Johannes Blom

Toward understanding nonparticipation in sigmoidoscopy screening for colorectal cancer

Understanding the reasons for nonparticipation in cancer screening may give clues about how to improve compliance. However, limited cooperation has hampered research on nonparticipant profiles. We took advantage of Swedens comprehensive demographic and health care registers to investigate characteristics of all participants and nonparticipants in a pilot program for colorectal cancer screening with sigmoidoscopy. A population‐based sample of 1986 Swedish residents 59–61 years old was invited. Registers provided information on each individuals gender, country of birth, marital status, education, income, hospital contacts, place of residence, distance to screening center and cancer within the family. Odds ratios (ORs) with 95% confidence intervals (CIs), modeled with multivariable logistic regression, estimated the independent associations between each background factor and the propensity for nonparticipation after control for the effects of other factors. All statistical tests were 2‐sided. Being male (OR = 1.27, 95% CI = 1.03–1.57, relative to female), unmarried or divorced (OR = 1.69, 95% CI = 1.23–2.30 and OR = 1.49, 95% CI = 1.14–1.95, respectively, relative to married) and having an income in the lowest tertile (OR = 1.68, 95% CI = 1.27–2.23, relative to highest tertile) was associated with increased nonparticipation. Living in the countryside or in small communities and having a documented family history of colorectal cancer was associated with better participation. Distance to the screening center did not significantly affect participation, nor did recent hospital care consumption or immigrant status. To increase compliance, invitations must appeal to men, unmarried or divorced people and people with low socioeconomic status.

Participation rates for organized colorectal cancer screening programmes: an international comparison.

Objective Participation, an indicator of screening programme acceptance and effectiveness, varies widely in clinical trials and population-based colorectal cancer (CRC) screening programmes. We aimed to assess whether CRC screening participation rates can be compared across organized guaiac fecal occult blood test (G-FOBT)/fecal immunochemical test (FIT)-based programmes, and what factors influence these rates. Methods Programme representatives from countries participating in the International Cancer Screening Network were surveyed to describe their G-FOBT/FIT-based CRC screening programmes, how screening participation is defined and measured, and to provide participation data for their most recent completed screening round. Results Information was obtained from 15 programmes in 12 countries. Programmes varied in size, reach, maturity, target age groups, exclusions, type of test kit, method of providing test kits and use, and frequency of reminders. Coverage by invitation ranged from 30–100%, coverage by the screening programme from 7–67.7%, overall uptake/participation rate from 7–67.7%, and first invitation participation from 7–64.3%. Participation rates generally increased with age and were higher among women than men and for subsequent compared with first invitation participation. Conclusion Comparisons among CRC screening programmes should be made cautiously, given differences in organization, target populations, and interpretation of indicators. More meaningful comparisons are possible if rates are calculated across a uniform age range, by gender, and separately for people invited for the first time vs. previously.

Five-year experience of organized colorectal cancer screening in a Swedish population – increased compliance with age, female gender, and subsequent screening round:

Objective To evaluate compliance by age, gender, and screening round in the population based Stockholm/Gotland colorectal cancer screening programme. Methods All individuals aged between 60 and 69 living in the counties of Stockholm and Gotland (Sweden) have, since 2008, successively been included in a colorectal cancer screening programme using biennial faecal occult blood tests (Hemoccult®). Personal invitations including test kits have been sent to home addresses, and individuals with a positive test result have been called to a defined clinic for an assessment colonoscopy. Descriptive statistics have been used to evaluate different aspects of compliance. Results Over the five-year period 2008–2012, more than 200,000 individuals from nine different birth cohorts have been invited, with a compliance rate of approximately 60%, which increased by age, female gender, and subsequent screening round. In total, 4,300 individuals (2.1%) with positive tests were referred to assessment colonoscopy, where 213 colorectal cancers were diagnosed. The compliance with the follow-up colonoscopies varied by year, and ranged from 85.6–92.4%. Conclusion The strong organization of the programme contributed to a high compliance rate, that increased by screening round. The lower participation rate among men and among individuals at younger ages needs further attention.

A 9-Year Follow-up Study of Participants and Nonparticipants in Sigmoidoscopy Screening: Importance of Self-Selection

Background: Self-selection may compromise cost-effectiveness of screening programs. We hypothesized that nonparticipants have generally higher morbidity and mortality than participants. Methods: A Swedish population-based random sample of 1,986 subjects ages 59 to 61 years was invited to sigmoidoscopy screening and followed up for 9 years by means of multiple record linkages to health and population registers. Gender-adjusted cancer incidence rate ratio (IRR) and overall and disease group-specific and mortality rate ratio (MRR) with 95% confidence intervals (95% CI) were estimated for nonparticipants relative to participants. Cancer and mortality rates were also estimated relative to the age-matched, gender-matched, and calendar period-matched Swedish population using standardized incidence ratios and standardized mortality ratios. Results: Thirty-nine percent participated. The incidence of colorectal cancer (IRR, 2.2; 95% CI, 0.8-5.9), other gastrointestinal cancer (IRR, 2.7; 95% CI, 0.6-12.8), lung cancer (IRR, 2.2; 95% CI, 0.8-5.9), and smoking-related cancer overall (IRR, 1.4; 95% CI, 0.7-2.5) tended to be increased among nonparticipants relative to participants. Standardized incidence ratios for most of the studied cancers tended to be >1.0 among nonparticipants and <1.0 among participants. Mortality from all causes (MRR, 2.4; 95% CI, 1.7-3.4), neoplastic diseases (MRR, 1.9; 95% CI, 1.1-3.5), gastrointestinal cancer (MRR, 4.7; 95% CI, 1.1-20.7), and circulatory diseases (MRR, 2.3; 95% CI, 1.2-4.2) was significantly higher among nonparticipants than among participants. Standardized mortality ratio for the studied outcomes tended to be increased among nonparticipants and was generally decreased among participants. Conclusion: Individuals who might benefit most from screening are overrepresented among nonparticipants. This self-selection may attenuate the cost-effectiveness of screening programs on a population level. (Cancer Epidemiol Biomarkers Prev 2008;17(5):1163–8)

Analysis of 39 Crohn's disease risk loci in Swedish inflammatory bowel disease patients

To the Editor: Whether Crohn’s disease (CD) and ulcerative colitis (UC) represent distinct disorders or comprise a continuum is a key question in inflammatory bowel disease (IBD). Recently, genome-wide association studies (GWAS) have identified several susceptibility loci, particularly for CD. This progress has enabled attempts to define the molecular similarity of IBD subtypes by specifically testing CD loci in UC. Here we extend this approach by genotyping a Swedish sample of 736 CD patients (age 49.4 15.9 SD, 50.9% males), 935 UC patients (age 51.6 13.1 SD, 54.2% males) and 1460 common controls (age 49.8 15.6 SD, 35.6% males) for 39 of 40 loci nominally associated with CD in a recent GWAS meta-analysis. IBD patients were recruited at the Karolinska University Hospital, Stockholm, and in other participating centers across Sweden. Diagnosis of IBD (CD or UC) was based on standard clinical, endoscopic, radiologic, and histologic criteria. Control individuals were Swedish healthy blood donors, and subjects free of inflammatory disease enrolled in the Swedish EIRA study of rheumatoid arthritis. Informed consent was obtained from all participants and local ethics committees approved the study. One single nucleotide polymorphism (SNP) was selected at each CD locus based on previous associations and genotyped with iPlex chemistry (www.sequenom.com). The average genotyping success rate was 96.3%, and no marker deviated significantly (P < 0.001) from Hardy–Weinberg equilibrium in controls. SNPs were tested for association with CD and UC by trend tests implemented in PLINK (pngu.mgh.harvard.edu/ purcell/plink), with >80% power to detect odds ratios >1.3 for 90% of the markers (risk allele frequency >0.10). A Bonferroni correction for the number of tested loci (39) was applied, which set P < 0.0013 as the level of significance in our experiment (Table 1). With the exception of IL23R and NOD2, few of the CD loci studied here have been investigated in Swedish CD patients. We replicate associations withstanding correction for multiple testing for SNPs in or near IL23R, IRGM, ZNF365, LRRK2, and C13orf31. Loci showing best nominal significance (P < 0.05) include regions harboring TNFSF18, IL18RAP, JAK2, CUL2, and NKX2-3, whereas other loci consistently replicated across different populations appeared only of marginal (ATG16L1, NOD2, and TNFSF15) or no relevance (C5orf56 and PTPN2) in our sample. In particular, the minor role of NOD2 in Swedish CD has been reported previously, and stems from the low frequency of its risk variants in Scandinavia. Three CD loci were associated with UC in our study after correction for multiple testing: those containing IL23R, MST1, and GSDMB. Interestingly, the latter 2 appeared to be relevant primarily to UC in our sample, an observation that diverges from previous reports in UK patients, where MST1 was found to be associated with both CD and UC, while the region harboring GSDMB did not show evidence of association with UC. One locus, CUL2, showed P-values nearing the Bonferroni significance level, and had similar effects on both CD and UC susceptibility. Finally, although type 2 errors cannot be excluded, another 8 CD loci also recently implicated in UC in different studies only showed nominal significance (C1orf81, BTNL2, JAK2) or were not associated in our sample (ILRAP18, IL12B, LYRM4, CDKAL1, STAT3), despite Swedish control frequencies similar to those of other European populations. Our findings are only partially concordant with previous results, and highlight the importance of assessing the relevance of genetic risk variants in different populations, even within Europe. Several GWA screens have been performed, and others are imminent. These rapidly increasing data promise to more conclusively define the genetic architecture of IBD, and the magnitude of the effects that specific risk alleles have in its various forms, and in different populations.

Sorting out measures and definitions of screening participation to improve comparability: The example of colorectal cancer

Participation is a key indicator of the potential effectiveness of any population-based intervention. Defining, measuring and reporting participation in cancer screening programmes has become more heterogeneous as the number and diversity of interventions have increased, and the purposes of this benchmarking parameter have broadened. This study, centred on colorectal cancer, addresses current issues that affect the increasingly complex task of comparing screening participation across settings. Reports from programmes with a defined target population and active invitation scheme, published between 2005 and 2012, were reviewed. Differences in defining and measuring participation were identified and quantified, and participation indicators were grouped by aims of measure and temporal dimensions. We found that consistent terminology, clear and complete reporting of participation definition and systematic documentation of coverage by invitation were lacking. Further, adherence to definitions proposed in the 2010 European Guidelines for Quality Assurance in Colorectal Cancer Screening was suboptimal. Ineligible individuals represented 1% to 15% of invitations, and variable criteria for ineligibility yielded differences in participation estimates that could obscure the interpretation of colorectal cancer screening participation internationally. Excluding ineligible individuals from the reference population enhances comparability of participation measures. Standardised measures of cumulative participation to compare screening protocols with different intervals and inclusion of time since invitation in definitions are urgently needed to improve international comparability of colorectal cancer screening participation. Recommendations to improve comparability of participation indicators in cancer screening interventions are made.

Results of collagen plug occlusion of anal fistula: a multicentre study of 126 patients

The Biodesign® anal fistula plug was introduced as a means of obliterating the fistula tract and promoting healing through biocompatibility. The results demonstrated unexplained variations from good to bad. This report analysed the results of a retrospective multicentre study.

Interval cancers in a guaiac-based colorectal cancer screening programme: Consequences on sensitivity

Objective To evaluate interval cancers in the population-based colorectal cancer screening programme of Stockholm/Gotland, Sweden. Methods From 2008, individuals aged 60–69 were invited to colorectal cancer screening using biennial guaiac-based faecal occult blood test (Hemoccult®). Interval cancers, defined as colorectal cancer among participants not diagnosed by the screening programme but registered in the Swedish cancer register, were evaluated by cross-checking the screening histories for all cancers in the region 2008–2012. Results Of 203,848 individuals from nine different birth cohorts who participated (∼60%), 4530 (2.2%) tested positive. All invited individuals were followed up for 24 months after invitation. The cancer register reported 557 colorectal cancer, 219 (39.3%) screen-detected cancers and 338 (60.7%) interval cancers, generating both test- and episode sensitivities of approximately 40% and an interval cancer-rate of 17.1/10,000 tests. Among individuals with positive tests without colorectal cancer diagnosed at work-up colonoscopy, 37 interval cancers (10.9%) occurred. There was statistically significant lower sensitivity in women, ranging 22.4–32.2%, compared with 43.2–52.0% in men. Age-group and tumour location were not strongly correlated to screen-detected cancer rates. The programme sensitivity increased by year (20.3–25.0%), with successively more colorectal cancers diagnosed within the expanding programme (11.6–16.2%). Conclusion Interval cancer is a quality indicator of a screening programme. As the interval cancer-rate determined in a well-organized population-based screening programme was actually higher than the screen-detected cancer rate, a change to a more sensitive screening test is indicated. The lower screen-detected cancers among women, and compliance and quality of work-up colonoscopies also need attention.

Once-only flexible sigmoidoscopy screening for adults aged 55–64 years old reduces the incidence of colorectal cancer and colorectal cancer deaths

Commentary on: AtkinWSEdwardsRKralj-HansI.; UK Flexible Sigmoidoscopy Trial Investigators. Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial. Lancet 2010;375:1624–33.