Advertisement

Beyond the SCENIC route: updates in chromoendoscopy and dysplasia screening in patients with inflammatory bowel disease

Published:August 04, 2021DOI:https://doi.org/10.1016/j.gie.2021.07.024

      Graphical abstract

      Abbreviations:

      CRC (colorectal cancer colorectal cancer), DCE (dye-spray chromoendoscopy), ESD (endoscopic submucosal dissection), HD (high definition), HGD (high-grade dysplasia), IBD (inflammatory bowel disease), IPAA (ileal pouch-anal anastamosis), NBI (narrow-band imaging), PSC (primary sclerosing cholangitis), SCENIC (Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients: International Consensus Recommendations), VCE (virtual chromoendoscopy), WLE (white-light endoscopy)
      Patients with Crohn’s disease affecting the colon and ulcerative colitis are known to be at increased risk for the development of dysplasia and colorectal cancer (CRC).
      • Freeman H.J.
      Colorectal cancer risk in Crohn's disease.
      ,
      • Eaden J.A.
      • Abrams K.R.
      • Mayberry J.F.
      The risk of colorectal cancer in ulcerative colitis: a meta-analysis.
      Unlike patients with sporadic CRC, patients with longstanding inflammatory bowel disease (IBD) who develop malignancy do so through different pathophysiologic mechanisms and with foreshortened time frames.
      • Foersch S.
      • Neurath M.F.
      Colitis-associated neoplasia: molecular basis and clinical translation.
      ,
      • Ullman T.
      • Croog V.
      • Harpaz N.
      • et al.
      Progression of flat low-grade dysplasia to advanced neoplasia in patients with ulcerative colitis.
      Furthermore, the gross appearance of dysplasia exhibits greater morphologic range in IBD patients, with subtler, flat lesions being commonplace.
      • Marion J.F.
      • Sands B.E.
      The SCENIC consensus statement on surveillance and management of dysplasia in inflammatory bowel disease: praise and words of caution.
      Reassuringly, in the era of biologic therapies, rates of IBD-related CRC and CRC-associated mortality have declined.
      • Soderlund S.
      • Brandt L.
      • Lapidus A.
      • et al.
      Decreasing time-trends of colorectal cancer in a large cohort of patients with inflammatory bowel disease.
      This shift in prevalence has coincided with improved colonoscopic resolution and the adoption of adjunct surveillance techniques such as dye-spray chromoendoscopy (DCE). These therapeutic advances have been embraced by all societal IBD surveillance guidelines, but have also sown confusion among practicing gastroenterologists as to the best surveillance strategy to prevent colon cancer in IBD patients.
      The SCENIC international consensus statement (Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients: International Consensus Recommendations), published both in Gastroenterology and Gastrointestinal Endoscopy in 2015, offered guidance on best practices in surveillance for and management of dysplasia in patients with longstanding IBD.
      • Laine L.
      • Kaltenbach T.
      • Barkun A.
      • et al.
      SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease.
      The SCENIC document reviewed and graded the evidence compiled up to that time and created a roadmap for further refinement in our approach to detecting dysplasia and preventing CRC and colorectal cancer death in patients with colitis.
      • Laine L.
      • Kaltenbach T.
      • Barkun A.
      • McQuaid K.R.
      SCENIC Guideline Development Panel. SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease.
      The SCENIC group endorsed use of high-definition (HD), rather than standard-definition, white-light endoscopy (WLE) and of DCE in the setting of standard-definition colonoscopy. DCE was conditionally recommended in the setting of HD endoscopy,
      • Marion J.F.
      • Waye J.D.
      • Present D.H.
      • et al.
      Chromoendoscopy-targeted biopsies are superior to standard colonoscopic surveillance for detecting dysplasia in inflammatory bowel disease patients: a prospective endoscopic trial.
      The hope of combining higher-definition colonoscopy with DCE would result in even earlier and more-frequent detection and more-precise definition of dysplastic lesions, thus sparing more patients colectomy and CRCs.
      • Cairns S.R.
      • Scholefield J.H.
      • Steele R.J.
      • et al.
      Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002).
      Much has changed in our understanding and approach to dysplasia surveillance in ulcerative and Crohn's colitis since the original publication of the SCENIC guidelines. The statement was released during a unique moment in IBD history; the incidence of CRC in both IBD patients and non-IBD patients was falling considerably, whereas the resolution of our colonoscopes was improving rapidly. Consensus was difficult to achieve given that the literature reflected earlier data from the low-resolution and, in some instances, pre-endoscopic era, with its emphasis on random biopsy sampling, as well as more recent data gathered using higher-resolution endoscopes with an emphasis on visually identifying dysplasia and managing it endoscopically.
      Contemporaneous advances in our understanding and ability to objectively measure chromostereopsis, our own optical limitations in depth perception at higher (red/green) wavelengths of light compared with blue, have paralleled our progress in endoscope resolution and furthered interest in optimizing our endoscopic perception.
      • Amateau S.K.
      • Canto M.I.
      Enhanced mucosal imaging.
      ,
      • Kodashima S.
      • Fujishiro M.
      Novel image-enhanced endoscopy with i-scan technology.
      Now that we are 5 years along on this journey, several important questions remain to be answered: What new knowledge have we obtained? How can we best apply our enhanced resolution and detection capabilities to the new level of CRC risk in this population? Finally, how should gastroenterologists be managing their patients with dysplasia in the current era?

      Redirecting Research Efforts

      The SCENIC consensus statement was successful in directing subsequent research efforts. New, randomized controlled trials comparing WLE with DCE have offered direct comparisons of DCE with HD-WLE for the detection of dysplasia in IBD in the half-decade since SCENIC’s publication, with major clinical implications for patients and practitioners.
      • Hoffman A.
      • Kagel C.
      • Goetz M.
      • et al.
      Recognition and characterization of small colonic neoplasia with high-definition colonoscopy using i-Scan is as precise as chromoendoscopy.
      • Bisschops R.
      • Bessissow T.
      • Joseph J.A.
      • et al.
      Chromoendoscopy versus narrow band imaging in UC: a prospective randomised controlled trial.
      • Efthymiou M.
      • Allen P.B.
      • Taylor A.C.
      • et al.
      Chromoendoscopy versus narrow band imaging for colonic surveillance in inflammatory bowel disease.
      Fewer risk-stratified procedures combined with advances in endoscopic submucosal resection techniques have broadened access to colon-sparing, minimally invasive therapies. A review of various international guidelines published since 2015 demonstrates increased agreement on recommendations for both timing and type of IBD CRC surveillance. Here, we endeavor to review these post-SCENIC developments in dysplasia surveillance and management in patients with longstanding Crohn’s and ulcerative colitis.

      Visual Definition of Dysplasia

      The SCENIC guidelines firmly established the visual appearance of dysplasia as central to endoscopic surveillance of patients with colitis (Table 1). The guidelines also found strong consensus on the wider adoption of HD colonoscopes for IBD surveillance despite the fact that the contribution of resolution in the detection of polyps in general population studies showed little improvement in polyp detection rates using higher-definition colonoscopies.
      • Ray A.
      • Hassan A.
      • Ekram N.
      • et al.
      High definition vs standard definition colonoscopy for polyp and adenoma detection in a screening population. A comparison in a “real-life setting”: 1889.
      • Longcroft-Wheaton G.
      • Brown J.
      • Cowlishaw D.
      • et al.
      High-definition vs. standard-definition colonoscopy in the characterization of small colonic polyps: results from a randomized trial.
      • Har-Noy O.
      • Katz L.
      • Avni T.
      • et al.
      Chromoendoscopy, narrow-band imaging or white light endoscopy for neoplasia detection in inflammatory bowel diseases.
      At the time, the assumption that HD detects more dysplasia than standard-definition colonoscopes in colitis had not been tested by randomized trial. The more recent DCE versus WLE dysplasia surveillance studies have all used HD technology. It is important to note that at the time of this writing (2021), the use of HD colonoscopes remains only at 77% in the United States (Personal communication from Jeffrey E. Daniels, Director of Marketing, Olympus, to James F. Marion, 2021). Thus, nearly 1 in every 4 patients may only have access to standard-definition colonoscopes and, therefore, without DCE, are being surveyed outside of current guidelines.
      Table 1Updates in detection methods, management, and follow-up surveillance in patients with longstanding colitis
      SCENIC recommendation (2015)Updates since SCENIC (2021)
      Detection method(s)
      • HD colonoscopy recommended for dysplasia surveillance
      • DCE recommended (over WLE) when using SD colonoscope
      • DCE suggested (over WLE) when using HD colonoscope
      • NBI not recommended over WLE when using SD colonoscope
      • NBI not suggested over WLE when using HD colonoscope
      • NBI not suggested over DCE when using HD colonoscope
      • HD colonoscopy recommended for dysplasia surveillance
      • DCE with targeted biopsy sampling recommended (over WLE) when using SD colonoscope
      • DCE, WLE, NBI, and VCE with targeted biopsy sampling all acceptable modalities for surveillance when using HD colonoscope; endoscopist should have training or expertise in dysplasia detection using method of choice
      • Random biopsy sampling (in addition to targeted biopsy sampling) should be used in highest risk patients, including those with PSC, previous neoplasia, active inflammation, or a tubular, scarred colon
      Management of dysplasia
      • Not included
      • EMR and ESD may be used to resect dysplastic lesions (both polypoid and flat)
      • Multidisciplinary approach with advanced endoscopist, colorectal surgeon, and IBD expert recommended
      Follow-up of polypoid lesions, after resection
      • Surveillance via colonoscopy recommended over colectomy
      • Surveillance via colonoscopy recommended over colectomy; optimal interval yet to be determined
      • More research is needed to determine optimal screening intervals in patients with prior HGD, large (>1 cm) lesions, multifocality
      • Consider a personalized approach with consideration to location, size, histology, timing (if recurrent dysplasia) of lesion
      Follow-up of flat lesions, after resection
      • Surveillance via colonoscopy suggested over colectomy
      • Surveillance via colonoscopy recommended over colectomy; optimal interval yet to be determined
      • More research is needed to determine optimal screening intervals in patients with prior HGD, multifocality
      • Consider a personalized approach with consideration to location, size, histology (low-grade dysplasia vs HGD), timing (if recurrent) of lesion
      Follow-up of endoscopically invisible lesions
      • Referral to endoscopist with expertise for DCE using HD colonoscope
      • Referral to endoscopist with expertise for DCE using HD colonoscope
      • Referral to colorectal surgeon for colectomy if dysplasia is endoscopically invisible despite use of DCE, NBI, VCE, and HD colonoscope
      DCE, Dye-spray chromoendoscopy; ESD, endoscopic submucosal dissection; HD, high definition; HGD, high-grade dysplasia; IBD, inflammatory bowel disease; NBI, narrow-band imaging; PSC, primary sclerosing cholangitis; SCENIC, Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients: International Consensus Recommendations; WLE, white-light endoscopy; SD, standard definition; VCE, virtual chromoendoscopy.
      The SCENIC guidelines were largely silent on pit pattern classifications because of the inconsistent application of these visual clues in the original chromoendoscopic literature. Gastroenterologists with access to HD technology have since used the enhanced view afforded by higher-resolution colonoscopes and DCE to devise a more refined visual definition of dysplasia. Dysplasia, when encountered, is now more commonly defined using the Paris classification, clarity of borders, presence or absence of depression and ulceration, and, more recently, a revival of the Kudo pit pattern to increase the sensitivity and specificity of visual identification.
      • Tanaka S.
      • Kaltenbach T.
      • Chayama K.
      • et al.
      High-magnification colonoscopy (with videos).
      ,
      • Kaltenbach T.R.
      • Soetikno R.M.
      • DeVivo R.
      • et al.
      Optimizing the quality of endoscopy in inflammatory bowel disease: focus on surveillance and management of colorectal dysplasia using interactive image- and video-based teaching.
      A 2017 study by Bisschops et al
      • Bisschops R.
      • Bessissow T.
      • Dekker E.
      • et al.
      Pit pattern analysis with high-definition chromoendoscopy and narrow-band imaging for optical diagnosis of dysplasia in patients with ulcerative colitis.
      demonstrated that in 27 patients (50 dysplastic lesions) with ulcerative colitis, differentiation of neoplastic versus non-neoplastic polyps was possible by using Kudo pit pattern alone. Images of the dysplastic lesions were reviewed by a group of 10 expert endoscopists, with moderate to high interobserver agreement. Additional visual refinements, such as those proposed by the Frankfurt Advanced Chromoendoscopic IBD Lesion Classification group,
      • Iacucci M.
      • McQuaid K.
      • Gui X.S.
      • et al.
      A multimodal (FACILE) classification for optical diagnosis of inflammatory bowel disease associated neoplasia.
      incorporate visual endoscopic descriptors including lesion morphology, surface and vascular architecture, borders, and the presence or absence of inflammation within a lesion. These more refined visual classifications have been embraced by both experts in IBD and advanced endoscopists, who are increasingly called in to manage dysplasia found in these patients.
      The unique visual challenge of dense pseudopolyposis in surveillance of patients was not directly addressed by the SCENIC guidelines. Refined classification methods using HD and DCE have sought to include the features of these polyps, but the challenge of surveying patients in whom dozens, or even hundreds, of pseudopolyps are found remains a daunting challenge with or without the use of DCE. Further, pseudopolyposis excluded many patients from the earlier DCE studies. Recent studies focusing on pseudopolyposis as an independent risk factor for colorectal neoplasia failed to demonstrate any enhanced risks of CRC among these patients.
      • Mahmoud R.
      • Shah S.C.
      • Ten Hove J.R.
      • et al.
      No association between pseudopolyps and colorectal neoplasia in patients with inflammatory bowel diseases.
      These data are reassuring and should hopefully reduce the likelihood that our patients will be referred for total colectomy merely for the transgression of having pseudopolyposis. The challenge of visually surveying these patients will continue to require patience and meticulousness on the part of the endoscopist.
      The refinement of the visual definition of dysplasia in IBD patients has greatly enhanced our view of the natural history of dysplasia in IBD. The emphasis has always been placed on avoidance of colectomy for these patients. However, the longer-term management of patients in whom low-grade dysplasia has been detected either serially or synchronously has not yet been fully addressed.

      Detection strategies: random biopsies, white light endoscopy, dye spray chromoendoscopy, or virtual chromoendoscopy?

      The SCENIC guidelines recommended the use of either DCE with targeted biopsy sampling or random biopsy sampling with HD-WLE (low quality of evidence).
      • Marion J.F.
      • Sands B.E.
      The SCENIC consensus statement on surveillance and management of dysplasia in inflammatory bowel disease: praise and words of caution.
      However, the low yield of random biopsy sampling has since been confirmed in multiple studies both in ulcerative colitis and Crohn's colitis over the last 17 years. Since the SCENIC guidelines, this has been reconfirmed except in extremely high-risk patients with longstanding colitis and primary sclerosing cholangitis (PSC). Random biopsy sampling of inactive or healed mucosa without other visual cues for dysplasia is unlikely to yield a pathologic diagnosis of dysplasia or impact clinical decision-making. Nonetheless, the question continues to be asked: Is random biopsy sampling useful for the detection of neoplasia in patients with IBD undergoing surveillance colonoscopy with HD scopes and DCE?
      In patients with colitis without additional risk factors (PSC, previous neoplasia, and a tubular colon), 4-quadrant random biopsy sampling has demonstrated only negligible utility.
      • Moussata D.
      • Allez M.
      • Cazals-Hatem D.
      • et al.
      Are random biopsies still useful for the detection of neoplasia in patients with IBD undergoing surveillance colonoscopy with chromoendoscopy?.
      Two large studies, by Moussata et al
      • Moussata D.
      • Allez M.
      • Cazals-Hatem D.
      • et al.
      Are random biopsies still useful for the detection of neoplasia in patients with IBD undergoing surveillance colonoscopy with chromoendoscopy?.
      in 2018 and Kandiah et al
      • Kandiah K.
      • Subramaniam S.
      • Thayalasekaran S.
      • et al.
      Multicentre randomised controlled trial on virtual chromoendoscopy in the detection of neoplasia during colitis surveillance high-definition colonoscopy (the VIRTUOSO trial).
      in 2020, of patients with colitis revealed the limited circumstances in which collection of random biopsy sampling might lead the endoscopist to stumble into a dysplasia diagnosis. Random biopsy sampling did identify a small number of additional dysplasia in IBD patients with comorbid PSC, a previous neoplasia, or a tubular, scarred colon (thereby preventing an en-face endoscopic view). Often these patients had declined colectomy, thus making them eligible for study inclusion. A 2021 study by Hu et al
      • Hu A.B.
      • Burke K.E.
      • Kochar B.
      • et al.
      Yield of random biopsies during colonoscopies in inflammatory bowel disease patients undergoing dysplasia surveillance.
      found that concomitant PSC, presence of active inflammation, and longer duration of disease increased the endoscopic yield of random biopsy sampling for detection of dysplasia. It should be noted that even in these highest-risk patients, the yield of random biopsy sampling remained relatively low. Therefore, the use of random biopsy sampling, even in highest-risk patients, remains an imprecise predictor of CRC risk and outcome. These patients have not been shown to benefit from visual screening using an HD colonoscope, whether or not chromoendoscopy is used.
      As of 2015, there was insufficient evidence to recommend a single method of surveillance for dysplasia, because studies with head-to-head comparisons of DCE versus other techniques were lacking. However, at that time, consensus opinion was that when performing HD colonoscopy, DCE should be used, rather than WLE alone. This recommendation was based on a single observational study of 75 patients that demonstrated superior dysplasia detection using DCE rather than HD-WLE.
      • Picco M.F.
      • Pasha S.
      • Leighton J.A.
      • et al.
      Procedure time and the determination of polypoid abnormalities with experience: implementation of a chromoendoscopy program for surveillance colonoscopy for ulcerative colitis.
      Meta-analyses and systemic reviews published since 2015 have offered conflicting views, with some suggesting equivalency in the use of HD-WLE and DCE for dysplasia detection
      • Iannone A.
      • Ruospo M.
      • Wong G.
      • et al.
      Chromoendoscopy for surveillance in ulcerative colitis and crohn's disease: a systematic review of randomized trials.
      ,
      • Feuerstein J.D.
      • Rakowsky S.
      • Sattler L.
      • et al.
      Meta-analysis of dye-based chromoendoscopy compared with standard- and high-definition white-light endoscopy in patients with inflammatory bowel disease at increased risk of colon cancer.
      and others continuing to find DCE to be a superior method.
      • Wan J.
      • Wang X.
      • Yang Z.P.
      • et al.
      Systematic review with meta-analysis: chromoendoscopy versus white light endoscopy in detection of dysplasia in patients with inflammatory bowel disease.
      The development of virtual modalities, including narrow-band imaging (NBI), i-SCAN (by PENTAX), and flexible spectral imaging color enhancement (FICE, by Fujinon, Tokyo, Japan), have added further complexity to the search for a single best dysplasia surveillance strategy. DCE has been criticized by some practitioners because of concerns about increased cost and the cumbersome nature of the procedure. These apprehensions have fueled a search for a virtual or digital alternative.
      • Kiesslich R.
      • Goetz M.
      • Hoffman A.
      • et al.
      New imaging techniques and opportunities in endoscopy.
      • Chung S.J.
      • Kim D.
      • Song J.H.
      • et al.
      Efficacy of computed virtual chromoendoscopy on colorectal cancer screening: a prospective, randomized, back-to-back trial of Fuji Intelligent Color Enhancement versus conventional colonoscopy to compare adenoma miss rates.
      • van den Broek F.J.
      • Fockens P.
      • van Eeden S.
      • et al.
      Endoscopic tri-modal imaging for surveillance in ulcerative colitis: randomised comparison of high-resolution endoscopy and autofluorescence imaging for neoplasia detection; and evaluation of narrow-band imaging for classification of lesions.
      • Gulati S.
      • Dubois P.
      • Carter B.
      • et al.
      A randomized crossover trial of conventional vs virtual chromoendoscopy for colitis surveillance: dysplasia detection, feasibility, and patient acceptability (CONVINCE).
      However, convincing data demonstrating superiority to the standard dye-spray technique have yet to be published. Although NBI technology is more widely available, the cost of installing new endoscopic system platforms (ie, i-SCAN) in an era of diminishing remuneration has hampered wider adoption of these strategies.
      One meta-analysis of 17 trials (6 with only abstracts available) by Resende et al
      • Resende R.H.
      • Ribeiro I.B.
      • de Moura D.T.H.
      • et al.
      Surveillance in inflammatory bowel disease: Is chromoendoscopy the only way to go? A systematic review and meta-analysis of randomized clinical trials.
      demonstrated the superiority of DCE when compared with standard-definition WLE, but noted the noninferiority of HD-WLE and virtual chromoendoscopy (VCE), including the use of NBI, i-SCAN, and flexible spectral imaging color enhancement, for dysplasia surveillance. Four small studies included in the meta-analysis directly compared NBI and DCE. However, the authors acknowledged a trend toward the superiority of DCE over other chromoendoscopic techniques.
      • Resende R.H.
      • Ribeiro I.B.
      • de Moura D.T.H.
      • et al.
      Surveillance in inflammatory bowel disease: Is chromoendoscopy the only way to go? A systematic review and meta-analysis of randomized clinical trials.
      A randomized controlled trial of 270 patients reported that neither i-SCAN nor HD-WLE was inferior to DCE, with HD-WLE alone sufficient to identify dysplastic or neoplastic lesions in IBD.
      • Iacucci M.
      • Kaplan G.G.
      • Panaccione R.
      • et al.
      A randomized trial comparing high definition colonoscopy alone with high definition dye spraying and electronic virtual chromoendoscopy for detection of colonic neoplastic lesions during IBD surveillance colonoscopy.
      A 2020 randomized controlled trial of 188 patients in the United Kingdom found no difference between the use of HD-WLE and i-SCAN but found both techniques to be superior to random biopsy sampling.
      • Kandiah K.
      • Subramaniam S.
      • Thayalasekaran S.
      • et al.
      Multicentre randomised controlled trial on virtual chromoendoscopy in the detection of neoplasia during colitis surveillance high-definition colonoscopy (the VIRTUOSO trial).
      Another meta-analysis, also from 2020, compared VCE (NBI and i-SCAN) with HD-WLE and DCE. When comparing DCE versus VCE in a per-patient analysis, the authors reported that VCE was not different from DCE for dysplasia (7 randomized controlled trials with 529 patients); however, when a per-dysplasia analysis was performed, VCE was found to be equivalent to DCE, but inferior to HD-WLE alone.
      • El-Dallal M.
      • Chen Y.
      • Lin Q.
      • et al.
      Meta-analysis of virtual-based chromoendoscopy compared with dye-spraying chromoendoscopy standard and high-definition white light endoscopy in patients with inflammatory bowel disease at increased risk of colon cancer.
      Notably, in 2019, the European Society of Gastrointestinal Endoscopy published guidelines that recommended either DCE or VCE with targeted biopsy sampling for detection of dysplasia during surveillance colonoscopy.
      • Bisschops R.
      • East J.E.
      • Hassan C.
      • et al.
      Advanced imaging for detection and differentiation of colorectal neoplasia: European Society of Gastrointestinal Endoscopy (ESGE) guideline—update 2019.
      Thus, it appears that all strategies (DCE, VCE, and HD-WLE) may be successfully used to detect dysplasia in the patient with longstanding colitis if surveillance is undertaken by an endoscopist with sufficient skill in performing the surveillance technique of choice. Random biopsy sampling continues to be useful in highest-risk patients: those with concomitant PSC, prior CRCs, or so-called lead pipe colons, where en-face visualization is anatomically impeded.

      Evolving Endoscopic Management of Dysplasia

      Perhaps the most profound impact of the SCENIC consensus document has been the wider adoption of EMR for the management of dysplastic lesions in patients with colitis. Dye spray allowed for enhanced definition of lesions using the Paris and Kudo pit pattern classifications to define the lesions clearly and then determine resectability. The use of hot or cold snares and the use of submucosal injection with blue dye contrast in such patients is now a standard practice in the gastroenterology community.
      Since the SCENIC guidelines, a wider application of advanced endoscopic techniques, such as endoscopic submucosal dissection (ESD), has been used to manage dysplasia and early neoplasm in patients with colitis (Fig. 1). Patients with scarred-down colons harboring large, flat, and even ulcerated lesions are successfully managed using ESD techniques. Successful resections are accomplished even where submucosal lift cannot be achieved. Defining these lesions and ensuring clear margins are the most common hindrances to successful ESD. The management of nonpolypoid lesions after endoscopic resection has increasingly come to resemble that of polypoid lesions. Complete endoscopic resection of nonpolypoid dysplasia can be safely achieved using HD delineation with DCE and subsequent ESD.
      • Yang D.H.
      • Rey I.
      Endoscopic submucosal dissection for colitis-associated dysplasia.
      New evidence supports the safety and efficacy of ESD to perform en-bloc resection of both flat and polypoid lesions.
      • Suzuki N.
      • Toyonaga T.
      • East J.E.
      Endoscopic submucosal dissection of colitis-related dysplasia.
      • Manta R.
      • Zullo A.
      • Telesca D.A.
      • et al.
      Endoscopic submucosal dissection for visible dysplasia treatment in ulcerative colitis patients: cases series and systematic review of literature.
      • Kinoshita S.
      • Uraoka T.
      • Nishizawa T.
      • et al.
      The role of colorectal endoscopic submucosal dissection in patients with ulcerative colitis.
      Flat lesions removed using ESD have been associated with increased development of metachronous dysplastic lesions in longer-term follow-up studies.
      • Matsumoto K.
      • Oka S.
      • Tanaka S.
      • et al.
      Long-term outcomes after endoscopic submucosal dissection for ulcerative colitis-associated dysplasia.
      This group may be a poor fit for the current guidelines, which emphasize the management of dysplasia found in polypoid lesions. Thus, the risk of continued surveillance of these patients (vs referral to a surgeon) must be carefully weighed.
      • Iacopini F.
      • Saito Y.
      • Yamada M.
      • et al.
      Curative endoscopic submucosal dissection of large nonpolypoid superficial neoplasms in ulcerative colitis (with videos).
      Figure thumbnail gr1
      Figure 1Endoscopic mucosal dissection in a patient with Crohn’s disease and dysplasia; final pathology demonstrated invasive adenocarcinoma with negative margins. A, A 25mm rectal lesion, low-grade dysplasia; B, Examination with NBI; C, Circumferential markings; D, Circumferential mucosa incision; E, Resection site after ESD. (Images provided by Nikhil A. Kumta, MD, MS).
      The behavior of the lesion during endoscopic resection can often be a clue as to the underlying pathology of the lesion. A “nonlift” sign (when submucosal injection fails to raise the lesion) is an ominous finding consistent with underlying invasive carcinoma, and the patient should therefore be referred for surgical resection. The difficulty in managing patients with extensive scarring because of longstanding colitis may make submucosal injection more difficult because of submucosal fibrosis.
      • Gordon I.O.
      • Agrawal N.
      • Willis E.
      • et al.
      Fibrosis in ulcerative colitis is directly linked to severity and chronicity of mucosal inflammation.
      If the surrounding mucosa cannot be raised, ESD can still be safely attempted but is more technically challenging.
      • Yang D.H.
      • Rey I.
      Endoscopic submucosal dissection for colitis-associated dysplasia.
      ,
      • Kinoshita S.
      • Nishizawa T.
      • Yahagi N.
      • et al.
      Endoscopic submucosal dissection in patients with ulcerative colitis.
      The en-bloc resection specimens produced by these advanced techniques require a higher level of endoscopic scrutiny and expertise that considers the margins and successful delineation of the lesion. Communication and collaboration with an expert pathologist are both critical in guiding subsequent management of these patients.
      Ultimately, any dysplasia that cannot be managed endoscopically will require surgical consultation and intervention. There is wide consensus that patients with either high-grade dysplasia (HGD) or carcinoma should not be routinely managed with ESD but rather an array of surgical resection options should be offered to these patients. Surgical referral offers several options short of total colectomy, including segmental resection, subtotal colectomy, or ileal pouch-anal anastamosis (IPAA) with residual cuff, but the guidelines for subsequent follow-up do not include recommendations for this growing group of patients.

      Selecting a Surveillance Strategy

      The burden of surveillance for our patients with colitis remains considerable in terms of both cost and time. The St Mark’s colitis surveillance experience in this regard is instructive: After 2627 colonoscopies in 600 patients followed for a period of 30 years, 30 cases of CRC were noted.
      • Rutter M.D.
      • Saunders B.P.
      • Wilkinson K.H.
      • et al.
      Thirty-year analysis of a colonoscopic surveillance program for neoplasia in ulcerative colitis.
      Among them, 14 CRC cases were diagnosed by surveillance colonoscopy, whereas the others were found incidentally by other means.
      • Rutter M.D.
      • Saunders B.P.
      • Wilkinson K.H.
      • et al.
      Thirty-year analysis of a colonoscopic surveillance program for neoplasia in ulcerative colitis.
      Thus, 88 colonoscopies were required to diagnose a single cancer. When compared with surveillance of sporadic polyps and CRC, 8 colonoscopies are required to diagnose 1 CRC and merely 10 are needed to diagnose a resectable cancer.
      • Kronborg O.
      • Fenger C.
      • Olsen J.
      • et al.
      Randomised study of screening for colorectal cancer with faecal-occult-blood test.
      Confusion about the benefits and concern about the true costs of cancer surveillance are not unique to patients with IBD and colitis; controversy continues to plague approaches to breast and prostate cancer screening and how to best respond to a positive screening test. Disagreement about appropriate surgical response to a screening outcome (eg, with preventative bilateral mastectomy or radical prostatectomy) has created considerable confusion among physicians and patients despite the low risk of cancer death for many of these patients.
      It is clear that careful stratification of patients with longstanding IBD is crucial for justifying costs, minimizing patient anxiety, and saving lives through early dysplasia detection and resection. If initial screening intervention is negative for dysplasia, optimal surveillance intervals remain a matter of some debate. British Society Guidelines suggest that patients should be risk-stratified to determine the appropriate interval for follow-up, with low-risk patients (those with quiescent disease or disease limited to the left-sided colon segment) receiving their next colonoscopy in 5 years.
      • Lamb C.A.
      • Kennedy N.A.
      • Raine T.
      • et al.
      British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults.
      U.S. guidelines continue to recommend more frequent surveillance for all patients, with repeat colonoscopies performed every 1 to 3 years.
      • Lichtenstein G.R.
      • Loftus E.V.
      • Isaacs K.L.
      • et al.
      ACG clinical guideline: management of Crohn's disease in adults.
      ,
      • Rubin D.T.
      • Ananthakrishnan A.N.
      • Siegel C.A.
      • et al.
      ACG clinical guideline: ulcerative colitis in adults.
      How to proceed after multiple colonoscopies without evidence of dysplasia remains unclear, unless patients have specific risk factors that would prompt more frequent evaluation, such as concomitant PSC or personal or family history of colon cancer.
      As more patients with dysplasia are being managed endoscopically and then surveilled annually, the number of polypectomies and endoscopic submucosal resections has increased. We are creating a new cohort of patients who fall in to the “previous dysplasia” risk category, but are including those with both multifocal dysplasia on a single colonoscopy, unifocal dysplasia found on serial colonoscopic examinations, and previous lesions requiring ESD, all of whom in the past would have undergone colectomy at an earlier stage in the same category as someone with a diminutive low-grade dysplasia removed by cold forceps. These patients are not in the same risk category and require endoscopic vigilance not outlined in current guidelines. Endoscopic management of HGD or carcinoma using ESD continues to fall outside current recommendations. These groups of patients, who have retained their colons despite histories of multifocal, serial, or even advanced neoplasia, represent a new and somewhat uncharted risk group. Long-term studies are ongoing and will need to be considered when formulating future guidelines for these patients.
      Patients who have previously undergone EMR for small or low-grade dysplastic lesions appear to have a low risk of developing postresection CRC and appear may continue to be surveilled according to the current guidelines.
      • Mohan B.P.
      • Khan S.R.
      • Chandan S.
      • et al.
      Endoscopic resection of colon dysplasia in patients with inflammatory bowel disease: a systematic review and meta-analysis.
      Application of standard surveillance guidelines to patients who have undergone ESD for larger, polypoid lesions or who were found have HGD on pathology, however, may place these patients at particular risk for developing overt malignancy.
      • Matsumoto K.
      • Oka S.
      • Tanaka S.
      • et al.
      Long-term outcomes after endoscopic submucosal dissection for ulcerative colitis-associated dysplasia.
      Some authors have recommended a surveillance interval of 12 months for patients in whom ESD of polypoid lesions less than 1 cm has been performed, but for lesions removed piecemeal or with size greater than 1 cm, surveillance colonoscopy should be performed within 3 to 6 months. These recommendations also include lesions with HGD if the patient is not a surgical candidate or declines surgery.
      • Hong S.N.
      Endoscopic therapeutic approach for dysplasia in inflammatory bowel disease.
      Gastroenterologists must carefully explain the increased risk of CRC and CRC death and continue to explore surgical options with patients progressing to this higher risk strata.

      Conclusions

      Advances in colonoscopic technology and endoscopic resection techniques in the years since the publication of the SCENIC guidelines have allowed for improved detection and management of dysplasia. These developments have also created new patient populations that require further study to identify optimal methods of and intervals for surveillance. Until more data are available, a personalized approach, with careful consideration of the patient’s inflammatory disease course, comorbidities, and prior history of dysplastic lesions, is needed.
      Many barriers remain in preventing widespread adoption of DCE into clinical practice since the SCENIC statement. DCE is not routinely included in endoscopic training outside of institutions with large IBD populations. Inconsistent access to dye-spray agents because of manufacturing issues and increased demand has also slowed adoption of the technique. For example, the cost of methylene blue has risen 10-fold over the last 5 years, further discouraging its use. Finally, unfamiliarity with DCE and conflicting professional society guideline recommendations have upset efforts to establish the technique as standard-of-care. These barriers are all surmountable with education, access to cheaper alternative dye agents, and coordination of gastroenterology professional society guidelines. Our patients will be best served if we move toward a more precise and less onerous surveillance strategy that stratifies by genuine risk and offers a personalized approach to the detection and management of dysplasia in those with IBD.
      • Kaltenbach T.R.
      • Soetikno R.M.
      • DeVivo R.
      • et al.
      Optimizing the quality of endoscopy in inflammatory bowel disease: focus on surveillance and management of colorectal dysplasia using interactive image- and video-based teaching.

      References

        • Freeman H.J.
        Colorectal cancer risk in Crohn's disease.
        World J Gastroenterol. 2008; 14: 1810-1811
        • Eaden J.A.
        • Abrams K.R.
        • Mayberry J.F.
        The risk of colorectal cancer in ulcerative colitis: a meta-analysis.
        Gut. 2001; 48: 526-535
        • Foersch S.
        • Neurath M.F.
        Colitis-associated neoplasia: molecular basis and clinical translation.
        Cell Mol Life Sci. 2014; 71: 3523-3535
        • Ullman T.
        • Croog V.
        • Harpaz N.
        • et al.
        Progression of flat low-grade dysplasia to advanced neoplasia in patients with ulcerative colitis.
        Gastroenterology. 2003; 125: 1311-1319
        • Marion J.F.
        • Sands B.E.
        The SCENIC consensus statement on surveillance and management of dysplasia in inflammatory bowel disease: praise and words of caution.
        Gastroenterology. 2015; 148: 462-467
        • Soderlund S.
        • Brandt L.
        • Lapidus A.
        • et al.
        Decreasing time-trends of colorectal cancer in a large cohort of patients with inflammatory bowel disease.
        Gastroenterology. 2009; 136 (quiz 818-9): 1561-1567
        • Laine L.
        • Kaltenbach T.
        • Barkun A.
        • et al.
        SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease.
        Gastroenterology. 2015; 148: 639-651
        • Laine L.
        • Kaltenbach T.
        • Barkun A.
        • McQuaid K.R.
        SCENIC Guideline Development Panel. SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease.
        Gastrointest Endosc. 2015; 81: 489-501.e26
        • Marion J.F.
        • Waye J.D.
        • Present D.H.
        • et al.
        Chromoendoscopy-targeted biopsies are superior to standard colonoscopic surveillance for detecting dysplasia in inflammatory bowel disease patients: a prospective endoscopic trial.
        Am J Gastroenterol. 2008; 103: 2342-2349
        • Cairns S.R.
        • Scholefield J.H.
        • Steele R.J.
        • et al.
        Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002).
        Gut. 2010; 59: 666-689
        • Amateau S.K.
        • Canto M.I.
        Enhanced mucosal imaging.
        Curr Opin Gastroenterol. 2010; 26: 445-452
        • Kodashima S.
        • Fujishiro M.
        Novel image-enhanced endoscopy with i-scan technology.
        World J Gastroenterol. 2010; 16: 1043-1049
        • Hoffman A.
        • Kagel C.
        • Goetz M.
        • et al.
        Recognition and characterization of small colonic neoplasia with high-definition colonoscopy using i-Scan is as precise as chromoendoscopy.
        Dig Liver Dis. 2010; 42: 45-50
        • Bisschops R.
        • Bessissow T.
        • Joseph J.A.
        • et al.
        Chromoendoscopy versus narrow band imaging in UC: a prospective randomised controlled trial.
        Gut. 2018; 67: 1087-1094
        • Efthymiou M.
        • Allen P.B.
        • Taylor A.C.
        • et al.
        Chromoendoscopy versus narrow band imaging for colonic surveillance in inflammatory bowel disease.
        Inflamm Bowel Dis. 2013; 19: 2132-2138
        • Ray A.
        • Hassan A.
        • Ekram N.
        • et al.
        High definition vs standard definition colonoscopy for polyp and adenoma detection in a screening population. A comparison in a “real-life setting”: 1889.
        Am J Gastroenterol. 2012; 107: S768-S769
        • Longcroft-Wheaton G.
        • Brown J.
        • Cowlishaw D.
        • et al.
        High-definition vs. standard-definition colonoscopy in the characterization of small colonic polyps: results from a randomized trial.
        Endoscopy. 2012; 44: 905-910
        • Har-Noy O.
        • Katz L.
        • Avni T.
        • et al.
        Chromoendoscopy, narrow-band imaging or white light endoscopy for neoplasia detection in inflammatory bowel diseases.
        Dig Dis Sci. 2017; 62: 2982-2990
        • Tanaka S.
        • Kaltenbach T.
        • Chayama K.
        • et al.
        High-magnification colonoscopy (with videos).
        Gastrointest Endosc. 2006; 64: 604-613
        • Kaltenbach T.R.
        • Soetikno R.M.
        • DeVivo R.
        • et al.
        Optimizing the quality of endoscopy in inflammatory bowel disease: focus on surveillance and management of colorectal dysplasia using interactive image- and video-based teaching.
        Gastrointest Endosc. 2017; 86: 1107-1117
        • Bisschops R.
        • Bessissow T.
        • Dekker E.
        • et al.
        Pit pattern analysis with high-definition chromoendoscopy and narrow-band imaging for optical diagnosis of dysplasia in patients with ulcerative colitis.
        Gastrointest Endosc. 2017; 86: 1100-1106
        • Iacucci M.
        • McQuaid K.
        • Gui X.S.
        • et al.
        A multimodal (FACILE) classification for optical diagnosis of inflammatory bowel disease associated neoplasia.
        Endoscopy. 2019; 51: 133-141
        • Mahmoud R.
        • Shah S.C.
        • Ten Hove J.R.
        • et al.
        No association between pseudopolyps and colorectal neoplasia in patients with inflammatory bowel diseases.
        Gastroenterology. 2019; 156: 1333-1344
        • Moussata D.
        • Allez M.
        • Cazals-Hatem D.
        • et al.
        Are random biopsies still useful for the detection of neoplasia in patients with IBD undergoing surveillance colonoscopy with chromoendoscopy?.
        Gut. 2018; 67: 616-624
        • Kandiah K.
        • Subramaniam S.
        • Thayalasekaran S.
        • et al.
        Multicentre randomised controlled trial on virtual chromoendoscopy in the detection of neoplasia during colitis surveillance high-definition colonoscopy (the VIRTUOSO trial).
        Gut. 2021 Sep; 70: 1684-1690
        • Hu A.B.
        • Burke K.E.
        • Kochar B.
        • et al.
        Yield of random biopsies during colonoscopies in inflammatory bowel disease patients undergoing dysplasia surveillance.
        Inflamm Bowel Dis. 2021; 27: 779-786
        • Picco M.F.
        • Pasha S.
        • Leighton J.A.
        • et al.
        Procedure time and the determination of polypoid abnormalities with experience: implementation of a chromoendoscopy program for surveillance colonoscopy for ulcerative colitis.
        Inflamm Bowel Dis. 2013; 19: 1913-1920
        • Iannone A.
        • Ruospo M.
        • Wong G.
        • et al.
        Chromoendoscopy for surveillance in ulcerative colitis and crohn's disease: a systematic review of randomized trials.
        Clin Gastroenterol Hepatol. 2017; 15: 1684-1697
        • Feuerstein J.D.
        • Rakowsky S.
        • Sattler L.
        • et al.
        Meta-analysis of dye-based chromoendoscopy compared with standard- and high-definition white-light endoscopy in patients with inflammatory bowel disease at increased risk of colon cancer.
        Gastrointest Endosc. 2019; 90: 186-195
        • Wan J.
        • Wang X.
        • Yang Z.P.
        • et al.
        Systematic review with meta-analysis: chromoendoscopy versus white light endoscopy in detection of dysplasia in patients with inflammatory bowel disease.
        J Dig Dis. 2019; 20: 206-214
        • Kiesslich R.
        • Goetz M.
        • Hoffman A.
        • et al.
        New imaging techniques and opportunities in endoscopy.
        Nat Rev Gastroenterol Hepatol. 2011; 8: 547-553
        • Chung S.J.
        • Kim D.
        • Song J.H.
        • et al.
        Efficacy of computed virtual chromoendoscopy on colorectal cancer screening: a prospective, randomized, back-to-back trial of Fuji Intelligent Color Enhancement versus conventional colonoscopy to compare adenoma miss rates.
        Gastrointest Endosc. 2010; 72: 136-142
        • van den Broek F.J.
        • Fockens P.
        • van Eeden S.
        • et al.
        Endoscopic tri-modal imaging for surveillance in ulcerative colitis: randomised comparison of high-resolution endoscopy and autofluorescence imaging for neoplasia detection; and evaluation of narrow-band imaging for classification of lesions.
        Gut. 2008; 57: 1083-1089
        • Gulati S.
        • Dubois P.
        • Carter B.
        • et al.
        A randomized crossover trial of conventional vs virtual chromoendoscopy for colitis surveillance: dysplasia detection, feasibility, and patient acceptability (CONVINCE).
        Inflamm Bowel Dis. 2019; 25: 1096-1106
        • Resende R.H.
        • Ribeiro I.B.
        • de Moura D.T.H.
        • et al.
        Surveillance in inflammatory bowel disease: Is chromoendoscopy the only way to go? A systematic review and meta-analysis of randomized clinical trials.
        Endosc Int Open. 2020; 8: E578-E590
        • Iacucci M.
        • Kaplan G.G.
        • Panaccione R.
        • et al.
        A randomized trial comparing high definition colonoscopy alone with high definition dye spraying and electronic virtual chromoendoscopy for detection of colonic neoplastic lesions during IBD surveillance colonoscopy.
        Am J Gastroenterol. 2018; 113: 225-234
        • El-Dallal M.
        • Chen Y.
        • Lin Q.
        • et al.
        Meta-analysis of virtual-based chromoendoscopy compared with dye-spraying chromoendoscopy standard and high-definition white light endoscopy in patients with inflammatory bowel disease at increased risk of colon cancer.
        Inflamm Bowel Dis. 2020; 26: 1319-1329
        • Bisschops R.
        • East J.E.
        • Hassan C.
        • et al.
        Advanced imaging for detection and differentiation of colorectal neoplasia: European Society of Gastrointestinal Endoscopy (ESGE) guideline—update 2019.
        Endoscopy. 2019; 51: 1155-1179
        • Yang D.H.
        • Rey I.
        Endoscopic submucosal dissection for colitis-associated dysplasia.
        Clin Endosc. 2019; 52: 120-128
        • Suzuki N.
        • Toyonaga T.
        • East J.E.
        Endoscopic submucosal dissection of colitis-related dysplasia.
        Endoscopy. 2017; 49: 1237-1242
        • Manta R.
        • Zullo A.
        • Telesca D.A.
        • et al.
        Endoscopic submucosal dissection for visible dysplasia treatment in ulcerative colitis patients: cases series and systematic review of literature.
        J Crohns Colitis. 2021; 15: 165-168
        • Kinoshita S.
        • Uraoka T.
        • Nishizawa T.
        • et al.
        The role of colorectal endoscopic submucosal dissection in patients with ulcerative colitis.
        Gastrointest Endosc. 2018; 87: 1079-1084
        • Matsumoto K.
        • Oka S.
        • Tanaka S.
        • et al.
        Long-term outcomes after endoscopic submucosal dissection for ulcerative colitis-associated dysplasia.
        Digestion. 2021; 102: 205-215
        • Iacopini F.
        • Saito Y.
        • Yamada M.
        • et al.
        Curative endoscopic submucosal dissection of large nonpolypoid superficial neoplasms in ulcerative colitis (with videos).
        Gastrointest Endosc. 2015; 82: 734-738
        • Gordon I.O.
        • Agrawal N.
        • Willis E.
        • et al.
        Fibrosis in ulcerative colitis is directly linked to severity and chronicity of mucosal inflammation.
        Aliment Pharmacol Ther. 2018; 47: 922-939
        • Kinoshita S.
        • Nishizawa T.
        • Yahagi N.
        • et al.
        Endoscopic submucosal dissection in patients with ulcerative colitis.
        Digestion. 2019; 99: 27-32
        • Rutter M.D.
        • Saunders B.P.
        • Wilkinson K.H.
        • et al.
        Thirty-year analysis of a colonoscopic surveillance program for neoplasia in ulcerative colitis.
        Gastroenterology. 2006; 130: 1030-1038
        • Kronborg O.
        • Fenger C.
        • Olsen J.
        • et al.
        Randomised study of screening for colorectal cancer with faecal-occult-blood test.
        Lancet. 1996; 348: 1467-1471
        • Lamb C.A.
        • Kennedy N.A.
        • Raine T.
        • et al.
        British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults.
        Gut. 2019; 68: s1-s106
        • Lichtenstein G.R.
        • Loftus E.V.
        • Isaacs K.L.
        • et al.
        ACG clinical guideline: management of Crohn's disease in adults.
        Am J Gastroenterol. 2018; 113: 481-517
        • Rubin D.T.
        • Ananthakrishnan A.N.
        • Siegel C.A.
        • et al.
        ACG clinical guideline: ulcerative colitis in adults.
        Am J Gastroenterol. 2019; 114: 384-413
        • Mohan B.P.
        • Khan S.R.
        • Chandan S.
        • et al.
        Endoscopic resection of colon dysplasia in patients with inflammatory bowel disease: a systematic review and meta-analysis.
        Gastrointest Endosc. 2021; 93: 59-67
        • Hong S.N.
        Endoscopic therapeutic approach for dysplasia in inflammatory bowel disease.
        Clin Endosc. 2017; 50: 437-445

      Linked Article