Dra. Beatriz Sicilia
Hospital Universitario de Burgos
Dra. Lara Arias
Hospital Universitario de Burgos
Dra. Raquel Vicente
Hospital Universitario Miguel Servet. Zaragoza

Patients with inflammatory bowel disease (IBD) of the colon have a higher risk of developing colorectal cancer (CRC) than the general population, with a prevalence of 3.7% and an incidence of 2% at 10 years according to established studies with an evident selection bias1. In the meta-analysis carried out in the Hospital de la Princesa, although this incidence has decreased in recent decades, it is still estimated that the risk of CRC is 1.21 times higher to that of the general population2.

The efficacy of the screening programme using colonoscopy in patients with IBD has not been assessed in randomised controlled trials. A Cochrane Review concludes that “there is no clear evidence that surveillance colonoscopy prolongs survival in patients with extensive colitis”3; however, it is true that, in the context of a follow-up programme, cancers are diagnosed at an earlier stage with a better prognosis, and, furthermore, indirect evidence has been found in retrospective case-control studies of a decrease in the death of patients with IBD associated with cancer diagnosed in follow-up programmes4,5,6. A retrospective population-based study reported a survival of 100% in CRC diagnosed in a follow-up programme compared to 74% in CRC cancers diagnosed outside of screening (p=0.042)7. In a recent Cochrane Review8 published in 2018 involving 7199 patients, all included in observational studies, it was concluded that the detection of CRC is significantly greater in the group without endoscopic follow-up (3.2%, 135/4256) compared to the endoscopic follow-up group (1.8%, 53/2895) (OR 0.58 (95%) CI: 0.42–0,80), p<0.001. Furthermore, endoscopic monitoring has been associated with a decrease in death due to CRC (8.5% vs 22.3%) (OR 0.36 (95% CI: 0.19–0.69), p=0.002) and an increase in the detection of CRC at early stages (15.5.% vs 7.7) (OR 5.40 (95% CI: 1.51–19.30), p=0.009).

Classically, patients with longstanding IBD were followed up with a conventional endoscope and with random biopsies. A total of 34 biopsies of all segments were required to detect dysplasia with a probability of 90%, and this number (64 biopsies) would have to be doubled if you wanted to increase this interval to 95%9. It is estimated that with this strategy, approximately 1 case of dysplasia is detected out of every 1505 biopsies performed10. However, in recent years, with improvements and advances in endoscopic technology, previously invisible dysplastic lesions will become visible11.

CHROMOENDOSCOPY

Several advanced endoscopy techniques are currently available and have been studied for their use in this specific scenario: comparing them with high-definition endoscopy (HDWLE) or with each other (dye chromoendoscopy or DCE), virtual chromoendoscopy (VCE), narrow band imaging (NBI or i-scan), and autofluorescence imaging (AFI). The results have been included in 4 meta-analyses12,13,14,15 with results that are not comparable with each other, as the selection criteria vary (some include conference abstracts, others include only randomised controlled trials (RCT) other RCTs and observational studies), which, added to the high heterogeneity and low quality of some of the studies, makes it difficult to draw conclusions.

Section II.4.2. Video 1: Panchromoendoscopy with indigo carmine 0.4% in a patient with ulcerative colitis of 18 years’ duration. Use of a spray catheter with visualization of the innominate lines and rounded and dotted crypts of the normal mucosa. Visualization of a flat-elevated lesion with well-defined margins and a minimally excavated center and a sessile, rounded lesion with a type IIIL mucosal pattern.

The randomised controlled trial (RCT) that showed the usefulness of dye-based chromoendoscopy (DCE) (Video 1) compared with white light for dysplasia detection in patients with longstanding IBD was published in 2003 by Kiesslich et al16. Later 5 further clinical trials were included in a meta-analysis17 published in 2011 with a total of 1277 patients that clearly showed the superiority of DCE both in the global detection of dysplastic lesions as well as in the detection of flat dysplastic lesions, multiplying this probability by 2-3 in the percentage of dysplasia detection per patient and by 4-5 in the detection of dysplasia per lesion. Therefore, the difference in dysplasia detection between chromoendoscopy and white light is 7% [IC 95%: 3.2-11.3] in the analysis per patient with a number needed to treat (NNT) of 14.3; with an absolute difference in lesions detected by targeted biopsies of 44% [IC95% 28.6-59.1] and flat lesions 27% [IC 95% 11.3-41.9], both favouring chromoendoscopy.

In the Italian meta-analysis13, the DCE method is significantly superior to HDWLE (5 studies included) with an OR of 4.218 IC95%: 1.240-14.345). These results have not been confirmed, however, in a more recent publication that only includes the 2 RCTs15 published up to that time. More recently a new RCT has shown the superiority of DCE over HDWLE18, obtaining similar real-life results published in the Spanish multi-centre series (Grupo endoCAR)19.

When analysing the usefulness of virtual chromoendoscopy (NBI/i-scan) (Video 2) compared to white light (WLE), none of the initially published clinical trials demonstrated its superiority20,21,22 and when the 3 RCTs that compared both the VCE technique (161 patients) with HDWLE (171 patients)23 were included, no differences were found in the detection of dysplasia per patient (RR 0.72; IC95%: 0.45-1.15). On the contrary, findings showed a statistical difference in favour of HDWLE in the screening analysis for lesion detection with dysplasia (RR 0.64; IC95% 0.48-0.90) without finding heterogeneity in either analyses (I2=0%) but decreasing the quality of the evidence due to imprecision in both.

Section II.4.2. Video 2: Crohn’s disease of the colon. Exploration with NBI in a patient with colonic CD of 15 years’ duration. You can see the brownish vascular network of the normal mucosa, the remains of feces in fuchsia color. Two flat lesions of about 4mm are observed that are difficult to visualize with white light. With NBI the lesions are more contrasted and are hypovascular, suggesting hyperplastic polyps.

The first study on the usefulness of dye chromoendoscopy (DCE) compared to virtual chromoendoscopy (VCE) was designed by the group of the Hospital Clínico Universitario de Barcelona, through a randomised control trial24 with 80 patients with longstanding IBD, undergoing dye chromoendoscopy and NBI endoscopy less than 8 weeks apart. No significant differences were detected in the diagnosis of dysplastic lesions, with chromoendoscopy being significantly superior in detecting lesions of any type. On account of these findings and assuming a 20% loss of lesions in screening colonoscopy in the normal population, which can be as high as 40% in a population with IBD, with NBI 6 lesions would be lost in absolute terms to the 2 lost by chromoendoscopy; therefore, chromoendoscopy is recommended above NBI in this specific scenario. A later Australian study with the same methodology endorsed these outcomes25. More recently, the Leuven group26 from Birmingham27, and once again a Spanish RCT28, published the results of their clinical trials using a different methodology by randomising patients to undergo a VCE or DCE. No differences were found between the 2 techniques in both studies in detecting dysplasia; however, this parallel methodology does not provide an estimate of dysplastic lesion losses in the same patient.

With this available evidence, multiple national and international clinical and endoscopic guidelines consider dye-based chromoendoscopy (DCE) as the gold standard technique for the screening of CRC in patients with longstanding IBD or with high risk of CRC. Examples are the British guidelines and the European guidelines (ECCO) with a level of evidence of 2 and grade B recommendation. The SCENIC international consensus31,32, endorsed by the American Society for Gastrointestinal Endoscopy (ASGE), states that when follow-up is performed with low-definition endoscopes, chromoendoscopy is recommended over high-definition endoscopy with moderate quality of evidence, and when high-definition endoscopes are used, chromoendoscopy is recommended over high-definition endoscopy with low quality of evidence. This SCENIC consensus31,32 has subsequently been endorsed by the Asian Pacific Association of Gastroenterology (APAGE)33 and the British Society of Gastroenterology (BSG)34. Recently the European Society of Gastrointestinal Endoscopy (ESGE)35 and the American Gastroenterology Association (AGA)36 have recommended the use of both types of chromoendoscopy (virtual or dye) for the screening of CRC in our patients with longstanding IBD of the colon if high-definition endoscopes (HDWLE) are available. The European guidelines explicitly state that initial training with DCE should be provided in order to gradually implement, if desired, VCE. These recommendations are set out in Table I.

Table 1. Recommendations for screening for cancer associated with colitis according to different guidelines.

Section II.4.2. Table 1: Recommendations for screening for cancer associated with colitis according to different guidelines.

IMPLEMENTATION OF CHROMOENDOSCOPY IN ENDOSCOPY UNITS. BARRIERS

However, despite all this scientific evidence in favour of the use of either virtual or dye-based chromoendoscopy, the implementation of both techniques in endoscopy units is slow, mainly due to a number of barriers, as discussed by a number of international experts who have already published in 2016 a consensus document37:

a. Barriers dependent on health personnel (doctors, nurses):

  • Lack of knowledge of technique and how to gain it. In this regard, it must be borne in mind that many endoscopists were trained before the era of image-enhanced endoscopy and the dependent observer variability also puts a certain brake on learning.
  • Variations in tools for the detection, diagnosis and resection of dysplasia, especially dysplasia in flat lesions.
  • Scepticism on the evidence for chromoendoscopy as the gold standard technique in this scenario. To improve this aspect, the first critical step is the acceptance by practitioners of the need to change their IBD surveillance practice based on such evidence. In this regard, the uniform guidelines for the use of chromoendoscopy (virtual or dye) as the choice technique in the surveillance and management of dysplasia in IBD are key tools.

a. Patient-dependent barriers:

  • Acceptation of screening methods. Despite improvements in endoscopic technique, colon preparation and sedation, there are still some patients who are reluctant to undergo endoscopy.
  • Insufficient endoscopic preparation due to problems or individual characteristics of certain patients (elderly patients, previous abdominal surgery, renal insufficiency, etc.), as well as inadequate preparation by the patient.

c. Global barriers:

  • The need for accessory equipment and supplies
  • The need for more time per procedure and the resulting management of endoscopy units with long waiting lists
  • Lack of coding of screening other than colonoscopy due to complexity and cost
  • Like of quality outcomes for follow-up of CRC in those patients with IBD (survival, reduced incidence of CRC, mortality, etc.)

RECOMMENDATIONS TO FACILITATE THE IMPLEMENTATION OF CHROMOENDOSCOPY TECHNIQUES IN ENDOSCOPY UNITS

Once the main barriers to the implementation of DCE in our units have been identified, this same consensus document recommends the following37:

  1. Systematic training using atlases, videos, web-based learning, attendance at specific courses and workshops, using detailed existing algorithms to perform pancolic DCE in IBD38,39
    • Learning and use of standardised terminology to characterise endoscopic and histological lesions of dysplasia (fig. 1, fig. 2, fig. 3 and fig. 4)
    • Uniformity in the notification of dysplasia and CRC to allow comparison of results between monitoring programmes
    • Knowledge of monitoring intervals and indications of DCE
  2. Familiarisation of the endoscopists in DCE protocols, both in equipment and material needed:
    • Type of endoscope and magnification (if possible),
    • Contrast agent and its concentration: indigo carmine/methylene blue,
    • Method of contrast application: use of spray catheter,
    • Inspection method with ability to discern lesions that are endoscopically resectable or otherwise refer for surgery,
    • Endoscopic resection techniques31,32,38.
  3. Hands-on learning with an experienced DCE endoscopist performing at least 5 DCE procedures.
  4. Quality monitoring by recording own dysplasia detection data and follow-up intervals.
    • Photo-documentation of injuries, important both as a quality item and for shared decision-making that may also have medical-legal implications. Images (photos or videos) should record landmarks in the colon (ileocecal valve, appendix, terminal ileum), the extent and severity of inflammation if present, the presence of strictures and perianal disease. Images of each focal lesion should also be obtained before and after staining, in addition to documenting the submucosal injection technique in the resections, the completeness of the resection and tattoos applied to lesions of concern (e.g. large unresected lesions or lesions with multiple or incomplete resections) may be documented.
    • Quality of endoscopic preparation.
    • Follow-up of dysplasia according to established algorithms.
    • Monitoring and review of quality measures, with the ultimate goal of avoiding unnecessary colectomies (proportion of procedures in which targeted biopsies are performed), proportion of patients detected with dysplasia, or with flat lesions, proportion of complete resection of lesions with dysplasia and interval cancer rate).

More recently the position of the European Society of Gastrointestinal Endoscopy (ESGE) for optical diagnostic training40 of neoplastic lesions in patients with IBD recommends the following steps in order to be able to perform a quality chromoendoscopy:

  1. Because there is no validated optical diagnosis course available for detection and characterisation of neoplastic lesions in IBD, a one-week rotation with an expert in optical diagnosis of this type of lesions is recommended using DCE, supplemented by videos, atlases and websites.
  2. Subsequently, it is recommended that the endoscopist should carry out at least 20 DCE, taking at least 20 targeted biopsies with subsequent histological verification, in addition to taking random biopsies of the 4 quadrants during this training phase every 10 cm.
  3. In the third phase, performing 20 DCE targeted biopsies without random biopsies is recommended.
  4. Finally, and after adequate DCE training, gradual steps should be taken towards acquiring competence in virtual chromoendoscopy (VCE) (fig. 5) by performing 20 VCEs with targeted biopsies, maintaining random biopsies of the 4 quadrants each 10 cm, to conclude with 20 VCE with targeted biopsies alone, without random biopsies.

To conclude, an important aspect of the implementation of chromoendoscopy is cost-effectiveness assessment. Although the cost of purchasing high-quality, high-definition endoscopic equipment (endoscopes, processors, monitors, etc.) is significant, in most of our hospitals such equipment is already available and widely used. The cost of the dye is variable and depends on the concentration and volume used, but it is usually low and much cheaper still if we use the magistral formula rather than commercial preparations with the appropriate dilution. The use of the dye for perfusion in the wash bottle or pump of the endoscopic equipment can also shorten scanning time and reduce costs by saving the expense of the catheter in some scans. However, we are often going to need a catheter spray to improve the visualisation of the lesions detected.

It is estimated that the average time to take a DCE is 11 minutes (range between 9 and 12 minutes) more than that of a standard colonoscopy when both targeted and random biopsies are taken . However, random biopsies in most procedures are not necessary, saving time and also decreasing the cost of the pathology report.

Finally, efficiency could be improved if the percentage of interval cancer decreases. In this regard, a cost-effectiveness study42 comparing different follow-up strategies concludes that chromoendoscopy is more cost-effective and less expensive than white light with biopsies at all follow-up intervals.

CONCLUSIONS

  • Chromoendoscopy, whether (VCE) or dye-based (DCE) is the gold standard technique in screening for cancer associated with colitis in our patients with longstanding inflammatory bowel disease.
  • The implementation in our units must be progressive and gradual, starting with DCE training by experts and then gradually moving on to the implementation of VCE if so desired.

REFERENCES

  1. Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut. 2001;48(4):526-535.
  2. Castano-Milla C, Chaparro M, Gisbert JP. Systematic review with meta-analysis: the declining risk of colorectal cancer in ulcerative colitis. Aliment Pharmacol Ther. 2014;39(7):645-659.
  3. Collins PD, Mpofu C, Watson AJ, et al. Strategies for detecting colon cancer and/ or dysplasia in patients with inflammatory bowel disease. Cochrane Database Syst Rev 2006:CD000279
  4. Velayos FS, Loftus EV Jr, Jess T, et al. Predictive and protective factors associated with colorectal cancer in ulcerative colitis: a case-control study. Gastroenterology. 2006;130:1941–9.
  5. Karlén P, Kornfeld D, Broström O, et al. Is colonoscopic surveillance reducing colorectal cancer mortality in ulcerative colitis? A population based case control study. Gut. 1998;42:711–4.
  6. Eaden J, Abrams K, Ekbom A, et al. Colorectal cancer prevention in ulcerative colitis: a case-control study. Aliment Pharmacol Ther. 2000;14:145–53.
  7. Lutgens MW, Oldenburg B, Siersema PD, et al. Colonoscopic surveillance improves survival after colorectal cancer diagnosis in inflammatory bowel dis- ease. Br J Cancer. 2009;101:1671–5.
  8. Bye, WA, Ma C, Nguyen TM, Parker CE, Jairath V, and East JE, Strategies for detecting colorectal cancer in Patients with Inflammatory Bowel disease: A Cochrane Systematic review and Meta-Analysis. Am J Gastroenterol 2018; 113:1801–1809
  9. Rubin CE, Haggitt RC, Burmer GC, et al. DNA aneuploidy in colonic biopsies predicts future development of dysplasia in ulcerative colitis. Gastroenterology. 1992;103(5):1611-20
  10. Rutter MD, Riddell RH. Colorectal dysplasia in inflammatory bowel disease: a clinicopathologic perspective. Clin Gastroenterol Hepatol. 2014;12:359–67.
  11. Cohen-Mekelburg S, Schneider Y, Gold S, Scherl E, Steinlauf A. Advances in the Diagnosis and Management of Colonic Dysplasia in Patients With Inflammatory Bowel Disease. Gastroenterol Hepatol (N Y). 2017;13(6):357-362
  12. Bessissov T, Dulai PS, Restellini S et al. Comparison of endoscopic dysplasia detection techniques in patients with ulcerative colitis: A systematic review and network meta-analysis. Inflamm Bowel Dis 2018; 24: 2518-2526.
  13. Imperatore N, Castiglione F, Testa A, et al. Augmented Endoscopy for Surveillance of Colonic Inflammatory Bowel Disease: Systematic Review with Network Meta-analysis. Journal of Crohn’s and Colitis, 2019, 714–724
  14. Iannone A, Ruospo M, Palmer SC et al. Systematic review with network meta-analysis: endoscopic techniques for dysplasia surveillance in inflammatory bowel disease. Aliment Pharmacol Ther 2019; 50: 858-871
  15. Resende RH, Ribeiro IB, Hourneaux de Moura DT et al. Surveillance in inflammatory bowel disease: is chromoendoscopy the only way to go? A systematic review and meta-analysis of randomized clinical trials. Endoscopy International open 2020; 08: E578-590
  16. Kiesslich R, Fritsch J, Holtmann M, et al. Methylene blue-aided chromoendoscopy for the detection of intraepithelial neoplasia and colon cancer in ulcerative colitis. Gastroenterology 2003; 124:880–8.
  17. Subramanian V, Mannath J, Ragunath K, Hawkey CJ. Meta-analysis: the diagnostic yield of chromoendoscopy for detecting dysplasia in patients with colonic inflammatory bowel disease. Aliment Pharmacol Ther 2011; 33:304–12
  18. Alexandersson B, Hamad Y, Andreasson A, et al. High definition chromoendoscopy superior to high definition white light endoscopy in surveillance of inflammatory bowel disease in a randomized trial. Clin Gastroenterol and hepatol 2020; 18: 2101-2107
  19. Carballal S, Maisterra S, López-Serrano A et al; EndoCAR group of the Spanish Gastroenterological Association and Spanish Digestive Endoscopy Society. Real-life chromoendoscopy for neoplasia detection and characterisation in long-standing IBD. Gut 2018; 67: 70-8
  20. Dekker E, van den Broek FJ, Reitsma JB, et al. Narrow-band imaging compared with conventional colonoscopy for the detection of dysplasia in patients with longstanding ulcerative colitis. Endoscopy 2007; 39:216-21.
  21. Van den Broek FJ Fockens P, van Eeden S, Stokkers PC, Ponsioen CY, Reitsma JB et al. Narrow-band imaging versus high-definition endoscopy for the diagnosis of neoplasia in ulcerative colitis Endoscopy 2011; 43: 108-15
  22. Ignjatovic A, East JE, Subramanian V, Suzuki N, Guenther T, Palmer N et al. Narrow band imaging for detection of dysplasia in colitis: a randomized controlled trial Am J Gastroenterol 2012; 107: 885-90
  23. El-Dallal M, Chen Y, Lin Q, et al. Meta-analysis of virtual-based chromoendoscopy compared with dye-spraying chromoendoscopy standard and high-definition white light endoscopy in patients with inflammatory bowel disease at increased risk of colon cancer. Inflamm Bowel Dis. 2020 Aug 20; 26 (9): 1319-1329.
  24. Pellise M, Lopez-Ceron M, Rodriguez de Miguel C, et al. Narrow-band imaging as an alternative to chromoendoscopy for the detection of dysplasia in long-standing inflammatory bowel disease: a prospective, randomized, crossover study. Gastrointest Endosc. 2011;74(4):840-848.
  25. Efthymiou M, Allen PB, Taylor AC, et al. Chromoendoscopy versus narrow band imaging for colonic surveillance in inflammatory bowel disease. Inflamm Bowel Dis. 2013;19(10):2132-2138.
  26. Bisschops R, Bessissow T, Joseph JA et al. Chromoendoscopy versus narrow band imaging in UC: a prospective randomised controlled trial. Gut. 2018 jun;67(6):1087-1094
  27. Iacucci M, Kaplan GG, Panaccione R et al. A randomized trial comparing high definition colonoscopy alone with high definition dye spraying and electronic virtual chromoendoscopy for detection of colonic neoplastic lesions during IBD surveillance colonoscopy. Am J Gastroenterol. 2018 Feb;113(2):225-234
  28. González-Bernardo O, Riestra S, Vivas S, de Francisco R, Pérez-Martínez I, Castaño-García A, Jiménez-Beltrán V, Rollé V, Suárez P, Suárez A. Chromoendoscopy with indigo carmine vs virtual chromoendoscopy (i-Scan 1) for neoplasia screening in patinets with inflammatory bowel disease: a prospective randomized study. Inflamm Bowel Dis. 2021 Jul 27;27(8):1256-1262
  29. Cairns SR, Scholefield JH, Steele RJ, et al. Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002). Gut. 2010;59(5):666-689.
  30. Magro F, Gionchetti P, Eliakim R et al for the European Crohn’s and Colitis Organization [ECCO]. Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 1: Definitions, Diagnosis, Extra-intestinal Manifestations, Pregnancy, Cancer Surveillance, Surgery, and Ileo-anal Pouch Disorders. Journal of Crohn’s and Colitis, 2017, 649–670
  31. Laine L, Kaltenbach T, Barkun A, et al.; SCENIC Guideline Development Panel. SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease. Gastroenterology. 2015;148:639–51.
  32. Laine L, Kaltenbach T, Barkun A, et al.; SCENIC Guideline Development Panel. SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease. Gastrointest Endosc. 2015;81:489–501.e26
  33. Ooi CJ, Makharia GK, Hilmi I, et al.; Asia Pacific Association of Gastroenterology (APAGE) Working Group on Inflammatory Bowel Disease. Asia Pacific Consensus Statements on Crohn’s disease. Part 1: definition, diagnosis, and epidemiology: (Asia Pacific Crohn’s disease consensus–part 1). J Gastroenterol Hepatol. 2016; 31:45–55
  34. Lamb CA, Kennedy NA, Raine T et al. British gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut. 2019 Dec; 68(Suppl 3): s1-s106
  35. Bisschops R, East JE, Hassan C, Hazewinkel Y, Kamiński MF, Neumann H, et al. Advanced imaging for detection and differentiation of colorectal neoplasia: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2019. Endoscopy. 2019 Dec;51(12):1155-1179
  36. Murthy, S.K.; Feuerstein, J.D.; Nguyen, G.C.; Velayos, F.S. AGA Clinical Practice Update on Endoscopic Surveillance and Management of Colorectal Dysplasia in Inflammatory Bowel Diseases: Expert Review. Gastroenterology 2021, 161, 1043–1051.e4
  37. Sanduleau S, Kaltenbach T, Barkun A, McCabe RP, Velayos F, Picco MF, Laine L, Soetkino R and Mc Quaid KR. A roadmap to the implementation of chromoendoscopy in inflammatory bowel disease colonoscopy surveillance practice. Gastrointest. endoscopy 2016;83 (1): 213-222
  38. Soetikno R, Subramanian V, Kaltenbach T et al. The detection of nonpolypoid (flat and depressed) colorectal neoplasms in patients with inflammatory bowel disease. Gastroenterology 2013; 144:1349-52; 52.e1-6
  39. Rutter M, Bernstein C, Matsumoto T, Kiesslich R, Neurath M. Endoscopic appearance of dysplasia in ulcerative colitis and the role of staining. Endoscopy. 2004;36(12):1109-1114
  40. Dekker E, Houwen BBSL, Puig I, Bustamante-Balén M, Coron E, Dobru DE, et al. Curriculum for optical diagnosis training in Europe: European Society of Gastrointestinal Endoscopy (ESGE) position statement. Endoscopy. 2020 Oct;52(10):899-923
  41. Rex DK. Compounding liquid indigo carmine from the solid powder form. Colonoscopy tip of the week: American Society for Gastrointestinal Endoscopy, 2015. Available at: http://www.informz.net/admin31/content/template.asp?sidZ12079&ptidZ446&brandidZ439&uidZ 93268696&miZ1920305&psZ12079.
  42. Konijeti GG, Shrime MG, Ananthakrishnan AN et al. Cost-effectiveness analysis of chromoendoscopy for colorectal cancer surveillance in patients with ulcerative colitis. Gastrointest Endosc 2014;79: 455-65.
  43. Farraye FA, Odze RD, Eaden J et al. AGA technical review on the diagnosis and management of colorectal neoplasia in inflammatory bowel disease. Gastroenterology 2010; 138:746–74
  44. Rubin DT, Ananthakrishnan AN, Siegel CA et al. ACG clinical guideline: ulcerative colitis in adults. Am J Gastroenterol. 2019 Mar; 114(3):384-413
  45. Leong, R, Dr Crispin Corte, Dr Cherry Koh, Dr Betty Wu, Dr Viraj Kariyawasam MBBS, MRCP, FRACP, Chetcuti, A, Cancer Council Australia Surveillance Colonoscopy Guidelines Working Party. Clinical practice guidelines for surveillance colonoscopy. Sydney: Cancer Council Australia. Available from: https://wiki.cancer.org.au/australia/Guidelines:Colorectal_cancer/Colonoscopy_surveillance