ABSTRACT
OBJECTIVE: Patients with ulcerative colitis (UC) 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 patients with UC with LGD and create a visual web tool to effectively communicate the risk. DESIGN: In our retrospective multicentre validated cohort study, adult patients with UC with an index diagnosis of LGD, identified from four UK centres between 2001 and 2019, were followed until progression to AN. In the discovery cohort (n=246), a multivariate risk prediction model was derived from clinicopathological features using Cox regression. Validation used data from three external centres (n=198). The validated model was embedded in a web tool to calculate patient-specific risk. RESULTS: Four clinicopathological variables were significantly associated with AN progression in the discovery cohort: endoscopically visible LGD >1 cm (HR 2.7; 95% CI 1.2 to 5.9), unresectable or incomplete endoscopic resection (HR 3.4; 95% CI 1.6 to 7.4), moderate/severe histological inflammation within 5 years of LGD diagnosis (HR 3.1; 95% CI 1.5 to 6.7) and multifocality (HR 2.9; 95% CI 1.3 to 6.2). In the validation cohort, this four-variable model accurately predicted future AN cases with overall calibration Observed/Expected=1.01 (95% CI 0.64 to 1.52), and achieved 100% specificity for the lowest risk group over 13 years of available follow-up. CONCLUSION: Multicohort validation confirms that patients with large, unresected, multifocal LGD and recent moderate/severe inflammation are at highest risk of developing AN. Personalised risk prediction provided via the Ulcerative Colitis-Cancer Risk Estimator ( www.UC-CaRE.uk ) can support treatment decision-making.
Subject(s)
Colitis, Ulcerative , Colitis-Associated Neoplasms , Colorectal Neoplasms , Adult , Cohort Studies , Colitis, Ulcerative/complications , Colitis, Ulcerative/pathology , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/etiology , Humans , Hyperplasia , Inflammation/complications , Retrospective Studies , Risk FactorsABSTRACT
AIMS: To compare the esophageal sensitivity to acid and saline in patients with symptomatic and asymptomatic erosive reflux disease (ERD), non-erosive reflux disease (NERD) and controls, and to assess the response to proton-pump inhibitors in patients with symptomatic ERD and NERD. METHODOLOGY: Patients with GERD and a control group of healthy asymptomatic volunteers were recruited. All subjects underwent esophagogastroduodenoscopy and the acid-saline perfusion test. Symptomatic ERD and NERD patients were given rabeprazole 20 mg twice daily for 2 weeks and their response to treatment assessed. RESULTS: A total of 105 subjects were recruited: ERD=37 (symptomatic=24, asymptomatic=13), NERD=34 and controls=34. During saline perfusion, only the NERD group recorded a significantly higher sensitivity score compared to controls (2.74±7.28 vs. 0) (p=0.035). During acid perfusion, symptomatic ERD (15.42±13.42) and NERD (16.71±15.04) had significantly higher scores versus controls and asymptomatic ERD patients (both p<0.001). The mean %∆ reflux symptom score following treatment was significantly higher in symptomatic ERD patients compared to NERD patients (89.08±21.67 vs. 58.53±32.54; p<0.001). CONCLUSIONS: Patients with NERD were a generally hypersensitive group while asymptomatic ERD patients represent a hyposensitive group of patients which merits further study.
