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

Author(s):  
Kit Curtius ◽  
Misha Kabir ◽  
Ibrahim Al Bakir ◽  
Chang-Ho Ryan Choi ◽  
Juanda Hartono ◽  
...  

AbstractBackground and AimsUlcerative 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.MethodsIn 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.ResultsFour 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.ConclusionMulti-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.

2018 ◽  
Vol 12 (supplement_1) ◽  
pp. S157-S158 ◽  
Author(s):  
M Kabir ◽  
K Curtius ◽  
I Al-Bakir ◽  
C -H R Choi ◽  
T Graham ◽  
...  

2019 ◽  
Vol 36 (6) ◽  
pp. 730-735 ◽  
Author(s):  
Elena C Harty ◽  
Jennifer G McIntosh ◽  
Adrian Bickerstaffe ◽  
Nadira Hewabandu ◽  
Jon D Emery

Abstract Objective Australia and New Zealand have the highest incidence of colorectal cancer (CRC) globally. Our research team has developed a CRC risk prediction tool for use in primary care to increase targeted screening. This study, Colorectal cancer RISk Prediction tool – patient (‘CRISP-P’), aimed to determine the following to inform a future trial design: (i) the feasibility of self-reporting; (ii) the feasibility of recruitment methods; and (iii) the prevalence of CRC risk. Methods Participants aged between 40 and 75 years were recruited consecutively from three primary care waiting rooms. Participants input data into CRISP on a tablet without receiving clinical advice. Feasibility was evaluated using recruitment rate, timely completion, a self-reported ‘ease-of-use’, score and field notes. Prevalence of CRC risk was calculated using the CRISP model. Results Five hundred sixty-one (90%) patients agreed to use the tool and 424 (84%) rated the tool easy to use. Despite this, 41% of people were unable to complete the questions without assistance. Patients who were older, without tertiary education or with English as their second language were more likely to require assistance (P < 0.001). Thirty-nine percent of patients were low risk, 58% at slightly increased and 2.4% were at moderately increased risk of developing colorectal cancer in the next 5 years. Conclusions The tool was perceived as easy to use, although older, less educated people, and patients with English as their second language needed help. The data support the recruitment methods but not the use of a self-completed tool for an efficacy trial.


2021 ◽  
Author(s):  
Minta Thomas ◽  
Lori C Sakoda ◽  
Jeffrey K Lee ◽  
Mark A Jenkins ◽  
Andrea Burnett-Hartman ◽  
...  

Gut ◽  
2018 ◽  
Vol 68 (6) ◽  
pp. 977-984 ◽  
Author(s):  
Ryan C Ungaro ◽  
Berkeley N Limketkai ◽  
Camilla Bjørn Jensen ◽  
Kristine Højgaard Allin ◽  
Manasi Agrawal ◽  
...  

ObjectiveThe benefit of continuing 5-aminosalicylate (5-ASA) in patients with ulcerative colitis (UC) who initiate anti-tumour necrosis factor-alpha (anti-TNF) biologics is unknown. We aimed to compare clinical outcomes in patients with UC already on 5-ASA who started anti-TNF and then either stopped or continued 5-ASA.DesignOur primary outcome was any adverse clinical event defined as a composite of new corticosteroid use, UC-related hospitalisation or surgery. We used two national databases: the United States (US) Truven MarketScan health claims database and the Danish health registers. Patients with UC who started anti-TNF after having been on oral 5-ASA for at least 90 days were included. Patients were classified as stopping 5-ASA if therapy was discontinued within 90 days of starting anti-TNF. We performed multivariable Cox regression models controlling for demographics, clinical factors and healthcare utilisation. Adjusted HRs (aHR) with 95% CI are reported comparing stopping 5-ASA with continuing 5-ASA.ResultsA total of 3589 patients with UC were included (2890 US and 699 Denmark). Stopping 5-ASA after initiating anti-TNF was not associated with an increased risk of adverse clinical events in the U.S. cohort (aHR 1.04; 95% CI 0.90 to 1.21, p=0.57) nor in the Danish cohort (aHR 1.09; 95% CI 0.80 to 1.49, p=0.60). Results were similar in sensitivity analyses investigating concomitant immunomodulator use and duration of 5-ASA treatment before initiating anti-TNF.ConclusionIn two national databases, stopping 5-ASA in patients with UC starting anti-TNF therapy did not increase the risk of adverse clinical events. These results should be validated in a prospective clinical trial.


2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S368-S369
Author(s):  
J Estorninho ◽  
P Freire ◽  
S Lopes ◽  
M Ferreira ◽  
M Ferreira ◽  
...  

Abstract Background Ulcerative colitis (UC) has been associated with an increased risk of colorectal cancer (CRC). Although dye spray chromoendoscopy showed superiority to standard colonoscopy in surveillance studies, with the availability of higher-resolution colonoscopes, the utility of chromoendoscopy (CE) has been questioned. We aimed to evaluate the risk of intraepithelial neoplasia (IN) after a high-quality screening colonoscopy (making use of CE or random biopsies (RB) and removing all detected lesions) in a population with longstanding UC and to identify potential risk factors for dysplasia incidence. Methods In a previous study, 145 patients with clinically and endoscopic longstanding (≥8 yr) distal/extensive UC without primary sclerosing cholangitis and/or history of IN were prospectively randomised to undergo CE or RB. In this study, after a median follow-up of 5 additional years, we evaluated subsequent IN incidence in these patients, submitted to surveillance colonoscopy. Patients without high-quality surveillance colonoscopy (with good bowel preparation and cecum intubation) using high-definition were excluded. Results One hundred and twenty-one patients were included. Nine had removed adenomas with low-grade dysplasia in the index colonoscopy. Now, in surveillance colonoscopy, we detected 9 (7.4%) IN: low-grade dysplasia was found in 8 (6.6%) patients and a colorectal adenocarcinoma in 1 (0.008%) patient. After multivariate analysis, IN was significantly associated with older age (68 vs. 52 years, p &lt; 0.05) and higher disease duration (26 vs. 20 years, p &lt; 0.05). No association was found between IN and previous detection of IN in screening colonoscopy sex, the CE or RB use in index colonoscopy, extent of disease, The presence of pseudopolyps, smoking habits, familial history of CRC or maintenance therapy for UC. Conclusion In this study, older patients and higher disease duration were associated with a higher risk of IN in surveillance colonoscopy.


2020 ◽  
Author(s):  
Hou-Qun Ying ◽  
Fan Sun ◽  
Wei Wang ◽  
Dan Cai ◽  
Ying Yang ◽  
...  

Abstract Background Evaluating chronic inflammation in colorectal cancer (CRC) may aid in identifying patients at the highest risk of recurrence or progression, and help inform clinical treatment decisions. Here, we report the effect of fibrinogen to pre-albumin ratio (FPR) in determining response to chemotherapy and reveal outcomes in CRC patients. Methods A total of 2917 eligible CRC patients from multiple-centers were enrolled, and the outcome of these patients was obtained by three years’ follow-up. Circulating fibrinogen, albumin, pre-albumin, CEA, CA199 and FPR were detected and calculated in these patients. Kaplan-Meier curves, Cox regression, time-dependent ROC, Harrell’s concordance index, calibration and decision curves were used to investigate the role of FPR in clinical outcome of CRC patients. Results Our results reveal significantly inferior outcomes in right- than left-sided patients with advanced CRC (stage III and IV), with preoperative FPR found to be a robust and independent prognostic factor for CRC at each stage. Moreover, prognostic nomograms, including FPR, effectively predicted clinical outcomes of the patients. Furthermore, preoperative FPR was significantly associated with chemotherapy efficacy. Specifically, low-grade (FPR < 15) and medium-grade (15 ≤ FPR < 20) FPR patients exhibited complete response to chemotherapy and attenuated chemosensitivity, respectively, whereas high-grade inflammation (FPR ≥ 20) conferred resistance to the treatment. Conclusion CRC-related inflammation affects response to chemotherapy and the resultant clinical outcomes. Circulating FPR is a simple, economically-friendly and robust independent prognostic factor for effectively predicting outcomes of CRC patients. Targeting chronic inflammation and its corresponding signaling pathway, coupled with measuring FPR, presents a novel approach for clinical management of CRC.


Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3575
Author(s):  
Chu-Yi Huang ◽  
Yu-Jing Fang ◽  
Alinuer Abulimiti ◽  
Xia Yang ◽  
Lei Li ◽  
...  

Polyamines (including putrescine, spermidine, and spermine) are small, cationic molecules that are necessary for cell proliferation and differentiation. Few studies have examined the association of dietary polyamines intake with colorectal cancer risk. The aim of this study was to evaluate total polyamines, putrescine, spermidine, and spermine intake in relation to colorectal cancer risk in China. In total, 2502 colorectal cancer cases and 2538 age-(5-year interval) and sex-matched controls were recruited from July 2010 to April 2019. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated by multivariable unconditional logistic regression after adjustment for various potential confounding factors. Higher intake of total polyamine, putrescine and spermidine was significantly associated with reduced risk of colorectal cancer. The adjusted ORs for the highest compared with the lowest quartile of intake were 0.60 (95% CI 0.50, 0.72; Ptrend < 0.001) for total polyamines, 0.35 (95% CI 0.29, 0.43; Ptrend < 0.001) for putrescine and 0.79 (95% CI 0.66, 0.95; Ptrend = 0.001) for spermidine, respectively. However, higher intake of spermine was associated with increased risk of colorectal cancer, with an adjusted OR of 1.58 (95% CI 1.29, 1.93; Ptrend < 0.001). This data indicate that higher intake of total polyamines, putrescine and spermidine, as well as lower intake of spermine, is associated with a decreased risk of colorectal cancer.


2018 ◽  
Vol 75 (5) ◽  
pp. 344-350 ◽  
Author(s):  
Wa Mwenga Walasa ◽  
Renee N Carey ◽  
Si Si ◽  
Lin Fritschi ◽  
Jane S Heyworth ◽  
...  

ObjectiveResearch indicates that shiftwork may be associated with increased risks of adverse health outcomes, including some cancers. However, the evidence of an association between shiftwork and colorectal cancer risk is limited and inconclusive. Further, while several possible pathways through which shiftwork might result in cancer have been proposed, few studies have taken these factors into account. We investigated the association between two types of shiftwork (graveyard shiftwork and early-morning shiftwork) and six mechanistic shiftwork variables (including light at night and phase shift) and the risk of colorectal cancer among females in an Australian population-based case–control study. Graveyard shiftwork was the primary exposure of interest.MethodsParticipants (350 cases and 410 controls) completed a lifetime occupational history, and exposure to each of the eight shiftwork variables was assigned to participants through a job exposure matrix. We used logistic regression to calculate odds ratios (OR) and corresponding 95% confidence intervals (CI) for the association between different shiftwork variables and the risk of colorectal cancer, adjusting for potential demographic, lifestyle and medical confounders.ResultsWorking in an occupation involving long-term exposure (>7.5 years) to graveyard shiftwork was not associated with colorectal cancer risk (adjusted OR 0.95, 95% CI 0.57 to 1.58). Similarly, no increased risks of colorectal cancer were seen for any of the other seven shiftwork variables examined.ConclusionsNo evidence of an increased risk of colorectal cancer among females who had worked in occupations involving shiftwork was observed in this study.


Gene ◽  
2018 ◽  
Vol 673 ◽  
pp. 174-180 ◽  
Author(s):  
Junyi Xin ◽  
Haiyan Chu ◽  
Shuai Ben ◽  
Yuqiu Ge ◽  
Wei Shao ◽  
...  

Author(s):  
Alyssa M Parian ◽  
Berkeley N Limketkai ◽  
Reezwana Chowdhury ◽  
Gala Godoy Brewer ◽  
George Salem ◽  
...  

Abstract Background Patients with long-standing ulcerative colitis (UC) are at an increased risk of colorectal cancer. Risk stratification is important to identify patients who require more frequent endoscopic surveillance. Serrated epithelial change (SEC) found in patients with long-standing colitis may be associated with neoplasia and serve as a marker to stratify patients at higher risk of colorectal cancer (CRC). Methods A case-control study was performed to compare the rates of neoplasia between UC patients with SEC and UC patients without SEC who were matched for age, disease duration, and disease extent. Paired tests, conditional logistic regression, and Kaplan-Meier analyses were used to compare groups. A systematic review with meta-analysis was performed, combining our local data with previously published data. Results This study included 196 UC patients without prior neoplasia, 98 with SEC and 98 without SEC. Ulcerative colitis patients with SEC had a significantly higher rate of synchronous or metachronous neoplasia than UC patients without SEC (26.5% vs 3.1%; P &lt; 0.001). Synchronous or metachronous high-grade dysplasia and CRC were found more frequently in UC patients with SEC than UC patients without SEC (11.2% vs 2.0%; P = 0.02). A meta-analysis was consistent with these findings, showing a higher rate of neoplasia in patients with SEC compared with those without SEC (16.4% vs 3.9%; P &lt; 0.001). Conclusion Serrated epithelial change is associated with a significantly increased risk of synchronous and metachronous neoplasia including high-grade dysplasia and CRC in patients with UC. Histopathological findings of SEC should warrant closer endoscopic surveillance for CRC.


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