Time to revise classification of phyllodes tumors of breast? Results of a French multicentric study

OBJECTIVE: To assess prognostic factors of recurrence of phyllodes tumors (PT) of the breast. METHODS: We performed a retrospective, multicentric cohort study, including all patients who underwent breast surgery for grade 1 (benign), 2 (borderline) or 3 (malignant) PT between 2000 and 2016 in five tertiary University hospitals, diagnosed according to World Health Organisation classification. RESULTS: 230 patients were included: 144 (63%), 60 (26%) and 26 (11%) with grade 1, 2 and 3 PT, respectively. Recurrence occurred in 10 (7%), 7 (12%) and 5 (19%) patients with grade 1, 2 and 3 PT, respectively. In univariate analysis, moderate to severe nuclear stromal pleomorphism (HR 8.00 [95% CI: 1.65-38.73], p < 0.009) was correlated with recurrence in all groups including grade 1 (HR 14.3 [95% CI: 1.29-160], p = 0.031). In multivariate analysis, surgical margin >5 mm, (HR 0.20 [95% CI: 0.06-0.63], p = 0.013) were significantly correlated with less recurrence in all PT grades. For grade 1 PT, there was also significantly less recurrence with surgical margin >5 mm, (HR 0.09 [95% CI: 0.01-0.85], p = 0.047) in multivariate analysis. CONCLUSION: The surgical margin should be at least 5 mm whatever the grade of PT. Moderate to severe nuclear stromal pleomorphism identified a subgroup of grade 1 PT with a higher rate of recurrence. This suggests that the WHO classification could be revised with the introduction of nuclear stromal pleomorphism to tailor PT management

Drug interventions for the treatment of obesity in children and adolescents

BACKGROUND: Child and adolescent obesity has increased globally, and can be associated with significant short- and long-term health consequences. OBJECTIVES: To assess the efficacy of drug interventions for the treatment of obesity in children and adolescents. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, PubMed (subsets not available on Ovid), LILACS as well as the trial registers ICTRP (WHO) and ClinicalTrials.gov. Searches were undertaken from inception to March 2016. We checked references and applied no language restrictions. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) of pharmacological interventions for treating obesity (licensed and unlicensed for this indication) in children and adolescents (mean age under 18 years) with or without support of family members, with a minimum of three months' pharmacological intervention and six months' follow-up from baseline. We excluded interventions that specifically dealt with the treatment of eating disorders or type 2 diabetes, or included participants with a secondary or syndromic cause of obesity. In addition, we excluded trials which included growth hormone therapies and pregnant participants. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data following standard Cochrane methodology. Where necessary we contacted authors for additional information. MAIN RESULTS: We included 21 trials and identified eight ongoing trials. The included trials evaluated metformin (11 trials), sibutramine (six trials), orlistat (four trials), and one trial arm investigated the combination of metformin and fluoxetine. The ongoing trials evaluated metformin (four trials), topiramate (two trials) and exenatide (two trials). A total of 2484 people participated in the included trials, 1478 participants were randomised to drug intervention and 904 to comparator groups (91 participants took part in two cross-over trials; 11 participants not specified). Eighteen trials used a placebo in the comparator group. Two trials had a cross-over design while the remaining 19 trials were parallel RCTs. The length of the intervention period ranged from 12 weeks to 48 weeks, and the length of follow-up from baseline ranged from six months to 100 weeks.Trials generally had a low risk of bias for random sequence generation, allocation concealment and blinding (participants, personnel and assessors) for subjective and objective outcomes. We judged approximately half of the trials as having a high risk of bias in one or more domain such as selective reporting.The primary outcomes of this review were change in body mass index (BMI), change in weight and adverse events. All 21 trials measured these outcomes. The secondary outcomes were health-related quality of life (only one trial reported results showing no marked differences; very low certainty evidence), body fat distribution (measured in 18 trials), behaviour change (measured in six trials), participants' views of the intervention (not reported), morbidity associated with the intervention (measured in one orlistat trial only reporting more new gallstones following the intervention; very low certainty evidence), all-cause mortality (one suicide in the orlistat intervention group; low certainty evidence) and socioeconomic effects (not reported).Intervention versus comparator for mean difference (MD) in BMI change was -1.3 kg/m(2) (95% confidence interval (CI) -1.9 to -0.8; P < 0.00001; 16 trials; 1884 participants; low certainty evidence). When split by drug type, sibutramine, metformin and orlistat all showed reductions in BMI in favour of the intervention.Intervention versus comparator for change in weight showed a MD of -3.9 kg (95% CI -5.9 to -1.9; P < 0.00001; 11 trials; 1180 participants; low certainty evidence). As with BMI, when the trials were split by drug type, sibutramine, metformin and orlistat all showed reductions in weight in favour of the intervention.Five trials reported serious adverse events: 24/878 (2.7%) participants in the intervention groups versus 8/469 (1.7%) participants in the comparator groups (risk ratio (RR) 1.43, 95% CI 0.63 to 3.25; 1347 participants; low certainty evidence). A total 52/1043 (5.0%) participants in the intervention groups versus 17/621 (2.7%) in the comparator groups discontinued the trial because of adverse events (RR 1.45, 95% CI 0.83 to 2.52; 10 trials; 1664 participants; low certainty evidence). The most common adverse events in orlistat and metformin trials were gastrointestinal (such as diarrhoea, mild abdominal pain or discomfort, fatty stools). The most frequent adverse events in sibutramine trials included tachycardia, constipation and hypertension. The single fluoxetine trial reported dry mouth and loose stools. No trial investigated drug treatment for overweight children. AUTHORS' CONCLUSIONS: This systematic review is part of a series of associated Cochrane reviews on interventions for obese children and adolescents and has shown that pharmacological interventions (metformin, sibutramine, orlistat and fluoxetine) may have small effects in reduction in BMI and bodyweight in obese children and adolescents. However, many of these drugs are not licensed for the treatment of obesity in children and adolescents, or have been withdrawn. Trials were generally of low quality with many having a short or no post-intervention follow-up period and high dropout rates (overall dropout of 25%). Future research should focus on conducting trials with sufficient power and long-term follow-up, to ensure the long-term effects of any pharmacological intervention are comprehensively assessed. Adverse events should be reported in a more standardised manner specifying amongst other things the number of participants experiencing at least one adverse event. The requirement of regulatory authorities (US Food and Drug Administration and European Medicines Agency) for trials of all new medications to be used in children and adolescents should drive an increase in the number of high quality trials

Détermination sur tissu endométrial néoplasique de profils d'expression de micro-ARNs associés à l'envahissement ganglionnaire dans le cancer de l'endomètre de type endométrioïde de stade précoce

Current histological classification of early-stage endometrial cancer (EC) may show insufficient accuracy to precisely predict lymph node metastases leading to potential over or under treatment. Hence, additional highly sensitive and specific molecular prognostic biomarkers correlated with prognostic factors, such as nodal involvement and lymphovascular space involvement (LVSI), are needed to better adapt surgical management and adjuvant therapies. We fstudied by microarray analysis microRNA expression profiles of formalin-fixed paraffin-embedded grade 1–2 supposed early-stage endometrioid adenocarcinomas specimen. The expression levels of 5 microRNAs (miR-34c-5p, -375, -184, -34c-3p, et -34b-5p) were lower in the EC with positive nodal status compared to those with negative nodal status. The expression levels of 3 microRNAs (miR-34c-5p, -23b-5p, et -23c) were lower in the EC with positive LVSI compared to those with negative LVSI. A quantitative reverse transcriptase–PCR assay was used to determine micro-RNAs thresholds correlated with prognostic factors. Women with a microRNA-184-fold change 0.30 (n=3; 11.5%), p=0.006. Women with a microRNA-34c-5p fold change 0.15 (n=0; 0.0%), p0,30, p=0,006. Les patientes avec seuil d'expression du micro-ARN-34c-5p 0,15 (0,0%), p<0,001. Ces profils d'expression de micro-ARNs fournissent les bases pour de nouvelles études sur la fonction des micro-ARNs dans le cancer de l'endomètre et pourraient constituer un nouvel outil au diagnostic du statut ganglionnaire

A Conversation with Michael A. Woodley of Menie, Yr.

Michael Anthony Woodley of Menie, Yr (Younger), is a British ecologist and evolutionary psychologist, whose research on secular trends in dierent aspects of human intelligence has earned him considerable notability.[...

A Conversation with Gerhard Meisenberg

Gerhard Meisenberg is a retired professor of biochemistry who lives in the Caribbean island nation of Dominica [...]</jats:p

Loi Évin, Publicité indirecte et marques

International audienceThe author presents the important place occupied by the notion of indirect advertising in the Evin Act. This notion makes the communication exercise around their brand by tobacco and alcohol actors perilous. The author also underlines that the notion of indirect advertising disturbs the competition game for other economic actors by generating a new form of conflict between brands.L’auteur présente l’importante place occupée par la notion de publicité indirecte dans la loi Évin. Cette notion rend périlleux l’exercice de communication autour de leur marque par les acteurs de tabac et d’alcool. L’auteur souligne également que la notion de publicité indirecte perturbe le jeu de la concurrence pour les autres acteurs économiques en générant une forme nouvelle de conflits entre des marques