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A subgroup of testicular seminomas has been reported to contain activating mutations in KIT, the transmembrane tyrosine kinase receptor encoded by the c-kit gene. Most mutations are in exon 17, although exon 11-activating mutations have recently been described. For patients refractory to standard therapeutic protocols for seminoma, the presence of c-kit-activating mutations in some of these neoplasms might suggest an alternative therapy with KIT targeting drugs. We used the novel mutation scanning technique, high-resolution melting amplicon analysis, to screen a series of 22 testicular seminomas for c-kit-activating mutations. Four cases (18%) had exon 17-activating mutations and these included D816Y, D816V, Y823N and one case that contained both D816E and D820H. A single case (5%) had an exon 11-activating mutation. Interestingly, the exon 11-activating mutation was L576P, the same mutation that characterizes the rare c-kit mutation-positive cases of malignant melanoma. Fluorescence in situ hybridization (FISH) for c-kit suggested that most seminomas are probably polysomic for c-kit and there was not a significant difference in c-kit FISH characteristics between the mutation-positive and mutation-negative cases. The use of high-resolution melting amplicon analysis as a screening technique will allow for the rapid identification of patients with testicular seminomas whose tumors contain c-kit-activating mutations. This could benefit patients whose tumors are refractory to standard therapeutic protocols.

Objectives The Scientific Advisory Committee on Nutrition (SACN) and the World Health Organisation (WHO) have recently updated nutritional guidelines for a reduced sugar intake. With the increased popularity of online health-food bloggers and 'refined-sugar free' recipes, this review looked to analyse recipes from popular online bloggers to validate the veracity of their 'sugar-free' and 'healthy' claims and assess their adherence to recently implemented nutritional guidelines.Method Four bloggers were randomly selected from the Amazon top 10 booklist and their online blogs were consulted for a selection of recipes which were then nutritionally analysed in relation to their sugar and fat content.Results Eighty percent of the recipes analysed contained more fat than a Mars bar and 70% contained more fat than a popular online cake recipe, while 25% of the recipes contained over half of the recommended daily sugar intake as advised by the SACN and the WHO. None of the bloggers analysed used evidence-based approaches for the advice on their blogs.Conclusion Bloggers offer an invaluable platform to disseminate dietary advice to the public; however the recipes in this analysis were not healthy alternatives. The challenge is for government and health organisations to use this platform to promote alternative healthy eating options that align to current national and international guidance.

Background Dental caries remains a significant public health problem, prevalence being linked to social and economic deprivation. Occlusal surfaces of first permanent molars are the most susceptible site in the developing permanent dentition. Cochrane reviews have shown pit and fissure sealants (PFS) and fluoride varnish (FV) to be effective over no intervention in preventing caries. However, the comparative cost and effectiveness of these treatments is uncertain. The primary aim of the trial described in this protocol is to compare the clinical effectiveness of PFS and FV in preventing dental caries in first permanent molars in 6-7 year-olds. Secondary aims include: establishing the costs and the relative cost-effectiveness of PFS and FV delivered in a community/school setting; examining the impact of PFS and FV on children and their parents/carers in terms of quality of life/treatment acceptability measures; and examining the implementation of treatment in a community setting. Methods/design The trial design comprises a randomised, assessor-blinded, two-arm, parallel group trial in 6–7 year old schoolchildren. Clinical procedures and assessments will be performed at 66 primary schools, in deprived areas in South Wales. Treatments will be delivered via a mobile dental clinic. In total, 920 children will be recruited (460 per trial arm). At baseline and annually for 36 months dental caries will be recorded using the International Caries Detection and Assessment System (ICDAS) by trained and calibrated dentists. PFS and FV will be applied by trained dental hygienists. The FV will be applied at baseline, 6, 12, 18, 24 and 30 months. The PFS will be applied at baseline and re-examined at 6, 12, 18, 24, and 30 months, and will be re-applied if the existing sealant has become detached/is insufficient. The economic analysis will estimate the costs of providing the PFS versus FV. The process evaluation will assess implementation and acceptability through acceptability scales, a schools questionnaire and interviews with children, parents, dentists, dental nurses and school staff. The primary outcome measure will be the proportion of children developing new caries on any one of up to four treated first permanent molars. Discussion The objectives of this study have been identified by the National Institute for Health Research as one of importance to the National Health Service in the UK. The results of this trial will provide guidance on which of these technologies should be adopted for the prevention of dental decay in the most susceptible tooth-surface in the most at risk children. Trial registrations ISRCTN ref: ISRCTN17029222 EudraCT: 2010-023476-23 UKCRN ref: 9273

Abstract Disclosure: S. Wagle: None. L. Lomo: None. R.L. Dood: None. B. Chadwick: None. D. Abraham: None. Introduction: Struma ovarii is a mono-dermal teratoma of the ovary that is composed of more than >50% of mature thyroid tissue. It accounts for 5% of ovarian teratomas and 1% of ovarian tumors. Although rare, it is seen in women between 40-60 years of age. Most of these tumors are found incidentally. Malignant struma ovarii is even rarer and the mutational profile of these tumors is neither well studied nor understood. We present an uncommon case of malignant struma with NRAS p.Q61R mutation yet with papillary and solid histologic patterns. Case Description: A 53-year-old female with no significant medical or family history presented with acute worsening of chronic lower abdominal pain and irregular menstruation. Her symptoms developed gradually over 6 months. A pelvic and abdominal CT identified a 9.7 cm cystic left ovarian mass without evidence of ascites or peritoneal masses. She underwent laparoscopic left salpingo-oophorectomy. Histopathology examination of the ovarian tumor revealed classical type, well-differentiated papillary, and solid patterns of thyroid carcinoma. The cells revealed nuclear enlargement, irregular nuclei, finely dispersed chromatin, distinct nucleoli, and nuclear grooves. Due to the histologic pattern of classical papillary thyroid cancer, BRAF V600E pyrosequencing was conducted, which revealed wild-type BRAF. This was followed by NGS when NRAS p.Q61R pathogenic variant was identified. Her thyroid ultrasound did not reveal actionable nodules. A TSH (2.17mU/ml) and thyroglobulin (7.6 ng/ml, TG ab neg) levels are consistent with a normal functioning thyroid gland. This patient's tumor findings are unique in that papillary thyroid carcinoma (PTC) and solid growth patterns are typically associated with the BRAF V600E mutation but rarely seen in the context of an RAS mutation. Discussion: Typically, thyroid cancers with papillary and solid variant features are associated with the BRAF V600E mutation. RAS-type tumors have follicular histologic architecture. BRAF and RAS mutations are mutually exclusive in tumors. Our patient’s malignant struma is unique in that it contained a wild-type BRAF and was positive for NRAS p.Q61R mutation. However, the histology was that of papillary and solid patterns. NRAS mutation with papillary histology combination is rare and is seen in 12% of thyroid cancers. The mutational profile of malignant struma ovarii has not been fully understood or studied due to their rarity. Presentation: 6/3/2024

Abstract #1003 Objective: To review the clinical, histological and mutation characteristics of thyroid cancer (TC) manifesting as skeletal metastasis. Methods: TC presenting with pathological bone fracture or as spinal cord compression is rare. Case Presentation: Seven pts, 4 men and 3 women presented with bony metastasis from unknown primary cancer. 3 of them manifested acute pathological fracture of long bones. Whole body MRI or PET scans are used for risk assessment and treatment planning in...

Differentiated thyroid cancer patients uncommonly present with bone metastasis as the initial manifestation. Their molecular profile is largely unknown. The aim of this study was to evaluate the histopathology, molecular profiles, and response to radioactive iodine therapy in these patients. Eight patients presented with symptomatic bone metastasis from an unknown primary tumor. We identified these patients by performing a retrospective chart review. Pathology slides were reviewed and the molecular analysis of 112 thyroid cancer-related genes was performed on bone metastasis specimens using targeted next-generation sequencing. These patients presented with long bone fractures, spinal cord compression, or intractable bone pain. Histopathologic analysis of the bone and thyroid tumor specimens revealed follicular variant of papillary carcinoma in 7 patients and tall cell variant papillary carcinoma in 1 patient. Primary tumor size ranged from 0.4 to 7.5 cm. All patients received high dose radioiodine therapy following thyroidectomy. Molecular analysis revealed telomerase reverse transcriptase ( ) mutations in 7 (88%) tumors, 4 (50%) contained co-occurring and RAS GTPase gene ( ) mutations, 2 had isolated mutations, and 1 had and proto-oncogene B-Raf ( ) V600E mutations, respectively. Tumors carrying , , or a combination of these mutations were radioiodine-avid, with predictable tumor response and reduction in serum thyroglobulin levels. One patient with radioiodine-refractory disease harbored and mutations. These results demonstrate that differentiated thyroid cancers presenting with bone metastasis independent of the primary tumor size have a high prevalence of mutations, frequently coexisting with mutations. This molecular signature may predict a favorable response to radioiodine therapy. = proto-oncogene B-Raf; = deoxyribonucleic acid; = differentiated thyroid cancer; = follicular variant; = papillary thyroid carcinoma; = radioactive iodine; = Ras GTPase gene; = telomerase reverse transcriptase; = thyroglobulin.