Critical appraisal:Schilling D, Spiethoff A, Rosenbaum A, Hartmann D, Eickhoff A, Jakobs R, et al 2005

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Critical Appraisal

Article being appraised

Schilling D, Spiethoff A, Rosenbaum A, Hartmann D, Eickhoff A, Jakobs R, et al. Does Cytokeratin7/20 immunoreactivity help to distinguish Barrett's esophagus from gastric intestinal metaplasia? Results of a prospective study of 75 patients. Pathol Res Pract 2005;200(11-12):801-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15792123.


Applicable clinical question

Key Facts

Study Design

diagnostic accuracy study

Number of Patients enrolled:

78

Number of Patients evaluated:

75

Number of samples:

Not applicable


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
Patient selection based on confirmed diagnosis following endoscopic examination and evaluation of H&E stained biopsies. Oesophageal biopsy sampling was performed using methylene blue stain to identify areas of columnar mucosa. The study included patients undergoing upper GI endoscopy for upper gastrointestinal symptoms with suspected long or short segment Barrett’s esophagus or with an endoscopically normal gastroesophageal junction.
Condition that defined entry into study
Seventy-eight patients were enrolled in this study, 26 with long-segments Barrett’s esophagus (BO), 21 with short-segments BO, 13 with intestinal metaplasia (IM) of the cardia and 18 with antral IM.
Setting
A single centre study performed at the Academic Medical Hospital of the University of Mainz, Ludwigshafen, Germany.
Was a diagnostic case-control design avoided?
Yes
Consecutive or random sample?
Unclear
Did the study avoid inappropriate exclusions?
Unclear
Reasons
It was stated that multiple biopsies taken per patient but unclear whether multiple biopsies were analysed. All results were reported in terms of patients but it was not stated whether all biopsies for this patient supported the result or only a subset. Exclusion criteria were antibiotic therapy within 10 days before admission, eradication therapy of Helicobactor pylori infection or gastrointestinal pathology related to portal hypertension.
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?
Low
Comments
Patient selection was designed to address whether cytokeratin immunohistochemical staining could be used to correctly distinguish long and short segment BO biopsies from gastric IM biopsies.
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. Dysplastic areas were excluded from analysis by these authors. All cases were evaluated independently by two pathologists. Disagreements were settled by common assessment.
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
Dysplastic areas of intestinal metaplasia were excluded from analysis (previously mentioned by Ormsby et al (2000) as a caveat in the method due to the absence of CK20 staining in areas of dysplasia or adenocarcinoma), which may skew reported results.
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. Alcian Blue pH 2.5 stain was used to positively identify mucin containing goblet cells. Endoscopic examination and biopsying was performed by experienced endoscopists.
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 esophagus, with additional 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 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?
No
What is the risk that the patient flow introduced bias?
Low
Comments
Patient specimens for both the index test and reference standard were taken in a single endoscopy session. No further interaction with the patients was required.
Size of effect
3 Reason for decision: The CK7 / CK20 immunostaining pattern showed high specificity (97%) but poor sensitivity (30%) in patients with short segment Barrett’s esophagus. For long segment Barrett’s esophagus sensitivity was only 17%. The reported 97% specificity refers to gastric IM in both the cardia and antrum. With respect to cardiac intestinal metaplasia only, the test is reported to be 100% specific. Multiple biopsies were taken per patient but it was unclear whether all biopsies were analysed. Results were reported in terms of patients but it was not stated whether all biopsies for this patient supported the result or only a subset. Implications of this on the reported sensitivity and specificity are unclear.
Relevance of evidence
4 Additional comments: Provides evidence that CK7/CK20 immunostaining pattern cannot be used to reliably differentiate between Barrett’s oesophagus (long or short segment BO) and gastric intestinal metaplasia. These results do not confirm the findings of Ormsby et al.
Result of appraisal

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Completed by

Melissa Thomas


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Article
Schilling D, Spiethoff A, Rosenbaum A, Hartmann D, Eickhoff A, Jakobs R, et al. Does Cytokeratin7/20 immunoreactivity help to distinguish Barrett's esophagus from gastric intestinal metaplasia? Results of a prospective study of 75 patients. Pathol Res Pract 2005;200(11-12):801-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15792123.
Assigned to
User:Reginald.lord
Topic area
Guidelines:Barrett's
Clinical question
Form
Form:Critical appraisal


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