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A 62-year-old male came to our clinic complaining of residual sensation of urine and urinary frequency. He was diagnosed with neurogenic bladder, and has been performing clean intermittent self catheterization once or twice a day. According to his urination record of voided volume (VV) and post-void residual urine volume (PVR) on every urination, we investigated the relationship between pre-void bladder capacity (BC) and PVR. BC was expressed as the sum of VV and PVR. The PVR of BC 300-400, 400-500, 500-600 and â§600 ml was 141.1, 167.7, 186.8 and 193.3 ml, respectively. PVR significantly increased as BC increased (pï¼0.01). Although there are few reports about the relationship between BC and PVR, the present results show that bladder over distension may reduce the contractility of the urinary bladder.
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Bexiga Urinaria Neurogênica/fisiopatologia , Bexiga Urinária/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , MicçãoRESUMO
OBJECTIVES: Primary androgen deprivation therapy (PADT) had been used extensively in Japan than in the USA and European countries regardless of the disease risk or patient's age. To illustrate the consequence of PADT from daily clinical practice, we evaluated the relationship among age, disease risk, and survival of patients with prostate cancer treated by PADT in largest Asian cohort. PATIENTS AND METHODS: The 19,246 men subjected to PADT enrolled in the Japan Study Group of Prostate Cancer were enrolled for the present analysis. Patients were divided into four groups based on age at diagnosis: age <66, 66-70, 71-75, and >75. Risk was stratified according to the Japan Cancer of the Prostate Risk Assessment (J-CAPRA). Multivariate competing risks regression analysis was performed for OS and PFS. RESULTS: There was downward stage migration over age. Among men aged >75 years, 34.1 % had nodal or distant metastatic disease. In contrast, 56.0 % of patients aged <66 years presented with advanced disease. The modality of hormonal therapy varied with age across risk groups; the younger age group showed a higher proportion of maximal androgen blockade, while the proportion of monotherapy use was higher in older men. The likelihood of low-risk disease by J-CAPRA classification increased significantly with increasing age (p < 0.0001 by Pearson's chi-square test). The same as OS, the PFS rate increased with age until after the age of 75. Men aged 71-75 had better survival rates even after adjustments for treatment modality alone, or for treatment modality plus disease risk. CONCLUSIONS: Age cohorts do affect orientation toward favorable disease course after PADT with men aged 71-75 being benefiting more from PADT than other age groups.
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Antagonistas de Androgênios/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/mortalidade , Fatores Etários , Idade de Início , Idoso , Humanos , Japão/epidemiologia , Estudos Longitudinais , Masculino , Terapia Neoadjuvante , Prognóstico , Neoplasias da Próstata/tratamento farmacológico , Sistema de Registros/estatística & dados numéricos , Taxa de SobrevidaRESUMO
PURPOSE: To determine the influence of maximal androgen blockade (MAB) and non-MAB hormonal therapy with an luteinizing hormone releasing hormone (LHRH) analog on overall survival of prostate cancer patients in the Japan Study Group of Prostate Cancer (J-CaP) registry according to risk, as assessed using the novel J-CAPRA risk instrument. To undertake a multivariate analysis combining J-CAPRA risk score, type of hormonal therapy and comorbidities, in order to assess their impact on overall survival. METHODS: The J-CaP database includes men in Japan diagnosed with any stage of prostate cancer between 2001 and 2003 and treated with primary androgen deprivation therapy (PADT), as monotherapy or in combination. A total of 26,272 men were enrolled and of these 19,265 were treated with PADT. This analysis was undertaken using the latest data set (30 April, 2010) including a total of 15,727 patients who received PADT and had follow-up data for periods ranging from 0 to 9.2 years. RESULTS: MAB for prostate cancer patients with intermediate- or high-risk disease has a significant benefit in terms of overall survival compared with LHRH analog monotherapy or surgical castration alone. Better results may be achieved in older (≥75 years) patients. Patient comorbidities are an important factor in determining overall survival, notably in older patients, and should be considered when selecting therapy. CONCLUSIONS: Based on large-scale registry data, this report is the first to analyze the outcomes of MAB therapy in patients with prostate cancer at a wide range of disease stages. MAB therapy may provide significant survival benefits in intermediate- and high-risk patients.
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OBJECTIVE: Sorafenib is an oral multi-kinase inhibitor of Raf-1, VEGF and PDGF receptors and others, resulting in tumor regression and anti-angiogenesis. We studied serum pancreatic enzyme increase associated with sorafenib treatment. PATIENTS AND METHODS: In a phase II study of Japanese patients with metastatic renal cell carcinoma, a total of 131 patients received sorafenib 400 mg twice per day. Serum levels of lipase and amylase were measured on day 7 and every 3-4 weeks thereafter during treatment period. When grade 3 or 4 enzyme abnormalities were observed, ultrasound or computed tomography scan was performed to detect pancreatitis. RESULTS: The incidence of all-grades lipase and amylase increases were 55. 7% and 38. 2%, respectively, while those of grade 3 or 4 were 30. 5% and 5. 3%, respectively. The majority of these events were observed in the first 3 weeks of sorafenib treatment. Grade 3 or 4 lipase increase was detected in 32 patients (24. 4%)on day 7 measurement. These abnormal elevations spontaneously resolved in all patients. Regarding grade 3 lipase increase, the median time to recovery to grade 2 and 1 were 7 and 14 days, respectively. Three patients required interruption of the treatment. No patient showed any clinical manifestation or abnormal imaging finding suggesting pancreatitis. CONCLUSION: Pancreatic enzyme increases observed frequently under sorafenib treatment were transient and asymptomatic. They were not related to symptomatic pancreatitis.
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Amilases/sangue , Benzenossulfonatos/efeitos adversos , Lipase/sangue , Pâncreas/efeitos dos fármacos , Pâncreas/enzimologia , Inibidores de Proteínas Quinases/efeitos adversos , Piridinas/efeitos adversos , Adulto , Idoso de 80 Anos ou mais , Benzenossulfonatos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Niacinamida/análogos & derivados , Compostos de Fenilureia , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/uso terapêutico , SorafenibeRESUMO
CONTEXT: The natural history of renal cell carcinoma (RCC) is highly unpredictable. Small renal masses may be accompanied by metastatic disease. Conversely, patients with locally advanced disease may enjoy long-term disease-free survival. OBJECTIVE: To review the status of prognostic factors in RCC. EVIDENCE ACQUISITION: A literature review was performed using the PubMed, MEDLINE, and Cochrane databases for articles published as of February 15, 2010. Electronic articles published ahead of print were also considered. Search was limited to the English language. Search was conducted using the following keywords: renal cell carcinoma, molecular, tissue, markers, blood, urine, progression, prognosis, risk factor, and survival. Studies were selected according to the relevance of the study, the number of patients included, originality, actuality, and clinical applicability of the results. EVIDENCE SYNTHESIS: Four areas of prediction were examined: (1) new RCC diagnostics, (2) RCC grade and stage at diagnosis, (3) disease progression, and (4) disease-specific mortality. All identified reports represented either case series or controlled studies. Although a large number of markers were identified, only a few were validated. Several prognostic factors were integrated in predictive or prognostic models. CONCLUSIONS: Several prognostic factors can help discriminate between favourable and unfavourable RCC phenotypes. Of those, several clinical, pathologic, and biologic markers have been tested and validated, and they are used in predictive and prognostic models. Nonetheless, the search continues, especially for informative markers predicting the response to targeted therapies.
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Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Biomarcadores Tumorais/análise , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/terapia , Progressão da Doença , Feminino , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/terapia , Masculino , Modelos Biológicos , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Fatores SexuaisRESUMO
UNLABELLED: What's known on the subject? and What does the study add? Interim result of this study had shown promising efficacy, with response rate of 14.7% and median PFS of 7.4 months, and good tolerability of sorafenib in previously-treated Japanese patients with metastatic RCC. Final result of the study adds: (1) the median overall survival of 25.3 months, which is longer than that in the global phase III study TARGET; (2) the response rate which elevated to 19.4% because of 6 late responders achieved after 9.2 months or longer of SD period; (3) lack of either unknown adverse events nor cumulative toxicity in the long-term use of sorafenib. OBJECTIVE: ⢠To explore the long-term efficacy and safety of sorafenib in Japanese patients with metastatic renal cell carcinoma (RCC) in a phase II trial. PATIENTS AND METHODS: ⢠In all, 131 Japanese patients with metastatic RCC who had received nephrectomy and failed at least one cytokine-containing systemic therapy received continuous sorafenib 400 mg twice daily, and the efficacy and safety parameters were evaluated in these patients, including objective response rate, progression-free survival and overall survival. RESULTS: ⢠Of the total, 129 patients were valid for intention-to-treat analyses and 131 patients were valid for safety analyses. ⢠Twenty-five patients (19.4%) had confirmed partial response and 87 patients (67.4%) had stable disease as best overall response. The 25 patients included six late-responders who achieved response after 9.2 months or longer of stable disease. The objective response rate and disease control rate were 19.4% and 73.6%, respectively. ⢠The median overall survival and median progression-free survival were 25.3 and 7.9 months, respectively. ⢠Safety profile was consistent with those previously reported, with hand-foot skin reaction (58.0%), lipase elevation (57.3%) and diarrhoea (42.7%) as the most frequently observed drug-related adverse events. Neither unknown adverse event nor cumulative toxicity was observed over the long-term use of sorafenib. ⢠Despite the dose discontinuation/interruption/reduction, the mean and median relative dose intensities were 86.4% and 97.4%, respectively. CONCLUSION: ⢠The final results of this trial showed that long-term use of sorafenib after cytokine treatment was well tolerated and provided new efficacy data, including late-response events and favourable overall survival in Japanese patients with metastatic RCC.
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Antineoplásicos/uso terapêutico , Benzenossulfonatos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Piridinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/secundário , Citocinas/uso terapêutico , Intervalo Livre de Doença , Humanos , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Niacinamida/análogos & derivados , Compostos de Fenilureia , Sorafenibe , Resultado do TratamentoRESUMO
Steroidogenic factor-1 (SF-1) is a nuclear orphan receptor, which is essential for adrenal development and regulation of steroidogenic enzyme expression. SF-1 is posttranslationally modified by small ubiquitin-related modifier-1 (SUMO-1), thus mostly resulting in attenuation of transcription. We investigated the role of sumoylation enzymes, Ubc9 and protein inhibitors of activated STAT1 (PIAS1), in SF-1-mediated transcription of steroidogenic enzyme genes in the adrenal cortex. Coimmunoprecipitation assays showed that both Ubc9 and PIAS1 interacted with SF-1. Transient transfection assays in adrenocortical H295R cells showed Ubc9 and PIAS1 potentiated SF-1-mediated transactivation of reporter constructs containing human CYP17, CYP11A1, and CYP11B1 but not CYP11B2 promoters. Reduction of endogenous Ubc9 and PIAS1 by introducing corresponding small interfering RNA significantly reduced endogenous CYP17, CYP11A1, and CYP11B1 mRNA levels, indicating that they normally function as coactivators of SF-1. Wild type and sumoylation-inactive mutants of Ubc9 and PIAS1 can similarly enhance the SF-1-mediated transactivation of the CYP17 gene, indicating that the coactivation potency of Ubc9 and PIAS1 is independent of sumoylation activity. Chromatin immunoprecipitation assays demonstrated that SF-1, Ubc9, and PIAS1 were recruited to an endogenous CYP17 gene promoter in the context of chromatin in vivo. Immunohistochemistry and Western blotting showed that SF-1, Ubc9, and PIAS1 were expressed in the nuclei of the human adrenal cortex. In cortisol-producing adenomas, the expression pattern of SF-1 and Ubc9 were markedly increased, whereas that of PIAS1 was decreased compared with adjacent normal adrenals. These results showed the physiological roles of Ubc9 and PIAS1 as SF-1 coactivators beyond sumoylation enzymes in adrenocortical steroidogenesis and suggested their possible pathophysiological roles in human cortisol-producing adenomas.
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Córtex Suprarrenal/enzimologia , Regulação Enzimológica da Expressão Gênica , Proteínas Inibidoras de STAT Ativados/metabolismo , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Fator Esteroidogênico 1/metabolismo , Ativação Transcricional , Enzimas de Conjugação de Ubiquitina/metabolismo , Linhagem Celular Tumoral , Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo , Citocromo P-450 CYP11B2/genética , Citocromo P-450 CYP11B2/metabolismo , Humanos , Regiões Promotoras Genéticas , Ligação Proteica , Proteínas Inibidoras de STAT Ativados/genética , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/genética , Esteroide 11-beta-Hidroxilase/genética , Esteroide 11-beta-Hidroxilase/metabolismo , Esteroide 17-alfa-Hidroxilase/genética , Esteroide 17-alfa-Hidroxilase/metabolismo , Fator Esteroidogênico 1/genética , Transcrição Gênica , Enzimas de Conjugação de Ubiquitina/genéticaRESUMO
Sorafenib (Nexavar) is an oral multi-kinase inhibitor that targets tumor growth and angiogenesis, having encouraging efficacy and tolerability in patients with metastatic renal cell carcinoma (RCC) and other tumors. However, hand-foot syndrome (HFS), a frequently reported adverse event under sorafenib treatment, sometimes causes interruption of the treatment or dose reduction. This study was conducted to review sorafenib-associated HSF in Japanese patients, to facilitate improvement of the management of HFS in clinical practice. We reviewed the combined results on HFS in three sorafenib studies in Japanese patients: (A) a phase II study of metastatic renal cell carcinoma; (B) a phase I study of solid tumor; and (C), phase I study of hepatocellular carcinoma. Severity of HFS was graded as 1-3 based on the modified grading scale of National Cancer Institute - Common Toxicity Criteria version 2.0 and Common Terminology Criteria for Adverse Events version 3.0. A total of 189 patients were included for analyses. The incidence of all-grade HFS was 51% (55% in A, 39% in B and 44% in C), and the incidence of grade 3 HFS was 7% (9% in A, 0% in B and 7% in C). Incidence of HFS seemed dose-dependent. These events were observed within 3-9 weeks after initiation of sorafenib treatment. The majority of HFS was manageable with symptomatic treatment and HFS caused permanent discontinuation of sorafenib in only one patient (in study A). The incidence of sorafenib-associated HFS is high compared to other adverse events. However, the present analyses showed that HFS under sorafenib treatment is well manageable in Japanese patients.
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Antineoplásicos/efeitos adversos , Benzenossulfonatos/efeitos adversos , Dermatoses do Pé/induzido quimicamente , Dermatoses da Mão/induzido quimicamente , Inibidores de Proteínas Quinases/efeitos adversos , Piridinas/efeitos adversos , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Humanos , Japão , Niacinamida/análogos & derivados , Compostos de Fenilureia , Sorafenibe , SíndromeRESUMO
OBJECTIVES: To examine whether candesartan enhances the cytotoxicity of cis-dichlorodiammineplatinum (CDDP) in mice with bladder cancer as a method to enhance the therapeutic effects of CDDP. CDDP is an antitumor agent conventionally used against bladder cancer; however, its therapeutic efficacy appears to not be fully satisfactory. Recent studies have shown the antitumor activity of the angiotensin II type 1 receptor antagonist candesartan. METHODS: A xenograft model was prepared in nude mice using human bladder cancer cells (KU-19-19). Candesartan (1 mg/kg/d) was administered daily by oral gavage from the day of implantation plus 28 days, and CDDP (1 mg/kg/d) was administered intraperitoneally from days 5 to 9. The microvessel density, vascular endothelial growth factor expression, and apoptosis were investigated immunohistochemically. RESULTS: Candesartan, CDDP, and candesartan-CDDP suppressed tumor growth to 41.9%, 33.8%, and 13.2%, respectively, of the tumor volume in the control group, showing that combined treatment significantly inhibited tumor growth compared with each single agent alone. The microvessel density was significantly decreased in the candesartan and candesartan-CDDP groups compared with the control group. Vascular endothelial growth factor expression was significantly decreased in the candesartan, CDDP, and candesartan-CDDP groups compared with the control group. The apoptotic index was significantly increased in the CDDP and candesartan-CDDP groups compared with the control and candesartan groups. CONCLUSIONS: It is quite likely that candesartan and CDDP suppressed tumor growth by inhibiting angiogenesis and inducing apoptosis, respectively. Furthermore, combined treatment with candesartan enhanced CDDP-induced cytotoxicity by further suppressing angiogenesis. These results suggest that candesartan could be a candidate for innovational therapy of bladder cancer.
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Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Antineoplásicos/uso terapêutico , Benzimidazóis/farmacologia , Cisplatino/uso terapêutico , Tetrazóis/farmacologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Animais , Compostos de Bifenilo , Modelos Animais de Doenças , Sinergismo Farmacológico , Humanos , Camundongos , Camundongos Nus , Transplante de Neoplasias , Transplante Heterólogo , Células Tumorais CultivadasRESUMO
OBJECTIVE: To assess whether tumour architecture can help to refine the prognosis of patients treated with nephroureterectomy (NU) for urothelial carcinoma (UC) of the upper urinary tract (UT), as the prognostic value of tumour architecture (papillary vs sessile) in UTUC remains elusive. PATIENTS AND METHODS: The study included 1363 patients with UTUC and treated with radical NU at 12 centres worldwide. All slides were re-reviewed according to strict criteria by genitourinary pathologists who were unaware of the findings of the original pathology slides and clinical outcomes. Gross tumour architecture was categorized as sessile vs papillary. RESULTS: Papillary growth was identified in 983 patients (72.2%) and sessile growth in 380 (27.8%). The sessile growth pattern was associated with higher tumour grade, more advanced stage, lymphovascular invasion, and metastasis to lymph nodes (all P < 0.001). In multivariable Cox regression analyses that adjusted for the effects of pathological stage, grade and lymph node status, tumour architecture (sessile or papillary) was an independent predictor of cancer recurrence (hazard ratio 1.5, P = 0.002) and cancer-specific mortality (1.6, P = 0.001). Adding tumour architecture increased the predictive accuracy of a model that comprised pathological stage, grade and lymph node status for predicting cancer recurrence and cancer-specific death by a minimal but statistically significant margin (gain in predictive accuracy 1% and 0.5%, both P < 0.001). CONCLUSION: The tumour architecture of UTUC is associated with established features of biologically aggressive disease, and more importantly, with prognosis after radical NU. Including tumour architecture in predictive models for disease progression should be considered, aiming to identify patients who might benefit from early systemic therapeutic intervention.
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Nefrectomia/métodos , Neoplasias Urológicas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Métodos Epidemiológicos , Feminino , Humanos , Excisão de Linfonodo/métodos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Fatores de Risco , Resultado do Tratamento , Ureter/cirurgia , Neoplasias Urológicas/cirurgiaRESUMO
PURPOSE: Recent studies suggest that alterations in chromatin structure by histone acetylation may have an important role in the neoplastic process. We evaluated histone H3 acetylation in renal cell carcinoma and the effects of a histone deacetylase inhibitor on renal cancer cell lines. MATERIALS AND METHODS: The expression of acetylated histone H3 (Lys9) in renal cell carcinoma and corresponding nonneoplastic tissue specimens was evaluated. We next assessed immunohistologically the relationships between acetylated histone H3 expression and clinicopathological parameters in 44 cases of renal cell carcinoma. Furthermore, we evaluated the effects of the histone deacetylase inhibitor depsipeptide on the renal cancer cell lines Caki-1, ACHN, 769P and 786O (ATCC). RESULTS: Acetylated histone H3 expression was decreased in 85.0% of renal cell carcinomas compared to levels in nonneoplastic tissue. Decreased expression was related to high nuclear tumor grade and advanced pathological tumor stage (p = 0.048 and 0.032, respectively). Depsipeptide inhibited cell line proliferation in a time and dose dependent manner. Depsipeptide induced apoptosis in Caki-1, ACHN and 786O, and induced G2 cell cycle arrest in 769P. Concomitantly depsipeptide increased acetylated histone H3 and p21(WAF/CIP1) expression, and induced Bcl-2 phosphorylation. CONCLUSIONS: These results suggest that the decreased acetylation of histone H3 is a common alteration in a malignant phenotype of renal cell carcinoma. Increasing the amount of acetylated histone H3 might be a therapeutic option for renal cell carcinoma.
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Carcinoma de Células Renais/metabolismo , Depsipeptídeos/farmacologia , Histona Desacetilases/farmacologia , Histonas/metabolismo , Neoplasias Renais/metabolismo , Acetilação , Análise de Variância , Apoptose/efeitos dos fármacos , Western Blotting , Ciclo Celular/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p21/efeitos dos fármacos , Humanos , Técnicas Imunoenzimáticas , Proteínas Proto-Oncogênicas c-bcl-2/efeitos dos fármacos , Estatísticas não Paramétricas , Células Tumorais CultivadasRESUMO
PURPOSE: We validated the 2001 Partin tables and developed an original nomogram for Japanese patients using the 2005 International Society of Urological Pathology consensus on Gleason grading. MATERIALS AND METHODS: Prostatectomy specimens from 1,188 Japanese men who underwent radical prostatectomy for clinically localized prostate cancer (cT1-2) between 1997 and 2005 were analyzed. Polychotomous logistic regression analysis was used to construct a nomogram to predict final pathological stage (organ confined disease, extraprostatic extension, seminal vesicle invasion and lymph node involvement) from 3 variables, including serum prostate specific antigen, clinical stage and biopsy Gleason score. The area under the ROC curve was used to compare the new nomogram with the Partin tables. RESULTS: Preoperative serum prostate specific antigen and biopsy Gleason score were higher in the Japanese cohort than in the Partin cohort. The distribution of clinical and final pathological stages was similar in the 2 cohorts. The AUC for predicting organ confined disease was 0.699 and 0.717 for data applied to the Partin tables and to the new nomogram, respectively. The AUC for predicting lymph node involvement was 0.793 and 0.863, respectively. CONCLUSIONS: To our knowledge this is the first preoperative nomogram developed for clinically localized prostate cancer in Japanese patients. Although the new nomogram predicted the pathological stage of prostate cancer in Japanese patients more accurately than the Partin tables, it did not satisfactorily predict organ confined disease. However, other predictive variables, such as more detailed pathological features of biopsy specimens or magnetic resonance imaging, may further improve prediction accuracy.
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Neoplasias da Próstata/patologia , Área Sob a Curva , Humanos , Japão , Modelos Logísticos , Masculino , Estadiamento de Neoplasias , Nomogramas , Valor Preditivo dos Testes , Cuidados Pré-Operatórios , Prostatectomia , Neoplasias da Próstata/cirurgia , Curva ROC , Sensibilidade e EspecificidadeRESUMO
A 61-year-old man who had been suffering from benign prostatic hyperplasia (BPH) for ten years visited our hospital complaining of dysuria and bladder pain. Abdominal X-ray showed a 2 cm calculus containing a needle-like shadow in the pelvis. Transurethral lithotripsy and trunsurethral resection of the prostate (TURP) were done. The calculus was a brown club-shaped bladder stone with the core being a 2 cm needle one side of which was broken. It was supposed to be an acupuncture needle that was retained in his back twenty years ago. This is the first case of a bladder stone secondary to migration of an acupuncture needle.
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Acupuntura/instrumentação , Migração de Corpo Estranho/complicações , Agulhas , Cálculos da Bexiga Urinária/etiologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: The clinical value of serum tartrate-resistant acid phosphatase (TRACP), prostate specific antigen (PSA), alkaline phosphatase (ALP), and prostatic acid phosphatase (PACP) for the prediction of bone metastases in prostate cancer were investigated. METHODS: TRACP, PACP, ALP, and PSA serum levels were measured in 215 patients with prostate cancer, including 160 without and 55 with bone metastases. Correlation of serum marker levels with bone metastases was assessed using receiver operating characteristics (ROC) analysis. Sensitivity, specificity, accuracy, positive and negative predictive values were calculated for each serum marker. Multivariate stepwise logistic regression analysis was used to identify independent predictors for the presence of bone metastasis. RESULTS: Mean serum TRACP, PACP, ALP, and PSA levels were significantly elevated in patients with bone metastases compared with those without (P < 0.05). PSA and PACP levels increased significantly with clinical stage of the disease, whereas TRACP and ALP levels only increased significantly in stage D2. Serum TRACP levels correlated significantly with extent of disease on bone scans. ROC analyses showed no significant differences in area under the curve for these markers. Logistic regression analysis demonstrated that PSA, ALP, and TRACP were significant predictors of bone metastasis. Predicted and observed risks of bone metastasis were well correlated when TRACP, ALP, and PSA were combined and bone scan could have been omitted in 70% of patients by assessing these three markers. CONCLUSIONS: Serum TRACP can be considered a useful predictor of bone metastases in prostate cancer. A combination of TRACP, ALP, and PSA can obviate the need for a bone scan in 70% of cases.
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Fosfatase Ácida/sangue , Fosfatase Alcalina/sangue , Neoplasias Ósseas/sangue , Neoplasias Ósseas/secundário , Isoenzimas/sangue , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Idoso , Biomarcadores/sangue , Humanos , Masculino , Valor Preditivo dos Testes , Fosfatase Ácida Resistente a TartaratoRESUMO
OBJECTIVES: To investigate the clinical value of prostate specific antigen velocity (PSAV) in predicting the extraprostatic extension of clinically localized prostate cancer. METHODS: One hundred and three patients who underwent radical prostatectomy for clinically localized prostate cancer were included in the analysis. The correlation between preoperative parameters, including PSA-based parameters, clinical stage, and histological biopsy findings, and the pathological findings were analyzed. Logistic regression analysis was performed to identify a significant set of independent predictors for the local extent of the disease. RESULTS: Sixty-four (60.2%) patients had organ confined prostate cancer and 39 (39.8%) patients had extraprostatic cancer. The biopsy Gleason score, PSA, PSA density, PSA density of the transition zone, and PSAV were significantly higher in the patients with extraprostatic cancer than in those with organ confined cancer. Multivariate logistic regression analysis indicated that the biopsy Gleason score, endorectal magnetic resonance imaging findings, and PSAV were significant predictors of extraprostatic cancer (P < 0.01). Probability curves for extraprostatic cancer were generated using these three preoperative parameters. CONCLUSIONS: The combination of PSAV, endorectal magnetic resonance imaging findings, and biopsy Gleason score can provide additional information for selecting appropriate candidates for radical prostatectomy.
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Imageamento por Ressonância Magnética , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Idoso , Biópsia , Humanos , Metástase Linfática , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Valor Preditivo dos Testes , RetoRESUMO
BACKGROUND: IL-6 has been reported to be a significant prognostic factor for prostate cancer and induces synthesis of C-reactive protein (CRP) by hepatocytes. The present study was undertaken to evaluate the clinical value of serum CRP in prostate cancer patients with metastases. METHODS: The prognostic significance of serum CRP as well as tumor histology, extent of disease (EOD) on bone scan, serum levels of prostate-specific antigen (PSA) and alkaline phosphatase (ALP) and hemoglobin was assessed using Cox's proportional hazards model analyses in 126 prostate cancer patients with metastases treated with endocrine therapy. RESULTS: Serum levels of CRP, PSA and ALP significantly increased and hemoglobin significantly decreased with advancing EOD grade. Univariate analysis demonstrated that EOD, CRP, PSA, ALP, hemoglobin and tumor histology are significantly associated with disease-specific survival. Multivariate analysis demonstrated that serum CRP and EOD were significant prognostic factors. The 5-year survival rates in low-risk patients (CRP < or = 0.15 mg/dl and EOD < or = 1) and high-risk patients (CRP > 0.15 mg/dl and EOD > or = 2) were 74 and 24%, respectively. CONCLUSION: These results indicate that a combination of serum CRP and EOD can identify patients with a poor prognosis who may be candidates for innovative treatments among prostate cancer patients with metastases.
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Adenocarcinoma/sangue , Adenocarcinoma/mortalidade , Neoplasias Ósseas/sangue , Neoplasias Ósseas/mortalidade , Proteína C-Reativa/análise , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/secundário , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Humanos , Masculino , Prognóstico , Cintilografia , Taxa de SobrevidaAssuntos
Carcinoma de Células Renais/epidemiologia , Neoplasias Renais/epidemiologia , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Programa de SEER , Fatores Sexuais , Análise de Sobrevida , Estados UnidosRESUMO
BACKGROUND: Based on the data of current status of endocrine therapy for prostate cancer registered in the Japan Study Group of Prostate Cancer (J-CaP), we conducted an analysis of primary androgen deprivation therapy (PADT) and an interim analysis of the prognosis. METHODS: Of the 26 272 cases registered in the server of J-CaP, the 19 409 cases initially receiving PADT were included in this study. The initial therapy was divided into eight categories according to its features. RESULTS: Of the 19 409 patients, 1513 (7.8%) were given anti-androgen monotherapy, 955 patients (4.9%) surgical castration only, 1001 patients (5.2%) surgical castration + anti-androgen, 3015 patients (15.5%) LHRH monotherapy, 1658 patients (8.5%) LH-RH + short-term anti-androgen, 10 434 patients (53.8%) LH-RH + anti-androgen, 37 patients (0.2%) watchful waiting and 796 patients (4.1%) other therapy. In progression-free survival, the prognosis was slightly better following maximum androgen blockade (MAB) in each stage. CONCLUSIONS: The pattern of PADT is more typical in Japan compared with that in the United States. Patients who received MAB accounted for 59.0% of all the patients. MAB tends to be more often selected for patients who are rated as being at high risk on the basis of high Gleason score or PSA level upon diagnosis in each clinical stage of the disease. Investigations of the outcome are on-going and they will make clear the significance of this trend in Japan.
Assuntos
Antineoplásicos Hormonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Neoplasias da Próstata/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anilidas/administração & dosagem , Dietilestilbestrol/administração & dosagem , Intervalo Livre de Doença , Seguimentos , Gosserrelina/administração & dosagem , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nitrilas/administração & dosagem , Orquiectomia , Prognóstico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Compostos de Tosil/administração & dosagemRESUMO
OBJECTIVE: Sorafenib (Nexavar) is an oral multi-kinase inhibitor that targets tumor growth and angiogenesis. This phase II study investigated efficacy, safety, and pharmacokinetics of sorafenib in Japanese patients with advanced renal cell carcinoma (RCC). METHODS: Nonrandomized, open-label study in Japanese patients with metastatic renal cell carcinoma who had received nephrectomy and failed >/=1 cytokine-containing therapy. The primary endpoint was response rate. Patients received sorafenib 400 mg twice daily (b.i.d.) on a continuous dosing schedule. RESULTS: A total of 129 patients (median age 63 years) were valid for intention-to-treat analyses. Confirmed partial responses were observed in 16 (12.4%) patients, and investigators assessed that 19 (14.7%) of the patients achieved a partial response. Stable disease was reported in 93 (72.1%) patients, and 103 (80.5%) patients had tumor shrinkage. Median progression-free survival was 224 days and the 25th percentile of overall survival was estimated at 288 days. The most frequently occurring drug-related adverse events (any grade) were elevated lipase (56%), hand-foot skin reaction (55%), alopecia (39%), increased amylase (38%), rash/desquamation (37%), and diarrhea (34%). A total of 14 (10.7%) patients had serious sorafenib-related adverse events, including one adverse event of worst grade 5 (dyspnea occurred 35 days after the last dose of study medication). The C(trough,steady state) values in RCC patients (n = 63) receiving sorafenib 400 mg b.i.d. were similar to those obtained from a Japanese phase I study involving patients with mixed solid tumors. CONCLUSION: Sorafenib showed encouraging efficacy and was well tolerated in Japanese patients with metastatic RCC.
Assuntos
Benzenossulfonatos/farmacocinética , Benzenossulfonatos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacocinética , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/farmacocinética , Piridinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Benzenossulfonatos/efeitos adversos , Carcinoma de Células Renais/secundário , Quimioterapia Adjuvante , Intervalo Livre de Doença , Toxidermias/etiologia , Feminino , Humanos , Lipase/efeitos dos fármacos , Lipase/metabolismo , Masculino , Pessoa de Meia-Idade , Nefrectomia , Niacinamida/análogos & derivados , Compostos de Fenilureia , Inibidores de Proteínas Quinases/efeitos adversos , Piridinas/efeitos adversos , SorafenibeRESUMO
This is the first report of direct evidence that metanephric adenoma cells produce erythropoietin and other types of cytokines, which may be the cause of the high incidence of erythrocytosis in patients with this tumor. The purpose of the study was to establish a metanephric adenoma cell line in vitro from nephrectomized tumor tissue in order to investigate the ability of metanephric adenoma cells to produce erythropoietin and other types of cytokines. The tumor tissue was obtained from a 16-year-old boy who had developed metanephric adenoma with erythrocytosis and was served for cell culture. Significantly high concentrations of erythropoietin, granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte-colony-stimulating factor (G-CSF), interleukin-6 (IL-6), and IL-8 were detected in the cell culture supernatant. Southern hybridization showed specific positive signals for GM-CSF, G-CSF, IL-6, IL-8 and erythropoietin. The number of chromosomes was 46-XY without any structural abnormalities in cytogenetic analysis of the cultured cells.