Endoscopic Detection and Removal of Colitis-Associated Dysplasia





List of Abbreviations


CD


Crohn’s disease


CI


Confidence interval


CRC


Colorectal cancer


DALM


Dysplasia-associated lesion or mass


EMR


Endoscopic mucosal resection


ESD


Endoscopic submucosal dissection


HDWL


High-definition white light


HGD


High-grade dysplasia


IBD


Inflammatory bowel disease


IT


Isolation tipped


LGD


Low-grade dysplasia


NBI


Narrow-band imaging


NNT


Number needed to treat


OR


Odds ratio


RCT


Randomized controlled trial


SCENIC


The International Consensus Statement on Surveillance and Management of Dysplasia in Inflammatory Bowel Disease


SDWL


Standard-definition white light


UC


Ulcerative colitis




Introduction


Long-standing ulcerative colitis (UC) and Crohn’s colitis patients are at increased risk of colorectal cancer (CRC) and interval CRC. The risk of interval CRC is estimated to be 3 times higher in colitic inflammatory bowel disease (IBD) patients compared with non-IBD patients (odds ratio [OR] for UC, 3.05; 95% confidence interval [CI] 2.4–3.8; OR for Crohn’s colitis, 3.07; 95% CI 2.2–4.2). Nearly one half of all CRC diagnosed during IBD surveillance are attributed to interval CRC. This risk can be partially explained by dysplasia evading endoscopic detection, as it is often nonpolypoid (flat or depressed). Another explanation could be the failure of extensive random biopsy strategy, and the impairment of mucosal inspection using this technique.


Most CRC in IBD patients are believed to arise from dysplasia. Risk factors for developing colitis-associated dysplasia include longer extent and duration of disease, activity, and severity of inflammation, primary sclerosing cholangitis, family history of colorectal cancer, and colonic pseudopolyps or strictures ( Table 19.1 ). Hence, regular colonoscopic surveillance for the detection of dysplasia and early CRC is crucial.



Table 19.1

Risk Factors for Colorectal Cancer in IBD








  • Longer extent and duration of disease



  • Activity and severity of inflammation



  • Primary sclerosing cholangitis



  • Family history of colorectal cancer



  • Pseudopolyps and strictures



  • Colorectal dysplasia





Surveillance Techniques


Limitations and failure of white-light colonoscopy in IBD surveillance has been highlighted for more than 2 decades. A metaanalysis of 10 prospective studies included 1225 patients with UC who underwent standard-definition white light (SDWL) colonoscopic surveillance. Forty patients had immediate colectomy after the diagnosis of dysplasia-associated lesion or mass (DALM). Cancer rates in biopsy proven high-grade dysplasia (HGD) and low-grade dysplasia (LGD) were 42% and 19%, respectively. In a US study of 55,000 Medicare patients diagnosed with colorectal cancer, IBD patients were 3 times more likely to have had a missed colorectal cancer after a recent colonoscopy than non-IBD patients. In a pooled analysis of 11 studies with 48,522 random biopsies from 1635 IBD patients, the number of detected dysplasia was only in 39 biopsies (0.08%).


Colonoscopic surveillance is challenging because of variability in endoscopic appearance and subtlety of dysplasia. In older fiberoptic and lower resolution endoscope systems, dysplasia was “invisible” as it was often discovered on random colonic biopsies. This was traditionally achieved by obtaining a minimum of 33 biopsies, by taking four-quadrant random biopsies every 10 cm in the colon, placed in separate containers, and taking more biopsies in the rectosigmoid colon. The limitations of white light with random biopsy in the detection of dysplasia, however, are many. The technique is inefficient, expensive, and inefficacious. It is estimated to only represent a colonic surface area <0.1%. Advancements in endoscopic technologies, such as high-definition resolution and enhanced contrast techniques, such as chromoendoscopy, have improved detection, characterization, and endoscopic management of colorectal neoplasia.


The majority of detected lesions are actually visible, well delineated, and potentially suitable for curative endoscopic resection. In 2004, a retrospective study of 525 patients long-standing UC who underwent SDWL surveillance colonoscopy with targeted biopsies of visible abnormal areas in addition to random biopsy showed almost 90% of dysplastic lesions were visible. Recognition of endoscopic features of dysplasia is pivotal for successful IBD surveillance colonoscopy. Features of dysplasia are subtle and difficult to appreciate. These features include slight elevation, focal friability, obscure vascular pattern, uneven redness, villous mucosa, or irregular nodularity ( Table 19.2 ).



Table 19.2

Endoscopic Features of Colorectal Dysplasia in IBD








  • Slightly elevated or depressed lesion



  • Focal friability



  • Obscure vascular pattern



  • Uneven redness or discoloration



  • Villous mucosa



  • Irregular nodularity





The SCENIC International Consensus


In 2015, the SCENIC International Consensus Statement on Surveillance and Management of Dysplasia in Inflammatory Bowel Disease (SCENIC) was developed by an international multidisciplinary expert panel and endorsed by multiple international gastrointestinal societies. This was an effort to determine the optimal method and standardize practice of surveillance and management of detected dysplasia in IBD. The SCENIC key recommendations for optimizing detection and management of dysplasia in IBD are:



  • 1.

    Using high-definition instead of standard-definition colonoscopes.


  • 2.

    Using chromoendoscopy with targeted biopsy is superior to white-light colonoscopy with random biopsy.


  • 3.

    Equipment-based chromoendoscopy (such as narrow-band imaging [NBI]) cannot replace dye-based chromoendoscopy.


  • 4.

    Using more accurate terminology for describing detected dysplasia as “endoscopically resectable” or “nonendoscopically resectable” and abandoning the use of “DALM,” “adenoma-like” and “non-adenoma-like.”


  • 5.

    Endoscopic removal of visible endoscopically resectable dysplasia rather than colectomy.


  • 6.

    After complete removal of endoscopically resectable polypoid dysplasia, surveillance colonoscopy is recommended rather than colectomy.


  • 7.

    After complete removal of endoscopically resectable nonpolypoid dysplasia, surveillance colonoscopy is suggested rather than colectomy.


  • 8.

    “Nonendoscopically resectable” dysplasia with indistinct borders confirmed by an endoscopist with expertise in IBD surveillance should be referred for surgery.


  • 9.

    Referral to an endoscopist with expertise in IBD surveillance using high-definition chromoendoscopy for patients with invisible dysplasia (confirmed by a GI pathologist).





Image-Enhanced Endoscopy


High-Definition White Light Is Superior to Standard-Definition White-Light Colonoscopy


High-definition (1080 system) endoscopy gives higher image details and improved resolution than the standard definition (480 system). High-definition white light (HDWL) colonoscopy improves colorectal neoplasia detection in IBD and non-IBD patients compared to SDWL colonoscopy. In a retrospective study comparing 209 HDWL colonoscopy and 160 SDWL in UC and Crohn’s disease patients, the adjusted prevalence for detecting any dysplasia or dysplasia on targeted biopsy was 2.21 (95% CI 1.09–4.45) and 2.99 (95% CI 1.16–7.79), respectively, in favor of HD colonoscopy. Experts recommend using HDWL colonoscopy rather than standard definition


Chromoendoscopy With Targeted Biopsy


Tada et al., first described chromoendoscopy using indigo carmine in 1976, where chromoendoscopy involves topical spraying of dye and stains to optimize detection and accurate real-time characterization of colonic mucosal lesions. The most widely used chromoendoscopic stains are indigo carmine and methylene blue. Indigo carmine is a contrast stain that is not absorbed by the colon. It highlights mucosal topography by pooling into crevices and grooves. Methylene blue is a vital stain that is transiently absorbed by normal colonic epithelium and is not absorbed by abnormal colonic epithelium caused by dysplasia or inflammation.


Chromoendoscopy Technique


Chromoendoscopy requires dyes and excellent bowel preparation for an effective technique. Excess water and debris are suctioned on scope insertion and prior to the application of dye. Diluted screening dye (indigo carmine 0.03%–0.1% or methylene blue 0.04%–0.1%) is applied on mucosal surface using applicators, such as syringes, foot pumps, or spray catheters segmentally starting at the caecum. To improve efficiency, the dye stream is sprayed onto the antigravity colonic surface to facilitate dye pooling. Once a colonic segment is completed, the scope is reinserted with collapsing the lumen to allow the dye to coat the entire lumen, and then excess dye is suctioned to allow mucosal inspection for dysplasia. Features of nonpolypoid dysplasia in IBD include mucosal surface unevenness (slight elevation or depression), focal friability, obscure vascular pattern, discoloration, villous, or nodular ( Table 19.2 ). Once a mucosal abnormality is detected, a more concentrated targeted dye (indigo carmine 0.13% or methylene blue 0.2%) may be sprayed through the working (biopsy) channel using a syringe to interrogate the lesion and delineate the margins to assess suitability of endoscopic resection.


Superiority of Chromoendoscopy With Targeted Biopsy


Chromoendoscopy with targeted biopsies increases the diagnostic yield for detecting colitis-associated neoplasia (six prospective and two randomized controlled trials) compared to white-light colonoscopy with random biopsies. In a metaanalysis of six clinical trials, chromoendoscopy with targeted biopsy had an incremental yield for detecting dysplasia by 7% per patient (95% CI 3.3%–10.3%) and the number needed-to-treat to find another patient with at least one dysplasia was 14.3 (range 9.7–30.3). Even in community practice, the yield of dysplasia detection is superior when using chromoendoscopy with targeted biopsies compared to white light with random biopsy. In a multicenter study of 900 patients undergoing chromoendoscopy with 4188 targeted biopsies detecting 8.3% patients with dysplasia (75 patients), the miss rate of dysplasia with additional 26,956 random biopsies was only 1% (9 patients). Another recent prospective multicenter study of 350 patients with 94 dysplastic lesions, the dysplasia detection incremental yield was 57.4% for chromoendoscopy with targeted biopsies over white light with random biopsies. The use of chromoendoscopy in IBD surveillance has been endorsed by gastrointestinal societies. The presence of strictures and pseudopolyps in IBD can limit the utility of chromoendoscopy with targeted biopsies. In such circumstances, random biopsy technique can be used, as strictures can often harbor malignancy. Despite the overwhelming evidence recommending colonoscopic surveillance using chromoendoscopy with targeted biopsy, widespread clinical implementation remains challenging.


Morphologic Description and Endoscopic Characterization of Inflammatory Bowel Disease Dysplasia


SCENIC proposed a new morphologic description, modified from the Paris classification, in an effort to unify terminology and standardize communication ( Table 19.3 ). It clearly defines the term endoscopically resectable as a lesion with identifiable distinct margins, appears to be completely removed on visual inspection after endoscopic resection, completely removed on histologic examination and is dysplasia free on confirmatory biopsies from mucosa immediately adjacent to the resection margin. This is in contrast to the previous confusing terminology such as DALM, adenoma-like and non-adenoma-like .



Table 19.3

The SCENIC Consensus Statement on Morphologic Terminology for Reporting Findings on Colonoscopic Surveillance of Patients With Inflammatory Bowel Disease















































Definition
Visible dysplasia Dysplasia identified on targeted biopsies from a lesion visualized at colonoscopy
Polypoid Lesion protruding from the mucosa into the lumen ≥2.5 mm
Pedunculated Lesion attached to the mucosa by a stalk
Sessile Lesion not attached to the mucosa by a stalk: entire base is contiguous with the mucosa
Nonpolypoid Lesion with little (<2.5 mm) or no protrusion above the mucosa
Superficial elevated Lesion with protrusion but <2.5 mm above the lumen (less than the height of the closed cup of a biopsy forceps)
Flat Lesion without protrusion above the mucosa
Depressed Lesion with at least a portion depressed below the level of the mucosa
General descriptors Ulcerated Ulceration (fibrinous-appearing base with depth) within the lesion
Border Distinct border Lesion’s border is discrete and can be distinguished from surrounding mucosa
Indistinct border Lesion’s border is not discrete and cannot be distinguished from surrounding mucosa
Invisible dysplasia Dysplasia identified on random (nontargeted) biopsies of colon mucosa without a visible lesion

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Dec 30, 2019 | Posted by in GASTROENTEROLOGY | Comments Off on Endoscopic Detection and Removal of Colitis-Associated Dysplasia
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