Intraoperative neuromonitoring (IONM) has been a commonly used technology during thyroid surgery aimed at reducing the incidence of recurrent laryngeal nerve palsy (RLNP), which is a severe complication and leads to significant impacts on a patient's life. In order to give a comprehensive assessment for potential benefits and disadvantage of IONM, this meta-analysis and systematic review discusses RLNP rate, predictive power, continuous intraoperative neuromonitoring (CIONM), and emphasises application during thyroid cancer surgeries. A literature search was performed in the following electronic databases: PubMed, Embase, and the Cochrane library from January 1, 2004 to July 30, 2016. After applying inclusion and exclusion criteria, 24 studies, including four prospective randomised trials, were selected. Heterogeneity of studies was checked by the Cochran Q test. Publication bias was assessed by funnel plots with Egger's linear regression test of asymmetry. Odds ratio (OR) was calculated by random effects model. Overall, 9203 patients and 17,203 nerves at risk (NAR) were included. Incidence of overall, transient, and persistent RLNP in IONM group were, respectively, 3.15%, 1.82%, and 0.67%, whereas for the ID group, they were 4.37%, 2.58%, and 1.07%. The summary OR of overall, transient, and persistent RLNP compared using IONM and ID were, respectively, 0.81 (95%CI 0.66-0.99), 0.76 (95%CI 0.61-0.94), and 0.78 (95%CI 0.55-1.09). The presented data showed benefits of reducing RLNP rate by using IONM, but without statistical significance for persistent RLNP rate. For patients with thyroid cancer who undergo total thyroidectomy, using IONM may improve the outcome by reducing amount of residual thyroid tissue. However, no benefits were found for thyroid reoperation; visual identification and careful dissection remain standard for this challenging procedure. In addition, the relative low positive predictive power indicated intermittent intraoperative neuromonitoring (IIONM) may not be reliable; but CIONM was showed to be a more promising method, with prudent approach.

Recently, some single-institution studies have reported risk factors of CLNM in cN0 PTC patients, but results from those studies are not consistent. The meta-analysis aimed to identify some risk factors that can be predictive of CLNM in cN0 PTC patients. We performed a systematic search for relevant literature published prior to December 2015 using the following search engines: PubMed, EMBASE, Ovid and Web of Science. We included retrospective, prospective, and observational studies that investigated the risk factors for CLNM in patients with cN0 PTC. Thirty-one studies, including 37,355 patients with cN0 PTC from seven countries were included in the meta-analysis. The pooled analysis indicated that age10 mm (OR = 2.61, 95%CI:2.27-3.00, P < 0.001), bilaterality (OR = 1.52, 95%CI:1.31-1.77, P < 0.001), multifocality (OR = 1.46, 95%CI: 1.31-1.61, P < 0.001), extracapsular invasion (OR = 2.10, 95%CI:1.81-2.43, P < 0.001), angiolymphatic invasion (OR = 8.02, 95%CI:5.00-12.87, P < 0.001), high histologic risk (OR = 2.62, 95%CI:2.13-3.22, P < 0.001) and BRAF(V600E) mutation (OR:1.78, 95%CI:1.38-2.30, P < 0.001) were significantly associated with CLNM, and upper third location (OR = 0.54, 95%CI:0.43-0.67, P < 0.001) and lymphocytic thyroiditis (OR = 0.64, 95%CI:0.42-0.97, P = 0.034) were decreased risk factors of CLNM. We identified several predictive factors for CLNM in cN0 PTC patients. Some certain risk factors could be considered in preoperative clinical decision regarding the necessity of prophylactic central lymph node dissection in cN0 PTC patients.

Background: The goal of this study was to identify the clinicopathological factors of co-existing papillary thyroid cancer (PTC) in patients with Hashimoto’s thyroiditis (HT) and provide information to aid in the diagnosis of such patients. Methods: This study included 6109 patients treated in a university-based tertiary care cancer hospital over a 3-year period. All of the patients were categorised based on their final diagnosis. Several clinicopathological factors, such as age, gender, nodular size, invasive status, central compartment lymph node metastasis (CLNM) and serum thyroid-stimulating hormone (TSH) level, were compared between the various groups of patients. Results: There were 653 patients with a final diagnosis of HT. More PTC was found in those with HT (58.3%; 381 of 653) than those without HT (2416 of 5456; 44.3%; p < 0.05). The HT patients with co-occurring PTC were more likely to be younger, be female, have smaller nodules and have higher TSH levels than those without PTC. A multivariate analysis indicated that the presence of HT and higher TSH levels were risk factors for a diagnosis of PTC. In the PTC patients, the presence of HT or another benign nodule was a protective factor for CLNM, whereas no significant association was found for TSH levels. Conclusion: PTC and HT have a close relationship in this region of highly prevalent HT disease. Based on the results of our study, we hypothesise that long-term HT leads to elevated serum TSH, which is the real risk factor for thyroid cancer.

Background: tRNA-derived small noncoding RNAs (sncRNAs) are mainly categorized into tRNA halves (tiRNAs) and fragments (tRFs). Biological functions of tiRNAs in human solid tumor are attracting more and more attention, but researches concerning the mechanisms in tiRNAs-mediated tumorigenesis are rarely. The direct regulatory relationship between tiRNAs and splicing-related proteins remain elusive. Methods: Papillary thyroid carcinoma (PTC) associated tRNA fragments were screened by tRNA fragments deep sequencing and validated by qRT-PCR and Northern Blot in PTC tissues. The biological function of tRNA fragments were assessed by cell counting kit, transwells and subcutaneous transplantation tumor of nude mice. For mechanistic study, tRNA fragments pull-down, RNA immunoprecipitation, Western Blot, Immunofluorescence, Immunohistochemical staining were performed. Results: Herein, we have identified a 33 nt tiRNA-Gly significantly increases in papillary thyroid cancer (PTC) based on tRFs & tiRNAs sequencing. The ectopic expression of tiRNA-Gly promotes cell proliferation and migration, whereas down-regulation of tiRNA-Gly exhibits reverse effects. Mechanistic investigations reveal tiRNA-Gly directly bind the UHM domain of a splicing-related RNA-binding protein RBM17. The interaction with tiRNA-Gly could translocate RBM17 from cytoplasm into nucleus. In addition, tiRNA-Gly increases RBM17 protein expression via inhibiting its degradation in a ubiquitin/proteasome-dependent way. Moreover, RBM17 level in tiRNA-Gly high-expressing human PTC tissues is upregulated. In vivo mouse model shows that suppression of tiRNA-Gly decreases RBM17 expression. Importantly, tiRNA-Gly can induce exon 16 splicing of MAP4K4 mRNA leading to phosphorylation of downstream signaling pathway, which is RBM17 dependent. Conclusions: Our study firstly illustrates tiRNA-Gly can directly bind to RBM17 and display oncogenic effect via RBM17-mediated alternative splicing. This fully novel model broadens our understanding of molecular mechanism in which tRNA fragment in tumor cells directly bind RNA binding protein and play a role in alternative splicing.

Although papillary thyroid cancer (PTC) has a good prognosis, its recurrence rate is high and remains a core concern in the clinic. Molecular factors contributing to different recurrence risks (RRs) remain poorly defined. Here, we perform an integrative proteogenomic and metabolomic characterization of 102 Chinese PTC patients with different RRs. Genomic profiling reveals that mutations in MUC16 and TERT promoter as well as multiple gene fusions like NCOA4-RET are enriched by the high RR. Integrative multi-omics analyses further describe the multi-dimensional characteristics of PTC, especially in metabolism pathways, and delineate dominated molecular patterns of different RRs. Moreover, the PTC patients are clustered into four subtypes (CS1: low RR and BRAF-like; CS2: high RR and metabolism type, worst prognosis; CS3: high RR and immune type, better prognosis; CS4: high RR and BRAF-like) based on the omics data. Notably, the subtypes display significant differences considering BRAF and TERT promoter mutations, metabolism and immune pathway profiles, epithelial cell compositions, and various clinical factors (especially RRs and prognosis) as well as druggable targets. This study can provide insights into the complex molecular characteristics of PTC recurrences and help promote early diagnosis and precision treatment of recurrent PTC.