scholarly journals IBD-Associated Dysplastic Lesions Show More Chromosomal Instability Than Sporadic Adenomas

2019 ◽  
Vol 26 (2) ◽  
pp. 167-180 ◽  
Author(s):  
Linda K Wanders ◽  
Martijn Cordes ◽  
Quirinus Voorham ◽  
Daoud Sie ◽  
Sara D de Vries ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Chromosomal Instability ◽  
Precursor Lesions ◽  
Increased Risk ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) patients are at increased risk of developing colorectal cancer. However, histologically, it is challenging to distinguish between IBD-associated dysplasia from sporadic adenomas. We have molecularly characterized these precursor lesions and show that IBD-associated dysplasia lesions are genomically much more unstable.

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

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.

scholarly journals Colorectal Cancer in Inflammatory Bowel Disease

2020 ◽  
Vol 33 (05) ◽  
pp. 305-317
Author(s):  
Martina Nebbia ◽  
Nuha A. Yassin ◽  
Antonino Spinelli
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Severe Disease ◽  
Critical Role ◽  
Mucosal Inflammation ◽  
Surgical Approaches ◽  
Increased Risk ◽  
Significant Difference ◽  
Inflammatory Bowel

AbstractPatients with inflammatory bowel disease (IBD) are at an increased risk for developing colorectal cancer (CRC). However, the incidence has declined over the past 30 years, which is probably attributed to raise awareness, successful CRC surveillance programs and improved control of mucosal inflammation through chemoprevention. The risk factors for IBD-related CRC include more severe disease (as reflected by the extent of disease and the duration of poorly controlled disease), family history of CRC, pseudo polyps, primary sclerosing cholangitis, and male sex. The molecular pathogenesis of inflammatory epithelium might play a critical role in the development of CRC. IBD-related CRC is characterized by fewer rectal tumors, more synchronous and poorly differentiated tumors compared with sporadic cancers. There is no significant difference in sex distribution, stage at presentation, or survival. Surveillance is vital for the detection and subsequently management of dysplasia. Most guidelines recommend initiation of surveillance colonoscopy at 8 to 10 years after IBD diagnosis, followed by subsequent surveillance of 1 to 2 yearly intervals. Traditionally, surveillance colonoscopies with random colonic biopsies were used. However, recent data suggest that high definition and chromoendoscopy are better methods of surveillance by improving sensitivity to previously “invisible” flat dysplastic lesions. Management of dysplasia, timing of surveillance, chemoprevention, and the surgical approaches are all areas that stimulate various discussions. The aim of this review is to provide an up-to-date focus on CRC in IBD, from laboratory to bedside.

Surveillance in inflammatory bowel disease: an overview

2019 ◽  
Vol 17 (8) ◽  
pp. 32-37
Author(s):  
Sara Koo ◽  
Jignesh Jatania ◽  
Colin Rees
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Disease Duration ◽  
The Other ◽  
Surveillance Colonoscopy ◽  
Targeted Biopsy ◽  
White Light Endoscopy ◽  
Increased Risk ◽  
Inflammatory Bowel

Patients with inflammatory bowel disease (IBD), including both ulcerative colitis and Crohn's disease, are at an increased risk of developing colorectal cancer. It is well accepted that this risk increases after 8–10 years of disease duration. Patients should be offered a surveillance colonoscopy after this time. Previously, white-light endoscopy with random biopsies every 10 cm was undertaken for surveillance, but recent evidence suggests that chromoendoscopy along with targeted biopsy is superior to this and the other available methods. This article reviews the available evidence for IBD surveillance, surveillance guidelines and the evidence for chromoendoscopy. Additionally, an overview of the assessment, reporting of any visible abnormal lesions and management of subsequently proven dysplastic lesions is given.

Increased risk of high-grade dysplasia and colorectal cancer in inflammatory bowel disease patients with recurrent low-grade dysplasia

2020 ◽  
Vol 91 (6) ◽  
pp. 1334-1342.e1 ◽  
Author(s):  
Michiel E. de Jong ◽  
Heleen Kanne ◽  
Loes H.C. Nissen ◽  
Joost P.H. Drenth ◽  
Lauranne A.A. P. Derikx ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
High Grade Dysplasia ◽  
Low Grade ◽  
High Grade ◽  
Increased Risk ◽  
Inflammatory Bowel ◽  
Low Grade Dysplasia

Lipidomics As Tools For Finding Biomarkers Of Intestinal Pathology: From Irritable Bowel Syndrome To Colorectal Cancer

2021 ◽  
Vol 22 ◽  
Author(s):  
Lorena Ortega Moreno ◽  
Pilar Navarro Sánchez ◽  
Raquel Abalo
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Irritable Bowel Syndrome ◽  
Bowel Disease ◽  
Screening Methods ◽  
Intestinal Diseases ◽  
Non Invasive ◽  
Increased Risk ◽  
Inflammatory Bowel ◽  
Irritable Bowel

: Lipidomics is an emerging and promising branch that analyses the different lipid mole-cules in a biological sample. It is considered a branch of metabolomics, which is defined as the comprehensive analysis of metabolites in a biological specimen. Nonetheless, in recent years lipidomics is becoming a distinct discipline in the biomedicine field. Lipids play important roles in many biological pathways and can work as biomarkers of disease or therapeutic targets for the treatment of diseases. The major lipidomics strategies are shotgun lipidomics and liquid chromatography coupled with mass spectrometry. Gastro-intestinal diseases, such as irritable bowel syndrome or inflammatory bowel disease, are chronic diseases that need non-invasive biomarkers for prognosis and diagnosis. Even more, patients with inflammatory bowel disease are at significantly increased risk of colorectal cancer, principally resulting from the pro-neoplastic effects of chronic intesti-nal inflammation. Current screening methods utilized globally include sigmoidoscopy or standard colonoscopy, but it is important to develop non-invasive and accurate screen-ing tools to facilitate early detection and precise staging of colorectal cancer. Disease progression and response to treatment may also benefit from the application of these potential new tools. This review focuses on studies that use lipidomics approaches to discover potential biomarkers for monitoring the mentioned intestinal diseases and, par-ticularly, tumor progression.

Inflammation and Cancer IV. Colorectal cancer in inflammatory bowel disease: the role of inflammation

2004 ◽  
Vol 287 (1) ◽  
pp. G7-G17 ◽  
Author(s):  
Steven H. Itzkowitz ◽  
Xianyang Yio
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Colonic Mucosa ◽  
Normal Colonic Mucosa ◽  
Sporadic Colorectal Cancer ◽  
Increased Risk ◽  
Inflammatory Bowel ◽  
Repair Genes

Patients with ulcerative colitis and Crohn's disease are at increased risk for developing colorectal cancer. To date, no known genetic basis has been identified to explain colorectal cancer predisposition in these inflammatory bowel diseases. Instead, it is assumed that chronic inflammation is what causes cancer. This is supported by the fact that colon cancer risk increases with longer duration of colitis, greater anatomic extent of colitis, the concomitant presence of other inflammatory manifestations such as primary sclerosing cholangitis, and the fact that certain drugs used to treat inflammation, such as 5-aminosalicylates and steroids, may prevent the development of colorectal cancer. The major carcinogenic pathways that lead to sporadic colorectal cancer, namely chromosomal instability, microsatellite instability, and hypermethylation, also occur in colitis-associated colorectal cancers. Unlike normal colonic mucosa, however, inflamed colonic mucosa demonstrates abnormalities in these molecular pathways even before any histological evidence of dysplasia or cancer. Whereas the reasons for this are unknown, oxidative stress likely plays a role. Reactive oxygen and nitrogen species produced by inflammatory cells can interact with key genes involved in carcinogenic pathways such as p53, DNA mismatch repair genes, and even DNA base excision-repair genes. Other factors such as NF-κB and cyclooxygenases may also contribute. Administering agents that cause colitis in healthy rodents or genetically engineered cancer-prone mice accelerates the development of colorectal cancer. Mice genetically prone to inflammatory bowel disease also develop colorectal cancer especially in the presence of bacterial colonization. These observations offer compelling support for the role of inflammation in colon carcinogenesis.

Dysplastic Lesions in Inflammatory Bowel Disease: Molecular Pathogenesis to Morphology

2013 ◽  
Vol 137 (3) ◽  
pp. 338-350 ◽  
Author(s):  
Kristina A. Matkowskyj ◽  
Zongming E. Chen ◽  
M. Sambasiva Rao ◽  
Guang-Yu Yang
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Human Cancer ◽  
Significant Risk ◽  
Molecular Pathogenesis ◽  
Field Cancerization ◽  
Molecular Events ◽  
Increased Risk ◽  
Inflammatory Bowel

Context.—Inflammatory bowel disease (IBD) is a long-standing chronic active inflammatory process in the bowel with increased risk for the development of colorectal carcinoma. Several molecular events involved in chronic active inflammatory processes contribute to multistage progression of human cancer development, including reactive oxygen and nitrogen species, aberrant arachidonic acid metabolites and cytokines/growth factors, and immune dysfunction. These molecular events in IBD lead to genetic abnormality and promote aberrant cell proliferation, which further lead to epithelial changes encompassing a broad spectrum from inflammation-induced hyperplasia to dysplasia. Objective.—To review the (1) epidemiologic and molecular pathogenesis of the risk for colorectal cancer in IBD, (2) morphologic characterization, biomarker(s), and classification of dysplastic lesions, and (3) clinical management of dysplastic lesions arising in IBD. Data Sources.—The different IBD-related dysplastic lesions are illustrated by using morphology in conjunction with molecular pathways, and the “field cancerization” theory and its potential significance are discussed with a review of the literature. Conclusions.—Patients with IBD are at increased risk of developing colorectal cancer. The risk of developing carcinoma is related to the extent/duration/activity of the patient's disease. There is no consensus regarding the extent of carcinoma risk associated with IBD; however, all would agree that patients with IBD represent a group at significant risk for developing carcinoma and as such, warrant adequate surveillance and prevention. With better screening modalities and detection/characterization of dysplastic lesions, IBD-associated serrated lesions, and “field cancerization,” we will improve our understanding of and approach to risk stratification.

scholarly journals Cancer Risk in Inflammatory Bowel Disease

1995 ◽  
Vol 9 (1) ◽  
pp. 23-26 ◽  
Author(s):  
Anders M Ekbom
Keyword(s):  
Colorectal Cancer ◽  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Bowel Disease ◽  
Colonic Involvement ◽  
Increased Risk ◽  
Inflammatory Bowel ◽  
Risk Of Cancer

There is an increased risk of cancer in both ulcerative colitis and Crohn's disease. In 3121 patients with ulcerative colitis, 225 cases of cancer were diagnosed compared with 142.1 expected (standardized incidence ratio [SIR] 1.6, 95% CI 1.4 to 1.8), and in 1655 patients with Crohn's disease, 58 cases of cancer were detected compared with 47.1 expected (SIR 1.2, 95% CI 0.9 to 1.6). After excluding colorectal cancer the observed number of malignancies was very close to that expected for ulcerative colitis (SIR 1.0, 95% CI 0.9 to 1.2) and for Crohn's disease (SIR 1.1, 95% CI 0.8 to 1.5). Thus, the increased risk of cancer in inflammatory bowel disease is confined to colorectal cancer. In Crohn's disease 12 cases of colorectal cancer were observed (SIR 2.5, 95% CI 1.3 to 4.3). The increased risk was confined to those with colonic involvement and young age at diagnosis. In patients with colonic involvement and younger than age 30 years at diagnosis, the SIR was 20.9 (95% CI 6.8 to 48.7) versus 2.2 for those older than 30 years at diagnosis (95% CI 0.6 to 5.7). In ulcerative colitis 91 cases of colorectal cancer were observed with an SIR of 5.7 (95% CI 4.6 to 7.0). Extensive disease and young age at diagnosis were independent risk factors. Pancolitis at diagnosis resulted in an SIR of 14.8 (95% CI 11.4 to 18.9), 2.8 in left-sided colitis (95% CI 1.6 to 4.4) and 1.7 in proctitis (95% CI 0.8 to 3.2). There is great variation in the risk estimates in different studies worldwide. Different treatment strategies could be an explanation, a hypothesis that was substantiated in a study of 102 cases of colorectal cancer among patients with ulcerative colitis compared with 196 controls. Pharmacological therapy with sulfasalazine entailed a strong protective effect against colorectal cancer (relative risk of 0.34, 95% CI 0.190 to 0.62).

scholarly journals Colorectal Cancer in Inflammatory Bowel Disease

2018 ◽  
Vol 31 (03) ◽  
pp. 168-178 ◽  
Author(s):  
Peter Higgins ◽  
Ryan Stidham
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Detection Techniques ◽  
Clinical Scenarios ◽  
Increased Risk ◽  
Consensus Statements ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

AbstractPatients with inflammatory bowel disease (IBD) are at significantly increased risk of colorectal cancer (CRC), principally resulting from the pro-neoplastic effects of chronic intestinal inflammation. Epidemiologic studies continue to highlight the increased risk of CRC in IBD. However, the incidence has declined over the past 30 years, attributed to both successful CRC-surveillance programs and improved control of mucosal inflammation. Risk factors that further increase the risk of IBD-related CRC include disease duration, extent and severity, the presence of inflammatory pseudopolyps, coexistent primary sclerosing cholangitis, and a family history of CRC. All major professional societies agree that IBD-CRC surveillance should occur more frequently than in the general population. Yet, guidelines and consensus statements differ on the surveillance schedule and preferred method of surveillance. Improved sensitivity to previously “invisible” flat dysplastic lesions using high definition and chromoendoscopy methods has resulted in many guidelines abandoning requirements for random untargeted biopsies of the colon. While colonic dysplasia remains a worrisome finding, and several clinical scenarios remain best addressed by total proctocolectomy due to concerns of synchronous undetected lesions and the unpredictable tempo of progression to malignancy, better detection techniques have also increased opportunities for endoscopic resection of dysplastic lesions that can be clearly delineated. Finally, the expanding armamentarium of medical options in IBD, including anti-tumor necrosis factor and anti-adhesion biologic therapies, have substantially improved our ability to control severe inflammation and likely reduce the risk of CRC over time.

scholarly journals Inflammatory Bowel Disease and Risk of Colorectal Cancer: An Overview From Pathophysiology to Pharmacological Prevention

2021 ◽  
Vol 12 ◽  
Author(s):  
Marianna Lucafò ◽  
Debora Curci ◽  
Martina Franzin ◽  
Giuliana Decorti ◽  
Gabriele Stocco
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Inflammatory Process ◽  
Current Knowledge ◽  
Genetic Alterations ◽  
Pharmacological Prevention ◽  
Increased Risk ◽  
Inflammatory Bowel

Increased risk of colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients has been attributed to long-standing chronic inflammation, with the contribution of genetic alterations and environmental factors such as the microbiota. Moreover, accumulating data indicate that IBD-associated CRC (IBD-CRC) may initiate and develop through a pathway of tumorigenesis distinct from that of sporadic CRC. This mini-review summarizes the current knowledge of IBD-CRC, focusing on the main mechanisms underlying its pathogenesis, and on the important role of immunomodulators and biologics used to treat IBD patients in interfering with the inflammatory process involved in carcinogenesis.

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