Thyroglossal duct cyst carcinoma with concurrent thyroid carcinoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Thyroglossal duct carcinoma is a very rare finding and its presentation is similar to that of a benign cyst, which is a relatively common developmental abnormality that may manifest as a midline, neck mass. In general the diagnosis of thyroglossal duct carcinoma is based on the pathologic examination of the mass, but needle aspiration cytology, ultrasound and computed tomography play a role in the differential diagnosis of malignancy.</p> <p>Case presentation</p> <p>A further case of thyroglossal duct carcinoma and concurrent thyroid carcinoma with locoregional lymph node metastases affecting a 40-year-old woman followed up for 4 years is presented and discussed.</p> <p>Conclusion</p> <p>Sistrunk's surgical technique must always be the initial treatment, but in case of carcinoma further surgery, that is, thyroidectomy with or without lymph node dissection, and treatment with radioactive iodine have to be considered according to the microscopic and clinical findings. Accurate pre-operative clinical and radiological evaluation should be performed in order to plan surgical strategy.</p

Integration of human adipocyte chromosomal interactions with adipose gene expression prioritizes obesity-related genes from GWAS

Increased adiposity is a hallmark of obesity and overweight, which affect 2.2 billion people world-wide. Understanding the genetic and molecular mechanisms that underlie obesity-related phenotypes can help to improve treatment options and drug development. Here we perform promoter Capture Hi-C in human adipocytes to investigate interactions between gene promoters and distal elements as a transcription-regulating mechanism contributing to these phenotypes. We find that promoter-interacting elements in human adipocytes are enriched for adipose-related transcription factor motifs, such as PPARG and CEBPB, and contribute to heritability of cis-regulated gene expression. We further intersect these data with published genome-wide association studies for BMI and BMI-related metabolic traits to identify the genes that are under genetic cis regulation in human adipocytes via chromosomal interactions. This integrative genomics approach identifies four cis-eQTL-eGene relationships associated with BMI or obesity-related traits, including rs4776984 and MAP2K5, which we further confirm by EMSA, and highlights 38 additional candidate genes

Untangling the relationship between diet and visceral fat mass through blood metabolomics and gut microbiome profiling

BACKGROUND/OBJECTIVES: Higher visceral fat mass (VFM) is associated with an increased risk for developing cardio-metabolic diseases. The mechanisms by which an unhealthy diet pattern may influence VF development has yet to be examined through cutting-edge multi-omic methods. Therefore, our objective was to examine the dietary influences on VFM and identify gut microbiome and metabolite profiles that link food intakes to VFM. SUBJECTS/METHODS: In 2218 twins with VFM, food intake and metabolomics data available we identified food intakes most strongly associated with VFM in 50% of the sample, then constructed and tested the ‘VFM diet score’ in the remainder of the sample. Using linear regression (adjusted for covariates, including BMI and total fat mass) we investigated associations between the VFM diet score, the blood metabolomics profile and the faecal microbiome (n=889), and confirmed these associations with VFM. We replicated top findings in monozygotic (MZ) twins discordant (greater than or equal to1 s.d. apart) for VFM, matched for age, sex and the baseline genetic sequence. RESULTS: Four metabolites were associated with the VFM diet score and VFM: hippurate, alpha-hydroxyisovalerate, bilirubin (Z,Z) and butyrylcarnitine. We replicated associations between VFM and the diet score (Beta[s.e.]: 0.281[0.091]; P=0.002), butyrylcarnitine (0.199[0.087]; P=0.023) and hippurate (−0.297[0.095]; P=0.002) in VFM-discordant MZ twins. We identified a single species, Eubacterium dolichum to be associated with the VFM diet score (0.042[0.011], P=8.47 × 10−5), VFM (0.057[0.019], P=2.73 × 10−3) and hippurate (−0.075[0.032], P=0.021). Moreover, higher blood hippurate was associated with elevated adipose tissue expression neuroglobin, with roles in cellular oxygen homeostasis (0.016[0.004], P=9.82 × 10−6). CONCLUSION: We linked a dietary VFM score and VFM to Eubacterium dolichum and four metabolites in the blood. In particular, the relationship between hippurate, a metabolite derived from microbial metabolism of dietary polyphenols, and reduced VFM, the microbiome and increased adipose tissue expression of neuroglobin provides potential mechanistic insight into the influence of diet on VFM

Identification of rare loss-of-function genetic variation regulating body fat distribution

This is the final version. Available on open access from Oxford University Press via the DOI in this recordData Availability: This research was conducted using the UK Biobank resource (application Nos. 44448 and 9905). Access to the UK Biobank genotype and phenotype data is open to all approved health researchers (http://www.ukbiobank.ac.uk/).CONTEXT: Biological and translational insights from large-scale, array-based genetic studies of fat distribution, a key determinant of metabolic health, have been limited by the difficulty in linking predominantly non-coding variants to specific gene targets. Rare coding variant analyses provide greater confidence that a specific gene is involved, but do not necessarily indicate whether gain or loss-of-function (LoF) would be of most therapeutic benefit. OBJECTIVE, DESIGN AND SETTING: To identify genes/proteins involved in determining fat distribution, we combined the power of genome-wide analysis of array-based rare, non-synonymous variants in 450,562 individuals of UK Biobank with exome-sequence-based rare loss of function gene burden testing in 184,246 individuals. RESULTS: The data indicates that loss-of-function of four genes (PLIN1 [LoF variants, p=5.86×10 -7], INSR [LoF variants, p=6.21×10 -7], ACVR1C [LoF + Moderate impact variants, p=1.68×10 -7; Moderate impact variants, p=4.57×10 -7] and PDE3B [LoF variants, p=1.41×10 -6]) is associated with a beneficial impact on WHRadjBMI and increased gluteofemoral fat mass, whereas LoF of PLIN4 [LoF variants, p=5.86×10 -7] adversely affects these parameters. Phenotypic follow-up suggests that LoF of PLIN1, PDE3B and ACVR1C favourably affects metabolic phenotypes (e.g. triglyceride [TG] and HDL cholesterol concentrations) and reduces the risk of cardiovascular disease, whereas PLIN4 LoF has adverse health consequences. INSR LoF is associated with lower TG and HDL levels but may increase the risk of type 2 diabetes. CONCLUSION: This study robustly implicates these genes in the regulation of fat distribution, providing new and in some cases somewhat counter-intuitive insight into the potential consequences of targeting these molecules therapeutically.Medical Research Council (MRC)National Institute for Health Research (NIHR)Wellcome TrustResearch Englan

Regeneration of an abnormal ipsilateral visuotectal projection in Xenopus is delayed by the presence of optic fibers from the other eye

Optic fiber regeneration was studied by [3H]proline autoradiography and by mapping electrophysiologically the direct visuotectal projections to the contralateral and ipsilateral tecta 12-16 wk after sectioning the right optic nerve in Xenopus 2 to 4 wk after metamorphosis. The experiments were carried out in 3 groups: (A) optic nerve section in newly metamorphosed animals with embryonic left-eye enucleation; (B) optic nerve section with simultaneous left-eye enucleation; and (C) optic nerve section with delayed left-eye enucleation 5-31 days prior to sacrifice. In all but 3 animals regenerated optic fibers were demonstrated morphologically both in the contralateral and ipsilateral tecta. The contralateral visuotectal projection was fully restored within the 12-16 wk in all animals. In animals with embryonic enucleation or in those where the enucleation was carried out simultaneously with optic nerve section, a direct ipsilateral visuotectal projection was established at the same time as the restoration of the contralateral projection. In contrast, no direct ipsilateral visuotectal projection was detectable in the presence of optic fibers from the other eye in the doubly innervated tecta. However, 14-31 days after the removal of the incumbent optic fibers by left-eye enucleation a direct visuotectal projection from the right eye to the ipsilateral tectum was established, and its polarity corresponded to the normal contralateral retinotectal projection. The apparent disparity between morphological and electrophysiological findings in the doubly innervated tectum suggests that superimposed optic fibers are unable to form normal synaptic relations with tectal neurons during early regeneration, delaying the establishment of the induced direct ipsilateral visuotectal projection.link_to_subscribed_fulltex

Impact of Neuroradiology-Based Peer Review on Head and Neck Radiotherapy Target Delineation.

Background and purposeWhile standard guidelines assist in target delineation for head and neck radiation therapy planning, the complex anatomy, varying patterns of spread, unusual or advanced presentations, and high risk of treatment-related toxicities produce continuous interpretive challenges. In 2007, we instituted weekly treatment planning quality assurance rounds as a joint enterprise of head and neck radiation oncology and neuroradiology. Here we describe its impact on head and neck radiation therapy target delineation.Materials and methodsFor 7 months, treatment planning quality assurance included 80 cases of definitive (48%) or postoperative (52%) head and neck radiation therapy. The planning CT and associated target volumes were reviewed in comparison with diagnostic imaging studies. Alterations were catalogued.ResultsOf the 80 cases, 44 (55%) were altered, and of these, 61% had clinically significant changes resulting in exclusion or inclusion of a distinct area or structure. Reasons for alteration included the following: gross or extant tumor, 26/44 (59%); elective or postoperative coverage, 25/44 (57%); lymph nodes, 13/44 (30%); bone, 7/44 (16%); skull base, 7/44 (16%); normal organs, 5/44 (11%); perineural, 3/44 (7%); distant metastasis, 2/44 (5%); and eye, 1/44 (2%). Gross tumor changes ranged from 0.5% to 133.64%, with a median change in volume of 5.95 mm3 (7.86%). Volumes were more likely to be increased (73%) than decreased (27%).ConclusionsA collaborative approach to head and neck treatment planning quality assurance has an impact. Cases likely to have challenging patterns of infiltrative, intracranial, nodal, orbital, or perineural spread warrant intensive imaging-based review in collaboration with a diagnostic neuroradiologist