[Active surveillance for thyroid micro-malignant nodules].

Objective: To evaluate the effect of ultrasound diagnosis of thyroid micro-malignant nodules and accumulate practical experience for the management of active surveillance for them, so as to avoid overtreatment. Methods: A total of 949 patients who were diagnosed with thyroid malignant nodules using ultrasonography, with the nodules being less than 1 cm in size and without regional lymph node metastasis or distant metastasis, were included. They were treated by the same surgeon of the Department of Head and Neck Surgery, Cancer Hospital, Chinese Academy of Medical Sciences from February 2014 to December 2020. 112 patients chose immediate surgery. The rest patients were asked to accept ultrasound examination every 6 months to 1 year. Follow-up endpoints: tumor size growth of 3 mm, tumor volume increase greater than 50%, lymph node metastasis or distant metastasis. Results: The median follow-up time was 19 months. 713 patients underwent surveillance for more than 6 months. Of the 713 patients, 570 (79.9%) were women, with mean age at 43.5 years old. Tumor progression was observed in 47 (6.6%) patients with a cumulative incidence of 2.7% (1 year), 7.2% (2 years) and 9.5% (3 years). In multivariate analysis, patient age [HR=0.508, 95%CI: 0.275-0.939, P=0.031], lesion number [HR=2.945, 95%CI: 1.593-5.444, P=0.001] and tumor size [HR=2.245, 95%CI: 1.202-4.192, P=0.011] at the beginning of observation were independent risk factors for tumor progression in patients with minimal thyroid malignant nodules during follow-up. During a median (range) active surveillance of 19 (6-80) months, 74 patients chose surgery during the surveillance. Among the 186 patients who underwent surgery, only 3 patients were diagnosed with fibrotic nodules in pathology, while the rest were papillary thyroid carcinoma. The ultrasound accuracy reached 98.4%(183/186). Conclusions: Ultrasonography is an effective method of diagnosing malignant thyroid nodules. Thyroid micro-malignant nodules progress slowly. As a result, it is safe to observe them instead of taking immediate surgery. Patient age, lesion number and tumor size at the beginning of observation are independent risk factors for the tumor progression of malignant nodules.

[Analysis of surgical strategy for pediatric papillary thyroid carcinoma with low-intermediate risk].

Objective: To explore the feasibility and rationality of lobectomy in the treatment of pediatric thyroid papillary carcinoma (PTC) with low-intermediate risk. Methods: The clinicopathological features and follow-up data of pediatric PTC with low-intermediate risk were reviewed from March 2000 to December 2018 in Cancer Hospital of Chinese Academy of Medical Sciences. The correlations between different surgical procedures and prognoses were evaluated. Propensity score matching(PSM) was used to adjust for risk factors, and the difference in prognoses between the total thyroidectomy (TT) group and the lobectomy (LT) group was compared. Results: A total of 140 patients were included in the study, including 36 males and 104 females. The age range was from 6-year-old to 18-year-old. There were 43 low-risk patients and 97 intermediate-risk patients. The median follow-up time was 87.5 months, ranging from 8 to 241 months, and 20 patients (14.3%) showed recurrence during the follow-up period. Univariate analysis showed that N1b, extrathyroidal extension, the number of lymph node metastasis>5, the ratio of lymph node metastasis≥0.19, and radioactive iodine treatment were risk factors for recurrence (all P value below 0.05), but multivariate analysis showed that only the ratio of lymph node metastasis≥0.19 (HR=8.69, 95%CI=1.08-70.21, P=0.043) was an independent risk factor for recurrence. There was no significant difference in the 5-year recurrence free survival rates between TT group and LT group before propensity score matching (82.8% vs. 86.5%, χ2=0.219, P=0.640) and after propensity score matching (89.6% vs. 90.4%, χ2=0.099, P=0.753). Conclusion: There is no significant difference in recurrence-free survival between TT group and LT group. Lobectomy is feasible for selective pediatric PTC with low-intermediate risk.

[Comparison of quality of life of hypopharyngeal squamous cell carcinoma patients after laryngeal preservation surgery and total laryngectomy].

Objective: To evaluate and compare the quality of life (QOL) in patients with hypopharyngeal squamous cell carcinoma after laryngeal preservation surgery and total laryngectomy. Methods: We selected parts of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and the Head and Neck Module (EORTC QLQ-C30 and EORTC QLQ-H&N35) and designed the QOL questionnaire. We investigated 42 patients with hypopharyngeal squamous cell carcinoma underwent laryngeal preservation surgery and 38 patients underwent total laryngectomy by QOL questionnaire and followed up their survival. Results: The somatic function dimension, psychological function dimension, and social function dimension of patients underwent laryngeal preservation surgery were (92.46±15.71), (80.56±22.67) and (90.08±19.50), respectively, which were higher than (79.39±32.75), (68.42±25.05) and (61.84±29.55) of the total laryngectomy group (P<0.05), while the economic dimension was not significantly different between the two groups (P>0.05). The social function dimension (including social support and socialization, family relationship) of laryngeal preservation surgery group were (89.04±25.47) for postoperative time < 70 months and (90.94±13.28) for postoperative time ≥70 months, which were higher than (65.48±29.14) and (57.35±30.32) of the total laryngectomy group (P<0.01). Conclusions: The somatic function dimension, psychological function and social function of patients with hypopharyngeal squamous cell carcinoma underwent laryngeal preservation surgery obtain a better QOL than patients underwent total laryngectomy. Therefore, we should improve the laryngeal function and QOL of patients under the premise of ensuring the survival rate.

SP1-induced upregulation of long noncoding RNA LINC00313 contributes to papillary thyroid cancer progression via the miR-422a.

OBJECTIVE: Long noncoding RNA LINC00313 (LINC00313) has been reported to be dysregulated in several tumors, including papillary thyroid carcinoma (PTC). Our present study aimed to further explore the potential mechanism of LINC00313 in the progression of papillary thyroid carcinoma (PTC). PATIENTS AND METHODS: RT-PCR was performed to detect the expression of LINC00313 in both PTC tissues and cell lines. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays were performed to explore whether SP1 could bind to the promoter region of LINC00313 and activate its transcription. The biological functional correlation of LINC00313 was determined by down-regulating the expression of LINC00313 on PTC cell proliferation, apoptosis, migration and invasion. The regulating relationship between LINC00313 and miR-422a was investigated in PTC cells using luciferase reporter assays. RESULTS: We observed that LINC00313 expression was significantly up-regulated in both PTC tissues and cell lines. Next, the results of bioinformatics analysis and luciferase reporter assays indicated that the transcription factor SP1 can bind to the promoter region of LINC00313 resulting in the overexpression of LINC00313 in PTC. Moreover, functional study revealed that knockdown of LINC00313 significantly suppressed cells proliferation, migration, invasion and EMT. Finally, our results indicated that LINC00313 functioned as an oncogene in PTC in part through serving as a competing endogenous RNA to modulate mi-422a expression. CONCLUSIONS: Overall, our data demonstrated that SP1-induced LINC00313 contributed to PTC progression by via competitively binding to miR-422a, which may provide a novel therapeutic strategy for PTC.

[Dye-tattooing under ultrasound guidance in preoperative localization of neck recurrences from thyroid cancer].

Objective: To evaluate the efficacy and safety of the application of dye-tattooing under ultrasound guidance in preoperative localization of neck recurrences from thyroid cancer. Methods: Between October 2014 to September 2016, 25 patients with 34 lesions were enrolled. There were 22 cases of papillary thyroid carcinoma and three cases of medullary thyroid carcinoma, all of which could not be detected by computed tomography. Surgeons located the recurrent lesions using dye-tattooing under ultrasound guidance along with radiologist three days before the operation. Results: All lesions were successfully located (100%), 32 of which were located directly and two of which were located indirectly. Postoperative pathological examination confirmed 25 metastases of papillary thyroid carcinoma, two metastases of medullary thyroid carcinoma, and seven cases of false positives. The accuracy of ultrasound diagnosis was 79.4%. After 15 months of follow-up, neither tumor residual nor recurrences was detected according to imaging tests. Conclusions: Dye-tattooing under ultrasound guidance represents a reliable and safe method for localization of neck recurrences from thyroid cancer. The cooperation between experienced surgeons and radiologists will be crucial to successful location.

[Clinical analysis of secondary cervical lymph node dissection in papillary thyroid carcinoma].

Objective: To investigate the value of secondary cervical lymph node dissection in papillary thyroid carcinoma (PTC). Methods: PTC patients with recurrence re-operated in a previously dissected area at our hospital during 2000-2016 were included in this analysis. Patients were divided according to the operative interval of 6 months. The level and number of lymph node metastasis and the number of lymph node dissection were analyzed to calculate the ratio of lymph node metastasis. Results: A total of 336 PTC patients received 360 side lateral cervical lymph nodes dissection. The ratio of recurrence in unilateral lateral neck is 92.9%(312/336). The ratio of recurrence in multiple levels (more than two regions) were 47.5% (171/360). The recurrence ratio of level Ⅱ, Ⅲ, Ⅳ and Ⅴ were 55.6%(200/360), 44.2%(159/360), 59.7%(215/360) and 10.3%(37/360), respectively. Lymph node metastases were inclined to level Ⅱ (33.6%) and Ⅳ (35.8%). The mean number of lymph node dissection and metastasis in the group of operative interval ≤ 6 months was 26.56 per case and 4.37 per case, respectively. The mean number of lymph node dissection and metastasis in the group of operative interval >6 months was 16.80 per case and 3.20 per case, respectively. The number of lymph node dissection and metastasis between these two groups were significantly different (P=0.001, P<0.001). Conclusions: Lymph node metastasis of PTC patients with secondary cervical lymph node dissection are inclined to level Ⅱ and level Ⅳ. Moreover, multi-level metastasis is not rare. Level Ⅱ and level Ⅳ require more attention in the first operation. Most of the patients undergo reoperation because of residual lymph nodes from the previous treatment. Normalization and completeness of the initial dissection are particularly important to PTC patients.

[Central compartment reoperation for recurrent/persistent differentiated thyroid cancer].

Objective: To analyze the incidences of complications after central compartment reoperation for recurrent/persistent differentiated thyroid cancer, and to investigate the safety and feasiblity of central compartment reoperation. Methord: A total of 109 patients who underwent central compartment reoperation for recurrent/persistent differentiated thyroid cancer from January 1, 2011 to March 31, 2016 in Cancer Hospital, Chinese Academy of Medical Sciences was analysed retrospectively, and the incidences of reoperation-related complications were evaluated. Results: Among 109 patients, only 10 (9.2%) patients were treated initially in our hospital and remaining patients (90.8%) treated initially in the other hospitals. Surgical approaches for thyroid beds: 61 patients (56.0%) underwent supplemented total thyroidectomy, 3 patients (2.8%) for removal of recurrent thyroid cancer, 2 patients (1.8%) with supplemented total thyroidectomy and removal of recurrent thyroid cancer, and 12 cases (11.0%) had bilateral thyroid lobectomy. Central compartment lymph node dissection: 66 patients (60.6%) underwent bilateral central neck dissection, 40 patients (36.7%) with unilateral central neck dissection. A total of 16 patients (14.7%) had complications. Transient and permanent vocal fold paralysis developed in 9(8.3%) and 2(1.8 %) patients, respectively. Transient and permanent hypoparathyroidism occurred in 2(1.8%) patients and 11 patients (10.1%), respectively. Postoperative bleeding happened in 1 patient (0.9%). with follow-up from 7 to 61 month, median follow-up was 17.2 months. All patients survived, with recurrence in 3 (2.8%) patients. Conclusions: It seems the incidences of complications for thyroid carcinoma reoperation in central compartment is low for the experienced surgeon. The reoperation was safe and feasible.

[Genotype-phenotype correlations in multiple endocrine neoplasia type 2].

OBJECTIVE: To evaluate the relationship between different RET mutations and the aggressiveness of hereditary medullary thyroid cancer (HMTC) or the presentation of other endocrine disorders in patients with multiple endocrine neoplasia type 2 (MEN2). METHODS: A total of 73 thyroid medullary carcinoma patients from 22 Chinese kindreds who were treated in our center from 2010 to 2015 were enrolled. RET genes in the patients and their relatives were screened. RESULTS: According to the clinical data and 2015 American Thyroid Association (ATA) guidelines, patients were classified into 3 RET mutation risk groups: Modest, 24 cases; High, 48 cases; and Highest, 1 case. Multivariate analysis showed an increased likelihood of MTC stage III or IV at diagnosis with increasing of age and risk. The likelihood increased 11.6% per year of age at surgery (95% confidence interval, 1.040-1.198; P=0.002). The likelihood in patients with high risk was 7.9 times higher than patients with modest risk (95% confidence interval, 1.607-38.717; P=0.003). Aside from one patient with MEN2B, other 72 patients were MEN2A, of them, 28 cases from 7 kindreds with classical MEN2A (codon 634 & 618), 14 cases from 3 kindreds with cutaneous lichen amyloidosis (codon 634), 4 cases from 1 kindred with Hirschsprung's disease (codon 620), and 26 cases from 10 kindreds with familial MTC. CONCLUSION: The aggressiveness of HMTC and the presentation of other endocrine diseases are related to specific RET mutations. For RET mutation carriers, MTC and other endocrine diseases should be diagnosed and treated early based on the RET genotypes.

[Methylation status of PCDH10 and RASSF1A gene promoters in colorectal cancer].

OBJECTIVE: To investigate the methylation status of promoters of protocadherin-10 (PCDH10) and Ras-association domain family 1A (RASSF1A) genes in colorectal cancer (CRC), and to study its relationship with development and progress of CRC. METHODS: Tumor tissues were collected from 75 CRC patients who received surgical treatment in the Affiliated Hospital of Guizhou Medical University in the period from 2007 to 2010. Methylation-specific polymerase chain reaction (MSP) was applied to detect the methylation status of PCDH10 and RASSF1A gene promoters in CRC and adjacent normal colorectal mucosa. The relationship between methylation of PCDH10 and RASSF1A and clinicopathological features of CRC was analyzed using chi-squared test. RESULTS: The rate of PCDH10 methylation in CRC tissue was significantly higher than that in colorectal normal mucosa (58.7%(44/75)vs 22.7%(17/75), P<0.01). There was no significantly correlation between methylation of PCDH10 and patients' age, gender, tumor site, Dukes stage, and lymph node metastasis(all P>0.05). The rate of RASSF1A methylation in CRC tissue was significantly higher than that in colorectal normal mucosa (64.6%(42/65)vs 15.4%(10/65), P<0.01). There was no significantly correlation between methylation of RASSF1A and patients' age, gender, and tumor site (all P>0.05), but the patients in high Dukes stages and with lymph node metastasis had higher RASSF1A methylation rate(92.9%(26/28)vs 43.2%(16/37), 92.9%(26/28)vs 43.2%(16/37), both P<0.05). CONCLUSIONS: CRC tissues demonstrate high level of methylation of PCDH10 and RASSF1A genes, which may play a crucial role in the pathogenesis of CRC. The aberrant hypermethylation of RASSF1A gene is observed in more advanced CRC, suggesting that the RASSF1A gene methylation may be related to progression of CRC.