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Colorectal Dysplasia in Patients With Inflammatory Bowel Diseases

Haleh Vaziri, MD
Assistant Professor of Medicine
Director, Inflammatory Bowel Disease Center
Associate Director, Gastroenterology-Hepatology Fellowship Program
University of Connecticut Health Center
Department of Medicine
Division of Gastroenterology and Hepatology
 

Chioma Ihunnah, MD, MPH
Gastroenterology & Hepatology Fellow
University of Connecticut Health Center
Department of Medicine
Division of Gastroenterology & Hepatology


 

The increased incidence of colorectal cancer (CRC) among patients with inflammatory bowel disease (IBD) drives the quest for an optimal dysplasia surveillance program. Risk factors for CRC in patients with IBD include the presence of extensive or pan-colitis, longer duration of disease, concomitant diagnosis of primary sclerosing cholangitis, family history of CRC, young age at the time of diagnosis and most importantly a personal history of dysplasia[i].

The optimal surveillance strategy in IBD patients is controversial. The incidence of dysplasia in IBD patients appears to be lower[ii] than had been previously reported[iii]. Initial surveillance guidelines recommended annual or biennial colonoscopy with biopsy or resection of suspicious lesions and 4-quadrant random biopsies every 10 centimeters[iv] based upon the belief that dysplasia was mostly invisible [v] A central limitation of this strategy was that at least 33 biopsies were required to achieve 90% sensitivity for dysplasia detection[vi]. Furthermore, with the advent of high-definition white light endoscopy (WLE), most dysplasia in IBD patients became endoscopically detectable8. Excellent bowel preparations with split-dosing bowel purgatives additionally improved the visibility of dysplastic lesions. As a result, the utility of random colon biopsies was debated given the low yield of these biopsies and the rarity of invisible dysplasia[vii] . Nevertheless, it appears that random biopsies can still identify dysplasia that is invisible even with high-definition WLE[viii],[ix]  and approximately 1.5% of patients with dysplasia would be missed if random biopsies were abandoned9.

Recently, the introduction of chromoendoscopy (CE) has revolutionized the surveillance of IBD patients. During CE, a topical dye is sprayed on the colonic mucosa with the aim of accentuating surface abnormalities. The two most commonly used dyes are methylene blue and indigo carmine. Methylene blue is an absorptive stain which colors normal tissue blue, while inflamed or dysplastic tissue has variable or absent absorption. Indigo carmine is a contrast stain, which highlights mucosal topography and accentuates contours of dysplastic lesions.  

Most studies9,[x],[xi] have demonstrated the superiority of CE over WLE in detection of dysplasia in IBD patients, although the retrospective study by Mooiweer and colleagues found that WLE-targeted biopsies had a higher yield of neoplasia compared to CE[xii]. The American Society of Gastrointestinal Endoscopy and several international society guidelines advocate for CE with targeted biopsies as the preferred surveillance strategy 9, 11, [xiii] . Although there is a strong recommendation for CE when using standard-definition scopes, there is only a conditional recommendation for its application when using high-definition scopes9. No specific recommendations have been made regarding random biopsies in patients who undergo high-definition colonoscopy or WLE plus CE. These methods presumably obviate the need for random biopsies.

Logistics of CE must be taken into consideration, such as cost, training requirements, quality metrics, CPT coding and staff training. Compared to random biopsies, CE has the potential for cost-savings[xiv] by collecting fewer specimens. Additionally, patients without evidence of dysplasia during this very sensitive exam can theoretically lengthen the interval between their colonoscopies, thus decreasing the total number of lifetime colonoscopies and associated costs per person, and overall. Conversely, CE increases the length of each procedure on average, [xv] and may alternatively create additional costs due to the increased number of colonoscopies and colectomies in patients in whom dysplasia is detected.

The long-term benefits of these surveillance strategies are important considerations when comparing different modalities.  Although most studies have shown that CE may unmask more dysplasia in patients, data regarding the long-term benefits of chromoendoscopy over WLE is sparse. The outcome of dysplasia detected by CE is unknown, which yields uncertainty in the management of these patients. In the longitudinal study by Marion et al., no cancer was found among colon specimens resected for dysplasia that had been identified during CE exams10. A negative CE exam has been suggested to be the best predictor of a dysplasia-free outcome10 , although larger, longitudinal studies are needed to confirm this benefit.

Regardless of the surveillance method, guidelines suggest that complete endoscopic resection of dysplasia, if possible, with biopsies of the surrounding mucosa to exclude the presence of dysplasia be performed11. Surveillance colonoscopy after complete resection of dysplasia is recommended, rather than colectomy.  Unresectable lesions, high-grade dysplasia found only on random biopsy, or multifocal low-grade dysplasia still may be indications for proctocolectomy.  Patients with confirmed invisible dysplasia should be referred to an endoscopist with expertise in IBD surveillance.

Patients and physicians should be aware of the limitations of dysplasia surveillance in IBD patients. While the presence of inflammation, limited bowel preparation, bowel strictures and pseudopolyposis may limit the effectiveness of these techniques for every gastroenterologist, the skill level of each gastroenterologist in detecting and adequately removing identified lesions varies widely. Other universal limitations include the reality that some endoscopists may not follow the guidelines in practice, and certainly some patients may not follow recommendations after detection of dysplasia. This permits several potential gaps in follow-up and allows for variable adherence by both patient and endoscopist.

Dysplasia surveillance has advanced significantly with the advent of high-definition WLE and CE, but more studies are needed to address the necessity of CE during high-definition exams. While CE offers enhanced visualization of mucosa and a higher yield for dysplasia detection, additional studies are needed to evaluate the practicality of this modality in busy clinical settings, the natural history of dysplasia found only with CE, and the potential for increased burden of protocolectomies in patients with dysplasia. One should always remember that while the immediate aim of surveillance is to detect dysplasia, the most important goal is to prevent colorectal cancer morbidity and mortality while avoiding unnecessary colectomy.

 

[i] Bernstein CN, Shanahan F, Weinstein WM. Are we telling patients the truth about surveillance colonoscopy in ulcerative colitis? Lancet. 1994; 343(8889):71-4

[ii] Lutgens MW1, van Oijen MG, van der Heijden GJ, et al. Declining risk of colorectal cancer in inflammatory bowel disease: an updated meta-analysis of population-based cohort studies. Inflamm Bowel Dis. 2013;19:789-799

[iii] Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a meta analysis.Gut.2001;48:526–535

[iv] Eaden JA, Mayberry JF. Guidelines for screening and surveillance of asymptomatic colorectal cancer in patients with inflammatory bowel disease. Gut 2002;51(Suppl 5): V10-2.

[v]Riddell RH, Goldman H and Ransohoff DF et al. Dysplasia in inflammatory bowel disease: standardized classification with provisional clinical applications. Hum Pathol. 1983; 14:931–968.

[vi] Rubin CE, Haggitt RC, Burmer GC et al. DNA aneuploidy in colonic biopsies predicts future development of dysplasia in ulcerative colitis.Gastroenterology 1992;103:1611-20.

[vii] van den Broek FJ, Stokkers PC, Reitsma JB, et al. Random biopsies taken during colonoscopic surveillance of patients with longstanding ulcerative colitis: low yield and absence of clinical consequences. Am J Gastroenterol. 2014;109(5):715-722.

[viii] 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. Inflamm Bowel Dis 2013;19:350–355.

[ix] Laine L, Kaltenbach T,Barkun A, et al. SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease. Gastroenterology. 2015;148:639–51.e28

[x] Marion JF, Waye JD, Israel Y et al. Chromoendoscopy Is More Effective Than Standard Colonoscopy in Detecting Dysplasia During Long-term Surveillance of Patients With Colitis. Clin Gastroenterol Hepatol. 2016 May;14(5):713-9

[xi]American Society for Gastrointestinal Endoscopy Standards of Practice Committee, Shergill AK, Lightdale JR  et al. The role of endoscopy in inflammatory bowel disease. Gastrointest Endosc. 2015;81(5):1101-21.e1-13

[xii] Mooiweer E, van der Meulen-de Jong AE, Ponsioen CY et al. Chromoendoscopy for Surveillance in Inflammatory Bowel Disease Does Not Increase Neoplasia Detection Compared With Conventional Colonoscopy With Random Biopsies: Results From a Large Retrospective Study. Am J Gastroenterol. 2015 Jul; 110(7):1014-21. Epub 2015 Mar 31.

[xiii] Mowat C, Cole A, Windsor A. Guidelines for the Management of Inflammatory Bowel Disease in Adults. Gut ;2011:571-607

[xiv] Konijeti GG, Shrime MG, Ananthakrishnan A, et al. Cost effectiveness analysis of chromoendoscopy for colorectal cancer surveillance in patients with ulcerative colitis. Gastrointest Endosc. Epub 2013 Nov 18.

[xv] Carballal S, Maisterra S, Lopez-Serrano A et al. Real-life chromoendoscopy for neoplasia detection and characterisation in long-standing IBD. Gut 2016;0:1–9.