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Jean-Jacques Patard

Publications and source records attributed to Jean-Jacques Patard.

At least 19 recordsLinked to original sources
PubMed2006

Renal cell carcinoma with nodal metastases in the absence of distant metastatic disease: prognostic indicators of disease-specific survival.

OBJECTIVES: Outcome of patients with exclusive renal cell carcinoma (RCC) nodal metastases without distant metastases is not extensively described. We explored the ability of standard risk factors such as tumour size, Fuhrman grade, histologic subtype and symptom classification to predict renal cell carcinoma-specific survival (RCC-SS). METHODS: Analyses targeted 171 patients with RCC nodal metastases and absence of distant metastases. Univariable, multivariable, and predictive accuracy analyses addressed RCC-SS with the intent of identifying independent and most informative predictors of RCC-SS in this cohort of patients. RESULTS: Median RCC-SS was 2.3 yr. Symptom classification (61.3%, p<0.001) demonstrated the highest univariable accuracy. In multivariable analyses, symptom classification contributed the most to the combined predictive accuracy of all variables (+4.2%, p<0.001), followed by Fuhrman grade (+2.3%) and histologic subtype (+1.0%). CONCLUSIONS: Renal cell carcinoma-specific survival of patients with exclusive nodal metastases may show important variability. In presence of systemic symptoms, survival is extremely poor. Substantially better survival may be expected in patients with local or no symptoms. This observation has important implications when adjuvant therapies are considered.

Adolescent↗
PubMed2006

Relationship between age at diagnosis and clinicopathologic features of renal cell carcinoma.

OBJECTIVES: To analyse the influence of age at diagnosis on tumour characteristics and cancer-specific survival in renal cell carcinoma (RCC). METHODS: Data on age, tumour characteristics, and survival for 4774 patients from 12 European RCC databases were recorded. Patients were divided into four groups according to age at diagnosis: < or =40, >40 and <60, > or =60 and <80, and > or =80 yr. The following variables were analysed: TNM stage, Fuhrman grade, tumour size, symptoms at diagnosis, ECOG performance status (PS), and cancer-specific survival. The groups were compared for usual clinical and pathologic variables, and cancer-specific survival. RESULTS: The four groups accounted for 288 (6%), 1839 (38.5%), 2499 (52.3%), and 148 cases (3.2%), respectively. Differences were found among groups for tumour stage, symptoms at diagnosis, ECOG PS, Fuhrman grade (p<0.001), tumour size, M stage, and histologic subtype (p: 0.02). Patients < or =40 yr were more likely to have papillary or chromophobe RCCs and less likely to have clear-cell RCCs. No significant difference was found among groups for N stage (p: 0.15). The 5-yr cancer-specific survival rates for the four age categories were 85%, 74%, 70%, and 69%, respectively. In multivariate analysis age category remained an independent prognostic parameter (p<0.001). CONCLUSIONS: Renal tumours diagnosed in younger age are characterized by lower tumour stages and grades as well as favourable histologic patterns compared with tumours in older patients. Basic research is required for explaining such a relationship between age, tumour aggressiveness, and therefore tumour biology.

Adult↗
PubMed2006

Sensitivity of prostate cells to TRAIL-induced apoptosis increases with tumor progression: DR5 and caspase 8 are key players.

BACKGROUND: As advanced prostate cancers are resistant to currently available chemotherapies, we evaluated the cytotoxic effect of TNF-related apoptosis-inducing ligand (TRAIL) and characterized the involvement of its five receptors DR4, DR5, DcR1, DcR2, and osteoprotegerin (OPG) and of the death-inducing signaling complex (DISC)-forming proteins caspase 8 and c-FLIP in prostate cell lines. METHODS: We used six prostate cell lines, each corresponding to a particular stage in prostate tumorigenesis, and analyzed TRAIL sensitivity in relation to TRAIL receptors' expression. RESULTS: TRAIL sensitivity was correlated with tumor progression and DR5 expression levels and apoptosis was exclusively mediated by DR5. DcR2 was significantly more abundant in tumor cells than in non-neoplastic ones and may contribute to partial resistance to TRAIL in some prostate tumor cells. Conversely, non-tumoral cells secreted high levels of OPG, which can protect them from apoptosis. Finally, caspase 8 expression levels were as DR5 directly correlated to TRAIL sensitivity in prostate tumor cells. CONCLUSION: TRAIL-induced apoptosis is closely related to the balanced expression of its different receptors in prostate cancer cells and their modulation could be of potential clinical value for advanced tumor treatment.

Androgens↗
PubMed2006

Tumor size improves the accuracy of TNM predictions in patients with renal cancer.

OBJECTIVES: Current staging for renal cancer (RC) does not directly rely on tumor size. We examined the increment in accuracy related to inclusion of pathologically determined tumor size in prediction of nodal metastases (N+), distant metastases (M+), and cancer-specific survival (CSS). METHODS: Partial or radical nephrectomy was performed in 2245 patients with clear cell histology. Pathologic stages were T1a in 566, T1b in 490, T2 in 303, T3 in 831, and T4 in 55 patients. Tumor size was 0.5-25 cm (mean, 6.8). Multivariate models relied on 1997 and 2002 TNM variables and addressed N+, M+ disease, and CCS. Their accuracy was compared according to either the presence or absence of tumor size. RESULTS: In all univariate and multivariate models, tumor size was a statistically significant predictor of all outcomes (p< or =0.001). In all multivariate models, tumor size added between 3.7% and 0.8% to predictive accuracy of either 1997 or 2002 TNM categories. CONCLUSIONS: Tumor size represents a highly significant, multivariate, and informative predictor of RC outcomes and may warrant inclusion in future TNM revisions.

Carcinoma, Renal Cell↗
PubMed2006

Understanding the importance of smart drugs in renal cell carcinoma.

OBJECTIVE: To understand the mode of action of the currently most investigated new drugs in renal cell carcinoma (RCC) and ultimately to analyze what should be the role of the urologist in this new therapeutic era. METHODS: A comprehensive review of the peer-reviewed literature was performed on the topic of molecular pathways involved in RCC angiogenesis, vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (VEGFR) and targeted molecular therapy for RCC. RESULTS: Von Hippel-Lindau (VHL) disease has provided a model for understanding that the early inactivation of the VHL gene was responsible for accumulation of hypoxia-inducible factor and therefore activation of hypoxia-inducible genes such as VEGF, platelet-derived growth factor, erythropoietin, carbonic anhydrase IX and tumor growth factor alpha. The fact that such VHL inactivation also was found in up to 70% of sporadic RCC has been the rationale for developing new drugs targeting VEGF, VEGFR, platelet-derived growth factor receptor and tyrosine kinase receptors that are required for intracellular transduction. CONCLUSION: Initial results from phase 2 trials in metastatic disease are very promising. There is a strong rationale for initiating adjuvant trials with those kind of agents in patients with high-risk localised tumors. Urologists who have a good understanding of prognostic parameters in localised RCC particularly should be involved in such new approaches.

Angiogenesis Inhibitors↗
PubMed2006

Prognostic value of thrombocytosis in renal cell carcinoma.

PURPOSE: We correlated platelet count to renal tumor characteristics, and evaluated the potential prognostic value of thrombocytosis in localized and metastatic tumors. MATERIALS AND METHODS: A total of 804 patients operated on for a renal tumor in 2 French centers were included in this study. In all cases TNM stage, Fuhrman grade, tumor size, nodal invasion, ECOG score, histological subtype and platelet count were recorded. Survival estimates were compared with the Kaplan-Meier method and multivariate analysis was performed using a Cox model. RESULTS: There were 538 (66.9%) males and 266 (33%) females (ratio 2.02) in the patient group. Median age was 62 years. T stages were T1, T2, T3 and T4 in 284 (35.3%), 116 (14.4%), 387 (48.1%) and 17 (2.1%), respectively. There were 112 (13.9%) and 126 (15.7%) patients with nodal and metastatic invasion, respectively. Platelet count was strongly correlated with T stage (p < 0.001), Fuhrman grade (p < 0.001), tumor size (p < 0.001), nodal invasion (p < 0.001) and the presence of distant metastasis (p = 0.01). In univariate analysis all studied factors were significantly predictive of survival (p = 0.0001). Thrombocytosis had an impact on prognosis in localized (p < 0.001) and metastatic (p = 0.003) disease. Several factors were retained in multivariate analysis, namely TNM stage, Fuhrman grade, tumor size, ECOG score and platelet count. In cases with a platelet count of less than 450,000/mm3, the 5-year survival rate was 70%, compared to 38% when the platelet count was 450,000/mm3 or greater. CONCLUSIONS: Platelet count appears to be an independent prognostic factor in renal cell carcinoma. It reflects a cascade of biological events correlated with tumor aggressiveness. This observation opens new perspectives for exploring carcinogenesis mechanisms and tumor progression in renal cell carcinoma.

Aged↗
PubMed2006

Spherical harmonics based intrasubject 3-D kidney modeling/registration technique applied on partial information.

This paper presents a three-dimensional (3-D) shape reconstruction/intrapatient rigid registration technique used to establish a Nephron-Sparing Surgery preoperative planning. The usual preoperative imaging system is the Spiral CT Urography, which provides successive 3-D acquisitions of complementary information on kidney anatomy. Because the kidney is difficult to demarcate from the liver or from the spleen only limited information on its volume or surface is available. In this paper, we propose a methodology allowing a global kidney spatial representation on a spherical harmonics basis. The spherical harmonics are exploited to recover the kidney 3-D shape and also to perform intrapatient 3-D rigid registration. An evaluation performed on synthetic data showed that this technique presented lower performance then expected for the 3-D shape recovering but exhibited registration results slightly more accurate as the iterative closest point technique with faster computation time.

Algorithms↗
PubMed2006

Laparoscopic management of a transitional cell carcinoma arising in a right ectopic ureter.

Ectopic ureter is a rare abnormality, so presenting a transitional cell carcinoma (TCC) arising from an ectopic ureter is extremely rare. We report here a case of a man with an invasive transitional cell carcinoma arising from a right ectopic ureter and managed by laparoscopy. To our knowledge, this is the fourth case described in the literature, and the second case of a TCC arising in a right ectopic ureter.

Carcinoma, Transitional Cell↗
PubMed2006

Susceptibility of human testis to human immunodeficiency virus-1 infection in situ and in vitro.

Semen represents the main vector for human immunodeficiency virus (HIV) dissemination worldwide and has been shown to harbor replication-competent virus despite otherwise effective highly active anti-retroviral therapy, which achieves undetectable viral load in plasma. Despite this, the origin of seminal HIV particles remains unclear, as does the question of whether the male genital tract organs contribute virus to semen. Here we investigated the presence of HIV receptors within the human testis using immunohistochemistry and quantitative real-time polymerase chain reaction. We also analyzed the infectivity of a dual tropic HIV-1 strain in an organotypic culture, as well as the impact of viral exposure on testosterone production. Our study establishes that CXCR4+, CCR5+, CD4+, and DC-SIGN+ cells are present within the interstitial tissue of human testis and that these molecules persist throughout our organotypic culture. Our data also reveal that the human testis is permissive to HIV-1 and supports productive infection, leaving testosterone production apparently unaffected. Infected cells appeared to be testicular macrophages located within the interstitial tissue. That the testis itself represents a potential source of virus in semen could play a role in preventing viral eradication from semen because this organ constitutes a pharmacological sanctuary for many current antiretrovirals.

DNA, Viral↗
PubMed2005

Proposal for revision of the TNM classification system for renal cell carcinoma.

BACKGROUND: The current study defined an optimal tumor size breakpoint to stratify localized renal cell carcinoma (RCC) into groups with significantly different cancer-related outcomes and proposed a revision of the TNM classification system. METHODS: The authors analyzed the data from 1138 patients who had undergone partial or radical nephrectomy for localized RCC at 7 European urologic centers. The optimal pathologic size breakpoint was calculated using the martingale residuals from a Cox proportional hazards regression model. RESULTS: The mean follow-up time was 87 months. The scatterplot of tumor size versus expected risk of death per patient suggested that an interval of 5-6 cm was appropriate. A total of 720 (63.3%) and 418 (36.7%) patients had tumors measuring < or = 5.5-cm and tumors measuring > 5.5-cm, respectively. Significant cancer-specific survival differences between the two groups of patients were reported in the series by all the centers participating in the study. On univariate analysis, the other variables found to be associated with cancer-specific survival were the patient's age, symptomatic tumor presentation, and the Fuhrman nuclear grade. On multivariate analysis, the pathologic stage of the primary tumor defined according to the 5.5-cm breakpoint was found to be an independent predictor of cancer-specific survival, as well as age, mode of presentation, and nuclear grade. According to the multivariate analysis, the authors clustered patients into 3 groups with statistically significant outcome differences: 1) patients with < or = 5.5-cm incidentally detected RCC; 2) patients with < or = 5.5-cm symptomatic RCC; and 3) patients with > 5.5-cm RCC. This cancer-related outcome stratification was valid regardless of the patient's age. CONCLUSIONS: The 5.5-cm breakpoint was found to be the optimal tumor size breakpoint with which to stratify patients with organ-confined RCC. The study supported the upgrade of the TNM classification system according to this breakpoint.

Adolescent↗
PubMed2005

Comparison of predictive accuracy of four prognostic models for nonmetastatic renal cell carcinoma after nephrectomy: a multicenter European study.

BACKGROUND: The objective of the current study was to compare, in a large multicenter study, the discriminating accuracy of four prognostic models developed to predict the survival of patients undergoing nephrectomy for nonmetastatic renal cell carcinoma (RCC). METHODS: A total of 2404 records of patients from 6 European centers were retrospectively reviewed. For each patient, prognostic scores were calculated according to four models: the Kattan model, the University of California at Los Angeles integrated staging system (UISS) model, the Yaycioglu model, and the Cindolo model. Survival curves were estimated by the Kaplan-Meier method and compared by the log-rank test. Discriminating ability was assessed by the Harrell c-index for censored data. The primary end point was overall survival (OS), and the secondary end points were cancer-specific survival (CSS) and disease recurrence-free survival (RFS). RESULTS: At last follow-up, 541 subjects had died of any causes, with a 5-year OS rate of 80%. The 5-year CSS and RFS rates were 85% and 78%, respectively. All models discriminated well (P < 0.0001). The c-indexes for OS were 0.706 for the Kattan nomogram, 0.683 for the UISS model, and 0.589 and 0.615 for the Yaycioglu and Cindolo models, respectively. The Kattan nomogram was found to improve discrimination substantially in the UISS intermediate-risk patients. CONCLUSIONS: The current study appears to better define the general applicability of prognostic models for predicting survival in patients with nonmetastatic RCC treated with nephrectomy. The results suggest that postoperative models discriminate substantially better than preoperative ones. The Kattan model was consistently found to be the most accurate, although the UISS model was only slightly less well performing. The Kattan model can be useful in the UISS intermediate-risk patients.

Adolescent↗
PubMed2005

Multiinstitutional European validation of the 2002 TNM staging system in conventional and papillary localized renal cell carcinoma.

BACKGROUND: The current study validated the 2002 edition of the TNM staging system in a multicenter, multinational European series of localized renal cell carcinoma (RCC). METHODS: The authors analyzed the clinical data of 2217 patients who had undergone radical or partial nephrectomy for localized RCC in 7 urologic centers. RESULTS: In the current study, 1065 patients (48%) were classified as having pT1a disease, 771 (34.8%) were classified as having pT1b disease, and 381 (17.2%) were classified as having pT2 disease. Tumor histotype was conventional RCC in 1886 patients (85%), papillary in 182 (8.2%) patients, chromophobe in 64 (2.9%) patients, and unclassified in 85 (3.8%) patients. The mean follow-up time was 65.36 +/- 52.09 months. The 5 and 10-year disease-specific survival probabilities were 95.3% and 91.4% in patients with pT1a disease, 91.4% and 83.4% in patients with pT1b disease, and 81.6% and 75.2% in patients with pT2 disease (log-rank test P value = 0.0000). The disease-specific survival rates of patients with pT1a RCC were significantly higher than those recorded in patients with pT1b and pT2 RCC. Similarly, the disease-specific survival probabilities of patients with pT1b RCC were significantly better than those of patients with pT2 RCC. Analyzing the seven series individually, the 2002 TNM staging system provided appropriate stratification for only one series. The 2002 TNM staging system allowed significant stratification of the cancer-related outcomes in the subgroup of patients with conventional RCC but not in those with papillary carcinomas. CONCLUSIONS: The application of the 2002 TNM staging system in the current multicenter series enabled the authors to demonstrate optimal stratification of patients with localized RCC. Stratifying by tumor histotype, the data coming from the whole group analysis were reconfirmed for clear cell RCC only.

Adolescent↗
PubMed2005

Prognostic value of histologic subtypes in renal cell carcinoma: a multicenter experience.

PURPOSE: To analyze to what extent histologic subtype is of prognostic importance in renal cell carcinoma based on a large, international, multicenter experience. PATIENTS AND METHODS: Four thousand sixty-three patients from eight international centers were included in this retrospective study. Histologic subtype (1997 International Union Against Cancer [UICC] criteria of tumor response), age, sex, TNM stage, Fuhrman grade, tumor size, Eastern Cooperative Oncology Goup performance status (ECOG PS), and overall survival were determined in all cases. The prognostic values of clear cell, papillary, and chromophobe histologic features were assessed by uni- and multivariate analysis using the Kaplan-Meier method and Cox model, respectively. RESULTS: Clear cell, papillary, and chromophobe carcinomas accounted for 3,564 (87.7%), 396 (9.7%) and 103 (2.5%) cases, respectively. In univariate analysis, a trend toward a better survival was observed when clear cell, papillary, and chromophobe histologies were considered prognostic categories (log-rank P = .0007). However, in multivariate analysis, TNM stage, Fuhrman grade and ECOG PS, but not histology, were retained as independent prognostic variables (P < .001). CONCLUSION: The stratification in three main renal cell carcinoma histologic subtypes as defined by the 1997 UICC-American Joint Committee on Cancer consensus should not be considered a major prognostic variable comparable to TNM stage, Fuhrman grade and ECOG PS.

Adolescent↗
PubMed2005

Dendritic cells are defective in breast cancer patients: a potential role for polyamine in this immunodeficiency.

INTRODUCTION: Dendritic cells (DCs) are antigen-presenting cells that are currently employed in cancer clinical trials. However, it is not clear whether their ability to induce tumour-specific immune responses when they are isolated from cancer patients is reduced relative to their ability in vivo. We determined the phenotype and functional activity of DCs from cancer patients and investigated the effect of putrescine, a polyamine molecule that is released in large amounts by cancer cells and has been implicated in metastatic invasion, on DCs. METHODS: The IL-4/GM-CSF (granulocyte-macrophage colony-stimulating factor) procedure for culturing blood monocyte-derived DCs was applied to cells from healthy donors and patients (17 with breast, 7 with colorectal and 10 with renal cell carcinoma). The same peroxide-treated tumour cells (M74 cell line) were used for DC pulsing. We investigated the effects of stimulation of autologous lymphocytes by DCs pulsed with treated tumour cells (DC-Tu), and cytolytic activity of T cells was determined in the same target cells. RESULTS: Certain differences were observed between donors and breast cancer patients. The yield of DCs was dramatically weaker, and expression of MHC class II was lower and the percentage of HLA-DR-Lin- cells higher in patients. Whatever combination of maturating agents was used, expression of markers of mature DCs was significantly lower in patients. Also, DCs from patients exhibited reduced ability to stimulate cytotoxic T lymphocytes. After DC-Tu stimulation, specific cytolytic activity was enhanced by up to 40% when DCs were from donors but only up to 10% when they were from patients. IFN-gamma production was repeatedly found to be enhanced in donors but not in patients. By adding putrescine to DCs from donors, it was possible to enhance the HLA-DR-Lin- cell percentage and to reduce the final cytolytic activity of lymphocytes after DC-Tu stimulation, mimicking defective DC function. These putrescine-induced deficiencies were reversed by treating DCs with all-trans retinoic acid. CONCLUSION: These data are consistent with blockade of antigen-presenting cells at an early stage of differentiation in patients with breast cancer. Putrescine released in the microenvironmement of DCs could be involved in this blockade. Use of all-trans retinoic acid treatment to reverse this blockade and favour ex vivo expansion of antigen-specific T lymphocytes is of real interest.

Aged↗