OBJECTIVES:Participation rates in fecal immunochemical test (FIT)-based colorectal cancer (CRC) screening differ across socio-demographic subgroups. The largest health gains could be achieved in subgroups with low participation rates and high risk of CRC. We investigated the CRC risk within different socio-demographic subgroups with low participation in the Dutch CRC screening program. STUDY DESIGN:Population-based cohort study. METHODS:All individuals invited for the Dutch CRC screening program in 2018 and 2019 were included. Data from a previous study, including screening data and demographic characteristics, were augmented with CRC diagnoses in 2018 and 2019. A multivariable logistic regression was used to assess the association between socio-demographic factors and risk of CRC. RESULTS:Overall participation was 72.3% and age-adjusted CRC incidence was 30.3 per 10,000 individuals. Males showed lower participation (69.7 %) but had a higher-than-average CRC risk (35.1). The difference in CRC risk between males and females was less pronounced among non-participants (OR: 1.28, 95% CI: 1.20-1.36) than participants (OR: 1.41, 95% CI: 1.35-1.47). Lower income groups also had lower participation (down to 60.0 %) and higher risk of CRC (down to 30.7), but the difference in CRC risk between low-income groups and high-income groups was only significant among participants (OR lowest vs highest quintile: 1.22, 95% CI: 1.14-1.32). Conversely, individuals with a Turkish/Moroccan migration background had lower participation (48.7 %), but their CRC risk was also lower (18.8; OR: 0.54, 95% CI: 0.46-0.63). CONCLUSIONS:CRC risk varies significantly between low-participation groups in the Dutch CRC screening program. Interventions should prioritize the most vulnerable groups, considering both participation and risk of CRC.

Gastric and colorectal cancer (CRC) are both one of the most common cancers worldwide. In many countries fecal immunochemical tests (FIT)-based CRC screening has been implemented. We investigated if FIT can also be applied for detection of H. pylori, the main risk factor for gastric cancer. This prospective study included participants over 18 years of age referred for urea breath test (UBT). Patients were excluded if they had used antibiotics/bismuth in the past 4 weeks, or a proton pomp inhibitor (PPI) in the past 2 weeks. Participants underwent UBT, ELISA stool antigen test in standard feces tube (SAT), ELISA stool antigen test in FIT tube (Hp-FIT), and blood sampling, and completed a questionnaire on user friendliness. UBT results were used as reference. A total of 182 patients were included (37.4% male, median age 52.4 years (IQR 22.4)). Of these, 60 (33.0%) tested H. pylori positive. SAT and Hp-FIT showed comparable overall accuracy 71.1% (95%CI 63.2–78.3) vs. 77.6% (95%CI 70.4–83.8), respectively (p = 0.97). Sensitivity of SAT was 91.8% (95%CI 80.4–97.7) versus 94.2% (95%CI 84.1–98.9) of Hp-FIT (p = 0.98). Serology scored low with an overall accuracy of 49.7% (95%CI 41.7–57.7). Hp-FIT showed the highest overall user convenience. FIT can be used with high accuracy and sensitivity for diagnosis of H. pylori and is rated as the most convenient test. Non-invasive Hp-FIT test is highly promising for combined upper and lower gastrointestinal (pre-) cancerous screening. Further research should investigate the clinical implications, benefits and cost-effectiveness of such an approach.

Therapeutic drug monitoring of adalimumab is useful to optimise the treatment of patients with inflammatory diseases, such as inflammatory bowel disease. A recent study reported the potential benefit of rapid testing for adalimumab concentrations as early as Week 4, using the RIDA®QUICK ADM Monitoring, to help predict later anti-drug antibody development and the need for dose intensification.1 Nevertheless, data regarding the performance of a rapid test in a routine clinical laboratory are scarce. In this study, we therefore aimed to evaluate and confirm the performance of the RIDA®QUICK ADM Monitoring in an routine diagnostics laboratory, the Gastroenterology and Hepatology Diagnostic Laboratory (Erasmus MC, Rotterdam, the Netherlands). A total of 56 anonymized patient samples were analysed using the RIDA®QUICK ADM Monitoring (R-Biopharm AG, Darmstadt, Germany) and results compared with a conventional ELISA, the apDia Adalimumab ELISA (apDia, Turnhout), also distributed by R-Biopharm as RIDASCREEN® ADM Monitoring. Six quality control samples, with a concentration within the assay analytical range, were used to verify the assay performance. The RIDA®QUICK ADM Monitoring was shown to correlate very well with the apDia Adalimumab ELISA (Pearson r coefficient of 0.91). The absolute bias between the two methods was 1.6 ± 2.2 µg/ml (Figure 1). Figure 1. Bland-Altman plot showing the absolute difference between the apDia Adalimumab ELISA and the RIDA®QUICK ADM Monitoring vs. the average of the two methods. The average bias was 1.6 ± 2.2 µg/ml (n = 56). Linear regression analysis showed no systemic or proportional bias between the RIDA®QUICK ADM Monitoring and apDia Adalimumab ELISA (y = 0.89 (±0.06)x – 0.48 (±0.69); y = RIDA®QUICK ADM Monitoring; x = apDia Adalimumab ELISA). In this study, we confirmed the performance of the RIDA®QUICK ADM Monitoring in a routine diagnostics laboratory, revealing a very good agreement with a conventional ELISA technique. The RIDA®QUICK ADM Monitoring allows to measure one sample at a time and has a turn-around time of only 20 min. Reference 1. Verstockt B, Moors G, Bian S, et al. Influence of early adalimumab serum levels on immunogenicity and long-term outcome of anti-TNF naive Crohn’s disease patients: the usefulness of rapid testing. Aliment Pharmacol Ther, 2018;48:731–739.

The number of octogenarians with rectal adenocarcinoma is growing. Current guidelines seem difficult to apply on octogenarians which may result in non-adherence. The aim of this retrospective cohort study is to give insight in occurrence of treatment-related complications, hospitalisations and survival among octogenarians treated according to guidelines versus octogenarians treated otherwise. 108 octogenarians with rectal adenocarcinoma were identified by screening of medical records. 22 patients were excluded for treatment process analysis because of stage IV disease or unknown stage. Baseline characteristics, diagnostic process, received treatment, motivation for deviation from guidelines, complications, hospitalisations and date of death were documented. Patients were divided in two groups depending on adherence to treatment guidelines. Differences in baseline characteristics, treatment-related complications and survival between both groups were evaluated. Diagnosis and treatment according to guidelines occurred in 95 and 54% of the patients, respectively. When documented, patient's preference and comorbidities were major reasons to deviate from guidelines. 66% of patients who were treated according to guidelines experienced complications versus 34% of those treated otherwise (p = 0.02). After adjustment for differences in age and polypharmacy, this association was not significant. Patients treated according to the guideline had better survival 18 months after diagnosis (80 versus 56%, p = 0.02). Treating octogenarians with rectal cancer according to guidelines seem to lead to better overall survival, but may lead to a high risk of complications. This may jeopardise quality of life. More and prospective studies in octogenarians with rectal cancer are needed to customize guidelines for these patients.

Objective Colorectal cancer screening programmes are implemented worldwide; many are based on faecal immunochemical testing (FIT). The aim of this study was to evaluate two frequently used FITs on participation, usability, positivity rate and diagnostic yield in population-based FIT screening. Design Comparison of two FITs was performed in a fourth round population-based FIT-screening cohort. Randomly selected individuals aged 50–74 were invited for FIT screening and were randomly allocated to receive an OC -Sensor (Eiken, Japan) or faecal occult blood (FOB)-Gold (Sentinel, Italy) test (March–December 2014). A cut-off of 10 µg haemoglobin (Hb)/g faeces (ie, 50 ng Hb/mL buffer for OC-Sensor and 59 ng Hb for FOB-Gold) was used for both FITs. Results In total, 19 291 eligible invitees were included (median age 61, IQR 57–67; 48% males): 9669 invitees received OC-Sensor and 9622 FOB-Gold; both tests were returned by 63% of invitees (p=0.96). Tests were non-analysable in 0.7% of participants using OC-Sensor vs 2.0% using FOB-Gold (p<0.001). Positivity rate was 7.9% for OC-Sensor, and 6.5% for FOB-Gold (p=0.002). There was no significant difference in diagnostic yield of advanced neoplasia (1.4% for OC-Sensor vs 1.2% for FOB-Gold; p=0.15) or positive predictive value (PPV; 31% vs 32%; p=0.80). When comparing both tests at the same positivity rate instead of cut-off, they yielded similar PPV and detection rates. Conclusions The OC-Sensor and FOB-Gold were equally acceptable to a screening population. However, FOB-Gold was prone to more non-analysable tests. Comparison between FIT brands is usually done at the same Hb stool concentration. Our findings imply that for a fair comparison on diagnostic yield between FIT's positivity rate rather than Hb concentration should be used. Trial registration number NTR5385; Results.

HBeAg seroconversion in HBV patients is considered an important event. We determined precore (PC) and base core promoter (BCP) mutations in 137 HBeAg-positive nucleos(t)ide analogues (NA) treated patients by INNO-LiPA HBV PreCore assay (Innogenetics). The majority of patients with nongenotype A had PC/BCP mutants present at baseline (P=0.02). During 29months of therapy, 45 patients achieved HBeAg seroconversion. Probability of HBeAg seroconversion was higher in patients with PC and/or BCP mutants (P=0.01). After HBeAg seroconversion, patients with BCP mutants had more HBeAg relapse (P=0.07), and PC mutants less often achieved HBV DNA<2000IU/mL (P=0.07).

after a decrease at T30, progressively increased up to T120, where they reached values higher than baseline (Vmax: T0 52.8±36.8cm/s, T30 45.4±17.4cm/s, T60 55.6±23.5 cm/s, T120 73.7±44.2cm/s; p: 0.04; Vmean: T0 36.4±27cm/s, T30 28.3±11.7 cm/s, T60 35.6±16 cm/s, T120 48.1±29 cm/s; p: 0.04).The Resistivity Index (RI) of the hepatic artery increased from T30 after meal (T0 0.62±0.07cm/s, T30 0.74±0.08cm/s; p: 0.02, T60 0.73±0.05cm/s; p: 0.02) and decreased at T120 (T120 0.69±0.08cm/s p: >0.05).Liver and spleen diameters did not show variations.Conclusions: LS transiently increases postprandially in relation to the meal-induced haemodynamic variations in portal and hepatic arterial flow, and returns to baseline 120 after the meal.LS evaluation should hence be performed fasting or at least 120 after a meal.

As chronic hepatitis C patients with progressive disease can present themselves with normal ALT levels, more sensitive biomarkers are needed. MicroRNAs are newly discovered small noncoding RNAs that are stable and detectable in the circulation. We aimed to investigate the association between hepatocyte-derived microRNAs in serum and liver injury in patients with chronic hepatitis C. The hepatocyte-derived miR-122 and miR-192 were analysed in sera of 102 chronic HCV-infected patients and 24 healthy controls. Serum levels of miR-122 and miR-192 correlated strongly with ALT (R = 0.67 and R = 0.65, respectively, P < 0.001 for both). Median levels of miR-122 and miR-192 in HCV-infected patients were 23 times and 8 times higher as in healthy controls (P < 0.001 for both). Even within the HCV-infected patients with a normal ALT (n = 38), the levels of miR-122 and miR-192 were 12 times and 4 times higher compared with healthy controls (P < 0.001 for both). Multivariate logistic regression analyses showed that only miR-122 was a significant predictor of the presence of chronic HCV infection (P = 0.026). Importantly, miR-122 was also superior in discriminating chronic HCV-infected patients with a normal ALT from healthy controls compared with the ALT level (AUC = 0.97 vs AUC = 0.78, P = 0.007). In conclusion, our study confirmed that liver injury is associated with high levels of hepatocyte-derived microRNAs in circulation and demonstrated that in particular miR-122 is a sensitive marker to distinguish chronic hepatitis C patients from healthy controls. More sensitive blood markers would benefit especially those patients with minor levels of hepatocellular injury, who are not identified by current screening with ALT testing.

OBJECTIVES:Patients with Barrett's esophagus (BE) have an increased risk of developing esophageal adenocarcinoma (EAC). As the absolute risk remains low, there is a need for predictors of neoplastic progression to tailor more individualized surveillance programs. The aim of this study was to identify such predictors of progression to high-grade dysplasia (HGD) and EAC in patients with BE after 4 years of surveillance and to develop a prediction model based on these factors. METHODS:We included 713 patients with BE (≥ 2 cm) with no dysplasia (ND) or low-grade dysplasia (LGD) in a multicenter, prospective cohort study. Data on age, gender, body mass index (BMI), reflux symptoms, tobacco and alcohol use, medication use, upper gastrointestinal (GI) endoscopy findings, and histology were prospectively collected. As part of this study, patients with ND underwent surveillance every 2 years, whereas those with LGD were followed on a yearly basis. Log linear regression analysis was performed to identify risk factors associated with the development of HGD or EAC during surveillance. RESULTS:After 4 years of follow-up, 26/713 (3.4%) patients developed HGD or EAC, with the remaining 687 patients remaining stable with ND or LGD. Multivariable analysis showed that a known duration of BE of ≥ 10 years (risk ratio (RR) 3.2; 95% confidence interval (CI) 1.3-7.8), length of BE (RR 1.11 per cm increase in length; 95% CI 1.01-1.2), esophagitis (RR 3.5; 95% CI 1.3-9.5), and LGD (RR 9.7; 95% CI 4.4-21.5) were significant predictors of progression to HGD or EAC. In a prediction model, we found that the annual risk of developing HGD or EAC in BE varied between 0.3% and up to 40%. Patients with ND and no other risk factors had the lowest risk of developing HGD or EAC (<1%), whereas those with LGD and at least one other risk factor had the highest risk of neoplastic progression (18-40%). CONCLUSIONS:In patients with BE, the risk of developing HGD or EAC is predominantly determined by the presence of LGD, a known duration of BE of ≥10 years, longer length of BE, and presence of esophagitis. One or combinations of these risk factors are able to identify patients with a low or high risk of neoplastic progression and could therefore be used to individualize surveillance intervals in BE.

OBJECTIVE:The population benefit of screening depends not only on the effectiveness of the test, but also on adherence, which, for colorectal cancer (CRC) screening remains low. An advance notification letter may increase adherence, however, no population-based randomized trials have been conducted to provide evidence of this. METHOD:In 2008, a representative sample of the Dutch population (aged 50-74 years) was randomized. All 2493 invitees in group A were sent an advance notification letter, followed two weeks later by a standard invitation. The 2507 invitees in group B only received the standard invitation. Non-respondents in both groups were sent a reminder 6 weeks after the invitation. RESULTS:The advance notification letters resulted in a significantly higher adherence (64.4% versus 61.1%, p-value 0.019). Multivariate logistic regression analysis showed no significant interactions between group and age, sex, or socio-economic status. Cost analysis showed that the incremental cost per additional detected advanced neoplasia due to sending an advance notification letter was € 957. CONCLUSION:This population-based randomized trial demonstrates that sending an advance notification letter significantly increases adherence by 3.3%. The incremental cost per additional detected advanced neoplasia is acceptable. We therefore recommend that such letters are incorporated within the standard CRC-screening invitation process.

This issue of Gut reports a very interesting article by Hol and colleagues1 (see page 62) which compares the results of a randomised controlled trial (RCT) of a 3-day guaiac-based faecal occult blood test (gFOBT), a 1-day immunochemical faecal occult blood test (FIT), and flexible sigmoidoscopy (SIG) for the screening of colorectal cancer (CRC). This is the first study to compare the three tests contemporarily by an RCT as far compliance and detection rates (DRs) of tests are concerned. For this reason the paper is positioned at a crucial point in the discussion on CRC screening. Several RCTs have been successfully concluded demonstrating the efficacy of gFOBT screening in reducing CRC mortality (range, 13–33%).2 Considering the limited impact of the gFOBT on mortality reduction, FITs have been introduced and several studies3 have demonstrated that FITs are more accurate than the gFOBT. Moreover, in the last two decades SIG has been proposed as a screening test for CRC based on the assumption that distal colonic significant neoplasia may be predictive of possible proximal neoplasia.4 5 6 In the existing literature SIG DRs proved to be consistently higher than FIT or gFOBT DRs as far as single rank of screening was considered.7 Participation in SIG screening is usually low, at about 30%,5 6 7 with the notable exception …

Background: Perceived burden of colorectal cancer (CRC) screening is an important determinant of participation in subsequent screening rounds and therefore crucial for the effectiveness of a screening programme. This study determined differences in perceived burden and willingness to return for a second screening round among participants of a randomised population-based trial comparing a guaiac-based faecal occult blood test (gFOBT), a faecal immunochemical test (FIT) and flexible sigmoidoscopy (FS) screening.Methods: A representative sample of the Dutch population (aged 50-74 years) was randomised to be invited for gFOBT, FIT and FS screening. A random sample of participants of each group was asked to complete a questionnaire about test burden and willingness to return for CRC screening.Results: In total 402/481 (84%) gFOBT, 530/659 (80%) FIT and 852/1124 (76%) FS screenees returned the questionnaire. The test was reported as burdensome by 2.5% of gFOBT, 1.4% of FIT and 12.9% of FS screenees (comparing gFOBT versus FIT p = 0.05; versus FS p < 0.001). In total 94.1% of gFOBT, 94.0% of FIT and 83.8% of FS screenees were willing to attend successive screening rounds (comparing gFOBT versus FIT p = 0.84; versus FS p < 0.001). Women reported more burden during FS screening than men (18.2% versus 7.7%; p < 0.001).Conclusions: FIT slightly outperforms gFOBT with a lower level of reported discomfort and overall burden. Both FOBTs are better accepted than FS screening. All three tests have a high level of acceptance, which may affect uptake of subsequent screening rounds and should be taken into consideration before implementing a CRC screening programme. (C) 2010 Elsevier Ltd. All rights reserved.

Immunochemical faecal occult blood testing (FIT) provides quantitative test results, which allows optimisation of the cut-off value for follow-up colonoscopy. We conducted a randomised population-based trial to determine test characteristics of FIT (OC-Sensor micro, Eiken, Japan) screening at different cut-off levels and compare these with guaiac-based faecal occult blood test (gFOBT) screening in an average risk population. A representative sample of the Dutch population (n=10 011), aged 50–74 years, was 1 : 1 randomised before invitation to gFOBT and FIT screening. Colonoscopy was offered to screenees with a positive gFOBT or FIT (cut-off 50 ng haemoglobin/ml). When varying the cut-off level between 50 and 200 ng ml−1, the positivity rate of FIT ranged between 8.1% (95% CI: 7.2–9.1%) and 3.5% (95% CI: 2.9–4.2%), the detection rate of advanced neoplasia ranged between 3.2% (95% CI: 2.6–3.9%) and 2.1% (95% CI: 1.6–2.6%), and the specificity ranged between 95.5% (95% CI: 94.5–96.3%) and 98.8% (95% CI: 98.4–99.0%). At a cut-off value of 75 ng ml−1, the detection rate was two times higher than with gFOBT screening (gFOBT: 1.2%; FIT: 2.5%; P<0.001), whereas the number needed to scope (NNscope) to find one screenee with advanced neoplasia was similar (2.2 vs 1.9; P=0.69). Immunochemical faecal occult blood testing is considerably more effective than gFOBT screening within the range of tested cut-off values. From our experience, a cut-off value of 75 ng ml−1 provided an adequate positivity rate and an acceptable trade-off between detection rate and NNscope.

Background and aim: Barrett esophagus (BE) is a premalignant disorder, predisposing to esophageal adenocarcinoma (EAC). The latter is assumed to develop through the cascade of intestinal metaplasia (IM), low-grade dysplasia (LGD) and high-grade dysplasia (HGD). For that reason, regular endoscopic and histologic follow-up is recommended in BE patients. It has been reported that the incidence of EAC and of BE is increasing over the last decades in Western countries, however these reported incidences show considerable variation. We evaluated the incidence of progression from no dysplasia (ND) towards LGD and from ND or LGD towards HGD and EAC in a Dutch BE cohort. Methods: In this prospective, multicenter cohort study, 783 BE patients were included with ND (n = 664) or LGD (n = 119) at baseline and a BE segment (with a histologic diagnosis of IM) of 2 cm or more. Endoscopic and histologic surveillance was performed according to the ACG guidelines (2002). The annual risk of progression towards LGD, HGD and EAC was analyzed with incidence densities. Results: After 2 years of follow-up, 80 (10%) patients were lost-to-follow-up. Of these, 15 patients had died from other causes than EAC and 65 patients refused further participation. The mean age (± SD) at baseline (n = 703) was 60.3 ± 11.1 years with 73% males. Five hundred-sixty-one of the remaining 703 (80%) BE patients were known with BE prior to this study with a median follow-up of 4.0 years (interquartile range 2.0 to 8.0). Mean (± SD) follow-up time in this study was 2.0 ± 0.4 years with a total of 1192 patient-years of follow-up for patients with only baseline ND and a total of 1383 patient-years of follow-up for patients with ND and LGD. Thirty-two of 604 BE patients with baseline ND developed LGD during 1192 patient-years of follow-up, which equals one LGD case per 37 patient-years. HGD developed in 11/703 BE patients, and EAC in 11/703 BE patients during 1383 patient-years of follow-up, which corresponds to one HGD case per 125 patient-years and one EAC case per 125 patient-years. This equals 22/703 BE patients with neoplastic progression during follow-up, yielding an incidence of one case HGD or EAC per 63 patient-years. Conclusion: In BE patients with a columnar BE-segment of two cm or more and ND or LGD at baseline, the annual risk of progression towards HGD or EAC is 1.6%. BE patients with baseline ND had an annual risk of developing LGD of 2.7%. Longer follow-up is however needed to accurately establish the natural history of BE.