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

SIMPLE SUMMARY: Colorectal cancer (CRC) screening participants with significant traces of hemoglobin in their stool have been reported to have higher mortality and different causes of death (other than CRC) compared to those without. We aimed to investigate these differences among screening participants after 33 years of follow-up. We confirmed that participants with detectable fecal hemoglobin were more likely to die in the study period and to die from different causes, such as cardiovascular and endocrine and hematological diseases, compared to those without detectable fecal hemoglobin. This confirms that fecal hemoglobin may have potential as a marker for diseases not directly related to the colon and rectum and may represent a target for future preventive measures. ABSTRACT: 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

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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-022-02724-3

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

Can coffee or chewing gum decrease transit times in Colon capsule endoscopy? A randomized controlled trial

Abstract Background A high rate of complete colon capsule endoscopy (CCE) investigations is required for a more widespread use of CCE. The objective of this study was to assess if coffee or chewing gum can increase excretion of the colon capsule within battery life time (excretion rate). Methods One hundred eighty six screening participants with a positive immunochemical fecal occult blood test were included in this single-centre randomized controlled trial with blinding of the investigators to the randomization. Participants received instant coffee, chewing gum or nothing in addition to the standard bowel preparation. Results The intention was to include 57 participants in the coffee group, 61 in the chewing gum group and 60 in the control group, on 8 participants data were missing. A total of 165 participants were included in a per protocol analysis. Exclusion was due to not receiving the allocated intervention (8 coffee, 4 chewing gum) and technical failure of the capsule (1 coffee). The excretion rate was 58% in the coffee group (n = 48), 63% in the chewing gum group (n = 57) and 55% in the control group (n = 60, p > 0.2). Transit times were similar in all groups. The excretion rate was low in participants who had transit times over 10 h (14%). A strong correlation was found between adequate cleansing and excretion of the capsule. There were no serious adverse events related to the interventions or CCE investigations. Conclusions Chewing gum and coffee did not improve excretion rate in this study. An effect of chewing gum could not be proven, possibly due to sample size. Since chewing gum might improve excretion rates, is cheap and has no known side effects, it needs to be considered in future bowel preparation trials for CCE. Trial registration NCT02303756, registered on December 1st 2014

Additional file 1: of Can coffee or chewing gum decrease transit times in Colon capsule endoscopy? A randomized controlled trial

Table S1. Bowel preparation with timing of PEG cleansing and boosters. Figure S1. Total transit time in categories of CCE investigations by intervention. (DOCX 31 kb)

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

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

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