[Lung cancer screening is not the right answer, a ban on smoking is]. / Bevolkingsonderzoek naar longkanker is niet het juiste antwoord.

The Minister of Health, Welfare and Sport of the Netherlands has asked the Dutch Health Council an advice on lung cancer screening. But even the target group will gain little: yearly approximately 90 fewer lung cancer deaths of over 8,000 due to smoking, and most if not all of them will die as quickly from other consequences of smoking. Moreover, lung cancer screening harms the population screened, as well as our society and health care providers. So how to stop this public health problem? Ban smoking. The health effects are much wider than lung cancer and start immediately. After 10 years, lung cancer risk of ex-smokers will be halved. After a few decades, over 8,000 people would not die from lung cancer anymore each year and, on top of that, over 10,000 less persons would die from the many other consequences of smoking. So only banning smoking is the answer -starting lung cancer screening is not a healthy answer.

Prospective cross-sectional study on faecal immunochemical tests: sex specific cut-off values to obtain equal sensitivity for colorectal cancer?

BACKGROUND: Faecal immunochemical tests (FITs) are commonly used in colorectal cancer (CRC) screening. Diagnostic accuracy of FIT differs between males and females. This so far unexplained difference could result in a dissimilarity in screening outcome between both sexes. The aim of this study is to compare sensitivity and specificity of a FIT between males and females, and study potential explanatory variables. METHODS: In this cross-sectional study, data were prospectively collected. 3,022 subjects performed a FIT prior to complete colonoscopy. Sensitivity, specificity, and ROC curves were compared for both sexes. Potential explanatory variables of the relation between sensitivity and sex were explored. RESULTS: At all cut-off values, FIT sensitivity for CRC was higher (range 13-23%) and specificity was lower (range 2-4%) in males compared to females. At 75 ng/ml, sensitivity for CRC was 93% in males compared to 71% in females (p = 0.03), and specificity was 90% in males compared to 93% in females (p = <0.05). For advanced adenomas, males had a slightly higher sensitivity and lower specificity (not significant). At 75 ng/ml, sensitivity for advanced adenomas was 33% in males compared to 29% in females (p = 0.46), and specificity was 93% in males compared to 95% in females (p = 0.22). ROC curves were similar for both sexes, and equal combinations of sensitivity and specificity could be achieved by adjusting the cut-off values. For CRC, the difference in sensitivity could not be explained by age or location of the tumour. CONCLUSIONS: FIT has a higher sensitivity and a lower specificity for CRC in males than in females. Equal test characteristics can be achieved by allowing separate cut-off values for both sexes. Location and age do not explain the observed differences in sensitivity.

Antidepressants and gastrointestinal symptoms in the general Dutch adult population.

BACKGROUND: Gastrointestinal symptoms are frequently reported adverse effects of antidepressants, but antidepressants are also a treatment modality in functional gastrointestinal disorders. We aimed to assess the association between antidepressant use and gastrointestinal symptoms in the general adult population. METHODS: We assessed gastrointestinal symptoms, medication use, and comorbidity through structured questionnaires in randomly selected individuals. We compared presence of gastrointestinal symptoms in respondents who reported antidepressant use with those who did not. We used multivariable regression analysis to verify the association between antidepressant use and gastrointestinal symptoms. RESULTS: In total, 16,758 questionnaires were returned and eligible for analysis. Antidepressant use was reported by 701 respondents (4.2%). Gastrointestinal symptoms were more frequently reported by antidepressant users compared with nonusers (40% vs 25%, P < 0.01). This apparent association between antidepressant use and gastrointestinal symptoms did not remain after adjusting for demographic factors, comorbidity, and use of other medications (adjusted odds ratio, 0.94; 95% confidence interval, 0.74-1.18). CONCLUSIONS: In our cross-sectional population-based study, we did not find an association between antidepressant use and gastrointestinal symptoms.

Gastrointestinal symptoms are still prevalent and negatively impact health-related quality of life: a large cross-sectional population based study in The Netherlands.

BACKGROUND: Over the last decades important risk factors for gastrointestinal symptoms have shifted, which may have changed its population prevalence. The aim of this study was to assess the current prevalence of gastrointestinal symptoms, appraise associated factors and assess health-related quality of life in the general population. METHODS: A total of 51,869 questionnaires were sent to a representative sample of the Dutch adult general population in December 2008. Demographic characteristics, gastrointestinal symptoms, health-related quality of life, medication use and co-morbidity were reported. We used multivariable logistic regression analysis to determine factors associated with gastrointestinal symptoms. RESULTS: A total of 18,317 questionnaires were returned, and 16,758 were eligible for analysis. Prevalence of gastrointestinal symptoms was 26%. Most frequent symptoms were bloating (63%), borborygmi (60%) and flatulence (71%). Female gender (adjusted OR (aOR) 1.59, 95% CI 1.43-1.77), asthma/COPD (aOR 1.47, 95% CI 1.21-1.79), use of paracetamol (aOR 1.33, 95% CI 1.20-1.47), antidepressants (aOR 1.56, 95% CI 1.22-2.00) and acid-suppressive medication were independently associated with presence of gastrointestinal symptoms. Age over 65 years (aOR 0.75, 95% CI 0.65-0.87), and use of statins (aOR 0.75, 95% CI 0.61-0.93) were associated with a lower prevalence of gastrointestinal symptoms. Respondents with gastrointestinal symptoms had a lower mean health-related quality of life of 0.81 (SD = 0.21) compared to 0.92 (SD = 0.14) for persons without gastrointestinal symptoms (P<0.01). CONCLUSIONS: Prevalence of gastrointestinal symptoms in the Dutch community is high and associated with decreased health-related quality of life.

Similar fecal immunochemical test results in screening and referral colorectal cancer.

AIM: To improve the interpretation of fecal immunochemical test (FIT) results in colorectal cancer (CRC) cases from screening and referral cohorts. METHODS: In this comparative observational study, two prospective cohorts of CRC cases were compared. The first cohort was obtained from 10 322 average risk subjects invited for CRC screening with FIT, of which, only subjects with a positive FIT were referred for colonoscopy. The second cohort was obtained from 3637 subjects scheduled for elective colonoscopy with a positive FIT result. The same FIT and positivity threshold (OC sensor; ≥ 50 ng/mL) was used in both cohorts. Colonoscopy was performed in all referral subjects and in FIT positive screening subjects. All CRC cases were selected from both cohorts. Outcome measurements were mean FIT results and FIT scores per tissue tumor stage (T stage). RESULTS: One hundred and eighteen patients with CRC were included in the present study: 28 cases obtained from the screening cohort (64% male; mean age 65 years, SD 6.5) and 90 cases obtained from the referral cohort (58% male; mean age 69 years, SD 9.8). The mean FIT results found were higher in the referral cohort (829 ± 302 ng/mL vs 613 ± 368 ng/mL, P = 0.02). Tissue tumor stage (T stage) distribution was different between both populations [screening population: 13 (46%) T1, eight (29%) T2, six (21%) T3, one (4%) T4 carcinoma; referral population: 12 (13%) T1, 22 (24%) T2, 52 (58%) T3, four (4%) T4 carcinoma], and higher T stage was significantly associated with higher FIT results (P < 0.001). Per tumor stage, no significant difference in mean FIT results was observed (screening vs referral: T1 498 ± 382 ng/mL vs 725 ± 374 ng/mL, P = 0.22; T2 787 ± 303 ng/mL vs 794 ± 341 ng/mL, P = 0.79; T3 563 ± 368 ng/mL vs 870 ± 258 ng/mL, P = 0.13; T4 not available). After correction for T stage in logistic regression analysis, no significant differences in mean FIT results were observed between both types of cohorts (P = 0.10). CONCLUSION: Differences in T stage distribution largely explain differences in FIT results between screening and referral cohorts. Therefore, FIT results should be reported according to T stage.

Hemorrhoids detected at colonoscopy: an infrequent cause of false-positive fecal immunochemical test results.

BACKGROUND: Colorectal cancer screening by fecal immunochemical tests (FITs) is hampered by frequent false-positive (FP) results and thereby the risk of complications and strain on colonoscopy capacity. Hemorrhoids might be a plausible cause of FP results. OBJECTIVE: To determine the contribution of hemorrhoids to the frequency of FP FIT results. DESIGN: Retrospective analysis from prospective cohort study. SETTING: Five large teaching hospitals, including 1 academic hospital. PATIENTS: All subjects scheduled for elective colonoscopy. INTERVENTIONS: FIT before bowel preparation. MAIN OUTCOME MEASUREMENTS: Frequency of FP FIT results in subjects with hemorrhoids as the only relevant abnormality compared with FP FIT results in subjects with no relevant abnormalities. Logistic regression analysis to determine colonic abnormalities influencing FP results. RESULTS: In 2855 patients, 434 had positive FIT results: 213 had advanced neoplasia and 221 had FP results. In 9 individuals (4.1%; 95% CI, 1.4-6.8) with an FP FIT result, hemorrhoids were the only abnormality. In univariate unadjusted analysis, subjects with hemorrhoids as the only abnormality did not have more positive results (9/134; 6.7%) compared with subjects without any abnormalities (43/886; 4.9%; P = .396). Logistic regression identified hemorrhoids, nonadvanced polyps, and a group of miscellaneous abnormalities, all significantly influencing false positivity. Of 1000 subjects with hemorrhoids, 67 would have FP results, of whom 18 would have FP results because of hemorrhoids only. LIMITATIONS: Potential underreporting of hemorrhoids; high-risk individuals. CONCLUSIONS: Hemorrhoids in individuals participating in colorectal cancer screening will probably not lead to a substantial number of false-positive test results.

Use of faecal markers in screening for colorectal neoplasia: a European group on tumor markers position paper.

Several randomized controlled trials have shown that population-based screening using faecal occult blood testing (FOBT) can reduce mortality from colorectal neoplasia. Based on this evidence, a number of countries have introduced screening for colorectal cancer (CRC) and high-risk adenoma and many others are considering its introduction. The aim of this article is to critically review the current status of faecal markers as population-based screening tests for these neoplasia. Most of the available faecal tests involve the measurement of either occult blood or a panel of DNA markers. Occult blood may be measured using either the guaiac faecal occult blood test (gFOBT) or a faecal immunochemical test (iFOBT). Although iFOBT may require a greater initial investment, they have several advantages over gFOBT, including greater analytical sensitivity and specificity. Their use results in improved clinical performance and higher uptake rates. Importantly for population screening, some of the iFOBTs can be automated and provide an adjustable cutoff for faecal haemoglobin concentration. However, samples for iFOBT, may be less stable after collection than for gFOBT. For new centres undertaking FOBT for colorectal neoplasia, the European Group on Tumour Markers recommends use of a quantitative iFOBT with an adjustable cutoff point and high throughput analysis. All participants with positive FOBT results should be offered colonoscopy. The panel recommends further research into increasing the stability of iFOBT and the development of improved and affordable DNA and proteomic-based tests, which reduce current false negative rates, simplify sample transport and enable automated analysis.

Colorectal cancer screening comparing no screening, immunochemical and guaiac fecal occult blood tests: a cost-effectiveness analysis.

Comparability of cost-effectiveness of colorectal cancer (CRC) screening strategies is limited if heterogeneous study data are combined. We analyzed prospective empirical data from a randomized-controlled trial to compare cost-effectiveness of screening with either one round of immunochemical fecal occult blood testing (I-FOBT; OC-Sensor®), one round of guaiac FOBT (G-FOBT; Hemoccult-II®) or no screening in Dutch aged 50 to 75 years, completed with cancer registry and literature data, from a third-party payer perspective in a Markov model with first- and second-order Monte Carlo simulation. Costs were measured in Euros (€), effects in life-years gained, and both were discounted with 3%. Uncertainty surrounding important parameters was analyzed. I-FOBT dominated the alternatives: after one round of I-FOBT screening, a hypothetical person would on average gain 0.003 life-years and save the health care system €27 compared with G-FOBT and 0.003 life years and €72 compared with no screening. Overall, in 4,460,265 Dutch aged 50-75 years, after one round I-FOBT screening, 13,400 life-years and €320 million would have been saved compared with no screening. I-FOBT also dominated in sensitivity analyses, varying uncertainty surrounding important effect and cost parameters. CRC screening with I-FOBT dominated G-FOBT and no screening with or without accounting for uncertainty.

Comparison of guaiac and immunological fecal occult blood tests in colorectal cancer screening: the patient perspective.

OBJECTIVE: Colorectal cancer (CRC) screening programs can decide upon the type of fecal occult blood test (FOBT): the guaiac FOBT (g-FOBT) or the immunological FOBT (i-FOBT). The effectiveness of any screening program depends not only on the diagnostic performance of the screening test but also on the compliance and general acceptance of the test by the public. Any decision on the type of FOBT for CRC screening should also take acceptation and perception into account. The aim of the present study was to study differences in patient perception between i-FOBT and g-FOBT and differences in perception and participation rates among relevant subgroups in a population based study. MATERIAL AND METHODS: Differences in patient perception of i-FOBT and g-FOBT and differences in perception and participation rates among relevant subgroups were investigated (n = 20,623) by sending a short questionnaire to all invited to the first Dutch CRC screening trial. RESULTS: i-FOBT was perceived significantly more favorable than g-FOBT. About 1275 (32%) participants reported the g-FOBT not easy to use, not easy to perform, disgusting or shameful compared to 742 (16%) for the i-FOBT (p < 0.001). The participation rate was significantly higher in those who received i-FOBT compared to the g-FOBT group: 6159 of 10,322 (60%) versus 4839 of 10,301 (47%) (p < 0.001). CONCLUSIONS: These findings support the selection of i-FOBT as the more appropriate test for population screening programs.

Exposure to colorectal examinations before a colorectal cancer diagnosis: a case-control study.

OBJECTIVES: To assess the prior exposure to colorectal examinations between colorectal cancer (CRC) patients and matched control participants to estimate the effect of these examinations on the development of CRC and to obtain insight into the background incidence of colorectal examinations. METHODS: A population-based case-control study was conducted within the Dutch Integrated Primary Care Information database over the period 1996-2005. All incident CRC cases were matched with up to 18 controls (n=7,790) for age, sex, index date (date of CRC diagnosis) and follow-up before diagnosis. All colorectal examinations performed in symptomatic participants in the period 0.5-5 years before index date were considered in the analyses. RESULTS: Within the source population of 457 024 persons, we identified 594 incident cases of CRC. In the period 0.5-5 years before index date 2.9% (17 of 594) of the CRC cases had undergone colorectal examinations, compared with 4.4% (346 of 7790) in the control population [odds ratio (ORadj): 0.56, 95% confidence interval (CI): 0.33-0.94]. For left-sided CRC, significantly more controls than cases had undergone a colorectal examination (4.7 vs. 2.0%, respectively, ORadj: 0.36, 95% CI: 0.17-0.76), which was not seen for right-sided CRCs (3.3 vs. 3.9%, respectively, ORadj: 0.98, 95% CI: 0.42-2.25). CONCLUSION: Patients diagnosed with CRC were less likely than controls to have had a colorectal examination in previous years, being more pronounced in patients diagnosed with left-sided CRCs. If diagnostic examinations have a similar protective effect as screening examinations, this finding supports the concept that colorectal examination can have a major impact on the reduction of CRC risk.

[Colorectal cancer screening: immunological test for faecal occult blood preferred]. / Bevolkingsonderzoek naar dikkedarmkanker. Bij voorkeur met een immunologische test op fecaal occult bloed.

In 2003, the European Commission advised the Member States to start colorectal cancer screening. More than 12 million Europeans have been tested to date, not only by means of faecal occult blood testing but often also by opportunistic endoscopy. Nearly all of the screening programmes concerned were opportunistic in nature. The Dutch government is currently considering the implementation of an organised screening programme for the detection of colorectal cancer. The question no longer seems to be whether a screening programme should be started but rather which screening test should be used. We argue that an immunological faecal occult blood test is to be preferred over other screening tests, such as endoscopy.

False negative fecal occult blood tests due to delayed sample return in colorectal cancer screening.

Delayed return of immunochemical fecal occult blood test (iFOBT) samples to a laboratory might cause false negatives because of hemoglobin degradation. Quantitative iFOBT's became increasingly more accepted in colorectal cancer screening. Therefore, we studied the effects of delay between sampling and laboratory delivery on iFOBT performance. IFOBT positivity (>or=50 ng/ml hemoglobin) in colorectal cancer screening participants without delay between sampling and laboratory delivery (<5 days), was compared with positivity in participants with >or=5 and >or=7 days delay. Additionally, positive tests were stored at room temperature and retested 5 times within 10-14 days. The sampling date was reported by 61% (n = 3,767) of the participants: in 19% delay was >or=5 days and in 5% >or=7 days. Compared with no-delay, the adenoma detection rate was already significantly decreased after >or=5 days delay (OR 0.6; 95%CI 0.4-0.9). We retested iFOBT samples of 170 positives of which 139 (82%) had a colonoscopy: 45 (32%) had advanced adenomas (not colorectal cancer) and 8 (6%) had colorectal cancer. Mean daily fecal hemoglobin decrease was 29 ng/ml (S.D. 38 and median 11 ng/ml). In patients with advanced adenomas, hemoglobin in the sample was <50 ng/ml in 5 (11%) 2-3 days after the initial test and in 16 (36%) after 10-14 days. Seven days after the initial test, 2 (25%) colorectal cancer patients became false negative. Both had stage I colorectal cancer and initial values below 100 ng/ml, where the average for stage I is 532 ng/ml. Delay in sample return increased false negative immunochemical FOBT's. Mainly precursor lesions, but also colorectal cancer, will be missed due to delayed sample return.

Proton pump inhibitors and the risk of colorectal cancer.

INTRODUCTION: Proton pump inhibitor (PPI) use is associated with increased serum gastrin levels and bacterial overgrowth, resulting in more toxic bile salt formation. Concern has risen that these factors may increase the risk of developing colorectal neoplasia. AIM: To investigate the association between the use of PPIs and the risk of colorectal cancer. METHODS: A population-based case-control study was conducted within the Dutch Primary Care Information (IPCI) database over the period 1996-2005. Cases with colorectal cancer were matched with up to 20 controls on age, gender, calendar time, and duration of follow-up prior to diagnosis. Cumulative exposure to PPIs was assessed in the 5 yr prior to diagnosis with a 1-yr lag time analysis. We calculated adjusted odds ratios (OR) with 95% confidence intervals (95% CI) using multivariate, conditional logistic regression analysis. RESULTS: Within the source population of 457,024 persons, we identified 595 colorectal cancer cases. The odds of colorectal cancer were not increased among patients ever using PPIs compared with patients who never used PPIs (OR 0.85, 95% CI 0.63-1.16). Also, the use of PPIs for >365 days was not associated with a greater risk of colorectal cancer (OR 0.79, 95% CI 0.44-1.41) compared with nonusers. The odds of colorectal cancer in neither the right nor the left hemicolon were significantly increased in patients using PPIs. CONCLUSION: The present study indicates no association between PPI use and the risk of colorectal cancer. Larger numbers of long-term PPI users are needed to confirm the absence of a risk-increasing effect of long-term PPI exposure.

Open-access upper gastrointestinal endoscopy a decade after the introduction of proton pump inhibitors and helicobacter pylori eradication: a shift in endoscopic findings.

BACKGROUND/AIM: Over the past 15 years, there were considerable changes in factors associated with the development and treatment of upper gastrointestinal symptoms, of which the introduction of proton pump inhibitors and Helicobacter pylori eradication in guidelines for treatment of patients with dyspepsia are the most prominent: findings at open-access upper gastrointestinal endoscopy have not been evaluated properly ever since. This study aims to compare the current prevalence of upper gastrointestinal endoscopic findings to the prevalence 15 years ago. METHODS: Data about endoscopic findings of consecutive patients for the first time referred for open-access upper gastrointestinal endoscopy between January 2002 and December 2004 was collected from medical files. The prevalence of each specific finding was compared with data described in three historical populations about 15 years ago. RESULTS: The current and historical study population consisted of 1,286 and 3,062 subjects, respectively. The prevalence of peptic ulcer disease and duodenitis significantly decreased by 12.6% (95% CI: 14.5-10.7) and 2.9% (95% CI: 4.5-1.3), respectively. On the other hand, the prevalence of reflux esophagitis and Barrett's esophagus both significantly increased by 6.9% (95% CI: 4.2-9.6) and 2.1% (95% CI: 0.8-4.4), respectively. CONCLUSIONS: Compared to 15 years ago, the prevalence of specific findings at open-access upper gastrointestinal endoscopy has changed considerably.