Complication rates associated with thyroid surgery can be evaluated only through analysis of case studies and follow-up data. This study covers postoperative data from 14,934 patients subjected to a follow-up of 5 years. Among them, 3130 (20.9%) underwent total lobectomy (TL), 9599 (64.3%) total thyroidectomy (TT), 1448 (9.7%) subtotal thyroidectomy with a monolateral remnant (MRST), and 757 (5.1%) subtotal thyroidectomy with bilateral remnants (BRST). A total of 6% of the patients had already been operated on. Persistent hypoparathyroidism occurred after 1.7% of all the operations, and temporary hypoparathyroidism was noted in 8.3%. Permanent palsy of the laryngeal recurrent nerve (LRN) occurred in 1.0% of patients, transient palsy in 2.0%, and diplegia in 0.4%. The superior laryngeal nerve was damaged in 3.7%; dysphagia occurred in 1.4% of cases, hemorrhage in 1.2%, and wound infection in 0.3%. No deaths were reported. A significant rate of LRN damage was noted, which has an important impact on the patient's social life. Hypoparathyroidism after total thyroidectomy is an important complication that can be successfully treated by therapy, although it is not always easily managed in special circumstances such as in young persons or pregnant women. The complications associated with thyroid surgery must be kept in mind so the surgeon can carefully evaluate the surgical and medical therapeutic options, have more precise surgical indications, and be able to give the patient adequate information.

The document includes recommendations regarding initial evaluation of thyroid nodules, clinical and ultrasound criteria for fine-needle aspiration biopsy, initial management of thyroid cancer including staging and risk assessment, surgical management, radioiodine remnant ablation, and levothyroxine therapy, short-term and long-term follow-up strategies, and management of recurrent and metastatic disease. The objective of this consensus is to inform clinicians, patients, researchers, and health policy makers about the best strategies (and their limitations) relating to the diagnosis and treatment of differentiated thyroid cancer.

2b Laryngoscope, 126:1260-1266, 2016.

BAG3 downmodulates the apoptotic response to TRAIL in human neoplastic thyroid cells. The protein is specifically expressed in thyroid carcinomas and not in normal thyroid tissue or goiter.

Functional inactivation of the tumor suppressor p27(kip1) in human cancer occurs either through loss of expression or through phosphorylation-dependent cytoplasmic sequestration. Here we demonstrate that dysregulation of the PI3K/AKT pathway is important in thyroid carcinogenesis and that p27(kip1) is a key target of the growth-regulatory activity exerted by this pathway in thyroid cancer cells. Using specific PI3K inhibitors (LY294002, wortmannin, and PTEN) and a dominant active AKT construct (myrAKT), we demonstrated that the PI3K/AKT pathway controlled thyroid cell proliferation by regulating the expression and subcellular localization of p27. Results obtained with phospho-specific antibodies and with transfection of nonphosphorylable p27(kip1) mutant constructs demonstrated that PI3K/AKT-dependent regulation of p27(kip1) mislocalization in thyroid cancer cells occurred via phosphorylation of p27(kip1) at T157 and T198 (but not at S10 or T187). Finally, we evaluated whether these results were applicable to human tumors. Analysis of 100 thyroid carcinomas indicated that p27(kip1) phosphorylation at T157/T198 and cytoplasmic mislocalization were preferentially associated with activation of the PI3K/AKT pathway. Thus the PI3/AKT pathway and its effector p27(kip1) play major roles in thyroid carcinogenesis.

BACKGROUND: Thyroid fine-needle aspiration (FNA) is a reliable and cost-effective diagnostic tool for establishing the nature of thyroid nodules, although up to 30% of FNAs are still classified as "indeterminate." Molecular testing of FNAs could improve preoperative diagnosis, thereby reducing unnecessary surgery. In this multicenter prospective study the authors investigated, using a 7-gene assay, the distribution and diagnostic impact of BRAF, RAS, RET/PTC, and PAX8/ PPARg, the most frequent genomic alterations occurring during thyroid oncogenesis. METHODS: In total, of 1172 routine FNAs from 7 centers in southern Italy were classified according to the Bethesda System for Reporting ThyroidCytopathology. Each specimen was tested, and molecular data were compared with available histology or cytologic follow-up. RESULTS: In particular, for atypia of undetermined significance/follicular lesion of undetermined significance cases, the 7-gene test confirmed the high positive predictive value of BRAFV600E and BRAF-like mutations (80%) and the moderate positive predictive value of RAS-like alterations (32.4%), suggesting different surgical management, depending on the type of mutation. The rate of mutation-positive FNAs was strictly related to the risk of malignancy of each diagnostic class, supporting the identification of prognostically relevant diagnostic categories. CONCLUSIONS:The 7-gene panel test improves the preoperative risk stratification of indeterminate thyroid FNAs, especially when considering the biologic significance of the different types of mutations. Moreover, the rate of mutation-positive FNAs is related to the risk of malignancy of each diagnostic class.

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