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Clinical Study On Follicular Thyroid Carcinoma And Significance Of Galectin-3Expression Test For Early Diagnosis

Posted on:2014-06-14Degree:DoctorType:Dissertation
Country:ChinaCandidate:X ChenFull Text:PDF
GTID:1264330401987357Subject:Surgical Oncology
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BackgroundFollicular thyroid carcinoma (FTC) is one type of differentiated thyroid carcinoma (DTC), which staging and therapeutic strategy is similar to Papillary Thyroid Carcinoma (PTC). However, FTC is more aggressive than PTC and easier to spread hematogenously with distant metastases, due to its clinicopathologic feature and biological behavior which is different from PTC. Some experts adviced FTC should be treated aggressively, including total thyroidectomy (TT)/near total thyroidectomy (NTT) followed by thyroid stimulating hormone (TSH) suppression therapy and radioiodine ablation (RAI). Generally, this aggressive therapeutic strategy was only accepted to treat patients with widely invasive follicular thyroid carcinoma (WIFTC) or with distant metastases. But for minimally invasive FTC (MIFTC), on the other hand, there was still a matter of controversy. The outcome of MIFTC is pretty good which will turn to be poor if patients developed early distant metastases. Any development of guideline which can select high risk patient and provide them better treatment would represent a significant advance in the management of thyroid carcinoma. Moreover, the diagnosis of FTC is difficult, the predictive values of preoperative fine needle aspiration cytology (FNAC) and frozen section (FS) were low. Many patients received surgical procedure for diagnostic purpose, and some others have to receive completion thyroidectomy soon after first operation.Recent decade, many molecular markers had been evaluated to improve diagnostic accuracy for follicular lesions. Galectin-3(GAL-3),a β-galactoside-binding molecule in the lectin group, was one of most frequently investigated molecular markers, be it in tissues or in cytological material of FNA. Large prospective studies have carried out to confirm the ability of galectin-3improving preoperative diagnostic accuracy for patients with follicular lesions.To this end, we built the database of thyroid carcinoma (TC) patients who were treated in the first affiliated hospital of Zhejiang University from January1997to June2011and discussed the epidemiology of TC patients in our hospital. Then FTC and MIFTC patients were selected from the database and followed up. The factors affecting the prognosis of FTC and MIFTC patients were analyzed. At the end, a meta-analysis on evaluating the accuracy of galectin-3expression test for follicular lesions was performed by using a search of PubMed, Cochrane Library, Wanfang data resource system, Chinese science and Technology Periodical Database and Chinese Biomedical Literature Database to provide the information for clinical practice.Part I:Building the database of thyroid carcinoma patients who were treated in the first affiliated hospital of Zhejiang University from1997-2011and analysing the clinical data of FTC patients.Objective:To build the database of TC patients for providing resource for basic and clinical research and for further research in part Ⅱ. Method:The clinical data of TC patients who were treated in the first affiliated hospital of Zhejiang university from January1997to June2011was collected to build the database of TC patients. The clinical information of FTC patients in database was selected and analyzed for the further research in part Ⅱ.Result:(1) From January1997to June2011, there were2437TC patients were treated in the first affiliated hospital of Zhejiang University, including2244cases of PTC (92.08%),134cases of FTC (5.5%),28cases of Medullary Thyroid Carcinoma (MTC)(1.15%).20cases of Anaplastic Thyroid Carcinoma (ATC)(0.82%) and11cases of other rare subtype (0.45%).In the first five years, there were227cases of TC patients accounted for9.31%of total, including200cases of PTC (88.1%),19cases of FTC (8.4%) and8cases others(3.5%); in the second five years, there were578cases of TC patients account for23.71%of total, including510cases of PTC (88.2%).45cases of FTC (7.8%) and23cases others (4%) and in the third five years, there were1632cases of TC patients account for66.97%of total, including1534cases of PTC (94%),70cases of FTC (4.3%) and28cases others(1.7%).(2) There were134cases of FTC patients were treated in our hospital in the last fifteen years. The incidence of thyroid carcinoma was3.01times higher in female than in male.71patients were older than45years of age,63patients below45years old. There were35patients whose tumor size bigger than4.0cm,99were smaller.95patients were in their Ⅰ TNM stage,16were in Ⅱ stage,17were in Ⅲ stage and6were in IV stage.25patients received lymph node dissection and109patients didn’t.82patients received TT/NTT,52received lobectomy (LC).Conclusion:(1) The amount of TC patients treated in the first affiliated hospital of Zhejiang University increased rapidly. Most of them were PTC. The ratio of PTC increased from88.1%in1997-2001to94.0%in2007-2011. The second part of TC was FTC, of which the ratio decreased from8.4%in1997-2001to4.3%in2007-2011.(2) The clinical features of TC patients were good. Patients were trend to be treated with total thyroidectomy and without lymph node dissection.Part II:The clinical study of outcome and prognostic factor of FTC and MIFTC patients.Objective:to investigate outcome and prognostic factors of FTC and MIFTC patients.Methods:The cumulative cause-specific survival (CSS) and disease-free survival (DFS) of FTC and MIFTC patients in our TC database were assessed and the prognosis factors were analyzed. The major variables including age at surgery (<45years vs.≥45years), sex, tumor size (<4.0cm vs.≥4.0cm), present of distant metastases or recurrence (DFS didn’t analyze by this variable), TNM classification staging, multiple lesions, operation procedure, lymph node dissection method. A univariate analysis was conducted in relation to CSS and DFS by the Kaplan-Meier method. Differences between groups were analyzed for significance by the log-rank test. Multivariate analysis was performed by using the Cox proportional regression model. P values<0.05were regarded as statistically significant.Result:(1) After excluding patients didn’t match the criterion,102cases of FTC patients were included and followed-up. Cause-specific death occurred in4patients. The overall5-years,10-year,15-year CSS rates were97%,91.6%,69%; The5-year and10-year CSS rates of patients older than45years of age were94.3%,82.5%; the5-year and10-year CSS rates of patients younger than45years of age were100%.12M0patients present distant metastases or recurrence in follow-up period,4patients presented distant metastases and8presented local recurrent or regional lymph node metastases. The overall5-year and10-year DFS rates were87.8%,75%; The5-year and10-year DFS rates of patients older than45years of age were83.1%,56.1%; the5-year and10-year DFS rates of patients younger than45year of age were92.9%,88%. Univariate analysis showed that CSS was affected by age, presentation of recurrence or metastasis, TNM stage. The prognosis was poorer in patients who were elder than45years old, presented recurrence or metastasis, with high TNM stage.(2)86cases of MIFTC patients were included in this study. Cause-specific death occurred in2patients. The overall5-years and10-year CSS rates were97.7%,89.6%; The5-year and10-year CSS rates of patients older than45years of age were97.1%,87.4%; the5-year and10-year CSS rates of patients younger than45year of age were100%.8MO patients presented distant metastases or recurrence in follow-up period,3patients presented distant metastases and5presented local recurrent or regional lymph node metastases. The overall5-year and10-year DFS rates were87.7%,83.3%; the5-year and10-year DFS rates of patients older than45years of age were81.8%,71.6%; the5-year and10-year DFS rates of patients younger than45year of age were94%. Univariate analysis showed that CSS was affected by presentation of recurrence or metastasis, TNM stage. The prognosis was poorer in patients who presented recurrence or metastases and in patients with high TNM stage. Multivariate Cox proportional hazards model analysis showed tumor size>4.0cm was independent factor that impact on DFS of MIFTC.Conclusion:The prognosis of FTC and MIFTC is good. Early treatment and close following-up are essential to improve the prognosis of patients with FTC.Part Ⅲ:A Meta-analysis on evaluating the diagnostic value of galectin-3expression test for follicular lesion with FNAC result of "follicular pattern" preoperatively.Objective:To evaluate the predictive value of galectin-3expression test to distinguish malignancy from thyroid lesions with FNAC result of "follicular pattern" preoperatively. Methods:A search of PUBMED, Cochrane library, Wanfang data resource system, Chinese science and Technology Periodical Database and Chinese Biomedical Literature Database was done from January1995to December2012. The prospective research on evaluating the predictive value of galectin-3expression test to distinguish malignancy from follicular lesions detected by FNAC preoperatively were collected and reviewed. The Summary Receiver Operating Characteristic (ROC) curve and meta-analysis were performed by meta-disc software version1.4.Result:8studies involving1082patients were included. The pooled sensitivity was0.83[95%CI (0.78to0.86)] and the pooled specificity was0.90[95%CI (0.88to0.92)]; the pooled positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were7.46[95%CI (5.06to10.99)] and0.21[95%CI (0.15to0.29)]. The pooled diagnostic odds ratio (DOR) was38.41[95%CI (21.90to67.35)].Conclusion:The galectin-3may well prove to be a useful tool for distinguishing malignancy from thyroid lesions with FNAC result of "follicular pattern" because of high sensitivity and specificity, but more high quality trials are required.
Keywords/Search Tags:thyroid carcinoma, follicular carcinoma, minimally invasive, meta-analysis, Galectin-3
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