The benefits of prophylactic central neck dissection (pCND) remain controversial in clinically node-negative (cN0) papillary thyroid carcinoma (PTC). The purpose of this study was to investigate the clinical impact of pCND with a large group of cN0 PTC patients. A total of 11,569 cN0 PTC patients who underwent thyroidectomy between January 1997 and June 2015 were investigated. Using Cox multivariate analysis, the prognostic impact of pCND was assessed using subset analyses according to various clinicopathologic conditions. Using propensity score matching, various surgical morbidities were assessed under adjusted conditions. Of 11,569 cN0 PTC patients, 8,735 (75.5%) underwent pCND. Prophylactic CND did not significantly decrease the risk of locoregional recurrence in cN0 PTC patients (adjusted hazard ratio [HR] = 0.874; p = 0.392). In addition, pCND did not significantly decrease the risk of locoregional recurrence in various surgical extents (lobectomy and ipsilateral pCND [adjusted HR = 0.636; p = 0.131], total thyroidectomy and ipsilateral pCND [adjusted HR = 0.775; p = 0.164], and total thyroidectomy and bilateral pCND [adjusted HR = 1.041; p = 0.821]). However, surgical morbidities, such as temporary vocal cord palsy (5.6% vs 2.5%; p = 0.001), temporary hypoparathyroidism (30.8% vs 16.7%; p < 0.001), and permanent hypoparathyroidism (3.5% vs 1.7%; p < 0.001) were significantly more frequent in the pCND(+) group. Given the lack of proven benefits and the clear evidence of morbidities, pCND cannot be recommended as a routine procedure. We suggest that CND be reserved for therapeutic situations.

Tumor necrosis factor (TNF)-α is one of the pro-inflammatory cytokines highly expressed in Helicobacter pylori that inhibits gastric acid secretion. In this study we determined the effect of silibinin on TNF-α-induced MMP-9 expression in gastric cancer cell lines. MMP-9 mRNA and protein expression was dose-dependently increased by TNF-α in SNU216 and SNU668 gastric cancer cells. On the other hand, TNF-α-induced MMP-9 expression was dose-dependently suppressed by silibinin. To verify the regulatory mechanism of silibinin on TNF-α-induced MMP-9 expression, the gastric cancer cell lines were pretreated with silibinin prior to TNF-α. TNF-α-induced MMP-9 expression was inhibited by the MEK1/2 specific inhibitor, UO126. Finally, we investigated the effect of adenoviral constitutively active (CA)-MEK and CA-Akt on MMP-9 expression. The expression of MMP-9 was significantly increased by CA-MEK overexpression, but not by CA-Akt overexpression. Taken together, we suggest that silibinin down-regulates TNF-α- induced MMP-9 expression through inhibition of the MEK/ERK pathway in gastric cancer cells.

The use of radioactive iodine (RAI) ablation in patients with intermediate-risk papillary thyroid carcinoma (PTC) who show microscopic extrathyroidal extension (ETE), regional lymph node (LN) metastasis, tumors with aggressive histology, or vascular invasion has been debated due to the lack of data regarding long-term prognosis in this risk group. Therefore, the purpose of this study was to resolve the controversy surrounding the prognostic benefit of RAI ablation, especially in intermediate-risk PTC patients. We retrospectively reviewed the medical records of 8297 intermediate-risk PTC patients who underwent primary total thyroidectomy with or without neck dissection at the Thyroid Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, between January 1997 and June 2015. Of these 8297 patients, 7483 (90.2%) received RAI ablation. After adjusting for clinicopathological characteristics, RAI ablation did not significantly decrease the risk of loco-regional recurrence (LRR) (adjusted hazard ratio (HR) 0.852, P 0.413). Moreover, RAI ablation did not decrease the risk of LRR even in intermediate-risk PTC patients with aggressive features such as BRAF positivity (adjusted HR 0.729, P 0.137), tumor size >1 cm (adjusted HR 0.762, P 0.228), multifocality (adjusted HR 1.032, P 0.926), ETE (adjusted HR 0.870, P 0.541), and regional LN metastasis (adjusted HR 0.804, P 0.349). Furthermore, high-dose RAI ablation (>100 mCi) did not significantly decrease the risk of LRR (adjusted HR 0.942, P 0.843). Therefore, RAI ablation in intermediate-risk PTC patients should be considered on the basis of tailored risk restratification.