Korean J Gastroenterol.  2025 Jan;85(1):34-43. 10.4166/kjg.2024.105.

Frequency and Risk Factors of Advanced Neoplasia in Korean Inflammatory Bowel Disease Patients with Low-grade Dysplasia

• Park YE
• Kim KO
• Kim DH
• Park SK
• Lee YJ
• Lee CK
• IBD Research Group of the Korean Association for the Study of Intestinal Diseases (KASID)

• KMID: 2565013
• DOI: http://doi.org/10.4166/kjg.2024.105

Abstract

Background/Aims
Studies on the clinical outcomes after detecting low-grade dysplasia (LGD) in patients with inflammatory bowel disease (IBD) are insufficient. This study evaluated the clinical features, frequency, and risk factors for advanced neoplasia in patients with IBD after an LGD diagnosis.
Methods
The medical records of 166 patients with IBD from six university hospitals in Korea from 2010 to 2019 were reviewed retrospectively. LGD was diagnosed in all patients during surveillance. The frequency and risk factors for advanced neoplasia were evaluated, and the clinical features of patients with and without advanced neoplasia were compared.
Results
Advanced neoplasia developed in 12 patients (six with large LGD, three with tubulovillous adenoma, and three with high-grade dysplasia), and all cases developed from UC. Patients with advanced neoplasia had significantly higher Mayo scores, and colitis-associated dysplasia was more common than sporadic lesions (83.3% vs. 29.9%; p<0.001). Multivariate analysis showed that colitis-associated LGD significantly increased the risk of developing advanced neoplasia (odds ratio [OR], 10.516; 95% confidence interval [CI], 2.064–53.577). Among patients with colitis-associated lesions, a significant risk factor for advanced neoplasia was a prior history of LGD (OR, 9.429; 95% CI, 1.330–66.863).
Conclusions
Advanced neoplasia developed in 7.2% of patients with IBD and LGD. Most advanced neoplasms developed from colitis-associated lesions, and the risk was higher in patients with a history of LGD before index colonoscopy.

Keyword

Colorectal neoplasm; Inflammatory bowel disease; Risk factors

Figure

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  Fig. 1 Flow diagram of patient selection. LGD, low grade dysplasia; IND, indefinite dysplasia; IBD, Inflammatory bowel disease; PSC, primary sclerosing cholangitis; HGD, high grade dysplasia; CRC, colorectal cancer.

Reference

1. Thia KT, Loftus EV Jr, Sandborn WJ, Yang SK. 2008; An update on the epidemiology of inflammatory bowel disease in Asia. Am J Gastroenterol. 103:3167–3182. DOI: 10.1111/j.1572-0241.2008.02158.x. PMID: 19086963.

2. Beaugerie L, Itzkowitz SH. 2015; Cancers complicating inflammatory bowel disease. N Engl J Med. 372:1441–1452. DOI: 10.1056/NEJMra1403718. PMID: 25853748.

3. Lutgens MW, van Oijen MG, van der Heijden GJ, Vleggaar FP, Siersema PD, Oldenburg B. 2013; Declining risk of colorectal cancer in inflammatory bowel disease: an updated meta-analysis of population-based cohort studies. Inflamm Bowel Dis. 19:789–799. DOI: 10.1097/MIB.0b013e31828029c0. PMID: 23448792.

4. Maaser C, Sturm A, Vavricka SR, et al. 2019; ECCO-ESGAR Guideline for Diagnostic Assessment in IBD Part 1: Initial diagnosis, monitoring of known IBD, detection of complications. J Crohns Colitis. 13:144–164. DOI: 10.1093/ecco-jcc/jjy113. PMID: 30137275.

5. Farraye FA, Odze RD, Eaden J, et al. 2010; AGA medical position statement on the diagnosis and management of colorectal neoplasia in inflammatory bowel disease. Gastroenterology. 138:738–745. DOI: 10.1053/j.gastro.2009.12.037. PMID: 20141808.

6. Rubin DT, Ananthakrishnan AN, Siegel CA, Sauer BG, Long MD. 2019; ACG clinical guideline: Ulcerative colitis in adults. Am J Gastroenterol. 114:384–413. DOI: 10.14309/ajg.0000000000000152. PMID: 30840605.

7. Lichtenstein GR, Loftus EV, Isaacs KL, Regueiro MD, Gerson LB, Sands BE. 2018; ACG clinical guideline: Management of Crohn's disease in adults. Am J Gastroenterol. 113:481–517. DOI: 10.1038/ajg.2018.27. PMID: 29610508.

8. Mooiweer E, van der Meulen-de Jong AE, Ponsioen CY, et al. 2015; Incidence of interval colorectal cancer among inflammatory bowel disease patients undergoing regular colonoscopic surveillance. Clin Gastroenterol Hepatol. 13:1656–1661. DOI: 10.1016/j.cgh.2015.04.183. PMID: 25956835.

9. Shah SC, Itzkowitz SH. 2022; Colorectal cancer in inflammatory bowel disease: Mechanisms and management. Gastroenterology. 162:715–730.e3. DOI: 10.1053/j.gastro.2021.10.035. PMID: 34757143. PMCID: PMC9003896.

10. De Jong ME, Van Tilburg SB, Nissen LHC, et al. 2019; Long-term risk of advanced neoplasia after colonic low-grade dysplasia in patients with inflammatory bowel disease: A nationwide cohort study. J Crohns Colitis. 13:1485–1491. DOI: 10.1093/ecco-jcc/jjz114. PMID: 31175827. PMCID: PMC6903794.

11. Pekow JR, Hetzel JT, Rothe JA, et al. 2010; Outcome after surveillance of low-grade and indefinite dysplasia in patients with ulcerative colitis. Inflamm Bowel Dis. 16:1352–1356. DOI: 10.1002/ibd.21184. PMID: 20027656. PMCID: PMC3046461.

12. Riddell RH, Goldman H, Ransohoff DF, et al. 1983; Dysplasia in inflammatory bowel disease: standardized classification with provisional clinical applications. Hum Pathol. 14:931–968. DOI: 10.1016/S0046-8177(83)80175-0. PMID: 6629368.

13. Mahmoud R, Shah SC, Torres J, et al. 2020; Association between indefinite dysplasia and advanced neoplasia in patients with inflammatory bowel diseases undergoing surveillance. Clin Gastroenterol Hepatol. 18:1518–1527.e3. DOI: 10.1016/j.cgh.2019.08.032. PMID: 31446183. PMCID: PMC7354098.

14. Choi CH, Jung SA, Lee BI, Lee KM, Kim JS, Han DS. 2009; Diagnostic guideline of ulcerative colitis. Korean J Gastroenterol. 53:145–160.

15. Ye BD, Jang BI, Jeen YT, Lee KM, Kim JS, Yang SK. 2009; Diagnostic guideline of Crohn's disease. Korean J Gastroenterol. 53:161–176.

16. Satsangi J, Silverberg MS, Vermeire S, Colombel JF. 2006; The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut. 55:749–753. DOI: 10.1136/gut.2005.082909. PMID: 16698746. PMCID: PMC1856208.

17. Lewis JD, Chuai S, Nessel L, Lichtenstein GR, Aberra FN, Ellenberg JH. 2008; Use of the noninvasive components of the Mayo score to assess clinical response in ulcerative colitis. Inflamm Bowel Dis. 14:1660–1666. DOI: 10.1002/ibd.20520. PMID: 18623174. PMCID: PMC2597552.

18. Schroeder KW, Tremaine WJ, Ilstrup DM. 1987; Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med. 317:1625–1629. DOI: 10.1056/NEJM198712243172603. PMID: 3317057.

19. Best WR, Becktel JM, Singleton JW, Kern F Jr. 1976; Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study. Gastroenterology. 70:439–444. DOI: 10.1016/S0016-5085(76)80163-1. PMID: 1248701.

20. Daperno M, D'Haens G, Van Assche G, et al. 2004; Development and validation of a new, simplified endoscopic activity score for Crohn's disease: the SES-CD. Gastrointest Endosc. 60:505–512. DOI: 10.1016/S0016-5107(04)01878-4. PMID: 15472670.

21. Gupta S, Lieberman D, Anderson JC, et al. 2020; Recommendations for follow-up after colonoscopy and polypectomy: A consensus update by the US multi-society task force on colorectal cancer. Gastrointest Endosc. 91:463–485.e5. DOI: 10.1016/j.gie.2020.01.014. PMID: 32044106. PMCID: PMC7389642.

22. Jung YS. 2023; Summary and comparison of recently updated post-polypectomy surveillance guidelines. Intest Res. 21:443–451. DOI: 10.5217/ir.2023.00107. PMID: 37915180. PMCID: PMC10626009.

23. The Paris endoscopic classification of superficial neoplastic lesions: esophagus, stomach, and colon: November 30 to December 1, 2002. Gastrointest Endosc. 2003; 58(6 Suppl):S3–43. DOI: 10.1016/S0016-5107(03)02159-X. PMID: 14652541.

24. Laine L, Kaltenbach T, Barkun A, McQuaid KR, Subramanian V, Soetikno R. SCENIC Guideline Development Panel. 2015; SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease. Gastroenterology. 148:639–651.e28. DOI: 10.1053/j.gastro.2015.01.031. PMID: 25702852.

25. Wijnands AM, Mahmoud R, Lutgens MWMD, Oldenburg B. 2021; Surveillance and management of colorectal dysplasia and cancer in inflammatory bowel disease: Current practice and future perspectives. Eur J Intern Med. 93:35–41. DOI: 10.1016/j.ejim.2021.08.010. PMID: 34481721.

26. Øresland T, Bemelman WA, Sampietro GM, et al. 2015; European evidence based consensus on surgery for ulcerative colitis. J Crohns Colitis. 9:4–25. DOI: 10.1016/j.crohns.2014.08.012. PMID: 25304060.

27. Bemelman WA, Warusavitarne J, Sampietro GM, et al. 2018; ECCO-ESCP consensus on surgery for Crohn's disease. J Crohns Colitis. 12:1–16. DOI: 10.1093/ecco-jcc/jjx061. PMID: 28498901.

28. Fearon ER, Vogelstein B. 1990; A genetic model for colorectal tumorigenesis. Cell. 61:759–767. DOI: 10.1016/0092-8674(90)90186-I. PMID: 2188735.

29. Frick A, Khare V, Paul G, et al. 2018; Overt increase of oxidative stress and DNA damage in murine and human colitis and colitis-associated neoplasia. Mol Cancer Res. 16:634–642. DOI: 10.1158/1541-7786.MCR-17-0451. PMID: 29378905.

30. Choi CH, Rutter MD, Askari A, et al. 2015; Forty-year analysis of colonoscopic surveillance program for neoplasia in ulcerative colitis: An updated overview. Am J Gastroenterol. 110:1022–1034. DOI: 10.1038/ajg.2015.65. PMID: 25823771. PMCID: PMC4517513.

31. Itzkowitz SH, Yio X. 2004; Inflammation and cancer IV. Colorectal cancer in inflammatory bowel disease: the role of inflammation. Am J Physiol Gastrointest Liver Physiol. 287:G7–17. DOI: 10.1152/ajpgi.00079.2004. PMID: 15194558.

32. Khan MA, Hakeem AR, Scott N, Saunders RN. 2015; Significance of R1 resection margin in colon cancer resections in the modern era. Colorectal Dis. 17:943–953. DOI: 10.1111/codi.12960. PMID: 25808496.

33. Stidham RW, Higgins PDR. 2018; Colorectal cancer in inflammatory bowel disease. Clin Colon Rectal Surg. 31:168–178. DOI: 10.1055/s-0037-1602237. PMID: 29720903. PMCID: PMC5929884.

34. Hnatyszyn A, Hryhorowicz S, Kaczmarek-Ryś M, et al. 2019; Colorectal carcinoma in the course of inflammatory bowel diseases. Hered Cancer Clin Pract. 17:18. DOI: 10.1186/s13053-019-0118-4. PMID: 31338130. PMCID: PMC6626407.

35. Wijnands AM, de Jong ME, Lutgens MWMD, Hoentjen F, Elias SG, Oldenburg B. Dutch Initiative on Crohn and Colitis (ICC). 2021; Prognostic factors for advanced colorectal neoplasia in inflammatory bowel disease: systematic review and meta-analysis. Gastroenterology. 160:1584–1598. DOI: 10.1053/j.gastro.2020.12.036. PMID: 33385426.

36. Lazaridis KN, LaRusso NF. 2016; Primary sclerosing cholangitis. N Engl J Med. 375:1161–1170. DOI: 10.1056/NEJMra1506330. PMID: 27653566. PMCID: PMC5553912.

37. Axelrad JE, Lichtiger S, Yajnik V. 2016; Inflammatory bowel disease and cancer: The role of inflammation, immunosuppression, and cancer treatment. World J Gastroenterol. 22:4794–4801. DOI: 10.3748/wjg.v22.i20.4794. PMID: 27239106. PMCID: PMC4873872.

38. Lamb CA, Kennedy NA, Raine T, et al. 2019; British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut. 68(Suppl 3):s1–s106. DOI: 10.1136/gutjnl-2019-318484. PMID: 31562236. PMCID: PMC6872448.

39. Magro F, Gionchetti P, Eliakim R, et al. 2017; 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. J Crohns Colitis. 11:649–670. DOI: 10.1093/ecco-jcc/jjx008. PMID: 28158501.

40. Saito Y, Otake Y, Sakamoto T, et al. 2013; Indications for and technical aspects of colorectal endoscopic submucosal dissection. Gut Liver. 7:263–269. DOI: 10.5009/gnl.2013.7.3.263. PMID: 23710305. PMCID: PMC3661956.

41. Mohan BP, Khan SR, Chandan S, et al. 2021; Endoscopic resection of colon dysplasia in patients with inflammatory bowel disease: a systematic review and meta-analysis. Gastrointest Endosc. 93:59–67.e10. DOI: 10.1016/j.gie.2020.06.048. PMID: 32592777.

42. Choi CH, Ignjatovic-Wilson A, Askari A, et al. 2015; Low-grade dysplasia in ulcerative colitis: risk factors for developing high-grade dysplasia or colorectal cancer. Am J Gastroenterol. 110:1461–1471. quiz 1472DOI: 10.1038/ajg.2015.248. PMID: 26416190. PMCID: PMC4697133.