| The incidence rate of thyroid cancer is increasing worldwide.Among them,the rapid growth of papillary thyroid microcarcinoma is the main reason.Most of the patients with papillary thyroid microcarcinoma have no clinical symptoms,which are found by routine physical examination.In recent years,the development and popularization of high frequency ultrasound and fine needle aspiration have further increased the diagnosis of thyroid papillary microcarcinoma.Most of them are low-risk.The recurrence rate is 1-5%and the10-year mortality rate is as low as 0.3%.Therefore,it has become a consensus to adopt a more conservative treatment strategy for low-risk papillary thyroid microcarcinoma.The incidence of high-risk papillary thyroid microcarcinoma is very low,and through surgery,iodine-131 and endocrine suppression treatment,most of them can achieve good therapeutic effect.However,whether some intermediate-risk papillary thyroid microcarcinoma should adopt conservative or relatively radical treatment strategy is still controversial,and there is no consensus among the treatment guidelines from various countries.For differentiated thyroid cancer,about 20-50%of the patients were found lateral cervical lymph node metastasis before operation.In papillary thyroid microcarcinoma,the incidence of lateral cervical lymph nodes was less than 10%.Preoperative ultrasound,computed tomography,fine needle aspiration and thyroglobulin-fine needle aspiration play an important role in the diagnosis of lateral neck metastasis,especially fine needle aspiration,which is considered as the"gold standard"for diagnosis.The guidelines of American Thyroid Association recommend fine needle aspiration only for suspicious lateral neck lymph nodes≥1cm.However,in clinical work,there are some cases with the diameter of the suspicious lymph nodes<1 cm.Because the diameter of the suspicious lymph nodes is small and adjacent to the important structure of the neck,it can not be diagnosed through the fine needle aspiration before the operation.The only way is removing the local lymph nodes during the operation and sending them for frozen section pathology,so as to achieve the purpose of diagnosis.However,the pathological diagnosis of lymph nodes during operation by frozen section may produce false positive and false negative results.Therefore,whether there are some risk factors to predict the risk of metastasis for suspected lymph nodes is still unknown.It has not been reported in relevant literature whether it could improve the accuracy of the diagnosis of lateral<1cm metastatic lymph nodes combined with the prediction model proposed by the risk factors.The suspicious lymph nodes of lateral neck should be removed by standardized therapeutic lateral neck dissection after definite diagnosis by preoperative imaging and fine needle aspiration.The lymph nodes inⅡa-Ⅳarea of the lateral neck are the most common metastatic sites of thyroid cancer.All therapeutic lateral neck dissection should be performed at least inⅡa-Ⅳarea.Compared with areaⅡ-Ⅳ,the rate of lymph node metastasis in areaⅤ(posterior cervical triangle)is relatively low.It is controversial whether routine dissection should be performed in levelⅤ.Compared with papillary thyroid cancer>1 cm,the degree of lateral cervical lymph node metastasis in papillary thyroid microcarcinoma is relatively less.Routine levelⅤdissection is also controversial in papillary thyroid microcarcinoma with lateral neck metastasis.Literature reported that patients with papillary thyroid microcarcinoma who have undergone total thyroidectomy would not benefit from postoperative iodine-131 therapy.Iodine 131 therapy will not reduce the recurrence,but will increase the possibility of other malignant tumors.However,a recent study found that postoperative iodine-131 treatment could not only reduce the recurrence of patients,reduce the possibility of distant metastasis,but also improve the specific mortality of patients with thyroid cancer.According to American Thyroid Association guidelines,the differentiated thyroid carcinoma with lateral lymph node metastasis is in the intermediate risk of recurrence.It is also controversialwhether the patients of intermediate risk should be treated with iodine-131.Whether the PTMC patients with lateral cervical lymph node metastasis should be treated with iodine-131has not been reported in the literature.PartⅠThe risk factors and prediction model of metastasis for lateral neck<1 cm suspected lymph node in papillary thyroid microcarcinomaFrom January 2009 to July 2019,the data of papillary thyroid microcarcinoma patients in the first hospital of Jilin University were analyzed retrospectively.159 patients with papillary thyroid microcarcinoma who underwent lateral neck lymph node dissection due to suspicious lateral neck<1 cm lymph nodes were selected.Preoperative ultrasound diagnosis was correct in 121 cases,the correct rate was 76.1%.Univariate and multivariate analysis showed that age≤38 years old,the largest papillary thyroid microcarcinoma in the upper part,and the presence of liquefaction or microcalcification in suspected lymph nodes were independent risk factors for lymph node metastasis(univariate analysis p=0.00,0.00,0.00;multivariate analysis p=0.00,0.02,0.00;OR=4.66[CI:1.78-12.21],3.04[CI:1.24-7.46],6.39[CI:1.85-22.00]).According to the data provided by the multivariate model,the predictive model for the diagnosis of suspected malignant<1cm lymph nodes was established as:P=e~x/(1+e~x).X=-1.29+(1.11×whether the tumor is located in the upper part)+(1.54×whether the age is≤38 years)+(1.85×whether the suspected lymph nodes have liquefaction/microcalcification).Among them,P is the prediction probability of malignancy,e is the natural logarithm,yes=1,no=0;According to the prediction model,we can calculate the value of malignancy probability,draw receiver operating characteristic curve with the reference of pathological results.The area under the curve is(0.832±0.03),95%confidence interval is(0.77-0.89),when the best cross-section value is 0.64,the sensitivity is 65.29%,and the specificity is 86.84%.Hosmer-lemeshow fit test was used to evaluate the predicted value and pathological results,X~2=6.214,p=0.623>0.05,which means both of which had good fitting and good prediction accuracy.Take the number of risk factors as the abscissa,the malignant prediction probability calculated by the prediction model as the ordinate,and we make box chart.There was a significant difference in malignant possibility among different number of risk factors(Kruskal Wallis test,p=0.00).Chi square trend analysis showed that with the increase of the number of risk factors,the malignant possibility of suspected lateral neck<1cm lymph nodes increased gradually(chi square trend test,p=0.00).PartⅡ Should levelⅤbe routinely removed in papillary thyroid microcarcinoma patients with lateral cervical lymph node metastasisFrom January 2009 to July 2017,papillary thyroid microcarcinoma underwent thyroid surgery in the first hospital of Jilin University were analyzed retrospectively.252 cases of papillary thyroid microcarcinoma with lateral cervical lymph node metastasis were selected.The mean follow-up time was 55.69±23.37 months.Among 252 enrolled patients,20(8.0%)had relapse.At the same time,the metastasis rates of levelⅡ,ⅢandⅣwere 56.5%,50.4%and 72.9%,respectively.Among 56 patients with level V dissection,only 12(21.4%)had lymph node metastasis in level V.In the clinical negative lateral neck level with no suspicious lymph nodes diagnosed by ultrasound,computed tomography or fine needle aspiration,the occult metastasis rate of levelⅡ,Ⅲ,ⅣandⅤwas 28.35%(45/159),26.1%(46/176),34.9%(38/109)and 6.4%(3/47),respectively.In order to compare the recurrence rate and surgical complications of papillary thyroid microcarcinoma patients with or without level V dissection,we first compared the general clinicopathological characteristics of the two groups,including gender,age,body mass index,bilateral,multifocal,extrathyroidal extension,pathological subtype,maximum tumor diameter,Hashimoto’s thyroiditis,lateral lymph node dissection,central lymph node metastasis,lateral lymph node metastasis,radioiodine 131,and compared the operators and follow-up time of two groups,which may affect the recurrence or surgical complications.There was no significant difference between the two groups.And,6.4%(3/47)of the patients who received level V dissection had relapse,and 8.2%(16/196)of the patients who did not receive level V dissection had relapse(p=1.00).Comparing disease-free survival ratebetween the two groups,the disease-free survival rate of level V dissection patients was not significantly reduced(HR=1.11[CI:0.38–3.21];p=0.85).In addition,according to whether to accept level V dissection or not,the hospitalization time,total cost,operation time,intraoperative blood loss,drainage volume,bleeding complications,incision infection,lymph leakage and shoulder syndrome of patients were compared.Routine level V dissection increased the length of stay and cost of patients(p=0.03;0.02).However,the complications associated with lateral neck dissection were lower in both groups,and there was no significant difference between the two groups.Univariate and multivariate analysis showed that simultaneous metastasis of lateral neckⅡ-Ⅳwas an independent risk factor for levelⅤmetastasis(univariate analysis p=0.04;multivariate analysis p=0.02,OR=8.6[CI:1.42-51.72];).PartⅢ Whether iodine-131 therapy should be performed in papillary thyroid microcarcinoma with lateral lymph node metastasisThe data of papillary thyroid microcarcinoma patients who received the initial surgical treatment of thyroid cancer in the first hospital of Jilin University from January 2005 to February 2015 were analyzed retrospectively.A total of 137 papillary thyroid microcarcinoma patients with lateral lymph node metastasis were included in this study,94of them had radioiodine-131 therapy and 43 had no radioiodine-131 therapy.There was no significant difference in age,sex,microscopic extrathyroidal extension,maximum tumor diameter,total tumor diameter,multifocal,bilateral,Hashimoto’s thyroiditis,pathological subtype,lateral neck dissection,central lymph node metastasis ratio,lateral lymph node metastasis ratio between the two groups.It was found that the disease-free survival rate of patients without radioiodine-131 was significantly lower than that of patients without radioiodine-131(p=0.0074).The 5-year and 10-year disease-free survival rates were93.02%and 87.5%in the radioiodine-131 negative group,and 100%and 96.81%in the radioiodine-131 positive group,respectively.Cox proportional risk analysis showed that central lymph node metastasis ratio≥0.5 and lateral lymph node metastasis ratio≥0.5were the risk factors for the recurrence of radioiodine-131(-)(HR=12.948[CI:2.610-64.229],p=0.002;HR=8.321[CI:1.234-32.321],p=0.031).Age,sex,microscopic extrathyroidal extension,maximum tumor diameter,total tumor diameter,multifocal,bilateral,Hashimoto’s thyroiditis,pathological subtype and lateral lymph node metastasis were not predictors of recurrence.Central lymph node metastasis ratio and lateral lymph node metastasis ratio were further analyzed by Cox proportional risk method.In radioiodine-131(-)group,central lymph node metastasis ratio≥0.5 and lateral lymph node metastasis ratio≥0.5 were still identified as risk factors for recurrence(HR=7.281[CI:1.804-17.554],p=0.010;HR=1.157[CI:1.0125-9.381],p=0.048).The disease-free survival rate of patients with central lymph node metastasis ratio≥0.5 and lateral lymph node metastasis ratio≥0.5was significantly lower(p<0.0001,p=0.0158).Therefore,CLNM ratio≥0.5 and lateral lymph node metastasis ratio≥0.5 were proved to be independent risk factors for recurrence in radioiodine-131(-)group.Conclusion:1.The age≤38 years old,the largest papillary thyroid microcarcinoma located in the upper part,the presence of liquefaction or microcalcification in suspected lymph nodes are independent risk factors of metastasis for suspected lateral neck<1cm lymph nodes in papillary thyroid microcarcinoma patients with lateral lymph node metastasis.The predictive model has better sensitivity and specificity for the diagnosis of suspected lateral neck<1 cm lymph nodes,and the diagnostic accuracy is higher.With the increase of the number of risk factors,the malignant possibility of the suspicious lateral neck<1cm lymph nodes increases gradually.It is feasible to evaluate the malignant possibility of the lymph nodes by the number of risk factors.However,a large number of independent case groups are still needed to verify the accuracy and stability of the prediction model.2.Because of the low rate of lymph node metastasis and recurrence in level V,routine level V dissection may prolong the length of hospital stay and increase the related costs.Therefore,we suggest that for papillary thyroid microcarcinoma patients with lateral lymph nodemetastasis who have not found metastasis in level V before operation,routine prophylactic level V dissection is not necessary.Prophylactic level V dissection may only be performed in patients with simultaneous metastasis of 3 regions(Ⅱ-Ⅳ).3.For papillary thyroid microcarcinoma with lateral lymph node metastasis,especially for papillary thyroid microcarcinoma with central lymph node metastasis ratio or lateral lymph node metastasis ratio≥0.5,radioiodine-131 is recommended.In future,a multicenter randomized controlled clinical trial is needed to evaluate the effect of radioiodine-131 on the recurrence rate,quality of life and other aspects of papillary thyroid microcarcinoma patients with lateral lymph node metastasis. |
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