RESUMO
Prostate cancer (PCa) is one of the most common cancers in the world. Inflammation has been described as a risk factor for PCa and depends on the production of cytokines in response to tissue damage or the presence of stimuli that induces cellular stress. Interindividual variation in cytokine production is partially controlled by single-nucleotide polymorphisms (SNPs) that have been associated with differential production of cytokines. We have recently showed that SNP-SNP interactions of cytokine genes are associated with PCa risk. However, little is known about the association of cytokine SNPs and PCa aggressiveness. In this study, we evaluated the association of 15 SNPs in five cytokine genes and aggressiveness of PCa in African- and Caucasian-American individuals. Caucasian Americans with the genotypes IL10-1082GG or IL1B+3954TT had 2.31-fold [95% confidence interval (CI) = 1.13-4.72] and 3.11 (95% CI = 1.20-8.06)-fold risk, respectively, of developing aggressive PCa, as compared with individuals without those genotypes. We did not find any associations in the African-American group. Using Multivariate Adaptive Regression Splines modeling for exploratory SNP-SNP interactions, our results showed that more aggressive PCa in Caucasians Americans is associated with the CT genotype at IL8-47 [odds ratios (OR) = 3.50; 95% CI = 1.13-10.88] or combined genotypes of IL1B-511CC and IL10-1082GG (OR = 3.38; 95% CI = 1.70-6.71). Unfortunately, the same analysis could not be performed in the African-Americans due to limited number of individuals. With limited sample size, the results from this study suggest that SNPs in cytokine genes may be associated with PCa aggressiveness. More extensive studies are warranted to validate our findings.
Assuntos
Citocinas/genética , Polimorfismo de Nucleotídeo Único/genética , Hiperplasia Prostática/genética , Neoplasias da Próstata/genética , População Branca/genética , Negro ou Afro-Americano/genética , Idoso , Estudos de Casos e Controles , DNA de Neoplasias/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/patologia , Neoplasias da Próstata/patologiaRESUMO
Prostate cancer (CaP) is the second leading cause of cancer death in American men. Chronic inflammation has been one of several factors associated with the development of CaP. Single-nucleotide polymorphisms (SNPs) in cytokine genes have been associated with increased inflammation, increased cytokine production and possibly increased CaP risk. However, the effects of cytokine SNPs on CaP susceptibility have not been consistent. Using the genomic DNA collected in a CaP case-control study (557 cases and 547 controls), we pilot tested the interactions of nine functionally characterized SNPs of three cytokine genes in CaP risk using the multivariate adaptive regression splines (MARS)-logit models. African-Americans with the IL10-819TT genotype had a lower CaP risk [odds ratio (OR) = 0.27, 95% confidence interval (CI) = 0.07-1.01], but subjects with the genotype combination of IL1B-511CT/TT and IL10-592CC had a higher CaP risk (OR = 2.56, 95% CI = 1.09-6.02). In Caucasians, higher CaP risk was associated with the IL10-1082AG/GG genotype (OR = 3.62, 95% CI = 1.42-9.28), the genotype combination of IL10-1082AA plus IL1B-31TT/TC (OR = 2.92, 95% CI = 1.13-7.55) and the genotype combination of TNF-238GG plus IL10-592AA (OR = 2.14, 95% CI = 1.05-4.38). Our results highlight the importance of cytokine SNPs and their interactions in CaP risk.
Assuntos
Citocinas/genética , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/genética , População Negra , Estudos de Casos e Controles , Predisposição Genética para Doença , Humanos , Masculino , Análise Multivariada , Neoplasias da Próstata/etnologia , Fatores de Risco , População BrancaAssuntos
Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/terapia , Invasividade Neoplásica/patologia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapia , Administração Intravesical , Idoso , Idoso de 80 Anos ou mais , Vacina BCG/uso terapêutico , Carcinoma de Células de Transição/mortalidade , Quimioterapia Adjuvante , Cistectomia/métodos , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Seleção de Pacientes , Prognóstico , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento , Neoplasias da Bexiga Urinária/mortalidadeRESUMO
OBJECTIVE: Percutaneous thermal ablation is an emerging technique in the management of renal cell carcinoma (RCC), with greatest efficacy in tumors < or = 3 cm. The purpose of this retrospective study was to evaluate the role and utility of pretreatment CT-guided biopsy in patients referred for percutaneous thermal ablation of renal tumors. CONCLUSION: Less than 5% of samples in our study were benign, and 11.8% were nondiagnostic. Biopsy in smaller lesions was less accurate; therefore biopsy is less useful for these renal lesions. Because fine-needle aspiration (FNA) has higher sensitivity than core biopsy, an appropriate algorithm may be to begin with FNA and reserve core biopsy for cases in which an onsite cytotechnologist is unavailable or deems the sample of inadequate cellularity.
Assuntos
Biópsia por Agulha/métodos , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Cuidados Pré-Operatórios/métodos , Cirurgia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Ablação por Cateter , Estudos de Coortes , Feminino , Humanos , Neoplasias Renais/diagnóstico por imagem , Masculino , Prognóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
PURPOSE: To assess whether a delay in initiating definitive therapy for clinically localized prostate cancer affects outcome. METHODS: We retrospectively reviewed 393 men with localized prostate cancer treated with radiation therapy or surgery without systemic therapy between 1991 and 2004. Data included: time from diagnosis to treatment initiation (more or less than 3 months); biopsy Gleason score grouped by low (2-6), intermediate (7), or high risk (8-10); clinical stage grouped by low (T1/T2a) or high risk (T2b or higher); pretreatment prostate-specific antigen (PSA) grouped by low (<10 ng/ml), intermediate (10-20), or high risk (>20); and biochemical recurrence-free survival. RESULTS: Median patient age was 63.1 years (range 39.7-79.5). Median pretreatment PSA was 6.5 ng/ml (range 0.4-411). Median time from diagnosis to treatment was 57 days (range 8-2927). A total of 310 patients (79%) were treated within 3 months. Median follow-up was 2.3 years (range 0.1-14.0). On univariate analysis using Kaplan-Meier survival curves and the log-rank test, only pretreatment PSA was associated with worse biochemical recurrence-free survival (P = 0.008). Biochemical recurrence-free survival was not associated with time from diagnosis to treatment (P = 0.28), clinical stage (P = 0.50), or biopsy Gleason score (P = 0.19). The results were the same when analyzed in a multivariable analysis using the Cox proportional hazards model. CONCLUSION: A delay in treatment of > or =3 months does not appear to affect adversely biochemical recurrence-free survival in patients who undergo definitive therapy for clinically localized prostate cancer in those with low risk features.
Assuntos
Recidiva Local de Neoplasia/diagnóstico , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Adulto , Idoso , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Fatores de TempoRESUMO
OBJECTIVE: The purpose of this study was to determine, in renal neoplasms, the size of ablation zones induced in vivo with percutaneous microwave probes and whether skip areas remain within the ablation zones. CONCLUSION: For a single 10-minute ablation, ablated volumes averaged 27 cm3 and 105 cm3 with a single-probe and a three-probe ablation array, respectively. There were no skip areas within the ablated zone. Microwave ablation can safely and quickly generate large ablation lesions and renal neoplasms.
Assuntos
Ablação por Cateter/métodos , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Micro-Ondas/uso terapêutico , Nefrectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hipertermia Induzida , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Cuidados Pré-OperatóriosRESUMO
BACKGROUND: Ultimately, patients with metastatic prostate cancer progress on androgen ablation therapy. The investigation of new chemotherapeutic regimens for the treatment of androgen-independent prostate cancer (AIPC) is essential. The authors conducted a Phase II trial with vinorelbine, doxorubicin, and daily prednisone (NAP) to investigate the antitumor activity and palliative response of this regimen in patients with AIPC. METHODS: Forty-six patients entered this Phase II combination chemotherapy trial. Patients were treated with both vinorelbine and doxorubicin at doses of 20 mg/m2 on Days 1, 8, and 15 every 28 days and prednisone 5 mg twice daily. Endpoints included prostate-specific antigen (PSA) response and palliation, as measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) instrument, the Brief Pain Inventory Scale, and a narcotic analgesic log. RESULTS: The median follow-up for all 46 patients was 13.4 months. Fifty-two percent of patients had impaired performance status at baseline. One responding patient remained on NAP and was progression-free at 11.5 months. Thirty-nine patients progressed, 3 patients died prior to response assessment, and 3 patients refused therapy. The median overall survival was 57 weeks (95% confidence interval [95% CI], 36-76 weeks), and the median time to disease progression was 17 weeks (range, 11-24 weeks). The PSA response among the 36 patients who completed 3 cycles of NAP was 42% (95% CI, 26-59%). There was a statistically significant improvement in quality of life measured both by the FACT-General instrument (P = .03) and the FACT-P instrument (P = .0006) over the 3 months compared with baseline measurements. Pain medicine use also improved: The median morphine equivalents among patients who were taking pain medications at the time of study enrollment showed a substantial decline after 1 cycle of treatment that was maintained. Pain (as assessed by the Brief Pain Inventory) improved compared with baseline pain at the 2nd-month assessment (worst pain, P = .08; least pain, P = .02; and average pain, P = .003). Overall, the regimen was tolerated well. The most common side effects were mild fatigue and gastrointestinal complaints (all of which were Grade 1 or 2 [according to Version 2.0 of the Expanded Common Toxicity Criteria]). Seventeen patients (37%) experienced Grade 3 or 4 neutropenia. Five patients (11%) developed a cardiac ejection fraction of <50% during treatment and had doxorubicin discontinued. No patients developed clinical congestive heart failure. CONCLUSIONS: The NAP combination produced substantive palliation and a moderate response rate in men with AIPC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doxorrubicina/administração & dosagem , Prednisona/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Vimblastina/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Esquema de Medicação , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Medição da Dor , Cuidados Paliativos , Antígeno Prostático Específico/análise , Vimblastina/administração & dosagem , VinorelbinaRESUMO
OBJECTIVES: To report a prospective trial of lycopene supplementation in biochemically relapsed prostate cancer. METHODS: A total of 36 men with biochemically relapsed prostate cancer were enrolled in a dose-escalating, Phase I-II trial of lycopene supplementation. Six consecutive cohorts of 6 patients each received daily supplementation with 15, 30, 45, 60, 90, and 120 mg/day for 1 year. The serum levels of prostate-specific antigen (PSA) and plasma levels of lycopene were measured at baseline and every 3 months. The primary endpoints were PSA response (defined as a 50% decrease in serum PSA from baseline), pharmacokinetics, and the toxicity/tolerability of this regimen. RESULTS: A total of 36 patients were enrolled. The median age was 74 years (range 56 to 83), with a median serum PSA at entry of 4.4 ng/mL (range 0.8 to 24.9). No serum PSA responses were observed, and 37% of patients had PSA progression. The median time to progression was not reached. Toxicity was mild, with 1 patient discontinuing therapy because of diarrhea. Significant elevations of plasma lycopene were noted at 3 months and then appeared to plateau for all six dose levels. The plasma levels for doses between 15 and 90 mg/day were similar, with additional elevation only at 120 mg/day. CONCLUSIONS: Lycopene supplementation in men with biochemically relapsed prostate cancer is safe and well tolerated. The plasma levels of lycopene were similar for a wide dose range (15 to 90 mg/day) and plateaued by 3 months. Lycopene supplementation at the doses used in this study did not result in any discernible response in serum PSA.
Assuntos
Adenocarcinoma/tratamento farmacológico , Anticarcinógenos/administração & dosagem , Carotenoides/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Adenocarcinoma/sangue , Adenocarcinoma/terapia , Idoso , Idoso de 80 Anos ou mais , Humanos , Licopeno , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/terapiaRESUMO
Complimentary and alternative medicines (CAM) have increased drastically in popularity in the past decade. These are largely in the form of nutritional supplements. Despite a wealth of information sources on the subject, the fundamental problem with CAM therapies is a dearth of evidence-based medicine. Advanced prostate cancer has significant long-term morbidity, and there is a growing interest in alternative and complimentary forms of therapy that will improve the outcomes of patients who have recurrent or advanced prostate cancer while obviating the need for more toxic forms of therapy. In this article we summarize the use of some of the more common CAM nutritional supplements and review the scientific data that are available to support their use.
Assuntos
Terapias Complementares , Neoplasias da Próstata/terapia , Antioxidantes/uso terapêutico , Carotenoides/uso terapêutico , Progressão da Doença , Humanos , Licopeno , Masculino , Extratos Vegetais/uso terapêutico , Neoplasias da Próstata/patologia , Vitamina D/uso terapêutico , Vitaminas/uso terapêuticoRESUMO
This study used the alkaline Comet assay to evaluate whether basal or H2O2-induced DNA damage is associated with prostate cancer (CaP) risk. Using lymphocyte samples from 158 CaP cases and 128 controls, collected in an ongoing case-control study, our results showed that basal DNA damage did not differ between cases and controls. However, the H2O2-induced DNA damage level was significantly higher in incident cases (mean +/- SD; 6.61 +/- 4.43, n = 102) than controls (5.30 +/- 3.60, n = 128) or prevalent cases (4.47 +/- 3.19; n = 56). Incident cases with a positive smoking history had significantly higher H2O2-induced DNA damage than never-smokers (7.57 +/- 4.82 versus 4.52 +/- 2.40; P < 0.001). Above-median H2O2-induced DNA damage was associated with a 1.61-fold increase in CaP risk [95% confidence interval (CI) = 0.92-2.81], after adjustment for age, race, benign prostatic hyperplasia (BPH), smoking history and family history (FH). Using the lowest quartile of H2O2-induced DNA damage as the referent group, the adjusted ORs for the 25th, 50th and 75th quartiles were 0.90 (95% CI = 0.39-2.05), 1.06 (95% CI = 0.48-2.35) and 2.05 (95% CI = 0.96-4.37), respectively (P = 0.046, test for linear trend). The association between CaP and DNA damage was modified by age, smoking history, family history and body mass index. Our results suggest that DNA damage may be associated with CaP risk. However, larger case-control and follow-up studies are warranted to further evaluate the potential application of the alkaline Comet assay in CaP risk assessment and prevention.
Assuntos
Dano ao DNA , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Fatores Etários , Idoso , Estudos de Casos e Controles , Ensaio Cometa/métodos , Humanos , Peróxido de Hidrogênio/farmacologia , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , RiscoRESUMO
Bladder cancer continues to provide urologists and researchers with a clinical and scientific challenge. Several urinary markers used in the detection and screening of patients with bladder cancer are currently under investigation. Improvements in intravesical therapy are proving to help decrease both tumor recurrence and progression in patients with high-risk disease. In patients with organ-confined, node-negative bladder cancer, radical cystectomy provides excellent local control and long-term disease-free survival. The use of an extended lymphadenectomy at the time of cystectomy may yield improved prognostic information as well as a potential survival benefit. Neoadjuvant chemotherapy and less toxic combination chemotherapy regimens are offering potential improvements in patients with extravesical or nodal extension. The current methods of detection, as well as available therapeutic treatment options are reviewed.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cistectomia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Humanos , Excisão de Linfonodo , Terapia Neoadjuvante , Prognóstico , Radioterapia Adjuvante , Fatores de Risco , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologiaRESUMO
PURPOSE: We assessed the safety and efficacy of the vitamin D analogue, 19-nor-1alpha-25-dihydroxyvitamin D2 (paricalcitol), in patients with androgen-independent prostate cancer. EXPERIMENTAL DESIGN: Patients received paricalcitol i.v. three times per week on an escalating dose of 5 to 25 microg (3-15 microg/m2). The primary end point was prostate-specific antigen (PSA) response. Secondary end points were characterization of toxicity in this population, changes in serum parathyroid hormone (PTH), and survival. RESULTS: A total of 18 patients were enrolled. No patient showed a sustained 50% drop in serum PSA, despite several large declines in PSA (e.g., 1,300 ng/mL). Paricalcitol was well tolerated. One instance of significant hypercalcemia, a serum calcium of 14.3 mg/dL, was observed at the highest dose (25 microg). At entry into the study, seven (41%) of the patients had elevated serum levels of PTH, which were significantly reduced by paricalcitol. Higher levels of serum PTH at study entry were significantly and negatively associated with survival (P<0.01). CONCLUSION: No objective responses were seen in the primary end point. However, elevated serum levels of PTH, a common feature of advanced prostate cancer, were reduced by paricalcitol. Because elevated PTH is associated with increased cardiovascular and skeletal morbidity, including an increased risk for pathologic fracture, further evaluation of paricalcitol in the reduction of skeletal morbidity in advanced prostate cancer is warranted.
Assuntos
Antineoplásicos/uso terapêutico , Ergocalciferóis/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Fosfatase Alcalina/sangue , Androgênios/metabolismo , Cálcio/sangue , Ergocalciferóis/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fósforo/sangue , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/mortalidade , Vitamina D/análogos & derivados , Vitamina D/sangueRESUMO
OBJECTIVE: The prognostic value of deoxyribonucleic acid (DNA) ploidy in renal cell carcinoma (RCC) is not well-defined among modern surgical nephrectomy series. We sought to determine which variables correlated with overall survival and recurrence-free survival in the modern era. METHODS: We reviewed all patients from 1992 to 2000, who prospectively had DNA ploidy analysis of their primary tumor determined at the time of nephrectomy for nonmetastatic RCC. Variables examined included age, gender, ethnicity, presentation (incidental vs. symptomatic), preoperative laboratory studies, American Society for Anesthesiology class, tumor size, tumor-nodes-metastasis stage, histology, Fuhrman grade, and diploid versus nondiploid tumor. Statistical analyses of overall survival and recurrence-free survival were performed using the Kaplan-Meier method, log-rank test, and Cox regression model using commercially available software. RESULTS: Sixty men and 41 women, median age 61 years (range, 23-85), were included. Pathologic stage included T1 (54 patients), T2 (14), and T3 (33). Eighty-four patients had conventional RCC. A total of 58 patients had well-differentiated (Fuhrman Grade 1 [12] or Grade 2 [46]), 28 had moderately differentiated (Grade 3), 12 had poorly differentiated tumors (Grade 4), and 3 were not specified. There were 52 patients who had diploid tumors, and 49 had aneuploid tumors. Median follow-up was 39 months (range, 0-109). Actuarial 5-year overall survival was 70%, and 5-year recurrence-free survival was 76%. Diploid tumors were significantly associated with better recurrence-free survival (P = 0.02) but not overall survival (P = 0.17). On multivariate analysis, the American Society for Anesthesiology class (P = 0.01), abnormal preoperative platelet count (P = 0.03), and tumor differentiation (P = 0.01) were independent predictors of overall survival, whereas only tumor differentiation (P = 0.05) was an independent predictor of recurrence-free survival. CONCLUSIONS: In the modern era, DNA ploidy is not an independent predictor of either overall survival or recurrence-free survival in patients with nonmetastatic RCC. The most important predictor of recurrence-free survival is tumor differentiation.
Assuntos
Carcinoma de Células Renais/mortalidade , DNA de Neoplasias/análise , Citometria de Fluxo/métodos , Neoplasias Renais/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Ploidias , Prognóstico , Recidiva , Taxa de SobrevidaRESUMO
The incidence of urethral TCC after radical cystectomy is approximately 8% overall. The most important risk factor for urethral TCC after radical cystectomy and urinary diversion is prostatic involvement by TCC, particularly stromal invasion. The safety of using the urethra for orthotopic urinary diversion seems to be best when intra-operative frozen section analysis of the urethral margin is performed at the time of radical cystectomy. There is provocative but unconfirmed evidence that orthotopic urinary diversion may be protective against the development of urethral TCC. Although most urethral "recurrences" occur within 5 years, delayed recurrences have been documented, mandating life-long follow-up of the retained urethra. Follow-up should include urinary cytology, either voided or urethral wash cytology as appropriate, with evaluation by endoscopy of any urethral related symptoms or change in voiding symptoms. The management of urethral TCC after cystectomy remains a total urethrectomy including excision of the meatus; however, in carefully selected patients with superficial disease and an orthotopic urinary diversion, urethra sparing may be attempted after a careful discussion with the patient. Survival after urethral TCC has generally been disappointing. The relative value of urethral versus original cystectomy pathologic stage and symptomatic versus nonsymptomatic recurrence in predicting survival remains controversial and awaits further studies that will most likely require the pooling of data from several large series.
Assuntos
Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/cirurgia , Cistectomia , Neoplasias Uretrais/etiologia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia , Carcinoma de Células de Transição/mortalidade , Feminino , Humanos , Masculino , Cuidados Pós-Operatórios , Fatores de Risco , Taxa de Sobrevida , Neoplasias Uretrais/mortalidade , Neoplasias Uretrais/patologia , Neoplasias da Bexiga Urinária/mortalidade , Derivação UrináriaRESUMO
PURPOSE OF REVIEW: This article reviews the recent literature concerning important issues in the management of patients with bladder cancer. A brief overview of all aspects of bladder cancer including the etiology, diagnosis, and treatment are discussed with a focus on recent advances. RECENT FINDINGS: Bladder cancer is a significant cause of morbidity and mortality. The treatment for bladder cancer should be based on individual patient risk assessment and should include a multidisciplinary approach. In patients with superficial bladder cancer, research has focused on improving and optimizing intravesical therapy to reduce tumor recurrence and progression as well as on methods to better select the most appropriate treatment for patients with high-risk features. The important prognostic and therapeutic role of lymphadenectomy during radical cystectomy has become apparent and recent work has attempted to better define what should be considered the standard for lymph node dissection. Finally, in an attempt to improve survival, advances have been made using systemic chemotherapy in both the perioperative settings as well as for treatment of metastatic bladder cancer. SUMMARY: Research continues to improve our understanding of bladder cancer. This ongoing investigation is currently being translated to the bedside with refinements in the diagnosis and treatment of patients with bladder cancer.
Assuntos
Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/terapia , Cistectomia , Humanos , Excisão de Linfonodo , Oncologia/tendências , Medição de Risco , Fatores de Risco , Neoplasias da Bexiga Urinária/etiologiaRESUMO
The development of normal and abnormal glandular structures in the prostate is controlled at the endocrine and paracrine levels by reciprocal interactions between epithelium and stroma. To study these processes, it is useful to have an efficient method of tissue acquisition for reproducible isolation of cells from defined histologies. Here we assessed the utility of a standardized system for acquisition and growth of prostatic cells from different regions of the prostate with different pathologies, and we compared the abilities of stromal cells from normal peripheral zone, benign prostatic hyperplasia (BPH-S), and cancer to induce the growth of a human prostatic epithelial cell line (BPH-1) in vivo. Using the tissue recombination method, we showed that grafting stromal cells (from any histology) alone or BPH-1 epithelial cells alone produced no visible grafts. Recombining stromal cells from normal peripheral zone with BPH-1 cells also produced no visible grafts (n = 15). Recombining BPH-S with BPH-1 cells generated small, well-organized, and sharply demarcated grafts approximately 3-4 mm in diameter (n = 9), demonstrating a moderate inductive ability of BPH-S. Recombining stromal cells from cancer with BPH-1 cells generated highly disorganized grafts that completely surrounded the host kidney and invaded into adjacent renal tissue, demonstrating induction of an aggressive phenotype. We conclude that acquisition of tissue from toluidine blue dye-stained specimens is an efficient method to generate high-quality epithelial and/or stromal cultures. Stromal cells derived by this method from areas of BPH and cancer induce epithelial cell growth in vivo, which mimics the natural history of these diseases.
Assuntos
Comunicação Celular , Endocrinologia/métodos , Próstata/patologia , Hiperplasia Prostática/fisiopatologia , Neoplasias da Próstata/fisiopatologia , Manejo de Espécimes/métodos , Células Estromais , Divisão Celular , Linhagem Celular , Corantes , Células Epiteliais/patologia , Humanos , Masculino , Hiperplasia Prostática/patologia , Neoplasias da Próstata/patologia , Cloreto de TolônioRESUMO
Because patients with hormone-refractory prostate carcinoma are a very diverse group, management of these patients represents a unique challenge. Despite much research, to the authors' knowledge few studies published to date have provided definitive treatment answers. The Society of Urologic Oncology (SUO) convened a multidisciplinary panel of urologists, oncologists, and radiation oncologists to develop a treatment algorithm for patients with hormone-refractory prostate carcinoma. The resulting treatment outline was based on a review of the literature review and on the expert opinions of the panelists. The current article provided a logical progression of treatment choices that included hormonal manipulations, chemotherapeutic options, and adjunctive therapies. Future clinical trials and therapies were also discussed by the authors. Management strategies should be targeted toward the individual patient. Although significant progress has been made in understanding and treating hormone-refractory prostate carcinoma, earlier interventions would be ideal and better therapeutic approaches to prolong survival are necessary.
Assuntos
Algoritmos , Antineoplásicos Hormonais/farmacologia , Antineoplásicos Hormonais/uso terapêutico , Carcinoma/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Carcinoma/patologia , Ensaios Clínicos como Assunto , Resistencia a Medicamentos Antineoplásicos , Humanos , Masculino , Cuidados Paliativos , Neoplasias da Próstata/patologia , Sociedades MédicasRESUMO
Neuroblastoma is extremely rare in adults. Advances in classification and therapy have been recently made by an analysis of pediatric tumors. We present the case of a 39-year-old man who had Stage 1 neuroblastoma with unfavorable histologic features that was treated with surgery only. Neuroblastoma should be considered as a diagnosis for adult patients with a suprarenal mass and, if confirmed, neuroblastoma in adults should be classified and treated according to pediatric guidelines.
Assuntos
Neoplasias das Glândulas Suprarrenais , Neuroblastoma , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia , Adulto , Humanos , Rim , Masculino , Neuroblastoma/patologia , Neuroblastoma/cirurgiaRESUMO
The ADP-ribosyltransferase (ADPRT) gene encodes a zinc-finger DNA-binding protein, poly(ADP-ribose) polymerase-1 (PARP-1), that modifies various nuclear proteins by poly(ADP-ribosyl)ation and functions as a key enzyme in the base excision repair pathway. We have conducted two studies to test whether an amino acid substitution variant, ADPRT V762A (T2444C), is associated with prostate cancer (CaP) risk and decreased enzyme function. The first study used genomic DNA samples from an ongoing, clinic-based case-control study (488 cases and 524 controls) to show that a higher percentage of the CaP cases carried the ADPRT 762 AA genotype than controls (4% versus 2%). In Caucasians, the AA genotype was significantly associated with increased CaP risk [odds ratio (OR), 2.65; 95% confidence interval (CI), 1.08-6.49], and the VA genotype was associated with a slight but not significantly increased CaP risk (OR, 1.18; 95% CI, 0.85-1.64) using VV as the referent group after adjustment for age, benign prostatic hyperplasia, and family history. Furthermore, this association was stronger in younger (<65) men (OR, 4.77; 95% CI, 1.01-22.44) than older (> or =65) men (OR, 1.78; 95% CI, 0.55-5.82). The second study used freshly isolated peripheral lymphocytes from 354 cancer-free subjects to demonstrate that the ADPRT 762 A allele contributed to significantly lower adenosine diphosphate ribosyl transferase (ADPRT)/PARP-1 activities in response to H2O2 in a gene dosage-dependent manner (P < 0.0001, test for linear trend). The PARP-1 activities (mean +/- SD dpm/10(6) cells) were 18,554 +/- 9,070 (n=257), 14,847 +/- 7,082 (n=86), and 12,155 +/- 6,334 (n=11) for VV, VA, and AA genotypes, respectively. This study is the first to provide evidence that the ADPRT V762A-genetic variant contributes to CaP susceptibility and altered ADPRT/PARP-1 enzyme function in response to oxidative damage.
Assuntos
ADP Ribose Transferases/genética , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/genética , ADP Ribose Transferases/deficiência , ADP Ribose Transferases/metabolismo , Idoso , Estudos de Casos e Controles , Predisposição Genética para Doença , Variação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Poli(ADP-Ribose) Polimerases/genéticaRESUMO
OBJECTIVES: To evaluate the utility of routine intraoperative frozen-section histologic analysis during partial nephrectomy to ensure negative surgical margins. Partial nephrectomy has gained acceptance for surgical treatment of small renal cancers. Many surgeons send specimens for intraoperative frozen section histologic analysis to ensure negative margins. METHODS: We reviewed the records of 78 patients who underwent partial nephrectomy for presumed malignancy. Patient demographics, intraoperative findings, and pathologic and clinical outcomes were analyzed. RESULTS: Seventy-nine partial nephrectomies were performed in 78 patients. Frozen sections were obtained intraoperatively in 76 cases. In 1 case (1.3%), a single margin was interpreted as positive for carcinoma, prompting deeper resection. The final histopathologic finding was interpreted as angiomyolipoma rather than carcinoma. The final pathologic examination revealed renal cell carcinoma in 52 (66%) of 79 cases. The mean oncologic follow-up was 16.2 months. One local recurrence was noted (1.9%). It arose in the resection bed 19 months after removal of a 4.5-cm tumor (pathologic Stage T3a). Both intraoperative frozen section margins and final pathologic margins were negative in this case. One patient developed pulmonary metastases and represented the only metastatic recurrence, as well as the only cancer-related death in our cohort (1.9%). CONCLUSIONS: Our data suggest that when partial nephrectomy is performed with attention to excising a perimeter of grossly normal-appearing parenchyma, sending specimens for intraoperative frozen section analyses may provide an unnecessary expense without providing meaningful, reliable information. Additional studies, including larger cohorts and extended follow-up, are needed to support these results.