Ultrasound Echogenicity of Papillary Thyroid Cancer Is Affected by Tumor Growth Patterns and Tumor Fibrosis.

BACKGROUND/AIM: The association between preoperative ultrasound (US) echogenicity and histopathological characteristics of papillary thyroid cancer (PTC) has been rarely investigated is not well characterized. This study evaluated a relationship between the clinical characteristics of PTC, histopathological phenomena including tumor growth patterns (TGPs) and tumor fibrosis (TF), and US echogenicity. PATIENTS AND METHODS: In total, 170 patients with PTC (<2 cm) underwent total thyroidectomy with central neck dissection. Demographics, US echogenicity, tumor size, extra-thyroidal extension (ETE), lymph node metastasis (LNM) within the central and lateral neck, TGPs, and TF percentage were reviewed. RESULTS: Patients with TGP II (encapsulated growth with partial pericapsular extension) and III (infiltrative growth) were more frequently burdened by ETE and lateral neck LNM compared to patients with TGP I (encapsulated growth with a well-defined cystic or solid characteristic). Older age was significantly deterministic of TGP III, and male gender and higher TF percentage were independent risk factors for lateral neck LNM. TGP III and TF were independent determining factors for marked hypoechogenicity on US. CONCLUSION: PTC with TGP II and III and higher tumor fibrosis exhibited more aggressive clinicopathologic behaviors. TGP III and TF were determinants for marked hypoechogenicity.

The fatty liver index, a simple and useful predictor of metabolic syndrome: analysis of the Korea National Health and Nutrition Examination Survey 2010-2011.

PURPOSE: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, and it is the hepatic manifestation of metabolic syndrome (MetS). We aimed to estimate the prevalence of NAFLD defined by the fatty liver index (FLI), in order to investigate the association between FLI and metabolic disorders and to determine the cutoff value of FLI to screen for MetS. SUBJECTS AND METHODS: This study utilized a national representative sample of Korean adults (the Korean National Health and Nutrition Examination Surveys) which was conducted in 2010-2011. A total of 10,107 adults aged 19 years or older were selected. NAFLD was diagnosed on the basis of an increased FLI (≥60) after the exclusion of alcohol or viral liver disease. RESULTS: NAFLD was identified in 1,134 subjects (age-standardized prevalence, 10.0%). When subjects were categorized into three groups by FLI (<20, 20-59, and ≥60), the higher FLI group showed a higher prevalence of hypertension (49.7% vs 14.4%), diabetes mellitus (DM; 20.4% vs 3.8%), and MetS (74.9% vs 7.4%). FLI was positively associated with age, body mass index, blood pressure, hemoglobin A1c, and homeostasis model assessment of insulin resistance (P for trend <0.001). In the multivariate analysis, the higher FLI group had a significantly higher risk for hypertension (OR =2.92, 95% CI =2.18-3.90, P<0.001), DM (OR =4.38, 95% CI =2.96-6.49, P<0.001), and MetS (OR =24.85, 95% CI =17.33-35.64, P<0.001). However, no increase was observed for cardiovascular disease after adjustment of other risk factors. The cutoff value of the FLI estimated to predict the presence of MetS was 20 (area under the curve 0.849, sensitivity 0.828, and negative predictive value 91.9%). CONCLUSION: NAFLD prevalence using FLI is significantly higher in subjects with metabolic disorder including MetS. FLI might be a useful screening tool to detect subjects who may require early management of MetS and who have a high cardiovascular risk.

Relative handgrip strength as a marker of metabolic syndrome: the Korea National Health and Nutrition Examination Survey (KNHANES) VI (2014-2015).

Purpose: Muscles play an important role in energy metabolism. Several studies have investigated the association between muscle mass and metabolic syndrome (MetS), reporting conflicting results. However, studies concerning the association between muscle strength and MetS are limited. We aimed to investigate the association between relative handgrip strength (HGS) and MetS in Korean adults. Participants and methods: We analyzed data from 5,014 Korean adults aged ≥20 years (2,472 men and 2,542 women) who participated in the Korea National Health and Nutrition Examination Survey (KNHANES) VI (2014-2015). Results: The increasing quartiles of relative HGS (defined as the sum of both hands' HGS divided by body mass index) were inversely associated with the risk of MetS in both men and women (OR, 0.37; 95% CI, 0.30-0.45, vs OR, 0.19; 95% CI, 0.14-0.27, respectively) after multivariable adjustment for age, region of residence, smoking status, heavy alcohol consumption, regular exercise, family income, and education level. On multivariable logistic regression analyses, participants with the highest relative HGS had a significant decrease in relative risk of MetS, compared with those with the lowest relative HGS. The multivariable-adjusted ORs (with 95% CIs) for MetS in quartiles 1, 2, 3, and 4 were 1.00, 0.72 (0.55-0.94), 0.34 (0.26-0.46), and 0.22 (0.15-0.32) in men and 1.00, 0.50 (0.36-0.68), 0.26 (0.17-0.40), and 0.16 (0.09-0.27) in women, respectively. Conclusion: Relative HGS showed a highly significant inverse association with the risk of MetS in Korean adults, and it can be a novel biomarker for assessing the risk of MetS.

Association between serum cystatin C and bone mineral density in Korean adults.

Background: Serum cystatin C has been known as a novel marker of preclinical renal dysfunction, and higher cystatin C levels are associated with increased risks of hip and nonvertebral fractures. However, there are few reports on the association between serum cystatin C and bone mineral density (BMD), especially in the Asian population. We evaluated the association between cystatin C levels and BMD of the spine and hip in Korean adults. Methods: A cross-sectional study was performed in 865 Korean adults (325 men and 540 women) who participated in a comprehensive medical examination program and underwent bone densitometry. Renal function was assessed by the estimated glomerular filtration rate (eGFR), which was calculated using an equation based on creatinine (eGFRcre) and cystatin C (eGFRcys). Results: The serum cystatin C level was negatively correlated with different types of BMD, including the lowest lumbar, total lumbar, femoral neck, and total femur BMD, in women, but not in men. Higher cystatin C levels were associated with a higher prevalence of osteoporosis in women (odds ratio [OR], 3.68; 95% confidence interval [CI], 1.69-8.03; P=0.001), but not in men (OR, 0.85; 95% CI, 0.30-2.38; P=0.761). However, this association was attenuated in the multivariable model adjusted for age, body mass index, serum 25-hydroxyvitamin D3, and creatinine (OR, 1.01; 95% CI, 0.38-2.71) in women. In addition, the eGFRcys showed a stronger positive correlation with BMD than the eGFRcre. Conclusion: Our findings suggest that serum cystatin C levels might help identify women with osteoporosis who are susceptible to fractures.

Prevalent Rate of Nonalbuminuric Renal Insufficiency and Its Association with Cardiovascular Disease Event in Korean Type 2 Diabetes.

BACKGROUND: Nonalbuminuric renal insufficiency is a unique category of diabetic kidney diseases. The objectives of the study were to evaluate prevalent rate of nonalbuminuric renal insufficiency and to investigate its relationship with previous cardiovascular disease (CVD) event in Korean patients with type 2 diabetes mellitus (T2DM). METHODS: Laboratory and clinical data of 1,067 subjects with T2DM were obtained and reviewed. Study subjects were allocated into four subgroups according to the CKD classification. Major CVD events were included with coronary, cerebrovascular, and peripheral vascular events. RESULTS: Nonalbuminuric stage ≥3 CKD group, when compared with albuminuric stage ≥3 CKD group, had shorter diabetic duration, lower concentrations of glycated hemoglobin, high density lipoprotein cholesterol, and high-sensitivity C-reactive protein, lower prevalent rates of retinopathy and previous CVD, and higher rate of treatment with angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers. Nonalbuminuric stage ≥3 CKD group showed a greater association with prior CVD events than no CKD group; however, albuminuric stage ≥3 CKD group made addition to increase prevalence of prior CVD events significantly when CKD categories were applied as covariates. Association of prior CVD events, when compared with normal estimated glomerular filtration rate (eGFR) and nonalbuminuria categories, became significant for declined eGFR, which was higher for eGFR of <30 mL/min/1.73 m², and albuminuria. CONCLUSION: The results show that subjects with nonalbuminuric stage ≥3 CKD is significantly interrelated with occurrence of prior CVD events than those with normal eGFR with or without albuminuria. Comparing with normal eGFR and nonalbuminuria categories, the combination of increased degree of albuminuria and declined eGFR is becoming significant for the association of prior CVD events.

Prevalence of Reduced Kidney Function by Estimated Glomerular Filtration Rate Using an Equation Based on Creatinine and Cystatin C in Metabolic Syndrome and Its Components in Korean Adults.

BACKGROUND: It is known that metabolic syndrome (MetS) is associated with chronic kidney disease. We evaluated and compared the prevalence of reduced kidney function in MetS and its components by estimated glomerular filtration rate (eGFR) using an equation based on creatinine (eGFRcr), cystatin C (eGFRcys), and combined creatinine-cystatin C (eGFRcr-cys) in Korean adults. METHODS: We analyzed data from 3,649 adults who participated in a comprehensive health examination. RESULTS: Mean values of eGFRcys were higher compared with mean values of eGFRcr (96.1±18.2 mL/min/1.73 m² vs. 91.2±13.6 mL/min/1.73 m²) in total subjects. The prevalence of reduced kidney function increased with age (9.6% for eGFRcys vs. 5.8% for eGFRcr-cys vs. 4.9% for eGFRcr, in subjects aged ≥60 years), and significantly increased with MetS, abdominal obesity, hypertension, high triglyceride, low high density lipoprotein (HDL), and high insulin resistance. The prevalence of MetS, abdominal obesity, hypertension, high insulin resistance, low HDL, and hepatic steatosis was significantly increased in subjects with reduced kidney function. This increased prevalence and the odds ratio of reduced kidney function for prevalence of MetS was highest for eGFRcys, followed by those of eGFRcr-cys, and eGFRcr. CONCLUSION: The prevalence of reduced kidney function by eGFR was significantly increased in subjects with MetS and its related components. eGFRcys and eGFRcr-cys were superior to eGFRcr in detecting reduced kidney function.

The Association of Serum Cystatin C with Glycosylated Hemoglobin in Korean Adults.

BACKGROUND: Cystatin C has been known to be associated not only with early renal impairment but also with the incidence of diabetic conditions (prediabetes plus diabetes). However, it is not clear whether cystatin C levels are associated with the prevalence of diabetic conditions in Asian populations. We evaluated this association using glycosylated hemoglobin (HbA1c) levels as the definition of diabetes in Korean adults. METHODS: We analyzed data from 1,559 Korean adults (937 men and 622 women) with available serum cystatin C and HbA1c values. RESULTS: The serum cystatin C levels in subjects with prediabetes and diabetes were significantly increased (0.91±0.14 mg/L in prediabetes and 0.91±0.17 mg/L in diabetes vs. 0.88±0.13 mg/L in patients with normal glucose levels, P=0.001). At increasing cystatin C levels, the prevalence of subjects with prediabetes (30.2% vs. 14.6%, P<0.001) and those with diabetes (10.6% vs. 8.0%, P<0.001) significantly increased in the group with the highest cystatin C levels. The group with the highest cystatin C levels had a significantly increased odds ratio (OR) for the presence of diabetic conditions compared to the group with the lowest values in total subjects (OR, 2.35; 95% confidence interval [CI], 1.54 to 3.58; P<0.001) and in women (OR, 4.13; 95% CI, 1.97 to 8.65; P<0.001), though there was no significant increase after adjusting for multiple variables. CONCLUSIONS: Higher levels of serum cystatin C are associated with an increased prevalence of diabetic conditions in Korean adults. Our findings may extend the positive association of cystatin C with diabetes incidence to an Asian population.

Lymph node status of lateral neck compartment in patients with N1b papillary thyroid carcinoma.

Conclusion Loco-regional recurrence-free survival was significantly decreased in the papillary thyroid cancer patients with > 6 metastatic lymph nodes and a lymph node ratio > 0.22. Also, the risk of lung metastasis was significantly increased in cases with bilateral neck node metastases. Objective This study focused on the metastatic lymph node status of the lateral neck compartment to understand its prognostic significance for loco-regional recurrence and distant metastasis. Methods Between January 2004 and December 2009, 1040 patients were diagnosed with papillary thyroid cancer and underwent treatment. Results In a multivariate analysis, sex, the number of metastatic lymph nodes, and the lymph node ratio was significantly associated with loco-regional recurrence. The sensitivity/specificity of > 6 metastatic lymph nodes for predicting recurrence was 64.0%/69.7%. The 5-year loco-regional recurrence-free survival of patients with 0-6 metastatic lymph nodes and > 6 metastatic lymph nodes were 93.4% and 79.2%, respectively. The 5-year loco-regional recurrence-free survival of patients with a lymph node ratio ≤ 0.22 and a lymph node ratio > 0.22 were 97.1% and 78.8%, respectively. In the multivariate analysis, only bilateral neck node metastases were significantly associated with lung metastasis.

Metastatic lymph node status in the central compartment of papillary thyroid carcinoma: A prognostic factor of locoregional recurrence.

BACKGROUND: The purpose of this study was to present our focus on the lymph node status in the central compartment and evaluate the relevant factors and disease recurrence. METHODS: Between January 2004 and December 2009, 1040 patients were diagnosed with papillary thyroid carcinoma (PTC) and underwent surgery. RESULTS: The number of metastatic lymph nodes was a significant predictor for recurrence conferring a hazard ratio of 1.36 (confidence interval = 1.103-1.680; p = .004). The receiver operating characteristic (ROC) curve was calculated to determine the cutoff number of lymph nodes that predicted recurrence with the highest sensitivity and specificity (area under the ROC curve, 0.794; SE, 0.077; p = .001). The sensitivity/specificity of >3 metastatic lymph nodes for predicting recurrence was 63.6%/77.0%, respectively. CONCLUSION: The number of metastatic lymph nodes in the central compartment was a statistical significant predictive factor associated with disease recurrence. Further study is required to confirm the relationship between the number of lymph nodes and disease recurrence. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1172-E1176, 2016.

Low serum TNF-related apoptosis-inducing ligand (TRAIL) levels are associated with acute ischemic stroke severity.

BACKGROUND: TNF-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor receptor superfamily and its serum level is known to be closely associated with future cardiovascular events and prognosis of various cardiovascular diseases. We investigated whether serum TRAIL levels are associated with the severity of acute ischemic stroke and specific stroke subtype. METHODS: We used an enzyme-linked immunosorbent assay to measure the serum TRAIL levels of 293 patients with acute ischemic stroke within 7 days of onset. Stroke subtype was classified as large artery atherosclerosis, cardioembolism, small vessel occlusion and other determined etiology. We used National Institute of Health Stroke Scale (NIHSS) score of first hospital day and stroke volume on diffusion-weighted imaging within 7 days of stroke onset for measuring the severity of acute ischemic stroke. RESULTS: The level of serum TRAIL showed significant negative correlations with NIHSS score and stroke volume. Serum TRAIL levels significantly decreased as the tertile of NIHSS score and stroke volume increased. The relative risk of patients with serum TRAIL<64.0 pg/mL for the presence of highest tertile of NIHSS score was significantly increased (adjusted OR [95%CI]; 7.07 [3.64-13.74]). Regarding stroke volume, the relative risk of patients with serum TRAIL<71.5 pg/mL for the presence of highest tertile of stroke volume was also significantly increased (adjusted OR [95%CI]; 2.81 [1.61-4.92]). There are no significant differences of serum TRAIL level among stroke subtypes. CONCLUSIONS: Low serum TRAIL levels were significantly associated with the acute ischemic stroke severity. This finding suggests that serum TRAIL might also have a role in acute ischemic stroke as well as other cardiovascular diseases.

Long Term Effect of High Glucose and Phosphate Levels on the OPG/RANK/RANKL/TRAIL System in the Progression of Vascular Calcification in rat Aortic Smooth Muscle Cells.

Osteoprotegerin (OPG), receptor activator of NF-κB ligand (RANKL)/receptor activator of NF-κB (RANK) axis, and TNF-related apoptosis-inducing ligand (TRAIL) participate in vascular calcification process including atherosclerosis, but their contributions under high glucose (HG) and phosphate (HP) condition for a long-term period (more than 2 weeks) have not been fully determined. In this study, we evaluated the effects of HG and HP levels over 2 or 4 weeks on the progression of vascular calcification in rat vascular smooth muscle cells (VSMCs). Calcium deposition in VSMCs was increased in medium containing HG (30 mmol/L D-glucose) with ß-glycerophosphate (ß-GP, 12 mmol/L) after 2 weeks and increased further after 4 weeks. OPG mRNA and protein expressions were unchanged in HG group with or without ß-GP after 2 weeks. However, after 4 weeks, OPG mRNA and protein expressions were significantly lower in HG group with ß-GP. No significant expression changes were observed in RANKL, RANK, or TRAIL during the experiment. After 4 weeks of treatment in HG group containing ß-GP and rhBMP-7, an inhibitor of vascular calcification, OPG expressions were maintained. Furthermore, mRNA expression of alkaline phosphatase (ALP), a marker of vascular mineralization, was lower in the presence of rhBMP-7. These results suggest that low OPG levels after long term HG and phosphate stimulation might reduce the binding of OPG to RANKL and TRAIL, and these changes could increase osteo-inductive VSMC differentiation, especially vascular mineralization reflected by increased ALP activity during vascular calcification.

Ultrasonographic findings relating to lymph node metastasis in single micropapillary thyroid cancer.

BACKGROUND: In thyroid cancer, preoperative ultrasonography (US) is performed to detect the primary tumor and lymph node metastasis (LNM), which are related to prognosis. This study examined the relationships between specific US findings and LNM in micropapillary thyroid cancer (MPTC). METHODS: Data on 220 patients with solitary MPTC who underwent total thyroidectomy and neck dissection between 2008 and 2009 were evaluated retrospectively. We classified the US findings according to the nature, shape, echogenicity, extent, margin, and calcification of the primary tumor and evaluated the correlations between these findings and those of LNM. RESULTS: Hypoechogenicity (odds ratio = 2.331, P = 0.025) and marked hypoechogenicity (OR = 4.032, P = 0.016) of MPTC were risk factors for central LNM. All of the patients with lateral cervical LNM showed hypoechogenicity or marked hypoechogenicity. Hypoechogenicity (odds ratio = 5.349, P = 0.047) and other types of calcification (odds ratio = 2.495, P = 0.010) were significant risk factors for lateral cervical LNM. CONCLUSIONS: Specific sonographic findings (hypoechogenicity or marked hypoechogenicity, and calcification) suggest LNM.

Comparison of serum ferritin and vitamin d in association with the severity of nonalcoholic Fatty liver disease in korean adults.

BACKGROUND: Increased serum ferritin and decreased vitamin D levels associated with nonalcoholic fatty liver disease (NAFLD). However, their association with the severity of NAFLD has not been fully evaluated. The aim of this study was to compare the association of serum ferritin and 25(OH)D3 levels with the severity of ultrasonographically detected NAFLD (US-NAFLD) and hepatic steatosis defined by fatty liver index (FLI) in Korean adults. METHODS: A cross-sectional analysis of clinical and anthropometric data, including serum ferritin and 25(OH)D3, from men (n=295) and women (n=263) who underwent a routine health check-up in 2012. RESULTS: In men, with an increase in the quartile of serum ferritin level, the incidences of subjects with metabolic syndrome (P=0.002), US-NAFLD (P=0.041), and FLI ≥60 (P=0.010) were significantly elevated. In women, the incidence of subjects with US-NAFLD was also significantly elevated with increases in the serum ferritin quartile (P=0.012). Regarding 25(OH)D3, no statistical differences were observed among the different quartiles in either gender. Serum ferritin level significantly increased as the severity of US-NAFLD increased (P<0.001); however, no significant differences in 25(OH)D3 level were observed in men. No significant differences in either serum ferritin or 25(OH)D3 level were observed among women with different levels of severity of US-NAFLD. CONCLUSION: Increased serum ferritin level showed a closer association with severity of NAFLD compared with level of serum vitamin D, suggesting that serum ferritin level may be a better marker than vitamin D level for predicting the severity of US-NAFLD and hepatic steatosis in a clinical setting.

Tumor location-dependent skip lateral cervical lymph node metastasis in papillary thyroid cancer.

BACKGROUND: Lateral cervical lymph node metastasis without central lymph node (CLN) metastasis is not infrequent in papillary thyroid cancer (PTC). This study was designed to investigate the frequency and pattern of skip metastasis in PTC. METHODS: We reviewed 131 patients who underwent total thyroidectomy with CLN dissection and selective lymph node dissection. Tumor location was classified in 3 areas (upper, middle, and lower third) based on preoperative ultrasonographic findings. RESULTS: All skip metastases occurred in patients whose tumors had been on the upper part of the thyroid (p < .001). Among 9 patients with skip metastasis, level III lymph nodes (66.7%) were the lymph nodes that were most frequently involved in skip metastasis. CONCLUSION: Primary tumors in the upper portion of the thyroid are closely linked to skip metastasis. Careful preoperative evaluation of lateral cervical lymph nodes is suggested when a tumor is in the upper portion.

Nodal status of central lymph nodes as a negative prognostic factor for papillary thyroid carcinoma.

BACKGROUND: The status of metastatic lymph nodes, including the size and extracapsular spread (ECS), in papillary thyroid cancer (PTC) has not been well established. This study evaluated the correlation between the specific status of central lymph node metastases (CLNM) and negative prognostic factors. METHODS: We reviewed 243 patients who underwent total thyroidectomy and neck dissection. The CLNM slides were reviewed and the relationship between the CLNM status and risk factors was analyzed. RESULTS: CLNM were found in 111 patients. ECS (+) was related to a large tumor, high number of CLNM, and large node (P < 0.05). Tumor size and number of CLNM were related to the ECS rate (OR = 3.861 and 2.491, respectively; P < 0.01) in a multivariate analysis. Large nodes (≥ 6 mm) were related to large tumor size, extrathyroidal extension, number of CLNM, and lateral cervical lymph node metastasis (LNM). Tumor size and LNM (OR = 4.519 and 7.811, respectively; P < 0.05) were related to large nodes in a multivariate analysis. CONCLUSIONS: ECS was related to node size, tumor size, and number of CLNM. Node size was related to tumor size and LNM. Thus, specific nodal status is a possible prognostic factor for PTC.

Frozen biopsy of central compartment in papillary thyroid cancer: quantitative nodal analysis.

BACKGROUND: Nodal metastasis in papillary thyroid cancer (PTC) usually occurs in the central compartment of the ipsilateral neck and spreads laterally. The purpose of this study was to evaluate the diagnostic accuracy of frozen biopsy for quantitative nodal evaluation of central neck metastasis in PTC. METHODS: In all, 252 patients with PTC underwent total thyroidectomy with bilateral central neck dissection (CND). All tissues from ipsilateral CND were examined by frozen biopsy. RESULTS: Among them, 53% of patients had central neck metastasis. The sensitivity and specificity of frozen biopsy for central neck metastasis were 92% and 99%, respectively. The positive predictive value and the negative predictive value were 99% and 84%, respectively. The diagnostic accuracy for the exact number of metastatic nodes was 91% compared to permanent biopsy. CONCLUSIONS: Frozen biopsy for quantitative analysis of central compartment is a useful tool for the precise evaluation of central lymphatic status intraoperatively with a high sensitivity and specificity.

Reactive oxygen and nitrogen species in pathogenesis of vascular complications of diabetes.

Macrovascular and microvascular diseases are currently the principal causes of morbidity and mortality in subjects with diabetes. Disorders of the physiological signaling functions of reactive oxygen species (superoxide and hydrogen peroxide) and reactive nitrogen species (nitric oxide and peroxynitrite) are important features of diabetes. In the absence of an appropriate compensation by the endogenous antioxidant defense network, increased oxidative stress leads to the activation of stress-sensitive intracellular signaling pathways and the formation of gene products that cause cellular damage and contribute to the vascular complications of diabetes. It has recently been suggested that diabetic subjects with vascular complications may have a defective cellular antioxidant response against the oxidative stress generated by hyperglycemia. This raises the concept that antioxidant therapy may be of great benefit to these subjects. Although our understanding of how hyperglycemia-induced oxidative stress ultimately leads to tissue damage has advanced considerably in recent years, effective therapeutic strategies to prevent or delay the development of this damage remain limited. Thus, further investigation of therapeutic interventions to prevent or delay the progression of diabetic vascular complications is needed.