SLC34A2 Up-regulation And SLC4A4 Down-regulation Correlates With Invasion, Metastasis, And The MAPK Signaling Pathway In Papillary Thyroid Carcinomas.

Papillary thyroid carcinoma (PTC) is one of the fastest growing endocrine system malignant carcinomas detected over the past decade. Unfortunately, more than 25% of PTC patients are characterized by their aggressiveness and subsequent metastasis; these characteristics usually indicate poor prognosis. Recently, increasing evidence has suggested that solute carrier (SLC) transporters may play a pivotal role in the initiation, invasion and metastasis of human carcinoma. However, the expression and clinicopathological significance of SLC transporters in patients with PTC remains undetermined. In this study, we aimed to elucidate how the differential expression of SLC transporters affects clinicopathological features, as well as determine the possible regulatory signaling pathways involved. Three differentially expressed SLC transporters were screened from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database using a bioinformatics approach. The results indicated that high SLC34A2 and low SLC4A4 protein expression exhibited a higher percentage of capsular invasion and extra-thyroid metastasis in patients. Logistic regression analysis showed that high SLC34A2 expression in tumors was identified as an independent risk factor for capsular invasion [odds ratio (OR)=11.400, 95% confidence interval (CI)=1.733-74.995, P=0.011] and extra-thyroid metastasis (OR=4.920, 95%CI=1.234-19.623, P=0.024), while low SLC4A4 expression in tumors was only identified as independent risk factors for extra-thyroid metastasis (OR=8.568, 95%CI =1.186-61.906, P=0.033). Specifically, for tumors with capsular invasion and extra-thyroid metastasis, the protein expression staining of SLC34A2 was markedly enhanced in the cytoplasm of follicular epithelial cells, contrastingly, SLC4A4 expression was notably weakened in the cytomembrane and nucleus. Intriguingly, both high SLC34A2 and low SLC4A4 protein expression were significantly linked to a high urinary iodine concentration in patients with PTC. Mechanistically, compared with adjacent normal thyroids, p-ERK was significantly up-regulated by 17.8% in the invading tumor; p-ERK, p-JNK, and p-P38 were markedly up-regulated by 29.2%, 67.1%, and 38.9% for metastatic tumors, respectively. Importantly, SLC4A4 negatively correlated with p-JNK (r=-0.696, P= 0.004) and p-P38 (r=-0.534, P=0.049). In conclusion, we suggest that up-regulated SLC34A2 (mainly in the cytoplasm) and down-regulated SLC4A4 (mainly in the cytomembrane and nucleus), which might be attributed to excess iodine intake, were closely linked to extra-thyroid metastasis in PTCs. Furthermore, this effect of SLC4A4 may be through the activation of JNK/P38 MAPK signaling pathway. Future in vivo and in vitro gain- or loss-of-function experiments are needed to verify these findings and further elucidate the deeper molecular mechanisms.

Association between excessive chronic iodine exposure and the occurrence of papillary thyroid carcinoma.

The aim of the present study was to elucidate the association between excessive chronic iodine exposure and the risk of developing papillary thyroid carcinoma (PTC). The demographic information and pathological characteristics of patients with thyroid nodules were retrieved from medical records at The Second Hospital of Shandong University. A fasting urine specimen was collected, and creatinine and urinary iodine concentration (UIC) were determined. The water iodine data from the domicile districts of these patients were collated from published reports. The results revealed that almost half of the patients with PTC (44.3%) also exhibited a high UIC (≥300 µg/l). Multivariate analysis revealed that the adjusted odds ratio for high UIC was 3.987 (95% CI: 1.355-11.736) and the adjusted area under the receiver operating characteristic curve was 0.776 (95% CI: 0.687-0.864), which was associated with PTC risk in patients with thyroid nodules. Integrated ecological assessment of chronic iodine exposures demonstrated that >80% (81.4%) of the patients with PTC who also exhibited a high UIC were from historically non-iodine-deficient regions, and 66.7% of patients with PTC who resided in historically iodine-excessive regions were characterized by high UICs. Importantly, a high UIC was significantly associated with capsular invasion and extrathyroid metastasis (P<0.05). Moreover, self-matching results indicated that, in patients with PTC, there were no significant differences in UIC grading between the pre- and postoperative specimens. In conclusion, excessive chronic iodine exposure is significantly associated with the risk of PTC, which contributes to increased capsular invasion and extrathyroid metastases. However, further research is required to validate these findings and to elucidate the potential molecular mechanisms involved.

CTEP Versus LESS Totally Extraperitoneal Hernioplasty.

BACKGROUND AND OBJECTIVES: The authors sought to assess and compare the surgical outcomes of laparoendoscopic single-port surgery (LESS) for totally extraperitoneal (LESS-TEP) hernioplasty and conventional totally extraperitoneal (CTEP) hernioplasty. METHODS: From March 2015 through May 2018, a retrospective analysis of postoperative outcomes was conducted that included 81 cases of LESS-TEP and 88 cases of CTEP hernioplasty patients. For postoperative indicator comparisons, a visual-analog pain scale and 5-level cosmesis evaluation sheet were applied. In addition, complications on postoperative outcomes following inguinal hernia repair surgery are discussed based on our analysis and surgical experience. RESULTS: All operations were successfully performed at different hospitals. Compared with the CTEP group, the operative time in the LESS-TEP group increased significantly (P < .05). However, the cosmetic outcome in the LESS-TEP group was rated higher than that in the CTEP group (P < .05). There was no significant difference between the 2 groups in hospitalization time, the incidence of complications, postoperative pain levels, or medical costs (P > .05). CONCLUSION: LESS-TEP is as feasible and safe as CTEP. The use of LESS-TEP successfully improved the cosmetic outcomes of inguinal hernia repair surgery with smaller and fewer scars for patients. As a new surgical treatment approach for inguinal hernias, the LESS-TEP technique is still not a necessary or efficacious surgical alternative strategy for CTEP, especially for surgeons who are less experienced in the technique.