An unusual diverticulum adjacent to two large colonic polyps; a case report.

BACKGROUND: Adenocarcinomas can arise in a variety of circumstances in which intestinal segments have been used for urinary diversions. Whereas ureterosigmoidostomy is the oldest and simplest form of continent urinary diversion it also seems to be the most dangerous in this regard. Herein we present a case of colonic neoplasia complicating a non-functioning ureterosigmoidostomy after 55 years; the longest latent period documented to date. CASE PRESENTATION: A 56-year-old lady born with congenital bladder exystrophy and who had a functional ileal conduit presented to us with a 6 month history of change in bowel habit and rectal bleeding. Prior to this she had had multiple abdominal surgeries as a child and had suffered from lifelong recurrent urinary tract infections. Colonoscopy revealed the presence of two large sessile polyps in close proximity to a diverticulum-like structure that after surgical resection turned out to be a non-functioning ureterosigmoidostomy from when she was an infant. CONCLUSIONS: Our case highlights the importance of enrolling patients with ureterosigmoidostomies into long-term colonoscopic surveillance programmes. This is also true for those patients who undergo revisional surgery but have preserved ureteric stumps. Endoscopists should be aware of the varied endoscopic appearances of the anastamosis in order to be able to recognise these structures when present.

Quality standards in upper gastrointestinal endoscopy: a position statement of the British Society of Gastroenterology (BSG) and Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland (AUGIS).

This document represents the first position statement produced by the British Society of Gastroenterology and Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland, setting out the minimum expected standards in diagnostic upper gastrointestinal endoscopy. The need for this statement has arisen from the recognition that while technical competence can be rapidly acquired, in practice the performance of a high-quality examination is variable, with an unacceptably high rate of failure to diagnose cancer at endoscopy. The importance of detecting early neoplasia has taken on greater significance in this era of minimally invasive, organ-preserving endoscopic therapy. In this position statement we describe 38 recommendations to improve diagnostic endoscopy quality. Our goal is to emphasise practices that encourage mucosal inspection and lesion recognition, with the aim of optimising the early diagnosis of upper gastrointestinal disease and improving patient outcomes.

Management of Barrett's high-grade dysplasia: initial results from a population-based national audit.

BACKGROUND AND AIMS: Previous studies reported significant variation in the management of patients with Barrett's esophagus. However, these are based on self-reported clinical practice. The aim of this study was to examine the management of high-grade dysplasia in Barrett's esophagus in England by using patient-level data and to compare practice with guidelines. METHODS: From April 2012 to March 2013, National Health Service (NHS) trusts in England prospectively collected data on patients newly diagnosed with high-grade dysplasia (HGD) of the esophagus as part of the National Oesophago-Gastric Cancer Audit. Data were collected on patient characteristics, diagnosis and endoscopic findings, treatment planning, and therapy. RESULTS: Between April 2012 and March 2013, NHS trusts reported 465 cases of HGD. Diagnosis was confirmed by a second pathologist in 79.4% of cases (270/340), and 86.0% (374/465) had their treatment planned at a multidisciplinary team meeting. A total of 290 patients (62.4%) were managed endoscopically (frequently with endoscopic resection or radiofrequency ablation), whereas 26 patients (5.6%) had esophagectomy. The proportion of patients managed by surveillance varied by age (P < .001), ranging from 19.5% in patients aged <65 years to 63.8% in patients aged ≥85 years. More patients received active treatment if their cases were discussed at a multidisciplinary meeting (73.5% vs 44.3%; P < .001) or managed at higher-volume trusts (87.8% vs 55.4%; P < .001). CONCLUSIONS: There was marked variation in the management of HGD across England, with a third of patients receiving no active treatment. Patients discussed at a specialist multidisciplinary meeting or managed in high-volume trusts were more likely to receive active treatment.

Chromoscopy versus conventional endoscopy for the detection of polyps in the colon and rectum.

BACKGROUND: Although conventional colonoscopy is the most accurate test available for the investigation of the colorectum for polyps, data exist that raise concerns about its sensitivity. Chromoscopy (spraying dye onto the surface of the colon to make polyps more visible) may be one way of enhancing the ability of colonoscopy to detect polyps, particularly diminutive flat lesions, which otherwise may be difficult to detect. OBJECTIVES: To determine whether the use of chromoscopy enhances the detection of polyps and neoplasia during endoscopic examination of the colon and rectum. SEARCH METHODS: We searched the following databases: Cochrane Colorectal Cancer Group Specialised Register (October 2015), Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library; Issue 10, 2015), MEDLINE (January 1950 to October 2015), EMBASE (January 1974 to October 2015), and ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform (both November 2015). We also handsearched abstracts from relevant meetings from 1980 to 2015. Search terms included 'randomised trials' containing combinations of the following: 'chromoscopy' 'colonoscopy' 'dye-spray' 'chromo-endoscopy' 'indigo-carmine' 'magnifying endoscopy'. SELECTION CRITERIA: We included all prospective randomised trials comparing chromoscopic with conventional endoscopic examination of the whole of the colon and rectum. We excluded studies of people with inflammatory bowel disease or polyposis syndromes and any studies that combined chromoscopy with additional interventions (cap assistance, water-perfused, etc.). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the methodological quality of potentially eligible trials, and two review authors independently extracted data from the included trials. Outcome measures included the detection of polyps (neoplastic and non-neoplastic), the detection of diminutive lesions, the number of participants with multiple neoplastic lesions, and the extubation time. MAIN RESULTS: We included seven trials (2727 participants) in this update. Five trials were of sufficiently similar design to allow for pooled results. Two trials differed substantially in design and were included in a subgroup analysis. All the trials had some methodological drawbacks. However, combining the results showed a significant difference in favour of chromoscopy for all detection outcomes. In particular, chromoscopy was likely to yield significantly more people with at least one neoplastic lesion (odds ratio (OR) 1.53, 95% confidence interval (CI) 1.31 to 1.79; 7 trials; 2727 participants), and at least one diminutive neoplastic lesion (OR 1.51, 95% CI 1.19 to 1.92; 4 trials; 1757 participants). Significantly more people with three or more neoplastic lesions were also detected, but only when studies that used high-definition colonoscopy in the control group were excluded (OR 4.63, 95% CI 1.99 to 10.80; 2 trials; 519 participants). None of the included studies reported any adverse events related to the use of the contrast dye. AUTHORS' CONCLUSIONS: There is strong evidence that chromoscopy enhances the detection of neoplasia in the colon and rectum. People with neoplastic polyps, particularly those with multiple polyps, are at increased risk of developing colorectal cancer. Such lesions, which presumably would be missed with conventional colonoscopy, could contribute to the interval cancer numbers on any surveillance programme.

Gastric Cancers Missed During Endoscopy in England.

BACKGROUND & AIMS: Single-center studies have estimated that 4.6% to 25.8% of gastric cancers are missed at endoscopy. We performed a population-based study to make a more precise estimate of factors associated with missed lesions in England. METHODS: We performed a retrospective population-based observational cohort study of 2727 patients diagnosed with gastric cancer from April 2011 through March 2012 in England, using linked records from 3 national data sets. The primary outcome was the proportion of patients who had undergone endoscopy in the 3 to 36 months before a diagnosis of gastric cancer. We determined this proportion for the entire cohort and for subgroups. RESULTS: Of the 2727 patients in the cohort, 8.3% (95% confidence interval, 7.2%-9.3%) underwent endoscopic evaluation in the 3 to 36 months before their diagnosis of gastric cancer. An endoscopy within 3 to 36 months of diagnosis was associated with a diagnosis of early stage cancer (stages 0 or 1, 11.5%; stage 2, 7.9%; stages 3 or 4, 6.9%; P = .01 for stage 0 or 1 vs stage 2 or greater), younger age at diagnosis (<55 y, 13.3% vs ≥55 y, 7.8%; P = .03), and female sex (10% of women vs 7.3% of men; P = .01). Gastric ulcers were detected in 15% of endoscopies performed at any time in the 3 years before cancer diagnosis, and in 64% of endoscopies performed 3 to 6 months before a diagnosis of gastric cancer. CONCLUSIONS: Based on a retrospective analysis of medical records in England, in 8.3% of patients with gastric cancer, their cancer was missed at endoscopy within the 3 previous years. A previous endoscopy detected benign gastric ulcers more frequently than any other lesion in patients who later were diagnosed with gastric cancer.

Position change during colonoscope withdrawal increases polyp and adenoma detection in the right but not in the left side of the colon: results of a randomized controlled trial.

BACKGROUND: It has been suggested that changing patient position during colonoscope withdrawal increases adenoma detection. The results of previous studies have been conflicting. OBJECTIVE: To evaluate whether routine position change during colonoscope withdrawal improves polyp detection. DESIGN: Randomized, 2-way, crossover study. SETTING: Teaching hospital. PATIENTS: A total of 130 patients attending for diagnostic colonoscopy. INTERVENTIONS: Patients undergoing colonoscopy had each colon segment examined twice: the right side of the colon (cecum to hepatic flexure) in the supine and left lateral position and the left side of the colon (splenic flexure and descending colon) in the supine and right lateral position. The transverse colon was examined twice in the supine position. MAIN OUTCOME MEASUREMENTS: The primary outcome measure was the polyp detection rate (≥1 polyp) per colon segment. Secondary outcome measures included the number and proportion of patients with ≥1 adenoma in each segment and adequacy of luminal distension (1 = total collapse and 5 = no collapse). RESULTS: Examination of the right side of the colon in the left lateral position significantly improved polyp detection (26.2% vs 17.7%; P = .01) and luminal distension (mean = 4.0 vs 3.5; P < .0001). Position change did not improve polyp detection in the left side of the colon (5.4% vs 4.6%; P = .99). There was no significant correlation between luminal distension and polyp detection in the right side of the colon (r = .03). LIMITATIONS: Single center and open study design. CONCLUSION: Examining the right side of the colon in the left lateral position increased polyp detection compared with examination in the supine position. Polyp detection in the left side of the colon was similar in the right lateral and supine positions. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01554098.).

A randomized comparison of cold snare polypectomy versus a suction pseudopolyp technique.

BACKGROUND: Cold snare techniques are widely used for removal of diminutive and small colorectal polyps. The influence of resection technique on the effectiveness of polypectomy is unknown. We therefore compared standard cold snare polypectomy with a newly described suction pseudopolyp technique, for completeness of excision and for complications. PATIENTS AND METHODS: In this single-center study, 112 patients were randomized to cold snare polypectomy or the suction pseudopolyp technique. Primary outcome was endoscopic completeness of excision. Consensus regarding the endoscopic assessment of completeness of excision was standardized and aided by chromoendoscopy. Secondary outcomes included: completeness of histological excision, polyp "fly away" and retrieval rates, early bleeding (48 hours), delayed bleeding (2 weeks), and perforation. RESULTS: 148 polyps were removed, with size range 3 - 7 mm, 60 % in the left colon, and 90 % being sessile. Regarding completeness of excision (with uncertain findings omitted): endoscopically, this was higher with the suction pseudopolyp technique compared with cold snare polypectomy but not statistically significantly so (73/74 [98.6 %] vs. 63/68 [92.6 %]; P = 0.08). A trend towards a higher complete histological excision rate with the suction pseudopolyp technique was also not statistically significant (45/59 [76.3 %] vs. 37/58 [63.8 %]; P = 0.14). Polyp retrieval rate was not significantly different (suction 68/76 [89.5 %] vs. cold snare 64/72 [88.9 %]; P = 0.91). No perforation or bleeding requiring hemostasis occurred in either group.  CONCLUSION: In this study both polypectomy techniques were found to be safe and highly effective, but further large multicenter trials are required.Clinical trial registration at www.clinicaltrials.gov: NCT02208401.

Magnetically steerable gastric capsule endoscopy is equivalent to flexible endoscopy in the detection of markers in an excised porcine stomach model: results of a randomized trial.

BACKGROUND AND STUDY AIMS: Capsule endoscopy is well tolerated but control of its movement is needed in order to visualize the whole gastric surface. Technological developments have produced an external magnet to allow manipulation of the capsule within the gastric cavity. The aim of this study was to compare magnetically steerable gastric capsule endoscopy (MSGCE) with flexible endoscopy for the detection of beads in a porcine stomach. MATERIALS AND METHODS: Beads were sewn onto the mucosal surface of 12 ex vivo porcine stomachs. Each model was examined by flexible endoscopy and MSGCE by two blinded investigators. MSGCE was performed according to a protocol using positional changes and magnetic steering. Outcome measures were number and location of beads identified, and duration of procedure. RESULTS: Flexible endoscopy identified 79 /90 beads (88 %), and MSGCE identified 80 /90 (89 %). The difference in sensitivities was 1.11 (95 % confidence interval 0.06 - 28.26). Thus, MSGCE was noninferior to flexible endoscopy. Mean examination times for flexible endoscopy and MSGCE were 3.34 minutes and 9.90 minutes, respectively. CONCLUSION: MSGCE was equivalent to conventional flexible endoscopy in the detection of beads in a porcine stomach model.

Polypectomy practices of sub-centimeter polyps in the English Bowel Cancer Screening Programme.

BACKGROUND: Most colonic polyps are small, and several polypectomy techniques are available. We aimed to describe the variation in polypectomy techniques employed for the removal of sub-centimeter polyps in relation to polyp characteristics, completeness of histological excision and safety. METHODS: Prospectively collected data relating to the removal of sub-centimeter polyps over a 3-year period (between January 2010 and December 2012) were retrieved from the English Bowel Cancer Screening Programme. RESULTS: A total of 147,174 sub-centimeter polyps were removed during 62,679 procedures. For pedunculated polyps, hot snare was most common in the left (median 92 %, IQR 83.3-97.0 %) and right colon (median 75 %, IQR 3-92 %). For non-pedunculated polyps, cold snare was most common in the right colon (median 24 %, IQR 9-47 %); whereas hot snare remained most common in the left colon (median 32 %, IQR 19-49 %). Surgeons were more likely than physicians to use diathermy-assisted techniques (65.6 vs. 56.5 %, p < 0.001). Twelve (0.03 %) bleeding episodes required transfusion with no polypectomy technique dominating and 16 (0.04 %) perforations with 81 % of polypectomies performed using diathermy-assisted techniques. There was substantial variation between screening centers for the completeness of histological excision. For non-pedunculated polyps, histologically confirmed complete excision was more after EMR (23.4 %) compared with other techniques (cold biopsy forceps 17.7 %, cold snare 15.1 %, hot biopsy forceps 19.1 %, hot snare 21.5 %). The use of cold techniques and EMR has increased over time, whereas the use of hot biopsy forceps and hot snare has decreased (p < 0.001). CONCLUSIONS: The removal of sub-centimeter polyps within the BCSP is safe despite wide variations in practice. The use of cold resection techniques and EMR has increased over time. The histological assessment for completeness of excision is limited and should be confirmed endoscopically at the time of polypectomy.

Cold snare polypectomy: does snare type influence outcomes?

BACKGROUND AND AIM: Cold snare techniques are widely used for the removal of small and diminutive polyps. The influence of snare type on the effectiveness of cold snare polypectomy is unknown. METHODS: Cold snare polypectomy of 3-7-mm polyps was undertaken using either a thin wire mini-snare (0.30 mm) or a thick wire mini-snare (0.47 mm). Primary outcome was endoscopic completeness of excision. Consensus regarding endoscopic assessment of completeness of excision was standardized and aided by chromoendoscopy. Secondary outcomes included: completeness of histological excision, polyp 'fly away', polyp retrieval rate, early or delayed bleeding and perforation. RESULTS: One hundred and fifty-seven polyps were removed ranging from 3 to 7 mm, 62% were situated in the left side of the colon and 89.4% were sessile. Endoscopic completeness of excision was significantly higher with the thin wire snare compared to the thick wire snare (90.2% vs 73.3%, P < 0.05). There was a numerical trend towards a higher complete histological excision rate with the thin wire snare, but this did not reach statistical significance (73.3% vs 65.2%, P = 0.4). There was a fair level of agreement (kappa = 0.36) between endoscopic and histological completeness of excision. Polyp 'fly away' occurred less often with the thin wire snare (14.6% vs 35.3%, P = 0.002), but there was no significant difference in polyp retrieval rate (84.3% vs 83.8%, P = 0.94). There were no complications with either snare. CONCLUSION: Snare type appears to be an important determinant of completeness of excision when removing small polyps by the cold snare technique.

A population-based, retrospective, cohort study of esophageal cancer missed at endoscopy.

BACKGROUND AND STUDY AIMS: Several studies have suggested that a significant minority of esophageal cancers are missed at endoscopy The aim of this study was to estimate the proportion of esophageal cancers missed at endoscopy on a national level, and to investigate the relationship between miss rates and patient and tumor characteristics. PATIENTS AND METHODS: This retrospective, population-based, cohort study identified patients diagnosed with esophageal cancer between April 2011 and March 2012 in England, using two linked databases (National Oesophago-Gastric Cancer Audit and Hospital Episode Statistics). The main outcome was the rate of previous endoscopy within 3 - 36 months of cancer diagnosis. This was calculated for the overall cohort and by patient characteristics, including tumor site and disease stage. RESULTS: A total of 6943 new cases of esophageal cancer were identified, of which 7.8 % (95 % confidence interval 7.1 - 8.4) had undergone endoscopy in the 3 - 36 months preceding diagnosis. Of patients with stage 0/1 cancers, 34.0 % had undergone endoscopy in the 3 - 36 months before diagnosis compared with 10.0 % of stage 2 cancers and 4.5 % of stage 3/4 cancers. Of patients with stage 0/1 cancers, 22.1 % were diagnosed after ≥ 3 endoscopies in the previous 3 years. Patients diagnosed with an upper esophageal lesion were more likely to have had an endoscopy in the previous 3 - 12 months (P = 0.040). The most common diagnosis at previous endoscopy was an esophageal ulcer (48.2 % of investigations). CONCLUSION: Esophageal cancer may be missed at endoscopy in up to 7.8 % of patients who are subsequently diagnosed with cancer. Endoscopists should make a detailed examination of the whole esophageal mucosa to avoid missing subtle early cancers and lesions in the proximal esophagus. Patients with an esophageal cancer may be misdiagnosed as having a benign esophageal ulcer.

Can an educational video improve the adequacy of bowel preparation for patients undergoing their first colonoscopy? Results of the EBOPS RCT.

Background and study aims The aim of this study was to assess the effect of an educational video on the quality of bowel preparation of patients from a UK population attending for their first colonoscopy. Patients and methods A prospective, endoscopist-blinded trial with 1:1 allocation was performed. Patients referred for their first colonoscopy were recruited between February 2019 and December 2019. All participants were prescribed Moviprep and received the trial site's standard written bowel preparation instructions, with the intervention group also receiving a bespoke educational video. Adequacy of bowel preparation (defined as a Boston Bowel Preparation Scale of ≥2 in each segment of the bowel) and polyp detection rates (PDRs) were compared. Fisher's chi squared test was utilized with P <0.05 as the threshold for significance. Results A total of 509 participants completed the trial from six centers; 251 were randomized to the intervention group. The mean age was 57 years and 52.3% were female. The primary endpoint was met with an adequacy rate of 216 of 251 (86.1%) in the intervention group, compared with 205 of 259 (79.1%) in the control group ( P <0.05, odds ratio [OR] 1.626, 95% CI 1.017-2.614). The PDR was significantly higher in the intervention group (39% vs 30%, OR 1.51, 95% CI 1.04-2.19, P <0.05). Conclusions An educational video leads to improved bowel preparation for patients attending for their first colonoscopy, and is also associated with greater detection of polyps. Widespread adoption of an educational video incurs minimal investment, but would reduce the number of inadequate procedures, missed pathology, and the cost that both these incur.

JAG consensus statements for training and certification in oesophagogastroduodenoscopy.

Introduction: Training and quality assurance in oesophagogastroduodenoscopy (OGD) is important to ensure competent practice. A national evidence-based review was undertaken to update and develop standards and recommendations for OGD training and certification. Methods: Under the oversight of the Joint Advisory Group (JAG), a modified Delphi process was conducted with stakeholder representation from British Society of Gastroenterology, Association of Upper Gastrointestinal Surgeons, trainees and trainers. Recommendations on OGD training and certification were formulated following literature review and appraised using Grading of Recommendations Assessment, Development and Evaluation. These were subjected to electronic voting to achieve consensus. Accepted statements were incorporated into the updated certification pathway. Results: In total, 32 recommendation statements were generated for the following domains: definition of competence (4 statements), acquisition of competence (12 statements), assessment of competence (10 statements) and post-certification support (6 statements). The consensus process led to following certification criteria: (1) performing ≥250 hands-on procedures; (2) attending a JAG-accredited basic skills course; (3) attainment of relevant minimal performance standards defined by British Society of Gastroenterology/Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland, (4) achieving physically unassisted D2 intubation and J-manoeuvre in ≥95% of recent procedures, (5) satisfactory performance in formative and summative direct observation of procedural skills assessments. Conclusion: The JAG standards for diagnostic OGD have been updated following evidence-based consensus. These standards are intended to support training, improve competency assessment to uphold standards of practice and provide support to the newly-independent practitioner.

Development and validation of a novel method for assessing competency in polypectomy: direct observation of polypectomy skills.

BACKGROUND: Despite its ubiquitous use over the past 4 decades, there is no structured, formal method with which to assess polypectomy. OBJECTIVE: To develop and validate a new method with which to assess competency in polypectomy. DESIGN: Polypectomy underwent task deconstruction, and a structured checklist and global assessment scale were developed (direct observation of polypectomy skills [DOPyS]). Sixty bowel cancer screening polypectomy videos were randomly chosen for analysis and were scored independently by 7 expert assessors by using DOPyS. Each parameter and the global rating were scored from 1 to 4 (scores ≥3 = competency). The scores were analyzed by using generalizability theory (G theory). SETTING: Multicenter. RESULTS: Fifty-nine of the 60 videos were assessable and scored. The majority of the assessors agreed across the pass/fail divide for the global assessment scale in 58 of 59 (98%) polyps. For G-theory analysis, 47 of the 60 videos were analyzed. G-theory analysis suggested that DOPyS is a reliable assessment tool, provided that it is used by 2 assessors to score 5 polypectomy videos all performed by 1 endoscopist. DOPyS scores obtained in this format would reflect the endoscopist's competence. LIMITATIONS: Small sample and polyp size. CONCLUSIONS: This study is the first attempt to develop and validate a tool designed specifically for the assessment of technical skills in performing polypectomy. G-theory analysis suggests that DOPyS could reliably reflect an endoscopist's competence in performing polypectomy provided a requisite number of assessors and cases were used.

Keratin 8 expression in colon cancer associates with low faecal butyrate levels.

BACKGROUND: Butyrate has been implicated in the mechanistic basis of the prevention of colorectal cancer by dietary fibre. Numerous in vitro studies have shown that butyrate regulates cell cycle and cell death. More recently we have shown that butyrate also regulates the integrity of the intermediate filament (IF) cytoskeleton in vitro. These and other data suggest a link between the role of diet and the implication of a central role for the keratin 8 (K8) as guardian of the colorectal epithelium. METHODS: In this cross-sectional study possible links between butyrate levels, field effects and keratin expression in cancer were addressed directly by analysing how levels of expression of the IF protein K8 in tumours, in adjacent fields and at a distant landmark site may be affected by the level of butyrate in the colon microenvironment. An immunohistochemical scoring protocol for K8 was developed and applied to samples, findings were further tested by immunoblotting. RESULTS: Levels of K8 in colorectal tumours are lower in subjects with higher levels of faecal butyrate. Immunoblotting supported this finding.Although there were no significant relationships with butyrate on the non-tumour tissues, there was a consistent trend in all measures of extent or intensity of staining towards a reduction in expression with elevated butyrate, consistent with the inverse association in tumours. CONCLUSIONS: The data suggest that butyrate may associate with down-regulation of the expression of K8 in the cancerized colon. If further validated these findings may suggest the chemopreventive value of butyrate is limited to early stage carcinogenesis as low K8 expression is associated with a poor prognosis.

Riboflavin depletion impairs cell proliferation in adult human duodenum: identification of potential effectors.

BACKGROUND AND AIMS: Riboflavin (vitamin B2) is an essential dietary component with a known function in oxidative metabolism. Our previous data using a rat model of riboflavin deficiency suggested that riboflavin also functions as a luminal signaling molecule regulating crypt development and cell turnover. Riboflavin deficiency is prevalent in both high- and low-income countries across the globe. This study aims to establish whether riboflavin deficiency has consequences for gastrointestinal (GI) morphology in adults and what the effects and effectors of any such alteration may be. METHODS: Duodenal biopsies and blood samples were collected from a cross-section of gastroscopy patients. Crypt morphology and cell division were studied by immunohistochemistry, and biochemical riboflavin status was determined. Additionally a cell culture model of riboflavin deficiency was developed and analyzed using a combination of flow cytometry, and microarray and clonogenic assays. RESULT: Duodenal crypts from subjects in the lowest quartile of riboflavin status were significantly shorter (P=0.023), less cellular (P=0.007), and had fewer cell divisions (P=0.034) than the crypts of subjects in the top quartile of riboflavin status. Following riboflavin depletion of colon cells in culture, cell cycle slowed. Microscopy revealed impaired mitosis and accumulation of aneuploid cells. Alterations in gene expression profiles reflected this alteration, with several mitosis-related genes altered, including AspM, cyclin B1, and Birc5 downregulated and Kif23 upregulated. Riboflavin depletion in vitro caused irreversible loss of proliferative potential of cells. CONCLUSIONS: Riboflavin depletion in adult humans impairs proliferation and proliferative potential of intestinal cells, which may have implications for gastrointestinal function.

Is it time we split bowel preparation for all colonoscopies? Outcomes from a national survey of bowel preparation practice in the UK.

INTRODUCTION: Adequate bowel preparation is a prerequisite for effective colonoscopy. Split bowel preparation results in optimal cleansing. This study assessed the bowel preparation regimes advised by endoscopy units across the UK, and correlated the differences with outcomes. METHODS: Trusts in the UK were surveyed, with data requested between January 2018 and January 2019, including: the type and timing of preparation, pre-endoscopy diet, adequacy rates and polyp detection. Trusts were grouped according to the timing of bowel preparation. χ2 test was used to assess for differences in bowel preparation adequacy. RESULTS: Moviprep was the first line bowel preparation in 79% of trusts. Only 7% of trusts advised splitting bowel preparation for all procedures, however, 91% used split bowel preparation for afternoon procedures. Trusts that split preparation for all procedures had an inadequacy rate of 6.7%, compared with 8.5% (p<0.001) for those that split preparation for PM procedures alone and 9.5% (p<0.001) for those that provided day before preparation for all procedures. Morning procedures with day-before preparation had a higher rate of inadequate cleansing than afternoon procedures that received split preparation (7.7% vs 6.5 %, p<0.001). The polyp detection rate for procedures with adequate preparation was 37.1%, compared with 26.4% for those that were inadequate. CONCLUSION: Most trusts in the UK do not provide instructions optimising the timing of bowel preparation prior to colonoscopy. This correlated with an increased rate of inadequate cleansing. Splitting bowel preparation is likely to reduce the impacts of poor cleansing: missed lesions, repeat colonoscopies and significant costs.

A study protocol to investigate the relationship between dietary fibre intake and fermentation, colon cell turnover, global protein acetylation and early carcinogenesis: the FACT study.

BACKGROUND: A number of studies, notably EPIC, have shown a descrease in colorectal cancer risk associated with increased fibre consumption. Whilst the underlying mechanisms are likely to be multifactorial, production of the short-chain fatty-acid butyrate fro butyratye is frequently cited as a major potential contributor to the effect. Butyrate inhibits histone deacetylases, which work on a wide range of proteins over and above histones. We therefore hypothesized that alterations in the acetylated proteome may be associated with a cancer risk phenotype in the colorectal mucosa, and that such alterations are candidate biomarkers for effectiveness of fibre interventions in cancer prevention. METHODS AN DESIGN: There are two principal arms to this study: (i) a cross-sectional study (FACT OBS) of 90 subjects recruited from gastroenterology clinics and; (ii) an intervention trial in 40 subjects with an 8 week high fibre intervention. In both studies the principal goal is to investigate a link between fibre intake, SCFA production and global protein acetylation. The primary measure is level of faecal butyrate, which it is hoped will be elevated by moving subjects to a high fibre diet. Fibre intakes will be estimated in the cross-sectional group using the EPIC Food Frequency Questionnaire. Subsidiary measures of the effect of butyrate on colon mucosal function and pre-cancerous phenotype will include measures of apoptosis, apoptotic regulators cell cycle and cell division. DISCUSSION: This study will provide a new level of mechanistic data on alterations in the functional proteome in response to the colon microenvironment which may underwrite the observed cancer preventive effect of fibre. The study may yield novel candidate biomarkers of fibre fermentation and colon mucosal function. TRIAL REGISTRATION NUMBER: ISRCTN90852168.