Objective The hobnail variant of papillary thyroid carcinoma (HVPTC) has emerged as a rare and aggressive variant of papillary thyroid carcinoma (PTC). We aim to determine the prevalence and clinicopathologic factors of HVPTC. Methods A systematic review of the literature for studies examining HVPTC was performed. Four databases (PubMed, Scopus, OVID, Cochrane library) were queried from inception of databases through March 20th, 2020. Results Sixteen studies with 124 cases of HVPTC were included. The mean age for all patients was 52.3 years. HVPTC had a prevalence of 1.08% out of all PTC cases, with a mean tumor size of 3.1 cm. In 62% and 50% of cases, lymphovascular invasion and extrathyroidal extension were present, respectively. Follow-up data, with a mean of 49.9 months, revealed a 66% rate of lymph node metastasis and 23% rate of distant metastasis. Tumors with ≥30% hobnail morphology had a 2.6-fold increased odds of developing lymph node metastasis compared with <30% hobnail morphology, however did not differ in rates of distant metastasis. Patients ≥55 years old had a 4.5-fold increased odds of distant metastasis and a 4.7-fold increased odds of lymphovascular invasion over patients <55. Conclusions High rates of locoregional and distant disease as well as high-risk pathological factors reveal the aggressive nature of HVPTC. Diagnostic criteria regarding percentage of hobnail morphology requires further refinement. Further studies are warranted in order to better understand how recognition of this high-risk variant impacts clinical treatment.
Objectives: The insulin-like growth factor-1 receptor (IGF1R) has been implicated in therapeutic resistance in head and neck squamous cell carcinoma (HNSCC), and small molecule tyrosine kinase inhibitors (TKIs) of IGF1R activity may have anticancer activity. Therefore, the relationship between survival and IGF1R expression was assessed for oral cavity (OC) cancer, and the antitumor effects of two IGF1R-TKIs, OSI-906 and BMS-754807, were evaluated in HNSCC cell lines in vitro.Methods: Clinical outcome data and tissue microarray immunohistochemistry were used to generate IGF1R expressionspecific survival curves. Immunoblot, alamarBlue proliferation assay, trypan blue exclusion viability test, clonogenic assay, flow cytometry, and reverse phase protein array (RPPA) were used to evaluate in vitro responses to IGF1R-TKIs.Results: For patients with stage III/IV OCSCC, higher IGF1R expression was associated with poorer overall 5-year survival (P = 0.029). Both BMS-754807 and OSI-906 caused dose-dependent inhibition of IGF1R and Akt phosphorylation and inhibited proliferation; BMS-754807 was more potent than OSI-906. Both drugs reduced HNSCC cell viability; only OSI-906 was able to eliminate all viable cells at 10 μM. The two drugs similarly inhibited clonogenic cell survival. At 1 μM, only BMS-754807 caused a fourfold increase in the basal apoptotic rate. RPPA demonstrated broad effects of both drugs on canonical IGF1R signaling pathways and also inhibition of human epidermal growth factor receptor-3 (HER3), Src, paxillin, and ezrin phosphorylation.Conclusion: OSI-906 and BMS-754807 inhibit IGF1R activity in HNSCC cell lines with reduction in prosurvival and proliferative signaling and with concomitant antiproliferative and proapoptotic effects. Such antagonists may have utility as adjuvants to existing therapies for HNSCC.
Objective Given the lack of evidence on patients with medically refractory vestibular migraine, this study aimed to identify factors associated with pharmacotherapy failure and progression to botulinum toxin injection in vestibular migraine. Methods A retrospective cohort study was conducted on definite vestibular migraine patients from September 2015 to July 2019 who completed the Dizziness Handicap Inventory at least six weeks apart.. Results The study comprised 47 patients (mean age = 50.2 ± 15.8 years), with a mean follow-up time of 6.0 ± 6.0 months. The mean pre-treatment Dizziness Handicap Inventory score was 57.5 ± 23.5, with a mean reduction of 17.3 ± 25.2 (p < 0.001) at last follow up. Oscillopsia (r = 0.458, p = 0.007), failure of first medication (r = 0.518, p = 0.001) and pre-treatment Dizziness Handicap Inventory question 15 (an emotional domain question) score (r = 0.364, p = 0.019) were the only variables significantly correlated with progression to botulinum toxin injection. Conclusion Motion hypersensitivity, failure of first medication, and fear of social stigmatisation suggest a decreased treatment response. These symptoms may require more aggressive treatment at an earlier stage.
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