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:Background & aimsHepatoblastoma (HB) and hepatocellular carcinoma (HCC) are the predominant liver cancers in children, though their respective treatment options and associated outcomes differ dramatically. Risk stratification using a combination of clinical, histological, and molecular parameters can improve treatment selection, but it is particularly challenging for tumors with mixed histological features, including those in the recently created hepatocellular neoplasm not otherwise specified (HCN NOS) provisional category. We aimed to perform the first molecular characterization of clinically annotated cases of HCN NOS.MethodsWe tested whether these histological features are associated with genetic alterations, cancer gene dysregulation, and outcomes. Namely, we compared the molecular features of HCN NOS, including copy number alterations, mutations, and gene expression profiles, with those in other pediatric hepatocellular neoplasms, including HBs and HCCs, as well as HBs demonstrating focal atypia or pleomorphism (HB FPAs), and HBs diagnosed in older children (>8).ResultsMolecular profiles of HCN NOS and HB FPAs revealed common underlying biological features that were previously observed in HCCs. Consequently, we designated these tumor types collectively as HBs with HCC features (HBCs). These tumors were associated with high mutation rates (∼3 somatic mutations/Mb) and were enriched with mutations and alterations in key cancer genes and pathways. In addition, recurrent large-scale chromosomal gains, including gains of chromosomal arms 2q (80%), 6p (70%), and 20p (70%), were observed. Overall, HBCs were associated with poor clinical outcomes.ConclusionsOur study indicates that histological features seen in HBCs are associated with combined molecular features of HB and HCC, that HBCs are associated with poor outcomes irrespective of patient age, and that transplanted patients are more likely to have good outcomes than those treated with chemotherapy and surgery alone. These findings highlight the importance of molecular testing and early therapeutic intervention for aggressive childhood hepatocellular neoplasms.Lay summaryWe 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 other childhood liver cancers.
Project description:ImportanceMore people are surviving long-term after diagnosis with hematologic malignant neoplasm (HMN), yet there are limited data on cancer-related cognitive impairment in people with HMN. Better understanding cognitive outcomes after HMN in older adults is important for patient counseling and management.ObjectiveTo model cognitive trajectories and rates of cognitive decline before and after HMN diagnosis in older adults compared with a matched noncancer cohort.Design, setting, and participantsIn this population-based cohort study, older adults from the Health and Retirement Study (HRS) diagnosed with HMN between 1998 and 2016 after age 65 years were matched 1:3 to participants without cancer from the same HRS wave using propensity scores incorporating variables relevant to cognition. Cognitive trajectories were modeled with piecewise linear splines, and rates of cognitive decline before, during, and after diagnosis were compared in the 2 groups. Data were analyzed from April 2022 to April 2024.ExposuresHMN diagnosis by Medicare diagnosis codes.Main outcomes and measuresCognitive function was assessed by the Langa-Weir cognitive summary score from 1992 to 2020. Sociodemographic and health-related variables relevant to cognition were incorporated into propensity scores.ResultsAt baseline, there were 668 participants in the HMN cohort (mean [SD] age, 76.8 [7.6] years; 343 [51.3%] male; 72 [10.8%] Black, 33 [4.9%] Hispanic, and 585 [87.6%] White) and 1994 participants in the control cohort (mean [SD] age, 76.5 [7.3] years; 1020 [51.2%] male; 226 [11.3%] Black, 91 [4.6%] Hispanic, and 1726 [86.6%] White). The HMN cohort consisted predominantly of more indolent diagnoses, and only 96 patients (14.4%) received chemotherapy. Before and in the 2 years around the time of diagnosis, the HMN and control cohorts had similar rates of cognitive decline. At 1 year postdiagnosis and beyond, the rate of cognitive decline was slower in the HMN cohort (-0.18; 95% CI, -0.23 to -0.14) than in the control group (-0.24; 95% CI, -0.26 to -0.23) (P = .02), but this difference was no longer significant after accounting for the competing risk of death (HMN group, -0.27; 95% CI, -0.34 to -0.19; control group, -0.30; 95% CI, -0.33 to -0.27; P = .48).Conclusions and relevanceIn this cohort study of older adults, the HMN and matched noncancer control cohorts had similar rates of cognitive decline before, during, and after diagnosis after accounting for the competing risk of death.
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:A 66-year-old woman presented with an incidental left thyroid nodule during a health examination. She had no voice change, shortness of breath, cough, or dysphagia. Repeated sonography showed a dynamic change of the lesion, which was more evident following soda consumption. A subsequent esophagography confirmed the diagnosis of a Killian-Jamieson diverticulum. This rare left-sided pharyngoesophageal diverticulum is often asymptomatic. On a sonography, air bubbles in the esophageal lumen can cause a ring-down artifact that mimics microcalcifications, which are characteristic of thyroid malignancy, and misdiagnosis may lead to unnecessary interventions, including fine-needle aspiration or thyroidectomy. A dynamic ultrasound, specifically done during soda consumption, offered a simple diagnostic distinction. No surgical intervention was pursued; the patient was monitored in the clinic.
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.