A Systematic Review of the Validity of
Endoscopic Ultrasound for Esophageal
Carcinoma Staging
3rd 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
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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
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EUS for Esophageal Carcinoma Staging
Introdução à Medicina
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.
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EUS for Esophageal Carcinoma Staging
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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.
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EUS for Esophageal Carcinoma Staging
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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
T0
T1
T2
T3
T4
N0
N1
a
See Fleming et al
Definition
No evidence of primary tumor
Tumor invades submucosa or lamina propria
Tumor invades muscularis propria
Tumor invades adventicia
Tumor invades adjacent structures
No regional lymph nodes involved
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
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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.
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EUS for Esophageal Carcinoma Staging
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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].
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http://www.b5orland-groover.com/articles/eus.htm
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EUS for Esophageal Carcinoma Staging
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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.

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EUS for Esophageal Carcinoma Staging
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METHODS:

Metanalysis

Data Source

Quality Criteria

Data to be extracted

Statistical analysis
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EUS for Esophageal Carcinoma Staging
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METHODS (I):
 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
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EUS for Esophageal Carcinoma Staging
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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”
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EUS for Esophageal Carcinoma Staging
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METHODS (III):

Data Source
79 articles
PUBMED: 106 articles
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75 articles
SCOPUS: 102 articles
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METHODS (IV):
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
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EUS for Esophageal Carcinoma Staging
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Start
Pubmed and
Scopus Search
FLOWCHART
181
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)
Yes
No
Included 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)
NO
Included by a 3rd
reviewer
Yes
54 included article
Yes
Read complete
article
Quality
10
10 articles included
Introduce dates in
SPSS
End
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No
Introduce dates in
Metadisc
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EUS for Esophageal Carcinoma Staging
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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).
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Methods: participants (4);data
collection (4); test methods (5);
statistical methods (2).
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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 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
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
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EUS for Esophageal Carcinoma Staging
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Endoscopic ultrasound
METHODS (VII):
T1
T2
T3
T4
N0
N1
N2
T1
 Extraction Data:
T2
 Data were extracted
according to TNM
classification for EUS and
surgery.
 Endoscope frequency, type
of instrument, number and
type of observers, number of
patients
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T3
Surge
ry
T4
N0
N1
N2
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EUS for Esophageal Carcinoma Staging
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METHODS (VIII):
 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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RESULTS (I):
 Extraction Data
Articles
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
VazquezSequeiros et al.
2001
Sónia J. Wakelin
et al. 2001
Ishaan Kalha et
al. 2004
Endoscope Frequency
7.5 MHz
12 MHz
20 MHz
Type of instrument
Olympus
Number of
observers
Number of
patients
3
171
Yes
Yes
_____
Yes
_____
_____
Olympus
_____
32
Yes
_____
_____
Toshiba
_____
37
_____
_____
EUS and EUS-FNA
_____
126
Yes
Yes
_____
Olympus
1
97
Yes
Yes
_____
GFUM20 radial
SCANNING device
4
61
Yes
Yes
Yes
Toshiba
1 or 2
107
Yes
Yes
_____
_____
_____
37
Yes
Yes
_____
EUM 20 oblique
echoendoscope
2
29
Yes
Yes
_____
Olympus
1
135
Yes
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EUS for Esophageal Carcinoma Staging
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RESULTS (II)
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
0
5
10
Introduction
15
Methods
20
25
Results
Graphic 1: Methodological Evaluation
Median: 16,5
Minimum: 11
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Maximum: 20
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EUS for Esophageal Carcinoma Staging
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RESULTS (III):
 Staging – T parameter Sensitivity and specificity
Graphic 2: T sensitivity
Graphic 3: T specificity
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EUS for Esophageal Carcinoma Staging
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RESULTS (IV):
 Staging - N parameter Sensitivity and specificity
Graphic 4: N sensitivity
Graphic 5: N specificity
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EUS for Esophageal Carcinoma Staging
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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
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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.
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EUS for Esophageal Carcinoma Staging
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DISCUSSION:

Although heterogeneous, EUS appears
to be more specific than sensitive.
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EUS for Esophageal Carcinoma Staging
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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
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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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