Critical appraisal:Kurtkaya-Yapicier O, Gencosmanoglu R, Avsar E, Bakirci N, Tozun N, Sav A 2003

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Critical Appraisal

Article being appraised

Kurtkaya-Yapicier O, Gencosmanoglu R, Avsar E, Bakirci N, Tozun N, Sav A. The utility of cytokeratins 7 and 20 (CK7/20) immunohistochemistry in the distinction of short-segment Barrett esophagus from gastric intestinal metaplasia: Is it reliable? BMC Clin Pathol 2003 Dec 2;3(1):5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/14651756.


Applicable clinical question

Key Facts

Study Design

diagnostic accuracy study

Number of Patients enrolled:

40

Number of Patients evaluated:

40

Number of samples:

46


Includes an economic evaluation

no

Evidence ratings

Level of evidence

III-3

Risk of bias
At risk of bias Comments: Please replace this text and include any additional comments in regards to your quality rating

Risk of bias assessment: diagnostic accuracy study

Patient Selection
Prior tests and any referral filters
Retrospective diagnostic case control study. Patient selection based on confirmed diagnosis following endoscopic examination and evaluation of H&E stained biopsies. Giemsa stain was used to confirm H.pylori gastritis and Periodic acid Schiff (PAS) and Slcian blue pH 2.5 to identify mucin-containing goblet cells. Cases without detected goblet cell metaplasia by Alcian blue stain were excluded.
Condition that defined entry into study
Endoscopy biopsy specimens of the patients referred from Marmara University Institute of Gastroenterology were reviewed from the files of the Department of Pathology at the same university between 1998 and 2002. Two groups of endoscopic biopsy specimens were examined, including 20 specimens of short-segment BO and 20 specimens with gastric intestinal metaplasia (9 cardia, 11 gastric body) accompanied by H.pylori associated gastritis. Six control biopsies were added retrospectively from patients whose biopsies showed normal SCJ (n=3) and normal cardia (n=3) microscopically.
Setting
A single centre study performed at the Marmara University Institute of Gastroenterology, Istanbul, Turkey.
Was a diagnostic case-control design avoided?
Yes
Consecutive or random sample?
No
Did the study avoid inappropriate exclusions?
Unclear
Reasons
Other than criteria used to select cases and controls, no additional exclusions were made that would bias analysis.
If comparing more than one index test was the design fully paired or paired randomly?
Not applicable
If a paired randomised design was used, was allocation to groups concealed and was the generation of allocation sequence adequate?
Not applicable
What is the risk that the selection of participants introduced bias?
High
Comments
The study used a case-control design rather than enrolling a representative group of patients who are eligible for testing. The criteria for patient selection in the study were very specific, and designed to address whether short segment BO could be distinguished from H-pylori associated gastric cardiac IM. Short segment BO patients who were H. pylori positive were excluded from the study, whereas the control gastric IM group were only included if they were H. pylori positive. The implications of H. pylori on CK7/CK20 immunostaining is not certain.
Index test 1
Describe index test and how it was conducted and interpreted
Index test is immunohistochemical staining of tissue sections for Cytokeratin-7 / Cytokeratin-20 (CK7/CK20) pattern for its utility in identification of Barrett’s oesophagus (BO), as hypothesized by Ormsby et al (1999). A Barrett’s CK7/ CK20 pattern was considered present if CK20 staining was seen in surface epithelium and superficial glands and diffuse CK7 staining was present in both superficial and deep glands in areas of intestinal metaplasia. Whether multiple pathologists undertook independent evaluation of the staining was not stated.
Were the index test results interpreted without knowledge of the results of the reference standard?
Unclear
If a threshold was used, was it pre-specified?
Not applicable
If two tests are being compared, have they been assessed independently / blind to each other?
Not applicable
What is the risk that the conduct or interpretation of the index test introduced bias?
Unclear
Comments
The number of pathologists performing the CK7/CK20 pattern analysis (and whether evaluation was performed independently) was not specified. Whether they were blinded to reference standard results is not known.
Index test 2
Describe index test and how it was conducted and interpreted, if applicable
Not applicable.
Were the index test results interpreted without knowledge of the results of the reference standard?
Not applicable
If a threshold was used, was it pre-specified?
Not applicable
What is the risk that the conduct or interpretation of the index test introduced bias?
Not applicable
Comments
Not applicable.
Reference Standard
Describe the reference standard and how it was conducted and interpreted
Reference standard was histological evaluation of H&E stained sections of FFPE tissue taken from biopsies during endoscopic examination. Periodic acid Schiff (PAS), Alcian blue pH 2.5 and Alcian blue pH 0.5 were used to identify neutral mucin, sialomucin and sulphomucin respectively. Giemsa stain was used to reveal H.pylori.
Is the reference standard likely to correctly classify the target condition?
Yes
Were the reference standard results interpreted without knowedge of the results of the index test/s?
Yes
Was the reference test standard independent of the index test?
(i.e. the index test did not form part of the reference standard)
Yes
What is the risk that the reference standard, its conduct or interpretation introduced bias?
Low
Comments
The reference standard used here is the universally accepted method for diagnosis of Barrett’s oesophagus, with the additional staining to identify mucin containing goblet cells and H. plyori.
Flow and timing
Describe any patients who did not receive the index test(s) and/or reference standard or who were excluded from the 2x2 table
All patients who received the index test also received the reference standard.
Describe the time interval and any interventions between index test(s) and reference standard
Tissue samples for the reference test and index test were taken at a single endoscopy session, hence no intervention between index test and reference standard is possible.
If a predictive test (the reference standard is a later event that the test aims to predict) were any subsequent interventions between test and later event blind to test result?
Not applicable
Was there an appropriate interval between index test(s) and reference standard?
Yes
Did either all participants or a random sample of participants receive a reference standard test?
Yes
Did all patients receive the same reference standard irrespective of index test result?
Yes
Were all test results including unclear results reported?
Yes
Were all patients included in the analysis?
Yes
What is the risk that the patient flow introduced bias?
Low
Comments
Patient specimens were selected from a database and tissue blocks were accessed to obtain samples. No further follow-up assessment with patients was undertaken.
Size of effect
3 Reason for decision: The study results indicate that that CK7 / CK20 immunostaining performs poorly to differentiate between H. pylori negative short-segment Barrett’s oesophagus and H-pylori associated gastric intestinal metaplasia. The sensitivity of cytokeratin immunostaining for identification of H. plyori negative short-segment Barrett’s oesophagus was particularly poor (sensitivity 10%, 95% CI 1-32%) with 100% specificity (95% CI 83-100%). There was no significant difference in the Barrett’s CK7/CK20 pattern between the two groups (p=0.487). Three of the short segment BO cases showed low grade dysplasia which was previously mentioned by Ormsby et al (2000) as a caveat in the method as there appeared to be an absence of CK20 staining in areas of dysplasia or adenocarcinoma.
Relevance of evidence
4 Additional comments: The study provides evidence about the accuracy of CK7/CK20 immunostaining compared to current standard method as the reference standard in a highly select (case-control) population.

The test requires endoscopic examination and tissue biopsies to be taken, thus it does not provide any procedural advantages over the current method.
The study does not assess the potential additional diagnostic value of CK7/CK20 immunostaining if introduced as an add-on test.
The study does not provide evidence to estimate the effect of testing on patient-relevant clinical outcomes.

Result of appraisal

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Completed by

Melissa Thomas


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Article
Kurtkaya-Yapicier O, Gencosmanoglu R, Avsar E, Bakirci N, Tozun N, Sav A. The utility of cytokeratins 7 and 20 (CK7/20) immunohistochemistry in the distinction of short-segment Barrett esophagus from gastric intestinal metaplasia: Is it reliable? BMC Clin Pathol 2003 Dec 2;3(1):5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/14651756.
Assigned to
User:Reginald.lord
Topic area
Guidelines:Barrett's
Clinical question
Form
Form:Critical appraisal


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