Gastroenterology 2016;-:1–3
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SELECTED SUMMARIES Marcia Cruz-Correa, Section Editor David Schwartz, Section Editor STAFF OF CONTRIBUTORS Joseph Anderson, White River Junction, VT Johanna L. Chan, Houston, TX Matthew A. Ciorba, St. Louis, MO Massimo Colombo, Milan, Italy Gregory A. Cote, Charleston, SC Evan S. Dellon, Chapel Hill, NC Alex Ford, Leeds, United Kingdom Lauren B. Gerson, San Francisco, CA David S. Goldberg, Philadelphia, PA Samir Gupta, San Diego, CA
Reena Khanna, London, Ontario, Canada W. Ray Kim, Rochester, MN Paul Y. Kwo, Indianapolis, IN Uma Mahadevan, San Francisco, CA Baha Moshiree, Miami, FL Swati G. Patel, Aurora, CO Laurent Peyrin-Biroulet, Vandoeuvre-lès-Nancy, France Jesus Rivera-Nieves, San Diego, CA
Is Chromoendoscopy Superior to Standard Colonoscopy for Long-term Surveillance of Patients With Inflammatory Bowel Disease? Marion JF, Waye JD, Israel Y, et al; Chromoendoscopy Study Group at Mount Sinai School of Medicine. Chromoendoscopy is more effective than standard colonoscopy in detecting dysplasia during long-term surveillance of patients with colitis. Clin Gastroenterol Hepatol 2016;14:713–719. Because patients with inflammatory bowel disease (IBD) are at increased risk for developing colorectal cancer (CRC), colonoscopies with random biopsies every 10 cm are recommended for surveillance of patients with longstanding disease. The goal of these random biopsies is to detect dysplasia in the patient’s colon, which may be a marker for synchronous CRC. Thus, identifying the best method for identifying patients with dysplasia is crucial for surveillance of IBD patients. The rationale for these random biopsies is that they may detect dysplasia that is not visible endoscopically. However, the usefulness of this approach has been debated in light of recent studies that have shown that random biopsies may have a low yield for dysplasia, especially when compared with targeted biopsies (Am J Gastroenterol 2015;110:1014– 1021). In addition, some studies suggest that most dysplasia may be endoscopically detectable in patients with colitis using high-definition white light endoscopy (WLE) (Inflam Bowel Dis 2013;19:350–3505) or chromoendoscopy (CE) (Aliment Pharmacol Ther 2011;33:304–312; Gastrointest Endosc 2015;81:489–501 e26). CE is considered a superior method for visualizing the colonic mucosal surface as compared with WLE, but data are conflicting. The Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients consensus (SCENIC) guidelines advocate the use of CE and targeted biopsies as the preferred surveillance program especially when standard definition scopes are used (Gastrointest Endosc 2015;81:489–501 e26.). In addition to whether CE may be the best choice for detecting dysplasia, another important issue that requires
Sameer Saini, Ann Arbor, MI Ekihiro Seki, Los Angeles, CA Amit Singal, Dallas, TX Ryan W. Stidham, Ann Arbor, MI Akbar Waljee, Ann Arbor, MI Sachin Wani, Aurora, CO Alastair J. M. Watson, Norwich, United Kingdom Yana Zavros, Cincinnati, OH
more data is the long-term benefit that is derived from surveillance with CE versus WLE. More efficient dysplasia detection may not translate to better outcomes, such as reduction of CRC risk. It is possible that CE may identify patients with less aggressive lesions. Unfortunately, the effectiveness of surveillance is not well-defined owing to the lack of randomized, controlled trials demonstrating a reduction in CRC incidence or mortality in IBD patients who are undergoing surveillance. Thus, more studies examining the long-term effectiveness of surveillance with CE are needed. Marion et al (Clin Gastroenterol Hepatol 2016;14:713– 719) provide longitudinal data from IBD patients who underwent surveillance colonoscopies with CE and WLE. This study was a follow-up analysis to a parent study or “Index Study” (Am J Gastroenterol 2008;103:2342–2349). In the Index Study, 102 patients had endoscopic IBD surveillance by 3 methods; random biopsy, targeted WLE (“no-dye”), and CE. The goal of the current study was to compare standard colonoscopy with CE for detecting dysplasia in IBD patients undergoing long-term surveillance. Of the 102 patients in the Index Study, 68 were followed for the current paper’s analysis from June 2006 through October 2011 at Mount Sinai Hospital for a median of 27.8 months. After completing the bowel prep, 2 passes of colonoscope were performed as part of a standardized protocol. The colonoscope was advanced to the ileocecal valve and the colon was subsequently examined from cecum to transverse colon while random biopsies were obtained. “No-dye” targeted sampling was also obtained during this part of the examination from visible lesions by using a biopsy forceps or snare. The scope was then advanced once again to the cecum and methylene blue was applied to the mucosa. Dye-targeted biopsies were obtained from visible lesions during the withdrawal from the cecum to the transverse colon. This entire process was repeated from transverse colon to rectum. An expert gastrointestinal pathologist, who was blinded to the method of tissue sampling, reviewed the specimens. A total of 208 procedures were performed on 68 patients during the follow up period, with an average of 3.15 procedures per patient (range, 1-5). Dysplasia was found in 6 lesions from 5 patients using random biopsies, 11 lesions from 11 patients using “no-dye” targeted WLE, and 27 lesions from 27 patients using CE. CE and targeted WLE
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Selected Summaries
Gastroenterology Vol.
were more likely to detect dysplasia when compared with the random biopsy method (odds ratio [OR], 5.4; 95% confidence interval [CI], 2.9-9.9; P < .001) and (OR, 2.3; 95% CI, 1.0-5.3; P ¼ .054), respectively. CE was also superior to “no-dye” targeted WLE (OR, 2.4, 95% CI, 1.4-4.0; P ¼ .001). The overall agreement between endoscopy and colectomy findings with regard to the presence or absence of dysplasia was 20% for random biopsy, 10% in “no-dye” targeted WLE and 80% in CE. The authors concluded that, based on these findings, CE was superior to random biopsy or WLE analyses in detecting dysplasia in surveillance of IBD patients and that a negative CE examination may be the best indicator of a dysplasia-free outcome. Comment. The current study (Clin Gastroenterol Hepatol 2016;14:713–719) has several important findings for endoscopists who perform surveillance colonoscopies for patients with IBD. The investigators observed that CE was superior for detection of dysplasia as compared with the “no-dye” targeted WLE approach or random biopsies. Their study also observed a higher overall agreement between endoscopy and colectomy findings with respect to presence or absence of dysplasia for dye-targeted examinations (80%) compared with “no-dye” target (10%) or random (20%) biopsies. Thus, their data suggest that CE may be superior to WLE biopsies, random or targeted, for the detection of dysplasia in the surveillance of IBD patients. A recent retrospective study observed that, contrary to the current study’s findings, the use of WLE with targeted biopsies yielded a neoplasia detection rate that was similar to CE (Am J Gastroenterol 2015;110:1014–1021). Were there aspects in the design of the current study that may have favored CE over WLE with respect to detecting dysplasia? In the Index Study paper (Am J Gastroenterol 2008;103:2342–2349), the authors provide more information regarding the protocol. Because the authors wanted to provide patients with a “1-visit” study, they used a “doublepass” protocol, with the dye portion following the WLE portion. The dye had to be conducted last because this could not be “undone.” However, could performing the WLE first have introduced bias into the study? The authors state that the WLE random biopsies had an advantage over the other 2 techniques because it was performed first. However, there may be other issues with this design. For example, it is not clear if the protocol allowed the endoscopist to obtain samples from the site of previous biopsies taken during the first pass with WLE. Although obtaining biopsies from these sites might increase the yield of CE, prohibiting the endoscopist from obtaining biopsies from those sites might have possibly decreased the yield. Thus, it is unclear if CE could identify all the dysplastic lesions, which had already been removed during WLE targeted examination. Another possible limitation is the use of standard colonoscopes instead of high-definition colonoscopes. This may have limited the sensitivity for WLE targeted biopsies. In addition, it may limit the generalizability of the results, because most endoscopy suites currently use high-definition colonoscopes. Although existing data allow for a strong recommendation for CE when using standard definition, the
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SCENIC guidelines state that there is only a conditional recommendation for CE when using high-definition colonoscopes (Gastrointest Endosc 2015;81:489–501 e26.). Thus, more studies comparing CE with high-definition rather than standard definition colonoscopes would provide data that would help to address whether CE is needed when high-definition colonoscopes are used. Another concern is the lack of data for colonoscopy quality measures. The authors state that patients with an inadequate bowel preparation, defined as >10% of colon mucosa obscured, were excluded. However, there are no specific data for bowel preparation quality before WLE random biopsies. Ideally, an adequate bowel preparation should have been present before WLE random biopsies. It is possible that the endoscopist cleaned the colon during the WLE random biopsy portion of the protocol, allowing for better visualization during the “no dye” targeted or CE portion. Another concern is the lack of withdrawal or examination time information. Is it possible that the increased dysplasia detection with CE was derived from a longer examination? Furthermore, information on the procedure time would be important for busy endoscopists with regard to choosing a method for surveillance. Another important finding was the absence of dysplasia related adverse events (CRC or surgery) in this cohort after the colon is found to be free of dysplasia with CE and WLE. Because patients were followed for a median time period of 27.8 months, this finding may have important implications for long-term surveillance programs. In addition, none of the 68 patients developed carcinoma during the entire followup period. Although the results may be limited by a small study size, the study enrolled a high-risk group. As detailed in the previous publication, the authors tell us that nearly 40% of the index group (39/102) were diagnosed previously with dysplasia. Thus, the finding of no carcinoma seems more impressive in light of the high-risk nature of the study sample. However, the lack of any cancers in the colons resected after CE examinations with dysplasia raises the question of the clinical significance of abnormalities detected by CE. Another important finding was the extremely low yield of random biopsies. These results confirm a previous study that observed that additional random biopsies in their WLE group only identified 1% more procedures with neoplasia than targeted biopsies alone (Am J Gastroenterol 2015;110:1014–1021). Thus, the use of CE and WLE as observed in the current study might obviate the need for random biopsies, reducing examination time, cost, and potential risk from many extra biopsies. This study has several strengths, which help to substantiate the findings. The 68 high-risk patients who were included in the study had sufficiently extensive disease to require endoscopic surveillance. In addition, each patient was analyzed in tandem by all 3 methods, allowing each patient to be their own control. Furthermore, the pathology specimens were reviewed by an expert gastrointestinal pathologist who was blinded to the method of specimen collection. Finally, the authors also examined other potential predictors of interest, such as age, presence of pseudopolyps,
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family history of CRC, the use of thiopurine and mesalamine, and exposure to calcium, folate, steroids, cyclosporine. One major issue to consider is the reluctance of practicing gastroenterologists to adopt CE owing to concerns regarding ease of use. Time constraints have been a salient issue. Although not included in the current study, the previous paper of the index study provides some time data. Whereas the WLE portion (targeted and random) took a median time of 22:11 minutes (range, 5:27–55:29), the dye portion had a time of 15:12 minutes (range, 5:09–28:35). If the CE obviates the need for random biopsies, as the study suggests, the time required for CE might make this method more attractive for practicing endoscopists. Another issue has been the potential training that is required for CE. In the previous publication, the authors reported that the participating endoscopists received a brief, didactic orientation on patient selection, protocol, pit pattern recognition, and dye application. Thus, the results of this study were obtained with training that would likely not be considered intrusive for practicing endoscopists. However, it should be recognized that the endoscopists in the current analysis were experienced in colitis surveillance and may not be representative of a community gastroenterologist. Finally, although not addressed in the current study, the choice of dye staining is also an important issue. The authors chose methylene blue, which is an absorptive stain as opposed to indigo carmine, a contrast stain. In our opinion, methylene
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blue is easier to use because excess dye can be washed off without disturbing the underlying dye stain. Despite some limitations, the findings in this prospective study shed some light on some previously unanswered questions regarding detection, management and outcome of dysplasia in these high-risk patients. The study provides a cogent argument for endoscopists to conduct surveillance with WLE and CE targeted biopsies. More longitudinal studies are needed to compare the outcome of surveillance techniques, especially high-definition WLE with targeted with or without random biopsies and CE. HALEH VAZIRI Division of Gastroenterology and Hepatology University of Connecticut School of Medicine Farmington, Connecticut JOSEPH C. ANDERSON Department of Veterans Affairs Medical Center White River Junction, Vermont and The Geisel School of Medicine at Dartmouth Hanover, New Hampshire and Division of Gastroenterology and Hepatology University of Connecticut School of Medicine Farmington, Connecticut The contents of this work do not represent the views of the Department of Veterans Affairs or the United States Government.
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