With increasing prevalence of thyroid nodules, clinicians are increasingly impelled to identify the optimal predictor of thyroid cancer, with the goal of guiding management based on assessed risk. Fine-needle aspiration cytology is the gold standard diagnostic method for thyroid nodules. However, fine-needle aspiration cytology is not perfect and adjuncts which might complement its predictive value are being investigated from several innovative perspectives. For these vigorous efforts, remarkable advances have been achieved in understanding several major biologic areas of thyroid cancer, including the molecular alterations for loss of radioiodine avidity of thyroid cancer, the pathogenic role of the MAP kinase and PI3K/Akt pathways and their related genetic alterations in thyroid tumorigenesis and pathogenesis. These exciting advances provide unprecedented opportunities for development of molecular-based novel diagnostic and therapeutic strategies for thyroid cancer. The common somatic genetic changes in thyroid cancer of follicular cell origin (RET/PTC, NTRK, RAS, BRAF, PAX8-PPARgamma) are generally mutually exclusive, with distinct genotype-histologic subtype associations of thyroid cancer. Mutation analysis in fine needle aspiration samples has been applied to improve the diagnostic accuracy. In studies regarding gene expression profiling, aberrant gene methylation and miRNA have shown significant progress toward identification of biomarkers that could improve the accuracy of fine needle aspiration cytology in the evaluation of patients with thyroid nodule and prediction of disease aggressiveness. Future clinical trials evaluating the accuracy and cost-effectiveness of applying these biomarkers in the management of thyroid neoplasm should be considered.
Biomarkers ; Biopsy, Fine-Needle ; Carcinogenesis ; Complement System Proteins ; Diagnosis* ; Gene Expression Profiling ; Humans ; Methylation ; MicroRNAs ; Phosphotransferases ; Prevalence ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroid Nodule

PURPOSE: Various endoscopic thyroidectomy procedures have been designed to minimize visible cervical scarring. However, endoscopic thyroidectomy is a technically challenging procedure that is performed by a limited surgeon. Robotic systems aida surgeon in performing minimally invasive head and neck surgery by offering superior visualization and dexterity. This study reports the initial experience of one surgeon with robotic thyroidectomy to assess the technical feasibility and safety of the approach. METHODS: One hundred four thyroid cancer patients (97 females, 7 males; mean age of 39.8±8.1 years) underwent robotic thyroidectomy using gasless transaxillary approach between November 2008 and October 2009 in Ajou University Hospital. All the procedures were completed successfully using the da Vinci surgical system without open conversion. Patient characteristics, postoperative clinical results, complications, and pathologic details were assessed. RESULTS: Total thyroidectomy was performed in 25 (24.0%) patients, subtotal thyroidectomy in 13 (12.5%) patients, and unilateral lobectomy in 66 (63.5%) patients. All patients underwent ipsilateral central compartment neck dissection, and two patients underwent selective lymph node (LN) dissection. The mean operation time was 134.5±47.2 min (range 61~310 min), in which the actual time for the thyroidectomy with lymphadenectomy (console time) was 56.4 min. (range 31~270). The mean number of LN resected was 3.9 (range 0~28). There were no serious complications. The mean hospital stay was 2.9±0.9 days (range 2~7). CONCLUSION: Robotic thyroidectomy is a feasible, safe, and cosmetically excellent procedure. The application of robotic technology for thyroid surgeries could be an alternative to endoscopic or conventional open thyroidectomy.
Cicatrix ; Female ; Head ; Humans ; Length of Stay ; Lymph Node Excision ; Lymph Nodes ; Male ; Neck ; Neck Dissection ; Thyroid Gland ; Thyroid Neoplasms ; Thyroidectomy*

Primary aldosteronism (PA) is a frequent cause of secondary hypertension and is amenable to surgical intervention when it is caused by aldosterone-producing adenoma (APA). Many patients, however, continue to require antihypertensive medications to control their blood pressure after adrenalectomy. The aim of this study was to determine the preoperative factors that predict clinical outcomes after adrenalectomy in patients with APA. We studied 27 patients (mean age 45+/-4 yr) who had APA and underwent unilateral adrenalectomy between December 1995 and September 2008 at our institution. Clinical and biochemical data were evaluated at baseline and after a mean follow-up of 51.8+/-47.0 months (range, 6-159). At the end of the follow-up, 16 patients (59.3%) were considered to experience "complete resolution" without postoperative medications, whereas 7 patients (25.9%) "improved" with medications and 4 patients (14.8%) were "uncontrolled." Three factors (< or =2 antihypertensive medications [P=0.007], duration of hypertension <6 yr [P=0.002], and serum aldosterone <350 pg/mL [P<0.001]) were the predictive for complete resolution in univariate analysis. Multivariate regression analysis showed that serum aldosterone level (<350 pg/mL) was the single most important factor that predicted complete resolution after surgery (P<0.001). The best preoperative clinical factor that predicted resolution of postoperative hypertension after adrenalectomy is serum aldosterone level (<350 pg/mL).
*Adrenalectomy ; *Adrenocortical Adenoma/complications/surgery ; Adult ; Aldosterone/*blood ; Female ; Humans ; *Hyperaldosteronism/complications/surgery ; *Hypertension/etiology/surgery ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome

The robotic approach is the new frontier of thyroid cancer surgery, with several advantages over conventional open and endoscopic techniques. Recent assessments of quality of life (QoL) outcomes have found that patients undergoing robotic thyroid surgery using transaxillary approach experience lower levels of dissatisfaction and regret than patients undergoing conventional open thyroid surgery, largely due to differences in cosmetic outcomes. Prospective trials evaluating functional parameters, including pain, neck discomfort, and sensory changes in the neck, have favored robotic over conventional open thyroid surgery. Similarly, objective and subjective evaluations of voice and swallowing discomfort were improved in patients undergoing robotic thyroidectomy. Thus, use of a robot results in overall increases in cosmetic satisfaction and decreases in several measures of postoperative discomfort compared with the conventional open thyroid technique. However, a proper evaluation of QoL requires long-term assessments, and randomized controlled trials are necessary to definitively establish the real benefits of robotic surgery. This review provides merits and demerits of robotic thyroidectomy and radical neck dissection, based on published data, as well as comparing QoL outcomes after robotic and conventional open thyroidectomy.
Deglutition ; Humans ; Neck ; Neck Dissection ; Neck Pain ; Quality of Life* ; Thyroid Gland* ; Thyroid Neoplasms ; Thyroidectomy ; Voice

PURPOSE: Regional lymph node (LN) metastases are detected in 57-85% of patients with papillary thyroid carcinoma (PTC) and are associated with increased tumor recurrence. However, the management of lymphatic disease in patients with PTC has been ongoing source of debate. We have prospectively assessed the usefulness and accuracy of sentinel LN (SLN) biopsy for the detection of LN metastases in patients with PTC on preoperative imaging using single photon emission computed tomography/computed tomography (SPECT/CT) and 99mTc phytate. METHODS: We prospectively assessed 39 patients with PTC who had risk factors for recurrence or with the necessity of intraoperative LN sampling for suspicious LN metastases on preoperative imaging from August 2010 to March 2011. The patients underwent preoperative lymphoscintigraphy and SPETC/CT and intraoperative SLN biopsy (SLNB). RESULTS: 99mTc lymphoscintigraphy and SPECT/CT localized SLN in 38 patients (97.4%), with the gamma probe identifying 2.15 mean SLNs in the lateral neck of the 39 patients. Skip metastasis was found in one patient, and lateral compartment LN metastasis in 17 (43.5%). The sensitivity, specificity, and accuracy of SLNB for lateral compartment LN metastasis were 88.2%, 100%, and 94.8%, respectively. SLNB was more accurate and useful for lateral than for central compartment LN metastasis. CONCLUSION: SPECT/CT improved SLN detection and anatomical localization compared with lymphoscintigraphy. SLNB in patients with risk factors for recurrence or the necessity of intraoperative LN sampling for suspected LN metastases on preoperative imaging was accurate in detecting LN metastases and may help in deciding whether to perform lateral compartment dissection in patients with PTC.
Biopsy ; Carcinoma ; Factor IX ; Humans ; Lymph Nodes ; Lymphatic Diseases ; Lymphoscintigraphy ; Neck ; Neoplasm Metastasis ; Nitriles ; Phytic Acid ; Prospective Studies ; Pyrethrins ; Recurrence ; Risk Factors ; Sensitivity and Specificity ; Sentinel Lymph Node Biopsy ; Thyroid Gland ; Thyroid Neoplasms ; Tomography, Emission-Computed, Single-Photon ; Tomography, X-Ray Computed

Background and Objectives: Although thyroid hormones affect human cancer progression, the regulatory mechanism of thyroid hormone receptors in carcinogenesis has not been elucidated. This study aimed to evaluate the expression pattern of the thyroid hormone receptor (TR) and its corepressors, and to investigate the clinical and biological functions of TR. Materials and Methods: Transcriptomic and clinical data for thyroid cancer were downloaded from The Cancer Genome Atlas. Paraffin-embedded tissue sections from patients who underwent thyroidectomy were used for immunohistochemistry. BCPAP cells were treated with T3 to investigate the thyroid hormone target genes. Thyroid hormone receptor alpha (THRA) and Thyroid hormone receptor beta (THRB) were knocked down by transient siRNA transfection. Results: THRA and THRB expression was lower in thyroid cancer tissues than in normal tissues. However, strong focal staining of TRβ was observed in the invasive front. High THRB expression was associated with high Silencing Mediator for Retinoid or Thyroid hormone receptor (SMRT) expression, older age, a high MACIS (distant Metastasis, patient Age, Completeness of resection, local Invasion, and tumor Size) score, more aggressive histological subtypes, more frequent extra-thyroidal extension, and advanced TNM stage. THRB expression was positively correlated with Hypoxia Inducible Factor 1 Subunit Alpha (HIF1A), L1 Cell Adhesion Molecule (L1CAM), and Lysyl Oxidase (LOX) expression. Thyroid hormone-induced HIF1A, L1CAM, and LOX upregulation was abolished by siTHRB but not siTHRA in BCPAP cells. High SMRT and high THRB groups (SMRT/THRB) presented more aggressive clinical features and showed an upregulation of HIF1A, L1CAM, and LOX, as well as of epithelial-mesenchymal transition (EMT)-related genes, causing changes in the tumor microenvironment. Conclusion Cooperative subtype switching from NCOR1/THRA to SMRT/THRB was thus related to aggressive clinical and molecular features, possibly related to EMT and EMT-related tumor microenvironment.

PURPOSE: Hurthle cell carcinoma (HCC) of the thyroid gland is a rare disease that represents 3% of all thyroid carcinomas. HCC has been known as a more aggressive disease than the usual differentiated thyroid carcinoma. However, the biologic behavior and optimal treatment have come under considerable debate in recent years. This study was performed to evaluate the clinicopathologic features and treatment outcome of HCC. METHODS: From April 1986 to August 2006, 18 patients with HCC and 216 patients with pure follicular carcinoma (PFC) underwent thyroidectomy at our institutions with a mean follow-up of 114 (range: 6~253) months. The clinicopathologic characteristics and treatment outcome of each group were compared, and the prognostic factors for disease-free survival were analyzed. RESULTS: There were 14 women and 4 men with a mean age of 50 (range: 26~76) years. Compared with PFC patients, all of clinicopathologic features of HCC patients were different (gender, age, tumor size, multifocality, angioinvaion, invasion to adjacent structures, the subclassification and initial distant metastasis), but the high incidence of bilaterality was similar to the PFC patients (P<0.0001). The cause- specific survival (CSS) rates at 10 years were 83.4% in the HCC patients and 89.3% in the PFC patients (P=0.702). Older age (greater than 45) (P=0.0125) and initial distant metastasis (P<0.0001) in the HCC patients, and an older age (P<0.0001), male gender (P=0.0039), angioinvasion (P= 0.0122), invasion to adjacent structures (P<0.0001), a widely invasive type (P=0.004) and initial distant metastasis (P<0.0001) in the PCC patients were independent prognostic factors for survival. CONCLUSION: After accounting for important biologic behaviors, patients with HCC had similar clinicopathologic characteristics and prognosis compared with that of the PFC patients. Therefore, HCC should be managed using the same treatment strategy as PFC.
Accounting ; Adenocarcinoma, Follicular ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Incidence ; Male ; Neoplasm Metastasis ; Prognosis ; Rare Diseases ; Thyroid Gland ; Thyroid Neoplasms ; Thyroidectomy ; Treatment Outcome

Cribriform-morular variant (CMV) is a rare histologic subtype of papillary thyroid carcinoma (PTC). Patients with familial adenomatous polyposis (FAP) could be associated with several comorbid diseases including thyroid cancer. Most thyroid cancers in them are PTCs, but infrequently CMV types can occur. The FAP concomitant CMV-PTCs are found predominantly in young women and reveals lower recurrence rate. Moreover, this variant shows circumscribed morphology and rarely metastasizes to node. Because the incidence of thyroid carcinoma is higher than that in general population, comprehensive evaluation of thyroid gland should be performed for the patients with FAP. Because thyroid cancer could be first manifestation of FAP, colonic screening should be considered in CMV-PTC patient. We report two cases of CMV-PTCs concurrent with FAP.
Adenomatous Polyposis Coli* ; Carcinoma, Papillary* ; Colon ; Female ; Humans ; Incidence ; Mass Screening ; Recurrence ; Thyroid Gland ; Thyroid Neoplasms

PURPOSE: Follicular thyroid carcinoma (FTC) is a relatively rare form of thyroid carcinoma that often presents at a more advanced stage of disease with a higher incidence of distant metastases because of its propensity for vascular invasion. However, FTC and papillary thyroid carcinoma (PTC) have similar prognoses when they are matched for age and stage. Therefore, this study was conducted to evaluate the useful prognostic factors and determine the optimal management of FTC. METHODS: This study was conducted on 216 patients with FTC who underwent thyroidectomy at our institutions between April 1986 and August 2006. The patients included 174 women and 42 men with a mean age of 41 (4~87) years, and patients underwent follow-up evaluation for a mean period of 114 (6~253) months. The potential risk factors for treatment outcome were calculated using multivariate analysis, and the prognostic accuracy of UICC/AJCC pTNM staging, AMES, AGES, MACIS, and Degroot classification for predicting survival were compared. RESULTS: During the follow-up period, 13 (6.0%) patients developed locoregional recurrences and 8 patients (3.7%) showed distant metastases. In addition, cause specific mortality was seen in 8 patients (3.7%). The overall survival and cause-specific survival (CSS) rates at 10 years were 95.4% and 89.3%, respectively, and these cases were accurately predicted by the AMES and pTNM staging systems. The Cox proportional hazards revealed that gender (P=0.015), angioinvasion (P=0.013), invasion to adjacent structure (P=0.003), widely invasive carcinoma (P=0.028), and distant metastases at the time of presentation (P<0.001) were independent prognostic factors for survival. CONCLUSION: The extent of surgery in cases of FTC should be individualized based on the clinicopathologic findings; Conservative surgery should be adequate for cases of minimally invasive FTC without angioinvasion, however total or near-total thyroidectomy should be conducted in cases of widely invasive and minimally invasive FTC with angioinvasion.
Adenocarcinoma, Follicular ; Carcinoma ; Female ; Follow-Up Studies ; Humans ; Incidence ; Male ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis ; Recurrence ; Risk Factors ; Thyroid Gland ; Thyroid Neoplasms ; Thyroidectomy ; Treatment Outcome

The clinical behaviors and treatment outcomes of thyroid carcinomas in patients with Graves' disease is a matter of controversy. This study aimed to identify the clinicopathologic features, treatment outcome, and the indicators for predicting recurrence, and to suggest the optimal extent of surgery in these patients. We retrospectively analyzed data of 58 patients who underwent surgical treatment for differentiated thyroid cancer and concurrent Graves' disease. The follow-up period ranged from 23 to 260 months (mean+/-standard devuation, 116.8+/-54.0). In our series, the mean age was 40.8+/-12.7 yr (range, 15-70), with a male-to-female ratio of 1: 6.25. The mean tumor size was 13+/-9 mm (range, 3-62). The surgical methods included 19 cases of total thyroidectomy, 38 cases of subtotal thyroidectomy, and 1 case of completion total thyroidectomy. Locoregional recurrence occurred in four patients (6.9%). The 10-yr overall survival and disease-free survival of patients were 95.8% and 91.1%, respectively. Age over 45 yr (p=0.031), tumor size over 10 mm (p=0.049), multiplicity (p=0.007), extracapsular invasion (p=0.021), and clinical cancer (p=0.035) were significantly more prevalent in patients with locoregional recurrence than in those without recurrence. We recommend that Graves' disease patients should undergo regular ultrasonography screening for early detection of thyroid carcinoma. We also suggest that the choice of extent of surgery should depend on the diagnostic timing (clinical or incidental) and factors for predicting recurrence.
Adult ; Comorbidity ; Disease-Free Survival ; Female ; Graves Disease/*complications/*therapy ; Humans ; Male ; Middle Aged ; Recurrence ; Thyroid Neoplasms/*complications/*therapy ; Time Factors ; Treatment Outcome