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Testicular cancer survivors (TCS) treated with platinum-based chemotherapy have an increased risk of colorectal cancer (CRC). We determined the yield of colonoscopy in TCS to assess its potential in reducing CRC incidence and mortality. We conducted a colonoscopy screening study among TCS in four Dutch hospitals to assess the yield of colorectal neoplasia. Neoplasia was defined as adenomas, serrated polyps (SPs), advanced adenomas (AAs: ≥10 mm diameter, high-grade dysplasia or ≥25% villous component), advanced serrated polyps (ASPs: ≥10 mm diameter or dysplasia) or CRC. Advanced neoplasia (AN) was defined as AA, ASP or CRC. Colonoscopy yield was compared to average-risk American males who underwent screening colonoscopy (n = 24,193) using a propensity score matched analysis, adjusted for age, smoking status, alcohol consumption and body mass index. A total of 137 TCS underwent colonoscopy. Median age was 50 years among TCS (IQR 43–57) vs 55 years (IQR 51–62) among American controls. A total of 126 TCS were matched to 602 controls. The prevalence of AN was higher in TCS than in controls (8.7% vs 1.7%; P =.0002). Nonadvanced adenomas and SPs were detected in 45.2% of TCS vs 5.5% of controls (P <.0001). No lesions were detected in 46.0% of TCS vs 92.9% of controls (P <.0001). TCS treated with platinum-based chemotherapy have a higher prevalence of neoplasia and AN than matched controls. These results support our hypothesis that platinum-based chemotherapy increases the risk of colorectal neoplasia in TCS. Cost-effectiveness studies are warranted to ascertain the threshold of AN prevalence that justifies the recommendation of colonoscopy for TCS.

Objective To assess the impact of delayed invitation on screen-detected and interval colorectal cancers (CRC) within a faecal immunochemical testing (FIT)-based CRC screening programme. Design All individuals that participated in 2017 and 2018 with a negative FIT and were eligible for CRC screening in 2019 and 2020 were included using individual-level data. Multivariable logistic regression analyses were used to assess the association between either the different time periods (ie, 'before', 'during' and 'after' the first COVID-19 wave) or the invitation interval on screen-detected and interval CRCs. Results Positive predictive value for advanced neoplasia (AN) was slightly lower during (OR=0.91) and after (OR=0.95) the first COVID-19 wave, but no significant difference was observed for the different invitation intervals. Out of all individuals that previously tested negative, 84 (0.004%) had an interval CRC beyond the 24 months since their last invitation. The time period of invitation as well as the extended invitation interval was not associated with detection rates for AN and interval CRC rate. Conclusion The impact of the first COVID-19 wave on screening yield was modest. A very small proportion of the FIT negatives had an interval CRC possibly due to an extended interval, which potentially could have been prevented if they had received the invitation earlier. Nonetheless, no increase in interval CRC rate was observed, indicating that an extended invitation interval up to 30 months had no negative impact on the performance of the CRC screening programme and a modest extension of the invitation interval seems an appropriate intervention.

Background: In 2014, the national population-based colorectal cancer (CRC) screening program was implemented in the Netherlands. Biennial fecal immunochemical testing (FIT) for hemoglobin (Hb) is used at a cut-off of 47 µg Hb per gram feces. The CRC screening program successfully started, with high participation rates and yield of screening. Now that the program has reached a steady state, there is potential to further optimize the program. Previous studies showed that prior fecal Hb (f-Hb) concentrations just below the FIT cut-off are associated with a higher risk for detection of advanced neoplasia (AN) at subsequent screening rounds. We aim to achieve a better balance between the harms and benefits of CRC screening by offering participants tailored invitation intervals based on prior f-Hb concentrations after negative FIT. Methods: This mixed-methods study will be performed within the Dutch national CRC screening program and will consist of: (1) a randomized controlled trial (RCT), (2) focus group studies, and (3) decision modelling. The primary outcome is the yield of AN per screened individual in personalized screening vs. uniform screening. Secondary outcomes are perspectives on, acceptability of and adherence to personalized screening, as well as long-term outcomes of personalized vs. uniform screening. The RCT will include 20,000 participants of the Dutch CRC screening program; 10,000 in the intervention and 10,000 in the control arm. The intervention arm will receive a personalized screening interval based on the prior f-Hb concentration (1, 2 or 3 years). The control arm will receive a screening interval according to current practice (2 years). The focus group studies are designed to understand individuals’ perspectives on and acceptability of personalized CRC screening. Results of the RCT will be incorporated into the MISCAN-Colon model to determine long-term benefits, harms, and costs of personalized vs. uniform CRC screening. Discussion: The aim of t

Background. Emerging evidence suggests a pivotal role for B-cell responses in the natural history of chronic hepatitis B. Serum levels of antibodies to hepatitis B core antigen (anti-HBc) vary across infection stages, but their role in predicting response to antiviral therapy is uncertain. Methods. Anti-HBc levels were assessed before peginterferon (PEG-IFN) therapy in patients with chronic hepatitis B who either started de novo PEG-IFN (n = 299; 195 hepatitis B e antigen [HBeAg] positive) or started PEG-IFN as add-on to an existing nucleo(s)tide analogue backbone (n = 91; all HBeAg-positive). Associations were explored between anti-HBc and (1) serum biomarkers, (2) liver histological findings, and (3) treatment response. Results. We studied 390 patients. The hepatitis B virus (HBV) genotype were A, B, C, and D in 24%, 9%, 16%, and 49%, respectively; 72% of patients were Caucasian. Among currently untreated HBeAg-positive patients, anti-HBc was correlated with HBV DNA, hepatitis B core-related antigen (HBcrAg), hepatitis B surface antigen (HBsAg), and HBV RNA, but not with alanine aminotransferase (ALT). Higher anti-HBc was associated with more severe histological inflammatory activity (P , .001), irrespective of HBeAg status. After de novo PEG-IFN, higher anti-HBc levels were associated with HBeAg loss, sustained response, HBsAg decline, and HBsAg clearance (P, .050). Among patients treated with add-on PEG-IFN, higher anti-HBc was associated with HBeAg loss (P = .01). Conclusions. Serum anti-HBc levels correlate with histological inflammatory activity. Higher anti-HBc levels were associated with favorable treatment outcomes. These findings suggest that anti-HBc could be used to select patients most likely to respond to immunomodulatory therapy.

Background CRC mortality rates are higher for individuals with a lower socioeconomic status (SES). Screening could influence health inequalities. We therefore aimed to investigate SES differences in participation and diagnostic yield of FIT screening. Methods All invitees in 2014 and 2015 in the Dutch national CRC screening programme were included in the analyses. We used area SES as a measure for SES and divided invitees into quintiles, with Quintile 1 being the highest SES. Logistic regression analysis was used to compare the participation rate, positivity rate, colonoscopy uptake, positive predictive value (PPV) and detection rate across the SES groups. Results Participation to FIT screening was significantly lower for Quintile 5 (67.0%) compared to the other Quintiles (73.0% to 75.1%; adjusted OR quintile 5 versus quintile 1: 0.73, 95%CI: 0.72–0.74), as well as colonoscopy uptake after a positive FIT (adjusted OR 0.73, 95%CI: 0.69–0.77). The detection rate per FIT participant for advanced neoplasia gradually increased from 3.3% in Quintile 1 to 4.0% in Quintile 5 (adjusted OR 1.20%, 95%CI 1.16–1.24). As a result of lower participation, the yield per invitee was similar for Quintile 5 (2.04%) and Quintile 1 (2.00%), both being lower than Quintiles 2 to 4 (2.20%-2.28%). Conclusions Screening has the potential to reduce health inequalities in CRC mortality, because of a higher detection in participants with a lower SES. However, in the Dutch screening programme, this is currently offset by the lower participation in this group.