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Original article Clinical endoscopy| Volume 97, ISSUE 4, P767-779.e6, April 2023

Endoscopic management of patients with high-risk colorectal colitis–associated neoplasia: a Delphi study

Open AccessPublished:December 09, 2022DOI:https://doi.org/10.1016/j.gie.2022.12.005

      Background and Aims

      Current guidelines recommend endoscopic resection of visible and endoscopically resectable colorectal colitis–associated neoplasia (CAN) in patients with inflammatory bowel disease (IBD). However, patients with high-risk CAN (HR-CAN) are often not amenable to conventional resection techniques, and a consensus approach for the endoscopic management of these lesions is presently lacking. This Delphi study aims to reach consensus among experts on the endoscopic management of these lesions.

      Methods

      A 3-round modified Delphi process was conducted to reach consensus among worldwide IBD and/or endoscopy experts (n = 18) from 3 continents. Consensus was considered if ≥75% agreed or disagreed. Quality of evidence was assessed by the criteria of the Cochrane Collaboration group.

      Results

      Consensus was reached on all statements (n = 14). Experts agreed on a definition for CAN and HR-CAN. Consensus was reached on the examination of the colon with enhanced endoscopic imaging before resection, the endoscopic resectability of an HR-CAN lesion, and endoscopic assessment and standard report of CAN lesions. In addition, experts agreed on type of resections of HR-CAN (< 20 mm, >20 mm, with or without good lifting), endoscopic success (technical success and outcomes), histologic assessment, and follow-up in HR-CAN.

      Conclusions

      This is the first step in developing international consensus–based recommendations for endoscopic management of CAN and HR-CAN. Although the quality of available evidence was considered low, consensus was reached on several aspects of the management of CAN and HR-CAN. The present work and proposed standardization might benefit future studies.

      Abbreviations:

      aCRN (advanced colorectal neoplasia), CAN (colitis-associated neoplasia), CD (Crohn’s disease), CRC (colorectal cancer), DSI (deep submucosal invasion), ESD (endoscopic submucosal dissection), HGD (high-grade dysplasia), HR-CAN (high-risk colitis-associated neoplasia), IBD (inflammatory bowel disease), LGD (low-grade dysplasia), LNPCP (large nonpedunculated colorectal polyp), UC (ulcerative colitis)
      American and European guidelines recommend endoscopic resection for visible and endoscopically resectable colorectal dysplasia in patients with inflammatory bowel disease (IBD).
      • Laine L.
      • Kaltenbach T.
      • Barkun A.
      • et al.
      SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease.
      • 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).
      • Annese V.
      • Daperno M.
      • Rutter M.D.
      • et al.
      European evidence based consensus for endoscopy in inflammatory bowel disease.
      Two meta-analyses provide support for this strategy but emphasize the need for close endoscopic follow-up because of the risk of recurrence (2-5.3/1000 person-years of follow-up) and metachronous dysplasia.
      • Wanders L.K.
      • Dekker E.
      • Pullens B.
      • et al.
      Cancer risk after resection of polypoid dysplasia in patients with longstanding ulcerative colitis: a meta-analysis.
      ,
      • 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.
      Endoscopic resection of colitis-associated neoplasia (CAN), especially of larger lesions, can be challenging because of ongoing inflammation, mucosal scarring, and submucosal fibrosis.
      • Shergill A.K.
      • Lightdale J.R.
      • Bruining D.H.
      • et al.
      American Society for Gastrointestinal Endoscopy Standards of Practice Committee
      The role of endoscopy in inflammatory bowel disease.
      Both EMR and endoscopic submucosal dissection (ESD) are used for the resection of CAN. These techniques are reportedly effective, safe in cases of sporadic adenomas, and associated with low proctocolectomy rates for neoplasia.
      • Repici A.
      • Pellicano R.
      • Strangio G.
      • et al.
      Endoscopic mucosal resection for early colorectal neoplasia: pathologic basis, procedures, and outcomes.
      ,
      • Repici A.
      • Hassan C.
      • De Paula Pessoa D.
      • et al.
      Efficacy and safety of endoscopic submucosal dissection for colorectal neoplasia: a systematic review.
      However, the optimal use of these techniques and follow-up strategy in CAN are presently unclear.
      Several studies have suggested that EMR and ESD are safe and feasible in the setting of CAN.
      • 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.
      • Nishio M.
      • Hirasawa K.
      • Ozeki Y.
      • et al.
      An endoscopic treatment strategy for superficial tumors in patients with ulcerative colitis.
      • Yadav S.
      • Loftus Jr., E.V.
      • Harmsen W.S.
      • et al.
      Outcome of endoscopic resection of colonic polyps larger than 10 mm in patients with inflammatory bowel disease.
      • Matsumoto K.
      • Oka S.
      • Tanaka S.
      • et al.
      Long-term outcomes after endoscopic submucosal dissection for ulcerative colitis-associated dysplasia.
      • Alkandari A.
      • Thayalasekaran S.
      • Bhandari M.
      • et al.
      Endoscopic resections in inflammatory bowel disease: a multicentre european outcomes study.
      • Yang D.H.
      • Kim J.
      • Song E.M.
      • et al.
      Outcomes of ulcerative colitis-associated dysplasia patients referred for potential endoscopic submucosal dissection.
      • Kochhar G.
      • Steele S.
      • Sanaka M.
      • et al.
      Endoscopic submucosal dissection for flat colonic polyps in patients with inflammatory bowel disease: a single-center experience.
      • Kinoshita S.
      • Nishizawa T.
      • Yahagi N.
      • et al.
      Endoscopic submucosal dissection in patients with ulcerative colitis.
      • Suzuki N.
      • Toyonaga T.
      • East J.E.
      Endoscopic submucosal dissection of colitis-related dysplasia.
      • Gulati S.
      • Emmanuel A.
      • Burt M.
      • et al.
      Outcomes of endoscopic resections of large laterally spreading colorectal lesions in inflammatory bowel disease: a single United Kingdom center experience.
      • Iacopini F.
      • Saito Y.
      • Yamada M.
      • et al.
      Curative endoscopic submucosal dissection of large nonpolypoid superficial neoplasms in ulcerative colitis (with videos).
      • Ngamruengphong S.
      • Aihara H.
      • Friedland S.
      • et al.
      Endoscopic submucosal dissection for colorectal dysplasia in inflammatory bowel disease: a US multicenter study.
      • Lightner A.L.
      • Vaidya P.
      • Allende D.
      • et al.
      Endoscopic submucosal dissection is safe and feasible, allowing for ongoing surveillance and organ preservation in patients with inflammatory bowel disease.
      • Kasuga K.
      • Yamada M.
      • Shida D.
      • et al.
      Treatment outcomes of endoscopic submucosal dissection and surgery for colorectal neoplasms in patients with ulcerative colitis.
      • Smith L.A.
      • Baraza W.
      • Tiffin N.
      • et al.
      Endoscopic resection of adenoma-like mass in chronic ulcerative colitis using a combined endoscopic mucosal resection and cap assisted submucosal dissection technique.
      These relatively small, retrospective studies comprised 552 patients (589 lesions).
      • 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.
      • Nishio M.
      • Hirasawa K.
      • Ozeki Y.
      • et al.
      An endoscopic treatment strategy for superficial tumors in patients with ulcerative colitis.
      • Yadav S.
      • Loftus Jr., E.V.
      • Harmsen W.S.
      • et al.
      Outcome of endoscopic resection of colonic polyps larger than 10 mm in patients with inflammatory bowel disease.
      • Matsumoto K.
      • Oka S.
      • Tanaka S.
      • et al.
      Long-term outcomes after endoscopic submucosal dissection for ulcerative colitis-associated dysplasia.
      • Alkandari A.
      • Thayalasekaran S.
      • Bhandari M.
      • et al.
      Endoscopic resections in inflammatory bowel disease: a multicentre european outcomes study.
      • Yang D.H.
      • Kim J.
      • Song E.M.
      • et al.
      Outcomes of ulcerative colitis-associated dysplasia patients referred for potential endoscopic submucosal dissection.
      • Kochhar G.
      • Steele S.
      • Sanaka M.
      • et al.
      Endoscopic submucosal dissection for flat colonic polyps in patients with inflammatory bowel disease: a single-center experience.
      • Kinoshita S.
      • Nishizawa T.
      • Yahagi N.
      • et al.
      Endoscopic submucosal dissection in patients with ulcerative colitis.
      • Suzuki N.
      • Toyonaga T.
      • East J.E.
      Endoscopic submucosal dissection of colitis-related dysplasia.
      • Gulati S.
      • Emmanuel A.
      • Burt M.
      • et al.
      Outcomes of endoscopic resections of large laterally spreading colorectal lesions in inflammatory bowel disease: a single United Kingdom center experience.
      • Iacopini F.
      • Saito Y.
      • Yamada M.
      • et al.
      Curative endoscopic submucosal dissection of large nonpolypoid superficial neoplasms in ulcerative colitis (with videos).
      • Ngamruengphong S.
      • Aihara H.
      • Friedland S.
      • et al.
      Endoscopic submucosal dissection for colorectal dysplasia in inflammatory bowel disease: a US multicenter study.
      • Lightner A.L.
      • Vaidya P.
      • Allende D.
      • et al.
      Endoscopic submucosal dissection is safe and feasible, allowing for ongoing surveillance and organ preservation in patients with inflammatory bowel disease.
      • Kasuga K.
      • Yamada M.
      • Shida D.
      • et al.
      Treatment outcomes of endoscopic submucosal dissection and surgery for colorectal neoplasms in patients with ulcerative colitis.
      • Smith L.A.
      • Baraza W.
      • Tiffin N.
      • et al.
      Endoscopic resection of adenoma-like mass in chronic ulcerative colitis using a combined endoscopic mucosal resection and cap assisted submucosal dissection technique.
      Most patients were diagnosed with ulcerative colitis (UC).
      • 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.
      • Nishio M.
      • Hirasawa K.
      • Ozeki Y.
      • et al.
      An endoscopic treatment strategy for superficial tumors in patients with ulcerative colitis.
      • Yadav S.
      • Loftus Jr., E.V.
      • Harmsen W.S.
      • et al.
      Outcome of endoscopic resection of colonic polyps larger than 10 mm in patients with inflammatory bowel disease.
      • Matsumoto K.
      • Oka S.
      • Tanaka S.
      • et al.
      Long-term outcomes after endoscopic submucosal dissection for ulcerative colitis-associated dysplasia.
      • Alkandari A.
      • Thayalasekaran S.
      • Bhandari M.
      • et al.
      Endoscopic resections in inflammatory bowel disease: a multicentre european outcomes study.
      • Yang D.H.
      • Kim J.
      • Song E.M.
      • et al.
      Outcomes of ulcerative colitis-associated dysplasia patients referred for potential endoscopic submucosal dissection.
      • Kochhar G.
      • Steele S.
      • Sanaka M.
      • et al.
      Endoscopic submucosal dissection for flat colonic polyps in patients with inflammatory bowel disease: a single-center experience.
      • Kinoshita S.
      • Nishizawa T.
      • Yahagi N.
      • et al.
      Endoscopic submucosal dissection in patients with ulcerative colitis.
      • Suzuki N.
      • Toyonaga T.
      • East J.E.
      Endoscopic submucosal dissection of colitis-related dysplasia.
      • Gulati S.
      • Emmanuel A.
      • Burt M.
      • et al.
      Outcomes of endoscopic resections of large laterally spreading colorectal lesions in inflammatory bowel disease: a single United Kingdom center experience.
      • Iacopini F.
      • Saito Y.
      • Yamada M.
      • et al.
      Curative endoscopic submucosal dissection of large nonpolypoid superficial neoplasms in ulcerative colitis (with videos).
      • Ngamruengphong S.
      • Aihara H.
      • Friedland S.
      • et al.
      Endoscopic submucosal dissection for colorectal dysplasia in inflammatory bowel disease: a US multicenter study.
      • Lightner A.L.
      • Vaidya P.
      • Allende D.
      • et al.
      Endoscopic submucosal dissection is safe and feasible, allowing for ongoing surveillance and organ preservation in patients with inflammatory bowel disease.
      • Kasuga K.
      • Yamada M.
      • Shida D.
      • et al.
      Treatment outcomes of endoscopic submucosal dissection and surgery for colorectal neoplasms in patients with ulcerative colitis.
      • Smith L.A.
      • Baraza W.
      • Tiffin N.
      • et al.
      Endoscopic resection of adenoma-like mass in chronic ulcerative colitis using a combined endoscopic mucosal resection and cap assisted submucosal dissection technique.
      Ten studies exclusively reported on ESD procedures,
      • 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.
      ,
      • Matsumoto K.
      • Oka S.
      • Tanaka S.
      • et al.
      Long-term outcomes after endoscopic submucosal dissection for ulcerative colitis-associated dysplasia.
      ,
      • Yang D.H.
      • Kim J.
      • Song E.M.
      • et al.
      Outcomes of ulcerative colitis-associated dysplasia patients referred for potential endoscopic submucosal dissection.
      • Kochhar G.
      • Steele S.
      • Sanaka M.
      • et al.
      Endoscopic submucosal dissection for flat colonic polyps in patients with inflammatory bowel disease: a single-center experience.
      • Kinoshita S.
      • Nishizawa T.
      • Yahagi N.
      • et al.
      Endoscopic submucosal dissection in patients with ulcerative colitis.
      • Suzuki N.
      • Toyonaga T.
      • East J.E.
      Endoscopic submucosal dissection of colitis-related dysplasia.
      ,
      • Iacopini F.
      • Saito Y.
      • Yamada M.
      • et al.
      Curative endoscopic submucosal dissection of large nonpolypoid superficial neoplasms in ulcerative colitis (with videos).
      • Ngamruengphong S.
      • Aihara H.
      • Friedland S.
      • et al.
      Endoscopic submucosal dissection for colorectal dysplasia in inflammatory bowel disease: a US multicenter study.
      • Lightner A.L.
      • Vaidya P.
      • Allende D.
      • et al.
      Endoscopic submucosal dissection is safe and feasible, allowing for ongoing surveillance and organ preservation in patients with inflammatory bowel disease.
      • Kasuga K.
      • Yamada M.
      • Shida D.
      • et al.
      Treatment outcomes of endoscopic submucosal dissection and surgery for colorectal neoplasms in patients with ulcerative colitis.
      whereas 5 studies described both ESD and EMR procedures
      • Nishio M.
      • Hirasawa K.
      • Ozeki Y.
      • et al.
      An endoscopic treatment strategy for superficial tumors in patients with ulcerative colitis.
      ,
      • Yadav S.
      • Loftus Jr., E.V.
      • Harmsen W.S.
      • et al.
      Outcome of endoscopic resection of colonic polyps larger than 10 mm in patients with inflammatory bowel disease.
      ,
      • Alkandari A.
      • Thayalasekaran S.
      • Bhandari M.
      • et al.
      Endoscopic resections in inflammatory bowel disease: a multicentre european outcomes study.
      ,
      • Gulati S.
      • Emmanuel A.
      • Burt M.
      • et al.
      Outcomes of endoscopic resections of large laterally spreading colorectal lesions in inflammatory bowel disease: a single United Kingdom center experience.
      ,
      • Smith L.A.
      • Baraza W.
      • Tiffin N.
      • et al.
      Endoscopic resection of adenoma-like mass in chronic ulcerative colitis using a combined endoscopic mucosal resection and cap assisted submucosal dissection technique.
      or ESD-assisted EMR.
      • Nishio M.
      • Hirasawa K.
      • Ozeki Y.
      • et al.
      An endoscopic treatment strategy for superficial tumors in patients with ulcerative colitis.
      ,
      • Yadav S.
      • Loftus Jr., E.V.
      • Harmsen W.S.
      • et al.
      Outcome of endoscopic resection of colonic polyps larger than 10 mm in patients with inflammatory bowel disease.
      ,
      • Alkandari A.
      • Thayalasekaran S.
      • Bhandari M.
      • et al.
      Endoscopic resections in inflammatory bowel disease: a multicentre european outcomes study.
      ,
      • Gulati S.
      • Emmanuel A.
      • Burt M.
      • et al.
      Outcomes of endoscopic resections of large laterally spreading colorectal lesions in inflammatory bowel disease: a single United Kingdom center experience.
      ,
      • Smith L.A.
      • Baraza W.
      • Tiffin N.
      • et al.
      Endoscopic resection of adenoma-like mass in chronic ulcerative colitis using a combined endoscopic mucosal resection and cap assisted submucosal dissection technique.
      A recent analysis of pooled data suggested en-bloc and R0 resection rates of 86% and 70%, respectively, for nonpolypoid lesions with a potential superiority for ESD.
      • Chen W.
      • Zhang Y.L.
      • Zhao Y.
      • et al.
      Endoscopic resection for non-polypoid dysplasia in inflammatory bowel disease: a systematic review and meta-analysis.
      After endoscopic resection, patients with nonpolypoid dysplasia seemed to have higher colorectal cancer (CRC) and metachronous neoplasia incidence rates, warranting closer endoscopic follow-up.
      • Chen W.
      • Zhang Y.L.
      • Zhao Y.
      • et al.
      Endoscopic resection for non-polypoid dysplasia in inflammatory bowel disease: a systematic review and meta-analysis.
      Of note, high-quality data from large prospective studies are lacking.
      Current recommendations in guidelines are largely based on expert opinion, and important questions concerning the endoscopic management of CAN remain unanswered.
      • Laine L.
      • Kaltenbach T.
      • Barkun A.
      • et al.
      SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease.
      • 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).
      • Annese V.
      • Daperno M.
      • Rutter M.D.
      • et al.
      European evidence based consensus for endoscopy in inflammatory bowel disease.
      This study aimed to generate a consensus on standardized endoscopic management of CAN based on current evidence and expert opinion.

      Methods

      Development of consensus statements and literature review

      A modified Delphi approach was used to reach consensus on statements concerning the endoscopic management of CAN.
      • Boulkedid R.
      • Abdoul H.
      • Loustau M.
      • et al.
      Using and reporting the Delphi method for selecting healthcare quality indicators: a systematic review.
      Members of the expert panel were invited by the senior authors (L.M.G.M. and B.O.) and had extensive IBD expertise (n = 9) and/or were EMR/ESD experts (n = 12). Before the first meeting in March 2021, a literature review was conducted by the study coordinator (M.T.J.B.) and 1 senior author (L.M.G.M.) in MEDLINE and EMBASE for relevant literature.
      Population, intervention, comparison, and outcomes (PICO) frameworks were developed for several statements. Search strings of the population, intervention, comparison, and outcomes are presented in Appendix 1 (available online at www.giejournal.org). This literature search and the results were shared with all invited experts. In the first phase, the literature was shared among all experts, and statements were drafted (Fig. 1). Three online meetings were organized to discuss and reach consensus on the proposed statements. After the meetings, participants were asked to vote electronically and provide feedback on the statements. For adjusted or new statements, the systematic review was updated. Feedback was incorporated into the second and third rounds of voting.
      Figure thumbnail gr1
      Figure 1Flowchart of consensus development.

      Electronic voting rounds

      Experts were asked to vote on statements on a 5-point Likert scale in 3 rounds of electronic voting ranging from “strongly disagree” to “strongly agree.” In the second and third rounds of voting, experts were given the overall results of each question of the prior voting round and their own voting. Only the study coordinator (M.T.J.B.) had access to the voting results. The senior authors were blinded to the feedback of the individual participants.

      Acceptance of statements and quality of evidence

      Consensus was defined as ≥75% agreement (“agree” and “strongly agree” or “disagree” and “strongly disagree”) on an individual statement. Participants were asked individually to assess the quality of evidence of the provided literature. Quality of evidence was assessed with the criteria of the Cochrane Collaboration Review Group.
      • van Tulder M.
      • Furlan A.
      • Bombardier C.
      • et al.
      Updated method guidelines for systematic reviews in the Cochrane Collaboration Back Review Group.
      The final recommendation for the quality of evidence was based on the majority of votes.

      Results

      Participants

      Eighteen experts from 10 countries and 3 continents were invited to participate. Response rates in the first, second, and third rounds of voting were 94.4% (n = 17), 66.7% (n = 12), and 94.4% (n = 17), respectively. Quality of evidence was assessed by 83.3% (n = 15) of the respondents.

      Consensus statements

      Results of the statements that reached consensus in the third and final round of voting are shown in Table 1. Consensus was reached on all statements (n = 14). Based on the statements, a flowchart was developed (Fig. 2). Details on the third and final round of voting are presented in Appendix 2 (available online at www.giejournal.org).
      Table 1Overview of consensus statements
      StatementAgreement gradeQuality of evidence
      1. We suggest adopting the term colitis-associated neoplasia (CAN) for all neoplastic lesions detected in a section of previously or presently inflamed colon.100%No evidence
      2. Extent of previous or present inflammation should have been or should be confirmed by endoscopy and/or histology.100%No evidence
      3. Nonpolypoid lesions and large (>20 mm) nonpedunculated colon polyps should be considered high-risk CAN.88.2%Limited evidence
      4. Careful examination of the colon (preferably using enhanced endoscopic imaging) should precede local excision of HR-CAN.100%Moderate evidence
      • 5.
        An HR-CAN lesion is considered endoscopically resectable if
      • 1.
        The lesion has distinct margins
      • 2.
        The lesion can (preferably) be removed en bloc with clear deep and lateral resection margins
      and there is no evidence of 3. Synchronous invisible dysplasia
      • 4.
        Moderate-to-severe inflammation of mucosa surrounding the area with HR-CAN interfering with delineation of the lesion
      • 5.
        Signs of deep submucosal invasion.
      76.5%Limited evidence
      6. Surgical resection is indicated when HR-CAN is nonresectable.100%Moderate evidence
      • 7.
        All suspected HR-CANs should be assessed according to a standardized approach and recorded in the endoscopy report. The description should include at least the following features:
      • 1.
        Size, delineation, and location
      • 2.
        Description of gross morphology a. Granular/nongranular
        • b.
          Paris classification
      • 3.
        Assessment of the pit and vascular pattern using enhanced endoscopic imaging
      • 4.
        Assessment of endoscopic activity of the colitis in the segment, harboring the dysplastic lesion (eg, using the Mayo subset index, UC endoscopic index of severity, or simple endoscopic score for CD).
      94.1%Limited evidence
      8. HR-CAN should preferably be removed en bloc to lower the risk of recurrence and optimize the histologic assessment.94.1%Limited evidence
      9. HR-CAN <20 mm with good lifting (Kato I and II) can be removed using en-bloc (including underwater) EMR.94.1%Moderate evidence
      10. HR-CAN <20 mm without good lifting (Kato III and IV) or HR-CAN >20 mm without signs of deep submucosal invasion should be removed with techniques that preferably allow en-bloc resection.82.4%No evidence
      11. Endoscopic local excision of HR-CAN should be performed by endoscopists with sufficient skills in both EMR and ESD techniques.88.2%No evidence
      12. Endoscopic resection should be captured by recording:
      • 1.
        Technical success a. En-bloc resection
        • b.
          R0 resection
        • c.
          Adverse events (intra- or postprocedural bleeding, perforation, postcoagulation syndrome, need of emergency surgery, other)
      • 2.
        Outcomes a. Local recurrence at 6 months and 3 years
        • b.
          Surgery for recurrence after 1, 3, and 5 years.
      82.4%No evidence
      13. The histologic report should at least include the following items:
      • 1.
        Size (mm)
      • 2.
        Grade of dysplasia according the World Health Organization classification
      • 3.
        Lateral resection margin (in mm, free if >.1 mm)
      • 4.
        Deep resection margin (in mm, free if >.1 mm)
      In case of submucosal invasion:
      • 1.
        Maximum depth of submucosal (Sm) invasion in μm (taken from the deepest margin of the muscularis mucosae)
      • 2.
        Lymphatic and/or venous invasion confirmed with D2-40 immunohistochemistry
      • 3.
        Tumor budding (Bd1-3) according to the International Tumor Budding Consensus Conference
      • 4.
        Grade of differentiation according to World Health Organization classification.
      94.1%No evidence
      14. After complete endoscopic resection of HR-CAN, assessment of local recurrence should be performed within 3 to 6 months and annually thereafter if no residual disease is found.88.2%Limited evidence
      ESD, Endoscopic submucosal dissection; HR-CAN, high-risk colitis-associated neoplasia; CD, Crohn's disease; UC, ulcerative colitis.
      Figure thumbnail gr2
      Figure 2Flowchart after detection of HR-CAN. Note: Details can be found in the statements in the text. HR-CAN, High-risk colitis-associated neoplasia.

      Nomenclature of high-risk CAN

      Statement 1: We suggest adoption of the term colitis-associated neoplasia (CAN) for all neoplastic lesions detected in a section of previously or presently inflamed colon.

      (Agreement, 100%; quality of evidence, no evidence)
      Patients with IBD have an increased risk of developing CRC.
      • Lutgens M.W.
      • van Oijen M.G.
      • van der Heijden G.J.
      • et al.
      Declining risk of colorectal cancer in inflammatory bowel disease: an updated meta-analysis of population-based cohort studies.
      Although most mechanisms underlying tumorigenesis in CAN are similar to those involved in sporadic CRC, timing and frequency of driver events differ.
      • Shah S.C.
      • Itzkowitz S.H.
      Colorectal cancer in inflammatory bowel disease: mechanisms and management.
      Also, endoscopic features and clinical behavior of CAN diverge from sporadic adenomas or CRC. To date, no clear definition of CAN is provided in the current literature and guidelines.
      • Laine L.
      • Kaltenbach T.
      • Barkun A.
      • et al.
      SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease.
      • 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).
      • Annese V.
      • Daperno M.
      • Rutter M.D.
      • et al.
      European evidence based consensus for endoscopy in inflammatory bowel disease.
      CAN develops in areas with chronic inflammation and may present as endoscopically visible or invisible lesions (the latter referring to lesions, identified by random biopsy sampling). Visible lesions can be classified morphologically into polypoid and nonpolypoid types.
      • Magro F.
      • Langner C.
      • Driessen A.
      • et al.
      European consensus on the histopathology of inflammatory bowel disease.
      Both colitis-associated adenomas and colitis-associated serrated lesions have been found to carry an increased risk of metachronous and synchronous multifocal visible dysplasia.
      • de Jong M.E.
      • Nagtegaal I.D.
      • Vos S.
      • et al.
      Increased colorectal neoplasia risk in patients with inflammatory bowel disease and serrated polyps with dysplasia.
      Neoplastic lesions that are encountered in (previously) noninflamed areas of the colon are considered to be sporadic adenomas and unrelated to colitis.
      • Bressenot A.
      • Cahn V.
      • Danese S.
      • et al.
      Microscopic features of colorectal neoplasia in inflammatory bowel diseases.
      Results from previous studies do not indicate an increased risk of CRC development after endoscopic removal of these lesions,
      • Connell W.R.
      • Lennard-Jones J.E.
      • Williams C.B.
      • et al.
      Factors affecting the outcome of endoscopic surveillance for cancer in ulcerative colitis.
      • Medlicott S.A.
      • Jewell L.D.
      • Price L.
      • et al.
      Conservative management of small adenomata in ulcerative colitis.
      • Engelsgjerd M.
      • Farraye F.A.
      • Odze R.D.
      Polypectomy may be adequate treatment for adenoma-like dysplastic lesions in chronic ulcerative colitis.
      • Odze R.D.
      • Farraye F.A.
      • Hecht J.L.
      • et al.
      Long-term follow-up after polypectomy treatment for adenoma-like dysplastic lesions in ulcerative colitis.
      • Rubin P.H.
      • Friedman S.
      • Harpaz N.
      • et al.
      Colonoscopic polypectomy in chronic colitis: conservative management after endoscopic resection of dysplastic polyps.
      even when the resected polyps contain high-grade dysplasia (HGD).
      • Blonski W.
      • Kundu R.
      • Furth E.F.
      • et al.
      High-grade dysplastic adenoma-like mass lesions are not an indication for colectomy in patients with ulcerative colitis.

      Statement 2: Extent of previous or present inflammation should have been or should be confirmed by endoscopy and/or histology.

      (Agreement, 100%; quality of evidence, no evidence)
      Confirmation of inflammation is warranted because CAN arises characteristically in previously or presently inflamed mucosa. Biopsy specimens can be used to discriminate between quiescent disease and different grades of disease activity.
      • Magro F.
      • Langner C.
      • Driessen A.
      • et al.
      European consensus on the histopathology of inflammatory bowel disease.
      ,
      • Pouw R.E.
      • Bisschops R.
      • Gecse K.B.
      • et al.
      Endoscopic tissue sampling—Part 2: lower gastrointestinal tract. European Society of Gastrointestinal Endoscopy (ESGE) guideline.
      According to the current European guidelines, biopsy specimens should be accompanied by clinical information such as endoscopic findings.
      • Magro F.
      • Langner C.
      • Driessen A.
      • et al.
      European consensus on the histopathology of inflammatory bowel disease.
      ,
      • Pouw R.E.
      • Bisschops R.
      • Gecse K.B.
      • et al.
      Endoscopic tissue sampling—Part 2: lower gastrointestinal tract. European Society of Gastrointestinal Endoscopy (ESGE) guideline.
      An adequate number of biopsy samples should be obtained from inflamed and noninflamed mucosa because mild or even severe inflammation can be detected in endoscopically normal-appearing mucosa.
      • Magro F.
      • Langner C.
      • Driessen A.
      • et al.
      European consensus on the histopathology of inflammatory bowel disease.
      Histologic disease activity in UC can be assessed with the use of validated histologic score indices (ie, Geboes score, Nancy Index, and Robarts Histopathology Index).
      • Mosli M.H.
      • Parker C.E.
      • Nelson S.A.
      • et al.
      Histologic scoring indices for evaluation of disease activity in ulcerative colitis.
      To date, there is no validated histologic scoring index for evaluation of Crohn’s disease (CD) activity.
      • Novak G.
      • Parker C.E.
      • Pai R.K.
      • et al.
      Histologic scoring indices for evaluation of disease activity in Crohn's disease.
      Several endoscopic scores have been established and used in clinical practice to monitor endoscopic activity for UC and CD. The most obvious candidates for UC are the formally validated UC endoscopic index of severity and UC colonoscopic index of severity, whereas in CD the CD endoscopic index of severity or the simple endoscopic score for CD can be used.
      • Travis S.P.
      • Schnell D.
      • Krzeski P.
      • et al.
      Developing an instrument to assess the endoscopic severity of ulcerative colitis: the Ulcerative Colitis Endoscopic Index of Severity (UCEIS).
      • Samuel S.
      • Bruining D.H.
      • Loftus Jr., E.V.
      • et al.
      Validation of the ulcerative colitis colonoscopic index of severity and its correlation with disease activity measures.
      • Mary J.Y.
      • Modigliani R.
      Development and validation of an endoscopic index of the severity for Crohn's disease: a prospective multicentre study. Groupe d'Etudes Thérapeutiques des Affections Inflammatoires du Tube Digestif (GETAID).
      • Daperno M.
      • D'Haens G.
      • Van Assche G.
      • et al.
      Development and validation of a new, simplified endoscopic activity score for Crohn's disease: the SES-CD.
      The latter scores were shown to be highly reproducible with demonstration of excellent interobserver agreement and have been prospectively validated.
      • Annese V.
      • Daperno M.
      • Rutter M.D.
      • et al.
      European evidence based consensus for endoscopy in inflammatory bowel disease.

      Statement 3: Nonpolypoid lesions and large (>20 mm) nonpedunculated colon polyps should be considered high-risk CAN.

      (Agreement, 88.2%; quality of evidence, limited evidence)
      Given its potentially worse outcome, an agreed definition of high-risk CAN (HR-CAN) is desirable because it constitutes the first step toward a coherent therapeutic strategy. Two studies identified nonpolypoid lesions as an independent risk factor for (advanced) colorectal neoplasia (aCRN) development in patients with IBD.
      • Cremer A.
      • Demetter P.
      • De Vos M.
      • et al.
      Risk of development of more-advanced lesions in patients with inflammatory bowel diseases and dysplasia.
      ,
      • Choi C.H.
      • Ignjatovic-Wilson A.
      • Askari A.
      • et al.
      Low-grade dysplasia in ulcerative colitis: risk factors for developing high-grade dysplasia or colorectal cancer.
      In addition, pooled data reported higher CRC and metachronous neoplasia incidence rates after endoscopic resection of nonpolypoid lesions as compared with polypoid lesions.
      • 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.
      In contrast, several studies have shown that polypoid lesions with low-grade dysplasia (LGD) or HGD in IBD patients have a low risk of future CRC.
      • Odze R.D.
      • Farraye F.A.
      • Hecht J.L.
      • et al.
      Long-term follow-up after polypectomy treatment for adenoma-like dysplastic lesions in ulcerative colitis.
      • Rubin P.H.
      • Friedman S.
      • Harpaz N.
      • et al.
      Colonoscopic polypectomy in chronic colitis: conservative management after endoscopic resection of dysplastic polyps.
      • Blonski W.
      • Kundu R.
      • Furth E.F.
      • et al.
      High-grade dysplastic adenoma-like mass lesions are not an indication for colectomy in patients with ulcerative colitis.
      ,
      • Choi C.H.
      • Ignjatovic-Wilson A.
      • Askari A.
      • et al.
      Low-grade dysplasia in ulcerative colitis: risk factors for developing high-grade dysplasia or colorectal cancer.
      ,
      • Kisiel J.B.
      • Loftus Jr., E.V.
      • Harmsen W.S.
      • et al.
      Outcome of sporadic adenomas and adenoma-like dysplasia in patients with ulcerative colitis undergoing polypectomy.
      Moreover, studies have shown that the risk of CRC was similar between polypoid lesions in diseased segments and sporadic adenomas in disease-free segments.
      • Odze R.D.
      • Farraye F.A.
      • Hecht J.L.
      • et al.
      Long-term follow-up after polypectomy treatment for adenoma-like dysplastic lesions in ulcerative colitis.
      ,
      • Kisiel J.B.
      • Loftus Jr., E.V.
      • Harmsen W.S.
      • et al.
      Outcome of sporadic adenomas and adenoma-like dysplasia in patients with ulcerative colitis undergoing polypectomy.
      Therefore, the risks of CRC in individuals with polypoid lesions, with and without IBD, can probably be considered comparable.
      Large nonpedunculated colorectal polyps (LNPCPs) are defined as sessile and flat lesions with a size ≥20 mm. LNPCPs are believed to be especially at risk of progression to submucosal invasive cancer.
      • Meulen L.W.T.
      • van der Zander Q.E.W.
      • Bogie R.M.M.
      • et al.
      Evaluation of polypectomy quality indicators of large nonpedunculated colorectal polyps in a nonexpert, bowel cancer screening cohort.
      Endoscopic resection of these lesions is technically more demanding because of their large size and lack of intraluminal protrusion. This translates into a higher risk of postresection adverse events and recurrence rates up to 30%.
      • Meulen L.W.T.
      • van der Zander Q.E.W.
      • Bogie R.M.M.
      • et al.
      Evaluation of polypectomy quality indicators of large nonpedunculated colorectal polyps in a nonexpert, bowel cancer screening cohort.
      ,
      • Hassan C.
      • Repici A.
      • Sharma P.
      • et al.
      Efficacy and safety of endoscopic resection of large colorectal polyps: a systematic review and meta-analysis.
      En-bloc resection might overcome the drawbacks associated with standard polypectomy in these cases.
      • Klein A.
      • Tate D.J.
      • Jayasekeran V.
      • et al.
      Thermal ablation of mucosal defect margins reduces adenoma recurrence after colonic endoscopic mucosal resection.
      To date, the literature concerning these lesions in the IBD population is virtually absent. Only 1 retrospective study reported a significant association of large polyps (defined as ≥1 cm) with the progression to aCRN (defined as HGD or CRC).
      • Choi C.H.
      • Ignjatovic-Wilson A.
      • Askari A.
      • et al.
      Low-grade dysplasia in ulcerative colitis: risk factors for developing high-grade dysplasia or colorectal cancer.
      Nevertheless, LNPCPs can be considered a high-risk factor in patients with IBD because of the risk of progression to submucosal invasion and the high risk of recurrence in the non-IBD population.

      Preresection assessment of HR-CAN

      Statement 4: Careful examination of the colon (preferably using enhanced endoscopic imaging) should precede local excision of HR-CAN.

      (Agreement, 100%; quality of evidence, moderate evidence)
      Pooled data showed that incidental synchronous CRC has been found in 2.7% and 13.7% of colectomy specimens of IBD patients with preoperative visible lesions containing LGD or HGD.
      • Kabir M.
      • Fofaria R.
      • Arebi N.
      • et al.
      Systematic review with meta-analysis: IBD-associated colonic dysplasia prognosis in the videoendoscopic era (1990 to present).
      Another study reported a pooled prevalence synchronous CRC rate of 17% in patients with UC after a preoperative diagnosis of LGD.
      • Fumery M.
      • Dulai P.S.
      • Gupta S.
      • et al.
      Incidence, risk factors, and outcomes of colorectal cancer in patients with ulcerative colitis with low-grade dysplasia: a systematic review and meta-analysis.
      Therefore, careful examination of the entire colon is warranted before a local excision.
      The use of high-definition white-light endoscopy or (dye or virtual) chromoendoscopy instead of standard white-light endoscopy is recommended.
      • 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.
      ,
      • Subramanian V.
      • Ramappa V.
      • Telakis E.
      • et al.
      Comparison of high definition with standard white light endoscopy for detection of dysplastic lesions during surveillance colonoscopy in patients with colonic inflammatory bowel disease.
      Add-on devices, such as distal attachment devices, to improve the adenoma detection rate in the non-IBD setting have been studied in 2 meta-network analyses. Both studies reported a significant increase of the adenoma detection rate for add-on devices as compared with standard colonoscopy.
      Mucosal flattening assisted colonoscopy (FAC) for improving adenoma detection rate: a systematic review with pairwise and network meta-analysis.
      ,
      • Facciorusso A.
      • Del Prete V.
      • Buccino R.V.
      • et al.
      Comparative efficacy of colonoscope distal attachment devices in increasing rates of adenoma detection: a network meta-analysis.
      Although no data are available in the IBD population, add-on devices may have an additional value for the detection of HR-CAN as well. We suggest using the term enhanced endoscopic imaging for these technologies (ie, high-definition white-light endoscopy or dye or virtual chromoendoscopy). In addition, add-on devices can be considered for the detection of HR-CAN.
      The recommendation to obtain random biopsy samples in the setting of (surveillance) endoscopies in the IBD population varies in the current guidelines.
      • Laine L.
      • Kaltenbach T.
      • Barkun A.
      • et al.
      SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease.
      • 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).
      • Annese V.
      • Daperno M.
      • Rutter M.D.
      • et al.
      European evidence based consensus for endoscopy in inflammatory bowel disease.
      Although the dysplasia yield of random biopsy sampling during surveillance in IBD is relatively low, 12% to 20% of the dysplastic specimens were obtained by random biopsy sampling in 2 studies.
      • Hu A.B.
      • Burke K.E.
      • Kochar B.
      • et al.
      Yield of random biopsies during colonoscopies in inflammatory bowel disease patients undergoing dysplasia surveillance.
      ,
      • 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?.
      A large cohort study reported a greater proportion of patients with neoplasia after targeted biopsy sampling (19.1%) as compared with random biopsy sampling (8.2%).
      • Gasia M.F.
      • Ghosh S.
      • Panaccione R.
      • et al.
      Targeted biopsies identify larger proportions of patients with colonic neoplasia undergoing high-definition colonoscopy, dye chromoendoscopy, or electronic virtual chromoendoscopy.
      Random biopsy sampling has a significant yield in IBD patients with a personal history of neoplasia, concomitant primary sclerosing cholangitis, or a tubular colon during colonoscopy.
      • 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?.
      Therefore, random biopsy sampling is recommended in this subset of patients before endoscopic resection of HR-CAN.

      Statement 5: An HR-CAN lesion is considered endoscopically resectable if

      • 1.
        The lesion has distinct margins
      • 2.
        The lesion can (preferably) be removed en bloc with clear deep and lateral resection margins
      and there is no evidence of
      • 3.
        Synchronous invisible dysplasia
      • 4.
        Moderate-to-severe inflammation of mucosa surrounding the area with HR-CAN interfering with delineation of the lesion
      • 5.
        Signs of deep submucosal invasion.
      (Agreement, 76.5%; quality of evidence, limited evidence)
      Although current guidelines recommend the endoscopic resection of visible CAN, it may be impossible to (completely) remove HR-CAN lesions when the above criteria are not met (Fig. 3).
      • Laine L.
      • Kaltenbach T.
      • Barkun A.
      • et al.
      SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease.
      • 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).
      • Annese V.
      • Daperno M.
      • Rutter M.D.
      • et al.
      European evidence based consensus for endoscopy in inflammatory bowel disease.
      Criteria for successful endoscopic resection are macroscopically identifiable, distinct margins and the absence of deep submucosal invasion (DSI) (Fig. 4). Proper delineation of dysplasia enables a complete, preferably en-bloc, resection, thereby improving the quality and reliability of histopathologic findings.
      • Pimentel-Nunes P.
      • Dinis-Ribeiro M.
      • Ponchon T.
      • et al.
      Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) guideline.
      Despite the use of enhanced endoscopic imaging, invisible dysplasia should be considered a contraindication for endoscopic resection and warrants consideration of surgical resection.
      • Thomas T.
      • Abrams K.A.
      • Robinson R.J.
      • et al.
      Meta-analysis: cancer risk of low-grade dysplasia in chronic ulcerative colitis.
      The experts agreed that signs of DSI, such as excavation and demarcated depressed areas, are a contraindication to endoscopic resection.
      • Lee B.I.
      • Matsuda T.
      Estimation of invasion depth: the first key to successful colorectal ESD.
      Recently pooled data reported an overall rate of lymph node metastasis of 11.2% in the presence of DSI in sporadic lesions (non-IBD patients).
      • Zwager L.W.
      • Bastiaansen B.A.J.
      • Montazeri N.S.M.
      • et al.
      Deep submucosal invasion is not an independent risk factor for lymph node metastasis in T1 colorectal cancer: a meta-analysis.
      Although this meta-analysis concluded that DSI is not a strong independent predictor for lymph node metastasis, an R0 resection was only achieved in 62% to 65% of the polyps with DSI after ESD.
      • Zwager L.W.
      • Bastiaansen B.A.J.
      • Montazeri N.S.M.
      • et al.
      Deep submucosal invasion is not an independent risk factor for lymph node metastasis in T1 colorectal cancer: a meta-analysis.
      Data on the correlation between DSI and en-bloc or R0 resection rates in HR-CAN are presently lacking, but in general signs of DSI are considered a contraindication for endoscopic resection in this setting. All cases of HR-CAN should be discussed at multidisciplinary team meetings before the endoscopic procedure to ensure the delivery of patient-specific management.
      Figure thumbnail gr3
      Figure 3In a tubular, scarred sigmoid (A) of a patient with ulcerative colitis, a 2.5 × 1.5-cm dysplastic field was identified (B). The lesion could not completely be delineated. Biopsy specimens from the surrounding normal-appearing mucosa revealed high-grade dysplasia. The patient was referred for proctocolectomy.
      Figure thumbnail gr4
      Figure 4A, A 75-year-old man with longstanding ulcerative colitis was referred for endoscopic resection of a 1.2 × 2.5-cm well-demarcated lesion in the rectum identified with chromoendoscopy. B, The lesion was successfully resected using endoscopic submucosal dissection. Histology revealed high-grade dysplasia.

      Statement 6: Surgical resection is indicated when HR-CAN is nonresectable.

      (Agreement, 100%; quality of evidence, moderate evidence)
      Nonpolypoid lesions and LNPCPs (ie, HR-CAN) are associated with a high risk of aCRN development.
      • Cremer A.
      • Demetter P.
      • De Vos M.
      • et al.
      Risk of development of more-advanced lesions in patients with inflammatory bowel diseases and dysplasia.
      ,
      • Choi C.H.
      • Ignjatovic-Wilson A.
      • Askari A.
      • et al.
      Low-grade dysplasia in ulcerative colitis: risk factors for developing high-grade dysplasia or colorectal cancer.
      ,
      • Meulen L.W.T.
      • van der Zander Q.E.W.
      • Bogie R.M.M.
      • et al.
      Evaluation of polypectomy quality indicators of large nonpedunculated colorectal polyps in a nonexpert, bowel cancer screening cohort.
      Thus, removal of these lesion types is warranted. Current international guidelines recommend surgery for endoscopically nonresectable lesions in the IBD population.
      • Laine L.
      • Kaltenbach T.
      • Barkun A.
      • et al.
      SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease.
      ,
      • Annese V.
      • Daperno M.
      • Rutter M.D.
      • et al.
      European evidence based consensus for endoscopy in inflammatory bowel disease.
      ,
      • Bemelman W.A.
      • Warusavitarne J.
      • Sampietro G.M.
      • et al.
      ECCO-ESCP consensus on surgery for Crohn's disease.
      Close endoscopic surveillance or segmental resection is proposed for LGD or patients who are at high risk for dismal postoperative outcomes.
      • Bemelman W.A.
      • Warusavitarne J.
      • Sampietro G.M.
      • et al.
      ECCO-ESCP consensus on surgery for Crohn's disease.
      A proctocolectomy is advised for aCRN because of the high rates of metachronous recurrence after segmental resection, based on a limited number of studies.
      • Bemelman W.A.
      • Warusavitarne J.
      • Sampietro G.M.
      • et al.
      ECCO-ESCP consensus on surgery for Crohn's disease.
      A recent multicenter, retrospective study reported similar long-term survival outcomes of segmental colectomy compared with proctocolectomy.
      • Sensi B.
      • Khan J.
      • Warusavitarne J.
      • et al.
      Long-term oncological outcome of segmental versus extended colectomy for colorectal cancer in Crohn's disease: results from an international multicentre study. [Erratum in: J Crohns Colitis. Epub 2022 Feb 16; Erratum in: J Crohns Colitis. Epub 2023 Feb 9].
      Because of the risk of progression to aCRN, the type of surgical resection should be discussed with a multidisciplinary team in which other prognostic risk factors for aCRN should be taken into account.
      • Wijnands A.M.
      • de Jong M.E.
      • Lutgens M.
      • et al.
      Prognostic Factors for advanced colorectal neoplasia in inflammatory bowel disease: systematic review and meta-analysis.
      If segmental resection is undertaken, continued close surveillance of the residual colon is imperative.

      Statement 7: All suspected HR-CANs should be assessed according to a standardized approach and recorded in the endoscopy report. The description should include at least the following features:

      • 1.
        Size, delineation, and location
      • 2.
        Description of gross morphology
        • a.
          Granular/nongranular
        • b.
          Paris classification
      • 3.
        Assessment of the pit and vascular pattern using enhanced endoscopic imaging
      • 4.
        Assessment of endoscopic activity of the colitis in the segment harboring the dysplastic lesion (eg, using the Mayo subset index, UC endoscopic index of severity, or simple endoscopic score for CD disease).
      (Agreement, 94.1%; quality of evidence, limited evidence)
      To date, minimum standardized endoscopy reporting elements for CAN lesions have not been established.
      • Pimentel-Nunes P.
      • Dinis-Ribeiro M.
      • Ponchon T.
      • et al.
      Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) guideline.
      ,
      • Kaltenbach T.
      • Anderson J.C.
      • Burke C.A.
      • et al.
      Endoscopic removal of colorectal lesions—recommendations by the US Multi-Society Task Force on Colorectal Cancer.
      ,
      • Ferlitsch M.
      • Moss A.
      • Hassan C.
      • et al.
      Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline.
      Standardized endoscopy reports are crucial for clinical management decision-making to facilitate longitudinal monitoring and enable the establishment of a potential relationship between morphology and histopathology.
      In line with recommendations for non-IBD–related dysplastic lesions, common endoscopic descriptors such as size, location, and description of gross morphology should be included in endoscopy reports.
      • Pimentel-Nunes P.
      • Dinis-Ribeiro M.
      • Ponchon T.
      • et al.
      Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) guideline.
      ,
      • Kaltenbach T.
      • Anderson J.C.
      • Burke C.A.
      • et al.
      Endoscopic removal of colorectal lesions—recommendations by the US Multi-Society Task Force on Colorectal Cancer.
      ,
      • Ferlitsch M.
      • Moss A.
      • Hassan C.
      • et al.
      Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline.
      The delineation of the lesion should be recorded in the standardized report to identify the lateral resection margins and enable en-bloc resection. Furthermore, the experts agreed to include an assessment of the granularity of the lesion because nongranular-type lesions have been associated with submucosal invasion, especially in the rectosigmoid.
      • Uraoka T.
      • Saito Y.
      • Matsuda T.
      • et al.
      Endoscopic indications for endoscopic mucosal resection of laterally spreading tumours in the colorectum.
      • Yamada M.
      • Saito Y.
      • Sakamoto T.
      • et al.
      Endoscopic predictors of deep submucosal invasion in colorectal laterally spreading tumors.
      • Bogie R.M.M.
      • Veldman M.H.J.
      • Snijders L.
      • et al.
      Endoscopic subtypes of colorectal laterally spreading tumors (LSTs) and the risk of submucosal invasion: a meta-analysis.
      The assessment of the Kudo pit pattern classification has shown high specificity and sensitivity (both 93%) in differentiating neoplastic lesions from non-neoplastic lesions in IBD patients.
      • Kiesslich R.
      • Fritsch J.
      • Holtmann M.
      • et al.
      Methylene blue-aided chromoendoscopy for the detection of intraepithelial neoplasia and colon cancer in ulcerative colitis.
      In addition, a prospective study and a randomized controlled trial reported that pit pattern types III to V were predictive of CAN.
      • Bogie R.M.M.
      • Veldman M.H.J.
      • Snijders L.
      • et al.
      Endoscopic subtypes of colorectal laterally spreading tumors (LSTs) and the risk of submucosal invasion: a meta-analysis.
      ,
      • Aladrén B.S.
      • González-Lama Y.
      • García-Alvarado M.
      • et al.
      Even non-experts identify non-dysplastic lesions in inflammatory bowel disease via chromoendoscopy: results of a screening program in real-life.
      Conversely, pit pattern types I and II were found to have a high negative predictive value for CAN.
      • Aladrén B.S.
      • González-Lama Y.
      • García-Alvarado M.
      • et al.
      Even non-experts identify non-dysplastic lesions in inflammatory bowel disease via chromoendoscopy: results of a screening program in real-life.
      ,
      • 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.
      In addition, irregular vascular patterns were identified as predictors for dysplasia in IBD patients.
      • Iacucci M.
      • McQuaid K.
      • Gui X.S.
      • et al.
      A multimodal (FACILE) classification for optical diagnosis of inflammatory bowel disease associated neoplasia.
      As noted previously, the presence of moderate-to-severe inflammation interferes with the detection of dysplasia and is therefore considered a contraindication for endoscopic resection of HR-CAN. Thus, a careful assessment of the endoscopic severity of the disease using a validated endoscopic score (eg, Mayo subset index score, UC endoscopic index of severity, and simple endoscopic score for CD) should be included in the endoscopy report.
      • Laine L.
      • Kaltenbach T.
      • Barkun A.
      • et al.
      SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease.
      • 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).
      • Annese V.
      • Daperno M.
      • Rutter M.D.
      • et al.
      European evidence based consensus for endoscopy in inflammatory bowel disease.

      Endoscopic resection of HR-CAN

      Statement 8: HR-CAN preferably should be removed en bloc to lower the risk of recurrence and optimize the histologic assessment.

      (Agreement, 94.1%; quality of evidence, limited evidence)
      Because of the higher CRC and metachronous neoplasia incidence rates after resection of nonpolypoid lesions and the potential risk of DSI of LNPCPs, en-bloc resection is preferred to lower the risk of recurrence.
      • Laine L.
      • Kaltenbach T.
      • Barkun A.
      • et al.
      SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease.
      ,
      • 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.
      ,
      • Hassan C.
      • Repici A.
      • Sharma P.
      • et al.
      Efficacy and safety of endoscopic resection of large colorectal polyps: a systematic review and meta-analysis.
      Furthermore, en-bloc resection enables a more accurate histopathologic evaluation of the resection margins and achievement of R0 resection.
      • Draganov P.V.
      • Aihara H.
      • Karasik M.S.
      • et al.
      Endoscopic submucosal dissection in North America: a large prospective multicenter study.
      Both EMR and ESD are commonly used endoscopic resection techniques allowing an en-bloc resection. In addition, endoscopic full-thickness resection and endoscopic intermuscular dissection, for rectal lesions with signs of DSI, are relatively new techniques for an en-bloc resection of colorectal lesions. Both techniques have recently been found to have high overall technical success and R0 resection rates in sporadic lesions, and further experience is required to determine the role of these techniques for managing HR-CAN.
      • McKechnie T.
      • Govind S.
      • Lee J.
      • et al.
      Endoscopic full-thickness resection for colorectal lesions: a systematic review and meta-analysis.
      ,
      • Moons L.M.G.
      • Bastiaansen B.A.J.
      • Richir M.C.
      • et al.
      Endoscopic intermuscular dissection for deep submucosal invasive cancer in the rectum: a new endoscopic approach.
      Whether endoscopic full-thickness resection or endoscopic intermuscular dissection can be successfully and safely used in HR-CAN is presently not clear because data for HR-CAN are not available.
      A recent meta-analysis reported pooled en-bloc and R0 resection rates of 86% and 70%, respectively, after a hybrid endoscopic resection technique (ie, a combination of EMR and ESD) or ESD of nonpolypoid lesions with a pooled recurrence rate of 8%.
      • Chen W.
      • Zhang Y.L.
      • Zhao Y.
      • et al.
      Endoscopic resection for non-polypoid dysplasia in inflammatory bowel disease: a systematic review and meta-analysis.
      En-bloc resection rates were significantly higher after ESD (93%) as compared with the hybrid technique (65%, P < .001).
      • Chen W.
      • Zhang Y.L.
      • Zhao Y.
      • et al.
      Endoscopic resection for non-polypoid dysplasia in inflammatory bowel disease: a systematic review and meta-analysis.
      In line with these findings, pooled R0 resection rates were higher using ESD (75%) versus the hybrid technique (60%) but did not reach significance (P = .454).
      • Chen W.
      • Zhang Y.L.
      • Zhao Y.
      • et al.
      Endoscopic resection for non-polypoid dysplasia in inflammatory bowel disease: a systematic review and meta-analysis.
      We recognized that long-term outcomes of these different techniques have not been published.
      Piecemeal resection does not always allow complete retrieval of the lesion, which renders complete histologic assessment sometimes difficult.
      • Ferlitsch M.
      • Moss A.
      • Hassan C.
      • et al.
      Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline.
      The data on piecemeal resection outcomes are conflicting. Piecemeal EMR has been shown to achieve excellent early- and long-term outcomes for >20-mm sporadic adenomas.
      • Pimentel-Nunes P.
      • Dinis-Ribeiro M.
      • Ponchon T.
      • et al.
      Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) guideline.
      But piecemeal resections of sporadic nonpolypoid lesions have also been associated with a pooled recurrence rate of 20% versus 3% after en-bloc resection.
      • Belderbos T.D.
      • Leenders M.
      • Moons L.M.
      • et al.
      Local recurrence after endoscopic mucosal resection of nonpedunculated colorectal lesions: systematic review and meta-analysis.
      The recurrence rate even exceeds 30% in larger polyps (>20 mm).
      • Klein A.
      • Tate D.J.
      • Jayasekeran V.
      • et al.
      Thermal ablation of mucosal defect margins reduces adenoma recurrence after colonic endoscopic mucosal resection.
      However, with the recent introduction of improved EMR techniques and the use of adjuvant thermal ablation (snare-tip soft coagulation or argon plasma coagulation) of the resected lesion margin, the risk of recurrence after a piecemeal resection has been significantly reduced.
      • Klein A.
      • Tate D.J.
      • Jayasekeran V.
      • et al.
      Thermal ablation of mucosal defect margins reduces adenoma recurrence after colonic endoscopic mucosal resection.
      ,
      • Chandan S.
      • Facciorusso A.
      • Ramai D.
      • et al.
      Snare tip soft coagulation (STSC) after endoscopic mucosal resection (EMR) of large (> 20 mm) non pedunculated colorectal polyps: a systematic review and meta-analysis.
      Because studies in IBD patients are virtually absent, it is not clear if these results can be extrapolated to the setting of HR-CAN.
      In conclusion, HR-CAN should preferably be removed en bloc to lower the risk of recurrence and optimize the histologic assessment. Advanced endoscopic resection techniques should be considered for the endoscopic resection of an HR-CAN lesion. According to the current evidence, ESD has higher en-bloc and R0 resection rates, which may be a reason to prefer ESD over EMR.

      Statement 9: HR-CAN <20 mm with good lifting (Kato I and II) can be removed using en-bloc (including underwater) EMR.

      (Agreement, 94.1%; quality of evidence, moderate evidence)
      No statements concerning HR-CAN and the use of particular endoscopic resection techniques are made in the current international guideline.
      • Pimentel-Nunes P.
      • Dinis-Ribeiro M.
      • Ponchon T.
      • et al.
      Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) guideline.
      ,
      • Kaltenbach T.
      • Anderson J.C.
      • Burke C.A.
      • et al.
      Endoscopic removal of colorectal lesions—recommendations by the US Multi-Society Task Force on Colorectal Cancer.
      ,
      • Ferlitsch M.
      • Moss A.
      • Hassan C.
      • et al.
      Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline.
      Moreover, no clear cutoff point for lesion size where an en-bloc resection can be considered safe and feasible has been defined. The decision for an en-bloc resection is mostly based on the morphology and size of the lesion.
      • Ferlitsch M.
      • Moss A.
      • Hassan C.
      • et al.
      Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline.
      To date, 4 relatively small retrospective studies have reported outcomes on EMR in patients with CAN.
      • Nishio M.
      • Hirasawa K.
      • Ozeki Y.
      • et al.
      An endoscopic treatment strategy for superficial tumors in patients with ulcerative colitis.
      ,
      • Yadav S.
      • Loftus Jr., E.V.
      • Harmsen W.S.
      • et al.
      Outcome of endoscopic resection of colonic polyps larger than 10 mm in patients with inflammatory bowel disease.
      ,
      • Alkandari A.
      • Thayalasekaran S.
      • Bhandari M.
      • et al.
      Endoscopic resections in inflammatory bowel disease: a multicentre european outcomes study.
      ,
      • Gulati S.
      • Emmanuel A.
      • Burt M.
      • et al.
      Outcomes of endoscopic resections of large laterally spreading colorectal lesions in inflammatory bowel disease: a single United Kingdom center experience.
      The outcomes of studies with a focus on resection technique (based on lesion size) were described in 3 studies.
      • Nishio M.
      • Hirasawa K.
      • Ozeki Y.
      • et al.
      An endoscopic treatment strategy for superficial tumors in patients with ulcerative colitis.
      ,
      • Yadav S.
      • Loftus Jr., E.V.
      • Harmsen W.S.
      • et al.
      Outcome of endoscopic resection of colonic polyps larger than 10 mm in patients with inflammatory bowel disease.
      ,
      • Alkandari A.
      • Thayalasekaran S.
      • Bhandari M.
      • et al.
      Endoscopic resections in inflammatory bowel disease: a multicentre european outcomes study.
      Nishio et al
      • Nishio M.
      • Hirasawa K.
      • Ozeki Y.
      • et al.
      An endoscopic treatment strategy for superficial tumors in patients with ulcerative colitis.
      described the results of endoscopic resection of superficial tumors in patients with UC. EMR was used for most polyps (62.0%) that were predominantly <20 mm (98%) and polypoid (68%). The overall en-bloc resection rate after EMR was 94%. The en-bloc resection rate after EMR as compared with ESD did not significantly differ in polyps <20 mm. The en-bloc resection rate in nonpolypoid lesions was significantly higher in ESD (100%) compared with EMR (85%, P = .044). Of note, documentation of the presence of submucosal fibrosis was not reported.
      • Nishio M.
      • Hirasawa K.
      • Ozeki Y.
      • et al.
      An endoscopic treatment strategy for superficial tumors in patients with ulcerative colitis.
      Yadav et al
      • Yadav S.
      • Loftus Jr., E.V.
      • Harmsen W.S.
      • et al.
      Outcome of endoscopic resection of colonic polyps larger than 10 mm in patients with inflammatory bowel disease.
      reported on the endoscopic treatment of polyps >10 mm in IBD patients, with 54.8% of polyps <20 mm. Most polyps (95.2%) were resected using EMR, yielding an en-bloc resection rate of 70.9%. A multicenter, retrospective study on the use of EMR or ESD in colitis-associated polyps (<20 mm in 90.8%) reported an overall en-bloc rate of 63% after EMR and 65.9% after ESD.
      • Alkandari A.
      • Thayalasekaran S.
      • Bhandari M.
      • et al.
      Endoscopic resections in inflammatory bowel disease: a multicentre european outcomes study.
      All lesions with submucosal fibrosis were resected with ESD or a “knife-assisted” resection.
      • Alkandari A.
      • Thayalasekaran S.
      • Bhandari M.
      • et al.
      Endoscopic resections in inflammatory bowel disease: a multicentre european outcomes study.
      Based on these results, the experts agreed that HR-CAN <20 mm with good lifting (Kato I and II) can be removed using en-bloc EMR. In sporadic adenomas, recent pooled data reported higher en-bloc rates and lower recurrence rates in favor of underwater EMR compared with conventional EMR.
      • Tziatzios G.
      • Gkolfakis P.
      • Triantafyllou K.
      • et al.
      Higher rate of en bloc resection with underwater than conventional endoscopic mucosal resection: a meta-analysis.
      The role of underwater EMR has not been studied in HR-CAN, but underwater EMR might be useful in the setting of these cases as well.

      Statement 10: HR-CAN <20 mm without good lifting (Kato III and IV) or HR-CAN >20 mm without signs of DSI should be removed with techniques that preferably allow en-bloc resection.

      (Agreement, 82.4%; quality of evidence, no evidence)
      Chronic inflammation (or submucosal invasion)-related submucosal fibrosis might lead to inadequate lifting and to incomplete resection of lesions if EMR is used.
      • Shergill A.K.
      • Lightdale J.R.
      • Bruining D.H.
      • et al.
      American Society for Gastrointestinal Endoscopy Standards of Practice Committee
      The role of endoscopy in inflammatory bowel disease.
      ,
      • Ferlitsch M.
      • Moss A.
      • Hassan C.
      • et al.
      Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline.
      ESD may overcome the limitations of EMR and should therefore be considered as a first choice to resect lesions when good lifting is not achieved.
      • Ferlitsch M.
      • Moss A.
      • Hassan C.
      • et al.
      Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline.
      The presence of concomitant submucosal fibrosis in CAN lesions is reported in most studies with a range from 28.6% to 100% of the cases.
      • 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.
      ,
      • Matsumoto K.
      • Oka S.
      • Tanaka S.
      • et al.
      Long-term outcomes after endoscopic submucosal dissection for ulcerative colitis-associated dysplasia.
      ,
      • Alkandari A.
      • Thayalasekaran S.
      • Bhandari M.
      • et al.
      Endoscopic resections in inflammatory bowel disease: a multicentre european outcomes study.
      ,
      • Kochhar G.
      • Steele S.
      • Sanaka M.
      • et al.
      Endoscopic submucosal dissection for flat colonic polyps in patients with inflammatory bowel disease: a single-center experience.
      • Kinoshita S.
      • Nishizawa T.
      • Yahagi N.
      • et al.
      Endoscopic submucosal dissection in patients with ulcerative colitis.
      • Suzuki N.
      • Toyonaga T.
      • East J.E.
      Endoscopic submucosal dissection of colitis-related dysplasia.
      • Gulati S.
      • Emmanuel A.
      • Burt M.
      • et al.
      Outcomes of endoscopic resections of large laterally spreading colorectal lesions in inflammatory bowel disease: a single United Kingdom center experience.
      • Iacopini F.
      • Saito Y.
      • Yamada M.
      • et al.
      Curative endoscopic submucosal dissection of large nonpolypoid superficial neoplasms in ulcerative colitis (with videos).
      • Ngamruengphong S.
      • Aihara H.
      • Friedland S.
      • et al.
      Endoscopic submucosal dissection for colorectal dysplasia in inflammatory bowel disease: a US multicenter study.
      ,
      • Kasuga K.
      • Yamada M.
      • Shida D.
      • et al.
      Treatment outcomes of endoscopic submucosal dissection and surgery for colorectal neoplasms in patients with ulcerative colitis.
      ,
      • Smith L.A.
      • Baraza W.
      • Tiffin N.
      • et al.
      Endoscopic resection of adenoma-like mass in chronic ulcerative colitis using a combined endoscopic mucosal resection and cap assisted submucosal dissection technique.
      In studies that reported relative high frequencies of submucosal fibrosis (>60%), en-bloc rates ranging from 78% to 100% after ESD were achieved.
      • Matsumoto K.
      • Oka S.
      • Tanaka S.
      • et al.
      Long-term outcomes after endoscopic submucosal dissection for ulcerative colitis-associated dysplasia.
      ,
      • Yang D.H.
      • Kim J.
      • Song E.M.
      • et al.
      Outcomes of ulcerative colitis-associated dysplasia patients referred for potential endoscopic submucosal dissection.
      • Kochhar G.
      • Steele S.
      • Sanaka M.
      • et al.
      Endoscopic submucosal dissection for flat colonic polyps in patients with inflammatory bowel disease: a single-center experience.
      • Kinoshita S.
      • Nishizawa T.
      • Yahagi N.
      • et al.
      Endoscopic submucosal dissection in patients with ulcerative colitis.
      • Suzuki N.
      • Toyonaga T.
      • East J.E.
      Endoscopic submucosal dissection of colitis-related dysplasia.
      ,
      • Iacopini F.
      • Saito Y.
      • Yamada M.
      • et al.
      Curative endoscopic submucosal dissection of large nonpolypoid superficial neoplasms in ulcerative colitis (with videos).
      ,
      • Ngamruengphong S.
      • Aihara H.
      • Friedland S.
      • et al.
      Endoscopic submucosal dissection for colorectal dysplasia in inflammatory bowel disease: a US multicenter study.
      ,
      • Smith L.A.
      • Baraza W.
      • Tiffin N.
      • et al.
      Endoscopic resection of adenoma-like mass in chronic ulcerative colitis using a combined endoscopic mucosal resection and cap assisted submucosal dissection technique.
      Of note, most of these lesions were nonpolypoid (76%-100%).
      • Matsumoto K.
      • Oka S.
      • Tanaka S.
      • et al.
      Long-term outcomes after endoscopic submucosal dissection for ulcerative colitis-associated dysplasia.
      ,
      • Yang D.H.
      • Kim J.
      • Song E.M.
      • et al.
      Outcomes of ulcerative colitis-associated dysplasia patients referred for potential endoscopic submucosal dissection.
      • Kochhar G.
      • Steele S.
      • Sanaka M.
      • et al.
      Endoscopic submucosal dissection for flat colonic polyps in patients with inflammatory bowel disease: a single-center experience.
      • Kinoshita S.
      • Nishizawa T.
      • Yahagi N.
      • et al.
      Endoscopic submucosal dissection in patients with ulcerative colitis.
      • Suzuki N.
      • Toyonaga T.
      • East J.E.
      Endoscopic submucosal dissection of colitis-related dysplasia.
      ,
      • Iacopini F.
      • Saito Y.
      • Yamada M.
      • et al.
      Curative endoscopic submucosal dissection of large nonpolypoid superficial neoplasms in ulcerative colitis (with videos).
      ,
      • Ngamruengphong S.
      • Aihara H.
      • Friedland S.
      • et al.
      Endoscopic submucosal dissection for colorectal dysplasia in inflammatory bowel disease: a US multicenter study.
      ,
      • Smith L.A.
      • Baraza W.
      • Tiffin N.
      • et al.
      Endoscopic resection of adenoma-like mass in chronic ulcerative colitis using a combined endoscopic mucosal resection and cap assisted submucosal dissection technique.
      Although the use of endoscopic full-thickness resection and endoscopic intermuscular dissection has not been assessed in patients with IBD, these new techniques may prove useful in the treatment of HR-CAN lesions with (severe) fibrosis.
      • Aslanian H.R.
      • Sethi A.
      • Bhutani M.S.
      • et al.
      ASGE Technology Committee
      ASGE guideline for endoscopic full-thickness resection and submucosal tunnel endoscopic resection.
      ,
      • Toyonaga T.
      • Ohara Y.
      • Baba S.
      • et al.
      Peranal endoscopic myectomy (PAEM) for rectal lesions with severe fibrosis and exhibiting the muscle-retracting sign.
      EMR and ESD are generally considered the preferable options for endoscopic removal of polyps >20 mm because of the limited size of the snare, difficulty in positioning the endoscope, and extension of the polyp over 1 or multiple folds.
      • Arezzo A.
      • Passera R.
      • Marchese N.
      • et al.
      Systematic review and meta-analysis of endoscopic submucosal dissection vs endoscopic mucosal resection for colorectal lesions.
      Pooled data suggest that ESD results in higher en-bloc and R0 resection rates as compared with EMR (93% vs 65% and 75% vs 60%, respectively) in the resection of large HR-CAN lesions (mean size, 31.4 mm).
      • Chen W.
      • Zhang Y.L.
      • Zhao Y.
      • et al.
      Endoscopic resection for non-polypoid dysplasia in inflammatory bowel disease: a systematic review and meta-analysis.
      No data on recurrence rates specific to the endoscopic resection techniques used were reported. A recent meta-analysis reported significantly lower recurrence rates after ESD as compared with EMR in large (>20 mm) sporadic colorectal nonpolypoid lesions.
      • Shahini E.
      • Passera R.
      • Lo Secco G.
      • et al.
      A systematic review and meta-analysis of endoscopic mucosal resection vs endoscopic submucosal dissection for colorectal sessile/non-polypoid lesions.
      Thus, ESD could be considered as the first choice of technique in the endoscopic resection of HR-CAN >20 mm without signs of submucosal invasion because of the higher technical successes and probable lower recurrence rates.

      Statement 11: Endoscopic local excision of HR-CAN should be performed by endoscopists with sufficient skills in both EMR and ESD techniques.

      (Agreement, 88.2%; quality of evidence, no evidence)
      To date, no studies are available comparing the outcomes of endoscopic resection of HR-CAN by expert versus nonexpert endoscopists. One older retrospective study by Brooker et al
      • Brooker J.C.
      • Saunders B.P.
      • Shah S.G.
      • et al.
      Endoscopic resection of large sessile colonic polyps by specialist and non-specialist endoscopists.
      reported that expert endoscopists had a significantly higher success rate as compared with nonexperts for the resection of sporadic sessile colonic polyps. The guideline of the European Society of Gastrointestinal Endoscopy recommends referring patients with nonlifting polyps without characteristics of DSI or lesions with high-risk features to an expert endoscopy center for evaluation before surgery is considered.
      • Pimentel-Nunes P.
      • Dinis-Ribeiro M.
      • Ponchon T.
      • et al.
      Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) guideline.
      ,
      • Ferlitsch M.
      • Moss A.
      • Hassan C.
      • et al.
      Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline.
      Furthermore, the guideline also states that large (>20 mm) sessile and laterally spreading or complex polyps should be removed by an appropriately trained and experienced endoscopist in an appropriately resourced endoscopy center. Finally, the guideline stipulates that ESD should be restricted to tertiary referral centers. The American Society for Gastrointestinal Endoscopy guideline states that referral to an expert or tertiary referral center is indicated for patients with lesions in a difficult location (eg, appendiceal valve) or if the endoscopist is not confident about removing the lesion.
      • Kaltenbach T.
      • Anderson J.C.
      • Burke C.A.
      • et al.
      Endoscopic removal of colorectal lesions—recommendations by the US Multi-Society Task Force on Colorectal Cancer.
      Both EMR and ESD can achieve an en-bloc resection of HR-CAN lesions. However, a recent meta-analysis suggested a superiority of ESD over EMR because of higher en-bloc and R0 resection rates in large nonpolypoid lesions.
      • Chen W.
      • Zhang Y.L.
      • Zhao Y.
      • et al.
      Endoscopic resection for non-polypoid dysplasia in inflammatory bowel disease: a systematic review and meta-analysis.
      In addition, ESD should be considered the first choice in cases of submucosal fibrosis. Because of the potential complexity of these procedures in patients with large nonpolypoid lesions or with submucosal fibrosis, we recommend referring patients with these kinds of lesions to centers experienced in EMR and ESD techniques.

      Outcomes and follow-up of endoscopic resection of HR-CAN

      Statement 12: Endoscopic resection should be captured by recording

      • 1.
        Technical success
        • a.
          En-bloc resection
        • b.
          R0 resection
        • c.
          Adverse events (intra- or postprocedural bleeding, perforation, postcoagulation syndrome, need of emergency surgery, other)
      • 2.
        Outcomes
        • a.
          Local recurrence at 6 months and 3 years
        • b.
          Surgery for recurrence after 1, 3, and 5 years.
      (Agreement, 82.4%; quality of evidence, no evidence)
      Endoscopy reporting elements capturing the different aspects of technical success and outcomes of endoscopic resection of HR-CAN lesions are currently not defined. Technical success in non-IBD lesions is often defined as the rates of en-bloc and R0 resection and adverse events. The most common adverse events for both EMR and ESD comprise bleeding and perforation.
      • Pimentel-Nunes P.
      • Dinis-Ribeiro M.
      • Ponchon T.
      • et al.
      Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) guideline.
      Although these adverse events can be predominantly managed conservatively, adverse event–related (emergency) surgery was reported in 1%.
      • Pimentel-Nunes P.
      • Dinis-Ribeiro M.
      • Ponchon T.
      • et al.
      Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) guideline.
      In addition, postcoagulation syndrome was considered an adverse event after endoscopic resection because the incidence varies from 1% (EMR) to 9% (ESD).
      • Hirasawa K.
      • Sato C.
      • Makazu M.
      • et al.
      Coagulation syndrome: delayed perforation after colorectal endoscopic treatments.
      Because of the incidence of these adverse events in combination with potential dismal outcomes, documentation of these adverse events is warranted. Local recurrence (at 6 months and 3 years) and surgery for recurrence (after 1, 3, and 5 years) were proposed as outcome measures for endoscopic resection of HR-CAN.

      Statement 13: The histologic report should at least include the following items:

      • 1.
        Size (in mm)
      • 2.
        Grade of dysplasia according the World Health Organization classification
      • 3.
        Lateral resection margin (in mm, free if >.1 mm)
      • 4.
        Deep resection margin (in mm, free if >.1 mm)
      In case of submucosal invasion:
      • 1.
        Maximum depth of submucosal (Sm) invasion in μm (taken from the deepest margin of the muscularis mucosae)
      • 2.
        Lymphatic and/or venous invasion confirmed with D2-40 immunohistochemistry
      • 3.
        Tumor budding (Bd1-3) according to the International Tumor Budding Consensus Conference
      • 4.
        Grade of differentiation according to World Health Organization classification.
      (Agreement, 94.1%; quality of evidence, no evidence)
      Standardization of the histologic reporting of HR-CAN is virtually absent in the current guidelines. A detailed pathology report containing a number of standard data elements is essential for clinical decision-making and facilitates future research in this field. These standard data elements are size in millimeters, grade of dysplasia according to the World Health Organization, and both lateral and vertical/deep resection margin in millimeters.
      • Pimentel-Nunes P.
      • Dinis-Ribeiro M.
      • Ponchon T.
      • et al.
      Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) guideline.
      ,
      • Kaltenbach T.
      • Anderson J.C.
      • Burke C.A.
      • et al.
      Endoscopic removal of colorectal lesions—recommendations by the US Multi-Society Task Force on Colorectal Cancer.
      ,
      • Ferlitsch M.
      • Moss A.
      • Hassan C.
      • et al.
      Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline.
      ,
      • Nagtegaal I.D.
      • Odze R.D.
      • Klimstra D.
      • et al.
      The 2019 WHO classification of tumours of the digestive system.
      A resection margin is considered free if it is >1-mm free margin, based on the fact that indeterminate margins or margins <1 mm are associated with high recurrence rates of 15% to 20%.
      • Butte J.M.
      • Tang P.
      • Gonen M.
      • et al.
      Rate of residual disease after complete endoscopic resection of malignant colonic polyp.
      For submucosal invasion, additional reporting on maximum depth of invasion (taken from the lowest fiber of the muscularis mucosae) and lymphatic and/or venous infiltration is recommended because it predicts lymph node metastasis.
      • Beaton C.
      • Twine C.P.
      • Williams G.L.
      • et al.
      Systematic review and meta-analysis of histopathological factors influencing the risk of lymph node metastasis in early colorectal cancer.
      Tumor cell budding appears to be a promising marker for lymph node metastasis as well and has been found to have therapeutic consequences in sporadic lesions.
      • Beaton C.
      • Twine C.P.
      • Williams G.L.
      • et al.
      Systematic review and meta-analysis of histopathological factors influencing the risk of lymph node metastasis in early colorectal cancer.
      Although the role of tumor budding in the setting of IBD is presently unclear, a study reported the prognostic value of tumor budding of CD-associated small-bowel carcinomas.
      • Arpa G.
      • Grillo F.
      • Giuffrida P.
      • et al.
      Separation of low- versus high-grade Crohn's disease-associated small bowel carcinomas is improved by invasive front prognostic marker analysis.
      Therefore, we suggest including tumor cell budding in the histology report after endoscopic resection of HR-CAN.

      Statement 14: After complete endoscopic resection of HR-CAN, assessment of local recurrence should be performed within 3 to 6 months and annually thereafter if no residual disease is found.

      (Agreement, 88.2%; quality of evidence, limited evidence)
      To date, no studies have been conducted to assess the optimal follow-up strategy after endoscopic resection of CAN lesions. The American Society for Gastrointestinal Endoscopy– endorsed guideline recommends endoscopic surveillance between 3 and 6 months after a complete endoscopic resection in IBD patients.
      • Laine L.
      • Kaltenbach T.
      • Barkun A.
      • et al.
      SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease.
      The European Society of Gastrointestinal Endoscopy recommends performing endoscopic surveillance 3 to 6 months after the index treatment. If no recurrence is found, a follow-up total colonoscopy should be scheduled after 1 year.
      • Pimentel-Nunes P.
      • Dinis-Ribeiro M.
      • Ponchon T.
      • et al.
      Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) guideline.
      ,
      • Ferlitsch M.
      • Moss A.
      • Hassan C.
      • et al.
      Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline.
      After piecemeal resection or in cases of positive lateral margins without an indication for surgery, colonoscopy with biopsy sampling at 3 months is recommended.
      • Pimentel-Nunes P.
      • Dinis-Ribeiro M.
      • Ponchon T.
      • et al.
      Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) guideline.
      ,
      • Kaltenbach T.
      • Anderson J.C.
      • Burke C.A.
      • et al.
      Endoscopic removal of colorectal lesions—recommendations by the US Multi-Society Task Force on Colorectal Cancer.
      ,
      • Ferlitsch M.
      • Moss A.
      • Hassan C.
      • et al.
      Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline.
      A recent randomized controlled trial by Nakajima et al
      • Nakajima T.
      • Sakamoto T.
      • Hori S.
      • et al.
      Optimal surveillance interval after piecemeal endoscopic mucosal resection for large colorectal neoplasia: a multicenter randomized controlled trial.
      studied the optimal interval for surveillance after piecemeal resection in non-IBD patients. All patients underwent postprocedural surveillance colonoscopy at 6, 12, and 24 months. The intervention group underwent an additional colonoscopy at 3 months. No significant differences in recurrence were observed between both groups.
      • Nakajima T.
      • Sakamoto T.
      • Hori S.
      • et al.
      Optimal surveillance interval after piecemeal endoscopic mucosal resection for large colorectal neoplasia: a multicenter randomized controlled trial.
      Therefore, agreement was reached that endoscopic surveillance should be performed within 3 to 6 months and annually thereafter if no residual disease is found after complete endoscopic resection of HR-CAN.

      Discussion

      The lack of high-quality evidence is the main limitation of this Delphi study. However, the methodologically rigorous and structured approach using a 3-step voting process allowed us to achieve consensus on the important and clinically relevant issues described here. The international expert panel from 12 different countries covered, in our view, the expertise relevant for the issues in question.
      In conclusion, this is the first step in developing international consensus–based recommendations for endoscopic management of HR-CAN. Although the quality of available evidence was considered low, consensus was reached on several aspects of the management of HR-CAN. The present work and proposed standardization might be a useful foundation for future studies by offering greater standardization to the approach to colorectal CAN.

      Appendix 1

      Search strings of the population, intervention, comparison, and outcomes

      Statement 3: Nonpolypoid lesions and large (>20 mm) nonpedunculated colon polyps should be considered high-risk CAN.
      Population, intervention, comparison, and outcomes
      Tabled 1
      QuestionWhich polyps have the highest risk for progression to cancer in IBD?
      PIBD patients with nonpolypoid or large (>20 mm) polyps
      IAll polyps
      CA specific risk profile based on descriptive features gross morphology and (virtual) chromoendoscopy
      OPercentage of risk of progression to cancer, risk of metachronous CAN
      Search string: population, intervention, comparison, and outcomes
      ((Inflammatory Bowel Diseases [MeSH Terms]) OR (Inflammatory Bowel Disease∗[Title/Abstract]) OR (inflammatory bowel disorder[Title/Abstract]) OR (IBD[Title/Abstract]) OR (colitis [MeSH Terms]) OR (colitis[Title/Abstract]) OR (ulcerative colitis[Title/Abstract]) OR (colitis ulcerosa[Title/Abstract]) OR (colitis, ulcerative[Title/Abstract]) OR (colitis gravis[Title/Abstract]) OR (proctocolitis[Title/Abstract]) OR (ulcerative proctocolitis[Title/Abstract]) OR (UC[Title/Abstract]) OR (Crohn Disease[Title/Abstract]) OR (Crohn’s Disease[Title/Abstract]) OR (CD[Title/Abstract]) OR (inflammation AND colon[Title/Abstract]))
      AND
      ((polyps [MeSH Terms] OR (polyp∗[Title/Abstract]) OR (lesion[Title/Abstract])) AND ((non-polypoid [Title/Abstract] OR non-pedunculated [Title/Abstract] OR large [Title/Abstract] OR >20mm [Title/Abstract]) AND (Intestine, large [MeSH Terms]) OR (Large intestine [Title/Abstract]) OR (Cecum[Title/Abstract]) OR (Colon[Title/Abstract]) OR (Colon ascendens[Title/Abstract]) OR (Ascending colon[Title/Abstract]) OR (Colon descendens[Title/Abstract]) OR (Descending colon[Title/Abstract]) OR (Proximal colon[Title/Abstract]) OR (Distal colon[Title/Abstract]) OR (Sigmoid[Title/Abstract]) OR (Sigmoid colon[Title/Abstract]) OR (Rectum[Title/Abstract]) OR (Colorectal[Title/Abstract])))
      AND
      ((Colorectal Neoplasms [MeSH Terms]) OR (colorectal neoplasm∗[Title/Abstract]) OR (Intestinal Neoplasms [MeSH Terms]) OR (intestinal neoplasm∗[Title/Abstract]) OR (neoplasms [MeSH Terms]) OR (neoplas∗[Title/Abstract]) OR (precancerous conditions [MeSH Terms]) OR (precancerous condition∗[Title/Abstract]) OR (cancer) OR (carcinoma∗) OR (adenocarcinoma [MeSH Terms]) OR (adenocarcinoma∗[Title/Abstract]) OR (malignancy[Title/Abstract]) OR (dysplasia[Title/Abstract]) OR (high-grade dysplasia[Title/Abstract]) OR (HGD[Title/Abstract]) OR (low-grade dysplasia[Title/Abstract]) OR (LGD[Title/Abstract]) OR (CRC[Title/Abstract]))
      Hits: 2.747
      Statement 8: HR-CAN should preferably be removed en bloc to lower the risk of recurrence and optimize the histologic assessment.
      Population, intervention, comparison, and outcomes
      Tabled 1
      QuestionIs en bloc resection preferred over a piecemeal resection for endoscopic resection of colitis-associated dysplasia?
      PPatients with HR-CAN in IBD
      IEn-bloc resection
      CPiecemeal resection
      OProgression to cancer, recurrence, need for surgery <12-24 months, histologic assessment
      Search string: population, intervention, comparison, and outcomes
      ((Inflammatory Bowel Diseases [MeSH Terms]) OR (Inflammatory Bowel Disease∗) OR (inflammatory bowel disorder) OR (IBD) OR (colitis [MeSH Terms]) OR (colitis) OR (ulcerative colitis) OR (colitis ulcerosa) OR (colitis, ulcerative) OR (colitis gravis) OR (proctocolitis) OR (ulcerative proctocolitis) OR (UC) OR (Crohn Disease) OR (Crohn’s Disease) OR (CD) OR (inflammation AND colon))
      AND
      ((Colorectal Neoplasms [MeSH Terms]) OR (colorectal neoplasm∗) OR (Intestinal Neoplasms [MeSH Terms]) OR (intestinal neoplasm∗) OR (neoplasms [MeSH Terms]) OR (neoplas∗) OR (precancerous conditions [MeSH Terms]) OR (precancerous condition∗) OR (cancer) OR (carcinoma∗) OR (adenocarcinoma [MeSH Terms]) OR (adenocarcinoma∗) OR (malignancy) OR (dysplasia) OR (high-grade dysplasia) OR (HGD) OR (low-grade dysplasia) OR (LGD) OR (CRC))
      AND
      ((en bloc resection) AND ((endoscopic mucosal resection) OR (EMR) OR (endoscopic submucosal dissection) OR (ESD) OR (endoscopic full thickness resection) OR (eFTR))
      AND
      (((piecemeal) AND (endoscopic mucosal resection) OR (EMR) OR (endoscopic resection)) OR (pEMR) OR (snare) OR (polypectomy)))
      Hits: 29
      Statement 9: HR-CAN <20 mm with good lifting (Kato I and II) can be removed using en-bloc (including underwater) EMR.
      Population, intervention, comparison, and outcomes
      Tabled 1
      QuestionCan en-bloc (underwater) EMR be performed for HR-CAN <20 mm with good lifting (Kato I and II)?
      PPatients with HR-CAN <20 mm with good lifting (Kato I and II)
      IEn-bloc (underwater) EMR
      COther techniques of resection
      OProgression to cancer, recurrence, need for surgery <12-24 months, histologic assessment
      Search string: population, intervention, comparison, and outcomes
      ((Inflammatory Bowel Diseases [MeSH Terms]) OR (Inflammatory Bowel Disease∗) OR (inflammatory bowel disorder) OR (IBD) OR (colitis [MeSH Terms]) OR (colitis) OR (ulcerative colitis) OR (colitis ulcerosa) OR (colitis, ulcerative) OR (colitis gravis) OR (proctocolitis) OR (ulcerative proctocolitis) OR (UC) OR (Crohn Disease) OR (Crohn’s Disease) OR (CD) OR (inflammation AND colon))
      AND
      ((Colorectal Neoplasms [MeSH Terms]) OR (colorectal neoplasm∗) OR (Intestinal Neoplasms [MeSH Terms]) OR (intestinal neoplasm∗) OR (neoplasms [MeSH Terms]) OR (neoplas∗) OR (precancerous conditions [MeSH Terms]) OR (precancerous condition∗) OR (cancer) OR (carcinoma∗) OR (adenocarcinoma [MeSH Terms]) OR (adenocarcinoma∗) OR (malignancy) OR (dysplasia) OR (high-grade dysplasia) OR (HGD) OR (low-grade dysplasia) OR (LGD) OR (CRC))
      AND
      ((en bloc resection) AND ((endoscopic mucosal resection) OR (EMR) OR (UEMR)))
      AND
      ((good lifting) OR (Kato I) OR Kato (II) OR (lifting) OR submucosal fibrosis))
      Hits: 9
      Statement 10: HR-CAN <20 mm without good lifting (Kato III and IV) or HR-CAN >20 mm without signs of deep submucosal invasion should be removed with techniques that preferably allow en-bloc resection.
      Population, intervention, comparison, and outcomes
      Tabled 1
      QuestionCan en bloc be performed for HR-CAN <20 mm without good lifting (Kato III and IV) or HR-CAN >20 mm without signs of deep submucosal invasion?
      PPatients with HR-CAN <20 mm without good lifting (Kato III and IV) or HR-CAN >20 mm without signs of deep submucosal invasion
      ITechniques allowing en-bloc resection
      COther techniques of resection
      OProgression to cancer, recurrence, need for surgery <12-24 months, histologic assessment
      Search string: population, intervention, comparison, and outcomes
      ((Inflammatory Bowel Diseases [MeSH Terms]) OR (Inflammatory Bowel Disease∗) OR (inflammatory bowel disorder) OR (IBD) OR (colitis [MeSH Terms]) OR (colitis) OR (ulcerative colitis) OR (colitis ulcerosa) OR (colitis, ulcerative) OR (colitis gravis) OR (proctocolitis) OR (ulcerative proctocolitis) OR (UC) OR (Crohn Disease) OR (Crohn’s Disease) OR (CD) OR (inflammation AND colon))
      AND
      ((Colorectal Neoplasms [MeSH Terms]) OR (colorectal neoplasm∗) OR (Intestinal Neoplasms [MeSH Terms]) OR (intestinal neoplasm∗) OR (neoplasms [MeSH Terms]) OR (neoplas∗) OR (precancerous conditions [MeSH Terms]) OR (precancerous condition∗) OR (cancer) OR (carcinoma∗) OR (adenocarcinoma [MeSH Terms]) OR (adenocarcinoma∗) OR (malignancy) OR (dysplasia) OR (high-grade dysplasia) OR (HGD) OR (low-grade dysplasia) OR (LGD) OR (CRC))
      AND
      ((en bloc resection) OR (endoscopic submucosal dissection) OR (ESD) OR (EMR))
      AND
      ((non-lifting) OR (Kato III) OR Kato (IV) OR (lifting) OR submucosal fibrosis))
      Hits: 17
      Statement 11: Endoscopic local excision of HR-CAN should be performed by endoscopists with sufficient skills in both EMR and ESD techniques.
      Population, intervention, comparison, and outcomes
      Tabled 1
      QuestionShould endoscopic resection of HR-CAN be formed by skilled/expert endoscopists?
      PPatients with HR-CAN suitable for endoscopic resection
      ISkilled/expert endoscopists
      CAll endoscopists
      OProgression to cancer, recurrence, need for surgery <12-24 months, histologic assessment
      Search string: population, intervention, comparison, and outcomes
      ((Inflammatory Bowel Diseases [MeSH Terms]) OR (Inflammatory Bowel Disease∗[Title/Abstract]) OR (inflammatory bowel disorder[Title/Abstract]) OR (IBD[Title/Abstract]) OR (colitis [MeSH Terms]) OR (colitis[Title/Abstract]) OR (ulcerative colitis[Title/Abstract]) OR (colitis ulcerosa[Title/Abstract]) OR (colitis, ulcerative[Title/Abstract]) OR (colitis gravis[Title/Abstract]) OR (proctocolitis[Title/Abstract]) OR (ulcerative proctocolitis[Title/Abstract]) OR (UC[Title/Abstract]) OR (Crohn Disease[Title/Abstract]) OR (Crohn’s Disease[Title/Abstract]) OR (CD[Title/Abstract]) OR (inflammation AND colon[Title/Abstract]))
      AND
      ((Colorectal Neoplasms [MeSH Terms]) OR (colorectal neoplasm∗ [Title/Abstract]) OR (Intestinal Neoplasms [MeSH Terms]) OR (intestinal neoplasm∗) OR (neoplasms [MeSH Terms]) OR (neoplas∗) OR (precancerous conditions [MeSH Terms]) OR (precancerous condition∗) OR (cancer) OR (carcinoma∗) OR (adenocarcinoma [MeSH Terms]) OR (adenocarcinoma∗) OR (malignancy) OR (dysplasia) OR (high-grade dysplasia) OR (HGD) OR (low-grade dysplasia) OR (LGD) OR (CRC))
      AND
      ((skilled) OR (expert) OR (skilled endoscopist∗) OR (expert endoscopist∗) OR (tertiary referral center) OR (expert center))
      AND
      ((en bloc resection) AND ((endoscopic mucosal resection) OR (EMR) OR (endoscopic submucosal dissection) OR (ESD) OR (endoscopic full thickness resection) OR (eFTR) OR (piecemeal) AND (endoscopic mucosal resection) OR (EMR) OR (endoscopic resection) OR (pEMR) OR (snare) OR (polypectomy))
      Hits: 3
      Population, intervention, comparison, and outcomes
      Tabled 1
      QuestionCan en-bloc resection be performed for HR-CAN >20 mm without signs of deep submucosal invasion?
      PPatients with HR-CAN >20 mm without signs of deep submucosal invasion
      IEn-bloc resection
      COther techniques of resection
      OProgression to cancer, recurrence, need for surgery <12-24 months, histologic assessment
      Search string: population, intervention, comparison, and outcomes
      ((Inflammatory Bowel Diseases [MeSH Terms]) OR (Inflammatory Bowel Disease∗) OR (inflammatory bowel disorder) OR (IBD) OR (colitis [MeSH Terms]) OR (colitis) OR (ulcerative colitis) OR (colitis ulcerosa) OR (colitis, ulcerative) OR (colitis gravis) OR (proctocolitis) OR (ulcerative proctocolitis) OR (UC) OR (Crohn Disease) OR (Crohn’s Disease) OR (CD) OR (inflammation AND colon))
      AND
      ((Colorectal Neoplasms [MeSH Terms]) OR (colorectal neoplasm∗) OR (Intestinal Neoplasms [MeSH Terms]) OR (intestinal neoplasm∗) OR (neoplasms [MeSH Terms]) OR (neoplas∗) OR (precancerous conditions [MeSH Terms]) OR (precancerous condition∗) OR (cancer) OR (carcinoma∗) OR (adenocarcinoma [MeSH Terms]) OR (adenocarcinoma∗) OR (malignancy) OR (dysplasia) OR (high-grade dysplasia) OR (HGD) OR (low-grade dysplasia) OR (LGD) OR (CRC))
      AND
      ((en bloc resection) OR (endoscopic submucosal dissection) OR (ESD))
      AND
      ((large polyp∗) OR (> 20 millimetres) OR (>20 mm))
      Hits: 46
      HR-CAN, High-risk colitis-associated neoplasia; IBD, inflammatory bowel disease.

      Appendix 2

      Detailed overview of the third and final round of voting for consensus agreement (n = 17) and assessment of quality of evidence (n = 15)

      Statement 1: We suggest to adopt the term colitis-associated neoplasia (CAN) for all neoplastic lesions detected in a section of previously or presently inflamed colon.
      Tabled 1
      Strongly disagree0%
      Disagree0%
      Neutral0%
      Agree52.9%
      Strongly agree47.1%
      No evidence40%
      Conflicting evidence6.7%
      Limited evidence33.3%
      Moderate evidence20%
      Strong evidence0%
      Agreement: 100%
      Quality of evidence: no evidence
      Statement 2: Extent of previous or present inflammation should have been or should be confirmed by endoscopy and/or histology.
      Tabled 1
      Strongly disagree0%
      Disagree0%
      Neutral0%
      Agree76.5%
      Strongly agree23.5%
      No evidence33.3%
      Conflicting evidence13.3%
      Limited evidence26.7%
      Moderate evidence26.7%
      Strong evidence0%
      Agreement: 100%
      Quality of evidence: no evidence
      Statement 3: Nonpolypoid lesions and large (>20 mm) nonpedunculated colon polyps should be considered high-risk CAN.
      Tabled 1
      Strongly disagree0%
      Disagree5.9%
      Neutral5.9%
      Agree58.8%
      Strongly agree29.4%
      No evidence20%
      Conflicting evidence20%
      Limited evidence40%
      Moderate evidence20%
      Strong evidence0%
      Agreement: 88.2%
      Quality of evidence: limited evidence
      Statement 4: Careful examination of the colon (preferably using enhanced endoscopic imaging) should precede local excision of HR-CAN.
      Tabled 1
      Strongly disagree0%
      Disagree0%
      Neutral0%
      Agree17.6%
      Strongly agree82.4%
      No evidence6.7%
      Conflicting evidence6.7%
      Limited evidence13.3%
      Moderate evidence60%
      Strong evidence13.3%
      Agreement: 100%
      Quality of evidence: moderate evidence
      Statement 5: An HR-CAN lesion is considered endoscopically resectable if
      • 1.
        The lesion has distinct margins
      • 2.
        The lesion can (preferably) be removed en bloc with clear deep and lateral resection margins
      and there is no evidence of
      • 3.
        Synchronous invisible dysplasia
      • 4.
        Moderate-to-severe inflammation of mucosa surrounding the area with HR-CAN interfering with delineation of the lesion
      • 5.
        Signs of deep submucosal invasion.
      Tabled 1
      Strongly disagree0%
      Disagree23.5%
      Neutral0%
      Agree47.1%
      Strongly agree29.4%
      No evidence20%
      Conflicting evidence0%
      Limited evidence46.6%
      Moderate evidence26.7%
      Strong evidence6.7%
      Agreement: 76.5%
      Quality of evidence: limited evidence
      Statement 6: Surgical resection is indicated when HR-CAN is nonresectable.
      Tabled 1
      Strongly disagree0%
      Disagree0%
      Neutral0%
      Agree47.1%
      Strongly agree52.9%
      No evidence26.7%
      Conflicting evidence0%
      Limited evidence20%
      Moderate evidence40%
      Strong evidence13.3%
      Agreement: 100%
      Quality of evidence: moderate evidence
      Statement 7: All suspected HR-CANs should be assessed according to a standardized approach and recorded to the endoscopy report. The description should include at least the following features:
      • 1.
        Size, delineation, and location
      • 2.
        Description of gross morphology
        • a.
          Granular/nongranular
        • b.
          Paris classification
      • 2.
        Assessment of the pit and vascular pattern using enhanced endoscopic imaging
      • 3.
        Assessment of endoscopic activity of the colitis in the segment, harboring the dysplastic lesion (eg, using the Mayo subset index, UC endoscopic index of severity, or simple endoscopic score for CD).
      Tabled 1
      Strongly disagree0%
      Disagree0%
      Neutral5.9%
      Agree41.2%
      Strongly agree52.9%
      No evidence26.7%
      Conflicting evidence0%
      Limited evidence33.3%
      Moderate evidence33.3%
      Strong evidence6.7%
      Agreement: 94.1%
      Quality of evidence: limited evidence
      Statement 8: HR-CAN should preferably be removed en bloc to lower the risk of recurrence and optimize the histologic assessment.
      Tabled 1
      Strongly disagree0%
      Disagree0%
      Neutral5.8%
      Agree47.1%
      Strongly agree47.1%
      No evidence26.7%
      Conflicting evidence6.6%
      Limited evidence40%
      Moderate evidence26.7%
      Strong evidence0%
      Agreement: 94.1%
      Quality of evidence: limited evidence
      Statement 9: HR-CAN <20 mm with good lifting (Kato I and II) can be removed using en-bloc (including underwater) EMR.
      Tabled 1
      Strongly disagree0%
      Disagree0%
      Neutral5.9%
      Agree76.5%
      Strongly agree17.6%
      No evidence20%
      Conflicting evidence6.7%
      Limited evidence40%
      Moderate evidence33.3%
      Strong evidence0%
      Agreement: 94.1%
      Quality of evidence: moderate evidence
      Statement 10: HR-CAN <20 mm without good lifting (Kato III and IV) or HR-CAN >20 mm without signs of deep submucosal invasion should be removed with techniques that preferably allow en-bloc resection.
      Tabled 1
      Strongly disagree5.9%
      Disagree0%
      Neutral11.8%
      Agree47.1%
      Strongly agree35.3%
      No evidence40%
      Conflicting evidence6.7%
      Limited evidence20%
      Moderate evidence33.3%
      Strong evidence0%
      Agreement: 82.4%
      Quality of evidence: no evidence
      Statement 11: Endoscopic local excision of HR-CAN should be performed by endoscopists with sufficient skills in both EMR and ESD techniques.
      Tabled 1
      Strongly disagree5.9%
      Disagree0%
      Neutral5.9%
      Agree29.4%
      Strongly agree58.8%
      No evidence40%
      Conflicting evidence6.7%
      Limited evidence40%
      Moderate evidence13.3%
      Strong evidence0%
      Agreement: 88.2%
      Quality of evidence: no evidence
      Statement 12: Endoscopic resection should be captured by recording
      • 1.
        Technical success
        • a.
          En-bloc resection
        • b.
          R0 resection
        • c.
          Adverse events (intra- or postprocedural bleeding, perforation, postcoagulation syndrome, need of emergency surgery, other)
      • 2.
        Outcomes
        • a.
          Local recurrence at 6 months and 3 years
        • b.
          Surgery for recurrence after 1, 3, and 5 years.
      Tabled 1
      Strongly disagree0%
      Disagree11.8%
      Neutral5.9%
      Agree58.9%
      Strongly agree23.5%
      No evidence53.3%
      Conflicting evidence0%
      Limited evidence53.3%
      Moderate evidence6.6%
      Strong evidence0%
      Agreement: 82.4%
      Quality of evidence: no evidence
      Statement 13: The histologic report should at least include the following items:
      • 1.
        Size (in mm)
      • 2.
        Grade of dysplasia according the World Health Organization classification
      • 3.
        Lateral resection margin (in mm, free if >.1 mm)
      • 4.
        Deep resection margin (in mm, free if >.1 mm)
      In case of submucosal invasion:
      • 1.
        Maximum depth of submucosal (Sm) invasion in μm (taken from the deepest margin of the muscularis mucosae)
      • 2.
        Lymphatic and/or venous invasion confirmed with D2-40 immunohistochemistry
      • 3.
        Tumor budding (Bd1-3) according to the International Tumor Budding Consensus Conference
      • 4.
        Grade of differentiation according to World Health Organization classification.
      Tabled 1
      Strongly disagree0%
      Disagree5.9%
      Neutral0%
      Agree52.9%
      Strongly agree41.2%
      No evidence33.3%
      Conflicting evidence13.4%
      Limited evidence26.7%
      Moderate evidence13.3%
      Strong evidence13.3%
      Agreement: 94.1%
      Quality of evidence: no evidence
      Statement 14: After complete endoscopic resection of HR-CAN, assessment of local recurrence should be performed within 3 to 6 months and annually thereafter if no residual disease is found.
      Tabled 1
      Strongly disagree0%
      Disagree0%
      Neutral11.8%
      Agree64.7%
      Strongly agree23.5%
      No evidence33.3%
      Conflicting evidence0%
      Limited evidence46.7%
      Moderate evidence20%
      Strong evidence0%
      Agreement: 88.2%
      Quality of evidence: limited evidence

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