Critical appraisal:Ormsby AH, Vaezi MF, Richter JE, Goldblum JR, Rice TW, Falk GW, et al 2000

From Clinical Guidelines Wiki

Critical Appraisal

Article being appraised

Ormsby AH, Vaezi MF, Richter JE, Goldblum JR, Rice TW, Falk GW, et al. Cytokeratin immunoreactivity patterns in the diagnosis of short-segment Barrett's esophagus. Gastroenterology 2000 Sep;119(3):683-90 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/10982762.


Applicable clinical question

Key Facts

Study Design

diagnostic accuracy study

Number of Patients enrolled:

127

Number of Patients evaluated:

118

Number of samples:

118


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. Patients identified from medical records. Patient selection based on confirmed diagnosis following endoscopic examination and evaluation of H&E stained biopsies. Helicobactor pylori infection status was available for patients as a result of an ongoing study assessing the role of H.pylori in patients with Barrett’s oesophagus.
Condition that defined entry into study
Endoscopic biopsy specimens from patients with long-segment Barrett’s Oesophagus (BO) (n=49), suspected short-segment BO (n=43) and gastric intestinal metaplasia (GIM) (n=26) were identified from medical records over 3 years, 1996-1998.
Setting
A single centre study performed at the Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Was a diagnostic case-control design avoided?
No
Consecutive or random sample?
No
Did the study avoid inappropriate exclusions?
Unclear
Reasons
A total of 127 patients were selected, with only 118 evaluated. 7 patients were excluded from analysis as a result of poor orientation of biopsy (required to differentiate superficial and deep mucosa). A further 2 patients were excluded due to interobserver discrepancies.
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?
Unclear
Comments
The study used a case-control design, rather than enrolling a representative group of patients who are eligible for testing. The definition of short-segment BO excluded cases where the BO was observed to be <5mm circumferentially above the proximal gastric folds (possible introduction of bias due to exclusion of a subset of patients with less extensive SSBO).
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. Independent assessment of CK7/CK20 staining was undertaken by two gastrointestinal pathologists with experience in the interpretation of cytokeratin immunoreactivity patterns obtained from a previously published study (Ormsby et al, 1999).
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
Interpretation was performed by two independent pathologists who had performed the evaluation in a previous study by the same group (Ormsby et al, 1999). Where there was interobserver disagreement between the two pathologists the patients were excluded.
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 from biopsies taken during endoscopic examination. Periodic acid Schiff (PAS) and Alcian blue pH 2.5 were used additionally to positively identify mucin-containing goblet cells.
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?
Unclear
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 PAS and Alcian Blue staining to identify mucin-containing goblet cells.
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 standard 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. For 2 patients there was disagreement between the two pathologists about the results and these patients were excluded. No further follow-up assessment with patients was required.
Size of effect
2 Reason for decision: Results indicate that CK7/CK20 immunostaining can identify both long-segment Barrett’s oesophagus and short-segment Barrett’s oesophagus with accuracy approaching the current standard method (as the reference standard). Cytokeratin staining pattern identified long-segment BE with a 98% sensitivity and short-segment BE with 82% sensitivity, and 100% specificity for distinguishing between BO and gastric IM. However it was noted that interpretation of the CK7/CK20 staining pattern is highly complex with several caveats that could result in misinterpretation, such as the absence of CK20 staining in areas of dysplasia/adenocarcinoma, the presence of CK7 staining in non-specialised columnar mucosa, and the weak intensity of CK7 in patients with Barrett’s mucosa.
Relevance of evidence
4 Additional comments: 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

Jutta's tick icon.png Included




Completed by

Melissa Thomas


Jutta's tick icon.png This appraisal has been completed.


Article
Ormsby AH, Vaezi MF, Richter JE, Goldblum JR, Rice TW, Falk GW, et al. Cytokeratin immunoreactivity patterns in the diagnosis of short-segment Barrett's esophagus. Gastroenterology 2000 Sep;119(3):683-90 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/10982762.
Assigned to
User:Reginald.lord
Topic area
Guidelines:Barrett's
Clinical question
Form
Form:Critical appraisal


Section below only relevant for Cancer Council Project Officer

Edit appraisal assignment