bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular pathways involved in hepatoblastoma tumorigenesis in trisomy 18.
Authors: Schepers Emily , Glaser Kathryn , Zwolshen Harrison , Bondoc Alexander 
Published: June 2023

e22015 Background: Trisomy 18 (T18) is the second most common aneuploidy caused by additional copies of chromosome 18. It occurs at a rate of 1 in 2000-6000 live births, with current 1-year survival rates between 5-10% of live births. Meta-analysis of tumor in T18 patients revealed 67 tumors, with 44 (66%) being HB. The contribution of underlying genetic alterations to tumorigenesis is incompletely understood. There is a reversed gender ratio in children with T18 and HB as well as more favorable histology and response to treatment. These suggest an alternative molecular pathway in these cases might promote tumorigenesis. Although there is an association between trisomy 18 and hepatoblastoma, the cause of this increased incidence is unknown. We hypothesize that SMAD4/TGFβ signaling in conjunction with canonical Wnt signaling has a role in T18 HB tumor development as well as a more fetal tumor histology. Methods: Seven patients with T18 were treated at CCHMC for HB. Five patient samples were collected at time of surgery for evaluation. Patient samples and data were collected with informed consent and institutional IRB approval. We performed transcriptomic analysis using RNA bulk sequencing data for five paired background and tumor samples. Further gene and protein expression were evaluated and compared to non-syndromic patients with HB. Histologic evaluation for tumor subtype and target proteins was performed. Results: Of the seven patients evaluated, six (85.7%) were female with a median age of diagnosis of 9 months. All patients underwent hepatectomy, with final pathology demonstrating predominantly fetal histology. All patients are currently in remission. Bulk RNAseq demonstrated upregulation of SMAD4 and TGFβ, as well as upregulation of canonical Wnt signaling pathway including Wnt3 and transcription factors Lef1, TCF4, and APC in tumor of T18 patients compared to background and non-syndromic HB patients. β-catenin immunostaining demonstrates increased or stabilized expression in tumor compared to background liver consistent with non-syndromic HB. Conclusions: We have identified a novel tumorigenic mechanism of HB in T18. Upregulation of SMAD4 in T18 results in increased TGFβ signaling, with potential crosstalk between SMAD4/TGFβ and Wnt/β-catenin signaling promoting cancer development. Further evaluation is required to understand the pathway crosstalk and impact of genetic mutation on pathway regulation.
Outcome of nasopharyngeal carcinoma (epithelial undifferentiated NOS) in children and adolescents: SEER database analysis.
Authors: Pendharkar Dinesh , Nirmal Garima , Ali Adnan , Gupta Neha 
Published: June 2023

e22016 Background: Nasopharyngeal carcinoma (NPC) is a rare malignant epithelial tumor of the nasopharynx and account for less than 1% of childhood tumors. Undifferentiated epithelial tumors are one of the commonest histologies. This study aimed to demonstrate the characteristics and outcome of NPC in children and adolescents. Methods: The Surveillance, Epidemiology and End Results database (SEER Research Data 18 Registries Nov 2020Sub (2000-2018)was analyzed for patients diagnosed with carcinoma undifferentiated NOS, NPC ( ICD-O-WHO-3 code 8020). Patients were excluded if the cause of death was not associated with their cancer according to SEER’s cancer-specific death categorization. Overall Survival were estimated using the Kaplan-Meier method, and variables were compared using the log-rank test. P values < .05 were considered significant. Results: A total of 62 patients aged ≤19 years with undifferentiated nasopharyngeal carcinoma were identified. The cohort included 39 (62.9%) males and 23 (37.1%) females .Among them, 40.3 % were white, 40.3% were black,17.7% were Asians/Pacific Islanders, and 1.6% were American Indian. The age of diagnosis distribution included 2 (3.2%)children with 5-9 year, 17 (27.4%) children with 10-14 years and 43(69.4%) children with 15-19 years. With a median follow up of 7.9 years, 3 year OS of the entire cohort was 84.5%. 3 year OS for children aged ≤14 years was 82.1% and for children aged 15-19 years was 85.5% (p- value = 0.649). When stratified by treatment era, the 3-year OS of all patients treated after 2009 was not statistically significant than those treated before (3-year OS, 85.5% vs 82%, P = .0649). Conclusions: Children and adolescents with undifferentiated epithelial neoplasm NOS, NPC had excellent survival. Age and treatment era has no prognostic impact on outcomes.
Pediatric carcinoid tumors of the lungs: A descriptive analysis.
Authors: Lee Dong-jin Joshua , Largen Joseph , Abid Kaamil , Hu Robert W. 
Published: June 2023

e22017 Background: From 1973 to 2012, the prevalence of neuroendocrine tumors in children was found to have increased by approximately 6-fold when using the Surveillance Epidemiology, and End Results. While carcinoid tumors in adults are mostly indolent, pediatric carcinoid tumors tend to carry worse prognoses. Our goal for this study is to describe the population of pediatric patients with pulmonary carcinoid tumors. Methods: We used the National Cancer Database to identify pediatric patients diagnosed with carcinoid tumors of the lungs between 2004-2020. Analysis was conducted with SPSS to determine frequency of cases in different demographics. Survival was assessed using Kaplan-Meier curves with significance set at p < 0.05. Results: Of the 125 patients identified, 55% of the patients were male and 45% female. Pulmonary carcinoid tumor patients were predominately white accounting for 80% of all cases. Black patients accounted for 14% of cases. The ages of diagnosis ranged from 3-17 years of age with the mean being 14.5 years of age. The majority of patients were diagnosed during their teenage years–84% were between the ages of 13 and 17 at diagnosis. Only one case was observed in a patient of age 6 or under. The median survival was 89 months. Univariate analysis revealed no significant difference in survival was seen in sex, race, or insurance groups. Charlson-Deyo score, however, did impact survival, where patients with a score of 2 had lower median survival time (36 months) compared to patients with a score of 1 (121 months) or 0 (87 months). Conclusions: Pediatric pulmonary carcinoid tumors are more commonly seen in white patients with most diagnoses occurring during patients’ teenage years (13-17). Age, sex, and race did not have a significant effect on survival although a Charlson-Deyo score of 2 was indicative of a worse prognosis when compared to a score of 1 or 0.
Cardiac iron overload in pediatric oncology and bone marrow transplant survivors.
Authors: Hans Rhea , Cleveland Celeste , Shah Sanjay , Wisotzkey Bethany , Walsh Alexandra Maria 
Published: June 2023

e22022 Background: Cardiovascular late effects are a leading cause of mortality and morbidity in childhood cancer and Bone Marrow Transplant (BMT) survivors. In patients receiving chronic red blood cell transfusions, excess iron may be deposited in the liver, heart, and pituitary gland. Iron overload cardiomyopathy is characterized as a restrictive physiology with early diastolic dysfunction ultimately progressing to end-stage dilated cardiomyopathy. Iron loading in the heart can also lead to arrhythmias and increase myocardial ischemia reperfusion injury due to increased formation of reactive oxygen species. It is not yet known whether high transfused packed red blood cell (PRBC) volumes in cancer and BMT patients leads to cardiac iron deposition, and whether iron-induced cardiac injury contributes to the known cardiovascular late effects in these patients. Methods: 83 childhood cancer and BMT survivors with elevated serum ferritin levels and subsequent liver Magnetic Resonance (MR) imaging were identified. 18 patients (21.7%) who had liver iron content of > 12mg/g (mean 16.0 ± 7.36 mg/g) also underwent Cardiac MRI (CMR) to determine cardiac iron content. Results: Median transfused blood volume was 393 ml/kg [95% Confidence Interval (CI) 170-780 ml/kg]. All 18 patients had at least one echocardiogram showing normal ventricular ejection fractions [mean 65.1 ± Standard Deviation (SD) 3.53%] and normal shortening fractions (mean 35.4 ± 3.67%). All patients had myocardial iron content within normal ranges (T2* relaxation time mean 35.1 msec ± 7.1 [normal >20 msec], mean ± SD iron content 0.63± 0.2 mg/g dry weight, range 0.5-1.1). There was no association of cardiac iron content with transfused blood volume, anthracycline dose (mg/m2) or liver iron content (Pearson Correlation Coefficients 0.27, 0.29 and 0.89 respectively). Conclusions: Childhood cancer and BMT patients receive multiple PRBC transfusions to treat symptomatic anemia. It is currently unknown whether excess iron deposition in the heart contributes to the cardiac effects of impaired diastolic function and ultimately systolic dysfunction. In this study, 11 of 18 patients (61.1%) with high levels of liver iron had at least 1 other risk factor for the development of future cardiac dysfunction (either anthracycline exposure, radiation to the chest or total body irradiation or both). Larger studies are needed to determine whether oncology patients with high levels of iron deposition in their liver are also at risk for clinically significant cardiac iron loading, and what risk factors may exist for elevated myocardial iron content.
SARS-CoV2 vaccination response in pediatric oncology patients.
Authors: D'Souza Amber Marie , Gnanamony Manu , Thomas Maria , Nguyen Thu Hien , de Alarcon Pedro Antonio 
Published: June 2023

e22023 Background: There remains limited knowledge about the immune response to SARS-COV2 vaccination in pediatric oncology patients, which is essential to provide appropriate counseling and risk adaptation in this vulnerable population. The goal of this study was to understand immunogenicity after vaccination in pediatric oncology patients and determine if certain clinical factors impacted response. Methods: After institutional review board approval, we consented patients in our clinic who had diagnosis of cancer, were 0-25 years old, and actively receiving therapy, including chemotherapy, immunotherapy, and targeted therapy. We excluded patients who were completely vaccinated prior to their cancer diagnosis. Blood samples were collected pre-vaccination, as well as 2, 6, and 8-12 weeks after vaccination. Healthy children who were fully vaccinated could also consent as controls, with samples collected up to 6 months from vaccination. Demographic data, history of COVID19 infection, and complete blood counts around time of vaccination were collected. To study immunogenicity, we measured neutralizing antibodies by enzyme-linked immunoassay (ELISA, GenScript) and interferon gamma (INFl) secretion, which measures T cell response to viral antigens, by enzyme-linked immunospot (ELISPOT, Mabtech). Results: 16 patients enrolled on study, for which 11 were evaluable along with 7 control patients. Seven patients had acute lymphoblastic leukemia, two had sarcomas, one had chronic myeloid leukemia, and one had Hodgkin lymphoma. Overall, the pediatric oncology patients had a worse immune response to vaccination compared to controls. Only one patient, who had COVID19 prior to vaccination, had similar responses to controls. Patients were divided into inadequate (n = 6) and adequate response (n = 5) based on semiquantitative analysis of immune response at 8-12 weeks post vaccination. Inadequate response was primarily seen in acute lymphoblastic leukemia patients (5 of 6 patients) and those receiving highly cytotoxic chemotherapy. Adequate response was seen in patients receiving oral therapy or chemoimmunotherapy. No patients received steroids around the time of vaccination. The inadequate response group had the lowest absolute lymphocyte counts (ALC), but ALC was variable in the adequate response group. Numbers were too small to note a difference based on age, gender, ethnicity, or type of vaccine. Conclusions: Pediatric oncology patients have a suboptimal immune response to SARS-COV2 vaccination. Malignancy type, therapy modality, and to a lesser extent, ALC at the time of vaccination, are all associated with worse immunogenicity. This study supports the need for additional doses and boosters to provide better protection against COVID19 in pediatric oncology patients.
Rates of colorectal cancer screening versus lung cancer screening: Where does the problem lie?
Authors: Menakuru Sasmith R. , Salih Ahmed , Dhillon Vijaypal S. , Hanna Nasser H. 
Published: June 2023

e22504 Background: In 2021, the U.S. Preventive Services Task Force recommended expanding the population who should undergo routine lung or colorectal cancer screening to include those between 50 and 80, with a 20-pack or more smoking history, and those who are currently smoking or have quit within the last 15 years. According to the Centers for Disease Control, 74.3% of the at-risk population undergo colorectal cancer screening. In contrast, according to the American Lung Association, only 5.8% of the eligible population undergoes lung cancer screening. Methods: This is a retrospective analysis of 158 patients who underwent colorectal cancer screening by colonoscopy between July 2022 and October 2022 at a high-volume hospital in Indiana. Patients were followed up in their primary care office between November 2022 and January 2023 to assess if they had also met the screening criteria for lung cancer with a low dose computed tomography (LDCT) scan. Patients who met the lung screening criteria were interviewed at their subsequent primary care appointment to evaluate their knowledge, attitudes, and compliance with lung cancer screening. Results: Of the 158 participants, 86 (54.4%) met the criteria for lung cancer screening with a LDCT. Only 5 (5.8%) of the eligible subjects underwent LDCT screening. 72 of the 81 patients who were not screened for lung cancer had scheduled follow-ups with their primary care provider during the study time frame. Of these 72 patients, 45 (62.5%) lacked knowledge about LDCT and lung cancer screening, despite meeting the criteria for it. 22 (30.5%) did not think they needed a LDCT, and 5 (6.9%) had no interest in screening despite previous awareness. All 72 patients who had colorectal cancer screening but not lung cancer screening were asked why they underwent the former but not the latter. 68 (94.4%) indicated that colonoscopy was recommended to them and that they knew someone in their families who had it done. Conclusions: Colon cancer screening rates remain high compared to lung cancer screening rates in an at-risk population. A lack of knowledge from patients is the primary reason for not receiving LDCT, despite receiving colon cancer screening.
Skin cancer screening and sun safety education program for high school students in southern California.
Authors: Savage David James , Gilbertson Riley 
Published: June 2023

e22505 Background: Decreasing unprotected exposure to ultraviolet (UV) radiation during childhood can significantly decrease the risk of developing skin cancer as an adult. School-based sun safety curricula have demonstrated efficacy in teaching young adults about the harms of prolonged, unprotected UV exposure and have been effective in increasing safety practices. This project provided a 50-min sun safety curriculum to high school students at a public high school in San Diego, CA just prior to the summer break in 2022. The curriculum addressed skin cancer risk factors, skin protection methods, the benefits of limiting lifetime UV exposure, and methods for performing a skin self exam. The study objective was to assess sun safety knowledge before and after the class, and measure behavior changes three months thereafter when students returned from summer break. Methods: The sun safety classes were taught in groups of 40-60 students across six class periods in June 2022. Students were asked to complete an anonymous pre-participation online survey assessing their knowledge of common skin cancer types and skin cancer risk factors. Students were taught the curriculum over 45 minutes with 5 minutes reserved for questions. Two follow-ups surveys were conducted with the students, one at the end of the class period and a second follow-up three months later. Follow-up surveys assessed retention of knowledge and changes in sun safety behavior. Students had the option of providing a cell phone number so they could be contacted to participate in the second follow-up survey. Results: The curriculum was taught to nine classes of approximately 300 students in a single day across six class periods. A total of 206 students completed the pre-participation survey. At the first follow-up, 95.1% of students completed the post-participation survey and students showed significant improvement in knowledge of common skin cancer types (12.6% pre-participation to 68.9% post-participation), skin cancer risk factors (11.2% pre-participation to 16.8% post-participation), and skin cancer prevention methods (22.8% pre-participation to 45.9% post-participation). For the second follow-up, 128 students provided contact information and the survey had a response rate of 71.5%. After 3 months, students demonstrated retention of knowledge of skin cancer types and risk factors. A majority (87.2%) of students indicated that their use of sunscreen had increased and 57.4% indicated that their use of sun protective barriers had increased over the summer because of this course. Conclusions: This pilot course demonstrates that targeted sun safety education for teenagers before summer break can significantly increase sun safety awareness, adoption of protective behaviors, and knowledge about skin cancer. Such an intervention can promote skin cancer awareness at a young age where behavior changes can decrease lifetime risk of skin cancer.
Breast malignancy after radioactive iodine ablation for thyroid pathology: A systematic review of the literature.
Authors: Yellamaty Victoria , Hamid Yumna , Efiom-Ekaha Daniel N. 
Published: June 2023

e22511 Background: Radioactive Iodine Ablation (RAI) is a procedure in which the administration of radioactive iodine is utilized to eradicate pathologic thyroid tissue. RAI is commonly used for thyroid malignancy and hyperthyroidism. Although RAI has been a mainstay of treatment for these diseases, there has been some controversy regarding the development of secondary primary malignancy after RAI. Breast cancer is a particular concern. As breast cancer is the second most common cancer for women in the United States, understanding its risk factors is a key component of public health. Methods: A systematic review was conducted following PRISMA guidelines. Inclusion criteria consisted of English language studies that evaluated the association between radioactive iodine ablation and secondary primary breast malignancy. The study was conducted from January 2023 until February 2023. Two independent researchers conducted the literature search utilizing PubMed, SCOPUS, JSTOR, and Wiley Library using standardized search terms. The titles and abstracts of these studies were independently screened, and further evaluated for relevancy. Qualitative data was then extracted and summarized. Results: Of the 386 manuscripts retrieved, 27 met inclusion criteria. These studies were published between 1983 – 2022. Of these, 15 articles reported no association between RAI and the development of secondary primary breast malignancy. Of the manuscripts which reported no association, 6 examined RAI for hyperthyroidism, and 9 examined RAI for thyroid malignancy. 12 studies reported an association between RAI and the development of secondary primary breast malignancy. Of the studies reporting an association, 1 examined RAI for hyperthyroidism, and the remaining 11 examined RAI for thyroid malignancy. For the single study that found an association in the case of hyperthyroidism, the researchers found a dose-dependent relationship. Conclusions: The literature surrounding secondary primary breast malignancy after RAI is controversial. This systematic review resulted in conflicting data regarding the association between radioactive iodine ablation for thyroid pathology and the development of secondary primary breast malignancy. The studies that suggested an association between RAI and secondary primary breast malignancy were overwhelmingly studies in which RAI was used for the treatment of thyroid malignancy. Some studies suggest a possible dose-dependent relationship between RAI and secondary primary breast malignancy, however this data is limited. Additional studies would be beneficial to address this gap in the literature.
Obesity and triple negative breast cancer diagnosis among premenopausal women.
Authors: Taylor Caitlin , Sheen Melanie Anne , Cattie Rabia , Chung Victoria , Henry Marcia , Olet Susan , Alberti Matthew , Yuan Helen , Peeples James , Saxena Raina 
Published: June 2023

e22513 Background: Obesity is a known risk factor for the development of postmenopausal breast cancer, specifically hormone-receptor positive breast cancer, and is associated with poor outcomes and decreased overall survival. While obesity in pre-menopausal patients is thought to be protective against the development of breast cancer, application across breast cancer subtypes remains less clear. Methods: We performed a retrospective analysis of 758 patients under 40 years of age diagnosed with breast cancer at our institution over 10 years. Variables including age at diagnosis, breast cancer subtype, race and BMI were evaluated. To assess the association between body mass index (BMI), race and triple negative breast cancer (TNBC), odds ratios (OR) and their associated 95% Confidence interval (CI) OR are reported. Results: Obese patients (BMI >30) were more likely to have TNBC compared with non-obese patients [OR=1.46, 95% CI [1.07 – 2.00), P=0.0161]. Black patients had a twofold likelihood of having TNBC compared with white patients regardless of BMI [OR=2.16, 95% CI [1.56 – 2.97), P<0.0001]. Conclusions: Obese patients under 40 years of age were more likely to be diagnosed with TNBC than non-obese patients. Our data highlights ongoing disparities among TNBC diagnosis and emphasizes the importance of weight loss interventions targeted towards premenopausal women at high risk for breast cancer. [Table: see text]