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.

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.

Surveillance of the small-bowel by capsule endoscopy in Lynch syndrome - A systematic review with meta-analysis.

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_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_MMR defects.

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.

Colon capsule retention in a patient with large bowel stenosis due to diverticulosis - a case report.

Capsule retention is a rare complication to capsule endoscopy. It is often asymptomatic and resolves itself spontaneously. In some cases, endoscopy or surgery is necessary to remove the capsule. Cases of capsule retention in the colon are not reported very often and precautions in subsequent investigations must be considered. We present a case of a 74-year-old woman who underwent colon capsule endoscopy (CCE) due to a positive fecal immunochemical test. The CCE was incomplete, and the patient was referred to conventional colonoscopy, which was complicated by perforation of the large bowel during the procedure. This lead to a CT scan showing the capsule proximal to a stenotic colon segment which was subsequently surgically removed. In patients who report lack of capsule excretion and stenosis is not verified, colonoscopy can be carried out, but with caution.

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.

AID-U-Net: An Innovative Deep Convolutional Architecture for Semantic Segmentation of Biomedical Images.

Semantic segmentation of biomedical images found its niche in screening and diagnostic applications. Recent methods based on deep learning convolutional neural networks have been very effective, since they are readily adaptive to biomedical applications and outperform other competitive segmentation methods. Inspired by the U-Net, we designed a deep learning network with an innovative architecture, hereafter referred to as AID-U-Net. Our network consists of direct contracting and expansive paths, as well as a distinguishing feature of containing sub-contracting and sub-expansive paths. The implementation results on seven totally different databases of medical images demonstrated that our proposed network outperforms the state-of-the-art solutions with no specific pre-trained backbones for both 2D and 3D biomedical image segmentation tasks. Furthermore, we showed that AID-U-Net dramatically reduces time inference and computational complexity in terms of the number of learnable parameters. The results further show that the proposed AID-U-Net can segment different medical objects, achieving an improved 2D F1-score and 3D mean BF-score of 3.82% and 2.99%, respectively.

The optimal use of colon capsule endoscopes in clinical practice.

Colon capsule endoscopy (CCE) has been available for nearly two decades but has grappled with being an equal diagnostic alternative to optical colonoscopy (OC). Due to the COVID-19 pandemic, CCE has gained more foothold in clinical practice. In this cutting-edge review, we aim to present the existing knowledge on the pros and cons of CCE and discuss whether the modality is ready for a larger roll-out in clinical settings. We have included clinical trials and reviews with the most significant impact on the current position of CCE in clinical practice and discuss the challenges that persist and how they could be addressed to make CCE a more sustainable imaging modality with an adenoma detection rate equal to OC and a low re-investigation rate by a proper preselection of suitable populations. CCE is embedded with a very low risk of severe complications and can be performed in the patient's home as a pain-free procedure. The diagnostic accuracy is found to be equal to OC. However, a significant drawback is low completion rates eliciting a high re-investigation rate. Furthermore, the bowel preparation before CCE is extensive due to the high demand for clean mucosa. CCE is currently not suitable for large-scale implementation in clinical practice mainly due to high re-investigation rates. By a better preselection before CCE and the implantation of artificial intelligence for picture and video analysis, CCE could be the alternative to OC needed to move away from in-hospital services and relieve long-waiting lists for OC.

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.

Annotation Tools in Gastrointestinal Polyp Annotation.

Capsule endoscopy (CE) is a valid alternative to conventional gastrointestinal (GI) endoscopy tools. In CE, annotation tools are crucial in developing large and annotated medical image databases for training deep neural networks (DNN). We provide an overview of the described and in-use various annotation systems available, focusing on the annotation of adenomatous polyp pathology in the GI tract. Some studies present promising results regarding time efficiency by implementing automated labelling features in annotation systems. Thus, data are inadequate regarding the general overview for users, and may also be more specific on which features provided are necessary for polyp annotation.

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.

Endoscopic full-thickness resection (eFTR) in colon and rectum: indications and outcomes in the first 37 cases in a single center.

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.

Comment on "Artificial intelligence in gastroenterology: A state-of-the-art review".

Colon capsule endoscopy (CCE) was introduced nearly two decades ago. Initially, it was limited by poor image quality and short battery time, but due to technical improvements, it has become an equal diagnostic alternative to optical colonoscopy (OC). Hastened by the coronavirus disease 2019 pandemic, CCE has been introduced in clinical practice to relieve overburdened endoscopy units and move investigations to out-patient clinics. A wider adoption of CCE would be bolstered by positive patient experience, as it offers a diagnostic investigation that is not inferior to other modalities. The shortcomings of CCE include its inability to differentiate adenomatous polyps from hyperplastic polyps. Solving this issue would improve the stratification of patients for polyp removal. Artificial intelligence (AI) has shown promising results in polyp detection and characterization to minimize incomplete CCEs and avoid needless examinations. Onboard AI appears to be a needed application to enable near-real-time decision-making in order to diminish patient waiting times and avoid superfluous subsequent OCs. With this letter, we discuss the potential and role of AI in CCE as a diagnostic tool for the large bowel.

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.

Erratum: Real-life practice data on colon capsule endoscopy: We need them fast!

[This corrects the article DOI: 10.1055/a-1728-9371.].

Idiopathic asymptomatic pneumoperitoneum in a patient with ureteric calculus and Crohn's disease.

A 46-year-old male referred to the Emergency Department with pain in the left flank. The patient suffered from Crohn's disease. He had not experienced any fever, and a urine strip showed signs of blood. A ureteric calculus was suspected and a computed tomography scan was performed, which surprisingly showed free intraperitoneal air (FIA) located along the ascending colon. The patient had no signs indicative of peritonitis and the spontaneous pneumoperitoneum was suspected. Pneumoperitoneum is often associated with severe intraabdominal pathology, such as perforation of the gastrointestinal tract, requiring acute surgical intervention. In ~10% of all cases of FIA, the cause is related to conditions not requiring prompt surgical intervention. Doctors need to recognize the rare condition of spontaneous pneumoperitoneum and correlate these findings to patient complaints to be able to choose the correct conservative strategy and to avoid unnecessary surgical procedures and risks for the patient.

The Effectiveness of a Very Low-Volume Compared to High-Volume Laxative in Colon Capsule Endoscopy.

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.

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.