyses. RESULTS: A total of 113 patients (57%) underwent radical retropubic prostatectomy and 85 patients (43%) underwent robot-assisted radical prostatectomy. The median follow-up period was 36 months. Downstaging occurred for 60 patients (30%), positive surgical margins were identified in 117 patients (59%), and biochemical recurrence was observed for 89 patients (45%). In the multivariate analyses, the independent preoperative predictors of biochemical recurrence were ≥50% proportion of positive biopsy cores [hazard ratio (HR): 2.858, P < 0.0001] and a biopsy Gleason score of ≥8 (HR: 1.800, P = 0.0093). The independent post-operative predictors of biochemical recurrence were positive surgical margins (HR: 2.490, P = 0.0018) and seminal vesicle invasion (HR: 2.750, P < 0.0001). CONCLUSIONS: Among patients with cT3 prostate cancer, the percentage of positive biopsy cores and the biopsy Gleason score should be considered to select treatment. Compared with radical retropubic prostatectomy, robot-assisted radical prostatectomy may be a feasible treatment option in this setting.


Assuntos
Recidiva Local de Neoplasia/patologia , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Idoso , Intervalo Livre de Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Cuidados Pré-Operatórios , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco
5.
Int J Urol ; 25(10): 871-878, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30103271

RESUMO

OBJECTIVES: To elucidate the effects of the preoperative albumin : globulin ratio on the survival of patients with upper tract urothelial carcinoma after radical nephroureterectomy. METHODS: We retrospectively reviewed 124 consecutive patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy at Chiba Cancer Center, Chiba, Japan between 2002 and 2015. The albumin : globulin ratio was defined: albumin / (total protein - albumin). Associations between preoperative clinicopathological factors, including the albumin : globulin ratio, and recurrence-free survival, cancer-specific survival and overall survival were assessed. The log-rank test and Cox proportional hazards models were used for univariate and multivariable analyses, respectively. The study cohort was separated into two groups based on the optimal albumin : globulin ratio cut-off value determined using receiver operating characteristic curve analysis. RESULTS: The median survival time was 55 months (interquartile range 28-76 months), and 31 patients died during follow up. A low preoperative albumin : globulin ratio <1.40 was associated with tumor grade and surgical margin status. Kaplan-Meier analyses showed that a low albumin : globulin ratio was more significantly correlated with worse recurrence-free survival, cancer-specific survival and overall survival. Multivariate analyses showed that a low albumin : globulin ratio was an independent predictive factor associated with poor recurrence-free survival (hazard ratio 3.758; P = 0.0028), cancer-specific survival (hazard ratio 5.687; P = 0.0044) and overall survival (hazard ratio 3.124; P = 0.0030). CONCLUSIONS: A low albumin : globulin ratio is an independent predictive factor associated with poor prognosis in upper tract urothelial carcinoma patients treated with radical nephroureterectomy.


Assuntos
Carcinoma de Células de Transição/cirurgia , Neoplasias Renais/cirurgia , Nefroureterectomia , Albumina Sérica Humana/análise , Soroglobulinas/análise , Neoplasias Ureterais/cirurgia , Idoso , Carcinoma de Células de Transição/sangue , Carcinoma de Células de Transição/mortalidade , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/sangue , Neoplasias Renais/mortalidade , Masculino , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Neoplasias Ureterais/sangue , Neoplasias Ureterais/mortalidade
6.
World J Urol ; 35(10): 1569-1575, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28397000

RESUMO

PURPOSE: To evaluate the efficacy of adjuvant systemic chemotherapy for locally advanced (pT3-4pN0/xM0) upper tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: We retrospectively reviewed the medical records of 109 patients with pT3-4pN0/xM0 UTUC who had undergone radical nephroureterectomy between 1996 and 2013 at our four institutions. The patients were divided into two groups: those who received adjuvant chemotherapy (AC group) and those who did not (surgery-alone: SA group). All chemotherapy regimens were cisplatin-based. Cox proportional hazards regression models addressed the associations between clinicopathological factors and recurrence-free survival (RFS) and cancer-specific survival (CSS). RESULTS: Forty-three (39.5%) out of the 109 patients underwent one to four cycles of adjuvant chemotherapy after nephroureterectomy. Median follow-up was 46.5 months. There were no significant differences in the background characteristics of the two groups, except for age. Recurrence developed in 11 (25.6%) and 29 (43.9%) patients in the AC and SA groups, respectively. Ultimately, six (14.0%) and 18 (27.3%) patients in the AC and SA groups, respectively, died of disease progression. On univariate analysis, hydronephrosis, nuclear grade, lymphovascular invasion, and adjuvant chemotherapy were significantly associated with both RFS and CSS. Charlson comorbidity index was associated only with CSS. On multivariate analysis, adjuvant chemotherapy was the only independent factor associated with improved RFS (p = 0.0178, HR = 0.41). Moreover, adjuvant chemotherapy (p = 0.0375, HR = 0.33), lower nuclear grade (p = 0.0070), and the absence of hydronephrosis (p = 0.0493) were independently associated with better CSS. CONCLUSION: Locally advanced (pT3-4pN0/xM0) UTUC patients who underwent cisplatin-based adjuvant chemotherapy demonstrated better RFS and CSS than those without adjuvant chemotherapy.


Assuntos
Carcinoma de Células de Transição/tratamento farmacológico , Cisplatino/uso terapêutico , Nefroureterectomia/métodos , Neoplasias Urológicas/tratamento farmacológico , Idoso , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/cirurgia , Quimioterapia Adjuvante/métodos , Progressão da Doença , Feminino , Humanos , Japão/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Invasividade Neoplásica , Estadiamento de Neoplasias , Avaliação de Processos e Resultados em Cuidados de Saúde , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/patologia , Neoplasias Urológicas/cirurgia , Urotélio/patologia
7.
Int J Clin Oncol ; 22(2): 359-365, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27747456

RESUMO

BACKGROUND: We evaluated short- and long-term renal function in patients after radical cystectomy with urinary diversion and identified risk factors for the deterioration of renal function. METHODS: This retrospective study comprised 91 patients who underwent radical cystectomy and urinary diversion for bladder cancer and survived ≥3 years after surgery. The estimated glomerular filtration rate (eGFR) was calculated, and longitudinal changes of eGFR were assessed. Deterioration in renal function in early and late postoperative years was defined as a ≥25 % decrease in the eGFR from preoperative to postoperative year one, and a reduction in the eGFR of >1 mL/min/1.73 m2 annually in subsequent years, respectively. Univariate and multivariate logistic regression analyses were used to evaluate its association with clinicopathologic features. RESULTS: The median follow-up period after surgery was 7 years (range 3-26). The mean eGFR decreased from preoperative 65.1 to 58.9 mL/min/1.73 m2 1 year after the surgery, followed by a continuous decline of ~1.0 mL/min/1.73 m2 per year thereafter. Multivariate analyses identified ureteroenteric stricture as the sole risk factor associated with early renal function deterioration [odds ratio (OR) 4.22, p = 0.037]. Diabetes mellitus (OR 8.24, p = 0.015) and episodes of pyelonephritis (OR 4.89, p = 0.038) were independently associated with the gradual decline in the late postoperative period. CONCLUSION: In cystectomy patients with urinary diversion, the rapid deterioration of renal function observed during the first year after surgery and the gradual but continuous decline in function thereafter were found to be associated with different risk factors.


Assuntos
Cistectomia/efeitos adversos , Taxa de Filtração Glomerular , Rim/patologia , Complicações Pós-Operatórias , Insuficiência Renal/etiologia , Neoplasias da Bexiga Urinária/cirurgia , Derivação Urinária/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Insuficiência Renal/diagnóstico , Estudos Retrospectivos , Fatores de Risco , Neoplasias da Bexiga Urinária/patologia
8.
Nihon Hinyokika Gakkai Zasshi ; 107(3): 189-192, 2016.
Artigo em Japonês | MEDLINE | ID: mdl-28740051

RESUMO

A 25 year-old man was admitted to our hospital with a left swelling testis. We diagnosed as left testicular tumor by ultrasound sonography and magnetic resonance imaging (MRI). Computed tomography (CT) showed no metastasis and tumor makers, ßHCG, AFP, LDH, were normal. A tumor was removed by left radical high orchiectomy and histological examination revealed large cell calcifying Sertoli cell tumor. He was given no adjuvant therapy. Neither recurrence nor metastasis has been found for 4 months after the operation.

9.
Nihon Hinyokika Gakkai Zasshi ; 107(2): 106-110, 2016.
Artigo em Japonês | MEDLINE | ID: mdl-28442668

RESUMO

The patient is a 43-year-old male, presented with numbness of the left lower extremities. Imaging studies showed a pelvic tumor 20 cm in diameter, involving the left ureter, left common iliac vessels, left internal and external iliac vessels, and inferior mesenteric artery, which was deemed unresectable. Tumor biopsy confirmed liposarcoma. As chemotherapy was not effective, he was referred to us. Following femoral-femoral artery bypass in advance, the tumor was resected with the sigmoid colon, left kidney, ureter, left iliac vessels, and interior mesenteric artery. Removal of the tumor caused massive venous hemorrhage from the pre-sacral plexus, which was scarcely managed by gauze packing. Open abdominal management was selected to avoid abdominal compartment syndrome by severe intestinal edema. The packed gauze was retrieved on the fourth post-operative day, with laparotomy closed. The postoperative course was uneventful.


Assuntos
Anastomose Cirúrgica/métodos , Bandagens , Perda Sanguínea Cirúrgica/prevenção & controle , Embolização Terapêutica/métodos , Artéria Femoral/cirurgia , Hemostasia Cirúrgica/métodos , Artéria Ilíaca , Lipossarcoma/cirurgia , Plexo Lombossacral , Neoplasias Pélvicas/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos , Adulto , Humanos , Hipertensão Intra-Abdominal/prevenção & controle , Masculino , Complicações Pós-Operatórias/prevenção & controle , Resultado do Tratamento
10.
Sci Rep ; 12(1): 11945, 2022 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-35831361

RESUMO

This study was to show the impact of 'prostate-muscle index (PMI)', which we developed as a novel pelvic cavity measurement, in patients undergoing robot-assisted radical prostatectomy (RARP). We defined PMI as the 'distance between the inner edge of the obturator internus muscle and the lateral edge of the prostate at the magnetic resonance imaging (MRI) slice showing the maximum width of the prostate'. Seven hundred sixty patients underwent RARP at the University of Tokyo Hospital from November 2011 to December 2018. MRI results were unavailable in 111 patients. In total, 649 patients were eligible for this study. Median values of blood loss and console time were 300 mL and 168 min. In multivariate analysis, body mass index (BMI), prostate volume-to-pelvic cavity index (PV-to-PCI), PMI, and surgical experience were significantly associated with blood loss > 300 mL (P = 0.0002, 0.002, < 0.0001, and 0.006 respectively). Additionally, BMI, PMI, and surgical experience were also significantly associated with console time > 160 min in multivariate analysis (P = 0.04, 0.004, and < 0.0001, respectively). In conclusion, PMI may provide useful information to surgeons and patients in preoperative decision-making.


Assuntos
Intervenção Coronária Percutânea , Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Masculino , Músculos/patologia , Próstata/diagnóstico por imagem , Próstata/patologia , Próstata/cirurgia , Prostatectomia/métodos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos
12.
Mol Clin Oncol ; 8(5): 665-670, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29725532

RESUMO

The clinical significance of random bladder biopsies in primary non-muscle-invasive bladder cancer is unclear. The present study investigated the significance of positive random bladder biopsies in primary T1 NMIBC. The present study retrospectively reviewed the records of 71 patients with primary pT1N0M0 bladder cancer who underwent transurethral resection of the bladder tumor (TURBT) and concomitant random bladder biopsy. A total of 12 patients who received cystectomy immediately following the TURBT were excluded, and the remaining 59 patients were included in the analysis. Random bladder biopsy was defined as a cold-cup biopsy of pre-specified normal-looking areas in the bladder. The association of clinicopathological factors, including random biopsy results, with intravesical recurrence were assessed by univariate and multivariate Cox proportional hazards analyses. Of the 59 patients, 15 (25%) demonstrated carcinoma in situ (CIS) lesions on random bladder biopsy: Five (33%) in biopsy specimens alone and the remaining 10 (67%) in biopsy and TUR specimens. Positive random biopsy was associated with preoperative positive urine cytology (P=0.011) and small size of the main tumor (P=0.008). Multivariate analysis demonstrated positive random biopsy as the sole independent poor prognostic factor for intravesical recurrence (hazard ratio: 4.69, P=0.014). The five patients who had CIS detected in biopsy specimens alone had worse, although non-significantly worse, recurrence-free survival compared with those with CIS detected in biopsy and TUR specimens (P=0.100). In conclusion, positive bladder random biopsy, equivalent to the presence of CIS, was an independent predictor of recurrence in primary T1 bladder cancer. Given that one-third of CIS lesions could not have been detected without biopsy, random bladder biopsy should be considered for patients with T1 tumors.

13.
Clin Genitourin Cancer ; 16(2): 142-148, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29042308

RESUMO

BACKGROUND: Abiraterone (AA) and enzalutamide (ENZA) are increasingly being used in chemotherapy-naive patients with metastatic castration-resistant prostate cancer owing to efficacy and favorable toxicity. However, the order in which they should be administered has not been determined. PATIENTS AND METHODS: We retrospectively reviewed the records of chemotherapy-naive patients with metastatic castration-resistant prostate cancer who had received sequential treatment with either AA followed by ENZA (AA-ENZA) or the converse (ENZA-AA). Prostate-specific antigen (PSA) response rates (defined as ≥ 50% PSA decline from baseline), first-line progression-free survival (PFS), second-line PFS, combined PFS (defined as first-line PFS plus second-line PFS), and overall survival are compared between the 2 sequence groups. RESULTS: A total of 97 patients received sequential treatment with AA and ENZA; 50 patients were in the AA-ENZA group, and 47 patients were in the ENZA-AA group. The PSA response rate to first-line treatment was not significantly different between AA (48%) and ENZA (51%) (P = .840). However, a significant difference was observed in the PSA response rate to second-line treatment (AA, 6.4% vs. ENZA, 30%; P = .004). The median combined PFS was not significantly different between sequence groups (hazard ratio, 0.71; 95% confidence interval, 0.46-1.08; log-rank P = .105). The order of addition also had no significant effect on median overall survival (hazard ratio, 0.98; 95% confidence interval, 0.64-1.52; log-rank P = .834). CONCLUSION: With the exception of the second-line PSA response, there was no significant difference in clinical outcomes between the AA-ENZA and ENZA-AA groups. Our results might be useful reference in daily practice, especially for patients who do not have a suitable general condition for chemotherapy.


Assuntos
Androstenos/administração & dosagem , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Androstenos/uso terapêutico , Benzamidas , Intervalo Livre de Doença , Esquema de Medicação , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Nitrilas , Feniltioidantoína/administração & dosagem , Feniltioidantoína/uso terapêutico , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/sangue , Estudos Retrospectivos , Resultado do Tratamento
14.
Clin Genitourin Cancer ; 15(6): e1073-e1080, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28826931

RESUMO

BACKGROUND: An important clinical question of great interest to clinicians is how to best sequence androgen receptor targeted agents (ARTAs) and chemotherapy for metastatic castration-resistant prostate cancer (mCRPC), but the answer is still unclear. MATERIALS AND METHODS: To evaluate and compare the clinical outcomes of ARTA and docetaxel (DTX) as second-line treatment in the post first-line ARTA, we conducted a retrospective analysis of chemotherapy-naive mCRPC patients who had received sequential treatment with ARTA followed by another ARTA (ARTA-ARTA) or ARTA followed by DTX (ARTA-DTX). RESULTS: A total of 97 patients were treated with the ARTA-ARTA sequence and 42 with the ARTA-DTX sequence. A prostate-specific antigen (PSA) response to the second-line treatment was observed in 18.6% in the ARTA-ARTA and in 33.3% in the ARTA-DTX sequence, but the difference in PSA response was not statistically significant (P = .057). The median progression-free survival (PFS) was significantly different between ARTA and DTX in the second-line treatment (hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.24-0.59; P < .001). The favorable outcome in the ARTA-DTX sequence compared with the ARTA-ARTA sequence remained (HR, 0.51, 95% CI, 0.33-0.80; P = .004) in the combined PFS (first-line PFS + second-line PFS). However, no statistically significant difference in overall survival (OS) between the 2 groups was observed (HR, 0.60; 95% CI, 0.34-1.09; P = .095). In multivariate analysis, the ARTA-DTX sequence was identified as an independent prognostic factor for combined PFS, but not OS. CONCLUSION: ARTA-DTX might improve clinical outcomes in terms of second-line PFS and combined PFS, compared with the ARTA-ARTA sequence. However, this significance was not observed for OS.


Assuntos
Acetato de Abiraterona/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Benzamidas , Intervalo Livre de Doença , Docetaxel , Resistencia a Medicamentos Antineoplásicos , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Nitrilas , Feniltioidantoína/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
15.
PLoS One ; 12(2): e0172341, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28241027

RESUMO

BACKGROUND: The benefit of adjuvant immunotherapy after nephrectomy in renal cell carcinoma (RCC) is controversial. The present study aimed to examine the possible benefit of adjuvant immunotherapy in various clinical settings. METHODS: We retrospectively reviewed 436 patients with pT1-3N0-2M0 RCC who underwent radical or partial nephrectomy with curative intent at our institution between 1981 and 2009. Of them, 98 (22.5%) patients received adjuvant interferon-α (IFN-α) after surgery (adjuvant IFN-α group), while 338 (77.5%) did not (control group). The primary endpoint was cancer-specific survival (CSS). Univariate and multivariate analyses were conducted using log-rank tests and Cox proportional hazards models, respectively. RESULTS: Fifty-two (11.9%) patients died from RCC with a median follow-up period of 96 months. Preliminary univariate analyses comparing CSS among treatment groups in each TNM setting revealed that CSS in the control group was equal or superior to that in the adjuvant IFN-α group in earlier stages, while the opposite trend was observed in more advanced stages. We evaluated the TNM cutoffs and demonstrated maximized benefit of adjuvant IFN-α in patients with pT2b-3cN0 (P = 0.0240). In multivariate analysis, ≥pT3 and pN1-2 were independent predictors for poor CSS in all patients. In the subgroups with ≥pT2 disease (n = 123), pN1-2 and no adjuvant treatment were significant poor prognostic factors. CONCLUSIONS: Adjuvant immunotherapy after nephrectomy may be beneficial in pT2b-3cN0 RCC. Careful consideration is, however, required for interpretation of this observational study because of its selection bias and adverse effects of IFN-α.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Carcinoma de Células Renais/terapia , Imunoterapia/métodos , Neoplasias Renais/terapia , Idoso , Carcinoma de Células Renais/cirurgia , Feminino , Humanos , Interferon-alfa/uso terapêutico , Japão , Estimativa de Kaplan-Meier , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Estadiamento de Neoplasias , Nefrectomia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento
16.
Eur J Pharm Biopharm ; 108: 25-31, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27553261

RESUMO

Drug absorption into the body is known to be greatly affected by the solubility of the drug itself. The active pharmaceutical ingredient efonidipine hydrochloride ethanolate (NZ-105) is a novel 1,4-dihydropyridine calcium antagonist that has a very low solubility in water. It is classified as a poorly soluble drug, and improvements in its solubility and higher bioavailability with oral administration are needed. In this study, employing microwave technology as a new means to improve solubility, we established a method for preparing solid dispersions using hydroxypropyl methylcellulose acetate succinate as a polymeric carrier and urea as a third component. This effective method has a treatment time of several minutes (simple) and does not require the use of organic solvents (low environmental impact). The third component, urea, acts to lower the melting point of NZ-105, which promotes amorphization. This greatly improves the solubility compared with the microwave-treated product of NZ-105/HPMC-AS binary system. The solid dispersion prepared with this method, in addition to evaluation in vitro, was tested in vivo using beagle dogs and shown to be effective from the eightfold improvement in absorption compared with NZ-105 alone based on the area under the curve.


Assuntos
Di-Hidropiridinas/química , Portadores de Fármacos/química , Nitrofenóis/química , Animais , Área Sob a Curva , Varredura Diferencial de Calorimetria , Di-Hidropiridinas/farmacocinética , Cães , Temperatura Alta , Espectroscopia de Ressonância Magnética , Masculino , Metilcelulose/análogos & derivados , Metilcelulose/química , Micro-Ondas , Nitrofenóis/farmacocinética , Compostos Orgânicos , Compostos Organofosforados/química , Compostos Organofosforados/farmacocinética , Solubilidade , Solventes/química , Ureia/química , Difração de Raios X
17.
Urol Oncol ; 34(2): 59.e9-13, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26411547

RESUMO

OBJECTIVE: To elucidate whether the lower ureteral lesion can predict subsequent intravesical recurrence (IVR) in patients with upper tract urothelial carcinoma (UTUC) who underwent radical nephroureterectomy (RNU). PATIENTS AND METHODS: We retrospectively reviewed 186 consecutive patients with UTUC who underwent RNU at our institution between 1996 and 2013. Associations of various clinicopathological factors with subsequent IVR were assessed. Lower ureteral lesion was defined as the pathologically confirmed lowest carcinoma component within 5 cm from the lower end of the ureter. The log-rank test and Cox proportional hazards model were used for univariable and multivariable analysis, respectively. RESULTS: Overall, 86 patients (46%) developed IVR during the follow-up, with a median follow-up period of 43 months (interquartile range: 17-79 mo). In all, 53 patients (28%) had lower ureteral lesions, and 34 (64%) of them developed IVR. Univariable analysis demonstrated that lower ureteral lesion was significantly associated with IVR, as well as tumor multifocality, lymphatic invasion, and history of bladder cancer. Multivariable analysis identified the lower ureteral lesion as a sole independent predictor of IVR (P = 0.0304, hazard ratio = 1.74). CONCLUSIONS: Lower ureteral lesion was an independent predictor of IVR in patients with UTUC treated with RNU. Such patients may deserve prophylactic treatment and intensive follow-up.


Assuntos
Nefrectomia/métodos , Ureter/patologia , Neoplasias Ureterais/cirurgia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Neoplasias Ureterais/patologia
18.
Intern Med ; 54(14): 1787-90, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26179537

RESUMO

Retroperitoneal tumors present diagnostic challenges, although a definitive diagnosis can be established based on a histopathological analysis. We herein report the case of a 62-year-old woman with a massive retroperitoneal tumor who was referred to our department for surgery. Although we initially planned to perform an incisional biopsy, we unexpectedly detected gingival swelling, and a gingival biopsy subsequently confirmed a pathological diagnosis of Burkitt's lymphoma (BL). We successfully avoided the use of more invasive diagnostic procedures and were able to promptly initiate chemotherapy. Obtaining an immediate pathological diagnosis is essential for providing successful treatment in such cases, as the disease is potentially curable with chemotherapy. BL should therefore be considered in the differential diagnosis of massive retroperitoneal tumors, highlighting the importance of routine systemic screening.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma de Burkitt/diagnóstico , Doenças da Gengiva/patologia , Neoplasias Retroperitoneais/diagnóstico , Biópsia , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/patologia , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Indução de Remissão , Neoplasias Retroperitoneais/patologia , Tomografia Computadorizada por Raios X
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