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

Discussion

This network meta-analysis found that standard definition white-light endoscopy and i-SCAN probably had lower odds of identifying participants with neoplastic lesions compared to chromoendoscopy. There was no evidence of detectable differences in the odds of identifying participants with neoplasia between chromoendoscopy and any other endoscopic technique, although chromoendoscopy had higher odds of detecting participants with any type of colonic lesion, including non-neoplastic ones, compared to autofluorescence and i-SCAN. Standard definition white-light endoscopy had lower odds of detecting nonpolypoid neoplastic lesions than full spectrum high definition white-light endoscopy, narrow band imaging, chromoendoscopy and high definition white-light endoscopy. There was no evidence of detectable differences in the odds of identifying nonpolypoid neoplasia in any other comparison between endoscopic techniques. Full spectrum high definition white-light endoscopy ranked as the best technique for identifying both participants with neoplasia and nonpolypoid lesions. This technique showed higher odds of detecting participants with neoplastic lesions than standard definition white-light endoscopy, i-SCAN and FICE. Full spectrum high definition white-light endoscopy also had higher odds of identifying nonpolypoid neoplasia compared with all other techniques, although these comparisons did not reach statistical significance and were mainly derived from indirect comparisons. There was no evidence of differences between endoscopic techniques in identifying low-grade or high-grade dysplastic lesions. Standard definition white-light endoscopy probably had lower odds of detecting neoplastic lesions by target biopsy and shorter procedural time compared to chromoendoscopy. Based on our findings, chromoendoscopy, high definition white-light endoscopy, narrow band imaging, autofluorescence, FICE and full spectrum high definition white-light endoscopy may be alternative endoscopic techniques for dysplasia surveillance in people with IBD, whereas standard definition white-light endoscopy and i-SCAN showed lower efficacy than chromoendoscopy, the recommended first-line approach in this setting. However, the discrepancy in our results between the estimated CI and the 95% prediction interval for the comparison between i-SCAN and chromoendoscopy indicates that i-SCAN efficacy requires further investigation. Additionally, considering the high prevalence of nonpolypoid neoplasia in people with IBD (23%-67%),[51,52] standard definition white-light endoscopy should not be used for neoplasia surveillance in this population. Finally, our results suggest that full spectrum high definition white-light endoscopy may represent the first-line endoscopic approach for dysplasia surveillance in IBD.

Two recently published systematic reviews with network meta-analysis compared the efficacy of different endoscopic techniques for dysplasia surveillance in people with IBD.[53,54] Imperatore et al[53] found a higher likelihood of identifying dysplasia with chromoendoscopy compared to white-light endoscopy (OR 2.12, CI 1.18–5.23), with no significant differences in any other comparison between endoscopic techniques. The authors analysed standard definition and high definition white-light endoscopy in the same intervention arm, although these techniques require distinct endoscopes which provide images at different resolution.[55] Our network meta-analysis confirmed that chromoendoscopy probably had higher odds of detecting participants with neoplastic lesions when compared with standard definition white-light endoscopy. Additionally, the authors included both randomised (11 trials) and observational studies in their review and performed a network meta-analysis for the single outcome of dysplasia detection, without providing network plots, endoscopic technique rankings or assessment of loop-specific and global network consistency. Bessissow et al[54] did not identify any statistically significant difference in the detection of dysplasia in any comparison between endoscopic techniques, with chromoendoscopy ranking as the best technique for dysplasia identification. These findings differ from our analysis because we found higher odds of identifying participants with neoplasia with chromoendoscopy compared to standard definition white-light endoscopy and i-SCAN, with full spectrum high definition white-light endoscopy ranking as the best endoscopic technique for this outcome. However, the authors of this network meta-analysis included a low number of randomised trials (eight studies), which investigated only four endoscopic techniques (ie chromoendoscopy, narrow band imaging, high definition white-light endoscopy and standard definition white-light endoscopy) for dysplasia surveillance in IBD. They also included in their analysis data from one crossover trial[31] that did not provide the results for the first phase of the study and performed a network meta-analysis for the single outcome of dysplasia detection, without providing the assessment of global network consistency. Finally, both previous network meta-analyses[53,54] did not report the efficacy of different endoscopic techniques on identifying morphological and histological subtypes of dysplastic lesions, detecting neoplasia by target biopsy, procedural time and adverse events.

We compared our findings with recommendations from key international guidelines, which indicate chromoendoscopy with target biopsy as the first-line approach for dysplasia surveillance in people with IBD.[8–11,13,14] White-light endoscopy with random biopsies is considered appropriate if chromoendoscopy is not available, while other endoscopic techniques are not recommended.[7,9,11,13] Our findings support the superiority of chromoendoscopy over standard definition white-light endoscopy and i-SCAN in detecting people with neoplasia. Standard definition white-light endoscopy also showed lower odds of detecting nonpolypoid neoplastic lesions compared with chromoendoscopy, high definition white-light endoscopy, narrow band imaging and full spectrum high definition white-light endoscopy. In contrary, we found similar efficacy in identifying people with neoplasia and detecting nonpolypoid neoplastic lesions when comparing chromoendoscopy with high definition white-light endoscopy, narrow band imaging, full spectrum high definition white-light endoscopy, FICE or autofluorescence. Thus, considering the prevalence of nonpolypoid dysplasia in this population (23%-67%),[51,52] white-light endoscopy with standard definition endoscopes should no more be proposed for dysplasia surveillance in IBD, while high definition white-light endoscopy, narrow band imaging, full spectrum high definition white-light endoscopy, FICE and autofluorescence may represent reasonable alternatives to chromoendoscopy. Finally, based on our results, we contend that more evidence is needed to clearly assess the efficacy of i-SCAN for dysplasia surveillance in IBD and evaluate the possible role of full spectrum high definition white-light endoscopy as the first-line endoscopic approach in this setting.

This systematic review with network meta-analysis compares eight different endoscopic techniques for dysplasia surveillance in IBD, with a comprehensive evaluation of efficacy and harms of these interventions. We assessed the totality of evidence, including a larger number of randomised trials (18 studies) in our analysis than existing network meta-analyses,[53,54] and limited analyses to randomised trials without incorporating cohort studies as in one[53] of the two previous reviews.

The study had limitations that should be considered in the interpretation of the results. First, eight out of 18 randomised trials included in our analysis had unclear/high risk of bias for most domains. The study limitations related to these trials and the imprecision in effect estimates, due to the amount of data available for analyses, were the main reasons for downgrading the evidence of certainty to low or very low for most endoscopic techniques. Second, we estimated very low odds ratio values and wide CI in most comparisons between FICE and other endoscopic techniques. This technique has been investigated in a single trial with a crossover study design, in which no neoplastic lesions were identified using FICE in the first phase of the trial.[35] This may have reduced precision in comparative estimates for FICE on assessed outcomes. Third, we could not perform subgroup analysis by IBD subtype (ulcerative colitis or Crohn's colitis) because 11 out of 18 trials included in our analyses enrolled only ulcerative colitis participants, while the remaining seven studies enrolled a mixed ulcerative and Crohn's colitis population and did not provide outcome data by disease subtype. Fourth, we could not analyse the diagnostic accuracy of high definition white-light endoscopy compared to dye-based and virtual chromoendoscopy on optical discrimination between neoplastic and non-neoplastic lesions. Only one[36] of the randomised trials included in our network meta-analysis assessed this endpoint, using histology as the reference standard. The authors found similar sensitivity and specificity to predict histology of colonic lesions for high definition white-light endoscopy, chromoendoscopy and i-SCAN. Fifth, we could not evaluate the effect of dysplasia surveillance on colorectal cancer-related mortality, as no selected trial included a follow-up period to capture this outcome. There is a need for high-quality trials investigating the impact of surveillance programs in people with IBD on colorectal incidence and mortality, since unequivocal evidence for the benefit of surveillance endoscopy on these relevant clinical outcomes is still lacking.[10,13] Finally, adverse events, all-cause mortality, interval cancer and health-related quality of life could not be analysed in the present network meta-analysis because few or no trials reported data on these outcomes. Gulati et al[35] analysed participants' experience in their study investigating chromoendoscopy versus FICE. However, they did not provide the results for the first phase of this randomised crossover trial.

The results of this network meta-analysis indicate that chromoendoscopy, high definition white-light endoscopy, narrow band imaging, autofluorescence, FICE and full spectrum high definition white-light endoscopy may be appropriate endoscopic techniques for dysplasia surveillance programs in people with IBD. On opposite, standard definition white-light endoscopy should not be proposed in this setting. Thus, if standard definition white-light endoscopy is the only available technique, patients with IBD should be referred to specialised endoscopic centres for dysplasia surveillance.

The efficacy of i-SCAN in dysplasia surveillance should be further investigated in randomised trials, based on the discrepancy in our results between the estimated CI and the 95% prediction interval for the comparison between this technique and chromoendoscopy. Full spectrum high definition white-light endoscopy may represent the best endoscopic technique to identify both participants with neoplasia and nonpolypoid lesions. However, currently only few endoscopic centres have full spectrum high definition white-light endoscopy available. Additionally, evidence supporting this technique mainly derives from indirect comparisons. Thus, there is a need for high-quality multi-centre randomised trials comparing full spectrum high definition white-light endoscopy with chromoendoscopy, which is currently recommended as the first-line endoscopic approach, to clearly assess if this technique may play a predominant role in dysplasia surveillance of IBD in the near future.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....