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Ulrik Deding,1,2 Lasse Kaalby,1,2 Gunnar Baatrup,1,2 Morten Kobaek-Larsen,1,2 Marianne Kirstine Thygesen,1,2 Owen Epstein,3 Thomas Bjørsum-Meyer1,2 1Department of Surgery, Odense University Hospital, Svendborg, Denmark; 2Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 3Institute for Minimally Invasive Gastroenterology, Royal Free London NHS Foundation Trust, London, UKCorrespondence: Ulrik Deding, Department of Surgery, Odense University Hospital, Baagøes Allé 15, SVB Bygning 13.02, Svendborg, 5700, Denmark, Tel +45 42574243, Email ulrik.deding@rsyd.dk; udeding@health.sdu.dkPurpose: To investigate whether the prokinetic prucalopride increases the completion rate of colon capsule endoscopy (CCE). Secondary outcomes included demographic distribution, polyp detection rate (PDR), distribution of Leighton–Rex grade, and adverse events.Patients and Methods: In a nested cohort within the CareForColon2015 trial, a subgroup of 406 individuals underwent CCE in 2021. The first half (control) received the standard bowel preparation and the second half (prucalopride) was supplemented with 2 mg of prucalopride. Transit times and bowel preparations were analyzed and completion rates calculated as those having timely transit and acceptable bowel cleanliness. Major adverse events were recorded continuously and minor adverse events were quantified from questionnaires.Results: The group demographics were homogenous. The prevalence ratio for complete CCE was 1.32 (CI 95% 1.15; 1.53) in the prucalopride group compared to the control group. Completion rate was 74.9% in the prucalopride group and 56.7% in the control group. The proportions of acceptable bowel preparation and complete transits were higher in the prucalopride group. The mean CCE transit time was 2 hours and 8 minutes faster in the prucalopride group. The PDR was higher in the intervention group with 55.7% compared to 36.0% in the control group for polyps greater than 9 mm, whereas the groups’ PDRs were similar for small and diminutive polyps. In all, 589 polyps (mean 2.9) were found in the prucalopride group compared to 522 polyps (mean 2.6) in the control group.Conclusion: Prucalopride led to an increase in CCE completion rates. The proportions of complete transits and acceptable bowel preparations were higher in the prucalopride group. The PDR was higher in the prucalopride group compared to the control group. No major adverse events were identified. Nausea, diarrhea, headache and fatigue were more commonly reported in the prucalopride group.Keywords: Resolor, prokinetic, polyps, bowel preparation, Leighton–Rex, video capsule endoscopy

Background: The diagnostic accuracy of colon capsule endoscopy (CCE) depends on a well-cleansed bowel. Evaluating the cleansing quality can be difficult with a substantial interobserver variation., Objectives: Our primary aim was to establish a standard of agreement for bowel cleansing in CCE based on evaluations by expert readers. Then, we aimed to investigate the interobserver agreement on bowel cleansing., Design: We conducted an interobserver agreement study on bowel cleansing quality., Methods: Readers with different experience levels in CCE and colonoscopy evaluated bowel cleansing quality on the Leighton-Rex scale and Colon Capsule CLEansing Assessment and Report (CC-CLEAR), respectively. All evaluations were reported on an image level. A total of 24 readers rated 500 images on each scale., Results: An expert opinion-based agreement standard could be set for poor and excellent cleansing but not for the spectrum in between, as the experts agreed on only a limited number of images representing fair and good cleansing. The overall interobserver agreement on the Leighton-Rex full scale was good (intraclass correlation coefficient (ICC) 0.84, 95% CI (0.82-0.85)) and remained good when stratified by experience level. On the full CC-CLEAR scale, the overall agreement was moderate (ICC 0.62, 95% CI (0.59-0.65)) and remained so when stratified by experience level., Conclusion: The interobserver agreement was good for the Leighton-Rex scale and moderate for CC-CLEAR, irrespective of the reader's experience level. It was not possible to establish an expert-opinion standard of agreement for cleansing quality in CCE images. Dedicated training in using the scales may improve agreement and enable future algorithm calibration for artificial intelligence supported cleansing evaluation., Trial Registration: All included images were derived from the CAREforCOLON 2015 trial (Registered with The Regional Health Research Ethics Committee (Registration number: S-20190100), the Danish data protection agency (Ref. 19/29858), and ClinicalTrials.gov (registration number: NCT04049357))., Competing Interests: Benedicte Schelde-Olesen has received honoraria and participated in advisory board meetings for Jinshan Ltd. Anastasios Koulaouzidis is shareholder of iCERV Ltd., has received consultancy fees and travel support from Jinshan Ltd., and has participated in advisory board meetings hosted by Dr FalkPharmaUK, Norgine, Jinshan, and ANKON. Emanuele Rondonotti has received honoraria from Fujifilm and consultancy fees from Medtronic. Xavier Dray has received lecture fees from Alfasigma, Bouchara, Recordati, Fujifilm, Medtronic, Norgine and Sandoz, has received consultancy fees from Norgine and Provepharma and is co-founder and shareholder of Augmented Endoscopy. Stefania Piccirelli has received a travel grant from AnX Robotica and honoraria from Malesci. Ulrik Deding, Ervin Toth, Konstantinos John Dabos, Abraham Eliakim, Cristina Carretero, Begoña González-Suárez, Thomas de Lange, Hanneke Beaumont, Uri Kopylov, Pierre Ellul, Enrique Pérez-Cuadrado-Robles, Alexander Robertson, Irene Stenfors, Alejandro Bojorquez, Gitte Grunnet Raabe, Reuma Margalit-Yehuda, Isabel Barba, Giulia Scardino, Salome Ouazana, Thomas Bjørsum-Meyer declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2024.)

Purpose: We aimed to develop a predictive tool for anastomotic leakage (AL) following colon cancer surgery by combining a clinical early warning score (EWS) with the C-reactive protein (CRP) level., Methods: The records of 1,855 patients who underwent colon cancer surgery at the Oxford University Hospitals NHS Foundation Trust between January 2013 and December 2018, with or without AL, were retrospectively reviewed. EWS and CRP levels were assessed daily from the first postoperative day until discharge. AL was defined as an anastomotic defect observed at reoperation, the presence of feculent fluid in a pelvic drain, or evidence of AL on computed tomography. The tool incorporated postoperative EWS and CRP levels for the accurate early detection of AL., Results: From postoperative days 3 to 7, the mean CRP level exceeded 200 mg/L in patients with AL and was under 200 mg/L in those without AL (P<0.05). From postoperative days 1 to 5, the mean EWS among patients with leakage exceeded 2, while scores were below 2 among those without leakage (P<0.05). Receiver operating characteristic curve analysis identified postoperative day 3 as the most predictive of early leakage, with cutoff values of 2.4 for EWS and 180 mg/L for CRP; this yielded an area under the curve of 0.87 (sensitivity, 90%; specificity, 70%)., Conclusion: We propose using an EWS of 2.4 and a CRP level of 180 mg/L on postoperative day 3 following colon surgery with anastomosis as threshold values to prompt investigation and treatment of AL.

Background and study aims Quality of bowel preparation and successful transit are critical factors for complete small bowel capsule endoscopy (SBCE) and colon capsule endoscopy (CCE). The aim of this systematic review with meta-analysis was to assess the impact of chewing gum as part of the bowel preparation regimen on the completion rate in both SBCE and CCE. Methods A systematic literature search was conducted in PubMed, Cochrane, Web of Science and Embase. Data were extracted upon quality assessment of included studies. Two reviewers conducted the screening process according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. Eighty-four studies met the search criteria and four randomized controlled trials were included in the meta-analysis, these were assessed for bias using Minors. Pooled completion rate of SBCE studies was defined as the primary outcome. Results Three randomized controlled trials were SBCE studies and one was a CCE study. The pooled completion rate (91%) was not significantly higher in SBCE patients who were given chewing gum after capsule ingestion compared to those who were not (85%). Variance information was not reported in all studies, and therefore, pooled transit time estimates could not be calculated. Conclusions Chewing gum has a good safety profile but has only been used as a booster in one CCE study and a few SBCE studies. More prospective randomized controlled trials, therefore, are needed to investigate the efficacy of chewing gum for achieving complete capsule examination., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: Social inequalities in colorectal cancer screening participation are evident. Barriers to screening participation include discomfort from diagnostic modalities. We aimed to describe the discomfort experienced from colonoscopy and colon capsule endoscopy (CCE) and investigate the discrepancy between expected and experienced discomfort stratified by socioeconomic status., Methods: A randomised controlled trial was conducted offering half of the colorectal cancer screening invitees the choice between CCE and colonoscopy after a positive faecal immunochemical test. This paper includes those who elected to undergo CCE. A positive CCE elicited referral for a therapeutic colonoscopy. Participants reported their discomfort from CCE and from any following colonoscopies in electronically distributed questionnaires. Discomfort was measured using visual analogue scales and compared between socioeconomic subgroups determined by educational level and income., Results: The experienced discomfort from CCE and colonoscopy differed significantly between educational levels but not income levels. The bowel preparation contributed the most to the experienced discomfort in both CCE and colonoscopy. The discrepancy between expected and experienced discomfort from colonoscopy increased with increasing educational and income levels. A similar trend was seen in CCE between educational levels but not income levels., Conclusions: None of the results indicated a higher discomfort in lower socioeconomic subgroups. Regardless of the investigation modality, the bowel preparation was the main contributor to experienced discomfort. The discrepancy between expected and experienced discomfort did not seem to be larger in lower socioeconomic subgroups, indicating that this is not a major barrier causing inequalities in screening uptake. This is the first study investigating individual discomfort discrepancy in both CCE and colonoscopy, while being able to stratify by socioeconomic status., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Gunnar Baatrup reports financial support was provided by 10.13039/501100004196OUH Innovation Fund. Gunnar Baatrup reports financial support was provided by 10.13039/501100010344Aage og Johanne Louis-Hansens Fond. Gunnar Baatrup reports financial support was provided by The Danish Cancer society. Gunnar Baatrup reports financial support was provided by The 10.13039/100004374Medtronic Research Foundation. Gunnar Baatrup reports financial support was provided by The Region of Southern Denmark's Excellence Centre., (© 2024 The Authors.)

Aim: Based on three randomised controlled trials performed more than a decade ago, several national guidelines recommend prolonged venous thromboprophylaxis for 28 days following elective surgery for colon cancer. None of these studies were conducted within enhanced recovery after surgery setting. Newer studies indicate that prolonged prophylaxis might not be necessary with enhanced recovery after surgery. We aimed to provide further evidence to this unresolved discussion., Method: Retrospective study of patients undergoing elective surgery for colon cancer stage I-III with enhanced recovery after surgery in the Capital Region of Denmark from 2014 to 2017. Patients were excluded if discharged on postoperative day 28 or later, dying before discharge, undergoing concomitant rectum resection, or discharged with vitamin K antagonists, direct-oral anticoagulants, or low molecular weight heparin treatment. All patients received only low-dose low molecular weight heparin as prophylaxis during their admission. The primary endpoint was symptomatic lower limb deep venous thrombosis or pulmonary embolism diagnosed within 60 days postoperatively., Results: Out of the included population of 1806 patients, only three experienced a symptomatic venous thromboembolic event; none was fatal. Two had pulmonary embolism associated with pneumonia, while one patient was diagnosed with lower limb deep venous thrombosis at postoperative day 15 after an uncomplicated course with first discharge at postoperative day 2., Conclusion: The risk of symptomatic venous thromboembolism after elective surgery for colon cancer with enhanced recovery after surgery seems negligible even without prolonged prophylaxis. The current guidelines need to be reconsidered., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background & Aims: The role of small-bowel (SB) cancer surveillance by capsule endoscopy (CE) in Lynch syndrome (LS) patients has been investigated in recent years, with contradicting results. This meta-analysis evaluates the diagnostic yield (DY) of CE as a screening tool in asymptomatic LS patients., Methods: A systematic literature search was performed for all studies reporting the results of SB cancer screening in patients with LS. The primary outcome was the evaluation of the DY of CE in this setting for consecutive screening rounds., Results: Five studies comprising 428 patients and CE 677 procedures were included for data extraction and statistical analysis. The estimated pooled DY for CE-identified pathological findings was 8% in the first screening round and 6% in the second. Limiting the analysis to histologically-confirmed pathological findings, the pooled DY of second-round screening dropped to 0%. The included studies showed a significantly different prevalence of pathogenic variants in mismatch repair (path&#95;MMR) genes, which underlie different cumulative incidences of extracolonic cancers., Conclusions: SB surveillance by CE with a 2-year interval in asymptomatic LS individuals does not appear to be an effective screening strategy. Confirmatory prospective studies in this context are needed, considering the different cumulative incidence of SB tumors according to underlying path&#95;MMR defects., Competing Interests: Conflict of interest The listed Authors declare the following potential COIs P.C.V.: lecture fees (Jinshan Ltd.) M.P.: lecture fees (Medtronic and Olympus) A.K.: co-founder and shareholder of AJM Medicaps; co-director and shareholder of iCERV Ltd.; consultancy fees (Jinshan Ltd.); travel support (Jinshan, Aquilant and Falk Pharma); research support (grant) from ESGE/Given Imaging Ltd. and (material) IntroMedic/SynMed; honoraria (Falk Pharma UK, Ferring, Jinshan, Medtronic). Member of Advisory board meetings (Falk Pharma UK, Tillots, ANKON). U.D., T.B-M., F.G., L.L.: no COIs, (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Aim: In the Danish Colorectal Cancer Screening Program (DCCSP), 37% of participants undergoing colonoscopy have a negative result with no obvious findings that can be attributed to a positive faecal immunochemical test (FIT). The aim of this work was to identify predictors for a negative colonoscopy in DCCSP participants with a positive FIT., Method: We included 73 655 FIT-positive DCCSP participants using the Danish Colorectal Cancer Screening Database and linked their screening results with data from several other national health registers. We stratified participants by all predictors, and compared them using multivariate logistic regression analysis. Results are reported as odds ratios (ORs)., Results: We found that having a condition linked to gastrointestinal bleeding, for example fissures, haemorrhoids and inflammatory bowel disease, was strongly associated with the probability of having a negative colonoscopy [OR 2.77 (95% CI 2.59, 2.96)]. FIT concentration was inversely related to the probability of a negative colonoscopy, the OR decreased steadily from 0.79 (95% CI 0.75, 0.83) in the 40-59 μg/g group, to 0.44 (95% CI 0.42, 0.46) in the ≥200 μg/g group. Women had a 1.64 (95% CI 1.59, 1.70) times higher probability of a negative colonoscopy than men., Conclusion: Our findings indicate that baseline conditions linked to gastrointestinal bleeding are an associating factor with having a negative colonoscopy. The same is true for low FIT concentration and female sex. Further studies with similar findings could suggest that an incorporation of these factors into a personalized screening approach by differentiating between diagnostic modalities could improve the process for the participant while alleviating the health care system., (© 2024 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Objective: To determine long-term survival in patients undergoing robot-assisted surgery (RAS) or laparoscopic surgery (LAS) for colon cancer., Background: The potential long-term benefits of RAS compared with LAS for colon cancer are not well examined. Using a register-based approach, we aimed to compare these 2 surgical platforms in an analysis of long-term outcomes, including recurrence-free survival and all-cause- and colon cancer-specific mortality., Methods: A nationwide register-based cohort study of patients with Union for International Cancer Control stage I-III colon cancer undergoing planned RAS or LAS from 2010 through 2018. Patient demographic, clinical, and pathological data were retrieved from Danish national registers. Survival and recurrence rates were estimated by Cox proportional hazard multivariate regression analysis adjusting for baseline covariates., Results: A total of 7565 patients [LAS=6905 (91%) and RAS=660 (9%)] were included in the complete case survival analysis. Patients undergoing LAS had a significantly increased risk of cancer recurrence [LAS=1178 (17.1%), RAS=82 (12.4%), P =0.002] with a mean follow-up time of 4.93 years (standard deviation 2.47). The survival analysis of recurrence-free survival favored RAS [hazard ratio adjusted =0.80, 95% CI (0.64-1.00), P =0.049]. No associations between the 2 surgical platforms were evident regarding all-cause [hazard ratio adjusted =0.98, 95% CI (0.82-1.17), P =0.783] or colon cancer-specific mortality [hazard ratio adjusted =0.89, 95% CI (0.67-1.18), P =0.405]., Conclusions: Adopting RAS for colon cancer was associated with improved recurrence-free survival. However, it did not cause a lower all-cause- or colon cancer-specific mortality., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

In vitro and animal studies have shown that carrot juice containing bioactive natural products, such as falcarinol (FaOH) and falcarindiol (FaDOH), can affect inflammation. The present study was designed to test whether oral intake of carrot juice containing the bioactive acetylenic oxylipins FaOH and FaDOH affects mediators of acute inflammation or the innate immune response in human blood. Carrot juice (500 mL) was administered orally to healthy volunteers, and blood samples were drawn before and 1 h after juice intake. Next, the blood samples were split in two, and one sample was stimulated ex vivo with lipopolysaccharide (LPS) and incubated at 37 °C for 24 h. The concentrations of 44 inflammatory cytokines and chemokines were examined using multiplex electrochemiluminescence analysis. In blood samples not stimulated with LPS, a significant increase in IL-15 was measured 1 h after carrot juice intake. Cytokines like IFN-ɣ, IL-12/IL-23(p40), IL-23, IL-17A, IL-17B, IL-17D, and IL-22 were significantly increased in LPS-stimulated blood samples after carrot juice intake. The upregulation of the immunostimulating cytokines belonging to the IL-23/IL-17 Th17 axis suggests that carrot juice intake could benefit diseases where inflammation plays a role, like in the early stages of diabetes or cancers.

Introduction: Follow-up after an episode of colonic diverticulitis is a common indication for colonoscopy, even though studies have shown a low risk of positive findings in this population. Our objective is to investigate colon capsule endoscopy (CCE) as a follow-up examination in patients with colonic diverticulitis compared with colonoscopy, particularly regarding patient satisfaction and clinical performance., Methods and Analysis: We will conduct a single-centre prospective randomised controlled trial. Patients seen at Odense University Hospital with acute diverticulitis confirmed by CT will be included and randomised to either follow-up by colonoscopy or CCE. Detection of suspected cancer, more than two polyps or any number of polyps larger than 9 mm in CCE will generate an invitation to a diagnostic colonoscopy for biopsies or polyp removal. We will compare colonoscopy and CCE regarding patient satisfaction and tolerance, the number of complete examinations, the number of patients referred to a subsequent colonoscopy after CCE and the prevalence of diverticula, polyps, cancers and other abnormal findings., Ethics and Dissemination: Informed consent will be obtained from all participants before randomisation. The study was approved by the regional ethics committee (ref. S-20210127) and the Danish Data Protection Agency (ref. 22/43235). After completion of the trial, we plan to publish two articles in high-impact journals. One article on both primary and secondary outcomes., Trial Registration Number: NCT05700981., Competing Interests: Competing interests: TB-M has received grants from the Region of Southern Denmark and the Centre of Clinical Implementation for Capsule Endoscopy (CICA). TB-M is member of an Advisory Board for Medtronic regarding optimising bowel preparation in colon capsule endoscopy. Anastasios Koulaouzidis is codirector and shareholder of iCERV Ltd. He has received consultancy fees and travel support from Jinshan Ltd, Diagmed Healthcare Ltd and research support (grant) from ESGE/Given Imaging Ltd and IntroMedic/SynMed, honoraria from Jinshan and Medtronic and has participated in advisory board meetings hosted by ANKON., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Individual income and educational level are associated with participation rates in colorectal cancer screening. We aimed to investigate the expected discomfort from the endoscopic diagnostic modalities of colonoscopy and colon capsule endoscopy in different socioeconomic groups as a potential barrier for participation. In a randomized clinical trial within the Danish colorectal cancer screening program, we distributed questionnaires to 2031 individuals between August 2020 and December 2022 to investigate the expected procedural and overall discomfort from investigations using visual analogue scales. Socioeconomic status was determined by household income and educational level. Multivariate continuous ordinal regressions were performed to estimate the odds of higher expected discomfort. The expected procedural and overall discomfort from both modalities were significantly higher with increasing educational levels and income, except for procedural discomfort from colon capsule endoscopy between income quartiles. The odds ratios for higher expected discomfort increased significantly with increasing educational level, whereas the differences between income groups were less substantial. Bowel preparation contributed most to expected discomfort in colon capsule endoscopy, whereas in colonoscopy, the procedure itself was the largest contributor. Individuals with prior experiences of colonoscopy reported significantly lower expected overall but not procedural discomfort from colonoscopy. The threshold for acceptable discomfort between subgroups is unknown, but the expected discomfort in colon capsule endoscopy and colonoscopy was higher in higher socioeconomic subgroups, suggesting that expected discomfort is not a significant contributor to the inequalities in screening uptake., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Population-based screening for colorectal cancer by a faecal immunochemical test (FIT) is recommended by the European Union. Detectable faecal haemoglobin can indicate colorectal neoplasia as well as other conditions. A positive FIT predicts an increased risk of death from colorectal cancer but might also predict an increased risk of all-cause mortality., Methods: A cohort of screening participants was followed using the Danish National Register of Causes of Death. Data were retrieved from the Danish Colorectal Cancer Screening Database supplemented with FIT concentrations. Colorectal cancer specific and all-cause mortality were compared between FIT concentration groups using multivariate cox proportional hazards regression models., Findings: In 444,910 Danes invited for the screening program, 25,234 (5·7%) died during a mean follow-up of 56·5 months. Colorectal cancer caused 1120 deaths. The risk of colorectal cancer death increased with the increasing FIT concentration. The hazard ratios ranged from 2·6 to 25·9 compared to individuals with FIT concentrations <4 μg hb/g faeces. Causes other than colorectal cancer caused 24,114 deaths. The risk of all-cause death increased with the increasing FIT concentration, with the hazard ratios ranging from 1·6 to 5·3 compared to individuals with FIT concentrations <4 μg hb/g faeces., Interpretation: The risk of colorectal cancer mortality increased with the increasing FIT concentrations even for FIT concentrations considered negative in all European screening programs. The risk of all-cause mortality was also increased for individuals with detectable faecal blood. For colorectal cancer specific mortality and all-cause mortality, the risk was increased at the FIT concentrations as low as 4-9 μg hb/g faeces., Funding: The study was funded by the Odense University Hospital grants A3610 and A2359., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To estimate the risk of interval colorectal cancer (CRC) in faecal immunochemical test (FIT) negative screening participants according to socioeconomic status., Design: In this register-based study, first round FIT negative (<20 µg hb/g faeces) screening participants (biennial FIT, citizens aged 50-74) were followed to estimate interval CRC risk. Multivariate Cox proportional hazard regression models estimated HRs based on socioeconomic status defined by educational level and income. Models were adjusted for age, sex and FIT concentration., Results: We identified 829 (0.7‰) interval CRC in 1 160 902 individuals. Interval CRC was more common in lower socioeconomic strata with 0.7‰ for medium-long higher education compared with 1.0‰ for elementary school and 0.4‰ in the highest income quartile compared with 1.2‰ in the lowest. These differences did not translate into significant differences in HR in the multivariate analysis, as they were explained by FIT concentration and age. HR for interval CRC was 7.09 (95% CI) for FIT concentrations 11.9-19.8 µg hb/g faeces, and 3.37 (95% CI) for FIT between 7.2 and 11.8 compared with those <7.2. The HR rose with increasing age ranging from 2.06 (95% CI 1.45 to 2.93) to 7.60 (95% CI 5.63 to 10.25) compared with those under 55 years., Conclusion: Interval CRC risk increased with decreasing income, heavily influenced by lower income individuals more often being older and having increased FIT concentrations. Individualising screening interval based on age and FIT result, may decrease interval CRC rates, reduce the social gradient and thereby increase the screening efficiency., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This study aimed to evaluate the impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) restrictions such as social distancing on the occurrence of acute gastroenteritis (AGE) among children. This study is a register-based study, including every child seen in the departments of paediatrics with the initial diagnosis of AGE in three neighbouring hospitals in Denmark, from March 2018 through February 2021. The study also included every positive stool sample for AGE-causing pathogens analysed in these three hospitals from children during the same period. The Wilcoxon rank-sum test was used to determine differences between the period during the SARS-CoV-2 restrictions and before. In all, 222,157 children were seen in the three paediatric departments during this period. Of these, 3917 children were diagnosed with AGE. We found a decrease of 46.6% in AGE-related visits per month after the SARS-CoV-2 restrictions were introduced compared to before ( p -value < 0.001). Positive stool samples decreased by 38.2% ( p -value = 0.008) during the restrictions. This study found that cases of paediatric AGE decreased significantly the during COVID-19 restrictions, suggesting that studies should be conducted to determine whether this reduction was a result of good hand hygiene and social distancing or just a result of altered health-seeking behaviour among children.

Background: Colon capsule endoscopy (CCE) was introduced in our department on two indications; following incomplete colonoscopy as an alternative to CT colonography, and in patients with a history of incomplete colonoscopy as an alternative to anesthesia-assisted (AA) colonoscopy. We aimed to compare the quality of CCE, defined by completion rate and polyp detection rate (PDR), with that of CT colonography and AA colonoscopy, respectively., Methods: Patients referred for CCE from May 2020 until November 2021 were consecutively included in this prospective cohort study. Demographics, indication and CCE outcomes were registered from the electronic patient record. Completion rate and PDR in CCE as an alternative to CT colonography were compared with those of a historical cohort undergoing CT colonography following incomplete colonoscopy. Completion rate and PDR in CCE as an alternative to AA colonoscopy were compared with those of a time true parallel cohort undergoing AA colonoscopy., Results: In 65 patients undergoing CCE, 36 (57%) were referred as an alternative to CT colonography. The completion rate in this group was 44% compared to 96% in CT colonography (p < 0.001). The PDR in complete CCE in this group was 75% in CCE compared to 20% in CT colonography (p < 0.001). The remaining 27 (43%) of the sample were referred for CCE as an alternative to AA colonoscopy. The completion rate in this group was 33% compared to 100% in AA colonoscopy (p < 0.001). The PDR in complete CCE in this group was 78% in CCE compared to 35% in AA colonoscopy (p = 0.013)., Conclusions: The completion rate of CCE following incomplete colonoscopy is inferior to that of CT colonography and AA colonoscopy. The PDR of CCE was high, indicating an acceptable sensitivity in complete investigations, but in our settings the completion rate of CCE on this indication is unacceptably low., Clinical Trial Registration: NCT04307901 (ClinicalTrials.gov, March 13, 2020)., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A prospectively followed Danish cohort of 55,756 citizens with an observation time upwards of 25 years was investigated for association between eating raw carrots on a regular basis and developing various adenocarcinoma-dominant cancers and leukemia. Mean age at inclusion was 56.2 years (SD 4.4 years), and 52% were females. A dose-dependent reduction in incidence was seen for cancer of the lung (HR 0.76, CI95% 0.66; 0.87) and pancreas (HR 0.79, CI95% 0.61; 1.03), as well as leukemia (HR 0.91, CI95% 0.68; 1.21). Only for lung cancer was the association significant. In the case of pancreatic cancer, a possible type 1 error was present due to a low number of cancers. In cases of breast and prostate cancer, no association and no dose response were demonstrated. The association seen for lung and pancreatic cancer parallels that earlier demonstrated for large bowel cancer and indicates a cancer-protective effect from daily intake of raw carrots not limited to gastrointestinal adenocarcinomas. Processed carrots exhibited no effect. The preventive effect could be due to the polyacetylenic compounds falcarinol and falcarindiol in carrots, whereas carotene may not have an effect. The polyacetylenes are inactivated by heating, supporting our findings that only raw carrot intake has an effect. Indirect evidence for the cancer preventive effect of carrots in humans has reached a level where a prospective human trial is now timely.

In vitro studies and animal studies have shown that chemical compounds contained in carrots, such as falcarinol and falcarindiol, can prevent inflammation. The present study was designed to test whether the oral intake of carrot juice containing falcarinol and falcarindiol affects the activity of cyclooxygenase (COX) enzymes and the secretion of inflammatory cytokines in human blood. Carrot juice (500 mL) was administered orally to healthy volunteers, and blood samples were drawn before and 1 h after juice intake at the time point when peak concentrations of falcarinol and falcariondiol have been shown in the blood. The blood samples were divided, and one sample was allowed to coagulate for 1 h at room temperature before analyzing the synthesis of thromboxane B2 (TBX2) by the COX1 enzyme using an enzyme linked immunosorbent assay (ELISA). The other blood samples were stimulated ex vivo with lipopolysaccharide and incubated at 37 °C for 24 h. The ELISA and cytokine multiplex analysis assessed the levels of COX-2-induced prostaglandin E2 (PGE2) and inflammatory markers interleukin (IL) 1α, IL1β, IL6, IL16, and tumor necrosis factor α (TNFα). Inflammatory cytokines such as IL1α and IL16 were significantly reduced in the LPS stimulated blood samples with higher concentrations of falcarinol and falcariondiol compared to the control samples taken before the intake of carrot juice. The levels of TBX2, PGE2, IL1β, IL6, and TNFα were not affected by the carrot juice intake blood samples not stimulated with LPS. In conclusion, carrot juice rich in the polyacetylens falcarinol and falcarindiol affects blood leukocytes, priming them to better cope with inflammatory conditions, evident by the reduced secretion of the proinflammatory cytokines IL1α and IL16.

Background: Colorectal cancer (CRC) screening reduces all-cause and CRC-related mortality. New research demonstrates that the faecal haemoglobin concentration (f-Hb) may indicate the presence of other serious diseases not related to CRC. We investigated the association between f-Hb, measured by a faecal immunochemical test (FIT), and both all-cause mortality and cause of death in a population-wide cohort of screening participants., Methods: Between 2014 and 2018, 1,262,165 participants submitted a FIT for the Danish CRC screening programme. We followed these participants, using the Danish CRC Screening Database and several other national registers on health and population, until December 31, 2018. We stratified participants by f-Hb and compared them using a Cox proportional hazards regression on all-cause mortality and cause of death reported as adjusted hazard ratios (aHRs). We adjusted for several covariates, including comorbidity, socioeconomic factors, demography and prescription medication., Results: We observed 21,847 deaths in the study period. Our multivariate analyses indicated an association relationship between increasing f-Hb and the risk of dying in the study period. This risk increased steadily from aHR 1.38 (95% CI: 1.32, 1.44) in those with a f-Hb of 7.1-11.9 μg Hb/g faeces to 2.20 (95% CI: 2.10, 2.30) in those with a f-Hb ≥60.0 μg Hb/g faeces, when compared to those with a f-Hb ≤7.0 μg Hb/g faeces. The pattern remained when excluding CRC from the analysis. Similar patterns were observed between incrementally increasing f-Hb and the risk of dying from respiratory disease, cardiovascular disease and cancers other than CRC. Furthermore, we observed an increased risk of dying from CRC with increasing f-Hb., Conclusions: Our findings support the hypothesis that f-Hb may indicate an elevated risk of having chronic conditions if causes for the bleeding have not been identified. The mechanisms still need to be established, but f-Hb may be a potential biomarker for several non-CRC diseases., (© 2023. The Author(s).)

Colon capsule endoscopy (CCE) is a promising modality for colonic investigations, but completion rates (CR) and adequate cleansing rates (ACR) must be improved to meet established standards for optical colonoscopy. Improvements should be made with patient acceptability in mind. We aimed to compare a very low-volume polyethylene glycol (PEG) laxative to a conventional high-volume laxative. We carried out a single-center retrospective comparative cohort study including patients referred for CCE. One hundred and sixty-six patients were included in the final analysis, with eighty-three patients in each group. We found a CR and ACR of 77% and 67% in the high-volume group and 72% and 75% in the very low-volume group, respectively. In the high-volume group, 54% had complete transit and adequate cleansing, whereas this was the case for 63% in the very low-volume group. No statistically significant difference in CR, ACR, or a combination of the two was found. A very low-volume bowel preparation regimen was non-inferior to a high-volume regimen before CCE in terms of CR and ACR.

Completing colon capsule endoscopy (CCE) investigations rely on successful transit and acceptable bowel preparation quality. We investigated the effect of adding castor oil to the CCE bowel preparation regimen on the completion rate using a meta-analysis of existing literature. We conducted a systematic literature search in PubMed, Web of Science, and Embase. Included studies underwent quality assessment, and data for meta-analysis were extracted. Pooled estimates for excretion rate and acceptable bowel preparation rate were calculated. We identified 72 studies matching our search criteria, and six were included in the meta-analysis. Three of the studies had control groups, although two used historical cohorts. The pooled excretion rate (92%) was significantly higher in patients who received castor oil than in those who did not (73%). No significant difference in acceptable colonic cleanliness was observed. Castor oil has been used in a few studies as a booster for CCE. This meta-analysis shows the potential for this medication to improve excretion rates, and castor oil could be actively considered in conjunction with other emerging laxative regimens in CCE. Still, prospective randomized trials with appropriate control groups should be conducted before any conclusions can be drawn. Prospero ID: CRD42022338939.

Background: Segmental resection of the colon or rectum for cancer is major surgery with substantial procedure-related morbidity and mortality. A steep increase in the frequency of early cancer and advanced adenoma detection has been evident these late years. Introducing more minimal invasive resection techniques may decrease procedure-related complications and mortality. We aimed to describe the results from introducing endoscopic full-thickness resection (eFTR) in a unit specialized in advanced endoscopic resection of colon neoplasias. Primary outcomes were R0 resection rate and complications., Methods: endoscopic full-thickness resection was introduced in our unit in 2017. Patients were referred for eFTR based on indications: (i) completion of resection after unexpected cancer, (ii) suspicion of or clinically confirmed early cancer (T1) without signs of dissemination, or (iii) adenomas not suitable for other endoscopic resection techniques due to difficult position or recurrence. Data on eFTR procedures and follow-up were retrieved from patient journals., Results: Thirty-seven eFTR procedures were commenced in the period of March 2017 until June 2020, and one of these was abandoned. The overall R0 resection rate was 83.3%. In subgroups of indications i-iii, it was 87.5, 80.0, and 80.0%, respectively. Three perforations and one case of late bleeding occurred. One patient died within 30 days due to late perforation. Six technical failures were evident including operator-induced failures. Five of the technical failures occurred in the first half of the procedures indicating the learning curve of the endoscopist., Conclusion: Implementation of the eFTR procedure has been largely successful, especially in patients referred for completion of resection after unexpected cancer. Complication rates were acceptable, and the technique and quality increased significantly during the study. Careful selection of patients for eFTR is crucial for achieving successful resection. Size and position of lesion seem more important than indication. eFTR is not effective for lesions > 30 mm., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Video-capsule endoscopy (VCE) reading is a time- and energy-consuming task. Agreement on findings between readers (either different or the same) is a crucial point for increasing performance and providing valid reports. The aim of this systematic review with meta-analysis is to provide an evaluation of inter/intra-observer agreement in VCE reading. A systematic literature search in PubMed, Embase and Web of Science was performed throughout September 2022. The degree of observer agreement, expressed with different test statistics, was extracted. As different statistics are not directly comparable, our analyses were stratified by type of test statistics, dividing them in groups of "None/Poor/Minimal", "Moderate/Weak/Fair", "Good/Excellent/Strong" and "Perfect/Almost perfect" to report the proportions of each. In total, 60 studies were included in the analysis, with a total of 579 comparisons. The quality of included studies, assessed with the MINORS score, was sufficient in 52/60 studies. The most common test statistics were the Kappa statistics for categorical outcomes (424 comparisons) and the intra-class correlation coefficient (ICC) for continuous outcomes (73 comparisons). In the overall comparison of inter-observer agreement, only 23% were evaluated as "good" or "perfect"; for intra-observer agreement, this was the case in 36%. Sources of heterogeneity (high, I 2 81.8-98.1%) were investigated with meta-regressions, showing a possible role of country, capsule type and year of publication in Kappa inter-observer agreement. VCE reading suffers from substantial heterogeneity and sub-optimal agreement in both inter- and intra-observer evaluation. Artificial-intelligence-based tools and the adoption of a unified terminology may progressively enhance levels of agreement in VCE reading.

Background and study aims  Of the participants in the Danish screening program, 89.9 % to 92.5 % have fecal immunochemical test (FIT) values < 10 μg/g feces (equivalent to 50 ng hemoglobin/mL buffer). This study aimed to investigate the risk of interval colorectal cancer (CRC) in this group before the next biennial screening round. Patients and methods  This cohort study included all citizens from the region of Southern Denmark who participated in the Danish bowel screening program from 2014 trough 2016 and had a FIT value < 10 μg/g feces. Individuals receiving a CRC diagnosis were identified through the national CRC registry, with a follow up of 2 years corresponding to the current screening interval. We also examined the 3-year CRC incidence. Hazard ratios (HRs) were estimated using univariate and multivariate Cox proportional hazard regression models. Results  Data from 185,654 citizens presenting with a FIT value < 10 μg/g feces were eligible for analysis. Overall, interval CRC incidence was 0.07 % within 2 years with HRs of 4.16 (95 % confidence interval [CI] 2.67;6.48) and 5.8 (95 % CI 3.34;10.05) for FIT values of 4 to 6.9 μg/g feces and 7 to 9.9 μg/g feces, respectively, compared to those having a FIT value below the limit of quantification of 4 μg/g feces. After 3 years, the overall CRC incidence increased to 0.14 %; however, this was not significant. Conclusions  This study demonstrates a positive correlation between FIT value and risk of interval cancer even for very low values. It further suggests that an increase in the screening interval could be reasonable in the low FIT categories., Competing Interests: Competing interests The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

The aim of this study is to investigate the association between socioeconomic status (SES) and the risk of having an incomplete colonoscopy (IC) in the Danish Colorectal Cancer (CRC) Screening Program. In this register-based study we included 71,973 participants who underwent colonoscopy after a positive fecal immunochemical test in the Danish CRC Screening Program. The main exposure, SES, was defined by income and education, and the outcome by complete or incomplete colonoscopy. Among the participants, 5428 (7.5%) had an incomplete colonoscopy. The odds ratio (OR) for ICs due to inadequate bowel preparation was 1.67 (95% CI: 1.46; 1.91) for income in the 1 quartile compared to income in the 4th quartile. ORs for income in the 2nd quartile was 1.38 (95% CI: 1.21; 1.56) and 1.17 (95% CI: 1.03; 1.33) for income in the 3rd quartile. For the educational level, an association was seen for high school/vocational education with an OR of 0.87 (95% CI: 0.79; 0.97) compared to higher education. For ICs due to other reasons, the level of income was associated with the risk of having an IC with an OR of 1.19 (95% CI: 1.05; 1.35) in the 1st quartile and an OR of 1.19 (95% CI: 1.06; 1.34) in the 2nd quartile. For the educational level, there were no significant associations. Low income is associated with high risk of having an IC, whereas educational level does not show the same unambiguous association.

Fecal hemoglobin (f-Hb) detected by the guaiac fecal occult blood test (gFOBT) may be associated with mortality and cause of death in colorectal cancer (CRC) screening participants. We investigated this association in a randomly selected population of 20,694 participants followed for 33 years. We followed participants from the start of the Hemoccult-II CRC trial in 1985-1986 until December 2018. Data on mortality, cause of death and covariates were retrieved using Danish national registers. We conducted multivariable Cox regressions with time-varying exposure, reporting results as crude and adjusted hazard ratios (aHRs). We identified 1766 patients with at least one positive gFOBT, 946 of whom died in the study period. Most gFOBT-positive participants (93.23%) died of diseases unrelated to CRC and showed higher non-CRC mortality than gFOBT-negative participants (aHR: 1.20, 95% CI 1.10-1.30). Positive gFOBT participants displayed a modest increase in all-cause (aHR: 1.28, 95% CI: 1.18-1.38), CRC (aHR: 4.07, 95% CI: 3.00-5.56), cardiovascular (aHR: 1.22, 95% CI: 1.07-1.39) and endocrine and hematological mortality (aHR: 1.58, 95% CI: 1.19-2.10). In conclusion, we observed an association between positive gFOBT, cause of death and mortality. The presence of f-Hb in the gFOBT might indicate the presence of systemic diseases.

Background and study aims  The Danish CareForColon2015 trial, launched in 2020 as part of the Danish Colorectal Cancer Screening program, is the largest randomized controlled trial to date on colon capsule endoscopy (CCE). This paper presents the interim analysis with the objective of ensuring the safety of patients in the intervention group and evaluating the clinical performance of the trial's predefined clinical parameters. Patients and methods  We evaluated the initial 234 CCEs according to quality, safety, and completion. The participation rates and preference distribution of all individuals invited were analyzed and sample size calculations were adjusted. Results  Fecal immunochemical test and diagnostic participation rates were 62.1 % and 91.1 %, respectively. The completion rate for CCEs was 67.9 % and the rate of conclusive investigations was 80.3 %. The polyp detection rate (PDR) was high (73.5 %), only two (0.85 %) technical failures in 234 videos were observed, and six suspected cancers were identified (2.6 %). No major adverse events were recorded. The required number of invitations had been underestimated due to inaccurate assumptions in sample size calculations. Conclusions  The trial was efficient and safe in terms of CCE quality and time to diagnostic investigation. Participation rates and PDRs were high. The proportion of suspected cancers was lower than expected and will be followed. The completion rate for CCEs was acceptable but lower than expected and the CCE procedure was reviewed for potential improvements and Resolor was added to the regime. The number of invitations for the intervention group of the trial has been adjusted from 62,107 to 185,153., Competing Interests: Competing interests The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background and study aims  The aim of this study was to introduce EndoConf, a reliable and easy-to-use tool capable of optimizing clinical care in endoscopy by reducing the number of repeat endoscopy procedures, providing continuous on-the-job clinical education, and allowing a smooth transition to the next level of artificial intelligence-supported systems. Patients and methods  We prospectively developed and improved a real-time conference system (EndoConf). EndoConf enables endoscopists to contact on-demand and in real time experienced endoscopists across other sites. After the initial introduction period, we registered all EndoConf-assisted procedures from our unit (Surgical Department of Odense University Hospital) over a 3-month period (Autumn of 2019). Results  Of 84 EndoConf-supported procedures, 58 were eligible for further analysis. Eventually, 38 calls were made, of which only four were technically of low quality (10.5 %) while three were not answered (7.9 %). Of the 35 (92.1 %) completed EndoConf calls; 24 were referred for endoscopic mucosal resection, six were referred for transanal microsurgery preceded by transrectal ultrasonography and three were referred for multidisciplinary conference, whereas in two cases, the lesion was resected during EndoConf. Conclusions  We found the EndoConf system to provide support that could reduce the number of unnecessary repeat endoscopic procedures while at the same time ensuring avoidance of any hazardous attempt at polypectomy., Competing Interests: Competing interests The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Colon capsule endoscopy as an alternative to colonoscopy for the diagnosis of colonic disease may serve as a less invasive and more tolerable investigation for patients. Our aim was to examine patient-reported outcomes for colon capsule endoscopy compared to conventional optical colonoscopy including preference of investigation modality, tolerability and adverse events. A systematic literature search was conducted in Web of Science, PubMed and Embase. Search results were thoroughly screened for in- and exclusion criteria. Included studies underwent assessment of transparency and completeness, after which, data for meta-analysis were extracted. Pooled estimates of patient preference were calculated and heterogeneity was examined including univariate meta-regressions. Patient-reported tolerability and adverse events were reviewed. Out of fourteen included studies, twelve had investigated patient-reported outcomes in patients who had undergone both investigations, whereas in two the patients were randomized between investigations. Pooled patient preferences were estimated to be 52% (CI 95%: 41-63%) for colon capsule endoscopy and 45% (CI 95%: 33-57%) for conventional colonoscopy: not indicating a significant difference. Procedural adverse events were rarely reported by patients for either investigation. The tolerability was high for both colon capsule endoscopy and conventional colonoscopy. Patient preferences for conventional colonoscopy and colon capsule endoscopy were not significantly different. Procedural adverse events were rare and the tolerability for colon capsule endoscopy was consistently reported higher or equal to that of conventional colonoscopy.

Background: Deferral of conventional surgery for rectal cancer after neo-adjuvant chemo-radiotherapy is gaining increasing interest, particularly for patients who are too frail to undergo major surgery but also those who wish to avoid the adverse effects of major surgery. We elected to undertake a pragmatic approach to include all comers in a cohort with the aim of reflecting the clinical outcomes for patients on a deferral from conventional rectal surgery pathway, treated with neo-adjuvant chemo-radiation (CRT) with or without selective local excision (LE) offered to those who failed to demonstrate a complete clinical response (cCR)., Methods: Rectal cancer patients treated with neo-adjuvant CRT were stratified to a group of complete responders to CRT on a "watch and wait" (WW) pathway and a group who were treated with an additional local excision for persistent tumour., Results: Regrowth was noted in 26% (11/42) in the WW group after 2 years surveillance, disease free survival was 94.5% (80-99%) at 1 year and 74.9% (44-76.4%) at 3 years. Recurrence was noted in 45% (10/22) in the CRT + LE group, disease free survival at 1 and 3 years was 74% (53.4-88.1) and 66.2% (45.6-82.4) respectively., Conclusion: A WW strategy for cCR is a viable pathway in the non-operative management of rectal cancer. We found the use of CRT + LE is a useful option for those who hope to avoid surgery but caution should be exercised due to substantially higher risk of recurrence., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In large bowel investigations using endoscopic capsules and upon detection of significant findings, physicians require the location of those findings for a follow-up therapeutic colonoscopy. To cater to this need, we propose a model based on tracking feature points in consecutive frames of videos retrieved from colon capsule endoscopy investigations. By locally approximating the colon as a cylinder, we obtained both the displacement and the orientation of the capsule using geometrical assumptions and by setting priors on both physical properties of the intestine and the image sample frequency of the endoscopic capsule. Our proposed model tracks a colon capsule endoscope through the large intestine for different prior selections. A discussion on validating the findings in terms of intra and inter capsule and expert panel validation is provided. The performance of the model is evaluated based on the average difference in multiple reconstructed capsule's paths through the large intestine. The path difference averaged over all videos was as low as 4±0.7 cm, with min and max error corresponding to 1.2 and 6.0 cm, respectively. The inter comparison addresses frame classification for the rectum, descending and sigmoid, splenic flexure, transverse, hepatic, and ascending, with an average accuracy of 86%.

Following incomplete colonoscopy (IC) patients often undergo computed tomography colonography (CTC), but colon capsule endoscopy (CCE) may be an alternative. We compared the completion rate, sensitivity and diagnostic yield for polyp detection from CCE and CTC following IC. A systematic literature search resulted in twenty-six studies. Extracted data included inter alia, complete/incomplete investigations and polyp findings. Pooled estimates of completion rates of CCE and CTC and complete colonic view rates (CCE reaching the most proximal point of IC) of CCE were calculated. Per patient diagnostic yields of CCE and CTC were calculated stratified by polyp sizes. CCE completion rate and complete colonic view rate were 76% (CI 95% 68-84%) and 90% (CI 95% 83-95%). CTC completion rate was 98% (CI 95% 96-100%). Diagnostic yields of CTC and CCE were 10% (CI 95% 7-15%) and 37% (CI 95% 30-43%) for any size, 13% (CI 95% 9-18%) and 21% (CI 95% 12-32%) for >5-mm and 4% (CI 95% 2-7%) and 9% (CI 95% 3-17%) for >9-mm polyps. No study performed a reference standard follow-up after CCE/CTC in individuals without findings, rendering sensitivity calculations unfeasible. The increased diagnostic yield of CCE could outweigh its slightly lower complete colonic view rate compared to the superior CTC completion rate. Hence, CCE following IC appears feasible for an introduction to clinical practice. Therefore, randomized studies investigating CCE and/or CTC following incomplete colonoscopy with a golden standard reference for the entire population enabling estimates for sensitivity and specificity are needed.

Introduction: The use of capsule endoscopy has become an approved method in small bowel diagnostics, but the same level of integration is not seen in large bowel diagnostics. We will use colon capsule endoscopy (CCE) as a filter test in colorectal cancer (CRC) screening between the faecal immunochemical test (FIT) and colonoscopy. We aim to investigate the clinical performance, population acceptability, and economic implications of the procedure in a large-scale clinical trial., Methods and Analysis: We will randomly allocate 124 214 Danish citizens eligible for participation in the national CRC screening programme within the Region of Southern Denmark to either an intervention group or a control group. Prior to submitting a FIT, citizens randomised to the intervention group will be informed about their opportunity to undergo CCE, instead of colonoscopy, if the FIT is positive. Suspected cancers; >3 adenomas <10 mm in size, 1 adenoma >10 mm in size or >4 adenomas regardless of size, detected during CCE will generate an invitation to colonoscopy as per regular screening guidelines, whereas citizens with suspected low risk polyps will re-enter the biennial screening programme. Citizens with no CCE findings will be excluded from screening for 8 years. In the control group, citizens will follow standard screening procedures., Ethics and Dissemination: All participants must consent prior to capsule ingestion. All collected data will be handled and stored in accordance with current data protection legislation. Approvals from the regional ethics committee (ref. S-20190100) and the Danish data protection agency have been obtained (ref. 19/29858)., Trial Registration Details: The study has been registered with ClinicalTrials.gov under: NCT04049357., Competing Interests: Competing interests: GB is financially supported by Medtronic but the company does not influence any scientific processes, and no investigator will receive any personal benefits., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Carrots are consumed worldwide. Several meta-analysis studies on carrot consumption have indicated that carrots play a central role as a protecting vegetable against development of different types of cancers. A cancer-preventive role of carrots is plausible because they are the main dietary source of the bioactive polyacetylenic oxylipins falcarinol (FaOH) and falcarindiol (FaDOH), which have shown anti-proliferative and anti-inflammatory activity in numerous in vitro studies. In addition, purified FaOH and FaDOH have, in recent studies in colorectal cancer (CRC)-primed rats, demonstrated an anti-neoplastic effect in a dose-dependent manner. The mechanisms of action for this effect appears to be due to inhibition of pro-inflammatory and transcription factor biomarkers for inflammation and cancer. However, studies of the CRC-preventive effect of carrots in a large cohort are still missing. We therefore examined the risk of being diagnosed with CRC as predicted by intake of carrots in a Danish population of 57,053 individuals with a long follow-up. Self-reported intake of raw carrots at a baseline of 2-4 carrots or more each week (>32 g/day) was associated with a 17% decrease in risk of CRC with a mean follow-up of >18 years, compared to individuals with no intake of raw carrots even after extensive model adjustments (HR 0.83 CI 95% 0.71; 0.98). An intake below 2-4 carrots each week (<32 g/day) was not significantly associated with reduced risk of CRC (HR 0.93 CI 95% 0.82; 1.06). The results of this prospective cohort study clearly support the results from studies in cancer-primed rats for CRC and hence a CRC-preventive effect of carrots.

Background: Social inequalities has been shown for participation in colorectal cancer screening and recently in the initial stool sample blood test. If these differences persist at follow-up colon examination after a positive stool test, it would suggest that social inequality in screening may be greater than the inequality observed in initial stool sample blood test., Methods: All data were derived from national registers. Using logistic regression analyses, odds of non-participation for follow-up colon examination were estimated based on age group, educational level, income quartile, immigration status and marital status in men and in women, who had participated in initial stool sample test for blood with a positive result., Results: Among 20 849 men and 16 565 women invited for follow-up colonoscopy in the period 2014-15, 10.63 and 11.37%, respectively, did not attend. In men, odds of non-participation were higher in the eldest, those with lower income and lower educational level, in immigrants and in singles. Odds ratio (OR) in males of highest income quartile was 0.54 [95% confidence interval (CI) 0.46; 0.63] compared with lowest income quartile. In women, the differences were not as large. OR in females of highest income quartile was 0.73 (95% CI 0.61; 0.87) compared with lowest income quartile., Conclusion: Sociodemographic differences in odds of non-participation exist in follow-up colon examination in the Danish colorectal cancer screening. Differences were evident in all subgroups of the male population. The same patterns were seen in women. Social inequalities in participation for follow-up colon examination can increase overall social inequality and consequently, lead to health disparities., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

Health information knowledge may affect attitude toward colorectal cancer screening, but the participation of health educated citizens are unknown. Therefore, we investigated non-participation in a sample of 886,088 invited participants, based on educational length, type, and level. Logistic regression analyses were conducted to estimate the odds of non-participation in Danish men and women based on educational type and length. Models were adjusted for age, income, marital status and immigration status. Information was derived from National registers. Men with long educational length level had increased odds of non-participation if their education was within the field of medicine/medical science (OR 1.87) or belonged to other long health educations, but not in nursing and health care, compared to other long educations after full model adjustment. Women with long educational length level had increased odds of non-participation if they were educated in the field of medicine/medical science (OR 1.47), whereas they had decreased odds in the fields of nursing and health care and other long health educations, compared to other long educations after full model adjustment. Men within short educational length level did not have different odds of nonparticipation, after full model adjustments, whereas women within short health educations were at increased odds in the youngest age group and at decreased odds in the eldest age group. Having an education in the field of medicine/medical science is associated with non-participation in colorectal cancer screening in Denmark 2014-2015. Opposite, an educational background in nursing and health care increased participation in women, but not in men., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To investigate the effect of sending out reminders for colorectal cancer screening on socioeconomic and demographic inequalities in screening uptake., Methods: All citizens aged 50-74 in Denmark are invited every 2 years for colorectal cancer screening. Non-participants receive an electronically distributed reminder. Data for these analyses were derived from national registers. Socioeconomic status was measured by income and educational level. Demographic variables included age, gender and marital status, and the analyses were stratified by immigration status. Logistic regression analyses were conducted to estimate the odds of non-participation for invited citizens and for reminded citizens divided by socioeconomic and demographic predictors., Results: Of 763,511 native Danes invited for screening from 2014 to 2015, 387,116 (50.70%) participated after the initial invitation and 133,470 after receiving a reminder. Differences in participation were present in relation to all subgroups among both the invited citizens and reminded citizens. Differences persisted after full model adjustments with reductions for demographic variables. Odds ratio (OR) for non-participation in the eldest age group was 0.32 (95% CI, 0.32; 0.33) before and 1.11 (95% CI 1, 0.08; 1.14) after the reminder, compared to those under 55 years. OR for the 4th income quartile was 0.54 (95% CI, 0.53; 0.55) before and 0.44 (95% CI, 0.43; 0.45) after the reminder, compared to 1st quartile., Conclusions: Reminders increased the overall participation, and the inequalities in participation in relation to demographic factors were reduced after the distribution of reminders. The age differences were especially reduced. The inequalities in participation related to socioeconomic status were, however, slightly increased after reminder distribution.

Background: Barriers such as language and literacy might complicate the participation procedure for immigrants in screening programs. We investigated the delivery of a suitable stool sample for participation in the Danish colorectal cancer screening by immigration background., Methods: National administrative registers were used to link results of faecal blood screening with immigrant status, age, sex, education, income, and marital status. Univariate and multivariate logistic regression models were used to estimate the odds of submitting an ineligible sample., Results: 558,104 individuals submitted a sample during 2014 and 2015. A total of 2,164 (0.4%) samples were ineligible for faecal analysis. The lowest proportions of ineligible samples were found in the highest educational level (0.2%) and highest income level (0.2%). The highest proportion of ineligible samples was seen in non-Western immigrants (1.6%). After adjustment for age, gender, educational level, income and marital status non-Western immigrants had an increased odds ratio (OR 3.64 CI95% 2.86;4.64) of submitting an ineligible sample, compared to native Danes. Western immigrants did not have an increased odds ratio., Conclusion: Non-Western immigrants have more than three times the risk of submitting an ineligible faeces sample for colorectal cancer screening than native Danes. Translation of invitation, information leaflet, and manual into other languages or targeted information for subgroups may help decrease the risk., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: Colorectal cancer screening by inviting citizens to complete a test for blood in faeces was initiated in Denmark in 2014. We have examined sociodemographic predictors that influence participation to identify factors that could be targeted to increase compliance., Methods: National registers were used to link data on invitations for colorectal cancer screening in Denmark from 2014 to 2015. Region of residence, age, gender, immigration status, income, educational level and marital status were identified. Logistic regression analysis was used to estimate the risk of non-participation for invited citizens while adjusting for all other sociodemographic variables., Results: A total of 854,237 individuals were included in the analysis. The national participation proportion was 65.33%, with significant differences between sociodemographic groups. Participation proportions were the lowest in non-Western immigrants (53.00%), individuals without a partner (54.05%) and those in the lowest income quartile (54.65%), with subgroup participation as low as 40.56%. The highest participation proportion was seen in individuals in the highest income quartile (71.56%). Region of residence, age, gender, educational level, income quartile, marital status and immigration status all had statistically significant independent differences in risk of non-participation after full model adjustment., Conclusion: Participation in colorectal cancer screening was high in Denmark in 2014 and 2015. Large differences in participation were seen between sociodemographic subgroups, potentially resulting in social inequality in the benefits from screening. Future efforts to increase participation should focus on the low compliance subgroups, such as singles, non-Western immigrants and people from the lowest socioeconomic groups.

Objective: Dyspepsia is a common condition and has a huge impact on quality of life and working capacity, but its causes are not well understood. An association between stress and dyspepsia has been debated for decades, but the issue has not been resolved. We examined the 3-year risk of redeeming a proton-pump inhibitor or an H2-receptor antagonist as a proxy of dyspepsia according to the level of perceived stress., Participants and Methods: Perceived stress was measured in a general health survey of 16 124 Danes aged older than 16 years of age in 2010 using Cohen's Perceived Stress Scale. Data were linked individually to national registries, including the Danish National Prescription Registry. The risk of redeeming a proton-pump inhibitor or an H2-receptor antagonist for quintiles of stress level was estimated using Cox proportional hazard regression., Results: In total, 2703 redeemed one of these drugs during the 33 months of follow-up. The cumulative incidence proportion of dyspepsia increased gradually, from 11.6 to 24.9%, with quintiles of stress. After full model adjustment, the four highest stress quintiles had a statistically significantly increased risk of redeeming a drug compared with the lowest stress quintile. The hazard ratios were 1.16 [95% confidence interval (CI): 1.00-1.34] for the second quintile, 1.21 (95% CI: 1.06-1.39) for the third quintile, 1.20 (95% CI: 1.05-1.38) for the fourth quintile, and 1.30 (95% CI: 1.12-1.50) for the fifth quintile., Conclusion: Higher levels of self-reported perceived everyday life stress increased the risk of redeeming a drug for dyspepsia significantly during 33 months of follow-up.

Background: The association between stress and peptic ulcers has been questioned since the discovery of helicobacter pylori. This study examined whether high perceived everyday life stress was associated with an increased risk of either receiving a triple treatment or being diagnosed with a peptic ulcer., Methods: Cohen's perceived stress scale measured the level of stress in a general health survey in 2010 of 17,525 residents of northern Jutland, Denmark, and was linked with National Danish registers on prescription drugs and hospital diagnoses. Cox proportional hazard regression was used to estimate the risk of either receiving a triple treatment or being diagnosed in a hospital with a peptic ulcer, in relation to quintiles of stress levels., Results: A total of 121 peptic ulcer incidents were recorded within 33 months of follow-up. The lowest stress group had a cumulative incidence proportion of either receiving triple treatment or being diagnosed with peptic ulcer of approximately 0.4%, whereas the highest stress group had a cumulative incidence proportion of approximately 1.2%. Compared with that of the lowest stress group, those in the highest stress group had a 2.2-fold increase in risk of either receiving triple treatment or being diagnosed with peptic ulcer (HR 2.24; CI 95% 1.16:4.35) after adjustment for age, gender, socioeconomic status, non-steroid anti-inflammatory drug use, former ulcer and health behaviours. There was no difference in risk between the four least stressed quintiles. Subgroup analysis of diagnosed peptic ulcer patients revealed the same pattern as the main analysis, although the results were not significant., Conclusion: The highest level of perceived everyday life stress raised the risk of either receiving triple treatment or being diagnosed with peptic ulcer during the following 33 months more than twice compared with that of the lowest level of perceived stress.

Background: Previous studies have shown that compared with abstinence and heavy drinking, moderate alcohol consumption is associated with a reduced risk of mortality among the general population and patients with heart failure and myocardial infarction. We examined the association between alcohol consumption and mortality in coronary artery bypass graft (CABG) patients., Method: We studied 1,919 first-time CABG patients using data on alcohol consumption and mortality obtained from Danish national registers from March 2006 to October 2011. Alcohol consumption was divided into the following groups: abstainers (0 units/week), moderate consumers (1-14 units/week), moderate-heavy drinkers (15-21 units/week) and heavy drinkers (>21 units/week). Hazard ratios (HR) of all-cause mortality were calculated using Cox proportional hazard regression analysis., Results: The median follow-up was 2.2 years [IQR 2.0]. There were 112 deaths, of which 96 (86 %) were classified as cardiovascular. Adjustments for age and sex showed no increased risk of all-cause mortality for the abstainers (HR 1.61, 95 % CI, 1.00-2.58) and moderate-heavy drinkers (HR 1.40, 95 % CI, 0.73-2.67) compared with moderate consumers. However, heavy drinkers had a high risk of all-cause mortality compared with moderate consumers (HR 2.44, 95 % CI, 1.47-4.04). A full adjustment showed no increase in mortality for the abstainers (HR 1.59, 95 % CI, 0.98-2.57) and moderate-heavy drinkers (HR 1.68, 95 % CI, 0.86-3.29), while heavy drinkers were associated with an increased mortality rate (HR 1.88, 95 % CI, 1.10-3.21). There was no increased risk of 30-day mortality for the abstainers (HR 0.74, 95 % CI, 0.23-2.32), moderate-heavy drinkers (HR 0.36, 95 % CI, 0.07-1.93) and heavy drinkers (HR 2.20, 95 % CI, 0.65-7.36)., Conclusion: There was no increased risk of mortality for abstainers (0 units/week) or moderate-heavy drinkers (15-21 units/week) following a CABG. Only heavy drinking (>21 units/week) were significantly associated with an increased mortality rate. These results suggest that only heavy drinking present a risk factor among CABG patients.