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.

miR-584 Suppresses Invasion and Cell Migration of Thyroid Carcinoma by Regulating the Target Oncogene ROCK1.

BACKGROUND: Uncovering the target gene of miR-584 to control thyroid carcinoma (TC) invasion and migration is of central importance in the diagnosis, treatment, and prognosis of TC. To validate whether miR-584 has a tumor-suppressive role in thyroid cancer cells by targeting ROCK1, a series of experiments were conducted to figure out the mechanism of action of miR-584. MATERIAL AND METHODS: Migration analyses and cell proliferation assays were performed using miR-584-transfected cells. The expression levels of miR-584 in TC were detected by using real-time polymerase chain reaction (PCR). Western blot analyses were conducted to find out the relationship between the tumor suppressor miR-584 and the target oncogene ROCK1 protein expression levels. Wound healing experiments were used to examine the relationships between miR-584 and the migration of thyroid cancer K1 cells and the effects of ROCK1 knockdown on K1 cell motility. RESULTS: Our results demonstrate that altering the miR-584 levels affects human thyroid cancer cell migration, but has no effect on cell proliferation. The relative ROCK-1 expression levels were 1 and 0.54 in the scrambled-sequence control group and the miR-584 group, respectively. K1 cells transfected with siRNA-ROCK-1 showed weaker cell migration than cells transfected with siRNA-NC (negative control); the cell motility ratios were 18% and 27%, respectively. CONCLUSION: These results indicate that miR-584 could inhibit the expression of ROCK1, and ROCK1 knockdown would further affect the migration ability of K1 cells.

AMD3100 reduces CXCR4-mediated survival and metastasis of osteosarcoma by inhibiting JNK and Akt, but not p38 or Erk1/2, pathways in in vitro and mouse experiments.

Osteosarcoma (OS) has an unfavorable prognosis and tends to metastasize to lung tissue. Although the CXCL12-CXCR4 axis appears to affect progression and metastasis in numerous tumors, its mechanism and downstream pathways in OS remain unclear. We used western blotting and flow cytometry to detect CXCR4 and CXCR7 expression in two OS cell lines (LM8 and Dunn). An MTT assay was used to evaluate the effects of CXCL12 and AMD3100, a specific CXCR4 antagonist, on cell viability. Flow cytometry was utilized to analyze changes in apoptosis induced by serum deprivation following treatment with CXCL12 and AMD3100. A Transwell assay was used to assess cell migration in response to CXCL12 and AMD3100. Western blotting was performed to identify the phosphorylation of signaling molecules (JNK, c-Jun, Akt, p38 and Erk1/2) and expression of caspase-3 and -8, and PARP. Mouse models were employed to evaluate AMD3100 inhibition of primary OS growth and lung metastasis in vivo. CXCR4 expression was detected in LM8 but not Dunn cells, and neither cell line expressed CXCR7. The addition of CXCL12 induced the survival and migration of serum-starved CXCR4+ LM8 cells activating JNK and Akt pathways, which were abrogated by adding AMD3100. However, similar results were not observed in CXCR4- Dunn cells. CXCL12 protected LM8, but not Dunn cells, from apoptosis induced by serum deprivation by suppressing PARP cleavage, which was partly reversed by AMD3100. In a mouse model, AMD3100 reduced primary tumor growth and lung metastasis compared with the controls. Thus, the CXCL12-CXCR4 axis regulated OS survival and metastasis through the JNK and Akt pathways, and blocking them with AMD3100 was found to be a potential OS treatment.

Association study of single nucleotide polymorphisms in mature microRNAs and the risk of thyroid tumor in a Chinese population.

MicroRNAs (miRNAs) are small non-coding RNA molecules that are involved in a variety of cellular functions. Single nucleotide polymorphisms (SNPs) have been identified in mature miRNAs (mmSNPs), some of which have been linked to cancer risk; however, it is unclear which mmSNPs contribute to the susceptibility to thyroid tumors. In the present study, we examined the influence of selected mmSNPs on the risk of thyroid tumor. After systematic in silico screening, seventeen mmSNPs were identified and genotyped in a Chinese population including 828 patients with papillary thyroid cancer (PTC), 488 patients with benign thyroid tumor (BN), and 1038 cancer-free controls. Multivariate logistic regression analyses were conducted to evaluate the association of SNP genotypes and alleles with the risk of developing PTC and BN. Three SNPs (rs67106263 in mir-3144, GA versus GG, OR = 1.35, 1.09-1.68; rs4919510 in mir-608, CC versus GG/GC, OR = 0.76, 0.60-0.97; and rs79402775 in mir-933, AA versus GG/GA, OR = 1.76, 1.00-3.12) were associated with PTC risk. A combined effect of unfavorable genotypes was observed to give increased PTC risk in a dose-dependent manner. In addition, three SNPs (rs10061133 in mir-449b, rs79402775 in mir-933 and rs4919510 in mir-608) showed at least borderline correlations with the risk of BN. False-positive report probability was assessed for significant findings. The rs67106263 SNP was associated with the expression level of mir-3144 in thyroid tissue. These results indicate that mmSNPs may contribute to genetic susceptibility to thyroid tumors. Large validation and functional studies are required to further explore the role of mmSNPs in carcinogenesis.

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.

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.

Lymph node ratio for postoperative staging of laryngeal squamous cell carcinoma with lymph node metastasis.

BACKGROUND: Lymph node metastasis has a significant impact on laryngeal cancer prognosis. The role of lymph node ratio (LNR, ratio of metastatic to examined nodes) in the staging of laryngeal cancer was not reported. PATIENTS AND METHODS: Records of laryngeal cancer patients with lymph node involvement from Surveillance, Epidemiology, and End Results database (SEER, training set, N = 1963) and Fudan University Shanghai Cancer Center (FDSCC, validating set, N = 27) were analyzed for the prognostic value of LNR. Kaplan-Meier survival estimates, the Log-rank χ² test and Cox proportional hazards model were used for univariate and multivariate analysis. Optimal LNR cutoff points were identified by X-tile. RESULTS: Optimal LNR cutoff points classified patients into three risk groups R1 (≤0.09), R2 (0.09-0.20) and R3 (>0.20), corresponding to 5-year cause-specific survival and overall survival in SEER patients of 55.1%, 40.2%, 28.8% and 43.1%, 31.5%, 21.8%, 2-year disease free survival and disease specific survival in FDSCC patients of 74.1%, 62.5%, 50.0%, and 67.7%, 43.2%, 25.0%, respectively. R3 stratified more high risk patients than N3 with the same survival rate, and R classification clearly separated N2 patients to 3 risk groups and N1 patients to 2 risk groups (R1-2 and R3). CONCLUSIONS: R classification is a significant prognostic factor of laryngeal cancer and should be used as a complementary staging system of N classification.

The role of the CXCL12-CXCR4/CXCR7 axis in the progression and metastasis of bone sarcomas (Review).

Bone sarcomas, which comprise less than 1% of all human malignancies, are a group of relatively rare mesenchymal-derived tumors. They are mainly composed of osteosarcoma, chondrosarcoma and Ewing's sarcoma. In spite of advances in adjuvant chemotherapy and wide surgical resection, prognosis remains poor due to the high propensity for lung metastasis, which is the leading cause of mortality in patients with bone sarcomas. Chemokines are a superfamily of small pro-inflammatory chemoattractant cytokines which can bind to specific G protein-coupled seven-span transmembrane receptors. Chemokine 12 (CXCL12), also designated as stromal cell-derived factor-1 (SDF-1), is able to bind to its cognate receptors, chemokine receptor 4 (CXCR4) and chemokine receptor 7 (CXCR7), with high affinity. The binding of CXCL12 to CXCR4/CXCR7 stimulates the activation of several downstream signaling pathways that regulate tumor progression and metastasis. In this review, the structure and function of CXCL12 and its receptors, CXCR4 and CXCR7, as well as many factors affecting their expression are discussed. Phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways are the two most important downstream pathways regulated by the CXCL12-CXCR4/CXCR7 interaction. CXCR4 expression in bone sarcomas, including tumor cells and samples and the correlation between CXCR4/CXCR7 expression and the survival of patients with bone sarcomas are also discussed. In addition, we review the involvement of the CXCL12­CXCR4/CXCR7 axis in the growth and metastasis of bone sarcomas and the targeting of this axis in preclinical studies.

Confirmation of papillary thyroid cancer susceptibility loci identified by genome-wide association studies of chromosomes 14q13, 9q22, 2q35 and 8p12 in a Chinese population.

BACKGROUND: Five single nucleotide polymorphisms (SNPs) were previously reported to be associated with thyroid cancer in European populations in two genome-wide association studies (GWAS): rs965513 (9q22.33), rs944289 (14q13.3), rs116909374 (14q13.3), rs966423 (2q35) and rs2439302 (8p12). Only the first two SNPs have been validated in independent populations and none were replicated in Chinese populations. METHODS: The above five SNPs were genotyped in 845 papillary thyroid cancer (PTC) and 503 benign thyroid tumour (BN) patients and 1005 controls in a Chinese population using the SNaPshot multiplex single nucleotide extension system. RESULTS: Significant associations were detected among PTC and rs944289 (p=8.007e-11), rs965513 (p=1.013e-4), rs966423 (p=1.688e-3) and rs2439302 (p=1.096e-4) in a dominant model, while the rs116909374 SNP was not detected in the Chinese population. The PTC risk increased with rise in accumulative numbers of risk alleles carried by individuals (p=5.929e-13). The PTC OR of carriers of six risk alleles (1.4% of the control population) was 23.587 compared with non-risk homozygotes (1.0% of the control population, with zero risk alleles). No individuals were homozygous for all the four SNPs (carriers of eight risk alleles) and only three PTC cases were carriers of seven risk alleles. A significant association between 14q13.3 SNP rs944289T and BN was also found (p=0.0014). CONCLUSIONS: Four candidate loci, rs965513 (9q22.33), rs944289 (14q13.3), rs966423 (2q35) and rs2439302 (8p12), identified by GWAS for PTC risk were confirmed in a Chinese population. The PTC risk of accumulative risk allele carriers increased with the number of risk alleles.

Association between the rs2910164 polymorphism in pre-Mir-146a sequence and thyroid carcinogenesis.

BACKGROUND: Rs2910164, a Single nucleotide polymorphism (SNP) located in the precursor microRNA sequence of miR-146a, is the only MicroRNA sequence SNP studied in papillary thyroid cancer (PTC). Association studies had been performed in US and UK-Northern European populations, but results were inconsistence. This study evaluated the association between rs2910164 and the risk of PTC as well as benign thyroid tumor (BN), and examined the clinicopathological characteristics of PTC and BN for different genotypes. METHODS: This case-control study genotyped rs2910164 in 753 PTCs, 484 BNs and 760 controls in a Chinese Han population. Clinicopathological and genetic data were collected and compared. Multivariate logistic regression was performed to calculate adjusted odds ratios (ORs). RESULTS: There were no differences in rs2910164 genotype distributions between the three groups. PTC cases with three genotypes (CC, CG, GG) had similar clinicopathological characteristics except the existence of "para-cancer" BN (PTC/BN, P = 0.006). PTC/BN patients were older (P = 0.009), and had smaller cancer lesions (P<0.001), lower serum thyrotropin levels (1.82±1.42 vs. 2.21±1.74, P = 0.04), and lower rates of level VI lymph node metastasis (20.8% vs. 52.7%, P<0.001) and lateral neck lymph node metastasis (11.5% vs. 23.0%, P = 0.011) compared with PTC only. Then we supposed a possible progression from BN to PTC which may involve rs2910164 in and performed a multivariate logistic regression analysis of PTC/BN and BN cases to determine risk factors of this progression. Results showed that the rs2910164 GG homozygote (OR = 2.25, 95% CI 1.22-4.14, P = 0.01) was the only risk factor in this study. CONCLUSION: Rs2910164 was not associated with increased risk of PTC and BN in Chinese patients, but may play a latent role in the transformation from BN to PTC.

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.

Predictive index for lymph node management of major salivary gland cancer.

OBJECTIVES/HYPOTHESIS: To find the risk factors of lymph node (LN) metastasis of salivary gland cancer and draw a scheme for LN management. STUDY DESIGN: Hospital-based retrospective study. METHODS: The records of salivary gland cancer patients treated at the Department of Head and Neck Surgery, Cancer Hospital, Fudan University, were entered in a database, and 219 consecutive patients with carcinomas of major salivary glands primarily operated on between January 1998 and January 2011 were chosen for univariate and multivariate analysis to identify risk factors for LN involvement. RESULTS: Fifty-eight (26.5%) patients had LN involvement. Factors associated with cervical LN involvement on univariate analysis included pathologic type, male sex, shorter duration of preoperative course, facial paralysis, advanced T stage, and major nerve, soft tissue, lymphatic/vascular (L/V), neural/perineural, and extracapsular invasion. Multivariate analysis identified major nerve invasion, histologic type, L/V invasion, and extracapsular invasion as significant factors for LN involvement. The proportion of patients with LN involvement with low (105), middle (61), high (34), and super high (19) predictive index scores based on the four risk factors were 3.8%, 27.9%, 55.9%, and 94.7%, respectively. CONCLUSIONS: A predictive index using the clinicopathologic factors described in this report can effectively stratify patients into risk groups for nodal metastasis. Comprehensive management based on this risk index should improve treatment outcomes for patients with salivary gland cancer.

Clinicopathologic study of 1176 salivary gland tumors in a Chinese population: experience of one cancer center 1997-2007.

CONCLUSION: Chinese patients have a higher rate of lymphoepithelial carcinoma (LEC) and salivary duct carcinoma (SDC). Comprehensive use of diagnostic modalities, neck dissection, and postoperative radiation will improve the treatment results for salivary gland tumors (SGTs). OBJECTIVES: To study the clinicopathological characteristics of SGTs in a Chinese population. METHODS: The records of SGT patients operated in a tertiary cancer hospital of China were retrieved. RESULTS: From December 1997 to December 2007, 289 malignant and 887 benign SGTs were operated at Cancer Hospital, Shanghai, China. Pleomorphic adenoma and Warthin's tumor were the most common types of SGT. Mucoepidermoid carcinoma (24.6% of malignant cases) and adenoid cystic carcinoma (18.0%) were the most frequent malignant cases, followed by acinic cell carcinoma (12.1%), LEC (9.7%), and SDC (9.3%). The sensitivity and specificity of ultrasound scan, fine needle aspiration biopsy, and frozen section were 58.3 and 88.6%, 87.2 and 96.7%, 86.9 and 99.6%, respectively. Neck dissections and postoperative radiation were carried out for 48.6 and 48.0% of carcinomas, respectively. The percentage of tumors by pathologic TNM stage were 23.7% for stage I, 32.9% for stage II, 17.3% for stage III, and 26.1% for stage IV. The 5-year overall survival rate was 88.0%.

Risk factors for neck nodal metastasis in papillary thyroid microcarcinoma: a study of 1066 patients.

CONTEXT: The surgical management of papillary thyroid microcarcinoma (PTMC), especially regarding the necessity of central lymph node dissection, remains controversial. OBJECTIVE: The objective of the study was to describe the clinicopathological features of PTMC and to identify the risk factors for central lymph node metastasis (CLNM) that can guide surgical strategies for patients with PTMC. DESIGN: In this retrospective cross-sectional study, risk factors and outcome variables were assessed at the time of surgery for the primary tumor. SETTING: The study was conducted at a university-based tertiary care cancer hospital. PATIENTS: Data from the medical records of 1066 consecutive patients diagnosed with PTMC over a 5-yr period were analyzed. RESULTS: Our multivariate logistic regression analysis found male gender, younger age (≤45 yr of age), multifocal lesions, extrathyroidal extension, and larger size of the primary tumor (>6 mm) to be associated with CLNM; multifocal lesions were associated with the highest risk (odds ratio 4.476, 95% confidence interval 2.975-6.735). Extrathyroidal extension, multifocal lesions, and CLNM were associated with lateral neck lymph node metastasis (LLNM). In patients with a solitary primary tumor, tumor location in the upper third of the thyroid lobe was associated with a lower risk of CLNM and a higher risk of LLNM. CONCLUSIONS: Prophylactic central lymph node dissection need be considered in PTMC patients presenting with risk factors. In PTMC patients with a solitary primary tumor, tumor location can assist in the evaluation of LLNM. We recommend multicenter research and long-term follow-up to better understand the risk factors and surgical management of PTMC.

Characteristics and prognosis of primary thyroid non-Hodgkin's lymphoma in Chinese patients.

BACKGROUND AND OBJECTIVES: There exists no universally accepted treatment for primary thyroid non-Hodgkin's lymphoma (TNHL) due to the rarity of this entity. The aim of this study is to assess the role of surgery and to explore prognostic factors in Chinese TNHL patients. METHODS: Patient presentations, pathologies, surgical interventions, multidisciplinary treatment, prognostic factors and the value of fine needle aspiration were analyzed. RESULTS: Between 1991 and 2007, 40 patients of TNHL were diagnosed. Thirty-eight patients underwent an initial surgical procedure. Further treatments consisted of radiotherapy or chemotherapy alone, and the majority of patients were treated with combined chemo-radiation. After a median follow-up of 95 months, the 5-year overall survival (OS) and relapse-free survival (RFS) was 82% and 74%, respectively. Survival curves showed no significant difference between therapeutic operations when compared with diagnostic operations. A univariate analysis showed both International Prognostic Index (IPI) and staging significantly influenced OS and RFS. In multivariate analysis, IPI was found to be the only prognostic factor. CONCLUSIONS: Combined chemotherapy and radiotherapy may offer better outcome without the need for extensive resection, and surgery should be reserved to providing tissue for diagnosis. The patients with low-intermediate risk (IPI = 2) or stage IIE need be treated more aggressively.

[Clinical and pathological analysis of central compartment dissection in patients with papillary thyroid cancer with negative clinical lymph node metastasis].

OBJECTIVE: To assess the significance of central compartment dissection in papillary thyroid cancer with negative clinical lymph node metastasis. METHODS: Clinical and pathological data of 641 papillary thyroid cancer patients with negative clinical lymph node metastasis who were treated from January 1998 to April 2006 were collected. The positive rate of the lymph nodes metastasis was analyzed. The relations between the central compartment lymph nodes and the patients' gender, age, tumor size and number were concerned. Among the 641 cases, 114 case who received operation more than five years were followed up for the relations between the pathological status of central compartment lymph nodes and ipsilateral neck metastasis or contra thyroid lobe recurrence. RESULTS: The median number of the central compartment lymph nodes was 4 each case and 53.0% (340/641) cases of papillary thyroid cancer patients with negative clinical lymph node metastasis had positive central compartment lymph nodes metastasis. Large tumor size and multiple origins were related to central compartment lymph nodes involvement, but the patients' gender or age was not. In the 114 follow-up cases, ipsilateral neck metastasis occurred in 12 cases, among which 11 cases had high positive central compartment lymph nodes metastasis. Contra thyroid lobe recurrence occurred in 5 cases, whose statuses of central compartment lymph nodes were different. CONCLUSIONS: Papillary thyroid cancer patients with negative clinical lymph node metastasis deserve formal central compartment dissection. The pathological status of central compartment lymph nodes relates to the tumor size and number. High positive rate of central compartment lymph nodes may lead to possible ipsilateral neck metastasis.

Sorafenib inhibits the angiogenesis and growth of orthotopic anaplastic thyroid carcinoma xenografts in nude mice.

Anaplastic thyroid carcinoma (ATC) remains one of the most lethal human cancers. We hypothesized that sorafenib, a multikinase inhibitor of the BRaf, vascular endothelial growth factor receptor-2, and platelet-derived growth factor receptor-beta kinase, would decrease tumor growth and angiogenesis in an orthotopic model of ATC. The in vitro antiproliferative and proapoptotic effects of sorafenib on ATC cell lines were examined. To study the in vivo effects of sorafenib on orthotopic ATC tumors in nude mice, sorafenib was given p.o. at 40 or 80 mg/kg daily. Intratumoral effects were studied using immunohistochemical analysis. The effect of sorafenib on survival of the mice was also studied. Sorafenib inhibited the in vitro proliferation of ATC cell lines. Sorafenib also significantly inhibited tumor angiogenesis via the induction of endothelial apoptosis in an orthotopic model of thyroid cancer. As result, the growth of orthotopic ATC xenografts was reduced and the survival of the test animals was improved. Sorafenib exerts significant antitumor activity in an orthotopic xenograft model of ATC via a potent antiangiogenic effect. The antiangiogenic effects of sorafenib suggest that its use in clinical setting may not depend on the BRAF mutational status of thyroid tumors. Given the lack of curative options for patients with ATC, sorafenib warrants further study as a therapeutic agent against ATC.

[Somatic mutations of mitochondrial DNA in thyroid papillary carcinoma].

OBJECTIVE: To analyze the somatic mutations in the D-loop of mtDNA and further evaluate the possibility of mitochondrial genetic instability in thyroid papillary carcinoma. METHODS: Hypervariable regions ( HVR-I and HVR-II) in the D-loop of mtDNA from the specimen of 35 thyroid papillary cancers and matched lymphocytes were amplified by PCR, and then were sequenced. RESULTS: Comparing the sequences of tumors to those of matched lymphocytes and normal thyroid tissues, 5 somatic mutations in 2 patients (5.7%) were found. Two mutations were insertions of C in a poly-cytidine (nt303) microsatellite, and 3 at positions 73, 152 and 194 in HVR-II. In addition, of the 294 genetic variants detected, 292 were previously recorded polymorphisms, whereas 2 were new polymorphisms (nt324:C-->G, nt16092:T-->A). CONCLUSIONS: Mutations in the D-loop of mtDNA were found in thyroid papillary cancers, this mutation rate was lower than the reported rate of alteration in tumors of epithelial origin, and further work is required to elucidate the relationship between this mutations and the development of thyroid papillary carcinoma.

[How to avoid hoarseness for operation of schwannoma of the cervical vagus nerve].

OBJECTIVE: To avoid hoarseness for operation of schwannoma of the cervical vagus nerve (SVN). METHODS: From Jan. 1997 to Sept. 2001, ten cases of SVN were operated. The procedures were as follows: Exposing the tumor and the vagus nerve, confirming its origin from the fascicle of recurrent laryngeal nerve (RLN) or the fascicle of non-RLN, making an small incision on the posterolateral surface of the tumor, usually posterior to the internal jugular vein, and then tearing and enlarging the small incision to enucleate the tumor. RESULTS: Two of the four cases of SVN originated from the fascicle of RLN happened temporary hoarseness and other two without hoarseness. All six cases of SVN originated from the fascicle of non-RLN, but one, happened no hoarseness. CONCLUSION: Above-mentioned technique is a good and reliable method to avoid hoarseness in the operation of SVN.