Diagnostic Value of Gadoxetic Acid Disodium (Gd-EOB-DTPA) for the Detection of Liver Metastases: A Meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

 LEIJun-qiang ^1,2 , MAWen-ting ¹ , WANGYin-zhong ¹ , LUYi ¹ , JIANGNan ¹ , YANGKe-hu ³

1. The First Clinical Medical College, LanZhou University, Lanzhou 73000, China;
2. Department of Radiology, First Hospital of LanZhou University, Lanzhou 73000, China;
3. Evidence-Based Medicine Center of Lanzhou University, Lanzhou 73000, China;

Corresponding author：

Keywords：

Gd-EOB-DTPA; Gadoxetic acid disodium; Primovist; Liver metastases; Diagnostic test; Meta-analysis

DOI：

10.7507/1672-2531.20150226

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Objective To systematically review the diagnostic value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for liver metastases. Methods We searched databases including CNKI, CBM, VIP, WanFang Data, PubMed, EMbase and The Cochrane Library from January 2011 to December 2014 to collect diagnostic tests about Gd-EOB-DTPA for liver metastases. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies by using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2) tool. Then, meta-analysis was performed by using Stata 12.0 software. Results A total of 15 studies from seven countries were included, involving 2 040 nodules from 701 patients. The results of meta-analysis showed that, the pooled sensitivity (Sen), specificity (Spe), positive likelihood ratio (+LR), negative likelihood ratio (-LR) and diagnostic odds ratio (DOR) of Gd-EOB-DTPA for liver metastases were 0.92 (95%CI 0.89 to 0.95), 0.94 (95%CI 0.89 to 0.97), 14.51 (95%CI 8.01 to 26.28), 0.08 (95%CI 0.06 to 0.12), and 177.98 (95%CI 89.50 to 353.94), respectively. The area under curve (AUC) of SROC was 0.97 (95%CI 0.95 to 0.98). The results of subgroup analysis showed that Gd-EOB-DTPA had better Sen in nodules >10 mm than the nodules ≤10 mm in diameter (>10 mm: pooled Sen=0.97, 95%CI 0.94 to 0.99; ≤10 mm: pooled Sen=0.75, 95%CI 0.65 to 0.85; P<0.001); The 3.0T MR had better Sen in diagnosing liver metastases compared with 1.5T MR (3.0T: pooled Sen=0.95, 95%CI 0.92 to 0.97; 1.5T: pooled Sen=0.90, 95%CI 0.87 to 0.94; P<0.001). Conclusion GdEOB-DTPA is of value for the detection of liver metastases. In particular, it is of high sensitivity for the detection of nodules larger than 10 mm, and for the cases using 3.0T high-field MR system. Due to limited quantity and quality of the included studies, more high-quality studies are required to verify the above conclusion.

Citation： LEIJun-qiang, MAWen-ting, WANGYin-zhong, LUYi, JIANGNan, YANGKe-hu. Diagnostic Value of Gadoxetic Acid Disodium (Gd-EOB-DTPA) for the Detection of Liver Metastases: A Meta-analysis. Chinese Journal of Evidence-Based Medicine, 2015, 15(12): 1378-1386. doi: 10.7507/1672-2531.20150226 Copy

1.	House MG, Ito H, Gönen M, et al. Survival after hepatic resection for metastatic colorectal cancer:trends in outcomes for 1, 600 patients during two decades at a single institution. J Am Coll Surg, 2010, 210(5):744-752.
2.	Robertson DJ, Stukel TA, Gottlieb DJ, et al. Survival after hepatic resection of colorectal cancermetastases:Anational experience. Cancer, 2009, 11(5):752-759.
3.	Chiappa A, Makuuchi M, Lygidakis NJ, et al. Expanding the role of hepatic resection in the age of multimodal therapy. Crit Rev Oncol Hematol, 2009, 72(1):65-75.
4.	Wei AC, Greig PD, Grant D, et al. Survival after hepatic resection for colorectal metastases:A 10 year experience. Ann Surg Oncol, 2008, 13(5):668-676.
5.	Konopke R, Kersting S, Distler M, et al. Prognostic factors and evaluation of a clinical score for predicting survival after resection of colorectal liver metastases. Liver Int, 2009, 29(1):89-102.
6.	Motosugi U, Ichikawa T, Sou H, et al. Distinguishing Hypervascular Pseudolesions of the Liver from Hypervascular Hepatocellular Carcinomas with Gadoxetic Acid-enhanced MR Imaging 1. Radiology, 2010, 256(1):151-158.
7.	Battaglia M, Bucher H, Egger M, et al. The Bayes Library of Diagnostic Studies and Reviews. 2nd edition, 2002.
8.	Whiting PF, Rutjes AW, Westwood ME. QUADAS-2:A Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies. Ann Intern Med, 2011, 155(8):529-536.
9.	Schreiter NF, Nogami M, Steffen I, et al. Evaluation of the potential of PET-MRI fusion for detection of liver metastases in patients with neuroendocrine tumours. European Radiology, 2012, 22(2):458-467.
10.	Goshima S, Kanematsu M, Watanabe H, et al. Hepatic hemangioma and metastasis:differentiation with gadoxetate disodium-Enhanced 3-T MRI. AJR Am J Roentgenol, 2010, 195(4):941-946.
11.	Lee MH, Kim SH, Kim H, et al. Differentiating focal eosinophilic infiltration from metastasis in the liver with gadoxetic acidenhanced magnetic resonance imaging. Korean J Radiol, 2011, 12(4): 439-449.
12.	Motosugi U, Ichikawa T, Onohara K, et al. Distinguishing hepatic metastasis from hemangioma using gadoxetic acid-enhanced magnetic resonance imaging. Invest Radiol, 2011, 46(6):359-365.
13.	钱海峰, 祝跃明, 吴晓, 等. 增强磁共振成像和扩散加权成像序列对肝转移瘤检出价值的比较. 中国医学科学院学报, 2012, 34(6): 621-624.
14.	Löwenthal D, Zeile M, Lim WY, et al. Detection and characterisation of focal liver lesions in colorectal carcinoma patients:comparison of diffusion-weighted and Gd-EOB-DTPA enhanced MR imaging. Eur Radiol, 2011, 21(4):832-840.
15.	Donati OF, Hany TF, Reiner CS, et al. Value of retrospective fusion of PET and MR images in detection of hepatic metastases: comparison with 18F-FDG PET/CT and Gd-EOB-DTPA-enhanced MRI. J Nucl Med, 2010, 51(5):692-699.
16.	Macera A, Lario C, Petracchini M, et al. Staging of colorectal liver metastases after reoperative chemotherapy. Diffusion-weighted imaging in combination with Gd-EOB-DTPA MRI sequences increases sensitivity and diagnostic accuracy. Eur Radiol, 2013,23(3):739-747.
17.	Seo HJ, Kim MJ, Lee JD, et al. Gadoxetate disodium-enhanced magnetic resonance imaging versus contrast-enhanced 18F-fluorodeoxyglucose positron emission tomography/computed tomography for the detection of colorectal liver metastases. Invest Radiol, 2011, 46(9):548-555.
18.	Kim YK, Lee YH, Kwak HS, et al. Detection of liver metastases: Gadoxetic acid-enhanced three-dimensional MR imaging versus ferucarbotran-enhanced MR imaging. Eur J Radiol, 2010, 73(1):131-136.
19.	Shimada K, Isoda H, Hirokawa Y, et al. Comparison of gadoliniumEOB-DTPA-enhanced and diffusion-weighted liver MRI for detection of small hepatic metastases. Eur Radiol, 2010, 20(11): 2690-2698.
20.	Chung WS, Kim MJ, Chung YE, et al. Comparison of gadoxetic acid-enhanced dynamic imaging and diffusion-weighted imaging for the preoperative evaluation of colorectal liver metastases. J Magn Reson Imaging, 2011, 34(2):345-353.
21.	Sofue K, Tsurusaki M, Tokue H, et al. Gd-EOB-DTPA-enhanced 3. 0 T MR imaging:quantitative and qualitative comparison of hepatocyte-phase images obtained 10 min and 20 min after injection for the detection of liver metastases from colorectal carcinoma. Eur Radiol, 2011, 21(11):2336-2343.
22.	Kulemann V, Schima W, Tamandl D, et al. Preoperative detection of colorectal liver meta stases in fatty liver:MDCT or MRI?. Eur J Radiol, 2011, 79(2):e1-e6.
23.	Muhi A, Ichikawa T, Motosugi U, et al. Diagnosis of colorectal hepatic metastases:Comparison of contrast-enhanced CT, contrastenhanced US, superparamagnetic iron oxide-enhanced MRI, and gadoxetic acid-enhanced MRI. J Magn Reson Imaging, 2011, 34(2): 326-335.
24.	Tackmann R, Schuetz G, Hamm B, et al. Quality of the reporting of diagnostic accuracy studies:STARD (Standards for the Reporting of Diagnostic accuracy studies). Rofo, 2010, 182(8):655-659.
25.	McAuley L, Ba'Pham, Tugwell P, et al. Does the inclusion of grey literature influence estimates of intervention effectiveness reported in meta-analyses? Lancet, 2000, 356(9237):1228-1231.
26.	Ferda J, Mirka H, Kastner J, et al. Detection of the colorectal carcinoma liver metastases with magnetic resonance after intravenous application of hepatocellular contrast agent (Gd-EOBDTPA), comparison with the intraoperative ultrasound. Ceska Radiologie, 2008, 62:60-65.
27.	Davey J, Turner RM, Clarke MJ, et al. Characteristics of metaanalyses and their component studies in the Cochrane Database of Systematic Reviews:a cross-sectional, descriptive analysis. BMC Med Res Methodol, 2011, 11:160.
28.	Gluud LL, Thorlund K, Gluud C, et al. Correction:reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses. Ann Intern Med, 2008, 149(3): 219.
29.	Kinkel K, Lu Y, Both M, et al. Detection of hepatic metastases from cancers of the gastrointestinal tract by using noninvasive imaging methods (US, CT, MR imaging, PET):a meta-analysis. Radiology, 2002, 224(3):748-756.
30.	Whiting P, Rutjes AW, Reitsma JB, et al. Sources of variation and bias in studies of diagnostic accuracy:a systematic review. Ann Intern Med, 2004, 140(3):189-202.
31.	Lijmer JG, Bossuyt PM, Heisterkamp SH. Exploring sources of heterogeneity in systematic reviews of diagnostic tests. Stat Med, 2004, 21(11):1525-1537.
32.	汪泽皓, 移康, 杨锐, 等. 抗聚丝蛋白抗体诊断类风湿性关节炎的 Meta分析. 中国循证医学杂志, 2012, 12(9):1076-1082.
33.	卢星如, 张皓, 王浩, 等. 磁共振成像诊断肺栓塞价值的Meta分析. 中国循证医学杂志, 2013, 13(2):160-164.
34.	安妮, 葛龙, 徐俊峰, 等. 酶免疫法对沙眼衣原体诊断价值的Meta 分析. 中国循证医学杂志, 2013, 13(2):165-169.
35.	孔维芳, 刘荣波, 王娜, 等. 多排螺旋CT泌尿系统造影三维重建技术诊断上尿路疾病的ROC分析. 中国循证医学杂志, 2013, 13(2): 143-148.
36.	张晓光, 帕丽达·帕尔哈提, 张雨, 等. 彩色多普勒超声对女性乳腺癌诊断价值的Meta分析. 中国循证医学杂志, 2013, 13(9):1073-1079.

1. House MG, Ito H, Gönen M, et al. Survival after hepatic resection for metastatic colorectal cancer:trends in outcomes for 1, 600 patients during two decades at a single institution. J Am Coll Surg, 2010, 210(5):744-752.
2. Robertson DJ, Stukel TA, Gottlieb DJ, et al. Survival after hepatic resection of colorectal cancermetastases:Anational experience. Cancer, 2009, 11(5):752-759.
3. Chiappa A, Makuuchi M, Lygidakis NJ, et al. Expanding the role of hepatic resection in the age of multimodal therapy. Crit Rev Oncol Hematol, 2009, 72(1):65-75.
4. Wei AC, Greig PD, Grant D, et al. Survival after hepatic resection for colorectal metastases:A 10 year experience. Ann Surg Oncol, 2008, 13(5):668-676.
5. Konopke R, Kersting S, Distler M, et al. Prognostic factors and evaluation of a clinical score for predicting survival after resection of colorectal liver metastases. Liver Int, 2009, 29(1):89-102.
6. Motosugi U, Ichikawa T, Sou H, et al. Distinguishing Hypervascular Pseudolesions of the Liver from Hypervascular Hepatocellular Carcinomas with Gadoxetic Acid-enhanced MR Imaging 1. Radiology, 2010, 256(1):151-158.
7. Battaglia M, Bucher H, Egger M, et al. The Bayes Library of Diagnostic Studies and Reviews. 2nd edition, 2002.
8. Whiting PF, Rutjes AW, Westwood ME. QUADAS-2:A Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies. Ann Intern Med, 2011, 155(8):529-536.
9. Schreiter NF, Nogami M, Steffen I, et al. Evaluation of the potential of PET-MRI fusion for detection of liver metastases in patients with neuroendocrine tumours. European Radiology, 2012, 22(2):458-467.
10. Goshima S, Kanematsu M, Watanabe H, et al. Hepatic hemangioma and metastasis:differentiation with gadoxetate disodium-Enhanced 3-T MRI. AJR Am J Roentgenol, 2010, 195(4):941-946.
11. Lee MH, Kim SH, Kim H, et al. Differentiating focal eosinophilic infiltration from metastasis in the liver with gadoxetic acidenhanced magnetic resonance imaging. Korean J Radiol, 2011, 12(4): 439-449.
12. Motosugi U, Ichikawa T, Onohara K, et al. Distinguishing hepatic metastasis from hemangioma using gadoxetic acid-enhanced magnetic resonance imaging. Invest Radiol, 2011, 46(6):359-365.
13. 钱海峰, 祝跃明, 吴晓, 等. 增强磁共振成像和扩散加权成像序列对肝转移瘤检出价值的比较. 中国医学科学院学报, 2012, 34(6): 621-624.
14. Löwenthal D, Zeile M, Lim WY, et al. Detection and characterisation of focal liver lesions in colorectal carcinoma patients:comparison of diffusion-weighted and Gd-EOB-DTPA enhanced MR imaging. Eur Radiol, 2011, 21(4):832-840.
15. Donati OF, Hany TF, Reiner CS, et al. Value of retrospective fusion of PET and MR images in detection of hepatic metastases: comparison with 18F-FDG PET/CT and Gd-EOB-DTPA-enhanced MRI. J Nucl Med, 2010, 51(5):692-699.
16. Macera A, Lario C, Petracchini M, et al. Staging of colorectal liver metastases after reoperative chemotherapy. Diffusion-weighted imaging in combination with Gd-EOB-DTPA MRI sequences increases sensitivity and diagnostic accuracy. Eur Radiol, 2013,23(3):739-747.
17. Seo HJ, Kim MJ, Lee JD, et al. Gadoxetate disodium-enhanced magnetic resonance imaging versus contrast-enhanced 18F-fluorodeoxyglucose positron emission tomography/computed tomography for the detection of colorectal liver metastases. Invest Radiol, 2011, 46(9):548-555.
18. Kim YK, Lee YH, Kwak HS, et al. Detection of liver metastases: Gadoxetic acid-enhanced three-dimensional MR imaging versus ferucarbotran-enhanced MR imaging. Eur J Radiol, 2010, 73(1):131-136.
19. Shimada K, Isoda H, Hirokawa Y, et al. Comparison of gadoliniumEOB-DTPA-enhanced and diffusion-weighted liver MRI for detection of small hepatic metastases. Eur Radiol, 2010, 20(11): 2690-2698.
20. Chung WS, Kim MJ, Chung YE, et al. Comparison of gadoxetic acid-enhanced dynamic imaging and diffusion-weighted imaging for the preoperative evaluation of colorectal liver metastases. J Magn Reson Imaging, 2011, 34(2):345-353.
21. Sofue K, Tsurusaki M, Tokue H, et al. Gd-EOB-DTPA-enhanced 3. 0 T MR imaging:quantitative and qualitative comparison of hepatocyte-phase images obtained 10 min and 20 min after injection for the detection of liver metastases from colorectal carcinoma. Eur Radiol, 2011, 21(11):2336-2343.
22. Kulemann V, Schima W, Tamandl D, et al. Preoperative detection of colorectal liver meta stases in fatty liver:MDCT or MRI?. Eur J Radiol, 2011, 79(2):e1-e6.
23. Muhi A, Ichikawa T, Motosugi U, et al. Diagnosis of colorectal hepatic metastases:Comparison of contrast-enhanced CT, contrastenhanced US, superparamagnetic iron oxide-enhanced MRI, and gadoxetic acid-enhanced MRI. J Magn Reson Imaging, 2011, 34(2): 326-335.
24. Tackmann R, Schuetz G, Hamm B, et al. Quality of the reporting of diagnostic accuracy studies:STARD (Standards for the Reporting of Diagnostic accuracy studies). Rofo, 2010, 182(8):655-659.
25. McAuley L, Ba'Pham, Tugwell P, et al. Does the inclusion of grey literature influence estimates of intervention effectiveness reported in meta-analyses? Lancet, 2000, 356(9237):1228-1231.
26. Ferda J, Mirka H, Kastner J, et al. Detection of the colorectal carcinoma liver metastases with magnetic resonance after intravenous application of hepatocellular contrast agent (Gd-EOBDTPA), comparison with the intraoperative ultrasound. Ceska Radiologie, 2008, 62:60-65.
27. Davey J, Turner RM, Clarke MJ, et al. Characteristics of metaanalyses and their component studies in the Cochrane Database of Systematic Reviews:a cross-sectional, descriptive analysis. BMC Med Res Methodol, 2011, 11:160.
28. Gluud LL, Thorlund K, Gluud C, et al. Correction:reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses. Ann Intern Med, 2008, 149(3): 219.
29. Kinkel K, Lu Y, Both M, et al. Detection of hepatic metastases from cancers of the gastrointestinal tract by using noninvasive imaging methods (US, CT, MR imaging, PET):a meta-analysis. Radiology, 2002, 224(3):748-756.
30. Whiting P, Rutjes AW, Reitsma JB, et al. Sources of variation and bias in studies of diagnostic accuracy:a systematic review. Ann Intern Med, 2004, 140(3):189-202.
31. Lijmer JG, Bossuyt PM, Heisterkamp SH. Exploring sources of heterogeneity in systematic reviews of diagnostic tests. Stat Med, 2004, 21(11):1525-1537.
32. 汪泽皓, 移康, 杨锐, 等. 抗聚丝蛋白抗体诊断类风湿性关节炎的 Meta分析. 中国循证医学杂志, 2012, 12(9):1076-1082.
33. 卢星如, 张皓, 王浩, 等. 磁共振成像诊断肺栓塞价值的Meta分析. 中国循证医学杂志, 2013, 13(2):160-164.
34. 安妮, 葛龙, 徐俊峰, 等. 酶免疫法对沙眼衣原体诊断价值的Meta 分析. 中国循证医学杂志, 2013, 13(2):165-169.
35. 孔维芳, 刘荣波, 王娜, 等. 多排螺旋CT泌尿系统造影三维重建技术诊断上尿路疾病的ROC分析. 中国循证医学杂志, 2013, 13(2): 143-148.
36. 张晓光, 帕丽达·帕尔哈提, 张雨, 等. 彩色多普勒超声对女性乳腺癌诊断价值的Meta分析. 中国循证医学杂志, 2013, 13(9):1073-1079.

Chinese Journal of Evidence-Based Medicine

Diagnostic Value of Gadoxetic Acid Disodium (Gd-EOB-DTPA) for the Detection of Liver Metastases: A Meta-analysis

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