Biomedical subjects

Hervé Lang

Publications and source records attributed to Hervé Lang.

10 recordsLinked to original sources

PubMed2006

MR Imaging of papillary renal neoplasms: potential application for characterization of small renal masses.

The purpose of our study was to evaluate the role of MRI in demonstrating the precise nature of papillary renal tumors (P RCC) and its potential application to select patients for partial surgery. Ninety-seven tumors less than or equal to 3 cm in size [55 papillary renal cell carcinoma - 42 clear cell renal carcinoma (CC RCC)] were preoperatively evaluated by MRI. Imaging findings were assessed with a special focus on the aspect of the tumoral process. Correlations were performed with pathologic staging after surgery. At pathology, 92 tumors were established to be staged p T1 and 5 were p T3 ( 3 cases of CC RCC and 2 cases of P RCC). Ninety-four percent of papillary tumors exhibited low signal intensity with homogeneous pattern on T2-weighted images. All clear cell carcinoma were hyperintense and heterogeneous on T2-weighted sequence. Enhancement was lower and delayed in the papillary type in comparison with the clear cell type. MRI is accurate enough to predict the 'histologic' nature of papillary renal carcinoma. It is an additional argument to propose that the tumor can be removed by partial surgery.

Adult↗

PubMed2006

The phosphoinositide 3-kinase/Akt pathway: a new target in human renal cell carcinoma therapy.

Metastatic renal cell carcinoma is resistant to current therapies. The phosphoinositide 3-kinase (PI3K)/Akt signaling cascade induces cell growth, cell transformation, and neovascularization. We evaluated whether targeting this pathway could be of therapeutic value against human renal cell carcinoma. The activation of the PI3K/Akt pathway and its role in renal cell carcinoma progression was evaluated in vitro in seven human cell lines by Western blot, cell counting, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, terminal deoxyribonucleotide transferase-mediated nick-end labeling assays, and fluorescence-activated cell sorting analysis, using two PI3K inhibitors, LY294002 and wortmannin, as well as by transfection with various Akt constructs and through Akt knockdown by small interfering RNA (siRNA). In vivo nude mice bearing human renal cell carcinoma tumor xenografts were treated with LY294002 (75 mg/kg/wk, 4 weeks, i.p.). Tumor growth was measured and tumors were subjected to Western blot and immunohistochemical analysis. Akt was constitutively activated in all cell lines. Constitutive phosphorylation of glycogen synthase kinase-3 (GSK-3) was observed in all cell lines, whereas forkhead transcription factor and mammalian target of rapamycin, although expressed, were not constitutively phosphorylated. Exposure to LY294002 or wortmannin decreased Akt activation and GSK-3 phosphorylation and reduced cell growth by up to 70% through induction of cell apoptosis. These effects were confirmed by transfection experiments with Akt constructs or Akt siRNA. Importantly, LY294002 induced up to 50% tumor regression in mice through tumor cell apoptosis. Tumor neovascularization was significantly increased by LY294002 treatment. Blood chemistries showed no adverse effects of the treatment. Our results suggest an important role of PI3K/Akt inhibitors as a potentially useful treatment for patients with renal cell carcinoma.

Animals↗

PubMed2006

[Reproducibility of Fuhrman nuclear grade: advantages of a two-grade system].

The Fuhrman nuclear grade is the reference histoprognostic grading system routinely used all over the world for renal cell carcinoma. Studies measuring the inter-observer and intra-observer concordance of Fuhrman grade show poor results in terms of reproducibility and repeatability. These variations are due to a certain degree of subjectivity of the pathologist in application of the definition of tumour grade, particularly nuclear grade. Elements able to account for this subjectivity in renal cell carcinoma are identified from a review of the literature. To improve the reliability of nuclear grade, the territory occupied by the highest grade must be specified and the grades should probably be combined. At the present time, regrouping of grade 1 and 2 tumours as low grade and grade 3 and 4 tumours as high grade would achieve better reproducibility, while preserving the prognostic: value for overall survival. The development of new treatment modalities and their use in adjuvant situations will imply the use of reliable histoprognostic factors to specify, indications.

Carcinoma, Renal Cell↗

PubMed2006

[Value of urinary microsatellite analysis in the diagnosis of renal cancer].

OBJECTIVE: To detect the presence of tumour DNA in urine of patients with renal cancer based on microsatellite analysis. MATERIAL AND METHOD: Blinded, comparative, experimental study conducted between July 1996 and December 2003. Preoperative urine and blood samples were collected from 69 patients with renal cancer (pT1 to pT4). The control population comprised 35 patients with a benign urological disease. Loss of heterozygosity (LOH) and allele amplification were investigated by analysing allele imbalances between urinary DNA and blood lymphocyte DNA. Twenty-six loci were analysed, including 23 microsatellites. We studied the sensitivity and specificity of this analysis as a function of stage, grade and invasion of renal cavities by the tumour. RESULTS: The sensitivity of the test was 61% for pT1a and the global sensitivity was 62.3%. A significant difference was observed in favour of low nuclear grades (p < 0.05). More than 80% of tumours detected were identified by 4 microsatellites. The specificity was 83%. Renal cavities were invaded by the tumour in 38% of cases. No correlation was observed between invasion of renal cavities and the result of the test. CONCLUSION: The results are encouraging, particularly for small tumours and justify development of clinical applications.

Adult↗

PubMed2005

Antitumor effect of parathyroid hormone-related protein neutralizing antibody in human renal cell carcinoma in vitro and in vivo.

Functional inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene occurs in 40-80% of human conventional renal cell carcinomas (RCCs). We showed recently that VHL-deficient RCCs expressed large amounts of parathyroid hormone-related protein (PTHrP), and that PTHrP, acting through the PTH1 receptor (PTH1R), plays an essential role in tumor growth. We also showed that PTHrP expression is negatively regulated by the VHL gene products (pVHL). Our goal was to determine whether blocking the PTHrP/PTH1R system might be of therapeutic value against RCC, independent of VHL status and PTHrP expression levels. The antitumor activity of PTHrP neutralizing antibody and of PTH1R antagonist were evaluated in vitro and in vivo in a panel of human RCC lines expressing or not pVHL. PTHrP is upregulated compared with normal tubular cells. In vitro, tumor cell growth and viability was decreased by up to 80% by the antibody in all cell lines. These effects resulted from apoptosis. Exogenously added PTHrP had no effect on cell growth and viability, but reversed the inhibitory effects of the antibody. The growth inhibition was reproduced by a specific PTH1R antagonist in all cell lines. In vivo, the treatment of nude mice bearing the Caki-1 RCC tumor with the PTHrP antibody inhibited tumor growth by 80%, by inducing apoptosis. Proliferation and neovascularization were not affected by the antiserum. Anti-PTHrP treatment induced no side effects as assessed by animal weight and blood chemistries. Current therapeutic strategies are only marginally effective against metastatic RCC, and adverse effects are common. This study provides a rationale for evaluating the blockade of PTHrP signaling as therapy for human RCC in a clinical setting.

Animals↗

PubMed2005

Multicenter determination of optimal interobserver agreement using the Fuhrman grading system for renal cell carcinoma: Assessment of 241 patients with > 15-year follow-up.

BACKGROUND: The Fuhrman system is the most widely used nuclear grading system for renal cell carcinoma (RCC). Although Fuhrman nuclear grade is widely accepted as a significant prognostic factor, its reproducibility, as reported in the limited number of series available in the literature, appears to be low. METHODS: Between 1980 and 1990, 255 cases of RCC (pT1-3bN0M0) were treated with radical nephrectomy at the Department of Urology, University Hospital, Strasbourg, France. In a retrospective multicenter study, 3 pathologists independently classified 241 of these 255 cases according to the Fuhrman grading system. The authors searched for optimal interobserver agreement by collapsing the grading system to a three-tiered scheme and then to a two-tiered scheme. In addition, overall survival curves were generated according to the classic four-tiered scheme and also according to the best collapsed scheme. The kappa index was used to assess the level of agreement between each pair of observers, and the Cox model was used for multivariate survival analyses. RESULTS: The mean interobserver kappa value was 0.22 (range, 0.09-0.36). The best concordance was obtained by collapsing to a system in which low-grade (Grade 1-2) disease was compared with high-grade (Grade 3-4) disease. Doing so improved the mean interobserver kappa value to 0.44 (range, 0.32-0.55). Fuhrman grade was an independent prognostic factor for all 3 pathologists (P = 0.01, P < 0.0001, and P = 0.004, respectively), and nuclear grade continued to have independent prognostic value after the optimal collapsing algorithm was performed (P = 0.004, P = 0.0003, and P = 0.005). CONCLUSIONS: Collapsing of the Fuhrman grading system to a two-tiered scheme led to an improvement in interobserver agreement while preserving the independent prognostic value of nuclear grade.

Adult↗

PubMed2004

Prognostic value of multifocality on progression and survival in localized renal cell carcinoma.

OBJECTIVE: Incidence of multifocality in Renal Cell Carcinoma (RCC) is estimated at between 5 and 25%. Multifocality has been largely studied because of the growing interest in conservative surgery which is a risk of local recurrence. The aim of this study is to evaluate the relationship between multifocality and other prognostic parameters and whether it is an independent prognostic factor. MATERIAL AND METHODS: From 1980 to 1990, 255 patients (median age: 60.9 years) were treated by radical nephrectomy for pT1 to pT3b N0M0 RCC. The median follow-up time was 183 months. Multifocality was defined as the existence of at least one other tumoral localization, macroscopically and microscopically diagnosed as renal cell carcinoma, in the same kidney. Studied parameters were: age, sex, side, size, stage, Fuhrman's grade, capsular invasion, renal vein involvement and microvascular invasion. Survival was assessed with Kaplan-Meier and Cox models. RESULTS: 37 cases of multifocal RCC were diagnosed (14.5%). There was only a significant correlation with stage (p=0.002) and with capsular invasion (p=0.002). No other factor was correlated with multifocality. It had no influence on the risk of metastatic progression, overall or specific survival. CONCLUSION: There is a significant correlation between capsular invasion and multifocality that has to be considered before proposing conservative surgery for a localized RCC. Multifocality has no influence on survival or metastatic progression in case of radical nephrectomy.

Adolescent↗

PubMed2004

Prognostic value of microscopic venous invasion in renal cell carcinoma: long-term follow-up.

OBJECTIVE: To assess the prognostic value of microscopic venous invasion (MVI) in a long-term follow-up series. PATIENTS AND METHOD: 255 patients had a radical nephrectomy between 1980 and 1990 for pT1 to pT3b N0 M0 renal cell carcinoma. We reviewed the disease free, specific and overall survival after 183 months of median follow-up. Survival analyses using Kaplan-Meier and Log-rank models for univariate comparisons and Cox proportional hazards model for multivariate analyses were performed. The studied variables were: age, size, side, extracapsular invasion, renal vein invasion, local stage, Fuhrman's grade and MVI. RESULTS: MVI was found in 74 cases (29%). The MVI was strongly correlated to metastases appearance and survival (p < 0.0001). Multivariate analysis of disease free survival showed the following independent variables: size (p < 0.0001) and Fuhrman's grade (p < 0.0001). For cancer specific survival, the analysis found size (p < 0.0001), age (p = 0.0005), Fuhrman's grade (p = 0.0035) and MVI (p = 0.016) with a relative risk of cancer related death of 2.16. Independent prognostic factors of overall survival were age (p < 0.0001), size (p < 0.0001), MVI (p = 0.015) and Fuhrman's grade (p = 0.045). The relative risk of cancer related death for MVI is 1.82. CONCLUSION: It seems that MVI is an independent prognostic factor of survival for patients with pT1 to pT3b N0 M0 renal cell carcinoma.

Adolescent↗

PubMed2004

[Kidney tumors].

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Humans↗

PubMed2003

[Extended total nephrectomy with laparoscopy in localized renal carcinoma. Report of 25 cases compared with 32 conventional surgical cases].

STUDY OBJECTIVE: To evaluate the benefits obtained during the learning phase of laparoscopic nephrectomy (LN) for clinical stage cT1 and cT2 renal cancers. PATIENTS AND METHODS: We retrospectively compared our first 25 cases of LN (13 right, 12 left) with 32 nephrectomies performed by Conventional Surgery (CS) (17 right, 15 left) between May 2000 and December 2001. The LN group comprised 18 men and 7 women with a mean age of 63.8 years. The CS group comprised 18 men and 14 women with a mean age of 67.7 years. Preoperative, intraoperative, postoperative and histological parameters were compared by analysis of the variance or nonparametric Mann-Whitney U test for quantitative variables and Chi-square test for qualitative data. RESULTS: Preoperative and histological parameters, blood loss, quantity and duration of analgesics and the complication rate were similar in the two groups. Resection was complete in every case. The mean duration of radical nephrectomy was significantly shorter by CS (p < 0.001). Return of bowel sounds was more rapid (p = 0.002) and patients were discharged from hospital earlier (p = 0.004) after LN. CONCLUSION: Laparoscopic nephrectomy for cancer must be performed by an operator experienced in laparoscopy. During the learning phase, this procedure provided benefits in terms of return of bowel sounds and length of hospital stay, which should encourage teams performing laparoscopy to perform radical nephrectomy by laparoscopy.

Adult↗