Colorectal cancer risk in bowel adenomas based on lifestyle exposures, tissue preconditioning and DNA methylation

BackgroundColorectal cancer (CRC) is associated with patient demographics, lifestyle exposures and molecular alterations. However, it is not possible to determine which adenomas will progress to CRC, as ethically it is unacceptable to leave and follow adenomas. We hypothesised that certain lifestyle exposures at high levels could precondition exposed bowel tissue by changing and aging it, increasing the risks of deleterious DNA methylation and genetic alterations. We used a novel study design comparing adenomas with concurrent CRC (thus more likely exposed to deleterious lifestyle effects) to single adenomas in bowels with no history of CRC; we called these high (HR) and low-risk (LR) adenomas respectively.MethodsWe carried out a discovery and replication epigenome-wide association study (EWAS) on 106 HR and 111 LR adenomas, profiled with MethylationEPIC BeadChips. In order, to identify differentially methylated positions (DMP), regions (DMR), and DNAm (DNAmethylation) lifestyle exposures and risks, with adjustment for confounders, and gene ontology (GO) and pathway enrichment. Then, two open-source gene expression omnibus (GEO) validation datasets (52, 57 and 49, 48 HR and LR normal bowel tissues respectively) were analysed for these DNAm lifestyle exposures and risks, with adjustment for confounders.ResultsOur EWAS found 5 Bonferroni significant DMPs with absolute delta betas ≥ 5%, and 14 significant DMRs with absolute mean DMR delta betas ≥ 5%, replicated in the GPX7, RGS3 and TMEM135 cancer-associated genes. DNAm high alcohol exposures were strongly associated with increased risk of HR adenomas (odds ratio (OR) per standard deviation (SD) = 2.16 (95% confidence interval (CI) 1.55 - 3.09, p-value = 9.7 × 10-6)). In the validation datasets, DNAm high alcohol (ORperSD = 2.12 (95% CI 1.35 - 3.55, p-value = 2.0 × 10-3) and ORperSD = 1.79 (95% CI 1.14 - 2.96, p-value = 1.7 × 10-2)), and high body mass index (BMI) exposures (ORperSD = 1.72 (95% CI 1.13 - 2.73, p-value = 1.5 × 10-2)) were associated with increased risk of HR normal bowel tissues.ConclusionsHigh alcohol and BMI exposures may precondition normal bowel tissues and adenomas for increased risk of DNA methylation alterations associated with CRC progression. The DNAm exposure signatures and our newly identified genes may be useful epigenetic biomarkers for CRC prevention.

Bowel monitoring in psychiatry of old age: a quality improvement project

AimsThis project aims to ensure all patients in the dementia ward 1 in Kingsway Care Centre, Dundee have daily bowel monitoring and achieve a normal bowel habit. The hypothesis is that patients are inadequately screened and substantial undiagnosed constipation exists.BackgroundConstipation has a prevalence of 16-50% among individuals over 65 years old in the community. Psychiatric illnesses are known risk factors with older psychiatric patients 3-6 times more likely to be constipated. Untreated constipation may progress to serious complications such as bowel obstruction and bowel perforation. Delirium, often mislabelled as worsening psychiatric symptoms, also may occur leading to additional psychotropic medications being prescribed, further worsening the constipation.MethodAll patients in Ward 1, Kingsway Care Centre Dundee over 4 months were included, amounting to 25 patients. Data were gathered from stool charts weekly. Quality improvement framework was followed with two plan-do-study-act (PDSA) cycles completed. Normal bowel function was assessed against ROME IV constipation criteria and less than 75% of Bristol stool type 6 or 7 due to the risk of overflow diarrhoea and laxative overuse. In the first PDSA cycle, stool charts were modified to account for patients independently mobilising to the bathroom and daily documentation even if bowel movements were uncertain. The second PDSA cycle introduced a sticker on charts folder to “ask the patient” along with a staff education leaflet on the complications of constipation. Data were anonymised and analysed with run charts using Microsoft Excel.ResultAt baselines, 50% of patients had a stool chart. This increased to 90% in cycle 1, 100% in cycle 2. 28% of patients had any stools documented at baselines. This increased to 31% in cycle 1, 59% in cycle 2. At baselines, 0% of patients had a normal bowel habit. This maintained at 0% in cycle 1 but increased to 13% in cycle 2. No serious complications were found in patients assisted with toileting. However, 34% of independently mobile patients developed serious complications.ConclusionPoor documentation existed in all patients, particularly those independently mobile. Independently mobile patients were particularly at risk of serious complications of constipation compared to assisted patients. Introduction of new stool charts in the first PDSA cycle resulted in increased documentation but limited benefit for identification of constipation. The second PDSA cycle, targeting staff education and compliance, showed an increase in identification of constipation indicating limited staff knowledge as a key barrier to improvement in patients’ bowel habit.

Bile pigment in small-bowel water content may reflect bowel habits: a retrospective analysis of a capsule endoscopy imaging series

Background: Pigmented bile salts darken the small-bowel lumen and are present with bile acid, which is involved in the development of bowel habits. The small-bowel water content (SBWC) in the ileum could represent the colonic environment, but no studies have focused on this feature. However, measurement of crude SBWC can be challenging because of the technical difficulty of the endoscopic approach without preparation. Our aim was to evaluate optically active bile pigments in the SBWC of patients with abnormal bowel habits using capsule endoscopy (CE) to investigate the impact of bile acid on bowel habits. Methods: The study population included 37 constipated patients, 20 patients with diarrhea, and 77 patients with normal bowel habits who underwent CE between January 2015 and May 2018. Patients with secondary abnormal bowel habits were excluded. In addition to conventional imaging, we used flexible spectral imaging color enhancement (FICE) setting 1 imaging, in which the effects of bile pigments on color are suppressed. Intergroup color differences of SBWC in the ileum (ΔE) were evaluated from conventional and FICE setting 1 images. Color values were assessed using the CIE L*a*b* color space. Differences in SBWC lightness (black to white, range 0–100) were also evaluated. Results: The ΔE values from the comparison of conventional images between patients with constipation and with normal bowel habits and between patients with diarrhea and with normal bowel habits were 12.4 and 11.2, respectively. These values decreased to 4.4 and 3.3, respectively, when FICE setting 1 images were evaluated. Patients with constipation and diarrhea had significantly brighter (34.4 versus 27.6, P < .0001) and darker (19.6 versus 27.6, P < .0001) SBWC lightness, respectively, than patients with normal bowel habits. The FICE setting 1 images did not reveal significant differences in SBWC lightness between those with constipation and with normal bowel habits (44.1 versus 43.5, P = .83) or between those with diarrhea and with normal bowel habits (39.1 versus 43.5, P = .20). Conclusions : Differences in SBWC color and darkness in the ileum appear to be attributable to bile pigments. Therefore, bile pigments in SBWC may reflect bowel habits.

P158 Semi-automated detection of qualitative features of Crohn’s disease activity found on CT-enterography using machine learning

Background Imaging is essential in the assessment of Crohn’s disease (CD) severity, phenotype, and therapeutic response. However, qualitative findings can be limited by interobserver variation and ambiguous feature definitions. Our aim was to evaluate computational approaches for identifying qualitative disease features using CT-enterography (CTE). Methods CD subjects with ileal CD and CTE imaging between 2009 and 2017 were retrospective identified at a single tertiary care centre. CTE scans were reviewed by two fellowship-trained abdominal radiologists who labelled diseased and normal bowel transitions agreeing on definitions of qualitative findings prior to labelling. Computed intestinal features were used by machine learning methods (k-nearest neighbour, support vector machines, random forest) to model regions of diseased bowel and predict qualitative findings with 5-fold cross validation. Cohen’s kappa with quadratic weighting was used to assess agreement between radiologists and model predictions. Results In 206 unique patients, 548 small bowel segments underwent paired radiologist review for qualitative imaging findings. Automated localisation of diseased vs. normal bowel segments had excellent performance, with an AUC, PPV, and NPV of 0.922, 0.924, and 0.918, respectively (Figure 1). Radiologist-to-Radiologist and Radiologist-to-automated prediction agreement on qualitative findings are shown in Table 1. Agreement on the degree of mural enhancement between radiologists was very good (k = 0.75,95% CI 0.68–0.82), with nearly identical agreement (k = 0.75, 95% CI 0.72–0.79) between radiologists and automated grading models. Conclusion Computer vision methods have excellent performance for automatically distinguishing diseased from normal ileum and show potential for qualitative disease assessments of Crohn’s disease on CTEs.

Bile pigment in small-bowel water content reflects bowel habits: a retrospective analysis of a capsule-endoscopy imaging series

Background Pigmented bile salts darken the small-bowel lumen and are present with bile acid, which is involved in the development of bowel habits. The small-bowel water content (SBWC) in the ileum could represent the colonic environment, although no studies have focused on this feature. However, measurement of the crude SBWC can be challenging because of the technical difficulty of the endoscopic approach without preparation. Our aim was to evaluate optically active bile pigments in the SBWC of patients with abnormal bowel habits using capsule endoscopy (CE), to investigate the impact of bile acid on bowel habits. In addition to conventional imaging, we used flexible spectral imaging color enhancement (FICE) setting 1 imaging, in which the effects of bile pigments on color are suppressed.Methods The study population included 37 constipated patients, 20 patients with diarrhea, and 77 patients with normal bowel habits who underwent CE between January 2015 and May 2018. Patients with secondary abnormal bowel habits were excluded. Intergroup color differences of SBWC in the ileum (ΔE) were evaluated from conventional and FICE setting 1 images. Color values were assessed using the CIE L*a*b* color space. Differences in lightness (black to white, range 0 to 100) of SBWC were also evaluated.Results Values of ΔE calculated from comparisons of conventional images of constipated and normal-bowel-habit patients, and patients with diarrhea and normal-bowel-habit patients were 11.3 and 10.7, respectively. These values decreased to 3.9 and 3.2, respectively, when FICE setting 1 images were evaluated. The SBWC lightness of patients with constipation and diarrhea was significantly brighter (34.0 versus 27.2, P < .0001) and darker (18.8 versus 27.2, P < .0001), respectively, compared with the normal-bowel-habit patients. Examination of the FICE setting 1 images did not reveal significant differences in SBWC lightness between the constipated and normal-bowel-habit groups (44.7 versus 46.7, P = .33) or between the diarrhea and normal-bowel-habit groups (44.7 versus 42.3, P = .39).Conclusions Differences in color and darkness of the SBWC in the ileum appear to be attributable to bile pigments. Therefore, bile pigments in SBWC could reflect bowel habits.

Early versus Late Oral Feeding on the Recovery of Normal Bowel Functions After Caesarean Section: A Randomized Controlled Study

Background. To compare early oral feeding (EF) versus late oral feeding (LF) on the return of normal bowel functions in spinally anesthetized women after having lower segment Caesarean section (LSCS). Secondary outcomes such as maternal satisfaction and gastrointestinal complications were also evaluated. Methods. Three-hundred and sixty-two singleton pregnant women undergoing elective LSCS with spinal anesthesia were assigned to receive either EF (n= 183) or LF (n= 179) after surgery. Participants began to take normal diet between immediately and 6 hours, or began sipping water after 12 hours and soft diet after 24 hours then normal diet after 48 hours of surgery. Results. The ages of participants ranged from 19 to 47, with a mean age of 35±12 years. There was no-loss follow up and no significant difference in patient characteristics. Participants given EF were more likely to experience bowel sound the next morning after surgery than patients given LF (EF 93% vs. LF 71%, P<0.05). However, there was no difference in time to passing flatus and time to passing stool. Maternal satisfaction, rated on a 5-point scale was significantly higher in the EF group. However, there was no significant difference in gastrointestinal complications between both groups. Conclusion. The findings of this trial support the recommendation of EF for women who undergo uncomplicated LSCS under spinal anesthesia.

Associations of chronic diarrhoea with non-alcoholic fatty liver disease and obesity-related disorders among US adults

Mechanisms explaining observed associations between diarrhoea and obesity or increased body mass index (BMI) are unclear.ObjectiveTo assess associations of bowel patterns with BMI, metabolic syndrome (MS), non-alcoholic fatty liver disease (NAFLD) and other obesity-related disorders.DesignWe performed a cross-sectional analysis of data from adults who completed bowel health questions for the 2005 to 2010 cycles of the National Health and Nutrition Examination Surveys. Relationships were examined using multinomial logistic regression. Confounding effects of demographics, smoking, alcohol and BMI were examined by sequential modelling.ResultsAmong 13 413 adults, weighted prevalence rates of constipation and diarrhoea were 8.9% and 6.6%, respectively. Mean BMI was associated with bowel patterns (p<0.001), and was higher with diarrhoea (30.3 kg/m2) versus normal bowel patterns (28.6 kg/m2) and with diarrhoea versus constipation (27.8 kg/m2). NAFLD was more prevalent (ORs, 95% CI) in diarrhoea versus normal bowel patterns (OR=1.34, 95% CI 1.01 to 1.78) or constipation (OR=1.45, 95% CI 1.03, 2.03) in adjusted analyses. The higher prevalence of MS in diarrhoea versus constipation (OR=1.27, 95% CI 0.97 to 1.67) was not independent of BMI.ConclusionsThese findings suggest an association between diarrhoea and NAFLD that is independent of BMI.

Fifteen-minute consultation on the healthy child: Bowel habit in infants and children

A common presentation to the general paediatric clinic is a child or young person’s difficult bowel habit, which is often a potent source of anxiety for parents and carers. A large proportion of these children will have a functional cause for their symptoms, with unnecessary investigation and non-evidence-based treatments adding to their difficulties. This article aims to explain what encompasses the normal bowel habit in children and young people, reassure where appropriate and identify those patterns that may be suggestive of a disorder or disease requiring treatment. We illustrate both extremes of the spectrum of normal bowel habit in children with two case studies.