1. A systematic review of the validity of endoscopic ultrasound for rectal carcinoma staging Adília Rafael, Agostinho Cordeiro, Alberto Lourenço, Alexandre Sarmento, Ana Isabel Ponte, Beatriz Noronha, Carolina Afonso, Catarina Gomes, Catarina Pedrosa, Cristina Duque Class 1 Supervisor: Mário Dinis Ribeiro Introduction to Medicine Porto Faculty of Medicine

2. Index 1) Introduction 2) Objective 3) Material and Methods 3.1) Study Design 3.2) Inclusion Criteria 3.3) Bibliographic research 3.4) Exclusion criteria 3.5) Methodological quality 3.6) Data extraction 4) Planning

3. Introduction ► Rectal cancer is the most lethal type of cancer within the Portuguese population.(ref) ► Its treatment depends on correct staging, and endoscopic ultrasound is one of the methods which makes it possible. ► It may be used either to determine candidacy for surgery or as a surveillance method after surgery, because the recurrence of local tumors is quite common. Lightdale, C. J., Advances in Endoscopic ultrassound: 13th International Symposium, Gastrointestinal endoscopy Vol 56, nº 4 (suppl), 2002

4. ► Rectal cancer is staged using the Tumor-Node-Metastasis (TNM) staging system. According to the EUS stage, the management of the cancer is also different: StageInvolvesManagement of cancer T1Mucosa/submucosaTransanal local resection T2Into the muscularis propriaRadical resection and/or postoperative radiation T3Into the perirectal fat Preoperative chemo radiation before radical resection T4Into adjacent organs N1Metastasis in 1 to 3 regional lymph nodes N2Metastasis in 4 or more regional lymph nodes Introduction Lightdale, C. J., Advances in Endoscopic ultrassound: 13th International Symposium, Gastrointestinal endoscopy Vol 56, nº 4 (suppl), 2002

5. Introduction

6. We aimed at analyzing the validity and consistency of EUS for rectal carcinoma staging in relation to surgical specimens. Objective N

7. Inclusion Criteria: ► The selected articles should describe studies designed to evaluate the accuracy of endoscopic ultrasound (EUS) in rectal carcinoma staging. ► The accuracy of EUS should be evaluated in a sample of patients with rectal carcinoma. ► The results of the application of EUS should be compared to the surgical specimen (gold standard). Material and Methods Study Design: Systematic Review

8. Material and Methods Bibliographic Research: According to the inclusion criteria, a bibliographic research was carried out in Medline using the following 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 ("Endosonography"[MeSH] AND ("Rectal neoplasms"[MeSH] OR "Colorectal neoplasms"[MeSH]))

9. ► This query was based on a search strategy in PubMed (MEDLINE) for publications about the evaluation of diagnostic accuracy, suggested by a research article (Devillé, W. L. et. al., Conducting systematic reviews of diagnostic studies: didactic guidelines). ► The research was limited to “items with abstracts” and items referring to “humans”. ► 131 abstracts were obtained. Material and Methods

10. Exclusion Criteria: ► Articles written in languages other than English, French or Spanish. ► Articles not evaluating diagnostic tests. ► Articles evaluating the accuracy of EUS in staging of other cancers rather than rectal carcinoma. Material and Methods

11. Exclusion Criteria for full papers: ► The article does not allow the construction of a 2x2 table (T & N both for EUS and surgical specimen). ► The paper is not available at the Porto Faculty of Medicine library (or IPO), in the World Wide Web or other possible sources.

12. Material and Methods ► The articles obtained in the bibliographic research were distributed to 5 groups of 2 elements each. ► A third element, the supervisor, was consulted in case of disagreement. ► Attending to the criteria defined, 68 articles were selected.

13. Methodological Quality: ► Each article will be submitted to evaluation by two reviewers that independently will grade them as far as quality is concerned. ► Disagreements will be solved by consensus or arbitration (by the supervisor). ► This stage will be based on the Standard for Reporting of Diagnostic Accuracy (STARD) checklist (Bossuyt, P. M. et. al., Towards Complete and Accurate Reporting of Studies of Diagnostic Accuracy: The STARD Initiative, Annals of Internal Medicine Vol 138 – nº1, 7 January 2003). Material and Methods

14. Section and topicDescribe # TITLE/ABSTRAC T/ KEYWORDS 1 The article as a study on diagnostic accuracy (recommend MeSH heading 'sensitivity and specificity') INTRODUCTION 2 The research question(s), such as estimating diagnostic accuracy or comparing accuracy between tests or across participant groups METHODS Participants3 The study population: the inclusion and exclusion criteria, setting(s) and location(s) where the data were collected 4 Participant recruitment: was this based on presenting symptoms, results from previous tests, or the fact that the participants had received the index test(s) or the reference standard? 5 Participant sampling: was this a consecutive series of patients defined by selection criteria in (3) and (4)? If not specify how patients were further selected. 6 Data collection: were the participants identified and data collected before the index test(s) and reference standards were performed (prospective study) or after (retrospective study)? Reference standard 7 The reference standard and its rationale Test methods8 Technical specification of material and methods involved including how and when measurements were taken, and/or cite references for index test(s) and reference standard 9 Definition and rationale for the units, cutoffs and/or categories of the results of the index test(s) and the reference standard 1010 The number, training and expertise of the persons (a) executing and (b) reading the index test(s) and the reference standard 1 Whether or not the reader(s) of the index test(s) and reference standard were blind (masked) to the results of the other test(s) and describe any information available to them STARD checklist Material and Methods

15. Statistical methods12 Methods for calculating measures of diagnostic accuracy or making comparisons, and the statistical methods used to quantify uncertainty (e.g. 95% confidence intervals) 13 Methods for calculating test reproducibility, if done RESULTS Participants14 When study was done, including beginning and ending dates of recruitment 15 Clinical and demographic characteristics (e.g. age, sex, spectrum of presenting symptom(s), comorbidity, current treatment(s), recruitment center) 16 How many participants satisfying the criteria for inclusion did or did not undergo the index test and/or the reference standard; describe why participants failed to receive either test (a flow diagram is strongly recommended) Reference standard17 Time interval and any treatment administered between index and reference standard 18 Distribution of severity of disease (define criteria) in those with the target condition; describe other diagnoses in participants without the target condition Test results19 A cross tabulation of the results of the index test(s) by the results of the reference standard; for continuous results, the distribution of the test results by the results of the reference standard 20 Indeterminate results, missing responses and outliers of index test(s) stratified by reference standard result and how they were handled 21 Adverse events of index test(s) and reference standard Estimation22 Estimates of diagnostic accuracy and measures of statistical uncertainty (e.g. 95% confidence intervals) 23 Estimates of variability of diagnostic accuracy between subgroups of participants, readers or centers, if done 24 Measures of test reproducibility, if done DISCUSSION 25 The clinical applicability of the study findings Material and Methods Bossuyt, P. M. et. al., Towards Complete and Accurate Reporting of Studies of Diagnostic Accuracy: The STARD Initiative, Annals of Internal Medicine Vol 138 – nº1, 7 January 2003

16. Data Extraction: ► Those two reviewers will also independently extract the required information from the primary studies. ► Disagreements should, in the same way as before, be recorded and resolved by consensus or arbitration. ► The data should be extracted using a standardised extraction form. Material and Methods Details will be requested from the authors of the studies.

17. Material and Methods ► Data to be extracted: ► Procedure; ► Year of procedures included in the study; ► Instrument (Pentax, Olympus; frequency 7.5 versus 12 versus 20 MHz); ► Instrument (flexible/rigid); ► Operator (single versus several; number of procedures per year); ► Reference (year/changes in cancer classification TNM); ► Lesion (stenotic lesions; location upper/lower rectum- exclude anal)

18. Material and Methods ► Sensitivity and specificity per article will be calculated based on the 2x2 tables. ► Homogeneity will be assessed and pooled results estimated if possible.

19. Planning