CC BY-NC-ND 4.0 · Endosc Int Open 2019; 07(04): E504-E513
DOI: 10.1055/a-0854-3785
Original article
Owner and Copyright © Georg Thieme Verlag KG 2019

Contrast-enhanced endoscopic ultrasound for the differential diagnosis between benign and malignant lymph nodes: a meta-analysis

Andrea Lisotti
1   Gastroenterology Unit, Department of Medical and Surgical Sciences, University of Bologna, Hospital of Imola, Imola, Bologna, Italy
,
Claudio Ricci
2   Department Medical and Surgical Sciences (DIMEC), University of Bologna, S.Orsola-Malpighi Hospital, Bologna, Italy
,
Marta Serrani
1   Gastroenterology Unit, Department of Medical and Surgical Sciences, University of Bologna, Hospital of Imola, Imola, Bologna, Italy
,
Claudio Calvanese
1   Gastroenterology Unit, Department of Medical and Surgical Sciences, University of Bologna, Hospital of Imola, Imola, Bologna, Italy
,
Sandro Sferrazza
1   Gastroenterology Unit, Department of Medical and Surgical Sciences, University of Bologna, Hospital of Imola, Imola, Bologna, Italy
,
Nicole Brighi
3   Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Oncology Unit, S. Orsola-Malpighi Hospital, Bologna, Italy
,
Riccardo Casadei
2   Department Medical and Surgical Sciences (DIMEC), University of Bologna, S.Orsola-Malpighi Hospital, Bologna, Italy
,
Pietro Fusaroli
1   Gastroenterology Unit, Department of Medical and Surgical Sciences, University of Bologna, Hospital of Imola, Imola, Bologna, Italy
2   Department Medical and Surgical Sciences (DIMEC), University of Bologna, S.Orsola-Malpighi Hospital, Bologna, Italy
› Author Affiliations
Further Information

Publication History

submitted 27 July 2018

accepted after revision 07 January 2019

Publication Date:
03 April 2019 (online)

Abstract

Background The differential diagnosis between benign and malignant lymph nodes (LNs) is crucial for patient management and clinical outcome. The use of contrast-enhanced endoscopic ultrasound (EUS) has been evaluated in several studies with diverse results. The aim of this meta-analysis was to evaluate the pooled diagnostic accuracy of contrast-enhanced EUS (CE-EUS) and contrast-enhanced harmonic EUS (CH-EUS) in this setting.

Methods A systematic electronic search was performed, including all original papers dealing with assessment of the nature of the LNs using CE-EUS or CH-EUS. A meta-analysis was performed to obtain pooled sensitivity, specificity, positive and negative likelihood ratio, and diagnostic odds ratio. The Summary Receiver Operating Characteristic (ROC) Curve method was used to calculate the area under the curve. Statistical analysis was carried out using Meta-Disc V.1.4, Stata V.12.0 and Review Manager V.5.2.

Results Among 210 pertinent studies, four (336 patients) were included in the analysis. The pooled sensitivity was 82.1 % (75.1 – 87.7 %) and pooled specificity was 90.7 % (85.9 – 94.3 %) with significant heterogeneity found in sensitivity; the positive-likelihood ratio (LR) was 7.77 (5.09 – 11.85) and the negative-LR was 0.15 (0.05 – 0.46); the pooled diagnostic odds ratio (DOR) was 54 (15 – 190). Subgroup analysis including studies performed using CH-EUS (two studies, 177 LNs) showed a pooled sensitivity of 87.7 % (77.0 – 93.9 %) and a pooled specificity of 91.8 % (84.5 % – 96.4 %) with no significant heterogeneity; the pooled positive-LR was 9.51 (4.95 – 18.28) and the pooled negative-LR was 0.14 (0.06 – 0.35); pooled DOR was 68.42 (15.5 – 301.4).

Conclusions From these data, CE-EUS is not recommended due to inadequate sensitivity. On the other hand, CH-EUS studies showed optimal accuracy (pooled sensitivity 87.7 % and specificity 91.8 %), comparable to elastography and even EUS-guided fine needle aspiration (EUS-FNA), suggesting a role in the diagnostic algorithm.

 
  • References

  • 1 Catalano MF, Sivak Jr MV, Rice T. et al. Endosonographic features predictive of lymph node metastasis. Gastrointest Endosc 1994; 40: 442-446
  • 2 Bhutani MS, Hawes RH, Hoffman BJ. A comparison of the accuracy of echo features during endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration for diagnosis of malignant lymph node invasion. Gastrointest Endosc 1997; 45: 474-479
  • 3 Faige DO. EUS in patients with benign and malignant lymphadenopathy. Gastrointest Endosc 2001; 53: 593-598
  • 4 Cui XW, Hocke M, Jenssen C. et al. Conventional ultrasound for lymph node evaluation, update 2013. Z Gastroenterol 2014; 52: 212-221
  • 5 Dietrich CF, Jenssen C, Arcidiacono PG. et al. Endoscopic ultrasound: Elastographic lymph node evaluation. Endosc Ultrasound 2015; 4: 176-190
  • 6 Cui XW, Jenssen C, Saftoiu A. et al. New ultrasound techniques for lymph node evaluation. World J Gastroenterol 2013; 19: 4850-4860
  • 7 Jenssen C, Hocke M, Fusaroli P. et al. EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part IV – EUS-guided Interventions: General aspects and EUS-guided sampling (Long Version). Ultraschall Med 2016; 37: E33-76
  • 8 Puli SR, Batapati Krishna Reddy J, Bechtold ML. et al. Endoscopic ultrasound: it’s accuracy in evaluating mediastinal lymphadenopathy? A meta-analysis and systematic review. World J Gastroenterol 2008; 14: 3028-3037
  • 9 Xu W, Shi J, Zeng X. et al. EUS elastography for the differentiation of benign and malignant lymph nodes: a meta-analysis. Gastrointest Endosc 2011; 74: 1001-1009
  • 10 Kojima S, Goto H, Hirooka Y. et al. Differentiation of benign and malignant lymph nodes with contrast-enhanced echolymphography using endoscopic ultrasound-guided puncture. Hepatogastroenterology 2003; 50: 1285-1291
  • 11 Fusaroli P, Napoleon B, Gincul R. et al. The clinical impact of ultrasound contrast agents in EUS: a systematic review according to the levels of evidence. Gastrointest Endosc 2016; 84: 587-596.e10
  • 12 University of Bristol. QUADAS-2. Available at: http://www.bristol.ac.uk/population-health-sciences/projects/quadas/quadas-2/
  • 13 Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 2005; 5: 13
  • 14 Irwig L, Bossuyt P, Glasziou P. et al. Designing studies to ensure that estimates of test accuracy are transferable. BMJ 2002; 324: 669-671
  • 15 Raslich MA, Markert RJ, Stutes SA. Selecting and interpreting diagnostic tests. Biochem Med 2007; 17: 151-161
  • 16 Glas AS, Lijmer JG, Prins MH. et al. The diagnostic odds ratio: a single indicator of test performance. J Clin Epidemiol 2003; 56: 1129-1135
  • 17 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177-188
  • 18 Swets JA. Measuring the accuracy of diagnostic systems. Science 1988; 240: 1285-1293
  • 19 Deeks JJ, Macaskill P, Irwig L. The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. J Clin Epidemiol 2005; 58: 882-893
  • 20 Moses LE, Shapiro D, Littenberg B. Combining independent studies of a diagnostic test into a summary ROC curve: data-analytic approaches and some additional considerations. Stat Med 1993; 12: 1293-1316
  • 21 Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21: 1539-1558
  • 22 Miyata T, Kitano M, Sakamoto H. et al. 348 Role of contrast-enhanced harmonic EUS in differentiating malignant from benign lymphadenopathy. Gastrointest Endosc 2013; 77: AB142
  • 23 Miyata T, Kitano M, Omoto S. et al. Contrast-enhanced harmonic endoscopic ultrasonography for assessment of lymph node metastases in pancreatobiliary carcinoma. World J Gastroenterol 2016; 22: 3381-3391
  • 24 Kanamori A, Hirooka Y, Itoh A. et al. Usefulness of contrast-enhanced endoscopic ultrasonography in the differentiation between malignant and benign lymphadenopathy. Am J Gastroenterol 2006; 101: 45-51
  • 25 Hocke M, Menges M, Topalidis T. et al. Contrast-enhanced endoscopic ultrasound in discrimination between benign and malignant mediastinal and abdominal lymph nodes. J Cancer Res Clin Oncol 2008; 134: 473-480
  • 26 Xia Y, Kitano M, Kudo M. et al. Characterization of intra-abdominal lesions of undetermined origin by contrast-enhanced harmonic EUS (with videos). Gastrointest Endosc 2010; 72: 637-642
  • 27 Naaktgeboren CA, van Enst WA, Ochodo EA. et al. Systematic overview finds variation in approaches to investigating and reporting on sources of heterogeneity in systematic reviews of diagnostic studies. J Clin Epidemiol 2014; 67: 1200-1209
  • 28 Leeflang MM, Rutjes AW, Reitsma JB. et al. Variation of a test’s sensitivity and specificity with disease prevalence. CMAJ 2013; 185: E537-544
  • 29 Dumonceau JM, Deprez PH, Jenssen C. et al. Indications, results, and clinical impact of endoscopic ultrasound (EUS)-guided sampling in gastroenterology: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline – Updated January 2017. Endoscopy 2017; 49: 695-714
  • 30 Hocke M, Ignee A, Dietrich C. Role of contrast-enhanced endoscopic ultrasound in lymph nodes. Endosc Ultrasound 2017; 6: 4-11
  • 31 Gong TT, Hu DM, Zhu Q. Contrast-enhanced EUS for differential diagnosis of pancreatic mass lesions: a meta-analysis. Gastrointest Endosc 2012; 76: 301-309
  • 32 Wu M, Li L, Wang J. et al. Contrast-enhanced US for characterization of focal liver lesions: a comprehensive meta-analysis. Eur Radiol 2018; 28: 2077-2088