Impact of major different variants of papillary thyroid microcarcinoma on the clinicopathological characteristics: the study of 1041 cases.

BACKGROUND: The incidence of papillary thyroid microcarcinoma (PTMC) has been increasing globally in the past few decades. PTMC does not have a distinctive morphology that results in differences in biological behavior. The aim of this study was to classify PTMCs according to the morphological features and explore the relationship with clinicopathological characteristics. Additionally, we sought to evaluate whether different variants of PTMC can be an independent predictor for lymph mode metastasis when considering other risk factors. METHODS: Between December 2014 and December 2015, 1041 PTMC cases undergoing surgical resection at Tianjin Medical University Cancer Institute and Hospital were reviewed retrospectively. Statistical analysis was performed to investigate the independent factors for lymph node metastasis in PTMC. RESULTS: Conventional variant PTMC (CPTMC), follicular variant PTMC (FPTMC), and encapsulated variant PTMC (EnPTMC) were major variants in PTMC, collectively accounting for 96.7% of the entire PTMC cohort.There were significant differences in clinicopathological characteristics among the three major variants. The frequency of aggressive parameters was significantly different among the three variants, including tumor size, minimal extrathyroidal extension (minimal ETE), and lymph node metastasis (all P < 0.05), being highest in CPTMC, lowest in EnPTMC, and intermediate in FPTMC. FPTMC (OR = 0.642, P = 0.003) and EnPTMC (OR = 0.540, P = 0.041) were independent protective factors for lymph node metastasis (LNM). In contrast, male gender (OR = 1.836, P = 0.000), age less than 45 years (OR = 1.457, P = 0.009), tumor size greater than 0.5 cm (OR = 1.453, P = 0.007), calcification (OR = 1.465, P = 0.016), minimal ETE (OR = 1.801, P = 0.001), and multifocality (OR = 1.721, P = 0.000) were independent risk factors for LNM. CONCLUSIONS: The present study demonstrates the distinct biological behaviors of the three major PTMC variants and establishes an aggressive order of CPTMC â‰« FPTMC > EnPTMC. It is necessary to take into consideration variant-related risks and other independent predictors for the determination of lymphadenectomy in patients with PTMC.

Loss of PTEN Expression Is Associated With High MicroRNA 24 Level and Poor Prognosis in Patients With Tongue Squamous Cell Carcinoma.

PURPOSE: The aim of this study was to detect the relationship between phosphatase and tensin homolog deletion on chromosome 10 (PTEN) and microRNA 24 (miR-24) and correlate PTEN expression with important clinical parameters of patients with tongue squamous cell carcinoma (TSCC). MATERIALS AND METHODS: In this retrospective case series, all TSCC patients treated at Tianjin Medical University Cancer Institute and Hospital between March 2005 and October 2011 were retrospectively reviewed. Demographic information and clinical data (histologic type, clinical stage, tumor differentiation, and so on) were collected. The miR-24 level was detected by quantitative reverse transcription-polymerase chain reaction. The PTEN level was analyzed by immunohistochemistry and quantitative reverse transcription-polymerase chain reaction. Data analyses were performed by Spearman correlation analysis, Pearson χ2 test, and paired t test. Kaplan-Meier curves, log-rank analyses, and a Cox proportional hazards model were used to evaluate the prognostic value of PTEN. RESULTS: A total of 90 patients (aged 59.4 ± 9.5 years, 53 men and 37 women) were identified. Loss of PTEN expression was detected in 27 of 90 tumors (30%)" in both occurrences [corrected]. The PTEN messenger RNA level was negatively correlated with the miR-24 level (r = -0.569, P < .01). PTEN expression also was negatively correlated with the miR-24 level (r = -0.621, P < .01). Furthermore, PTEN expression was significantly lower in cancer tissues than in adjacent normal tissues, and its expression was negatively correlated with clinical stage (P < .01) and positively correlated with differentiation (P < .05) in TSCC patients. In addition, the Kaplan-Meier curve indicated that loss of PTEN expression resulted in poor survival of TSCC patients (P < .01). Multivariate analysis indicated that PTEN expression level and clinical stage may be independent prognostic factors for TSCC patients. CONCLUSIONS: This study suggested that PTEN expression was negatively correlated with the miR-24 level in TSCC. The loss of PTEN expression may serve as a predictor of unfavorable prognosis for TSCC patients.

[Clinical and biological features of familial nonmedullary thyroid carcinoma].

OBJECTIVE: To analyze the clinical and biological features of familial nonmedullary thyroid carcinoma (FNMTC). METHODS: Clinical data of 66 FNMTC cases of 32 pedigrees was retrospectively analyzed, compared with that of 182 control cases taken randomly from the patients with sporadic papillary thyroid carcinoma (SPTC), who were diagnosed and treated in Tianjin Cancer Hospital between January 2008 and November 2012. The features of FNMTC of the first and second generations were objectively analyzed. Some data quoted from the literature were also used for the analysis. RESULTS: The median age at diagnosis of all the 66 FNMTC patients was 44 years, and 57 (86.4%) were females. Moreover, 71.2% (47 patients, 23 pedigrees) of the FNMTC patients exhibited a sibling relationship, and 28.8% (19 patients, 9 pedigrees) of the FNMTC patients exhibited a parent-offspring relationship, and 9 cases in the first generation and 10 cases in the second generation. There were significant differences between the FNMTC group and SPTC group in terms of tumor multicentricity, tumor bilaterality, lymph node metastasis, central lymph node metastasis, concomitant chronic thyroiditis and recurrence (P < 0.05). Compared with SPTC, sibling FNMTC presented a higher rate of central lymph node metastasis, while parent-offspring FNMTC showed frequent tumor bilaterality and a higher rate of recurrence (P < 0.05). Besides, patients in the second generation were diagnosed at an earlier age and had a higher male rate, the tumors were more frequently multifocal and bilateral, and had a higher rate of lymph node metastasis. CONCLUSIONS: FNMTC may be more aggressive than SPTC and patients in the second generation may exhibit the "anticipation" phenomenon. It's necessary to make sufficient detailed interrogation and long-term follow-up of the patients and their family for providing individual recommendations for clinical management.

Analysis of Surgical Outcomes in Endoscopic-Assisted Lateral Neck Dissection.

BACKGROUND: Currently, endoscopic-assisted lateral neck dissection (EALND) is performed to reduce postoperative scarring of the anterior neck. This study aimed to compare surgical outcomes between EALND and conventional open lateral neck dissection (COLND) for papillary thyroid carcinoma (PTC) with lateral lymph node metastases (LNM). METHODS: The study reviewed 103 PTC patients who were classified on the basis of surgical type and statistically compared using propensity score matching analysis. RESULTS: The mean operation time is longer, and the cost of surgery is higher in the EALND group than COLND group (all p < 0.05). The numbers of retrieved and positive level II LNs, the rate of level II LNs detection between two groups do not differ significantly (all p > 0.05). The incidence of postoperative neck numbness is lower, and patients are more satisfied with postoperative neck scarring in the EALND group than COLND group (all p < 0.05). The common complications of two groups are transient recurrent laryngeal nerve injury and transient hypoparathyroidism. CONCLUSIONS: EALND is safe and feasible compared with COLND. The incision is more aesthetically satisfactory, which makes EALND a surgical approach for PTC patients with lateral LNM. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2221-2227, 2024.

TET3 Mediates 5hmC Level and Promotes Tumorigenesis by Activating AMPK Pathway in Papillary Thyroid Cancer.

Thyroid cancer is the most common endocrine malignant tumor. The accurate risk stratification and prognosis assessment is particularly important for patients with thyroid cancer, which can reduce the tumor recurrence rate, morbidity, and mortality effectively. DNA methylation is one of the most widely studied epigenetic modifications. Many studies have shown that 5hmC-mediated demethylation played an important role in tumors. The hydroxylation of 5mC is catalyzed by ten-eleven translocation dioxygenase (TET). In this study, we first found that the abnormal expression of 5hmC was closely related to microcarcinoma, multifocal, extraglandular invasion and lymph node metastasis of thyroid carcinoma. Then, we identified TET3 was differentially expressed in thyroid cancers and normal tissues from the TET family. TET3 can promote the proliferation, migration, and invasion of thyroid cancer. TET3-mediated 5hmC can regulate the transcription of AMPK pathway-related genes to activate the AMPK pathway and autophagy and therefore promote PTC proliferation. These findings provide a preclinical rationale for the design of novel therapeutic strategies for this target to improve the clinical outcome of patients with PTC.

Preoperative supplementation of calcitriol and calcium relieves symptom and extent of hypocalcemia in patients undergoing total thyroidectomy and bilateral central compartment neck dissection: A prospective, randomized, open-label, parallel-controlled clinical study.

Background: Hypocalcemia is the most common complication that challenges surgeons performing total thyroidectomy. Conventional postoperative calcium and calcitriol supplement has been reportedly effective; however, a time lag has been reported before taking effect. Therefore, the role of preoperative strategy is yet to be determined. Study design: In this prospective, randomized, open-label, parallel-controlled phase II clinical study (registration number: ChiCTR2200059815), a short-term preoperative administration of calcitriol and calcium was proposed in 210 patients undergoing total thyroidectomy and bilateral central compartment neck dissection. Patients were recruited and randomized (1:1:1) into three groups: (A) combined (preoperative calcitriol and calcium), (B) calcium only (preoperative calcium only), and (C) control (no preoperative intervention). Finally, a total of 172 patients were qualified for final analysis. Results: Our data showed that 16 of 63 patients (25.4%) in the combined group had symptomatic hypocalcemia, whereas more patients from the control group (25 of 57 patients, 43.9%, P = 0.033) had symptomatic hypocalcemia. Further, the postoperative calcium level in the combined group is higher than in the control group (2.15 ± 0.15 vs. 2.09 ± 0.15 mmol/L, P = 0.031). Moreover, patients from the combined group showed lower calcium rates of <2.00 mmol/L (12.7% vs. 28.1%, P = 0.036). Remarkably, compared with the control group, patients with transient hypoparathyroidism in the combined group showed fewer rates for both symptomatic and biochemical hypocalcemia (28.6% vs. 61.1% for symptomatic hypocalcemia; 47.6% vs. 75% for biochemical hypocalcemia). Patients without transient hypoparathyroidism in all three groups showed no significant difference in rates for either symptomatic or biochemical hypocalcemia, indicating that this preoperative strategy is only effective for patients with transient hypoparathyroidism. We did not observe such beneficial effects in patients from the calcium group. Conclusions: Preoperative administration of calcitriol and calcium could reduce symptomatic and biochemical hypocalcemia, especially for those with transient hypoparathyroidism. Moreover, this maneuver could be recommended as a clinical routine in patients undergoing total thyroidectomy and bilateral central compartment neck dissection. Clinical Trial Registration: http://www.chictr.org.cn/edit.aspx?pid=164316&htm=4, identifier ChiCTR2200059815.

[Expression of LOX and MMP-2 in gastric cancer tissue and the effects of LOX and MMP-2 on tumor invasion and metastasis].

OBJECTIVE: To compare the expressions of lysyl oxidase (LOX) and matrix metalloproteinases-2 (MMP-2) in gastric cancer and pericancerous tissues, in gastric cancers with and without lymph node metastasis, and to analyze the effects of LOX and MMP-2 on tumor invasion and metastasis. METHODS: Gastric cancer and pericancerous tissues were collected from 46 patients who underwent surgery. Levels of LOX and MMP-2 mRNA were detected by RT-PCR. Protein abundance of LOX and MMP-2 was examined using Western blot. RESULTS: Expressions of LOX and MMP-2 mRNA, and protein in 46 gastric cancers were significantly higher than that in 46 pericancerous tissues. In gastric cancer with lymph node metastasis, the levels of LOX and MMP-2 mRNA and protein were higher than those in gastric cancers without lymph node metastasis (P < 0.05). In the groups of gastric cancer with lymph node metastasis, expression of LOX was positively correlated with MMP-2 protein expression (P < 0.01). CONCLUSIONS: Expressions of LOX and MMP-2 in gastric cancer tissues are significantly higher than that in pericancerous tissues. The expressions of LOX and MMP-2 in gastric cancer with lymph node metastasis are higher than that in gastric cancer without lymph node metastasis. Expressions of LOX and MMP-2 are positively correlated. The results suggest that LOX and MMP-2 may promote the growth and metastasis of gastric cancer.

[Analysis of variation trends of thyroid cancer treated in Tianjin Cancer Hospital form 1954 to 2009].

OBJECTIVE: To investigate and analyze the variation trends in the pathological composition of thyroid cancer patients treated in Tianjin Cancer Hospital from 1954 to 2009. METHODS: To retrospectively analyze the incidence and clinical features of different pathological types of thyroid cancers in 4342 patients between different time periods from 1954 to 2009. RESULTS: In the four main pathological types of thyroid cancers, the component ratio of papillary thyroid cancer in every period was 68.1%, 78.3%, 81.3%, 82.1%, 85.8%, respectively, while the morbidity of patients with papillary thyroid carcinoma concurrent with Hashimoto's thyroiditis was increased, so was the proportion of tumors in diameter < or = 2 cm. The proportion of follicular thyroid carcinoma and anaplastic thyroid carcinoma was decreasing accordingly; however, the proportion of medullary thyroid carcinoma did not change significantly. CONCLUSIONS: The pathological classification of the thyroid carcinoma patients has significant changes in the 4342 cases treated in our Hospital from 1954 to 2009. The proportion of papillary carcinoma is increased, while that of follicular carcinoma and anaplastic carcinoma is decreased. The reasons might attribute to the improved level of consultations and iodized diet or other factors.

A CRISPR-Cas9-Based Near-Infrared Upconversion-Activated DNA Methylation Editing System.

DNA methylation is a kind of a crucial epigenetic marker orchestrating gene expression, molecular function, and cellular phenotype. However, manipulating the methylation status of specific genes remains challenging. Here, a clustered regularly interspaced palindromic repeats-Cas9-based near-infrared upconversion-activated DNA methylation editing system (CNAMS) was designed for the optogenetic editing of DNA methylation. The fusion proteins of photosensitive CRY2PHR, the catalytic domain of DNMT3A or TET1, and the fusion proteins for CIBN and catalytically inactive Cas9 (dCas9) were engineered. The CNAMS could control DNA methylation editing in response to blue light, thus allowing methylation editing in a spatiotemporal manner. Furthermore, after combination with upconversion nanoparticles, the spectral sensitivity of DNA methylation editing was extended from the blue light to near-infrared (NIR) light, providing the possibility for remote DNA methylation editing. These results demonstrated a meaningful step forward toward realizing the specific editing of DNA methylation, suggesting the wide utility of our CNAMS for functional studies on epigenetic regulation and potential therapeutic strategies for related diseases.

Analysis of differential BRAF(V600E) mutational status in high aggressive papillary thyroid microcarcinoma.

Papillary thyroid cancers often occur as microcarcinoma. Some papillary thyroid microcarcinoma (PTMC) have been considered to be high aggressive according to advanced disease stages, extrathyroidal extension, and severe cervical lymph node metastasis. Although several factors are thought to predict the occurrence of aggressiveness from PTMCs, the origin of aggressiveness has been rarely studied. To answer this question, the correlation between BRAF(V600E) mutation and high aggressive PTMCs was investigated. The clinicopathological characteristic of totally 64 cases of PTMCs was investigated and the BRAF(V600E) mutational status of them was identified. BRAF(V600E) mutation was exclusively detected in PTMCs (37.5%). The data provided no correlation between the occurrence of BRAF(V600E) mutations and clinicopathological parameters, such as sex, age, and tumor-like lesions combination. The prevalence of BRAF(V600E) mutation of PTMCs with high aggressiveness (advanced disease stages, extrathyroidal extension, and nodal metastasis) was significantly higher (p < 0.05) than that of PTMCs without aggressive behavior. The BRAF(V600E) mutated PTMCs exhibited signs of higher aggressiveness than PTMCs without the mutation. BRAF(V600E) mutation may be a marker of high aggressiveness in PTMCs.

High expression of NUCB2 promotes papillary thyroid cancer cells proliferation and invasion.

BACKGROUND: NUCB2, a novel multifunctional protein containing several functional domains, was newly found to play important roles in many cancers, but its role in papillary thyroid cancer (PTC) is not well investigated. Therefore, our study was performed to explore the functions of NUCB2 in PTC. METHODS: NUCB2 protein level was analyzed by immunohistochemistry. Data analyses were made by performing chi-squared test. Quantitative reverse-transcription PCR, Western blot, colony formation, MTT, and transwell invasion assays were performed to test the expression levels and functions of NUCB2 in PTC. RESULTS: In PTC tissues, NUCB2 protein expression level was positively correlated with extrathyroidal extension, TNM stage, and tumor size of PTC patients. In vitro experiments demonstrated that knockdown of NUCB2 using specific shRNA for NUCB2 significantly impaired cell proliferation and invasion of PTC cell lines. In vivo, silencing of NUCB2 inhibited the growth of tumors in mice. CONCLUSION: These results suggested a novel function of NUCB2 in the process of proliferation and invasion in PTC. NUCB2 may be considered a potent prognostic factor in PTC.

EGFR inhibition enhances the antitumor efficacy of a selective BRAF V600E inhibitor in thyroid cancer cell lines.

BRAF V600E is the most common genetic alteration in thyroid cancer and is indicative of a relatively poor prognosis. A selective inhibitor of BRAF V600E has been proposed as a novel treatment for patients with thyroid cancer exhibiting BRAF V600E mutations. However, this inhibitor has demonstrated a limited therapeutic effect. In the present study, possible adaptive mechanisms of resistance of thyroid cancer cells to the specific BRAF V600E inhibitor, PLX4032, were investigated. MTT assays were performed to determine the anti-proliferative efficiencies and half maximal inhibitory concentration (IC50) of inhibitory treatments. The level of phosphorylated ERK was used to evaluate the activity of the mitogen assisted protein kinase (MAPK) pathway. Flow cytometry was performed to evaluate the rate of apoptosis. The IC50 measurements of PLX4032 in K1 and BCPAP cells were 0.550 and 1.772 µM, respectively. Co-treatment with an endothelial growth factor receptor (EGFR) inhibitor decreased the IC50 of PLX4032 to 0.206 µM, and prolonged the inhibitory effect of PLX4032 in K1 cells. In cells treated with PLX4032 alone, the MAPK pathway was reactivated after 24 h. However, the addition of an EGFR inhibitor suppressed this reactivation and increased the rate of apoptosis. In summary, the present study demonstrated that thyroid cancer harboring the BRAF V600E mutation was resistant to a selective BRAF inhibitor due to reactivation of the MAPK pathway. Co-treatment with an EGFR inhibitor increased antitumor efficacy and suppressed resistance to the BRAF V600E inhibitor.

Suberoyl bis-hydroxamic acid activates Notch1 signaling and induces apoptosis in anaplastic thyroid carcinoma through p53.

Anaplastic thyroid cancer (ATC), usually derived from well-differentiated thyroid cancers is one of the most lethal human endocrine malignancies. In the present study, we report that in human ATC tumor tissue samples exist undetectable Notch1 and the active Notch1 intracellular domain could not be detected in ATC-CAL-62 cells. Interesting, suberoyl bis-hydroxamic acid (SBHA) administration could induce Notch1 intracellular domain levels in a dose-dependent manner, coupled with the increase of p53 and p21. Furthermore, ectopic expression of Notch1 or deletion of p53 with small-interfering RNA was able to abolish the effects of SBHA to elevation of Notch1 and p53 in ATC cells. As a result, SBHA treatment efficiently induced ATC cell apoptosis. These results indicate that SBHA may play antitumor functions via regulating Notch1/p53 signals, and highlight that SBHA could have clinical potential to benefit the therapy of ATC patients.

Case Report of Birt-Hogg-Dubé Syndrome: Germline Mutations of FLCN Detected in Patients With Renal Cancer and Thyroid Cancer.

Birt-Hogg-Dubé (BHD) is a rare autosomal dominant inherited syndrome that is characterized by the presence of fibrofolliculomas and/or trichodiscomas, pulmonary cysts, spontaneous pneumothorax, and renal tumors. Here, the 2 patients we reported with renal cell carcinomas and dermatological features were suspected to be suffering from BHD syndrome. Blood samples of these patients were sent for whole exon sequencing performed by Sanger sequencing. Eight mutations, including 5 mutations, which were mapped in noncoding region, 1 synonymous mutation, and 2 missense mutations, were detected in the FLCN gene in both patients. The 2 missense mutations, predicted to be disease-causing mutation or affecting protein function by MutationTaster and SIFT, confirmed the diagnosis. In addition, the 2 patients were also affected with papillary thyroid cancer. Total thyroidectomy and prophylactic bilateral central lymph node dissection were performed for them and the BHD-2 also received lateral lymph node dissection. Pathology reports showed that the patients had lymph node metastasis in spite of small size of thyroid lesions.The 2 missense mutations, not reported previously, expand the mutation spectrum of FLCN gene associated with BHD syndrome. For the thyroid cancer patients with BHD syndrome, total thyroidectomy and prophylactic bilateral central lymph node dissection may be suitable and the neck ultrasound may benefit BHD patients and their family members.

miR-24 promotes the proliferation, migration and invasion in human tongue squamous cell carcinoma by targeting FBXW7.

Recent studies suggest that aberrant expression of miR-24 is linked to various human cancers, including tongue squamous cell carcinoma (TSCC). F-box and WD-40 domain protein 7 (FBXW7), a tumor-suppressor gene, is responsible for the degradation of several proto-oncogenes. However, the function and mechanism of miR-24 and FBXW7 in TSCC remains unclear. In the present study, we found that miR-24 was increased in TSCC tissues and cell lines, and that upregulation of miR-24 was associated with advanced clinical stage and a shorter overall survival of TSCC patients. Inhibition of miR-24 significantly suppressed the proliferation, migration and invasion of TSCC cells in vitro. Furthermore, miR-24 repressed FBXW7 expression by directly binding to the 3-untranslated region of FBXW7. Moreover, the suppression of FBXW7 increased the proliferation, migration and invasion of TSCC cells, and the restoration of FBXW7 substantially attenuated the oncogenic effects of miR-24. In conclusion, our results demonstrated that upregulation of miR-24 was associated with tumor progression and poor prognosis in TSCC patients, and that overexpression of miR-24 was correlated with the proliferation, migration and invasion of TSCC cells in vitro, at least partially through regulation of its functional target FBXW7. Thus, miR-24 may serve as a novel potential biomarker for the prognosis of TSCC patients.

MicroRNA-24 induces cisplatin resistance by targeting PTEN in human tongue squamous cell carcinoma.

BACKGROUND: miR-24 is one of the most significantly up-regulated miRNAs in tongue squamous cell carcinoma (TSCC). PTEN plays an important role in the cell survival and cisplatin resistance of multiple cancers. However, it remains unclear what role does function and mechanism of miR-24 and PTEN play in TSCC. METHODOLOGY/PRINCIPAL FINDINGS: In this study, miR-24 expression was detected in 79 cases of paired TSCC and normal tissues and 8 TSCC cell lines by real-time PCR and the relevance between miR-24 expression and clinicopathological parameters were analyzed. Further, we demonstrated that deregulation of miR-24 was found to associate with high grade and late stage tumor. In addition, miR-24 induces cell survival and cisplatin resistance through targeting 3'-UTR region of the PTEN, which leads to downregulation of PTEN protein and activation of Akt pro-survival pathway. CONCLUSIONS/SIGNIFICANCE: In conclusion, our results demonstrated that deregulation of miR-24 is a recurrent event in human tongue squamous cell carcinoma and associate with tumor progression and that miR-24 induces cell survival and cisplatin resistance primarily through targeting PTEN/Akt pathway. Thus, miR-24 could be important targets for intervention of this malignancy.

Diagnostic value of elastosonography for thyroid microcarcinoma.

OBJECTIVE: To assess the diagnostic value of elastosonography for thyroid microcarcinoma (TMC), particularly with regard to elasticity score (ES) and strain ratio (SR). METHODS: Conventional ultrasound and elastosonography were performed for 487 thyroid micronodules before surgery. We set the histology as the reference standard. The ES and SR values, as well as their diagnostic threshold and efficiency, were compared and analyzed by the receiver-operating characteristic (ROC) curve. Additional comparisons between TMC patients with and without extracapsular extension were also performed. RESULTS: Statistically significant differences (P<0.05) in both ES and SR values were detected among the TMC and benign groups. The area under the ROC curve of SR was significantly greater than that of ES (0.956 and 0.844, respectively; P<0.05). Using ES⩾3 and SR⩾3.65 as diagnostic threshold values, the diagnostic sensitivity, specificity, and accuracy of ES for differentiating benign and malignant nodules were 79.9%, 72.3%, and 80.5%, respectively, whereas those of SR were 86.6%, 85.3%, and 89.4%, respectively. The maximum diameter, microcalcification status, aspect ratio, bilateral cervical lymph node metastasis, and SR values of nodules with extracapsular extension (A1 subgroup) were greater than those of nodules without extracapsular extension (A2 subgroup). CONCLUSIONS: Elasticity imaging technology not only can help differentiate between benign and malignant thyroid micronodules but also allow SR values to provide accurate and objective information on tissue hardness and to predict TMC extracapsular extension or even bilateral cervical lymph node metastasis.

TLR3 correlated with cervical lymph node metastasis in patients with papillary thyroid cancer.

Papillary thyroid cancer (PTC) is the most rapidly increasing endocrine malignancy worldwide. Although less aggressive than the majority malignancies, PTC exhibits extensive cervical lymph node metastasis in early stage of PTC. However, the underlying molecular mechanism of this early-metastasis remains unknown. Toll like receptors (TLRs) constitute a crucial component of the innate immune response to bacterial and viral pathogens. Emerging evidence suggests that TLRs play important roles in cancer progression, invasion and immune evasion, whereas whether TLRs have any role in PTC remains to be clarified. In this study, we found that TLR3 was present in both PTC specimen and various thyroid cancer cell lines. Further IHC analysis of 63 PTC patients revealed that TLR3 expression was associated with cervical metastasis, but not correlated with patients' TNM staging, extrathyroidal invasion. In addition, TLR3 promoted migration of K1 cells in vitro. Activation of TLR3 increased cancer stem cell marker and migration promoting CD44 expression in vitro, indicating that TLR3 might promote metastasis of PTC via modulating CD44 expression. Taken together, our data revealed that TLR3 is correlated with cervical metastasis of PTC and might be an essential prognostic indicator and target for PTC metastasis.

[Harmonic scalpel versus conventional resection in thyroid surgery: a meta analysis on the safety outcomes].

OBJECTIVE: To compare the safety between harmonic scalpel and conventional resection in total or near total thyroidectomy with meta-analysis. METHODS: The prospective randomized controlled studies were searched for in electronic databases (MEDLINE, EMBASE, Cochrane Library). Meta analysis of acquired data was performed through the use of RevMan 5.2 software. RESULTS: According to the inclusion criterion, 13 articles were enrolled which compared on the safety between harmonic scalpel and conventional resection in thyroid surgery. A total of 1620 patients with thyroid tumor were enrolled, including 802 patients in harmonic scalpel group and 818 patients in conventional resection group. Compared with conventional resection group, the harmonic scalpel group showed shorter time of surgery, the weighted mean difference (WMD) and their 95% confidence interval (95%CI) was -21.06[-25.65, -16.47], Z = 8.99, P < 0.00001; less intra-operative blood loss, WMD and 95%CI was -14.36[-20.67, -8.06], Z = 4.46, P < 0.00001; less post-operative drain output (WMD and 95%CI was -7.47[-11.35, -3.58], Z = 3.77, P = 0.0002); less hospitalization charges (WMD and 95%CI was -117.97[-131.65, -104.29], Z = 16.90, P < 0.00001). The incidence of postoperative transient recurrent laryngeal nerve dysfunction and transient hypocalcemia were similar in both groups. CONCLUSION: Using the harmonic scalpel in thyroid surgery was as safe as that of the conventional technique with the advantage of shorter time of surgery, less intraoperative blood loss and less postoperative drain output.

[Role of Ang-2, Tie-2 and VEGFR-2 in angiogenesis in colorectal carcinoma and their prognostic value].

OBJECTIVE: To study the expression of angiotensin-2 (Ang-2), Tie-2 and vascular endothelial growth factor receptor-2 (VEGFR-2) in colorectal cancer and analyze their relationship with the occurrence, recurrence, metastasis, angiogenesis and prognosis of colorectal cancer. METHODS: Immunohistochemistry with SP method was used to detect the expressions of Ang-2, Tie-2 and VEGFR-2 in 118 colorectal cancer, 40 adjacent normal tissue and 40 benign colorectal lesion specimens. RESULTS: The positivity rates of Ang-2, Tie-2 and VEGFR-2 in colorectal cancer tissue were 74.58%, 69.49%, and 61.02%, respectively, significantly higher than those in the adjacent normal tissues (25.00%, 17.50%, and 17.50%, P<0.05) and benign colorectal lesion tissues (35.00%, 32.50%, and 32.50%, P<0.05). The rates of two or three coexpression were significantly higher than that of a single expression in the cancer tissues (61.02% vs 15.25%). The microvascular density (MVD) of colorectal cancer tissues was 31.43∓10.50, significantly higher than that of the adjacent normal tissues (10.61∓3.76) and benign colorectal lesions (16.89∓3.83) (P<0.05). The expressions of Ang-2, Tie-2, and VEGFR-2 were positively correlated with carcinoembryonic antigen (CEA) and MVD (P<0.05). The expression of Ang-2, but not Tie-2 and VEGFR-2, was positively correlated with CA199. Ang-2, Tie-2, and VEGFR-2 expressions showed significant differences between cases with tumor recurrence/metastasis and those without 5 years after radical mastectomy, and were all positively correlated with the 5-year survival rates (P<0.05). CONCLUSION: Ang-2, Tie-2 and VEGFR-2 are involved in the development, invasion, metastasis, and prognosis of colorectal cancer, and play important roles in the angiogenesis of the tumors.