scholarly journals Colorectal Cancer in Inflammatory Bowel Disease

2018 ◽  
Vol 31 (03) ◽  
pp. 168-178 ◽  
Author(s):  
Peter Higgins ◽  
Ryan Stidham

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.

Author(s):  
Ga Hee Kim ◽  
Yeong Chan Lee ◽  
Tae Jun Kim ◽  
Eun Ran Kim ◽  
Sung Noh Hong ◽  
...  

Abstract Background and Aims Although recent studies have reported that inflammatory bowel disease [IBD] is associated with the development of neurodegenerative diseases via chronic intestinal inflammation and the gut-brain axis, there is insufficient evidence supporting this notion. The aim of this study was to determine the risk of neurodegenerative diseases including Parkinson’s disease [PD] and Alzheimer’s disease [AD] in patients with IBD. Methods Using the National Health Insurance Service data for the entire Korean population, we identified patients with IBD and controls from 2009 to 2011 and followed them up until 2017. We selected the controls in a 1:4 ratio based on age and sex for comparison with cases. Results Of 24 830 IBD patients and 99 320 non-IBD controls, 98 IBD patients and 256 controls developed PD, and 644 IBD patients and 2303 controls developed AD. The overall neurodegenerative disease risk was higher in IBD patients (PD: adjusted hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.24-1.97; AD: adjusted HR, 1.14; 95% CI, 1.05-1.25). Younger IBD patients aged 40-65 years had a higher risk of PD compared with controls [adjusted HR, 2.34; 1.63-3.35]. In contrast, patients aged ≥65 years had an increased risk of AD compared with controls [adjusted HR, 1.14; 1.04-1.25]. In a nested case-control study of the IBD cohort, patients aged ≥65 years and the female sex were risk factors for AD, whereas living in an urban area was protective against AD. Conclusions The risk of neurodegenerative diseases was higher in IBD patients than in the non-IBD population.


Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1398 ◽  
Author(s):  
Fernando Castro ◽  
Heitor S. P. de Souza

Dramatic changes in the environment and human lifestyle have been associated with the rise of various chronic complex diseases, such as inflammatory bowel disease (IBD). A dysbiotic gut microbiota has been proposed as a crucial pathogenic element, contributing to immune imbalances and fostering a proinflammatory milieu, which may be associated with disease relapses or even the initiation of IBD. In addition to representing important regulators of the mucosal immunity and the composition of the gut microbiota, food components have been shown to be potential environmental triggers of epigenetic modifications. In the context of chronic intestinal inflammation, dietary habits and specific food components have been implicated as important modulators of epigenetic mechanisms, including DNA methylation, which may predispose a person to the increased risk of the initiation and evolution of IBD. This review provides novel insights about how dietary factors may interact with the intestinal mucosa and modulate immune homeostasis by shaping the intestinal ecosystem, as well as the potential influence of diet in the etiopathogenesis and management of IBD.


2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A38-A38
Author(s):  
Shilpa Ravindran ◽  
Heba Sidahmed ◽  
Harshitha Manjunath ◽  
Rebecca Mathew ◽  
Tanwir Habib ◽  
...  

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.


Author(s):  
Giorgos Bamias ◽  
Theresa T Pizarro ◽  
Fabio Cominelli

Abstract Intestinal fibrosis is a late-stage phenotype of inflammatory bowel disease (IBD), which underlies most of the long-term complications and surgical interventions in patients, particularly those with Crohn’s disease. Despite these issues, antifibrotic therapies are still scarce, mainly due to the current lack of understanding concerning the pathogenetic mechanisms that mediate fibrogenesis in patients with chronic intestinal inflammation. In the current review, we summarize recent evidence regarding the cellular and molecular factors of innate and adaptive immunity that are considered critical for the initiation and amplification of extracellular matrix deposition and stricture formation. We focus on the role of cytokines by dissecting the pro- vs antifibrotic components of the immune response, while taking into consideration their temporal association to the progressive stages of the natural history of IBD. We critically present evidence from animal models of intestinal fibrosis and analyze inflammation-fibrosis interactions that occur under such experimental scenarios. In addition, we comment on recent findings from large-scale, single-cell profiling of fibrosis-relevant populations in IBD patients. Based on such evidence, we propose future potential targets for antifibrotic therapies to treat patients with IBD.


2019 ◽  
Vol 25 (38) ◽  
pp. 5191-5217 ◽  
Author(s):  
Hai-tao Xiao ◽  
Bo Wen ◽  
Xiang-chun Shen ◽  
Zhao-xiang Bian

Inflammatory bowel disease (IBD) is an uncontrolled chronic inflammatory intestinal disorder, which requires medications for long-term therapy. Facing the challenges of severe side effects and drug resistance of conventional medications, to develop the strategies meet the stringent safety and effectiveness in the long-term treatment are urgent in the clinics. In this regard, a growing body of evidence confirms plant-sourced phenols, such as flavonoids, catechins, stilbenes, coumarins, quinones, lignans, phenylethanoids, cannabinoid phenols, tannins, phenolic acids and hydroxyphenols, exert potent protective benefits with fewer undesirable effects in conditions of acute or chronic intestinal inflammation through improvement of colonic oxidative and pro-inflammatory status, preservation of the epithelial barrier function and modulation of gut microbiota. In this review, the great potential of plant-sourced phenols and their action mechanisms for the treatment or prevention of IBD in recent research are summarized, which may help further development of new preventive/adjuvant regimens for IBD.


2020 ◽  
Vol 33 (05) ◽  
pp. 305-317
Author(s):  
Martina Nebbia ◽  
Nuha A. Yassin ◽  
Antonino Spinelli

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.


2019 ◽  
Vol 17 (8) ◽  
pp. 32-37
Author(s):  
Sara Koo ◽  
Jignesh Jatania ◽  
Colin Rees

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.


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 ◽  
...  

2019 ◽  
Vol 26 (2) ◽  
pp. 167-180 ◽  
Author(s):  
Linda K Wanders ◽  
Martijn Cordes ◽  
Quirinus Voorham ◽  
Daoud Sie ◽  
Sara D de Vries ◽  
...  

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.


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