The Positive Lymph Node Number and Postoperative N-Staging Used to Estimate Survival in Patients with Differentiated Thyroid Cancer: Results from the Surveillance, Epidemiology, and End Results Dataset (1988-2008).

BACKGROUND: Lymph node metastasis is important when evaluating the prognosis of patients with differentiated thyroid cancer (DTC). However, the current N-staging system cannot fully reflect the clinical significance of cervical lymph node metastasis in DTC. In this study, we employed Surveillance, Epidemiology, and End Results (SEER)-registered DTC cases with lymph node metastasis to determine whether the positive lymph node number (PLNN) could be used to improve stratification of patients in terms of survival. METHODS: We used the SEER dataset to identify all DTC patients with at least one positive cervical lymph node who were examined between 1988 and 2008. Multivariable modeling was used to compare cancer-specific survival (CSS) and overall survival (OS) and to calculate different PLNN cutoff points. RESULTS: In total, 14,359 pN + DTC patients identified in the SEER were included. In multivariate Cox regression analysis, the PLNN was significantly associated with both CSS and OS, whereas neither the lymph node ratio (LNR) nor the (numbers of) lymph nodes examined (LNE) were so associated. The highest C-index value (0.933) and the lowest AIC value (9362.687) obtained indicated that the PLNN better predicted the CSS of DTC than did the LNR or LNE. As the p values for both CSS and OS were minimized, and as the PLNN performed best when cases were grouped, PLNN cutoff points of 10 and 3/10 efficiently stratified DTC patients into two and three levels, respectively. Based on the 3/10 trichotomy, the benefits of radioactive iodine (RAI) treatment were evaluated for each group. Such treatment afforded about a 10% survival benefit in patients with more than 10 lymph node metastases. CONCLUSIONS: Compared with the LNR and LNE under different statistical models, PLNN was superior in terms of DTC staging. A cutoff point of 3/10 was optimal for stratifying patients according to prognosis and was of clinical significance in terms of RAI treatment selection.

Bilaterality weighs more than unilateral multifocality in predicting prognosis in papillary thyroid cancer.

Papillary thyroid cancer (PTC) often presents as multifocal tumor;, however, whether multifocality is associated with poor prognosis remains controversial. The aims of this retrospective study were to identify the characteristics of PTC with multifocal tumors and evaluate the association between the location and prognosis. We reviewed the medical records of 496 patients who underwent total thyroidectomy for PTC. Patients were classified as three groups: N1 (solitary tumor), N2 (2 or more foci within unilateral lobe of thyroid), and N3 (bilateral tumors, at least one tumor focus for each lobe of thyroid). We analyzed the differences of clinicopathologic features and clinical outcomes among the three groups. Cox regression model was used to assess the relation between the different locations of multifocal tumors and prognosis. Although the differences of clinicopathologic features such as the size of tumor, extrathyroidal extension, and cervical lymph node metastasis were not significant among the three groups, the bilateral-multifocality was proved to be an independent risk factor for neck recurrence (hazard ratio (HR) = 4.052, 95 % confidence interval (CI) 2.070-7.933), distant metastasis (HR = 3.860, 95 % CI 1.507-9.884), and cancer death (HR = 7.252, 95 % 2.189-24.025). In addition, extrathyroidal extension (HR = 2.291, 95 % CI 1.185-4.427) and older age >45 years (HR = 6.721, 95 % CI 2.300-19.637) were also significant predictors for neck recurrence and cancer death, respectively. Therefore, bilateral-multifocality as an indicator for more extensive tumor location could be used to assess the risk of recurrence and mortality in PTC. Given the poor prognosis associated with bilateral-multifocality and other risk factors, aggressive therapy and intensive follow-up were recommended for PTC patients with them.

The impact of coexistent Hashimoto's thyroiditis on lymph node metastasis and prognosis in papillary thyroid microcarcinoma.

The impact of coexistent Hashimoto's thyroiditis (HT) on lymph node metastasis (LNM) and prognosis in papillary thyroid microcarcinoma (PTMC) remains controversial. We evaluated the association of coexistent HT with clinicopathologic parameters, LNM, and prognosis by retrospectively reviewing a series of consecutive patients treated for PTMC at Fudan University Cancer Center from January 2005 to December 2010. Of all 1,250 patients with complete data for analysis, 364 (29.1 %) had coexistent HT (HT group) and 886 patients (70.9 %) had no evidence of HT (control group). The HT group had higher proportion of female (87.9 vs 70.1 %) patients, higher mean level of thyroid-stimulating hormone (TSH) (2.39 vs 2.00 mIU/L), and lower incidence of extrathyroidal extension (7.4 vs 11.7 %) than those in the control group. However, the incidence of LNM and recurrence was similar between the two groups, and HT was not associated with LNM and recurrence. A series of clinicopathologic factors identified for predicting LNM and recurrence in the control group did not show any prediction in the HT group. In summary, this study suggested that coexistent HT had insignificant protective effect on LNM and prognosis in PTMC, which was inconsistent with prior studies. Further studies aiming to determine novel predictors are recommended in PTMC patients with coexistent HT.

Risk Factors for Central Compartment Lymph Node Metastasis in Papillary Thyroid Microcarcinoma: A Meta-Analysis.

BACKGROUND: The surgical management of papillary thyroid microcarcinoma (PTMC), especially regarding the necessity of central lymph node dissection (CLND), remains controversial. This meta-analysis was conducted to investigate the clinicopathologic factors predictive of central compartment lymph node metastasis (CLNM) in patients diagnosed with PTMC. METHODS: PubMed, EMBASE, Ovid, Web of Science, and the Cochrane Library were searched from their inception to September 2013. Published studies that explored the association between clinicopathologic factors and CLNM in PTMC patients were included. From the identified studies, we extracted the number of individuals with or without each risk factor to calculate the CLNM-positive proportions and used fixed/random-effects models for the meta-analyses of overall relative risk (RR). The pooling analysis on the association between CLNM or the different CLNDs and prognosis was also conducted. RESULTS: A total of 19 eligible studies that included 8345 patients were identified. Three studies did therapeutic CLND, while the other 16 studies performed prophylactic CLND in PTMC patients. Meta-analyses revealed that CLNM was associated with male gender (RR = 1.36; 95 % CI 1.22-1.52, p = 0.001), younger age (<45 years; RR = 1.15; 95 % CI 1.04-1.27, p = 0.006), larger tumor size (>5 mm; RR = 1.51 95 % CI 1.32-1.65, p = 0.001), multifocality (RR = 1.40; 95 % CI 1.27-1.54, p = 0.001), and extrathyroidal extension (RR = 1.81; 95 % CI 1.34-2.43, p = 0.001). Meta-regression analysis indicated that a disparity in the proportion of PTMC patients with CLNM in each study was the main factor resulting in heterogeneity among the 19 studies. In addition, the pooling analyses suggested that CLNM did not significantly predict neck recurrences [hazard ratio (HR) = 0.95, 95 % CI 0.67-1.22, p = 0.054], and the prophylactic CLND group did not improve local control significantly compared to the therapeutic group (RR = 0.96, 95 % CI 0.46-2.01, p = 0.544). CONCLUSION: Prophylactic CLND may be performed in PTMC patients with clinically uninvolved central lymph nodes but with high risk factors; multicenter studies with long-term follow-up are recommended to better understand the risk factors and surgical management for central nodes in PTMC.

Number of tumor foci predicts prognosis in papillary thyroid cancer.

BACKGROUND: Papillary thyroid cancer (PTC) often presents as multifocal. However, the association of multifocality with poor prognosis remains controversial. The aim of this retrospective study was to identify the characteristics of PTC with multiple foci and to evaluate the association between multifocality and prognosis. METHODS: We reviewed the medical records of 496 patients who underwent total thyroidectomy for PTC. Patients were classified as G1 (1 tumor focus), G2 (2 foci), and G3 (3 or more foci). We analyzed the clinicopathological features and clinical outcomes in each classification. A Cox regression model was used to assess the relationship between multifocality and recurrence or cancer mortality. RESULTS: The G1, G2 and G3 groups included 287, 141 and 68 patients, respectively. The mean age was 47.1±16.1 yr in G1, 41.1±18.4 yr in G2, and 35.5±15.9 yr in G3 and differed significantly among the 3 groups (p=0.001). The proportion of extrathyroidal extension, central lymph node metastasis (CLNM), and lateral lymph node metastasis (LLNM) in the G1 to G3 groups increased with increasing number of tumor foci. The Kaplan-Meier curves revealed that G3 had the shortest recurrence-free survival, and differences were significant among the 3 groups (p=0.001, Log Rank test). Furthermore, cancer-specific survival rates decreased significantly with increasing number of tumor foci (p=0.041). Independent predictors of recurrence by multivariate Cox analysis included >3 tumor foci [HR 2.60, 95% confidence interval (CI) 1.53-4.39, p=0.001] and extrathyroidal extension (HR 1.95, CI 1.12-3.38, p=0.018). CONCLUSION: An increase in the number of tumors is associated with a tendency toward more aggressive features and predicts poor prognosis in PTC.

The chemokine receptor-CXCR2 plays a critical role in the invasion and metastases of oral squamous cell carcinoma in vitro and in vivo.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the most common cancers in the world with about 50% survival rate over 5 years. OSCC has a highly invasive potency and frequently metastasizes to the cervical lymph nodes, which is the principle reason leading to poor prognosis. CXCR2, the receptor of CXC chemokines, has been reported to be involved in invasion and metastasis in multiple types of malignancy. However, the accurate role of CXCR2 in OSCC has been little noticed. METHODS: In this study, we determined the expression of CXCR2 in OSCC using immunohistochemical staining (IHC) and analyzed the association between the expression of CXCR2 and the biobehavior of OSCC. Then, we established stable OSCC cell lines with interference of CXCR2 and observed the effect of CXCR2 knockdown on cell proliferation, migration, invasion, and morphological changes in vitro and in vivo. RESULTS: CXCR2 was positively expressed in 55.3% of OSCC patients and was statistically associated with the high cervical lymph node metastasis in OSCC. CXCR2 silencing markedly inhibited migration and invasion of OSCC cells in vitro and in vivo. Moreover, CXCR2 silencing led to morphological changes and decreased lamellipodial structures in OSCC cells. However, CXCR2 silencing showed no effect on proliferation of OSCC cells in vitro and in vivo. CONCLUSIONS: CXCR2 plays a critical role in the invasion and metastases of OSCC. And it is probably by regulating actin cytoskeletal remodeling that CXCR2 takes part in the invasion and metastases of OSCC.

Association of the miR-149 Rs2292832 polymorphism with papillary thyroid cancer risk and clinicopathologic characteristics in a Chinese population.

(1) BACKGROUND: The genetic predisposition to papillary thyroid cancer (PTC) is far from clearly elucidated. Rs2292832 is a genetic polymorphism that located in the precursor of mir-149 and has been studied in diverse cancers. Thus far, the role of rs2292832 in PTC tumorigenesis and progression was unclear; (2) METHOD: Rs2292832 was genotyped in 838 PTCs, 495 patients with thyroid benign tumors (BNs) and 1006 controls in a Chinese Han population. Clinicopathological data was collected and compared. The expression level of mature mir-149 was examined in 55 normal thyroid tissue samples; (3) RESULTS: The CC genotype of rs2292832 was significantly associated with an increased risk of PTC compared with TT homozygote (OR = 1.60, 95% CI: 1.72-2.20, p = 0.003) and TT/TC combined genotype (OR = 1.54, 95% CI: 1.14-2.09, p = 0.005). Rs2292832 is an independent risk factor correlated with tumor invasion (p = 0.006) and higher T stage in PTC patients (p = 0.007), but uncorrelated with short-term disease persistence of PTC. PTC subjects carrying CC genotype have lower mir-149-5p expression than those with TC genotype (p = 0.002). Twelve predicted target genes have been identified by collaboratively using computational tools; (4) CONCLUSION: Rs2292832 was possibly involved in the susceptibility and local progression of PTC in Chinese patients, by altering the expression level of mir-149-5p and its target genes.

The clinical features of papillary thyroid cancer in Hashimoto's thyroiditis patients from an area with a high prevalence of Hashimoto's disease.

BACKGROUND: The goal of this study was to identify the clinicopathological factors of co-existing papillary thyroid cancer (PTC) in patients with Hashimoto's thyroiditis (HT) and provide information to aid in the diagnosis of such patients. METHODS: This study included 6109 patients treated in a university-based tertiary care cancer hospital over a 3-year period. All of the patients were categorised based on their final diagnosis. Several clinicopathological factors, such as age, gender, nodular size, invasive status, central compartment lymph node metastasis (CLNM) and serum thyroid-stimulating hormone (TSH) level, were compared between the various groups of patients. RESULTS: There were 653 patients with a final diagnosis of HT. More PTC was found in those with HT (58.3%; 381 of 653) than those without HT (2416 of 5456; 44.3%; p < 0.05). The HT patients with co-occurring PTC were more likely to be younger, be female, have smaller nodules and have higher TSH levels than those without PTC. A multivariate analysis indicated that the presence of HT and higher TSH levels were risk factors for a diagnosis of PTC. In the PTC patients, the presence of HT or another benign nodule was a protective factor for CLNM, whereas no significant association was found for TSH levels. CONCLUSION: PTC and HT have a close relationship in this region of highly prevalent HT disease. Based on the results of our study, we hypothesise that long-term HT leads to elevated serum TSH, which is the real risk factor for thyroid cancer.

Salvage surgery for neck residue or recurrence of nasopharyngeal carcinoma: a 10-year experience.

BACKGROUND: To assess the outcome of and determine prognostic factors for neck residue or recurrence of nasopharyngeal carcinoma (NPC) in patients treated with a salvage neck dissection. MATERIALS AND METHODS: Over a 10-year period (from January 1998 through December 2007) in a tertiary hospital, we systematically reviewed the clinical charts of 355 patients with NPC who were diagnosed with neck residue or recurrence of nasopharyngeal carcinoma, after radical definitive radiotherapy with or without chemotherapy. RESULTS: The group with recurrent nodal disease consisted of 285 patients (80.3%), while the group with residual nodal disease included 70 patients (19.7%). There were no patients died of the surgery complications. Overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) were 54.11, 35.01, and 55.59%, respectively, at 3-year, and 26.03, 22.65, and 27.84%, respectively, at 5-year. The local control rate in the neck was 70.92% at 3 years and 60.98% at 5 years. For all the 3 survival outcomes (OS, DFS, and DSS) and the local control rate of disease in the neck, there were significant differences between the "residue group" and "recurrence group." CONCLUSIONS: Radical neck dissection is proven to be safe and effective in the treatment of the neck failure. Our study has demonstrated that it may be possible to choose the selective lymph node dissection for patients of the residue group.

Prognostic and clinical significance of HOXC9 and HOXD10 in papillary thyroid cancer.

BACKGROUND: The homebox superfamily play an important role in tumorigenesis. HOXC9 and HOXD10 were reported playing critical roles in tumor progression in many malignant tumors. This study aimed to research the expression of HOXC9 and HOXD10 in papillary thyroid cancer, and to verify the prognostic and clinical significance of HOXC9 and HOXD10. METHODS: Immunohistochemistry was used to determine the expression of HOXC9 and HOXD10 in 98 pairs of papillary thyroid cancer and paracancer tissues. Clinicopathologic data were collected and analyzed to verify the prognostic and clinical significance of HOXC9 and HOXD10. RESULTS: The expression of HOXC9 and HOXD10 decreased in papillary thyroid cancer. The low expression of HOXC9 was associated with Hashimoto's thyroiditis and lymph node metastasis (P<0.05). The low expression of HOXD10 was associated with extrathyroidal extension and lymph node metastasis (P<0.05). The co-expression rates of HOXC9 and HOXD10 was 44.90%. The low expression of both HOXC9 and HOXD10 was associated with lymph node metastasis (P<0.05). CONCLUSIONS: The expression of HOXC9 and HOXD10 was downregulated in papillary thyroid cancer. Low expression of HOXC9 and HOXD10 might be related to the malignancy of papillary thyroid cancer. HOXC9 and HOXD10 may be used as diagnostic and prognostic biomarkers in the future.

Prognostic evaluation model for papillary thyroid cancer: a retrospective study of 660 cases.

BACKGROUND: Prognostic evaluation model for papillary thyroid cancer is very important for guiding the personalized treatment and follow-up strategy. There are imperfections in the system existed, and there is no suitable prognostic model for Chinese population. METHODS: This study was based on the clinic and follow-up data of 660 patients received surgical treatments in the Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center from 2000 to 2005. Cox univariate/multivariate analysis was used to explore the influence factors of prognosis, and nomogram model was performed to establish a prognostic prediction system. RESULTS: Totally, 660 patients for initial treatment were included in our analysis with a median follow-up of 113.5 months. Five-, 10- and 15-year disease-free survival rate was 95.5%, 90.2% and 89.2%. Five-, 10- and 15-year overall survival rate was 99.7%, 99.2% and 99.1%. Residual tumor was associated with overall survival [hazard ratio (HR) 20.9, 95% confidence interval (CI): 2.3-187.6, P<0.05]. Age of onset (HR 2.00, 95% CI: 1.17-3.42, P<0.05) and the dimension of lymph nodes involved (0.2-3 cm: HR 3.67, 95% CI: 1.13-11.87, P<0.05; >3 cm: HR 5.20, 95% CI: 1.31-20.65, P<0.05) were independent influence factors of disease-free survival. The nomogram model for predicting prognosis of papillary thyroid cancer was established with a moderate predictive value (c-index 0.71, 95% CI: 0.57-0.84). CONCLUSIONS: The prognosis of papillary thyroid cancer is very good after appropriate treatment. Age and the dimension of lymph nodes involved were independent influence factors of disease-free survival for papillary thyroid cancer. A prognostic prediction model for Chinese population was established with moderate predictive value. A study with larger samples and including more factors of prognosis is necessary to increase the predictive value of model.

Multiple lectin assays in detecting glycol-alteration status of serum NRG1 in papillary thyroid cancer.

BACKGROUND: Neuregulin 1 (NRG1) is a membrane glycoprotein mediating cell-to-cell signaling and has a crucial role in the growth and development of various organ systems. Our study explored its diagnostic value in distinguishing BRAF V600E mutant status in papillary thyroid cancer (PTC) patients by analyzing multiple glycan patterns of serum NRG1 through lectin assays. METHODS: We first extracted serum from PTC patients and tested BRAF V600E mutation by immunohistochemical (IHC) staining. Then we applied antibody overlay lectin microarray and lectin blot to detect glycol-alterations of NRG1. Then Aleuria aurantia lectin (AAL) ELISA was performed according to ELISA index to test the protein fucosylation level of NRG1 (Fuc-NRG1). RESULTS: We got glycan profiles of 14 lectins, including GNL, GSL2, AAL, BPL, ECL, CAL, NML, HHL, PHA-L, RCA-I, ConA, DBA, PWA and LEL. Six of them, namely, GSL2, BPL, NML, HHL, PHA-L and LEL, had significantly increased binding affinity capacity in BRAF(+) PTC compared with BRAF(-) PTC controls. LEL, BPL and NML tended to bind to NRG1 in BRAF(+) PTC group. Both AAL ELISA and protein ELISA assays showed that the fucosylated structures of NRG1 had a remarkable increase in BRAF V600E mutant PTC patients compared with BRAF wild type PTC controls. CONCLUSIONS: This study sheds a new light on the role of NRG1 glycosylation in PTC. NRG1 could serve as a supplementary glycobiomarker for BRAF indicator in discrimination of PTC patients with BRAF wild type negative fine needle aspiration results.

The extent of lymph node yield in central neck dissection can be affected by preoperative and intraoperative assessment and alter the prognosis of papillary thyroid carcinoma.

BACKGROUND: Lymph node yield (LNY) was implemented in the stratification of papillary thyroid cancer (PTC) patients. The effect of LNY may be related to the extent of surgery. This study aims to identify influencing factors for LNY in central compartment neck dissection (CND). METHODS: Data of 13 712 consecutive PTC patients were analyzed retrospectively. Risk factors for LNY in CND and distribution characteristics of LNY were evaluated. Its relationship with prognosis was studied in another cohort of 136 cases. RESULTS: LNY in therapeutic CND was significantly higher than prophylactic CND (Unilateral: 5.55 ± 3.79 vs 3.41 ± 2.77; Bilateral: 8.90 ± 5.10 vs 6.47 ± 4.17, P < .001). Other independent factors included extranodal extension (ETE), tumor size, and concurrent Hashimoto's thyroiditis. The inconsistency distribution of LNY in bilateral CND was associated with preoperative and intraoperative assessment. Patients with significant difference between major and minor LNY suffered from poorer prognosis (10y-RFS: 58.3% vs 92.0%; HR = 6.719, 95%, P < .0001). CONCLUSIONS: CND surgical procedure, ETE, and Hashimoto's thyroiditis were independent factors of LNY. Inconsistent distribution of LNY was associated with prognosis of bilateral PTC patients. The impact of preoperative and intraoperative assessment on the actual extent of CND can be used to explain the relationship between LNY and PTC prognosis.

The association between tumor's location and cervical lymph nodes metastasis in papillary thyroid cancer.

BACKGROUND: Papillary thyroid cancer (PTC) has a strong propensity to metastasize to the cervical lymph nodes. Little was known currently about whether tumor's location would influence the risk of lymph node metastasis in PTC. METHODS: The study enrolled PTC patients who underwent primary surgical therapy in our center for small unifocal tumor. The tumor's location was evaluated by ultrasound in three axes, three planes and 3D space. Logistic univariate and multivariate analysis were applied to explore the association between tumors' location and the risk of lymph node metastasis in PTC. Different localization methods of thyroid tumors were evaluated using ROC curve. RESULTS: Totally 1,266 PTC patients were enrolled in this study. Univariate and multivariate analyses showed that gender, age, tumor size and tumor's location (in longitudinal axis, longitudinal sagittal plane, longitudinal coronal plane, sagittal coronal plane and 3D space) was associated with central lymph node dissection (CLND); gender, tumor size and tumor's location (in longitudinal axis, coronal axis, longitudinal sagittal plane, longitudinal coronal plane, sagittal coronal plane and 3D space) was related with lateral lymph node dissection (LLND) (P<0.05). In the ROC curve analysis, the 3D location showed the highest predictive value of lymph node metastasis (C-statistics: 0.724 for CLNM; 0.763 for LLNM). The middle posterior lateral (OR=2.575, P=0.028), inferior anterior central (OR=2.829, P=0.016), inferior posterior lateral (OR=2.759, P=0.039) and isthmus tumors (OR=4.526, P=0.001) were at a higher risk of CLNM, and the middle anterior central tumors (OR=0.102, P=0.015) were related with lower risk of LLNM. CONCLUSIONS: Stereotactic localization showed the highest predictive value of lymph node metastasis. The middle posterior lateral, inferior anterior central, inferior posterior lateral and isthmus tumors were at a higher risk of CLNM when compared to other locations. For such patients, careful preoperative evaluation of nodal status should be done.

Metabolic reprogramming and its clinical application in thyroid cancer.

Warburg found that tumor cells exhibit high-level glycolysis, even under aerobic condition, which is known as the 'Warburg effect'. As systemic changes in the entire metabolic network are gradually revealed, it is recognized that metabolic reprogramming has gone far beyond the imagination of Warburg. Metabolic reprogramming involves an active change in cancer cells to adapt to their biological characteristics. Thyroid cancer is a common endocrine malignant tumor whose metabolic characteristics have been studied in recent years. Some drugs targeting tumor metabolism are under clinical trial. This article reviews the metabolic changes and mechanisms in thyroid cancer, aiming to find metabolic-related molecules that could be potential markers to predict prognosis and metabolic pathways, or could serve as therapeutic targets. Our review indicates that knowledge in metabolic alteration has potential contributions in the diagnosis, treatment and prognostic evaluation of thyroid cancer, but further studies are needed for verification as well.

Effects of tumor size on prognosis in differentiated thyroid carcinoma smaller than 2 cm.

Benefits of subdividing small-differentiated thyroid carcinoma (sDTC) by tumor size are controversial. We conducted a meta-analysis to investigate whether tumor size is associated with prognosis of sDTC. PubMed and Web of Science databases were searched from their inception to September 2018. The identified studies according to the inclusion/exclusion criteria were analyzed using fixed/random-effects models. Data were calculated and results of the meta-analysis were expressed as odd ratio (OR). sDTC was classified as S1 (≤1 cm) and S2 (>1 cm and ≤2 cm). A systematic analysis was performed to compare the difference of recurrence, survival and clinicopathological factors between the two subgroups of sDTC (S1 vs. S2). A total of 21 studies published between 2004 and 2017 enrolling 219,291 patients were included. Findings showed that, S2 was associated with higher recurrence risk compared with S1 (OR=1.575, 95% CI=1.428-1.738; P<0.05). There was no statistical difference in survival between S1 and S2, but significant statistical heterogeneity (OR=1.160, 95% CI=0.810-1.662; P=0.448; I2=75.8%). Meta-regression analysis revealed publication year potentially caused the heterogeneity (P<0.05). Comparison of small papillary thyroid carcinoma alone agreed with the results of sDTC. T1b increased the risk of recurrence (OR=1.520; 95% CI=1.072-2.155; P<0.05) and death (OR=1.504; 95% CI 1.353-1.672; P<0.05) compared with T1a. S2 associated with extrathyroidal extension (OR=2.575; 95% CI=1.603-4.135; P<0.05), bilaterality (OR=2.278; 95% CI=1.905-2.723; P<0.05), vascular invasion (OR=4.494; 95% CI=2.812-7.183; P<0.05) and lymph node metastases (OR=1.12; 95% CI=1.10-1.14; P<0.05). Our analysis suggested it is necessary to subdivide sDTC into S1 and S2 owing to their different effects on prognosis, especially recurrence.

Incidentally simultaneous occurrence of RET/PTC, H4-PTEN and BRAF mutation in papillary thyroid carcinoma.

Because interaction existed between PTEN and RET-RAS-RAF-MAPK pathway, H4-PTEN (a newly identified gene rearrangement), RET/PTC and BRAF mutation were scanned in 125 Chinese patients with papillary thyroid carcinoma (PTC). H4-PTEN were detected in 9.6% of PTC and the frequency of the occurrence of BRAF mutation and/or RET/PTC in H4-PTEN positive tumors was extremely high (75%). On the other hand, age has an important effect on the aberration formation and young age renders more prone to multi-genetic events. A combinational scanning of these involved changes will improve the predictive value of molecular aberrations in the treatment of PTC.

Long-term impact of initial surgical and medical therapy on young patients with papillary thyroid cancer and bilateral cervical metastases.

BACKGROUND: There are few reviews on the clinical features and prognosis of young patients with papillary thyroid cancer and bilateral cervical metastases. We have investigated the long-term impact of initial surgical and medical therapy on such patients. METHODS: A retrospective study was performed on 24 young patients (11 females and 13 males) with papillary thyroid cancer and bilateral cervical lymph node metastases, ranging in age from 11 to 20 years (mean age, 16.6 years), who were treated in our institution from 1 January 1970 to 31 December 1985. RESULTS: All the patients in this group were followed up for 20 years. The survival of the patients at 20 years was 91.7%. The recurrence of local tumor and distant metastases was 20.8% and 12.5%, respectively. Based on analysis of the clinical data, we determined that the completeness of the surgical excision had a significant correlation with tumor recurrence. CONCLUSION: These young patients with papillary thyroid cancer and cervical metastases have a good prognosis after suitable treatment.

[Predictive factors for level VI lymph node metastasis in papillary thyroid microcarcinoma].

OBJECTIVE: To determine the predictive factors for level VI lymph node (LN) metastasis in thyroid papillary microcarcinoma (PTMC). METHODS: From November 2005 to January 2007, 86 patients with PTMC with a lateral cN0 were treated by thyroidectomy and elective level VI LN dissection without comprehensive lateral neck dissection. The data from the cases were analyzed retrospectively to determine the predictive factors for level VI LN metastasis. RESULTS: Forty cases (46.5%) of the patients were found with level VI LN metastasis. Tumor size (> or = 5 mm), thyroid capsular invasion or extracapsular invasion, enlarged level VI LN size (> or = 4 mm) were found significantly related to level VI LN metastasis on univariate analysis (P < 0.05). Tumor size (> or = 5 mm) and thyroid capsular invasion or extracapsular invasion were found to be independent predictive factors for level VI LN metastasis on multivariate analysis (P < 0.05). CONCLUSIONS: Thyroid capsular invasion or extracapsular invasion, tumor size (> or = 5 mm) were significantly associated with level VI LN metastasis in patients with PTMC. Elective neck dissection in level VI should be considered particularly in patients with thyroid capsular invasion or extracapsular invasion and a tumor greater than 5 mm.

Verteporfin inhibits papillary thyroid cancer cells proliferation and cell cycle through ERK1/2 signaling pathway.

Verteporfin, a FDA approved second-generation photosensitizer, has been demonstrated to have anticancer activity in various tumors, but not including papillary thyroid cancer (PTC). In current pre-clinical pilot study, we investigate the effect of verteporfin on proliferation, apoptosis, cell cycle and tumor growth of PTC. Our results indicate verteporfin attenuates cell proliferation, arrests cell cycle in G2/S phase and induces apoptosis of PTC cells. Moreover, treatment of verteporfin dramatically suppresses tumor growth from PTC cells in xenograft mouse model. We further illustrate that exposure to MEK inhibitor U0126 inactivates phosphorylation of ERK1/2 and MEK in verteporfin-treated PTC cells. These data suggest verteporfin exhibits inhibitory effect on PTC cells proliferation and cell cycle partially via ERK1/2 signalling pathway, which strongly encourages the further application of verteporfin in the treatment against PTC.