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As the most common endocrine malignant tumor,the incidence rate of thyroid cancer is increasing year by year.However,the vast majority of subtypes have a good prognosis after traditional surgery,TSH suppression therapy and 131I treatment.With the progressive development of modern medicine,for a few thyroid cancers with poor effects of traditional treatment,molecular diagnosis and targeted therapy have further enriched the therapeutic means of thyroid cancer,in which BRAF mutation is widely present in thyroid cancer,but it often shows primary resistance or poor response to 131I therapy.The factors leading to primary or secondary resistance to targeted drugs with BRAF mutation may include genomic instability,expansion of resistant clones,occurrence of intrinsic mutations,or novel genetic and epigenetic alterations.In this article,we will review the research progress in targeted therapy resistance in BRAF-mutant thyroid cancer.
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Objectives:To analyze the clinical features and prognosis of patients with medullary thyroid carcinoma combined with papillary thyroid carcinoma (combined carcinoma).Methods:The clinical data of 24 patients admitted to Tianjin Medical University Cancer Hospital from Nov 2012 to Dec 2019 were retrospectively analyzed. The treatment methods, pathological results, and prognosis of all patients were examined.Results:The results showed that combined carcinoma accounted for 10.0% (24/241) of all medullary thyroid carcinoma cases. In the combined cancer group, 45.8% (11/24) patients had lymph node metastasis, and the type of metastasis matched the largest lesion. There were no significant differences in gendex ratio ( χ2=0.164, P>0.05), age at onset ( t=1.381, P>0.05), maximum diameter of lesion ( Z=-1.733, P>0.05), multifocality ( χ2=2.695, P>0.05), and lymph node metastasis in the central ( χ2=1.625, P>0.05) and lateral neck regions ( χ2=1.537, P>0.05) between combined cancer patients and those with MTC alone. The median follow-up time for the 24 patients was 77.6 months. Local recurrence was observed in 2 cases, while no distant metastasis was found. There were no significant differences in disease-free survival, disease-specific survival, and overall survival between combined cancer and pure MTC groups (all P>0.05). Conclusion:The pathological characteristics and prognosis of medullary thyroid carcinoma combined with papillary thyroid carcinoma are similar to those of pure MTC. Therefore, clinical treatment decisions can be similar to pure MTC.
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Objective:To evaluate postoperative calcitonin level as a prognostic marker in long-term follow-up of medullary thyroid carcinoma(MTC).Methods:Clinical data of 146 MTC cases treated at Tianjin Medical University Cancer Institute and Hospital from Jan 2011 to Dec 2019 were reviewed retrospectively. The relationship between postoperative calcitonin and disease-free survival was analyzed. According to the level of calcitonin six months after operation, patients were divided into normal level group and elevated group.Results:The median tumor size in those 146 cases was (1.78±1.22)cm, and 81 cases had lymph node metastasis. After 6 months of follow-up, 89 cases had normal calcitonin, with median tumor size of (1.63±1.20)cm, and 35 cases had lymph node metastasis . After a median follow-up of 56 months, 78 patients had normal calcitonin, 11 patients had biochemical relapse, 3 patients had structural relapse, and no patients died. 57 cases had a higher calcitonin ,median tumor size (1.97±1.22)cm, 46 cases had lymph node metastasis, 5 cases had distant metastasis, 18 cases had structural recurrence, and 7 patients died. Univariate analysis showed that lymph node metastasis, TNM stage, preoperative calcitonin, lymph node dissection and postoperative calcitonin were correlated with long-term disease-free survival (all P < 0.05). Multivariate analysis showed that postoperative calcitonin and TNM stage were an independent prognosis factor for disease-free survival in MTC patients (all P < 0.05). Conclusion:Postoperative calcitonin is a independent prognostic marker for long-term disease-free survival in MTC patients.
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Objective:This study aimed to investigate the risk features of postoperative tumor recurrence of medullary thyroid carcinoma.Methods:One hundred and seventy two patients with medullary thyroid carcinoma diagnosed at Tianjin Cancer Hospital between Jan 2010 and Jan 2018 were enrolled in this study. Based on the follow-up results, patients were divided into tumor recurrence and non-tumor recurrence group. US features,clinicopathological characteristics and somatic RET mutations were evaluated between the two groups. The cut-off values of pre-and post-operative serum calcitonin were calculated by ROC curve.Univariate and multivariate analysis were adopted between the two groups to determine independent risk factors for tumor recurrence of MTC.Tumor-free survival was determined by Kaplan-Meier analysis.Results:Univariate analysis showed that preoperative serum calcitonin≥1 367 pg/ml ( χ2=18.909, P=0.000), postoperative serum calcitonin ≥61 pg/ml ( χ2=72.278, P=0.000), mulifocality ( χ2=11.787, P=0.001),lesions in both lobes ( χ2=10.452, P=0.003), extrathyroidal invasion ( χ2=14.511, P=0.000), T3+T4-staging ( χ2=11.920, P=0.001)、TNMⅢ+Ⅳ-staging ( χ2=18.915, P=0.000), ACR TI-RADS 5 ( χ2=7.162, P=0.006) and RET mutation ( χ2=10.937, P=0.001) were significantly related to tumor recurrence of medullary thyroid carcinoma. Multivariate analysis demonstrated that postoperative serum calcitonin≥61 pg/ml ( OR=22.323, 95%CI: 6.370-78.236) and RET mutation ( OR=4.054, 95%CI: 1.354-12.139) were the independent factors related to tumor recurrence of medullary thyroid carcinoma.The survival curves of MTC patients showed a significantly lower percentage of surviving patients in the group with postoperative serum calcitonin ≥61 pg/ml ( P=0.000) or RET mutations ( P=0.001). Conclusions:Postoperative serum calcitonin ≥61 pg/ml and oncogenic RET mutation were the independent risk factors for tumor recurrence of MTC.Patients with postoperative serum calcitonin ≥61 pg/ml or a RET mutation tended to have a shorter tumor-free survival.
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Objective:To compare the prognosis of patients with unilateral sporadic medullary thyroid carcinoma treated by different surgical selection, and analyze the independent risk factors affecting the prognosis.Methods:One hundred and twenty-six patients at Tianjin Medical University Cancer Institute and Hospital from Feb 2011 to Oct 2018 were retrospectively divided into group A (total thyroiclectomy) and group B (unilateral lobectomy).Results:There were no significant differences in postoperative recurrence rate ( χ2=0.394, P=0.530), mortality ( χ2=3.175, P=0.146), biochemical cure rate ( χ2=0.613, P=0.434), progression free survival and overall survival ( P=0.278, 0.175) between group A and group B; Tumor diameter ≥4 cm and lateral cervical lymph node metastasis were independent risk factors affecting the overall survival. The incidence of postoperative temporary hypocalcemia ( χ2=5.068, P=0.024) and permanent hypocalcemia ( χ2=6.590, P=0.010) in group A was higher than that in group B. Conclusions:Ipsolateral thyroidectomy can be applied to patients with unilateral sporadic medullary thyroid carcinoma with similar long term prognosis and tower incidence of temporary hypocalcemia and permanent hypocalcemia compared to total thyroidectomy.
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Objective:To investigate the difference of clinicopathological characteristics between mixed medullary and papillary carcinoma of thyroid and medullary carcinoma coexistent with papillary carcinoma.Method:The clinicopathological data of 3 MMPTC cases and 9 MTC-PTC cases treated at Tianjin Medical University Cancer Institute & Hospital during the past ten years were retrospectively analyzed. The differences in clinical characteristics, pathological characteristics, immunohistochemistry results, treatment and prognosis of the two groups were compared.Results:In the MMPTC group, the median onset-age was 59 years old. 3 patients were all medullary carcinoma colliding with micropapillary carcinoma. The immunohistochemistry results showed that medullary carcinoma and papillary carcinoma showed their distinctive immunohistochemical characteristics. The lymph node metastasis rate was 66.7% (2/3). In MTC-PTC group, the median onset-age was 55; 8 out of 9 patients had an increased preoperative calcitonin level. Medullary carcinoma and papillary carcinoma showed their distinctive immunohistochemical characteristics. Four out of the 9 cases had lymph node metastasis.Conclusion:Compared with MTC-PTC, MMPTC is more common in middle-aged and elder patients, with higher lymph node metastasis rate. The pathogenesis of MTC-PTC is similar to papillary thyroid carcinoma, and the treatment should be individualized. The prognosis of these two groups of patients is fair.
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Objective:To evaluate the clinical and ultrasonographic features for early diagnosis and prediction of lateral cervical lymph node metastasis of medullary thyroid microcarcinoma.Methods:From Jan 2010 to Jan 2020 233 patients undergoing primary surgery were categorized as "medullary thyroid microcarcinoma" and "medullary thyroid macrocarcinoma". The preoperative clinical and ultrasonographic characteristics, the diagnostic positive rate of preoperative serum calcitonin and fine needle aspiration (FNA) were investigated between two groups. All patients with medullary thyroid microcarcinoma were divided on the basis of wether there was lateral cervical lymph node metastasis.Results:There were statistically significant differences in initial diagnostic method(χ 2=32.290, P=0.000), TNM staging(χ 2=50.300, P=0.000) between medullary thyroid microcarcinoma and medullary thyroid macrocarcinoma. Medullary thyroid microcarcinoma showed more malignant ultrasonic features. The diagnostic accuracy of preoperative serum calcitonin was higher than FNA for medullary thyroid micro carcinoma(χ 2=47.933, P=0.000). Multivariate regression analysis demonstrated that the abutment/perimeter ≥1/4( OR=25.475, 95%CI: 2.320-279.771), preoperative serum calcitonin >65 ng/L( OR=32.663, 95%CI:2.433-438.409) were the independent factor for lateral cervical lymph node metastases of medullary thyroid microcarcinoma. Conclusions:The combination of ultrasonography and serum calcitonin helps establish early diagnosis of medullary thyroid microcarcinoma. Medullary thyroid microcarcinoma with the abutment/perimeter ≥1/4, serum calcitonin >65 ng/L predicts lateral cervical lymph node metastases.
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Objective:To analyze the clinicopathological characteristics of papillary thyroid carcinoma (PTC) in obese children and adolescents.Methods:From Jan 2012 to Dec 2015, 59 school-age PTC children and adolescents admitted to Tianjin First Central Hospital and Tianjin Medical University Tumor Hospital were recruited for retrospective case-control study. By using the chi-square test, the clinicopathological characteristics of obese children and adolescents with papillary thyroid carcinoma were analyzed. Kaplan-Meier method was used to analyze the factors significantly related to the recurrence.Results:Compared with patients of normal weight, overweight and obese patients were older (χ 2=4.250, P=0.039), and had multifocal tumors (χ 2=5.281, P=0.022) and higher recurernce rate (χ 2=4.861, P=0.027) .Compared with normal-weight children and adolescents with PTC, overweight or obese children and adolescents with PTC significantly had higher recurrence rate (χ 2=4.466, P=0.035); In addition, tumor diameters >1 cm (χ 2=5.453, P=0.020) and patients with multifocal tumors (χ 2=7.218, P=0.007) were also more likely to suffer recurrence. Conclusion:Among children and adolescent patients with papillary thyroid cancer, obesity is significantly related to multifocal tumors and higher recurernce rate.
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Objective:To investigate the BRAF(V600E)gene mutation of pediatric papillary thyroid carcinoma (PTC) and refine their clinicopathological correlates. Methods:Tumor tissue samples of pediatric PTCs (≤18 years old) were collected from tumor tissue bank of Tianjin Medical University Cancer Institute and Hospital from January 2012 to December 2016.The medical records of 22 patients with pediatric PTC were reviewed retrospectively.The frequencies of BRAF(V600E) mutation were evaluated and the correlation between BRAF(V600E) mutation and clinical characteristics were analyzed. Results:BRAF(V600E) mutations were present in 45.5% of cases (10 cases). BRAF(V600E) mutation in pediatric PTC was obviously lower than that in adults PTC(77.7%) ( χ2=11.250, P=0.001). BRAF(V600E) mutation in>12-year-old group (66.7%) was remarkably higher than that in ≤12-year-old group (20.0%) ( P<0.05). BRAF(V600E) mutation in female (69.2%) was greatly higher than that in male (11.1%) ( P<0.05). There was no significant correlation with BRAF(V600E) mutation and multiple tumor, tumor size, highly invasive subtype, extrathyroidal extension, lymph node metastasis and radiological history of infants (all P>0.05). The median follow-up time was 45 months.No patients died and BRAF(V600E) mutation was not associated with the increase of recurrence rate ( P>0.05). Conclusions:BRAF(V600E)gene mutation in pediatric PTC is lower than that in adults. BRAF(V600E) mutation does not portend a more aggressive clinical biological behavior in pediatric PTC.
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Objective:To evaluate the role of Tg in diagnosis of lateral cervical lymph node recurrence in papillary thyoid cancer(PTC)after radioactive iodine(RAI) therapy.Methods:From Jan 2012 to Aug 2018, 22 PTC patients who received RAI therapy after operation were reoperated for lateral cervical lymph node recurrence. The clinical data was retrospectively analyzed.Results:The median recurrence time was 30.5 (5-86) months. All 22 patients received RAI therapy after the first operation, and the median dose of RAI was 250mCi(100-700 mCi) and the episode of RAI therapy ranged from 1 to 4. All 22 PTC patients underwent neck reoperation, among which 20 cases were identified to have lymph node metastasis. The median number of lymph nodes dissected was 31 (8-83) and median number of metastatic lymph nodes was 4 (1-19) . The diagnostic accuracy of ultrasonography in detecting lymph node metastasis was 90.9%. Before reoperation, the median Tg was 1.305 (0.10-99.51) μg/L, with the cutoff value of Tg being 0.2 μg/L, and its sensitivity and specificity were 80.0% and 100%, respectively. The median stimulated Tg was 5.89 (0.14-255.80) μg/L in the 10 patients, with the cutoff value of stimulated Tg of 2 μg/L, and its sensitivity and specificity were 88.9% and 100%, respectively.Conclusions:The serum Tg level is helpful for monitoring the recurence of PTC, but recurrence cannot be completely ruled out for those with low Tg.
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As a treatment option for cancer, thermal ablation has satisfactory effects on many types of solid tumors (such as liver and renal cancers). However, its clinical applications for the treatment of thyroid nodules and metastatic cervical lymph nodes are still under debate both in China and abroad. In 2015, the “Zhejiang Expert consensus on thermal ablation for thyroid benign nodules, microcarcinoma, and metastatic cervical lymph nodes (2015 edition),” was released by the Thyroid Cancer Committee of Zhejiang Anti-Cancer Association, China. To further standardize the application of thermal ablation for thyroid tumors, the Thyroid Tumor Ablation Experts Group of Chinese Medical Doctor Association has organized many seminars and finally produced a consensus to formulate the “Expert consensus workshop report: Guidelines for thermal ablation of thyroid tumors (2019 edition).”
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Objective:To examine the expression of MHC class Ⅱ in medullary thyroid carcinoma(MTC) and analyze its clinical significance.Methods:98 MTC patients treated at Tumor Hospital of Tianjin Medical University from Jan 2010 to Dec 2018 were included for the study. Immunohistochemistry was used to detect the expression of MHC class Ⅱ molecule .Results:The high expression of MHC class Ⅱ was not correlated with age (χ 2=0.900, P=0.410), multifocal (χ 2=0.295, P=0.672), bilateral (χ 2=2.957, P=0.127), T stage (χ 2=0.554, P=0.457), but correlated with gender (χ 2=5.227, P=0.025), preoperative calcitonin level (χ 2=6.663, P=0.019), lymph node metastasis (χ 2=21.651, P<0.001) and AJCC stage (χ 2=19.522, P<0.001). Overall survival rate of patients with high expression of MHC class Ⅱ was 97.4%.It was significantly higher than that of patients with low expression 66.1% ( P=0.016 3). COX regression model showed that age >55 years old ( HR=4.129, P=0.009), T stage ( HR=3.265, P=0.024) were independent risk factors for the prognosis of MTC patients. High expression of MHC class Ⅱ molecules ( HR=0.103, P=0.030) was a protective factor for the prognosis of MTC patients. Conclusion:The MTC patients with high expression of MHC class Ⅱ have a better prognosis.
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Objectives To study the clinical characteristics,diagnosis,treatment and prognosis of cancer metastases to the thyroid gland.Methods At Tianjin Medical University Cancer Hospital,from 1980 to 2016 30 patients were identified with a metastatic malignant tumor of the thyroid gland.Results Primary tumor sites were in the esophagus (26.7％),lung (16.7％),and kidney (13.3％).The median age at discovery of thyroid metastasis was 56 years old.The time lapse ranged from 0 to 108 months.There were 18 patients with metachronous metastasis with median survival of 36 months,12 patients were with synchronous metastasis,and the median survival was 8 months (P ＜ 0.01).20 patients were treated with thyroid surgery,and of which 15 patients were given post-op radiotherapy and chemotherapy.Patients who underwent thyroid resection had a median survival of 15 months,while that was 8 months in those without thyoid surgery (P ＜ 0.01).Conclusions Metastases to the thyroid gland is a rare clinical phenomenon,the prognosis of patients is mainly related to the biological behavior of primary tumors,but surgical resection and combined treatment can increase the survival rate.
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Objective To investigate the correlation between ultrasonographic features of papillary thyroid microcarcinoma (PTMC) and cervical lymph node metastasis.Methods We reviewed 575 PTMC pathologically confirmed after operation in Tianjin Cancer Hospital,analyzing the ultrasonographic characteristics of primary site and risk factors of cervical lymph node metastasis.Results The univariate analysis showed that diameter ＞ 5 mm,length over breadth ratio ＞ 1,multifocality,ill-defined margin,hypoechogenicity,micro-calcification,capsule invasion ＞ 1/4 perimeter of PTMC were significantly associated with cervical lymph node metastasis.Lower pole nodules were correlated with central lymph nodes metastasis.By multivariate analysis micro-calcification,capsule invasion ＞ 1/4 perimeter of PTMC were independent risk factors for cervical lymph node metastasis.Diameter ＞ 5 mm and micro-calcification were independent risk factors of skip metastasis of ipsilateral lymph nodes.Conclusions Micro-calcification,capsule invasion ＞ 1/4 perimeter of PTMC are independent risk factors for cervical lymph node metastasis in PTMC patients.
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Objective To explore the clinico-pathological characteristics and treatment of thyroid carcinoma in patients under 14 years old.Method The clinical and pathological data of 61 children 14 years old or younger treated for differentiated thyroid carcinoma (DTC) from Jan 2005 to Dec 2014 were retrospectively analyzed.Results There were 26 males and 35 females with the sex ratio of 1 ∶ 1.35.All the 61 patients underwent surgery including lobectomy for ipsilateral foci in 11 cases and total or near total thyroidectomy for bilateral or multi-foci in 50 cases.5 patients had not lymph node metastasis.56 patients had central compartment metastasis and 47 patients had lateral cervical lymph node metastasis.9 patients had distant metastasis and the affected organ was lung.Pathology for all the 61 patients was thyroid papillary carcinoma,35 patients were of highly invasive subtype.The median follow-up time was 3 years and 6 months (30-116 months) with a total survival rate of 100％ while 4 patients suffered from recurrence.Conclusions For below 14 years old DTC patients,the prognosis is better than in adults.The rate of bilateral lesions or multiple foci in ipsilateral lobe and central compartment lymph node or lateral neck lymph node metastasis was higher than in adults.Furthermore,highly invasively pathological subtype is more common in younger patients.
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The incidence of thyroid cancer has increased sharply in recent years,and it has become one of the most common types of malignant cancers. Understanding of the underlying pathology both at home and abroad has developed rapidly over the past ten years.In addition,standardized diagnostic protocols and treatments in China have greatly improved.This review summarizes progress in the past ten years and outlined the prospects for the future of research and treatment of thyroid cancer.
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Thyroid carcinoma is the most common cancer that affects the endocrine system.With the development of research meth-ods and techniques of various disciplines,the clinical diagnosis,treatment,and understanding of thyroid carcinoma are constantly pro-gressing.In the latest edition of the National Comprehensive Cancer Network(NCCN)guidelines,the preoperative evaluation of thy-roid nodules,the mode and range of the operation,and the treatment involving postoperative thyroid stimulating hormone(TSH)sup-pression have changed,all of which can provide a reference for the diagnosis and treatment of thyroid nodules.
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Objective To investigate the distinct clinicopathological characteristics among different variants of papillary thyroid microcarcinoma(PTMC).Methods The clinicopathological data of 600 PTMC patients treated in Tianjin Medical University Cancer Hospital from July 2015 to December 2015 were analyzed retrospectively.Chi-square test was used to compare the distinct clinicopathological features among different variants and multivariate Logistic regression analysis was performed for independent predictors for lymph node metastasis (LNM).Results Conventional variant (43.0％),follicular variant (46.7％),and encapsulated variant (7.7％),accounted for 97.3％ of all cases.Follicular variant had the largest tumor size and encapsulated variant had highest rate of calcification and no extrathyroidal extension.The incidence of LNM was the highest in conventional variant followed by follicular variant and then by encapsulated variant.Maleness,age ＜ 45,calcification,minimal extrathyroidal extension and multifocality were independent risk predictors for LNM.Conclusions Follicular variant are the most common in PTMC,whose aggressiveness is far below conventional variant PTMC patients.Independent risk predictors for cervical LNM were maleness,age ＜ 45,tumor calcification,minimal extrathyroidal extension and multifocality.
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Objective@#To screen genes related to familial non-medullary thyroid carcinoma (FNMTC) using next-generation sequencing (NGS).@*Methods@#A panel of NGS was designed and sequencing was performed for DNA samples extracted from peripheral blood leukocytes of FNMTC patients and sporadic non-medullary thyroid carcinoma (SNMTC) cases, respectively, and gene mutations were screened. In addition, the clinicopathological characteristics, including tumor size, extension of surgery, lymph node metastasis and extra-thyroidal extension, were compared between patients with or without mutations.@*Results@#In 63 NMTC samples, 45 mutations were detected on 13 genes. 37 germline mutations were detected in 47 FNMTC patients, while 8 germline mutations were detected in 16 SNMTC patients. In 8 FNMTC family lineages, the same mutations were carried by FNMTC patients from the same pedigree. The number of carriers of mutations was 29 in the 47 FNMTC patients and 6 in the 16 SNMTC patients, with a non-significant difference (P= 0.092). Among the FNMTC patients, there were 22 patients with central lymph node metastasis in the 29 mutation-positive patients, significantly more than 7 in the 16 mutation-negative cases (P= 0.031). As for the parentage, there were 3 patients with central lymph node involvement among the 7 patients of parent generation, while all the 9 patients of offspring generation had central lymph node metastasis (P=0.019).@*Conclusions@#This panel of NGS can be used to screen mutant susceptibility gene of FNMTC patients, and the findings may be helpful for early detection of FNMTC patients and predicting the disease risk to familial members of FNMTC patients.
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Objective:To discuss the causes and effective measures of prevention and treatment of chylous fistula after central lymph node dissection (CLND) of thyroid cancer. Methods:A total of 6 127 patients who underwent CLND of thyroid cancer in the Tianjin Medical University Cancer Institute and Hospital between July 2013 and June 2015 were analyzed;of which, 14 patients acquired the complication of postoperative chylous fistula. The following conservative treatments were initially performed:systemic therapy, local pressure bandaging, normal pressure drainage, 50%glucose injection, or pingyangmycin injection through a drainage tube. Surgical op-eration was then conducted when the efficacy of the treatment was poor. Results:After the conservative treatment of the 14 patients, the drainage volume gradually decreased in 12 patients, and surgery was performed on the remaining two patients. Conclusion:The CLND of thyroid cancer must be carefully conducted to prevent postoperative chylous fistula. An active conservative treatment must be the first option when chylous fistula occurs. Surgery must only be performed if the treatment is invalid.