Factors predictive of lymph node metastasis in the follicular variant of papillary thyroid carcinoma

BACKGROUND: The treatment of papillary thyroid carcinomas larger than 1 cm usually consists of total thyroidectomy and central lymph node dissection (LND). In patients with the follicular variant of papillary thyroid carcinoma (FVPTC), preoperative cytology and intraoperative frozen-section analysis cannot always establish the diagnosis. The aim of this study was to evaluate predictive factors for lymph node metastasis in patients with FVPTC and to identify patients who might benefit from LND. METHODS: The study included patients with FVPTC treated by total thyroidectomy and LND between 2000 and 2010 in four departments. When fewer than six non-involved lymph nodes were removed, the patient was excluded from the analysis. RESULTS: Some 199 patients were included. The median tumour size was 17 (range 1-85) mm, and tumours were classified as T1a in 28 patients, T1b in 40, T2 in 53, and T3 in 78. Eighty-one patients (40·7 per cent) had lymph node metastasis (51 classified as N1a and 30 as N1b). Four risk factors were predictive of lymph node metastasis in the multivariable analysis: multifocality (odds ratio (OR) 2·36, 95 per cent confidence interval 1·15 to 4·86), angiolymphatic invasion (OR 3·67, 1·01 to 13·36), absence of tumour capsule (OR 3·00, 1·47 to 6·14) and tumour involvement of perithyroid tissue (OR 3·89, 1·85 to 8·18). The rate of lymph node metastasis varied between 14 and 94 per cent depending on the presence of risk factors. CONCLUSION: The rate of lymph node metastasis in patients with FVPTC varies widely according to the presence or absence of predictive risk factors

Simulation of a liquid-vapour compressible flow by a Lattice Boltzmann Method

International audienceThis work is devoted to the numerical resolution of a compressible three-phase flow with phase transition by a Lattice-Boltzmann Method (LBM). The flow presents complex features and large variations of physical quantities. The LBM is a robust numerical method that is entropy stable and that can be extended to second order accuracy without additional numerical cost. We present preliminary numerical results, which confirm its competitiveness compared to other Finite Volume methods

Simulated climate near steep topography: Sensitivity to numerical methods for atmospheric transport

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94798/1/grl24350.pd

Time Until Partial Response in Metastatic Adrenocortical Carcinoma Long-Term Survivors

A partial response (PR) has been proposed as a surrogate for overall survival in advanced adrenocortical carcinoma (ACC). The primary endpoint of the study was to characterize the time until a PR in patients with metastatic ACC treated with a standard therapy is achieved. Long-term survivors were selected to allow evaluation of delayed tumor response to mitotane. Records from patients with metastatic ACC that survived for > 24 months were retrieved. Tumor response was analyzed according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Time until a tumor response, after treatment initiation or therapeutic plasma mitotane level, was analyzed. Sixty-eight patients were analyzed. The first-line systemic therapy was mitotane as a monotherapy (M) (n = 57) or cytotoxic polychemotherapy plus/minus mitotane (PC ± M) (n = 11). The second-line therapy was M (n = 2) or PC ± M (n = 41). Thirty-two PRs occurred in 30/68 patients (44.1%): this was obtained for 13 (40.6%) during M and during PC ± M for 19/32 responders (59.4%). PRs were observed within 6 months of starting M or PC ± M in 76.9 and 94.7% of responses, respectively, within 6 months of therapeutic plasma mitotane being first observed in 88.9% of responses with M and in 53.3% of responses with PC ± M. All PRs (but one) occurred within 1 year after initiating treatment. To conclude, Most patients with metastatic ACC and long survival times had PRs within the first 6 months of standard systemic therapy, and almost all within the first year. The absence of response after that period could be considered as a treatment failure. Maintenance of mitotane therapy in non-responders after 1 year should be questioned in future randomized trials

Vandetanib for the Treatment of Advanced Medullary Thyroid Cancer Outside a Clinical Trial: Results from a French Cohort

BACKGROUND: A randomized phase III trial demonstrated that vandetanib treatment is effective in patients with metastatic medullary thyroid cancer (MTC), leading to regulatory approval, but its use may be associated with toxicities that require specific monitoring and management. The objective of the present study performed in France was to describe the toxicity profile and efficacy of vandetanib treatment when given outside any trial. METHODS: Sixty-eight patients were treated with vandetanib in the frame of a temporary use authorization (ATU) in France from August 2010 to February 2012, when the drug was available on request for patients with locally advanced or metastatic MTC. Patients were registered by the French health authorities, and characteristics, treatment parameters, toxicity profile, and efficacy were retrospectively reviewed. Eight patients were excluded from the analysis because vandetanib treatment was not administered (n=3), had been given in a trial before ATU (n=3), or was given for a non-MTC cancer (n=2). RESULTS: Data from the 60 MTC patients were analyzed. Mean age was 58 years (range 11-83 years), 39 patients were male, and six had hereditary MTC. Fifty-six (93%) had metastatic disease in the mediastinum (82%), bones (65%), liver (53%), or lung (53%), and four had only locally advanced disease. At the time of study evaluation, with a median follow-up of 20 months and a median duration of treatment of 9.7 months (range 0.3-36 months), 15 patients were continuing vandetanib treatment (range 18-36 months). Median progression-free survival was 16.1 months. Twenty-five patients discontinued treatment for disease progression (range 0.3-29 months). Best tumor response was a complete response in one patient, a partial response in 12 (20%), stable disease in 33 (55%), and progression in seven patients (12%). All patients had at least one adverse event (AE) during treatment. The main AEs were skin toxicity, diarrhea, and asthenia. Sixteen patients (27%) discontinued treatment for toxicity, and one patient died from vandetanib-induced cardiac toxicity. CONCLUSIONS: Vandetanib is an effective option for patients with advanced MTC. AEs should be monitored carefully and should be minimized by educating both patients and care providers and by applying symptomatic treatment and dose reduction

French Endocrine Society Guidance on endocrine side-effects of immunotherapy

The management of cancer patients has changed due to the considerably more frequent use of immune checkpoint inhibitors (ICPI). However, the use of ICPI has a risk of side-effects, particularly endocrine toxicity. Since the indications for ICPI are constantly expanding due to their efficacy, it is important that endocrinologists and oncologists know how to look for this type of toxicity and how to treat it when it arises. In view of this, the French Endocrine Society initiated the formulation of a consensus document on ICPI-related endocrine toxicity. In this paper, we will introduce data on the general pathophysiology of endocrine toxicity, we will then outline expert opinion focusing primarily on methods for screening, management and monitoring for endocrine side-effects in patients treated by ICPI. We will then look in turn at endocrinopathies that are induced by ICPI including dysthyroidism, hypophysitis, primary adrenal insufficiency and fulminant diabetes. In each chapter, expert opinion will be given on the diagnosis, management and monitoring for each complication. These expert opinions will also discuss the methodology for categorizing these side-effects in oncology using \u27Common terminology criteria for adverse events\u27 (CTCAE) and the difficulties in applying this to endocrine side-effects in the case of these anti-cancer therapies. This is shown in particular by certain recommendations that are used for other side-effects (high-dose corticosteroids, contra-indicated in ICPI for example), and that cannot be considered as appropriate in the management of endocrine toxicity, as it usually does not require ICPI withdrawal or high dose glucocorticoid intake

Predicted Benign and Synonymous Variants in CYP11A1 Cause Primary Adrenal Insufficiency Through Missplicing.

Primary adrenal insufficiency (PAI) is a potentially life-threatening condition that can present with nonspecific features and can be difficult to diagnose. We undertook next generation sequencing in a cohort of children and young adults with PAI of unknown etiology from around the world and identified a heterozygous missense variant (rs6161, c.940G>A, p.Glu314Lys) in CYP11A1 in 19 individuals from 13 different families (allele frequency within undiagnosed PAI in our cohort, 0.102 vs 0.0026 in the Genome Aggregation Database; P A, Thr330 = ; c.1173C>T, Ser391 =). Although p.Glu314Lys is predicted to be benign and showed no loss-of-function in an Escherichia coli assay system, in silico and in vitro studies revealed that the rs6161/c.940G>A variant, plus the c.990G>A and c.1173C>T changes, affected splicing and that p.Glu314Lys produces a nonfunctional protein in mammalian cells. Taken together, these findings show that compound heterozygosity involving a relatively common and predicted "benign" variant in CYP11A1 is a major contributor to PAI of unknown etiology, especially in European populations. These observations have implications for personalized management and demonstrate how variants that might be overlooked in standard analyses can be pathogenic when combined with other very rare disruptive changes.Medical Research Council UK Project (grant MR/K020455/1 to L.A.M.).J.C.A. is a Wellcome Trust Senior Research Fellow in Clinical Science (grants 098513/Z/12/Z and 209328/Z/17/Z) with research support from Great Ormond Street Hospital Children’s Charity (grant V2518) and the National Institute for Health Research, Great Ormond Street Hospital Biomedical Research Centre (grant IS-BRC-1215-20012).Funding also included support from The Mater Medical Research Institute (to M.H.) and National Institutes of Health (grant R01GM086596 to R.J.A.)

Simulation of a liquid-vapour compressible flow by a Lattice Boltzmann Method

This work is devoted to the numerical resolution of a compressible three-phase flow with phase transition by a Lattice-Boltzmann Method (LBM). The flow 5 presents complex features and large variations of physical quantities. The LBM is a robust numerical method that is entropy stable and that can be extended to second order accuracy without additional numerical cost. We present preliminary numerical results, which confirm its competitiveness compared to other Finite Volume methods. 1

La chirurgie thyroïdienne chez le patient obèse : une revue de la littérature

International audienceLe nombre d’interventions de chirurgie bariatrique a été multiplié par 4 ces 10 dernières années en raison de l’épidémie des cas d’obésité, qui a triplé dans la population générale lors des quatre dernières décennies. De façon concomitante, le nombre de patients obèses ou ayant été opérés d’une chirurgie bariatrique candidats à une chirurgie thyroïdienne a donc considérablement augmenté. La proportion des patients obèses représente actuellement 10 à 20 % des patients thyroïdectomisés dans les cohortes françaises. De plus, la fréquence des pathologies thyroïdiennes bénignes et malignes semble être influencée par l’obésité, unhazard ratio d’environ 1,8 pour les cancers thyroïdiens ayant été mis en évidence chez la femme obèse. Si l’obésité ne semble pas influencer la morbidité postopératoire spécifique de la thyroïdectomie, un antécédent de chirurgie bariatrique malabsorptive doit inciter à la plus grande prudence en cas de chirurgie thyroïdienne, car il expose à un risque important d’hypocalcémie sévère (plus de 60 % des cas dans certaines études) nécessitant une supplémentation intraveineuse dans environ 20 % des cas. Dans cette dernière situation, une supplémentation vitamino-calcique périopératoire est indispensable. Par ailleurs, les doses de lévothyroxine à visée substitutive devraient aussi être adaptées chez les patients obèses, calculées non pas à partir du poids réel, mais à partir du poids idéal. L’objectif de cette revue est de discuter l’influence de l’obésité sur l’évolution des pathologies nodulaires et néoplasiques thyroïdiennes, sur la morbidité de la chirurgie thyroïdienne ainsi que sur les traitements médicamenteux postopératoires. L’impact de la chirurgie bariatrique sur ces différentes étapes est également discuté