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 Introdução à Medicina Faculty of Medicine – University of Porto 1

EUS for Esophageal Carcinoma Staging Introdução à Medicina 

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 Faculty of Medicine – University of Porto 2

EUS for Esophageal Carcinoma Staging

INTRODUCTION (I)

Introdução à Medicina  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.

Faculty of Medicine – University of Porto 3

EUS for Esophageal Carcinoma Staging Introdução à Medicina

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.

Faculty of Medicine – University of Porto 4

EUS for Esophageal Carcinoma Staging

INTRODUCTION (III):

Introdução à Medicina  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].

TNM classification Definition T0 T1 No evidence of primary tumor Tumor invades submucosa or lamina propria T2 T3 T4 N0 Tumor invades muscularis propria Tumor invades adventicia Tumor invades adjacent structures No regional lymph nodes involved N1 a See Fleming et al Regional lymph nodes present [3]J. Vickers and D. Alderson. Oesophageal cancer staging using endoscopic ultrasonography.1998,85,994-998.

ª Fleming I, Cooper JS, Hensen DE, et al., editors. AJCC cancer staging manual (esophagus), 5th ed. Philadelphia: Lippincott-Raven, 1997:65-69.

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EUS for Esophageal Carcinoma Staging

INTRODUCTION (IV):

Staging:

   Computerized tomography scan (CT-scan) Magnetic resonance (MRI) Endoscopic ultrassound (EUS) [4].

Introdução à Medicina [4]Kiran S. Parmar,MD,Joseph B.Zwischenberger,MD,Angela L. Reeves,CGRN and Irving Wacman,MD 2002,73:916-21.

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EUS for Esophageal Carcinoma Staging

INTRODUCTION (V):

Introdução à Medicina 

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].

Faculty of Medicine – University of Porto http://www.b5orland-groover.com/articles/eus.htm

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EUS for Esophageal Carcinoma Staging Introdução à Medicina

AIM:



The aim

of this study is to evaluate the consistency and validity of EUS namely in determining T3 + T4 or N+ for esphageal cancer.

Faculty of Medicine – University of Porto 8

EUS for Esophageal Carcinoma Staging

METHODS:

 Metanalysis  Data Source  Quality Criteria  Data to be extracted  Statistical analysis Faculty of Medicine – University of Porto Introdução à Medicina 9

EUS for Esophageal Carcinoma Staging

METHODS (I):

Introdução à Medicina 

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.

Walter L. Devillé at al.”Conducting systematic reviews of diagnostic studies: didactic guidelines”. BMC Medical Research Methodology 2002, 2:9 Faculty of Medicine – University of Porto 10

EUS for Esophageal Carcinoma Staging

METHODS (II):

Introdução à Medicina 

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” Faculty of Medicine – University of Porto 11

EUS for Esophageal Carcinoma Staging

METHODS (III):



Data Source

Introdução à Medicina

79 articles 27 75 articles

PUBMED: 106 articles SCOPUS: 102 articles Faculty of Medicine – University of Porto 12

EUS for Esophageal Carcinoma Staging

METHODS (IV):

Introdução à Medicina   

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 Faculty of Medicine – University of Porto 13

EUS for Esophageal Carcinoma Staging

FLOWCHART

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) Introdução à Medicina Start Pubmed and Scopus Search Articles found : 181

181

Revision of titles and abstracts Yes 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) Excluded by 2 reviewers No No Included by 2 reviewers NO Included by a 3 rd reviewer Yes 54 included article Yes Read complete article Quality End Introduce dates in SPSS Introduce dates in Metadisc Faculty of Medicine – University of Porto 14

EUS for Esophageal Carcinoma Staging Introdução à Medicina

METHODS (V): 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)

Results:

participants (3); test results (2); estimates (2).

Methods:

participants (4);data collection (4); test methods (5); statistical methods (2). Faculty of Medicine – University of Porto 15

EUS for Esophageal Carcinoma Staging Introdução à Medicina

METHODS (VI):

Section

Introduction Methods

Participants Data collection Test methods Statistical methods

Results

Participants Test results Estimates State the research questions or study aims Inclusion criteria for the study population Exclusion criteria for the study population Setting where the data were collected Location where the data were collected Participants where selected based on diagnosis and not over another staging procedure Clinical diagnosis and inclusion was made before knowledge of reference test Consecutive sample Before or after the index tests and reference test (prospective or retrospective studies) Reference standard (reference of TN of surgery) and its rationale Technical specifications of frequency of the endoscope) material (type of instrument and/or How measurement were taken When were measurement taken Definition of categories (T and N) cut-off points for reference standard or clinical outcome (death for instance) Readers of reference and index tests where or where not blind to the results of other tests Methods for calculating or comparing measurements of diagnostic accuracy, and the statistical methods used to quantify uncertainty Methods for calculating test reproducibility, if done Demographic information (age, sex) Clinical characteristics of the study population (spectrum of disease) and severity Number of participants satisfying the criteria for inclusion that did not undergo the index tests and/or the reference standard; describe why participants failed to receive either tests A cross tabulation of the results of the index tests by the results of the reference standard Time between the index test and the reference test, and any treatment administrated between Estimates of diagnostic accuracy and measurements of statistical uncertainty Estimates of test reproducibility, if done 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 Faculty of Medicine – University of Porto 16

EUS for Esophageal Carcinoma Staging Introdução à Medicina

METHODS (VII):



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 T1 T2 T3

Surge ry

T4 N0 N1 N2 T1 T2

Endoscopic ultrasound

T3 T4 N0 N1 N2 Faculty of Medicine – University of Porto 17

EUS for Esophageal Carcinoma Staging

METHODS (VIII):

Introdução à Medicina 

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.

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EUS for Esophageal Carcinoma Staging

RESULTS (I):

 Extraction Data Articles T. Lok Tio et al. 1989 M. J. Hodijek et al. 1993 Endoscope Frequency 7.5 MHz 12 MHz 20 MHz Yes Yes Yes _____ _____ _____ Type of instrument Olympus Olympus S. Natsugoe et al. 1996 Yes Ernesto Laterza et al. 1999 Gregory Zuccaro et al. 1999 Jan Heidemann et al. 2000 L. B. Nesje et al. 2000 Enrique Vazquez Sequeiros et al. 2001 Sónia J. Wakelin et al. 2001

Ishaan Kalha et al. 2004

Yes Yes Yes Yes Yes Yes Yes _____ _____ Yes Yes Yes Yes Yes Yes _____ _____ _____ _____ Yes _____ _____ _____ Toshiba EUS and EUS-FNA Olympus GFUM20 radial SCANNING device Toshiba _____ EUM 20 oblique echoendoscope Olympus Number of observers 3 _____ _____ _____ 1 4 1 or 2 _____ 2 1 Introdução à Medicina Number of patients 171 32 37 126 97 61 107 37 29 135 Faculty of Medicine – University of Porto 19

EUS for Esophageal Carcinoma Staging

RESULTS (II)

Introdução à Medicina

Methodological Quality Evaluation

T. Lok Tio et al. 1989 M. J. Hodijek et al. 1993 S. Natsugoe et al. 1996 Ernesto Laterza et al. 1999 Gregory Zuccaro et al. 1999 Jan Heidemann et al. 2000 L. B. Nesje et al. 2000 Enrique Vazquez-Sequeiros et al. 2001 Sónia J. Wakelin et al. 2001 Ishaan Kalha et al. 2004 Median: 16,5 Minimum: 11 0 5 10 15 20 25 Introduction Methods Results Graphic 1: Methodological Evaluation Maximum: 20 Faculty of Medicine – University of Porto 20

EUS for Esophageal Carcinoma Staging

RESULTS (III):

 Staging – T parameter Sensitivity and specificity Introdução à Medicina Graphic 2: T sensitivity Faculty of Medicine – University of Porto Graphic 3: T specificity 21

EUS for Esophageal Carcinoma Staging

RESULTS (IV):

 Staging - N parameter Sensitivity and specificity Introdução à Medicina Graphic 4: N sensitivity Faculty of Medicine – University of Porto Graphic 5: N specificity 22

EUS for Esophageal Carcinoma Staging Introdução à Medicina

DISCUSSION:

 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.

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EUS for Esophageal Carcinoma Staging

DISCUSSION:

Introdução à Medicina 

In T specificity the article with a more discrepant result is

L. B. Nesje et all. 2000

MHz has frequency. . Its results can be explained because it is the only one that uses 20



The reason for the discrepancy visualized in the graphics related to N sensitivity may be related to the changes that the esophagus.

chemotherapy and radiation

(treatments used) have on the intrawall layers of

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EUS for Esophageal Carcinoma Staging

DISCUSSION:

Introdução à Medicina 

Although heterogeneous, EUS appears to be more specific than sensitive.

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EUS for Esophageal Carcinoma Staging Introdução à Medicina

LIMITS:

   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.

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EUS for Esophageal Carcinoma Staging Introdução à Medicina

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.

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