Eui Young Kim

Change of serum antithyroglobulin antibody levels is useful for prediction of clinical recurrence in thyroglobulin-negative patients with differentiated thyroid carcinoma.

OBJECTIVES The aim of the study was to evaluate the usefulness of the antithyroglobulin autoantibody (TgAb) value at 6-12 months after remnant ablation in predicting recurrence in differentiated thyroid carcinoma patients who had undetectable thyroglobulin (Tg) values. The change in TgAb concentration measured between the time of remnant ablation (TgAb1) and 6-12 months thereafter (TgAb2) was also evaluated as a possible prognostic indicator. PATIENTS AND METHODS Patients with differentiated thyroid carcinoma who underwent total thyroidectomy followed by (131)I remnant ablation between 1995 and 2003 at the Asan Medical Center (Seoul, Korea) were enrolled. Of these, 824 patients with undetectable Tg at 6-12 months after remnant ablation during thyroid hormone withdrawal were the subjects of this study. RESULTS TgAb2 was positive in 56 patients. Ten of 56 patients (18%) with positive TgAb2 had recurrence, whereas only 10 of 768 patients (1%) with negative TgAb2 had recurrence during 73.6 months of follow-up (P < 0.001). The change between TgAb1 and TgAb2 levels was evaluated in patients with positive TgAb2. TgAb concentration decreased by more than 50% in 21 patients (group 1) and by less than 50% in 16 patients (group 2), and it increased in 19 patients (group 3). The recurrence rates in groups 1, 2, and 3 were 0, 19, and 37%, respectively (P = 0.016). CONCLUSIONS Serum TgAb levels measured at 6-12 months after remnant ablation could predict recurrence in patients with undetectable Tg values. In patients with undetectable Tg and positive TgAb values, a change in TgAb concentration during the early postoperative period may be a prognostic indicator of recurrence.

Coexistence of chronic lymphocytic thyroiditis is associated with lower recurrence rates in patients with papillary thyroid carcinoma.

Objective  The effect of coexistent chronic lymphocytic thyroiditis (CLT) on prognosis in papillary thyroid carcinoma (PTC) patients remains controversial. We evaluated the influence of coexistent CLT on prognostic outcome and the association of coexistent CLT with clinicopathological parameters.

The Outcomes of First Reoperation for Locoregionally Recurrent/Persistent Papillary Thyroid Carcinoma in Patients Who Initially Underwent Total Thyroidectomy and Remnant Ablation

CONTEXT The primary treatment of locoregionally recurrent/persistent papillary thyroid cancer (PTC) is surgical removal by reoperation. However, there had been only limited number of reports on the outcome of reoperation. OBJECTIVE This study was to evaluate the efficacy of the first reoperation for locoregionally recurrent/persistent papillary thyroid carcinoma and the usefulness of stimulated thyroglobulin for evaluating efficacy of reoperation. DESIGN AND SETTINGS This was a retrospective observational cohort study in a tertiary referral hospital. PATIENTS A total of 83 patients, who underwent initial total thyroidectomy and nodal dissection with radioactive iodine remnant ablation, received reoperation for locoregionally recurrent/persistent PTC and were included in this study. Stimulated thyroglobulin levels were assessed before and after reoperation. MAIN OUTCOME MEASURES We assessed biochemical remission (stimulated thyroglobulin <1 ng/ml) after reoperation and evaluated second clinical recurrence-free survival rate according to stimulated thyroglobulin value. RESULTS There was a significant positive correlation between the numbers of resected malignant lymph nodes and the reduction in stimulated thyroglobulin level after reoperation. Biochemical remission was achieved in 51% of patients who underwent first reoperation. Patients with stimulated thyroglobulin level greater than 5 ng/ml after first reoperation had a greater chance of a second clinical recurrence (the estimated 5 yr clinical recurrence free survival rate, 94 ± 3 vs.74 ± 9%, log rank statistics 15.8, df = 1, P < 0.001). CONCLUSION Surgery is an effective option for managing locally recurrent/persistent PTC. Stimulated thyroglobulin is a useful marker for evaluating efficacy of reoperation and predicting second recurrence in locoregionally recurrent/persistent PTC.

Empiric High-Dose 131-Iodine Therapy Lacks Efficacy for Treated Papillary Thyroid Cancer Patients with Detectable Serum Thyroglobulin, but Negative Cervical Sonography and 18F-Fluorodeoxyglucose Positron Emission Tomography Scan

CONTEXT Some patients with elevated serum thyroglobulin (Tg) but a negative diagnostic whole body scan (WBS) after initial therapy for differentiated thyroid carcinoma may benefit from empirical radioactive iodine (RAI) therapy. However, previous studies enrolled patients with negative diagnostic WBS, regardless of neck ultrasonography (USG) and/or (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET), which have become the preferred diagnostic procedures in such patients. OBJECTIVE The aim of this study was to evaluate the usefulness of empirical RAI therapy in patients with elevated stimulated Tg level and negative USG/FDG-PET findings after initial therapy for papillary thyroid carcinoma (PTC). DESIGN This comparative study enrolled 39 patients with elevated stimulated Tg, negative diagnostic WBS, and negative USG/FDG-PET 1 yr after initial treatment. Empirical RAI therapy was performed in 14 patients (treatment group), whereas 25 patients were followed up without therapy (control group). RESULTS There was no significant between-group difference in basal clinicopathological parameters. None of the 14 patients in the treatment group showed iodine uptake on posttreatment WBS. Five of 14 patients (36%) in the treatment group and eight of 25 (32%) in the control group had recurrence during the median 37 months of follow-up (P = 0.99). Changes in serum stimulated Tg concentrations did not differ between the two groups. CONCLUSION Empirical RAI therapy and posttreatment WBS were not useful diagnostically or therapeutically in patients with positive serum stimulated Tg if such patients had negative USG and negative FDG-PET findings after initial treatment of PTC.

Concurrent occurrence of medullary thyroid carcinoma and papillary thyroid carcinoma in the same thyroid should be considered as coincidental

Objectives  The simultaneous occurrence of medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC) in the same thyroid gland is documented. In this study, we evaluated the prevalence and characteristics of patients with concurrent MTC and PTC.

Long-term clinical outcome of differentiated thyroid cancer patients with undetectable stimulated thyroglobulin level one year after initial treatment.

BACKGROUND Measurement of the serum thyroglobulin (Tg) level with TSH stimulation (sTg) is the cornerstone of monitoring for the recurrence or persistence of differentiated thyroid cancer (DTC) in patients who have undergone surgery and remnant ablation. However, there have been several reports that an undetectable sTg could not predict the absence of future recurrence. The aim of this study was to evaluate the long-term outcome of DTC patients who achieved biochemical remission (BR, defined as sTg<1 ng/mL) after initial treatment, and to determine the role of repeated sTg measurement in detecting a clinical recurrence. METHODS This is a retrospective observational cohort study in a tertiary referral hospital. There were 1010 DTC patients who achieved BR at 12 months after the initial treatment (surgery and ablation), and they were eligible for analysis. Among them, 787 patients had values of repeated sTg. RESULTS Thirteen out of 1010 (1.3%) patients had clinical recurrences during a median 84 months of follow-up. All of the clinical recurrences were limited to the cervical lymph nodes without clinical evidence of distant metastasis. Among 787 patients with available repeated sTg, 10 had clinical recurrences (5 out of 750 patients with repeated sTg<1 ng/mL and 5 out of 37 patients with repeated sTg ≥ 1 ng/mL). Patients with repeated sTg ≥ 1 ng/mL had a much greater chance of disease recurrence (log-rank statistics=43.7, df=1, p<0.001). CONCLUSIONS About 1% of DTC patients who had sTg<1 ng/mL 12 months after initial treatment had a clinical recurrence. All of clinical recurrences were loco-regional recurrences. Although repeated sTg measurement can be helpful to predict recurrence, we could not recommend it for surveillance in patients with BR due to its very low yield.

Effects of different doses of radioactive iodine for remnant ablation on successful ablation and on long-term recurrences in patients with differentiated thyroid carcinoma.

ObjectivesThe aim of this study was to compare ablation success and disease-free survival (DFS) on the basis of different ablation doses. MethodsThis retrospective study enrolled differentiated thyroid carcinoma patients who underwent total thyroidectomy and radioactive remnant ablation at the Asan Medical Center between January 2000 and December 2004. Radioactive iodine doses of 30 mCi (group A), 80 mCi (group B), and 150 mCi (group C) were administered according to the patients’ risk of recurrences based on the clinicopathologic parameters at the time of surgery. Ablation success was defined as absence of abnormal uptake on diagnostic whole-body scan. ResultsAmong 1024 patients, successful ablation was achieved in 81.7% in group A, in 89.5% in group B, and in 94.8% in group C (P<0.001). A total of 100 patients (9.8%) had clinical recurrences during 6.6 years of median follow-up. DFS was evaluated according to ablation success in each dose group. There were no significant differences in DFS. Side effects of radioactive iodine were negligible with dose up to 80 mCi; however, 2% of patients developed permanent salivary dysfunction in group C. ConclusionIn cases of different ablation doses administered according to patients’ risk of recurrences, we found that a higher dose of radioiodine was associated with a higher rate of ablation success compared with lower doses. However, successful ablation was not associated with a reduction in clinical recurrences. The optimal dose for ablation must be adjusted according to the risk group of individual patients to avoid unnecessary radiation and maximize therapeutic efficacy.

Adjuvant Radioactive Therapy after Reoperation for Locoregionally Recurrent Papillary Thyroid Cancer in Patients Who Initially Underwent Total Thyroidectomy and High-Dose Remnant Ablation

CONTEXT Some patients have elevated stimulated thyroglobulin (sTg) concentrations after reoperation for locoregionally recurrent/persistent papillary thyroid cancer (PTC). Little is known, however, about the efficacy of adjuvant radioactive iodine (RAI) therapy in these patients. OBJECTIVE The objective of the study was to evaluate the efficacy of adjuvant RAI therapy in patients with elevated sTg after reoperation for locally recurrent/persistent PTC. DESIGN AND SETTINGS This was a retrospective observational cohort study in a tertiary referral hospital. PATIENTS We evaluated 45 consecutive patients with sTg greater than 2 ng/ml after reoperation for locoregionally recurrent PTC, all of whom had previously undergone initial total thyroidectomy followed by high-dose RAI remnant ablation. Of these 45 patients, 23 received adjuvant RAI therapy (adjuvant group) and 22 did not (control group). MAIN OUTCOME MEASURES Main outcome measures included changes in sTg concentration after reoperation and disease-free survival. RESULTS Over time, there were no significant differences in mean sTg concentration in the adjuvant (P = 0.35) and control (P = 0.74) groups. Only 15% of patients in the adjuvant group and 33% in the control group showed a greater than 50% decrease in sTg level from baseline. There were no between-group differences in changes (P = 0.83) or percent decrease (P = 0.97) in sTg concentration and no difference in clinical recurrence-free survival (P = 0.20). CONCLUSION In patients who still have elevated sTg after reoperation for locally recurrent/persistent PTC, adjuvant RAI therapy compared with no additional RAI therapy resulted in no significant differences in the subsequent sTg changes or the recurrence-free survival.

Basal STAT3 activities are negatively correlated with tumor size in papillary thyroid carcinomas

Backgrounds: Signal transducer and activators of transcription-3 (STAT3) plays a critical role in promoting survival and cell growth as well as facilitating angiogenesis and metastasis in several cancers. Aim: This investigation focused on evaluation of STAT3 activities in human papillary thyroid cancers (PTC). Methods: STAT3 activities of nuclear extracts of tumor tissue were measured from 35 PTC patients using enzyme-linked immunosorbent assay-based kits. Results: STAT3 activities of PTC tissues were significantly lower than those of surrounding normal thyroid tissues [0.36 (interquartile range 0.24–0.72) vs 0.50 (0.29–1.11) arbitrary units, p<0.01]. We further analyzed the association between STAT3 activity and clinicopathologic factors in PTC tissue. Tumors with size ≥2 cm displayed significantly lower STAT3 activities than those <2 cm [0.25 (0.21–0.37) vs 0.53 (0.37–0.61) arbitrary units, p<0.01]. Notably, tumor size was inversely correlated with STAT3 activities in T1799A BRAF mutation-positive cases (Rs=−0.58, p<0.05), but not mutation-negative cases. Conclusions: STAT3 activities of PTC measured via DNA binding are suppressed in contrast to other human cancers. Tumor size larger than 2 cm is the only clinicopathologic parameter associated with low STAT3 activity. Moreover, tumor size appears inversely correlated with STAT3 activity, specifically in T1799A BRAF mutation-positive cases.

Long-term consequence of elevated thyroglobulin in differentiated thyroid cancer.

BACKGROUND Serum thyroglobulin (Tg) is the most sensitive biomarker for recurrence of differentiated thyroid cancer (DTC). We have assessed the changing pattern of stimulated Tg (sTg) and the clinical course of patients with no structural evidence of disease (NSED), based on imaging studies such as neck ultrasonography (US), fluorodeoxyglucose positron emission tomography, and/or chest computed tomogram (CT). We sought to determine if, in patients with DTC who had been treated with bilateral thyroidectomy and remnant ablation with radioactive iodine, sTg 1 year (sTg1) after initial treatment and repeated sTg measurements, 1-2 years after sTg1, helped predict the long-term outcome with respect to structural recurrence and biochemical remission (BR), which is defined as sTg <1 ng/mL. METHODS We retrospectively assessed the records of patients with DTC who had been treated with bilateral thyroidectomy and remnant ablation with radioactive iodine between 1995 and 2004. The study included 186 patients who had NSED with sTg1 ≥2 ng/mL and subsequent sTg measurements (sTg2) without additional treatment. Patients were classified into three groups based on their sTg1 measurements: Group A, 2-4.9 ng/mL; Group B, 5-19.9 ng/mL; and Group C, ≥20 ng/mL. Patients were also classified into two groups based on whether sTg2, 1-2 years after sTg1, had decreased by ≥50% (Group 1) or had either decreased by <50% or increased (Group 2). sTg was measured every 1-2 years until structural recurrence or BR. RESULTS Patients remaining in NSED showed a decrease in serial sTg. Of patients in Groups A, B, and C, 41%, 17%, and 1%, respectively, achieved BR, and there was a significant difference in the BR rate between Groups 1 and 2 (p<0.001). In patients with structural recurrence, serial sTg generally did not decrease from sTg1. There was a significant difference in the recurrence rate among Groups A, B, and C (p=0.005) and between Groups 1 and 2 (p<0.001). CONCLUSIONS We found that 41% of patients with sTg1 in the range 2-5 ng/mL achieved BR, and that sTg1 and percent change of subsequent sTg were predictive of BR. Repeated sTg measurements are useful for predicting patient prognosis in patients with DTC.