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Abstract Comparative studies of cancer‐related genes not only provide novel information about their evolution and function but also an understanding of cancer as a driving force in biological systems and species’ life histories. So far, these studies have focused on mammals. Here, we provide the first comparative study of cancer‐related gene copy number variation in fish. Fishes are a paraphyletic group whose last common ancestor is also an ancestor of the tetrapods, and accordingly, their tumour suppression mechanisms should include most of the mammalian mechanisms and also reveal novel (but potentially phylogenetically older) previously undetected mechanisms. We have matched the sequenced genomes of 65 fish species from the Ensemble database with the cancer gene information from the COSMIC database. By calculating the number of gene copies across species using the Ensembl CAFE data (providing species trees for gene copy number counts), we used a less resource‐demanding method for homolog identification. Our analysis demonstrates a masked relationship between cancer‐related gene copy number variation (CNV) and maximum lifespan in fish species, suggesting that a higher number of copies of tumour suppressor genes lengthens and the number of copies of oncogenes shortens lifespan. Based on the positive correlation between the number of copies of tumour suppressors and oncogenes, we show which species have more tumour suppressors in relation to oncogenes. It could be suggested that these species have stronger genetic defences against oncogenic processes. Fish studies could be a largely unexplored treasure trove for understanding the evolution and ecology of cancer, providing novel insights into the study of cancer and tumour suppression, in addition to fish evolution, life‐history trade‐offs, and ecology.

Due to the interconnectedness of aquatic ecosystems through the highly effective marine and atmospheric transport routes, all aquatic ecosystems are potentially vulnerable to pollution. Whilst links between pollution and increased mortality of wild animals have now been firmly established, the next steps should be to focus on specific physiological pathways and pathologies that link pollution to wildlife health deterioration. One of the pollution-induced pathologies that should be at the centre of attention in ecological and evolutionary research is cancer, as anthropogenic contamination has resulted in a rapid increase of oncogenic substances in natural habitats. Whilst wildlife cancer research is an emerging research topic, systematic reviews of the many case studies published over the recent decades are scarce. This research direction would (1) provide a better understanding of the physiological mechanisms connecting anthropogenic pollution to oncogenic processes in non-model organisms (reducing the current bias towards human and lab-animal studies in cancer research), and (2) allow us to better predict the vulnerability of different wild populations to oncogenic contamination. This article combines the information available within the scientific literature about cancer occurrences in aquatic and semi-aquatic species. For the first aim, we use available knowledge from aquatic species to suggest physiological mechanisms that link pollution and cancer, including main metabolic detoxification pathways, oxidative damage effects, infections, and changes to the microbiome. For the second aim, we determine which types of aquatic animals are more vulnerable to pollution-induced cancer, which types of pollution are mainly associated with cancer in aquatic ecosystems, and which types of cancer pollution causes. We also discuss the role of migration in exposing aquatic and semi-aquatic animals to different oncogenic pollutants. Finally, we suggest novel research avenues, including experimental approaches, analysis of the effects of pollutant cocktails and long-term chronic exposure to lower levels of pollutants, and the use of already published databases of gene expression levels in animals from differently polluted habitats.

Objective: Colonoscopy-related adverse events increase the burden of colorectal cancer (CRC) screening. This cross-sectional study evaluates adverse events during and after colonoscopy in a large, randomised CRC screening trial in Norway comparing sigmoidoscopy to immunochemical testing for faecal blood., Methods: We included all individuals who underwent colonoscopy at two screening centres between 2012 and 2020. From medical records, we retrieved data on adverse events during and within 30 days after colonoscopy and classified them according to the American Society for Gastrointestinal Endoscopy lexicon for endoscopic adverse events. Multivariable logistic regression models were fitted to identify risk factors for adverse events., Results: Of the 10 244 included individuals, 242 (2.4%) had at least one adverse event that was possibly, probably, or definitively related to the colonoscopy. 188 (1.8%) had mild adverse events, 50 (0.49%) had moderate, 3 (0.03%) had severe, and 1 had a fatal adverse event. The most frequent adverse events were lower gastrointestinal bleeding (0.86%), abdominal pain (0.48%), vasovagal reaction (0.39%), postpolypectomy syndrome (0.20%), and perforation (0.08%). 23 (0.22%) individuals had non-gastrointestinal adverse events. Risk factors associated with adverse events were older age, female sex, screening centre, anticoagulant therapy, number of polypectomies, size of lesion removed, presence of proximal lesion, and adenocarcinoma. Adverse event rates per endoscopist ranged from 0% to 4.9%., Conclusion: Adverse events after colonoscopy of screening positives occurred in about 2 out of 100 procedures. Three-quarters of events were mild. Awareness of risk factors may help endoscopists to mitigate the risk., Trial Registration Number: NCT01538550., Competing Interests: Competing interests: The bowel preparation used for colonoscopy was provided free of charge by Ferring Pharmaceuticals. SOF reports Chairman, The Norwegian Society of Clinical Nutrition and Metabolism; Council Member, European Society for Clinical Nutrition and Metabolism outside of the submitted work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The positivity thresholds of faecal immunochemical testing (FIT) in colorectal cancer (CRC) screening vary between countries., Aims: To explore the trade-off between colonoscopies performed, adverse events and lesions detected at different FIT thresholds in a Norwegian CRC screening trial., Methods: We included first participation in biennial FIT screening for 47,265 individuals aged 50-74 years. Individuals with FIT > 15 μg Hb/g faeces were referred for colonoscopy. We estimated the number of colonoscopies, adverse events, screen-detected CRCs, advanced adenomas and serrated lesions expected at FIT thresholds currently or recently used in other European countries ranging between 20 and 150 μg/g., Results: At the 15 μg/g threshold (Norway), 3705 participants underwent colonoscopy, of whom 203 had CRC, 1119 advanced adenomas and 256 advanced serrated lesions. Using a 47 μg/g threshold, 1826 (49.3%) individuals would have undergone colonoscopy, and 154 (75.9%) would have been diagnosed with CRC, 702 (62.7%) with advanced adenoma and 128 (50.0%) with advanced serrated lesion compared to the 15 μg/g threshold. At 150 μg/g, the corresponding figures would have been 838 (22.6%) undergoing colonoscopy, 114 (56.2%) with CRC, 345 (30.8%) advanced adenoma and 54 (21.1%) advanced serrated lesions. The detection rate of stage I CRC was 0.22% at 15 μg/g and 0.11% at 150 μg/g. Post-colonoscopy bleeding rates were 0.8% and 1.7%, respectively., Conclusions: Increasing the FIT threshold reduces colonoscopy demand, but substantially decreases lesion detection and unfavourably changes CRC stage distribution. The risk of adverse events at colonoscopy increased with FIT threshold, requiring country-specific information on adverse events., Trial Registration: Clinicaltrials.gov identifier: NCT01538550., (© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background and Study Aims: Long-time follow-up of sigmoidoscopy screening trials has shown reduced incidence and mortality of colorectal cancer (CRC), but inadequate bowel cleansing may hamper efficacy. The aim of this study was to assess the impact of bowel cleansing quality in sigmoidoscopy screening., Patients and Methods: Individuals 50 to 74 years old who had a screening sigmoidoscopy in a population-based Norwegian, randomized trial between 2012 and 2019, were included in this cross-sectional study. The bowel cleansing quality was categorised as excellent, good, partly poor, or poor. The effect of bowel cleansing quality on adenoma detection rate (ADR) and referral to colonoscopy was evaluated by fitting multivariable logistic regression models., Results: 35,710 individuals were included. The bowel cleansing at sigmoidoscopy was excellent in 20,934 (58.6%) individuals, good in 6580 (18.4%), partly poor in 7097 (19.9%) and poor in 1099 (3.1%). The corresponding ADRs were 17.0%, 16.6%, 14.5%, and 13.0%. Compared to participants with excellent bowel cleansing, those with poor bowel cleansing had an odds ratio for adenoma detection of 0.66 (95% confidence interval 0.55-0.79). We found substantial differences in the assessment of bowel cleansing quality among endoscopists., Conclusions: Inadequate bowel cleansing reduces the efficacy of sigmoidoscopy screening, by lowering ADR. A validated rating scale and improved bowel preparation are needed to make sigmoidoscopy an appropriate screening method., Trial registration Clinicaltrials.gov (NCT01538550).

Introduction: To examine the association between low-dose aspirin use and risk of colorectal cancer (CRC)., Methods: In this nationwide cohort study, we identified individuals aged 50 years or older residing for 6 months or more in Norway in 2004-2018 and obtained data from national registers on drug prescriptions, cancer occurrence, and sociodemographic factors. Multivariable Cox regression models were used to estimate the association between low-dose aspirin use and CRC risk. In addition, we calculated the number of CRC potentially averted by low-dose aspirin use., Results: We included 2,186,390 individuals. During the median follow-up of 10.9 years, 579,196 (26.5%) used low-dose aspirin, and 38,577 (1.8%) were diagnosed with CRC. Current use of aspirin vs never use was associated with lower CRC risk (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.84-0.90). The association was more pronounced for metastatic CRC (HR 0.79; 95% CI 0.74-0.84) than regionally advanced (HR 0.89; 95% CI 0.85-0.92) and localized CRC (HR 0.93; 95% CI 0.87-1.00; P heterogeneity = 0.001). A significant trend was found between duration of current use and CRC risk: HR 0.91 (95% CI 0.86-0.95) for <3 years, HR 0.85 (0.80-0.91) for ≥3 and <5 years, and HR 0.84 (0.80-0.88) for ≥5 years of use vs never use ( P trend < 0.001). For past use, HR were 0.89 (95% CI 0.84-0.94) for <3 years, 0.90 (0.83-0.99) for ≥3 and <5 years, and 0.98 (0.91-1.06) for ≥5 years since last use vs never use ( P -trend < 0.001). We estimated that aspirin use averted 1,073 cases of CRC (95% CI 818-1,338) in the study period., Discussion: In this nationwide cohort, use of low-dose aspirin was associated with a lower risk of CRC., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Introduction: Organized cancer screening programs should be equally accessible for all groups in society. We assessed differences in participation in colorectal cancer (CRC) screening among different immigrant groups., Methods: Between 2012 and 2019, 140,000 individuals aged 50 to 74 years were randomly invited to sigmoidoscopy or repeated faecal immunochemical test (FIT) in a CRC screening trial. In this study, we included 46,919 individuals invited to sigmoidoscopy and 70,018 invited to the first round of FIT between 2012 and 2017. We examined difference in participation between non-immigrants and immigrants, and within different immigrant groups by geographic area of origin, using logistic regression models, adjusted for several sociodemographic factors and health factors., Results: In total, we included 106,695 non-immigrants and 10,242 immigrants. The participation rate for FIT was 60% among non-immigrants, 58% among immigrants from Western countries and 37% among immigrants from non-Western countries. The participation rate for sigmoidoscopy was 53% among non-immigrants, 48% among immigrants from Western countries and 23% among immigrants from non-Western countries. Compared to non-immigrants, multivariate adjusted odds ratio for non-participation in FIT screening was 1.13 (95% confidence interval 1.04-1.23) and 1.82 (1.69-1.96) for immigrants from Western and non-Western countries. The corresponding numbers in sigmoidoscopy screening were 1.34 (1.21-1.48) and 2.83 (2.55-3.14). The lowest participation was observed in immigrants from Eastern Europe, Northern Africa and Western Asia, and South-Central Asia., Conclusion: Participation in CRC screening in Norway was particularly low among non-Western immigrants, which could put them at increased risk for late stage diagnosis of CRC. Participation was lower in sigmoidoscopy screening than in FIT screening, especially among immigrants from non-Western countries., Competing Interests: SB is due to receive personal fees from Gilead outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bhargava, Botteri, Berthelsen, Iqbal, Randel, Holme and Berstad.)

Background: The possible protective effect of aspirin on risk of colorectal cancer (CRC) is still highly debated., Methods: We used data from Bowel Cancer Screening in Norway, a trial randomizing individuals from general population, aged 50-74 years, to flexible sigmoidoscopy or faecal immunochemical test (FIT), to study the association between aspirin use and detection of CRC and two CRC precursors: adenomas and advanced serrated lesions (ASL). Prescriptions of low-dose aspirin were obtained from Norwegian prescription database. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs)., Results: Among 64,889 screening participants (24,159 sigmoidoscopy, 40,730 FIT), 314 (0.5%) had CRC, 6,208 (9.6%) adenoma and 659 (1.0%) ASL. Overall and short-term use (<3 years) of low-dose aspirin, versus no use, were not associated with any colorectal lesion. Long-term use (≥3 years) was associated with lower detection of CRC (overall OR 0.66, 95%CI 0.46-0.93; sigmoidoscopy: 0.56, 0.33-0.97; FIT: 0.72, 0.45-1.15), adenomas in sigmoidoscopy arm (overall OR 0.95, 95%CI 0.87-1.03; sigmoidoscopy: 0.89, 0.80-0.99; FIT: 1.03, 0.89-1.18), but not ASLs. We did not observe significant differences in the effect of aspirin according to the location of colorectal lesions., Conclusion: Our results suggest that long-term use of aspirin might have a protective effect against adenomas and colorectal cancer, but not ASLs., Competing Interests: Declaration of Competing Interest The authors declare no potential conflict of interests. This study was funded by the Norwegian Research Council (project number: 301628). The funders had no role in the design of the study, the data collection, the analysis or interpretation of the data, or the writing of the article., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Repeated rounds of faecal immunochemical testing (FIT) for occult blood is a common method for screening for colorectal cancer (CRC). However, the time interval between FIT rounds is not thoroughly investigated. In a CRC screening trial in South-Eastern Norway, individuals were invited for biennial FIT between 2012 and 2019. The positivity threshold was >15 mcg haemoglobin/g faeces (mcg/g). Due to organizational challenges, the interval between screening rounds randomly varied between 1.5 and 3.5 years, forming a natural experiment. We investigated the detection rate of CRC and advanced neoplasia (AN: CRC or advanced adenoma) at the subsequent round (FIT 2 ), according to the faecal haemoglobin concentration (f-Hb) at the initial screening round (FIT 1 ), and time between the two screening rounds. 18 522 individuals with negative FIT 1 who attended FIT 2 were included in this study. 245 AN were detected at FIT 2 , of which 34 were CRC. The CRC detection rate at FIT 2 for participants with FIT 1  = 0 mcg/g was 0.09% while it was 0.28% for participant with 0 > FIT 1  ≤ 15 mcg/g; odds ratio (OR) 3.22, 95% CI 1.49-6.95. For each 3 months' increment between FITs, the OR for detecting CRC was 1.33 (95% CI 0.98-1.79), while the OR was 1.13 (1.02-1.26) for AN. Individuals with FIT 1 -value of 0 mcg/g, had a lower AN detection rate compared with participants with 0 > FIT 1  ≤ 15 mcg/g, irrespective of time between tests. Although CRC and AN detection rates increase with increasing time interval between FITs, individuals with undetectable f-Hb at first screen have substantially lower risk of CRC at the next screening round compared with individuals with detectable f-Hb., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Introduction: The effectiveness of colorectal cancer screening programs depends on the participation rate. This study examined the association between type and severity of mental illness and colorectal cancer screening participation., Methods: Between 2012 and 2017, a total of 46,919 individuals were invited to sigmoidoscopy screening in Norway, and 70,019 were invited to fecal immunochemical testing. In 2022, logistic regression was used to evaluate the association between the use of antipsychotics, anxiolytics, hypnotics, and antidepressants in the year preceding the screening invitation and screening participation, adjusted for demographic and socioeconomic factors. Defined daily doses of individual drugs were used to assess dose‒response relationships., Results: Overall, 19.2% (24.8% of women, 13.4% of men) of all invitees used at least 1 psychotropic medication. Nonparticipation in the 2 arms combined was associated with the use of anxiolytics (60.7% in users vs 43.2% in nonusers; OR=1.53; 95% CI=1.45, 1.62) and antipsychotics (64.3% vs 43.8%; OR=1.41; 95% CI=1.30, 1.53) and increased with higher doses for both drugs. Hypnotics and antidepressants were only weakly associated with nonparticipation in higher doses. Participation rates were 57.3%, 52.3%, 42.9%, and 35.4% in those prescribed 0, 1, 2, and 3-4 classes of psychotropic medications, respectively. The associations between the use of psychotropic medications and nonparticipation were similar for the 2 screening tests., Conclusions: These findings show significant disparities in colorectal cancer screening participation for individuals with mental illness, independent of the screening method. Moreover, screening participation varied depending on the type and severity of mental illness. Targeted interventions are warranted to ensure that people with mental illness are supported to access the benefits of colorectal cancer screening., (Copyright © 2022 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: High participation rates are important for a colorectal cancer (CRC) screening programme to be effective. Having a long travelling distance to screening centres may impede participation., Methods: We analysed the association between driving time from home address to screening centre and participation among individuals invited to screening with faecal immunochemical test (FIT) (n = 68,624) or sigmoidoscopy (n = 46,076) in a randomized trial in Norway in 2012-17. Two screening centres were involved. We fitted multiple logistic regression models, adjusted for demographic, socioeconomic and health characteristics, and reported odds ratios (OR) with 95% confidence intervals (CI)., Results: Participation rates were 58.9 % (n = 40,445) for FIT and 51.9 % (n = 23,911) for sigmoidoscopy. In sigmoidoscopy, participation was 56.9 % and 47.9 % in those living < 20 and > 60 min by car from the screening centres, respectively. For each 10 min driving time increase, OR for participating in sigmoidoscopy screening was 0.93 (95 % CI 0.91-0.95). There was a significant difference between the two screening centres (p-value for heterogeneity <0.001). Participation in FIT screening were 61.2 % and 57.1 % in those with < 20 and > 60 min driving time, respectively, and the OR was 0.98 (95 % CI 0.96-0.99) for each 10 min increase (heterogeneity between screening methods, P-value <0.001). Among those with a positive FIT, compliance to colonoscopy was higher in those living < 20 compared to > 60 min from the centres (95.1 % vs. 92.9 %, respectively, OR 0.86; 95 % CI 0.77-0.93 for each 10 min increase)., Conclusions: Driving time to screening centre was a significant predictor of participation, mainly in sigmoidoscopy. There were local differences in the impact of driving time on participation. Driving time also affected compliance to colonoscopy after a positive FIT. When planning a CRC screening programme, one should consider offering people living far from screening sites special assistance to facilitate their participation., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Public health systems should guarantee universal access to health care services, including cancer screening. We assessed whether certain population subgroups were underrepresented among participants in colorectal cancer screening with sigmoidoscopy and faecal immunochemical testing (FIT). Between 2012 and 2019, about 140 000 individuals aged 50 to 74 years were randomly invited to once-only sigmoidoscopy or first round of FIT screening. Our study included 46 919 individuals invited to sigmoidoscopy and 70 019 to FIT between 2012 and 2017. We used logistic regression models to evaluate if demographic and socioeconomic factors and use of certain drugs were associated with participation. Twenty-four thousand one hundred and fifty-nine (51.5%) individuals attended sigmoidoscopy and 40 931 (58.5%) FIT screening. Male gender, young age, low education and income, being retired or unemployed, living alone, being an immigrant, long driving time to screening centre, and use of antidiabetic and psychotropic drugs were associated with low participation in both screening groups. Many of these factors also predicted low acceptance of colonoscopy after positive FIT. While male gender, young age and living alone were more strongly associated with nonparticipation in FIT than sigmoidoscopy, low education and income, being retired or immigrant and long driving time were more strongly associated with nonparticipation in sigmoidoscopy than FIT. In conclusion, participation was lower in sigmoidoscopy than FIT. Predictors of nonparticipation were similar between arms. However, low socioeconomic status, being an immigrant and long driving time affected participation more in sigmoidoscopy screening, suggesting that FIT may guarantee more equal access to screening services than sigmoidoscopy., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: Consistent participation in colorectal cancer (CRC) screening with repeated fecal immunochemical test (FIT) is important for the success of the screening program. We investigated whether lifestyle risk factors for CRC were related to inconsistent participation in up to four rounds of FIT-screening., Method: We included data from 3,051 individuals who participated in up to four FIT-screening rounds and returned a lifestyle questionnaire. Using logistic regression analyses, we estimated associations between smoking habits, body mass index (BMI), physical activity, alcohol consumption, diet and a healthy lifestyle score (from least favorable 0 to most favorable 5), and inconsistent participation (i.e. not participating in all rounds of eligible FIT screening invitations)., Results: Altogether 721 (24%) individuals were categorized as inconsistent participants Current smoking and BMI ≥30 kg/m 2 were associated with inconsistent participation; odds ratios (ORs) and 95% confidence intervals (CIs) were 1.54 (1.21-2.95) and 1.54 (1.20-1.97), respectively. A significant trend towards inconsistent participation by a lower healthy lifestyle score was observed (p < 0.05)., Conclusions: Lifestyle behaviors were associated with inconsistent participation in FIT-screening. Initiatives aimed at increasing participation rates among those with the unhealthiest lifestyle have a potential to improve the efficiency of screening., (© 2022. The Author(s).)

Background: Women are at high risk for painful colonoscopy. Pain, but also sedation, are barriers to colorectal cancer (CRC) screening participation. In a randomised controlled trial, we compared on-demand with pre-colonoscopy opioid administration to control pain in women at CRC screening age., Methods: Women, aged 55-79 years, attending colonoscopy at two Norwegian endoscopy units were randomised 1:1:1 to (1) fentanyl on-demand, (2) fentanyl prior to colonoscopy, or (3) alfentanil on-demand. The primary endpoint was procedural pain reported by the patients on a validated four-point Likert scale and further dichotomized for the study into painful (moderate or severe pain) and non-painful (slight or no pain) colonoscopy. Secondary endpoints were: willingness to repeat colonoscopy, adverse events, cecal intubation time and rate, and post-procedure recovery time., Results: Between June 2017 and May 2020, 183 patients were included in intention-to-treat analyses in the fentanyl on-demand group, 177 in the fentanyl prior to colonoscopy group, and 179 in the alfentanil on-demand group. Fewer women receiving fentanyl prior to colonoscopy reported a painful colonoscopy compared to those who were given fentanyl on-demand (25.2% vs. 44.1%, p  < .001). There was no difference in the proportion of painful colonoscopies between fentanyl on-demand and alfentanil on-demand (44.1% vs. 39.5%, p  = .40). No differences were observed for adverse events or any of the other secondary endpoints between the three groups., Conclusions: Fentanyl prior to colonoscopy provided better pain control than fentanyl or alfentanil on-demand. Fentanyl before colonoscopy should be recommended to all women at screening age. Trial registration: Clinicaltrials.gov (NCT01538550). Norwegian Medicines Agency (16/16266-13). EU Clinical Trials Register (EUDRACTNR. 2016-005090-13).

Background: Colorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway. We aim to develop a microbiome-based classification algorithm to identify advanced colorectal lesions in screening participants testing positive for an immunochemical fecal occult blood test (FIT). We will also examine interactions with host factors, diet, lifestyle and prescription drugs. The prospective nature of the study also enables the analysis of changes in the gut microbiome following the removal of precancerous lesions., Methods: The CRCbiome study recruits participants enrolled in the Bowel Cancer Screening in Norway (BCSN) study, a randomized trial initiated in 2012 comparing once-only sigmoidoscopy to repeated biennial FIT, where women and men aged 50-74 years at study entry are invited to participate. Since 2017, participants randomized to FIT screening with a positive test result have been invited to join the CRCbiome study. Self-reported diet, lifestyle and demographic data are collected prior to colonoscopy after the positive FIT-test (baseline). Screening data, including colonoscopy findings are obtained from the BCSN database. Fecal samples for gut microbiome analyses are collected both before and 2 and 12 months after colonoscopy. Samples are analyzed using metagenome sequencing, with taxonomy profiles, and gene and pathway content as primary measures. CRCbiome data will also be linked to national registries to obtain information on prescription histories and cancer relevant outcomes occurring during the 10 year follow-up period., Discussion: The CRCbiome study will increase our understanding of how the gut microbiome, in combination with lifestyle and environmental factors, influences the early stages of colorectal carcinogenesis. This knowledge will be crucial to develop microbiome-based screening tools for CRC. By evaluating biomarker performance in a screening setting, using samples from the target population, the generalizability of the findings to future screening cohorts is likely to be high., Trial Registration: ClinicalTrials.gov Identifier: NCT01538550 ., (© 2021. The Author(s).)

Background & Aims: The comparative effectiveness of sigmoidoscopy and fecal immunochemical testing (FIT) for colorectal cancer (CRC) screening is unknown., Methods: Individuals aged 50-74 years living in Southeast Norway were randomly invited between 2012 and 2019 to either once-only flexible sigmoidoscopy or FIT screening every second year. Colonoscopy was recommended after sigmoidoscopy if any polyp of ≥10 mm, ≥3 adenomas, any advanced adenomas, or CRC was found or, subsequent to, FIT >15 μg hemoglobin/g feces. Data for this report were obtained after complete recruitment in both groups and included 2 full FIT rounds and part of the third round. Outcome measures were participation, neoplasia detection, and adverse events. Age-standardized detection rates and age-adjusted odds ratios (ORs) were calculated., Results: We included 139,291 individuals: 69,195 randomized to sigmoidoscopy and 70,096 to FIT. The participation rate was 52% for sigmoidoscopy, 58% in the first FIT round, and 68% for 3 cumulative FIT rounds. Compared to sigmoidoscopy, the detection rate for CRC was similar in the first FIT round (0.25% vs 0.27%; OR, 0.92; 95% confidence interval [CI], 0.75-1.13) but higher after 3 FIT rounds (0.49% vs 0.27%; OR, 1.87; 95% CI, 1.54-2.27). Advanced adenoma detection rate was lower in the first FIT round compared to sigmoidoscopy at 1.4% vs 2.4% (OR, 0.57; 95% CI, 0.53-0.62) but higher after 3 cumulative FIT rounds at 2.7% vs 2.4% (OR, 1.14; 95% CI, 1.05-1.23). There were 33 (0.05%) serious adverse events in the sigmoidoscopy group compared to 47 (0.07%) in the FIT group (P = .13)., Conclusions: Participation was higher and more CRC and advanced adenomas were detected with repeated FIT compared to sigmoidoscopy. The risk of perforation and bleeding was comparable. Clinicaltrials.gov, Number: NCT01538550., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Lifestyle factors may help to identify individuals at high-risk for colorectal cancer (CRC)., Aims: To examine the association between lifestyle, referral for follow-up colonoscopy and proximal neoplasia detection in CRC screening., Methods: In this observational study, 14,832 individuals aged 50-74 years were invited to faecal immunochemical test (FIT) or sigmoidoscopy screening. Advanced lesions (AL), including advanced adenomas, advanced serrated lesions and CRC were divided according to location: distal-only, or proximal with or without distal AL. We collected information on smoking habit, body mass index and alcohol intake through a questionnaire., Results: Out of 3,318 FIT and 2,988 sigmoidoscopy participants, 516 (16%) and 338 (11%), respectively, were referred for follow-up colonoscopy after a positive screening test. Two-hundred-and-fifty-six (4%) had distal-only and 119 (2%) proximal AL. In FIT participants, obesity and high alcohol intake were associated with proximal AL; odds ratio (95% confidence interval) 2.68 (1.36-5.26) and 2.16 (1.08-4.30), respectively. In sigmoidoscopy participants, current smoking was associated with proximal AL; 4.58 (2.24-9.38), and current smoking and obesity were associated with referral for colonoscopy; 2.80 (2.02-3.89) and 1.42 (1.01-2.00), respectively., Conclusion: Current smoking, obesity and high alcohol intake were associated with screen-detected proximal colorectal AL. Current smoking and obesity were associated with referral for follow-up colonoscopy in sigmoidoscopy screening., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Artificial intelligence is currently a hot topic in medicine. However, medical data is often sparse and hard to obtain due to legal restrictions and lack of medical personnel for the cumbersome and tedious process to manually label training data. These constraints make it difficult to develop systems for automatic analysis, like detecting disease or other lesions. In this respect, this article presents HyperKvasir, the largest image and video dataset of the gastrointestinal tract available today. The data is collected during real gastro- and colonoscopy examinations at Bærum Hospital in Norway and partly labeled by experienced gastrointestinal endoscopists. The dataset contains 110,079 images and 374 videos, and represents anatomical landmarks as well as pathological and normal findings. The total number of images and video frames together is around 1 million. Initial experiments demonstrate the potential benefits of artificial intelligence-based computer-assisted diagnosis systems. The HyperKvasir dataset can play a valuable role in developing better algorithms and computer-assisted examination systems not only for gastro- and colonoscopy, but also for other fields in medicine.

Background & Aims: The fecal immunochemical test (FIT) is the tool most frequently used for colorectal cancer (CRC) screening worldwide. It is unclear how the use of aspirin and oral anticoagulants in the screening population affects the diagnostic performance of FIT., Methods: We performed a cross-sectional study in an ongoing CRC screening trial in Norway. Participants aged 50-74 years with a positive result from an FIT (>15 μg hemoglobin/g feces) and subsequent colonoscopy (reference standard) were included. Those who used regular aspirin, warfarin, or direct-acting oral anticoagulants (DOACs) were defined as users. Non-users were matched according to age, sex, screening center, and screening round. The primary outcomes were the positive predictive value (PPV) for CRC and advanced adenoma., Results: Among 4908 eligible participants, 1008 used aspirin, 147 used warfarin, 212 used DOACs, and 3541 were non-users. CRCs were found in 234 individuals and advanced adenomas in 1305 individuals. The PPV for CRC was 3.8% for aspirin users vs 6.4% for matched non-users (P = .006), The PPV for advanced adenoma in aspirin users was 27.2% vs 32.6% for matched non-users (P = .011). For DOAC, the PPV for CRC was 0.9% in users vs 6.8% in matched non-users (P = .001). The PPV for advanced adenoma in DOAC users was 20.5% vs 32.4% in matched non-users (P = .002). There was no significant difference in PPV for CRC or advanced adenoma in warfarin users compared to non-users., Conclusions: In a large screening cohort in Norway, regular use of aspirin and particularly DOACs, were associated with lower PPV of FIT for detection of CRCs and advanced adenomas. ClinicalTrials.gov ID NCT01538550., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)