247 research outputs found
On the residual finiteness of outer automorphisms of relatively hyperbolic groups
We show that every virtually torsion-free subgroup of the outer automorphism
group of a conjugacy separable relatively hyperbolic group is residually
finite. As a direct consequence, we obtain that the outer automorphism group of
a limit group is residually finite.Comment: 11 pages, 1 figure. Section 3 is replaced by Theorem 1.3. More
detailed arguments. Added new references. To appear in Journal of Pure and
Applied Algebr
A new mouse model of poorly differentiated thyroid carcinoma and its implications for human disease.
Nodules et carcinomes thyroïdiens
Face à l’augmentation des incidentalomes thyroïdiens, la gestion appropriée des
nodules thyroïdiens est primordiale afin de permettre la détection des cancers relevants
et d’éviter le surdiagnostic et le surtraitement des microcarcinomes papillaires.
Cet article décrit les grandes lignes de la prise en charge en tenant compte
des nouvelles recommandations
Increased Pituitary Fluorine-18-Fluorodeoxyglucose Uptake in Patients with Differentiated Thyroid Cancer in Hypothyroidism versus under Recombinant Human Thyroid-Stimulating Hormone Stimulation.
The incidental pituitary hypermetabolism on 18F-FDG PET/CT should be further evaluated for discriminating between pathologic and physiologic uptake, but a recent study suggests that pituitary hypermetabolism is common in patients with differentiated thyroid carcinoma (DTC) undergoing thyroid hormone withdrawal (THW). The aim of this retrospective study was to compare pituitary metabolism in patients with DTC undergoing 18F-FDG PET/CT under THW versus recombinant human thyroid-stimulating hormone (rhTSH) stimulation. We confirmed a higher pituitary SUVmax and SUVratio with a higher prevalence of pituitary hypermetabolism in the THW group compared to the rhTSH group. A positive correlation between serum TSH levels and pituitary SUVmax was observed only in the THW group. The present findings support the hypothesis that pituitary hypermetabolism on 18F-FDG PET/CT in patients with DTC undergoing THW is a common physiological response to hypothyroidism. Awareness of this physiological hypermetabolism is important to avoid potential pitfalls in image interpretation that could trigger unnecessary investigations
Endocrine and neuroendocrine cytopathology.
Cytology is an easily-accessible, cost-effective, and safe procedure for the initial evaluation of most endocrine/neuroendocrine lesions. Both fine-needle aspiration cytology and exfoliative cytology have shown good sensitivity and specificity in detecting endocrine/neuroendocrine benign proliferations and malignancies. Thanks to its utility for early diagnosis, cytology has contributed to the decline in mortality of endocrine/neuroendocrine neoplasms. The endocrine system comprises different endocrine organs, such as the thyroid, adrenal glands, paraganglia, parathyroid, pancreas, hypothalamus, pituitary gland, ovaries and testes, which can give rise to non-neoplastic, benign and malignant proliferations. In addition, several neuroendocrine cells do not form specific endocrine organs, but are widely present along other systems, notably in the lungs and in the gastrointestinal tract. The general diagnostic approach to proliferations originating from neuroendocrine cells is similar to that of endocrine organs. This review focuses on the cytological features of neuroendocrine proliferations, with particular emphasis on their most common sites of origin, i.e. the thyroid, pancreas, lungs and skin. Ancillary approaches applied to cytological material to improve diagnosis will also be discussed
Uptake of 99mTc-MIBI by Sclerosing Pneumocytoma Raising a False Suspicion of Metastasis From Medullary Thyroid Carcinoma.
Technetium-99m methoxy isobutyl isonitrile ( <sup>99m</sup> Tc-MIBI; sestamibi) single-photon emission computed tomography (SPECT)/computed tomography (CT) performed for preoperative localization of parathyroid adenomas or for other indications can reveal incidentalomas. Interpretation of such findings can be challenging, particularly when thyroid or other endocrine tumors are also present. Preoperative staging of a 59-year-old female patient with medullary thyroid carcinoma (MTC) showing moderate hypermetabolism on <sup>18</sup> F-fluorodeoxyglucose positron emission tomography/CT also detected a slightly hypermetabolic pulmonary nodule (standardized uptake value normalized by body weight max = 2.0 g/mL). A sestamibi SPECT/CT performed because of concomitant primary hyperparathyroidism showed increased uptake by both the MTC and the pulmonary nodule, raising suspicion of MTC metastasis. Lung wedge resection biopsy revealed a sclerosing pneumocytoma (SPC), a rare benign pulmonary tumor not previously known to retain sestamibi. In contrast to classical knowledge that sestamibi uptake by tumors is associated with its retention by mitochondria, immunohistochemical analyses showed that the mitochondrial content of the patient's SPC was low. This case illustrates the behavior of SPC in sestamibi scintigraphy and indicates that SPC is a potential cancer mimicker in this setting
CRISPR/Cas9 genome-wide screening identifies KEAP1 as a sorafenib, lenvatinib, and regorafenib sensitivity gene in hepatocellular carcinoma.
Sorafenib is the first-line drug used for patients with advanced hepatocellular carcinoma (HCC). However, acquired sorafenib resistance in cancer patients limits its efficacy. Here, we performed the first genome-wide CRISPR/Cas9-based screening on sorafenib-treated HCC cells to identify essential genes for non-mutational mechanisms related to acquired sorafenib resistance and/or sensitivity in HCC cells. KEAP1 was identified as the top candidate gene by Model-based Analysis of Genome-wide CRISPR/Cas9 Knockout (MAGeCK). KEAP1 disrupted HCC cells were less sensitive than wild-type cells in short- and long-term sorafenib treatments. Compared to wild-type cells, KEAP1-disrupted cells showed lower basal and sorafenib-induced reactive oxygen species (ROS) levels and were more resistant to oxidative stress-induced cell death. The absence of KEAP1 led to increased activity of Nrf2, a key transcription factor controlling antioxidant responses, as further evidenced by increased expression of Nrf2-controlled genes including NQO1, GPX2 and TXNRD1, which were positively associated with chemoresistance. In addition, KEAP1 disruption counteracted the reduction of cell viability and the elevation of ROS caused by lenvatinib, a drug that recently showed clinical efficacy as a first-line treatment for unresectable HCC. Finally, Keap1 disruption also increased the resistance of cells to regorafenib, a recently approved drug to treat HCC as a second line therapy. Taken together, our data indicate that deregulation of the KEAP1/Nrf2 pathway following KEAP1 inactivation contributes to sorafenib, lenvatinib, and regorafenib resistance in human HCC cells through up-regulation of Nrf2 downstream genes and decreased ROS levels
Approach to cytological indeterminate thyroid nodules.
The indeterminate thyroid nodules diagnosed by fine-needle aspiration cytology (FNAC)represents a problem for both cytopathologists and clinicians. The former sometimes use this diagnostic category as a sort of basket, putting in cases that they do not know exactly how to classify. The latter are faced with a highly variable risk of malignancy and consequently the management remains a challenge. On the histopathological side, the new WHO classification of tumors of the thyroid introduced the concept of tumors with uncertain and low malignant potential, and the concept of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), whose prognosis and management are still to be completely elucidated. While the risk of malignancy of the indeterminate diagnostic category has decreased due to the re-classification of certain types of papillary thyroid carcinomas of the follicular variant into a low malignant potential form (the NIFTP), cases diagnosed cytologically as indeterminate will probably increase in the future to avoid false positive diagnosis. Thus, the indeterminate thyroid diagnostic category still remains a challenge, both at the diagnostic level and for its management. The new version of the Bethesda system for reporting thyroid cytopathology suggests managing these patients with a repeat FNA, diagnostic lobectomy and/or molecular testing
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