Distinct risk factors of lateral lymph node metastasis in patients with papillary thyroid cancer based on age stratification.

INTRODUCTION: Studies have revealed that age is associated with the risk of lateral lymph node metastasis (LLNM) in papillary thyroid cancer (PTC). This study aimed to identify the optimal cut point of age for a more precise prediction model of LLNM and to reveal differences in risk factors between patients of distinct age stages. METHODS: A total of 499 patients who had undergone thyroidectomy and lateral neck dissection (LND) for PTC were enrolled. The locally weighted scatterplot smoothing (LOWESS) curve and the 'changepoint' package were used to identify the optimal age cut point using R. Multivariate logistic regression analysis was performed to identify independent risk factors of LLNM in each group divided by age. RESULTS: Younger patients were more likely to have LLNM, and the optimal cut points of age to stratify the risk of LLNM were 30 and 45 years old. Central lymph node metastasis (CLNM) was a prominent risk factor for further LNM in all patients. Apart from CLNM, sex(p = 0.033), tumor size(p = 0.027), and tumor location(p = 0.020) were independent predictors for patients younger than 30 years old; tumor location(p = 0.013), extra-thyroidal extension(p < 0.001), and extra-nodal extension(p = 0.042) were independent risk factors for patients older than 45 years old. CONCLUSIONS: Our study could be interpreted as an implication for a change in surgical management. LND should be more actively performed when CLNM is confirmed; for younger patients with tumors in the upper lobe and older patients with extra-thyroidal extension tumors, more aggressive detection of the lateral neck might be considered.

Clinical factors associated with severe surgical complications in patients with hypopharyngeal cancer: a single-center case-cohort study.

BACKGROUND: Surgical complications are a major concern in the surgical treatment of hypopharyngeal cancer. OBJECTIVE: To identify clinical factors that predispose patients with hypopharyngeal cancer to severe surgical complications. MATERIALS AND METHODS: The data of 449 patients who were underwent surgery as a part of the initial treatment with curative intent or as salvage treatment were retrospectively reviewed. The Chi-square test and logistic regression were used to evaluate the association of different factors with severe surgical complications. RESULTS: The incidence of severe complications was 22% (99/449), and 10 patients (2.2%) experienced rupture of the carotid artery. Multivariate analysis identified T3/4 stage (p = .002, odds ratio (OR) = 1.58, 95% confidence interval (CI) 1.177-2.122), radiotherapy (RT) (p < .001, OR = 2.744, 95% CI 1.680-4.482), diabetes mellitus (DM) (p = .007, OR = 2.697, 95% CI 1.308-5.56), and nonprimary closure (p = .008, OR = 1.992, 95% CI 1.193-3.327) as significant risk factors for severe surgical complications. CONCLUSIONS AND SIGNIFICANCE: T3/4 stage, RT, nonprimary closure, and DM were independent predisposing factors for severe surgical complications in our study population of hypopharyngeal cancer patients. Taking measures to lower the tumor stage and simplify the surgical procedure may be crucial in reducing the incidence of severe surgical complications among these patients.

The role of multifocality in predicting central lymph node metastasis in initially treated 18-55 years old female patients with unilateral papillary thyroid microcarcinoma.

Objective: To determine the predictive ability of multifocality for central lymph node metastasis in initially treated 18-55 years old female patients with unilateral papillary thyroid microcarcinoma. Study design: Retrospective review. Setting: Tertiary medical center. Methods: We retrospectively collected clinical data from initially treated papillary thyroid microcarcinoma (PTMC) patients at Cancer Hospital Chinese Academy of Medical and sciences between January 1st, 2018, and December 31st, 2018. Data from 975 initially treated 18-55 years old female patients with unilateral PTMC was collected. We also collected data from 340 initially treated 18-55 years old male patients with unilateral PTMC patients to compare the results between genders. Clinicopathological factors associated with central lymph node metastasis (CLNM) were investigated by univariate and multivariate analysis. Results: (1) In the female group, there were 196 (20.1%) cases that had tumor multifocality, including 126 (12.9%) with 2 foci and 70 (7.2%) with >2 foci. The risk of CLNM in patients with 2 foci was not significantly higher than patients with 1 focus (37.3% vs 38.6%, P=0.775). However, diagnosed with >2 foci were independently and positively correlated with CLNM (OR=2.708, 95%CI=1.592-4.607, P<0.001), as was tumor diameter >0.55cm (OR=2.047, 95%CI=1.535-2.730, P<0.001). (2) In the male group, the risk of CLNM with 2 foci was significantly higher than 1 focus (P=0.008). Compared to female patients, the risk of CLNM was significantly higher in patients with 1 focus (P<0.001) or 2 foci (P<0.001). Conclusion: In summary, the risk of CLNM in patients with 2 foci was not significantly higher than patients with 1 focus, while multifocality with over 2 foci was an independent risk factor of CLNM. Therefore, multifocality in this subgroup should not be simply defined as "more than 1 focus". Future models that include multifocality as a predictive factor for cervical lymph node metastasis could consider stratifying the cohort into smaller subgroups for more accurate conclusions.

Involvement of KLRK1 in immune infiltration of head and neck squamous cell carcinoma correlates with favorable prognosis.

Head and neck squamous cell carcinoma (HNSCC) is a malignancy commonly found in the head and neck region, with a low 5-year survival rate. Although immunotherapy has made significant progress, its efficacy in HNSCC treatment remains unsatisfactory. Killer cell lectin-like receptor K1 (KLRK1), a marker highly expressed in immune cells, can bind to its ligands expressed by cancer cells to exert its antitumor effect. However, the role of KLRK1 in HNSCC has yet to be studied extensively. This study aimed to explore the involvement of KLRK1 in immune infiltration of HNSCC and its correlation with prognosis. We analyzed KLRK1 expression data from the Cancer Genome Atlas database. The relationship between KLRK1 and immune cell infiltration has also been investigated. Finally, we analyzed the association between the expression of KLRK1 and its ligands and the prognosis of patients with HNSCC. We found that KLRK1 was highly expressed in HNSCC and correlated with better prognosis. KLRK1 expression was correlated with age, histological grade, HPV infection, pT, pN, pTNM stage, primary site, and survival status. High expression levels of KLRK1 have been linked to high levels of immune cell infiltration, particularly CD4/8 (+) T lymphocytes. Among the ligands of KLRK1, UL16 binding protein (ULBP) 1-3 showed high expression, which was associated with an increased risk of death. Notably, the expression of KLRK1 was negatively correlated with ULBP1-3. Patients with high levels of ULBP2/3 expression in tonsil carcinoma had poorer prognosis than those with low levels (P < .01), whereas ULBP1 expression levels had no significant effect on tonsil carcinoma prognosis (P = .770). The expression levels of ULBP1/3 were correlated with worse prognosis in patients with laryngeal cancer (P < .05), whereas there was no significant correlation between ULBP2 expression levels and overall survival (P = .269). Our study revealed that KLRK1 is highly expressed in HNSCC and is associated with a better prognosis and immune infiltration. Patients with high expression of KLRK1 ligands exhibited worse prognoses, possibly because of the expression of more soluble ligands.

Evaluation of serum B7-H3 expression, ultrasound and clinical characteristics to predict the risk of cervical lymph node metastases in papillary thyroid carcinoma by nomogram.

BACKGROUND: Improving the preoperative diagnosis of cervical lymph node metastasis (LNM) will help improve the clinical outcomes of papillary thyroid carcinoma (PTC) patients. B7-H3, as an immune checkpoint of the B7 family, is highly expressed in PTC tissues and related to LNM and prognosis. We aimed to explore the clinical values of serum B7-H3 (sB7-H3) in predicting LNM in PTC by a nomogram prediction model. METHODS: From September 2019 to May 2021, a total of 344 PTC patients with primary surgery in our hospital were enrolled in this research. Enzyme-linked Immunosorbent Assay (ELISA) was used to detect sB7-H3 from the peripheral blood of PTC patients and normal controls. We created a nomogram prediction model in combination with sB7-H3 expression, clinical and ultrasound characteristics to predict LNM in the early stage. RESULTS: Gender (p = 0.001), age (p = 0.015), tumor size (p < 0.001), number of tumors (p = 0.021) and sB7-H3 expression (p = 0.003) were independent risk factors for LNM in PTC. All the factors were included in the nomogram. The area under the curve (AUC) was 73.9% (95% CI, 68.12%-79.69%). CONCLUSION: The nomogram is helpful in assessing the risk of LNM in PTC. sB7-H3 has excellent potential in predicting LNM in patients with PTC as an adjunctive ultrasound tool.

A nomogram to predict lateral lymph node metastases in lateral neck in patients with medullary thyroid cancer.

Background: Medullary thyroid cancer (MTC) can only be cured by surgery, but the management of lateral lymph nodes is controversial, especially for patients with cN0+cN1a. To address this challenge, we developed a multivariate logistic regression model to predict lateral lymph node metastases (LNM). Methods: We retrospectively collected clinical data from 124 consecutive MTC patients who underwent initial surgery at our institution. The data of 82 patients (from 2010 to 2018) and 42 patients (from January 2019 to November 2019) were used as the training set for building the model and as the test set for validating the model, respectively. Results: In the training group, the multivariate analyses indicated that male and MTC patients with higher preoperative basal calcitonin levels were more likely to have lateral LNM (P = 0.007 and 0.005, respectively). Multifocal lesions and suspected lateral LNM in preoperative ultrasound (US) were independent risk factors (P = 0.032 and 0.002, respectively). The identified risk factors were incorporated into a multivariate logistic regression model to generate the nomogram, which showed good discrimination (C-index = 0.963, 95% confidence interval [CI]: 0.9286-0.9972). Our model was validated with an excellent result in the test set and even superior to the training set (C-index = 0.964, 95% CI: 0.9121-1.000). Conclusion: Higher preoperative basal calcitonin level, male sex, multifocal lesions, and lateral lymph node involvement suspicion on US are risk factors for lateral LNM. Our model and nomogram will objectively and accurately predict lateral LNM in patients with MTC.

Isthmectomy is effective and sufficient for selected patients with the isthmus-confined solitary papillary thyroid carcinoma.

BACKGROUND: To retrospectively analyze the outcomes of patients treated with isthmusectomy for a solitary papillary thyroid carcinoma (PTC) confined to the isthmus, and re-assess the role of isthmusectomy in these patients. METHODS: The medical records of 65 patients who underwent isthmusectomy for a solitary PTC confined to the isthmus at the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College between 1985 and 2015 were retrospectively reviewed. Demographic data, surgical procedures, pathological characteristics, stages, and outcomes were analyzed. RESULTS: Patients' median age was 39 years (range, 19-63), and the majority were female (86.2% female, 13.8% male). All patients had a solitary PTC confined to the isthmus and were treated with isthmusectomy. Pretracheal lymph node dissection was performed in 34 patients, in which unilateral central neck dissection was performed in 4 patients and bilateral central neck dissection in 2 patients. Microscopic extrathyroidal extension (ETE) was observed in 23 (35.4%) patients, and macroscopic ETE was observed in 3 (4.6%) patients. Thirty-eight (58.5%) patients were stage pT1a, 19 (29.2%) patients were stage pT1b, 5 (7.7%) patients were stage pT2, and 3 (4.6%) patients were stage p3b. Fifteen (23.1%) patients were stage pN1a. Median follow-up time was 78 months (range, 12-274). Two patients experienced a recurrence and both achieved remission after re-operation. The 10-year recurrence-free survival was 92.1%. The 10-year overall survival and disease specific survival were 98.3% and 100%, respectively. CONCLUSIONS: Isthmusectomy is effective and sufficient for select patients with a solitary PTC confined to the isthmus.

Is new American Thyroid Association risk classification for hereditary medullary thyroid carcinoma applicable to Chinese patients? A single-center study.

OBJECTIVE: The American Thyroid Association (ATA) proposed a new risk classification for hereditary medullary thyroid carcinoma (MTC) in 2015. This study aimed to assess whether the new guidelines are suitable for the Chinese population, and reported our experience on prophylactic thyroidectomy. METHODS: A total of 73 patients from 22 families were screened as rearranged during transfection (RET) mutation carriers from 2010 to 2016 in Cancer Hospital, Chinese Academy of Medical Science; the medical history for each patient was collected. Based on the initial treatment, we identified the risk factors for poor prognosis by univariate and multivariate logistic regression. Then, 4 RET mutation carriers were enrolled for prophylactic thyroidectomy, and their pathological data and follow-up outcomes were recorded. RESULTS: In univariate and multivariate logistic regression analyses, age at initial surgery and risk classification were significant risk factors for stage III/IV hereditary MTC at initial diagnosis. The likelihood was increased by 11.6% per year of age at initial surgery [95% confidence interval (95% CI), 1.040-1.198; P=0.002). It was 7.888 times more likely to have III/IV stage disease for ATA highest risk patients, compared to ATA moderate risk individuals (95% CI, 1.607-38.717; P=0.003). Postoperative pathological results showed all 4 multiple endocrine neoplasia type 2A (MEN2A) patients had C-cell hyperplasia (CCH); multifocal malignancies were detected in 3 of them. All 4 patients were cured biochemically, and none developed permanent hypoparathyroidism. CONCLUSIONS: In Chinese individuals, hereditary MTC aggressiveness is in line with the new ATA risk classification. Germline RET gene mutation carriers should undergo prophylactic thyroidectomy according to basal serum calcitonin levels.

Screening of RET gene mutations in Chinese patients with medullary thyroid carcinoma and their relatives.

The rearranged during transfection (RET) gene is a proto-oncogene; active mutations frequently occur in medullary thyroid carcinoma (MTC). This study investigated the spectrum of germline RET mutations and clinical features in Chinese hereditary MTC patients. A total of 53 family members from 11 different hereditary MTC families were recruited for detection of RET exon 8, 10, 11, 13, 14, 15, and 16 mutations, in genomic DNA from peripheral blood leucocytes using polymerase chain reaction (PCR) and direct DNA sequencing. Of the 53 participants, eight different germline RET mutations were detected in 37 individuals. These RET mutations were distributed in exons 10, 11, 13, and 16. The most frequent RET mutation was localized at exon 11 codon 634 (67.6 %; 25/37) and the most prevalent mutation was C634R (37.8 %; 14/37). The most frequent phenotype was multiple endocrine neoplasia type 2A (MEN2A). The incidences of MTC, pheochromocytoma, and hyperparathyroidism in the MEN2A patients were 100, 36.4 and 18.2 %, respectively. The phenotype of families with Y606C or L790F mutation was categorized as familial medullary thyroid carcinoma. Moreover, one proband was identified with multiple endocrine neoplasia type 2B and carried a de novo mutation of M918T. Two families with C618S/Y mutation were categorized as unclassified multiple endocrine neoplasia type 2. Our results further substantiate that most germline mutations of the RET proto-oncogene were localized at codon 634 in Chinese hereditary MTC patients and carriers. RET mutation at codon 634 was always associated to the phenotype of MEN2A. Screening of RET mutations should be probably limited to exons 10, 11, 13 and 16 initially to be cost-effective in China.

[Clinical experience with the supraclavicular flap to reconstruct head and neck defects].

OBJECTIVE: To evaluate the efficacy of pedicled supraclavicular artery island flaps for head and neck reconstruction. METHODS: Reconstructive surgeries for head and neck oncologic defects were performed with the pedicled supraclavicular artery island flaps in 10 patients from May 2013 to December 2014 and the cases were review. Among them, 6 were performed for hypopharyngeal cancer, 2 for oral tongue cancer, 1 for oral base cancer and 1 for cervical esophageal cancer. The size of the flaps was measured in (5-8) cm × (6-12) cm. RESULTS: Seven flaps survived, one flap failured and two flaps had partial necrosis. Donor sites were closed primarily without morbidity. CONCLUSION: The pedicled supraclavicular artery island flap is an easy harvesting and reliable for head and neck reconstruction, especially suitable for otolaryngo-head and neck surgeon and maxillofacial surgeon in the local hospital.

[Digital and three-demention print technique in reconstruction for complex defect after resection of jaw neoplasms].

OBJECTIVE: To evaluate the application of digital and three-demention (3D) print technique in reconstruction of complex jaw defect after removal of maxillofacial cancer. METHODS: From May 2013 to January 2015, 10 cases were enrolled in the study, 3 were maxillary defects and 7 were mandibular defects. The process included preoperative computer aided design, template and model manufacture with 3D Printer, intraoperative ablation and shaping of fibula based on template, flap suture and vessel anastomosis. RESULTS: All the cases were successfully operated according to preoperative computer aided design, and all the fibulas and skin islands survived. All the cases had regular diet 2 weeks after surgery and showed satisfying appearance. CONCLUSION: Digital and 3D print technique has good practicability in reconstruction of complex jaw defect with free fibula.

[Head and neck neurofibromas: analysis of 46 cases].

OBJECTIVE: To investigate the surgical mode, recurrence and prognosis for patients with head and neck neurofibromas and explore their treatment strategies. METHODS: The clinicopathological features, operation mode, prognosis and neural function of 46 patients with head and neck neurofibroma were analyzed retrospectively, and 41 of the cases were followed up for 24-170 months (median 74 months). RESULTS: Among the 41 followed-up patients, 26 patients were cured and 15 patients were not cured (two died). The cure rate of the neurofibromas with neurofibromatosis type 1 (NF1) and the neurofibromas without NF1 were 42.9% and 85.0%, respectively (P = 0.005). The cure rate of localized, aggressive, diffuse and beaded neurofibromas were 100.0%, 46.6%, 40.0% and 66.7%, respectively (P = 0.009). The cure rate of radical resection (including expanding excision and complete resection) and partial resection were 73.5% and 14.3%, respectively (P = 0.011). The cure rates of expanding excision and partial resection were 80.0% and 14.3% (P = 0.029). The cure rates of complete resection and partial resection were 70.8% and 14.3%, respectively (P = 0.026). However, the cure rates of expanding excision and complete resection were not significantly different (P = 0.581). Multivariate Cox model analysis indicated that thoroughness of surgery was the independent risk factor for the prognosis for patients with head and neck neurofibromas. CONCLUSIONS: Neurofibroma is a kind of aggressive benign tumors. Some neurofibromas have a high recurrence rate and low recovery rate, and some nerves are essay to be injured in the operation. Lots of factors impact on the prognosis and recovery of the neural function. Therefore, operation opportunity and mode should be carefully selected.

[Cervical lymph node metastasis in medullary thyroid carcinoma].

OBJECTIVE: To study the patterns of cervical lymph node metastasis of medullary thyroid carcinoma. METHODS: Ninety-one patients with medullary thyroid carcinoma first treated between January 1999 and October 2014 were analyzed retrospectively. Of 91 patients, 39 cases presented with clinical negative node (cN0) and 52 cases with clinical positive node (cN+). Central compartment dissection was performed in all cases. Lateral neck dissection was performed in 52 cN+ cases (71 sides). All neck dissection specimens were obtained and analyzed for lymph node (LN) involvement with respect to neck levels. The distribution of LN with metastasis was studied in cN+ patients and the following factors were used to study the predictive value of central compartment LN metastasis: sex, age, family history, tumor size, bilateral tumor, multifocality of the tumor, extracapsular spread, and remote metastasis. Univariate analysis with the χ(2) test was used to analyze the statistical correlation between central compartment LN metastasis and other clinical factors. Multiple logistic regression analysis was used to identify the factors related to central compartment metastasis. RESULTS: Neck and bilateral neck metastasis rates were 73.6%, 19.8% respectively. Metastasis rates in central compartment and superior mediastinal region were 68.1% and 27.5% respectively. The central compartment metastasis rate was 33.3% in cN0 patients and 94.2% in cN+ patients. The superior mediastinal metastasis rate was 2.6% in cN0 patients and 46.2% in cN+ patients. Extracapsular spread was an independent predictive factor for central compartment metastasis (χ(2)=15.592, P=0.000, OR=12.876). The incidences of LN metastases at level II, III, IV, V were 62.9%,84.5%,83.1%,50.0% in cN+ patient, respectively. Multi-sites were involved. The possibility of lateral neck metastasis was higher when preoperative value of calcitonin was higher than 300 ng/L (66.7% vs 28.6%, χ(2)=5.771, P=0.016). CONCLUSIONS: Cervical lymph node metastasis of medullary thyroid carcinoma is higher. Central compartment dissection is necessary in cN0 patients with extracapsular spread. Neck dissection from level II to level VII was necessary in cN+ patients. Preoperative value of calcitonin maybe can predict the lateral neck metastasis incidence.

The BRAFT1799A mutation is not associated with occult contralateral carcinoma in patients with unilateral papillary thyroid microcarcinoma.

BACKGROUND: The phenomenon of occult carcinoma maybe observed in patients with clinically unilateral papillary thyroid microcarcinoma (PTMC). Although many studies have reported that the BRAFT1799A mutation is associated with aggressive PTMC, the relationship between BRAFT1799A mutation and occult carcinoma is unclear. The aim of this study was to investigate the risk factors, including BRAFT1799A mutation, for occult contralateral carcinoma in clinically unilateral PTMC accompanied by benign nodules in the contralateral lobe. MATERIALS AND METHODS: From January 2011 to December 2013,we prospectively enrolled 89 consecutive PTMC patients with clinically unilateral carcinoma accompanied by benign nodules in the contralateral lobe who received a total thyroidectomy and cervical lymph node dissection. BRAFT1799A mutation was tested by pyrosequencing on postoperative paraffin specimens. The frequency and predictive factors for occult contralateral carcinoma were analyzed with respect to the following variables: age, gender, family history, tumor size, presence of Hashimoto thyroiditis, extrathyroidal extension, central lymph node metastasis, multifocality of primary tumor, or BRAFT1799A mutation. RESULTS: A total of 36 patients (40.4%) had occult PTMC in the contralateral lobe. The median diameter of the occult tumors was 0.33±0.21 cm. The BRAFT1799A mutation was found in 38 cases (42.7%). According to the univariate analysis, there were no significant differences between the presence of occult contralateral carcinoma and age, gender, family history, tumor size, presence of Hashimoto thyroiditis, extrathyroidal extension, central lymph node metastasis, multifocality of primary tumor, or BRAFT1799A mutation. CONCLUSIONS: Using current methods, it is difficult to preoperatively identify patients with PTMC, and further research is needed to determine predictive factors for the presence of occult contralateral carcinoma in patients with unilateral PTMC.

[Larynx preservation and hypopharyngeal reconstruction in posterior hypopharyngeal wall sqamous cell carcinoma].

OBJECTIVE: To study the larynx preservation after resection of posterior hypopharygeal wall squamous cell carcinoma. METHODS: Retrospective review of 13 patients who underwent resection of posterior hypopharyngeal wall squamous cell carcinoma from October 2004 to May 2013. Of 13 patients, 6 had T2 lesions and 7 had T3 lesions. Two underwent salvage surgery, 2 with concurrent chemoradiotherapy before surgery, 2 with no radiotherapy and other 7 with postoperative radiotherapy (55 Gy). Repair with flap was not required in 6 cases, and repair with free skin graft was performed in 1 case, submental flap for 1 case, supraclavicular artery flap for 1 case, radial forearm flaps for 3 cases, and anterolateral thigh flap for 1 case for laryngopharyngeal reconstruction. RESULTS: The 3 year over all survival rate and disease-specific survival rate were 51.6%. Surgical complications included 3 fistula, 1 wound infection, and 1 wound effusion. The rate of decanulation was 100%, and all patients were with oral feeding. CONCLUSION: Different flaps can be used to reconstruct a functional larynx after resection of posterior hypopharyngeal wall squamous cell carcinoma, patients having good quality of life.

[Clinical role of BRAF V600E mutation testing in thyroid nodules].

OBJECTIVE: To evaluate the clinical role of BRAF V600E mutation testing in fine-needle aspirates (FNA) of thyroid nodules. METHODS: This study included 83 nodules in 80 patients who underwent FNA from March 2013 to September 2013. Cytological specimens were collected and BRAF exon 15 was examined by polymerase chain reaction (PCR). DNA sequencing and analysis were performed. Diagnostic performances of cytology and cytology with BRAF V600E mutation analysis were compared according to postoperative pathological diagnosis. The relation of BRAF V600E mutation with clinical factors including sex and age of patients, tumor size, lymph node metastasis, multifocality, and AJCC stage were analyzed. RESULTS: Of 83 nodules, 33 nodules were clinically observed, and 48 nodules underwent surgery, and suggestions of surgery were refused in 2 nodules. Among 48 nodules with surgery, BRAF V600E mutation was found in 25 nodules with histologic confirmation of papillary thyroid carcinoma after thyroidectomy, 13 of the 25 nodules were cytologically diagnosed as carcinoma and 12 were indeterminate. Among the 23 BRAF V600E negative noodles, 5 were cytologically diagnosed as carcinoma, 2 were benign, and 16 were indeterminate; 15 nodules were histologic confirmation of papillary thyroid carcinoma after thyroidectomy, 1 nodule was medullary thyroid carcinoma, and 7 nodules were benign. Biomolecular analysis significantly increased cytology sensitivity for papillary thyroid carcinoma from 43.9% to 73.2% (P < 0.05). Direct DNA sequencing showed that the presence of BRAF V600E mutation was 62.5% in 40 thyroid papillary nodules. There were 16 BRAF-positive nodules (80.0%) among 20 papillary thyroid nodules with extrathyroidal extension, however there were 9 BRAF-negative nodules (45.0%) among 20 papillary thyroid nodules without extrathyroidal extension. Univariate analysis indicated the BRAF V600E mutation was associated with extrathyroidal extension (χ² = 5.227, P = 0.022), but not with sex, age, tumor size, lymph node metastasis, multifocality and AJCC stage. CONCLUSION: BRAF V600E mutation analysis can significantly improve FNA diagnostic accuracy and maybe useful for prediction of high-risk of thyroid carcinoma.

[Prediction of occult carcinoma in contralateral nodules for unilateral papillary thyroid carcinoma].

OBJECTIVE: To investigate the risks for occult carcinoma in contralateral nodules for unilateral papillary thyroid carcinoma. METHODS: The study included 157 consecutive cases of unilateral papillary thyroid carcinoma with benign nodules in the contralateral lobe identified by preoperative ultrasound or fine-needle aspiration from January 2011 to December 2013. The patients received total thyroidectomies and neck lymph node dissections. The frequency and predictive factors for contralateral occult carcinoma in these patients were analyzed. RESULTS: A total of 68 patients (43.3%) had occult papillary thyroid carcinoma in the contralateral lobe and the maximum diameter of contralateral occult papillary carcinoma ranged from 0.1 to 1.2 cm, including ≤ 0.5 cm in 56 patients, 0.5-1.0 cm in 9 patients and >1.0 cm in 3 patients respectively. In univariate analysis, occult carcinoma in the contralateral lobe was associated with patient age (χ(2) = 7.266, P = 0.007) and pathologically multifocality in the ipsilateral lobe (χ(2) = 5.090, P = 0.024), but not with family history, tumor size, thyroid function, Hashimoto's thyroiditis, perithyroidal invasion, multifocality in the ipsilateral lobe, clinically or pathologically node-negative neck. In multivariate Logistic an analysis, age (OR = 1.054, P = 0.001) and multifocality in the ipsilateral lobe on final pathology (OR = 2.443, P = 0.021) were independent predictive factors for contralateral occult papillary thyroid carcinoma. CONCLUSIONS: Occult carcinoma is common in the contralateral "benign" nodules in patients with unilateral papillary thyroid carcinoma especially in young patients or the cases with multifocal tumors.

[Factors related to central lymph node metastasis in different subregions for unilateral papillary thyroid carcinoma with clinical N0 stage].

OBJECTIVE: To study clinicopathologic factors related to central lymph node (CLN) metastasis in different subregions for unilateral papillary thyroid carcinoma (PTC) with clinical N0. METHODS: A total of 145 PTC cases with clinical N0 treated in the same group of the department of head and neck surgery, Cancer Hospital, Chinese Academy of Medical Science between Jan. 2011 and Jan. 2014 was analysed retrospectively. Clinicopathologic factors related to CLN metastasis in different subregions were analyzed, including sex, age, tumor size, extrathyroidal extension, and multifocal tumor. RESULTS: CLN metastases existed in 57.9% (84/145) cases and the incidences of ipsilateral paratracheal, pretracheal, and prelaryngeal metastasis were 53.8%, 24.1% and 11.3% respectively. Right paratracheal lymph node metastasis occurred in anterior (17/38, 44.7%) and posterior (12/38, 31.6%) to the recurrent laryngeal nerve. Multivariate analysis indicated that extrathyroidal extension (OR = 4.49, 95%CI 1.80-11.20, P = 0.001) and tumor size (OR = 2.17, 95%CI 1.06-4.45, P = 0.034) were independent risk factors for ipsilateral paratracheal CLN metastasis; ipsilateral paratracheal CLN metastasis (OR = 2.12, 95%CI 0.08-4.60, P = 0.003) was an independent risk factor for pretracheal CLN metastasis. CONCLUSIONS: A high risk of CLN metastasis especially ipsilateral paratracheal metastasis exists in DTC with clinical N0. Ipsilateral paratracheal, pretracheal and prelaryngeal CLN dissection should be conducted when maximum tumor diameter more than 1 cm or extrathyroidal extension. CLN anterior and posterior to the recurrent larygeal nerve should be removed simultaneously when the ipsilateral paratracheal CLN metastasis at right side. Total thyroidectomy and contralateral paratracheal CLN dissection should be conciderded in multifocal tumor.

Functional polymorphisms in FAS and FASL contribute to risk of squamous cell carcinoma of the larynx and hypopharynx in a Chinese population.

Accumulating evidences indicate that the functional FAS-1377G>A, -670A>G and FASL-844T>C polymorphisms affect the risk of several kinds of cancers. However, their roles in the development of larynx and hypopharynx squamous cell carcinoma (SCC) were still unknown in the Chinese. In the current study, we examined whether these functional genetic variants were associated with the risk of larynx and hypopharynx squamous SCC in a Han Chinese population. The FAS and FASL polymorphisms were genotyped in 300 patients with laryngeal and hypopharyngeal SCC and 300 control subjects by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Logistic regression analysis revealed that subjects carrying the FASL-844CT or TT genotype had a significantly decreased risk of developing laryngeal and hypopharyngeal SCC [odds ratio (OR)=0.69; 95% confidence interval (CI)=0.51-0.93; P=0.016; or, OR=0.41; 95% CI=0.20-0.86; P=0.009] compared with those carrying the CC genotype. Joint gene-smoking and gene-drinking effects were also observed, with the OR of CC genotype for smokers or drinkers were 5.15 (95%CI=3.24-8.97) or 12.52 (95%CI=7.31-22.47), respectively. Therefore, the FASL-844T>C polymorphism is associated with genetic susceptibility of developing laryngeal and hypopharyngeal SCC in a Han Chinese population.

[Significance of selective neck dissection in patients with cN0 thyroid carcinoma].

OBJECTIVE: To investigate the significance of selective neck dissection in patients with cN0 thyroid carcinoma who have a high-risk of lateral neck lymph node metastasis. METHODS: Sixty three patients with cN0 thyroid carcinoma who have a high-risk of lateral neck lymph node metastasis were prospectively studied at the Department of Head and Neck Surgery, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between August 2006 and June 2011. The patients with cN0 thyroid carcinoma easy to occur neck lymph node metastasis include: The maximum diameter of primary tumor is ≥ 2 cm; The primary tumor invaded the thyroid capsule; Lymph node metastasis in level VI is found; Lymph node enlargement in level III or/and IV were detected preoperatively by ultrasonography, but not considered as metastasis. The surgical procedure is that the selective neck dissection in level III and IV is performed depending on the collar incision of thyroid surgery. The lymph node chosen from the specimen has a frozen section. If lymph node metastasis is found in the frozen section, a functional neck dissection should be performed through prolonging the collar incision. RESULTS: All cases were pathologically confirmed as thyroid papillary carcinoma. The occult metastasis rate of lateral neck lymph nodes was 39.7%. According to the univariate analysis, the patients with thyroid capsule invasion and lymph node metastasis in level VI were more likely to have lateral neck lymph node metastasis, and the occult metastasis rate was 46.9% and 54.3%, respectively (P = 0.028, P = 0.008), and there were statistically no significant difference in the primary tumor size and the preoperative neck lymph node status by ultrasonography with occult metastasis of lateral neck lymph nodes (P = 0.803 and P = 0.072). According to the multivariate analysis, there was a significant correlation only between the lymph node metastasis in level VI and occult metastasis of lateral neck lymph nodes (P = 0.017), but there was no significant correlation with the thyroid capsule invasion, primary tumor size and neck lymph node status by preoperative ultrasonography in prediction of occult metastasis of lateral neck lymph nodes (all P > 0.05). CONCLUSIONS: Selective neck dissection is feasible for the patients with cN0 thyroid carcinoma who have a high-risk lateral neck lymph node metastasis and the lateral occult metastatic lymph node can be promptly found and removed. We suggest that the selective neck dissection for level III and IV should be routinely performed in cN0 thyroid carcinoma patients with thyroid capsule invasion and lymph node metastasis in level VI.