Can we stop routine biopsy of post-endoscopic mucosal resection scars?

Endoscopic mucosal resection (EMR) is internationally accepted as the gold standard, first-line intervention for large nonpedunculated colorectal polyps. The technique has been incrementally refined over the past decade to allow safe and effective removal of large nonpedunculated colorectal polyps in all areas of the colon, including challenging locations such as the anorectal junction or ileocecal valve. Safety issues have been addressed with techniques to reduce the risks of clinically significant post-EMR bleeding and deep mural injury. Outcomes have also been improved with strategies to detect and predict submucosal invasion so that the optimum resection approach can be chosen [1].

Residual or recurrent adenoma (RRA) has remained a persistent challenge; however, the advent of margin thermal ablation (MTA) has largely addressed this. A randomized controlled trial of MTA for lesions ≥ 20 mm using snare tip soft coagulation (STSC) demonstrated a significant reduction in recurrence at the first surveillance colonoscopy 6 months after the initial EMR (21.0 % versus 5.2 %; relative risk [RR] 0.25; 95 %CI 0.13–0.48) [2]. This was then re-demonstrated in a prospective multicenter international study, which showed that where MTA was applied uniformly and completely, RRA was only evident in 1.4 % of cases at the first surveillance colonoscopy [3]. With careful attention to technique, complete snare resection and adjuvant MTA, the vexing problem of recurrence is finally being addressed.

“The study adds to mounting evidence that high confidence optical diagnosis is highly accurate for the exclusion of residual or recurrent adenoma. All endoscopists assessing endoscopic mucosal resection scars should use a combination of high definition white-light endoscopy and narrow-band imaging (or competing optical technology) with a standardized protocol in order to achieve reliable high confidence results.

Despite these major advances in minimizing RRA, it remains important that any recurrence is detected and treated. Current international guidelines [4] [5] recommend routine biopsy of the post-EMR scar to exclude recurrence. These recommendations are based on low levels of evidence, influenced by early EMR studies that showed a high rate of histological recurrence in scars without macroscopic evidence of RRA. More recent evidence has shown that with appropriate training and the use of high definition endoscopes with digital chromoendoscopy, recurrence can be excluded with a high level of certainty. A prospective single-center study of 183 post-EMR scars in the pre-MTA era showed that for lesions ≥ 20 mm in size, scars were easy to detect and the absence of RRA was highly predictable [6]. The addition of narrow-band imaging (NBI) to high definition white-light endoscopy (HD-WLE) improved the sensitivity from 66.7 % to 93.3 %. The negative predictive value (NPV) for combined HD-WLE and NBI was 98.6 % (95 %CI 95.1 %–99.8 %). In a similar multicenter international study involving experts (ESCAPE), four imaging modalities were used to assess recurrence [7]. A total of 255 EMR scars were examined and the prevalence of RRA was 24 %. The NPV for high confidence predictions with HD-WLE was 98.1 % (95 %CI 94.7 %–99.4 %), HD-WLE with near focus was 98.8 % (95 %CI 95.6 %–99.7 %), NBI was 98.8 % (95 %CI 95.6 %–99.7 %), and NBI with near focus was 100 % (95 %CI 97.8 %–100 %) [7]. A further study (NBI-SCAR) developed and validated an NBI classification for RRA using videos rated by endoscopists with varying levels of experience (trainees and experts) [8]. The NPV for high confidence predictions using this system was 100 % (95 %CI 96.1 %–100 %), although it has not been validated in a clinical setting. Scar distortion related to the effect of prior clip placement is known as “clip artifact”; this can also be reliably distinguished from true recurrence [9]. These studies clearly demonstrate that recurrence can be reliably excluded and show that the addition of NBI or near focus improves predictions.

In this issue of Endoscopy, João et al. report on a randomized controlled trial comparing HD-WLE with NBI for the prediction of histological recurrence after EMR of lesions ≥ 20 mm [10]. The study included 203 scars and RRA was confirmed histologically in 29.6 %. Recurrence was not evaluated using a standard protocol, but all participating endoscopists and pathologists were experts from high volume centers. The techniques were equivalent for excluding RRA, with an NPV of 96 % (95 %CI 93 %–99 %) for NBI compared with 93 % (95 %CI 89 %–97 %) for HD-WLE (P = 0.06). The authors concluded that using either HD-WLE or NBI would achieve an NPV of over 90 %, meeting the Preservation and Incorporation of Valuable endoscopic Innovations (PIVI) threshold for allowing routine biopsy to be avoided.

The study adds to mounting evidence that high confidence optical diagnosis is highly accurate for the exclusion of RRA. All endoscopists assessing EMR scars should use a combination of HD-WLE and NBI with a standardized protocol in order to achieve reliable high confidence results. Where a low confidence prediction is made or recurrence is evident, then biopsies should be taken, followed by complete resection or avulsion. Extrapolating evidence from the success of MTA techniques and cold avulsion with STSC (CAST) [11] for nonlifting lesions, we would recommend STSC of the resection defect to minimize the risk of recurrence at the subsequent surveillance colonoscopy ([Fig. 1], [Fig. 2]).

Fig. 1 Proposed Westmead algorithm for evaluating recurrence following endoscopic mucosal resection of lesions ≥ 20 mm. *The aim of treatment of recurrence is to create a flat, white denatured, nonbleeding scar (blood compromises interpretation of the scar). EMR, endoscopic mucosal resection; HD-WLE, high definition white-light endoscopy; NBI, narrow-band imaging; CAST, cold avulsion and snare tip soft coagulation; STSC, snare tip soft coagulation; DMI, deep mural injury.

Fig. 2 Overt recurrence in an endoscopic mucosal resection (EMR) scar. a Extensive 20 mm recurrence 6 months after hemi-circumferential EMR of laterally spreading lesion at the splenic flexure. b Virtual chromoendoscopy evaluation of the recurrence. c Nonlifting. d Endoscopic removal by combination 10 mm hot snare/cold avulsion snare tip soft coagulation with adjuvant soft coagulation of the avulsion bed (CAST). e Thermal ablation of the post-resection margin using snare tip. f Clip closure of the area of CAST with type 2 deep mural injury according to the Sydney classification.

The PIVI NPV threshold is set at 90 %, which is a relatively low bar to clear and permits some diagnostic inaccuracy. If recurrence rates are very high, technologies that only just clear this threshold may still miss several RRAs. The João et al. study and others examining the use of NBI all report NPVs of over 95 %, reducing this risk. In addition, contemporary EMR with MTA should result in recurrence rates of under 5 %, meaning the absolute number of missed cases will be low.

It is possible that a very small number of RRAs are microscopic and undetectable using existing optical techniques. This emphasizes the importance of the second surveillance colonoscopy. Most recurrence is unifocal, diminutive, and easily treatable, so even in the rare setting where microscopic RRA is not detected at the initial surveillance examination, subsequent follow-up should capture these lesions. Surveillance is mandatory even in the absence of RRA owing to the high risk of synchronous and metachronous neoplasia associated with large nonpedunculated colorectal polyps ≥ 20 mm in size [12].

Despite all this attention devoted to detection of RRA, the key focus for all endoscopists performing EMR should be to prevent RRA occurring in the first instance. RRA can be reduced to negligible rates provided that high quality EMR of appropriately selected lesions is performed with attention to complete snare resection and adjuvant MTA. Several studies examining the prediction of RRA occurred prior to the era of MTA when recurrence rates were regularly over 15 %. Contemporary studies from expert centers that are committed to high quality EMR should now be achieving overall RRA rates of under 5 %. Updated international guidelines should recommend that biopsy is now not required for high confidence predictions made by experts using a standardized imaging protocol. Moreover, attention to evidence-based techniques to reduce RRA should be prioritized, so that RRA is relegated to the past, along with other EMR challenges.

Publikationsverlauf

Artikel online veröffentlicht:
01. Juni 2023

• References

• 1 Burgess NG, Hourigan LF, Zanati SA. et al. Risk stratification for covert invasive cancer among patients referred for colonic endoscopic mucosal resection: a large multicenter cohort. Gastroenterology 2017; 153: 732-742
• 2 Klein A, Tate DJ, Jayasekeran V. et al. Thermal ablation of mucosal defect margins reduces adenoma recurrence after colonic endoscopic mucosal resection. Gastroenterology 2019; 156: 604-613
• 3 Sidhu M, Shahidi N, Gupta S. et al. Outcomes of thermal ablation of the mucosal defect margin after endoscopic mucosal resection: a prospective, international, multicenter trial of 1000 large nonpedunculated colorectal polyps. Gastroenterology 2021; 161: 163-170
• 4 Ferlitsch M, Moss A, Hassan C. et al. Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Endoscopy 2017; 49: 270-297
• 5 Kaltenbach T, Anderson JC, Burke CA. et al. Endoscopic removal of colorectal lesions – recommendations by the US Multi-Society Task Force on Colorectal Cancer. Gastrointest Endosc 2020; 91: 486-519
• 6 Desomer L, Tutticci N, Tate DJ. et al. A standardized imaging protocol is accurate in detecting recurrence after EMR. Gastrointest Endosc 2017; 85: 518-526
• 7 Kandel P, Brand EC, Pelt J. et al. Endoscopic scar assessment after colorectal endoscopic mucosal resection scars: when is biopsy necessary (EMR Scar Assessment Project for Endoscope (ESCAPE) trial). Gut 2019; 68: 1633-1641
• 8 Zorron Cheng Tao Pu L, Chiam KH, Yamamura T. et al. Narrow-band imaging for scar (NBI-SCAR) classification: from conception to multicenter validation. Gastrointest Endosc 2020; 91: 1146-1154
• 9 Pellisé M, Desomer L, Burgess NG. et al. The influence of clips on scars after EMR: clip artifact. Gastrointest Endosc 2016; 83: 608-616
• 10 João M, Areia M, Pinto Pais T. et al. Can white-light endoscopy or narrow-band imaging avoid biopsy of colorectal endoscopic mucosal resection scars? A multicenter randomized single-blind crossover trial. Endoscopy 2023; 55: 601-607
• 11 Tate DJ, Bahin FF, Desomer L. et al. Cold-forceps avulsion with adjuvant snare-tip soft coagulation (CAST) is an effective and safe strategy for the management of non-lifting large laterally spreading colonic lesions. Endoscopy 2018; 50: 52-62
• 12 O’Sullivan T, Tate D, Sidhu M. et al. The surface morphology of large nonpedunculated colonic polyps predicts synchronous large lesions. Clin Gastroenterol Hepatol 2023; DOI: 10.1016/j.cgh.2023.01.034.