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Background: Adjuvant sunitinib has significantly improved disease-free survival versus placebo in patients with renal cell carcinoma at high risk of recurrence post-nephrectomy (hazard ratio 0.76; 95% confidence interval, 0.59-0.98; two-sided P = 0.03). We report safety, therapy management, and patient-reported outcomes for patients receiving sunitinib and placebo in the S-TRAC trial. Patients and methods: Patients were stratified by the University of California, Los Angeles Integrated Staging System and Eastern Cooperative Oncology Group performance status score, and randomized (1 : 1) to receive sunitinib (50 mg/day) or placebo. Single dose reductions to 37.5 mg, dose delays, and dose interruptions were used to manage adverse events (AEs). Patients' health-related quality of life, including key symptoms typically associated with sunitinib, were evaluated with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Results: Patients maintained treatment for 9.5 (mean, SD 4.4) and 10.3 (mean, SD 3.7) months in the sunitinib and placebo arms, respectively. In the sunitinib arm, key AEs occurred â¼1 month (median) after start of treatment and resolved within â¼3.5 weeks (median). Many (40.6%) AEs leading to permanent discontinuation were grade 1/2, and most (87.2%) resolved or were resolving by 28 days after last treatment. Patients taking sunitinib showed a significantly lower EORTC QLQ-C30 overall health status score versus placebo, although this reduction was not clinically meaningful. Patients reported symptoms typically related to sunitinib treatment with diarrhea and loss of appetite showing clinically meaningful increases. Conclusions: In S-TRAC, AEs were predictable, manageable, and reversible via dose interruptions, dose reductions, and/or standard supportive medical therapy. Patients on sunitinib did report increased symptoms and reduced HRQoL, but these changes were generally not clinically meaningful, apart from appetite loss and diarrhea, and were expected in the context of known sunitinib effects. Clinical trial registration: ClinicalTrials.gov, NCT00375674.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Sunitinibe/uso terapêutico , Carcinoma de Células Renais/patologia , Quimioterapia Adjuvante , Gerenciamento Clínico , Método Duplo-Cego , Seguimentos , Humanos , Agências Internacionais , Neoplasias Renais/patologia , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Prospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Preclinical studies showing that pomegranate juice and its components inhibit prostate cancer led to multiple clinical trials to determine whether pomegranate products could slow the growth of prostate cancer. This review summarizes the preclinical data and discusses the results of the clinical trials. METHODS: Trials targeted patients on active surveillance, neoadjuvant patients, patients with biochemical recurrence (BCR) following local therapy for prostate cancer, and patients with metastatic castration-resistant prostate cancer (mCRPC). RESULTS: In the BCR patient population, early phase II trials of both pomegranate juice and extract showed significant lengthening of PSA doubling time (PSADT), and confirmed the safety of pomegranate products. While a placebo-controlled phase III trial determined that pomegranate extract did not significantly prolong PSADT in BCR patients, a preplanned subset analysis of patients with the manganese superoxide dismutase (MnSOD) AA genotype showed greater PSADT lengthening on the pomegranate extract arm. In the neoadjuvant population, a large trial demonstrated a significant increase in urolithin A and a non-significant reduction in 8-hydroxy-2-deoxyguanosine, a marker of oxidation in prostate cancer tissue, on the pomegranate arm vs the placebo arm. In addition, a randomized clinical trial of a polyphenol-rich multicomponent food supplement that included a 31.25% pomegranate extract found significant slowing of PSA increase in the food supplement arm vs placebo in men on active surveillance and those experiencing BCR. CONCLUSIONS: Pomegranate juice and extract are safe but did not significantly improve outcomes in BCR patients in a large placebo-controlled trial. However a subset of BCR patients with the MnSOD AA genotype appear to respond positively to the antioxidant effects of pomegranate treatment. Phase II trials of 100% pomegranate products in neoadjuvant patients and patients with mCRPC were negative. A multicomponent food supplement showed promising results in a phase II study in active surveillance and BCR patients.
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Calicreínas/sangue , Lythraceae , Extratos Vegetais/administração & dosagem , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/dietoterapia , Sucos de Frutas e Vegetais , Humanos , Masculino , Neoplasias da Próstata/sangue , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: The primary objective of this study was to compare the effects of pomegranate juice on PSA doubling times (PSADT) in subjects with rising PSA levels after primary therapy for prostate cancer. METHODS: Double-blind, placebo-controlled multi-institutional study, evaluated the effects of pomegranate liquid extract on serum PSA levels. The primary end point of this study was change in serum PSADT. Additional secondary and exploratory objectives were to evaluate the safety of pomegranate juice and to determine the interaction of manganese superoxide dismutase (MnSOD) AA genotype and pomegranate treatment on PSADT. RESULTS: One-hundred eighty-three eligible subjects were randomly assigned to the active and placebo groups with a ratio of 2:1 (extract N=102; placebo N=64; juice N=17). The majority of adverse events were of moderate or mild grade. Median PSADT increased from 11.1 months at baseline to 15.6 months in the placebo group (P<0.001) compared with an increase from 12.9 months at baseline to 14.5 months in the extract group (P=0.13) and an increase from 12.7 at baseline to 20.3 in the juice group (P=0.004). However, none of these changes were statistically significant between the three groups (P>0.05). Placebo AA patients experienced a 1.8 month change in median PSADT from 10.9 months at baseline to 12.7 months (P=0.22), while extract patients experienced a 12 month change in median PSADT from 13.6 at baseline to 25.6 months (P=0.03). CONCLUSIONS: Compared with placebo, pomegranate extract did not significantly prolong PSADT in prostate cancer patients with rising PSA after primary therapy. A significant prolongation in PSADT was observed in both the treatment and placebo arms. Men with the MnSOD AA genotype may represent a group that is more sensitive to the antiproliferative effects of pomegranate on PSADT; however, this finding requires prospective hypothesis testing and validation.
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Antineoplásicos Fitogênicos/uso terapêutico , Lythraceae/química , Extratos Vegetais/uso terapêutico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/tratamento farmacológico , Idoso , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/efeitos adversos , Terapia Combinada , Progressão da Doença , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Extratos Vegetais/administração & dosagem , Extratos Vegetais/efeitos adversos , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Superóxido Dismutase/genética , Resultado do TratamentoRESUMO
Multiple strands of research provide growing evidence that diet, nutrition, and life style play a role in the development and the course of urological diseases. Numerous micronutrients and polyphenols found in soy, green tea, and many fruits and vegetables have been described to impact diseases including erectile dysfunction, benign prostatic hyperplasia, and prostate cancer. However, oftentimes these reports lack both a scientific rationale and supportive evidence base. The efficacy of pomegranate, on the other hand, in the modulation of central biological processes like inflammation, hypoxia, and oxidative stress that are important in the pathogenesis of urological maladies has been robustly demonstrated in preclinical in vitro and in vivo studies. Moreover, clinical trials have further supported its use in the treatment of several diseases, in particular in the management of prostate cancer. Herein, we critically review the scientific knowledge about the current role and future prospects for the use of pomegranate extracts in the therapy of erectile dysfunction, benign prostatic hyperplasia, and prostate cancer.
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INTRODUCTION: Robotic assistance during laparoscopic surgery for pelvic organ prolapse rapidly disseminated across the United States without level I data to support its benefit over traditional open and laparoscopic approaches [1]. This manuscript describes design and methodology of the Abdominal Colpopexy: Comparison of Endoscopic Surgical Strategies (ACCESS) Trial. METHODS: ACCESS is a randomized comparative effectiveness trial enrolling patients at two academic teaching facilities, UCLA (Los Angeles, CA) and Loyola University (Chicago, IL). The primary aim is to compare costs of robotic assisted versus pure laparoscopic abdominal sacrocolpopexy (RASC vs LASC). Following a clinical decision for minimally-invasive abdominal sacrocolpopexy (ASC) and research consent, participants with symptomatic stage≥II pelvic organ prolapse are randomized to LASC or RASC on the day of surgery. Costs of care are based on each patient's billing record and equipment costs at each hospital. All costs associated with surgical procedure including costs for robot and initial hospitalization and any re-hospitalization in the first 6weeks are compared between groups. Secondary outcomes include post-operative pain, anatomic outcomes, symptom severity and quality of life, and adverse events. Power calculation determined that 32 women in each arm would provide 95% power to detect a $2500 difference in total charges, using a two-sided two sample t-test with a significance level of 0.05. RESULTS: Enrollment was completed in May 2011. The 12-month follow-up was completed in May 2012. CONCLUSIONS: This is a multi-center study to assess cost as a primary outcome in a comparative effectiveness trial of LASC versus RASC.
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Colposcopia/métodos , Pesquisa Comparativa da Efetividade/métodos , Laparoscopia/métodos , Robótica/métodos , Prolapso Uterino/cirurgia , Colposcopia/economia , Análise Custo-Benefício , Feminino , Humanos , Laparoscopia/economia , Estudos Multicêntricos como Assunto/métodos , Complicações Pós-Operatórias , Anos de Vida Ajustados por Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Robótica/economia , Método Simples-CegoRESUMO
PURPOSE: Our objective was to compare oncologic results of nephron sparing surgery (NSS) versus radical nephrectomy (RN) in T1aN0-x M0 papillary renal cell carcinoma (PRCC). PATIENTS AND METHODS: We retrospectively reviewed 277 patients treated for a pT1aN0M0 PRCC selected from an academic database from 12 centres. We compared the clinico-pathological features by using Chi-square and Student statistical analyses. Survivals analyses using Kaplan-Meier and Log-rank models were performed. RESULTS: The two groups were composed by 186 patients treated by NSS and 91 by RN. The TNM stage was fixed and the two groups were, in terms of age and Fuhrman grade, comparable. Median age at diagnosis was 59 years (27-85). Median tumor size was 2.7 cm (0.4-4). The average follow-up was 49 months (1-246). Very few events arose in both groups: two local recurrences were observed in the NSS group (1.07%), three patients died of cancer in the NSS treated group (1.6%) and five in the RN treated group (5.5%). The five and 10 cancer-specific survival rate were comparable in the two groups (98% vs. 100% and 98% vs. 97%). The specific survival curves were perfectly similar for both groups (log rank test, p=0.25). CONCLUSION: NSS is equivalent to RN as far as oncologic control of pT1aN0M0 PRCC is concerned.
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Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Nefrectomia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos RetrospectivosRESUMO
PURPOSE: TG4010 is a recombinant MVA vector expressing the tumor-associated antigen MUC1 and IL2. We explored the effect two schedules of TG4010 on PSA in men with PSA progression. PATIENTS AND METHODS: A randomized phase II trial was conducted in 40 patients with PSA progression. Patients had PSA doubling times less than 10 months, with no overt evidence of disease. Patients received either weekly subcutaneous injection (sc) of TG4010 10(8) pfu for 6 weeks, then one injection every 3 weeks or sc injection of TG4010 10(8) pfu every 3 weeks. RESULTS: The primary endpoint of a 50% decrease in PSA values from baseline was not observed. Nevertheless, 13 of 40 patients had a more than two fold improvement in PSA doubling time. Ten patients had their PSA stabilized for over 8 months. Therapy was well tolerated. CONCLUSIONS: Although the primary endpoint was not achieved, there is evidence of biologic activity of TG4010 in patients with PSA progression, further investigation in prostate cancer is warranted.
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Vacinas Anticâncer/uso terapêutico , Glicoproteínas de Membrana/uso terapêutico , Antígeno Prostático Específico/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Idoso , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/efeitos adversos , Progressão da Doença , Esquema de Medicação , Humanos , Imunoterapia/métodos , Injeções Subcutâneas , Interleucina-2/imunologia , Masculino , Glicoproteínas de Membrana/administração & dosagem , Glicoproteínas de Membrana/efeitos adversos , Pessoa de Meia-Idade , Mucina-1/imunologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/imunologia , Fatores de Tempo , Resultado do TratamentoRESUMO
Interleukin-2 (IL-2) remains the mainstay of treatment for metastatic renal cell carcinoma (RCC), but minimally invasive surgical techniques have provided new options for the combined treatment of RCC. Two patients with metastatic RCC to the head and neck treated by combined laser-induced thermal therapy and IL-2 were described in this case report. Both patients had an extended survival compared to the historical survival of 10 months for metastatic RCC but eventually succumbed to progressive disease. The authors' initial experience with metastatic RCC suggests that laser thermoablation and immunotherapy in selected patients with metastatic RCC is warranted as a palliative treatment, but a larger study with long-term follow-up is necessary to determine the effectiveness of this approach.
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Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/terapia , Neoplasias de Cabeça e Pescoço/secundário , Neoplasias de Cabeça e Pescoço/terapia , Interleucina-2/uso terapêutico , Neoplasias Renais/patologia , Terapia a Laser/métodos , Cuidados Paliativos/métodos , Carcinoma de Células Renais/imunologia , Terapia Combinada , Evolução Fatal , Feminino , Neoplasias de Cabeça e Pescoço/imunologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The impact of the fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism on bladder cancer is unknown. We found no clear correlations between the FGFR4 genotype and risk of bladder cancer or pathological parameters. Neither the polymorphism nor TP53 mutation status was an independent predictor of prognosis, but they might act jointly on the disease-specific survival of patients.
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Genes p53/genética , Polimorfismo de Nucleotídeo Único/genética , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/mortalidade , Idoso , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Análise de Sobrevida , Taxa de SobrevidaRESUMO
OBJECTIVES: To describe a new surgical approach to third-generation cryoablation of the prostate and present our preliminary results. METHODS: The technique is detailed and demonstrated in a Web-based video- clip tutorial. Ninety-two men underwent prostate cryoablation (71 primary ablations, 19 salvage procedures, and 2 repeated cryoablations), using direct transperineal placement of ultrathin probes through a 17-gauge brachytherapy template. RESULTS: No fistulous or major complications were observed. Eight patients (8.3%) had minor complications. In 36 patients, the follow-up period was long enough to permit nadir prostate-specific antigen (PSA) evaluation. In 31 (86%), the nadir PSA was 0.5 ng/mL or less. In 5 patients, the nadir PSA was greater than 0.5 ng/mL. The workup revealed systemic failure in 3 patients and inadequate eradication of the prostate gland in 2 patients. In 18 (86%) of 21 androgen-ablation-naive patients, the nadir PSA was 0.5 ng/mL or less. Nine (43%) had an undetectable nadir PSA and 3 had a nadir PSA of greater than 0.5 ng/mL. CONCLUSIONS: A modified, less-invasive approach to cryoablation of the prostate is presented. The preliminary results do not show an increased rate of complications compared with other published series. The clinical outcome data are preliminary. Longer follow-up data are required to draw conclusions concerning efficacy.
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Criocirurgia/métodos , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/instrumentação , Criocirurgia/efeitos adversos , Criocirurgia/instrumentação , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Prostatectomia/efeitos adversos , Prostatectomia/instrumentação , Neoplasias da Próstata/sangue , Estudos RetrospectivosRESUMO
Immunotherapy targeting for the induction of a T-cell-mediated antitumor response in patients with renal cell carcinoma (RCC) appears to hold significant promise. Here we describe a novel RCC vaccine strategy that allows for the concomitant delivery of dual immune activators: G250, a widely expressed RCC associated antigen; and granulocyte/macrophage-colony stimulating factor (GM-CSF), an immunomodulatory factor for antigen-presenting cells. The G250-GM-CSF fusion gene was constructed and expressed in Sf9 cells using a baculovirus expression vector system. The Mr 66,000 fusion protein (FP) was subsequently purified through a 6xHis-Ni2+-NTA affinity column and SP Sepharose/fast protein liquid chromatography. The purified FP retains GM-CSF bioactivity, which is comparable, on a molar basis, to that of recombinant GM-CSF when tested in a GM-CSF-dependent cell line. When combined with interleukin 4 (IL-4; 1000 units/ml), FP (0.34 microg/ml) induces differentiation of monocytes (CD14+) into dendritic cells (DCs) expressing surface markers characteristic for antigen-presenting cells. Up-regulation of mature DCs (CD83+CD19-; 17% versus 6%) with enhanced expression of HLA class I and class II antigens was detected in FP-cultured DCs as compared with DCs cultured with recombinant GM-CSF. Treatment of peripheral blood mononuclear cells (PBMCs) with FP alone (2.7 microg/10(7) cells) augments both T-cell helper 1 (Th1) and Th2 cytokine mRNA expression (IL-2, IL-4, GM-CSF, IFN-gamma, and tumor necrosis factor-alpha). Comparison of various immune manipulation strategies in parallel, bulk PBMCs treated with FP (0.34 microg/ml) plus IL-4 (1000 units/ml) for 1 week and restimulated weekly with FP plus IL-2 (20 IU/ml) induced maximal growth expansion of active T cells expressing the T-cell receptor and specific anti-RCC cytotoxicity, which could be blocked by the addition of anti-HLA class I, anti-CD3, or anti-CD8 antibodies. In one tested patient, an augmented cytotoxicity against lymph node-derived RCC target was determined as compared with that against primary tumor targets, which corresponded to an 8-fold higher G250 mRNA expression in lymph node tumor as compared with primary tumor. The replacement of FP with recombinant GM-CSF as an immunostimulant completely abrogated the selection of RCC-specific killer cells in peripheral blood mononuclear cell cultures. All FP-modulated peripheral blood mononuclear cell cultures with antitumor activity showed an up-regulated CD3+CD4+ cell population. These results suggest that GM-CSF-G250 FP is a potent immunostimulant with the capacity for activating immunomodulatory DCs and inducing a T-helper cell-supported, G250-targeted, and CD8+-mediated antitumor response. These findings may have important implications for the use of GM-CSF-G250 FP as a tumor vaccine for the treatment of patients with advanced kidney cancer.
Assuntos
Antígenos de Neoplasias/imunologia , Carcinoma de Células Renais/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Neoplasias Renais/imunologia , Proteínas Recombinantes de Fusão/imunologia , Linfócitos T Citotóxicos/imunologia , Animais , Apresentação de Antígeno/imunologia , Antígenos de Neoplasias/genética , Baculoviridae/genética , Vacinas Anticâncer/genética , Vacinas Anticâncer/imunologia , Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/terapia , Citocinas/biossíntese , Citocinas/genética , Células Dendríticas/citologia , Células Dendríticas/imunologia , Regulação Neoplásica da Expressão Gênica , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Humanos , Neoplasias Renais/sangue , Neoplasias Renais/terapia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Proteínas Recombinantes de Fusão/genética , Spodoptera/virologia , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologiaRESUMO
PURPOSE: Our understanding of the natural history of renal cell carcinoma, the role of nephrectomy, the benefits of immunotherapy and the possibilities of new technologies are evolving and being integrated with advances in classification and staging. We reviewed the relevant literature to clarify these pertinent questions and provide a current review of the changes in the epidemiology, treatment and prognosis of patients with renal cell carcinoma. MATERIALS AND METHODS: We comprehensively reviewed the peer reviewed literature on the current management of and results of treatment for renal cell carcinoma. RESULTS: The incidence of and mortality from renal cell carcinoma have continuously increased during the last 50 years. Despite this increase in the number of new patients and consequently the number of deaths yearly the percent of those surviving for 5 years has notably improved. Factors related to improved survival include advances in renal imaging, earlier diagnosis, improved staging, better understanding of prognostic indicators, refinement in surgical technique and the introduction of immunotherapy approaches for advanced disease. CONCLUSIONS: Currently patients with localized and metastatic renal cell carcinoma have had improvements in outlook and the therapeutic options available have expanded.
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Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/epidemiologia , Carcinoma de Células Renais/fisiopatologia , Progressão da Doença , Humanos , Imunoterapia , Incidência , Neoplasias Renais/diagnóstico , Neoplasias Renais/epidemiologia , Neoplasias Renais/fisiopatologia , Metástase Neoplásica , Estadiamento de Neoplasias , Nefrectomia , Prognóstico , Análise de SobrevidaAssuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Estadiamento de Neoplasias/métodos , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/cirurgia , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/cirurgia , Los Angeles/epidemiologia , Reprodutibilidade dos Testes , Taxa de SobrevidaRESUMO
PURPOSE: We provide an overview of advances in molecular based therapeutic strategies for prostate cancer and summarize the studies presented at the Society of Urologic Oncology Biotechnology Forum in 2000. MATERIALS AND METHODS: Three promising new treatment strategies are presented, and a critique of the advantages and limitations of each is offered by a leading expert in the field. RESULTS: Treatment results and the current state of dendritic cell based immunotherapy, monoclonal antibody therapy and anti-apoptotic treatment approaches are presented. CONCLUSIONS: Currently patients with advanced prostate carcinoma have expanded therapeutic options available in the form of molecular based phases II and III clinical trials.
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Neoplasias da Próstata/terapia , Anticorpos Monoclonais/uso terapêutico , Apoptose , Ensaios Clínicos como Assunto , Células Dendríticas , Humanos , Imunoterapia/métodos , Masculino , Estadiamento de Neoplasias , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/patologiaRESUMO
Conventional therapy for metastatic renal cell carcinoma is associated with a poor response rate and few patients are long-term survivors. The occurrence of spontaneous regression and the prolonged latency period between primary tumor removal and the appearance of metastases in some patients suggest the existence of important host immune responses to autologous tumor cells. With the advent of molecular gene transfer techniques and increased knowledge of the basic pathways of immune activation, the field of cancer immunotherapy has finally begun to develop novel and effective approaches for harnessing the immune system as a therapeutic agent. Current immunotherapy and gene therapy strategies, including methods of cytokine delivery and tumor-cell-based vaccines, are presented.
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Carcinoma de Células Renais/terapia , Terapia Genética , Imunoterapia , Neoplasias Renais/terapia , Vacinas Anticâncer , HumanosRESUMO
PURPOSE: We analyzed the effects of the change in TNM classification from the 1987 to the 1997 version and suggest a modified tumor size cutoff point between T stages 1 and 2 for renal cell carcinoma. MATERIALS AND METHODS: We evaluated a database containing the records of 661 patients who underwent nephrectomy between 1989 and 1999. The effect of the change in TNM classification on the distribution of patients between stages, the rates of M+ and N+ disease, and the local and distant recurrence rates were outlined for 280 patients with T stages 1 and 2 disease. The Cox model was used to identify the optimal cutoff point between T1 and T2 disease, and the resulting effect of adopting this cutoff was outlined. RESULTS: A total of 174 and 128 cases were down staged from 1987 version stage T2 to 1997 version stage T1 and from 1987 TNM stage II to 1997 TNM stage I, respectively. Survival was not significantly different in patients with 1997 TNM stages I and II disease due to a lack of survival difference during the first 2 years of followup. Stage shift also caused an increase in average tumor size, the proportion of patients with high grade cancer, and M+ and N+ disease at diagnosis in 1997 stages T1 and T2 as well as an increase in the proportion of 1997 stage T2N0M0 cases at diagnosis with systemic failure. Analysis of 11 potential cutoff points between 1 and 10 cm. revealed that 4.5 cm. was most predictive of patients survival (hazards ratio 4.99, p = 0.0001). Using this cutoff resulted in improved discriminatory power of the TNM classification and a moderating effect on the distribution of patients, average tumor size, high grade disease, M+ and N+ disease at diagnosis, and systemic failure between T(14.5) and T(24.5) compared with 1997 T1 and T2. CONCLUSIONS: Our data imply that the current cutoff point of 7 cm. between stages T1 and T2 tumors is too high. Lowering the cutoff to 4.5 cm. resulted in better discriminatory power of the TNM classification in our dataset. This observation should be further validated by external data.
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Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Estadiamento de Neoplasias/classificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/cirurgia , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Nefrectomia/métodos , Prognóstico , Sensibilidade e Especificidade , Análise de SobrevidaRESUMO
Twenty-four patients with locally advanced prostate cancer (CaP) were enrolled in a phase I clinical trial using gene-based immunotherapy. A functional DNA-lipid complex encoding the interleukin 2 (IL-2) gene (Leuvectin; Vical, San Diego, CA) was administered intraprostatically into the hypoecogenic tumor lesion, using transrectal ultrasound guidance. Two groups of patients having locally advanced tumors were enrolled to receive a treatment regimen composed of two serial intraprostatic injections of the IL-2 gene agent administered 1 week apart. The first groups of patients included radical prostatectomy candidates who subsequently underwent surgery after the completion of the treatment regimen. The second group consisted of patients who had failed a prior therapy. Prostate specimens of the treated areas were attained after treatment and compared with the transrectal biopsies performed at baseline to assess for any responses. IL-2 gene therapy was well tolerated, with no grade 3 or 4 toxic reactions occurring. The most commonly reported symptoms were mild hematuria, transient rectal bleeding, and perineal discomfort that are likely attributable to the injection itself. During the entire course of treatment, there were no significant changes in American Urologic Association (AUA) symptom scores, in hematologic disturbances, electrolyte imbalances, or hepatic functions. Evidence of systemic immune activation was observed after IL-2 gene therapy, based on an increase in the intensity of T cell infiltration seen on immunohistochemical analysis of tissue samples from the injected tumor sites, and based on increased proliferation rates of peripheral blood lymphocytes that were cocultured with patient serum collected after treatment. Furthermore, transient decreases in serum prostate-specific antigen (PSA) (responders) were seen in 16 of 24 patients (67%) on day 1. Fourteen of the patients persisted in this decrease to day 8 (58%). In eight patients the PSA level rose (nonresponders). More patients (9 to 10) in the group that failed prior therapy responded to the IL-2 gene injections (chi-square test, p = 0.04), and 6 of the 9 also had lower than baseline PSA levels at week 10 after treatment. To the best of our knowledge, this is the first clinical study of its kind aimed at exploring the role of IL-2-based gene therapy in CaP patients. This phase I trial demonstrated the safety of intraprostatic Leuvectin injection, with transient PSA-based responses seen after therapy.
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Terapia Genética/métodos , Interleucina-2/genética , Lipídeos/uso terapêutico , Plasmídeos/uso terapêutico , Neoplasias da Próstata/terapia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Divisão Celular , Separação Celular , Citometria de Fluxo , Terapia Genética/efeitos adversos , Humanos , Imuno-Histoquímica , Leucócitos Mononucleares/metabolismo , Lipídeos/efeitos adversos , Masculino , Fenótipo , Plasmídeos/efeitos adversos , Antígeno Prostático Específico/biossíntese , Neoplasias da Próstata/diagnóstico por imagem , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Linfócitos T/citologia , Linfócitos T/metabolismo , Fatores de Tempo , UltrassonografiaRESUMO
Blunt trauma to the penis is an uncommon injury in young children. We present two cases of blunt penile trauma secondary to mechanical compression from a toilet seat.
Assuntos
Algoritmos , Pênis/lesões , Pré-Escolar , Humanos , Masculino , Treinamento no Uso de Banheiro , Ferimentos e Lesões/terapiaRESUMO
Most of the open renal procedures have been duplicated or approximated by laparoscopy. Past concerns about increased operative time, cost, resection completeness, and port site metastases are being overruled or put into perspective as experience with laparoscopic radical nephrectomy (LRN) is gained: necessary skills can be acquired, operative times are approaching those for open procedure, and a 14% difference in cost is counterbalanced by reduced postoperative expenditures. Moreover, LRN is acknowledged by its quality-of-life advantages-reduced morbidity and improved cosmetic outcome. Disease-free rate with LRN at last follow-up is 100% for TNM stage I and 89% +/- 6.6 for stage II (1997 classification). Complications are acceptable with an 8% to 35% incidence of minor complications and a 3% to 19% incidence of severe complications. Conversion to an open procedure occurs in 0% to 10% of cases. The procedure's limitations and the appropriate criteria for patient selection are evident. The learning process is believed to last for approximately 20 procedures and patient selection is based on both clinical criteria and one's insight on his location on the learning curve. Therefore, LRN is becoming the treatment of choice for most TNM stages I and II renal tumors. Moreover, recent data advocating pre-immunotherapy nephrectomy in metastatic patients may permit laparoscopic nephrectomy to further benefit selected metastatic patients by potentially shortening the time interval from nephrectomy to immunotherapy and improving immune responsiveness.
Assuntos
Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Laparoscopia/métodos , Nefrectomia/métodos , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/patologiaRESUMO
Advances in our understanding of the pathogenesis, behavior, and importance of prognostic factors for renal cell carcinoma (RCC) have paved the way for increased sophistication in its classification and staging. In the past, lack of consistent classification and terminology for RCC histology and staging has complicated comparability of clinical studies looking at patient prognosis and response to treatment. In this review, the results of international consensus efforts to achieve uniform classification systems for RCC are outlined and some future directions are considered.