Factors associated with negative colonoscopy in participants with a positive faecal immunochemical test from the Danish Colorectal Cancer Screening Program - a population-based study.

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.

Long-term Outcomes of Robot-assisted Versus Laparoscopic Surgery for Colon Cancer: A Nationwide Register-based Cohort Study.

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.

Colon CApsule endoscopy compared to conventional COlonoscopy in patients with colonic DIverticulitis: the study protocol for a randomised controlled superiority trial (CACODI trial).

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.

Socioeconomic differences in expected discomfort from colonoscopy and colon capsule endoscopy.

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.

Socioeconomic inequalities in interval colorectal cancer are explained by differences in faecal haemoglobin concentration and age: a register-based cohort study.

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.

Faecal haemoglobin concentration predicts all-cause mortality.

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.

Carrot Intake and Risk of Developing Cancer: A Prospective Cohort Study.

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.

Faecal haemoglobin concentrations are associated with all-cause mortality and cause of death in colorectal cancer screening.

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.

Colon capsule endoscopy following incomplete colonoscopy in routine clinical settings.

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).

Castor Oil in Bowel Preparation Regimens for Colon Capsule Endoscopy: A Systematic Review with Meta-Analysis.

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.

Inter/Intra-Observer Agreement in Video-Capsule Endoscopy: Are We Getting It All Wrong? A Systematic Review and Meta-Analysis.

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, I2 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.

The Effect of Prucalopride on the Completion Rate and Polyp Detection Rate of Colon Capsule Endoscopies.

Purpose: 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.

Odds of Incomplete Colonoscopy in Colorectal Cancer Screening Based on Socioeconomic Status.

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.

Cause of Death, Mortality and Occult Blood in Colorectal Cancer Screening.

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.

Colon capsule endoscopy in colorectal cancer screening: Interim analyses of randomized controlled trial CareForColon2015.

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.

Long-term Functional Urinary and Sexual Outcomes in Patients with Anorectal Malformations-A Systematic Review.

CONTEXT: Long-term urinary and sexual outcomes after repair of anorectal malformations (ARMs) are currently affected by concomitant malformations of the urinary tract and genitalia, sacral anomalies, and the surgical approach. However, the overall prevalence of urinary and sexual dysfunction remains unclear. OBJECTIVE: To evaluate the prevalence of urinary and sexual dysfunction in patients aged >10 yr after repair of ARM in infancy. EVIDENCE ACQUISITION: A systematic literature review was performed using the Medline, Embase, and Cochrane databases. Selected studies were reviewed according to the Consolidated Standards of Reporting Trials (CONSORT) and Standards for the Reporting of Diagnostic Accuracy Studies (STARD) criteria. We included studies reporting the prevalence of the following outcomes: urinary incontinence (UI), lower urinary tract symptoms (LUTS), neurogenic bladder dysfunction (NBD), sexual dysfunction (SD), erectile dysfunction (ED), ejaculatory dysfunction, and birth rate. We initially identified 588 studies, of which 17 were included for evidence synthesis. EVIDENCE SYNTHESIS: A probabilistic meta-analysis on each subgroup revealed the following combined prevalence estimates: UI 16% (95% confidence interval [CI] 7-27%), LUTS/NBD 36% (95% CI 13-62%), SD among women 50% (95% CI 34-66%), ED 12% (95% CI 7-18%), ejaculatory dysfunction 16% (95% CI 9-25%), and birth rate 20% (95% CI 7-38%). Subgroup analysis showed a higher prevalence of ED and ejaculatory dysfunction among patients with high ARM severity when compared to low ARM severity. CONCLUSIONS: Among patients undergoing ARM repair, we found a high prevalence of long-term impairment of UI, ED, and SD. We stress the need for larger multicentre trials with more comparable populations to optimise treatment and follow-up regimens. PATIENT SUMMARY: We reviewed long-term outcomes for patients with anorectal malformations who underwent surgery and found that both urinary incontinence and sexual dysfunctions are common for both males and females.

Effects of Screening Compliance on Long-term Reductions in All-Cause and Colorectal Cancer Mortality.

BACKGROUND & AIMS: Randomized trials have shown that biennial fecal occult blood test (FOBT) screening reduces mortality from colorectal cancer (CRC), but not overall mortality. Differences in benefit for men vs women, and by age, are unknown. We sought to evaluate long-term reduction in all-cause and CRC-specific mortality in men and women who comply with offered screening, and in different age groups, using individual participant data from 2 large randomized trials of biennial FOBT screening, compared with an intention to treat analysis. METHODS: We updated the CRC and all-cause mortality from the Danish CRC screening trial (n = 61,933) through 30 years of follow up and pooled individual participant data with individual 30-year follow-up data from the Minnesota Colon Cancer Control trial (n = 46,551). We compared the biennial screening groups to usual care (controls) in individuals 50-80 years old using Kaplan Meier estimates of relative risks and risk differences, adjusted for study differences in age, sex, and compliance. RESULTS: Through 30 years of follow up, there were 33,478 (71.9%) and 33,479 (72.2%) total deaths and 1023 (2.2%) and 1146 (2.5%) CRC deaths in the biennial screening (n = 46,553) and control groups (n = 46,358), respectively. Among compliers, biennial FOBT screening significantly reduced CRC mortality by 16% (relative risk [RR], 0.84; 95% CI, 0.74-0.96) and all-cause mortality by 2% (RR, 0.98; 95% CI, 0.97-0.99). Among compliers, the reduction in CRC mortality was larger for men (RR, 0.75; 95% CI, 0.62-0.90) than women (RR, 0.91; 95% CI, 0.75-1.09). The largest reduction in CRC mortality was in compliant men 60-69 years old (RR, 0.59; 95% CI, 0.42-0.81) and women 70 years and older (RR, 0.53; 95% CI, 0.30-0.94). CONCLUSIONS: Long-term CRC mortality outcomes of screening among compliers using biennial FOBT are sustained, with a statistically significant reduction in all-cause mortality. The reduction in CRC mortality is greater in men than women-the benefit in women lags that of men by about 10 years.

Diagnostic accuracy of capsule endoscopy compared with colonoscopy for polyp detection: systematic review and meta-analyses.

BACKGROUND: Colon capsule endoscopy (CCE) is a technology that might contribute to colorectal cancer (CRC) screening programs as a filter test between fecal immunochemical testing and standard colonoscopy. The aim was to systematically review the literature for studies investigating the diagnostic yield of second-generation CCE compared with standard colonoscopy. METHODS: A systematic literature search was performed in PubMed, Embase, and Web of Science. Study characteristics including quality of bowel preparation and completeness of CCE transits were extracted. Per-patient sensitivity and specificity were extracted for polyps (any size, ≥ 10 mm, ≥ 6 mm) and lesion characteristics. Meta-analyses of diagnostic yield were performed. RESULTS: The literature search revealed 1077 unique papers and 12 studies were included. Studies involved a total of 2199 patients, of whom 1898 were included in analyses. The rate of patients with adequate bowel preparation varied from 40 % to 100 %. The rates of complete CCE transit varied from 57 % to 100 %. Our meta-analyses demonstrated that mean (95 % confidence interval) sensitivity, specificity, and diagnostic odds ratio were: 0.85 (0.73-0.92), 0.85 (0.70-0.93), and 30.5 (16.2-57.2), respectively, for polyps of any size; 0.87 (0.82-0.90), 0.95 (0.92-0.97), and 136.0 (70.6-262.1), respectively, for polyps ≥ 10 mm; and 0.87 (0.83-0.90), 0.88 (0.75-0.95), and 51.1 (19.8-131.8), respectively, for polyps ≥ 6 mm. No serious adverse events were reported for CCE. CONCLUSION: CCE had high sensitivity and specificity for per-patient polyps compared with standard colonoscopy However, the relatively high rate of incomplete investigations limits the application of CCE in a CRC screening setting.

Colon Capsule Endoscopy vs. CT Colonography Following Incomplete Colonoscopy: A Systematic Review with Meta-Analysis.

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.

Colon capsule endoscopy in colorectal cancer screening: a randomised controlled trial.

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.