Hye In Kim

Prognostic value of the eighth edition AJCC TNM classification for differentiated thyroid carcinoma

BACKGROUND The prognostic value of the proposed eighth edition of the American Joint Committee on Cancer (AJCC) tumor, node, and metastasis (TNM) classification is currently unclear. The aim of the study was to evaluate the prognostic value of the eighth edition of the AJCC TNM classification. METHODS We retrospectively assessed 3176 patients with differentiated thyroid carcinoma (DTC) who underwent thyroidectomy at a tertiary Korean hospital from 1996 to 2005. Cancer-specific survival (CSS) was analyzed using the Kaplan-Meier method and compared using the log-rank test. Performance of the eighth edition TNM with respect to prediction of CSS was assessed against the current seventh edition. RESULTS Upon reclassification according to the eighth edition, 37.6% of patients were down-staged. The proportions of stage I and II tumors increased from 61.9% to 81.1% and from 1.7% to 16.0%, respectively, whereas those of stage III and IVB (formerly IVC in the seventh edition) decreased from 27.6% to 2.3% and 0.8% to 0.5%, respectively. The proportions of variance explained (PVEs) for the ability of the eighth and the seventh edition to predict CSS were 3.9% and 2.9%, respectively. The C-index values were 0.765 (95% confidence interval 0.764-0.766) for the eighth edition and 0.736 (0.735-0.737) for the seventh edition. CONCLUSION Our results demonstrate that the eighth edition TNM more accurately predicts CSS for patients with DTC than does the seventh edition.

Rigiflex lithography-based nanodot arrays for localized surface plasmon resonance biosensors

We present a facile and robust means of fabricating metallic nanodot arrays for localized surface plasmon resonance (LSPR) biosensors through the strategic coupling of a polymeric template prepared with rigiflex lithography and a subsequent metallization via electrodeposition. Rigiflex lithography provides the capability to realize large-scale nanosized features as well as process flexibility during contact molding. In addition, the electrodeposition process enables wet-based nanoscale metallization with high pattern fidelity and geometric controllability. Generated metallic nanodot arrays can be used as a general platform for LSPR biosensors via the sequential binding of chemicals and biomolecules. Extinction spectra of the corresponding LSPR signal are measured with UV-vis-NIR spectroscopy, from which the pattern size and shape dependence of LSPR are readily confirmed. The feasibility of a very sensitive biosensor is demonstrated by the targeted binding of human immunoglobulin G, yielding subnanomolar detection capability with high selectivity.

High serum TSH level is associated with progression of papillary thyroid microcarcinoma during active surveillance

Objective Thyroid-stimulating hormone (TSH) is a growth factor affecting initiation or progression of papillary thyroid cancer (PTC), which supports TSH suppressive therapy in patients with PTC. In patients with papillary thyroid microcarcinoma (PTMC) during active surveillance, however, the association between serum TSH level and growth of PTMC has not been demonstrated. Patients We analyzed 127 PTMCs in 126 patients under active surveillance with serial serum TSH measurement and ultrasonography. Design The patients were categorized into groups with the highest, middle, and lowest time-weighted average of TSH (TW-TSH). PTMC progression was defined as a volume increase of ≥50% compared with baseline. Kaplan-Meier survival analysis according to TW-TSH groups and Cox proportional hazard modeling was performed. We identified the cutoff point for TSH level by using maximally selected log-rank statistics. Results During a median follow-up of 26 months, PTMC progression was detected in 28 (19.8%) patients. Compared with the lowest TW-TSH group, the adjusted hazard ratio (HR) for PTMC progression in the highest TW-TSH group was significantly higher [HR 3.55; 95% confidence interval (CI), 1.22 to 10.28; P = 0.020], but that in the middle TW-TSH group was not (HR 1.52; 95% CI, 0.46 to 5.08; P = 0.489). The cutoff point for the serum TSH level for PTMC progression was 2.50 mU/L. Conclusions Sustained elevation of serum TSH levels during active surveillance is associated with PTMC progression. Maintaining a low-normal TSH range with levothyroxine treatment during active surveillance of PTMC might be considered in future studies.

First Report of Familial Dysalbuminemic Hyperthyroxinemia With an ALB Variant.

Familial dysalbuminemic hyperthyroxinemia (FDH) is an inherited disease characterized by increased circulating total thyroxine (T4) levels and normal physiological thyroid function. Heterozygous albumin gene (ALB) variants have been reported to be the underlying cause of FDH. To our knowledge, there have been no confirmed FDH cases in Korea. We recently observed a female patient with mild T4 elevation (1.2 to 1.4-fold) and variable levels of free T4 according to different assay methods. Upon Sanger sequencing of her ALB, a heterozygous c.725G>A (p.Arg242His) variant was identified. The patients father and eldest son had similar thyroid function test results and were confirmed to have the same variant. Although the prevalence of FDH might be very low in the Korean population, clinical suspicion is important to avoid unnecessary evaluation and treatment.

Development of thyroid dysfunction is associated with clinical response to PD-1 blockade treatment in patients with advanced non-small cell lung cancer

ABSTRACT Purpose: Drugs that blockade interaction between programmed cell-death protein 1 (PD-1) and its ligand (PD-L1) are promising. Immune-related adverse events (irAEs) might be associated with favorable clinical outcomes, and thyroid dysfunction is one of the most common irAE. We evaluated the association of thyroid dysfunction during PD-1 blockade with the treatment efficacy in patients with non-small cell lung cancer (NSCLC). Experimental Design: A total 58 patients with stage IV NSCLC treated with PD-1 blockade were enrolled. Patients were categorized into thyroid dysfunction and euthyroid groups. Overall survival (OS) and progression-free survival (PFS) of the two groups were compared. Patients, tumor, and medication factors were adjusted using Cox proportional hazard modeling. Objective response rate (RR) and durable control rate were assessed according to the severity of thyroid dysfunction. Results: OS [median 118.0 (73.0-267.0) vs. 71.0 (28.0-160.0) days, log-rank P = 0.025] and PFS [118.0 (73.0-267.0) vs. 61.0 (28.0-130.0), log-rank P = 0.014] were longer in the thyroid dysfunction group. After adjustment, thyroid dysfunction was an independent predictive factor for favorable outcome [adjusted HR = 0.11 (95% CI) 0.01-0.92 for overall death; 0.38 (0.17-0.85) for disease progression]. The severity of thyroid dysfunction was associated with durable control rate (P for trend = 0.008). Conclusions: Thyroid dysfunction during PD-1 blockade is associated with treatment response and could provide supplementary information for immune monitoring in patients with advanced NSCLC.

Validation of dynamic risk stratification in pediatric differentiated thyroid cancer

PurposeThere has been increasing interest in a risk-adopted management strategy known as dynamic risk stratification following the revised American Thyroid Association guidelines for differentiated thyroid cancer. We aimed to evaluate the usefulness of dynamic risk stratification for predicting structural disease in pediatric differentiated thyroid cancer patients.MethodsWe retrospectively reviewed 130 pediatric differentiated thyroid cancer patients (≤19 years) who were treated between 1996 and 2015 at Samsung Medical Center. Patients were stratified according to three American Thyroid Association initial risk group (low, intermediate, or high risk) and four dynamic risk stratification group (excellent, indeterminate, biochemical incomplete, or structural incomplete).ResultsBased on dynamic risk stratification strategy, structural disease was identified 3.9% in the excellent group, 9.7% in the indeterminate group, 76.9% in the biochemical incomplete group, and 100% in the structural incomplete group. The hazard ratios of the structural disease were 18.10 (P < 0.001) in the biochemical incomplete group, and 19.583 (P < 0.001) in the structural incomplete group compared to the excellent group. The prevalence of structural disease also increased as American Thyroid Association initial risk classification increased (5.9% in the low-risk group, 13.6% in the intermediate-risk group, and 45% in the high-risk group). The hazard ratios of structural disease in the high-risk group was 10.296 (P < 0.001) in compared to the low-risk group.ConclusionDynamic risk stratification based on patient responses to initial therapy was able to effectively predict the risk of structural disease in a pediatric population, and as a follow-up strategy, may work as well in pediatric differentiated thyroid cancer patients as it does in adult differentiated thyroid cancer patients.

The Hidden Culprit: A Case of Repeated Anaphylaxis to Cremophor

Drug-induced anaphylaxis is a big pitfall in patients receiving antineoplastic chemotherapy. We report a case of lung cancer patient who experienced two near-fatal anaphylactic reactions that resulted from paclitaxel and multivitamin, seperately. Recurrent severe reactions to different agents led to further investigation to which material the patient was hypersensitive. The skin prick test revealed sensitization to cremophor, which is a commonly used emulsifying agent. This case emphasizes the importance of correctly identifying the culprit drug of anaphylaxis to avoid potentially fatal reaction.

Refining the eighth edition AJCC TNM classification and prognostic groups for papillary thyroid cancer with lateral nodal metastasis

BACKGROUND In the eighth edition, TNM staging system omits location of nodal metastasis as a criterion for staging patients with papillary thyroid cancer (PTC). Accordingly, all of non-metastatic N1b PTC patients are classified as stage I or II solely according to an age-cutoff of 55 years. We hypothesized that incorporating other lymph node (LN) factors into TNM staging system would better predict cancer-specific mortality (CSM) in N1b patients. METHODS We enrolled 745 N1b PTC patients without distant metastasis. Alternative prognostic LN factors and cut-off points were assessed using Cox regression and time-dependent ROC analysis. Alternative prognostic groupings were derived based on minimal hazard differences for CSM among groups stratified by LN risk and age. We assessed accuracy of CSM prediction. RESULTS Lateral LN ratio (LNR) >0.3 and largest LN size >3 cm were prognostic factors for CSM. Stage II patients (eighth edition) with LN risk (lateral LNR >0.3 or largest LN size >3 cm) had a much higher CSM rate (20.9%) than those in the same stage without LN risk (3.2%). Alternative prognostic grouping (Group 1, <55 years without LN risk; Group 2, <55 years with LN risk or ≥55 years without LN risk; and Group 3, ≥55 with LN risk) achieved higher proportions of variance explained (PVEs) for predicting CSM (10.7%) than those of the eighth edition TNM staging system (4.8%). CONCLUSIONS The proposed grouping for N1b patients using LN risk can distinguish patients with poor prognosis from those with good prognosis better than the eighth edition TNM staging system.

Subclinical thyroid dysfunction and risk of carotid atherosclerosis

Background The effect of subclinical thyroid dysfunction on vascular atherosclerosis remains uncertain. The objective of this study was to elucidate the association between sustained subclinical thyroid dysfunction and carotid plaques, which are an early surrogate marker of systemic atherosclerosis. Methods The study included 21,342 adults with consistent thyroid hormonal status on serial thyroid function tests (TFTs) and carotid artery duplex ultrasonography at a health screening center between 2007 and 2014. The effect of subclinical thyroid dysfunction on baseline carotid plaques and newly developed carotid plaques during 5-year follow-up was determined by logistic regression analyses and GEE (Generalized Estimating Equations), respectively. Results Carotid plaques were more common in the subclinical hypothyroidism (55.6%) than the euthyroidism (47.8%) at baseline. However, in multivariable analysis, thyroid status was not a significant risk for the carotid plaques at baseline. Instead, traditional cardiovascular risk factors, such as age (P <0.001), systolic blood pressure (P = 0.023), fasting blood glucose (P = 0.030), and creatinine (P = 0.012) were associated with baseline carotid plaques in subclinical hypothyroidism. In longitudinal analyses of subjects who were followed up for more than 5 years, there was no significant difference in the cumulative incidence of new carotid plaques according to time between subjects with subclinical hypothyroidism and those with euthyroidism (P = 0.392). Conclusions Sustained subclinical thyroid dysfunction did not affect the baseline or development of carotid plaques in healthy individuals.

Delayed TSH recovery after dose adjustment during TSH-suppressive levothyroxine therapy of thyroid cancer

Delayed thyroid‐stimulating hormone (TSH) recovery during treatment of Graves’ disease is caused by long‐term excessive thyroid hormone, which results in downregulation of pituitary thyrotrophs. However, it is unknown whether delayed TSH recovery exists after levothyroxine (LT4) dose reduction in patients with differentiated thyroid cancer (DTC) after long‐term TSH suppression.