Single Flexible Sigmoidoscopy Screening Research Articles

Effectiveness of Colorectal Cancer (CRC) Screening on All-Cause and CRC-Specific Mortality Reduction: A Systematic Review and Meta-Analysis.

(1) Background: The aim of this study was to pool and compare all-cause and colorectal cancer (CRC) specific mortality reduction of CRC screening in randomized control trials (RCTs) and simulation models, and to determine factors that influence screening effectiveness. (2) Methods: PubMed, Embase, Web of Science and Cochrane library were searched for eligible studies. Multi-use simulation models or RCTs that compared the mortality of CRC screening with no screening in general population were included. CRC-specific and all-cause mortality rate ratios and 95% confidence intervals were calculated by a bivariate random model. (3) Results: 10 RCTs and 47 model studies were retrieved. The pooled CRC-specific mortality rate ratios in RCTs were 0.88 (0.80, 0.96) and 0.76 (0.68, 0.84) for guaiac-based fecal occult blood tests (gFOBT) and single flexible sigmoidoscopy (FS) screening, respectively. For the model studies, the rate ratios were 0.45 (0.39, 0.51) for biennial fecal immunochemical tests (FIT), 0.31 (0.28, 0.34) for biennial gFOBT, 0.61 (0.53, 0.72) for single FS, 0.27 (0.21, 0.35) for 10-yearly colonoscopy, and 0.35 (0.29, 0.42) for 5-yearly FS. The CRC-specific mortality reduction of gFOBT increased with higher adherence in both studies (RCT: 0.78 (0.68, 0.89) vs. 0.92 (0.87, 0.98), model: 0.30 (0.28, 0.33) vs. 0.92 (0.51, 1.63)). Model studies showed a 0.62-1.1% all-cause mortality reduction with single FS screening. (4) Conclusions: Based on RCTs and model studies, biennial FIT/gFOBT, single and 5-yearly FS, and 10-yearly colonoscopy screening significantly reduces CRC-specific mortality. The model estimates are much higher than in RCTs, because the simulated biennial gFOBT assumes higher adherence. The effectiveness of screening increases at younger screening initiation ages and higher adherences.

Long-Term Follow-up of the Italian Flexible Sigmoidoscopy Screening Trial.

Recent reports showed that the protective effect of flexible sigmoidoscopy (FS) screening was maintained up to17 years, although differences were reported by sex. To assess long-term reduction of colorectal cancer (CRC) incidence and mortality after a single FS screening. Parallel randomized controlled trial. (ISRCTN registry number: 27814061). 6 centers in Italy. Persons aged 55 to 64 years expressing interest in having FS screening if invited, recruited from 1995 to 1999 and followed until 2012 (incidence) and 2014 to 2016 (mortality). Eligible persons were randomly assigned (1:1 ratio) to either the once-only FS screening group or control (usual care) group. Incidence and mortality rate ratios (RRs) and rate differences. A total of 34272 persons (17136 in each group) were included in the analysis; 9911 participants had screening in the intervention group. Median follow-up was 15.4 years for incidence and 18.8 years for mortality. Incidence of CRC was reduced by 19% (RR, 0.81 [95% CI, 0.71 to 0.93]) in the intention-to-treat (ITT) analysis, comparing the intervention with the control group, and by 33% (RR, 0.67 [CI, 0.56 to 0.81]) in the per protocol (PP) analysis, comparing participants screened in the intervention group with the control persons. Colorectal cancer mortality was reduced by 22% (RR, 0.78 [CI, 0.61 to 0.98]) in the ITT analysis and by 39% (RR, 0.61 [CI, 0.44 to 0.84]) in the PP analysis. Incidence of CRC was statistically significantly reduced among both men and women. Colorectal cancer mortality was statistically significantly reduced among men (ITT RR, 0.73 [CI, 0.54 to 0.97]) but not among women (ITT RR, 0.90 [CI, 0.59 to 1.37]). Self-selection of volunteers from the general population sample targeted for recruitment may limit generalizability. The strong protective effect of a single FS screening for CRC incidence and mortality was maintained up to 15 and 19 years, respectively. Italian Association for Cancer Research, Italian National Research Council, Istituto Oncologico Romagnolo, Fondo "E. Tempia," University of Milan, and Local Health Unit ASL-Torino.

Long term effects of once-only flexible sigmoidoscopy screening after 17 years of follow-up: the UK Flexible Sigmoidoscopy Screening randomised controlled trial

SummaryBackgroundColorectal cancer is the third most common cancer worldwide. Previous analyses have only reported follow-up after flexible sigmoidoscopy for a maximum of 12 years. We aimed to examine colorectal cancer incidence and mortality after a single flexible sigmoidoscopy screening and 17 years of follow-up.MethodsIn this multicentre randomised trial (UK Flexible Sigmoidoscopy Screening Trial), done between Nov 14, 1994, and March 30, 1999, 170 432 eligible men and women, who had indicated on a previous questionnaire that they would probably attend screening if invited, were randomly assigned (1:2) to an intervention group (offered flexible sigmoidoscopy screening) or a control group (not contacted). Randomisation was done centrally in blocks of 12, and stratified by trial centre, general practice, and household type. The nature of the intervention did not allow the staff to be masked to arm of the trial; however, randomisation was done in batches so that the control group and participants not yet randomised were unaware of their allocation status. The primary outcomes were incidence and mortality of colorectal cancer. Hazard ratios (HRs) and 95% CIs for colorectal cancer incidence and mortality were estimated for intention-to-treat and per-protocol analyses. The trial is registered with ISRCTN, number 28352761.FindingsOur cohort analysis included 170 034 people: 112 936 in the control group and 57 098 in the intervention group, 40 621 (71%) of whom were screened and 16 477 (29%) were not screened. During screening and a median of 17·1 years' follow-up, colorectal cancer was diagnosed in 1230 individuals in the intervention group and 3253 in the control group, and 353 individuals in the intervention group versus 996 individuals in the control group died from colorectal cancer. In intention-to-treat analyses, colorectal cancer incidence was reduced by 26% (HR 0·74 [95% CI 0·70–0·80]; p<0·0001) in the intervention group versus the control group and colorectal cancer mortality was reduced by 30% (0·70 [0·62–0·79]; p<0·0001) in the intervention group versus the control group. In per-protocol analyses, adjusted for non-compliance, colorectal cancer incidence and mortality were 35% (HR 0·65 [95% CI 0·59–0·71]) and 41% (0·59 [0·49–0·70]) lower in the screened group.InterpretationA single flexible sigmoidoscopy continues to provide substantial protection from colorectal cancer diagnosis and death, with protection lasting at least 17 years.FundingNational Institute for Health Research Efficacy and Mechanism Evaluation.

Flexible sigmoidoscopy: more than a unilateral breast exam?

Upon reviewing the many wonderful articles and perspective pieces in this Special Issue of Digestive Diseases and Sciences prior to publication, it occurred to me that an important method of screening had not been covered. While in 2010 in the USA \6 % of respondents aged 50–75 reported having screening flexible sigmoidoscopy performed within 5 years (an additional 1.3 % had sigmoidoscopy plus fecal occult blood testing) [1, 2], flexible sigmoidoscopy remains part of the menu of screening options recommended by several professional society guidelines [3–6]. Four recent randomized trials also provide (arguably) the largest body of prospective evidence demonstrating the role of colorectal cancer (CRC) screening in reducing CRC-related mortality of any screening method [7–10]. I therefore decided that it was important to at least provide a brief perspective on flexible sigmoidoscopy as a CRC screening tool, including why it is not used more today in the USA. Four large prospective randomized trials of flexible sigmoidoscopy for CRC screening were published in highimpact journals between 2004 and 2014, having been initiated in the 1990s when flexible sigmoidoscopy was a more common screening tool than in the USA today (Table 1) [7–10]. The trials from the UK (the UK Flexible Sigmoidoscopy Trial), Italy (the Italian Randomized Controlled Trial-SCORE), the USA (the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial-PLCO), and Norway (the Norwegian Colorectal Cancer Prevention Trial-NORCAPP) differ in several ways including how participants were recruited, the number of screening examinations performed, degree of screening outside the trial (‘‘contamination’’), and what findings at sigmoidoscopy generated a subsequent colonoscopy. All, however, demonstrated similar relative and absolute reductions in CRC incidence and cancer-related incidence and mortality. The UK Flexible Sigmoidoscopy Screening Trial is a randomized trial which tested the hypothesis that a single flexible sigmoidoscopy screening examination offered at approximately 60 years of age can lower the incidence and mortality of CRC [7]. CRC incidence and mortality were reduced by 23 and 31 %, respectively, in the intention-totreat analysis (33 and 43 %, respectively, based on perprotocol analysis); incidence of cancer of the rectum and sigmoid was reduced by 36 % in the intention-to-treat analysis and 50 % in the per-protocol analysis. These data have resulted in once in a lifetime flexible sigmoidoscopy being included as an option in the UK National Health Service Bowel Cancer Screening Programme (FOBT is the other option). The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) enrolled 154,900 subjects of age 55–74 years in a prospective randomized trial that compared flexible sigmoidoscopy with repeat screening at 3 or 5 years to a usual-care control group [8]. Flexible sigmoidoscopy reduced CRC incidence by 21 % with a benefit observed in both the proximal and distal colon and reduced overall mortality by 26 % (intention-to-treat analyses). Mortality from distal CRC (distal to the splenic flexure) was reduced by 50 %, whereas mortality from proximal CRC was unaffected. The Italian Randomized Controlled Trial (SCORE) demonstrated that once-only sigmoidoscopy significantly reduced CRC incidence by 18 % and insignificantly reduced mortality by 22 % in intention-to-treat analyses; in R. S. Bresalier (&) Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1466, Houston, TX 77030, USA e-mail: rbresali@mdanderson.org

Reappraisal of the options for colorectal cancer screening in England

The aim was to use newly available data to estimate the cost effectiveness and endoscopy requirements of screening options for colorectal cancer (CRC) to inform screening policy in England. A state transition model simulated the life experience of a cohort of individuals in the general population of England with normal colon/rectal epithelium through to the development of adenomas and CRC and subsequent death. CRC natural history model parameters and screening test characteristics were estimated simultaneously by a process of model calibration. This process was fitted to observed data on CRC incidence in the absence of screening, data from existing screening programmes, and data from the UK flexible sigmoidoscopy (FS) screening trial. The costs, effects and resource impact were evaluated for a range of screening options involving the guaiac or immunochemical faecal occult blood test (gFOBT/iFOBT) and FS. The model suggests that screening strategies involving FS or iFOBT may produce additional benefits compared with the current policy of biennial gFOBT for 60-74-year-olds. The age at which a single FS screen results in the greatest quality-adjusted life year gain was 55, with similar gains for ages between 52 and 58. Strategies which combined FS and iFOBT showed further benefits and improved economic outcomes. Strategies which combine different screening modalities may provide greater clinical and economic benefits. The collection of comprehensive screening data using a uniform format will enable comparative analysis across screening programmes in different countries, will improve our understanding of the disease and will allow identification of optimal screening modalities.

Once-Only Sigmoidoscopy in Colorectal Cancer Screening: Follow-up Findings of the Italian Randomized Controlled Trial--SCORE

A single flexible sigmoidoscopy at around the age of 60 years has been proposed as an effective strategy for colorectal cancer (CRC) screening. We conducted a randomized controlled trial to evaluate the effect of flexible sigmoidoscopy screening on CRC incidence and mortality. A questionnaire to assess the eligibility and interest in screening was mailed to 236,568 men and women, aged 55-64 years, who were randomly selected from six trial centers in Italy. Of the 56,532 respondents, interested and eligible subjects were randomly assigned to the intervention group (invitation for flexible sigmoidoscopy; n = 17,148) or the control group (no further contact; n = 17,144), between June 14, 1995, and May 10, 1999. Flexible sigmoidoscopy was performed on 9911 subjects. Intention-to-treat and per-protocol analyses were performed to compare the CRC incidence and mortality rates in the intervention and control groups. Per-protocol analysis was adjusted for noncompliance. A total of 34,272 subjects (17,136 in each group) were included in the follow-up analysis. The median follow-up period was 10.5 years for incidence and 11.4 years for mortality; 251 subjects were diagnosed with CRC in the intervention group and 306 in the control group. Overall incidence rates in the intervention and control groups were 144.11 and 176.43, respectively, per 100,000 person-years. CRC-related death was noted in 65 subjects in the intervention group and 83 subjects in the control group. Mortality rates in the intervention and control groups were 34.66 and 44.45, respectively, per 100,000 person-years. In the intention-to-treat analysis, the rate of CRC incidence was statistically significantly reduced in the intervention group by 18% (rate ratio [RR] = 0.82, 95% confidence interval [CI] = 0.69 to 0.96), and the mortality rate was non-statistically significantly reduced by 22% (RR = 0.78; 95% CI = 0.56 to 1.08) compared with the control group. In the per-protocol analysis, both CRC incidence and mortality rates were statistically significantly reduced among the screened subjects; CRC incidence was reduced by 31% (RR = 0.69; 95% CI = 0.56 to 0.86) and mortality was reduced by 38% (RR = 0.62; 95% CI = 0.40 to 0.96) compared with the control group. A single flexible sigmoidoscopy screening between ages 55 and 64 years was associated with a substantial reduction of CRC incidence and mortality.

Single Flexible Sigmoidoscopy Screening Associated With Reduced Colorectal Cancer

Single Flexible Sigmoidoscopy Screening Associated With Reduced Colorectal Cancer

285 The European Achalasia Trial: A Randomized Multi-Centre Trial Comparing Endoscopic Pneumodilation and Laparoscopic Myotomy as Primary Treatment of Idiopathic Achalasia

Introduction A once-only flexible sigmoidoscopy (FS) screening at age around 60 has been proposed as a cost-effective and acceptable method of reducing colorectal cancer (CRC) incidence and mortality. We undertook a large randomised controlled trial in a general population sample to compare CRC incidence and mortality rates following a single FS screen. Methods and baseline results Between 1994 and 1999, we sent a questionnaire to 375 744 men and women, aged 55 to 64 years, in 14 UK centres, asking whether they would have the FS screening if invited. Those who responded ‘yes definitely' or ‘yes probably' and were found to be eligible (n = 170 432) were randomised to the control or intervention arms of the trial in a 2:1 ratio. Of 57 254 people invited, 40 674 (71%) were screened. Following screening, 38 525 (95%) had either no pathology or only low-risk adenomas and were discharged and 2051 had high risk adenomas detected and underwent colonoscopy. Biannual updates on status (emigration, cancer diagnoses or deaths) were obtained by matching with the National Health Service Central Register, Office of National Statistics, UK cancer registries, and Hospitals Episodes Statistics records. Results of follow-up The median follow-up time to death, emigration or 31st December 2008 is currently 11 years. A total of 2491 participants developed CRC during 1.85 million person years of follow-up: 1523 developed a distal cancer (rectum or sigmoid colon), 894 developed cancer in the proximal colon, 34 developed cancer in both sites, and in 40 cases the site was not known. On an intent-to-treat analysis, a significant reduction in incidence of total and distal CRC was observed among those invited for screening. A greater reduction was seen among those who attended for screening. Colorectal cancer mortality rates were also reduced significantly. Adjustment for self-selection bias in attenders using Cuzick et al's method (Stat Med 1997;16:1017-29) made little difference to the rate ratios or significance. Conclusion By 11 years, total and distal colorectal cancer incidence rates were reduced significantly among people offered a single flexible sigmoidoscopy screen between ages 55 and 64 years, and so far no attenuation of effect has been observed. Detailed results will be presented.

283 UK Flexible Sigmoidoscopy Screening Trial: Colorectal Cancer Incidence and Mortality Rates at 11 Years After a Single Screening Examination

Introduction A once-only flexible sigmoidoscopy (FS) screening at age around 60 has been proposed as a cost-effective and acceptable method of reducing colorectal cancer (CRC) incidence and mortality. We undertook a large randomised controlled trial in a general population sample to compare CRC incidence and mortality rates following a single FS screen. Methods and baseline results Between 1994 and 1999, we sent a questionnaire to 375 744 men and women, aged 55 to 64 years, in 14 UK centres, asking whether they would have the FS screening if invited. Those who responded ‘yes definitely' or ‘yes probably' and were found to be eligible (n = 170 432) were randomised to the control or intervention arms of the trial in a 2:1 ratio. Of 57 254 people invited, 40 674 (71%) were screened. Following screening, 38 525 (95%) had either no pathology or only low-risk adenomas and were discharged and 2051 had high risk adenomas detected and underwent colonoscopy. Biannual updates on status (emigration, cancer diagnoses or deaths) were obtained by matching with the National Health Service Central Register, Office of National Statistics, UK cancer registries, and Hospitals Episodes Statistics records. Results of follow-up The median follow-up time to death, emigration or 31st December 2008 is currently 11 years. A total of 2491 participants developed CRC during 1.85 million person years of follow-up: 1523 developed a distal cancer (rectum or sigmoid colon), 894 developed cancer in the proximal colon, 34 developed cancer in both sites, and in 40 cases the site was not known. On an intent-to-treat analysis, a significant reduction in incidence of total and distal CRC was observed among those invited for screening. A greater reduction was seen among those who attended for screening. Colorectal cancer mortality rates were also reduced significantly. Adjustment for self-selection bias in attenders using Cuzick et al's method (Stat Med 1997;16:1017-29) made little difference to the rate ratios or significance. Conclusion By 11 years, total and distal colorectal cancer incidence rates were reduced significantly among people offered a single flexible sigmoidoscopy screen between ages 55 and 64 years, and so far no attenuation of effect has been observed. Detailed results will be presented.

284 Laparoscopic Antireflux Surgery vs Long-Term Esomeprazole Treatment for Chronic GERD. Final Results After 5 Yrs of Follow up in the Lotus Study

Introduction A once-only flexible sigmoidoscopy (FS) screening at age around 60 has been proposed as a cost-effective and acceptable method of reducing colorectal cancer (CRC) incidence and mortality. We undertook a large randomised controlled trial in a general population sample to compare CRC incidence and mortality rates following a single FS screen. Methods and baseline results Between 1994 and 1999, we sent a questionnaire to 375 744 men and women, aged 55 to 64 years, in 14 UK centres, asking whether they would have the FS screening if invited. Those who responded ‘yes definitely' or ‘yes probably' and were found to be eligible (n = 170 432) were randomised to the control or intervention arms of the trial in a 2:1 ratio. Of 57 254 people invited, 40 674 (71%) were screened. Following screening, 38 525 (95%) had either no pathology or only low-risk adenomas and were discharged and 2051 had high risk adenomas detected and underwent colonoscopy. Biannual updates on status (emigration, cancer diagnoses or deaths) were obtained by matching with the National Health Service Central Register, Office of National Statistics, UK cancer registries, and Hospitals Episodes Statistics records. Results of follow-up The median follow-up time to death, emigration or 31st December 2008 is currently 11 years. A total of 2491 participants developed CRC during 1.85 million person years of follow-up: 1523 developed a distal cancer (rectum or sigmoid colon), 894 developed cancer in the proximal colon, 34 developed cancer in both sites, and in 40 cases the site was not known. On an intent-to-treat analysis, a significant reduction in incidence of total and distal CRC was observed among those invited for screening. A greater reduction was seen among those who attended for screening. Colorectal cancer mortality rates were also reduced significantly. Adjustment for self-selection bias in attenders using Cuzick et al's method (Stat Med 1997;16:1017-29) made little difference to the rate ratios or significance. Conclusion By 11 years, total and distal colorectal cancer incidence rates were reduced significantly among people offered a single flexible sigmoidoscopy screen between ages 55 and 64 years, and so far no attenuation of effect has been observed. Detailed results will be presented.

Developments in early rectal cancer treatment

Bowel cancer screening will change how rectal cancer presents. Data from the two UK pilots has shown that 49–62% of screen-detected tumours are ‘early’ (pT1–2N0M0; Stage I) [ 1 UK Flexible Sigmoidoscopy Screening Trial Investigators Single flexible sigmoidoscopy screening to prevent colorectal cancer: baseline findings of a UK multicentre randomised trial. Lancet. 2002; 359: 1291-1300 Abstract Full Text Full Text PDF PubMed Scopus (458) Google Scholar , 2 UK Colorectal Cancer Screening Pilot Group Results of the first round of a demonstration pilot of screening for colorectal cancer in the United Kingdom. BMJ. 2004; 329: 133 Crossref PubMed Google Scholar ]. Radical total mesorectal excision (TME) offers high rates of cure for early rectal cancer; only 3–6% of patients subsequently relapse [ 3 Bentrem DJ Okabe S Wong WD et al. T1 adenocarcinoma of the rectum: transanal excision or radical surgery?. Ann Surg. 2005; 242: 472-477 PubMed Google Scholar , 4 Endreseth BH Myrvold HE Romundstad P Hestvik UE Bjerkeset T Wibe A Transanal excision vs. major surgery for T1 rectal cancer. Dis Colon Rectum. 2005; 48: 1380-1388 Crossref PubMed Scopus (188) Google Scholar , 5 Peeters KC Marijnen CA Nagtegaal ID et al. The TME trial after a median follow-up of 6 years: increased local control but no survival benefit in irradiated patients with resectable rectal carcinoma. Ann Surg. 2007; 246: 693-701 Crossref PubMed Scopus (896) Google Scholar ]. There are concerns, however, that radical surgery, which evolved to treat locally advanced, symptomatic tumours, may not be the optimal method of treatment for early (screen detected) tumours.

Colorectal cancer screening with the addition of flexible sigmoidoscopy to guaiac-based faecal occult blood testing: A French population-based controlled study (Wintzenheim trial)

Objective To assess the feasibility, participation and neoplasia yield of adding a flexible sigmoidoscopy (FS) once in a lifetime to a colorectal cancer screening programme with guaiac-based faecal occult blood test (gFOBT). Methods A total of 4771 average risk residents aged 50–74 of a canton of the Haut-Rhin, a French administrative area, were invited every other year to participate in an organised screening programme with gFOBT. Of them, those aged 55–64 (1824 people) were, in addition, invited once by mail to visit their general practitioner (GP) for a screening with FS performed by a gastroenterologist. Results In all, 2717 people (56.9%) (95% confidence interval (CI) 55.5–58.4) were screened with one or other of the two tests or with both tests. Compliance was 56.7% (55.3–58.1) with gFOBT and 20.9% (19.1–22.8) with FS. Both tests were performed by 20.2% (18.4–22.1) of people. Compliance with FS was 1.9% in people who had not complied with gFOBT and 31.9% in people who complied. The latter was ⩾50% in patients of 26 motivated GPs. The detection rate for advanced neoplasia was 17.7 per 1000 people screened (12.7–22.6) with the combined procedure, more than three times higher than that with gFOBT alone. Conclusion A population-based screening programme with the addition of FS to gFOBT is feasible and safe through an organisation involving GPs. The performances of the two screening tools are complementary: high compliance – low yield for gFOBT and vice versa for FS. The addition of a single FS screening in people aged 55–64 to an organised programme with biennial gFOBT in people aged 50–74 is a colorectal cancer screening option that deserves further exploration.

Options for Screening for Colorectal Cancer

Unlike other types of cancer, there are several options for screening for colorectal cancer (CRC). The most extensively examined method, faecal occult blood testing (FOBT), has been shown, in three large randomized trials, to reduce mortality from CRC by up to 20% if offered biennally and possibly more if offered every year. Recently published data from the US trial suggest that CRC incidence rates are also reduced by up to 20%, but only after 18 years. In this study, the number of positive slides was associated with the positive predictive value both for CRC and adenomas larger than 1 cm, suggesting that the reduction in CRC incidence was caused by the identification and removal of large adenomas. In this respect, this study supports the concept that removing adenomas prevents CRC. More efficient methods of detecting adenomas include the use of colonoscopy or flexible sigmoidoscopy (FS). Considerable evidence exists from case-control and uncontrolled cohort studies to suggest that endoscopic screening by sigmoidoscopy reduces incidence of distal colorectal cancer. However, in the absence of evidence from a randomized trial, several countries have been reluctant to introduce endoscopic screening. Three trials are currently in progress (in the UK, Italy and the US) to address this issue. Two of these trials are examining the hypothesis that a single FS screen at around age 55-64 might be a cost-effective and acceptable method for reducing CRC incidence rates. Recruitment and screening are now complete in both studies and the first analysis of results on incidence rates is expected in 2004. Colonoscopy screening at 10-year intervals has recently been endorsed in the US on the basis that the reductions in incidence observed with distal CRC screening can be extrapolated to the proximal colon. However, data are lacking and a pilot study for a trial of the acceptability and efficacy of colonoscopy screening is in progress in the US. It has also been suggested that FOBT testing should be used to detect proximal CRC missed by sigmoidoscopy screening, but the small amount of published data suggest that supplementing FS with FOBT offers very little advantage over FS alone. Other forms of CRC screening are under investigation and represent exciting options for the future. Extraction of DNA from stool is now feasible and a number of research groups have shown high sensitivity for CRC using a panel of DNA markers including mutations in k-ras, APC, p53 and BAT26. Data so far indicate that, with the exception of k-ras, these markers are highly specific and therefore represent a significant improvement over FOBT. Whether these tests will replace or supplement existing methods of screening has yet to be determined. It has been suggested that BAT26, which is a marker of microsatellite instability, a feature of proximal sporadic CRC, might be a useful adjunct to sigmoidoscopy screening. Others have suggested that a test for occult blood should be included with the DNA markers to further increase sensitivity. It is not yet known how sensitive these markers are for adenomas--it is only by detecting adenomas that CRC incidence rates can be reduced. A final exciting new option for screening is virtual colonoscopy (VC), which by screening out people without neoplasia allows colonoscopy to be reserved for patients requiring a therapeutic intervention. The sensitivity of VC for large adenomas and CRC appears to be high, although results vary by centre and there is a steep learning curve. Sensitivity for small adenomas is low, but perhaps it is less essential to find such lesions. Some groups have suggested that virtual colonoscopy might be a useful option for investigating patients who test positive with stool-based screening tests. Whichever CRC screening method is finally chosen (and there is no reason why several methods should not ultimately be available), high quality endoscopy resources will always be required to investigate and treat neoplastic lesions detected.

Diagnostic Yield in a Biennial Hemoccult-II Screening Program Compared to a Once-only Screening with Flexible Sigmoidoscopy and Hemoccult-II

Background: Flexible sigmoidoscopy (FS) has a higher degree of sensitivity for detecting colorectal neoplasia in the left side of the colon than Hemoccult-II (H-II). However, no randomized controlled trial has compared a single FS screening with H-II screening program (annual or biennial) despite with well-documented mortality reduction from colorectal cancer (CRC) in the latter. The aim was to compare the diagnostic yield of colorectal neoplasia in two aged-matched groups from two different randomized screening trials; one group screened by a single FS+H-II, the other with biennial H-II over the course of 16 years. Methods: 24,465 persons invited to participate in the Funen biennal H-II screening program were compared with 4,460 similar persons invited to another Funen trial using a single FS+H-II. Results: Compliance in the biennial H-II program was 65.5% during the first screening round compared to 39.8% for FS+H-II. The cumulative number of persons with positive tests was 8.2% (positive H-II) in the biennial H-II program during 16 years and 20.3% (polyps > 3 mm in diameter seen at FS or positive H-II) for once-only FS+H-II. The diagnostic yield of CRC per 1,000 screened was 9.9 in the biennial H-II program and 6.6 after FS+H-II (6.5 and 2.7 per 1,000 invited). The yield of advanced adenomas (≥ 10 mm and/or villous structure and/or severe dysplasia) was 2.3% in the H-II program and 3.3% after FS+H-II among the screened persons, but this difference disappeared when persons invited, but not necessarily screened, were compared (1.5% versus 1.3%). Conclusion: Screening with H-II in a biennial screening program during 16 years detected more CRCs than a single screening with FS+H-II and a similar number of advanced adenomas.

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

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. 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. 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.