1. 1 A Systematic Review of the Validity of Endoscopic Ultrasound for Esophageal Carcinoma Staging 3 rd presentation Class 3: Ana Maria Reis, Ana Margarida Rodrigues, Ana Raquel Marçôa, Ana Raquel Freitas, Ana Raquel Marques, Ana Raquel Barreira, Ana Coelho, Ana Rita Linhas, Ana Rita Maia, Ana Rita Dias, Luís Gomes, Miguel Castro. Project Manager: Mário Dinis Ribeiro Faculty of Medicine – University of Porto Introdução à Medicina

2. EUS for Esophageal Carcinoma Staging Faculty of Medicine – University of Porto 2 Sistematic Review to evaluate validity of a diagnosis test: EUS Sensitivity: probability of, being ill, have a positive test Especificity: probability of, not being ill, have a negative test

3. Introdução à Medicina EUS for Esophageal Carcinoma Staging Faculty of Medicine – University of Porto 3 INTRODUCTION (I) Esophageal cancer is the eighth most common cancer in the world [1]. Patients with esophageal cancer have less than 10% 5-year survival despite advances in multimodality therapy [1]. [1] Allan Pickens, MDª, Mark B., Orringer, MDª. Geographical distribution and racial disparity in esophageal cancer.2003, 76:S1367-S1369.

4. Introdução à Medicina EUS for Esophageal Carcinoma Staging Faculty of Medicine – University of Porto 4 INTRODUCTION (II): Curative attempts:  Surgery  Chemotherapy  Radiation [2]. [2]Kiran S.Parmar,MD,Joseph B. Zwischenberger,MD,Angela L. Reeves,CGRN and Irving Wacman,MD.Clinical Impact of Endoscopic Ultrasound-Guided Fine Needle Aspiration of Celiac Axis Lymph Nodes (M1a Disease) in Esophageal Cancer.2002,73:916-21.

5. Introdução à Medicina EUS for Esophageal Carcinoma Staging Faculty of Medicine – University of Porto 5 INTRODUCTION (III): The esophageal cancer is usually treated according to tumour stage as defined in the TNM system developed by the American Joint Commission on Cancer [3]. ª Fleming I, Cooper JS, Hensen DE, et al., editors. AJCC cancer staging manual (esophagus), 5th ed. Philadelphia: Lippincott-Raven, 1997:65-69. [3]J. Vickers and D. Alderson. Oesophageal cancer staging using endoscopic ultrasonography.1998,85,994-998.

6. Introdução à Medicina EUS for Esophageal Carcinoma Staging Faculty of Medicine – University of Porto 6 INTRODUCTION (IV): Staging:  Computerized tomography scan (CT-scan)  Magnetic resonance (MRI)  Endoscopic ultrassound (EUS) [4]. [4]Kiran S. Parmar,MD,Joseph B.Zwischenberger,MD,Angela L. Reeves,CGRN and Irving Wacman,MD 2002,73:916-21.

7. Introdução à Medicina EUS for Esophageal Carcinoma Staging Faculty of Medicine – University of Porto 7 INTRODUCTION (V): Endoscopic ultrasound (EUS) has a central role in the initial staging of esophageal cancer, most notably because of its accuracy in determining depth of tumour invasion and regional lymph node metastases [4]. http://www.b5orland-groover.com/articles/eus.htm

8. Introdução à Medicina EUS for Esophageal Carcinoma Staging Faculty of Medicine – University of Porto 8 The aim of this study is to evaluate the consistency and validity of EUS namely in determining T3 + T4 or N+ for esphageal cancer. AIM:

9. Introdução à Medicina EUS for Esophageal Carcinoma Staging Faculty of Medicine – University of Porto 9 Metanalysis Data Source Quality Criteria Data to be extracted Statistical analysis METHODS:

10. Introdução à Medicina EUS for Esophageal Carcinoma Staging Faculty of Medicine – University of Porto 10  Data Source: Articles were searched using MEDLINE data base using the following clinical QUERY: (((((((((((("sensitivity and specificity"[All Fields]) OR "sensitivity and specificity/standards"[All Fields]) OR "specificity"[All Fields]) OR "screening"[All Fields]) OR "false positive"[All Fields]) OR "false negative"[All Fields]) OR "accuracy"[All Fields]) OR (((("predictive value"[All Fields] OR "predictive value of tests"[All Fields]) OR "predictive value of tests/standards"[All Fields]) OR "predictive values"[All Fields]) OR "predictive values of tests"[All Fields])) OR (("reference value"[All Fields] OR “reference values"[All Fields]) OR "reference values/standards"[All Fields])) OR ((((((((((("roc"[All Fields] OR "roc analyses"[All Fields]) OR "roc analysis"[All Fields]) OR "roc and"[All Fields]) OR "roc area"[All Fields]) OR "roc auc"[All Fields]) OR "roc characteristics"[All Fields]) OR "roc curve"[All Fields]) OR "roc curve method"[All Fields]) OR "roc curves"[All Fields]) OR "roc estimated"[All Fields]) OR "roc evaluation"[All Fields])) OR "likelihood ratio"[All Fields]) AND notpubref [sb])). AND (("Endosonography"[MeSH] AND "Esophageal Neoplasms"[MeSH] staging) NOT cardia)  LIMITS: title/abstract. METHODS (I): Walter L. Devillé at al.”Conducting systematic reviews of diagnostic studies: didactic guidelines”. BMC Medical Research Methodology 2002, 2:9

11. Introdução à Medicina EUS for Esophageal Carcinoma Staging Faculty of Medicine – University of Porto 11 METHODS (II):  Data Source: Articles were also searched using Scopus data base using the following clinical QUERY: “Endoscopic ultrasound” OR “endosonography” AND “Esophageal carcinoma” OR “esophageal neoplasm” AND NOT “Cardia”

12. Introdução à Medicina EUS for Esophageal Carcinoma Staging Faculty of Medicine – University of Porto 12 METHODS (III): Data Source 79 articles 75 articles 27 PUBMED: 106 articlesSCOPUS: 102 articles

13. Introdução à Medicina EUS for Esophageal Carcinoma Staging Faculty of Medicine – University of Porto 13 Inclusion Criteria:  Staging of esophageal carcinoma  Endoscopic ultrasound or ecoendoscopy  Surgery (gold standard) Exclusion Criteria:  Cardia  Articles that are not in Portuguese, English, French and Spanish  Case reports  Other classification of staging other than TNM classification of malignant tumours  Extracted data unable to fill a 2 by 2 table of results (*) (*) only aplied to entire article METHODS (IV):

14. Introdução à Medicina EUS for Esophageal Carcinoma Staging Faculty of Medicine – University of Porto 14 FLOWCHART 181 10 127 excluded articles: - cardia (n=13); - articles not English, Portuguese, French or Spanish (n=9); - case reports (n= 25); - Other classification of staging other than TNM classification of malignant tumours (n= 46) - extracted data unable to fill a 2 by 2 table of results (n=37) - Articles not found (n=10)

15. Introdução à Medicina EUS for Esophageal Carcinoma Staging Faculty of Medicine – University of Porto 15 Quality Criteria  After being selected, the articles had to be evaluated relatively to their methodological quality.  The assessment of the methodological quality of each study was performed using a scale ranged from 0 to 24 points according to the following points: Introduction (1) Methods: participants (4);data collection (4); test methods (5); statistical methods (2). Results: participants (3); test results (2); estimates (2). METHODS (V):

16. Introdução à Medicina EUS for Esophageal Carcinoma Staging Faculty of Medicine – University of Porto 16 METHODS (VI): Patrick M. Bossuyt et al. “Towards Complete and Accurate Reporting of Studies of Diagnostic Accuracy: The STARD Initiative”. Ann Intern Med. 2003; 138:40-44

17. Introdução à Medicina EUS for Esophageal Carcinoma Staging Faculty of Medicine – University of Porto 17  Extraction Data:  Data were extracted according to TNM classification for EUS and surgery.  Endoscope frequency, type of instrument, number and type of observers, number of patients Endoscopic ultrasound T1T2T3T4N0N1N2 Surge ry T1 T2 T3 T4 N0 N1 N2 METHODS (VII):

18. Introdução à Medicina EUS for Esophageal Carcinoma Staging Faculty of Medicine – University of Porto 18  Data were introduced in SPSS data base.  Data were introduced in Metadisc.  Statistical analysis:  Data analysed in Metadisc.  Chi-square test was used to statistically test the presence of heterogeneity.  Forrest Plots with results grouped by dates, frequency and number of patients. METHODS (VIII):

19. Introdução à Medicina EUS for Esophageal Carcinoma Staging Faculty of Medicine – University of Porto 19 RESULTS (I):  Extraction Data

20. Introdução à Medicina EUS for Esophageal Carcinoma Staging Faculty of Medicine – University of Porto 20 RESULTS (II) Graphic 1: Methodological Evaluation Median: 16,5Minimum: 11Maximum: 20

21. Introdução à Medicina EUS for Esophageal Carcinoma Staging Faculty of Medicine – University of Porto 21 RESULTS (III):  Staging – T parameter Sensitivity and specificity Graphic 2: T sensitivity Graphic 3: T specificity

22. Introdução à Medicina EUS for Esophageal Carcinoma Staging Faculty of Medicine – University of Porto 22 RESULTS (IV):  Staging - N parameter Sensitivity and specificity Graphic 4: N sensitivity Graphic 5: N specificity

23. Introdução à Medicina EUS for Esophageal Carcinoma Staging Faculty of Medicine – University of Porto 23 All grafics, except grafic 5 for N specificity, show heterogeneity (p < 0,05). Results were grouped by frequency, dates, number of patients. Subgroup analysis didn’t explain heterogeneity. DISCUSSION:

24. Introdução à Medicina EUS for Esophageal Carcinoma Staging Faculty of Medicine – University of Porto 24 DISCUSSION: In T specificity the article with a more discrepant result is L. B. Nesje et all. 2000. Its results can be explained because it is the only one that uses 20 MHz has frequency. The reason for the discrepancy visualized in the graphics related to N sensitivity may be related to the changes that chemotherapy and radiation (treatments used) have on the intrawall layers of the esophagus.

25. Introdução à Medicina EUS for Esophageal Carcinoma Staging Faculty of Medicine – University of Porto 25 Although heterogeneous, EUS appears to be more specific than sensitive. DISCUSSION:

26. Introdução à Medicina EUS for Esophageal Carcinoma Staging Faculty of Medicine – University of Porto 26 Not all the articles had classifications for both T’s and N’s. Secondary data. Articles included that are not in the Internet, FMUP Library or IPO Library. LIMITS:

27. Introdução à Medicina EUS for Esophageal Carcinoma Staging Faculty of Medicine – University of Porto 27 CONCLUSION: As the results are heterogeneous, it hasn’t been possible to do a metanalysis. EUS should continue to be used as a diagnostic test in staging esophageal carcinoma.