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Serge Koscielny

Publications and source records attributed to Serge Koscielny.

15 recordsLinked to original sources
PubMed2006

Prognostic value of angiogenesis evaluated with high-frequency and colour Doppler sonography for preoperative assessment of primary cutaneous melanomas: correlation with recurrence after a 5 year follow-up period.

OBJECTIVE: To study the value of high-frequency sonography (HFS) and colour Doppler sonography (CDS) in evaluating the 5 year metastatic potential of primary cutaneous melanomas (CM). MATERIALS AND METHODS: 111 CM were studied before surgical resection and 107 were depicted on HFS. The maximal HFS thickness was measured and compared with the Breslow thickness. A CDS study was performed in each tumour. RESULTS: HFS thickness ranged from 0.26 to 8.0 mm and Breslow thickness from 0.15 to 8.0 mm. HFS and Breslow thickness correlated strongly (r > 0.93). Intratumour vessels were depicted in 43 of the 107 CM, of which 40 were thicker than 2 mm. The median follow-up was 61 months and 27 patients developed relapses. In the univariate analyses, neovascularization visualized with CDS, sonographic thickness and the Breslow thickness were significantly linked to relapses (p < 0.0001), as were lymph node status and ulceration (p = 0.007 and 0.004). CONCLUSION: Vascularization was observed mainly in thick primary melanoma. A median follow-up of 5 years showed the prognostic value of angiogenesis evaluated by CDS.

Adult↗
PubMed2006

Modification of behavior with 50% nitrous oxide/oxygen conscious sedation over repeated visits for dental treatment a 3-year prospective study.

In various medical domains, inhalation of nitrous oxide (N2O) in oxygen (O2) is indicated to alleviate pain and anxiety during routine treatment. Repeat treatment may often be indicated. Little data are available, however, to evaluate the long-term efficacy and side effects of reiterated N2O/O2 sedation. The aim of this study was to compare behavior during dental treatment under a premix of 50% N2O/O2 between first experience and repeat experiences of sedation in a cohort of uncooperative patients. Five hundred forty-three patients (age range, 1-94 years; mean, 17 +/- 16 years) experiencing conscious sedation for dental treatment for the first time were recruited at a special care unit during 3 years. A modified Venham scale was used to evaluate patient behavior at 5 steps during each session. Completion of planned treatment and occurrence of adverse side effects of sedation were additional criteria. Patients experienced sedation for the first time for 378 sessions, and the session was a repeat experience in 843 cases (number of visits: range, 1-6). Patient cooperation significantly improved during visits at first contact with the dentist and when applying the mask (P < 0.0001, between sessions 1 and 2). Between the first and the third sessions, the percentage of very uncooperative patients decreased from 23% to 3.7% at first contact with the dentist and from 22.3% to 8.5% on application of the mask. Experience of reiterated dental treatment under sedation with 50% N2O/O2 premix helps uncooperative patients to cope with dental treatment in the long term.

Adolescent↗
PubMed2005

False discovery rate, sensitivity and sample size for microarray studies.

MOTIVATION: In microarray data studies most researchers are keenly aware of the potentially high rate of false positives and the need to control it. One key statistical shift is the move away from the well-known P-value to false discovery rate (FDR). Less discussion perhaps has been spent on the sensitivity or the associated false negative rate (FNR). The purpose of this paper is to explain in simple ways why the shift from P-value to FDR for statistical assessment of microarray data is necessary, to elucidate the determining factors of FDR and, for a two-sample comparative study, to discuss its control via sample size at the design stage. RESULTS: We use a mixture model, involving differentially expressed (DE) and non-DE genes, that captures the most common problem of finding DE genes. Factors determining FDR are (1) the proportion of truly differentially expressed genes, (2) the distribution of the true differences, (3) measurement variability and (4) sample size. Many current small microarray studies are plagued with large FDR, but controlling FDR alone can lead to unacceptably large FNR. In evaluating a design of a microarray study, sensitivity or FNR curves should be computed routinely together with FDR curves. Under certain assumptions, the FDR and FNR curves coincide, thus simplifying the choice of sample size for controlling the FDR and FNR jointly.

Algorithms↗
PubMed2005

Phase II study of concomitant chemoradiotherapy in bulky refractory or chemoresistant relapsed lymphomas.

PURPOSE: To evaluate the local efficacy of concomitant chemoradiotherapy in patients with mostly refractory lymphoma. METHODS AND MATERIALS: Patients with refractory or chemoresistant-relapsed lymphoma and bulky life-threatening masses were included in this study. A split course of concomitant radiotherapy and chemotherapy (mostly cisplatin and etoposide) was delivered during a 6-week period. Weekly blood tests and a clinical examination using the Radiation Therapy Oncology Group guidelines were performed to assess acute toxicity. The tumor response was evaluated 1-3 months after treatment and at regular follow-up visits. RESULTS: We enrolled 21 patients in the study between January 1998 and April 2003. Of the 21 patients, 60% had disseminated disease with bulky tumor masses and 85% had refractory lymphoma, of which most had been treated with at least two different chemotherapy regimens before concomitant chemoradiotherapy. Seventy-five percent received regimens containing cisplatinum and etoposide. The median radiation dose was 40 Gy (range, 12-62.5 Gy). Grade 3-4 hematologic toxicity and mucositis was observed in 70% and 30% of cases respectively, without any deaths. The overall response and complete remission rate was 70% and 20%, respectively. The 1-year overall survival and local progression-free survival rate was 20.4% and 54%, respectively. Three patients with localized disease were still alive 16, 33, and 48 months after treatment. CONCLUSION: Concomitant chemoradiotherapy for refractory or chemoresistant-relapsed lymphoma induced high hematologic toxicity, but seemed adequate for controlling local bulky tumor masses. No toxicity-related death was observed.

Adult↗
PubMed2005

Decision making process in oncology practice: is the information available and what should it consist of?

In terms of systemic chemotherapy, the oncologist is often faced with the difficulty to discriminate between several options, at least according to evidence-based medicine. The aim of the present report was to assess to what extent the efficacy-related parameters required for the decision making process are reported in clinical trials. The analysis was restricted to lung, breast, colorectal and ovarian cancers. It included 135 phase II trials published in 1999, and 79 phase III trials published between 1991 and 2000. Response duration was mentioned in one-half and one-fourth of phases II and III trials, respectively. Only one-half of the trials reported time to progression (TTP). Finally, 28% of phase II and 44% of phase III trials reported RR, TTP and progression rates. The study indicates that the information available from reported clinical trials needs to be upgraded and homogenised in order to improve the decision making process in oncology.

Clinical Trials as Topic↗
PubMed2005

Results of two randomized trials evaluating adjuvant anthracycline-based chemotherapy in 1146 patients with early breast cancer.

Two randomized trials evaluated the effect of 6 courses of anthracycline-based chemotherapy in early breast cancer. A total of 1146 patients were included: 311 high-risk node-negative premenopausal patients and 835 high-risk node-negative or node-positive postmenopausal patients. Patients were randomized after surgery to receive either no chemotherapy (control group) or 6 courses of anthracycline-based chemotherapy (CT group). Postmenopausal patients received adjuvant tamoxifen for at least two years. Radiotherapy was delivered after completion of chemotherapy in the CT group. The 10-year disease-free survival (DFS) rates were 60% in the control group and 65% in the CT group (log-rank test, p = 0.01). The 10-year distant metastasis rates were 28% and 23% (p = 0.02), and the 10-year local recurrence rates were 12% and 10%, respectively (p = 0.24). Chemotherapy was significantly less effective in post-menopausal patients with estrogen receptor-positive tumors. Adjuvant anthracycline-based chemotherapy yielded a significant benefit for DFS by lowering the risk of distant metastases. After up to 10 years of follow-up, deferring radiotherapy after chemotherapy did not compromise local control.

Adult↗
PubMed2004

High level of glutathione-S-transferase pi expression in mantle cell lymphomas.

PURPOSE: Prognosis of mantle cell lymphoma (MCL) remains poor. Patients who achieve a response to first line therapy usually relapse, and the probability of cure remains low. Glutathione-S-transferase pi (GST-pi) overexpression has been associated with alkylating agents and anthracycline resistance. GST-pi gene is located in 11q13 and is coamplified along with CCND1 gene in some human solid tumors. EXPERIMENTAL DESIGN: We performed immunohistochemical analysis of GST-pi expression in 24 consecutive MCLs, 12 follicular lymphomas (FLs), and 69 diffuse large B-cell lymphomas (DLBCLs). Cases were classified in three groups: high GST-pi expression (> 50% of cells were stained), moderate (5 to 50% cells were stained), or absent (< 5% cells were stained). GST-pi and CCND1 mRNA levels were also assessed by real-time reverse transcription-PCR analysis. RESULTS: All MCLs exhibit high GST-pi protein expression, compared with 29% of the DLBCLs and none of the FLs. MCLs expressed high levels of GST-pi and CCND1 mRNAs compared with DLBCLs and FLs. There was a strong relation between GST-pi and CCND1 mRNAs transcript levels in MCLs but not in DLBCLs. In conclusion, protein and mRNA GST-pi expression is high in MCL compared with FL and DLBCL. CONCLUSIONS: Overexpression of CCND1 in MCL is associated with a transcriptional up-regulation of the GST-pi gene. Our results suggest that the glutathione system could play a role in drug resistance in MCL.

Adult↗
PubMed2004

Validation of a new method for quantifying in vivo murine tumor necrosis by sonography.

RATIONALE AND OBJECTIVES: At present, the gold standard to evaluate tumor necrosis is histology. We described here a new method to quantify the degree of tumor necrosis by ultrasonography. This technique combines ultrasound exploration of tissue and post-treatment of the numerical sequences using a dedicated software to evaluate backscattered power within the tumor. MATERIALS AND METHODS: In order to establish that the backscattered power could be considered as a relevant marker of tumor necrosis, we performed (1) intra- and interoperator reproducibility in estimation of tumor dimensions obtained on sonographic scans; and (2) intra- and interoperator reproducibility in quantification of backscattered power in postprocessing using the HDILab software. The third part of the study consisted of correlating the degree of tumor necrosis estimated by histology and the ultrasound backscattered power, both obtained on xenografted melanomas at different days after tumor transplantation. RESULTS: Results concerning tumor size estimations and quantification of echogenicity were reproducible (coefficient of variation < 4.33%). The degree of necrosis measured in histology and echogenicity were significantly negatively correlated (P < 0.003). CONCLUSION: In conclusion, backscattered power could be considered as a relevant parameter to quantify tumor necrosis in vivo.

Animals↗
PubMed2004

The efficacy of premixed nitrous oxide and oxygen for fiberoptic bronchoscopy in pediatric patients: a randomized, double-blind, controlled study.

STUDY OBJECTIVE: s: The aim of the study was to evaluate the efficacy and safety of premixed 50% nitrous oxide and oxygen on the quality of sedation and pain control during fiberoptic bronchoscopy (FB) in children. DESIGN: A prospective, randomized, double-blind study. SETTING: Pediatric pulmonary department in a pediatric tertiary university hospital. PATIENTS: One hundred five children aged 1 month to 18 years. INTERVENTIONS: Patients inhaled after sedation and local anesthesia either premixed 50% nitrous oxide and oxygen (nitrous oxide group) or premixed 50% nitrogen and oxygen (control group) during FB. MEASUREMENT AND RESULTS: The rate of failure was significantly greater in the control group (62%) than in the nitrous oxide group (21%, p = 0.00003). The efficacy of premixed 50% nitrous oxide and oxygen was also demonstrated with higher satisfaction scores (p = 0.000001), lower Children's Hospital of Eastern Ontario Pain Scores (p = 0.002), better visual analog scale ratings (p = 0.03), and improved behavior scores. Side effects were minor and similar in both groups. CONCLUSIONS: This study demonstrates the improved efficacy of sedation, pain control, and safety of premixed 50% nitrous oxide and oxygen for FB in children.

Adolescent↗
PubMed2003

High-frequency sonography and color Doppler in the management of pigmented skin lesions.

We aimed to evaluate high-frequency sonography (HFS) coupled with color Doppler in the management of pigmented skin lesions (PSL). HFS examination was performed in 111 patients with 130 PSL. A color Doppler study was conducted in 107 lesions, to assess intralesional vascularization. Imaging findings were compared with histologic diagnosis. In the case of melanoma, sonographic and histologic maximum thickness measurements were compared. HFS showed 114 of the 130 lesions. Among the detected lesions, HFS alone provided 100% sensitivity and 100% specificity in the distinction of melanoma/nevi from other lesions, and 100% sensitivity and 32% specificity in the distinction of melanomas from nonmelanoma lesions. Sonographic and histologic measurement of melanoma thickness strongly correlated (r > 0.96, p < 0.001). Color Doppler detection of intralesional vessels had a 100% specificity and 34% sensitivity in the distinction of melanomas from other PSL. HFS coupled with color Doppler is a simple, reliable tool for PSL management.

Adolescent↗
PubMed2003

Therapy-related myelodysplasia and/or acute myeloid leukaemia after autologous haematopoietic progenitor cell transplantation in a prospective single centre cohort of 221 patients.

To evaluate the incidence and the predictive signs of therapy-related myelodysplasia and/or acute myeloid leukaemia (tMDS/tAML), we undertook a prospective study over a 4-year period of 221 patients who underwent autologous haematopoietic progenitor cell transplantation. Only seven patients (3.1%) were identified to have tMDS/tAML. Peripheral cytopenia was the first sign; diagnosis could be achieved by cytological analysis of bone marrow smears using World Health Organization criteria. All patients presented with bi- or trilineage dysplasia. Haematopoietic reconstitution was significantly delayed in patients progressing to tMDS/tAML compared with the control group. Typical cytogenetic abnormalities were observed in five of seven patients. The mean time interval between transplantation and cytological diagnosis, or detection of cytogenetic abnormalities, was 20.0 months and 31.2 months respectively. Pantelomeric fluorescence analysis using quantitative fluorescence in situ hybridization enabled us to make two major observations: (i) the fluorescence intensity in metaphases of all autografted patients was weak, and highly variable between tMDS patients; (ii) a drastic reduction of the telomere fluorescence intensity was observed in two patients who rapidly evolved to acute leukaemia. In conclusion, early detection of tMDS/tAML could be achieved by close follow-up of the bone marrow repopulation, and confirmed by cytological bone marrow examination and cytogenetic study. Our results address the implication of several factors, such as the initial telomeric status, and the effect of cytogenetic abnormalities and clonal expansion on bone marrow repopulation.

Acute Disease↗
PubMed2002

Prognostic value of angiogenesis evaluated with high-frequency and color Doppler sonography for preoperative assessment of melanomas.

OBJECTIVE: The aim of our study was to confirm the value of high-frequency and color Doppler sonography in evaluating the metastatic potential of melanomas. SUBJECTS AND METHODS: Sixty-nine histologically proven melanomas in 67 patients were prospectively studied before surgical resection. A morphologic study was performed with a 20-MHz probe. The maximal thickness of tumors was measured and compared with the Breslow index. A color Doppler sonographic analysis of neovascularization was performed with a 13-MHz probe to depict intratumoral vessels. RESULTS: Of the 69 melanomas, 65 were depicted on sonography. Tumor thickness ranged from 0.26 to 8.0 mm as measured by sonography and from 0.15 to 8.0 mm according to the Breslow index. Sonographic measurements correlated strongly with the Breslow index (r > 0.96). Surgical reexcision was necessary in 33 tumors with a Breslow index exceeding 1 mm, but reexcision could have been avoided in 31 of these cases had the initial surgical planning been based on high-frequency sonographic measurements. Among the 62 patients studied with color Doppler sonography, intratumoral vessels were depicted on color Doppler sonography in 21 melanomas, all of which were thicker than 2 mm. The median follow-up was 40 months. Eleven patients developed metastases, and all except one had a vascularized melanoma. In the univariate analyses, neovascularization visualized with sonography and the Breslow index were both significantly linked to the occurrence of metastases (p < 0.0001). In the multivariate Cox proportional hazards regression analysis, neovascularization was the only significant parameter. CONCLUSION: This study confirms that prognostic value of angiogenesis evaluated with color Doppler sonography could be used to identify melanomas with a high metastatic potential.

Adult↗
PubMedDate not supplied

Prediction of cancer outcome with microarrays: a multiple random validation strategy.

BACKGROUND: General studies of microarray gene-expression profiling have been undertaken to predict cancer outcome. Knowledge of this gene-expression profile or molecular signature should improve treatment of patients by allowing treatment to be tailored to the severity of the disease. We reanalysed data from the seven largest published studies that have attempted to predict prognosis of cancer patients on the basis of DNA microarray analysis. METHODS: The standard strategy is to identify a molecular signature (ie, the subset of genes most differentially expressed in patients with different outcomes) in a training set of patients and to estimate the proportion of misclassifications with this signature on an independent validation set of patients. We expanded this strategy (based on unique training and validation sets) by using multiple random sets, to study the stability of the molecular signature and the proportion of misclassifications. FINDINGS: The list of genes identified as predictors of prognosis was highly unstable; molecular signatures strongly depended on the selection of patients in the training sets. For all but one study, the proportion misclassified decreased as the number of patients in the training set increased. Because of inadequate validation, our chosen studies published overoptimistic results compared with those from our own analyses. Five of the seven studies did not classify patients better than chance. INTERPRETATION: The prognostic value of published microarray results in cancer studies should be considered with caution. We advocate the use of validation by repeated random sampling.

Gene Expression Profiling↗