Inflammatory bowel diseases are characterised by inflammation that compromises the integrity of the epithelial barrier. The intestinal epithelium is not only a static barrier but has evolved complex ...mechanisms to control and regulate bacterial interactions with the mucosal surface. Apical tight junction proteins are critical in the maintenance of epithelial barrier function and control of paracellular permeability. The characterisation of alterations in tight junction proteins as key players in epithelial barrier function in inflammatory bowel diseases is rapidly enhancing our understanding of critical mechanisms in disease pathogenesis as well as novel therapeutic opportunities. Here we give an overview of recent literature focusing on the role of tight junction proteins, in particular claudins, in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer.
Early diagnosis and the optimal control of inflammation, with a continuous cycle of assessment, treatment, monitoring, and adjustment of therapy, is best practice for the management of inflammatory ...bowel disease. However, patients express frustration with ongoing challenging symptoms, often discordant with inflammation, including abdominal pain, fatigue, depression, anxiety, and emotional wellness; these are often not optimally addressed by inflammatory bowel disease clinicians due to lack of time or resources. This review will highlight the burden of these symptoms and issues, suggest ways of assessing these in clinical practice, highlight the importance of acknowledging and validating the symptoms and issues with patients, reassuring them that they are being heard, and discuss different possible models of service delivery for psychosocial support, from fully integrated gastropsychology models to referral pathways that optimize community support. We suggest the importance of the treat-to-target concept, where the target is not only control of inflammation but also emotional wellness.
This study provides an overview of the largest and longest-running colonoscopic surveillance program for colorectal cancer (CRC) in patients with long-standing ulcerative colitis (UC).
Data were ...obtained from medical records, endoscopy, and histology reports. Primary end points were defined as death, colectomy, withdrawal from surveillance, or censor date (1 January 2013).
A total of 1,375 UC patients were followed up for 15,234 patient-years (median, 11 years per patient). CRC was detected in 72 patients (incidence rate (IR), 4.7 per 1,000 patient-years). Time-trend analysis revealed that although there was significant decrease in incidence of colectomy performed for dysplasia (linear regression, R=-0.43; P=0.007), IR of advanced CRC and interval CRC have steadily decreased over past four decades (Pearson's correlation, -0.99; P=0.01 for both trends). The IR of early CRC has increased 2.5-fold in the current decade compared with past decade (χ(2), P=0.045); however, its 10-year survival rate was high (79.6%). The IR of dysplasia has similarly increased (χ(2), P=0.01), potentially attributable to the recent use of chromoendoscopy that was twice more effective at detecting dysplasia compared with white-light endoscopy (χ(2), P<0.001). CRCs were frequently accompanied by synchronous CRC or spatially distinct dysplasia (37.5%). Finally, the risk of CRC was not significantly different between "indefinite" or low-grade dysplasia (log-rank, P=0.78).
Colonoscopic surveillance may have a significant role in reducing the risk of advanced and interval CRC while allowing more patients to retain their colon for longer. Given the ongoing risk of early CRC, patients with any grade of dysplasia who are managed endoscopically should be monitored closely with advanced techniques.
Ulcerative colitis: an update Segal, Jonathan P; LeBlanc, Jean-Frédéric; Hart, Ailsa L
Clinical medicine,
March 2021, 2021-03-00, 20210301, Letnik:
21, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Ulcerative colitis is a relapsing and remitting disease that is increasing in incidence and prevalence. Management aims to achieve rapid resolution of symptoms, mucosal healing and improvement in a ...patient’s quality of life. 5-aminosalicylate acid medications remain the first-line treatment for mild to moderate disease. In the event of suboptimal response to these medications, escalation to immunosuppressive medications and biologics may be necessary. Importantly, despite best medical therapy, surgery may be required in a proportion of patients. The future will likely see an array of new therapeutic options for those with ulcerative colitis with the potential for a more personalised treatment approach.
Clonal evolution of colorectal cancer in IBD Choi, Chang-Ho R; Bakir, Ibrahim Al; Hart, Ailsa L ...
Nature reviews. Gastroenterology & hepatology,
04/2017, Letnik:
14, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Optimizing the management of colorectal cancer (CRC) risk in IBD requires a fundamental understanding of the evolutionary process underpinning tumorigenesis. In IBD, clonal evolution begins long ...before the development of overt neoplasia, and is probably accelerated by the repeated cycles of epithelial wounding and repair that are characteristic of the condition. Here, we review the biological drivers of mutant clone selection in IBD with particular reference to the unique histological architecture of the intestinal epithelium coupled with the inflammatory microenvironment in IBD, and the unique mutation patterns seen in IBD-driven neoplasia when compared with sporadic adenomas and CRC. How these data can be leveraged as evolutionary-based biomarkers to predict cancer risk is discussed, as well as how the efficacy of CRC surveillance programmes and the management of dysplasia can be improved. From a research perspective, the longitudinal surveillance of patients with IBD provides an under-exploited opportunity to investigate the biology of the human gastrointestinal tract over space and time.
The human gut virome includes a diverse collection of viruses that infect our own cells as well as other commensal organisms, directly impacting on our well-being. Despite its predominance, the ...virome remains one of the least understood components of the gut microbiota, with appropriate analysis toolkits still in development. Based on its interconnectivity with all living cells, it is clear that the virome cannot be studied in isolation. Here we review the current understanding of the human gut virome, specifically in relation to other constituents of the microbiome, its evolution and life-long association with its host, and our current understanding in the context of inflammatory bowel disease and associated therapies. We propose that the gut virome and the gut bacterial microbiome share similar trajectories and interact in both health and disease and that future microbiota studies should in parallel characterize the gut virome to uncover its role in health and disease.
Crohn's perianal fistulas are challenging for patients and clinicians. Many do not respond to available treatments and despite recommendations by a global consensus, there are currently no specific ...patient-derived quality of life tools to measure response to treatment. We present a new validated patient-reported outcome measure (PROM) for this complicated disease phenotype.
A draft questionnaire was generated using unstructured qualitative patient interviews on the experience of living with Crohn's perianal fistula, a nationwide multidisciplinary consensus exercise, a systematic review of outcomes assessing medical/surgical/combined treatment and a patient and public involvement day. Psychometric properties were assessed including construct validity (by comparison with the Hospital Anxiety and Depression Scale (HADS) and the UK Inflammatory Bowel Disease Questionnaire (UK-IBDQ)), and reliability and responsiveness was assessed by test-retest analysis.
Data from 211 patients contributed to development of a final 28-item questionnaire. The Crohn's Anal Fistula Quality of Life (CAF-QoL) demonstrated good internal consistency (Cronbach's alpha 0.88), excellent stability (intraclass correlation 0.98) and good responsiveness and construct validity, with positive correlation with the UK-IBDQ and HADS.
The CAF-QoL scale is ready for use as a PROM in research and clinical practice. It complements objective clinical evaluation of fistula by capturing impact on the patient.
The aim of this study was to identify risk factors associated with development of high-grade dysplasia (HGD) or colorectal cancer (CRC) in ulcerative colitis (UC) patients diagnosed with low-grade ...dysplasia (LGD).
Patients with histologically confirmed extensive UC, who were diagnosed with LGD between 1993 and 2012 at St Mark's Hospital, were identified and followed up to 1 July 2013. Demographic, endoscopic, and histological data were collected and correlated with the development of HGD or CRC.
A total of 172 patients were followed for a median of 48 months from the date of initial LGD diagnosis (interquartile range (IQR), 15-87 months). Overall, 33 patients developed HGD or CRC (19.1% of study population; 20 CRCs) during study period. Multivariate Cox proportional hazard analysis revealed that macroscopically non-polypoid (hazard ratio (HR), 8.6; 95% confidence interval (CI), 3.0-24.8; P<0.001) or invisible (HR, 4.1; 95% CI, 1.3-13.4; P=0.02) dysplasia, dysplastic lesions ≥1 cm in size (HR, 3.8; 95% CI, 1.5-13.4; P=0.01), and a previous history of "indefinite for dysplasia" (HR, 2.8; 95% CI, 1.2-6.5; P=0.01) were significant contributory factors for HGD or CRC development. Multifocal dysplasia (HR, 3.9; 95% CI, 1.9-7.8; P<0.001), metachronous dysplasia (HR, 3.5; 95% CI, 1.6-7.5; P=0.001), or a colonic stricture (HR, 7.4; 95% CI, 2.5-22.1; P<0.001) showed only univariate correlation to development of HGD or CRC.
Lesions that are non-polypoid or endoscopically invisible, large (≥1 cm), or preceded by indefinite dysplasia are independent risk factors for developing HGD or CRC in UC patients diagnosed with LGD.
PDF
