UTILITY OF ULTRASOUND VERSUS GENE EXPRESSION CLASSIFIER IN THYROID NODULES WITH ATYPIA OF UNDETERMINED SIGNIFICANCE.

OBJECTIVE: Thyroid nodules with fine-needle aspiration (FNA) cytology categorized as atypia of undetermined significance (AUS) often undergo additional diagnostic analysis with the Afirma Gene Expression Classifier (GEC), which classifies these as either high probability of being benign (GEC-B) or suspicious for malignancy (GEC-S). Our goal was to assess the clinical validity and utility of GEC in the evaluation of AUS cytology and evaluate the performance of ultrasonography (USG) for predicting malignancy in this subset. METHODS: We conducted a study with a retrospective cohort of patients from January 2012 to January 2014 who had FNA of thyroid nodules >1 cm in size with AUS cytology. RESULTS: Cleveland Clinic Florida has an overall prevalence of AUS of 5%. A total of 119 cases with nodules >1 cm in size were reported as AUS. Forty-eight (40.3%) had a GEC performed after the first FNA (AUS-1), and 27 of these were GEC-S. Of those 27, 21 went for surgery and 14 (66.6%) had thyroid cancer on histopathology. The remaining 71 with AUS-1 were sent for a second FNA: 19 nodules were benign and did not undergo further evaluation, while the remaining 52 were reported as AUS for the second consecutive time (AUS-2). AUS-2 samples were sent for GEC. Of these 52 AUS-2, 38 (73.1%) were reported as GEC-S. Thirty-five went for surgery and 32 (91.4%) had confirmed malignancy on histopathology. Positive predictive value (PPV) was 91.4% for AUS-2 and 66.6% for AUS-1. Moreover, AUS-2 nodules that were hypoechoic and solid on USG showed a PPV of 92% for malignancy. CONCLUSION: In our practice, the diagnostic accuracy to predict malignancy with GEC for AUS-1 nodules was poor (PPV, 66.6%). The PPV of GEC testing was markedly higher at 91.4% performed after two consecutive AUS cytologies. AUS-2 nodules that were solid and hypoechoic on USG also had a high probability to be malignant (PPV, 92%). We recommend repeat FNA on AUS-1 nodules rather than proceeding directly to GEC testing. Also, we suggest that among AUS-2 nodules, surgery can be recommended when USG shows solid and hypoechoic features with GEC testing reserved for the remainder. ABBREVIATIONS: AUS = atypia of undetermined significance FNA = fine-needle aspiration GEC = gene expression classifier GEC-B = GEC-benign GEC-S = GEC-suspicious for malignancy NPV = negative predictive value PPV = positive predictive value USG = ultrasonography.

SHOULD FNA BE PERFORMED IN PATIENTS WITH A MULTINODULAR GOITER AND COMPRESSIVE SYMPTOMS?

OBJECTIVE: In this study, we aimed to determine whether preoperative thyroid fine-needle aspiration (FNA) in patients with multinodular goiter (MNG) and compressive symptoms influences the type of thyroid surgery performed, the incidence of recurrent thyroid cancer, or the need for successive surgery. METHODS: We retrospectively reviewed the charts of 431 patients who underwent thyroidectomy at our institution from 2008 to 2011. Patients who presented with compressive symptoms and no prior FNA at initial presentation were included in this study. RESULTS: Eighty patients met the criteria for our study, of which 46 (57.5%) underwent FNA prior to surgery and 34 (42.5%) were referred to surgery without FNA. The prevalence rates of malignancy (>1 cm) on surgical pathology in the FNA and non-FNA groups were 41% (n = 19) and 38% (n = 13), respectively. There was no statistically significant difference between the rate of total/subtotal thyroidectomies (71.7% in FNA vs. 79.4% in non-FNA, P = .31), lobectomies/partial thyroidectomies (28.3% in FNA vs. 20.5% in non-FNA, P = .43), neck lymph node dissections (P = .89) or subsequent surgeries (P = .72) between the 2 groups. CONCLUSION: Our findings show that preoperative FNA in patients with an MNG and compressive symptoms does not influence the type of surgery performed, short-term outcomes, or the need for subsequent surgeries. Further studies are needed to validate the need for preoperative FNA in such patients. ABBREVIATIONS: FNA = fine-needle aspiration MNG = multinodular goiter WHO = World Health Organization.

Cardiovascular effects of the DPP-4 inhibitors.

Type 2 Diabetes continues to rise in prevalence throughout the globe, and cardiovascular diseases remain the most common cause of morbidity and mortality among patients. Dipeptidyl-peptidase-4 (DPP-4) inhibitors are a newer class of oral anti-hyperglycemic agents whose effect is mediated through the incretin hormones, GLP-1 and GIP. In this review, we discuss the incretin system, DPP-4 inhibitors and their mechanism of action and, principally, the potential impact of DPP-4 inhibition on the cardiovascular system. Some pre-clinical data, small mechanistic studies and post-hoc analyses of randomized clinical trials suggest a possible beneficial effect on cardiovascular risk. However, the relationship between DPP-4 inhibition and actual cardiovascular outcomes remains unknown. We therefore also review ongoing large, randomized clinical trials examining this very question.