BRAF V600E as an accurate marker to complement fine needle aspiration (FNA) cytology in the guidance of thyroid surgery in the Chinese population: evidence from over 1000 consecutive FNAs with follow-up.

BACKGROUND: Currently, several commercial molecular tests have been developed for reclassifying thyroid nodules with indeterminate fine needle aspiration cytology. These tests are quite expensive and not available in China. Previous studies demonstrated a very high prevalence of the BRAF V600E mutation in Asian people. A high incidence may result in a robust sensitivity. We conducted this study to determine the prevalence of BRAF V600E mutation and its ability to reclassify cytologically indeterminate thyroid nodules in the Chinese population. METHODS: Between January 2016 and October 2018, consecutive patients who underwent a fine needle aspiration procedure and agreed to provide materials for molecular analysis in our hospital were recruited in this study. All were followed up until they had a thyroidectomy and a final pathological diagnosis or until January 2019 (those did not have surgery). RESULTS: A total of 1960 patients were included in this study. Until January 2019, 1240 patients underwent surgery. Using histopathological diagnosis as a gold standard, the overall sensitivity and specificity of the BRAF V600E mutational analysis for the discrimination of benign nodules from cancer in thyroid fine needle aspiration samples were 83.3% (81.0-85.3%) and 96.0% (77.7-99.8%), respectively, with an area under the ROC curve of 0.90 (95% CI 0.85-0.95, P < 0.001). Among cases with indeterminate cytology, BRAF-positive cases were showing malignancy in the final pathology, and BRAF-negative cases were showing safer to be followed up. CONCLUSION: The BRAF V600E mutation is highly prevalent in the Chinese population and can accurately complement cytopathology in the guidance of thyroid surgery.Mini-abstract: The BRAF V600E mutation has both high specificity and sensitivity to predict thyroid malignancy in the Chinese population. It can accurately complement cytopathology in the guidance of thyroid surgery.

Safety of central compartment neck dissection for transoral endoscopic thyroid surgery in papillary thyroid carcinoma.

BACKGROUND: Remote access and endoscopic thyroid surgery has been gaining popularity because it allows patients to avoid a visible scar in the neck. There is limited data on transoral endoscopic thyroidectomy when it relates to patients with papillary thyroid carcinoma. We aim to evaluate the safety of ipsilateral central compartment dissection for patients who undergo transoral thyroidectomy (thyroidectomy vestibular approach-compartment lymph node dissection). PATIENTS AND METHODS: A total of 80 patients who underwent thyroidectomy vestibular approach-compartment lymph node dissection for papillary thyroid carcinoma from June 2015 to September 2016 were identified. Over the same period, a matched cohort of 80 patients who underwent open thyroidectomy with routine ipsilateral central compartment dissection was also identified (Open-compartment lymph node dissection). The two groups were analyzed in terms of patient characteristics, perioperative clinical results and post-operative outcomes. RESULTS: All patients were female with a mean age of 32-year. There was no difference in mean maximum tumor size and number of lymph nodes dissected. Moreover, there was no difference in average positive lymph nodes between thyroidectomy vestibular approach-compartment lymph node dissection and Open-compartment lymph node dissection (1.48 vs 1.08, P = 0.647). Operative time was longer in the thyroidectomy vestibular approach-compartment lymph node dissection group (193 vs 102 min, P < 0.001). Thyroidectomy specific complications were similar with rates of temporary recurrent laryngeal nerve palsy of 6.3 vs 8.8% and temporary hypocalcemia rates of 2.5 vs 5% in the thyroidectomy vestibular approach-compartment lymph node dissection and Open-compartment lymph node dissection groups, respectively. CONCLUSIONS: Thyroidectomy vestibular approach-compartment lymph node dissection is a feasible and safe option for select patients with papillary thyroid carcinoma who require central node dissection compared with Open-compartment lymph node dissection, and can be a viable alternative for patients wishing to avoid a visible scar.

Defining a New Tumor Dimension in Staging of Papillary Thyroid Carcinoma.

BACKGROUND: Cervical lymph node metastasis is a vital factor associated with local recurrence in papillary thyroid carcinoma (PTC). Tumor size is used in the staging of PTC because it represents the tumor load. This study compared two methods of tumor size assessment to predict tumor behavior in the relationship between size and cervical node involvement for patients with PTC. METHODS: The study enrolled 1084 patients who underwent initial thyroid surgery and had a pathologic diagnosis of PTC between 2012 and 2014 at The Second Affiliated Hospital Zhejiang University School of Medicine. Cervical lymph node metastasis (LNM) risk was analyzed according to the clinicopathologic features. For each patient with multifocal disease, two tumor size estimates were used: (1) the dominant focus size and (2) the aggregate size, calculated as the sum of the maximal diameters of all tumor foci. RESULTS: Of the 1084 patients, 294 (27.1%) had multifocal cancer lesions, and 49% of these patients had cervical LNM, compared with 38.1% who had unifocal disease (P = 0.001). The use of aggregate dimension significantly increased the tumor size and reclassified significant numbers of multifocal PTCs to a more advanced T stage. This aggregate dimension took account of all tumor foci and predicted LNM risk at a proportion identical with that for size-matched, unifocal tumors. CONCLUSION: Multifocality together with aggregate tumor size is a more accurate predictor of node status and, by inference, tumor behavior in the relationship between tumor size and cervical node involvement.

"Scarless" (in the neck) endoscopic thyroidectomy (SET) with ipsilateral levels II, III, and IV dissection via breast approach for papillary thyroid carcinoma: a preliminary report.

BACKGROUND: Endoscopic thyroidectomy with level II dissection has previously been reported to be performed endoscopically via various approaches. However, very few reports were available regarding level II dissection performed via the breast approach. In this article, we reported a series of 12 papillary thyroid carcinoma (PTC) patients with scarless (in the neck) endoscopic thyroidectomy (SET) via breast approach to level II dissection and evaluated its feasibility and safety. METHODS: Between January 2011 and March 2013, 12 PTC female patients with suspected lymph node metastasis at level II, III, or IV were selected for this procedure. After completing thyroidectomy and central compartment dissection, dissection of ipsilateral levels II, III, and IV was performed. The steps of endoscopic lateral neck dissection were similar to those of conventional surgery except that the lateral cervical compartment was exposed by splitting the sternocleidomastoid muscle (SCM) longitudinally and dividing between the strap muscles and the anterior margin of the SCM. RESULTS: This procedure was carried out in all of the 12 patients (Table 1). Mean operative time was 243 min (range 165-355 min). Nine patients (75 %) had lymph node metastasis in the lateral compartment confirmed on the final pathological report. Mean lymph node yield (LNY) in the lateral compartment (including ipsilateral level II, III, and IV dissection) was 21.8 (range 5-42). Five patients (41.6 %) had lymph node metastasis in the ipsilateral level II. The mean LNY in the ipsilateral level II was 6.7 (range 1-14). In 1 of the 12 patients, bleeding from injury to the internal jugular vein in level II was encountered intraoperatively, and a 4-cm upper neck transverse incision was made to stop the bleeding. Average postoperative hospital stay was 5.0 days (range 3-7 days). Table 1 Original article on endoscopic lateral neck dissection (including level II) by other authors Author (Ref.) Year Mean age (years) Tumor size (cm) No. of patients M:F Tech. Type of operation Mean LNY in lateral zone Mean operative time (min) Postoperative bleeding Chyle leakage Mean PHS (days) Wu et al. [13] 2013 43.2 1.88 26 6:20 VAT SLND 8.3 137.7 None None 3.6 Lee et al. [8] 2013 40.2 1.39 62 5:57 Robot MRND 32.8 271.8 None None 6.9 Kang et al. [5] 2012 35.8 1.14 56 10:46 Robot MRND 31.1 277.4 1 5 6 Kang et al. [6] 2011 NA NA 36 NA Robot MRND 27.7 280.91 1 3 NA Kang et al. [4] 2009 NA NA 13 NA AP MRND/SLND 18.8 286 NA NA 5.3 Current article 31.2 1.67 12 0:12 SET SLND 21.8 243 None None 5 Ref. references, No. number, M male, F female, Tech. technique, LNY lymph node yield, PHS postoperative hospital stay, VAT video-assisted thyroidectomy, SLND selective lateral neck dissection, MRND modified radical neck dissection, AP axillary approach, NA not available CONCLUSIONS: According to the present SET data, level II dissection by SET was a feasible and safe procedure. With reasonable costs and satisfactory cosmetic results, oncoplastic SET via breast approach might gain wider acceptance in the near future.

[Three-dimensional total endoscopic thyroidectomy for thyroid carcinoma: a series of 32 cases].

OBJECTIVE: To summarize the experiences of applying three-dimensional (3D) technique in scarless endoscopic thyroidectomy (SET) via anterior chest approach. METHODS: Medical records of patients who undenvent SET using 3D technique from December 2013 to May 2014 were retrospectively reviewed. A total of 32 patients who had a preoperative ultrasound-guided fine-needle aspiration cytology diagnosis of unilateral papillary thyroid carcinoma and underwent lobectomy associated with central lymph node dissection were included in this study. All patients were female with a mean age of (37 ± 10) years at diagnosis. In addition, 45 female patients who underwent traditional endoscopic thyroidectomy at the same period were randomly selected as control. RESULTS: All surgical procedures were successfully finished. The mean surgical time in 3D group was (91. 7 ± 11. 4) minutes, and mean hospitalization time was (3. 2 ± 0. 5) days. Contemporary hoarseness was observed in one patient, and no bleeding, infection, hypocalcemia and other postsurgical complications were observed. Compared to the traditional endoscopic surgery group, 3 D group had significantly shorter surgical time of lobectomy ((23. 2 ± 5. 1) minutes vs. (28. 0 ± 5. 0) minutes, t = 4. 156, P = 0. 000). Negative results were seen in the time taking of creating surgical space ((14. 6 ± 3. 3) minutes vs. (15. 6 ± 2. 5) minutes), central lymph node dissection ((25. 1 ± 5. 4) minutes vs. (24. 4 ± 6. 3) minutes) and total surgical time ((91.7 ± 11. 4) minutes vs. (96. 1 ± 13. 0) minutes). CONCLUSION: Application of 3D technique in endoscopic surgery can offer 3D vision of the surgical field, thus significantly shorten lobectomy time and more easily to achieve fine dissection and functional protection of recurrent laryngeal nerves, parathyroids and other vital anatomic structures.

Genetic variation in the major mitotic checkpoint genes and risk of breast cancer: a multigenic study on cancer susceptibility.

The mitotic checkpoint system is a mechanism essential for maintaining genomic stability and defects which have been linked to cancer development. We conducted this hospital-based case-control study to investigate whether genetic variants in three major spindle checkpoint genes (BUB3, MAD2L1, and BUB1) had any bearing on an individual risk of breast cancer (BC). A total of 462 incident BC patients and 529 cancer-free controls were enrolled in this study. Results showed that neither variants in BUB3 nor variants in MAD2L1 caused any significant effect on the risk of BC. However, the variant rs12623473 in BUB1 was significantly associated with increased BC risk with the odds ratio (OR) of 1.30 (95 % confidence interval (CI) 1.03-1.64) under the allelic model. The estimated population attributable risk of one copy of the risk allele for developing BC was 10.3 %. The bioinformatics analysis suggested that this variant may regulate the transcriptional ability of BUB1.

Association between polymorphisms within the susceptibility region 8q24 and breast cancer in a Chinese population.

Recent publications have found associations between single-nucleotide polymorphisms (SNPs) in 8q24 and the risk of breast cancer (BC) in some populations, but the conclusions are inconsistent. In order to further investigate the association between variants in this region and BC risk in Chinese population, we conducted an independent hospital-based case-control study to discern the effects of these SNPs on BC risk. We genotyped three 8q24 SNPs (rs13281615, rs6983267, and rs9642880) in 485 cases and 530 cancer-free controls. The results indicated that the rs13281615 G allele significantly increased BC risk, with an odds ratio (OR) of 1.23 (95% confidence interval (CI) = 1.03-1.46) under the allelic model. Besides, stratification analysis reported that the significant association remained in the estrogen receptor (ER)+/progesterone receptor (PR)+ subgroup with a P value of 0.007 under the allelic model (OR = 1.33, 95% CI = 1.08-1.63). For the rs9642880 variant, only a feeble association was observed for the GT genotype compared with the GG genotype (OR = 1.33, 95% CI = 1.01-1.74). In addition, there was a negligible association between rs6983267 and BC risk in the ER-/PR- subgroup. However, no significant finding was observed in the overall participants. The findings suggested that polymorphisms in 8q24 may contribute to susceptibility to BC risk. However, functional studies are warranted to further elucidate the mechanisms of the association.

Multifocality and total tumor diameter predict central neck lymph node metastases in papillary thyroid microcarcinoma.

PURPOSE: To identify the subgroup of high-risk papillary thyroid microcarcinoma (PTMC) inclined to lymph node metastasis (LNM). METHODS: Patients who underwent total thyroidectomy with central neck dissection and had a pathologic diagnosis of PTMC between 2003 and 2010 at Wuhan Union Hospital were identified. The frequency of LNM was retrospectively analyzed according to the clinicopathological features. For multifocal lesions, total tumor diameter (TTD) was calculated as the sum of the maximal diameter of each lesion. Last, a meta-analysis was performed with respect to multifocality and LNM in the PTMCs. RESULTS: The proportion of LNM was similar between multifocal PTMCs with TTD ≤ 1 cm and unifocal tumors with diameter ≤ 1 cm (37.5 vs. 30%, P = 0.463). LNM frequency was also similar between multifocal PTMCs with 1 < TTD ≤ 2 cm (TTD greater than 1 cm but less than or equal to 2 cm) and unifocal tumors with 1 < diameter ≤ 2 cm (56.8 vs. 64.9%, P = 0.330). However, LNM frequency was significantly higher in multifocal PTMCs with TTD > 1 cm than unifocal tumors with diameter ≤ 1 cm (60.4 vs. 30%, P < 0.001). A meta-analysis of nine publications plus our own data with a total 1,586 PTMCs demonstrated that multifocality was significantly associated with LNM risk (odds ratio 1.9, 95% confidence interval 1.5-2.4). CONCLUSIONS: Multifocal PTMC with TTD > 1 cm has a similar risk of LNM as a clinical papillary cancer. Routine central neck dissection is recommended in this subgroup of patients.

Clinicopathological features of breast cancer with different molecular subtypes in Chinese women.

A retrospective study was performed to explore the relationship between molecular subtypes and clinicopathological features of breast cancer in Chinese women. Six hundred and twenty-eight Chinese women with breast cancer were classified into four molecular subtypes according to their estrogen receptor (ER), progesterone receptor (PR) and Her-2 status. The prevalence rate of each molecular subtype was analyzed. Relationship between the subtypes and clinicopathologic features was determined. The distribution of molecular subtypes was as follows: luminal A 46.5%, luminal B 17.0%, basal 21.5%, HER2/neu 15.0%. The subtypes had no significant difference under different menopausal status. However, in the age-specific groups, the age group of ≤35 years was more likely to get basal cell-like cancer (36.9%). Statistically significant differences were found among molecular subtypes by age, nuclear grade, tumor size, lymph node (LN) metastasis, tumor stage by American Joint Committee on Cancer (AJCC), radiotherapy but not by chemotherapy, types of surgery. After adjusting for several relative confounding factors, the basal subtype more likely had lower nodal involvement in both the incidence of LN metastasis (≥1 positive LN) and incidence of high-volume LN metastasis (≥4 positive LN). The HER2/neu subtype had higher nodal involvement in the incidence of high-volume LN metastases. After adjusting for relative confounding factors, the HER2/neu subtype more likely had higher AJCC tumor stages. It was suggested that there existed close relationship between molecular subtypes and clinicopathological features of breast cancer. In addition, the breast cancer subtypes have been proven to be an independent predictor of LN involvement and AJCC tumor stage. These findings are very important for understanding the occurrence, development, prognosis and treatment of breast cancer in Chinese population.

Individual and combined effects of MDM2 SNP309 and TP53 Arg72Pro on breast cancer risk: an updated meta-analysis.

The tumor suppressor gene TP53 and its negative regulator murine double minute 2 are involved in multiple cellular pathways. Two potentially functional single nucleotide polymorphisms (SNPs) MDM2 SNP309 and TP53 R72P have been extensively investigated to be associated with breast cancer risk. However, the original studies as well as the subsequent meta-analysis, have yielded contradictory results for the individual effect of the two SNPs on breast cancer risk, plus that conflicting results also existed for the combined effects of MDM2 SNP309 and TP53 R72P on breast cancer risk. This meta-analysis aimed to clarify the individual and combined effects of these two genes on breast cancer risk. We performed a meta-analysis of publications with a total 9,563 cases and 9,468 controls concerning MDM2 SNP309 polymorphism and 19,748 cases and 19,962 controls concerning TP53 R72P. Odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of the association. In overall meta-analysis, individuals with the MDM2 SNP309TG genotype were associated with a borderline higher breast cancer risk than those with TT genotype (OR = 1.11, 95 % CI: 1.00-1.24, P (heterogeneity) = 0.007), whereas the TP53 R72P CC or GC genotype had no effects on breast cancer risk. In the stratified analyses, a significant association between MDM2 SNP309 and breast cancer risk were observed in Asian, but null significant association between TP53 R72P and breast cancer risk were found even in various subgroups. Moreover, no significant combined effects of MDM2 SNP309 and TP53 R72P were observed on breast cancer risk. The borderline association between MDM2 SNP309 and breast cancer risk in overall analysis should be treated with caution, and no significant combined effects for the two SNPs on breast cancer risk suggested functional investigations warranted to explore the molecular mechanism of the TP53-MDM2 circuit genes.

Micropatterned Poly(D,L-Lactide-Co-Caprolactone) Conduits With KHI-Peptide and NGF Promote Peripheral Nerve Repair After Severe Traction Injury.

Severe traction injuries after stretch to peripheral nerves are common and challenging to repair. The nerve guidance conduits (NGCs) are promising in the regeneration and functional recovery after nerve injuries. To enhance the repair of severe nerve traction injuries, in this study KHIFSDDSSE (KHI) peptides were grafted on a porous and micropatterned poly(D,L-lactide-co-caprolactone) (PLCL) film (MPLCL), which was further loaded with a nerve growth factor (NGF). The adhesion number of Schwann cells (SCs), ratio of length/width (L/W), and percentage of elongated SCs were significantly higher in the MPLCL-peptide group and MPLCL-peptide-NGF group compared with those in the PLCL group in vitro. The electromyography (EMG) and morphological changes of the nerve after severe traction injury were improved significantly in the MPLCL-peptide group and MPLCL-peptide-NGF group compared with those in the PLCL group in vivo. Hence, the NGCs featured with both bioactive factors (KHI peptides and NGF) and physical topography (parallelly linear micropatterns) have synergistic effect on nerve reinnervation after severe traction injuries.

Thyroid paraganglioma accompanied by lymph node metastasis or trachea invasion: A case report.

Thyroid paraganglioma (TP) is an uncommon neuroendocrine tumor with potential for misdiagnosis. Case 1 (male; 44 years old) presented with hoarseness for 3 months. A 2.5-cm gray nodule in the left thyroid was diagnosed as TP by immunohistochemistry. Lymph node metastasis was confirmed by H&E staining and immunohistochemistry. The patient was followed-up for 3 years without any signs of recurrence or metastasis. Case 2 (female; 39 years old) presented with an asymptomatic but rapidly growing thyroid nodule. The patient underwent thyroidectomy 8 years ago (2008) and was diagnosed with TP postoperatively. The patient was diagnosed with recurrence and exhibited trachea invasion. Thyroidectomy and partial trachea resection were performed. A literature review revealed that 62 other cases of TP have been reported, and most of them exhibited low malignant potential. However, the two cases presented in the current case report exhibited a high malignant potential, accompanied by lymph node metastasis or trachea invasion, and these features imply that the choice of treatment for patients should be based on their different degrees of malignancy.

The patterns and treatment of postoperative hemorrhage and hematoma in total endoscopic thyroidectomy via breast approach: experience of 1932 cases.

PURPOSE: Postoperative hemorrhage and hematoma formation is a potentially lethal complication in thyroid surgery, although the patterns and treatment of hemorrhage after total endoscopic thyroidectomy (TET) via breast approach has not been reported previously. We aim to share our experience about postoperative bleeding. METHODS: A retrospective analysis of 1932 patients who underwent TET from April 2008 to May 2018 in our institution was carried out. The patterns of postoperative hemorrhage and hematoma formation that need surgical treatment were summarized and focused on the relation to the source of bleeding and the time interval between first surgery and hemorrhage. Related risk factors were analyzed by univariate or multivariate analysis processes. RESULTS: The overall rate of hemorrhage and hematoma occurrence was only 0.724% (14 in 1932 patients). Of them, 12 occurred in the first 24 h after surgery, and the other two occurred after withdrawal of the drainage tube. The principle independent risk factors for postoperative hemorrhage and hematoma were age (older than 35 years old) and lateral compartment dissection (LCD) revealed by multivariate regression. During re-exploration, obvious bleeding points were detected in 13 patients. Among them, 12 bled from the vessels in the main trocar cavity and another 1 bled from a broken vein located between the two heads of the sternocleidomastoid (SCM) muscle with LCD. CONCLUSIONS: Hemorrhage after TET usually occurs within 24 h, and the main video trocar cavity was the area most likely to bleed. Age and LCD may increase the bleeding risk. Appropriate dissection level is the main solution to prevent postoperative hemorrhage.

Transoral endoscopic thyroid surgery via the tri-vestibular approach with a hybrid space-maintaining method: A preliminary report.

BACKGROUND: Transoral endoscopic thyroid surgery has been introduced in a few institutions. The purpose of this study was to present an innovative hybrid space-maintaining method for the tri-vestibular approach. METHODS: Eighteen consecutive patients underwent transoral endoscopic thyroidectomy. Three incisions were made in the vestibule. The surgical space was maintained with CO2 insufflation along with a suspension device. Thyroidectomy and central neck dissection (CND) were performed safely and effectively. RESULTS: The mean operation time was 124 minutes for a simple lobectomy, subtotal thyroidectomy, and isthmectomy in 8 patients, 172 minutes for hemithyroidectomy with ipsilateral CND in 8 patients, and 205 minutes for total thyroidectomy with ipsilateral CND in 7 patients. Transient superior laryngeal nerve (SLN) injury occurred in 3 patients and transient mental nerve injury was found in 1 patient. No evidence of recurrence or metastasis was found at follow-up. CONCLUSION: This approach brings satisfactory cosmetic effect along with minimal invasion. Further study is needed to verify its validity.

Fine-Needle Aspiration Versus Frozen Section in the Evaluation of Malignant Thyroid Nodules in Patients With the Diagnosis of Suspicious for Malignancy or Malignancy by Fine-Needle Aspiration.

CONTEXT: - The Bethesda System for Reporting Thyroid Cytopathology recommends against the use of intraoperative frozen section (FS) during lobectomy of a thyroid nodule with a fine-needle aspiration (FNA) diagnosis of malignant. Bethesda recommendations for FS in the FNA category of suspicious for malignancy (SFM) is less well-defined. In some institutions in China, FS examination is performed during lobectomy even for FNA-proven malignant cases. OBJECTIVE: - -To compare the efficacy of FNA versus FS in the evaluation of malignant thyroid lesions. DESIGN: - A 3-year retrospective analysis from a single institution was performed on cases with an FNA diagnosis of SFM or malignant with subsequent FS examination during thyroidectomy. The results of FNA and FS findings were compared to the final thyroidectomy pathology. RESULTS: - -A total of 5832 thyroidectomy procedures were performed: 1265 cases had FNA and FS results available. Fine-needle aspiration gave a diagnosis of SFM to 306 cases and a diagnosis of malignant to 821 cases. Of the SFM cases, 10.5% (32 of 306) had benign/indeterminate, 4.6% (14 of 306) suspicious, and 84.9% (260 of 306) malignant FS results. Final pathology showed 56.3% (18 of 32), 64.3% (9 of 14), and 100% (260 of 260) malignancy rates, respectively. For the malignant FNA group, 10.0% (82 of 821) had benign/indeterminate, 4.4% (36 of 821) suspicious, and 85.6% (703 of 821) malignant FS results. The final pathology showed 96.4% (79 of 82), 97.2% (35 of 36), and 99.9% (702 of 703) malignancy rates, respectively. CONCLUSIONS: - Frozen section should not be performed for the malignant FNA category because FS evaluation may result in 10% falsely negative findings. Performing FS for SFM may be better justified; however, more than half of FS cases read as benign in this category had malignant final pathology. Therefore, caution should be taken for FS results even in the SFM group.

LncRNA-SLC6A9-5:2: A potent sensitizer in 131I-resistant papillary thyroid carcinoma with PARP-1 induction.

Recent studies have indicated that long non-coding RNAs play crucial roles in numerous cancers, including thyroid cancer, while their function in the mechanism of thyroid cancer 131I resistance has not been elucidated to date. The present study identified a functional long non-coding RNA, SLC6A9-5:2, which was involved in the radioactive therapy resistance of thyroid cancer. We demonstrated that SLC6A9-5:2 was remarkably downregulated in 131I-resistant thyroid cancer cell lines and 131I-insensitive patients and was positively correlated with Poly (ADP-ribose) polymerase 1 (PARP-1) expression and its activation. After downregulating SLC6A9 or blocking PARP-1 artificially, the sensitive thyroid cancer cells mostly displayed a tolerant phenotype under 131I exposure. Furthermore, SLC6A9-5:2 overexpression was positively correlated with PARP-1 mRNA and protein levels, which restored the sensitivity of resistant thyroid cancer cells. The present study further revealed that cancer cell death was primarily caused by ATP exhaustion in excessive DNA repair with high PARP-1 activity. In patients with thyroid cancer, a positive correlation between SLC6A9-5:2 and PARP-1 was identified, and low SLC6A9-5:2 expression was associated with a worse prognosis of papillary thyroid carcinoma. Hence, our data provide a new lncRNA-mediated regulatory mechanism implying that SLC6A9-5:2 can be used as a novel therapeutic target for 131I-resistant thyroid cancer.

Thyroid dysfunction, either hyper or hypothyroidism, promotes gallstone formation by different mechanisms.

We have investigated comprehensively the effects of thyroid function on gallstone formation in a mouse model. Gonadectomized gallstone-susceptible male C57BL/6 mice were randomly distributed into three groups each of which received an intervention to induce hyperthyroidism, hypothyroidism, or euthyroidism. After 5 weeks of feeding a lithogenic diet of 15% (w/w) butter fat, 1% (w/w) cholesterol, and 0.5% (w/w) cholic acid, mice were killed for further experiments. The incidence of cholesterol monohydrate crystal formation was 100% in mice with hyperthyroidism, 83% in hypothyroidism, and 33% in euthyroidism, the differences being statistically significant. Among the hepatic lithogenic genes, Trß was found to be up-regulated and Rxr down-regulated in the mice with hypothyroidism. In contrast, Lxrα, Rxr, and Cyp7α1 were up-regulated and Fxr down-regulated in the mice with hyperthyroidism. In conclusion, thyroid dysfunction, either hyperthyroidism or hypothyroidism, promotes the formation of cholesterol gallstones in C57BL/6 mice. Gene expression differences suggest that thyroid hormone disturbance leads to gallstone formation in different ways. Hyperthyroidism induces cholesterol gallstone formation by regulating expression of the hepatic nuclear receptor genes such as Lxrα and Rxr, which are significant in cholesterol metabolism pathways. However, hypothyroidism induces cholesterol gallstone formation by promoting cholesterol biosynthesis.

Implementation of Intraoperative Neuromonitoring for Transoral Endoscopic Thyroid Surgery: A Preliminary Report.

BACKGROUND: Transoral endoscopic approach is the natural orifice surgery applied in thyroidectomy to achieve an excellent cosmetic result. Recurrent laryngeal nerve (RLN) injury is the most common complication and little advancement was achieved in the previous clinical studies of transoral thyroid surgery. Herein, we introduced the method of intraoperative neuromonitoring (IONM) for transoral endoscopic thyroid surgery. MATERIALS AND METHODS: Patients with thyroid carcinoma received transoral endoscopic thyroid surgery through vestibular approach (TOETVA) for thyroidectomy and central node dissection (CND). IONM was implemented to identify whether the RLN benefited from oral tracheal intubation. The laryngeal electromyography (EMG) response, operation time, number of CND, drainage volume, hospital duration, surgical complications, and cosmetic results were evaluated. RESULTS: From August to October 2015, 10 cases were performed with TOETVA and IONM. All EMG responses were recorded intraoperatively, and no case experienced transient or permanent RLN palsy. The operation time ranged from 130 to 215 minutes in ipsilateral lobectomy with CND, whereas bilateral lobectomy with ipsilateral CND lasted 345 minutes. The number of CNDs ranged from three to eight. The average time of drainage extubation and discharge was 4 days (3-5 days) postoperatively. All patients were satisfied with the cosmetic results, and no infection was observed at lip wound or in the anterior neck region. CONCLUSION: IONM system implemented in transoral thyroid surgery was feasible and serviceable in preventing RLN injury. The method of TOETVA shows promise for thyroidectomy with CND due its ideal cosmetic results.

A common polymorphism near the ESR1 gene is associated with risk of breast cancer: evidence from a case-control study and a meta-analysis.

BACKGROUND: Genome-wide association studies have reported that a polymorphism near the estrogen receptor gene (ESR1) (rs2046210) is associated with a risk of breast cancer, with the A allele conferring an increased risk. However, considering the controversial results from more recent replicated studies, we conducted a case-control study in an independent Chinese Han population and a meta-analysis to clarify the association of this polymorphism with breast cancer risk. METHOD AND FINDINGS: A hospital-based case-control study including 461 cases and 537 controls from a Chinese Han population was conducted initially, and this study showed that the rs2046210 A allele was significantly associated with breast cancer risk, with an OR of 1.32 (95% CI  = 1.10-1.59). Subsequently, a meta-analysis integrating the current study and previous publications with a total of 53,379 cases and 55,493 controls was performed to further confirm our findings. Similarly, a significant association between this polymorphism and breast cancer risk was also observed in the overall population especially among Asians, with ORs for per A allele of 1.14 (95% CI  = 1.10-1.18) in the overall population and 1.27 (95% CI  = 1.23-1.31) in the Asian population. CONCLUSION: Our results provide strong evidence to support that the common polymorphism near the ESR1 gene, rs2046210, is associated with an increased risk of breast cancer in Asian and European populations but not in Africans, although the biological mechanisms need to be further investigated.