Parenchymal microcalcifications in the thyroid gland: Clinical significance and management strategy.

This study is firstly, to investigate the presence of microcalcification among the patients who underwent thyroid ultrasound and biopsy and to evaluate the incidence of intrathyroid lymphatic spread and cervical lymph node metastasis of thyroid cancer with thyroid microcalcifications. Also, we compared the diagnostic performance between fine needle aspiration (FNA) and core needle biopsy (CNB) for assessing parenchymal microcalcifications in the thyroid gland. We retrospectively assessed total 66 patients with thyroid microcalcifications on ultrasound. The histopathologic characteristics of the surgical specimens considered as the gold standard for diagnosing malignancy. Patients with surgically proven malignancy were evaluated for multifocality, intrathyroid lymphatic spread in the opposite lobe, or cervical lymph node metastasis. Among the 66 confirmed patients, 53 patients had malignant lesions (80.3%) and 13 patients had benign lesions (19.7%). The pathologic results of the 44 patients who underwent total thyroidectomy. Among them, 33 patients (75%) showed multifocality, 30 patients (68.2%) showed intrathyroid lymphatic tumor spread. CNB was performed on 41 patients, and FNA was performed on 54 patients. Both CNB and FNA were performed on 29 patients. There were no statistical differences in terms of diagnostic performance between CNB and FNA. Thyroid microcalcifications demonstrate a high prevalence of malignancy. Both CNB and FNA demonstrate similar diagnostic accuracies.

Dysfunctional pancreatic cells differentiated from induced pluripotent stem cells with mitochondrial DNA mutations.

Diabetes mellitus (DM) is a serious disease in which blood sugar levels rise abnormally because of failed insulin production or decreased insulin sensitivity. Although many studies are being conducted for the treatment or early diagnosis of DM, it is not fully understood how mitochondrial genome (mtDNA) abnormalities appear in patients with DM. Here, we induced iPSCs from fibroblasts, PBMCs, or pancreatic cells of three patients with type 2 DM (T2D) and three patients with non-diabetes counterpart. The mtDNA mutations were detected randomly without any tendency among tissues or patients. In T2D patients, 62% (21/34) of iPSC clones harbored multiple mtDNA mutations, of which 37% were homoplasmy at the 100% mutation level compared to only 8% in non-diabetes. We next selected iPSC clones that were a wild type or carried mutations and differentiated into pancreatic cells. Oxygen consumption rates were significantly lower in cells carrying mutant mtDNA. Additionally, the mutant cells exhibited decreased production of insulin and reduced secretion of insulin in response to glucose. Overall, the results suggest that screening mtDNA mutations in iPSCs from patients with T2D is an essential step before pancreatic cell differentiation for disease modeling or autologous cell therapy. [BMB Reports 2022; 55(9): 453-458].

Down-regulated surfactant protein B in obese asthmatics.

BACKGROUND: Obesity is a common comorbid condition in adult asthmatics and known as a feature of asthma severity. However, the molecular mechanism under obesity-induced inflammation has not yet been fully understood. OBJECTIVE: Considering the essential role of hydrophobic surfactant protein B (SP-B) in lung function, SP-B was targeted to examine its involvement in the development of obesity-induced airway inflammation in asthmatics. METHODS: The aim was to examine an alteration in circulating SP-B according to obesity in adult asthmatics, 129 asthmatics were enrolled and classified into 3 groups (obese, overweight and normal-weight groups) according to body mass index (BMI). Circulating SP-B levels were determined by enzyme-linked immunosorbent assay. Four single nucleotide polymorphisms of SFTPB gene were genotyped. Serum ceramide levels were measured by liquid chromatography-tandem mass spectrometry. RESULTS: Significantly lower serum SP-B levels were noted in the obese group than in the overweight or normal-weight group (p = .002). The serum SP-B level was significantly correlated with serum levels of C18:0 ceramide and transforming growth factor beta 1 as well as BMI (r = -0.200; r = -0.215; r = -0.332, p < .050 for all). An inverse correlation was noted between serum SP-B and fractional exhaled nitric oxide levels in female asthmatics (r = -0.287, p = .009). Genetic predisposition of the SFTPB gene at 9306 A>G to the obese and overweight groups was noted. CONCLUSION: Obesity altered ceramide metabolism leading to pulmonary surfactant dysfunction and impaired resolution of airway inflammation, finally contributing to the phenotypes of obese asthmatics.

Study of hospitalization and mortality in Korean diabetic patients using the diabetes complications severity index.

BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) is expected to increase from 7.7% in 2017 to 8.4% in 2045 worldwide. Diabetes complications contribute to morbidity and mortality. To evaluate whether the diabetes complications severity index (DCSI) was associated with increased risks of mortality and hospitalization. METHODS: A retrospective cohort study was conducted using the National Health Insurance Database (NHID) sample cohort of 1,102,047 patients (2002-2015) in Korea. Diabetes complications were evaluated at 2 years after the initial diagnosis and during the subsequent follow-up period (mean duration 6.56 ± 2.81 years). The type and severity of complications were evaluated on the basis of the International Classification of Disease Ninth (ICD-9) codes used in DCSI with 7 categories and 55 subcategories of complications. The Cox proportional hazard and Poisson regression models were used to evaluate the mortality and hospitalization rates. The incidence and relative risk of diabetes complications as well as the risk of mortality and hospitalization were the main outcome measures. RESULTS: A total of 27,871 patients were finally included and grouped by the number of complications present at 2 years. Four hundred ninety patients (5.37%) died without complications, 659 (7.31%) died with one complication and 1153 (11.85%) died with two or more complications. As DCSI at index date increased, the risk of additional new diabetes complications increased by 26% [relative risk (RR) 1.26, 95% CI 1.25-1.27]. The risks of mortality and hospitalization were linearly related to DCSI [hazard ratio 1.13 (95% CI 1.11-1.16), relative risk 1.04 (95% CI 1.03-1.06)]. CONCLUSIONS: Patients with higher incidence and severity of diabetes complications have increased risks of mortality and hospitalization.

Metabolic shift favoring C18:0 ceramide accumulation in obese asthma.

BACKGROUND: Obesity associated with various complications has increased worldwide. Body weight gain alters lipid metabolites (especially sphingolipids) contributing to obesity-induced inflammation. However, the significance of the metabolites in the development of obese asthma is not yet clear. METHODS: The serum levels of sphingolipids were measured using liquid chromatography-tandem mass spectrometry in obese controls (n = 7) and patients with asthma: the obese group (BMI > 25 kg/m2 , n = 13) vs the nonobese (n = 28) group. To examine the relationship between metabolic changes in sphingolipids and macrophage polarization, public microarray data were analyzed. In addition, the alteration in sphingolipid metabolism was investigated in wild-type BALB/c mice fed a high-fat diet. RESULTS: The obese asthma had higher levels of serum C18:0 and C20:0 ceramides than the nonobese asthma group (P = .028 and P = .040, respectively). The value of the serum C18:0 ceramide (184.3 ng/mL) for discriminating the obese asthma from the nonobese asthma group showed 53.9% sensitivity and 85.7% specificity (AUC = 0.721, P = .024). The microarray data showed significantly increased ceramide synthesis and metabolic shift to ceramide accumulation during M1 macrophage polarization in humans. Increased airway hyperresponsiveness, M1 macrophage polarization, and C18:0 ceramide levels were noted in obese mice, but not in nonobese mice. Increased expression of ceramide synthase (CerS) 1 and CerS6 (not CerS2) was noted in lung tissues of obese mice. CONCLUSION: Alteration in sphingolipid metabolism favoring ceramide accumulation (especially long-chain ceramides) may contribute to developing obese asthma.

Ceramide/sphingosine-1-phosphate imbalance is associated with distinct inflammatory phenotypes of uncontrolled asthma.

BACKGROUND: Asthma is associated with inflammatory dysregulation, but the underlying metabolic signatures are unclear. This study aimed to classify asthma inflammatory phenotypes based on cellular and metabolic features. METHODS: To determine cellular and metabolic profiles, we assessed inflammatory cell markers using flow cytometry, sphingolipid (SL) metabolites using LC-MS/MS, and serum cytokines using ELISA. Targeted gene polymorphisms were determined to identify genetic predispositions related to the asthma inflammatory phenotype. RESULTS: In total, 137 patients with asthma and 20 healthy controls (HCs) were enrolled. Distinct cellular and metabolic profiles were found between them; patients with asthma showed increased expressions of inflammatory cell markers and higher levels of SL metabolites compared to HCs (P < .05 for all). Cellular markers (CD66+ neutrophils, platelet-adherent eosinophils) and SL metabolic markers (C16:0 and C24:0 ceramides) for uncontrolled asthma were also identified; higher levels were observed in uncontrolled asthma compared to controlled asthma (P < .05 for all). Asthmatics patients with higher levels of CD66+ neutrophils had lower FEV1(%), higher ACQ (but lower AQLO) scores, and higher sphingosine and C16:0 ceramide levels compared to those with low levels of CD66+ neutrophils. Asthmatics patients with higher levels of platelet-adherent eosinophils had higher S1P levels compared to those with lower levels of platelet-adherent eosinophils. Patients carrying TT genotype of ORMDL3 had more CD66+ neutrophils; those with AG/ GG genotypes of SGMS1 exhibited higher platelet-adherent eosinophils. CONCLUSION: Patients with uncontrolled asthma possess distinct inflammatory phenotypes including increased CD66+ neutrophils and platelet-adherent eosinophils, with an imbalanced ceramide/S1P rheostat, potentially involving ORMDL3 and SGMS1 gene polymorphisms. Ceramide/S1P synthesis could be targeted to control airway inflammation.

Safety and Efficacy of Radiofrequency Ablation for Nonfunctioning Benign Thyroid Nodules in Children and Adolescents in 14 Patients over a 10-Year Period.

PURPOSE: To evaluate the efficacy and safety of radiofrequency (RF) ablation for nonfunctioning benign thyroid nodules in children and adolescents. MATERIALS AND METHODS: Fourteen pediatric patients (10 female, 4 male; mean age 15.7 ± 2.3 years, range 12-19 years) with nonfunctioning benign thyroid nodules (mean longest diameter 3.7 ± 1.1 cm, range 2.0-5.6 cm) treated with the use of RF ablation from 2005 to 2015 were evaluated. The inclusion criteria for RF ablation therapy were (i) age <20 years, (ii) benign cytological confirmation by ≥2 separate fine-needle aspiration or core needle biopsies, (iii) pressure symptoms or cosmetic problems caused by thyroid nodules, (iv) absence of any suspicious feature as determined with the use of ultrasound (US), (v) normal serum levels of thyroid hormone and thyrotropin, and (vi) follow-up of >6 months. RF ablation was performed with the use of an RF generator and an 18-gauge internally cooled electrode. RF ablation was performed under local anesthesia without conscious sedation or general anesthesia. Changes in nodules on follow-up US, changes in symptomatic and cosmetic scores, and complications arising during or after RF ablation were evaluated. RESULTS: Mean follow-up period was 36.9 ± 21.7 months (range 6-69 months). At last follow-up visits, mean longest nodule diameter and volume had decreased significantly (3.7 ± 1.1 cm vs 1.4 ± 0.9 cm and 14.6 ± 13.3 mL vs 1.7 ± 4.4 mL; P < 0.001). Both cosmetic and compressive symptoms significantly improved (3.8 ± 0.6 vs 1.4 ± 0.6 and 3.4 ± 1.0 vs 0.1 ± 0.4; P < 0.001). The mean number of ablation sessions was 2.1 ± 1.2 (range 1-5 sessions) and no major complication was encountered during or after RF ablation. CONCLUSIONS: RF ablation might be a safe and effective treatment modality for nonfunctioning benign thyroid nodules in children and adolescents.

Effects of sarpogrelate on microvascular complications with type 2 diabetes.

Background Diabetes is a major cause of microvascular complications. Renin-angiotensin-aldosterone blockers have been known to have the benefits of delaying onset and progression of diabetic complications including nephropathy. Objective To evaluate the effect of sarpogrelate, an antiplatelet agent, on the new onset diabetic complications in patients with type 2 diabetes mellitus. Setting A 1108-bed tertiary university hospital in Korea. Methods A retrospective cohort study was conducted using electronic medical records between 2010 and 2015 in Korea. The study cohort of the propensity score matched patients with or without sarpogrelate was evaluated for the diabetic complications identified with the diagnosis codes in T2DM patients on the metformin based antidiabetic therapy. Nephropathy was further evaluated for progression of kidney function. Main outcome measure The incidence of composite microvascular complications included nephropathy, neuropathy, and retinopathy. Results The 1:2 propensity score matched 478 out of 14,440 patients were included in the final analysis with or without sarpogrelate (162 vs. 316 patients). The incidence of nephropathy, neuropathy, and retinopathy was 1.23% versus 5.38% (HR 0.21, 95% CI 0.05-0.92), 1.23% versus 4.43% (HR 0.26, 95% CI 0.06-1.14), and 6.17% versus 6.33% (HR 0.93, 95% CI 0.43-1.97) with sarpogrelate and without sarpogrelate, respectively. Changes in the estimated glomerular filtration rate and urine albumin creatinine ratio were not significantly different between the groups. Conclusion In Korean patients, sarpogrelate, an antiplatelet agent, was associated with reducing the incidence and progression of nephropathyin type 2 diabetes, but not associated with the composite endpoints including neuropathy and retinopathy.

Radiofrequency ablation of small follicular neoplasms: initial clinical outcomes.

BACKGROUND: In thyroid gland, radiofrequency ablation (RFA) has been applied to both recurrent cancers and benign nodules, although, according to the American Thyroid Association (ATA) and the Korean Society of Thyroid Radiology (KSThR) guidelines, surgery is the first-line treatment for follicular neoplasm. However, it has been argued that follicular neoplasm with lower risk of malignancy can be managed by close follow-up. In this study, we evaluated the effectiveness of RFA of small follicular neoplasms, examining reductions in volume and related clinical problems, and making observations over long-term follow-up. METHODS: We evaluated 10 follicular neoplasms in 10 patients who were treated with RF ablation between 2009 and 2011. A RF generator and an 18-gauge internally cooled electrode were used to perform complete ablation of the whole nodules. Changes in nodules or ablated zones on follow-up ultrasound, and complications during and after RF ablation were evaluated. RESULTS: The mean follow-up period was 66.4 ± 5.1 months (range: 60-76 months). In eight patients, single session of RF ablation was sufficient, while two patients required two sessions. There was a significant reduction in the mean volume (99.5 ± 1.0%) of lesions, with eight ablated lesions (8/10, 80%) disappearing completely on follow-up. No recurrences were found in any ablated zones at last follow-up. Transient mild neck pain (n = 6) occurred during the procedure without requiring any medication. CONCLUSION: In addition to active surveillance, RF ablation may be an effective and safe alternative for the management of patients with small (<2 cm) follicular neoplasm suspected on thyroid biopsy and who strongly refuse surgery.

Exploration of the Sphingolipid Metabolite, Sphingosine-1-phosphate and Sphingosine, as Novel Biomarkers for Aspirin-exacerbated Respiratory Disease.

Sphingolipid (SL) metabolites have been suggested to be important inflammatory mediators in airway inflammation and asthma. However, little is known about SL metabolites in aspirin-exacerbated respiratory disease (AERD). We aimed to explore the potential AERD biomarkers by conducting lipidomics targeting SL metabolites. The levels of SL metabolites in serum and urine samples from 45 AERD patients and 45 aspirin-tolerant asthma (ATA) patients were quantified through mass spectrometry. During the lysine-aspirin bronchoprovocation test (ASA-BPT), the levels of serum sphingomyelin (SM) were significantly decreased in AERD (P < 0.05) but not in ATA. The serum SM levels were positively correlated with airway responsiveness to methacholine. At the basal status before the ASA-BPT, the levels of serum sphingosine-1-phosphate (S1P) and urine sphingosine were significantly higher in the AERD patients compared with that of ATA patients (P < 0.001) and were positively correlated with a greater decrease in FEV1 (%) values following the ASA-BPT test (P < 0.001 for each), and with serum periostin level (P < 0.05 for each). This study is the first to evaluate serum S1P and urine sphingosine as potential biomarkers of AERD as well as to examine the metabolic disturbance of SL in AERD patients.

Ultrastructural comparison of porcine putative embryonic stem cells derived by in vitro fertilization and somatic cell nuclear transfer.

The ultrastructure of porcine putative embryonic stem cells and porcine fetal fibroblasts (PFFs) was analyzed by transmission electron microscopy. The aim of this study was to compare the features of organelles in in vitro fertilization (IVF) derived porcine embryonic stem cells (IVF-pESCs) and somatic cell nuclear transfer (SCNT) derived pESCs (SCNT-pESCs). Also, the features of organelles in high-passage IVF-pESCs were compared with those in low-passage cells. The ultrastructure of PFFs showed rare microvilli on the cell surfaces, polygonal or irregular nuclei with one to two reticular-shaped nucleoli and euchromatin, low cytoplasm-to-nucleus ratios, rare ribosomes, rare rough endoplasmic reticulum, elongated mitochondria, rich lysosomes and rich phagocytic vacuoles. IVF-pESCs showed rare microvilli on the cell surfaces, round or irregular nuclei with one to two reticular-shaped nucleoli and euchromatin, low cytoplasm-to-nucleus ratios, rich ribosomes, long stacks of rough endoplasmic reticulum, elongated mitochondria, rare lysosomes and rare autophagic vacuoles. By contrast, SCNT-pESCs showed rich microvilli with various lengths and frequencies on the cell surfaces, polygonal nuclei with one reticular shaped nucleoli and heterochromatin, high cytoplasm-to-nucleus ratios, rare ribosomes, rare rough endoplasmic reticulum, round mitochondria, rich lysosomes and rich phagocytic vacuoles with clear intercellular junctions. Furthermore, high-passage IVF-pESCs showed irregularly shaped colonies, pyknosis and numerous lysosomes associated with autophagic vacuoles showing signs of apoptosis. In conclusion, this study confirms that the ultrastructural characteristics of pESCs differ depending on their origin. These ultrastructural characteristics might be useful in biomedical research using pESCs, leading to new insights regarding regenerative medicine and tissue repair.

Putative embryonic stem cells derived from porcine cloned blastocysts using induced pluripotent stem cells as donors.

The establishment of porcine embryonic stem cells (ESCs) would have great impact in biomedical studies and preclinical trials through their use in genetic engineering. However, authentic porcine ESCs have not been established until now. In this study, a total of seven putative ESC lines were derived from porcine embryos of various origins, including in vitro fertilization, parthenogenetic activation, and, in particular, induced pluripotent stem (iPS) nuclear transfer (NT) from a donor cell with induced pluripotent stem cells (iPSCs). To characterize these cell lines, several assays including an assessment of intensive alkaline phosphatase activity, karyotyping, embryoid body formation, expression analysis of the pluripotency-associated markers, and the three germ layerassociated markers were performed. Based on quantitative polymerase chain reaction, the expression levels of REX1 and FGFR2 in iPS-NT lines were higher than those of cells of other origins. Additionally, only iPS-NT lines showed multiple aberrant patterns of nuclear foci elucidated by immunofluorescence staining of H3K27me3 as a marker of the state of X chromosome inactivation and a less mature form of mitochondria like naive ESCs, by transmission electron microscopy. Together, these data suggested that established putative porcine ESC lines generally exhibited a primed pluripotent state, like human ESCs. However, iPS-NT lines have especially unique characteristics distinct from other origins because they have more epigenetic instability and naive-like mitochondrial morphology than other putative ESC lines. This is the first study to establish and characterize the iPSC-derived putative ESC lines and compare them with other lines derived from different origins in pigs.

Effect of ganglioside GT1b on the in vitro maturation of porcine oocytes and embryonic development.

Ganglioside is an acidic glycosphingolipid with sialic acids residues. This study was performed to investigate the effect and mechanism of ganglioside GT1b in porcine oocytes in the process of in vitro maturation (IVM) and preimplantation development. Metaphase II (MII) rates were significantly (P < 0.05) different between the control group and the 5 nM GT1b treatment group. Intracellular glutathione (GSH) levels in oocytes matured with 5 nM and 20 nM and GT1b decreased significantly (P < 0.05). The 10 nM group showed a significant (P < 0.05) decrease in intracellular reactive oxygen species (ROS) levels compared with the control group. Subsequently, the level of intracellular Ca(2+) in oocytes treated with different concentrations of GT1b was measured. Intracellular Ca(2+) was significantly (P < 0.05) increased with a higher concentration of GT1b in a dose-dependent manner. Real-time PCR was performed and showed that the expression of bradykinin 2 receptor (B2R) and calcium/calmodulin-dependent protein kinase II delta (CaMKIIδ) in cumulus cells was significantly (P < 0.05) decreased in the 20 nM GT1b treatment group. Treatment with 5 nM GT1b significantly (P < 0.05) decreased the expression of CaMKIIδ. In oocytes, treatment with 5 nM GT1b significantly (P < 0.05) decreased CaMKIIγ and POU5F1 (POU domain, class 5, transcription factor 1). However, treatment with 20 nM GT1b significantly (P < 0.05) increased the expression of POU5F1. Finally, embryonic developmental data showed no significant differences in the two experiments (parthenogenesis and in vitro fertilization). In conclusion, the results of the present study indicated that GT1b plays an important role in increasing the nuclear maturation rate and decreasing the intracellular ROS levels during IVM. However, GT1b inhibited maturation of the cytoplasm by maintaining intracellular Ca(2+) in the process of oocyte maturation regardless of the cell cycle stage. Therefore, GT1b is thought to act on another mechanism that controls intracellular Ca(2+).

Pathology Reporting of Thyroid Core Needle Biopsy: A Proposal of the Korean Endocrine Pathology Thyroid Core Needle Biopsy Study Group.

In recent years throughout Korea, the use of ultrasound-guided core needle biopsy (CNB) has become common for the preoperative diagnosis of thyroid nodules. However, there is no consensus on the pathology reporting system for thyroid CNB. The Korean Endocrine Pathology Thyroid Core Needle Biopsy Study Group held a conference on thyroid CNB pathology and developed guidelines through contributions from the participants. This article discusses the outcome of the discussions that led to a consensus on the pathology reporting of thyroid CNB.

Changes in the spinal curvature, degree of pain, balance ability, and gait ability according to pregnancy period in pregnant and nonpregnant women.

[Purpose] The aim of this study was to investigate the changes in pain intensity, spinal curvature, and balance and gait ability according to the pregnancy period. [Subjects] Nineteen pregnant women and fifteen nonpregnant women were recruited in this study. [Methods] The pain intensity, spinal curvature, gait, and balance of pregnant women were measured according to the pregnant period (2nd and 3rd trimester). The changes in the pregnant women were also compared with those in the nonpregnant women. [Results] The pain intensity and spinal curvature in the third trimester of pregnancy were significantly increased compared with the second trimester. Only the lumbar spine curvature in the third trimester pregnancy was significantly greater in the pregnant women than in non-pregnant women. The gait velocity and cadence in the third trimester of pregnancy showed a significant decrease compared with the second trimester. The gait speed in the second and third trimester of pregnancy showed a significant decrease in the pregnant women compared with nonpregnant women. Balance in the third trimester of pregnancy showed significant improvement compared with the second trimester. The balance of the pregnant women showed a significant decrease compare with that nonpregnant women only on unstable surfaces. [Conclusion] These research findings can be used as basic data for health promotion programs for sound daily activities in pregnant women.

The ultrasonography features of hyalinizing trabecular tumor of the thyroid gland and the role of fine needle aspiration cytology and core needle biopsy in its diagnosis.

BACKGROUND: Hyalinizing trabecular tumor (HTT) of the thyroid gland is a rare, benign neoplasm of follicular cell origin. Misdiagnosis of HTT as either papillary or medullary thyroid carcinoma after fine-needle aspiration (FNA) may lead to unnecessary surgery. PURPOSE: To evaluate the ultrasonography (US) findings of HTT of the thyroid gland and the role of FNA cytology and core needle biopsy (CNB) in its diagnosis. MATERIAL AND METHODS: Data from 24 patients with a histopathological diagnosis of HTT between January 2000 and May 2013 were retrospectively analyzed. US findings were categorized according to shape, margin, orientation, echogenicity, composition, calcification, and vascularity. Cytologic and histologic results of FNA, CNB, and surgery were reviewed. RESULTS: US revealed the following tumor features: oval-to-round (24/24), solid (22/24), smooth margin (21/24), hypoechoic or marked hypoechogenicity (18/24), and peri- and/or intranodular vascularity (17/17). Malignant US features such as marked hypoechogenicity (n = 7) and a spiculated margin (n = 3) were also observed. Final confirmation was by surgery in 22 patients and by CNB in two patients. All 19 patients who underwent FNA were initially misdiagnosed, including 12 with malignancies and five with atypia of undetermined significance. All four patients who underwent CNB were correctly diagnosed with HTT. The histology of CNB specimens suggested HTT, which was confirmed by immunostaining of MIB-1. CONCLUSION: HTT should be suspected when the cytological diagnosis of papillary thyroid carcinoma is made after FNA without malignant US findings. CNB could prevent unnecessary surgery for HTT.

Single-session treatment of benign cystic thyroid nodules with ethanol versus radiofrequency ablation: a prospective randomized study.

PURPOSE: To compare volume reduction of single-session ethanol ablation (EA) and radiofrequency (RF) ablation for cystic thyroid nodule treatment. MATERIALS AND METHODS: All patients gave written informed consent to participate in this prospective institutional review board-approved study. From May 6, 2010, to August 8, 2011, in this single-institutional, noninferiority trial, 50 patients, each with a single cystic thyroid nodule, were randomly assigned to EA (25 patients; mean age for women, 45.7 years, and for men, 37.5 years) or RF ablation (25 patients; mean age for women, 45.1 years, and for men, 43.7 years) treatment. Internal fluid was aspirated prior to EA or RF ablation. Primary end point was the volume reduction ratio (percentage) at 6-month follow-up; the noninferiority margin was chosen as -8% (EA minus RF ablation). Secondary end points included therapeutic success rate, improvement of symptoms and cosmetic problems, and number of major complications. Analysis was performed primarily in intention-to-treat manner. A one-sided 95% confidence interval (CI) for the mean difference in volume reduction ratio 6 months after treatment was calculated to test for noninferiority. Subsequent superiority comparison of EA with RF ablation on a condition of establishment of the noninferiority of EA to RF ablation was preplanned and used two-sided 95% CI of the outcome difference. RESULTS: The mean volume reduction was 96.9% in EA and 93.3% in RF ablation (n = 21 for each) (difference, 3.6%; lower bound of the one-sided 95% CI of the difference, 1.2%), thus demonstrating the noninferiority of EA to RF ablation. Two-sided 95% CI of the outcome difference was 0.7% to 6.5%, demonstrating significant superiority of EA to RF ablation. All patients demonstrated therapeutic success (P > .99). Mean symptom and cosmetic scores showed no significant difference in either group (P = .806 and P = .682, respectively). There were no major complications (P > .99). CONCLUSION: EA may be the first-line treatment modality for cystic thyroid nodules, which has comparable therapeutic efficacy to, but is less expensive than, RF ablation.

Diagnostic accuracy of fine-needle aspiration versus core-needle biopsy for the diagnosis of thyroid malignancy in a clinical cohort.

OBJECTIVES: To retrospectively compare the accuracy of fine-needle aspiration (FNA) and core-needle biopsy (CNB) for the diagnosis of thyroid malignancy METHODS: We evaluated the results of FNA and CNB in 555 consecutive thyroid nodules with final diagnoses (malignancy 318, benign 237). All patients underwent FNA and CNB simultaneously for each nodule. We assessed the sensitivity, specificity and accuracy of FNA, CNB and FNA/CNB for the diagnosis of thyroid malignancy. RESULTS: The sensitivity of FNA, CNB and FNA/CNB for thyroid malignancy was 68.6%, 86.8% and 90.6%, specificity 100%, 99.2% and 99.2%, and accuracy 82.0%, 92.1% and 94.2%, respectively. The sensitivity and accuracy of CNB or FNA/CNB for thyroid malignancy were significantly higher than those of FNA (P < 0.001). Compared with CNB alone, FNA/CNB was more accurate for thyroid malignancy only in small nodules less than 1 cm (P < 0.001). CONCLUSIONS: Our clinical cohort data demonstrated that CNB was more accurate for the diagnosis of thyroid malignancy than FNA, and FNA/CNB was more accurate than CNB alone in small thyroid nodules. CNB will play a complementary role in optimal surgical decision-making and the management of thyroid nodules. KEY POINTS: • CNB was more accurate for the diagnosis of malignancy than FNA. • Combined FNA/CNB was more accurate than CNB alone in small thyroid nodules. • CNB should play at least a complementary role in managing thyroid nodules.

Core-needle biopsy is more useful than repeat fine-needle aspiration in thyroid nodules read as nondiagnostic or atypia of undetermined significance by the Bethesda system for reporting thyroid cytopathology.

BACKGROUND: Thyroid nodules with fine-needle aspiration (FNA) readings of nondiagnostic or atypia of undetermined significance (AUS), also referred to as follicular lesion of undetermined significance (FLUS) are problematic for their optimal management. The usefulness of performing a core-needle biopsy (CNB) to clarify whether these nodules are benign or malignant has not been established. The purpose of the present study was to determine whether CNB provides better diagnostic information than repeat FNA (rFNA) in thyroid nodules having nondiagnostic or AUS/FLUS readings. MATERIALS AND METHODS: The Bethesda System for Reporting Thyroid Cytopathology was used for FNA readings and for CNB readings. The study included 225 thyroid nodules from 220 consecutive patients who previously had nondiagnostic (Group N-DIAG, n=64) or AUS/FLUS (Group AF, n=161) FNA readings. All patients simultaneously underwent rFNA and CNB of each nodule. The nondiagnostic and AUS/FLUS readings by rFNA and by CNB were compared. The diagnostic sensitivities of rFNA and CNB for malignancy in thyroid nodules were also assessed. Statistical analysis was performed using a McNemar's test. RESULTS: In N-DIAG Group, the nondiagnostic readings for the CNBs were lower than that those for rFNAs (1.6% vs. 28.1%, p<0.001). In the AF Group, the AUS/FLUS readings for the CNBs were lower than those for the rFNAs (23.6% vs. 39.8%, p<0.001). The inconclusive diagnoses (nondiagnostic or AUS/FLUS) for the CNBs were lower than those for the rFNAs in Group N-DIAG (12.5% vs. 45.3%, p<0.001) and Group AF (26.7% vs. 49.1%, p<0.001). The sensitivity of CNB for thyroid malignancy was higher than that of rFNA in Group N-DIAG (100% vs. 71.4%, p=0.125) and Group AF (78.5% vs. 55.4%, p<0.001). CONCLUSION: After patients have had one FNA of a thyroid nodule yielding inconclusive diagnostic results (nondiagnostic or AUS/FLUS), CNB is more useful than rFNA for reducing the frequency of inconclusive diagnostic results. CNB will improve the diagnostic performance for malignancy more than rFNA in thyroid nodules that on the first FNA had nondiagnostic or AUS/FLUS readings.

Radiofrequency ablation (RFA) of benign thyroid nodules in patients with incompletely resolved clinical problems after ethanol ablation (EA).

BACKGROUND: Although ethanol ablation (EA) is effective, refractory cases have been reported in 5-25% of patients, with a marked decline in efficacy on subsequent reattempt. The aim of this study was to evaluate the role of radiofrequency ablation (RFA) after EA of benign thyroid nodules in patients with incompletely resolved initial clinical problems. METHODS: Among 137 patients with 137 benign thyroid nodules who underwent EA, 27 patients (M:F = 5:22; mean age = 38 years, range = 21-60 years) underwent additional RFA if all of the following criteria were fulfilled: (1) complaint of incompletely resolved clinical problems, (2) demonstration of remaining solid component with internal vascularity on 1-month follow-up power Doppler US, and (3) patient desire for additional treatment. After RFA, there was improvement of clinical symptoms and characteristics and volume reduction of the treated nodules as seen on US; complications were evaluated at each follow-up. RESULTS: The mean follow-up duration was 21.2 months (range = 6-38 months) after RFA. The mean symptom grading score of 10-cm visual analog scale, the mean cosmetic grading score on a 4-point scale, and the mean volume reduction of thyroid nodules were all significantly decreased from those seen before RFA (2.4-1.1, 3.7-1.5, and 4.2-1.1, respectively) (P < 0.05). There were no major complications. CONCLUSIONS: RFA is an effective and safe method for treating benign thyroid nodules in patients with incompletely resolved clinical problems following EA.