Faculty of Medicine – University of Porto

1

A Systematic Review of the Validity of Endoscopic Ultrasound for Esophageal

Carcinoma Staging3rd 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

Faculty of Medicine – University of Porto 2

Introdução à MedicinaEUS for Esophageal Carcinoma Staging

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



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.



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.



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].TNM classification Definition T0 No evidence of primary tumor T1 Tumor invades submucosa or lamina propria T2 Tumor invades muscularis propria T3 Tumor invades adventicia T4 Tumor invades adjacent structures N0 No regional lymph nodes involved N1 Regional lymph nodes present a See Fleming et al

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.



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.



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



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:



Metanalysis

Data Source

Quality Criteria

Data to be extracted

Statistical analysis

METHODS:



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



METHODS (II):

Data Source: Articles were also searched using Scopus data baseusing the following clinical QUERY:

“Endoscopic ultrasound” OR “endosonography”AND

“Esophageal carcinoma” OR “esophageal neoplasm”AND NOT“Cardia”



METHODS (III):

Data Source

79 articles 75 articles27

PUBMED: 106 articles SCOPUS: 102 articles



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):



Start

Pubmed and Scopus Search

Articles found : 181

Revision of titles and abstracts

Excluded by 2 reviewers

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)

Included by 2 reviewers

Yes

No

Yes

Yes

No

End

Included by a 3rd reviewer

NO

54 included article

Read complete article

Quality

10 articles included

Introduce dates in SPSS

Introduce dates in Metadisc

FLOWCHART181

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)



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):



METHODS (VI):Section Introduction State the research questions or study aims Methods Participants Inclusion criteria for the study population Exclusion criteria for the study population Setting where the data were collected Location where the data were collected

Data collection 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)

Test methods Reference standard (reference of TN of surgery) and its rationale

Technical specifications of material (type of instrument and/or frequency of the endoscope)

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

Statistical methods

Methods for calculating or comparing measurements of diagnostic accuracy, and the statistical methods used to quantify uncertainty

Methods for calculating test reproducibility, if done Results Participants 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

Test results 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 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



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

T1 T2 T3 T4 N0 N1 N2

Surgery

T1

T2

T3

T4

N0

N1

N2

METHODS (VII):



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):



RESULTS (I): Extraction Data

Endoscope Frequency Articles 7.5 MHz 12 MHz 20 MHz

Type of instrument Number of observers

Number of patients

T. Lok Tio et al. 1989 Yes Yes _____ Olympus

3 171

M. J. Hodijek et al. 1993 Yes _____ _____ Olympus _____ 32

S. Natsugoe et al. 1996 Yes _____ _____ Toshiba _____ 37

Ernesto Laterza et al. 1999

Yes _____ _____ EUS and EUS-FNA _____ 126

Gregory Zuccaro et al. 1999 Yes Yes _____ Olympus 1 97

Jan Heidemann et al. 2000 Yes Yes _____ GFUM20 radial

SCANNING device 4 61

L. B. Nesje et al. 2000 Yes Yes Yes Toshiba 1 or 2 107

Enrique Vazquez-Sequeiros et al. 2001

Yes Yes _____ _____ _____ 37

Sónia J. Wakelin et al. 2001 Yes Yes _____ EUM 20 oblique

echoendoscope 2 29

Ishaan Kalha et al. 2004 Yes Yes _____ Olympus 1 135



RESULTS (II)

Graphic 1: Methodological Evaluation

Median: 16,5 Minimum: 11 Maximum: 20

Methodological Quality Evaluation

0 5 10 15 20 25

Ishaan Kalha et al. 2004Sónia J. Wakelin et al. 2001

Enrique Vazquez-Sequeiros et al. 2001L. B. Nesje et al. 2000

Jan Heidemann et al. 2000Gregory Zuccaro et al. 1999Ernesto Laterza et al. 1999

S. Natsugoe et al. 1996M. J. Hodijek et al. 1993

T. Lok Tio et al. 1989

Introduction Methods Results



RESULTS (III): Staging – T parameter Sensitivity and specificity

Graphic 2: T sensitivity

Graphic 3: T specificity



RESULTS (IV): Staging - N parameter Sensitivity and specificity

Graphic 4: N sensitivity

Graphic 5: N specificity



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:



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.



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

DISCUSSION:



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:



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.

Documents

Faculty of Medicine – University of Porto