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Background There is debate on the best method of colorectal cancer(CRC) surveillance in inflammatory bowel disease(IBD). We examined how gastroenterologists around the world practise CRC surveillance and manage dysplastic lesions in IBD. Methods A 22-question survey was emailed to gastroenterologists from 34 countries. It included questions on resources for, frequency and mode of CRC surveillance, and management of colorectal dysplasia. The Fisher's exact test and logistic regression were used to evaluate differences among respondents in various domains. Results There were 217 eligible responses, with majority of gastroenterologists working in public hospitals(76%), and treating >10 IBD patients weekly(71%). High-definition white light endoscopy(HDWLE) was available in 93.1% of the centres. The most preferred mode of surveillance was HDWLE with dye-spray chromoendoscopy and targeted biopsies(41.2%). Less than 50% of physicians reported using chromoendoscopy in >50% of cases, citing time as limiting factor(73.7%). Sixty-three percent of gastroenterologists "infrequently"( 10 mm(67.2%), including those >20 mm with low grade dysplasia(LGD)(49.8%), and non-polypoid lesions >10 mm without dysplasia(56.9%). For non-polypoid lesions >20 mm with low- and high-grade dysplasia, referral to expert endoscopists was the preferred option. Conclusion The most preferred method of colorectal cancer surveillance was HDWLE with chromoendoscopy and targeted biopsies. Random biopsies were infrequently performed. The uptake of chromoendoscopy for surveillance in practice was low, with time as the limiting factor. We also observed that physicians varied in their approach in removal of endoscopically resectable dysplastic lesions.

Background: The rationale behind this study was to find out the frequency of dysplasia and colorectal cancer (CRC) in young patients with ulcerative colitis (UC) using histopathological examination. This facilitated early detection of dysplasia and CRC by regular endoscopic biopsies and also guided physicians on appropriate surveillance and management, thus improved outcome. Methods: It was a prospective cross-sectional study conducted at the Department of Pathology, PIMS, Islamabad. Seventy-six biopsies of already diagnosed cases of UC of young patients aged between 15 and 40 years of either gender were included. Specimens were fixed in 10% buffer formalin, paraffin embedded followed by cutting, slide preparation, and staining with hematoxylin and eosin (H&E) stain, and examined under light microscope. Statistical package for social sciences (SPSS 21) was used for data compilation and analysis. Mean and standard deviation were calculated for quantitative variables. Frequency and percentage were calculated for qualitative variables. Results: There were 13 (17.2%) patients who were diagnosed with colorectal dysplasia, 3 (4.0%) with indefinite for dysplasia, 8 (10.5%) with low-grade dysplasia, and 2 (2.6%) with high-grade dysplasia. There were three (3.9%) patients who were diagnosed for colorectal carcinoma, one (1.3%) with grade 1, one (1.3%) with grade 2, and one (1.3%) with grade 3 CRC. Conclusion: Routine biopsies can identify dysplastic epithelium, which is an established sign for synchronized carcinoma with ulcerative colitis, and give the rationale for surveillance of the patients.

In patients with ulcerative colitis or Crohn colitis, the risk for dysplasia and colorectal cancer increases with disease duration, and early detection by surveillance colonoscopy has been the mainstay for preventive treatment. For these diseases in which the clinical management relies heavily upon pathologic interpretation, the diagnosis and grading of dysplasia remains inherently challenged by interobserver variability. This diagnostic challenge is coupled with new developments in endoscopic techniques resulting in relatively rapid shifts in terminology and changes in the macroscopic classification of dysplastic lesions. This article provides pathologists with an update on the preferred macroscopic classification, details the histologic features of dysplasia and utility of immunohistochemistry, and provides a historical context for outdated terminology.

Introduction: The rationale behind this study was to determine the burden of dysplasia and colorectal cancer in young patients with ulcerative colitis on histopathological examination. This facilitated early detection of dysplasia and colorectal cancer by regular endoscopic biopsies will guide the physicians on appropriate surveillance and management. Objectives: To determine the frequency of colorectal dysplasia and colorectal cancer on histopathological examination in young (15-40 years) patients with ulcerative colitis. Patients and Methods: 76 biopsies of already diagnosed cases of UC of young patients aged between 15-40 years of either gender were included. Specimens were fixed in 10% buffer formalin, paraffin embedded followed by cutting, slide preparation and staining with hematoxylin and eosin stain and examined under light microscope. Results: There were 13 (17.2%) patients who were diagnosed for colorectal dysplasia, 03 (3.9%) with indefinite for dysplasia; 08 (10.5%) with low grade; and 02 (2.6%) with high-grade dysplasia. There were 03 (3.9%) patients who were diagnosed for colorectal carcinoma, 01 (1.3%) with grade 1; 01 (1.3%) with grade 2; and 01 (1.3 %) with grade three colorectal cancer. Conclusion: Routine biopsies can identify dysplastic epithelium, an established marker for coexisting malignancy in patients with ulcerative colitis, and provide the rationale for surveillance of these patients.

Two-photon excitation of label-free tissue is of increasing interest, as advances have been made in endoscopic clinical application of multiphoton microscopy, such as second harmonic generation (SHG) scanning endoscopy used to monitor cervical collagen in mice1. We used C57BL mice as a model to investigate the progression of gastrointestinal structures, specifically glandular area and circularity. We used multiphoton microscopy to image ex-vivo label-free murine colon, focusing on the collagen structure changes over time, in mice ranging from 10 to 20 weeks of age. Series of images were acquired within the colonic and intestinal tissue at depth intervals of 20 microns from muscularis to the epithelium, up to a maximum depth of 180 microns. The imaging system comprised a two-photon laser tuned to 800nm wavelength excitation, and the SHG emission was filtered with a 400/40 bandpass filter before reaching the photomultiplier tube. Images were acquired at 15 frames per second, for 200 to 300 cumulative frames, with a field of view of 261um by 261um, and 40mW at sample. Image series were compared to histopathology H&E slides taken from adjacent locations. Quantitative metrics for determining differences between murine glandular structures were applied, specifically glandular area and circularity.

A multi-wavelength prism coupling refractometer is utilized to measure the angular reflectance of freshly excised human intestinal tissue specimens. Based on reflectance data, the real and imaginary part of the refractive index is calculated via Fresnel analysis for three visible (blue, green, red) and two near-infrared (963 nm and 1551 nm) wavelengths. Averaged values of the complex refractive index and corresponding Cauchy dispersion fits are given for the mucosa, submucosa and serosa layers of the colorectal wall at the normal state. The refractive constants of tumorous and normal mucosa are then cross-compared for the indicative cases of one patient diagnosed with a benign polyp and three patients diagnosed with adenocarcinomas of different phenotype. Significant index contrast exists between the normal and diseased states, indicating the potential use of refractive index as a marker of colorectal dysplasia.

When I was training in gastroenterology in the early to mid 1990s, the study of inflammatory owel disease (IBD) was a relatively small and quiet backater of the specialty. Almost 2 decades later, the Immuology, Microbiology, and Inflammatory Bowel Disease ection of the AGA receives more abstract submissions for igestive Diseases Week than any other section of the ociety. At many medical centers, cadres of gastroenterolgists, so-called IBDologists, have further subspecialized uch that their entire practices are devoted to the care of atients with these conditions. These changes reflect the act that large-scale advances have been made in the asessment and treatment of IBD, and the understanding hat the care of these patients requires a unique skill set. he goal of this textbook is to provide a “cutting-edge” pdate to the rapidly evolving field, and is geared toward he general gastroenterologist and the gastroenterology ellow. The book is handbook-sized, 322 pages long, and comosed of 19 chapters. Most chapters contain between 50 nd 120 references. In other words, this book is not ompeting with “reference-type” textbooks containing 00-reference chapters. I would view it more along the ines of an overview or clinical handbook. Many of the chapters are written by prominent experts n the field. The book kicks off with a very interesting istorical overview of IBD written by none other than rofessor Joseph B. Kirsner, followed by a concise expert erspective on IBD epidemiology. An update on the geetics of IBD serves as a good lead-in to the chapter on athophysiology, which covers not only changes in the ecal microbiome, but also how the identification of geetic loci such as CARD15 and ATG16L1 has led to a aradigm shift in interest from acquired to innate immuity and the handling of bacterial products by the epitheium. Five chapters review the evidence base for the use f specific medication classes, including 5-aminosalicyates, corticosteroids, immunosuppressive drugs, biologic gents, and antibiotics/probiotics. The differences in the are of children and adolescents with Crohn’s disease and lcerative colitis are summarized nicely. The remaining c hapters cover surgical therapies, special considerations in omen with IBD, radiographic methods of diagnosis and isease assessment, serologic and endoscopic diagnostic odalities, the clinical utility of serologic markers and hiopurine metabolite monitoring, colorectal dysplasia nd cancer, managing patients with ostomies, and ecoomic considerations. One of the final chapters is an ssembly of 16 color photomicrographs to review the istology of IBD. This book succeeds in providing an update to the eneral gastroenterologist and the gastroenterology fellow n the field of IBD. For gastroenterologists who already re subspecialized as “IBDologists,” this book may not be omprehensive enough as a definitive reference textbook, ut it could still serve as a portable, quick-reference guide. his book suffers from the same problem as virtually all edical textbooks—it is difficult to remain relevant in a apidly changing field when time from chapter submision to publication is long. For example, only about half f the chapters contain references dated 2008 or later. Bottom Line: This textbook serves as a concise overiew of the pathogenesis, diagnosis, and treatment of IBD.

Context.—Colorectal cancer, the most lethal long-term complication of chronic inflammatory bowel disease (IBD), is the culmination of a complex sequence of molecular and histologic derangements of the intestinal epithelium that are initiated and at least partially sustained by chronic inflammation. Dysplasia, the earliest histologic manifestation of this process, plays an important role in cancer prevention by providing the first clinical alert that this sequence is underway and serving as an endpoint in colonoscopic surveillance of patients at high risk for colorectal cancer. Objective.—To review the histology, nomenclature, clinical implications, and molecular pathogenesis of dysplasia in IBD. Data Source.—Literature review and illustrations from case material. Conclusions.—The diagnosis and grading of dysplasia in endoscopic surveillance biopsies play a decisive role in the management of patients with IBD. Although interpathologist variation, endoscopic sampling problems, and incomplete information regarding the natural history of dysplastic lesions are important limiting factors, indirect evidence that surveillance may be an effective means of reducing cancer-related mortality in the population with IBD has helped validate the histologic criteria, nomenclature, and clinical recommendations that are the basis of current practice among pathologists and clinicians. Emerging technologic advances in endoscopy may permit more effective surveillance, but ultimately the greatest promise for cancer prevention in IBD lies in expanding our thus far limited understanding of the molecular pathogenetic relationships between neoplasia and chronic inflammation.

Background: Surveillance colonoscopy in inflammatory bowel diseases (IBDs) is advocated for early diagnosis of neoplasia but is imperfect because some patients develop cancer despite surveillance. We sought to determine if any endoscopic factors during surveillance colonoscopy were associated with the diagnosis of colorectal dysplasia before the development of cancer. Methods: We reviewed the Mayo Clinic endoscopic database and medical records of patients with IBD who underwent surveillance colonoscopy between January 2002 and November 2003. Associations were sought between endoscopic factors and the diagnosis of dysplasia. Among 635 IBD patients, 24 (3.8%) had flat dysplasia and 12 (1.9%) had IBD-related polypoid dysplasia. In 28 patients (4.4%), sporadic tubular adenoma was identified. Colonoscopies in which flat dysplasia was identified varied in duration from 7 to 81 minutes (median, 24.5 min) compared with 3 to 70 minutes (median, 22 min) for those in which dysplasia was not found. Results: Using logistic regression analysis, we found that every additional minute in total colonoscopy time increased the flat dysplasia diagnosis rate by 3.5% (P = 0.0157). There was a significant correlation between median surveillance colonoscopy duration per endoscopist and flat dysplasia diagnosis rate (P = 0.0066). The number of biopsies taken during the procedures with flat dysplasia ranged from 6 to 36 (median, 28) compared with 2 to 54 (median, 25) in those without flat dysplasia. There was no significant effect of biopsy number of dysplasia diagnosis. Conclusions: Our results show that the practice of surveillance colonoscopy varies greatly among endoscopists, and longer procedure duration is significantly associated with the likelihood of dysplasia diagnosis.

Primary sclerosing cholangitis (PSC) is a biliary destructive disease mostly affecting patients with ulcerative colitis (UC). PSC has been suggested to be an independent risk factor for the development of colorectal malignancy in UC. Patients with PSC also have an increased risk of developing cholangiocarcinoma. This study aimed at assessing the cumulative risk of colorectal neoplasia in PSC and UC, and also to determine risk factors for the development of cholangiocarcinoma. Fifty-eight PSC patients were included. Forty PSC patients having extensive UC were each matched to two control patients of the same age, with extensive colitis and a comparable duration of the colitis, but without PSC. All UC patients had been under colonoscopic surveillance with multiple biopsies. Among the 40 PSC patients with UC, 16 developed colonic dysplasia or carcinoma, versus 10 in the control group (P < .001). The absolute cumulative risk of developing colorectal dysplasia/carcinoma in the PSC/UC groups was 9%, 31%, and 50% after 10, 20, and 25 years of disease duration. In the group with UC only, the corresponding risk was 2%, 5%, and 10%, respectively (P < .001). Ten patients with PSC developed cholangiocarcinoma, all but one having UC. In the control group, no cholangiocarcinoma occurred. Patients with PSC and UC with colorectal neoplasia developed cholangiocarcinoma significantly more often compared with patients with UC and PSC without colonic dysplasia/carcinoma (P < .02). This study demonstrates not only that patients with PSC and UC have a significantly higher risk of developing colorectal neoplasia compared with patients having UC only, but also that patients with PSC and UC having colorectal neoplasia are more prone to develop cholangiocarcinoma.

Objective Screening for colorectal cancer (CRC) is currently performed using bright-field colonoscopy, which has low specificity and sensitivity for the detection of early dysplasia in the colon. Fluorescently labeled lectins have been applied topically for detecting glycosylation changes in early dysplastic lesions in the esophagus, providing a route for improved endoscopic detection using fluorescence endoscopy [1]. We have identified here fluorescently labeled lectins that can detect changes in glycosylated biomarkers on the surface epithelium of early dysplasia in CRC. These probes may enable fluorescence-guided resection of dysplastic lesions at colonoscopy and subsequent automated assessment of colon histopathology. Study Design Ninety-nine colon lesions in 48 patients (34 males, 14 females; mean patient age 68.8 ± 8.3 yr, range 53-95 yr) were identified during routine colonoscopy at Addenbrooke's Hospital, Cambridge, UK. Lesions suspected of being dysplastic or neoplastic, were detected using magnification colonoscopy or surgery, and removal performed at biopsy (11.7%) and/or polypectomy (62.1%), or partial colon resection (11.7%). Colon histological sections were stained with fluorescently labeled lectins, and the lectin binding to surface epithelium, which would be observable in colonoscopy, was compared with conventional histopathology for the presence of disease and disease stage. Results Normal colonic epithelium (NE) occupied 40.1% of the area of all sections, hyperplastic polyps (HP) occupied 10.2%, low- (LGD) dysplasia 25.6%, high-grade (HGD) dysplasia 13.9%, and adenocarcinoma (C) 10.2%, as assessed by conventional histopathology based on H&E staining. Lesions were located in the ascending (10.4%), transverse (15.6%), descending (14.3%), sigmoid (42.9%) colon and rectum (7.8%), with the mean lesion size being 16.0 ± 14.2 mm (range 2-60 mm). The lectin wheat germ agglutinin (WGA), when fluorescently-labeled, was capable of distinguishing epithelial regions containing NE from regions containing LGD, HGD and cancer, with >81% sensitivity, >79% specificity and >93% positive predictive value. Conclusions Automated analysis of fluorescently-labeled WGA binding to the surface epithelium of excised colon sections may be used for improving the assessment of early dysplasia in CRC. The same fluorescent lectin may also be useful as a topical imaging agent for improving detection of early dysplasia using fluorescence colonoscopy, increasing the early diagnosis of CRC and improving patient survival. References 1. Bird-Lieberman, E.L., Neves, A.A. et al. (2012). Nat Med. 18(2): p. 315-21. Citation Format: ANDRE NEVES, JOE KUO, Ashraf Ibrahim, KEVIN BRINDLE. molecular imaging of early colorectal dysplasia using fluorescently-labeled lectins. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-122. doi:10.1158/1538-7445.AM2015-LB-122

We validate specific binding activity of a fluorescence-labeled peptide to colorectal dysplasia in living mice using a miniature, flexible, fiber microendoscope that passes through the instrument channel of an endoscope. The microendoscope delivers excitation light at 473 nm through a fiber-optic bundle with outer diameter of 680 µm to collect en face images at 10 Hz with 4 µm lateral resolution. We applied the FITC-labeled peptide QPIHPNNM topically to colonic mucosa in genetically engineered mice that spontaneously develop adenomas. More than two-fold greater fluorescence intensity was measured from adenomas compared to adjacent normal-appearing mucosa. Images of adenomas showed irregular morphology characteristic of dysplasia.