Cumulative Histologic Inflammation Predicts Colorectal Neoplasia in Ulcerative Colitis: A Validation Study

Yvellez, Olivia; Rai, Victoria; Sossenheimer, Philip H.; Hart, John; Turner, Jerrold R.; Weber, Christopher; Jurdi, Katia El; Rubin, David T.

doi:10.1093/ibd/izaa047

Cited by 36 publications

(28 citation statements)

References 13 publications

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“…[2][3][4][5] Cumulative inflammatory burden scores have been hypothesized to be more direct and reliable predictors for the risk of (a)CRN. Indeed, recent studies support this concept, [41][42][43] although how to construct the optimal cumulative inflammatory burden score is not clear. It can be questioned whether surrogate markers for inflammation should still be used to stratify patients.…”

Section: Summary Of Identified Risk Factors For Advanced Colorectal Nmentioning

confidence: 99%

Prognostic Factors for Advanced Colorectal Neoplasia in Inflammatory Bowel Disease: Systematic Review and Meta-analysis

et al. 2021

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BACKGROUND AND AIMS: Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal cancer (CRC). We performed a systematic review and meta-analysis to identify all prognostic factors for advanced colorectal neoplasia (aCRN, high-grade dysplasia or Q5 CRC) in patients with IBD. METHODS: A systematic literature search was conducted according to the MOOSE Q6 guidelines. Risk of bias was assessed using the Quality in Prognostic Studies tool. Random-effects models were created separately for odds and hazard ratios, different study designs, and univariable or multivariable data. The evidence for all prognostic factors was categorized as Q7 'weak,' 'moderate,' or 'strong,' based on estimate of effect sizes, heterogeneity, and risk of bias. RESULTS: A total of 164 studies were included allowing Q8 pooled analysis of 31 potential prognostic factors. In the univariable analysis, the evidence for extensive disease was classified as strong while evidence for low-grade dysplasia, strictures, primary sclerosing cholangitis, post Q9 -inflammatory polyps, family history of CRC, and ulcerative colitis versus Crohn's disease was considered moderate. Evidence for any dysplasia, colon segment resection, aneuploidy, male sex Q10 and age was classified as weak. In addition, histologic inflammation was identified as a risk factor in multivariable analysis (weak evidence). The evidence for the protective factors colonoscopic surveillance, 5-ASA Q11 , thiopurines, and smoking was moderate in univariable analysis. Multivariable analysis provided weak evidence for statin use. CONCLUSIONS: In this systematic review and meta-analysis Q12 we identified 13 risk factors and 5 protective factors for aCRN in IBD patients, based

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Section: Summary Of Identified Risk Factors For Advanced Colorectal Nmentioning

confidence: 99%

Prognostic Factors for Advanced Colorectal Neoplasia in Inflammatory Bowel Disease: Systematic Review and Meta-analysis

et al. 2021

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“…Future studies will benefit from large cohort sizes, detailed metadata, considerate sample collection and storage techniques, and robust statistical approaches in order to address the many challenges associated with meta-omics research. However, there are studies that show that colon neoplasia is most likely to develop in the setting of active inflammation and is unlikely to develop in the absence of inflammation ( Rubin et al, 2013 ; Shaffer et al, 2021 ; Yvellez et al, 2021 ). The association of meta-omics changes with other non-IBD chronic immune mediated inflammatory diseases suggests that the intestinal microbial milieu may drive systemic inflammation ( Forbes et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Microbiome-Mediated Immune Signaling in Inflammatory Bowel Disease and Colorectal Cancer: Support From Meta-omics Data

Pratt

Forbes

Knox

et al. 2021

Front. Cell Dev. Biol.

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Chronic intestinal inflammation and microbial dysbiosis are hallmarks of colorectal cancer (CRC) and inflammatory bowel diseases (IBD), such as Crohn’s disease and ulcerative colitis. However, the mechanistic relationship between gut dysbiosis and disease has not yet been fully characterized. Although the “trigger” of intestinal inflammation remains unknown, a wealth of evidence supports the role of the gut microbiome as a mutualistic pseudo-organ that significantly influences intestinal homeostasis and is capable of regulating host immunity. In recent years, culture-independent methods for assessing microbial communities as a whole (termed meta-omics) have grown beyond taxonomic identification and genome characterization (metagenomics) into new fields of research that collectively expand our knowledge of microbiomes. Metatranscriptomics, metaproteomics, and metabolomics are meta-omics techniques that aim to describe and quantify the functional activity of the gut microbiome. Uncovering microbial metabolic contributions in the context of IBD and CRC using these approaches provides insight into how the metabolic microenvironment of the GI tract shapes microbial community structure and how the microbiome, in turn, influences the surrounding ecosystem. Immunological studies in germ-free and wild-type mice have described several host-microbiome interactions that may play a role in autoinflammation. Chronic colitis is a precursor to CRC, and changes in the gut microbiome may be an important link triggering the neoplastic process in chronic colitis. In this review, we describe several microbiome-mediated mechanisms of host immune signaling, such as short-chain fatty acid (SCFA) and bile acid metabolism, inflammasome activation, and cytokine regulation in the context of IBD and CRC, and discuss the supporting role for these mechanisms by meta-omics data.

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“…Previous data from St Mark’s have demonstrated that the cumulative burden of inflammation (CIB) in the preceding years can predict the incidence of colonic neoplasia including large non-polypoid LGD, HGD and CRC [HR: 2.1 per 10-unit increase in CIB (equivalent of 10, 5 or 3.3 years of continuous mild, moderate or severe active histological inflammation); 95% CI 1.4 - 3.0; P<0.001] 18 . The predictive ability of the histologic CIB has been recently validated in an external centre 27 . This is in line with the theory that episodic inflammatory insults followed by mucosal healing encourage colonic epithelial cells to acquire carcinogenic genomic instability and mutations, conferring them a survival advantage to clonally proliferate and develop neoplastic lesions 28,29 .…”

Section: Discussionmentioning

confidence: 99%

Multi-centre derivation and validation of a colitis-associated colorectal cancer risk prediction web-tool

Curtius

Kabir

Bakir

et al. 2020

Preprint

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Background and Aims Ulcerative colitis (UC) patients diagnosed with low-grade dysplasia (LGD) have increased risk of developing advanced neoplasia (AN; high-grade dysplasia or colorectal cancer). We aimed to develop and validate a predictor of AN risk in UC patients with LGD and create a visual web-tool to effectively communicate the risk. Methods In our retrospective multi-centre validated cohort study, adult UC patients with an index diagnosis of LGD, identified from four UK centres between 2001-2019, were followed until progression to AN. In the discovery cohort (n=248), a multivariate risk prediction model was derived from clinicopathological features using Cox regression. Validation used data from 3 external centres (n=201). The validated model was embedded in a web-based tool to calculate and illustrate patient-specific risk. Results Four endoscopic variables were significantly associated with future AN progression in the discovery cohort: endoscopically visible LGD > 1 cm (HR = 2.8; 95% CI 1.3-6.0), incomplete endoscopic resection (HR = 2.9; 95% CI 1.3-6.5), moderate/severe histological inflammation within 5 years of LGD diagnosis (HR = 3.0; 95% CI 1.3-6.7), and multifocality (HR = 2.8; 95% CI 1.3-6.1). In the validation cohort, this 4-variable model accurately predicted future AN cases with overall calibration Observed/Expected = 1 (95% CI 0.63-1.5), and achieved perfect specificity for the lowest predicted risk group over 13 years of follow-up. Conclusion Multi-cohort validation confirms that patients with large, unresected, and multifocal LGD and recent moderate/severe inflammation are at the highest risk of developing AN. Personalised risk prediction provided via the Ulcerative Colitis-Cancer Risk Estimator web-tool (www.UC-CaRE.uk) can be used to support treatment decision-making.

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Cumulative Histologic Inflammation Predicts Colorectal Neoplasia in Ulcerative Colitis: A Validation Study

Cited by 36 publications

References 13 publications

Prognostic Factors for Advanced Colorectal Neoplasia in Inflammatory Bowel Disease: Systematic Review and Meta-analysis

Prognostic Factors for Advanced Colorectal Neoplasia in Inflammatory Bowel Disease: Systematic Review and Meta-analysis

Microbiome-Mediated Immune Signaling in Inflammatory Bowel Disease and Colorectal Cancer: Support From Meta-omics Data

Multi-centre derivation and validation of a colitis-associated colorectal cancer risk prediction web-tool

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