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High Diagnostic Accuracy and Safety of Endoscopic Ultrasound-Guided Fine-Needle Aspiration in Malignant Lymph Nodes: A Systematic Review and Meta-Analysis

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Abstract

Background and Aims

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is increasingly being used for diagnosing lymphadenopathy. We aim to systematically review the accuracy of EUS-FNA in differentiating benign and malignant mediastinal and abdominal lymph nodes (LNs).

Methods

A comprehensive literature search was performed on multiple electronic databases through February 2020. A random or fixed effect model generated the pooled sensitivity, specificity, likelihood ratio (LR), and diagnostic odds ratio (DOR) of EUS-FNA. Subgroup analyses and meta-regression were used to explore sources of heterogeneity.

Results

Twenty-six studies involving 2753 patients with 2833 LNs were included. In the differential diagnosis of benign and malignant LNs, EUS-FNA had a pooled sensitivity, specificity, positive LR, and negative LR of 87% (95% confidence interval [CI] 86–90%), 100% (95% CI 99–100%), 68.98 (95% CI 42.10–113.02), and 0.14 (95% CI 0.11–0.17), respectively. The pooled rate of adverse events associated with EUS-FNA was 1.57% (95% CI 1.06–2.24%). The summary receiver operating characteristic (SROC) yielded an area under the curve (AUC) of 0.9912. EUS-FNA performed in mediastinal LNs gained a sensitivity of 85% (95% CI 81–88%), while in abdominal LNs, it reached 87% (95% CI 82–91%). The sensitivity of the subgroup with rapid on-site evaluation (ROSE) was 91% (95% CI 89–93%), while non-ROSE was 85% (95% CI 82–87%).

Conclusions

EUS-FNA is a sensitive, highly specific, and safe method for distinguishing benign and malignant mediastinal or abdominal LNs. However, the sensitivity of EUS-FNA still varies significantly among different centers.

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References

  1. Bem C, Patil PS, Bharucha H, et al. Importance of human immunodeficiency virus-associated lymphadenopathy and tuberculous lymphadenitis in patients undergoing lymph node biopsy in Zambia. Br J Surg. 1996;83:75–78.

    CAS  PubMed  Google Scholar 

  2. Vilmann P, Clementsen PF, Colella S, et al. Combined endobronchial and esophageal endosonography for the diagnosis and staging of lung cancer: European Society of Gastrointestinal Endoscopy (ESGE) Guideline, in cooperation with the European Respiratory Society (ERS) and the European Society of Thoracic Surgeons (ESTS). Endoscopy. 2015;47:545–559.

    PubMed  Google Scholar 

  3. Habermann CR, Weiss F, Riecken R, et al. Preoperative staging of gastric adenocarcinoma: comparison of helical CT and endoscopic US. Radiology. 2004;230:465–471.

    PubMed  Google Scholar 

  4. De Potter T, Flamen P, Van Cutsem E, et al. Whole-body PET with FDG for the diagnosis of recurrent gastric cancer. Eur J Nucl Med Mol Imaging. 2002;29:525–529.

    PubMed  Google Scholar 

  5. Annema JT, Versteegh MI, Veselic M, et al. Endoscopic ultrasound-guided fine-needle aspiration in the diagnosis and staging of lung cancer and its impact on surgical staging. Journal of Clinical Oncology. 2005;23:8357–8361.

    PubMed  Google Scholar 

  6. Puri R, Mangla R, Eloubeidi M, et al. Diagnostic yield of EUS-guided FNA and cytology in suspected tubercular intra-abdominal lymphadenopathy. Gastrointest Endosc. 2012;75:1005–1010.

    PubMed  Google Scholar 

  7. Li C, Shuai Y, Zhou X. Endoscopic ultrasound guided fine needle aspiration for the diagnosis of intra-abdominal lymphadenopathy: a systematic review and meta-analysis. Scand J Gastroenterol. 2020;55:114–122.

    PubMed  Google Scholar 

  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.

    PubMed  PubMed Central  Google Scholar 

  9. Whiting P, Rutjes AW, Reitsma JB, et al. The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol. 2003;3:25.

    PubMed  PubMed Central  Google Scholar 

  10. Miller RG. The jackknife—a review. Biometrika. 1974;61:1–15.

    Google Scholar 

  11. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–1558.

    PubMed  Google Scholar 

  12. Higgins JP, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–560.

    PubMed  PubMed Central  Google Scholar 

  13. Guyatt GH, Oxman AD, Kunz R, et al. GRADE guidelines: 7. Rating the quality of evidence–inconsistency. J Clin Epidemiol. 2011;64:1294–1302.

    PubMed  Google Scholar 

  14. Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719–748.

    CAS  PubMed  Google Scholar 

  15. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–188.

    CAS  PubMed  Google Scholar 

  16. 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.

    CAS  PubMed  Google Scholar 

  17. Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology. 1982;143:29–36.

    CAS  PubMed  Google Scholar 

  18. Zamora J, Abraira V, Muriel A, et al. Meta-DiSc: a software for meta-analysis of test accuracy data. BMC Med Res Methodol. 2006;6:31.

    PubMed  PubMed Central  Google Scholar 

  19. Fritscher-Ravens A, Sriram PV, Bobrowski C, et al. Mediastinal lymphadenopathy in patients with or without previous malignancy: EUS-FNA-based differential cytodiagnosis in 153 patients. Am J Gastroenterol. 2000;95:2278–2284.

    CAS  PubMed  Google Scholar 

  20. Wiersema MJ, Vazquez-Sequeiros E, Wiersema LM. Evaluation of mediastinal lymphadenopathy with endoscopic US-guided fine-needle aspiration biopsy. Radiology. 2001;219:252–257.

    CAS  PubMed  Google Scholar 

  21. Chhieng DC, Jhala D, Jhala N, et al. Endoscopic ultrasound-guided fine-needle aspiration biopsy: a study of 103 cases. Cancer. 2002;96:232–239.

    PubMed  Google Scholar 

  22. Larsen SS, Krasnik M, Vilmann P, et al. Endoscopic ultrasound guided biopsy of mediastinal lesions has a major impact on patient management. Thorax. 2002;57:98–103.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Chen VK, Eloubeidi MA. Endoscopic ultrasound-guided fine needle aspiration is superior to lymph node echofeatures: a prospective evaluation of mediastinal and peri-intestinal lymphadenopathy. Am J Gastroenterol. 2004;99:628–633.

    PubMed  Google Scholar 

  24. Südhoff T, Hollerbach S, Wilhelms I, et al. Clinical utility of EUS-FNA in upper gastrointestinal and mediastinal disease. Deutsche Medizinische Wochenschrif.. 2004;129:2227–2232.

    Google Scholar 

  25. Savides TJ, Perricone A. Impact of EUS-guided FNA of enlarged mediastinal lymph nodes on subsequent thoracic surgery rates. Gastrointest Endosc. 2004;60:340–346.

    PubMed  Google Scholar 

  26. Kramer H, Sanders J, Post WJ, et al. Analysis of cytological specimens from mediastinal lesions obtained by endoscopic ultrasound-guided fine-needle aspiration. Cancer. 2006;108:206–211.

    PubMed  Google Scholar 

  27. Yasuda I, Tsurumi H, Omar S, et al. Endoscopic ultrasound-guided fine-needle aspiration biopsy for lymphadenopathy of unknown origin. Endoscopy. 2006;38:919–924.

    CAS  PubMed  Google Scholar 

  28. Eloubeidi MA, Tamhane A. Prospective assessment of diagnostic utility and complications of endoscopic ultrasound-guided fine needle aspiration. Dig Dis. 2008;26:356–363.

    PubMed  Google Scholar 

  29. Salom F, Mangialavori L, Roseau G, et al. Contribution of endoscopic ultrasound-guided fine-needle aspiration in the workup of mediastinal lymph nodes. Gastroenterolo Clin Biol. 2010;34:88–94.

    CAS  Google Scholar 

  30. Dhir V, Mathew P, Bhandari S, et al. Endosonography-guided fine needle aspiration cytology of intra-abdominal lymph nodes with unknown primary in a tuberculosis endemic region. J Gastroenterol Hepatol. 2011;26:1721–1724.

    PubMed  Google Scholar 

  31. Kushnir VM, Wani SB, Hovis CE, et al. The role of endoscopic ultrasound (EUS) in the diagnosis of unexplained lymphadenopathy: a single center experience. Gastrointest Endosc. 2011;73:AB178.

    Google Scholar 

  32. Korenblit J, Anantharaman A, Loren DE, et al. The role of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for the diagnosis of intra-abdominal lymphadenopathy of unknown origin. J Intervent Gastroenterol. 2012;2:172–176.

    Google Scholar 

  33. Hegade VS, Saralaya D, Jowett S, et al. Endoscopic ultrasound guided fine needle aspiration (EUS-FNA) in suspected sarcoidosis—a 4-year experience from a single centre. Gut. 2012;61:A387–A388.

    Google Scholar 

  34. Coe A, Conway J, Evans J, et al. The yield of EUS-FNA in undiagnosed upper abdominal adenopathy is very high. J Clin Ultrasound: JCU. 2013;41:210–213.

    PubMed  Google Scholar 

  35. Srinivasan R, Bhutani MS, Thosani N, et al. Clinical impact of EUS-FNA of mediastinal lymph nodes in patients with known or suspected lung cancer or mediastinal lymph nodes of unknown etiology. J Gastrointest Liver Dis. 2012;21:145–152.

    Google Scholar 

  36. Bohle W, Meier C, Zoller WG. Validity of endoscopic ultrasonography-guided fine needle aspiration of mediastinal and abdominal lymph nodes in daily clinical practice. Deutsche Medizinische Wochenschr. 2013;138:412–417.

    CAS  Google Scholar 

  37. Jamil LH, Kashani A, Scimeca D, et al. Can endoscopic ultrasound distinguish between mediastinal benign lymph nodes and those involved by sarcoidosis, lymphoma, or metastasis? Dig Dis Sci. 2014;59:2191–2198.

    PubMed  Google Scholar 

  38. Paik WH, Park Y, Park DH, et al. Prospective evaluation of new 22 gauge endoscopic ultrasound core needle using capillary sampling with stylet slow-pull technique for intra-abdominal solid masses. J Clin Gastroenterol. 2015;49:199–205.

    PubMed  Google Scholar 

  39. Redondo-Cerezo E, Martinez-Cara JG, Esquivias J, et al. Endoscopic ultrasonography-fine needle aspiration versus PET-CT in undiagnosed mediastinal and upper abdominal lymphadenopathy: a comparative clinical study. Eur J Gastroenterol Hepatol. 2015;27:455–459.

    PubMed  Google Scholar 

  40. Chin YK, Iglesias-Garcia J, de la Iglesia D, et al. Accuracy of endoscopic ultrasound-guided tissue acquisition in the evaluation of lymph nodes enlargement in the absence of on-site pathologist. World J Gastroenterol. 2017;23:5755–5763.

    PubMed  PubMed Central  Google Scholar 

  41. Okasha H, Elkholy S, Sayed M, et al. Endoscopic ultrasound-guided fine-needle aspiration and cytology for differentiating benign from malignant lymph nodes. Arab J Gastroenterol. 2017;18:74–79.

    PubMed  Google Scholar 

  42. Wang JL, Chen Q, Wu XL, et al. Role of endoscopic ultrasound-guided fine-needle aspiration in evaluating mediastinal and intra-abdominal lymphadenopathies of unknown origin. Oncol Lett. 2018;15:6991–6999.

    PubMed  PubMed Central  Google Scholar 

  43. Fujii Y, Kanno Y, Koshita S, et al. Predictive factors for inaccurate diagnosis of swollen lymph nodes in endoscopic ultrasound-guided fine needle aspiration. Clin Endosc. 2019;52:152–158.

    PubMed  PubMed Central  Google Scholar 

  44. Junare PR, Jain S, Rathi P, et al. Endoscopic ultrasound-guided-fine-needle aspiration/fine-needle biopsy in diagnosis of mediastinal lymphadenopathy—a boon. Lung India. 2020;37:37–44.

    PubMed  Google Scholar 

  45. Wallace MB, Pascual JM, Raimondo M, et al. Minimally invasive endoscopic staging of suspected lung cancer. JAMA. 2008;299:540–546.

    CAS  PubMed  Google Scholar 

  46. Silvestri GA, Gonzalez AV, Jantz MA, et al. Methods for staging non-small cell lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143:e211S–e250S.

    PubMed  Google Scholar 

  47. Schmidt-Hansen M, Baldwin DR, Zamora J. FDG-PET/CT imaging for mediastinal staging in patients with potentially resectable non-small cell lung cancer. JAMA. 2015;313:1465–1466.

    CAS  PubMed  Google Scholar 

  48. Keswani RN, Early DS, Edmundowicz SA, et al. Routine positron emission tomography does not alter nodal staging in patients undergoing EUS-guided FNA for esophageal cancer. Gastrointest Endosc. 2009;69:1210–1217.

    PubMed  Google Scholar 

  49. Catalano MF, Sivak MV Jr, Rice T, et al. Endosonographic features predictive of lymph node metastasis. Gastrointest Endosc. 1994;40:442–446.

    CAS  PubMed  Google Scholar 

  50. 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.

    PubMed  Google Scholar 

  51. Song HJ, Kim JO, Eun SH, et al. Endoscopic ultrasonographic findings of benign mediastinal and abdominal lymphadenopathy confirmed by eus-guided fine needle aspiration. Gut Liver. 2007;1:68–73.

    PubMed  PubMed Central  Google Scholar 

  52. 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;74:1001–1115.e11154.

    PubMed  Google Scholar 

  53. 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.

    PubMed  Google Scholar 

  54. Lisotti A, Ricci C, Serrani M, et al. Contrast-enhanced endoscopic ultrasound for the differential diagnosis between benign and malignant lymph nodes: a meta-analysis. Endosc Int Open. 2019;7:E504–E513.

    PubMed  PubMed Central  Google Scholar 

  55. Yoshida K, Iwashita T, Uemura S, et al. Efficacy of contrast-enhanced EUS for lymphadenopathy: a prospective multicenter pilot study (with videos). Gastrointest Endosc. 2019;90:242–250.

    PubMed  Google Scholar 

  56. Wang KX, Ben QW, Jin ZD, et al. Assessment of morbidity and mortality associated with EUS-guided FNA: a systematic review. Gastrointest Endosc. 2011;73:283–290.

    PubMed  Google Scholar 

  57. Yasufuku K, Chiyo M, Sekine Y, et al. Real-time endobronchial ultrasound-guided transbronchial needle aspiration of mediastinal and hilar lymph nodes. Chest. 2004;126:122–128.

    PubMed  Google Scholar 

  58. Adams K, Shah PL, Edmonds L, et al. Test performance of endobronchial ultrasound and transbronchial needle aspiration biopsy for mediastinal staging in patients with lung cancer: systematic review and meta-analysis. Thorax. 2009;64:757–762.

    CAS  PubMed  Google Scholar 

  59. Herth FJ, Krasnik M, Kahn N, et al. Combined endoscopic-endobronchial ultrasound-guided fine-needle aspiration of mediastinal lymph nodes through a single bronchoscope in 150 patients with suspected lung cancer. Chest. 2010;138:790–794.

    PubMed  Google Scholar 

  60. Sehgal IS, Dhooria S, Aggarwal AN, et al. Impact of rapid on-site cytological evaluation (ROSE) on the diagnostic yield of transbronchial needle aspiration during mediastinal lymph node sampling: systematic review and meta-analysis. Chest. 2018;153:929–938.

    PubMed  Google Scholar 

  61. Keswani RN, Krishnan K, Wani S, et al. Addition of endoscopic ultrasound (EUS)-guided fine needle aspiration and on-site cytology to EUS-guided fine needle biopsy increases procedure time but not diagnostic accuracy. Clin Endosc. 2014;47:242–247.

    PubMed  PubMed Central  Google Scholar 

  62. Rodrigues-Pinto E, Jalaj S, Grimm IS, et al. Impact of EUS-guided fine-needle biopsy sampling with a new core needle on the need for onsite cytopathologic assessment: a preliminary study. Gastrointest Endosc. 2016;84:1040–1046.

    PubMed  Google Scholar 

  63. De Moura DTH, McCarty TR, Jirapinyo P, et al. Endoscopic ultrasound fine-needle aspiration versus fine-needle biopsy for lymph node diagnosis: a large multicenter comparative analysis. Clin Endosc. 2019;. https://doi.org/10.5946/ce.2019.170.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Ribeiro A, Vazquez-Sequeiros E, Wiersema LM, Wang KK, Clain JE, Wiersema MJ. EUS-guided fine-needle aspiration combined with flow cytometry and immunocytochemistry in the diagnosis of lymphoma. Gastrointest Endosc. 2001;53:485–491.

    CAS  PubMed  Google Scholar 

  65. Nakahara O, Yamao K, Bhatia V, et al. Usefulness of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for undiagnosed intra-abdominal lymphadenopathy. J Gastroenterol. 2009;44:562–567.

    PubMed  Google Scholar 

  66. Wallace MB, Kennedy T, Durkalski V, et al. Randomized controlled trial of EUS-guided fine needle aspiration techniques for the detection of malignant lymphadenopathy. Gastrointest Endosc. 2001;54:441–447.

    CAS  PubMed  Google Scholar 

  67. Bardales RH, Stelow EB, Mallery S, et al. Review of endoscopic ultrasound-guided fine-needle aspiration cytology. Diagn Cytopathol. 2006;34:140–175.

    PubMed  Google Scholar 

  68. LeBlanc JK, Ciaccia D, Al-Assi MT, et al. Optimal number of EUS-guided fine needle passes needed to obtain a correct diagnosis. Gastrointest Endosc. 2004;59:475–481.

    PubMed  Google Scholar 

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Funding

This study was funded by the Science and Technology Plan Grant (No. M201504) from the Esophageal Cancer Research Institute of Guangdong Province, China, and the Group Assistance Plan in Tibet of the National Natural Science Foundation of China (No. XZ2019ZR-ZY60(Z)).

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Authors and Affiliations

  1. Department of Endoscopy, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People’s Republic of China

    Linbin Chen, Yin Li, Xiaoyan Gao, Shiyong Lin, Longjun He, Guangyu Luo, Jianjun Li, Chunyu Huang, Guobao Wang, Qing Yang & Hongbo Shan

  2. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China

    Linbin Chen, Yin Li, Xiaoyan Gao, Shiyong Lin, Longjun He, Guangyu Luo, Jianjun Li, Chunyu Huang, Guobao Wang, Qing Yang & Hongbo Shan

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  1. Linbin Chen
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Correspondence to Hongbo Shan.

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The study protocol was prospectively registered in PROSPERO (http://www.crd.york.ac.uk/PROSPERO; registration number: CRD42020171901).

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Chen, L., Li, Y., Gao, X. et al. High Diagnostic Accuracy and Safety of Endoscopic Ultrasound-Guided Fine-Needle Aspiration in Malignant Lymph Nodes: A Systematic Review and Meta-Analysis. Dig Dis Sci 66, 2763–2775 (2021). https://doi.org/10.1007/s10620-020-06554-2

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