A SYSTEMATIC REVIEW OF THE VALIDITY OF ENDOSCOPIC ULTRASOUND FOR GASTRIC CARCINOMA STAGING

A SYSTEMATIC REVIEW OF THE A SYSTEMATIC REVIEW OF THE

VALIDITY OF ENDOSCOPIC VALIDITY OF ENDOSCOPIC

ULTRASOUND FOR GASTRIC ULTRASOUND FOR GASTRIC

CARCINOMA STAGINGCARCINOMA STAGINGTurma 15Turma 15

SupervisorsSupervisorsProf. Doutor Altamiro da Costa PereiraProf. Doutor Altamiro da Costa Pereira

Prof. Doutor Mário Dinis RibeiroProf. Doutor Mário Dinis Ribeiro

Serviço de Bioestatísca e Informática MédicaServiço de Bioestatísca e Informática MédicaFaculdade de Medicina da Universidade do PortoFaculdade de Medicina da Universidade do Porto

2005/20062005/2006

BACKGROUNDBACKGROUND

Gastric CancerGastric Cancer

Gastric carcinoma is one of the most common Gastric carcinoma is one of the most common

malignancies throughout the world, although its malignancies throughout the world, although its

incidence has decreased over the past decades.incidence has decreased over the past decades.

After liver, colon and breast cancer is the fourth most After liver, colon and breast cancer is the fourth most

common malignant disease.common malignant disease.Tseng, LJ, Tseng, LJ, et alet al, Hep-gastro, 2000, 47:897-900, Hep-gastro, 2000, 47:897-900

Early detection and diagnosis are crucial for a Early detection and diagnosis are crucial for a

successful treatment.successful treatment.

Clinical staging of gastric cancer is important in Clinical staging of gastric cancer is important in

designing the strategy of treatment.designing the strategy of treatment.Sandhu IS, et al.; Medclin N Am 86; 2002; 1289-1317Sandhu IS, et al.; Medclin N Am 86; 2002; 1289-1317

Validity of EUS in Gastric Cancer


Endoscopic Ultrasound (EUS)Endoscopic Ultrasound (EUS)

EndoscopicEndoscopic UltrasoundUltrasound ( (EUS) combinesEUS) combines endoscopyendoscopy andand

ultrasoundultrasound inin orderorder toto obtain images and information obtain images and information

about the digestive tractabout the digestive tract andand thethe surroundingsurrounding tissuetissue

andand organsorgansSandhu IS, et al.; Medclin N Am 86; 2002; 1289-1317Sandhu IS, et al.; Medclin N Am 86; 2002; 1289-1317

It may be used for preoperative staging of gastric It may be used for preoperative staging of gastric

cancer, but performance values given in the literature cancer, but performance values given in the literature

differdifferKelly eKelly et alt al, Gut,2001 Oct; 49 (4): 534-9, Gut,2001 Oct; 49 (4): 534-9

The system most often used to stage stomach cancer The system most often used to stage stomach cancer

is TNM systemis TNM system



Primary Aim: Primary Aim:

To evaluate the validity and To evaluate the validity and

consistency of endoscopic ultrasound consistency of endoscopic ultrasound

in diagnosis of gastric cancer staging.in diagnosis of gastric cancer staging.


MATERIAL AND METHODSMATERIAL AND METHODS

Study DesignStudy Design

Systematic ReviewSystematic Review



Data search:Data search:

QueryQuery

(((((((((((sensitivity and specificity OR sensitivity and (((((((((((sensitivity and specificity OR sensitivity and specificity/standards) OR specificity) OR screening) OR false positive) OR false specificity/standards) OR specificity) OR screening) OR false positive) OR false negative) OR accuracy) OR ((((predictive value OR predictive value of tests) OR negative) OR accuracy) OR ((((predictive value OR predictive value of tests) OR predictive value of tests/standards) OR predictive values) OR predictive values of predictive value of tests/standards) OR predictive values) OR predictive values of tests)) OR ((reference value OR reference values) OR reference values/standards)) tests)) OR ((reference value OR reference values) OR reference values/standards)) OR (((((((((((roc OR roc analyses) OR roc analysis) OR roc and OR roc area) OR roc OR (((((((((((roc OR roc analyses) OR roc analysis) OR roc and OR roc area) OR roc auc) OR roc characteristics) OR roc curve) OR roc curve method) OR roc curves) auc) OR roc characteristics) OR roc curve) OR roc curve method) OR roc curves) OR roc estimated) OR roc evaluation)) OR likelihood ratio) AND human) Field: All OR roc estimated) OR roc evaluation)) OR likelihood ratio) AND human) Field: All Fields, Limits: 10 Years, Humans, MEDLINE Fields, Limits: 10 Years, Humans, MEDLINE

ANDAND

"Endosonography"[MeSH]"Endosonography"[MeSH]

ANDAND

("Stomach Neoplasms"[MeSH] AND "Neoplasm Staging"[MeSH]) NOT ("Stomach Neoplasms"[MeSH] AND "Neoplasm Staging"[MeSH]) NOT "Lymphoma"[MeSH]"Lymphoma"[MeSH]

Devillé et al, BMC Medical Research Methodology, 2002; 2:9



Inclusion CriteriaInclusion Criteria

Studies of validity of EUS Studies of validity of EUS versusversus surgical surgical

specimens in patients with gastric carcinoma specimens in patients with gastric carcinoma

(GOLD STANDARD)(GOLD STANDARD)

Language (english, french and spanish)Language (english, french and spanish)



Exclusion CriteriaExclusion Criteria

Impossibility of constructing a 2x2 tableImpossibility of constructing a 2x2 table

No reference to the TNM classificationNo reference to the TNM classification

Papers unavailable on the Internet or at FMUP or IPO Papers unavailable on the Internet or at FMUP or IPO

librarieslibraries

Abstract unavailable on Medline or ScopusAbstract unavailable on Medline or Scopus



Flow Chart with MethodsFlow Chart with Methods



StartBibliographic

research

Total of articles (Scopus+Medline)

N=117

Inclusion Criteria:

a) Studies of validity of EUS versus surgical specimens in patients with gastric carcinomab)Language (english, french and spanish)

Do the articles fill this criteria?

Exclusion Criteria:a) Impossibility of constructing a 2x2 tableb) No reference to the TNM classificationc) Papers unavailable on the Internet or at FMUP or IPO librariesd) Abstract unavailable on Medline or Scopus

ArticleIncluded (n = 102)

Yes

Do the articles fill this criteria?

NoArticle

Included (n = 52)

Yes

No

Articles review by 2 reviewers

Quality Criteria

Is it valid?

Article Included (n = 14)

Total Article Excluded (n = 103)

Yes

No

Extract Data

End

Articles excluded by the exclusion criteriaa) 14 articlesb) 10 articlesc) 19 articlesd) 7 articles


Article’s QualityArticle’s Quality


Bossuyt et al, Ann Intern Med, 2003; 138: 40-44


Data ExtractedData Extracted

Year of procedureYear of procedure

Patients in studyPatients in study

Quality criteriaQuality criteria

Relation between gold standard and EUS diagnosis for T and N Relation between gold standard and EUS diagnosis for T and N

staging (true positives, true negatives, false positives, false staging (true positives, true negatives, false positives, false

negatives), in different thresholdsnegatives), in different thresholds

InstrumentInstrument

- BrandBrand

- FrequencyFrequency

Operator (single vs several)Operator (single vs several)


Data Base


Statistical AnalysisStatistical Analysis

SensitivitySensitivity

- Proportion of ill individuals whose test is positiveProportion of ill individuals whose test is positive

SpecificitySpecificity

- Proportion of not ill individuals whose test is Proportion of not ill individuals whose test is

negative negative


RESULTSRESULTS


Articles Description

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Art

icle

s's

nu

mb

er

1975 1980 1985 1990 1995 2000 2005Year of procedure

Art

icle

’s

nu

mb

er

RESULTSRESULTS


Total number of patients of the study

• Median 114

• Minimum 22

• Maximum 1120


RESULTSRESULTS



Quality assessmentQuality assessment

1 2 3 4 5 6 7 8 9 10 11 12 13 14

Article's id

0

5

10

15

20

25

Re

su

lts

of

the

sta

rd

ta

ble

Resu

lts

of

stard

ta

ble

RESULTSRESULTS


Instrument

Olympus51%

Pentax14%

Bruel & Kjaer 14%

Unknown21%


RESULTSRESULTS


Results for T stagingResults for T staging

Sensitivity – T1 vs T2 T3 T4Sensitivity – T1 vs T2 T3 T4

RESULTSRESULTS



Specificity – T1 vs T2 T3 T4Specificity – T1 vs T2 T3 T4

RESULTSRESULTS



SROC – T1 vs T2 T3 T4SROC – T1 vs T2 T3 T4

RESULTSRESULTS



Sensitivity – T1 T2 vs T3 T4Sensitivity – T1 T2 vs T3 T4

RESULTSRESULTS



Specificity – T1 T2 vs T3 T4Specificity – T1 T2 vs T3 T4

RESULTSRESULTS



SROC – T1 T2 vs T3 T4SROC – T1 T2 vs T3 T4

RESULTSRESULTS



Sensitivity – T1 T2 T3 vs T4Sensitivity – T1 T2 T3 vs T4

RESULTSRESULTS



Specificity – T1 T2 T3 vs T4Specificity – T1 T2 T3 vs T4

RESULTSRESULTS



SROC – T1 T2 T3 vs T4SROC – T1 T2 T3 vs T4

RESULTSRESULTS


Results for N stagingResults for N staging

Sensitivity – N0 vs N+Sensitivity – N0 vs N+

RESULTSRESULTS



Specificity – N0 vs N+Specificity – N0 vs N+

RESULTSRESULTS



SROC – N0 vs N+SROC – N0 vs N+

DISCUSSIONDISCUSSION

Comparison between all thresholds:Comparison between all thresholds:



The first threshold (T1 vs T2 T3 T4) has The first threshold (T1 vs T2 T3 T4) has the best sensitivitythe best sensitivity..

Specificity has the best results in the Specificity has the best results in the third threshold (T1 T2 T3 vs T4).third threshold (T1 T2 T3 vs T4).

EUS is a reliable method to EUS is a reliable method to

detect the stages T1 vs T2 and T3 detect the stages T1 vs T2 and T3

vs T4.vs T4.



Sensitivity and specificity were higher for T Sensitivity and specificity were higher for T staging than for N stagingstaging than for N staging

EUS is a better diagnosis method for EUS is a better diagnosis method for determination of the tumour determination of the tumour penetration depth (T staging) than for penetration depth (T staging) than for lymphatic nodes invasion (N staging)lymphatic nodes invasion (N staging)



Comparison with literature:

The very limited penetration depth of early tumors can

be clearly displayed and reliably determined on EUS

scanning

Together with reports elsewhere, it is accepted that

EUS is an accurate staging modality in most cases,

with a few exceptions of overstaging and understaging.WD, et al, World J Grastroent, 2003;9(2):254-257


STUDY LIMITATIONSSTUDY LIMITATIONS

Bibliographic research restricted to Medline and ScopusBibliographic research restricted to Medline and Scopus

Lack of information regarding to Lack of information regarding to methodologicalmethodological

procedures, in the papersprocedures, in the papers

Inclusion and exclusion criteriaInclusion and exclusion criteria

Language restrictionsLanguage restrictions

Abstract unavailable on Medline and ScopusAbstract unavailable on Medline and Scopus


GANTT’SGANTT’S MAPMAP


Gantt’s Map

REFERENCESREFERENCES

Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwing LM, Irwing LM, et alet al. . Towards complete and accurate reporting of Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD iniative. Ann Intern studies of diagnostic accuracy: the STARD iniative. Ann Intern Med. 2003 Jan 7; 138: 40-44.Med. 2003 Jan 7; 138: 40-44.

Devillé WL, Buntinx F, Boputer LM, Montori VM, de Vet HCW, Devillé WL, Buntinx F, Boputer LM, Montori VM, de Vet HCW, van der Windt DAWM, van der Windt DAWM, etet alal. . Conducting systematic reviews of Conducting systematic reviews of diagnostic studies: didactic guidelines. BMC Medical Research diagnostic studies: didactic guidelines. BMC Medical Research Methodology. 2002; 2: 9.Methodology. 2002; 2: 9.

Kelly S, Harris KM, Berry E, Hutton J, Roderick P, Cullingworth J, Kelly S, Harris KM, Berry E, Hutton J, Roderick P, Cullingworth J, et alet al. A systematic review of the staging performance of . A systematic review of the staging performance of endoscopic ultrasound in gastro-oesophageal carcinoma. Gut. endoscopic ultrasound in gastro-oesophageal carcinoma. Gut. 2001 Oct; 49(4): 534-9. Cited in PubMed; PMID 11559651.2001 Oct; 49(4): 534-9. Cited in PubMed; PMID 11559651.

Tseng, LJ, Lin- Ray MD, Thian-Lok MD, Tseng, LJ, Lin- Ray MD, Thian-Lok MD, et al. Video- Endoscopic et al. Video- Endoscopic Ultrasound in staging gastric carcinoma. Hepato- Ultrasound in staging gastric carcinoma. Hepato- Gastroenterology 200; 47:897- 900.Gastroenterology 200; 47:897- 900.

Sandhu IS, Manoop S, Bhutani, MD. Gastrointestinal Sandhu IS, Manoop S, Bhutani, MD. Gastrointestinal endoscopic ultrasonography. Medclin N Am 86. 2002; 1289 – endoscopic ultrasonography. Medclin N Am 86. 2002; 1289 – 1317.1317.


A SYSTEMATIC REVIEW OF THE VALIDITY OF ENDOSCOPIC ULTRASOUND FOR GASTRIC CARCINOMA STAGING

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