Critical appraisal:McIntire MG, Soucy G, Vaughan TL, Shahsafaei A, Odze RD 2011 3

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Critical Appraisal

Article being appraised

McIntire MG, Soucy G, Vaughan TL, Shahsafaei A, Odze RD. MUC2 is a highly specific marker of goblet cell metaplasia in the distal esophagus and gastroesophageal junction. Am J Surg Pathol 2011 Jul;35(7):1007-13 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21602660.


Applicable clinical question

Key Facts

Study Design

diagnostic accuracy study

Number of Patients enrolled:

Not applicable

Number of Patients evaluated:

Not applicable

Number of samples:

Not applicable


Includes an economic evaluation

no

Evidence ratings

Level of evidence

III-1


Risk of bias assessment: diagnostic accuracy study

Patient Selection
Prior tests and any referral filters
The study utilised mucosal biopsies from 100 patients selected from a large community clinic-based cohort of chronic gastroesophageal reflux disease (GERD) sufferers, aged 31 to 80 years, evaluated prospectively in the western part of Washington State in the USA. Non of the patients revealed ulceration, dysplasia or adenocarcinoma. All patients underwent an upper endoscopy for symptoms of GERD and had 4 quadrant biopsies obtained from the squamocolumnar junction (SCJ) and from the tubular oesophagus proximal to the SCJ.
Condition that defined entry into study
The 100 patients included in this study were randomly selected on the basis of the presence or absence of goblet cells in their mucosal biopsies. All patients had well-definied pathologic, endoscopic and clinical information obtained in a prospective manner.
Setting
Patients were selected from a community clinic-based study in the western part of Washington State in the USA between 1997 and 2000.
Was a diagnostic case-control design avoided?
Yes
Consecutive or random sample?
Yes
Did the study avoid inappropriate exclusions?
Yes
Reasons
No patients were excluded following selection.
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 enriched for the presence of columnar epithelium in the oesophagus by using a cohort with chronic GERD. Random selection was used to select the 50 patients comprising each of the study group (columnar epithelium containing goblet cells) and the control group (columnar epithelium without goblet cells).
Index test 1
Describe index test and how it was conducted and interpreted
The index test was immunohistochemical staining for MUC2 in formalin-fixed paraffin-embedded (FFPE) mucosal biopsies from both distal oesophagus and gastroesophageal junction (GEJ). Immunostained stlides were evaluated in a blinded manner without knowledge of the clinical, histological or endoscopic features of the patient. Random cases from both groups (>20%) were evaluated by a second pathologist with 100% concordance between the two pathologists. The test was interpreted in a binary fashion with the presence of any MUC2 staining (whether in goblet cells or non-goblet columnar epithelium) considered positive and no staining considered negative.
Were the index test results interpreted without knowledge of the results of the reference standard?
Yes
If a threshold was used, was it pre-specified?
Yes
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?
Low
Comments
The MUC2 evaluation was performed in a blinded manner and random cases confirmed by a second independent pathologist.
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 endoscopy, with 4 quadrant biopsies obtained from the squamocolumnar junction (SCJ) and from the tubular oesophagus, proximal to the SCJ. Biopsies were fixed in formalin, embedded in paraffin and stained with hemotoxylin and eosin (H&E). All biopsies were reviewed to confirm the presence or absence of goblet cells in the columnar portion of the biopsies.
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
All biopsies were evaluated for evidence that the columnar portion of the tissue was obtained from the distal oesophagus rather than the proximal stomach by showing features such as multi-layered epithelium, oesophageal ducts/glands (features only present in distal oesophagus).
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 received both the reference test and the index test.
Describe the time interval and any interventions between index test(s) and reference standard
The time interval between performing the reference test and the index test was not noted. However it is inferred that the index test is performed on FFPE sections that were used for the reference test.
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
No patients were excluded. All 100 selected from the reference standard results received the index test.
Size of effect
2 Reason for decision: MUC2 staining of the non-goblet epithelium is a reasonably sensitive (78%) and highly specific (96%) predictive biomarker for the presence of goblet cells in the patient.
Relevance of evidence
2 Additional comments: Provides evidence that the MUC2 test can help diagnose Barrett's Oesophagus and overcome problems of sampling bias during endoscopy. Does not provide evidence that using the test improves outcomes for the patient.
Result of appraisal

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Melissa Thomas


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Article
McIntire MG, Soucy G, Vaughan TL, Shahsafaei A, Odze RD. MUC2 is a highly specific marker of goblet cell metaplasia in the distal esophagus and gastroesophageal junction. Am J Surg Pathol 2011 Jul;35(7):1007-13 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21602660.
Assigned to
User:angelique.levert
Topic area
Guidelines:Barrett's
Clinical question
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Form:Critical appraisal


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