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1.
J Med Screen ; 26(1): 11-18, 2019 03.
Article in English | MEDLINE | ID: mdl-30282520

ABSTRACT

OBJECTIVE: To investigate the outcomes of biennial guaiac faecal occult blood test (gFOBT) screening after once-only flexible sigmoidoscopy (FS) screening. METHODS: Between 1994 and 1999, as part of the UK FS Screening Trial (UKFSST), adults aged 55-64 were randomly allocated to an intervention group (offered FS screening) or a control group (not contacted). From 2006, a subset of UKFSST participants (20,895/44,041 intervention group; 41,497/87,149 control group) were invited to biennial gFOBT screening by the English Bowel Cancer Screening Programme. We analysed gFOBT uptake, test positivity, yield of colorectal cancer (CRC), and positive predictive value (PPV) for CRC, advanced adenomas (AAs), and advanced colorectal neoplasia (ACN: AA/CRC). RESULTS: Uptake of gFOBT at first invitation was 1.9% lower (65.7% vs. 67.6%, p < 0.01) among intervention versus control group participants. Positivity was 0.4% lower (2.0% vs. 2.4%, p < 0.01) and CRC yield was 0.08% lower (0.19% vs. 0.27%, p = 0.14). PPVs were also lower in the intervention versus control group, at 10.3% vs. 12.3% ( p = 0.44) for CRC, 22.7% vs. 31.4% ( p < 0.01) for AA, and 33.0% vs. 43.7% ( p < 0.01) for ACN. Among those who refused FS ( n = 5532), gFOBT uptake at first invitation was 47.7%, CRC yield was 0.25%, and PPV for ACN was 46.2%. Among FS attenders ( n = 15,363), uptake was 72.2%, CRC yield was 0.18%, and PPV for ACN was 27.9%. CONCLUSIONS: Uptake, positivity and PPV of gFOBT screening were reduced following prior offer of FS screening. However, a quarter of FS screened participants receiving a diagnostic examination after positive gFOBT were diagnosed with ACN.


Subject(s)
Colorectal Neoplasms/diagnosis , Occult Blood , Patient Compliance , Sigmoidoscopy , Aged , Female , Guaiac , Humans , Male , Mass Screening , Middle Aged , State Medicine , United Kingdom
2.
Gut ; 68(9): 1642-1652, 2019 09.
Article in English | MEDLINE | ID: mdl-30538097

ABSTRACT

OBJECTIVE: The English Bowel Cancer Screening Programme (BCSP) recommends 3 yearly colonoscopy surveillance for patients at intermediate risk of colorectal cancer (CRC) postpolypectomy (those with three to four small adenomas or one ≥10 mm). We investigated whether faecal immunochemical tests (FITs) could reduce surveillance burden on patients and endoscopy services. DESIGN: Intermediate-risk patients (60-72 years) recommended 3 yearly surveillance were recruited within the BCSP (January 2012-December 2013). FITs were offered at 1, 2 and 3 years postpolypectomy. Invitees consenting and returning a year 1 FIT were included. Participants testing positive (haemoglobin ≥40 µg/g) at years one or two were offered colonoscopy early; all others were offered colonoscopy at 3 years. Diagnostic accuracy for CRC and advanced adenomas (AAs) was estimated considering multiple tests and thresholds. We calculated incremental costs per additional AA and CRC detected by colonoscopy versus FIT surveillance. RESULTS: 74% (5938/8009) of invitees were included in our study having participated at year 1. Of these, 97% returned FITs at years 2 and 3. Three-year cumulative positivity was 13% at the 40 µg/g haemoglobin threshold and 29% at 10 µg/g. 29 participants were diagnosed with CRC and 446 with AAs. Three-year programme sensitivities for CRC and AAs were, respectively, 59% and 33% at 40 µg/g, and 72% and 57% at 10 µg/g. Incremental costs per additional AA and CRC detected by colonoscopy versus FIT (40 µg/g) surveillance were £7354 and £180 778, respectively. CONCLUSIONS: Replacing 3 yearly colonoscopy surveillance in intermediate-risk patients with annual FIT could reduce colonoscopies by 71%, significantly cut costs but could miss 30%-40% of CRCs and 40%-70% of AAs. TRIAL REGISTRATION NUMBER: ISRCTN18040196; Results.


Subject(s)
Colonic Polyps/surgery , Colonoscopy/methods , Early Detection of Cancer/methods , Occult Blood , Adenoma/diagnosis , Adenoma/surgery , Aged , Colonic Polyps/diagnosis , Colonoscopy/economics , Colorectal Neoplasms/diagnosis , Cost-Benefit Analysis , Early Detection of Cancer/economics , England , False Negative Reactions , Female , Health Care Costs/statistics & numerical data , Humans , Male , Middle Aged , Population Surveillance/methods , Predictive Value of Tests , Sensitivity and Specificity
3.
J Med Screen ; 25(2): 70-75, 2018 06.
Article in English | MEDLINE | ID: mdl-28467146

ABSTRACT

Objectives The English Bowel Cancer Screening Programme offers biennial guaiac faecal occult blood test (gFOBT) screening to 60-74-year-olds. Participants with positive results are referred for follow-up, but many do not have significant findings. If they remain age eligible, these individuals are reinvited for gFOBT screening. We evaluated the performance of repeat screening in this group. Methods We analysed data on programme participants reinvited to gFOBT screening after either previous negative gFOBT ( n = 327,542), or positive gFOBT followed by a diagnostic investigation negative for colorectal cancer (CRC) or adenomas requiring surveillance ( n = 42,280). Outcomes calculated were uptake, test positivity, yield of CRC, and positive predictive value (PPV) of gFOBT for CRC. Results For participants with a previous negative gFOBT, uptake in the subsequent screening round was 87.5%, positivity was 1.3%, yield of CRC was 0.112% of those adequately screened, and the PPV of gFOBT for CRC was 9.1%. After a positive gFOBT and a negative diagnostic investigation, uptake in the repeat screening round was 82.6%, positivity was 11.3%, CRC yield was 0.172% of participants adequately screened, and the PPV of gFOBT for CRC was 1.7%. Conclusion With high positivity and low PPV for CRC, the suitability of routine repeat gFOBT screening in two years among individuals with a previous positive test and a negative diagnostic examination needs to be carefully considered.


Subject(s)
Adenoma/diagnosis , Colorectal Neoplasms/diagnosis , Guaiac , Occult Blood , Aged , Colonoscopy/methods , Early Detection of Cancer/methods , England , Female , Humans , Male , Middle Aged , Predictive Value of Tests , State Medicine
4.
Gut ; 66(7): 1181-1196, 2017 07.
Article in English | MEDLINE | ID: mdl-28450390

ABSTRACT

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).


Subject(s)
Colonic Polyps/diagnosis , Colonic Polyps/surgery , Polyps/diagnosis , Polyps/surgery , Rectal Diseases/diagnosis , Rectal Diseases/surgery , Adenoma/diagnosis , Adenoma/genetics , Adenoma/surgery , Adenomatous Polyposis Coli/diagnosis , Benchmarking , Biomarkers/analysis , Cell Transformation, Neoplastic , Colitis/complications , Colonic Polyps/genetics , Colonoscopy , CpG Islands/genetics , DNA/isolation & purification , DNA Methylation , Feces/chemistry , Humans , Parasympatholytics/therapeutic use , Polyps/genetics , Precancerous Conditions/diagnosis , Precancerous Conditions/surgery , Rectal Diseases/genetics , Terminology as Topic , Watchful Waiting
6.
Eur Radiol ; 26(12): 4313-4322, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27048534

ABSTRACT

OBJECTIVES: The aim of this study was to compare the morphology, radiological stage, conspicuity, and computer-assisted detection (CAD) characteristics of colorectal cancers (CRC) detected by computed tomographic colonography (CTC) in screening and symptomatic populations. METHODS: Two radiologists independently analyzed CTC images from 133 patients diagnosed with CRC in (a) two randomized trials of symptomatic patients (35 patients with 36 tumours) and (b) a screening program using fecal occult blood testing (FOBt; 98 patients with 100 tumours), measuring tumour length, volume, morphology, radiological stage, and subjective conspicuity. A commercial CAD package was applied to both datasets. We compared CTC characteristics between screening and symptomatic populations with multivariable regression. RESULTS: Screen-detected CRC were significantly smaller (mean 3.0 vs 4.3 cm, p < 0.001), of lower volume (median 9.1 vs 23.2 cm3, p < 0.001) and more frequently polypoid (34/100, 34 % vs. 5/36, 13.9 %, p = 0.02) than symptomatic CRC. They were of earlier stage than symptomatic tumours (OR = 0.17, 95 %CI 0.07-0.41, p < 0.001), and were judged as significantly less conspicuous (mean conspicuity 54.1/100 vs. 72.8/100, p < 0.001). CAD detection was significantly lower for screen-detected (77.4 %; 95 %CI 67.9-84.7 %) than symptomatic CRC (96.9 %; 95 %CI 83.8-99.4 %, p = 0.02). CONCLUSIONS: Screen-detected CRC are significantly smaller, more frequently polypoid, subjectively less conspicuous, and less likely to be identified by CAD than those in symptomatic patients. KEY POINTS: • Screen-detected colorectal cancers (CRC) are significantly smaller than symptomatic CRC. • Screening cases are significantly less conspicuous to radiologists than symptomatic tumours. • Screen-detected CRC have different morphology compared to symptomatic tumours (more polypoid, fewer annular). • A commercial computer-aided detection (CAD) system was significantly less likely to note screen-detected CRC.


Subject(s)
Colonic Neoplasms/pathology , Rectal Neoplasms/pathology , Aged , Colonic Neoplasms/diagnostic imaging , Colonography, Computed Tomographic/methods , Early Detection of Cancer , Female , Humans , Male , Mass Screening/methods , Middle Aged , Multicenter Studies as Topic , Neoplasm Staging , Observer Variation , Occult Blood , Prospective Studies , Randomized Controlled Trials as Topic , Rectal Neoplasms/diagnostic imaging , Retrospective Studies , Sensitivity and Specificity
7.
Cancer ; 122(6): 826-39, 2016 Mar 15.
Article in English | MEDLINE | ID: mdl-26828588

ABSTRACT

BACKGROUND: New screening tests for colorectal cancer continue to emerge, but the evidence needed to justify their adoption in screening programs remains uncertain. METHODS: A review of the literature and a consensus approach by experts was undertaken to provide practical guidance on how to compare new screening tests with proven screening tests. RESULTS: Findings and recommendations from the review included the following: Adoption of a new screening test requires evidence of effectiveness relative to a proven comparator test. Clinical accuracy supported by programmatic population evaluation in the screening context on an intention-to-screen basis, including acceptability, is essential. Cancer-specific mortality is not essential as an endpoint provided that the mortality benefit of the comparator has been demonstrated and that the biologic basis of detection is similar. Effectiveness of the guaiac-based fecal occult blood test provides the minimum standard to be achieved by a new test. A 4-phase evaluation is recommended. An initial retrospective evaluation in cancer cases and controls (Phase 1) is followed by a prospective evaluation of performance across the continuum of neoplastic lesions (Phase 2). Phase 3 follows the demonstration of adequate accuracy in these 2 prescreening phases and addresses programmatic outcomes at 1 screening round on an intention-to-screen basis. Phase 4 involves more comprehensive evaluation of ongoing screening over multiple rounds. Key information is provided from the following parameters: the test positivity rate in a screening population, the true-positive and false-positive rates, and the number needed to colonoscope to detect a target lesion. CONCLUSIONS: New screening tests can be evaluated efficiently by this stepwise comparative approach.


Subject(s)
Biomarkers, Tumor/analysis , Colorectal Neoplasms/diagnosis , Early Detection of Cancer/methods , Evaluation Studies as Topic , Mass Screening/methods , Occult Blood , Research Design , Case-Control Studies , Clinical Trials as Topic , Colonoscopy , False Positive Reactions , Humans , Practice Guidelines as Topic/standards , Reproducibility of Results , Sample Size
8.
Cancer Epidemiol ; 39 Suppl 1: S139-52, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26596722

ABSTRACT

In order to update the previous version of the European Code against Cancer and formulate evidence-based recommendations, a systematic search of the literature was performed according to the methodology agreed by the Code Working Groups. Based on the review, the 4th edition of the European Code against Cancer recommends: "Take part in organized cancer screening programmes for: Bowel cancer (men and women); Breast cancer (women); Cervical cancer (women)." Organized screening programs are preferable because they provide better conditions to ensure that the Guidelines for Quality Assurance in Screening are followed in order to achieve the greatest benefit with the least harm. Screening is recommended only for those cancers where a demonstrated life-saving effect substantially outweighs the potential harm of examining very large numbers of people who may otherwise never have, or suffer from, these cancers, and when an adequate quality of the screening is achieved. EU citizens are recommended to participate in cancer screening each time an invitation from the national or regional screening program is received and after having read the information materials provided and carefully considered the potential benefits and harms of screening. Screening programs in the European Union vary with respect to the age groups invited and to the interval between invitations, depending on each country's cancer burden, local resources, and the type of screening test used For colorectal cancer, most programs in the EU invite men and women starting at the age of 50-60 years, and from then on every 2 years if the screening test is the guaiac-based fecal occult blood test or fecal immunochemical test, or every 10 years or more if the screening test is flexible sigmoidoscopy or total colonoscopy. Most programs continue sending invitations to screening up to the age of 70-75 years. For breast cancer, most programs in the EU invite women starting at the age of 50 years, and not before the age of 40 years, and from then on every 2 years until the age of 70-75 years. For cervical cancer, if cytology (Pap) testing is used for screening, most programs in the EU invite women starting at the age of 25-30 years and from then on every 3 or 5 years. If human papillomavirus testing is used for screening, most women are invited starting at the age of 35 years (usually not before age 30 years) and from then on every 5 years or more. Irrespective of the test used, women continue participating in screening until the age of 60 or 65 years, and continue beyond this age unless the most recent test results are normal.


Subject(s)
Early Detection of Cancer/standards , Neoplasms/diagnosis , Neoplasms/prevention & control , Practice Guidelines as Topic/standards , Female , Humans , Male
9.
Cancer Prev Res (Phila) ; 6(2): 119-28, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23233733

ABSTRACT

Curcumin, the main constituent of turmeric, is suspected to possess cancer chemopreventive properties. Pharmacokinetic and pharmacodynamic parameters have been reported, but few data exist describing whether methodologies are suitably robust for curcuminoid detection in colonic biopsy specimens. Information on the acceptability of prolonged administration of daily curcumin is not available. This is of vital importance to implement chemoprevention strategies. This study aimed to quantify levels of curcuminoids in colorectal mucosa of patients undergoing colorectal endoscopy or surgical resection and to obtain information on the acceptability and compliance with daily curcumin. Curcumin C3 complex (2.35 g) was administered to patients once daily for 14 days before endoscopic biopsy or colonic resection. Safety and tolerance were monitored. Analysis of curcuminoids in plasma, urine, and colonic mucosa was conducted by ultraperformance liquid chromatography (UPLC)-UV with characterization by liquid chromatography/tandem mass spectrometry (LC/MS-MS). Twenty-four of 26 patients commencing curcumin completed the course. Six patients reported mild gastrointestinal adverse events. Curcuminoids were detectable in nine of 24 plasma samples, 24 of 24 urine samples, and in the colonic mucosa of all 23 biopsied participants. Mean tissue levels were 48.4 µg/g (127.8 nmol/g) of parent curcuminoids. The major conjugate, curcumin glucuronide, was detectable in 29 of 35 biopsies. High levels of topical curcumin persisted in the mucosa for up to 40 hours postadministration. Sixteen participants (67%) stated that they would take curcumin long-term should it be of proven benefit. In summary, pharmacologically active levels of curcumin were recovered from colonic mucosa. The regimen used here seems safe, and patients support its use in long-term trials.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Carcinoma/drug therapy , Colon/metabolism , Colorectal Neoplasms/drug therapy , Curcumin/pharmacokinetics , Patient Acceptance of Health Care , Administration, Oral , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/adverse effects , Biological Availability , Carcinoma/metabolism , Carcinoma/pathology , Carcinoma/urine , Colon/drug effects , Colon/pathology , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Colorectal Neoplasms/urine , Curcumin/administration & dosage , Curcumin/adverse effects , Female , Humans , Intestinal Mucosa/drug effects , Intestinal Mucosa/pathology , Intestinal Mucosa/physiopathology , Male , Middle Aged , Patient Acceptance of Health Care/statistics & numerical data , Patient Compliance/statistics & numerical data , Pilot Projects , Time Factors
10.
Int J Cancer ; 130(12): 2961-73, 2012 Jun 15.
Article in English | MEDLINE | ID: mdl-21792895

ABSTRACT

The International Colorectal Cancer Screening Network was established in 2003 to promote best practice in the delivery of organized colorectal cancer screening programs. To facilitate evaluation of such programs, we defined a set of universally applicable colorectal cancer screening measures and indicators. To test the feasibility of data collection, we requested data on these variables and basic program characteristics from 26 organized full programs and 9 pilot programs in 24 countries. The size of the target population for each program varied considerably from a few thousand to 36 million. The majority of programs used fecal occult blood tests for primary screening, with more using guaiac than immunochemical tests. There was wide variation in the ability of screening programs to report the requested measures and in the values reported. In general, pilot programs were more likely to provide screening measure values than were full programs. As expected, detection rates for polyps and neoplasia were substantially higher in programs screening with endoscopy than in those using fecal occult blood tests. It is hoped that the screening measures and indicators, once revised in the light of this survey, will be adopted and used by existing programs and those in the early planning stages, allowing international comparison with the goal of improved colorectal cancer screening quality.


Subject(s)
Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/prevention & control , Early Detection of Cancer/methods , Early Detection of Cancer/standards , Guaiac , Humans , Mass Screening/methods , Mass Screening/standards , Occult Blood , Reference Standards
11.
J Natl Cancer Inst ; 103(17): 1310-22, 2011 Sep 07.
Article in English | MEDLINE | ID: mdl-21852264

ABSTRACT

BACKGROUND: A single flexible sigmoidoscopy at around the age of 60 years has been proposed as an effective strategy for colorectal cancer (CRC) screening. METHODS: 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. RESULTS: 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. CONCLUSION: A single flexible sigmoidoscopy screening between ages 55 and 64 years was associated with a substantial reduction of CRC incidence and mortality.


Subject(s)
Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/epidemiology , Early Detection of Cancer/methods , Mass Screening/methods , Sigmoidoscopy , Colorectal Neoplasms/mortality , Colorectal Neoplasms/prevention & control , Female , Follow-Up Studies , Humans , Incidence , Italy/epidemiology , Male , Middle Aged , Odds Ratio , Patient Compliance , Sigmoidoscopy/standards , Surveys and Questionnaires , Time Factors
12.
Prev Med ; 51(6): 505-8, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20950640

ABSTRACT

OBJECTIVE: The screening context may provide a "teachable moment" for promoting health behaviours. The present study examined the impact on diet, alcohol and physical activity of providing individually-tailored advice in the context of flexible sigmoidoscopy (FS) screening. METHOD: Adults (n=365) aged 58-59 years who attended FS screening between 2006 and 2008 and had no abnormalities detected were randomised to one of three groups: (i) control (usual care); (ii) standard leaflet on healthy lifestyle; or (iii) standard leaflet plus brief, tailored feedback based on information from the pre-screening questionnaire. A 6-month follow-up questionnaire assessed group differences in fruit and vegetable consumption, alcohol intake and physical activity. RESULTS: More people in the tailored group were meeting the 5-a-day fruit and vegetable recommendation at 6 months (OR: 2.28, CI[1.09, 4.76]). For physical activity there was a non-significant trend towards meeting current activity guidelines in the tailored group (OR: 1.26, CI[0.62, 2.55]). Alcohol intake was low overall and did not change in any group. CONCLUSION: Tailored advice given in the context of cancer screening may provide an opportunity to improve dietary behaviours. Further research is needed to determine whether screening provides a unique "teachable moment" or if similar effects can be achieved in other health settings.


Subject(s)
Colorectal Neoplasms/prevention & control , Counseling/methods , Health Promotion , Life Style , Adult , Alcohol Drinking , Colorectal Neoplasms/diagnosis , Diet , Early Detection of Cancer/methods , Humans , London , Motor Activity , Pilot Projects , Risk Reduction Behavior , Sigmoidoscopy
13.
J Med Screen ; 17(3): 152-7, 2010.
Article in English | MEDLINE | ID: mdl-20956726

ABSTRACT

The International Colorectal Cancer Screening Network (ICRCSN) is a global consortium of initiatives delivering organized colorectal cancer (CRC) screening to their populations. The aim of the Network is to promote improvements in quality assurance (QA) and programme evaluation to maximize the benefit and to minimize the risk associated with CRC screening. ICRCSN currently includes 41 member initiatives from 27 countries. The ICRCSN held its second international meeting in Oxford in September 2008 with representatives from 24 countries. This report summarizes the presentations and discussions, the feedback from participants on their current and future needs and the potential role of the ICRCSN in supporting those needs.


Subject(s)
Colorectal Neoplasms/diagnosis , Early Detection of Cancer/standards , Mass Screening/standards , Humans , Mass Screening/methods
14.
Lancet ; 375(9726): 1624-33, 2010 May 08.
Article in English | MEDLINE | ID: mdl-20430429

ABSTRACT

BACKGROUND: Colorectal cancer is the third most common cancer worldwide and has a high mortality rate. We tested the hypothesis that only one flexible sigmoidoscopy screening between 55 and 64 years of age can substantially reduce colorectal cancer incidence and mortality. METHODS: This randomised controlled trial was undertaken in 14 UK centres. 170 432 eligible men and women, who had indicated on a previous questionnaire that they would accept an invitation for screening, were randomly allocated to the intervention group (offered flexible sigmoidoscopy screening) or the control group (not contacted). Randomisation by sequential number generation was done centrally in blocks of 12, with stratification by trial centre, general practice, and household type. The primary outcomes were the incidence of colorectal cancer, including prevalent cases detected at screening, and mortality from colorectal cancer. Analyses were intention to treat and per protocol. The trial is registered, number ISRCTN28352761. FINDINGS: 113 195 people were assigned to the control group and 57 237 to the intervention group, of whom 112 939 and 57 099, respectively, were included in the final analyses. 40 674 (71%) people underwent flexible sigmoidoscopy. During screening and median follow-up of 11.2 years (IQR 10.7-11.9), 2524 participants were diagnosed with colorectal cancer (1818 in control group vs 706 in intervention group) and 20 543 died (13 768 vs 6775; 727 certified from colorectal cancer [538 vs 189]). In intention-to-treat analyses, colorectal cancer incidence in the intervention group was reduced by 23% (hazard ratio 0.77, 95% CI 0.70-0.84) and mortality by 31% (0.69, 0.59-0.82). In per-protocol analyses, adjusting for self-selection bias in the intervention group, incidence of colorectal cancer in people attending screening was reduced by 33% (0.67, 0.60-0.76) and mortality by 43% (0.57, 0.45-0.72). Incidence of distal colorectal cancer (rectum and sigmoid colon) was reduced by 50% (0.50, 0.42-0.59; secondary outcome). The numbers needed to be screened to prevent one colorectal cancer diagnosis or death, by the end of the study period, were 191 (95% CI 145-277) and 489 (343-852), respectively. INTERPRETATION: Flexible sigmoidoscopy is a safe and practical test and, when offered only once between ages 55 and 64 years, confers a substantial and longlasting benefit. FUNDING: Medical Research Council, National Health Service R&D, Cancer Research UK, KeyMed.


Subject(s)
Colorectal Neoplasms/prevention & control , Sigmoidoscopy , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Female , Humans , Male , Middle Aged
15.
J Med Screen ; 16(3): 124-30, 2009.
Article in English | MEDLINE | ID: mdl-19805753

ABSTRACT

OBJECTIVES: To examine the psychological impact of being assigned to colonoscopic surveillance following detection of adenomatous polyps at flexible sigmoidoscopy (FS) screening. SETTING: Participants invited for screening in 12 of the 14 study centres in the UK FS Trial. METHODS: A postal survey following FS screening assessed bowel cancer worry, psychological distress, generalized anxiety, bowel symptoms, general practitioner (GP) visits, positive emotional consequences of screening, and reassurance among people with no polyps (n = 26,573), lower-risk polyps removed at FS (n = 7401) and higher-risk polyps who underwent colonoscopy and were either assigned to colonoscopic surveillance (n = 1543) or discharged (n = 183). A sub-sample (n = 6389) also completed a questionnaire prior to screening attendance that measured bowel cancer worry, generalized anxiety, bowel symptoms and GP visits, making it possible to examine longitudinal changes in this group. RESULTS: People offered surveillance reported lower psychological distress and anxiety than those with either no polyps or lower-risk polyps. The surveillance group also reported more positive emotional benefits of screening than the other outcome groups. Post-screening bowel cancer worry and bowel symptoms were higher in people assigned to surveillance, but both declined over time, reaching levels observed in either one or both of the other two groups found to have polyps, suggesting these results were a consequence of polyp detection rather than surveillance per se. Few differences were observed between the group assigned surveillance and the group discharged following colonoscopy. CONCLUSION: The results of the current study are broadly reassuring and indicate that referral for colonoscopic surveillance is not associated with adverse psychological consequences.


Subject(s)
Colonoscopy/psychology , Colorectal Neoplasms/psychology , Sigmoidoscopy/psychology , Stress, Psychological/psychology , Adenomatous Polyps/diagnosis , Colonic Polyps/diagnosis , Colonoscopy/methods , Colorectal Neoplasms/diagnosis , Female , Humans , Male , Mass Screening/adverse effects , Mass Screening/psychology , Middle Aged , Sigmoidoscopy/methods , Stress, Psychological/epidemiology , Stress, Psychological/etiology , Surveys and Questionnaires
16.
Health Expect ; 12(1): 18-26, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19250149

ABSTRACT

OBJECTIVE: To explore information needs and preferences on diagnostic bowel tests and elicit preferences for CT colonography (CTC) vs. colonoscopy (CC). BACKGROUND: CTC is a new technology for large-bowel imaging that has been widely assumed to be more acceptable than CC because it is non-invasive. DESIGN: Semi-structured focus groups discussing information choices and procedure preferences. SETTING AND PARTICIPANTS: Non-patient sample of 26 asymptomatic volunteers (mean age 64 years). MAIN OUTCOME MEASURES: Information choices and CC-vs.-CTC preferences were recorded following stepwise presentation of different test attributes. Qualitative thematic analysis was used to examine transcripts of group discussions. RESULTS: On the basis of minimal information about the two tests, a majority of participants preferred CTC to CC (65% vs. 11%), while 24% had no preference. However, once they had received information on all aspects, this was reversed, with 80% of participants preferring CC compared with 8% preferring CTC. Thematic analysis of the discussion showed that participants almost unanimously considered information about test sensitivity to be the most important feature, and perceived relatively modest differences in test sensitivity to be highly significant. Information about risks and side-effects was considered to be the second most important aspect and attracted questions about risks of bowel perforation and health consequences following exposure to radiation. CONCLUSIONS: Patients place high value on quality rather than comfort for medical investigations. This has important implications for the development of educational materials supporting informed choice as well as future directions in refinement of CTC technology.


Subject(s)
Choice Behavior , Colonography, Computed Tomographic , Colonoscopy , Patient Satisfaction , Aged , Female , Focus Groups , Humans , Male , Middle Aged , United Kingdom
17.
Int J Cancer ; 122(6): 1357-67, 2008 Mar 15.
Article in English | MEDLINE | ID: mdl-18033685

ABSTRACT

Although in its infancy, organized screening for colorectal cancer (CRC) in the general population is increasing at regional and national levels. Documenting and describing these initiatives is critical to identifying, sharing and promoting best practice in the delivery of CRC screening. Subsequently, the International Colorectal Cancer Screening Network (ICRCSN) was established in 2003 to promote best practice in the delivery of organized screening programs. The initial aim was to identify and document organized screening initiatives that commenced before May 2004. Each identified initiative was sent 1 questionnaire per screening modality: fecal occult blood test, flexible sigmoidoscopy or total colonoscopy. Information was collected on screening methodology, testing details and initiative status. In total, 35 organized initiatives were identified in 17 countries, including 10 routine population-based screening programs, 9 pilots and 16 research projects. Fecal occult blood tests were the most frequently used screening modality, and total colonoscopy was seldom used as a primary screening test. The eligible age for screening ranged from 40 years old to no upper limit; most initiatives included participants aged 50 to 64. Recruitment was usually done by a mailed invitation or during a visit to a family physician. In conclusion, this is the first investigation describing the delivery of CRC screening protocols to various populations. The work of the ICRCSN is enabling valuable information to be shared and a common nomenclature to be established.


Subject(s)
Colorectal Neoplasms/diagnosis , Mass Screening/methods , Aged , Aged, 80 and over , Colonoscopy , Colorectal Neoplasms/epidemiology , Geography , Humans , Middle Aged , Occult Blood , Sigmoidoscopy
18.
Cancer J ; 13(4): 263-70, 2007.
Article in English | MEDLINE | ID: mdl-17762762

ABSTRACT

PURPOSE: Guidelines for colonoscopic surveillance after the removal of colorectal polyps already exist in the United Kingdom and United States. However, there is a continuing need to build up an evidence base on the likely effect of different follow-up policies for specific current findings. This article reports on the colonoscopic surveillance of a cohort of patients in Taiwan. The risk of various outcomes at the second examination is assessed according to findings at the first examination and the interval between examinations. PATIENTS AND METHODS: Data from baseline and follow-up examinations for 2,287 individuals attending the National Taiwan University Hospital were collected retrospectively. Multivariate logistic regression was used to identify risk factors for the following 4 outcomes: any positive findings; multiple (> or =3) polyps; large (> or =10 mm) polyp(s); or villous adenoma(s) or cancer. The effect of the interval between examinations was assessed in all models. RESULTS: Older age was an independent risk factor for all outcomes. The number of baseline polyps was a significant risk factor for both positive results and multiple polyps, more severe baseline histology was a risk factor for large polyps and villous adenomas/cancer, and larger baseline polyps were a risk factor for large polyps at follow-up. Interval time was only an independent risk factor for villous adenomas/cancer, which tended to be found at shorter follow-up times. The total number of abnormalities found at follow-up was significantly related to the number of follow-up examinations but not to the total follow-up time. CONCLUSIONS: Results suggest that, with the possible exception of subjects with villous adenomas at baseline, most reexaminations can safely be delayed for > or =5 years. In the majority of cases staff at the hospital were correctly identifying those subjects at particularly high risk and assigning shorter follow-up intervals accordingly. Models indicate that many of the findings seen at follow-up were due to missed baseline findings.


Subject(s)
Adenomatous Polyps/diagnosis , Adenomatous Polyps/surgery , Colonic Polyps/diagnosis , Colonic Polyps/surgery , Colonoscopy , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/surgery , Proctoscopy , Adult , Aged , Endoscopy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Taiwan , Treatment Outcome
19.
Carcinogenesis ; 28(4): 875-82, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17082176

ABSTRACT

NADP(H):quinone oxidoreductase 1 (NQO1) and microsomal epoxide hydrolase (EPHX1, also mEH) are attractive candidate enzymes for association with colorectal neoplasia because they metabolize a number of compounds including polycyclic aromatic hydrocarbons (PAHs) that have been linked with colorectal carcinogenesis. We examined the relationship between NQO1C609T, mEH3, mEH4 and risk of sporadic distal colorectal adenomas in one of the largest case-control studies of 946 polyp-free controls and 894 cases, all participants of the UK Flexible Sigmoidoscopy Screening (UKFSS) Trial. The polymorphisms were examined as independent risk factors and evidence for interaction with smoking and alcoholic drinks was sought. The NQO1 609*T allele was positively associated with high-risk adenoma in this population [odds ratio (OR), 1.36; 95% confidence interval (CI), 1.02-1.83]. Elevated risk estimates were seen in smokers independently of the genotype but the association was stronger among current smokers with the heterozygous variant genotype (OR, 4.24; 95% CI, 2.54-7.09). It was reported for the first time that the association between alcohol and colorectal adenoma was modified by NQO1C609T genotype, such that the relation between alcohol and colorectal adenoma was stronger among those with the common C/C genotype (OR, 1.49; 95% CI, 1.11-2.02; P-interaction = 0.024). There was no association between mEH3 and mEH4 variants and colorectal adenoma risk and no effect modification by alcohol and smoking. These findings provide evidence for an important role of the NQO1C609T polymorphism in susceptibility of colorectal adenomas. Alcohol increases risk of colorectal adenoma in carriers of the high-activity genotype possibly through enhanced activation of alcohol-related procarcinogens.


Subject(s)
Adenoma/genetics , Alcohol Drinking , Colorectal Neoplasms/genetics , Epoxide Hydrolases/genetics , NAD(P)H Dehydrogenase (Quinone)/genetics , Polymorphism, Genetic , Smoking , Adenoma/pathology , Aged , Case-Control Studies , Colorectal Neoplasms/pathology , Diet , Female , Genetic Predisposition to Disease , Genotype , Humans , Male , Mass Screening , Middle Aged , Odds Ratio , Risk Factors
20.
Cancer Causes Control ; 17(6): 793-801, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16783607

ABSTRACT

OBJECTIVE: The purpose of this study was to further evaluate the role of low activity MTHFR variants as well as to explore interactive effects between alcoholic drink consumption and MTHFR variants and risk of distal colorectal adenomatous polyps. METHODS: We examined the relationship between MTHFR C677T and A1298C gene polymorphisms and risk of distal adenomas in one of the largest case control studies of 946 polyp-free controls and 894 cases, all participants of the UK Flexible Sigmoidoscopy Screening Trial (UKFSS). RESULTS: Investigation of the effect of the MTHFR C677T polymorphism in this large UKFSS study revealed no overall association on adenoma risk (P>0.05). However the MTHFR 1298C allele was linked, for the first time, to high risk adenomas, although in males only (odds ratio (OR) for A/C+C/C compared with A/A 1.55; 95% confidence interval (CI), 1.08-2.22; P=0.018). CONCLUSIONS: In this, the largest study of these polymorphisms in relation to colorectal adenoma, there was no evidence for an interaction with alcohol in combination with the variant forms of MTHFR (P>0.05).


Subject(s)
5,10-Methylenetetrahydrofolate Reductase (FADH2)/genetics , Adenoma/genetics , Adenomatous Polyps/genetics , Colorectal Neoplasms/genetics , Polymorphism, Single Nucleotide/genetics , Adenoma/enzymology , Aged , Alcohol Drinking , Case-Control Studies , Colorectal Neoplasms/enzymology , Female , Gene Frequency , Genetic Predisposition to Disease , Humans , Male , Mass Screening , Middle Aged , Risk Factors , Sigmoidoscopy/methods
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