Assessment of Bone Marrow Involvement in B-Cell non-Hodgkin Lymphoma Using Immunoglobulin Gene Rearrangement Analysis with Next-Generation Sequencing.

BACKGROUND: Assessment of bone marrow involvement (BMI) in non-Hodgkin lymphoma (NHL) is crucial for determining patient prognosis and treatment strategy. We assessed the prognostic value of next-generation sequencing (NGS)-based immunoglobulin (Ig) gene clonality analysis as an ancillary test for BMI evaluation in NHL. METHODS: A retrospective cohort of 124 patients newly diagnosed with B-cell NHL between 2019 and 2022 was included. NGS-based Ig clonality analysis was conducted using LymphoTrak IGH FR1 Assay and IGK Assay (Invivoscribe Technologies, San Diego, CA, USA) on BM aspirate samples, and the results were compared with those of histopathological BMI (hBMI). RESULTS: Among the 124 patients, hBMI was detected in 16.9% (n = 21). The overall agreement of BMI between Ig clonality analyses and histopathological analysis for IGH, IGK, and either IGH or IGK was 86.3%, 92.7%, and 90.3%. The highest positive percent agreement was observed with clonal rearrangements of either IGH or IGK gene (90.5%), while the highest negative percent agreement was observed with clonal rearrangement of IGK gene (96.1%). For the prediction of hBMI, positive prediction value ranged between 59.1% and 80.0% and the negative prediction value ranged between 91.3% and 97.9%. CONCLUSION: NGS-based clonality analysis is an analytic platform with a substantial overall agreement with histopathological analysis. Assessment of both IGH and IGK genes for the clonal rearrangement analysis could be considered for the optimal diagnostic performance of BMI detection in B-cell NHL.

Limitations of fine-needle aspiration and core needle biopsies in the diagnosis of tall cell variant of papillary thyroid carcinoma.

BACKGROUND: The tall cell variant papillary thyroid carcinoma (TCV-PTC) shows aggressive behaviour. Thus far, the diagnosis of TCV-PTC can only be confirmed using the postoperative specimen. This study aims to evaluate whether fine-needle aspiration (FNA) or core needle biopsy (CNB) could diagnose TCV-PTC preoperatively. METHODS: This is a retrospective cohort study. We included adult patients diagnosed with TCV-PTC or PTC with tall cell features (TCF) at final surgical pathology between January 2015 and December 2018. Preoperative histology was reviewed for six cytomorphologic features suggesting TCV-PTC in FNA or the percentage of tall cells in the CNB specimen. The postoperative pathology was also reviewed to confirm the percentage of tall cells. RESULTS: A total of 119 patients were included in this study; 35 (29%) patients with PTC with TCF served as controls. The most frequent cytomorphological feature in FNA samples of TCV-PTC was tall columnar cells, including single tombstone-like cells (70%). Among 43 TCV-PTC evaluated by FNA, 3 FNA (7%) revealed the absence of any of the six cytomorphologic features suggesting TCV-PTC. When we defined 30% of tall cells in CNB specimens as a cutoff suggesting TCV-PTC, only 16 (41%) TCV-PTCs could be preoperatively detected, and 3 (7%) TCV-PTCs did not have any tall cells. The proportion of tall cells was not associated with the postoperative percentage of tall cells. CONCLUSION: Both cytomorphologic features in FNA and the percentage of tall cells in CNB present limitations for use as accurate preoperative diagnostic tools of TCV-PTC.

Prognostic outcomes of cytomegalovirus reactivation after autologous stem cell transplantation.

Background: Cytomegalovirus (CMV) reactivation is a common complication in patients undergoing allogeneic stem cell transplantation. However, the incidence of CMV reactivation is low after autologous stem cell transplantation (auto-SCT), and the prognostic value of CMV reactivation remains controversial. Moreover, reports on late CMV reactivation after auto-SCT are limited. We aimed to analyze the association between CMV reactivation and survival outcomes and develop a predictive model for late CMV reactivation in patients undergoing auto-SCT. Methods: Data of 201 patients who underwent SCT at the Korea University Medical Center from 2007 to 2018 were collected. We analyzed prognostic factors for survival outcomes after auto-SCT and risk factors for late CMV reactivation using a receiver operating characteristic curve. Then, we developed a predictive risk model for late CMV reactivation based on results of the risk factor analysis. Results: Early CMV reactivation was significantly associated with better overall survival (OS) (hazard ratio [HR], 0.329; P = 0.045) in patients with multiple myeloma; however, no significant differences were observed in patients with lymphoma. For late CMV reactivation, a serum lactate dehydrogenase level greater than the upper limit of normal (HR, 2.251; P = 0.027) and late CMV reactivation (HR, 2.964; P = 0.047) were independent risk factors for poor OS, while lymphoma diagnosis (vs. multiple myeloma; HR, 0.389; P = 0.016) was an independent risk factor for good OS. In risk factor analysis for late CMV reactivation, T-cell lymphoma diagnosis (odds ratio [OR], 8.499; P = 0.029), ≥ two prior chemotherapies (OR, 8.995; P = 0.027), failure to achieve complete response (CR) after transplantation (OR, 7.124; P = 0.031), and early CMV reactivation (OR, 12.853; P = 0.007) were significantly associated with late CMV reactivation. To develop the predictive risk model for late CMV reactivation, a score (1 to 1.5) was assigned for each of the above-mentioned variables. The optimal cutoff value (1.75 points) was calculated using the receiver operating characteristic curve. The predictive risk model showed good discrimination, with an area under the curve of 0.872 (standard error, 0.062; P < 0.001). Conclusions: Late CMV reactivation was an independent risk factor for inferior OS, whereas early CMV reactivation was associated with better survival in patients with multiple myeloma. This risk prediction model could be helpful in identifying high-risk patients who require monitoring for late CMV reactivation and potentially benefit from prophylactic or preemptive therapy.

Prognosis of Patients with 1-4 cm Papillary Thyroid Cancer Who Underwent Lobectomy: Focus on Gross Extrathyroidal Extension Invading Only the Strap Muscles.

BACKGROUND: This study was designed to evaluate the prognostic implication of gross extrathyroidal extension (ETE) invading the strap muscles after thyroid lobectomy in patients with 1-4 cm papillary thyroid cancer (PTC). METHODS: This retrospective cohort study included patients with 1-4 cm PTC who underwent thyroid lobectomy from 2005 to 2012. Overall, 595 patients were enrolled after excluding patients with aggressive variants of PTC, gross ETE into a major neck structure, and lateral cervical lymph node (LN) metastasis. We evaluated the risk factors for structural recurrence after lobectomy in 1-4 cm PTC. RESULTS: Seventy-eight patients (13.1%) had gross ETE invading only the strap muscles. During the median follow-up period of 7.7 years, structural recurrence was confirmed in 35 patients (5.9%). The presence of gross ETE was an independent risk factor for structural recurrence (hazard ratio 2.54, 95% confidence interval 1.19-5.44; p = 0.016). Subgroup analysis of patients with gross ETE showed that 11 and 47 patients had low- and intermediate-risk LN metastasis, respectively. A significant difference in recurrence-free survival was observed according to the degree of cervical LN metastasis (p = 0.03). Those without LN metastasis or low-risk LNs had a 75% lower risk of recurrence when compared with those with both gross ETE and intermediate-risk LNs. CONCLUSION: Gross ETE and intermediate-risk cervical LN metastasis were associated with a significantly high risk of recurrence after lobectomy in patients with 1-4 cm PTC. Completion thyroidectomy would be considered in this subgroup of patients but not in all patients with gross ETE invading only the strap muscles.

Comparison Between Familial and Sporadic Non-medullary Thyroid Carcinoma: A Retrospective Individual Risk Factor-Matched Cohort Study.

BACKGROUND: This study aimed to compare clinicopathologic features and outcomes between patients with familial non-medullary thyroid carcinoma (FNMTC) and patients with sporadic non-medullary thyroid carcinoma (SNMTC) after performing individual risk factor-matching. Additionally, the study evaluated a dynamic risk stratification (DRS) system to validate its usefulness for familial-type thyroid carcinoma. METHODS: After individual risk factor-matching, 286 patients remained in the FNMTC group, and 858 patients were assigned to the SNMTC group consisting of papillary thyroid carcinoma (PTC). The prognostic outcomes were compared between the two groups in a matched cohort. RESULTS: During the mean follow-up period of 142 months, recurrences were experienced by 64 patients in the sporadic group (7.5%) and 29 patients in the familial group (10.1%). In the multivariate analysis, the independent risk factors for recurrence were primary tumor size (p = 0.033), gross extrathyroidal extension (p = 0.001), and lymph node metastasis (p < 0.001). The independent risk factors did not include family history alone (p = 1.101) or the number of affected family members (p = 0.122 for 2 members and p = 0.625 for ≥ 3 members). In this matched-cohort study, the DRS system was well adjusted in the FNMTC and SNMTC groups. Moreover, the proportion of DRS categories and the recurrence rate in each DRS category were similar between the familial and sporadic groups. CONCLUSIONS: Family history did not present a statistically significant association with a poor prognosis for PTC patients. With a family history of PTC alone, less aggressive treatment could be considered. In this matched cohort, DRS was adjusted well and could be useful in predicting prognosis, even for PTC patients with a family history of PTC.

Clinical implications of age and excellent response to therapy in patients with high-risk differentiated thyroid carcinoma.

BACKGROUND: Patients with American Thyroid Association (ATA) high-risk differentiated thyroid carcinoma (DTC) have poor clinical outcomes. This study aimed to evaluate the clinical implications of age and response to therapy classification in patients with ATA high-risk DTC. DESIGN AND PATIENTS: This study included 222 patients with high-risk DTC who initially underwent therapy between 2000 and 2010 in a single tertiary center in Korea. We evaluated the prognostic parameters associated with progression-free survival (PFS) and disease-specific survival (DSS) with a focus on age and achieving an excellent response (ER). RESULTS: During the median follow-up period of 11.3 years, disease progression was detected in 77 patients (34.7%), and disease-specific mortality was reported in 31 patients (14.0%). Older age (≥55 years) and not achieving ER (not-ER) were independent risk factors associated with PFS (age, p < .001; not-ER, p < .001) and DSS (age, p < .001; not-ER, p = .015). Of the 74 patients in the ER group, 7 (9.5%) displayed disease progression and 1 (1.4%) died from DTC. There were no significant differences in PFS and DSS according to age in the ER group. However, older patients had significantly worse PFS and DSS than younger patients in the not-ER group (p = .002 and p < .001, respectively). CONCLUSIONS: Response to therapy classification is important for predicting PFS and DSS in patients with high-risk DTC. Patients in the ER group had a relatively good prognosis, but disease progression occurred in 9.5% of patients. Age was a key predictor of both PFS and DSS in high-risk patients who did not achieve ER.

Prognostic role of the lymphocyte-to-monocyte ratio for clinical outcomes of patients with progressive radioiodine-refractory differentiated thyroid carcinoma treated by sorafenib.

OBJECTIVES: The lymphocyte-to-monocyte ratio (LMR) reflects the status of tumour-infiltrating immune cells and host immunity. The LMR has been reported as a prognostic marker in various cancers. The present study evaluated the role of the LMR as a prognostic marker in patients with progressive radioiodine-refractory (RAIR) differentiated thyroid carcinoma (DTC). DESIGN: Retrospective cohort study. PATIENTS: Forty patients with progressive RAIR DTC who were treated by sorafenib with available baseline complete blood cell count data. MEASUREMENTS: We assessed the response rate, progression-free survival (PFS) and overall survival (OS). RESULTS: The patients were divided into low and high LMR groups based on their baseline LMRs (<4, n = 22, 55% and ≥4, n = 18, 45%, respectively). There were no significant differences in baseline characteristics between the groups. The OS curves differed significantly based on the LMR. The median OS of the low LMR group was 24.3 months and that of the high LMR group was not reached until the end of observation period (P = .015). The PFS curves and median PFS also differed significantly based on the LMR values (P = .019). In multivariate analysis, low LMR was an independent risk factor for all-cause mortality in patients with progressive RAIR DTC (hazard ratio, 2.64; 95% confidence interval: 1.04-6.72, P = .041). CONCLUSION: A low LMR was associated with poor response rate, PFS and OS in patients with progressive RAIR DTC treated with sorafenib. Thus, LMR could be a simple prognostic biomarker in patients with progressive RAIR DTC.

Modified risk stratification based on cervical lymph node metastases following lobectomy for papillary thyroid carcinoma.

OBJECTIVE: Evidence for American Thyroid Association (ATA) risk stratification stems largely from studies involving patients undergoing total thyroidectomy. We aimed to assess the risk of recurrence according to the present ATA risk stratification system in patients who underwent lobectomy. DESIGN: Retrospective cohort study. PATIENTS: Patients who underwent thyroid lobectomy for 1-4 cm-sized papillary thyroid carcinoma (n = 571). MEASUREMENTS: Disease-free survival (DFS) was compared according to the ATA risk stratification, and specific lymph node (LN) characteristics were evaluated to modify the ATA criteria with a higher predictability for recurrence. RESULTS: Based on the ATA risk stratification, 439 patients (61.1%) were classified into intermediate- or high-risk group, and consideration for completion thyroidectomy is suggested by ATA guidelines for these patients. However, no significant differences were found in DFS among the low-, intermediate- and high-risk groups (P = .9). In contrast, when patients were stratified according solely to the LN criteria from the ATA risk stratification, only 127 patients (22.2%) had intermediate risk (intermediate-N1a) and exhibited significantly poorer DFS than those with N0 disease (P = .035). Modifying the intermediate-N1a criteria by adding the extranodal extension (ENE) status and omitting the clinical nodal disease enabled the subclassification of 19 patients (3%) with a high risk for recurrence. CONCLUSIONS: The present study suggests that risk stratification based solely on LN metastases is more reasonable for predicting structural persistence/recurrence following lobectomy than that based on the overall ATA criteria. Considering the ENE status can assist in selecting patients with a high risk of recurrence to minimize further treatments.

Nationwide study of paroxysmal nocturnal hemoglobinuria in South Korea: paradox of eculizumab.

Eculizumab is effective in managing patients with paroxysmal nocturnal hemoglobinuria (PNH). In South Korea, the financial support for eculizumab therapy is extended by the National Health Insurance Services (NHIS) only to patients with high-risk PNH for approximately 10 years. In this study, we performed a nationwide analysis of the real-world efficacy of eculizumab therapy in patients diagnosed with PNH between January 1, 2002, and December 31, 2016, by using the NHIS database. Patients treated with eculizumab (the eculizumab-treated group) exhibited a significantly higher survival rate than patients not treated with eculizumab (the eculizumab-untreated group), with 4-year survival rates after propensity score matching of 98.31% and 79.67%, respectively (p = 0.0489). The mean red blood cell (RBC) transfusion units per 12 months after eculizumab therapy were significantly lower than that before eculizumab therapy (5.75 units vs. 12.28 units, p < 0.0001). The median time for the first transfusion in the eculizumab-treated group was significantly longer than that in the eculizumab-untreated group. The 4-year transfusion-independence rate for the eculizumab-treated group was significantly higher than that for the eculizumab-untreated group (20.81% vs. 10.24%, p = 0.078). There was no significant difference between the two groups in the incidence of new documented complications related to PNH. In conclusion, eculizumab therapy for patients with high-risk PNH may effectively improve the survival rate and reduce the transfusion requirement. Paradoxically, eculizumab-treated patients with severe PNH exhibit a higher survival rate than eculizumab-untreated patients with less severe PNH.

The value of preoperative antithyroidperoxidase antibody as a novel predictor of recurrence in papillary thyroid carcinoma.

The link between chronic lymphocytic thyroiditis (CLT) and papillary thyroid carcinoma (PTC) is widely recognized. Considering the strong association between raised antithyroidperoxidase antibody (TPOAb) and CLT, we postulated that the preoperative TPOAb can predict the prognosis of PTC, particularly for recurrence. A total of 2,070 patients who underwent total thyroidectomy for classical type PTC with tumor size ≥1 cm and with available data on preoperative TPOAb and TgAb were enrolled to compare disease-free survival (DFS) according to the presence of preoperative TPOAb, TgAb, and coexistent CLT. Patients with positive preoperative TPOAb had a significantly better DFS compared to patients without positive preoperative TPOAb (hazard ratio (HR) 0.53; 95% confidence interval (CI) 0.30-0.94, p = 0.028) while no difference in DFS was found according to preoperative TgAb status. Positive preoperative TPOAb was an independent prognostic factor for structural persistent/recurrent disease after adjustment for major preoperative risk factors such as age, sex, and tumor size (HR 0.52, 95% CI 0.28-0.99, p = 0.048). Although the coexistence of CLT lowered the risk for structural persistence/recurrence in univariate analysis (HR 0.52, 95% CI 0.31-0.86, p = 0.012), it was not an independent favorable prognostic factor by multivariate analysis (HR 0.65, 95% CI 0.38-1.10, p = 0.106). However, when coexistent CLT was combined with positive preoperative TPOAb, it indicated an independent protective role in structural persistent/recurrent disease (HR 0.39, 95% CI 0.16-0.98, p = 0.045). Our study clearly showed that presence of preoperative TPOAb can be a novel prognostic factor in predicting structural persistence/recurrence of PTC.

Clinical Significance of Gross Invasion of Strap Muscles in Patients With 1- to 4-cm-Sized Papillary Thyroid Carcinoma Undergoing Lobectomy.

BACKGROUND: Given the emerging evidence supporting the lack of prognostic significance of gross extrathyroidal extension invading only strap muscles (strap-gETE), this study investigated whether lobectomy is feasible for patients with strap-gETE. METHODS: A retrospective cohort study was conducted with 636 patients who had 1- to 4-cm-sized papillary thyroid carcinoma (PTC) treated with thyroid lobectomy. Patients with gross invasion of perithyroidal organs other than strap muscles or synchronous distant metastasis were excluded from the study. Disease-free survival (DFS) was compared according to the presence of strap-gETE. RESULTS: Strap-gETE was present in 50 patients (7.9%), with the remaining 586 patients (92.1%) showing no evidence of gETE. During the median follow-up period of 7.4 years, 6% of the patients with strap-gETE and 5.1% of the patients without gETE experienced structural persistent/recurrent disease (p = 0.99). No differences in DFS were observed between the two groups (hazard ratio [HR], 1.24; 95% confidence interval [CI], 0.38-4.08; p = 0.720). After adjustment for five major risk factors (age, gender, tumor size, multifocality, and cervical lymph node metastasis status) in the multivariate analysis, the presence of strap-gETE did not exhibit an independent role in the development of structural persistent/recurrent disease (HR 1.05; 95% CI 0.24-4.53, p = 0.950). CONCLUSIONS: Strap-gETE did not increase the risk of structural persistent/recurrent disease for the patients who underwent lobectomy for 1- to 4-cm-sized PTC. The study data support the limited role of strap-gETE in clinical outcomes and may broaden the indications for lobectomy for patients with PTCs.

Impact of delayed radioiodine therapy in intermediate-/high-risk papillary thyroid carcinoma.

OBJECTIVE: It remains unclear whether the time interval between total thyroidectomy and radioactive iodine therapy (RAIT) affects clinical outcomes in papillary thyroid carcinoma (PTC). Therefore, we evaluated the impact of timing of the first post-thyroidectomy RAIT in intermediate-to-high-risk PTC. DESIGN AND PATIENTS: This retrospective propensity score-matched cohort study included 720 PTC patients who received RAIT for <90 or 90-180 days (early and delayed groups, n = 360 each) after thyroidectomy. Responses to therapy, disease-free survival (DFS) and overall survival (OS) were compared between the two groups. RESULTS: After matching, the baseline characteristics of the 360 patients in each group were similarly adjusted. Within the first 2 years after initial therapy, the number of patients classified into excellent, indeterminate, biochemical incomplete and structural incomplete response categories were 221 (61%), 74 (21%), 39 (11%) and 26 (7%) in the early group, and 204 (57%), 73 (20%), 59 (16%) and 24 (7%) in the delayed group, respectively. There was no significant difference in response to therapy between the two groups (P = 0.183). During the median follow-up of 8.6 years, there was no significant difference in DFS (P = 0.060) and OS (P = 0.400) curves between the two groups. Delayed RAIT was not significantly associated with worse DFS (HR = 1.3, 95% CI 0.9-1.8, P = 0.061) or OS (HR = 1.5, 95% CI 0.6-3.4, P = 0.388). CONCLUSIONS: Delaying the first RAIT until 180 days after total thyroidectomy had no impact on restaging, recurrence and mortality in intermediate-to-high-risk PTC.

Single-dose etoposide is an effective and safe protocol for stem cell mobilization in patients with multiple myeloma.

BACKGROUND: Single-dose etoposide was used an outpatient-based protocol for mobilization in patients with multiple myeloma (MM) for autologous stem cell transplantation (ASCT). Thus, we retrospectively analyzed the efficacy and safety of our one-day protocol in comparison with that of previous methods. METHODS: We retrospectively analyzed 168 patients with MM who underwent peripheral blood stem cell collection for upfront ASCT between 2008 and 2018. The mobilization protocols included G-CSF alone (G-mobilization), one-day 375 mg/m2 of etoposide (E375), two-days of 375 mg/m2 of etoposide (E750), or one-day high-dose (3.5 g/m2 ) cyclophosphamide (HD CY). For comparison of efficacy of each protocol, collected CD34+ cells over 4 × 106 /kg and under 2 × 106 /kg were defined as "adequate harvest" and "harvest failure," respectively. RESULTS: The median number of collected CD34+ cells was 5.58 × 106 /kg in patients receiving single-dose etoposide, and the percentage of uncomplicated optimal harvest of E375 (65.6%, 21/32) was significantly higher than that of E750 (41.9%, 13/31) and HD CY (31.3%, 15/48). The E375 showed the highest rate of adequate harvest (96.9%, 31/32) compared to that of E750 (87.1%), HD CY (75.0%), and G-mobilization (59.6%). Most E375 patients achieved adequate harvest without complication (29/32, 90.6%), the CD34+ cell collection yield on apheresis days one and two of E375 was not significantly different from that of E750, and no harvest failures occurred for E375. Neutrophil and platelet engraftments were significantly faster in E375 than other groups (P < .001). CONCLUSIONS: The use of single-dose etoposide could be an effective and safe method for mobilization in patients with MM.

Influence of coexistent Hashimoto's thyroiditis on the extent of cervical lymph node dissection and prognosis in papillary thyroid carcinoma.

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.

Serum thyroid-stimulating hormone levels and smoking status: Data from the Korean National Health and Nutrition Examination Survey VI.

OBJECTIVE: We aimed to evaluate differences in serum thyroid-stimulating hormone (TSH) levels according to smoking status and urine iodine concentration (UIC) in a healthy Korean population using data from the Sixth Korean National Health and Nutrition Examination Survey (KNHANES VI). STUDY DESIGN: Sixth Korean National Health and Nutrition Examination Survey (2013-2015) is a nationwide, cross-sectional survey of the Korean population. PATIENTS: Research subjects were selected by two-stage stratified cluster sampling of the population and housing census data. A total of 5639 subjects aged >18 years, who were not pregnant, and had undergone thyroid function testing during the survey period, were included. MEASUREMENT: The level of serum TSH according to smoking status, iodine intake and presence of TPOAb were evaluated. RESULTS: In the reference population, mean serum TSH level in current smokers (1.87 mIU/L, 95% CI, 0.52-5.37 mIU/L) was significantly lower than that in nonsmokers (2.33 mIU/L, 95% CI, 0.79-6.69 mIU/L, P < .001). The rate of thyroperoxidase antibody (TPOAb) positivity was higher in never smoker (7.7%) than past smokers (5.1%) and current smokers (4.7%), but sex-specific rate of TPOAb was not different according to smoking status. The lower serum TSH levels in current smokers were more apparent in iodine-deficient subjects (UIC < 100 µg/L), and this change was diminished in subjects with UICs between 100 and 299 µg/L. The difference in serum TSH levels in current smokers disappeared in subjects with UICs ≥ 300 µg/L. CONCLUSIONS: Smoking is associated with a left-shift in serum TSH level that is more apparent in iodine-deficient subjects. Smoking status is not associated with the presence of TPOAb or iodine intake. The results suggest that smoking has a direct effect on thyroid function that is not mediated by autoimmune processes in the thyroid gland.

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.

Lack of Efficacy of Radioiodine Remnant Ablation for Papillary Thyroid Microcarcinoma: Verification Using Inverse Probability of Treatment Weighting.

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.

Features of papillary thyroid microcarcinoma associated with lateral cervical lymph node metastasis.

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.

Optimal cut-off age in the TNM Staging system of differentiated thyroid cancer: is 55 years better than 45 years?

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.