Long-term outcomes of lobectomy for papillary thyroid carcinoma with high-risk features.

BACKGROUND: Lobectomy is not advocated for papillary thyroid carcinoma (PTC) with high-risk features, although there is no high-level evidence showing that this is an inferior strategy. This study aimed to examine the association between the extent of surgery and survival of patients with PTC and high-risk features. METHODS: Consecutive patients with PTC and at least one high-risk feature treated in 2000-2012 were included in the study. High-risk features were defined as: primary tumour larger than 4 cm, gross extrathyroidal extension, macroscopic multifocality, and confirmed nodal metastasis including pathological lateral neck metastasis (pN1b) or more than five central lymph node metastases. Cox proportional hazards models were employed to measure the association between the extent of surgery and disease-specific survival (DSS) in the whole cohort and in a matched-pair analysis. RESULTS: Among a total of 2059 patients with high-risk features, 1224 underwent lobectomy and 835 had total thyroidectomy. Patients who underwent total thyroidectomy had significantly higher rates of bilateral cancer than those who had a lobectomy (79.4 versus 2.7 per cent respectively), macroscopic multifocality (80.8 versus 32.8 per cent) and bilateral neck metastasis (30.9 versus 3.3 per cent) (all P < 0.001). With a median follow-up of 93 months, multivariable analysis showed that the extent of surgery was not associated with DSS in the whole cohort (hazard ratio 1.36, 95 per cent c.i. 0.75 to 2.48; P = 0.310). After 1 : 1 case-control matching of 528 patients, no significant difference between lobectomy and total thyroidectomy groups was observed with respect to the 10-year DSS rate (94.3 versus 95.2 per cent respectively; P = 0.323) or 10-year recurrence-free survival rate (75.8 versus 79.2 per cent; P = 0.784). CONCLUSION: Lobectomy was not associated with significantly worse outcomes for patients with PTC and high-risk features.

Prophylactic central neck dissection has no advantage in patients with metastatic papillary thyroid cancer to the lateral neck.

BACKGROUND: Papillary thyroid cancer (PTC) usually metastasizes via lymphatic channels in a sequential fashion, first to the central compartment, followed by the lateral neck. PTC patients diagnosed with lateral neck disease (N1b) without proof for central involvement traditionally undergo prophylactic central neck dissection (pCND). However, substantial evidence on outcomes to support this approach is lacking. MATERIALS AND METHODS: We conducted a dual center retrospective study to compare the rate of central neck recurrence between N1b PTC patients undergoing pCND and those spared pCND. All patients diagnosed with N1b PTC who underwent total thyroidectomy and lateral neck dissections with or without pCND between January 1998 and December 2015 were included in this study. The rates of central neck recurrences were compared between the groups. RESULTS: The 111 patients who met the inclusion criteria were 44 females (39.6%) and 67 males (60.4%), with a mean age of 50.2 ± 17.7 years, and a mean follow-up of 10.2 ± 5.3 years. Sixty patients (54.1%) underwent a pCND and 51 patients (45.9%) did not (non-pCND). During follow-up, 18 patients (16.2%) had level VI recurrences, 13 in the pCND group and 5 in the non-pCND group. Cox-regression models with propensity scoring did not reveal any inclination or an advantage for performing pCND. CONCLUSION: The present study demonstrated no advantage in performing pCND to prevent central neck recurrence among PTC patients with lateral neck involvement only. These findings question the need for pCND in patients without clinical evidence of central neck disease.

Analysis of risk factors and prognosis in differentiated thyroid cancer with focus on minimal extrathyroidal extension.

AIMS: In contrast to all prior AJCC/TNM classifications for differentiated thyroid cancer (DTC) the 8th edition does not take minimal extrathyroidal extension (M-ETE) into consideration for local tumor staging. We therefore aimed to retrospectively assess the specific impact of M-ETE on the outcome of M-ETE patients treated in our clinic. METHODS: DTC patients with M-ETE and a follow-up time of ≥ 5 years were included and matched with an identical number of patients without M-ETE, but with equal histopathological tumor subtype and size. The frequency of initially metastatic disease among groups was compared using Fisher's exact test, the recurrence rate by virtue of log-rank test. Fisher's exact test and multivariate analysis were used to account for the presence of confounding risk factors. RESULTS: One hundred sixty patients (80 matching pairs) were eligible. With other confounding risk factors being equal, the prevalence of N1-/M1-disease at initial diagnosis was comparable among groups (M-ETE: 42.5 %; no M-ETE: 32.5 %; p = 0.25). No differences with regard to the recurrence rate were shown. However, M-ETE patients were treated with external beam radiation therapy more often (16.3 % vs. 1.3 %; p = 0.004) and received higher median cumulative activities of 131I (10.0 vs. 8.0 GBq; p < 0.001). DISCUSSION: Although having played a pivotal role for local tumor staging of DTC for decades M-ETE did not increase the risk for metastases at initial diagnosis and the recurrence rate in our cohort. Patients with M-ETE had undergone intensified treatment, which entails a possible confounding factor that warrants further investigation in randomized controlled trials.

Features and outcome of differentiated thyroid carcinoma associated with Graves' disease: results of a large, retrospective, multicenter study.

BACKGROUND: Whether differentiated thyroid cancer (DTC) occurring concomitantly with Graves' disease (GD) is more aggressive and bound to a less favorable outcome is controversial. OBJECTIVE: Aim of this multicenter retrospective study was to compare baseline features and outcome of DTC patients with GD (DTC/GD+) or without GD (DTC/GD-). PATIENTS: Enrolled in this study were 579 patients referred to five endocrine units (Cagliari, Pavia, Pisa, Siena, and Varese) between 2005 and 2014: 193 patients had DTC/GD+ , 386 DTC/GD-. Patients were matched for age, gender and tumor size. They underwent surgery because of malignancy, large goiter size, or relapse of hyperthyroidism in GD. RESULTS: Baseline DTC features (histology, lymph node metastases, extrathyroidal extension) did not differ in the two groups, except for multifocality which was significantly more frequent in DTC/GD+ (27.5% vs. 7.5%, p < 0.0001). At the end of follow-up (median 7.5 years), 86% of DTC/GD+ and 89.6% DTC/GD- patients were free of disease. Patients with persistent or recurrent disease (PRD) had "biochemical disease" in the majority of cases. Microcarcinomas were more frequent in the DTC/GD+ group (60% vs. 37%, p < 0.0001) and had an excellent outcome, with no difference in PRD between groups. However, in carcinomas ≥ 1 cm, PRD was significantly more common in DTC/GD+ (24.4% vs. 11.5%; p = 0.005). In the whole group, univariate and multivariate analyses showed that GD+ , lymph node involvement, extrathyroidal invasion, multifocality and tall cell histotype were associated with a worse outcome. Female gender and microcarcinomas were favorable features. No association was found between baseline TSH-receptor antibody levels and outcome. Graves' orbitopathy (GO) seemed to be associated with a better outcome of DTC, possibly because patients with GO may early undergo surgery for hyperthyroidism. CONCLUSIONS: GD may be associated with a worse outcome of coexisting DTC only if cancer is ≥ 1 cm, whereas clinical outcome of microcarcinomas is not related to the presence/absence of GD.

The Prognosis of Papillary Thyroid Cancer with Initial Distant Metastasis is Strongly Associated with Extensive Extrathyroidal Extension: A Retrospective Cohort Study.

BACKGROUND: Extensive extrathyroidal extension (ETE) has a significant role in the prognosis of papillary thyroid cancer (PTC) without distant metastasis, but its role in PTC with initial distant metastasis has never been studied. This study aimed to evaluate the prognostic significance of extensive ETE regarding disease progression, survival, and remission in PTC patients with initial distant metastasis. METHODS: This retrospective cohort study included PTC patients with initial distant metastasis who underwent total thyroidectomy with a median follow-up period of 6.7 years. The prognostic significance of extensive ETE was assessed in terms of time to tumor progression (TTP), cancer-specific survival (CSS), and cumulative incidence of remission with all-cause death as the competing event. RESULTS: The study enrolled 64 patients. Of these patients, 21 (32.8%) had extensive ETE, which was associated with a shorter TTP (adjusted hazard ratio [HR], 4.10; p = 0.015) and a lower CSS rate (p = 0.002, log-rank), particularly for patients 55 years of age or older with stage 4b disease (10-year CSS rate: 33.3% in those with and 92.3% in those without extensive ETE; p = 0.017). Additionally, remission was observed only in patients without extensive ETE (10-year cumulative incidence of remission: 0.0% in those with and 29.3% in those without extensive ETE; p = 0.013). CONCLUSIONS: Extensive ETE of the primary lesion results in poorer prognoses for PTC patients with initial distant metastasis. The high CSS rate for patients with stage 4b PTC but no extensive ETE indicates that the prognosis of this patient population should be distinguished from that of other stage 4 cases.

Long-Term Prognosis of Unilateral and Multifocal Papillary Thyroid Microcarcinoma After Unilateral Lobectomy Versus Total Thyroidectomy.

BACKGROUND: Multifocal papillary thyroid microcarcinoma (PTMC) has been associated with poor outcomes; however, we often encounter pathologically confirmed unilateral multifocal PTMC after surgery. To date, no consensus on the proper surgical extent for patients with this form of PTMC has been reported. OBJECTIVE: The aim of this study was to analyze the effect of the type of surgical treatment on disease recurrence in patients with unilateral multifocal PTMC. METHODS: We retrospectively analyzed data from 255 patients with unilateral, multifocal, node-negative PTMC between March 1999 and December 2012. We evaluated two groups of patients: those who underwent unilateral lobectomy (Group I, n = 127) and those who underwent total thyroidectomy (Group II, n = 128). During the follow-up period, which lasted a median of 94.8 months, we assessed locoregional recurrence (LRR). RESULTS: There was no statistically significant difference between the two groups with regard to LRR at follow-up (3.15% for Group I vs. 0.78% for Group II; p = 0.244). The association between the type of surgical treatment and LRR remained nonsignificant after adjusting for potential confounders such as age, tumor size, microscopic extrathyroidal extension, and lymphovascular invasion (p = 0.115). During follow-up, the incidence of transient hypocalcemia (0% vs. 8.6%; p = 0.001) and vocal fold paralysis (1.6% vs. 9.4%; p = 0.011) was higher in Group II than in Group I. CONCLUSIONS: Even though randomized controlled trials are the only option to obtain a definitive answer to this question, unilateral lobectomy may be a safe operative option for selected patients with unilateral, multifocal, node-negative PTMC.

Superior Located Papillary Thyroid Microcarcinoma is a Risk Factor for Lateral Lymph Node Metastasis.

BACKGROUND: It is important to identify prognostic factors for lateral lymph node metastasis (LLNM) in papillary thyroid microcarcinoma (PTMC) because they determine the extent of surgery. Several similarly designed studies have investigated predictors of LLNM, but with no more than 1000 cases. In addition, there are no recommendations or guidelines covering the differences in risk by tumor location. This study is the largest, using a papillary thyroid microcarcinoma population with 2967 patients. The purpose of this study is to address predictive factors of LLNM, focusing on lesion location. PATIENTS AND METHODS: We retrospectively reviewed the data of 2967 PTMC patients who underwent total thyroidectomy and central neck dissection and/or lateral neck dissection (unilateral or bilateral) between January 1997 and June 2015. RESULTS: On multivariate analysis, superior lesion [adjusted odds ratio (OR) 3.32, p < 0.000], male gender (adjusted OR 1.39, p = 0.0047), age under 45 years (adjusted OR 1.42, p = 0.015), and central lymph node metastasis (adjusted OR 3.40, p < 0.000) were significant predictors of high-risk LLNM. Superior lesion [hazard ratio (HR) 2.32, p = 0.005] and central lymph node metastasis (CLNM, HR 7.12, p < 0.000) were significant risk factors for locoregional recurrence (LRR). To reduce the effect of selection bias, we performed propensity score matching analysis with regard to tumor location. With a total of 1138 patients with matched data and 569 patients for each location, superior lesion (adjusted OR 3.17, p < 0.000), age under 45 years (adjusted OR 1.73, p = 0.005), and CLNM (adjusted OR 2.77, p < 0.000) were independent predictive factors of LLNM. Superior lesion (HR 2.28, p = 0.04) and CLNM (HR 5.32, p = 0.001) were significant risk factors for LRR. CONCLUSIONS: In addition to young age, male gender, and CLNM identified in previous studies, meticulous assessment for LLNM is required in PTMC patients when lesions are located in the superior pole of the thyroid during preoperative evaluation or postoperative follow-up, because superior located papillary microcarcinoma is a risk factor for LLNM and LRR.

Extrathyroidal Extension: Does Strap Muscle Invasion Alone Influence Recurrence and Survival in Patients with Differentiated Thyroid Cancer?

BACKGROUND: According to the 8th edition American Joint Committee on Cancer staging system, extrathyroidal extension (ETE) and primary tumor size remain the principle determinants of T stage. However, impact of gross ETE into strap muscles on survival remains controversial. PATIENTS AND METHODS: A retrospective review of 2084 patients with ≤ 4 cm nonmetastatic differentiated thyroid cancer who underwent surgery between 2000 and 2015 was conducted. Patients were divided into three groups according to degree of ETE: no ETE (group 1), ETE into perithyroidal soft tissue (group 2), and gross ETE into strap muscle (group 3). Survivals were analyzed using Kaplan-Meier method and compared using log-rank test. Factors predictive of survival were analyzed using Cox proportional hazard model. RESULTS: Ten-year disease-free survival (DFS) of patients in groups 1-3 was 90, 82, and 83%, respectively (p = 0.003). On multivariate analysis, age ≥ 55 years, male sex, and pathologic N1b category predicted significantly worse DFS, while ETE into perithyroidal soft tissue or gross strap muscle invasion did not predict worse DFS. Overall survival (p = 0.957) and disease-specific survival (p =0.910) were not significantly different between the three groups. There was a statistically significant difference in locoregional recurrence-free survival between groups 1 and 2 [HR 2.02, 95% CI 1.06-3.94]. CONCLUSION: Gross strap muscle invasion may not be an important survival prognostic factor for staging purposes. Although both gross strap muscle invasion and perithyroidal soft tissue extension may be predictive for locoregional recurrence, the distinction between them may not be as important for postoperative risk stratification.

Central Lymph Node Status has Significant Prognostic Value in the Clinically Node-Negative Tall-Cell Variant of Papillary Thyroid Cancer Regardless of T-Staging and Radioactive Iodine Administration: First Evidence From a Population-Based Study.

BACKGROUND: The prognostic value of central lymph node (CLN) status in papillary thyroid cancer (PTC) remains controversial. This study aimed to provide the first evidence on this issue for the aggressive tall-cell variant (TCV) subtype. METHODS: The study identified TCV patients from the Surveillance, Epidemiology, and End Results database. The Kaplan-Meier method, log-rank test, and multivariate Cox regression models were used for analysis. RESULTS: Of the 744 patients included, 404 were recorded as N0, which were pathologically or only clinically confirmed. Overall survival (OS) and cancer-specific survival (CSS) did not differ significantly between the N0 and pN1a patients (p > 0.05). To investigate the reason, the N0 patients were subdivided according to the number of examined lymph nodes (ELN). The patients with a N0 diagnosis confirmed by two or more ELNs (N0-e2+) showed significantly better outcomes than the pN1a patients and their N0 counterparts without ELN (N0-e0) (p < 0.05), whereas the N0-e0 and pN1a groups demonstrated comparable outcomes in both the log-rank and multivariate analyses (p > 0.05). Moreover, the subgroup analyses showed that even among the patients with early T-staging (T1-T2) or receipt of radioactive iodine (RAI) therapy, the N0-e0 patients still demonstrated compromised OS compared with the N0-e2+ group (p < 0.05). CONCLUSION: The cN0 patients without ELN (N0-e0) had outcomes similar to those of the pN1a patients, but showed a poorer OS than the N0-e2+ group regardless of T-staging and RAI administration, suggesting that occult CLN metastases might act as a negative prognosticator in cN0 TCV. Therefore, prophylactic central neck dissection might be considered for biopsy-proven cN0 TCV patients. Prospective studies are expected to further validate our conclusions.

Survival in patients with medullary thyroid cancer after less than the recommended initial operation.

BACKGROUND AND OBJECTIVES: We aimed to evaluate the disease specific-survival (DSS) of patients with Medullary Thyroid Cancer (MTC) confined to the central neck based on the extent of the initial operation. METHODS: This retrospective review of patients with MTC from the SEER registry from 2004 to 2012 excluded patients with lateral neck involvement or distant metastases. RESULTS: The cohort (n = 766) included 85(11%) less than total thyroidectomies (TT), 212(28%) TT alone, and 469(61%) TT with lymph node excision. Mean tumor size was similar (2.2cm for

Dynamic risk stratification in papillary thyroid carcinoma measuring 1 to 4 cm.

BACKGROUND AND OBJECTIVES: This study aimed to validate the dynamic risk stratification (DRS) system, evaluate its correlation with structural recurrence, and assess the clinicopathological risk factors associated with a nonexcellent response to initial therapy in patients with papillary thyroid cancer (PTC) measuring 1 to 4 cm. METHODS: A total of 762 patients with classic PTC measuring 1 to 4 cm were classified into four categories based on their response to initial therapy 2 years postoperatively. RESULTS: Structural recurrent disease occurred in 4.7%, 17.1%, 48.4%, and 83.9% of patients with excellent, indeterminate, biochemically incomplete, and structurally incomplete responses, respectively, at the time of the last follow-up. The response to initial therapy in the DRS was one of the independent risk factors for structural recurrence. The disease-free survival curves of patients with different responses showed significant differences (P < 0.001). Extensive extrathyroidal extension, lymph node (LN) metastasis, number of metastatic LNs greater than 2.0, metastatic LN ratio greater than 0.22, and extranodal extension were independent risk factors for nonexcellent response to initial therapy. CONCLUSIONS: DRS can be a useful tool in predicting structural recurrence and guiding postoperative management and follow-up strategies in patients with PTC measuring 1 to 4 cm.

Racial disparities of differentiated thyroid carcinoma: clinical behavior, treatments, and long-term outcomes.

BACKGROUND: The incidence of thyroid cancer in black Americans is significantly lower than that in white Americans, and the impact of race on the prognosis of thyroid cancer remains controversial. The purpose of this study was to determine the risk factors for survival in black and white patients and to compare the survival of differentiated thyroid carcinoma subtypes between these two races. We further investigated the association of lymph node and distant metastases with races. METHODS: This is a retrospective analysis using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. A total of 70,346 cases were included in our study. Patients' demographics and cancer- and treatment-related characteristics were compared between the black and white Americans using chi-square and Fisher's exact tests. For multivariate analysis, Cox proportional hazards regression were used to assess the association between potential risk factors and the survival in black and white patients. RESULT: Black Americans had a worse overall survival than white Americans (HR = 1.127, P = 0.002). While disease-specific survival (DSS) was comparable, the risk factors for DSS were different between white and black Americans. Black Americans had less lymph node metastasis of classical variant papillary thyroid carcinoma (CPTC, OR = 0.476, P < 0.001) and follicular variant papillary thyroid carcinoma (FVPTC, OR = 0.522, P < 0.001), but not follicular thyroid carcinoma (FTC). However, black Americans with FVPTC, but not CPTC or FTC, had a higher potential of distant metastasis (OR = 1.715, P = 0.026). Furthermore, only white patients with tumor > 2 cm and lymph node metastasis benefited from radioactive iodine. CONCLUSIONS: The risk factors for DSS were significantly different in white and black patients. The impact of race should be considered in treatment strategy for thyroid cancer.

Changes in standardized mortality rates from thyroid cancer in Korea between 1985 and 2015: Analysis of Korean national data.

BACKGROUND: The incidence of thyroid cancer has increased very rapidly in Korea; however, most previous studies suggested that the mortality rate for thyroid cancer remained stable. The objective of the current study was to evaluate recent changes in standardized thyroid cancer mortality using data from Statistics Korea. METHODS: Population and mortality data from 1985 through 2015 were obtained from Statistics Korea. Age-standardized mortality rates (ASMRs) from thyroid cancer per 100,000 population were calculated based on the World Health Organization standard population. RESULTS: In Korea, the ASMRs from thyroid cancer increased from 0.17 (95% confidence interval [CI], 0.17-0.18) per 100,000 in 1985 to 0.85 (95% CI, 0.83-0.86) per 100,000 in 2004, which was the highest among all countries. Subsequently, the ASMRs continuously decreased to 0.42 (95% CI, 0.41-0.43) per 100,000 between 2004 and 2015. The estimated annual percent change (APC) from 1985 to 2004 was 7.94 (95% CI, 6.43-9.46), and the corresponding value from 2004 to 2015 was -4.10 (95% CI, -5.76 to -2.40). Changes in the ASMRs reflected similar patterns in men (1985-2003: APC, 8.51; 2003-2015: APC, -4.32) and women (1985-2004: APC, 7.62; 2004-2015: APC, -4.38) and were also observed in older patients (aged ≥ 55 years). CONCLUSIONS: Thyroid cancer mortality in Korea increased until 2004 and then continuously decreased until 2015. Increases in the early diagnosis of thyroid cancer, changes in exposure to risk factors, and standardization in diagnosis and treatment may be associated with the decrease in thyroid cancer mortality in Korea. Cancer 2017; 123:4808-14. © 2017 American Cancer Society.

Total thyroidectomy may be more reasonable as initial surgery in unilateral multifocal papillary thyroid microcarcinoma: a single-center experience.

BACKGROUND: The extent of surgery in patients with unilateral multifocal papillary thyroid microcarcinoma (UMPTMC) remains to be controversial. Aimed to improve surgical management of UMPTMC, this study was performed to identify the recurrence of UMPTMC and analyze its predictive factors. METHODS: This study was approved by the Ethical Committee of The First Hospital of the Jilin University, and written informed consent was given by participants for their clinical records to be used in this study. We retrospectively analyzed a total of 97 consecutive patients who underwent initial surgery for the treatment of UMPTMC at The First Hospital of Jilin University, between October 2005 and October 2006. RESULTS: Altogether, 97 patients of UMPTMC have been enrolled in our study, in which 57 cases were performed with hemithyroidectomy (HT) while other 40 cases with total thyroidectomy (TT). The sum diameter of all tumors >1 cm was more frequent in HT group than in TT group (40.35 vs 20%; p = 0.046). Positive central lymph nodes were found more frequently in the TT patients than in the HT patients (80 vs 59.65%; p = 0.046). Tumor recurrence was seen more frequently in the HT cases than in the TT cases (26 vs 5%; p = 0.007). The disease-free survival period was significantly shorter for the HT patients than for the TT patients (p = 0.0059 by the log-rank test). The disease-free survival rates at 5 and 10 years were 91.23 and 73.68%, respectively, in the HT group and 100 and 92.5%, respectively, in the TT group. Univariate analysis by Cox's proportional hazards method showed male gender, sum diameter of all tumors >1 cm, and central lymph node metastases (CLNM) to be risk factors for recurrence of HT patients. Male gender and sum diameter >1 cm were factors identified for multivariate analysis by Cox's proportional hazards method which yielded risk ratios of 3.037 [CI 1.026-8.988; p = 0.045] and 5.475 [CI 1.389-21.572; p = 0.015] in the HT group. CONCLUSIONS: In summary, with an increased risk of recurrence, TT may be more reasonable as initial surgery in UMPTMC, especially with male gender and total tumor diameter greater than 1 cm.

Postoperative radioactive iodine-131 ablation is not necessary among patients with intermediate-risk differentiated thyroid carcinoma: a population-based study.

OBJECTIVE: To assess the effectiveness of radioactive iodine (RAI) ablation among patients with intermediate-risk differentiated thyroid cancer (DTC) following surgery. SUBJECTS AND METHODS: This population based study obtained information from the Surveillance, Epidemiology, and End Results (SEER) Program Research Data (1973-2013). National Cancer Institute, DCCPS, Surveillance Research Programme, Surveillance Systems Branch, released April 2016, based on the November 2015 submission. A total of 93,530 patients with primary thyroid cancer were identified in the SEER database during the period of 2004-2013 and focused on patients with DTC post-operatively treated or not treated with radioactive iodine (RAI). From these 9,127 patients were selected who had intermediate-risk DTC. A total of 8,601 patients were included in this study. For the overall population, the mean age of the population was 47.3 years and the majority were female (70.5%). RESULTS: Kaplan-Meier analysis found the mean overall survival time (os) for subjects with no radiation therapy which was 112.9 months and 114.9 months for those who received RAI ablation treatment (P<0.001). However, thyroid cancer-specific survival was not significantly different between treatment groups (117.7 vs. 118.0 months, log-rank test P=0.164). Overall survival and thyroid cancer-specific 1 year, 5 years, and 10-years survival rates were ≥89.8% and were similar between both treated groups. Multivariate analysis found age, gender, histologic type, and degree of lymph node metastases to be associated with OS, and age, gender, degree of lymph node metastasis and extra-thyroid tumor spread were independent factors for cancer-specific survival. In DTC patients with intermediate cancer risk multivariate analysis found that RAI was associated with a reduced risk of mortality compared with no radiation therapy (HR=0.710, 95% CI: 0.562-0.897, P=0.004) but no significant difference was seen in cancer-specific survival, either based on whole study population or on tumor size category. CONCLUSION: In DTC patients with intermediate cancer risk although postoperative RAI ablation following surgery showed a benefit in overall survival, no significant difference was seen in cancer-specific survival, either based on whole study population or on tumor size category.

Patients Treated at Low-Volume Centers have Higher Rates of Incomplete Resection and Compromised Outcomes: Analysis of 31,129 Patients with Papillary Thyroid Cancer.

BACKGROUND: Data on the importance of margin status after total thyroidectomy for papillary thyroid cancer (PTC) remain limited. This study sought to identify factors associated with positive margins and to determine the impact of positive margins on survival for patients with PTC. METHODS: The National Cancer Data Base (1998-2006) was queried for patients with PTC who had undergone total thyroidectomy. The patients were divided into three groups based on margin status (negative, microscopically positive, and macroscopically positive). Patient demographic, clinical, and pathologic features were evaluated. A binary logistic regression model was developed to identify factors associated with positive margins. A Cox proportional hazards model was developed to identify factors associated with survival. RESULTS: Of the 31,129 patients enrolled in the study, 91.3 % had negative margins, 8.1 % had microscopically positive margins, and 0.6 % had macroscopically positive margins. The patients with negative margins were younger and more likely to be female, white, covered by private insurance, and treated at an academic or high-volume center (p < 0.05). They had smaller tumors and were less likely to have advanced-stage disease. After multivariable adjustment, increasing patient age [odds ratio (OR) = 1.02; p < 0.01], government insurance (OR = 1.20; p < 0.01), and no insurance (OR = 1.34; p = 0.01) were associated with positive margins. Reception of surgery at a high-volume facility (OR = 0.72; p < 0.01) was protective. After multivariable adjustment, both microscopically [hazard ratio (HR), 1.49; p < 0.01] and macroscopically positive margins (HR = 2.38; p < 0.01) were associated with compromised survival. CONCLUSIONS: Several vulnerable patient populations have a higher risk of incomplete resection after thyroidectomy for PTC. High-risk thyroid cancer patients should be referred to high-volume centers to optimize outcomes.

The influence of American Society of Anesthesiologists Physical Status on patient morbidity and survival after total thyroidectomy.

In cases of thyroid papillary carcinoma, a less aggressive cancer, surgeons may hesitate to perform total thyroidectomy on patients with poor general condition because these may experience longer survival without undergoing surgery. To investigate the influence of general patient condition on the patients' survival who received total thyroidectomy, we utilized the American Society of Anesthesiologists Physical Status (ASA-PS). We retrospectively reviewed all patients undergoing total thyroidectomy under general anesthesia and graded by ASA-PS between 2004 and 2014. Patients with anaplastic carcinoma and metastatic thyroid renal cell carcinoma were excluded. There were 77 (30%), 149 (58%), and 30 (12%) ASA-PS 1, 2, and 3 cases, respectively. Patient age increased significantly with increasing ASA-PS score (median age of 53, 64, and 71 years for ASA-PS 1, 2, and 3). Hospitalization periods extended significantly for patients with ASA-PS 3. Twenty patients died during the study (3.89 median years). Five-year overall survival rates were 100%, 93%, and 79% for ASA-PS 1, 2 and 3, respectively. Patients in the ASA-PS 1 group had significantly better prognosis by log-rank test. Univariate analysis showed an increased risk of death as ASA-PS score increased (hazard ratio: 3.03, 95% confidence interval: 1.55-5.92, p=0.00). In multivariate analysis, including patient age and presence of malignancy, patient age was the only significant predictor of overall survival (hazard ratio: 1.09 by year, 95% confidence interval: 1.03-1.14, p=0.00). We concluded that a high ASA-PS score should not inhibit performance of total thyroidectomy if a patient's age is suitable for the surgery.

Post-Chernobyl incidence of papillary thyroid cancer among Belgian children less than 15 years of age in April 1986: a 30-year surgical experience.

OBJECTIVE: We raised the question of a possible relationship in Belgium between the occurrence of papillary thyroid carcinoma (PTC) and age of children (<15 years) at the time of the Chernobyl nuclear plant accident in April 1986. SETTING: Referral university centre for endocrine surgery. MATERIAL AND METHODS: Thirty-year prospective study of the experience of a surgical team with PTC since the Chernobyl accident, taken out of 2349 patients operated on for any thyroid lesions from April 1986 to April 2015, comparing the incidence of PTC by age groups. MAIN OUTCOME MEASUREMENT: Comparison of PTC incidence in patients >15 years (group A) and children <15 years (group B) in April 1986. RESULTS: Out of a total of 2349 patients having undergone thyroid surgery for all types of lesions during 30 year after Chernobyl and born before April 1986, 2164 were >15 years of age at the time of the nuclear accident (group A) and 175 developed PTC (8.1%) compared to 36 PTC (19.5%) that occurred in 185 children <15 years of age (group B) in April 1986 (p < 0.001). CONCLUSIONS: Radiation exposure affected residents of countries (including Belgium) well beyond Ukraine and Belarus. This was demonstrated by a 1990 meteorological report. Over 30 years, there has been a persistent higher incidence of PTC among Belgian children below the age of 15 years at the time of the Chernobyl accident. This relationship with age has even been strengthened by the implementation of more sophisticated immunohistochemical biomarkers diagnostic technology since April 2011.

Should small papillary thyroid cancer be observed? A population-based study.

BACKGROUND: Some centers have advocated selecting patients with small papillary thyroid cancer (PTC) to undergo active surveillance without surgical treatment. The objectives of the current study were to analyze thyroid cancer (TC)-related mortality in a population-based cohort and to determine the impact of small PTCs (defined as tumors ≤ 2 cm in greatest dimension) on TC-related mortality. METHODS: Data on patients with TC of follicular cell origin from the National Cancer Institute's Surveillance, Epidemiology, and End Results 17 Registries database (1988-2007) were used to analyze the characteristics of PTCs ≤ 2 cm in patients who died from TC-related causes. The effects of clinical features on disease-specific survival were analyzed. RESULTS: Over the 20-year study period, the rate of TC-related mortality was 2.8% (n = 1753 of 61,523 patients). Of the patients who died from TC-related causes, 38% had PTC, 10% had follicular TC, and 31.3% had anaplastic TC. PTCs ≤ 2 cm accounted for 12.3% of TC-related mortalities. Compared with patients who did not experience TC-related mortality from PTCs ≤ 2 cm, there were significantly higher rates of men (30% vs 17%; P < .01), patients aged ≥ 45 years (92% vs 52%; P < .01), tumors measuring >1 cm (59% vs 46%; P < .01), extrathyroid extension (41% vs 11%; P < .01), lymph node metastases (77% vs 28%; P < .01), and distant metastases (31% vs 1%; P < .01) among the patients who died from PTCs ≤ 2 cm. Independent risk factors for death from PTCs ≤ 2 cm included age ≥ 45 years, lymph node and distant metastases, extrathyroid extension, and undergoing less than thyroid lobectomy. CONCLUSIONS: Because 12.3% of patients who experienced TC-related deaths had PTCs ≤ 2 cm despite undergoing thyroidectomy, the current results indicate that nonoperative management for patients who have PTCs ≤ 2 cm should be used with caution. Patients aged ≥ 45 years with PTCs ≤ 2 cm should undergo thyroidectomy.

Tumor genotype determines phenotype and disease-related outcomes in thyroid cancer: a study of 1510 patients.

OBJECTIVES: To correlate thyroid cancer genotype with histology and outcomes. BACKGROUND: The prognostic significance of molecular signature in thyroid cancer (TC) is undefined but can potentially change surgical management. METHODS: We reviewed a consecutive series of 1510 patients who had initial thyroidectomy for TC with routine testing for BRAF, RAS, RET/PTC, and PAX8/PPARG alterations. Histologic metastatic or recurrent TC was tracked for 6 or more months after oncologic thyroidectomy. RESULTS: Papillary thyroid cancer (PTC) was diagnosed in 97% of patients and poorly differentiated/anaplastic TC in 1.1%. Genetic alterations were detected in 1039 (70%); the most common mutations were BRAFV600E (644/1039, 62%), and RAS isoforms (323/1039, 31%). BRAFV600E-positive PTC was often conventional or tall cell variant (58%), with frequent extrathyroidal extension (51%) and lymph node metastasis (46%). Conversely, RAS-positive PTC was commonly follicular variant (87%), with infrequent extrathyroidal extension (4.6%) and lymph node metastasis (5.6%). BRAFV600E and RET/PTC-positive PTCs were histologically similar. Analogously, RAS and PAX8/PPARG-positive PTCs were histologically similar. Compared with RAS or PAX8/PPARG-positive TCs, BRAFV600E or RET/PTC-positive TCs were more often associated with stage III/IV disease (40% vs 15%, P < 0.001) and recurrence (10% vs 0.7%, P < 0.001; mean follow-up 33 ± 21 mo). Distant metastasis was highest in patients with RET/PTC-positive TC (10.8%, P = 0.02). CONCLUSIONS: In this large study of prospective mutation testing in unselected patients with TC, molecular signature was associated with distinctive phenotypes including cancers, with higher risks of both distant metastasis and early recurrence. Preoperative genotype provides valuable prognostic data to appropriately inform surgery.