scholarly journals Evaluation of global and intragenic hypomethylation in colorectal adenomas improves patient stratification and colorectal cancer risk prediction

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Carla Debernardi ◽  
Laura Libera ◽  
Enrico Berrino ◽  
Nora Sahnane ◽  
Anna Maria Chiaravalli ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Cancer Risk ◽  
Risk Prediction ◽  
Methylation Status ◽  
Low Risk ◽  
Colorectal Adenomas ◽  
Dna Hypomethylation ◽  
High Risk Patients ◽  
Risk Patients

Abstract Background Aberrant DNA hypomethylation of the long interspersed nuclear elements (LINE-1 or L1) has been recognized as an early event of colorectal transformation. Simultaneous genetic and epigenetic analysis of colorectal adenomas may be an effective and rapid strategy to identify key biological features leading to accelerated colorectal tumorigenesis. In particular, global and/or intragenic LINE-1 hypomethylation of adenomas may represent a helpful tool for improving colorectal cancer (CRC) risk stratification of patients after surgical removal of polyps. To verify this hypothesis, we analyzed a cohort of 102 adenomas derived from 40 high-risk patients (who developed CRC in a post-polypectomy of at least one year) and 43 low-risk patients (who did not develop CRC in a post-polypectomy of at least 5 years) for their main pathological features, the presence of hotspot variants in driver oncogenes (KRAS, NRAS, BRAF and PIK3CA), global (LINE-1) and intragenic (L1-MET) methylation status. Results In addition to a significantly higher adenoma size and an older patients’ age, adenomas from high-risk patients were more hypomethylated than those from low-risk patients for both global and intragenic LINE-1 assays. DNA hypomethylation, measured by pyrosequencing, was independent from other parameters, including the presence of oncogenic hotspot variants detected by mass spectrometry. Combining LINE-1 and L1-MET analyses and profiling the samples according to the presence of at least one hypomethylated assay improved the discrimination between high and low risk lesions (p = 0.005). Remarkably, adenomas with at least one hypomethylated assay identified the patients with a significantly (p < 0.001) higher risk of developing CRC. Multivariable analysis and logistic regression evaluated by the ROC curves proved that methylation status was an independent variable improving cancer risk prediction (p = 0.02). Conclusions LINE-1 and L1-MET hypomethylation in colorectal adenomas are associated with a higher risk of developing CRC. DNA global and intragenic hypomethylation are independent markers that could be used in combination to successfully improve the stratification of patients who enter a colonoscopy surveillance program. Graphic abstract

scholarly journals Colorectal cancer risk following polypectomy in a multicentre, retrospective, cohort study: an evaluation of the 2020 UK post-polypectomy surveillance guidelines

Gut ◽  
2021 ◽  
pp. gutjnl-2020-323411
Author(s):  
Amanda J Cross ◽  
Emma C Robbins ◽  
Kevin Pack ◽  
Iain Stenson ◽  
Bhavita Patel ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
General Population ◽  
Cox Regression ◽  
Population Based ◽  
Low Risk ◽  
High Grade Dysplasia ◽  
High Grade ◽  
High Risk Patients ◽  
Risk Patients

ObjectiveColonoscopy surveillance aims to reduce colorectal cancer (CRC) incidence after polypectomy. The 2020 UK guidelines recommend surveillance at 3 years for ‘high-risk’ patients with ≥2 premalignant polyps (PMPs), of which ≥1 is ‘advanced’ (serrated polyp (or adenoma) ≥10 mm or with (high-grade) dysplasia); ≥5 PMPs; or ≥1 non-pedunculated polyp ≥20 mm; ‘low-risk’ patients without these findings are instead encouraged to participate in population-based CRC screening. We examined the appropriateness of these risk classification criteria and recommendations.DesignRetrospective analysis of patients who underwent colonoscopy and polypectomy mostly between 2000 and 2010 at 17 UK hospitals, followed-up through 2017. We examined CRC incidence by baseline characteristics, risk group and number of surveillance visits using Cox regression, and compared incidence with that in the general population using standardised incidence ratios (SIRs).ResultsAmong 21 318 patients, 368 CRCs occurred during follow-up (median: 10.1 years). Baseline CRC risk factors included age ≥55 years, ≥2 PMPs, adenomas with tubulovillous/villous/unknown histology or high-grade dysplasia, proximal polyps and a baseline visit spanning 2–90 days. Compared with the general population, CRC incidence without surveillance was higher among those with adenomas with high-grade dysplasia (SIR 1.74, 95% CI 1.21 to 2.42) or ≥2 PMPs, of which ≥1 was advanced (1.39, 1.09 to 1.75). For low-risk (71%) and high-risk (29%) patients, SIRs without surveillance were 0.75 (95% CI 0.63 to 0.88) and 1.30 (1.03 to 1.62), respectively; for high-risk patients after first surveillance, the SIR was 1.22 (0.91 to 1.60).ConclusionThese guidelines accurately classify post-polypectomy patients into those at high risk, for whom one surveillance colonoscopy appears appropriate, and those at low risk who can be managed by non-invasive screening.

scholarly journals Accuracy of upper endoscopies with random biopsies to identify patients with gastric premalignant lesions who can safely be exempt from surveillance

2021 ◽  
Vol 24 (3) ◽  
pp. 680-690
Author(s):  
Michiel C. Mommersteeg ◽  
Stella A. V. Nieuwenburg ◽  
Wouter J. den Hollander ◽  
Lisanne Holster ◽  
Caroline M. den Hoed ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
High Risk ◽  
Low Risk ◽  
Premalignant Lesions ◽  
High Risk Patients ◽  
European Guidelines ◽  
Progression Of Disease ◽  
Risk Patients ◽  
Progression Risk

Abstract Introduction Guidelines recommend endoscopy with biopsies to stratify patients with gastric premalignant lesions (GPL) to high and low progression risk. High-risk patients are recommended to undergo surveillance. We aimed to assess the accuracy of guideline recommendations to identify low-risk patients, who can safely be discharged from surveillance. Methods This study includes patients with GPL. Patients underwent at least two endoscopies with an interval of 1–6 years. Patients were defined ‘low risk’ if they fulfilled requirements for discharge, and ‘high risk’ if they fulfilled requirements for surveillance, according to European guidelines (MAPS-2012, updated MAPS-2019, BSG). Patients defined ‘low risk’ with progression of disease during follow-up (FU) were considered ‘misclassified’ as low risk. Results 334 patients (median age 60 years IQR11; 48.7% male) were included and followed for a median of 48 months. At baseline, 181/334 (54%) patients were defined low risk. Of these, 32.6% were ‘misclassified’, showing progression of disease during FU. If MAPS-2019 were followed, 169/334 (51%) patients were defined low risk, of which 32.5% were ‘misclassified’. If BSG were followed, 174/334 (51%) patients were defined low risk, of which 32.2% were ‘misclassified’. Seven patients developed gastric cancer (GC) or dysplasia, four patients were ‘misclassified’ based on MAPS-2012 and three on MAPS-2019 and BSG. By performing one additional endoscopy 72.9% (95% CI 62.4–83.3) of high-risk patients and all patients who developed GC or dysplasia were identified. Conclusion One-third of patients that would have been discharged from GC surveillance, appeared to be ‘misclassified’ as low risk. One additional endoscopy will reduce this risk by 70%.

scholarly journals A Novel Epigenetic Machine Learning Model to Define Risk of Progression for Hepatocellular Carcinoma Patients

2021 ◽  
Vol 22 (3) ◽  
pp. 1075
Author(s):  
Luca Bedon ◽  
Michele Dal Bo ◽  
Monica Mossenta ◽  
Davide Busato ◽  
Giuseppe Toffoli ◽  
...  
Keyword(s):  
Machine Learning ◽  
Hepatocellular Carcinoma ◽  
High Risk ◽  
Progression Free Survival ◽  
Low Risk ◽  
Functional Enrichment ◽  
Free Survival ◽  
High Risk Patients ◽  
Risk Of Progression ◽  
Risk Patients

Although extensive advancements have been made in treatment against hepatocellular carcinoma (HCC), the prognosis of HCC patients remains unsatisfied. It is now clearly established that extensive epigenetic changes act as a driver in human tumors. This study exploits HCC epigenetic deregulation to define a novel prognostic model for monitoring the progression of HCC. We analyzed the genome-wide DNA methylation profile of 374 primary tumor specimens using the Illumina 450 K array data from The Cancer Genome Atlas. We initially used a novel combination of Machine Learning algorithms (Recursive Features Selection, Boruta) to capture early tumor progression features. The subsets of probes obtained were used to train and validate Random Forest models to predict a Progression Free Survival greater or less than 6 months. The model based on 34 epigenetic probes showed the best performance, scoring 0.80 accuracy and 0.51 Matthews Correlation Coefficient on testset. Then, we generated and validated a progression signature based on 4 methylation probes capable of stratifying HCC patients at high and low risk of progression. Survival analysis showed that high risk patients are characterized by a poorer progression free survival compared to low risk patients. Moreover, decision curve analysis confirmed the strength of this predictive tool over conventional clinical parameters. Functional enrichment analysis highlighted that high risk patients differentiated themselves by the upregulation of proliferative pathways. Ultimately, we propose the oncogenic MCM2 gene as a methylation-driven gene of which the representative epigenetic markers could serve both as predictive and prognostic markers. Briefly, our work provides several potential HCC progression epigenetic biomarkers as well as a new signature that may enhance patients surveillance and advances in personalized treatment.

scholarly journals Does socioeconomic status make a difference? A register-based study on the extent to which cardiovascular screening in patients with inflammatory arthritis leads to recommended follow-up in general practice

RMD Open ◽  
2020 ◽  
Vol 6 (2) ◽  
pp. e000940
Author(s):  
Anette Hvenegaard Kjeldgaard ◽  
Kim Hørslev-Petersen ◽  
Sonja Wehberg ◽  
Jens Soendergaard ◽  
Jette Primdahl
Keyword(s):  
Blood Pressure ◽  
Socioeconomic Status ◽  
High Risk ◽  
Secondary Care ◽  
Inflammatory Arthritis ◽  
Low Risk ◽  
Risk Screening ◽  
High Risk Patients ◽  
Eular Recommendations ◽  
Risk Patients

ObjectiveTo investigate to what extent patients with inflammatory arthritis (IA) follow recommendations given in a secondary care nurse-led cardiovascular (CV) risk screening consultation to consult their general practitioner (GP) to reduce their CV risk and whether their socioeconomic status (SES) affects adherence.MethodsAdults with IA who had participated in a secondary care screening consultation from July 2012 to July 2015, based on the EULAR recommendations, were identified. Patients were considered to have high CV risk if they had risk Systematic COronary Risk Evaluation (SCORE) ≥5%, according to the European SCORE model or systolic blood pressure ≥145 mmHg, total cholesterol ≥8 mmol/L, LDL cholesterol ≥5 mmol/L, HbA1c ≥42 mmol/mol or fasting glucose ≥6 mmol/L. The primary outcome was a consultation with their GP and at least one action focusing on CV risk factors within 6 weeks after the screening consultation.ResultsThe study comprised 1265 patients, aged 18–85 years. Of these, 336/447 (75%) of the high-risk patients and 580/819 (71%) of the low-risk patients had a GP consultation. 127/336 (38%) of high-risk patients and 160/580 (28%) of low-risk patients received relevant actions related to their CV risk, for example, blood pressure home measurement or prescription for statins, antihypertensives or antidiabetics. Education ≥10 years increased the odds for non-adherence (OR 0.58, 95% CI 0.0.37 to 0.92, p=0.02).Conclusions75% of the high-risk patients consulted their GP after the secondary care CV risk screening, and 38% of these received an action relevant for their CV risk. Higher education decreased adherence.

scholarly journals A STING-related prognostic score predicts high-risk patients of colorectal cancer and provides insights into immunotherapy

2021 ◽  
Vol 9 (1) ◽  
pp. 14-14
Author(s):  
Si-Yuan Chen ◽  
Siyu Chen ◽  
Wanjing Feng ◽  
Ziteng Li ◽  
Yixiao Luo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Prognostic Score ◽  
High Risk Patients ◽  
Risk Patients

scholarly journals Changes in patient activation following cardiac rehabilitation using the Active+me digital healthcare platform during the COVID-19 pandemic: a cohort evaluation

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Gabbi Frith ◽  
Kathryn Carver ◽  
Sarah Curry ◽  
Alan Darby ◽  
Anna Sydes ◽  
...  
Keyword(s):  
Blood Pressure ◽  
High Risk ◽  
Cardiac Rehabilitation ◽  
Group Analysis ◽  
Patient Activation ◽  
Low Risk ◽  
Smart Device ◽  
Face To Face ◽  
High Risk Patients ◽  
Risk Patients

Abstract Background Restrictions on face-to-face contact, due to COVID-19, led to a rapid adoption of technology to remotely deliver cardiac rehabilitation (CR). Some technologies, including Active+me, were used without knowing their benefits. We assessed changes in patient activation measure (PAM) in patients participating in routine CR, using Active+me. We also investigated changes in PAM among low, moderate, and high risk patients, changes in cardiovascular risk factors, and explored patient and healthcare professional experiences of using Active+me. Methods Patients received standard CR education and an exercise prescription. Active+me was used to monitor patient health, progress towards goals, and provide additional lifestyle support. Patients accessed Active+me through a smart-device application which synchronised to telemetry enabled scales, blood pressure monitors, pulse oximeter, and activity trackers. Changes in PAM score following CR were calculated. Sub-group analysis was conducted on patients at high, moderate, and low risk of exercise induced cardiovascular events. Qualitative interviews explored the acceptability of Active+me. Results Forty-six patients were recruited (Age: 60.4 ± 10.9 years; BMI: 27.9 ± 5.0 kg.m2; 78.3% male). PAM scores increased from 65.5 (range: 51.0 to 100.0) to 70.2 (range: 40.7 to 100.0; P = 0.039). PAM scores of high risk patients increased from 61.9 (range: 53.0 to 91.0) to 75.0 (range: 58.1 to 100.0; P = 0.044). The PAM scores of moderate and low risk patients did not change. Resting systolic blood pressure decreased from 125 mmHg (95% CI: 120 to 130 mmHg) to 119 mmHg (95% CI: 115 to 122 mmHg; P = 0.023) and waist circumference measurements decreased from 92.8 cm (95% CI: 82.6 to 102.9 cm) to 85.3 cm (95% CI 79.1 to 96.2 cm; P = 0.026). Self-reported physical activity levels increased from 1557.5 MET-minutes (range: 245.0 to 5355.0 MET-minutes) to 3363.2 MET-minutes (range: 105.0 to 12,360.0 MET-minutes; P < 0.001). Active+me was acceptable to patients and healthcare professionals. Conclusion Participation in standard CR, with Active+me, is associated with increased patient skill, knowledge, and confidence to manage their condition. Active+me may be an appropriate platform to support CR delivery when patients cannot be seen face-to-face. Trial registration As this was not a clinical trial, the study was not registered in a trial registry.

P3609Temporal trends of the management and outcomes of patients after myocardial infarction according to the risk for recurrent cardiovascular events

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Grinberg ◽  
T Bental ◽  
Y Hammer ◽  
A R Assali ◽  
H Vaknin-Assa ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
High Risk ◽  
Cardiovascular Events ◽  
Risk Group ◽  
Temporal Trends ◽  
High Risk Group ◽  
Low Risk ◽  
Intermediate Risk ◽  
High Risk Patients ◽  
Risk Patients

Abstract Background Following Myocardial Infarction (MI), patients are at increased risk for recurrent cardiovascular events, particularly during the immediate period. Yet some patients are at higher risk than others, owing to their clinical characteristics and comorbidities, these high-risk patients are less often treated with guideline-recommended therapies. Aim To examine temporal trends in treatment and outcomes of patients with MI according to the TIMI risk score for secondary prevention (TRS2°P), a recently validated risk stratification tool. Methods A retrospective cohort study of patients with an acute MI, who underwent percutaneous coronary intervention and were discharged alive between 2004–2016. Temporal trends were examined in the early (2004–2010) and late (2011–2016) time-periods. Patients were stratified by the TRS2°P to a low (≤1), intermediate (2) or high-risk group (≥3). Clinical outcomes included 30-day MACE (death, MI, target vessel revascularization, coronary artery bypass grafting, unstable angina or stroke) and 1-year mortality. Results Among 4921 patients, 31% were low-risk, 27% intermediate-risk and 42% high-risk. Compared to low and intermediate-risk patients, high-risk patients were older, more commonly female, and had more comorbidities such as hypertension, diabetes, peripheral vascular disease, and chronic kidney disease. They presented more often with non ST elevation MI and 3-vessel disease. High-risk patients were less likely to receive drug eluting stents and potent anti-platelet drugs, among other guideline-recommended therapies. Evidently, they experienced higher 30-day MACE (8.1% vs. 3.9% and 2.1% in intermediate and low-risk, respectively, P<0.001) and 1-year mortality (10.4% vs. 3.9% and 1.1% in intermediate and low-risk, respectively, P<0.001). During time, comparing the early to the late-period, the use of potent antiplatelets and statins increased among the entire cohort (P<0.001). However, only the high-risk group demonstrated a significantly lower 30-day MACE (P=0.001). During time, there were no differences in 1-year mortality rate among all risk categories. Temporal trends in 30-day MACE by TRS2°P Conclusion Despite a better application of guideline-recommended therapies, high-risk patients after MI are still relatively undertreated. Nevertheless, they demonstrated the most notable improvement in outcomes over time.

scholarly journals Stage IV Colorectal Cancer Patients with High Risk Mutation Profiles Survived 16 Months Longer with Individualized Therapies

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 393
Author(s):  
Alexander Hendricks ◽  
Anu Amallraja ◽  
Tobias Meißner ◽  
Peter Forster ◽  
Philip Rosenstiel ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Practice ◽  
High Risk ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Standard Of Care ◽  
High Risk Patients ◽  
Risk Patients ◽  
Individualized Treatments ◽  
Colorectal Cancer Patients

Personalized treatment vs. standard of care is much debated, especially in clinical practice. Here we investigated whether overall survival differences in metastatic colorectal cancer patients are explained by tumor mutation profiles or by treatment differences in real clinical practice. Our retrospective study of metastatic colorectal cancer patients of confirmed European ancestry comprised 54 Americans and 54 gender-matched Germans. The Americans received standard of care, and on treatment failure, 35 patients received individualized treatments. The German patients received standard of care only. Tumor mutations, tumor mutation burden and microsatellite status were identified by using the FoundationOne assay or the IDT Pan-Cancer assay. High-risk patients were identified according to the mutational classification by Schell and colleagues. Results: Kaplan–Meier estimates show the high-risk patients to survive 16 months longer under individualized treatments than those under only standard of care, in the median (p < 0.001). Tumor mutation profiles stratify patients by risk groups but not by country. Conclusions: High-risk patients appear to survive significantly longer (p < 0.001) if they receive individualized treatments after the exhaustion of standard of care treatments. Secondly, the tumor mutation landscape in Americans and Germans is congruent and thus warrants the transatlantic exchange of successful treatment protocols and the harmonization of guidelines.

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