Project description:We molecularly characterized a class of histologically aggressive childhood liver cancers and showed that these tumors are clinically aggressive and that their observed histological features are associated with underlying recurrent molecular features. We proposed a diagnostic algorithm to identify these cancers using a combination of histological and molecular features, and our analysis suggested that these cancers may benefit from specialized treatment strategies that may differ from treatment guidelines for hepatoblastomas and hepatocellular carcinomas.
Project description:We molecularly characterized a class of histologically aggressive childhood liver cancers and showed that these tumors are clinically aggressive and that their observed histological features are associated with underlying recurrent molecular features. We proposed a diagnostic algorithm to identify these cancers using a combination of histological and molecular features, and our analysis suggested that these cancers may benefit from specialized treatment strategies that may differ from treatment guidelines for hepatoblastomas and hepatocellular carcinomas.
Project description:This study aims to test computer-aided diagnosis (CAD) for thyroid nodules in clinical ultrasonography (US) practice with a focus towards identifying thyroid entities associated with CAD system misdiagnoses. Two-hundred patients referred to thyroid US were prospectively enrolled. An experienced radiologist evaluated the thyroid nodules and saved axial images for further offline blinded analysis using a commercially available CAD system. To represent clinical practice, not only true nodules, but mimicking lesions were also included. Fine needle aspiration biopsy (FNAB) was performed according to present guidelines. US features and thyroid entities significantly associated with CAD system misdiagnosis were identified along with the diagnostic accuracy of the radiologist and the CAD system. Diagnostic specificity regarding the radiologist was significantly (p < 0.05) higher than when compared with the CAD system (88.1% vs. 40.5%) while no significant difference was found in the sensitivity (88.6% vs. 80%). Focal inhomogeneities and true nodules in thyroiditis, nodules with coarse calcification and inspissated colloid cystic nodules were significantly (p < 0.05) associated with CAD system misdiagnosis as false-positives. The commercially available CAD system is promising when used to exclude thyroid malignancies, however, it currently may not be able to reduce unnecessary FNABs, mainly due to the false-positive diagnoses of nodule mimicking lesions.
Project description:AimPSMA (prostate-specific membrane antigen) is physiologically expressed in normal prostate tissue and over expressed in prostate cancer cells, therefore constituting a potential target for antibody-based radioligand therapy. Very recent imaging findings reported PSMA-PET/CT uptake in various thyroid lesions. We were therefore encouraged to systematically analyse PSMA expression in different benign and malignant thyroid lesions.MethodsImmunohistochemistry was used to detect PSMA expression in 101 thyroid lesions, while neovasculature was identified by CD34 immunostaining.ResultsPSMA expression in the neovasculature was significantly more frequent in malignant tumors (36/63; 57.1%) compared to benign diseases (5/38; 13.2%; p = 0.0001). In addition, PSMA expression levels in the neovasculature of poorly and undifferentiated thyroid cancers were significantly higher compared to differentiated thyroid tumors (p = 0.021). However, one case with a strong expression in follicular adenoma was identified.ConclusionsWe conclude that neovascular PSMA expression is common in thyroid cancer but may also rarely be found in benign thyroid diseases, such as follicular adenoma. High expression in the tumor-associated neovasculature is predominantly found in poorly differentiated and undifferentiated (anaplastic) thyroid cancer. This knowledge is highly relevant when interpreting PSMA/PET-CT scans from patients with prostate cancer. In addition, our findings might provide a rationale for further evaluation of PSMA-targeted anti-neovascular or radioligand therapy in metastatic dedifferentiated thyroid cancer.
Project description:ObjectiveThe controversy that iodized salt may increase the risk of thyroid disorders has been aroused in China during the past decade. Most of studies focused on adult rather than children. We aimed to explore whether iodized salt was associated with an increased risk of thyroid nodule in Chinese children.MethodsThe cross-sectional study was conducted in Hangzhou, China, in 2010. Iodized salt intake, urine iodine concentration (UIC) and thyroid nodule (by ultrasonography) were measured in 3026 children. The associations of iodized salt with thyroid nodule were evaluated using multiple logistic regression models.ResultsThe prevalence of thyroid nodule was 10.59% among Chinese children. Girls (11.89%) had higher prevalence of thyroid nodule than boys (9.26%). No significant association was observed between type of salt and thyroid nodule in pooled samples, boys and girls, respectively. Similar associations were observed between UIC and thyroid nodule. There was no significant association between milk consumption and thyroid nodule as well.ConclusionThe present study indicated that non-iodized salt may not increase the risk of thyroid nodules among Chinese children. Similar associations were observed between milk consumption, UIC and thyroid nodules.
Project description:AimPrevious investigations have shown that end-stage renal disease (ESRD) is associated with an increased risk of malignancies. The aim of this study was to explore the association between ESRD in patients undergoing maintenance haemodialysis (HD) and the incidence of malignancies according to age.MethodsWe analysed a nationwide cohort retrieved from Taiwan's National Health Insurance Research Database to study the incidence of malignancies in patients who were and were not receiving HD. One million beneficiaries were randomly selected and followed from 2005 to 2013. Of these 1?000?000 patients, 3055 developed ESRD and commenced maintenance HD during this period. For each HD patient, four age-, gender- and diabetes-matched controls were selected from the database (n?=?12?220). We further stratified the patients according to age. The study endpoint was the occurrence of malignancy.ResultsThe incidence rates of malignancy were 6.8% and 4.9% in the HD and control groups, respectively. Competing risk regression analysis indicated that age, HD, male gender and diabetes were associated with an increased risk of malignancy. When further stratified according to age, the odds ratios of developing cancer were 5.8, 1.9, 1.9 and 1.5 among the HD patients aged <40?years, 40-49?years, 50-59?years and 60-69?years, respectively.ConclusionThe patients with ESRD who received HD had a significantly higher cumulative risk of malignancy, especially those with a young age. Therefore, specialized cancer screening protocols for young HD patients might help to prolong their lifespan.
Project description:ImportanceAlthough the increased incidence of second primary malignant neoplasms (SPMs) is a well-known late effect after cancer, few studies have compared survival after an SPM to survival of the same cancer occurring as first primary malignant neoplasm (PM) by age.ObjectiveTo assess the survival impact of SPMs in adolescents and young adults (AYAs) (15-39 years) compared with that of pediatric (<15 years) and older adult (?40 years) patients with the same SPMs.Design, setting, and participantsThis was a population-based, retrospective cohort study of patients with cancer in 13 Surveillance, Epidemiology and End Results regions in the United States diagnosed from 1992 to 2008 and followed through 2013. Data analysis was performed between June 2016 and January 2017.Main outcomes and measuresFive-year relative survival was calculated overall and for each cancer occurring as a PM or SPM by age at diagnosis. The impact of SPM status on cancer-specific death was examined using multivariable Cox proportional hazards regression.ResultsA total of 15?954 pediatric, 125?750 AYAs, and 878?370 older adult patients diagnosed as having 14 cancers occurring as a PM or SPM were included. Overall, 5-year survival after an SPM was 33.1% lower for children, 20.2% lower for AYAs, and 8.3% lower for older adults compared with a PM at the same age. For the most common SPMs in AYAs, the absolute difference in 5-year survival was 42% lower for secondary non-Hodgkin lymphoma, 19% for secondary breast carcinoma, 15% for secondary thyroid carcinoma, and 13% for secondary soft-tissue sarcoma. Survival by SPM status was significantly worse in younger vs older patients for thyroid, Hodgkin lymphoma, non-Hodgkin lymphoma, acute myeloid leukemia, soft-tissue sarcoma, and central nervous system cancer. Adolescents and young adults with secondary Hodgkin lymphoma (hazard ratio [95% CI], 3.5 [1.7-7.1]); soft-tissue sarcoma (2.8 [2.1-3.9]); breast carcinoma (2.1 [1.8-2.4]); acute myeloid leukemia (1.9 [1.5-2.4]); and central nervous system cancer (1.8 [1.2-2.8]) experienced worse survival compared with AYAs with the same PMs.Conclusion and relevanceThe adverse impact of SPMs on survival is substantial for AYAs and may partially explain the relative lack of survival improvement in AYAs compared with other age groups. The impact of a particular SPM diagnosis on survival may inform age-specific prevention, screening, treatment, and survivorship recommendations.
Project description:The main types of thyroid neoplasms, follicular adenoma (FA), follicular thyroid carcinoma (FTC), classical and follicular variants of papillary carcinoma (clPTC and fvPTC), and anaplastic thyroid carcinoma (ATC), differ in prognosis, progression rate and metastatic behaviour. Specific patterns of lncRNAs involved in the development of clinical and morphological features can be presumed. LncRNA landscapes within distinct benign and malignant histological variants of thyroid neoplasms were not investigated. The aim of the study was to discover long noncoding RNA landscapes common and specific to major benign and malignant histological subtypes of thyroid neoplasms. LncRNA expression in FA, FTC, fvPTC, clPTC and ATC was analysed with comprehensive microarray and RNA-Seq datasets. Putative biological functions were evaluated via enrichment analysis of coexpressed coding genes. In the results, lncRNAs common and specific to FTC, clPTC, fvPTC, and ATC were identified. The discovered lncRNAs are putatively involved in L1CAM interactions, namely, pre-mRNA processing (lncRNAs specific to FTC); PCP/CE and WNT pathways (lncRNAs specific to fvPTC); extracellular matrix organization (lncRNAs specific to clPTC); and the cell cycle (lncRNAs specific to ATC). Known oncogenic and suppressor lncRNAs (RMST, CRNDE, SLC26A4-AS1, NR2F1-AS1, and LINC00511) were aberrantly expressed in thyroid carcinomas. These findings enhance the understanding of lncRNAs in the development of subtype-specific features in thyroid cancer.
Project description:Introduction: Classical congenital adrenal hyperplasia is associated with an increased risk of obesity and cardiometabolic disease. The aim of the study was to determine if this is also true for non-classical congenital adrenal hyperplasia (NCCAH). Methods: A retrospective, cross-sectional, single-center study design was used. Data were collected on 114 patients (92 female) with NCCAH diagnosed during childhood/adolescence at a tertiary medical center. Patients were classified by treatment status at the last clinic visit. Outcome measures were assessed at diagnosis and the last clinic visit: weight status, body composition, blood pressure, lipid profile, and glucose metabolism. The prevalence of overweight/obesity was compared to the parental prevalence, and for patients aged 11-20 years, to the Israeli National Survey. Results: Mean age was 7.9 ± 4.2 years at diagnosis and 17.1 ± 6.9 years at the last follow-up. At the last clinic visit, 76 patients were under treatment with glucocorticoids, 27 were off-treatment (previously treated), and 11 had never been treated. The rate of obesity (11.4%) was similar to the parental rates, and the rate of overweight was significantly lower. In patients 11-20 years old, rates of obesity or obesity + overweight were similar to the general Israeli population (11.4 vs. 15.1%, P = 0.24 and 34.2 vs. 41.6% P = 0.18, respectively). No significant difference was found between glucocorticoid-treated and off-treatment patients in any of the metabolic or anthropometric parameters evaluated, except for a lower mean fat mass (% of body weight) in off-treatment patients (23.0 ± 7.7% vs. 27.8 ± 6.8%, P = 0.06). Systolic hypertension was found in 12.2% of NCCAH patients either treated or untreated. Conclusion: NCCAH diagnosed in childhood, whether treated or untreated, does not pose an increased risk of overweight, obesity, or metabolic derangements in adolescence and early adulthood.