Surveillance for dysplasia in inflammatory bowel disease: it is time to move forward

The decision of whether or not to use chromoendoscopy with targeted biopsy (CETB) to detect dysplasia in patients with inflammatory bowel disease (IBD) ought to follow the principle of rational decision-making. But many, including key opinion leaders, are still on the fence.

In order to understand how this phenomenon against rational decision-making is occurring, let’s look at [Fig. 1]. Suppose there are 100 gold coins scattered somewhat obscurely in a room. People can follow pathway A or B to find them. Using rational decision-making, people will likely follow pathway A, which has an expected yield of 91 gold coins, rather than pathway B, which has an expected yield of only nine gold coins. Finding dysplasia is a lot more important than finding gold. Therefore, use of the same rational decision-making principle and evidence-based medicine (EBM) ought to be even more important. If these principles were followed, CETB ought to be practiced more widely as EBM shows that use of CETB in 100 patients with dysplasia would be expected to identify 91 patients, as compared to random biopsy, which would be expected to identify only nine patients (ten times more patients!). Why do people go against rational decision-making and EBM, and instead do random biopsies? Perhaps there are barriers that prevent them from using CETB.

Fig. 1 Using rational decision-making, when faced with a decision of whether to take option A, which has an expected payoff of 91 gold coins, or option B, which has an expected value of nine gold coins, people will choose option A. Finding dysplasia is much more important than findings gold coins, so following the principles of rational decision-making becomes even more applicable. Out of 100 patients with dysplasia, the expected value for the use of chromoendoscopy and targeted biopsy is 91 patients being found. In comparison, the use of random biopsy has an expected value of only nine patients being found.

Is there a lack of data supporting the use of CETB? The key reason for using CETB is the detection of flat dysplasia, which can be quite challenging in patients with IBD colitis. Jaramillo et al. [1] have shown that flat dysplasia is the most common morphology in patients with ulcerative colitis. Rutter et al. [2] and others have shown that most dysplastic lesions are visible (including flat lesions) when CETB is used. Many comparative studies that support CETB have been published [3].

Is there a lack of guidelines? The SCENIC guideline, which was endorsed by multiple gastroenterology and endoscopy societies from around the world, summarized the currently available data [4]. Other recent guidelines also suggest the use of CETB rather than random biopsy [5] [6], and more studies supporting CETB have been published. Rubin and colleagues [7] recently showed that, when used in patients referred for management of dysplasia, CETB led to the finding of more synchronous dysplastic and even cancerous lesions that had not been visualized by the referring physicians. Other studies, including randomized clinical trials, have shown the higher yield and cost-effectiveness of CETB [3] [8] [9].

Is there a lack of description of the technique or the lack of an atlas? The consensus statements of SCENIC and multiple other resources on the CETB technique are available free online [10] [11] [12] [13] [14].

Available publications suggest that the barriers to the use of CETB have been lowered, yet some still seem to yearn to find other reasons to avoid using CETB. Some appear to believe that dysplastic lesions found on chromoendoscopy are often small and hence are less important. This belief is certainly contrary to the evidence about flat neoplasia that is available in the literature. Flat neoplasia, which often requires image-enhanced endoscopy to detect and to manage it, has the highest risk of containing early cancer [15].

Dr. ten Hove and colleagues, in this month’s issue of Endoscopy [16], studied the implications and outcome of low grade dysplasia (LGD) found during surveillance of IBD patients using chromoendoscopy versus white-light endoscopy (WLE). They used a retrospective observational study of a large cohort of patients from three Dutch tertiary-referral medical centers over 14 years (2000 – 2014). Patients were enrolled into the study following the identification of their first LGD lesion. Endoscopists with experience in IBD surveillance performed chromoendoscopy. Lesions detected with targeted biopsies were considered visible and were stratified based on the endoscopy technique used, standard definition resolution (SDR-WLE; 80 patients), high definition resolution (HDR-WLE; 21 patients) and chromoendoscopy (32 patients). Lesions found on random biopsies were considered invisible (26 patients). It is noteworthy that the majority of visible lesions (74 %) were resected endoscopically.

Only 10 patients went on to develop advanced neoplasia – defined as high grade dysplasia and colorectal carcinoma (CRC) – on follow up, with an incidence rate of 1.3 cases per 100 patient-years. No significant difference in the progression to advanced neoplasia was found between the endoscopy techniques. No advanced neoplasia was detected in the chromoendoscopy group over a median of 24 months. In the HDR-WLE group, one patient developed CRC 13 months after the index lesion in the same colonic segment. The index lesion was incompletely resected in this case. The highest rate of progression to advanced neoplasia was seen in the invisible LGD group (2.29 per 100 patient-years; P = 0.27, when compared to visible lesions), likely owing to that fact that the “invisible” index dysplasia was only biopsied (incompletely removed), so residual dysplastic tissue was present and later progressed to advanced neoplasia.

When the resected lesions were analyzed separately based on the detection technique, no advanced neoplasia was seen after endoscopic resection of a LGD lesion detected with HDR-WLE (17 lesions) or chromoendoscopy (20 lesions). In contrast, from 52 lesions detected with SDR-WLE and reported to have been resected endoscopically, five patients went on to develop advanced neoplasia. The authors couldn’t identify any independent risk factors for progression in this cohort (such as multifocality, distal localization, or diagnosis of primary sclerosing cholangitis), but the number of advanced neoplasias was small. This study seems to suggest that there is only a modest incidence in the rate of progression to advanced neoplasia for LGD lesions in IBD (overall incidence of 1.34 per 100 patient-years). They concluded that there is no difference in the incidence rate of advanced neoplasia on follow-up for LGD lesions detected with either chromoendoscopy or WLE.

Unfortunately, Dr. ten Hove and colleagues were not able to answer their question. Their data were markedly limited. In addition, the follow-up period was much lower for the patients who had chromoendoscopy than for the patients who had random biopsies taken (2 years vs. 6 years). These issues limit the validity of this study. Most importantly, the lesions were removed after their detection. Therefore, the true natural history of these lesions could not have been be assessed. At present, it is commonly accepted that all neoplasia is to be removed. In fact given this standard practice of removing all neoplasia it would not be possible to answer their original question.

Should the quest to find reasons not to use CETB be continued? Such a quest would be unfortunate. Each study is time-consuming, costly, and unlikely to be useful. It is difficult to refute the accumulated higher quality EBM regarding the advantage of CETB as compared with random biopsy. Instead of continuing to perform retrospective studies to look at the value of CETB we need studies that help us to progress. We need to get the appropriate coding for performing CETB. We need to disseminate and to improve CETB [3] [7] [8] [9]. Studies are needed to find lower cost indigo carmine. The list continues.

It is time to move forward from the use of random biopsy, and we hope that future studies are directed towards making progress in endoscopy.

• References

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