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1.
Int J Urol ; 29(12): 1477-1487, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36070138

RESUMO

OBJECTIVE: Novel androgen receptor axis-targeted agents (ARATAs) have been developed for mCRPC and improved overall survival (OS). Here, we aimed to find predictors who will receive the greatest benefits from ARATAs. METHODS: We previously performed a multicenter study to identify prognostic factors for metastatic hormone-sensitive prostate cancer (mHSPC, n = 148) and mCRPC (n = 99), and showed that the bone scan index (BSI) was one of the significant prognostic factors for 3-year OS (PROSTAT-BSI study). mHSPC progressed to mCRPC (n = 101), for which 69 patients were treated with (n = 39) or without ARATAs (n = 30, prior to the approval of ARATAs). The 69 patients were divided into two groups according to patient factors, and these cohorts were further divided into two subgroups by usage of ARATAs. OS was compared between subgroups in each group. RESULTS: The predictors were age (<71.4 years), serum levels of C-reactive protein (≥0.16 ng/ml) and alkaline phosphatase (≥548 U/L), time to PSA progression after ADT (<8.9 months), the lowest PSA level (≥1 ng/ml) after ADT, and the rate of PSA decline 3 months after ADT (<0.987), whereas hemoglobin levels, PSA before ADT, Gleason scores, existence of visceral metastases, and BSI were not. CONCLUSIONS: The present study identified predictors for the effectiveness of ARATAs. The number of bone metastases (≒BSI), existence of visceral metastases, and Gleason scores, which were identified as high-risk factors in the LATITUDE study and disease volume in CHAARTED criteria, did not appear to be useful for predicting effectiveness from ARATAs.


Assuntos
Antineoplásicos , Neoplasias de Próstata Resistentes à Castração , Neoplasias da Próstata , Masculino , Humanos , Idoso , Antígeno Prostático Específico , Receptores Androgênicos , Neoplasias da Próstata/patologia , Antagonistas de Androgênios/uso terapêutico , Antineoplásicos/uso terapêutico , Estudos Retrospectivos
2.
Int J Urol ; 28(9): 955-963, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34148264

RESUMO

OBJECTIVE: To determine prognostic factors including the Bone Scan Index in prostate cancer patients receiving standard hormonal therapy and chemotherapy. METHODS: This multicenter Prostatic Cancer Registry of Standard Hormonal and Chemotherapy Using Bone Scan Index study involved 30 hospitals and enrolled 247 patients (age 71 ± 8 years) with metastatic hormone-sensitive prostate cancer (n = 148) under hormone therapy and metastatic castration-resistant prostate cancer (n = 99) under chemotherapy. The Bone Scan Index (%) was determined by whole-body bone scintigraphy using 99m Tc-methylenediphosphonate. Patients were classified into tertiles and binary groups, and predictors of all-cause death including Bone Scan Index, prostate-specific antigen, and bone metabolic markers were determined using survival and proportional hazard analyses. RESULTS: During a mean follow-up period of 716 ± 404 days, 81 (33%) of the patients died, and 3-year mortality rates were 20% and 52% in the metastatic hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer groups, respectively. Survival analysis showed that a Bone Scan Index >3.5% was a significant determinant of death in the metastatic hormone-sensitive prostate cancer group, whereas prostate-specific antigen >55 ng/mL before chemotherapy was a determinant of prognosis in the metastatic castration-resistant prostate cancer group. A Bone Scan Index >3.5% was also associated with a high incidence of prostate-specific antigen progression in the metastatic hormone-sensitive prostate cancer group. Patients with metastatic hormone-sensitive prostate cancer and a better Bone Scan Index response (>45%) to treatment had lower mortality rates than those without such response. CONCLUSION: The Bone Scan Index and hot spot number are significant determinants of 3-year mortality, and combining the Bone Scan Index with prostate-specific antigen should contribute to the management of prostate cancer patients with bone metastasis.


Assuntos
Neoplasias Ósseas , Neoplasias de Próstata Resistentes à Castração , Neoplasias da Próstata , Idoso , Neoplasias Ósseas/diagnóstico por imagem , Estudos de Coortes , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Antígeno Prostático Específico , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Sistema de Registros
3.
Acta Med Okayama ; 73(3): 269-272, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31235976

RESUMO

Nephron-sparing treatment should be offered whenever possible to avoid dialysis in allograph cases. Cryoablation is a new treatment option for treating small-sized renal cell cancer (RCCs). We report a case of RCC arising in a kidney allograft treated by cryoablation. To our knowledge, this is the first case in Asia of RCC in a renal allograft treated using cryoablation. Contrast-enhanced CT-guided percutaneous renal needle biopsy and cryoablation were used to identify the RCC, which could not be identified by other techniques. The postoperative course was uneventful. Contrast-enhanced CT also showed no recurrence or metastases at the 6-month follow-up.


Assuntos
Carcinoma de Células Renais/diagnóstico por imagem , Criocirurgia/métodos , Neoplasias Renais/diagnóstico por imagem , Transplante de Rim , Tomografia Computadorizada por Raios X/métodos , Carcinoma de Células Renais/cirurgia , Meios de Contraste , Humanos , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Intensificação de Imagem Radiográfica , Transplante Homólogo
4.
J Urol ; 199(4): 933-939, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29037861

RESUMO

PURPOSE: In patients with urothelial carcinoma CIS (carcinoma in situ) generally has a poor prognosis. However, to our knowledge the outcomes of pure/primary CIS and the behavior of CIS concomitant with pTa-pT4 upper tract urothelial carcinoma managed by nephroureterectomy have not been previously specified. We explored the biological and prognostic features of concomitant CIS compared with those of pure/primary CIS. MATERIALS AND METHODS: We queried a multicenter upper tract urothelial carcinoma database. Data from NUOG (Nishinihon Uro-Oncology Group) were analyzed, including patient gender, age, presence of bladder cancer and pT stage. Clinicopathological features were compared between the different subtypes. Cancer specific and overall survival, and the relative excess risk of death were estimated by CIS subtype. RESULTS: We identified 163 patients with CIS in the upper urinary tract, of whom pure/primary CIS was noted in 24.5%. In the concomitant CIS cohort the pathological diagnosis of the nonCIS region was pTa, pT1, pT2, pT3 and pT4 in 4.9%, 22.8%, 25.2%, 44.7% and 1.6% of patients, respectively. The sensitivity of a selective urine cytology test was higher in the pure/primary CIS group than in the concomitant CIS group (60.0% vs 37.4%). At a median followup of 32 months 10-year estimated mean cancer specific survival was 92.4 months (range 83.7 to 101.0) in the overall CIS cohort. Ten-year estimated mean cancer specific survival in patients with pure/primary CIS was significantly longer than in patients with concomitant carcinoma in situ (111.8 months, range 101.0 to 122.6 vs 85.89, range 75.3 to 96.5, log rank p = 0.007). CONCLUSIONS: Patients presenting with concomitant CIS have a worse outcome than those who present with pure/primary CIS, suggesting a need to differentiate these 2 entities in the treatment decision process.


Assuntos
Carcinoma in Situ/cirurgia , Carcinoma de Células de Transição/cirurgia , Neoplasias Renais/cirurgia , Nefroureterectomia , Neoplasias Ureterais/cirurgia , Idoso , Idoso de 80 Anos ou mais , Carcinoma in Situ/mortalidade , Carcinoma in Situ/patologia , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Rim/patologia , Rim/cirurgia , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Resultado do Tratamento , Ureter/patologia , Ureter/cirurgia , Neoplasias Ureterais/mortalidade , Neoplasias Ureterais/patologia
5.
BJU Int ; 121(5): 764-773, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29281857

RESUMO

OBJECTIVES: To describe the clinicopathological characteristics and prognosis of subsequent non-muscle-invasive bladder cancer (NMIBC) after radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC), and particularly its response to intravesical Bacillus Calmette-Guérin (BCG). PATIENTS AND METHODS: An observational study was conducted in 1463 patients with UTUC who had undergone RNU and in 1555 patients with primary NMIBC. Of the 1463 patients with UTUC, 256 (17%) subsequently developed NMIBC (UTUC-NMIBC group) and were available for the analysis. The clinicopathological background and outcomes, including intravesical recurrence-free survival and bladder progression-free survival, were compared between the patients with UTUC-NMIBC and the patients with primary NMIBC treated with intravesical BCG. Propensity score matching was performed to adjust for the potential differences in the backgrounds of the two groups. To validate the utility of the CUETO scoring model in the UTUC-NMIBC group, risk scores were calculated and compared with the published probabilities for recurrence and progression. RESULTS: Compared with the unadjusted primary NMIBC group (n = 352), the UTUC-NMIBC group (n = 75) were found to have a worse prognosis for intravesical recurrence and progression, before propensity score matching. After propensity score matching for potential confounding factors, however, a worse prognosis was observed only for intravesical recurrence. The validation test of the CUETO scoring model for the UTUC-NMIBC group showed a significant difference in the rate of intravesical recurrence and progression for the 0-4 and 5-6 score groups between the UTUC-NMIBC group and the CUETO risk table reference data. CONCLUSION: Compared with the primary NMIBC group, the UTUC-NMIBC group had a worse prognosis after intravesical BCG, especially with regard to intravesical recurrence. This suggests that patients with UTUC-NMIBC are inherently poor responders to BCG exposure. An optimal treatment strategy and risk scoring model to select patients for adjuvant intravesical BCG, chemotherapy or immediate radical cystectomy should be established.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Vacina BCG/uso terapêutico , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Nefroureterectomia , Neoplasias Uretrais/cirurgia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Neoplasias Uretrais/patologia , Neoplasias da Bexiga Urinária/patologia
6.
BMC Nephrol ; 19(1): 341, 2018 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-30497395

RESUMO

BACKGROUND: Peritoneal dialysis (PD)-associated infection caused by Mycobacterium spp. is rare. Mycobacterium abscessus is one of the most resistant acid-fast bacteria, and treatment is also the most difficult and refractory. Thus, we report a case of PD-associated peritonitis caused by Mycobacterium abscessus that was difficult to treat and led to PD failure. CASE PRESENTATION: We recently encountered a 56-year-old man who developed PD-associated infection. We initially suspected exit-site infection (ESI) and tunnel infection (TI) caused by methicillin-resistant coagulase-negative Staphylococcus. However, antibiotic therapy did not provide any significant improvement. Thus, we performed simultaneous removal and reinsertion of a PD catheter at a new exit site. The patient subsequently developed peritonitis and Mycobacterium abscessus was detected in the peritoneal effluent. Thus, the reinserted catheter was removed, hemodialysis was started, and the patient was eventually discharged. CONCLUSIONS: In cases of refractory ESI or TI, it is important to consider non-tuberculous mycobacteria as the potentially causative organism. Even if acid-fast bacterial staining is negative or not performed, detection of Gram-negative bacillus may lead to suspicion and early identification of Mycobacterium spp. In PD-associated infection by Mycobacterium abscessus, catheter removal is necessary in many cases. Simultaneous removal and reinsertion of the catheter is not recommended, even in cases of ESI or TI. Reinsertion should only be attempted after complete resolution of peritoneal symptoms. After removal of the catheter, careful follow-up is necessary, paying attention to complications such as wound infection, peritonitis, and ileus. In addition, the selection and treatment period of antibiotics in PD-associated infection by Mycobacterium abscessus remains unclear, and it is an important topic for future discussion.


Assuntos
Infecções Relacionadas a Cateter/diagnóstico , Cateteres de Demora/efeitos adversos , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Mycobacterium abscessus/isolamento & purificação , Diálise Peritoneal/efeitos adversos , Infecções Relacionadas a Cateter/complicações , Cateteres de Demora/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/complicações , Diálise Peritoneal/instrumentação
7.
Int J Urol ; 25(5): 492-499, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29633398

RESUMO

OBJECTIVE: To present the study design and rationale of Prostatic Cancer Registry of Standard Hormonal and Chemotherapy Using Bone Scan Index, a prospective study aiming to determine the role of the bone scan index, the amount of bone metastasis, in the treatment and prognosis of prostate cancer patients. METHODS: A total of 237 patients were recruited at 30 hospitals in Japan. All had prostate cancer with bone metastasis and were scheduled to undergo either hormonal therapy (group H) or chemotherapy (group C). Bone scans were carried out with 99m Tc-methylenediphosphonate. Follow-up studies are planned to continue for 3 years, and changes in biochemical and tumor markers in response to hormonal therapy and chemotherapy will be recorded in addition to skeletal-related events, recurrence, disease progression and death. RESULTS: The basic characteristics of the patients (n = 200) at the time of registration during December 2016 were as follows: mean age 71 ± 8 years; median bone scan index calculated on-site 1.9% (range 0.02-13.3%); median number of hot spots 18 (range 1-128); median prostate-specific antigen 155 ng/mL (range 0.04-22 412 ng/mL); and the most frequent Gleason score 9 (47%). The prostate-specific antigen value was higher in group H than group C (288 vs 33 ng/mL, P < 0.0001), whereas bone scan indexes were comparable (1.7 vs 2.3%, not significant) between the two groups. Liver metastasis was more frequent in group C than group H (6.1% vs 0.8%, P = 0.035). CONCLUSIONS: The baseline characteristics of the Prostatic Cancer Registry of Standard Hormonal and Chemotherapy Using Bone Scan Index database have been established. This collaborative study can now proceed with clarifying the role of the bone scan index for patient management including treatment strategies and prognosis.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Osso e Ossos/diagnóstico por imagem , Neoplasias da Próstata/patologia , Cintilografia , Idoso , Biomarcadores Tumorais , Progressão da Doença , Seguimentos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Sistema de Registros , Índice de Gravidade de Doença
9.
Hinyokika Kiyo ; 63(4): 157-161, 2017 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-28506053

RESUMO

A 76-year-old man was introduced to our department with a right kidney stone. On the basis of further examination, he was diagnosed with a 23 mm right kidney stone accompanied with a horseshoe kidney. Retrograde pyelography and diuretic renogram revealed a non-obstructed right ureteropelvic junction. Finally, we chose laparoscopic pyelolithotomy via peritoneal approach because the stone was large and accompanied with a horseshoe kidney. The surgery took 165 minutes and the estimated blood loss was 25 ml. There were no minor or major complications. Because horseshoe kidney has anatomical abnormalities, it seems to be necessary to consider a different treatment strategy from that of an upper urinary tract stone in a healthy kidney. We assume that laparoscopic pyelolithotomy is an effective and safe procedure for renal pelvic stones in the case of a horseshoe kidney.


Assuntos
Cálculos Renais/cirurgia , Rim/cirurgia , Laparoscopia , Procedimentos Cirúrgicos Urológicos , Idoso , Humanos , Rim/patologia , Cálculos Renais/diagnóstico por imagem , Cálculos Renais/patologia , Laparoscopia/métodos , Masculino
10.
Jpn J Clin Oncol ; 46(12): 1148-1155, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27576438

RESUMO

OBJECTIVE: We investigated chronological changes in the outcomes of patients with upper urinary tract urothelial carcinoma treated in the past two decades, during which there was an important change in treatment paradigm. METHODS: A retrospective review was conducted of 1180 urinary tract urothelial carcinoma patients who underwent radical nephroureterectomy in multicenter collaborative institutions between 1996 and 2015. The patients were divided into four groups according to the year when radical nephroureterectomy was performed, as follows: 1996-2000 (period 1; P1), 2001-05 (P2), 2006-10 (P3) and 2011-15 (P4). Variables including tumor grade, T and N categories, administration of perioperative chemotherapy and treatment outcomes were compared among the four groups. RESULTS: There were 146 (12%), 312 (27%), 459 (39%) and 263 (22%) patients in the P1, P2, P3 and P4 groups, respectively. The proportion of patients harboring pT2/3 and Grade 3 tumors increased gradually from 42% (P1) to 58% (P4) and from 49% (P1) to 65% (P4), respectively. The 5-year disease-free survival rates were 74%, 74%, 73% and 75%, and the 5-year overall survival rates were 74%, 65%, 67% and 72% for the P1, P2, P3, and P4 groups, respectively. Multivariate analysis with adjustment for possible confounding factors revealed no significant differences in disease-specific survival, overall survival or intravesical recurrence-free survival among the four groups. CONCLUSIONS: Despite advances in diagnostic instruments, surgery and systemic chemotherapy, the clinical outcome of urinary tract urothelial carcinoma after radical surgery has not significantly improved over the last two decades, and further research is therefore required.


Assuntos
Carcinoma/cirurgia , Neoplasias Ureterais/cirurgia , Adulto , Idoso , Carcinoma/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Nefrectomia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Neoplasias Ureterais/mortalidade
11.
BMC Cancer ; 15: 942, 2015 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-26626260

RESUMO

BACKGROUND: Cytochrome P450 1B1 (CYP1B1) has been shown to be up-regulated in many types of cancer including renal cell carcinoma (RCC). Several reports have shown that CYP1B1 can influence the regulation of tumor development; however, its role in RCC has not been well investigated. The aim of the present study was to determine the functional effects of CYP1B1 gene on tumorigenesis in RCC. METHODS: Expression of CYP1B1 was determined in RCC cell lines, and tissue microarrays of 96 RCC and 25 normal tissues. To determine the biological significance of CYP1B1 in RCC progression, we silenced the gene in Caki-1 and 769-P cells by RNA interference and performed various functional analyses. RESULTS: First, we confirmed that CYP1B1 protein expression was significantly higher in RCC cell lines compared to normal kidney tissue. This trend was also observed in RCC samples (p < 0.01). Interestingly, CYP1B1 expression was associated with tumor grade and stage. Next, we silenced the gene in Caki-1 and 769-P cells by RNA interference and performed various functional analyses to determine the biological significance of CYP1B1 in RCC progression. Inhibition of CYP1B1 expression resulted in decreased cell proliferation, migration and invasion of RCC cells. In addition, reduction of CYP1B1 induced cellular apoptosis in Caki-1. We also found that these anti-tumor effects on RCC cells caused by CYP1B1 depletion may be due to alteration of CDC20 and DAPK1 expression based on gene microarray and confirmed by real-time PCR. Interestingly, CYP1B1 expression was associated with CDC20 and DAPK1 expression in clinical samples. CONCLUSIONS: CYP1B1 may promote RCC development by inducing CDC20 expression and inhibiting apoptosis through the down-regulation of DAPK1. Our results demonstrate that CYP1B1 can be a potential tumor biomarker and a target for anticancer therapy in RCC.


Assuntos
Carcinoma de Células Renais/genética , Proteínas Cdc20/genética , Citocromo P-450 CYP1B1/genética , Proteínas Quinases Associadas com Morte Celular/genética , Neoplasias Renais/genética , Apoptose , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Proteínas Cdc20/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Citocromo P-450 CYP1B1/metabolismo , Proteínas Quinases Associadas com Morte Celular/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Regulação para Cima
12.
Acta Radiol ; 56(2): 250-6, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24518687

RESUMO

BACKGROUND: There is a significant correlation between tumor size and tumor grade for clear-cell renal cell carcinoma (RCC) in pathology. Thus, apparent diffusion coefficient (ADC) of clear-cell RCC might be influenced by tumor size. PURPOSE: To compare the utility of tumor size and ADC for distinguishing low-grade from high-grade clear-cell RCC. MATERIAL AND METHODS: Forty-nine patients undergoing preoperative magnetic resonance imaging were retrospectively assessed. ADC values were calculated using b-value combinations of 0 and 800 s/mm(2) at 1.5 T. Two radiologists in consensus measured ADC values via small region of interest (ROI) (mean ROI area, 88.8 mm(2); range, 80-108 mm(2)) placement on an area of solid tumor on a single slice. Maximum tumor diameter was measured at the maximum tumor area. A single pathologist reviewed all pathological slides to determine the nuclear grade according to the Fuhrman classification. The utility of ADC, tumor size, and ADC/size ratio for distinguishing low-grade from high-grade tumors was assessed. Receiver-operating characteristic (ROC) analysis and regression analysis of the each index were performed. The correlation between ADC and tumor size was also investigated. RESULTS: The 49 clear-cell RCC included 34 low-grade and 15 high-grade tumors. The differences of ADC, tumor size, and ADC/size ratio between high-grade and low-grade tumors were statistically significant (P <0.05). The area under the ROC curve of ADC, tumor size, and ADC/size ratio were 0.802, 0.763, and 0.804 respectively. However, using regression analysis, only ADC (P <0.05) was statistically significant index as independent risk factors for high-grade clear-cell RCC. Moreover, weak significant correlation was observed between tumor size and ADC (R(2) = 0.3865, P <0.01). CONCLUSION: There was a weak significant correlation between tumor size and ADC value of clear-cell RCC. Using ROC and regression analysis, ADC was statistically significant index for distinguishing low-grade from high-grade clear-cell RCC more than tumor size and ADC/size ratio.


Assuntos
Carcinoma de Células Renais/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Renais/patologia , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Carga Tumoral
13.
Tumour Biol ; 35(10): 10223-30, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25027399

RESUMO

The cytochrome P450 1B1 (CYP1B1) enzyme activates xenobiotics to reactive forms as well as convert estradiol to 4-hydroxy-estradiol that has been shown to play a role in the carcinogenesis process of the kidney in male but not female animals. Prior reports show polymorphic variants of CYP1B1 to alter catalytic activity, and thus, we hypothesize that polymorphisms of the CYP1B1 gene are involved in the malignant transformation of the renal cell in men. The genetic distributions of five CYP1B1 polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism in 480 normal healthy subjects and 403 sporadic renal cell carcinoma cases. All subjects were Caucasian men. The sites evaluated were codons 48 (C → G, Arg → Gly, rs10012), 119 (G → T, Ala → Ser, rs1056827), 432 (C → G, Leu → Val, rs1056836), 449 (C → T, Asp, rs1056837), and 453 (A → G, Asn → Ser, rs1800440). A trend was demonstrated for the 432 Val/Val (χ2, P = 0.06) and 449 T/T (χ2, P = 0.1) genotypes to play a protective role against renal cancer. Odds ratio (95 % confidence interval) for Val/Val compared to Leu/Leu at codon 432 was 0.65 (0.44-0.95) and T/T compared to C/C at codon 449 was 0.67 (0.45-0.99). Codons 432 and 449 were observed to be linked (D = 0.24), and haplotype involving 432 Val and 449 T was significantly reduced in cancer cases (P = 0.04). No association was found, however, when analyzing polymorphic sites with clinical stage of cancer. These results demonstrate polymorphisms of CYP1B1 to be associated with renal carcinogenesis and are of importance in understanding their role in the pathogenesis of renal cell carcinoma.


Assuntos
Carcinoma de Células Renais/genética , Citocromo P-450 CYP1B1/genética , Predisposição Genética para Doença/genética , Neoplasias Renais/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/enzimologia , Genótipo , Humanos , Neoplasias Renais/enzimologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Fatores de Risco
15.
Urol Oncol ; 41(11): 458.e9-458.e19, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37798145

RESUMO

OBJECTIVES: Limited information is currently available on the efficacy and safety of axitinib for metastatic renal cell carcinoma (mRCC) patients with renal impairment. Therefore, the present study investigated the efficacy and toxicity of axitinib in patients with chronic kidney disease. METHODS: Post-hoc analyses were performed on a Japanese multicenter cohort study of 477 mRCC patients who received axitinib followed by 1 or 2 regimens of systemic antiangiogenic therapy between January 2012 and December 2016. Differences in clinical characteristics and the efficacy and safety of axitinib were assessed based on pretreatment renal function. RESULTS: Patients were categorized into the following 5 renal function groups according to baseline renal function: estimated glomerular filtration rate (eGFR) ≥60 ml/min (n = 133), 45 ml/min ≤eGFR <60 ml/min (n = 153), 30 ml/min ≤eGFR< 45 ml/min (n = 130), eGFR <30 ml/min (n = 45), and dialysis (n = 16). Median progression-free survival (PFS) (95% confidence interval [CI]) in the 5 groups was 11 (8-16), 14 (11-19), 14 (10-19), 12 (8-24), and 6 (3-NR) months, respectively (p = 0.781). After adjustments for treatment-related confounders, the renal function group was not a significant prognostic factor for PFS. Objective response rates in the 5 groups were 22%, 23%, 23%, 18%, 20%, and 38%, respectively (p = 0.468). Regarding adverse events of all grades, hypertension (p = 0.0006) and renal and urinary disorders (p < 0.0001) were more frequently observed in the eGFR <30 ml/min group than in the other groups. CONCLUSIONS: Since renal function at the initiation of treatment with axitinib does not adversely affect the efficacy of VEGF-TKI therapy, clinicians do not need to avoid its administration to mRCC patients with impaired renal function in consideration of the risk of progression to end-stage renal disease.


Assuntos
Antineoplásicos , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Axitinibe/uso terapêutico , Carcinoma de Células Renais/patologia , Antineoplásicos/efeitos adversos , Estudos de Coortes , Neoplasias Renais/patologia , Indazóis/efeitos adversos , Resultado do Tratamento
16.
BJU Int ; 110(11 Pt B): E628-34, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22788759

RESUMO

UNLABELLED: What's known on the subject? and What does the study add? A bone scan index (BSI) can quantify the extent of bone involvement and response to treatment, but it has not been widely accepted, because of its time-consuming nature. The study is the first to demonstrate that automated BSI calculated with a computer-assisted diagnosis system is effective in judging the chemotherapeutic response of bone metastatic lesions in patients with castration-resistant prostate cancer. OBJECTIVE: • To evaluate the value of an automated bone scan index (aBSI), calculated using a computer-assisted diagnosis system, to indicate chemotherapy response and to predict prognosis in patients with castration-resistant prostate cancer (CRPC) with bone metastasis. PATIENTS AND METHODS: • Forty-two consecutive CRPC patients underwent taxane-based chemotherapy between November 2004 and March 2011 at our institution. • The aBSIs were retrospectively calculated at the diagnosis of CRPC and 16 weeks after starting chemotherapy. • Cox proportional hazards regression models were applied to multivariate analyses with and without aBSI response in addition to the basic model. • Based on the difference in the concordance index (c-index) between each model, the prognostic relevance of adding the aBSI response was determined. RESULTS: • A decrease in aBSI was found in 28 patients (66.7%), whereas a response was shown by bone scan in only 23.8% of patients. • Patients with a reduction in aBSI had longer overall survival (OS) in comparison with the other patients (P= 0.0157). • Multivariate analysis without aBSI response showed that performance status (P= 0.0182) and PSA response (P= 0.0375) were significant prognosticators. • By adding the aBSI response to this basic model, the prognostic relevance of the model was improved with an increase in the c-index from 0.621 to 0.660. CONCLUSIONS: • The aBSI reflected the chemotherapy response in bone metastasis. • The index detected small changes of bone metastasis response as quantified values and was a strong prognostic indicator for patients with CRPC.


Assuntos
Neoplasias Ósseas/mortalidade , Orquiectomia , Neoplasias da Próstata/secundário , Imagem Corporal Total/métodos , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Progressão da Doença , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Modelos de Riscos Proporcionais , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/cirurgia , Cintilografia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Taxa de Sobrevida/tendências
17.
BJU Int ; 110(11 Pt C): E1212-7, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23046198

RESUMO

UNLABELLED: What's known on the subject? and What does the study add? The process of bladder regeneration with a bladder acellular matrix graft (BAMG) is thought to be accelerated by administration of vascular endothelial growth factor into the host bladder. In the present study, we showed that simultaneous implantation of bilateral ureters into a BAMG after a partial cystectomy is reasonable and provides an increased opportunity to the bio-scaffold for communication with host tissues from which a blood supply and stem cells will be generated. OBJECTIVE: • To evaluate if the implantation of bilateral ureters into a bladder acellular matrix graft (BAMG) at the time of its implantation would enhance bladder regeneration in a partial substitution BAMG. MATERIALS AND METHODS: • Partial cystectomies were performed under general anaesthesia in 12 pigs, followed by augmentation with a BAMG. • Six (ureteric implantation group) also received simultaneous implantation of bilateral ureters into the BAMG, while the remaining six (control group) did not have ureteric implantation. • In both groups, bladder regeneration was evaluated using endoscopic and histopathological methods at 1, 2, 4, and 8 weeks after implantation. RESULTS: • At 1 week after BAMG implantation, there were significant inflammatory changes on the host bladder in both groups, while no significant endoscopic changes were seen on the BAMG luminal surfaces. • At 2 weeks, inflammatory changes were diminished and epithelialisation on the BMAG was identified, especially near the host bladder in both groups. • Similarly, epithelialisation on the BAMG near the implanted ureters was seen in the ureteric implantation group. • At 4 and 8 weeks, epithelialisation remained in progress in both groups, although it was more active and expansive in the ureteric implantation group. CONCLUSIONS: • In our porcine model, endoscopic and histopathological examinations showed that simultaneous implantation of bilateral ureters into a BAMG enhanced epithelialisation of the AMG. • This new approach using host ureters and bladder as a potential source of bladder regeneration may provide for rapid and complete regeneration of a bladder substitute.


Assuntos
Cistectomia/métodos , Sobrevivência de Enxerto/fisiologia , Procedimentos de Cirurgia Plástica/métodos , Regeneração , Ureter/cirurgia , Doenças da Bexiga Urinária/cirurgia , Bexiga Urinária/fisiologia , Animais , Sistema Livre de Células/transplante , Modelos Animais de Doenças , Feminino , Suínos , Bexiga Urinária/transplante , Doenças da Bexiga Urinária/patologia
18.
Arch Gynecol Obstet ; 285(5): 1493-6, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22113464

RESUMO

Tumor excision and dermal-flap skin graft operations were performed on a 72-year-old woman diagnosed with extramammary Paget's disease at our hospital in August 2001. Paget cells were identified in the external urethral meatus even though nine local excisions of recurrent tumors had been performed. She was suffered from severe vesical pain from May 2007. Urine cytology was class V and physical examination revealed redness in external urethral meatus. Pelvic MRI did not show apparent lymph node swelling and the endoscopic multiple biopsies performed at multiple bladder mucosa and distal urethra. Pathological diagnosis of the endoscopic biopsy showed multiple Paget cells from urethra, posterior and bilateral lateral wall, and bladder neck. Because Paget's disease may infiltrate bladder mucosa and cause severe vesical pain due to bladder invasion, total cystorethrectomy, ileal conduit, and external skin excision were performed. Pathological findings were continuous infiltration of Paget cells from external urethral meatus to bladder mucosa.


Assuntos
Doença de Paget Extramamária/secundário , Uretra/patologia , Neoplasias da Bexiga Urinária/secundário , Bexiga Urinária/patologia , Neoplasias Vulvares/patologia , Idoso , Feminino , Humanos
20.
Anticancer Res ; 42(3): 1465-1475, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35220240

RESUMO

BACKGROUND/AIM: To assess the efficacy of novel therapeutic agents, such as androgen receptor axis-targeted agents (ARATs) and cabazitaxel, for relapse of metastatic castration-resistant prostate cancer (mCRPC) after docetaxel in real-world practice, we performed a subanalysis using database from PROSTAT-BSI, a prospective observational study to evaluate the utility of software for quantifying bone metastases on bone scintigraphy. PATIENTS AND METHODS: Patients with clinically relapsed mCRPC after docetaxel treatment who received the new agents (NEW group) and those who did not (standard of care, SOC group) were included; patients who received ARAT before DOC treatment were excluded. Overall survival (OS) after docetaxel treatment was compared between the NEW and SOC groups. RESULTS: Patients in the NEW group had significantly better OS from the start of docetaxel than those in the SOC group (the median OS in NEW and SOC was 28.9 months vs. 14.5 months, respectively). Furthermore, regardless of the time from androgen-deprivation therapy to the start of docetaxel at mCRPC, the NEW group had a better OS from relapse after docetaxel than the SOC group. CONCLUSION: In clinical practice, OS of patients with relapse after docetaxel was significantly improved in the NEW group over the SOC group.


Assuntos
Antagonistas de Receptores de Andrógenos/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Docetaxel/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Receptores de Andrógenos/efeitos adversos , Antineoplásicos/efeitos adversos , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/secundário , Bases de Dados Factuais , Docetaxel/efeitos adversos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia , Recidiva , Taxoides/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
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