A systematic review of the validity of endoscopic ultrasound for rectal carcinoma staging Class 1: Adília Rafael, Agostinho Cordeiro, Alberto Lourenço, Alexandre Sarmento, Ana Beatriz Noronha, Ana Carolina Afonso, Ana Catarina Gomes, Ana Catarina Pedrosa, Ana Cristina Duque, Ana Isabel Ponte Supervisors: Altamiro da Costa Pereira, MD, PhD; Mário Dinis Ribeiro, MD, PhD Introduction to Medicine; Porto Faculty of Medicine 2006

Index 1) Introduction 2) Objective 3) Material and Methods 3.1) Study design 3.2) Inclusion Criteria 3.3) Exclusion criteria 3.4) Bibliographic research 3.5) Methodological quality 3.6) Data extraction 5) Results 5.1) T Staging 5.2) N Staging 6) Conclusion 7) Website 8 ) Planning 9) Acknowledgements

► Rectal cancer is the cancer with the highest rate of mortality within the Portuguese population. [Pinheiro et al, 2003] ► More than 2000 scientific papers published in the literature have demonstrated EUS’s high accuracy for the diagnosis and staging of rectal cancer. [Fusaroli and Caletti, 2005] ► Rectal cancer is staged using Tumor-Node- Metastasis (TNM) staging system. [Savides and Master, 2002] Introduction

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 Savides T, Master S. EUS in rectal cancer. Gastrointestinal Endoscopy, Vol 56, No 4, ► According to the EUS stage, the management of the cancer is different. [Savides and Master, 2002]

To evaluate the validity and consistency of EUS for rectal carcinoma staging in relation to surgical specimens in identifying the patients as T3/T4 and N+. Objective

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

Material and Methods Exclusion Criteria ► The article describes a systematic review. ► The article uses a different reference standard. ► The article evaluates the accuracy of EUS in staging of other cancers rather than rectal carcinoma. ► The article does not allow the construction of a 2x2 table (for EUS and surgical specimen). ► The article is written in languages other than English, French, Spanish or Portuguese. ► The full paper is not available on the Internet, in the facilities of the Faculty of Medicine, IPO or in the local libraries.

Bibliographic Research: 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 (("Endoscopic Ultrasound" [All Fields] OR "Endosonography"[All Fields]) AND ("Rectal neoplasms"[All Fields] OR "Colorectal neoplasms"[All Fields])) Material and Methods ► 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

Material and Methods Methodological Quality: Each article was submitted to evaluation by two reviewers, who independently graded them as far as quality was concerned. ► Disagreements were solved by consensus or arbitration (by the supervisor). ► Methodological quality was evaluated according to 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

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

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

Material and Methods Data extracted ► Information about the study : location, initial number of participants, final number of participants, including mean age and number of feminine and masculine participants. ► Results: number of true positives, false positives, true negatives and false positives in TNM staging. ► Information about the equipment used: type of instrument, brand, number of operators. ► Quality assessment: presence or absence of the items in STARD checklist.

Article Akasu T, 1997 Sailer M, 1997 Maldjian C, 1998 Nishimori H, 1998 Blomquist L, 1999 Lee P, 1999 Hunerbein M, 1999 Kazuya A, 2000 Akasu T, 2000 Gualdi F, 2000 Hunerbein M, 2000 Akahoshi K, 2001 Kalantzis C, 2002 Starck M, 2002 Scott R, 2002 Tseng Y, 2002 Garcia-Aguilar J, 2002 Fuchsjager M, 2002 Bali C, 2004 Hurlstone P, Final number of participants Quality (STARD checklist items) Brand of instrument used Olympus Combison Olympus B&K Missing value Olympus B&K Olympus Missing value B&K Olympus Results

T staging: Specificity (articles ordered by date of publication) Results

Sensitivity

Results Specificity and Sensitivity (articles ordered by final number of participants in the study )

Number of participants>60

Results Specificity and Sensitivity (articles ordered by brand of instrument used in the study)

Number of participants>60 and using Olympus

Results N-staging: Specificity (articles ordered by date of publication)

Results Sensitivity

Results Specificity and Sensitivity (articles ordered by final number of participants in the study )

Number of participants>60

Results Specificity and Sensitivity (articles ordered by brand of instrument used in the study )

Conclusion As far as T staging (T1+T2 vs T3+T4), EUS validity results are heterogenous across studies. ► However, when more than 60 patients and Olympus instruments are used both high sensitivity = 0.95 and high specificity = 0.87 are found. T Staging ► The results were very heterogeneous ► Although no pooled results can be used, a high specificity was found in studies with more than 60 participants included. N Staging

Conclusion Some limitations in our study may be the cause of some heterogeneity ► Only the articles written in English, French, Spanish and Portuguese were read; ► The research was performed in a single database - Medline; ► The articles obtained were collected from IPO, Faculty of Medicine and the Internet, neglecting all other possible sources.

Conclusion It seems that beyond training, further improvement in N staging should be studied: redefinition of N involvement in EUS EUS improvement (new instruments) EUS is more accurate in defining T stage (wall involvement) than N stage.

Website

Planning

Professor Altamiro da Costa Pereira Professor Mário Dinis Ribeiro Acknowledgements