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.

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 Impact of medical therapies for inflammatory bowel disease on the severity of COVID-19: a systematic review and meta-analysis

2021 ◽  
Vol 8 (1) ◽  
pp. e000774
Author(s):  
Fatema Alrashed ◽  
Robert Battat ◽  
Israa Abdullah ◽  
Aline Charabaty ◽  
Mohammad Shehab
Keyword(s):  
Systematic Review ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Meta Analysis ◽  
Severe Disease ◽  
Aminosalicylic Acid ◽  
Icu Admission ◽  
Increased Risk ◽  
Inflammatory Bowel ◽  
Medical Therapies

BackgroundDuring COVID-19 pandemic, the safety of medical therapies for inflammatory bowel disease (IBD) in relation to COVID-19 has emerged as an area of concern. This study aimed to evaluate the association between IBD therapies and severe COVID-19 outcomes.MethodWe performed a systematic review and meta-analysis of all published studies from December 2019 to August 2021 to identify studies that reported severe COVID-19 outcomes in patients on current IBD therapies including 5-aminosalicylic acid (5-ASA), immunomodulators, corticosteroids, biologics, combination therapy, or tofacitinib.ResultsTwenty-two studies were identified. Corticosteroids (risk ratio (RR) 1.91 (95% CI 1.25 to 2.91, p=0.003)) and 5-ASA (RR 1.50 (95% CI 1.17 to 1.93, p=0.001)) were associated with increased risk of severe COVID-19 outcomes in patients with IBD patients. However, possible confounders for 5-ASA use were not controlled for. Sub-analysis showed that corticosteroids increased the risk of intensive care unit (ICU) admission but not mortality. Immunomodulators alone (RR 1.18 (95% CI 0.87 to 1.59, p=0.28)) or in combination with anti-TNFs ((RR 0.96 (95% CI 0.80 to 1.15, p=0.63)), tofacitinib (RR 0.81 (95% CI 0.49 to 1.33, p=0.40)) and vedolizumab ((RR 1.02 (95% CI 0.79 to 1.31, p=0.89)) were not associated with severe disease. Anti-TNFs (RR 0.47 (95% CI 0.40 to 0.54, p<0.00001)) and ustekinumab (RR 0.55 (95% CI 0.43 to 0.72, p<0.00001)) were associated with decreased risk of severe COVID-19.ConclusionIn patients with IBD, the risk of severe COVID-19 is higher among patients receiving corticosteroids. Corticosteroid use was associated with ICU admission but not mortality. The risk is also higher among patients receiving 5-ASAs. However, patient-level data were lacking and insufficient data existed for meta-regression analyses to adjust for confounding. Vedolizumab, tofacitinib, and immunomodulators alone or in combination with anti-TNF were not associated with severe disease. Anti-TNFs, and ustekinumab were associated with favourable outcomes.

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

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.

scholarly journals Inflammatory Bowel Disease Patients’ Perspectives during COVID-19 Pandemic: Results from a Portuguese Survey

2021 ◽  
pp. 1-9
Author(s):  
Joana Branco Revés ◽  
Catarina Frias-Gomes ◽  
Bárbara Morão ◽  
Catarina Nascimento ◽  
Carolina Palmela ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Immunosuppressive Therapy ◽  
Bowel Disease ◽  
Severe Disease ◽  
Professional Life ◽  
Professional Activity ◽  
Biologic Treatment ◽  
Increased Risk ◽  
Inflammatory Bowel ◽  
The Impact

<b><i>Introduction:</i></b> Patients with inflammatory bowel disease (IBD) do not seem to be at increased risk of infection by SARS-CoV-2, but there is a concern whether immunosuppressive therapy may be associated with more severe disease. Several clinical practice recommendations have been published to help guide IBD care during the COVID-19 pandemic. Nonetheless, few studies have addressed patients’ perspectives and fears. We aimed to evaluate Portuguese IBD patients’ perspectives on the clinical management of their disease during the SARS-CoV-2 pandemic as well as the impact on their professional life. <b><i>Methods:</i></b> An anonymous electronic survey was created using REDCap and was distributed by the Portuguese Association of Inflammatory Bowel Disease (APDI) between May and August 2020. Patients’ perspectives on immunosuppressive therapy, disease management, interaction with gastroenterology departments, and the impact of the pandemic in their professional life were assessed. Patients’ proposals to improve medical care were also evaluated. Descriptive analysis and logistic regression were performed. <b><i>Results:</i></b> A total of 137 participants answered the survey (79.6% females, mean age 41.7 ± 12.1 years). Although having IBD and receiving treatment with immunosuppressors (thiopurines, steroids, or biologics) were considered promotors of anxiety, most patients (85.4%) agreed that disease remission was a priority and only a minority of patients interrupted their treatment during the pandemic. In multivariate analysis, active disease, biologic treatment, and use of corticosteroids in the last 3 months were perceived by the patients as high-risk features for increased risk of SARS-Cov-2 infection and more severe disease. Fifty-nine patients (44%) believed that their follow-up was influenced by the pandemic and only 58.8% felt that they had the opportunity to discuss their therapeutic options with their doctor. Sixty-three patients (46.0%) were working from home during the pandemic, although this decision was related to IBD and immunosuppressive therapy in only 36.5 and 39.7% of the cases, respectively. Areas where care could have been improved during the pandemic were identified by patients, namely enhancement of the communication with IBD professionals, conciliation of telemedicine with face-to-face appointments, and facilitation of the interaction between patients and employers. <b><i>Conclusion:</i></b> Most patients agreed that maintaining IBD remission is crucial, and only a minority of the patients stopped their treatment as per their own initiative. IBD status only had a small influence on patients’ professional activity during the COVID-19 outbreak, with most changes being related to the pandemic itself.

scholarly journals Malignancy and Mortality in Pediatric-onset Inflammatory Bowel Disease: A Systematic Review

2018 ◽  
Vol 24 (4) ◽  
pp. 732-741 ◽  
Author(s):  
Martine A Aardoom ◽  
Maria E Joosse ◽  
Andrica C H de Vries ◽  
Arie Levine ◽  
Lissy de Ridder
Keyword(s):  
Systematic Review ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Meta Analysis ◽  
Severe Disease ◽  
Fatal Outcome ◽  
Patient Specific ◽  
Specific Information ◽  
Increased Risk ◽  
Inflammatory Bowel

Abstract Background Cancer and death are the most severe outcomes that affect patients with inflammatory bowel disease (IBD). These outcomes are even more severe if they occur at a young age but are rare, even in the general population. We conducted a systematic review to provide an overview of all reported pediatric (PIBD) patients with severe outcome. Methods A literature search identified publications that reported development of cancer or fatal outcome in PIBD patients. Studies were eligible for inclusion when (1) article written in English, (2) original data, (3) individual patient information, (4) full text available, (5) study population consisting of patients diagnosed with IBD under the age of 19 years, and (6) who developed malignancy or fatality at any point later in life. Results A total of 98 included studies comprised data of 271 PIBD patients who developed cancer and/or fatal outcome at any point later in life. Meta-analysis demonstrated an increased risk for cancer in PIBD patients (pooled standardized incidence ratio 2.23, 95% CI: 1.98–2.52). The most frequent type of non-fatal cancer was lymphoma, whereas colorectal carcinomas were the most frequently reported type of fatal cancer in PIBD patients and were particularly associated with primary sclerosing cholangitis. The majority of patients with noncancer-related fatal outcomes were diagnosed with ulcerative colitis and most often died due to infectious complications or severe disease-associated complications. Conclusions The data in this review confirm that PIBD associated malignancy and mortality are rare and detailed clinical characteristics are limited. Prospective and international collaborations are needed to obtain more detailed patient-specific information, which is necessary to investigate the relationship between severe outcomes in PIBD patients and the currently used therapeutic strategies.

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.

Association Between Inflammatory Bowel Disease and Dementia: A Retrospective Cohort Study

2021 ◽  
pp. 1-8
Author(s):  
Rebecca Zingel ◽  
Jens Bohlken ◽  
Karel Kostev
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Cumulative Incidence ◽  
Critical Role ◽  
Proportional Hazard ◽  
Cox Proportional Hazard ◽  
Increased Risk ◽  
Inflammatory Bowel ◽  
General Practices ◽  
Incidence Of Dementia

Background: The critical role of inflammatory processes in the pathogenesis of dementia has recently been established. Objective: The aim of this study was to investigate the association between inflammatory bowel disease (IBD) and dementia risk in patients followed in general practices in Germany. Methods: This study included patients aged over 60 with an initial diagnosis of IBD (Crohn’s Disease (CD), ulcerative colitis (UC)) who were followed in 1,159 German general practices between January 1995 and December 2014. IBD patients were matched to healthy patients using propensity scores based on age, gender, index year, insurance type and comorbidities. Kaplan-Meier curves were used to study the development of dementia in patients with or without IBD within up to 15 years of the index date. Cox proportional hazard regression models were used to estimate the relationship between IBD and dementia. Results: The study included 3,850 patients with and 3,850 patients without IBD and revealed a higher cumulative incidence of dementia in IBD patients than in non-IBD patients after the follow-up period. The cumulative incidence of dementia differed within IBD subtypes; it was significantly higher in UC patients than in CD patients. Cox proportional hazard models showed that IBD is associated with a 1.22-fold increase in the risk (95% CI: 1,07–1,39) of developing dementia. UC patients had a 1.25-fold higher risk of developing dementia (95% CI: 1.07–1.46). CD is not significantly associated with an increased risk of dementia (HR: 1.17, 95% CI: 0.93–1.47). Conclusion: A positive association between IBD and dementia was found in patients followed in general practices in Germany.

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.

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