Catherine Mercier

Preoperative chemoradiation in potentially resectable pancreatic adenocarcinoma: feasibility, treatment effect evaluation and prognostic factors, analysis of the SFRO-FFCD 9704 trial and literature review

BACKGROUND We explored the feasibility and the histologic assessment of treatment effect of preoperative chemoradiation in patients presenting with resectable pancreatic adenocarcinoma. PATIENTS AND METHODS Treatment consisted of concurrent radiotherapy (50 Gy within 5 weeks) and chemotherapy with 5-fluorouracil (300 mg/m(2)/day, 5 days/week, weeks 1-5) and cisplatin (20 mg/m(2)/day, days 1-5 and 29-33), followed by surgical resection of the pancreatic tumor in patients without progression. RESULTS In all, 41 patients were enrolled; 38 (93%) received >or=47 Gy; 30 patients (73%) received >or=75% of the prescribed doses of chemotherapy. Among 40 assessable patients, 27 (67.5%; 95% confidence interval 50.9% to 81.4%) were successfully treated (entire dose of radiation, >or=75% of the chemotherapy dose, no grade 4 non-hematologic toxicity). In all, 26 patients (63%) underwent surgical resection with curative intent and 21 (80.7%) had R0 resection. A total of 13 of 26 specimens (50%) presented a major pathologic response (>or=80% of severely degenerative cancer cells), with one complete pathologic response. Operative mortality was 2.8%. The local recurrence and 2-year survival rates were 4% and 32%, respectively, for the 26 operated patients. CONCLUSIONS This proposed preoperative scheme is feasible, does not prevent successful surgery, and provides antitumoral effect associated with major histopathological response in 50% of patients and a high R0 resection rate.

Histopathological response to preoperative chemoradiation for resectable pancreatic adenocarcinoma: the French Phase II FFCD 9704-SFRO Trial.

Purpose:This study suggests that pancreatic adenocarcinoma is a chemoradiosensitive tumor and that preoperative chemoradiation provides antitumoral effect associated with major histopathological response in 50% of patients and a high R0 resection rate. Evaluation of histopathological response to neoadjuvant therapy may serve as a surrogate marker for treatment efficacy and remains an active area of investigation. Objectives:The chemoradiosensitivity of pancreatic adenocarcinoma has not yet fully been assessed. The purpose of this study is to determine the efficacy of preoperative chemoradiation, measured by the impact on the R0 resection rate and the histopathological response rate in patients presenting with resectable pancreatic adenocarcinoma. Methods:Patients with localized, potentially resectable pancreatic adenocarcinoma were treated with 50 Gy irradiation combined with 5-fluorouracil by continuous infusion (300 mg · m−2 · d−1; day 1–5; week 1–5) and cisplatin (20 mg · m−2 · d−1; day 1–5 and day 29–33). Patients presenting with resectable disease at restaging, without metastatic dissemination, underwent surgical resection. Results:Forty-one patients were enrolled. Twenty-seven patients (67.5%) completed chemoradiation receiving at least 75% prescribed chemotherapy dose without grade 4 nonhematological toxicity. Twenty-six patients (63%) underwent surgical resection with curative intent and 21 (80.7%) had R0 resection. Thirteen of 26 specimens (50%) presented a major pathologic response with more than 80% of severely degenerative cancer cells. Complete pathologic response was observed in one specimen. Median survival time and 2-year survival rate were 9.4 months and 20% for the entire cohort. The local recurrence and 2-year survival rates were 4% and 32%, respectively, for the 26 operated patients. Conclusions:This study suggests that some pancreatic adenocarcinomas are chemoradiosensitive and that preoperative chemoradiation provides antitumoral effect associated with major histopathological response in 50% of patients and a high R0 resection rate. Further research is needed to determine the biologic difference between responders and nonresponders, to evaluate the predictive value of treatment response parameters, and to optimize the chemoradiation regimen.

Recent Human Sexual Dimorphism Study Using Cephalometric Plots on Lateral Teleradiography and Discriminant Function Analysis

Abstract:  The examination of skull sexual dimorphism has been the subject of numerous morphologic and craniometric studies, but the disadvantage of these studies is that they are dependent on the experience of the operator and involve subjectivity. In 1996, a team from Taiwan refined the methods enabling the sex of an individual to be determined using cephalometric plots made from lateral teleradiography. To validate their work using a European population, 114 dry skulls (59 men and 55 women) were examined. Cephalometric plots were made on lateral teleradiography with an orthodontic software and 18 cephalometric variables were analyzed. Sex was determined with 95.6% accuracy using the 18 variables discriminant function. A subset of eight variables was selected and could predict sex with the same accuracy. In conclusion, it can be said that skull‐sexing methods using lateral teleradiography seem always suitable but the most indicative variables could differ relative to the ethnic population concerned.

Growth Hormone to Improve Short Bowel Syndrome Intestinal Autonomy A Pediatric Randomized Open-Label Clinical Trial

BACKGROUND The ability of growth hormone (GH) to promote the weaning-off of parenteral nutrition (PN) in short bowel syndrome (SBS) is unclear. No randomized controlled study is available in children. This study was undertaken to determine if GH could enhance the weaning off of PN in PN-dependent children with SBS. METHODS A prospective randomized open-label multicenter study was performed in 14 patients (mean age, 9 ± 1.4 years) with SBS (average small bowel length, 33 cm) and long-term PN dependency (8 years) on an unrestricted diet. A standardized PN decrease with and without GH (0.14 mg/kg/d) was conducted. The patients were randomized to either a GH group (4 months of GH) or a control (CTR) group (4 months without GH, followed by 4 months with GH). Blood tests and a nutrition assessment of enteral and parenteral intakes were performed. Groups were compared with the Wilcoxon test. RESULTS Treatment with GH did not improve the weaning off of PN (decrease in PN caloric intake of 32.5% ± 9.6% in the GH group vs 35.2% ± 8.7% in the CTR group, nonsignificant). In the CTR group, GH treatment induced an additional but not statistically significant decrease of 8.8% ± 12.4% in daily calories. Parenteral needs returned to near basal rates 6 months after GH discontinuation (GH: 77.6% ± 10.6% vs CTR: 73.2% ± 7.4%). Weight decreased slightly in both groups. No biological parameters varied significantly. CONCLUSIONS GH did not improve the weaning off of PN in PN-dependent children with SBS.

Efficacy of a home-based intervention programme on the physical activity level and functional ability of older people using domestic services: A randomised study

ObjectiveOur main objective was to assess whether a home-based program supervised by home helpers (HH) during their normal working hours can prevent excessive sedentariness (mainly maximum walking time and distance) and preserve functional status in elderly people at risk for frailty or disability and using domestic services.DesignA four-month, open label, randomised trial with two groups called “prevention” and “control”.SettingIn the homes of study participants.ParticipantsThe participants were all over 78 years old, lived independently at home, and received the visits of HHs at least once a week.InterventionThe intervention combined a self-administered exercise program, with 10 g amino-acid supplementation under the supervision of HHs.MeasurementsMain outcome measures included physical activity (the PASE questionnaire), functional tests, nutritional and autonomy scores, and compliance (50% or more was considered satisfactory). Non-parametric methods were used for comparisons between the two groups. A linear regression model was fitted to assess the effect of the intervention on the relative variation of outcomes, adjusted for unbalanced baseline co-variables.ResultsOne hundred and two persons (prevention n=53, control n=49) with a median age of 85 years were included. Their median Activities of Daily Living and Instrumental Activities of Daily Living (LADL) scores were 6 and 7 respectively. Twenty-three (44%) were good compilers for both interventions. The maximum walking time remained stable while decreasing by 25% in the control group (p=0.0015); and fewer participants had a worsened IADL score in the prevention group (p=0.05). The baseline IADL Score was significantly associated with good compliance to the prevention program (p=0.0011). In good compliers, maximum walking distance and maximum walking time increased by 29.15% (0.0 to 66.7) and 33.3% (−20.0 to 50.0) respectively.ConclusionThis study confirms the feasibility of a prevention program supervised by HHs, and some benefit from the intervention and identifies predictors for better compliance. It will help in the design of prevention trials for elderly people at risk for frailty.

The effect of methylphenidate on neurofibromatosis type 1: a randomised, double-blind, placebo-controlled, crossover trial

BackgroundNeurofibromatosis type 1 (NF1) is an autosomal dominant disorder with an estimated prevalence of about 1/3000, independent of ethnicity, race, or gender. Attention Deficit Hyperactivity like Disorder (ADHD)-like characteristics are often reported in patients with NF1. We hypothesised that learning disabilities in NF1 children were related to ADHD symptoms. Treatment with methylphenidate (MPD) has improved learning disabilities in ADHD by acting on neurotransmitters. Our objective was to evaluate its efficacy on ADHD-like symptoms in neurofibromatosis type 1 children (7–12 years).MethodsThis was a randomised, double blind, placebo controlled, and crossover trial comparing 0.5 to 0.8 mg/kg/d of MPD as it is indicated for ADHD to placebo in NF1 children with ADHD-like symptoms. Children aged 7 to 12 years were eligible when their IQ was between 80 and 120. The total follow-up was 9 weeks including 4 weeks for each period and 1 week wash out. Fifty subjects (25 for each period) were required for testing the primary study hypothesis. The main outcome was an improvement in scores on the simplified Conners’ Parent Rating Scale.ResultsThirty-nine patients were included between April 2004 and December 2010. Twenty participants received MPD and 19 placebo during the first period. They all completed the trial. MPD decreased the simplified Conners by 3.9 points (±1.1, p = 0. 0003).ConclusionsThis is the first randomised controlled trial showing the short-term benefit of MPD on simplified Conners scores in NF1 children.Trial registrationClinicalTrials.gov NCT00169611.

Mixed-model of ANOVA for measurement reproducibility in proteomics.

This work is a statistical analysis of reproducibility of a MALDI-TOF mass spectrometry experiment. Its aim is to evaluate measurement variability and compare peak intensities from two types of MALDI-TOF platforms. We compared and commented on the abilities of Principal Component Analysis and mixed-model analysis of variance to evaluate the biological variability and the technical variability of peak intensities in different patients. The properties and hypotheses of both methods are summarized and applied to spectra from plasma of patients with Hodgkin lymphoma. Principal Component Analysis checks rapidly the balance between the two variabilities; however, a mixed-model analysis of variance is necessary to quantify the biological and technical components of the experimental variance as well as their interactions and to split the total variance into between-subjects and within-subject components. The latter method helped to assess the reproducibility of measurements from two MALDI-TOF platforms and to decompose the technical variability according to the experimental design.

In normal knees, joint space width (JSW) is correlated with the intermargin distance (IMD), a measure of medial tibial plateau alignment. Variations in IMD explain variability in JSW in serial radiographs

OBJECTIVE To ascertain the importance of alignment of the medial tibial plateau (MTP), as determined by the distance between the anterior and posterior margins of the plateau (intermargin distance [IMD]), for measurements of joint space width (JSW) in radiographs of normal knees. METHODS JSW and IMD were measured in paired baseline and 12-month knee films of 122 subjects from the osteoarthritis initiative (OAI). Relationships between JSW and IMD, and between the variation in JSW and variation in IMD, were evaluated. RESULTS In cross-sectional analysis, a non-linear relationship existed between JSW and the concurrent IMD. With poor MTP alignment (IMD>1.7 mm), a 1.0-mm increase in IMD resulted in a 0.16-mm (95%CI: 0.11-0.21) increase in JSW (P<0.0001). In a longitudinal analysis, the effect of IMD variation on variation in JSW was also highly significant (P<0.0001). A variation of 1 mm between IMD(Baseline) and IMD(12month) was associated with a 0.10-mm (95% CI: 0.06-0.13) variation in JSW, with variations in JSW and IMD occurring in the same direction. An IMD variation less than or equal to 1.0mm was determined to be acceptable for accurate evaluation of JSW in serial radiographs. CONCLUSION The error in measurement of JSW caused by variation in IMD in serial radiographs of normal knees can be as large, or larger, than the mean rate of 12-month joint space narrowing (JSN) in OA knees. MTP alignment and replication of alignment in serial knee films are required for accurate determination of JSN in OA knee.

Importance of data structure in comparing two dimension reduction methods for classification of microarray gene expression data

BackgroundWith the advance of microarray technology, several methods for gene classification and prognosis have been already designed. However, under various denominations, some of these methods have similar approaches. This study evaluates the influence of gene expression variance structure on the performance of methods that describe the relationship between gene expression levels and a given phenotype through projection of data onto discriminant axes.ResultsWe compared Between-Group Analysis and Discriminant Analysis (with prior dimension reduction through Partial Least Squares or Principal Components Analysis). A geometric approach showed that these two methods are strongly related, but differ in the way they handle data structure. Yet, data structure helps understanding the predictive efficiency of these methods. Three main structure situations may be identified. When the clusters of points are clearly split, both methods perform equally well. When the clusters superpose, both methods fail to give interesting predictions. In intermediate situations, the configuration of the clusters of points has to be handled by the projection to improve prediction. For this, we recommend Discriminant Analysis. Besides, an innovative way of simulation generated the three main structures by modelling different partitions of the whole variance into within-group and between-group variances. These simulated datasets were used in complement to some well-known public datasets to investigate the methods behaviour in a large diversity of structure situations. To examine the structure of a dataset before analysis and preselect an a priori appropriate method for its analysis, we proposed a two-graph preliminary visualization tool: plotting patients on the Between-Group Analysis discriminant axis (x-axis) and on the first and the second within-group Principal Components Analysis component (y-axis), respectively.ConclusionDiscriminant Analysis outperformed Between-Group Analysis because it allows for the dataset structure. An a priori knowledge of that structure may guide the choice of the analysis method. Simulated datasets with known properties are valuable to assess and compare the performance of analysis methods, then implementation on real datasets checks and validates the results. Thus, we warn against the use of unchallenging datasets for method comparison, such as the Golub dataset, because their structure is such that any method would be efficient.

ADHD in childhood epilepsy: Clinical determinants of severity and of the response to methylphenidate

Attention‐deficit/hyperactivity disorder (ADHD) is commonly observed in children with epilepsy. However, factors associated with the development of ADHD and which might help to guide its therapeutic management, remain an issue of debate.