Time for New Practices? Dysplasia Surveillance in IBD Patients

The link between chronic inflammatory bowel disease (IBD) and colon cancer is well established. Colorectal cancer (CRC) is increased in patients with IBD involving at least one-third of the colon, and it is important to remember that it is the same for Crohn’s disease and ulcerative colitis. Classically, the risk of CRC was estimated to be as high as 18 percent at 30 years. However, more recent studies indicate the risk of CRC is only slightly higher than the general population, though it does occur at an earlier age. In addition to extent of disease, a number of risk factors increase the risk of CRC in patients with IBD, including duration of disease, disease activity, primary sclerosing cholangitis (PSC), family history of CRC, prior dysplasia and endoscopic findings of prior severe disease (strictures, pseudopolyps and foreshortened colon). Though there are clear recommendations to screen for CRC in IBD, the ideal method to detect dysplasia and reduce the risk of CRC is still evolving.

According to the AGA guidelines, all patients with IBD should undergo a white-light screening colonoscopy eight years after disease diagnosis. In our practice, we utilize large-cap biopsy forceps to optimize the pathology specimens, with four samples taken every 10 centimeters and a minimum of 32 samples obtained from the colon. Given that most CRCs in IBD develop distally, we sample more from the rectosigmoid. After the initial screening procedure, those patients with disease involving one-third of the colon or more require ongoing surveillance. The interval for subsequent procedures is still up for debate. The AGA guidelines recommend that initially white-light colonoscopy be performed every one-to-two years. Following two colonoscopies that are negative for dysplasia, the interval may be extended to once every one-to-three years. However, patients with PSC should continue receiving annual colonoscopies. The British Society of Gastroenterology indicates that in low-risk patients a five-year interval may be appropriate. In our practice, we advise yearly colonoscopies for patients with ongoing disease activity or with additional risk factors for CRC; other patients we typically survey every other year.

Similar to patients without IBD, the most important aspect of colonoscopies is a high-quality visual inspection of the mucosa as several recent studies demonstrate that most dysplasia in IBD is visible. An excellent bowel prep and adequate irrigation and suctioning of residual stool are critical. Even with an ideal bowel preparation, our current methods to detect subtle dysplasia are still suboptimal. The use of random biopsies results in sampling of less than 0.1 percent of the colon. While the use of narrow-band imaging may increase polyp detection in routine colonoscopy, it has not been shown to increase the yield of dysplasia in IBD and is not recommended. Over the last number of years, studies have focused on the use of chromoendoscopy as a means to improve dysplasia detection and characterization. The recent SCENIC guidelines recommend routine use of chromoendoscopy, using either indigo carmine or methylene blue even with high-definition endoscopes, but the supporting evidence remains low quality. In our practice, we typically reserve chromoendoscopy for patients who have dysplasia identified on white- light colonoscopy and those at higher risk of CRC, including those with PSC and history of dysplasia. To date, the most important technique we find in screening for dysplasia is careful examination of the colon using high-definition white-light colonoscopy.

When performing chromoendoscopy, we first evaluate each segment of colon with high-definition white-light evaluation, and then we reintroduce the scope through that segment spraying with diluted methylene blue. For routine chromoendoscopy, we use a dilution of 20ml of methylene blue into 500cc of water. For ease, we attach the diluted methylene blue directly to our water jet and utilize the food pedal. Additionally, we still perform four-quadrant biopsies every 10 centimeters from the distal colon, and we also target any suspicious lesions. In high-risk patients with PSC or a history of invisible dysplasia, in addition to performing chromonendoscopy, we typically continue to perform 32 biopsies throughout the colon. Though more time consuming, we feel that combining white-light endoscopy, random biopsies and chromoendoscopy is the most thorough technique to detect dysplasia, but we want to stress that we believe a careful white-light examination is paramount.


The most important technique we find in screening for dysplasia is careful examination of the colon using high-definition white-light colonoscopy.


If a suspicious area of dysplasia or polyp is identified on colonoscopy, it should be characterized using the nomenclature recommended in the SCENIC guidelines. Visible dysplasia is described as polypoid or nonpolypoid. The borders of the dysplasia should be defined as distinct or indistinct. This determines if the area is endoscopically resectable or not. The underlying pit pattern should also be described. Whenever dysplasia is identified, we recommend performing additional biopsies from around the lesion (placed in separate specimen jars). This helps determine if the dysplastic area has been fully excised or if there is residual dysplastic tissue that was not identified endoscopically. Patients with polypoid dysplasia that is fully resected and without dysplasia elsewhere can be closely followed with colonoscopy according to the SCENIC guidelines. Typically, we repeat a colonoscopy with chromoendoscopy every six months until there are two negative examinations, and then we extend the interval to yearly. If the pathology from random biopsies during chromoendoscopy indicates invisible dysplasia or if the visible lesion is not felt to be endoscopically resectable, we recommend referral for surgery. If random biopsies taken during a white-light examination are noted to be dysplastic, we recommend repeating the colonoscopy with chromoendoscopy (with particular care paid to the area in question) and performing additional biopsies. If an unresectable lesion is found or invisible dysplasia is confirmed, we recommend surgery. In contrast, if an endoscopically resectable lesion is identified and the biopsies of the surrounding mucosa are nondysplastic, we recommend close surveillance with chromoendoscopy.

At this time, the ideal surveillance interval and technique to screen for dysplasia and CRC in IBD is evolving. If studies continue to show the risk of CRC in IBD is indeed declining, it is likely the frequency of colonoscopies will decrease. As there is some data to suggest that mucosal healing may be associated with a reduction in CRC, such patients with mucosal healing and without other risk factors may be ideal candidates for less frequent surveillance, though this needs further study. Similarly, the optimal method to identify dysplasia is still developing, and more studies comparing high-definition white-light endoscopy and chromoendoscopy are awaited. Studies are also needed to clarify the ideal biopsy technique when using chromoendoscopy to determine if only targeted biopsies are adequate or some random biopsies are still required. Additionally, there are a number of new technologies that incorporate virtual chromoendoscopy (e.g. FICE, i-SCA, FUSE) that appear promising, but, for now, the most important aspect remains a very careful examination with high-definition white-light endoscopy.

Dr. Feuerstein has no conflicts to disclose. Dr. Cheifetz has done consulting for AbbVie, Janssen, Takeda, Pfizer, Samsung and Miraca Labs.

References
1.Laine, L., Kaltenbach, T., Barkun, A., McQuaid, K.R., Subramanian, V., Soetikno, R., East, J.E., Farraye, F.A., Feagan, B., Ioannidis, J., Kiesslich, R. SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease. Gastroenterology. 2015;148(3):639–651.
2.Marion, J.F., Waye, J.D., Israel, Y., Present, D.H., Suprun, M., Bodian, C., Harpaz, N., Chapman, M., Itzkowitz, S., Abreu, M.T., Ullman, T.A. Chromoendoscopy is more effective than standard colonoscopy in detecting dysplasia during long-term surveillance of patients with colitis. Clin Gastroenterol Hepatol. 2016;14(5):713–719.
3. Ananthakrishnan, A.N., Cagan, A., Cai, T., Gainer, V.S., Shaw, S.Y., Churchill, S., Karlson, E.W., Murphy, S.N., Kohane, I., Liao, K.P. Colonoscopy is associated with a reduced risk for colon cancer and mortality in patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol. 2015;13(2):322–329.
4. Farraye, F.A., Odze, R.D., Eaden, J., Itzkowitz, S.H. AGA medical position statement on the diagnosis and management of colorectal neoplasia in inflammatory bowel disease. Gastroenterology. 2010;138(2):738–745.

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