Why it’s time for updated U.S. colorectal cancer prevention guidelines in inflammatory bowel disease

Abstract 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.

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Reappraising Risk Factors for Inflammatory Bowel Disease-associated Neoplasia: Implications for Colonoscopic Surveillance in IBD

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjaa040 ◽

2020 ◽

Vol 14 (8) ◽

pp. 1172-1177 ◽

Cited By ~ 2

Author(s):

Shailja C Shah ◽

Steven H Itzkowitz

Keyword(s):

Colorectal Cancer ◽

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Disease Duration ◽

Colorectal Neoplasia ◽

Current Guideline ◽

Colonoscopic Surveillance ◽

Inflammatory Bowel ◽

Colorectal Cancer Prevention ◽

Prevention Approach

Abstract One of the most feared complications of inflammatory bowel disease [IBD]-associated colitis is colorectal cancer. When considering the substantial increase in the prevalence of IBD, without any anticipated decline, coupled with decreasing colectomy rates for dysplasia and expanding medical options for effectively controlling inflammation, it is predicted that the pool of people living with—and ageing with—colonic IBD, who are recommended to undergo lifelong colonoscopic surveillance for colorectal neoplasia, will strain existing resources and challenge the sustainability of current guideline-based surveillance recommendations. At the same time, we are missing the opportunity for early detection in a group that is overlooked as high-risk, as a substantial proportion of colorectal cancers are being diagnosed in individuals with colonic IBD who have disease duration shorter than when guidelines recommend surveillance initiation. Here, we reappraise: 1] inflammation as a dynamic risk factor that considers patients’ cumulative course; 2] time of screening initiation that is not based primarily on absolute disease duration; and 3] surveillance intervals as an iterative determination based on individual patient factors and consecutive colonoscopic findings. This Viewpoint supports a paradigm shift that will ideally result in a more effective and higher-value colorectal cancer prevention approach in IBD.

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P175 COLORECTAL CANCER RISK IN INFLAMMATORY BOWEL DISEASE FOLLOWING LIVER TRANSPLANTATION FOR PRIMARY SCLEROSING CHOLANGITIS

Gastroenterology ◽

10.1053/j.gastro.2017.11.227 ◽

2018 ◽

Vol 154 (1) ◽

pp. S93-S94

Author(s):

Derrick Eichele ◽

Benita McVicker ◽

Renee Young ◽

Marco Olivera

Keyword(s):

Colorectal Cancer ◽

Inflammatory Bowel Disease ◽

Liver Transplantation ◽

Cancer Risk ◽

Primary Sclerosing Cholangitis ◽

Bowel Disease ◽

Sclerosing Cholangitis ◽

Colorectal Cancer Risk ◽

Inflammatory Bowel

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Faculty Opinions recommendation of The effects of aminosalicylates or thiopurines on the risk of colorectal cancer in inflammatory bowel disease.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727127611.793549048 ◽

2018 ◽

Author(s):

Eduard Stange ◽

Jan Wehkamp

Keyword(s):

Colorectal Cancer ◽

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Inflammatory Bowel

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Possible Molecular Mechanisms by which Vitamin D Prevents Inflammatory Bowel Disease and Colitis-associated Colorectal Cancer

Current Medicinal Chemistry ◽

10.2174/0929867323666161202153028 ◽

2017 ◽

Vol 24 (9) ◽

pp. 911-917 ◽

Cited By ~ 4

Author(s):

Zijian Luan ◽

Yiming Ma ◽

Yu Xin ◽

Jiaming Qian ◽

Hongying Wang

Keyword(s):

Colorectal Cancer ◽

Inflammatory Bowel Disease ◽

Vitamin D ◽

Bowel Disease ◽

Molecular Mechanisms ◽

Inflammatory Bowel

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37 Monitoring the evolution of inflammatory bowel disease (IBD) in pediatric and adult cohorts of patients to identify biomarkers to predict cancer risk

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0037 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A38-A38

Author(s):

Shilpa Ravindran ◽

Heba Sidahmed ◽

Harshitha Manjunath ◽

Rebecca Mathew ◽

Tanwir Habib ◽

...

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Colorectal Cancer ◽

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Mesenchymal Transition ◽

Increased Risk ◽

Hamad Medical Corporation ◽

Inflammatory Bowel ◽

Left And Right

BackgroundPatients with inflammatory bowel disease (IBD) have increased risk of developing colorectal cancer (CRC), depending on the duration and severity of the disease. The evolutionary process in IBD is driven by chronic inflammation leading to epithelial-to-mesenchymal transition (EMT) events in colonic fibrotic areas. EMT plays a determinant role in tumor formation and progression, through the acquisition of ‘stemness’ properties and the generation of neoplastic cells. The aim of this study is to monitor EMT/cancer initiating tracts in IBD in association with the deep characterization of inflammation in order to assess the mechanisms of IBD severity and progression towards malignancy.Methods10 pediatric and 20 adult IBD patients, admitted at Sidra Medicine (SM) and Hamad Medical Corporation (HMC) respectively, have been enrolled in this study, from whom gut tissue biopsies (from both left and right side) were collected. Retrospectively collected tissues (N=10) from patients with malignancy and history of IBD were included in the study. DNA and RNA were extracted from fresh small size (2–4 mm in diameter) gut tissues using the BioMasher II (Kimble) and All Prep DNA/RNA kits (Qiagen). MicroRNA (miRNA; N=700) and gene expression (N=800) profiling have been performed (cCounter platform; Nanostring) as well as the methylation profiling microarray (Infinium Methylation Epic Bead Chip kit, Illumina) to interrogate up to 850,000 methylation sites across the genome.ResultsDifferential miRNA profile (N=27 miRNA; p<0.05) was found by the comparison of tissues from pediatric and adult patients. These miRNAs regulate: i. oxidative stress damage (e.g., miR 99b), ii. hypoxia induced autophagy; iii. genes associated with the susceptibility to IBD (ATG16L1, NOD2, IRGM), iv. immune responses, such as TH17 T cell subset (miR 29). N=6 miRNAs (miR135b, 10a196b, 125b, let7c, 375) linked with the regulation of Wnt/b-catenin, EM-transaction, autophagy, oxidative stress and play role also in cell proliferation and mobilization and colorectal cancer development were differentially expressed (p<0.05) in tissues from left and right sides of gut. Gene expression signature, including genes associated with inflammation, stemness and fibrosis, has also been performed for the IBD tissues mentioned above. Methylation sites at single nucleotide resolution have been analyzed.ConclusionsAlthough the results warrant further investigation, differential genomic profiling suggestive of altered pathways involved in oxidative stress, EMT, and of the possible stemness signature was found. The integration of data from multiple platforms will provide insights of the overall molecular determinants in IBD patients along with the evolution of the disease.Ethics ApprovalThis study was approved by Sidra Medicine and Hamad Medical Corporation Ethics Boards; approval number 180402817 and MRC-02-18-096, respectively.

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