Seo Ki Kim

Role of BRAF V600E mutation as an indicator of the extent of thyroidectomy and lymph node dissection in conventional papillary thyroid carcinoma

BACKGROUND The extent of surgery for papillary thyroid carcinoma (PTC) is associated strongly with disease persistence, recurrence, and mortality. It is difficult, however, to determine the optimal extent for surgery. The BRAF mutation is well known for its diagnostic and prognostic value in PTC. Among the variants of PTC, the clinical importance of the BRAF mutation has been associated particularly with conventional PTC. The goal of this study was to clarify the role of the BRAF mutation as a determinant for the operative extent in conventional PTC. METHODS Histopathology and BRAF mutation status of 3,019 patients with conventional PTC were analyzed. With regard to the extent of surgery in PTC, focus was given to the factors of tumor bilaterality, central lymph node metastasis (CLNM), and lateral lymph node metastasis. In addition, the prognostic impact of BRAF mutation on loco-regional recurrence was investigated. RESULTS The BRAF mutation was found to be an independent indicator of tumor bilaterality (odds ratio [OR] 1.484, P = .010); however, it was not an independent indicator of CLNM (OR 1.167, P = .254) or lateral lymph node metastasis (OR 0.647, P = .384). Moreover, it was not an independent indicator of CLNM in either the therapeutic or prophylactic central neck dissection. Finally, BRAF mutation positivity did not increase the risk of loco-regional recurrence (adjusted hazard ratio = 0.829, P = .523). CONCLUSION The BRAF mutation is a possible indicator for determining the extent of thyroidectomy required but not for the extent of lymph node dissection and prognosis in patients with conventional PTC.

Chronic lymphocytic thyroiditis and BRAF V600E in papillary thyroid carcinoma

It has been reported that papillary thyroid carcinoma (PTC) with chronic lymphocytic thyroiditis (CLT) is less associated with extrathyroidal extension (ETE), advanced tumor stage and lymph node (LN) metastasis. Other studies have suggested that concurrent CLT could antagonize PTC progression, even in BRAF-positive patients. Since the clinical significance of the BRAF mutation has been particularly associated with conventional PTC, the purpose of this study was to determine the clinical significance of CLT according to BRAF mutation status in conventional PTC patients. We retrospectively reviewed the medical records of 3332 conventional PTC patients who underwent total thyroidectomy with bilateral central neck dissection at the Thyroid Cancer Center of Samsung Medical Center between January 2008 and June 2015. In this study, the prevalence of BRAF mutation was significantly less frequent in conventional PTC patients with CLT (76.9% vs 86.6%). CLT was an independent predictor for low prevalence of ETE in both BRAF-negative (OR=0.662, P=0.023) and BRAF-positive (OR=0.817, P=0.027) conventional PTC patients. In addition, CLT was an independent predictor for low prevalence of CLNM in both BRAF-negative (OR=0.675, P=0.044) and BRAF-positive (OR=0.817, P=0.030) conventional PTC patients. In conclusion, BRAF mutation was significantly less frequent in conventional PTC patients with CLT. However, CLT was an independent predictor for less aggressiveness in conventional PTC patients regardless of BRAF mutation status.

Prediction Table and Nomogram as Tools for Diagnosis of Papillary Thyroid Carcinoma: Combined Analysis of Ultrasonography, Fine-Needle Aspiration Biopsy, and BRAF V600E Mutation

AbstractAlthough ultrasonography (US)-guided fine-needle aspiration biopsy (FNAB) is the most reliable diagnostic modality for evaluating thyroid nodules, 10% to 40% of FNAB samples yield indeterminate findings. The BRAF V600E mutation, a highly specific molecular marker for papillary thyroid carcinoma (PTC), well known for its prognostic value, has dubious diagnostic value because of its low sensitivity. Novel strategies are clearly needed to distinguish PTC, which represents the majority of thyroid malignancies, from other thyroid nodules.The records of 3297 patients with surgically proven PTC were retrospectively reviewed. A prediction table and nomogram were designed using a combination of diagnostic parameters for US, FNAB, and the BRAF V600E mutation. For the nomogram, parameters were proportionally assigned 0 to 100 points according to their regression coefficient for PTC.The probability of PTC for thyroid nodules with intermediate-risk (IR) US and atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) FNAB was significantly dependent on BRAF V600E mutation status based on our prediction table (negative, 29.2% vs positive, 87.5%; P < 0.001). By our nomogram, the probability of PTC for thyroid nodules with IR US, AUS/FLUS FNAB, and positive BRAF V600E mutation was approximately 85% to 90%.We strongly recommend preoperative evaluation of the BRAF V600E mutation in indeterminate thyroid nodules. The prediction table and nomogram developed in this study could help clinicians and patients easily assess the probability of PTC in the preoperative period.

Total thyroidectomy versus lobectomy in conventional papillary thyroid microcarcinoma: Analysis of 8,676 patients at a single institution

BACKGROUND Because there is a controversy regarding the management of papillary thyroid microcarcinoma, the purpose of this study was to compare lobectomy with total thyroidectomy as a primary operative treatment for papillary thyroid microcarcinoma. Loco‐regional recurrence in the contralateral remnant lobe can be managed safely by completion thyroidectomy via the previous scar. However, reoperation for operation bed (thyroidectomy site) or regional lymph node (central or lateral) recurrence generally is associated with morbidity. Therefore, we analyzed overall loco‐regional recurrence and loco‐regional recurrence outside of the contralateral remnant lobe separately. METHODS We retrospectively reviewed 8,676 conventional patients with papillary thyroid microcarcinoma who underwent thyroidectomy. RESULTS Lobectomy was performed in 3,289 (37.9%) patients, and total thyroidectomy was performed in 5,387 (62.1%) patients. Total thyroidectomy significantly decreased the risk of overall loco‐regional recurrence (adjusted hazard ratio 0.398, P < .001). However, total thyroidectomy did not significantly decrease the risk of loco‐regional recurrence outside of the contralateral remnant lobe (adjusted hazard ratio 0.880, P = .640). Particularly in conventional papillary thyroid microcarcinoma patients with multifocality, total thyroidectomy significantly decreased the risk of overall loco‐regional recurrence (adjusted hazard ratio 0.284, P = .002) and loco‐regional recurrence outside of the contralateral remnant lobe (adjusted hazard ratio 0.342, P = .020). CONCLUSION Although lobectomy is associated with contralateral remnant lobe recurrence, lobectomy did not increase the risk of loco‐regional recurrence outside of the contralateral remnant lobe in patients with papillary thyroid microcarcinoma, except in those with multifocality. Because recurrence in the contralateral remnant lobe can be managed safely by completion thyroidectomy, lobectomy may be a safe operative option for select patients with papillary thyroid microcarcinoma without multifocality.

Influence of Body Mass Index and Body Surface Area on the Behavior of Papillary Thyroid Carcinoma

BACKGROUND Previous studies have examined the relationship between body mass index (BMI) and the behavior of papillary thyroid carcinomas (PTC). However, the results are inconsistent. The purpose of this study was to clarify the association between PTC behavior and anthropometric parameters including BMI and body surface area (BSA). METHODS This study retrospectively reviewed 5081 PTC patients who underwent total thyroidectomy with bilateral central neck dissection between January 2002 and June 2015. Because of sexual dimorphism in obesity, analyses were conducted separately for men and women. The World Health Organization BMI classification was used to classify patients as normal (18.5 ≤ BMI <25 kg/m(2)), overweight (25 ≤ BMI <30 kg/m(2)), or obese (BMI ≥30 kg/m(2)). Since no consensus for BSA categorization exists, enrolled patients were grouped into BSA quartiles by sex: women BSA1 (BSA <1.52 m(2)), BSA2 (1.52 ≤ BSA <1.59 m(2)), BSA3 (1.59 ≤ BSA <1.67 m(2)), and BSA4 (BSA ≥1.67 m(2)); and men BSA1 (BSA <1.77 m(2)), BSA2 (1.77 ≤ BSA <1.86 m(2)), BSA3 (1.86 ≤ BSA <1.96 m(2)), and BSA4 (BSA ≥1.96 m(2)). RESULTS In women, overweight (adjusted odds ratio [OR] = 1.187, p = 0.042) and obese (adjusted OR = 2.231, p < 0.001) were independent predictors for multiplicity. Furthermore, overweight (adjusted OR = 1.237, p = 0.012) and obese (adjusted OR = 1.789, p = 0.005) were independent predictors for extrathyroidal extension (ETE). However, higher BMI was not an independent predictor for bilaterality or central lymph node metastasis (CLNM). In addition, higher BSA-BSA3 (adjusted OR = 1.205, p = 0.049) and BSA4 (adjusted OR = 1.524, p < 0.001)-was an independent predictor for multiplicity. However, higher BSA was not a predictor for bilaterality, ETE, or CLNM. In men, higher BMI and BSA were not predictors for multiplicity, bilaterality, ETE, or CLNM. CONCLUSIONS In women with PTC, higher BMI was an independent predictor for multiplicity and ETE. Furthermore, higher BSA was an independent predictor for multiplicity. However, BMI and BSA were not predictors for the PTC behavior in men.

Follicular and Diffuse Sclerosing Variant Papillary Thyroid Carcinomas as Independent Predictive Factors of Loco-Regional Recurrence: A Comparison Study Using Propensity Score Matching

BACKGROUND Only about half of papillary thyroid carcinoma (PTC) cases are classified as conventional PTC (CV-PTC), whereas various histologic variants constitute the remaining cases. Since controversies about the clinical behavior and outcomes of PTC variants continue, the purpose of this study was to compare the outcomes of patients with PTC variants who were treated at a large tertiary referral center in Korea. METHODS The medical records for 15,598 CV-PTCs, 435 follicular variants of PTC (FV-PTCs), and 66 diffuse sclerosing variants of PTC (DSV-PTCs) were retrospectively reviewed. Loco-regional recurrences (LRR) among PTC variants were compared using propensity score matching. RESULTS Analysis I compared CV-PTC with FV-PTC. After rigorous matching, 367 pairs were established. Recurrence-free survival (RFS) rates in CV-PTC were 96.1% at 5 years, 92.2% at 10 years, and 92.2% at 15 years, while those for FV-PTC were 98.8% at 5 years, 98.8% at 10 years, and 98.8% at 15 years (p = 0.026). Analysis II compared CV-PTC with DSV-PTC. Rigorous matching yielded 56 pairs. RFS rates for CV-PTC were 87.4% at 5 years, 87.4% at 10 years, and 87.4% at 15 years, while those for DSV-PTC were 68.9% at 5 years, 57.5% at 10 years, and were not available at 15 years (p = 0.013). CONCLUSIONS Compared with CV-PTC, FV-PTC showed less aggressive behaviors and more favorable outcomes. However, DSV-PTC showed more aggressive behaviors and a less favorable outcome than CV-PTC did. Therefore, the management strategy and follow-up plan for PTC should be differentiated according to the histologic variant.

Radioactive iodine ablation may not decrease the risk of recurrence in intermediate-risk papillary thyroid carcinoma

The use of radioactive iodine (RAI) ablation in patients with intermediate-risk papillary thyroid carcinoma (PTC) who show microscopic extrathyroidal extension (ETE), regional lymph node (LN) metastasis, tumors with aggressive histology, or vascular invasion has been debated due to the lack of data regarding long-term prognosis in this risk group. Therefore, the purpose of this study was to resolve the controversy surrounding the prognostic benefit of RAI ablation, especially in intermediate-risk PTC patients. We retrospectively reviewed the medical records of 8297 intermediate-risk PTC patients who underwent primary total thyroidectomy with or without neck dissection at the Thyroid Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, between January 1997 and June 2015. Of these 8297 patients, 7483 (90.2%) received RAI ablation. After adjusting for clinicopathological characteristics, RAI ablation did not significantly decrease the risk of loco-regional recurrence (LRR) (adjusted hazard ratio (HR) 0.852, P 0.413). Moreover, RAI ablation did not decrease the risk of LRR even in intermediate-risk PTC patients with aggressive features such as BRAF positivity (adjusted HR 0.729, P 0.137), tumor size >1 cm (adjusted HR 0.762, P 0.228), multifocality (adjusted HR 1.032, P 0.926), ETE (adjusted HR 0.870, P 0.541), and regional LN metastasis (adjusted HR 0.804, P 0.349). Furthermore, high-dose RAI ablation (>100 mCi) did not significantly decrease the risk of LRR (adjusted HR 0.942, P 0.843). Therefore, RAI ablation in intermediate-risk PTC patients should be considered on the basis of tailored risk restratification.

Nomogram for predicting central node metastasis in papillary thyroid carcinoma

There was a difficulty for detecting Central lymph node metastasis (CLNM) in papillary thyroid carcinoma (PTC) patients. Therefore, the purpose of this study was to design a nomogram for predicting CLNM.

BRAF V600E mutation: Differential impact on central lymph node metastasis by tumor size in papillary thyroid carcinoma.

The necessity of prophylactic central neck dissection is one of debating issues in the treatment of papillary thyroid carcinoma (PTC). In a previous study, the predictive value of BRAF mutation for lymph node metastasis was only significant in 0.5 to 1.0 cm PTC. Thus, we assess the predictive value of BRAF mutation for central lymph node metastasis according to tumor size.