Tzu-Chieh Chao

Well-Differentiated Thyroid Carcinoma with Concomitant Hashimoto’s Thyroiditis Present with Less Aggressive Clinical Stage and Low Recurrence

Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) are the most common differentiated thyroid cancers. Previous studies report that Hashimoto’s thyroiditis (HT) concomitant with PTC is unusual and improves prognosis compared to classical PTC. Few previous studies address FTC concomitant with HT. In this study, we retrospectively analyzed data from one institution and compared clinical presentations and results of treatment of PTC and FTC with and without HT. In addition, studies comparing presentation and long term follow-up prognosis in classical PTC and FTC were conducted. A total of 1,788 PTC patients and 209 FTC patients underwent thyroidectomy with or without lymph node dissection and follow-up at Chang Gung Medical Center in Linkou, Taiwan. All thyroid carcinomas were pathologically classified according to World Health Organization criteria. Histological patterns of PTC were categorized as classical PTC, or PTC with HT. Follicular thyroid carcinoma patients were categorized as FTC or FTC with HT. The dataset contained a total of 1,703 PTC cases categorized as classical PTC, 85 cases of PTC with HT, 201 cases of FTC and eight cases of FTC with HT. Analysis of Classification of Malignant Tumors (TNM) stage revealed a higher percentage of classical PTC in stage IV than HT group (12.03% vs. 4.70%). Mean tumor size of classical PTC was larger than HT group. Although 42.3% of FTC cases presented with distant metastases, no cases of FTC with HT presented with distant metastasis. Cancer-specific mortality was higher in classical PTC group than in PTC with HT. There was 53.2% of FTC without HT assigned recurrent status, and six of them died of thyroid cancer. No cancer mortality or recurrence in HT with FTC. PTC and FTC with HT presented with better clinical stage and better prognosis after same therapeutic modality. In conclusions, both PTC and FTC with HT have less aggressive clinical presentation and better prognosis.

Diagnostic and therapeutic strategies for minimally and widely invasive follicular thyroid carcinomas

The purpose of this study is to investigate diagnostic and therapeutic strategies that will enable easy differentiation between minimally invasive follicular carcinoma (MIFC) and widely invasive follicular carcinoma (WIFC). We retrospectively reviewed 234 follicular thyroid carcinoma cases to compare the diagnostic and therapeutic characteristics between the minimally and the widely invasive types. Eighty-nine patients were diagnosed with MIFC (mean age, 39.2 ±14.9 years) and 145 were diagnosed with WIFC (mean age, 49.0 ± 17.7 years). Low diagnostic accuracy from preoperative cytology and frozen sections resulted in 60 patients undergoing subtotal thyroidectomies and 57 cases required a second operation for complete thyroidectomy. Patients in the MIFC group were younger, and had small-sized tumors, lower postoperative thyroglobulin levels, lower recurrent rates and lower cancer mortality rates than those in the WIFC group. Diagnostic accuracy from frozen sections in the WIFC group was relatively better. After a mean follow-up period of 9.0±0.4 years, 41 of the 234 (17.5%) patients with follicular thyroid carcinoma had died due to thyroid cancer. All MIFC patients remained disease-free or had a recurrence-free status. In conclusion, both WIFC and MIFC are difficult to diagnose on the basis of preoperative examinations and frozen sections. Patients diagnosed with MIFC had responded positively to the treatment; however, for patients diagnosed with WIFC to become disease-free, early diagnosis and aggressive surgical therapies in combination with (131)I therapy were required.

Identifying Differentially Expressed Genes Associated with Metastasis of Follicular Thyroid Cancer by cDNA Expression Array

Patients with follicular thyroid carcinoma have a higher incidence of metastasis than papillary thyroid carcinoma when thyroid cancer is diagnosed. The cDNA expression array technology is utilized herein to profile differentially expressed genes from metastatic human follicular thyroid carcinoma and reveal new tumor markers as well as target genes for therapeutic intervention. Tissue samples were obtained during surgical resection of the thyroid follicular carcinoma and metastatic tissue in the brain of the same patient. Two identical Atlas human cDNA expression arrays were hybridized with 32P-labeled cDNA probes derived from RNA of either primary thyroid cancer or metastatic tissue. Parallel analysis of the hybridized signals allowed us to identify the alteration of gene expression in the metastasis process. Eighteen genes significantly overexpressed and 40 genes significantly underexpressed were identified in the metastatic thyroid cancer. Genes that displayed an altered expression were associated with the processes of cell cycle regulation, apoptosis, DNA damage response, angiogenesis, cell adhesion and mobility, invasion, and immune response. An expression profile of genes that are associated with metastasis process of follicular thyroid cancer was also discussed. Further investigation is required to understand the precise relationship between the altered expression of these genes and the metastasis process of follicular thyroid cancer.

Early Recurrence of Papillary and Follicular Thyroid Carcinoma Predicts a Worse Outcome

BACKGROUND The occurrence of recurrent papillary and follicular thyroid carcinomas is not unusual. Numerous studies have reported the association between risk factors of initial surgery and recurrence of papillary and follicular thyroid carcinomas. However, we do not have sufficient data to analyze the time of postoperative recurrence associated with therapeutic results and cancer mortality. We hypothesized that an early recurrence of papillary and follicular thyroid cancers implies a rapid growth of cancer resulting in high mortality rate. METHODS We conducted a retrospective study in a medical center in northern Taiwan. The investigation included 2148 cases of papillary and follicular thyroid carcinoma, including 325 recurrent cases during the period between 1977 and 2006. The studied cases were categorized into early or late recurrence groups. Cases with an early recurrence were defined as those in which recurrence occurred in the first year following thyroid surgery. RESULTS Tumor size, radioactive iodide treatment, multifocality, and tumor-node metastasis stage were independent predictors of recurrence. After a mean follow-up of 8.7 +/- 0.1 years, death due to thyroid cancer was observed to occur in 105 (32.3%) recurrent cases. Among the 325 recurrent cases, early recurrence was detected in 185 cases, and late recurrence was detected in 140 cases. Early recurrence was mostly observed in older male patients; a high mortality rate was associated with these cases. Distant metastases were observed in about 80% of the cases in the early recurrence group, whereas localized metastases in the neck region were observed in more than half the cases in the late recurrence group. The percentage of patients with a non-disease-free status and distant metastases in the early recurrence group was higher than that in the late recurrence group. The 10-year disease-specific survival rates were 52.5% and 85.1% for the early and late recurrence groups, respectively. CONCLUSIONS Early recurrent papillary and follicular thyroid carcinomas are associated with high mortalities. Tumor size and multifocality deserve consideration as indicators of recurrence. Therefore, patients whose primary follicular or papillary thyroid carcinoma has features associated with early recurrence should probably receive more aggressive initial treatment.

Characteristics of thyroid carcinomas in aging patients

To investigate the clinical features of thyroid cancer in aging patients and to present the results of treatment. From this we can provide bases for earlier diagnoses and better treatment of thyroid malignancies in older patients.

Postoperative recurrence of papillary thyroid carcinoma with lymph node metastasis

: The purpose of this study was to retrospectively analyze the features of patients with papillary thyroid carcinoma (PTC) presenting with neck lymph node (LN) metastasis.

Prognosis of Multifocal Papillary Thyroid Carcinoma

This study was to investigate the clinical features and therapeutic outcomes of multifocal papillary thyroid microcarcinoma (PTMC). A total of 2,418 papillary thyroid carcinoma (PTC) patients had undergone thyroidectomy in one medical center between 1977 and 2010. There were 483 (20.0%) diagnosed with multifocal PTC. The percentage of multifocal PTC was higher in PTMC patients (22.0%) than in non-PTMC patients (19.5%). Demographic and clinical characteristics of PTMC and multifocal PTC in PTC patients were traced. Multifocal PTC patients presented with smaller tumors at an older age, and a higher percentage underwent total or complete thyroidectomy. These patients also showed a higher incidence of postoperative disease progression than did unifocal PTC patients. Comparison of 483 patients with multifocal PTMC and non-PTMC tumors showed a higher incidence of postoperative disease progression in patients with non-PTMC; otherwise, there was no statistical difference in disease-specific and total mortality between these two groups. In conclusion, the incidence of multifocal PTMC was not lower than that of non-PTMC, and postoperative therapies were necessary for both multifocal PTMC and non-PTMC patients.

Vascular endothelial growth factors and angiopoietins in presentations and prognosis of papillary thyroid carcinoma.

Angiogenesis from thyroid cancer cell plays the important roles in post‐surgical persistent, recurrent, and metastatic papillary thyroid cancer (PTC). This study is to investigate the expression of angiopoietin‐1 (Ang‐1), angiopoietin‐2 (Ang‐2), Tek/Tie‐2 receptor, and vascular endothelial growth factors (VEGF) in normal, benign thyroid tissues and different stage of PTC. We expect angiogenetic factors are important in the presentation of local‐regional neck or distant metastases in PTC.

Prognostic significance of pituitary tumour‐transforming gene‐binding factor (PBF) expression in papillary thyroid carcinoma

Pituitary tumour‐transforming gene (PTTG)‐binding factor (PBF), originally known as PTTG1 interacting protein (PTTG1IP), has been found to be significantly increased in well‐differentiated thyroid cancer and independently associated with early tumour recurrence.

Trends in the Clinical Characteristics of Patients with Papillary Thyroid Carcinoma in Taiwan

The incidence of thyroid cancer is influenced by many factors including socioeconomic status. As economic conditions have improved in Taiwan, the increased frequency of medical examinations in the general population has led to earlier diagnosis of this indolent malignancy. The purpose of this retrospective study was to compare the clinical characteristics of cases of papillary thyroid cancer diagnosed over a 6-year period from 1993 to 1998 with those patients diagnosed from 1977 to 1992 at a single medical center. Of the 1,485 pathologically verified cases of thyroid cancer from 1977 to 1998, 1,093 had papillary thyroid carcinoma. The mean age of these patients was 40.4 ± 14.6 years. In order to identify trends in the characteristics of patients with thyroid cancer, patients were divided into those diagnosed before and those diagnosed after 1993. Patients diagnosed in these two time periods were also categorized into disease-free or non-disease-free groups depending on their status at the end of 1998. Actuarial survival rates were calculated using the Kaplan-Meier method. Multivariate analysis was performed to assess the independent effect of these variables using the Cox model. By December 1998, 61 (5.6%) of the 1,093 patients with papillary thyroid carcinoma had died. Among them, only 35 (3.2%) patients had died of thyroid cancer. The 5-year Greenwood survival probabilities for the groups diagnosed before and after 1993 were 0.9412 and 0.9817, respectively. The patients diagnosed after 1993 received more aggressive surgical procedures, had smaller tumor size, lower postoperative thyroglobulin levels, less advanced clinical stage at the time of diagnosis, showed more disease-free survival, and a lower mortality rate. In conclusion, the results of this study show that patients with a diagnosis of papillary thyroid cancer after 1993 had a smaller tumor size and a better prognosis than those diagnosed before 1993. This finding emphasizes the importance of early detection in thyroid cancer.