3303jum387-530online_Layout 1 2/19/14 1:38 PM Page 495
ORIGINAL RESEARCH
Real-time Ultrasound Elastography for Differentiation of Benign and Malignant Thyroid Nodules A Meta-analysis Jiasi Sun, MM, Jingyu Cai, MM, Xuemei Wang, MD Objectives—The clinical challenge of managing thyroid nodules nowadays is to diagnose the minority of malignant disease. Real-time ultrasound elastography, which can measure tissue elasticity, is used as a complement to conventional sonography for improving the diagnosis of thyroid tumors. There are 2 common criteria for evaluating an elastogram: the elasticity score and strain ratio. This meta-analysis was performed to expand on a previous meta-analysis to assess the diagnostic power of ultrasound elastography in differentiating benign and malignant thyroid nodules for elasticity score and strain ratio assessment. Methods—The MEDLINE, EMBASE, PubMed, and Cochrane Library databases up to January 31, 2013, were searched. The pooled sensitivity, specificity, and summary receiver operating characteristic curve were obtained from individual studies with a randomeffects model. The extent and sources of heterogeneity were explored. Results—A total of 5481 nodules in 4468 patients for elasticity score studies and 1063 nodules in 983 patients for strain ratio studies were analyzed. The overall mean sensitivity and specificity of ultrasound elastography for differentiation of thyroid nodules were 0.79 (95% confidence interval [CI], 0.77–0.81) and 0.77 (95% CI, 0.76–0.79) for elasticity score assessment and 0.85 (95% CI, 0.81–0.89) and 0.80 (95% CI, 0.77–0.83) for strain ratio assessment, respectively. The areas under the curve for the elasticity score and strain ratio were 0.8941 and 0.9285. Conclusions—These results confirmed those obtained in the previous meta-analysis. Ultrasound elastography has high sensitivity and specificity for identification of thyroid nodules. It is a promising tool for reducing unnecessary fine-needle-aspiration biopsy. Received March 20, 2013, from the Departments of Ultrasound (J.S., X.W.) and General Surgery (J.C.), First Affiliated Hospital of China Medical University, Shenyang, China. Revision requested May 14, 2013. Revised manuscript accepted for publication July 13, 2013. Address correspondence to Xuemei Wang, MD, Department of Ultrasound, First Affiliated Hospital of China Medical University, 155 Nanjing N St, Heping District, 110001 Shenyang, Liaoning, China. E-mail: [email protected]
Abbreviations
CI, confidence interval; QUADAS, Quality Assessment of Diagnostic Accuracy Studies; ROC, receiver operating characteristic doi:10.7863/ultra.33.3.495
Key Words—elasticity score; elastography; general ultrasound; meta-analysis; strain ratio; thyroid nodules
A
thyroid nodule is the result of abnormal growth of thyroid cells containing malignant or benign cells within the thyroid gland. The main clinical concern for managing thyroid nodules is to exclude malignant diseases, which account for 4% to 6% of all thyroid nodules.1 Sonography is the most frequently used method to diagnose thyroid diseases; however, we have to draw attention to the fact that its efficacy in the differentiation between the benign and malignant thyroid nodules is relatively low.2 Fineneedle-aspiration (FNA) biopsy is a minimally invasive procedure and has been proven to be an efficient tool for thyroid cancer diagnosis, with sensitivity of up to 93% presently.3,4 Nevertheless, the requirement for a highly qualified cytologist and the possibility of repeated biopsy to gain adequate results limit the use of this method.5
©2014 by the American Institute of Ultrasound in Medicine | J Ultrasound Med 2014; 33:495–502 | 0278-4297 | www.aium.org
3303jum387-530online_Layout 1 2/19/14 1:39 PM Page 496
Sun et al—Real-time Elastography of Thyroid Nodules: A Meta-analysis
The suspicion of malignancy is related to the substantial firmness of thyroid nodules. Palpation is the oldest and fundamental detection method for diagnosis of thyroid lesions. However, palpation is a subjective method that can be easily influenced by the size and location of the nodule as well as the experience of examiner.6 Real-time ultrasound elastography, sometimes called “electronic palpation,” is a new technique that has been used to acquire information on tissue stiffness noninvasively in recent years. This technique was first implemented by Ophir et al7 in 1991 and was designed on the basis of the mechanism that softer parts of tissues deform more easily than harder parts under compression, and the degree of distortion of a tissue under an external force can be recorded, thus allowing an objective determination of tissue stiffness. Nowadays, there are 2 general criteria for evaluating the diagnostic efficacy of ultrasound elastography. The first is qualitative assessment with the elasticity score, and the second is quantitative assessment with the strain ratio, which shows tissue stiffness mostly by a second-generation ultrasound elastographic device. A previous meta-analysis8 assessed the overall performance of ultrasound elastography in workups of thyroid nodules for qualitative assessment and included 7 qualitative and 2 quantitative studies. Most of those studies with small numbers of nodules had low statistical power. The aim of this meta-analysis was to update the previous one to evaluate the utility of ultrasound elastography in differentiating benign and malignant thyroid nodules for qualitative and quantitative assessment.
Materials and Methods Literature Search We searched the MEDLINE, EMBASE, PubMed, and Cochrane Library databases up to January 31, 2013, for relevant articles published in English using the terms “elastography,” “ultrasonoelastography,” and “thyroid.” Studies were included in the analysis if they met the following inclusion criteria: publications in English; studies with human participants; a sample size of at least 10 nodules; use of thyroid fine-needle-aspiration biopsy and/or histology as the reference standard; qualitative and/or quantitative analysis of the performance of ultrasound elastography for identification of the thyroid nodules; and inclusion of the necessary data to calculate the true-positive, false-positive, true-negative, and false-negative diagnostic results for differentiation of benign and malignant thyroid nodules. Data Extraction and Assessment The relevant data were extracted by each observer sepa-
496
rately using a standardized form. The quality of all included studies was assessed with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. Disagreements were resolved by discussion. Data elements that were collected included the first author’s name, year of publication, original country, study design, study details (number and age of patients, number of nodules available for analysis, percentage of malignant nodules, and percentage of surgical reference) score scale, and cutoff point for strain ratio estimation. The true-positive, false-positive, true-negative, and false-negative results were recorded. Data Analysis Heterogeneity was tested by the I2 inconsistency index and χ2 test. If the value of the I 2 index is greater than 50%, it means that more heterogeneity exists beyond that from chance.9 As for the χ2 test, P < .05 confirmed the existence of heterogeneity between studies. Because of a priori assumptions about the likelihood of heterogeneity between the primary studies, the pooled analysis across all studies for the initial meta-analysis was performed with a randomeffects model.10 Summary receiver operating characteristic (ROC) curves were constructed to express the test parameter results as diagnostic odds ratios. The Q* index (the point where sensitivity was equal to specificity on the summary ROC curve) was also reported. Meta-regression was used to measure the potential sources of heterogeneity in the results of the following variables: continent of study origin, nodule number, reference standard, response to question 1 on the QUADAS survey, and elasticity score pattern. A subgroup analysis was conducted to explore the differences in performance for different subgroups. The Egger test was performed to assess publication bias in the included studies. We examined the influence of individual studies on the overall effect estimate by using an influence analysis in which the meta-analysis estimates were computed by omitting one study at a time. All analyses were performed with Stata version 11.0 statistical software (StataCorp, College Station, TX) and Meta-DiSc version 1.4 software (http://www.hrc.es/investigacion/metadisc_en.htm).11 P < .05 indicated statistical significance.
Results Description and Quality of Studies The abstracts and titles of 122 primary studies were identified for an initial review. Finally, there were 31 studies meeting inclusion criteria in our meta-analysis.12–42 Table 1 presents the main characteristics of the studies. Qualitative elasticity score analysis was obtained in 22 studies,14–34,42
J Ultrasound Med 2014; 33:495–502
3303jum387-530online_Layout 1 2/19/14 1:39 PM Page 497
Sun et al—Real-time Elastography of Thyroid Nodules: A Meta-analysis
quantitative strain ratio analysis in 2,12–13 and both qualitative and quantitative analysis in 7.35–41 There were a total of 5481 nodules in 4468 patients for elasticity score studies and 1063 nodules in 983 patients for strain ratio studies. The median age across the all studies was 49.17 years (range, 38.0–61.80 years). With regard to the 29 studies that evaluated ultrasound elastography by the elasticity score, 17 described the measurement on a numeric scale of 1–4; 6 described a scale of 1–5; 4 described a scale of 1– 3; and 2 described a scale of 1–6. The 31 included studies, which were published as full articles, had very good quality scores according to the QUADAS criteria. Ten studies had a negative response to question 1, which was concerned with whether the spectrum of patients was representative of the patients who would receive the test in practice. Positive response rates of 100% were obtained on other questions.
Summary Estimates of Sensitivity and Specificity The pooled sensitivity and specificity of the included studies obtained from the random-effects model are presented in Table 2. The pooled sensitivities were 0.79 (95% confidence interval [CI], 0.77–0.81) for elasticity score assessment and 0.85 (95% CI, 0.81–0.89) for strain ratio assessment. The pooled specificities were 0.77 (95% CI, 0.76–0.79) for elasticity score assessment and 0.80 (95% CI, 0.77–0.83) for strain ratio assessment. Therefore, the sensitivity and specificity estimates for strain ratio assessment were a little higher than those for elasticity score assessment. A significant advantage was not observed for strain ratio assessment. Forest plots for the sensitivities and specificities of the elasticity score and strain ratio for ultrasound elastography in the workup of thyroid nodules are shown in Figures 1–4. Considering the conflicting role of ultrasound elastography in thyroid nodules with indeter-
Table 1. Main Characteristics of the Included Studies Measurement Patients (Quan = 1; SR (Analyzed Study Mean Qual = 2; ES Scale Estimation Malignant Surgical Nodules), n Design Age, y Both = 3) (Cutoff) Cutoff Nodules, % Reference, %
Reference
Country (y)
Cantisani et al12
Italy (2012) Italy (2012) China (2012) Germany (2012) Germany (2012) Turkey (2013) China (2012) Korea (2012) Italy (2009) China (2010) Italy (2007) Italy (2012) Italy (2011) Romania (2012) Germany (2010) Italy (2010) Poland (2010) China (2009) Egypt (2012) Italy (2012) Italy (2008) Spain (2011) Italy (2012) China (2011) China (2011) China (2013) China (2012) Japan (2005) Turkey (2012) Japan (2010) USA (2013)
Cantisani et al13 Hong et al14 Bojunga et al15 Friedrich-Rust et al16 Yerli et al17 Shuzhen18 Moon et al19 Rubaltelli et al20 Wang et al21 Rago et al22 Ragazzoni et al23 Lippolis et al24 Stoian et al25 Friendrich-Rust et al26 Rago et al27 Gietka-Czernel et al28 Hong et al29 Mansor et al30 Trimboli et al31 Asteria et al32 Merino et al33 Cappelli et al34 Xing et al35 Ding et al36 Wang et al37 Ning et al38 Lyshchik et al39 Ünlütürk et al40 Kagoya et al41 Azizi et al42
140 (140) 97 (97) 243 (329) 138 (158) 55 (60) 64 (72) 244 (291) 676 (703) 40 (51) 51 (51) 92 (92) 115 (132) 102 (102) 69 (107) 56 (53) 176 (195) 52 (71) 90 (145) 40 (45) 446 (498) 67 (86) 103 (106) 101 (159) 86 (98) 125 (125) 167 (168) 99 (99) 31 (52) 194 (237) 44 (47) 702 (912)
Pro 38.0 Pro 54.0 Pro 45.3 Unclear 52.0 Pro 51.3 Pro Unclear Unclear 43.38 Pro 48.9 Pro 55.0 Pro 48.6 Unclear 42.0 Pro 54.0 Unclear 46.5 Pro 50.08 Pro 53.5 Pro 44.0 Unclear 45.0 Pro 46.0 Pro 41.175 Pro 53.4 Pro 52.97 Pro 58.0 Pro 56.87 Pro 47.0 Ret 48.16 Pro 47.04 Pro 48.74 Pro 49.7 Pro 44.42 Unclear 61.8 Pro 48.5
1 1 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 3 3 3 3 3 3 3 2
2.05 2.0 6 (3/4) 4 (2/3) 4 (2/3) 5 (3/4) 5 (2/3) 4 (2/3) 4 (2/3) 5 (3/4) 5 (3/4) 4 (2/3) 4 (2/3) 4 (3/4) 4 (2/3) 3 (1/2) 5 (3/4) 6 (3/4) 4 (2/3) 4 (2/3) 4 (2/3) 3 (1/2) 3 (2/3) 4 (2/3) 4 (2/3) 5 (3/4) 4 (3/4) 4 (3/4) 3 (2/3) 4 (2/3) 4 (2/3)
3.79 2.73 3.855 4.225 4.0 2.1 1.5
28.6 38.1 37.0 13.3 5.0 13.9 22.6 30.9 21.6 63.0 34.0 30.3 35.3 15.94 13.2 20.0 31.0 33.8 8.9 25.0 19.8 9.4 9.4 45.9 44.8 30.95 32.3 42.3 25.0 23.4 9.4
100 100 100 40.5 20.0 33.3 100 31.4 42.5 100 100 100 100 100 43.0 100 56.3 100 0 11.0 29.1 100 100 100 Unclear 0 45.5 98.1 26.0 19.4 27.9
ES indicates elasticity score; Pro, prospective design; Qual, qualitative; Quan, quantitative; Ret, retrospective design; and SR, strain ratio.
J Ultrasound Med 2014; 33:495–502
497
3303jum387-530online_Layout 1 2/19/14 1:39 PM Page 498
Sun et al—Real-time Elastography of Thyroid Nodules: A Meta-analysis
minate or nondiagnostic cytologic findings,12,23,24,27,40 especially given the very low sensitivity reported by Lippolis et al,24 we extracted the necessary data to perform a subgroup analysis. The sensitivity and specificity were 0.89 (95% CI, 0.81–0.95) and 0.65 (95% CI, 0.58–0.70) for elasticity score assessment and 0.86 (95% CI, 0.73–0.94) and 0.88 (95% CI, 0.80–0.93) for strain ratio assessment, respectively. The results of the Egger test indicated that there were no publication biases for elasticity score assessment (P = .094) and strain ratio assessment (P = .58). An influence analysis showed that omission of any study made no difference in the summary effect estimate, so our metaanalysis was stable and reliable. Study Heterogeneity High heterogeneity was observed in both test sensitivity (χ2 = 139.81; P
ORIGINAL RESEARCH
Real-time Ultrasound Elastography for Differentiation of Benign and Malignant Thyroid Nodules A Meta-analysis Jiasi Sun, MM, Jingyu Cai, MM, Xuemei Wang, MD Objectives—The clinical challenge of managing thyroid nodules nowadays is to diagnose the minority of malignant disease. Real-time ultrasound elastography, which can measure tissue elasticity, is used as a complement to conventional sonography for improving the diagnosis of thyroid tumors. There are 2 common criteria for evaluating an elastogram: the elasticity score and strain ratio. This meta-analysis was performed to expand on a previous meta-analysis to assess the diagnostic power of ultrasound elastography in differentiating benign and malignant thyroid nodules for elasticity score and strain ratio assessment. Methods—The MEDLINE, EMBASE, PubMed, and Cochrane Library databases up to January 31, 2013, were searched. The pooled sensitivity, specificity, and summary receiver operating characteristic curve were obtained from individual studies with a randomeffects model. The extent and sources of heterogeneity were explored. Results—A total of 5481 nodules in 4468 patients for elasticity score studies and 1063 nodules in 983 patients for strain ratio studies were analyzed. The overall mean sensitivity and specificity of ultrasound elastography for differentiation of thyroid nodules were 0.79 (95% confidence interval [CI], 0.77–0.81) and 0.77 (95% CI, 0.76–0.79) for elasticity score assessment and 0.85 (95% CI, 0.81–0.89) and 0.80 (95% CI, 0.77–0.83) for strain ratio assessment, respectively. The areas under the curve for the elasticity score and strain ratio were 0.8941 and 0.9285. Conclusions—These results confirmed those obtained in the previous meta-analysis. Ultrasound elastography has high sensitivity and specificity for identification of thyroid nodules. It is a promising tool for reducing unnecessary fine-needle-aspiration biopsy. Received March 20, 2013, from the Departments of Ultrasound (J.S., X.W.) and General Surgery (J.C.), First Affiliated Hospital of China Medical University, Shenyang, China. Revision requested May 14, 2013. Revised manuscript accepted for publication July 13, 2013. Address correspondence to Xuemei Wang, MD, Department of Ultrasound, First Affiliated Hospital of China Medical University, 155 Nanjing N St, Heping District, 110001 Shenyang, Liaoning, China. E-mail: [email protected]
Abbreviations
CI, confidence interval; QUADAS, Quality Assessment of Diagnostic Accuracy Studies; ROC, receiver operating characteristic doi:10.7863/ultra.33.3.495
Key Words—elasticity score; elastography; general ultrasound; meta-analysis; strain ratio; thyroid nodules
A
thyroid nodule is the result of abnormal growth of thyroid cells containing malignant or benign cells within the thyroid gland. The main clinical concern for managing thyroid nodules is to exclude malignant diseases, which account for 4% to 6% of all thyroid nodules.1 Sonography is the most frequently used method to diagnose thyroid diseases; however, we have to draw attention to the fact that its efficacy in the differentiation between the benign and malignant thyroid nodules is relatively low.2 Fineneedle-aspiration (FNA) biopsy is a minimally invasive procedure and has been proven to be an efficient tool for thyroid cancer diagnosis, with sensitivity of up to 93% presently.3,4 Nevertheless, the requirement for a highly qualified cytologist and the possibility of repeated biopsy to gain adequate results limit the use of this method.5
©2014 by the American Institute of Ultrasound in Medicine | J Ultrasound Med 2014; 33:495–502 | 0278-4297 | www.aium.org
3303jum387-530online_Layout 1 2/19/14 1:39 PM Page 496
Sun et al—Real-time Elastography of Thyroid Nodules: A Meta-analysis
The suspicion of malignancy is related to the substantial firmness of thyroid nodules. Palpation is the oldest and fundamental detection method for diagnosis of thyroid lesions. However, palpation is a subjective method that can be easily influenced by the size and location of the nodule as well as the experience of examiner.6 Real-time ultrasound elastography, sometimes called “electronic palpation,” is a new technique that has been used to acquire information on tissue stiffness noninvasively in recent years. This technique was first implemented by Ophir et al7 in 1991 and was designed on the basis of the mechanism that softer parts of tissues deform more easily than harder parts under compression, and the degree of distortion of a tissue under an external force can be recorded, thus allowing an objective determination of tissue stiffness. Nowadays, there are 2 general criteria for evaluating the diagnostic efficacy of ultrasound elastography. The first is qualitative assessment with the elasticity score, and the second is quantitative assessment with the strain ratio, which shows tissue stiffness mostly by a second-generation ultrasound elastographic device. A previous meta-analysis8 assessed the overall performance of ultrasound elastography in workups of thyroid nodules for qualitative assessment and included 7 qualitative and 2 quantitative studies. Most of those studies with small numbers of nodules had low statistical power. The aim of this meta-analysis was to update the previous one to evaluate the utility of ultrasound elastography in differentiating benign and malignant thyroid nodules for qualitative and quantitative assessment.
Materials and Methods Literature Search We searched the MEDLINE, EMBASE, PubMed, and Cochrane Library databases up to January 31, 2013, for relevant articles published in English using the terms “elastography,” “ultrasonoelastography,” and “thyroid.” Studies were included in the analysis if they met the following inclusion criteria: publications in English; studies with human participants; a sample size of at least 10 nodules; use of thyroid fine-needle-aspiration biopsy and/or histology as the reference standard; qualitative and/or quantitative analysis of the performance of ultrasound elastography for identification of the thyroid nodules; and inclusion of the necessary data to calculate the true-positive, false-positive, true-negative, and false-negative diagnostic results for differentiation of benign and malignant thyroid nodules. Data Extraction and Assessment The relevant data were extracted by each observer sepa-
496
rately using a standardized form. The quality of all included studies was assessed with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. Disagreements were resolved by discussion. Data elements that were collected included the first author’s name, year of publication, original country, study design, study details (number and age of patients, number of nodules available for analysis, percentage of malignant nodules, and percentage of surgical reference) score scale, and cutoff point for strain ratio estimation. The true-positive, false-positive, true-negative, and false-negative results were recorded. Data Analysis Heterogeneity was tested by the I2 inconsistency index and χ2 test. If the value of the I 2 index is greater than 50%, it means that more heterogeneity exists beyond that from chance.9 As for the χ2 test, P < .05 confirmed the existence of heterogeneity between studies. Because of a priori assumptions about the likelihood of heterogeneity between the primary studies, the pooled analysis across all studies for the initial meta-analysis was performed with a randomeffects model.10 Summary receiver operating characteristic (ROC) curves were constructed to express the test parameter results as diagnostic odds ratios. The Q* index (the point where sensitivity was equal to specificity on the summary ROC curve) was also reported. Meta-regression was used to measure the potential sources of heterogeneity in the results of the following variables: continent of study origin, nodule number, reference standard, response to question 1 on the QUADAS survey, and elasticity score pattern. A subgroup analysis was conducted to explore the differences in performance for different subgroups. The Egger test was performed to assess publication bias in the included studies. We examined the influence of individual studies on the overall effect estimate by using an influence analysis in which the meta-analysis estimates were computed by omitting one study at a time. All analyses were performed with Stata version 11.0 statistical software (StataCorp, College Station, TX) and Meta-DiSc version 1.4 software (http://www.hrc.es/investigacion/metadisc_en.htm).11 P < .05 indicated statistical significance.
Results Description and Quality of Studies The abstracts and titles of 122 primary studies were identified for an initial review. Finally, there were 31 studies meeting inclusion criteria in our meta-analysis.12–42 Table 1 presents the main characteristics of the studies. Qualitative elasticity score analysis was obtained in 22 studies,14–34,42
J Ultrasound Med 2014; 33:495–502
3303jum387-530online_Layout 1 2/19/14 1:39 PM Page 497
Sun et al—Real-time Elastography of Thyroid Nodules: A Meta-analysis
quantitative strain ratio analysis in 2,12–13 and both qualitative and quantitative analysis in 7.35–41 There were a total of 5481 nodules in 4468 patients for elasticity score studies and 1063 nodules in 983 patients for strain ratio studies. The median age across the all studies was 49.17 years (range, 38.0–61.80 years). With regard to the 29 studies that evaluated ultrasound elastography by the elasticity score, 17 described the measurement on a numeric scale of 1–4; 6 described a scale of 1–5; 4 described a scale of 1– 3; and 2 described a scale of 1–6. The 31 included studies, which were published as full articles, had very good quality scores according to the QUADAS criteria. Ten studies had a negative response to question 1, which was concerned with whether the spectrum of patients was representative of the patients who would receive the test in practice. Positive response rates of 100% were obtained on other questions.
Summary Estimates of Sensitivity and Specificity The pooled sensitivity and specificity of the included studies obtained from the random-effects model are presented in Table 2. The pooled sensitivities were 0.79 (95% confidence interval [CI], 0.77–0.81) for elasticity score assessment and 0.85 (95% CI, 0.81–0.89) for strain ratio assessment. The pooled specificities were 0.77 (95% CI, 0.76–0.79) for elasticity score assessment and 0.80 (95% CI, 0.77–0.83) for strain ratio assessment. Therefore, the sensitivity and specificity estimates for strain ratio assessment were a little higher than those for elasticity score assessment. A significant advantage was not observed for strain ratio assessment. Forest plots for the sensitivities and specificities of the elasticity score and strain ratio for ultrasound elastography in the workup of thyroid nodules are shown in Figures 1–4. Considering the conflicting role of ultrasound elastography in thyroid nodules with indeter-
Table 1. Main Characteristics of the Included Studies Measurement Patients (Quan = 1; SR (Analyzed Study Mean Qual = 2; ES Scale Estimation Malignant Surgical Nodules), n Design Age, y Both = 3) (Cutoff) Cutoff Nodules, % Reference, %
Reference
Country (y)
Cantisani et al12
Italy (2012) Italy (2012) China (2012) Germany (2012) Germany (2012) Turkey (2013) China (2012) Korea (2012) Italy (2009) China (2010) Italy (2007) Italy (2012) Italy (2011) Romania (2012) Germany (2010) Italy (2010) Poland (2010) China (2009) Egypt (2012) Italy (2012) Italy (2008) Spain (2011) Italy (2012) China (2011) China (2011) China (2013) China (2012) Japan (2005) Turkey (2012) Japan (2010) USA (2013)
Cantisani et al13 Hong et al14 Bojunga et al15 Friedrich-Rust et al16 Yerli et al17 Shuzhen18 Moon et al19 Rubaltelli et al20 Wang et al21 Rago et al22 Ragazzoni et al23 Lippolis et al24 Stoian et al25 Friendrich-Rust et al26 Rago et al27 Gietka-Czernel et al28 Hong et al29 Mansor et al30 Trimboli et al31 Asteria et al32 Merino et al33 Cappelli et al34 Xing et al35 Ding et al36 Wang et al37 Ning et al38 Lyshchik et al39 Ünlütürk et al40 Kagoya et al41 Azizi et al42
140 (140) 97 (97) 243 (329) 138 (158) 55 (60) 64 (72) 244 (291) 676 (703) 40 (51) 51 (51) 92 (92) 115 (132) 102 (102) 69 (107) 56 (53) 176 (195) 52 (71) 90 (145) 40 (45) 446 (498) 67 (86) 103 (106) 101 (159) 86 (98) 125 (125) 167 (168) 99 (99) 31 (52) 194 (237) 44 (47) 702 (912)
Pro 38.0 Pro 54.0 Pro 45.3 Unclear 52.0 Pro 51.3 Pro Unclear Unclear 43.38 Pro 48.9 Pro 55.0 Pro 48.6 Unclear 42.0 Pro 54.0 Unclear 46.5 Pro 50.08 Pro 53.5 Pro 44.0 Unclear 45.0 Pro 46.0 Pro 41.175 Pro 53.4 Pro 52.97 Pro 58.0 Pro 56.87 Pro 47.0 Ret 48.16 Pro 47.04 Pro 48.74 Pro 49.7 Pro 44.42 Unclear 61.8 Pro 48.5
1 1 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 3 3 3 3 3 3 3 2
2.05 2.0 6 (3/4) 4 (2/3) 4 (2/3) 5 (3/4) 5 (2/3) 4 (2/3) 4 (2/3) 5 (3/4) 5 (3/4) 4 (2/3) 4 (2/3) 4 (3/4) 4 (2/3) 3 (1/2) 5 (3/4) 6 (3/4) 4 (2/3) 4 (2/3) 4 (2/3) 3 (1/2) 3 (2/3) 4 (2/3) 4 (2/3) 5 (3/4) 4 (3/4) 4 (3/4) 3 (2/3) 4 (2/3) 4 (2/3)
3.79 2.73 3.855 4.225 4.0 2.1 1.5
28.6 38.1 37.0 13.3 5.0 13.9 22.6 30.9 21.6 63.0 34.0 30.3 35.3 15.94 13.2 20.0 31.0 33.8 8.9 25.0 19.8 9.4 9.4 45.9 44.8 30.95 32.3 42.3 25.0 23.4 9.4
100 100 100 40.5 20.0 33.3 100 31.4 42.5 100 100 100 100 100 43.0 100 56.3 100 0 11.0 29.1 100 100 100 Unclear 0 45.5 98.1 26.0 19.4 27.9
ES indicates elasticity score; Pro, prospective design; Qual, qualitative; Quan, quantitative; Ret, retrospective design; and SR, strain ratio.
J Ultrasound Med 2014; 33:495–502
497
3303jum387-530online_Layout 1 2/19/14 1:39 PM Page 498
Sun et al—Real-time Elastography of Thyroid Nodules: A Meta-analysis
minate or nondiagnostic cytologic findings,12,23,24,27,40 especially given the very low sensitivity reported by Lippolis et al,24 we extracted the necessary data to perform a subgroup analysis. The sensitivity and specificity were 0.89 (95% CI, 0.81–0.95) and 0.65 (95% CI, 0.58–0.70) for elasticity score assessment and 0.86 (95% CI, 0.73–0.94) and 0.88 (95% CI, 0.80–0.93) for strain ratio assessment, respectively. The results of the Egger test indicated that there were no publication biases for elasticity score assessment (P = .094) and strain ratio assessment (P = .58). An influence analysis showed that omission of any study made no difference in the summary effect estimate, so our metaanalysis was stable and reliable. Study Heterogeneity High heterogeneity was observed in both test sensitivity (χ2 = 139.81; P
