Systematic Review With Network Meta-Analysis

Endoscopic Techniques for Dysplasia Surveillance in Inflammatory Bowel Disease

Andrea Iannone; Marinella Ruospo; Suetonia C. Palmer; Mariabeatrice Principi; Michele Barone; Alfredo Di Leo; Giovanni F. M. Strippoli

Disclosures

Aliment Pharmacol Ther. 2019;50(8):858-871. 

In This Article

Results

Study Characteristics

The search retrieved 565 citations (Figure 1). Twenty-one trials involving 2889 participants with IBD were eligible for inclusion in the review.[29–49] We could not extract data from three crossover trials[31,32,41] because results at the end of the first phase of the study were not reported. Thus, 18 trials involving 2638 participants were included in our analysis.[29,30,33–40,42–49] Table S2 shows the study design, interventions and population characteristics in the 21 trials included in the review.

Figure 1.

Summary of study retrieval and identification for network meta-analysis

The number of participants enrolled in each trial ranged between 20[32] and 305.[29] In nine[30,31,34,35,39–42,45] of 21 included trials, a total of 125 participants were excluded after randomisation for insufficient bowel preparation, active colonic inflammation, short disease duration or lack of compliance with the study protocol. Fourteen trials[30–32,34,37,39–41,43,44,46–49] included only participants with ulcerative colitis, six trials[29,33,35,38,42,45] enrolled participants with both ulcerative colitis and Crohn's disease, and one trial included participants with ulcerative colitis, Crohn's disease and unclassified colitis.[36]

Eight endoscopic techniques for dysplasia surveillance were evaluated: chromoendoscopy (13 trials), high definition white-light endoscopy (9 trials), narrow band imaging (8 trials), standard definition white-light endoscopy (6 trials), autofluorescence (3 trials), i-SCAN (2 trials), full spectrum high definition white-light endoscopy (Endochoice, Alpharetta, USA) (1 trial) and Fujinon intelligent colour enhancement FICE (Fujifilm, Tokyo, Japan) (1 trial). Full spectrum high definition white-light endoscopy has additional lateral camera lenses, providing a 330 degree field of view as opposed to the 170 degree field of view of conventional forward-viewing endoscopes.[50] We received additional unpublished information from the authors of two trials.[34,48]

Risk of Bias

Random sequence generation was adequate in nine trials and unclear in the remaining 12 (Figure S1). The risk of bias for allocation concealment was low in one trial and high or unclear in the other trials. Masking of participants, investigators and outcome assessment was adequate in 14 trials and unclear in the remaining seven. Ten trials were characterised by completeness of outcome reporting, while 11 were at high or unclear risk of bias for this domain. The risk of selective reporting bias was low in 13 and high or unclear in eight.

Supplementary Figure 1.

A. Risk of bias graph: review authors' judgments about each risk of bias item presented as percentages across all included studies; B. Risk of bias summary: review authors' judgments about each risk of bias item for each included study.

Network Consistency

Figure 2 and Figure S2 show the networks of individual endoscopic techniques for all outcomes. Included trials were deemed sufficiently comparable by population, intervention and study characteristics (Table S2) to be summarised using network meta-analysis. Pairwise and network meta-analysis estimates were similar in magnitude (Table 1, Table 2 and Table 3; Table S3, Table S4, Table S5 and Table S6) and there was evidence of no loop-specific inconsistency between direct and indirect evidence (Figure S3). The design-by-treatment interaction approach did not identify global inconsistency in any outcome network (Table S7).

Figure 2.

Graphic representation of endoscopic technique comparisons for (A) number of participants with one or more neoplastic lesions, (B) number of participants with any type of lesion, (C) number of nonpolypoid neoplastic lesions, (D) number of low-grade dysplastic lesions, and (E) number of high-grade dysplastic lesions. Connecting lines represent head-to-head technique comparisons, indicated by the connected nodes (size proportional to the number of trials evaluating the endoscopic technique). Numbers above and below the lines indicate studies and participants respectively. Line thickness is proportional to the number of trials comparing the two endoscopic techniques. Abbreviations: HD, high definition; SD, standard definition; NBI; narrow band imaging; FICE, Fujinon intelligent colour enhancement

Supplementary Figure 2.

Graphic representation of endoscopic technique comparisons for (A) number of neoplastic lesions detected by target biopsy, and (B) procedural time.
Connecting lines represent head-to-head technique comparisons, indicated by the connected nodes (size proportional to the number of trials evaluating the endoscopic technique). Numbers above and below the lines indicate studies and participants, respectively. Line thickness is proportional to the number of trials comparing the two endoscopic techniques.
HD, high definition; SD, standard definition; NBI; narrow band imaging.

Supplementary Figure 3.

Inconsistency plots for number of (A) participants with one or more neoplastic lesions, (B) participants with any type of lesion, (c) non-polypoid neoplastic lesions, (D) low-grade dysplastic lesions, and (E) high-grade dysplastic lesions.
AF, autofluorescence; CE, chromoendoscopy; HD, high definition white light endoscopy; IS, i-SCAN; NBI, narrow band imaging.
Inconsistency plots could not be created for "number of dysplastic lesions detected by target biopsy" and "procedural time" due to the absence of triangular or quadrantic loops.

Outcomes

Endoscopic technique effects in pairwise and network meta-analyses for the considered outcomes are reported in Table 1, Table 2 and Table 3 and Table S3, Table S4, Table S5 and Table S6. GRADE assessments for the comparison of each endoscopic technique with chromoendoscopy, the recommended first-line approach for dysplasia surveillance in IBD, on number of participants with one or more neoplastic lesions, number of participants with any type of lesion, number of nonpolypoid neoplastic lesions, number of low-grade dysplastic lesions and number of high-grade dysplastic lesions are provided in Table 4.

Number of Participants With one or More Neoplastic Lesions. Eighteen trials involving 2543 participants evaluated the effect of different endoscopic techniques on the number of participants who were identified to have one or more neoplastic lesions (Figure 2A). Standard definition white-light endoscopy (OR 0.44, CI 0.26–0.73; high certainty evidence) and i-SCAN (OR 0.47, CI 0.25–0.90; moderate certainty evidence) probably had lower odds of detecting participants with neoplasia compared to chromoendoscopy (Table 1 and Table 4). Differently from the estimated CI, the 95% prediction interval for the comparison between i-SCAN and chromoendoscopy included the null value (ie '1') (Figure S4A). A 95% prediction interval takes into consideration the full uncertainty around the intervention estimate, providing a range of values that includes, with 95% confidence, effect estimates from future studies. Standard definition white-light endoscopy (OR 0.14, CI 0.02–0.86; low certainty evidence), i-SCAN (OR 0.15, CI 0.02–0.88; low certainty evidence) and FICE (OR 0.02, CI 0.00–0.77; low certainty evidence) may have lower odds of identifying participants with neoplasia compared to full spectrum high definition white-light endoscopy (Table 1). The 95% prediction interval for these comparisons included the null value (Figure S4A). Standard definition white-light endoscopy may have also lower odds of detecting participants with neoplasia compared to narrow band imaging (OR 0.44, CI 0.23–0.99; low certainty evidence) (Table 1), with the 95% prediction interval including the null value (Figure S4A). High definition white-light endoscopy may have higher odds of identifying participants with neoplasia compared to i-SCAN (OR 1.73, CI 1.01–2.96; low certainty evidence) (Table 1), with the 95% prediction interval including the null value (Figure S4A).

Supplementary Figure 4.

Interval plots for number of (A) participants with one or more neoplastic lesions, (B) participants with any type of lesion, (C) non-polypoid neoplastic lesions, (D) low-grade dysplastic lesions, (E) high-grade dysplastic lesions, (F) number of neoplastic lesions identified by target biopsy, and (G) procedural time.
AF, autofluorescence; CE, chromoendoscopy; HD, high-definition white light endoscopy; SD, standard-definition white light endoscopy; IS, i-SCAN; NBI, narrow band imaging; FSHD, full spectrum high-definition white light endoscopy; FICE, Fujinon intelligent colour enhancement; PrI, prediction interval.
Mean difference values for procedural time (Supplementary Figure 4G) are expressed in minutes.

Full spectrum high definition white-light endoscopy ranked as the best endoscopic technique to detect participants with one or more neoplastic lesions (Figure 3). There was moderate confidence in hierarchical ranking for study limitations.

Figure 3.

Rankings of endoscopic techniques for number of participants with one or more neoplastic lesions, number of nonpolypoid neoplastic lesions, number of low-grade dysplastic lesions and number of high-grade dysplastic lesions. The lines show the probability of the technique ranking between best (=1) and worst (=8) for each outcome, and the peak indicates the ranking with the highest probability for the corresponding endoscopic technique. For example, for number of participants with one or more neoplastic lesions, full spectrum high definition white-light endoscopy demonstrates a higher probability of ranking best (=1) compared to all other endoscopic techniques. Rankogram lines without marked peaks indicate similar probabilities of all rankings and lower confidence in comparative ranking of the relevant endoscopic technique for the specific outcome. Abbreviations: HD, high definition; SD, standard definition; NBI; narrow band imaging; FICE, Fujinon intelligent colour enhancement

There was no evidence of publication bias for this outcome (Figure S5A).

Supplementary Figure 5.

Comparison adjusted funnel plots for (A) number of participants with one or more neoplastic lesions, (B) number of non-polypoid neoplastic lesions, (C) number of low-grade dysplastic lesions, and (D) number of high-grade dysplastic lesions.
HD, high definition; SD, standard definition; NBI, narrow band imaging; FICE, Fujinon intelligent colour enhancement.
Funnel plots could not be created for number of participants with any type of lesion, number of neoplastic lesions detected by target biopsy, and procedural time due to the paucity of trials.

Number of Participants With any Type of Lesion. Seven trials involving 1246 participants evaluated the effect of five endoscopic techniques (chromoendoscopy, high definition white-light endoscopy, narrow band imaging, autofluorescence and i-SCAN) on the number of participants who were identified to have one or more colonic lesions of any type (including neoplastic and non-neoplastic lesions) (Figure 2B). Autofluorescence (OR 0.42, CI 0.24–0.73; high certainty evidence) and i-SCAN (OR 0.46, CI 0.22–0.95; moderate certainty evidence) probably had lower odds of detecting participants with any type of lesion compared to chromoendoscopy (Table 4 and Table S3). The 95% prediction interval for the comparison between i-SCAN and chromoendoscopy included the null value (Figure S4B). Narrow band imaging probably had higher odds of detecting participants with any type of lesion compared to autofluorescence (OR 2.20, CI 1.06–4.56; moderate certainty evidence) (Table S3), with the 95% prediction interval including the null value (Figure S4B).

Chromoendoscopy ranked as the best endoscopic technique to detect participants with any type of lesion (Figure S6A), with moderate confidence in hierarchical ranking for study limitations.

Supplementary Figure 6.

Rankings of endoscopic techniques from best to worst for (A) number of participants with any type of lesion, (B) number of neoplastic lesions detected by target biopsy, and (C) procedural time.
HD, high definition; SD, standard definition; NBI; narrow band imaging.

We could not assess publication bias for this outcome due to the paucity of trials.

Number of Nonpolypoid Neoplastic Lesions. The network for number of nonpolypoid neoplastic lesions included 10 trials involving 1336 participants (Figure 2C). Standard definition white-light endoscopy probably had lower odds of detecting nonpolypoid neoplastic lesions compared to high definition white-light endoscopy (OR 0.14, CI 0.02–0.93; moderate certainty evidence), chromoendoscopy (OR 0.13, CI 0.04–0.49; moderate certainty evidence), narrow band imaging (OR 0.09, CI 0.02–0.46; moderate certainty evidence) and full spectrum high definition white-light endoscopy (OR 0.01, CI 0.00–0.34; moderate certainty evidence) (Table 2 and Table 4). The 95% prediction interval for these comparisons included the null value (Figure S4C). There was no evidence of detectable differences in the odds of detecting nonpolypoid neoplasia in any other comparison between endoscopic techniques (moderate to low certainty evidence) (Table 2 and Table 4).

Full spectrum high definition white-light endoscopy ranked as the best endoscopic technique for this outcome, with moderate confidence in hierarchical ranking for imprecision (Figure 3).

There was no evidence of publication bias for this outcome (Figure S5B).

Number of Low-grade and High-grade Dysplastic Lesions. The networks for number of low-grade and high-grade dysplastic lesions included 14 trials involving 1736 participants (Figure 2D,E). There was no evidence of detectable differences between interventions in the odds of detecting low-grade (moderate to very low certainty evidence) (Table S4) and high-grade (moderate to very low certainty evidence) (Table S5) dysplastic lesions. There was limited confidence in hierarchical endoscopic technique rankings for number of low-grade and high-grade dysplastic lesions for study limitations and imprecision (Figure 3).

There was no evidence of publication bias for these outcomes (Figure S5C,D).

Number of Neoplastic Lesions Detected by Target Biopsy and Procedural Time. Six trials involving 1048 participants evaluated the effect of five endoscopic techniques (chromoendoscopy, high definition white-light endoscopy, narrow band imaging, standard definition white-light endoscopy and autofluorescence) on number of neoplastic lesions detected by target biopsy (Figure S2A). Standard definition white-light endoscopy probably had lower odds of detecting neoplastic lesions by target biopsy compared to chromoendoscopy (OR 0.27, CI 0.08–0.91; moderate certainty evidence) (Table 3), with the 95% prediction interval including the null value (Figure S4F). There was no evidence of detectable differences in any other comparison between interventions (low to very low certainty evidence) (Table 3). Chromoendoscopy ranked as the best endoscopic technique to detect neoplastic lesions by target biopsy (Figure S6B), with limited confidence in hierarchical ranking for study limitations and imprecision.

The network for procedural time included five trials (675 participants) evaluating the effect of four endoscopic techniques (chromoendoscopy, high definition white-light endoscopy, standard definition white-light endoscopy and full spectrum high definition white-light endoscopy) (Figure S2B). Standard definition white-light endoscopy was probably associated with a shorter procedural time than chromoendoscopy (MD –14.81 minutes, CI –25.03 to –4.06 minutes; moderate certainty evidence) (Table S6), with the 95% prediction interval including the null value (ie '0') (Figure S4G). There was no evidence of detectable differences in procedural time in any other comparison between endoscopic techniques (low to very low certainty evidence) (Table S6). Standard definition white-light endoscopy ranked as the best endoscopic technique for procedural time (Figure S6C). There was low confidence in hierarchical ranking for study limitations and imprecision.

We could not assess publication bias for number of neoplastic lesions detected by target biopsy and procedural time due to the paucity of trials (<10 studies).

Adverse Events. Eight trials[34–37,39,42,47,48] involving 1050 participants evaluated adverse events associated with the different endoscopic techniques. We could not perform a network meta-analysis for this outcome because six of these trials did not report any endoscopic procedure-related side effects. The remaining two studies[42,48] described a total of 28 participants with adverse events: 24 complained of abdominal pain or discomfort with high definition white-light endoscopy (14 participants), full spectrum high definition white-light endoscopy (nine participants) or autofluorescence (one participant); three had intraprocedural mild bleeding with chromoendoscopy (two participants) or autofluorescence (one participant); and one experienced bowel perforation with chromoendoscopy.

Other Outcomes. No trial provided data on health-related quality of life, all-cause mortality, colorectal cancer-related mortality and interval colorectal cancer.

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