Assessment of Radiofrequency Ablation for Papillary Microcarcinoma of the Thyroid: A Systematic Review and Meta-analysis.

IMPORTANCE: Papillary microcarcinomas of the thyroid (mPTCs) account for an increasing proportion of thyroid cancers in past decades. The use of radiofrequency ablation (RFA) has been investigated as an alternative to surgery. The effectiveness and safety of RFA has yet to be determined. OBJECTIVE: To evaluate the effectiveness and safety of RFA for low-risk mPTC. DATA SOURCES: Embase, MEDLINE via Ovid, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and the top 100 references of Google Scholar were searched from inception to May 28, 2021. STUDY SELECTION: Articles reporting on adult patients with mPTC treated with RFA were included. Studies that involved patients with pre-ablation lymph node or distant metastases, recurrence of disease, or extrathyroidal extension were excluded. Final article selection was conducted by multiple reviewers based on consensus. The proportion of eligible articles was 1%. DATA EXTRACTION AND SYNTHESIS: This meta-analysis was conducted in accordance with the MOOSE guidelines. Random and fixed-effect models were applied to obtain pooled proportions and 95% CIs. MAIN OUTCOMES AND MEASURES: The primary outcome was the complete disappearance rate of mPTC. Secondary outcomes were tumor progression and complications. RESULTS: Fifteen studies were included in this meta-analysis. A total of 1770 patients (1379 women [77.9%]; mean [SD] age, 45.4 [11.4] years; age range, 42.5-66.0 years) with 1822 tumors were treated with RFA; 49 tumors underwent 1 additional RFA session and 1 tumor underwent 2 additional RFA sessions. Mean (SD) follow-up time was 33.0 (11.4) months (range, 6-131 months). The pooled complete disappearance rate at the end of follow-up was 79% (95% CI, 65%-94%). The overall tumor progression rate was 1.5% (n = 26 patients), local residual mPTC in the ablation area was found in 7 tumors (0.4%), new mPTC in the thyroid was found in 15 patients (0.9%), and 4 patients (0.2%) developed lymph node metastases during follow-up. No distant metastases were detected. Three major complications occurred (2 voice changes lasting >2 months and 1 cardiac arrhythmia). Minor complications were described in 45 patients. CONCLUSIONS AND RELEVANCE: The findings of this systematic review and meta-analysis suggest that RFA is a safe and efficient method to treat selected low-risk mPTCs. Radiofrequency ablation could be envisioned as step-up treatment after local tumor growth under active surveillance for an mPTC or initial treatment in patients with mPTCs with anxiety about active surveillance.

The Human Glycoprotein Salivary Agglutinin Inhibits the Interaction of DC-SIGN and Langerin with Oral Micro-Organisms.

Salivary agglutinin (SAG), also known as gp340 or SALSA, is a glycoprotein encoded by the Deleted in Malignant Brain Tumours 1 gene and is abundantly present in human saliva. SAG aggregates bacteria and viruses, thereby promoting their clearance from the oral cavity. The mucosa lining the oral cavity contains dendritic cells (DC) and Langerhans cells (LC), which express the C-type lectin receptors (CLR) DC-SIGN and Langerin, respectively. Both DC-SIGN and Langerin recognise mannose and fucose carbohydrate structures on pathogens and self-glycoproteins to regulate immunity and homeostasis. The purpose of this study was to investigate whether SAG interacts with these CLR and whether this interferes with the binding to oral pathogens. We show that whole parotid saliva and SAG, when coated to microplates, strongly interact with DC-SIGN and Langerin, probably via mannose and fucose structures. Also, primary human DC and LC bind parotid saliva and SAG via DC-SIGN and Langerin, respectively. Furthermore, SAG binding to DC-SIGN or Langerin prevented binding to the micro-organisms Candida albicans and Escherichia coli which express mannose and fucose-containing glycan structures. Thus, binding of saliva glycoprotein SAG to DC-SIGN and Langerin may inhibit pathogen-DC/LC interactions, and could prove to be a new immunomodulatory mechanism of SAG.

Complement activation by salivary agglutinin is secretor status dependent.

After mucosal damage or gingival inflammation, complement proteins leak into the oral cavity and mix with salivary proteins such as salivary agglutinin (SAG/gp-340/DMBT1). This protein is encoded by the gene Deleted in Malignant Brain Tumors 1 (DMBT1), and it aggregates bacteria, viruses and fungi, and activates the lectin pathway of the complement system. In the lectin pathway, carbohydrate structures on pathogens or altered self cells are recognized. SAG is highly glycosylated, partly on the basis of the donor's blood group status. Whereas secretors express Lewis b, Lewis y, and antigens from the ABO-blood group system on SAG, non-secretors do not. Through mannose-binding lectin (MBL) binding and C4 deposition assays, we aimed to identify the chemical structures on SAG that are responsible for complement activation. The complement-activating properties of SAG were completely abolished by oxidation of its carbohydrate moiety. SAG-mediated activation of complement was also inhibited in the presence of saccharides such as fucose and Lewis b carbohydrates, and also after pretreatment with the fucose-binding lectin, Anguilla anguilla agglutinin. Complement activation was significantly (p<0.01) higher in secretors than in non-secretors. Our results suggest that fucose-rich oligosaccharide sidechains, such as Lewis b antigens, are involved in the activation of complement by SAG.