Low-Grade Dysplasia in Ulcerative Colitis: Risk Factors for Developing High-Grade Dysplasia or Colorectal Cancer

Abstract

OBJECTIVES: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).METHODS: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.RESULTS: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.CONCLUSIONS: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.

DNA Methylation and Mutation of Small Colonic Neoplasms in Ulcerative Colitis and Crohnʼs Colitis

“…Recent univariate and multivariate analyses on the natural history of IBD patients under surveillance suggest that dysplastic lesions <1 cm may not independently raise the risk of subsequent HGD or CRC. (24) The size of sporadic colorectal neoplasms appears to correlate with the quantity of exfoliated DNA. (18, 25) However, in IBD, neither the full clinical significance of small neoplastic or serrated lesions nor their contributions to measurable DNA in stool are understood at this time.…”

Gleaning Insights from Fecal Microbiota Transplantation and Probiotic Studies for the Rational Design of Combination Microbial Therapies

“…Ulcerations, goblet cell depletion, and fewer crypts are also observed. In advanced disease, epithelial cells may undergo dysplasia and increase the risk of epithelial cancer (202,203). Symptoms of mild to moderate disease may include rectal bleeding, diarrhea, and abdominal cramping, while more severe cases may present with fever, weight loss, anemia, and severe abdominal pain (22).…”

Evolution of Premalignant Disease

“…Beyond conventional pathologic staging, increasingly significant risk stratification is made possible based on additional morphological detail, such as premalignant lesion shape in colitis patients (Choi et al 2015) and size (Anaparthy et al 2013), and further still with the addition of genetic, epigenetic, and copy number markers correlated with malignant progression. A review by Kinzler and colleagues provides examples of recent studies that show the ability of genomic profiling to provide insight into premalignancy and application to cancer prevention (Kinzler et al 2016).…”