Pituitary adenomas are currently classified by histological, immunocytochemical and numerous ultrastructural characteristics lacking unequivocal prognostic correlations. We investigated the ...prognostic value of a new clinicopathological classification with grades based on invasion and proliferation. This retrospective multicentric case–control study comprised 410 patients who had surgery for a pituitary tumour with long-term follow-up. Using pituitary magnetic resonance imaging for diagnosis of cavernous or sphenoid sinus invasion, immunocytochemistry, markers of the cell cycle (Ki-67, mitoses) and p53, tumours were classified according to size (micro, macro and giant), type (PRL, GH, FSH/LH, ACTH and TSH) and grade (grade 1a: non-invasive, 1b: non-invasive and proliferative, 2a: invasive, 2b: invasive and proliferative, and 3: metastatic). The association between patient status at 8-year follow-up and age, sex, and classification was evaluated by two multivariate analyses assessing disease- or recurrence/progression-free status. At 8 years after surgery, 195 patients were disease-free (controls) and 215 patients were not (cases). In 125 of the cases the tumours had recurred or progressed. Analyses of disease-free and recurrence/progression-free status revealed the significant prognostic value (
p
< 0.001;
p
< 0.05) of age, tumour type, and grade across all tumour types and for each tumour type. Invasive and proliferative tumours (grade 2b) had a poor prognosis with an increased probability of tumour persistence or progression of 25- or 12-fold, respectively, as compared to non-invasive tumours (grade 1a). This new, easy to use clinicopathological classification of pituitary endocrine tumours has demonstrated its prognostic worth by strongly predicting the probability of post-operative complete remission or tumour progression and so could help clinicians choose the best post-operative therapy.
Background
RAS
and K601E
BRAF
mutations are not a reliable indicator of malignancy in fine-needle aspirations (FNA) of thyroid indeterminate cytologic nodules. We aimed to evaluate the histologic ...characteristics, the risk of malignancy associated with such mutations in FNA and their potential interest for preoperative clinical management of nodules.
Methods
We evaluated 69 indeterminate thyroid nodules with
RAS
or K601E
BRAF
mutations with available histopathologic follow-up. All FNA specimens were indeterminate according to the thyroid Bethesda system. Diagnosis of malignant, benign or indolent neoplasms was classified according to 2017 WHO classification. Carcinoma, NIFTP (noninvasive follicular thyroid neoplasm with papillary-like features) and WDTUMP (well-differentiated tumor of uncertain malignant potential) were considered “surgical,” as they require surgical excision. Adenoma was considered “non-surgical.” The risk of malignancy and the risk of “surgical disease” were evaluated.
Results
Pathologic evaluation of the 69 mutated nodules demonstrated benign, indolent and malignant histology in 17 cases (25%), 21 cases (30%) and 31 cases (45%), respectively. The risk of malignancy was 45%, and the risk of surgical disease was 75%. The majority of carcinomas were a follicular variant of papillary thyroid carcinoma. On follow-up, there have been no recurrences to date.
Conclusion
Preoperative
RAS
or
BRAF
K601E mutations detection in cytologic indeterminate thyroid nodules carries a high risk of surgical disease and may benefit from surgical management. Most surgical lesions harboring those mutations are low-risk tumors, which may be in favor of an initial lobectomy.
In this article a review of low temperature (LT) (≤500 °C) process modules in view of 3-D sequential integration is presented. First, both the bottom device thermal stability and intermediate back ...end of line (iBEOL) versus thermal anneal and ns-laser anneal is determined, setting up the top device temperature fabrication process at 500 °C during a couple of hours. Then, the full LT process flow with process modules developed at 500 °C is exposed. Great progress and breakthrough for high performance (HP) digital stacked FETs has been made recently. Areas previously considered as potential showstoppers have been overcome: 1) efficient contamination containment for wafers with Cu/ultra low-<inline-formula> <tex-math notation="LaTeX">{k} </tex-math></inline-formula> (ULK) iBEOL enabling their reintroduction in front end of line (FEOL) for top FET processing; 2) low-resistance poly-Si gate for the top FETs and solutions for improving gate-stack reliability; and 3) full LT raised source drain (RSD) epitaxy including surface preparation combined with SiCO 400 °C spacer and SPER junctions activation. Finally, the first functional nMOS and pMOS demonstration with a 500 °C thermal budget (TB) is highlighted.
Objective
Liquid‐based (LB)‐FNA is widely recognized as a reliable diagnostic method to evaluate thyroid nodules. However, up to 30% of LB‐FNA remain indeterminate according to the Bethesda system. ...Use of molecular biomarkers has been recommended to improve its pathological accuracy but implementation of these tests in clinical practice may be difficult. Here, we evaluated feasibility and performance of molecular profiling in routine practice by testing LB‐FNA for BRAF, N/HRAS and TERT mutations.
Methods
We studied a large prospective cohort of 326 cases, including 61 atypia of undetermined significance, 124 follicular neoplasms, 72 suspicious for malignancy and 69 malignant cases. Diagnosis of malignancy was confirmed by histology on paired surgical specimen.
Results
Mutated LB‐FNAs were significantly associated with malignancy regardless of the cytological classification. Overall sensitivity was 60% and specificity 89%. Importantly, in atypia of undetermined significance and follicular neoplasm patients undergoing surgery according to the Bethesda guidelines, negative predictive values were 85.4% and 90% respectively. TERT promoter mutation was rare but very specific for malignancy (5.5%) suggesting that it could be of interest in patients with indeterminate cytology.
Conclusions
Mutation profiling can be successfully performed on thyroid LB‐FNA without any dedicated sample in a pathology laboratory. It is an easy way to improve diagnostic accuracy of routine LB‐FNA and may help to better select patients for surgery and to avoid unnecessary thyroidectomies.
Mutation profiling can be successfully performed on residual material of thyroid LB‐FNA without any dedicated sample in a pathology lab. It is an easy way to improve diagnostic accuracy of LB‐FNA with indeterminate cytology in routine practice and may help to better select patients for surgery and to avoid unnecessary thyroidectomies.
We present, for the first time, a new CV based technique to extract the Active Dopant Profile under the spacer in thin film FDSOI devices (CV-AJP). The methodology is successfully applied to FDSOI ...devices fabricated at 500°C for 3D sequential integration. It shows that the ION/ IOFF trade-off relies mainly on the chemical dopant introduction below the offset spacer, as the activation level obtained with thermal activation is found to be high enough. The LT device demonstrated in this work, already outperforms the literature. The active profile extraction also allows to draw guidelines for further device performance improvement: using a scaled SiCO spacer (5,5nm) allows to circumvent the negligible dopant diffusion at 500°C without dynamic performance penalty due to its low-k dielectric value.
Non-alcoholic steatohepatitis is frequent in Type II (non-insulin-dependent) diabetes mellitus and can lead to fibrosis and cirrhosis. The interindividual variability in the occurrence of ...nonalcoholic steatohepatitis suggests, however, a genetic modulation. Microsomal triglyceride transfer protein (MTP) is necessary for the assembly and secretion of VLDL and when the protein is not functional, such as in abetalipoproteinaemia, a steatohepatitis occurs. We therefore assessed the association between a functional polymorphism in the promoter region of MTP gene (-493 G/T) and the biological features of steatohepatitis in Type II diabetic patients.
We studied 271 patients with Type II diabetes. Determination of -493 G/T polymorphism was made by PCR-RFLP. Increased liver enzymes were used as surrogates of liver steatosis and alanine aminotransferase concentration was the outcome variable for the multivariate analysis. Liver ultrasonography was available for a subgroup of patients with newly diagnosed diabetes.
The proportion of patients with increased alanine aminotransferase was higher in GG than in GT and TT subgroups (23%, 11% and 6%, respectively, p = 0.01). Additionally, patients with high alanine aminotransferase concentrations were more likely to be young (p = 0.01), male (p = 0.001), obese (p = 0.04) and have low HDL-cholesterol (p = 0.01). In multivariate analysis, the MTP genotype was independently associated with alanine aminotransferase concentration (p = 0.0023) as well as sex and body mass index but not HDL-cholesterol.
The -493 G/T MTP gene polymorphism is associated with biological surrogates of steatohepatitis in patients with Type II diabetes. The G allele which is responsible for a decrease in MTP gene transcription is prone to increase the intrahepatic triglycerides content, conferring by this a genetic susceptibility for steatohepatitis.
For the first time FDSOI CMOS transistors with Si- monocrystalline channel have been fabricated at a temperature below 500°C. High performance PMOS (Ion=450μA/μm (V dd -0.9V) @ Ioff=-2nA/μmLg=35nm) ...with low overlap capacitance (0.46fF/μm per device), low gate resistance (10Ω) at Low Temperature (L T) enables to achieve good RF Figure-Of-Merit (FOM) with Fmax values up to 170GHz. In addition, we demonstrate for the first time the full functionality of Ring Oscillators (RO) and SRAM bitcells processed at 500°C, paving the way for a high-performance 3D sequential CMOS integration.
La chirurgie transphénoïdale reste à ce jour le seul traitement curateur dans l’acromégalie avec normalisation rapide de l’IGF-1. La sélection de patients pouvant bénéficier d’une chirurgie curatrice ...reste toutefois difficile. Objectifs (1) Évaluer les facteurs pronostiques de l’issue de la chirurgie dans l’acromégalie afin de mieux cibler les patients candidats à une chirurgie première. (2) Comparer les profils histologiques tumoraux des patients guéris vs. non guéris. Patients et méthodes Étude rétrospective monocentrique, de 63 patients acromégales opérés de 2009 à 2015, par le même chirurgien. Analyse des caractéristiques cliniques, biologiques pré- et postopératoire à 3 mois, IRM préopératoires (taille, invasion, signal T2) et histologiques (classification pronostique, granulation). Résultats Trois mois après la chirurgie, le taux de rémission défini par la normalisation de l’IGF-1 et/ou de GH/HGPO < 1,2 mUI/L était de 50,8 %. En analyse univariée, aucun critère clinico-biologique n’était prédictif de guérison. Les patients non guéris par la chirurgie présentaient des tumeurs plus invasives (Knops ≥ 3) ( p < 0,05), avec un diamètre plus important ( p < 0,05), comparés aux patients en rémission. Le signal tumoral en T2 n’était pas prédictif de guérison. Les caractéristiques histologiques étaient différentes dans les 2 groupes, avec des tumeurs de plus haut grade dans le groupe non guéris ( p < 0,05). En analyse multivariée, l’invasion du sinus caverneux à l’IRM reste le facteur pronostique majeur du risque de non-guérison (OR 3,8 ; IC 0,9 ; 16,5). Discussion La taille et le caractère invasif de la tumeur semblent être les meilleurs facteurs pronostiques de l’issue chirurgicale.
Objectif L’objectif de cette étude observationnelle était d’évaluer la relation entre les signes cliniques et la radiologie dans le syndrome de Kallmann. Design et patients Nous avons réalisé une ...étude observationnelle des IRMs de 17 patients classés cliniquement comme syndrome de Kallmann. Nous avons analysé qualitativement et quantitativement la base du crâne et la région des bulbes olfactifs. Résultats Nous avons pu observer une anomalie de la profondeur des sulci chez 16 des 17 patients, ainsi que des anomalies malformatives des fosses olfactives et des angles ethmoïdaux chez 16 patients. Concernant les analyses génétiques, parmi les 13 patients ayant eu un test génétique, 7 mutations ont été identifiées. Conclusion L’imagerie apporte un réel bénéfice dans le diagnostic du syndrome de Kallmann. En effet, nous observons dans cette étude une corrélation entre la radiologie et la clinique. L’imagerie permet également de différencier le syndrome de Kallmann des formes non syndromiques d’hypogonadismes hypogonadotrophiques. La génétique dans ce syndrome peut être utilisée en complément de la clinique et de l’imagerie. En effet, dans notre étude, une mutation a été identifiée chez moins de la moitié des sujets.
Introduction Les inhibiteurs de tyrosine kinase (ITK) sont maintenant indiqués en première intention dans les formes agressives et symptomatiques de cancer médullaire de la thyroïde (CMT) avancé. ...Cependant, le recours à la chimiothérapie peut se justifier chez les patients non répondeurs ou présentant des contre-indications aux ITK. Objectifs Rapporter l’effet d’une chimiothérapie par 5-Fluorouracile (5-FU) et dacarbazine chez 4 patients traités entre 2011 et 2014 pour un CMT avancé et rapidement progressif. Méthodes La réponse tumorale a été évaluée selon les critères RECIST 1.0. La méthylation du promoteur de MGMT a été analysée par pyroséquençage. Résultats Deux patients ont présenté une réponse objective prolongée (réduction tumorale de 50 % et 55 % respectivement, maintenue pendant 12 mois pour les deux patients), accompagnée d’une amélioration spectaculaire de l’état général et d’une diminution de 79 % et 86 % de la calcitonine sérique. Une réponse partielle a été obtenue chez un 3e patient et le 4e a été non répondeur. Pour l’ensemble des 4 patients, la survie sans progression médiane a été de 8,5 mois (3–12) et la survie globale médiane de 13,5 mois (5–27). Une diminution de la calcitonine à 3 mois était associée à la présence d’une réponse tumorale. Le statut MGMT n’était pas un facteur prédictif de réponse. Aucun effet secondaire majeur n’a été observé. Conclusion Le taux de réponse était élevé dans cette petite série (75 %). L’association 5-FU-Dacarbazine peut constituer une alternative aux ITK. Les facteurs prédictifs de réponse au traitement restent à identifier.
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