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.

Studies of salivary pepsin in patients with gastro-oesophageal reflux disease.

BACKGROUND: Gastro-oesophageal reflux disease (GERD) is difficult to diagnose without invasive testing. Peptest (RD Biomed, Hull, UK) is a recently marketed diagnostic tool which aims to quantify salivary pepsin as a marker of reflux, providing a rapid alternative to invasive procedures. AIM: To evaluate optimal timing for sampling, and to evaluate the accuracy of Peptest against an independent measure. METHODS: Thirty diagnosed GERD patients (12 female, mean age 49 [range 20-72]) and 20 asymptomatic subjects (14 female, mean age 56 [range 21-56]) were subject to diurnal saliva sampling, with additional samples for 60 minutes following self-reported reflux symptoms and triggering of a proximal reflux alarm. Saliva samples were split and were analysed by both Peptest and ELISA with operators for each blinded to sample identity. RESULTS: Salivary pepsin was detectable in most patients and most volunteers. Peptest scores were significantly lower for patients than controls (P < 0.005). ELISA scores showed no difference between patients and controls. There was no effect of diurnal sampling time (P = 0.75) or time after symptoms (P = 0.76) on Peptest readout. There was no correlation between Peptest and Pepsin ELISA (P = 0.55); Bland-Altman analysis suggested no agreement between the tests (P = 0.414). Receiver-operator curve suggests that neither Peptest (P = 0.3328) nor pepsin (P = 0.4476) is useful for predicting GERD. CONCLUSION: Salivary pepsin is not a reliable tool for the diagnosis of GERD.

Coding of Barrett's oesophagus with high-grade dysplasia in national administrative databases: a population-based cohort study.

OBJECTIVES: The International Classification of Diseases 10th Revision (ICD-10) system used in the English hospital administrative database (Hospital Episode Statistics (HES)) does not contain a specific code for oesophageal high-grade dysplasia (HGD). The aim of this paper was to examine how patients with HGD were coded in HES and whether it was done consistently. SETTING: National population-based cohort study of patients with newly diagnosed with HGD in England. The study used data collected prospectively as part of the National Oesophago-Gastric Cancer Audit (NOGCA). These records were linked to HES to investigate the pattern of ICD-10 codes recorded for these patients at the time of diagnosis. PARTICIPANTS: All patients with a new diagnosis of HGD between 1 April 2013 and 31 March 2014 in England, who had data submitted to the NOGCA. OUTCOMES MEASURED: The main outcome assessed was the pattern of primary and secondary ICD-10 diagnostic codes recorded in the HES records at endoscopy at the time of diagnosis of HGD. RESULTS: Among 452 patients with a new diagnosis of HGD between 1 April 2013 and 31 March 2014, Barrett's oesophagus was the only condition coded in 200 (44.2%) HES records. Records for 59 patients (13.1%) contained no oesophageal conditions. The remaining 193 patients had various diagnostic codes recorded, 93 included a diagnosis of Barrett's oesophagus and 57 included a diagnosis of oesophageal/gastric cardia cancer. CONCLUSIONS: HES is not suitable to support national studies looking at the management of HGD. This is one reason for the UK to adopt an extended ICD system (akin to ICD-10-CM).

Reduced keratin expression in colorectal neoplasia and associated fields is reversible by diet and resection.

BACKGROUND: Patients with adenomatous colonic polyps are at increased risk of developing further polyps suggesting field-wide alterations in cancer predisposition. The current study aimed to identify molecular alterations in the normal mucosa in the proximity of adenomatous polyps and to assess the modulating effect of butyrate, a chemopreventive compound produced by fermentation of dietary residues. METHODS: A cross-sectional study was undertaken in patients with adenomatous polyps: biopsy samples were taken from the adenoma, and from macroscopically normal mucosa on the contralateral wall to the adenoma and from the mid-sigmoid colon. In normal subjects biopsies were taken from the mid-sigmoid colon. Biopsies were frozen for proteomic analysis or formalin-fixed for immunohistochemistry. Proteomic analysis was undertaken using iTRAQ workflows followed by bioinformatics analyses. A second dietary fibre intervention study arm used the same endpoints and sampling strategy at the beginning and end of a high-fibre intervention. RESULTS: Key findings were that keratins 8, 18 and 19 were reduced in expression level with progressive proximity to the lesion. Lesional tissue exhibited multiple K8 immunoreactive bands and overall reduced levels of keratin. Biopsies from normal subjects with low faecal butyrate also showed depressed keratin expression. Resection of the lesion and elevation of dietary fibre intake both appeared to restore keratin expression level. CONCLUSION: Changes in keratin expression associate with progression towards neoplasia, but remain modifiable risk factors. Dietary strategies may improve secondary chemoprevention. TRIAL REGISTRATION NUMBER: ISRCTN90852168.

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.

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.).

Sedation practice and comfort during colonoscopy: lessons learnt from a national screening programme.

AIM: Medication may be used to manage discomfort during colonoscopy but practice varies. The relationship between medication use and comfort during colonoscopy was examined in the English Bowel Cancer Screening Programme. METHODS: Data related to patient comfort and medication use from all 113,316 examinations performed within the English Bowel Cancer Screening Programme between 1 January 2010 and 31 December 2012 were analysed. Comfort was rated on the five-point Modified Gloucester Comfort Scale: 1, no discomfort; 5, severe discomfort. Scores of 4 and 5 were considered to indicate significant discomfort. Correlations between the proportion of examinations associated with significant discomfort and the amounts of medication used by colonoscopists were assessed using Spearman's ρ. Logistic regression modelling examined the independent predictors of significant discomfort. RESULTS: Patients had a mean age of 65.7 years, and 58% were male. Examinations were performed by 290 endoscopists. In 91% of examinations, there was no significant discomfort reported during examination; however, there was considerable variation between individual colonoscopists (range 76.1-99.2%).Intravenous sedation and opiate analgesia were used during most examinations, but there was wide variation between colonoscopists, with a median (range) usage of 95.1% (4.1-100%) and 97.3% (5.6-100%), respectively. There was no association between the amount of sedation and analgesia used and significant discomfort (ρ<0.2). On multivariate analysis, significant discomfort was found to be more common among female individuals [odds ratio (OR)=2.0], on incomplete examinations (OR=6.7), and among patients with diverticulosis (OR=1.4). CONCLUSION: There was wide variation in medication practice among English screening colonoscopists, but this was unrelated to the occurrence of significant discomfort.

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.

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.

A randomized controlled trial comparing continuous and as-required nitrous oxide use during screening colonoscopy.

BACKGROUND AND STUDY AIMS: Entonox is a 50 : 50 combination of nitrous oxide and oxygen, which may be used to manage pain during colonoscopy. The optimal mode of Entonox administration is unknown. The aim of this study was therefore to compare continuous and as-required Entonox use. PATIENTS AND METHODS: Patients attending for screening colonoscopy at a single centre were randomized to continuous or as-required Entonox use. The primary outcome measure was the patient's overall pain rating at the time of discharge (verbally administered numerical ratings scale, 0=no pain and 10=extreme pain). Secondary outcome measures included the patients' experience of pain during the colonoscopy (rated every 2 min), side effects and the need for rescue intravenous medications. RESULTS: A total of 108 patients were randomized, and 100 completed the study (46 continuous, 54 as required). The overall pain scores at discharge did not differ between those who used Entonox continuously and as required (mean=2.4 vs. 3.2, P=0.08). There were also no differences in the experience of pain during colonoscopy (mean=1.8 vs. 2.2, P=0.28; peak=4.2 vs. 4.8, P=0.26; and area under curve=23 vs. 30, P=0.24). Patients with high anxiety had greater overall pain scores (mean=3.7 vs. 2.4, P=0.03). Light headedness occurred more often with continuous Entonox use (48 vs. 21%, P=0.009). CONCLUSION: Among patients attending for screening colonoscopy, comfort ratings were similar in those using Entonox continuously and as required, but light headedness was more common with continuous use (NCT identifier: 01865721).

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.

Nitrous oxide use during colonoscopy: a national survey of English screening colonoscopists.

INTRODUCTION: Nitrous oxide can improve patient experience during colonoscopy, and its rapid elimination minimises after effects and inconvenience. Despite its advantages, nitrous oxide is used infrequently in the UK. We sought to understand the reasons for its low use. METHODS: Colonoscopists within the English Bowel Cancer Screening Programme (BCSP) were invited to participate in a web-based survey assessing the availability, current practices and perceptions towards nitrous oxide. Respondents were able to select predefined answers or offer written responses. Free text responses were assessed using thematic analysis. RESULTS: The survey was completed by 68% of the English BCSP colonoscopists. Nitrous oxide was available to 73% of respondents but with considerable regional variation. Most colonoscopists rated the properties of nitrous oxide favourably and would use it if they had a colonoscopy themselves. Despite this, nearly half used it in less than 20% of examinations. 80% instruct patients to use nitrous oxide as required, and differences in how it was used in combination with intravenous sedation and analgesia were reported. Written responses suggest nitrous oxide is often used in the patients who are expected to have the least discomfort. CONCLUSIONS: Most colonoscopists perceive that nitrous oxide is effective and reduces inconvenience and would use it themselves if they required a colonoscopy. Studies to improve patient selection and optimise the use of nitrous oxide would be of value.

Impact of route to diagnosis on treatment intent and 1-year survival in patients diagnosed with oesophagogastric cancer in England: a prospective cohort study.

OBJECTIVE: To investigate the relationship between the route to diagnosis, patient characteristics, treatment intent and 1 -year survival among patients with oesophagogastric (O-G) cancer. SETTING: Cohort study in 142 English NHS trusts and 30 cancer networks. PARTICIPANTS: Patients diagnosed with O-G cancer between October 2007 and June 2009. DESIGN: Prospective cohort study. Route to diagnosis defined as general practitioner (GP) referral-urgent (suspected cancer) or non-urgent, hospital consultant referral, or after an emergency admission. Logistic regression was used to estimate associations and adjust for differences in casemix. MAIN OUTCOME MEASURES: Proportion of patients diagnosed by route of diagnosis; proportion of patients selected for curative treatment; 1-year survival. RESULTS: Among 14 102 cancer patients, 66.3% were diagnosed after a GP referral, 16.4% after an emergency admission and 17.4% after a hospital consultant referral. Of the 9351 GP referrals, 68.8% were urgent. Compared to urgent GP referrals, a markedly lower proportion of patients diagnosed after emergency admission had a curative treatment plan (36% vs 16%; adjusted OR=0.62, 95% CI 0.52 to 0.74) and a lower proportion survived 1 year (43% vs 27%; OR 0.78; 95% CI 0.68 to 0.89). Urgency of GP referral did not affect treatment intent or survival. Routes to diagnosis varied across cancer networks, with the adjusted proportion of patients diagnosed after emergency admission ranging from 8.7 to 32.3%. CONCLUSIONS: Outcomes for cancer patients are worse if diagnosed after emergency admission. Primary care and hospital services should work together to reduce rates of diagnosis after emergency admission and the variation across cancer networks.

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.

Re-organisation of oesophago-gastric cancer care in England: progress and remaining challenges.

BACKGROUND: Oesophago-gastric cancer services in England have been extensively reorganised since 2001 to deliver a centralised, specialist-led service. Our aim was to assess how well the National Health Service (NHS) in England met organisational standards for oesophago-gastric cancer care. METHODS: Questionnaires that asked about the provision of staging investigations, curative and palliative treatments and key personnel were sent in September 2007 to the lead clinician for oesophago-gastric cancer at all 30 cancer networks and 156 NHS acute trusts in England. RESULTS: Responses were received from all networks and 81% of NHS trusts. All networks provided essential staging investigations and a range of endoscopic palliative therapies. Only 16 of the 30 cancer networks discussed all patients at the specialist multi-disciplinary team meeting and 11 networks had not fully centralised curative surgery. There was also variation between NHS trusts in the integration of the palliative care team, the availability of nurse specialists and the use of dietitians to provide nutritional support. CONCLUSION: There has been considerable progress in reforming oesophago-gastric cancer services but the process of reorganisation is still incomplete and regional differences in service provision exist that may lead to variation in patient outcomes.

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.