Eun Ju Son

Thyroid imaging reporting and data system for US features of nodules: a step in establishing better stratification of cancer risk.

PURPOSE To develop a practical thyroid imaging reporting and data system (TIRADS) with which to categorize thyroid nodules and stratify their malignant risk. MATERIALS AND METHODS The institutional review board approved this retrospective study, and the requirement to obtain informed consent for the review of images and records was waived. From May to December 2008, ultrasonographically (US)-guided fine-needle aspiration biopsy (FNAB) was performed in 3674 focal thyroid nodules in 3414 consecutive patients. The study included the 1658 thyroid nodules (≥1 cm in maximum diameter at US) in 1638 patients (1373 women, 265 men) for which pathologic diagnosis or follow-up findings were available. Univariate and multivariate analyses with generalized estimating equations were performed to investigate the relationship between suspicious US features and thyroid cancer. A score for each significant factor was assigned and multiplied by the β coefficient obtained for each significant factor from multivariate logistic regression analysis. Scores for each significant factor were then added, resulting in an equation that fitted the probability of malignancy in thyroid nodules. The authors evaluated the fitted probability by using a regression equation; the risk of malignancy was determined according to the number of suspicious US features. RESULTS The following US features showed a significant association with malignancy: solid component, hypoechogenicity, marked hypoechogenicity, microlobulated or irregular margins, microcalcifications, and taller-than-wide shape. As the number of suspicious US features increased, the fitted probability and risk of malignancy also increased. Positive predictive values according to the number of suspicious US features were significantly different (P < .001). CONCLUSION Risk stratification of thyroid malignancy by using the number of suspicious US features allows for a practical and convenient TIRADS.

Can Vascularity at Power Doppler US Help Predict Thyroid Malignancy

PURPOSE To retrospectively evaluate the diagnostic performance of power Doppler ultrasonography (US) in depicting vascularity and to determine whether the combination of vascularity and suspicious gray-scale US features is more useful in predicting thyroid malignancy than are gray-scale features alone. MATERIALS AND METHODS This was an institutional review board-approved retrospective study, with waiver of informed consent. A total of 1083 thyroid nodules in 1024 patients (median age, 51 years; range, 16-83 years), consisting of 886 women (median age, 50 years; range, 16-83 years) and 138 men (median age, 53 years; range, 19-74 years), were included. Nodules with marked hypoechogenicity, noncircumscribed margins, microcalcifications, and taller-than-wide shape were classified as suspicious according to gray-scale US criteria. Vascularity was classified as none, peripheral, and intranodular. The diagnostic performance of gray-scale and power Doppler US features was compared and classified as follows: criterion 1, any single suspicious gray-scale US feature; criterion 2, addition of any vascularity as one of the suspicious features to criterion 1; criterion 3, addition of peripheral vascularity to criterion 1; criterion 4, addition of intranodular vascularity to criterion 1; criterion 5, addition of no vascularity to criterion 1; criterion 6, American Association of Clinical Endocrinologists and Associazione Medici Endocrinology guidelines--all hypoechoic nodules with at least one of the following US features: irregular margins, intranodular vascular spots, taller-than-wide shape, or microcalcifications. RESULTS Of 1083 nodules, 814 were benign and 269 were malignant. Intranodular vascularity was frequently seen in benign nodules and no vascularity was more frequent in malignant nodules (P < .0001, respectively). The area under the receiver operating characteristic curve (A(z)) of criterion 1 was superior (A(z) = 0.851) to that of criteria 2 (A(z) = 0.634), 3 (A(z) = 0.752), 4 (A(z) = 0.733), 5 (A(z) = 0.718), and 6 (A(z) = 0.806) (P < .0001). CONCLUSION Vascularity itself or a combination of vascularity and gray-scale US features was not as useful as the use of suspicious gray-scale US features alone for predicting thyroid malignancy.

Interobserver Agreement in Assessing the Sonographic and Elastographic Features of Malignant Thyroid Nodules

OBJECTIVE The objective of our study was to investigate interobserver agreement for the diagnosis of malignant thyroid nodules using conventional B-mode ultrasound and real-time freehand ultrasound elastography. MATERIALS AND METHODS Between December 2007 and February 2008, 45 patients (age range, 19-73 years; mean age +/- SD, 45.0 +/- 12.2 years) with 52 thyroid nodules were examined with conventional B-mode ultrasound and real-time freehand ultrasound elastography. All the patients were scheduled to undergo thyroid surgery because a thyroid nodule had been proven malignant on aspiration cytology. Three radiologists independently performed conventional ultrasound and elastography and analyzed the ultrasound images. Using conventional ultrasound, observers recorded the following information about nodular features: composition (solid, cystic, or mixed cystic-solid), echogenicity (hyperechoic, isoechoic, hypoechoic, or markedly hypoechoic), margin (well circumscribed, microlobulated, or irregular), calcification (negative [no calcifications]; microcalcification, macrocalcification, or mixed-type calcifications), and shape (parallel or nonparallel). Observers determined the Ueno classification and area ratio for each nodule using ultrasound elastography. Interobserver agreement was evaluated with Spearmans correlation analysis for all findings except the area ratio, for which Pearsons correlation analysis was used. A p < 0.05 was considered to indicate statistical significance. RESULTS Statistically significant (p < 0.05) concordance among the three radiologists was found on conventional ultrasound for most features except echogenicity and margin of thyroid nodules. The highest value of concordance on conventional ultrasound was achieved for composition (Spearmans correlation coefficient, 0.70-1.00), followed by shape (0.48-0.79) and calcification (0.47-0.62). The least concordant findings on conventional ultrasound were nodular echogenicity (0.04-0.45) and margin (0.03-0.29). However, there was no statistically significant concordance on elastography for the Ueno classification (Spearmans correlation coefficient, 0.08-0.22; p > 0.05) or the area ratio (Pearsons correlation coefficient, -0.03 to 0.23; p > 0.05). CONCLUSION Statistically significant concordance among radiologists about most features of malignant thyroid nodules was seen with conventional ultrasound; however, ultrasound elastography did not show reliable interobserver agreement for the diagnosis of malignant thyroid nodules.

Excitatory actions of GABA in the suprachiasmatic nucleus.

Neurons in the suprachiasmatic nucleus (SCN) are responsible for the generation of circadian oscillations, and understanding how these neurons communicate to form a functional circuit is a critical issue. The neurotransmitter GABA and its receptors are widely expressed in the SCN where they mediate cell-to-cell communication. Previous studies have raised the possibility that GABA can function as an excitatory transmitter in adult SCN neurons during the day, but this work is controversial. In the present study, we first tested the hypothesis that GABA can evoke excitatory responses during certain phases of the daily cycle by broadly sampling how SCN neurons respond to GABA using extracellular single-unit recording and gramicidin-perforated-patch recording techniques. We found that, although GABA inhibits most SCN neurons, some level of GABA-mediated excitation was present in both dorsal and ventral regions of the SCN, regardless of the time of day. These GABA-evoked excitatory responses were most common during the night in the dorsal SCN region. The Na+-K+-2Cl− cotransporter (NKCC) inhibitor, bumetanide, prevented these excitatory responses. In individual neurons, the application of bumetanide was sufficient to change GABA-evoked excitation to inhibition. Calcium-imaging experiments also indicated that GABA-elicited calcium transients in SCN cells are highly dependent on the NKCC isoform 1 (NKCC1). Finally, Western blot analysis indicated that NKCC1 expression in the dorsal SCN is higher in the night. Together, this work indicates that GABA can play an excitatory role in communication between adult SCN neurons and that this excitation is critically dependent on NKCC1.

Value of US Correlation of a Thyroid Nodule with Initially Benign Cytologic Results

PURPOSE To investigate the value of ultrasonographic (US) features in thyroid nodules with initially benign cytologic results. MATERIALS AND METHODS The institutional review board approved this retrospective study and required neither patient approval nor informed consent for the review of images and records. From October 2003 to February 2006, 6118 focal thyroid nodules in 6025 consecutive patients underwent US-guided fine-needle aspiration biopsy (FNAB). This study included 1343 nodules 1 cm or larger in 1302 patients that were diagnosed as benign at initial cytologic evaluation and underwent pathologic or follow-up study. We compared the risk of malignancy according to US findings and calculated the likelihoods of different subgroups having benign nodules. RESULTS In total, 26 (1.9%) malignant and 1317 (98.1%) benign nodules were found according to reference standards. If initial cytologic results showed benign thyroid nodules, the likelihood of the nodule actually being benign was 98.1%. When a thyroid nodule had benign results at both initial and repeat FNAB, the likelihood increased to 100%. The likelihood of having a benign thyroid nodule with suspicious US features was lower (79.6%) than having a benign thyroid nodule with negative US features (99.4%, P<.001). In the nodule with benign features at initial US, the risk of malignancy for a thyroid nodule with an increase in size at follow-up US was slightly higher (1.4%) than that of a thyroid nodule with no interval change or decrease in size, but it was not significantly different (0.5%, P = .354). CONCLUSION Repeat FNAB should be performed for thyroid nodules that have suspicious US features, even if the initial cytologic results indicate that it is a benign lesion.

Interobserver and intraobserver variations in ultrasound assessment of thyroid nodules

BACKGROUND Thyroid ultrasound (US) is used as the first diagnostic tool to assess the management of the disease. In spite of its importance, US is a very subjective method and highly dependent on the skill of the performer. There have been few reports evaluating thyroid US performance and even fewer reports of observer variability in US assessment. Therefore, we evaluated inter- and intraobserver variations in US assessment of thyroid nodules and diagnosis among four radiologists and estimated its diagnostic accuracy. METHODS A total of 204 thyroid nodules in 144 patients were reviewed. There were 89 benign and 115 malignant cases. Four radiologists with more than 5 years of experience independently reviewed US images twice at 6-week intervals. Echogenicity, composition, margin, shape, calcification, vascularity, and final assessment were evaluated. Inter- and intraobserver variations were determined with Cohens kappa statistics, and accuracy was calculated. RESULTS For interobserver variations, echogenicity showed slight agreement (kappa = 0.34); composition, margin, calcification, and final assessment had fair agreement (kappa = 0.59, 0.42, 0.58, and 0.54, respectively); shape and vascularity showed substantial agreement (kappa = 0.61 and 0.64, respectively). For intraobserver variability, almost all showed substantial agreement (kappa > 0.61). Overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for the four radiologists were 88.2%, 78.7%, 76.2%, 89.6%, and 82.8%, respectively. CONCLUSIONS Experienced radiologists showed more than a moderate degree of agreement in US assessment of thyroid nodules, and their final assessments were highly accurate.

How to combine ultrasound and cytological information in decision making about thyroid nodules

The purpose of this study was to evaluate the role of sonographic-cytological correlation in determining which nodules should be reaspirated to reduce the false-negative rate of fine-needle aspiration biopsy (FNAB). A retrospective cohort study was performed on a database of 568 patients with 672 focal thyroid nodules. An independent two-sample t-test was used to compare the risk of malignancy according to clinical factors. We evaluated the risk stratification of malignancy according to US groupings and cytological results. Additionally, we calculated the false-negative rate of FNAB and investigated the cytological results of repeat aspiration. The malignancy rate (92.2–98.5%) was high in thyroid nodules designated “malignant” or “suspicious for papillary carcinoma” on FNAB, regardless of US features. In contrast, when focal thyroid nodules had “benign” readings on FNAB, the malignancy rate was lower for the “probably benign” US features (2.9%) than for the suspicious nodules (56.6%). The false-negative rate of FNAB was 5.8%. Repeat aspiration revealed “suspicious for malignancy” or “malignancy” results in 15 (93.8%) of 16 thyroid cancers with “benign” results on initial aspirate. This study demonstrated repeat FNAB should be performed on focal thyroid nodules with suspicious US features even when initial FNAB results are benign.

Extrathyroid Extension of Well-Differentiated Papillary Thyroid Microcarcinoma on US

BACKGROUND Extrathyroidal extension is an important factor to determine the extent of thyroid surgery. The aim of the present study was to evaluate the usefulness of high-resolution ultrasound (US) for predicting the extrathyroidal extension of papillary thyroid microcarcinoma (PTMC). METHODS This study included a total of 221 PTMCs in 181 patients. PTMC was defined as thyroid papillary carcinoma equal or less than 1 cm in size. The US findings, such as contact and disruption of thyroid capsule, were evaluated to predict the extrathyroidal extension of thyroid carcinoma. We calculated the diagnostic accuracy and odds ratio for each US finding. RESULTS Of the 221 PTMCs, extrathyroidal extension was present in 89 (40.3%) based on pathologic results. The mean size was not significantly different between PTMCs with and without extrathyroidal extension (p = 0.527). When the degree of contact was high, extrathyroidal extension of the thyroid cancer was high (p < 0.0001). Considering the odds ratio, Az value, and positive predictive value of each US finding, more than 25% contact with the adjacent capsule is the most accurate measurement for predicting extrathyroidal extension. CONCLUSIONS This study suggests that the presence and degree of contact between a PTMC and the adjacent capsule as found on preoperative US can provide an useful predictive information about an extrathyroidal extension.

Papillary microcarcinoma of the thyroid: predicting factors of lateral neck node metastasis.

BackgroundPreoperative prediction of lateral lymph node metastasis (LNM) is important to prevent recurrence; however, there are few published data in predicting factors of lateral LNM before surgery. The present study investigated the factors affecting LNM in patients with papillary thyroid microcarcinoma (PTMC).MethodsA retrospective cohort study was conducted with data obtained from 671 patients with PTMC between 2004 and 2006. We reviewed the clinical, ultrasound (US), and pathology records of patients and analyzed the association between lateral LNM and clinical factors, US features of PTMC, and pathologic features.ResultsThe rate of lateral LNM was 3.7% in 671 PTMCs. We found a statistically significant association between lateral LNM and US features of PTMC (upper pole location, contact of >25% with the adjacent capsule, and presence of calcifications), and pathologic features (central LNM) in multivariate analysis (P < .05). The odds ratios of statistically significant factors were 4.7 (95% confidence interval [95% CI], 1.8–12.6), 10.8 (95% CI, 3.3–34.6), 4.8 (95% CI, 1.6–13.7), and 6.9 (95% CI, 2.4–20) at upper pole location, contact of >25% with the adjacent capsule, presence of calcifications on US, and pathologic central LNM, respectively.ConclusionsIn patients with PTMC, independent factors in predicting lateral LNM were US features of PTMC (upper pole location, >25% contact with the adjacent capsule, and presence of calcifications) and pathologic features (central LNM). When these US features are detected on preoperative US, lateral neck nodes should be meticulously evaluated by a multimodal approach.

Sonographic differentiation of thyroid nodules with eggshell calcifications.

Objective. The purpose of this study was to assess the role of known suspicious sonographic findings and to find other additional sonographic findings to differentiate benign and malignant thyroid nodules with “eggshell” calcifications. Methods. Our Institutional Review Board approved this retrospective study, and informed consent was not required. We reviewed sonographic findings of thyroid nodules in 795 patients who underwent thyroid surgery in our institution between August 2006 and February 2007. Ninety‐three thyroid nodules with eggshell calcifications in 92 patients were included in this study. Each lesion was evaluated for known suspicious sonographic criteria, including marked hypoechogenicity, irregular or microlobulated margins, and a taller‐than‐wide shape, as well as 2 additional sonographic findings: a hypoechoic halo and disruption of eggshell calcifications (halo and disrupted calcification rim). The sensitivity and specificity based on the sonographic criteria were calculated and compared among the 2 types of criteria. Results. Among the 93 thyroid nodules, 59 were malignant and 34 were benign. The halo and disrupted calcification rim showed higher sensitivity (62.7% and 76.3%, respectively) than any of the known suspicious sonographic criteria (40.7%, 35.6%, and 55.9%). The combination of both the halo and the disrupted calcification rim showed significantly higher sensitivity (93.2%) than the combination of the known suspicious sonographic criteria (78%; P < .05), although both had the same specificity (64.7%). Conclusions. In thyroid nodules with eggshell calcifications but no other calcifications, the findings of a peripheral halo and disruption of the eggshell calcifications may be more useful sonographic predictors of malignancy than hypoechogenicity, microlobulated margins, and a taller‐than‐wide shape.