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.

[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.

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.

[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.

Free perforator flap transfer for reconstruction of skull base defects after resection of advanced recurrent tumor.

BACKGROUND: Skull base reconstruction is challenging due to its proximity to important anatomical structures. This report evaluates the use of perforator flaps for reconstruction of skull base defects after advanced recurrent tumor resection. METHODS: Fourteen free perforator flaps were transferred to reconstruct skull base defects in 14 consecutive patients, from October 2004 to May 2011. All patients had advanced recurrent neoplasms that were previously treated with either radiation therapy or surgery. The surgical defects were reconstructed using various perforator flaps mainly the deep inferior epigastric artery perforator flaps, anterolateral thigh (ALT) flaps, or thoracodorsal artery perforator flaps. The outcomes following reconstruction and associated complications were evaluated. RESULTS: The overall free flap success rate was 93% (13/14). One ALT flap was lost. Three patients (20%) had a cerebrospinal fluid fistula, and two of them developed meningitis. No complications were observed at the donor site. CONCLUSIONS: The use of perforator flaps may be a viable option for reconstruction of skull base defects after the resection of advanced recurrent tumor.

[Clinical features of familial non-medullary thyroid cancer patients].

OBJECTIVE: To analyze the clinical features of familial non-medullary thyroid cancers, and to discuss their management. METHODS: Sixty thyroid cancer patients with familial non-medullary thyroid cancer (FNMTC) history during Sep. 2003 to Sep. 2012 were collected as study group, and another 60 sporadic thyroid cancer patients were randomly chosen as control. We compared the differences of their clinical features. RESULTS: All the patients were diagnosed as thyroid papillary carcinoma. The study group included 40 female and 20 male patients. There were 16 cases in stage T1, 37 in stage T3, and 7 in stage T4. The patients were 21-66-year old ( median age 42-years). The control group included 49 female and 11 male patients. The patients were 24- to 78-year old, and the median age was 45.5 years. 43.3% of the patients in the study group and 18.3% of the patients in the control group had bilateral carcinomas (P = 0.003). There were multifocal lesions in 53.3% of the patients in the study group and 35.0% of the control group, local invasion in 73.3% of the patients in the study group and 55.0% of the control group, and coexisting benign thyroid diseases in 81.7% of the patients of the study group and 50.0% of the control group (P < 0.05 for all). There were cervical lymph node metastases in 60.0% of the patients in the study group and 38.3% in the control group (P = 0.018). In the study group, 32 cases were of parent-offspring type and 28 cases of sibling type. Among the parent-offspring type patients, the median onset age of the first generation offsprings was 58 years, and that of the second generation offsprings was 32 years (P < 0.001). CONCLUSIONS: Familial nonmedullary thyroid cancer, especially in parent-offspring type patients, is more aggressive than sporadic nonmedullary thyroid cancer, and often involves bilateral lobes, has multifocality, and combines with benign thyroid diseases. We recommend a total thyroidectomy for treatment, and to screen all the family members >20 years old, with ultrasonography for early diagnosis and treatment.

[Preliminary study of patterns of level IIb lymph node metastasis in papillary thyroid carcinoma].

OBJECTIVE: To evaluate the factors related to level IIb lymph node(LN) metastasis in papillary thyroid carcinoma (PTC). Method The medical records of 63 PTC patients were reviewed. The patients underwent neck dissection (ND) between January 2011 and December 2012, who were determined with pathologically lateral cervical LN metastasis. A total of 67 ND specimens were obtained and analyzed for LN involvement with respect to neck levels. The relation of level IIb LN metastasis with clinical factors, including age and sex of patients, tumor size, location, multifocality, extracapsular spread (ECS) and stage of primary PTC, coexistence of lymphocytic thyroiditis, distribution of metastasis LN in different levels, fusion and extracapsular invasion of LN were analyzed with univariate analysis and χ(2) test. SPSS 14.0 software was used to analyze the data. RESULTS: Of 63 patients, 41 patients revealed thyroid tumor maximum diameter more than 1 centimeter, 26 patients with tumor located in the upper 1/3 thyroid lobe, 39 patients with multiplicity of thyroid tumor and 54 patients with ECS, 54 patients with pathological T3/T4a stage, 15 patients with coexisting lymphocytic thyroiditis. Among the 67 ND specimens, 12 specimens (17.9%) showed level IIb LN metastasis and the incidences of LN metastasis at level IIa, III, IV, V, VI, IIa+III, III+IV, and IIa+III+IV were 56.7%, 86.6%, 68.7%, 22.4%, 86.6%, 52.2%, 55.2%, 37.3%, respectively. Of the 38 ND specimens with level IIa LN metastases, 10 were positive in level IIb(26.3%). But of 29 ND specimens without level IIa LN metastases, only 2 were positive in level IIb. A univariate analysis revealed that level IIa LN metastasis was a significant predictive factor for level IIb LN metastasis (χ(2) = 4.219, P = 0.040). CONCLUSION: The incidence of LN metastasis to level IIb is low in PTC, which is less when level IIa is not involved.

[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.

[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.