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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Efficacy of confocal laser endomicroscopy for discriminating colorectal neoplasms from non-neoplasms: a systematic review and meta-analysis

P Su, Y Liu, S Lin, K Xiao, P Chen, S An, J He, and Y Bai.

Review published: 2013.

CRD summary

This review concluded that confocal laser endomicroscopy accurately differentiated between colorectal neoplasms and non-neoplasms, in patients with an indication for colorectal cancer. Given the high variation between trials and potential limitations in the statistical methods, it is difficult to assess the reliability of the findings. The authors' conclusions and recommendations for practice should be interpreted with caution.

Authors' objectives

To assess the accuracy of confocal laser endomicroscopy in discriminating between colorectal neoplasms and non-neoplasms, and to compare its diagnostic accuracy with that of chromoendoscopy.


Ten databases, including PubMed and The Cochrane Library, were searched for articles published between 2000 and 2012, without language restrictions. Search terms were reported. Reference lists of retrieved articles were manually screened.

Study selection

Eligible for inclusion were clinical trials assessing the accuracy of confocal laser endomicroscopy in diagnosing colorectal neoplasms in adults (18 years or older) with indications for screening or surveillance. Eligible trials had to present sufficient data to calculate sensitivity and specificity; use histological biopsy as the standard to diagnose colorectal neoplasms; and use the World Health Organization's Classification of Tumours or Vienna pattern as reference criteria. Trials were excluded if they did not blind pathologists and endoscopists to each other's diagnosis; reported retracted data; or did not account for over 40% of their data.

In most of the included trials, suspicious lesions were predefined by chromoendoscopy or conventional white-light endoscopy, then re-examined for neoplasms using endoscope or probe confocal laser endomicroscopy. Ten trials used real-time assessment, and five used blinded assessment based on videos. Most trials used intravenous fluorescein as the contrast agent. Participants included patients with inflammatory bowel disease or polyps, or those who were under surveillance.

The authors did not state how many reviewers screened articles for inclusion.

Assessment of study quality

Two reviewers independently assessed the methodological quality of the trials, using the modified QUADAS tool. Trials with at least six of the 13 criteria assessed as 'no' or 'unclear' were considered to be at a high risk of bias and were not included in the meta-analyses.

Data extraction

For trials assessing the discriminatory accuracy of confocal endomicroscopy, outcome data were extracted into 2x2 tables (true or false positives, and true or false negatives) to calculate sensitivity and specificity. For trials comparing the diagnostic accuracy of confocal endomicroscopy with that of chromoendoscopy, the relative risks and 95% confidence intervals were extracted.

Trial authors were contacted for further information if necessary. Two reviewers independently extracted the data, and discrepancies were resolved by referral to a third reviewer.

Methods of synthesis

Bivariate or DerSimonian and Laird random-effects models were used to combine the sensitivity and specificity. Summary receiver operating characteristic curves, using the Moses-Shapiro-Littenberg model, and the area under the curve were presented (these methods take into account the trade-off between sensitivity and specificity). The Spearman coefficient was used to determine whether there was a threshold effect. Relative risks and 95% confidence intervals were combined in meta-analyses.

Statistical heterogeneity was assessed using X² and I² (I² between 50% and 75% indicated moderate heterogeneity; over 75% indicated high heterogeneity). Subgroup analyses were performed to explore the diagnostic accuracy of video versus real-time confocal classification of colorectal lesions. Other subgroups and sensitivity analyses were explored. Univariate regression was conducted to assess the effects of the subgroup variables on the findings.

Publication bias was assessed using funnel plots.

Results of the review

Fifteen single-centre trials (719 patients; 2,290 specimens) were included in the review. The average QUADAS score was 11.2; all trials avoided differential verification bias and incorporation bias, and all of them blinded assessors to the reference standard and index test results.

The 15 trials showed that confocal endomicroscopy had high sensitivity (94%, 95% CI 88 to 97) and specificity (95%, 95% CI 89 to 97) for discriminating between colorectal neoplasms and non-neoplasms. The area under the curve was 0.97. There was no evidence of a threshold effect using the Spearman coefficient.

Subgroup analyses showed that real-time endomicroscopy sensitivity (96%) and specificity (97%) were significantly higher than video assessment (sensitivity 85%, specificity 82%, p<0.001). This was confirmed by the summary receiver operating characteristic curve.

The results from other subgroup and sensitivity analyses were reported. The authors stated that heterogeneity was relatively high across the trials, but some subgroup analyses had lower levels.

Four randomised controlled trials compared confocal endomicroscopy with chromoendoscopy: sensitivity and specificity were similar for comparisons between magnifying or virtual chromoendoscopy and real-time or video confocal endomicroscopy.

Adverse events were briefly discussed. There was no evidence of publication bias in the funnel plot.

Authors' conclusions

The evidence suggested that confocal laser endomicroscopy could accurately differentiate between colorectal neoplasms and non-neoplasms, and it was better using conventional endoscopy.

CRD commentary

The review question and supporting inclusion criteria were clearly stated. A satisfactory search of the literature was reported, but it was unclear whether this was performed by two people, so reviewer error and bias cannot be ruled out. Trial quality was assessed and the results were fully reported; the trials appeared to be generally of high quality.

Few patient details were reported and sample sizes were generally small. The authors acknowledged that the trials comparing the accuracy of endomicroscopy and chromoendoscopy might have been underpowered. They used various methods to synthesise and explore the data, but it may have been more appropriate to use alternatives to the Moses-Shapiro-Littenberg model. The authors reported that heterogeneity was high, and this remained high for some subgroup analyses.

Given the high variation between trials and potential limitations in the methods used to synthesise the data, it is difficult to assess the reliability of the findings and the authors' conclusions and recommendations for practice should be interpreted with caution.

Implications of the review for practice and research

Practice: The authors stated that confocal laser endomicroscopy should be implemented as the standard colonoscopy with traditional endoscopic techniques, rather than alone.

Research: The authors stated that further studies were needed to investigate the effects of dye and digital chromoendoscopy on endomicroscopy performance; to directly compare chromoendoscopy and endomicroscopy; to directly compare different contrast agents, using the same endoscopy methods; and to assess the cost-effectiveness of confocal laser endomicroscopy.


No funding received.

Bibliographic details

Su P, Liu Y, Lin S, Xiao K, Chen P, An S, He J, Bai Y. Efficacy of confocal laser endomicroscopy for discriminating colorectal neoplasms from non-neoplasms: a systematic review and meta-analysis. Colorectal Disease 2013; 15(1): e1-e12. [PubMed: 23006609]



Indexing Status

Subject indexing assigned by NLM


Biopsy; Colon /pathology; Colonoscopy /methods; Colorectal Neoplasms /pathology; Coloring Agents /diagnostic use; Confidence Intervals; Humans; Microscopy, Confocal; Rectum /pathology; Sensitivity and Specificity



Date bibliographic record published


Date abstract record published


Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 23006609

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