Update on Pediatric Thyroid Cancer Incidence and Mortality Trends in the United States, 2000-2018.

Thyroid cancer is the most common endocrine malignancy in the pediatric population. A recent study has revealed a recent decline in overall US thyroid cancer incidence rates. The aim of this study is to assess whether there has been a corresponding decline in incidence rates in the pediatric population. We used the Surveillance, Epidemiology, and End Results (SEER) database to analyze the pediatric thyroid cancer incidence rate. The results demonstrate that the incidence rate of pediatric thyroid cancer continued to increase from 2000 to 2018. Future studies are needed to understand how recent changes in guidelines are affecting incidence rates.

Characterization of urethral fibrosis in a rabbit model: Potential roles of Wnt-ß catenin pathway and epithelial to mesenchymal transition.

AIM: To elucidate the precise cellular and molecular mechanisms that underlie urethral fibrogenesis. METHODS: Endoluminal electrocautery injury (using Karl Storz 10 Fr. Pediatric urethroscope) was employed in male rabbits (n = 6) to create mucosal injury. Retrograde urethrogram (RUG) and endoluminal ultrasound techniques were used to assess severity and changes in luminal cross-sectional area. Six control rabbits were subjected to sham injury, in which the electrocautery was inserted but not powered. Urethral tissues were harvested 30 days postinjury and subjected to RNA sequencing and quantitative polymerase chain reaction (qPCR) to determine changes in gene expression. Histological, immunostaining, and Western blot studies were used to determine changes in protein expression of known markers of fibrosis (eg, collagen, Integrinαv, GIV/Girdin, transforming growth factor-ß (TGF-ß), and pSMAD1,2,3). RESULTS: Trichrome staining confirmed increased connective tissue in urethral scar tissues. Immunostaining revealed a potential role for epithelial to mesenchymal cell transition (EMT) and positive labeling for all fibrotic markers (eg, collagen-1, Integrin αv, GIV/Girdin, transforming growth factor-ß (TGF-ß), and SMAD1,2,3). Western blot analysis confirmed increased protein levels of these fibrotic markers. CONCLUSION: Our RNA sequencing and qPCR studies, in conjunction with our protein data, suggest that urethral mucosal fibrogenesis may be mediated by novel fibrogenic signaling pathways involving Wnt-ß catenin, TGF-ß, GIV/Girdin, and EMT which lead to increased collagen deposition. Therapeutic strategies targeting these pathways may be beneficial in attenuating fibrogenesis and stricture progression.

Brain metastases from esophageal cancer: A retrospective review from a single institution.

PURPOSE: Patients with brain metastases (BrM) from esophageal cancer have poor prognosis, the incidence of which is expected to rise due to improved survival from the primary tumor and increased neuroimaging. We aimed to identify patient and esophageal cancer characteristics associated with shorter survival in patients with BrM and, secondly, to compare the prognosis of patients with HER2 overexpression. METHODS: We retrospectively reviewed patients with BrM from esophageal cancer at a single institution from 2008-2021. We collected patient demographics, primary tumor and BrM characteristics, and treatment. Our primary outcome was median survival from the time of BrM. RESULTS: The median age at primary diagnosis was 66.5 years and 86% were male. Of the 49 patients, 71% had adenocarcinoma, 20% squamous cell carcinoma and 8% other. 71% of patients presented with stage III or IV disease, including 16% with synchronous primary and BrM. The median time to BrM was 10.1 months (IQR 1.7-22.8) and the median survival from BrM was 8.4 months (95%CI 4.8-16.8). On multivariable analysis, treatment with stereotactic radiosurgery (HR=0.19;p=0.04), surgical resection (HR 0.24;p=0.03) and immunotherapy (HR 0.19;p=0.04) were associated with increased survival while KPS ≤70 (HR=13.2;p<0.001) was associated with decreased survival. HER2 overexpression was found in 22% of patients, but we noted no survival difference (5.2 months HER2+ versus 9.8 months HER2neg;p=0.95). CONCLUSION: The median survival from esophageal-to-brain metastasis was 8.4 months. Patients with a single lesion, KPS score >70, and treatment with surgical resection was correlated with improved survival. Further, HER2+ patients had distinct patient and BrM characteristics.

Induction of Airway Hypersensitivity to Ovalbumin and Dust Mite Allergens as Mouse Models of Allergic Asthma.

Mouse models of allergic asthma have been utilized to establish the role of T helper type 2 (Th2) cells in driving lung inflammation, airway hyperresponsiveness, and obstruction. Here, we present the allergic asthma models, in which mice are hypersensitized to ovalbumin (OVA) and house dust mite (HDM). These models mimic the major characteristics of human asthma including the eosinophilic inflammation and hyperactivity of the airway, overproduction of Th2 cytokines in the lung, and elevated total and allergen-specific immunoglobulin E (IgE) in serum.

Evaluation of Age- and Radical-Prostatectomy Related Changes in Male Pelvic Floor Anatomy Based on Magnetic Resonance Imaging and 3-Dimensional Reconstruction.

PURPOSE: Puborectalis muscles (PRM) and ischiocavernosus muscles (ICM) play important roles in urinary continence and male erectile functions. Understanding of anatomy and surgical-injury related changes to these muscles is critical to monitor changes in continence or erectile function. Anatomical description of these muscles has undergone revisions because these conclusions were derived from cadavers. Our objectives were to: (i) elucidate male pelvic muscles by in-vivo magnetic resonance imaging (MRI) and 3-dimensional (3-D) reconstruction of these images and (ii) compare PRM and ICM thickness in healthy volunteers and symptomatic patients. MATERIALS AND METHODS: Healthy young male (mean age, 25 years; n=5), older male (age, 65-70 years; n=5), and post-prostatectomy patients with erectile dysfunction and urinary incontinence (age, 65-70 years; n=5) were scanned on a 3T-magnetic resonance scanner. Images were acquired from slices above urinary bladder base to urethra entry into penis. Pelvic bone, bladder/urethra, corpus cavernosum, ICM, PRM, and prostate were segmented. 3-D models of each structure were generated and assembled into composite images, and ICM and PRM thicknesses were calculated. RESULTS: We successfully reconstructed 3-D male pelvic floor anatomy including ICM, PRM, bladder, urethra, bulbospongiosus, corpus cavernosa, prostate and bones from the two groups. We documented significant reduction in PRM and ICM thickness in older men. CONCLUSIONS: This is perhaps the first 3-D reconstruction of male pelvic floor structures based on in-vivo MRI in healthy and symptomatic patients. Observed reduction in PRM and ICM thickness is possibly due to age-related atrophy.

MicroRNAs and Their Targetomes in Tumor-Immune Communication.

The development of cancer is a complex and dynamically regulated multiple-step process that involves many changes in gene expression. Over the last decade, microRNAs (miRNAs), a class of short regulatory non-coding RNAs, have emerged as key molecular effectors and regulators of tumorigenesis. While aberrant expression of miRNAs or dysregulated miRNA-mediated gene regulation in tumor cells have been shown to be capable of directly promoting or inhibiting tumorigenesis, considering the well-reported role of the immune system in cancer, tumor-derived miRNAs could also impact tumor growth through regulating anti-tumor immune responses. Here, we discuss howmiRNAs can function as central mediators that influence the crosstalk between cancer and the immune system. Moreover, we also review the current progress in the development of novel experimental approaches for miRNA target identification that will facilitate our understanding of miRNA-mediated gene regulation in not only human malignancies, but also in other genetic disorders.

miRNA-Microbiota Interaction in Gut Homeostasis and Colorectal Cancer.

Gut homeostasis is maintained by dynamic host-microbiota interactions. Recently, miRNAs have emerged as key molecular regulators in the mediation of such interactions. Here, we discuss the role of a host miRNA-microbiome axis in gut homeostasis and colorectal cancer (CRC) and the involvement of diet and microbial metabolites in miRNA-mediated intestinal health.