British Society of Gastroenterology position statement on serrated polyps in the colon and rectum

Serrated polyps have been recognised in the last decade as important premalignant lesions accounting for between 15% and 30% of colorectal cancers. There is therefore a clinical need for guidance on how to manage these lesions; however, the evidence base is limited. A working group was commission by the British Society of Gastroenterology (BSG) Endoscopy section to review the available evidence and develop a position statement to provide clinical guidance until the evidence becomes available to support a formal guideline. The scope of the position statement was wide-ranging and included: evidence that serrated lesions have premalignant potential; detection and resection of serrated lesions; surveillance strategies after detection of serrated lesions; special situations-serrated polyposis syndrome (including surgery) and serrated lesions in colitis; education, audit and benchmarks and research questions. Statements on these issues were proposed where the evidence was deemed sufficient, and re-evaluated modified via a Delphi process until >80% agreement was reached. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tool was used to assess the strength of evidence and strength of recommendation for finalised statements. Key recommendation: we suggest that until further evidence on the efficacy or otherwise of surveillance are published, patients with sessile serrated lesions (SSLs) that appear associated with a higher risk of future neoplasia or colorectal cancer (SSLs ≥10 mm or serrated lesions harbouring dysplasia including traditional serrated adenomas) should be offered a one-off colonoscopic surveillance examination at 3 years (weak recommendation, low quality evidence, 90% agreement).

European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition--Colonoscopic surveillance following adenoma removal.

Multidisciplinary, evidence-based guidelines for quality assurance in colorectal cancer screening and diagnosis have been developed by experts in a project coordinated by the International Agency for Research on Cancer. The full guideline document covers the entire process of population-based screening. It consists of 10 chapters and over 250 recommendations, graded according to the strength of the recommendation and the supporting evidence. The 450-page guidelines and the extensive evidence base have been published by the European Commission. The chapter on colonoscopic surveillance following adenoma removal includes 24 graded recommendations. The content of the chapter is presented here to promote international discussion and collaboration by making the principles and standards recommended in the new EU Guidelines known to a wider professional and scientific community. Following these recommendations has the potential to enhance the control of colorectal cancer through improvement in the quality and effectiveness of surveillance and other elements in the screening process, including multi-disciplinary diagnosis and management of the disease.

European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition--Quality assurance in endoscopy in colorectal cancer screening and diagnosis.

Multidisciplinary, evidence-based guidelines for quality assurance in colorectal cancer screening and diagnosis have been developed by experts in a project coordinated by the International Agency for Research on Cancer. The full guideline document covers the entire process of population-based screening. It consists of 10 chapters and over 250 recommendations, graded according to the strength of the recommendation and the supporting evidence. The 450-page guidelines and the extensive evidence base have been published by the European Commission. The chapter on quality assurance in endoscopy includes 50 graded recommendations. The content of the chapter is presented here to promote international discussion and collaboration by making the principles and standards recommended in the new EU Guidelines known to a wider professional and scientific community. Following these recommendations has the potential to enhance the control of colorectal cancer through improvement in the quality and effectiveness of endoscopy and other elements in the screening process, including multidisciplinary diagnosis and management of the disease.

Perceived barriers to flexible sigmoidoscopy screening for colorectal cancer among UK ethnic minority groups: a qualitative study.

OBJECTIVES: Evidence from existing UK screening programmes indicates disparities in uptake rates between UK ethnic minorities and the white majority population. The aim of this study was to explore barriers to the uptake of flexible sigmoidoscopy (FS) screening among UK ethnic minority populations. Specifically, beliefs about bowel cancer, perceived barriers to the test and ideas about ways to increase uptake were investigated. METHODS: Nine focus groups were conducted with a total of 53 participants from African-Caribbean, Gujarati Indian, Pakistani and white British communities. The topic guide was based on the Health Belief Model. Discussions were subject to framework analysis. RESULTS: Most participants expressed limited awareness of bowel cancer and cited this as a barrier to screening attendance. Anxiety regarding the invasiveness of the test, the bowel preparation and fear of a cancer diagnosis were common barriers across all ethnic groups. Language difficulties, failure to meet religious sensitivities and the expression of culturally influenced health beliefs were all discussed as specific barriers to uptake. Ethnically tailored health promotion and general practitioner involvement were recommended as ways of overcoming such barriers. CONCLUSIONS: The study was the first attempt to qualitatively explore barriers to FS bowel cancer screening in UK ethnic minorities. Most barriers were shared by all ethnic groups but health educators should supplement approaches designed for the majority to incorporate the specific needs of individual minority groups to ensure equitable access.

Effective screening for bowel cancer: a United kingdom perspective.

Bowel cancer is a major cause of morbidity and death and is a high cost to health care systems. Screening currently offers the best chance of improving outcomes from bowel cancer. When introducing screening, the problems encountered in other cancers need to be avoided to maximize benefits and minimize harms.

The effect of cigarette smoking use and cessation on serum insulin-like growth factors.

The patterns of risk association between circulating levels of insulin-like growth factor (IGF)-I, and its main binding protein, IGFBP-3, differ between smoking and nonsmoking-related cancers. To investigate this observation further, we measured serum IGF-I, IGF-II and IGF-binding protein-3 concentrations in 232 men and 210 women (aged 55-64 years), and related peptide levels to smoking characteristics. Current smoking was associated with significant reductions in mean IGFBP-3 levels in men assessed by the number of cigarettes smoked daily (P(trend)=0.007) and pack-years smoked (P(trend)=0.03). Mean IGF-I levels decreased with increasing cigarette use in men (P(trend)=0.11). There were no patterns of association between smoking and IGF peptides in women. For male former vs never smokers, there were no differences in mean IGF-I and IGFBP-3 concentrations, suggesting that smoking cessation is associated with normalisation of peptide concentrations.

Predictive value of rectal bleeding for distal colonic neoplastic lesions in a screened population.

The aim of this study was to determine the diagnostic value of rectal bleeding for distal colorectal cancer (CRC), or large (> or =10 mm) adenomas among an average-risk population. A cross-sectional survey was conducted among individuals aged 55-64 years, who attended sigmoidoscopy (FS) screening in the context of a multicentre randomised trial of FS screening for CRC. Sensitivity, specificity and positive predictive value (PPV) of rectal bleeding for large distal adenomas or CRC were calculated. Rectal bleeding was reported by 8.8% of 8507 patients examined (15% of those with large adenomas and 29% of those with CRC). The risk of CRC was increased when bleeding was associated with an altered bowel habit: odds ratio (OR)=10.42; 95% Confidence Interval (CI): 4.08-26.59; the corresponding OR for isolated bleeding was 5.29 (95% CI: 2.28-12.30). Rectal bleeding carries an increased risk of distal neoplastic lesions. However, most lesions are detected among asymptomatic subjects. This finding suggests that screening represents the optimal strategy to detect CRC or large adenomas in the distal colon in the targeted age range.

An ancestral Ashkenazi haplotype at the HMPS/CRAC1 locus on 15q13-q14 is associated with hereditary mixed polyposis syndrome.

The putative locus for hereditary mixed polyposis syndrome (HMPS) in a large family of Ashkenazi descent (SM96) was previously reported to map to chromosome sub-bands 6q16-q21. However, new clinical data, together with molecular data from additional family members, have shown 6q linkage to be incorrect. A high-density genomewide screen for the HMPS gene was therefore performed on SM96, using stringent criteria for assignment of affection status to minimize phenocopy rates. Significant evidence of linkage was found only on a region on chromosome 15q13-q14. Since this region encompassed CRAC1, a locus involved in inherited susceptibility to colorectal adenomas and carcinomas in another Ashkenazi family (SM1311), we determined whether HMPS and CRAC1 might be the same. We found that affected individuals from both families shared a haplotype between D15S1031 and D15S118; the haplotype was rare in the general Ashkenazi population. A third informative family, SM2952, showed linkage of disease to HMPS/CRAC1 and shared the putative ancestral haplotype, as did a further two families, SMU and RF. Although there are probably multiple causes of the multiple colorectal adenoma and cancer phenotype in Ashkenazim, an important one is the HMPS/CRAC1 locus on 15q13-q14.

Single flexible sigmoidoscopy screening to prevent colorectal cancer: baseline findings of a UK multicentre randomised trial.

BACKGROUND: This randomised controlled trial is examining the hypothesis that a single flexible sigmoidoscopy screening offered at around age 60 years can lower the incidence and mortality of colorectal cancer. We report here on acceptability, safety, feasibility, and yield. METHODS: Men and women aged 55-64 years, in 14 UK centres, who responded to a mailed questionnaire that they would attend for flexible sigmoidoscopy screening if invited, were randomly assigned screening or control (ratio one to two). The control group was not contacted. Small polyps were removed during screening, and colonoscopy was undertaken if high-risk polyps (three or more adenomas, size 1 cm or greater, villous, severely dysplastic, or malignant) were found. FINDINGS: Of 354,262 people asked about their interest in having flexible sigmoidoscopy screening, 194,726 (55%) responded positively, and 170,432 eligible individuals were randomised. Attendance among those assigned screening was 71% (40,674 of 57,254). 2131 (5%) were classified as high-risk and referred for colonoscopy; 38,525 with no polyps or only low-risk polyps detected were discharged. Distal adenomas were detected in 4931 (12.1%) and distal cancer in 131 (0.3%). Proximal adenomas were detected in 386 (18.8% of those undergoing colonoscopy) and proximal cancer in nine cases (0.4%). 62% of cancers were Dukes' stage A or locally excised. There was one perforation after flexible sigmoidoscopy and four after colonoscopy. An average of 48 people were screened, and two or three colonoscopy referrals generated, per centre each week. Interpretation Our flexible sigmoidoscopy screening regimen is acceptable, feasible, and safe. The prevalence of neoplasia is high, and colonoscopy referral rates of 5% are acceptable.

Rectal retroflexion: an essential part of lower gastrointestinal endoscopic examination.

PURPOSE: Retroflexion of the endoscope during rectal examination may increase diagnostic yield but is not routinely performed because of concerns about safety and a lack of appreciation of its importance. The purpose of this study was to examine the yield, safety, and tolerance of endoscopic rectal retroflexion. METHODS: Prospective cohorts of subjects undergoing unsedated screening flexible sigmoidoscopy were examined with and without routine retroflexion. Pain scores were recorded. RESULTS: A total of 526 subjects (mean age 60 (range, 55-66) years) underwent flexible sigmoidoscopy in the first period when the endoscope was not routinely retroflexed. Of these, 480 (mean age 60 (range, 55-66) years) were subsequently examined with routine retroflexion. Retroflexion was impossible in 17 subjects (3.5 percent) because of discomfort. In the second group, 12 subjects (2.5 percent) had polyps in the lower rectum seen only on retroflexion. Of these, eight had metaplastic and four had adenomatous polyps (3 tubular <5 mm, 1 tubulovillous 15 mm). There was no difference in mean pain scores between the groups (no retroflexion = 2.13, retroflexion = 2.18). CONCLUSION: With an adenoma pick-up rate of 8 to 12 percent for screening flexible sigmoidoscopy, retroflexion increases adenoma detection by approximately 1 percent without adverse effects and should be an integral part of flexible sigmoidoscopy.

Design of a multicentre randomised trial to evaluate flexible sigmoidoscopy in colorectal cancer screening.

A randomised, controlled trial in progress in 14 United Kingdom and six Italian centres is evaluating screening for colorectal cancer using a single flexible sigmoidoscopy (FS) at around the age of 60 with removal during FS of all small adenomas, and colonoscopy for "high risk" polyps. The regimen aims to ensure that 95% of people (with either no polyps or only low risk polyps) complete the entire screening process in a single visit. This paper describes the rationale and design of the trial. Participants were patients aged between 55 and 64 on the lists of designated general practitioners (GPs) who were not excluded by their GP. A two stage recruitment procedure was employed to raise compliance rates in the intervention group. Potentially eligible persons were sent an "interest in screening" questionnaire; those who responded positively were randomised to the intervention or control groups. The trial is sufficiently large to estimate within narrow confidence intervals the magnitude of benefit and the duration of effect and optimum age for a single screen. It also examines the feasibility and acceptability of the screening regimen, and will identify training and quality assurance issues. Recruitment and screening are now complete and all baseline data have been collected. The first analysis of the effect on colorectal cancer incidence and mortality rates and suitability for a national screening programme can be expected in 2004.

Microsatellite instability: application in hereditary non-polyposis colorectal cancer.

Colorectal cancer (CRC) is a significant cause of mortality in Western populations. About 15% of CRC patients report a family history of the disease. Studies on individuals with a genetic predisposition to CRC have been responsible for significant advances in the understanding of this disease. Thus, although developments in molecular biology have been mainly restricted to a minority of individuals with a hereditary background, information obtained from this group may affect the diagnosis and therapy of sporadic CRCs as well. Deficiency in the DNA mismatch repair (MMR) system results in microsatellite instability (MSI). Individuals from hereditary non-polyposis colorectal cancer (HNPCC) kindreds with germline mutations in genes involved in MMR may benefit from clinical screening programs. The higher frequency of MSI in HNPCC than in sporadic tumours suggests that involvement of MMR genes in sporadic adenomas may be uncommon. Consequently

High-risk colorectal adenomas and serum insulin-like growth factors.

BACKGROUND: This study investigated the hypothesis that circulating levels of insulin-like growth factor (IGF) I and its main binding protein (IGFBP-3) predict for the presence of colorectal adenomas, surrogate markers of colorectal cancer risk. METHODS: Within the Flexi-Scope Trial (healthy volunteers aged 55-64 years), at one study centre, IGF-I and IGFBP-3 levels in serum samples collected prospectively from 442 attendants were measured. Of these, 100 individuals underwent a complete screening colonoscopy. There were 47 normal examinations, while in 11 examinations low-risk adenomas and in 42 examinations high-risk adenomas were identified. Estimates of relative risk (RR) for the adenomatous stages were calculated by means of unconditional logistic regression, adjusting for known risk factors. RESULTS: Mean serum IGF-I and IGFBP-3 levels were similar in individuals with a normal colonoscopy finding and in those with low-risk adenomas. By contrast, the mean(s.d.) serum IGF-I level was increased (190(53) versus 169(54) microg/l; P = 0.06) and the serum IGFBP-3 concentration was significantly decreased (3.22(0.60) versus 3.47(0.62) mg/l; P = 0.05) in individuals with high-risk adenomas compared with levels in those with normal colonoscopy and low-risk adenomas combined. Levels were unaffected by removal of the adenomas. With high-risk adenoma as the dependent factor, regression models demonstrated a significant positive association with IGF-I after controlling for IGFBP-3 (RR per one standard deviation (1s.d.) change 4.39 (95 per cent confidence interval (c.i.) 1.31-14.7); P = 0.02) and, independently, an inverse association with IGFBP-3 after adjustment for IGF-I (RR per 1s.d. change 0.41 (95 per cent c.i. 0. 20-0.82); P = 0.01). CONCLUSION: These findings suggest that circulating IGF-I and IGFBP-3 levels are related to future colorectal cancer risk and, specifically, may predict adenoma progression.

Circulating insulin-like growth factor II and colorectal adenomas.

Circulating insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) may be risk factors for the development of colorectal cancer. On the other hand, IGF-II and IGFBP-2 are overexpressed in colorectal carcinomas. These contrasting backgrounds led us to investigate the relationship between serum IGF-I, IGF-II, IGFBP-2, and IGFBP-3 and the presence of colorectal adenomas, known precursors of colorectal carcinoma, in 345 volunteers attending a screening flexible sigmoidoscopy trial (entry criteria: healthy, aged 55-64 yr). The most striking finding was an elevated mean serum IGF-II in individuals with adenomas (n = 52) compared with controls (mean difference, 139 ng/mL; 95% confidence intervals, 82, 196; P < 0.0001). Logistic regression adjusting for confounding factors confirmed the significant association between IGF-II and adenoma occurrence (P < 0.0001) and revealed an additional positive association with serum IGFBP-2 (P < 0.0001). However, there was no association found between either serum IGF-I and/or IGFBP-3 and the presence of adenomas. Additionally, in 31 individuals with adenomas in whom levels were determined pre- and postpolypectomy, there was a significant fall in mean IGF-II (P < 0.001) and IGFBP-2 (P < 0.001) after adenoma removal, but no difference in IGF-II and IGFBP-2 concentrations between repeated samples in 20 individuals without adenomas. Immunohistochemical studies demonstrated IGF-II expression in 83% of all adenomas, which contrasted with absent expression in normal colonic expression and hyperplastic polyps. This study has shown for the first time that serum IGF-II may be a tumor marker in individuals with colorectal adenomas. Further studies are needed to validate these relationships in larger populations, including individuals undergoing colonoscopy.