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Background: Although shear wave elastography (SWE) is reported to be useful in detecting malignant thyroid nodules, it shows a wide range of cut-off values of elasticity index (EI) in detecting malignant nodules. The cause of discrepancy remains unclear. Fibrosis of the tumors is known to increase the EI in SWE, and matching of SWE and surgical histopathology has not been fully illustrated in thyroid cancer. We aimed to evaluate the reproducibility of the new total nodular region of interest (ROI) method excluding the subjective features of focal circular ROI placement and to determine the lesion that causes the elevation of EI on SWE and on histopathology., Methods: A total of 29 thyroid cancers from 28 patients were included. We evaluated the reproducibility of EI in the new total nodular ROI using Q-Box Trace program and compared the EI in focal nodular ROI using a 3-mm circular area. We analyzed the correlation between fibrosis and EI., Result: The coefficient of variation (CV) of the intrarater assay was significantly lower in total nodular ROI than in focal nodular ROI within the image in rater 1 (1.7% vs. 13.4%, p < 0.001) and in rater 2 (1.4% vs. 16.9%, p < 0.001) and in different images in rater 1 (7.6% vs. 12.3%, p = 0.040) and in rater 2 (7.5% vs. 19.8%, p = 0.004). Moreover, CV of the interrater assay showed similar results (14.9% vs. 19%, p = 0.030). Interrater intraclass correlation coefficient showed better agreement in total nodular ROI than in focal nodular ROI (0.863 vs. 0.783). The degree of fibrosis on histopathology showed significant correlations with EI (E Mean , p < 0.001; E Max , p = 0.027), and the location of fibrosis was concordant with the high EI area on SWE., Conclusion: Our study revealed that the new total nodular ROI method showed higher reproducibility and better agreement in intra- and interrater assay than the focal nodular ROI method, suggesting a valuable and standardized method in clinical practice. Moreover, our results showed that fibrosis in the histopathology increased EI on SWE and might lead to the discrepancy of the cut-off values in detecting thyroid cancer.

Background: Low-risk patients with differentiated thyroid cancer can be treated with thyroid lobectomy. Serial measurements of serum thyroglobulin (Tg) are recommended for surveillance, but the cutoff values indicating recurrence are not known. This study documented the natural course of serum Tg levels during follow-up after lobectomy for low-risk papillary thyroid carcinoma (PTC) and evaluated whether changes in serum Tg levels predict disease recurrence., Methods: This historical cohort study included 208 patients with low-risk PTC who underwent lobectomy but did not require hormone replacement. Postoperative serum Tg levels and Tg/thyrotropin (TSH) ratios and neck ultrasound were evaluated during a follow-up period with a median of 6.9 years., Results: The serum Tg levels increased gradually, and the proportion of patients with levels >10 ng/dL increased annually by 13.9%, 18.8%, 22.1%, 21.9%, 28.4%, and 28.9% during the six-year follow-up period (β = 0.574, p = 0.027). The relative serum Tg levels increased by 10% annually (β = 0.105, p < 0.001), and the levels of Tg and Tg/TSH ratios in 19 patients with recurrent disease did not differ significantly (β = 0.150, p = 0.090). Patients without recurrent disease were more likely to have serum Tg levels increased by >20% (p = 0.022). There were no significant differences in the proportions of patients with serum Tg levels increased by ≥50% or ≥100% in terms of the disease recurrence., Conclusions: Serum Tg levels and the Tg/TSH ratio increased gradually after lobectomy in patients with and without recurrences, without any significant differences. Periodic measurements of serum Tg levels seem to have limited value in predicting recurrent PTCs after lobectomy.

Background: Regional lymph node metastases (LNM) have prognostic significance in differentiated thyroid cancer (DTC). However, there was no distinction between N1a and N1b in the final staging classification in the eighth edition of the tumor-node-metastasis (TNM) staging system. This study aimed to evaluate the prognostic implication of N1b classification for predicting disease-specific survival (DSS) in DTC patients with stage I/II disease., Methods: A total of 3089 patients with stage I/II DTC who underwent thyroid surgery between 1996 and 2005 were included. DSS was evaluated according to N classification and number of LNM. A modification of the TNM was assessed that classified N1b cases in patients aged ≥55 years as stage IIB and the remaining cases as stage IIA., Results: The mean patient age was 45.6 years, and the median follow-up period was 10.0 years. In patients aged ≥55 years, patients with N1b had significantly poorer DSS compared to those with N0 (hazard ratio [HR] = 11.0; p < 0.001) and N1a (HR = 4.2; p = 0.013). The large-volume LNM group had significantly poorer DSS compared to the N0 (HR = 10.1; p < 0.001) and small-volume LNM (HR = 3.9; p = 0.019) groups. When patients were reclassified using the modified TNM staging system, DSS was significantly poorer in stage IIB patients than in stage IIA patients (HR = 2.9; p = 0.030)., Conclusions: N1b classification has a significant prognostic implication in patients with stage I/II DTC, especially in older patients. Modified TNM staging employing N1b classification could be more useful for the prediction of DSS.

Background: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is an indolent thyroid tumor previously known as noninvasive subtype of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC). The absence of BRAF V600E mutations has been considered characteristic of NIFTPs. However, a recent study from Korea found that 28.6% of NIFTPs harbored a BRAF mutation. This study evaluated BRAF and RAS mutations in NIFTPs and invasive subtype of EFVPTCs., Methods: This study enrolled 32 patients with NIFTP and 48 with invasive EFVPTC. BRAF, NRAS, HRAS, and KRAS mutations were evaluated by direct sequencing using DNA from fresh-frozen tissues and formalin-fixed, paraffin-embedded tissue samples., Results: The primary tumor size of NIFTP was smaller than that of invasive EFVPTC (median 2.8 cm vs. 3.2 cm; p = 0.03). Cervical lymph node metastases were found in only four (8%) patients with invasive EFVPTC. There was no BRAF mutation in NIFTPs, whereas invasive EFVPTCs had three (6%) BRAF V600E mutations and one (2%) BRAF K601E mutation. RAS mutations were detected in 15 (47%) NIFTPs and 22 (46%) invasive EFVPTCs. NRAS mutations in codon 61 were the most common mutations in NIFTPs (34%) and invasive EFVPTCs (27%). There was no significant difference in the frequency of RAS mutations between the two groups., Conclusions: There was no BRAF mutation in any of the NIFTPs. RAS mutations, particularly mutations in codon 61 of NRAS, were the most common mutations in both NIFTPs and invasive EFVPTCs. The presence of a RAS mutation is not helpful for preoperative differentiation between NIFTPs and invasive EFVPTCs.

Background: The risk of recurrence in patients with differentiated thyroid cancer (DTC) can be estimated based on their response to initial therapy. The aim of this study was to evaluate an adequate follow-up strategy for DTC patients with an excellent response by assessing the characteristics of structural recurrence., Methods: This historical cohort study included 1359 DTC patients who had excellent response to total thyroidectomy with radioactive iodine remnant ablation., Results: Among 1359 patients, 703 (54%) patients were classified as stage I according to the seventh tumor node metastasis staging system, and 987 (73%) patients were classified as intermediate risk according to the American Thyroid Association's risk stratification after initial therapy. During a median of 8.7 years of follow-up, only 13 (1%) patients were confirmed to have structural recurrence. All of the recurrences were locoregional disease, and there were no distant metastases. Recurrences were detected late at a median of 5.5 years after the initial surgery (range 3.6-10.7 years). All structural recurrences were detected on neck ultrasonography. Non-stimulated serum thyroglobulin (Tg) was detectable (≥0.2 ng/mL) in four (31%) patients, and serum anti-Tg antibodies were positive in one (8%) patient. However, non-stimulated serum Tg levels were stably low (<0.2 ng/mL) in eight (62%) patients when recurrences were detected. In addition to these 13 patients, 14 patients also presented with biochemical persistent disease at the end of follow-up., Conclusions: Recurrences of DTC in patients with an excellent response to initial therapy were detected relatively late. The intensity and frequency of follow-up of neck ultrasonography as well as serum Tg and anti-Tg antibody measurements should be reduced, especially within five years of the initial therapy, in DTC patients who have an excellent response.

Objective: Previous studies did not focus on the differences in the extent of cervical lymph node (LN) dissection according to coexistent Hashimoto's thyroiditis (HT) in patients with papillary thyroid carcinoma (PTC) and its clinical impact. We aimed to determine whether extensive cervical LN dissection is responsible for favourable clinical outcomes in PTC patients with HT and whether the coexistence of HT itself has an independent protective effect regardless of LN status., Design: Retrospective cohort study., Patients: 1369 patients with PTC who underwent total thyroidectomy with central compartment neck dissection., Measurements: Metastatic LN ratio, defined as number of metastatic LNs divided by number of removed LNs, was used to evaluate the extent of LN dissection as well as the status of LN metastasis. Disease-free survival and dynamic risk stratification were compared for clinical outcomes., Results: Presence of HT did not lower the risk of cervical LN metastasis (61.6% in patients with HT vs 65.1% in patients without HT, P = .292). Patients with HT had significantly larger numbers of removed LNs than patients without HT (11 vs 8, respectively, P < .001). Accordingly, metastatic LN ratio was smaller in patients with HT (P = .002), which was independently associated with structural persistent/recurrent disease (hazard ratio [HR] 2.33, 95% confidence interval [CI] 1.30-4.16, P = .004). HT itself was negatively associated with structural persistent/recurrent disease after adjustment for other clinicopathological factors (HR 0.39, 95% CI 0.18-0.87, P = .020)., Conclusions: Coexistence of HT itself is an independent factor associated with favourable outcome in PTC patients, regardless of the extent of LN dissection., (© 2017 John Wiley & Sons Ltd.)

Background: Large-volume lymph node metastasis (LNM) is associated with poor clinical outcomes in papillary thyroid microcarcinoma (PTMC) patients. However, sensitivity in the detection of central neck LNM on preoperative neck ultrasonography (US) is believed to be low. The aim of this study is to investigate the preoperative clinical factors associated with large-volume LNM in clinical N0 PTMC patients., Methods: In all, 2329 clinical N0 PTMC patients who underwent total thyroidectomy with prophylactic central lymph node (LN) dissection were evaluated. The LNM status of these patients was divided into three groups by the number of metastatic nodes: no LNM, small-volume LNM (≤5 metastatic LNs), and large-volume LNM (>5 metastatic LNs). The correlations between age, sex, and other clinical factors and large-volume LNM were evaluated., Results: Large-volume LNM was found in 94 (4.0%) patients. Young (<40 years old) and male patients tended to have large-volume LNM (p for trend <0.001). Young age (odds ratio [OR] = 2.69 [confidence interval (CI) 1.64-4.32], p < 0.001) and male sex (OR = 5.79 [CI 3.67-9.10], p < 0.001) were independent risk factors for large-volume LNM in multivariate analyses. The prevalence of large-volume LNM ranged from 24% in male patients <40 years of age to only 2% in female patients aged ≥40 years. Multifocal tumors and presence of extrathyroidal extension were also considered risk factors for large-volume LNM., Conclusions: Large-volume LNM was more frequently found in young (<40 years) and male patients. These findings support the notion that surgery rather than observation may be favored in young and male clinically LN negative PTMC patients as a primary therapeutic option.

Objective: To evaluate the efficacy and prognostic validity for disease-specific survival (DSS) of the eighth edition American Joint Committee on Cancer/Union for International Cancer Control tumor-node-metastasis (TNM) staging system (TNM-8) compared to the seventh edition (TNM-7) in patients with differentiated thyroid carcinoma (DTC)., Methods: The seventh and eighth editions of the TNM staging system were applied to 1613 DTC patients who underwent thyroid surgery between 1996 and 2003. The proportion of variation explained and Harrell's c-index were evaluated to compare the predictive capability of DSS., Results: The mean age of the patients was 44.7 years, and the median follow-up period was 11.2 years. When TNM-8 was applied, 63% of T3 and 3% of N1b DTCs were downgraded to T1/T2 and N1a, respectively. About 38% of patients were downstaged according to TNM-8. The 10-year DSS rates in TNM-7 stages I, II, III, and IV were 99.7%, 98.2%, 98.8%, and 83.2%, respectively. Those in TNM-8 stages I, II, III, and IV were 99.6%, 95.4%, 72.3%, and 48.6%, respectively. The proportion of variation explained values of TNM-7 and TNM-8 were 6.0% and 7.0%, respectively. The Harrell's c-index of TNM-7 was 0.86 and that of TNM-8 was 0.88., Conclusions: A significant number of patients were reclassified to lower stages with the application of TNM-8 compared to TNM-7. Applying TNM-8 could improve the accuracy of the staging system for predicting DSS in patients with DTC.

Background: Thyrotropin (TSH) suppression has improved the clinical outcomes of patients with differentiated thyroid cancer (DTC). However, the efficacy of TSH suppressive therapy (TST) is unclear in patients with low-risk DTC. This study aimed to evaluate the efficacy of TST and optimal TSH levels of patients with low-risk DTC., Methods: This retrospective propensity score-matched cohort study included DTC patients (n = 446) who underwent lobectomy from 2002 to 2008 with or without TST (TST group and No-TST group). Disease-free survival (DFS) and dynamic risk stratification were compared between both groups using serum TSH levels., Results: Approximately 74% of TST patients and 11% of No-TST patients had suppressed serum TSH levels (<2 mIU/L). The median follow-up period was 8.6 years. During follow-up, the disease recurred in 10 (2.7%) patients, with no significant difference in DFS between the groups (p = 0.63). The proportion of patients with excellent treatment response was similar between the TST (65.2%) and No-TST (64.4%) groups. Incomplete biochemical response was noted in 17.2% of the TST group patients and 9.4% of the No-TST group patients. No significant difference was observed in the DFS between both groups by comparing serum TSH level (p = 0.57)., Conclusions: TST did not improve clinical outcomes, and serum TSH levels were not associated with recurrence in patients with low-risk small DTC. No clinical benefits were shown for TSH suppression in low-risk patients who underwent lobectomy. Thus, levothyroxine is not necessary for patients without evidence of hypothyroidism.

Background: Most of the increase in thyroid cancer in recent decades has been due to papillary thyroid microcarcinoma (PTMC). We evaluated the efficacy of radioiodine remnant ablation (RRA) in patients with PTMC., Methods: This historical cohort study included 1932 PTMC patients without lateral cervical lymph node (LN) or distant metastasis who underwent total thyroidectomy (TT) during the median 8.3 years of follow-up. The clinical outcomes of patients with or without RRA were compared using weighted logistic regression models with the inverse probability of treatment weighting (IPTW) method and considering risk factors, including age, sex, primary tumor size, extrathyroidal extension, multifocality, and central cervical LN metastasis., Results: The median primary tumor size of the RRA group was significantly larger than that of the no-RRA group (0.7 vs. 0.5 cm, P < 0.001). There were significantly more patients with multifocality, extrathyroidal extension, and cervical LN metastasis in the RRA group compared with the no-RRA group. There was no significant difference in recurrence-free survival between the two groups (P = 0.11). Cox proportional-hazard analysis with IPTW by adjusting for clinicopathological risk factors demonstrated no significant difference in recurrence of PTMC according to RRA treatment (hazard ratio [HR] 2.02; 95% confidence interval [CI] 0.65-6.25; P = 0.2)., Conclusions: RRA had no therapeutic effect on the clinical outcomes of patients with PTMC who underwent TT. Surgical treatment without RRA could be applicable for patients with PTMC if there is no evidence of lateral cervical LN metastasis or distant metastasis.

Background: The clinical course of patients with lung metastases of differentiated thyroid carcinoma (DTC) vary, and cancer-specific survival (CSS) can be associated with tumor burden. This study evaluated the growth kinetics of lung metastases from DTC using serial chest computed tomography for Response Evaluation Criteria in Solid Tumors assessment and its prognostic implications., Methods: Forty-four patients with macronodular lung metastases (≥1 cm) of DTC were included. The time intervals to disease progression of lung metastases were measured and compared to CSS rates., Results: On the basis of the time to progression, 15 (34%), 17 (39%), and 12 (27%) patients were classified into the slow (≥3 years), moderate (1-3 years), and rapid groups (<1 year), respectively. The growth kinetics of lung metastases exhibited a linear pattern in the three groups. The doubling time of tumor burden was 1.8 years (R 2  = 0.973, p = 0.013) in the rapid group, and the estimated doubling time of the tumor burden in the moderate and slow groups was 5.9 years and 19.3 years, respectively. No independent variable predicted the growth kinetics of lung metastases. In multivariate analysis, disease progression within the first year was an independent predictor of CSS (hazard ratio = 8.6; p = 0.003)., Conclusions: This is the first study to demonstrate objectively that tumor growth kinetics within the first year are an independent predictor of CSS in patients with macronodular lung metastases. Performing chest computed tomography at least twice a year in the early phase of the disease in patients with macronodular lung metastases may be helpful for identifying high-risk patients who are eligible for treatment with tyrosine kinase inhibitors.

Objective: Active surveillance is an option for patients with papillary thyroid microcarcinoma (PTMC). However, the long-term clinical outcomes after delayed surgery remain unclear. We compared the long-term clinical outcomes of PTMC patients according to the time interval between initial diagnosis and surgery., Design and Methods: In this individual risk factor-matched cohort study, PTMC patients were classified into three groups according to the delay period: ≤6 months, 6-12 months and >12 months. Patients were matched by age, sex, extent of surgery, initial tumor size as measured by ultrasonography (US), and by the presence of extrathyroidal extension, multifocal tumors and central cervical lymph node metastasis. We compared the dynamic risk stratification (DRS) and the development of structural persistent/recurrent disease of patients., Results: A total of 2863 patients were assigned to three groups. Their mean age was 50 years, 81% were female and 66% underwent lobectomy. The mean tumor size at the initial US was 0.63 cm. There were no significant differences in clinicopathological characteristics between groups after individual risk factor matching. Comparison of the DRS revealed no significant difference according to the delay period ( P  = 0.07). During the median 4.8 years of follow-up, there were no significant differences in the development of structural recurrent/persistent disease ( P  = 0.34) and disease-free survival ( P  = 0.25) between groups., Conclusions: In PTMC patients, delayed surgery was not associated with higher risk of structural recurrent/persistent disease compared to immediate surgery. These findings support the notion that surgical treatment can be safely delayed in patients with PTMC under close monitoring., (© 2017 European Society of Endocrinology.)

Objectives: Papillary thyroid microcarcinoma (PTMC) has an excellent prognosis with an indolent disease course. However, some PTMCs have an aggressive course with lateral cervical lymph node (LCLN) metastasis or distant metastasis. This study aimed to evaluate the pre-operative features of PTMC associated with LCLN metastasis., Design and Patients: This retrospective cohort study with a nested, matched case-control design included 199 PTMC patients with LCLN metastasis at initial surgery (N1b group) and 196 PTMC patients without any LN metastasis or persistent disease (N0 NED group) as controls; primary tumour sizes were matched., Results: Compared with the N0 NED group, the N1b group was younger (<50 years) and more likely to be male (P = 0·002 and P = 0·003, respectively). On pre-operative neck ultrasonography (US), N1b group PTMCs were more commonly associated with a location in the upper lobes of the thyroid, or in the subcapsular area and microcalcifications than N0 NED group PTMCs (all P < 0·001). An increase in the number of these features was significantly associated with a higher risk of LCLN metastasis (P < 0·001). Evaluation of the clinical and pre-operative US characteristics of 26 patients with confirmed LCLN recurrence after initial treatment of clinical N0 PTMCs revealed that the distribution of the number of suspicious features in these patients was similar to that of the N1b group., Conclusions: Papillary thyroid microcarcinomas in young (<50 years) or male patients, with an upper lobe or subcapsular location, and with microcalcification have a higher risk of LCLN metastasis. Individualized management according to the number of these suspicious features may be needed for small thyroid nodules., (© 2017 John Wiley & Sons Ltd.)

Context: Papillary thyroid microcarcinoma (PTMC) usually has an excellent prognosis., Objective: To evaluate the three-dimensional structures of PTMCs, using serial neck ultrasonography (US) in patients under active surveillance., Design and Setting: A retrospective cohort study., Participants: In total, 192 patients diagnosed with PTMC under active surveillance for >1 year were included in a median 30-month follow-up. Changes in tumor size were evaluated not only using the maximal tumor diameter but also the tumor volume., Results: The median age of patients was 51.3 years and 145 patients (76%) were female. The median initial maximal tumor diameter and tumor volume were 5.5 mm and 48.8 mm3, respectively. The tumor size increased in 27 patients (14%); 23 patients showed a tumor volume increase >50% without a maximal diameter increase of ≥3 mm. The other four patients had both an increasing tumor volume and increasing maximal tumor diameter ≥3 mm. One patient (0.5%) had newly appeared cervical lymph node (LN) metastasis at 3 years after the initial diagnosis. There were no significant risk factors associated with increased tumor size, such as age, sex, or Hashimoto thyroiditis. Twenty-four patients (13%) underwent delayed thyroid surgery at a median of 31.2 months and seven (29%) had cervical LN metastasis on pathologic examination., Conclusion: Some PTMCs could grow significantly after a relatively short period of active surveillance. We also found that the change in tumor volume was more sensitive to detect tumor progression than the change in the maximal tumor diameter., (Copyright © 2017 Endocrine Society)

Background: Papillary thyroid cancer (PTC) is a common malignancy diagnosed during pregnancy. However, there is little information on the behavior of PTC during pregnancy. The aim of this study was to evaluate the natural course of PTC in pregnant women., Methods: The study included 19 patients with PTC who delayed thyroid surgery because they were diagnosed with PTC just before or during the early stages of pregnancy. Serial neck ultrasonography (US) was used to evaluate PTCs before surgical treatment and the clinical outcomes after surgery., Results: The median maximal PTC size at initial diagnosis on US was 0.91 cm (interquartile range [IQR] 0.61-1.11), and 13/19 (68.4%) patients had micro-PTCs (≤1 cm). The median maximal PTC size after a median 9.5 months of follow-up was 0.98 cm (IQR 0.72-1.12). There were three (16%) patients who showed a size increase, and five (26%) patients showed a volume increase during the follow-up periods. There was no clinically relevant change in the maximal tumor size during the follow-up period (p = 0.16). Serial US measurements of PTC size in seven available patients in each trimester showed no significant differences between the different trimesters (first vs. second trimester p = 0.81; second vs. third trimester p = 0.99). No newly developed lesions in the thyroid or cervical lymph nodes were detected by neck US during the follow-up period. Among 19 patients, 16 underwent thyroid surgery after delivery, and the median duration from diagnosis to surgery was 11.9 months., Conclusions: No clinically relevant changes associated with a progression of PTC were observed during pregnancy. Delayed thyroid surgery with active surveillance can be an appropriate approach for pregnant patients with PTC.

Background: Increased incidence of small differentiated thyroid cancer (DTC) has emphasized the need for risk stratification and individualized disease management for these low risk DTCs. The aim of this study was to validate a new dynamic risk stratification (DRS) system for the prediction of structural recurrent/persistent disease in patients with DTC treated without radioactive iodine (RAI) remnant ablation therapy., Methods: This historical cohort study included 357 patients with DTC treated with lobectomy or total thyroidectomy without RAI therapy. We stratified patient response to initial treatment as excellent, indeterminate, biochemical incomplete, and structural incomplete according to the DRS system., Results: During a median follow-up of 8.6 years, 3.6% patients had structural recurrent DTC. The response was excellent in 71.7% patients, indeterminate in 18.5%, biochemical incomplete in 8.4%, and structural incomplete in 1.4%. There were significant differences in DFS among the DRS groups (p < 0.001). The hazard ratio (HR) of recurrent/persistent disease was significantly higher in the biochemical incomplete group (HR = 20.8, p < 0.001) and structural incomplete group (HR = 243.3, p < 0.001) compared with the excellent group. However, the Tumor Node Metastasis staging system and the American Thyroid Association initial risk classification did not effectively predict recurrence of DTC., Conclusions: The new DRS system was effective for predicting risk of recurrent/persistent disease in patients with DTC who underwent lobectomy or total thyroidectomy without RAI remnant ablation.

Context: Lobectomy is preferred in thyroid cancer to decrease surgical complications and avoid lifelong thyroid-hormone replacement. However, postoperative hypothyroidism, requiring thyroid-hormone replacement, may occur., Objective: We aimed to identify the incidence and risk factors of postoperative hypothyroidism to develop a surveillance strategy after lobectomy for papillary thyroid microcarcinoma (PTMC)., Methods: This historical cohort study involved 335 patients with PTMC treated by lobectomy. Postoperative thyroid functions were measured regularly, and patients were prescribed levothyroxine according to specific criteria. Patients not satisfying hormone-replacement criteria were closely followed up., Results: Postoperative hypothyroidism occurred in 215 patients (64.2%) including 5 (1.5%) with overt hypothyroidism and 210 (62.7%) with subclinical hypothyroidism. Forty patients (11.9%) were required thyroid hormone replacement. One hundred nineteen patients (33.5%) experienced temporary hypothyroidism and spontaneously recovered to euthyroid state. High preoperative thyroid-stimulating hormone (TSH) was the most important factor predicting postoperative hypothyroidism and failure of recover from hypothyroidism (odds ratio [OR], 2.82 and 1.77; 95% confidence interval [CI], 2.07 to 3.95 and 1.22 to 2.63; P < 0.001 and 0.002, respectively). Of the 215 patients eventually developing postoperative hypothyroidism, 70 (32.6%) developed hypothyroidism after the first postoperative year. Postoperative 1-year TSH levels were able to differentiate patients developing late hypothyroidism or euthyroidism (OR, 2.29; 95% CI, 1.68 to 3.26; P < 0.001)., Conclusions: Preoperative and postoperative TSH levels might be predictive for patients who develop postlobectomy hypothyroidism and identify those requiring long-term surveillance for hypothyroidism. Additionally, mild postoperative hypothyroidism cases should be followed up without immediate levothyroxine replacement with the expectation of spontaneous recovery., (Copyright © 2017 by the Endocrine Society)

Objective: Papillary thyroid microcarcinoma (PTMC) accounts for most of the increase in thyroid cancer in recent decades. We compared clinical outcomes and surgical complications of lobectomy and total thyroidectomy (TT) in PTMC patients., Design and Methods: In this retrospective individual risk factor-matched cohort study, 2031 patients with PTMC were initially included. Patients who underwent lobectomy or TT were one-to-one matched according to individual risk factors, including age, sex, primary tumor size, extrathyroidal extension, multifocality and cervical lymph node (LN) metastasis., Results: In total, 688 patients were assigned to each group. During the median 8.5 years of follow-up, 26 patients (3.8%) in the lobectomy group and 11 patients (1.6%) in the TT group had recurrences. The relative risk of recurrence was significantly less in the TT than that in the lobectomy group (hazard ratio (HR) 0.41; 95% confidence interval (CI) 0.21-0.81; P = 0.01). Most recurrences (84.6%) in the lobectomy group occurred in the contralateral lobe, and all patients were disease-free after completion of thyroidectomy. There were no significant differences in recurrence-free survival between the two groups after exclusion of contralateral lobe recurrences (HR, 2.75; 95% CI, 0.08-8.79; P = 0.08). There were significantly more patients with transient and permanent hypoparathyroidism in the TT than that in the lobectomy group (P < 0.001)., Conclusions: Lobectomy could be appropriate for most patients with PTMC when there is no evidence of extrathyroidal disease in the preoperative work-up. Preoperative and postoperative imaging studies are important for patients who undergo lobectomy for PTMC, because most recurrences are in the contralateral lobe., (© 2017 European Society of Endocrinology.)

Objective: Age >45 years is included as a variable in the tumor, node, metastases (TNM) staging of differentiated thyroid cancer (DTC), but a higher cut-off value has been suggested to be more clinically relevant and prevent over-staging. We evaluated the optimal age cut-off to predict disease-specific survival (DSS) in patients with DTC., Design and Patients: This cohort study included 6333 patients with DTC who underwent thyroid surgery at two tertiary referral centres between 1996 and 2005. The optimal age cut-off value between 45 and 65 years for prediction of DSS was assessed. The proportion of variation explained (PVE) and Harrell's c-index was calculated to compare the predictability of each model., Results: The median age of patients was 46·0 years (IQR 37·8-54·6), and 5498 (87%) were female. Median follow-up period was 10·0 years, and 10-year DSS rate was 98%. Using TNM staging with 45 years as the cut-off (TNM45), 10-year DSS rates of stage I-IV were 99·4%, 96·1%, 97·7% and 85·9%, respectively (PVE = 3·0%, Harrell's c-index = 0·693); and using 55 years as the cut-off (TNM55), 99·4%, 92·2%, 95·3% and 79·7%, respectively (PVE = 4·3%, Harrell's c-index = 0·776). On receiver operating characteristic curve analysis, the optimal age cut-off for prediction of DSS was 55·4 years (area under the curve = 0·837, P < 0·001). About 20% of patients were down-staged to stage I using TNM55 compared to that using TNM45., Conclusions: The cut-off age of 55 years was more appropriate for TNM staging to achieve better predictability for DSS in patients with DTC. This change would prevent over-staging in low-risk patients and prevent over-aggressive treatment., (© 2016 John Wiley & Sons Ltd.)

Background: For patients with lung metastases of differentiated thyroid carcinoma (DTC), there is no consensus on the maximal size of metastatic lesions to use when determining the intensity of follow-up and additional therapeutic options. This study evaluated the clinical outcomes and survival of patients with metastatic DTC confined to the lung, using the maximal diameter of lung lesions in the initial computed tomography., Methods: This retrospective cohort study included 112 DTC patients with metastases confined to the lung. The clinical responses were evaluated according to changes in the serum levels of stimulated thyroglobulin or antithyroglobulin antibody, disease status was evaluated according to radiological findings, progression-free survival (PFS), and cancer-specific survival (CSS)., Results: Macronodular lung metastases (≥1 cm) were observed in 27 (24%) patients, and these patients had significantly poor biochemical responses and disease status (p < 0.001, and p < 0.001, respectively), irrespective of radioactive iodine (RAI) avidity. After adjusting for age, sex, primary tumor size, extrathyroidal invasion, cervical lymph node metastasis, time of lung metastasis, and RAI avidity, the macronodular group also had shorter PFS and CSS (p = 0.009 and p = 0.03, respectively) than the micronodular group. From the multivariate analyses, RAI avidity was not an independent prognostic factor predicting PFS and CSS. In the subgroup analyses, RAI avidity was a significant prognostic factor associated with better PFS and CSS (p = 0.013 and p = 0.021, respectively) in the micronodular group only., Conclusions: The initial largest diameter of metastatic lesions is the most important prognostic factor for predicting poor clinical outcomes and survival in patients with metastatic DTC confined to the lung.

Background: The BRAFV600E mutation is the most common genetic alteration identified in papillary thyroid carcinoma (PTC). Because of its costs effectiveness and sensitivity, direct Sanger sequencing has several limitations. The aim of this study was to evaluate the efficiency of immunohistochemistry (IHC) as an alternative method to detect the BRAFV600E mutation in preoperative and postoperative tissue samples. Methods: We evaluated 71 patients who underwent thyroid surgery with the result of direct sequencing of the BRAFV600E mutation. IHC staining of the BRAFV600E mutation was performed in 49 preoperative and 23 postoperative thyroid specimens. Results: Sixty-two patients (87.3%) had PTC, and of these, BRAFV600E was confirmed by direct sequencing in 57 patients (91.9%). In 23 postoperative tissue samples, the BRAFV600E mutation was detected in 16 samples (70%) by direct sequencing and 18 samples (78%) by IHC. In 24 fine needle aspiration (FNA) samples, BRAFV600E was detected in 18 samples (75%) by direct sequencing and 16 samples (67%) by IHC. In 25 core needle biopsy (CNB) samples, the BRAFV600E mutation was detected in 15 samples (60%) by direct sequencing and 16 samples (64%) by IHC. The sensitivity and specificity of IHC for detecting the BRAFV600E mutation were 77.8% and 66.7% in FNA samples and 99.3% and 80.0% in CNB samples. Conclusion: IHC could be an alternative method to direct Sanger sequencing for BRAFV600E mutation detection both in postoperative and preoperative samples. However, application of IHC to detect the BRAFV600E mutation in FNA samples is of limited value compared with direct sequencing. [ABSTRACT FROM AUTHOR]