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Background & Aims: For colorectal cancer (CRC) screening to be effective, it is important that screen-detected cancers are found at an early stage. Studies on stage distribution of screen-detected CRC at repeat screening of large population-based fecal immunochemical test (FIT)-based screening programs and the impact of FIT cut-off values on staging currently are lacking., Methods: We obtained data for FIT-positive participants (FIT cut-off, 47 μg hemoglobin/g feces) at their first or second (ie, repeat) screening from the Dutch National Screening Database from 2014 to 2018. Tumor characteristics were acquired through linkage with The Netherlands Cancer Registry. We compared stage at diagnosis (I-II vs III-IV) of CRCs detected at a first or second screening. In addition, we analyzed the hypothetical yield and stage distribution of CRC for different FIT cut-off values up to 250 μg hemoglobin/g feces., Results: At the first and second screenings, respectively, 15,755 and 3304 CRCs were detected. CRCs detected at the first or second screening were equally likely to be stages I to II (66.5% vs 67.7%; relative risk, 1.02; 95% CI, 1.00-1.05). A hypothetical increase of the FIT cut-off value from 47 μg to 250 μg resulted in a reduction of detected CRCs by 88.3% and 79.0% at the first or second screening, respectively. Even then, the majority of detected CRCs (63%-64%) still would be diagnosed at stages I to II., Conclusions: FIT-based screening is effective in downstaging CRC, and also at repeat screening. Increasingly, the FIT cut-off level has a limited impact on the stage distribution of detected CRCs, although it greatly affects CRC detection and thus is important to keep low., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: We set out to evaluate the performance of a multitarget stool DNA (MT-sDNA) in an average-risk colonoscopy-controlled colorectal cancer (CRC) screening population. MT-sDNA stool test results were evaluated against fecal immunochemical test (FIT) results for the detection of different lesions, including molecularly defined high-risk adenomas and several other tumor characteristics., Methods: Whole stool samples (n = 1,047) were prospectively collected and subjected to an MT-sDNA test, which tests for KRAS mutations, NDRG4 and BMP3 promoter methylation, and hemoglobin. Results for detecting CRC (n = 7), advanced precancerous lesions (advanced adenoma [AA] and advanced serrated polyps; n = 119), and non-AAs (n = 191) were compared with those of FIT alone (thresholds of 50, 75, and 100 hemoglobin/mL). AAs with high risk of progression were defined by the presence of specific DNA copy number events as measured by low-pass whole genome sequencing., Results: The MT-sDNA test was more sensitive than FIT alone in detecting advanced precancerous lesions (46% (55/119) vs 27% (32/119), respectively, P < 0.001). Specificities among individuals with nonadvanced or negative findings (controls) were 89% (791/888) and 93% (828/888) for MT-sDNA and FIT testing, respectively. A positive MT-sDNA test was associated with multiple lesions (P = 0.005), larger lesions (P = 0.03), and lesions with tubulovillous architecture (P = 0.04). The sensitivity of the MT-sDNA test or FIT in detecting individuals with high-risk AAs (n = 19) from individuals with low-risk AAs (n = 52) was not significantly different., Discussion: In an average-risk screening population, the MT-sDNA test has an increased sensitivity for detecting advanced precancerous lesions compared with FIT alone. AAs with a high risk of progression were not detected with significantly higher sensitivity by MT-sDNA or FIT.

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., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Systematic evaluation and validation of new prognostic and predictive markers, technologies and interventions for colorectal cancer (CRC) is crucial for optimizing patients' outcomes. With only 5-15% of patients participating in clinical trials, generalizability of results is poor. Moreover, current trials often lack the capacity for post-hoc subgroup analyses. For this purpose, a large observational cohort study, serving as a multiple trial and biobanking facility, was set up by the Dutch Colorectal Cancer Group (DCCG)., Methods/design: The Prospective Dutch ColoRectal Cancer cohort is a prospective multidisciplinary nationwide observational cohort study in the Netherlands (yearly CRC incidence of 15 500). All CRC patients (stage I-IV) are eligible for inclusion, and longitudinal clinical data are registered. Patients give separate consent for the collection of blood and tumor tissue, filling out questionnaires, and broad randomization for studies according to the innovative cohort multiple randomized controlled trial design (cmRCT), serving as an alternative study design for the classic RCT. Objectives of the study include: 1) systematically collected long-term clinical data, patient-reported outcomes and biomaterials from daily CRC practice; and 2) to facilitate future basic, translational and clinical research including interventional and cost-effectiveness studies for both national and international research groups with short inclusion periods, even for studies with stringent inclusion criteria., Results: Seven months after initiation 650 patients have been enrolled, eight centers participate, 15 centers await IRB approval and nine embedded cohort- or cmRCT-designed studies are currently recruiting patients., Conclusion: This cohort provides a unique multidisciplinary data, biobank, and patient-reported outcomes collection initiative, serving as an infrastructure for various kinds of research aiming to improve treatment outcomes in CRC patients. This comprehensive design may serve as an example for other tumor types.

Background: Faecal immunochemical testing (FIT) for colorectal cancer (CRC) screening has suboptimal sensitivity for detecting advanced neoplasia. To increase its performance, FIT could be combined with other risk factors., Aim: To evaluate the incremental yield of a screening programme using a positive FIT or a CRC family history, to offer a diagnostic colonoscopy., Methods: For this post hoc analysis, data were collected in the colonoscopy arm of a colonoscopy or colonography for screening study. In this study, 6600 randomly selected, asymptomatic men and women (50-75 years) were invited for screening colonoscopy. 1112 Participants completed a FIT and a questionnaire prior to colonoscopy. We compared the yield of FIT-only and FIT combined with CRC family history, defined as having one or more first-degree relatives with CRC., Results: At a 10 μg Hb/g faeces FIT-positivity threshold the combined strategy would increase the yield from 36 (3.2%; CI: 2.4-4.5%) to 53 (4.8%; CI: 3.7-6.2%) cases of advanced neoplasia, at the expense of 148 additional negative colonoscopies. Sensitivity in detecting advanced neoplasia would increase from 36% (CI: 26-46%) to 52% (CI: 42-63%), whereas specificity would decrease from 93% (CI: 92-95%) to 79% (CI: 76-81%). The strategy will be preferred if one accepts 8.8 false positives for every additional participant in whom advanced neoplasia can be detected., Conclusions: Offering colonoscopy to those with a positive FIT or CRC family history increases the yield of a FIT-based screening programme. Depending on the number of negative colonoscopies one accepts, this combined approach can be considered for improving CRC screening., (© 2016 John Wiley & Sons Ltd.)

Objective: Since the publication of the first Asia Pacific Consensus on Colorectal Cancer (CRC) in 2008, there are substantial advancements in the science and experience of implementing CRC screening. The Asia Pacific Working Group aimed to provide an updated set of consensus recommendations., Design: Members from 14 Asian regions gathered to seek consensus using other national and international guidelines, and recent relevant literature published from 2008 to 2013. A modified Delphi process was adopted to develop the statements., Results: Age range for CRC screening is defined as 50-75 years. Advancing age, male, family history of CRC, smoking and obesity are confirmed risk factors for CRC and advanced neoplasia. A risk-stratified scoring system is recommended for selecting high-risk patients for colonoscopy. Quantitative faecal immunochemical test (FIT) instead of guaiac-based faecal occult blood test (gFOBT) is preferred for average-risk subjects. Ancillary methods in colonoscopy, with the exception of chromoendoscopy, have not proven to be superior to high-definition white light endoscopy in identifying adenoma. Quality of colonoscopy should be upheld and quality assurance programme should be in place to audit every aspects of CRC screening. Serrated adenoma is recognised as a risk for interval cancer. There is no consensus on the recruitment of trained endoscopy nurses for CRC screening., Conclusions: Based on recent data on CRC screening, an updated list of recommendations on CRC screening is prepared. These consensus statements will further enhance the implementation of CRC screening in the Asia Pacific region., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Introduction: Uptake is an important determinant of the effectiveness of population-based screening. Uptake of colorectal cancer (CRC) screening generally remains sub-optimal., Aim: To determine factors influencing the decision whether to participate or not among individuals invited for faecal occult blood test (FOBT) or flexible sigmoidoscopy (FS) screening., Methods: A questionnaire was sent to a stratified random sample of individuals aged 50-74, previously invited for a randomised CRC screening trial offering FOBT or FS, and a reference group from the same population not previously invited (screening naïve group). The questionnaire assessed reasons for (non)-participation, individuals' characteristics associated with participation, knowledge, attitudes and level of informed choice., Results: The response rate was 75% (n=341/452) for CRC screening participants, 21% (n=676/3212) for non-participants and 38% (n=192/500) for screening-naïve individuals. The main reasons for FOBT and FS participation were acquiring certainty about CRC presence and possible early CRC detection. Anticipated regret and positive attitudes towards CRC screening were strong predictors of actual participation and intention to participate in a next round. The main reason for non-participation in FOBT screening was lack of abdominal complaints. Non-participation in FS screening was additionally influenced by worries about burden. Eighty-one percent of participants and 12% of non-participants made an informed choice on participation., Conclusion: Only 12% of non-participants made an informed choice not to participate. These results imply that governments and/or organizations offering screening should focus on adequately informing and educating target populations about the harms and benefits of CRC screening. This may impact uptake of CRC screening., (Copyright © 2013. Published by Elsevier Ltd.)

Background and Study Aims: The assessment of indications for follow-up colonoscopy may help to improve the allocation of available endoscopy resources. The aim of this study was to assess the timing of early follow-up colonoscopy and surveillance utilization in relation to adenoma detection rate (ADR) at follow-up., Methods: An assessment of the timing and yield of follow-up colonoscopies was performed in patients with non-inflammatory bowel disease (IBD) in a Dutch multicenter study. The primary outcome was the number of patients with a prior (index) colonoscopy. The necessity for follow-up procedures was assessed using the ADR., Results: Of 4800 consecutive patients undergoing a colonoscopy, 1249 non-IBD patients had undergone an index colonoscopy. Of these, follow-up procedures were performed within 1 year in 27 % (331/1249). Excluding incomplete colonoscopy, incomplete polypectomy, or poor bowel preparation on index, the ADR on early follow-up was 4 % for symptomatic and 26 % for asymptomatic patients. Among the asymptomatic patients with a follow-up colonoscopy at > 1 year (n = 463), an ADR of 23 % (108/463) was found. In 27 % of these patients, the observed surveillance intervals were in accordance with American Gastroenterological Association (AGA) surveillance recommendations; 60 % were classified as over-utilization and 13 % as under-utilization according to the AGA. Optimal utilization follow-up colonoscopies had higher ADRs on follow-up compared with over-utilized procedures (31 % vs. 17 %; P < 0.001)., Conclusions: Follow-up colonoscopy in symptomatic patients within a year has limited value in terms of adenoma detection. A considerable proportion of surveillance colonoscopies are performed too early according to current guidelines, resulting in low detection rates. Both aspects can be targeted for optimal usage in endoscopic capacity., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objectives: Computed tomography (CT) colonography cost assumptions so far ranged from 346 to 594 per procedure, based on clinical CT reimbursement rates. The aim of our study was to estimate the costs in a screening situation., Methods: Data were collected within an invitational population-based CRC screening trial (n = 2,920, age 50-75 years) with a dedicated CT-screening setting. Unit costs were calculated per action, per invitee and per participant (depending on adherence) and per individual with detected advanced neoplasia. Sensitivity analyses were performed, and alternative scenarios were considered., Results: Of the invitees, 47.2 % were reminded, 38.8 % scheduled for an intake, 37.2 % scheduled for CT colonography, 33.6 % underwent CT colonography and 1.1 % needed a re-examination. Lesions ≥ 10 mm were detected in 2.9 % of the invitees. Invitation costs were Euro 5.57. Costs per CT colonography (intake to results) were Euro 144.00. Extra costs of communication of positive results were Euro 9.00. Average costs of invitational-based CT colonography screening were Euro 56.97 per invitee, Euro 169.40 per participant and Euro 2,772.51 per individual with detected advanced neoplasia., Conclusions: Dutch costs of CT-screening were substantially lower than the cost assumptions that were used in published cost-effectiveness analyses on CT colonography screening. This finding indicates that previous cost-effectiveness analyses should be updated, at least for the Dutch situation.

Population-based screening for early detection and treatment of colorectal cancer (CRC) and precursor lesions, using evidence-based methods, can be effective in populations with a significant burden of the disease provided the services are of high quality. Multidisciplinary, evidence-based guidelines for quality assurance in CRC screening and diagnosis have been developed by experts in a project co-financed by the European Union. The 450-page guidelines were published in book format by the European Commission in 2010.  They include 10 chapters and over 250 recommendations, individually graded according to the strength of the recommendation and the supporting evidence. Adoption of the recommendations can improve and maintain the quality and effectiveness of an entire screening process, including identification and invitation of the target population, diagnosis and management of the disease and appropriate surveillance in people with detected lesions. To make the principles, recommendations and standards in the guidelines known to a wider professional and scientific community and to facilitate their use in the scientific literature, the original content is presented in journal format in an open-access Supplement of Endoscopy. The editors have prepared the present overview to inform readers of the comprehensive scope and content of the guidelines.

Background and Study Aims: Time limitations and unwanted health effects may act as barriers to participation in colorectal cancer (CRC) screening. The aim of the study was to measure the time requirements and health effects of colonoscopy and computed tomography colonography (CTC) screening., Patients and Methods: This was a prospective diary study in a consecutive sample within a randomized controlled CRC screening trial, comparing primary colonoscopy and CTC screening for average-risk individuals aged 50 - 74 years. The diary ended when all screening-related complaints had passed., Results: The diary was returned by 75 % (241/322) of colonoscopy and 75 % (127/170) of CTC screenees. The median interval between leaving home and returning from the examination was longer for colonoscopy (4 hours and 18 minutes [4:18], interquartile range [IQR] 3:30 - 5:00) than for CTC (2:30 hours, IQR 2:06 - 3:00; P < 0.001). Similarly, the time to return to routine activities was longer after colonoscopy (3:54 hours, IQR 1:48 - 15:00) than after CTC (1:36 hours, IQR 0:54 - 4:42). The duration of screening-related symptoms after the examination was shorter for colonoscopy (11:00 hours, IQR 2:54 - 20:00) than for CTC (22:00 hours; IQR 5:30 - 47:00; P < 0.001). Abdominal complaints were reported more frequently after CTC. Anxiety, pain, and quality of life worsened during the screening process, with no differences between the two examinations., Conclusions: Compared with colonoscopy, CTC screening required less time and allowed screenees to return to their daily activities more quickly. In contrast, CTC was associated with a twofold longer duration of screening-related symptoms. Feelings of anxiety, pain, and quality of life scores were similar during colonoscopy and CTC screening. These results should be incorporated into cost-effectiveness analyses of CRC screening techniques., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Data on clinical characteristics of patients with inflammatory bowel disease (IBD)-related colorectal cancer (CRC) are scarce and mainly originate from tertiary referral centres. We studied patient and disease characteristics of IBD-related CRC in a nationwide IBD cohort in general hospitals. Main outcome parameters were time to develop CRC, and factors associated with early CRC development., Methods: All IBD patients diagnosed with CRC between 1 January 1990 and 1 July 2006 were identified using a nationwide automated pathology database (PALGA). Patient charts were assessed to confirm diagnosis and collect clinical data. Early CRC was defined as CRC diagnosed less than 8 years after IBD diagnosis. Statistical analysis was performed using descriptive statistics, independent t tests, binary logistic regression and Cox-regression analysis., Results: Diagnosis of IBD-related CRC was confirmed in 251 patients (171 ulcerative colitis, 77 Crohn's disease, 3 unclassified colitis), 161 males (64 %). Median time from IBD diagnosis to CRC diagnosis was 12 years (IQR 4-20); 89 patients (35 %) developed early CRC. Type of IBD, gender, concomitant PSC, pseudopolyps, extent of inflammation, and medication use were not related to early CRC (p > 0.05). IBD diagnosis at older age (HR for 10 years older age 2.25; 95 % CI 1.92-2.63) was related to early CRC. Twenty-three patients (12 %) had been included in a surveillance programme prior to CRC diagnosis. Patients in the surveillance group had a significantly better tumor stage (p = 0.004)., Conclusions: We emphasize the problem of a high proportion of IBD-associated CRCs developing before the recommended start of surveillance. Therefore, we suggest that older age at IBD onset could be an additional factor to start surveillance in IBD patients.

Background and Study Aims: Colonoscopy is increasingly performed by nurse endoscopists. We aimed to assess the endoscopic quality and patient experience of these procedures., Patients and Methods: This prospective multicenter study analyzed 100 consecutive colonoscopies each for 10 trained nurse endoscopists with respect to endoscopic quality and patient experience. Colonoscopies were performed under the supervision of a gastroenterologist, using the techniques and protocols of the participating hospitals. Patient experience was assessed using a questionnaire., Results: Most nurse endoscopists were female (90 %; median age 43 [range 35 - 49]). Before the start of the study, they had performed a median of 528 colonoscopies (range 208 - 2103). For the 1000 patients, mean age was 56 ± 15 years; 55 % were women; and 96 % were in class I or II according to the American Society of Anesthesiologists' physical status classification system. Colonoscopies were performed for screening or surveillance in 42 %; for symptomatic indications in 58 % of patients. The unassisted cecal intubation rate was 94 %; the mean withdrawal time was 10 ± 5 minutes. The adenoma detection rate was 26.7 %. In 229 of the colonoscopies (23 %), the nurse endoscopists required assistance from the supervising gastroenterologist. The complication rate was 0.2 %: one perforation and one cardiopulmonary complication. The questionnaire was completed by 734 /1000 patients (73 %) and of these 694 /734 (95 %) were satisfied with the endoscopic procedure. Among the respondents 530 /734 (72 %) had no specific preference for a physician or nurse endoscopist, whereas 113 /734 (15 %) preferred a physician endoscopist, and 91 /734 (12 %) preferred a nurse endoscopist., Conclusion: The nurse endoscopists performed colonoscopies according to the internationally recognized quality standards and with high patient satisfaction., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Little is known about the effect of participating in a colorectal cancer (CRC) screening programme on quality of life (QOL), neither for participants with a negative nor for those with a positive test result. These findings, however, are important to evaluate the impact of CRC screening., Methods: Participants from CRC screening trials were sent a questionnaire, which included validated measures on generic health-related QOL, generic anxiety and screen-specific anxiety. Both faecal immunochemical test (FIT) and flexible sigmoidoscopy (FS) participants, either with negative or positive test results, were addressed., Results: The response rate was 73% (1289 out of 1772) for FIT and 78% (536 out of 689) for FS participants, with mean ages varying from 63-66 years. Positive FIT participants had worse physical (PCS-12, 47.1 vs 48.3, P=0.02), but equal mental QOL scores (MCS-12, 51.1 vs 51.6, P=0.26). Positive and negative FS participants had similar QOL scores. Both FIT and FS participants with a positive test result reported more screen-specific anxiety than negative FIT and FS participants. Positive and negative FS participants had similar generic anxiety scores., Conclusion: Our findings indicate that the burden of participating in CRC screening may be limited. Conducting a prospective study to confirm these results is recommended.

Objective: Fecal immunochemical testing (FIT) is increasingly used for colorectal cancer (CRC) screening. We aimed to estimate its diagnostic accuracy in invitational population screening measured against colonoscopy., Methods: Participants (50-75 years) in an invitational primary colonoscopy screening program were asked to complete one sample FIT before colonoscopy. We estimated FIT sensitivity, specificity, and predictive values in detecting CRC and advanced neoplasia (carcinomas and advanced adenomas) for cutoff levels of 50 (FIT50), 75 (FIT75), and 100 (FIT100) ng hemoglobin (Hb)/ml, corresponding with, respectively, 10, 15 and 20 μg Hb/g feces., Results: A total of 1,256 participants underwent a FIT and screening colonoscopy. Advanced neoplasia was detected by colonoscopy in 119 (9%), 8 (0.6%) of them had CRC. At FIT50, 121 (10%) had a positive test result; 45 (37%) had advanced neoplasia and 7 (6%) had CRC. A total of 74 of 1,135 FIT50 negatives (7%) had advanced neoplasia including 1 (0.1%) CRC. FIT50 had a sensitivity of 38% (95% confidence interval (CI): 29-47) for advanced neoplasia and 88% (95% CI: 37-99) for CRC at a specificity of 93% (95% CI: 92-95) and 91% (95% CI: 89-92), respectively. The positive and negative predictive values for FIT50 were 6% (95% CI: 3-12) and almost 100% (95% CI: 99-100) for CRC, and 37% (95% CI: 29-46) and 93% (95% CI: 92-95) for advanced neoplasia. The sensitivity and specificity of FIT75 for advanced neoplasia were 33% (95% CI: 25-42) and 96% (95% CI: 94-97). At FIT100, 71 screenees (6%) had a positive test result. The sensitivity and specificity of FIT100 were for advanced neoplasia 31% (95% CI: 23-40) and 97% (95% CI: 96-98), and for CRC 75% (95% CI: 36-96) and 95% (95% CI: 93-96). The area under curve for detecting advanced neoplasia was 0.70 (95% CI: 0.64-0.76). FIT had a similar sensitivity for proximal and distal advanced neoplasia at cutoffs of 50 (38% vs. 37%; P=0.99), 75 (33% vs. 31%; P=0.85) and 100 (33% vs. 29%; P=0.68) ng Hb/ml., Discussion: Nine out of ten screening participants with CRC and four out of ten with advanced neoplasia will be detected using one single FIT at low cutoff. Sensitivity in detecting proximal and distal advanced neoplasia is comparable.

Background: A pre-colonoscopy consultation in colorectal cancer (CRC) screening is necessary to assess a screenee's general health status and to explain benefits and risks of screening. The first option allows for personal attention, whereas a telephone consultation does not require travelling. We hypothesised that a telephone consultation would lead to higher response and participation in CRC screening compared with a face-to-face consultation., Methods: A total of 6600 persons (50-75 years) were 1:1 randomised for primary colonoscopy screening with a pre-colonoscopy consultation either face-to-face or by telephone. In both arms, we counted the number of invitees who attended a pre-colonoscopy consultation (response) and the number of those who subsequently attended colonoscopy (participation), relative to the number invited for screening. A questionnaire regarding satisfaction with the consultation and expected burden of the colonoscopy (scored on five-point rating scales) was sent to invitees. Besides, a questionnaire to assess the perceived burden of colonoscopy was sent to participants, 14 days after the procedure., Results: In all, 3302 invitees were allocated to the telephone group and 3298 to the face-to-face group, of which 794 (24%) attended a telephone consultation and 822 (25%) a face-to-face consultation (P=0.41). Subsequently, 674 (20%) participants in the telephone group and 752 (23%) in the face-to-face group attended colonoscopy (P=0.018). Invitees and responders in the telephone group expected the bowel preparation to be more painful than those in the face-to-face group while perceived burden scores for the full screening procedure were comparable. More subjects in the face-to-face group than in the telephone group were satisfied by the consultation in general: (99.8% vs 98.5%, P=0.014)., Conclusion: Using a telephone rather than a face-to-face consultation in a population-based CRC colonoscopy screening programme leads to similar response rates but significantly lower colonoscopy participation.

Multidisciplinary, evidence-based guidelines for quality assurance in colorectal cancer screening and diagnosis have been developed by experts in a project coordinated by the International Agency for Research on Cancer. The full guideline document covers the entire process of population-based screening. It consists of 10 chapters and over 250 recommendations, graded according to the strength of the recommendation and the supporting evidence. The 450-page guidelines and the extensive evidence base have been published by the European Commission. The chapter on management of lesions detected in colorectal cancer screening includes 32 graded recommendations. The content of the chapter is presented here to promote international discussion and collaboration by making the principles and standards recommended in the new EU Guidelines known to a wider professional and scientific community. Following these recommendations has the potential to enhance the control of colorectal cancer through improvement in the quality and effectiveness of the screening process, including multi-disciplinary diagnosis and management of the disease., (© Georg Thieme Verlag KG Stuttgart · New York.)

Multidisciplinary, evidence-based guidelines for quality assurance in colorectal cancer screening and diagnosis have been developed by experts in a project coordinated by the International Agency for Research on Cancer. The full guideline document covers the entire process of population-based screening. It consists of 10 chapters and over 250 recommendations, graded according to the strength of the recommendation and the supporting evidence. The 450-page guidelines and the extensive evidence base have been published by the European Commission. The chapter on colonoscopic surveillance following adenoma removal includes 24 graded recommendations. The content of the chapter is presented here to promote international discussion and collaboration by making the principles and standards recommended in the new EU Guidelines known to a wider professional and scientific community. Following these recommendations has the potential to enhance the control of colorectal cancer through improvement in the quality and effectiveness of surveillance and other elements in the screening process, including multi-disciplinary diagnosis and management of the disease., (© Georg Thieme Verlag KG Stuttgart · New York.)

Multidisciplinary, evidence-based guidelines for quality assurance in colorectal cancer screening and diagnosis have been developed by experts in a project coordinated by the International Agency for Research on Cancer. The full guideline document covers the entire process of population-based screening. It consists of 10 chapters and over 250 recommendations, graded according to the strength of the recommendation and the supporting evidence. The 450-page guidelines and the extensive evidence base have been published by the European Commission. The chapter on quality assurance in endoscopy includes 50 graded recommendations. The content of the chapter is presented here to promote international discussion and collaboration by making the principles and standards recommended in the new EU Guidelines known to a wider professional and scientific community. Following these recommendations has the potential to enhance the control of colorectal cancer through improvement in the quality and effectiveness of endoscopy and other elements in the screening process, including multidisciplinary diagnosis and management of the disease., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background and Study Aim: While colonoscopy screening is widely used in several European countries and the United States, there are no randomized trials to quantify its benefits. The Nordic-European Initiative on Colorectal Cancer (NordICC) is a multinational, randomized controlled trial aiming at investigating the effect of colonoscopy screening on colorectal cancer (CRC) incidence and mortality. This paper describes the rationale and design of the NordICC trial., Study Design: Men and women aged 55 to 64 years are drawn from the population registries in the participating countries and randomly assigned to either once-only colonoscopy screening with removal of all detected lesions, or no screening (standard of care in the trial regions). All individuals are followed for 15 years after inclusion using dedicated national registries. The primary end points of the trial are cumulative CRC-specific death and CRC incidence during 15 years of follow-up. POWER ANALYSIS: We hypothesize a 50 % CRC mortality-reducing efficacy of the colonoscopy intervention and predict 50 % compliance, yielding a 25 % mortality reduction among those invited to screening. For 90 % power and a two-sided alpha level of 0.05, using a 2:1 randomization, 45 600 individuals will be randomized to control, and 22 800 individuals to the colonoscopy group. Interim analyses of the effect of colonoscopy on CRC incidence and mortality will be performed at 10-year follow-up., Conclusions: The aim of the NordICC trial is to quantify the effectiveness of population-based colonoscopy screening. This will allow development of evidence-based guidelines for CRC screening in the general population., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background and Study Aim: Colorectal cancer (CRC) screening guidelines recommend surveillance after polypectomy. There is variation in the surveillance intervals that are being advised. This variation also affects adherence. Surveillance intervals need to be based on risk factors at index. We therefore aimed to systematically review risk factors of adenoma findings at surveillance colonoscopy., Methods: A systematic literature search was performed up to September 2009. Studies that reported on follow-up colonoscopy findings with stratification for index characteristics were included. Pooled relative risks (RR) were calculated using random effects models, and heterogeneity was determined by means of the I2-statistic., Results: A total of 27 studies met the inclusion criteria. The most important risk factors for adenoma findings were the presence on index colonoscopy of the following: advanced adenomas (RR: 1.81), ≥ 3 adenomas (RR: 1.64), size ≥ 10 mm (RR: 1.66), and age ≥ 60 years (RR: 1.65). The presence of villous adenomas, high grade dysplasia, proximal adenomas, and male gender were associated with less profound increases in RR. Marked variation in study design and substantial heterogeneity between studies was observed., Conclusions: Convincing evidence exists that patients with advanced adenomas, ≥ 3 adenomas, adenomas ≥ 10 mm, or age ≥ 60 years have an increased risk of adenoma recurrence. The evidence for other baseline findings for an increased risk of adenoma recurrence is inconclusive. Marked variation and consistently lower RRs in studies of medium or low quality emphasize the necessity for well performed and well reported studies. Given the high impact of surveillance on patients and service providers, there is need for further assessment of the risk(s) of adenoma recurrence., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: The difference in mortality between emergency and elective surgery for malignant colonic obstruction is more than 5% in healthy patients below the age of 65 and increases with age to around 20%. Emergency surgery can be avoided by endoscopic placement of a self-expandable metal stent (SEMS)., Aim: To evaluate the effectiveness and safety of SEMS as 'bridge to surgery'., Method: Between January 2001 and July 2008, SEMS were placed for acute malignant colonic obstruction in 45 patients (median age 72 years, range 35-91)., Results: The procedure was technically successful in 43 patients (94%) with resolution of obstructive symptoms within 48 h in 87% of the patients. No perforations occurred during the procedure or while awaiting surgery. Two (4%) patients required a second endoscopic procedure. All patients underwent a single-stage surgical procedure. Postoperative mortality was 2.2% (n = 1). Histology showed advanced colorectal cancer (T3-4N1-2M0-1) in 75% of the patients., Conclusion: SEMS placement is a safe and effective procedure as bridge to surgery in patients presenting with colonic obstruction due to colorectal malignancy. This procedure carries a risk of serious complications well below that of the reported difference in mortality between emergency an elective surgery., (Copyright © 2011 S. Karger AG, Basel.)

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 50-74years) 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., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Liver transplant patients (LTx) have an increased risk for developing de novo malignancies, but for colorectal cancer (CRC) this risk is less clear. We aimed to determine whether the CRC risk post-LTx was increased. A systematic search was performed in MEDLINE and Cochrane databases to identify studies published between 1986 and 2008 reporting on the risk of CRC post-LTx. The outcomes were (1) CRC incidence rate (IR per 100,000 person-years (PY)) compared to a weighted age-matched control population using SEER and (2) relative risk (RR) for CRC compared to the general population. If no RR data were available, the RR was estimated using SEER. Twenty-nine studies were included. The overall post-LTx IR was 119 (95% CI 88-161) per 100,000 PY. The overall RR was 2.6 (95% CI 1.7-4.1). The non-primary sclerosing cholangitis (PSC) IR was 129 per 100,000 PY (95% CI 81-207). Compared to SEER (71 per 100,000 PY), the non-PSC RR was 1.8 (95% CI 1.1-2.9). In conclusion, the overall transplants and the subgroup non-PSC transplants have an increased CRC risk compared to the general population. However, in contrast to PSC, non-PSC transplants do not need an intensified screening strategy compared to the general population until a prospective study further defines recommendations.

Background: Guidelines underline the role of individual preferences in the selection of a screening test, as insufficient evidence is available to recommend one screening test over another. We conducted a study to determine the preferences of individuals and to predict uptake for colorectal cancer (CRC) screening programmes using various screening tests., Methods: A discrete choice experiment (DCE) questionnaire was distributed among naive subjects, yet to be screened, and previously screened subjects, aged 50-75 years. Subjects were asked to choose between scenarios on the basis of faecal occult blood test (FOBT), flexible sigmoidoscopy (FS), total colonoscopy (TC) with various test-specific screening intervals and mortality reductions, and no screening (opt-out)., Results: In total, 489 out of 1498 (33%) screening-naïve subjects (52% male; mean age+/-s.d. 61+/-7 years) and 545 out of 769 (71%) previously screened subjects (52% male; mean age+/-s.d. 61+/-6 years) returned the questionnaire. The type of screening test, screening interval, and risk reduction of CRC-related mortality influenced subjects' preferences (all P<0.05). Screening-naive and previously screened subjects equally preferred 5-yearly FS and 10-yearly TC (P=0.24; P=0.11), but favoured both strategies to annual FOBT screening (all P-values <0.001) if, based on the literature, realistic risk reduction of CRC-related mortality was applied. Screening-naive and previously screened subjects were willing to undergo a 10-yearly TC instead of a 5-yearly FS to obtain an additional risk reduction of CRC-related mortality of 45% (P<0.001)., Conclusion: These data provide insight into the extent by which interval and risk reduction of CRC-related mortality affect preferences for CRC screening tests. Assuming realistic test characteristics, subjects in the target population preferred endoscopic screening over FOBT screening, partly, due to the more favourable risk reduction of CRC-related mortality by endoscopy screening. Increasing the knowledge of potential screenees regarding risk reduction by different screening strategies is, therefore, warranted to prevent unrealistic expectations and to optimise informed choice.

Background: Screening for colorectal cancer (CRC) is widely accepted, but there is no consensus on the preferred strategy. We conducted a randomised trial comparing participation and detection rates (DR) per screenee of guaiac-based faecal occult blood test (gFOBT), immunochemical FOBT (FIT), and flexible sigmoidoscopy (FS) for CRC screening., Methods: A representative sample of the Dutch population (n = 15 011), aged 50-74 years, was 1:1:1 randomised prior to invitation to one of the three screening strategies. Colonoscopy was indicated for screenees with a positive gFOBT or FIT, and for those in whom FS revealed a polyp with a diameter > or = 10 mm; adenoma with > or = 25% villous component or high grade dysplasia; serrated adenoma; > or = 3 adenomas; > or = 20 hyperplastic polyps; or CRC., Results: The participation rate was 49.5% (95% confidence interval (CI) 48.1 to 50.9%) for gFOBT, 61.5% (CI, 60.1 to 62.9%) for FIT and 32.4% (CI, 31.1 to 33.7%) for FS screening. gFOBT was positive in 2.8%, FIT in 4.8% and FS in 10.2%. The DR of advanced neoplasia was significantly higher in the FIT (2.4%; OR, 2.0; CI, 1.3 to 3.1) and the FS arm (8.0%; OR, 7.0; CI, 4.6 to 10.7) than the gFOBT arm (1.1%). FS demonstrated a higher diagnostic yield of advanced neoplasia per 100 invitees (2.4; CI, 2.0 to 2.8) than gFOBT (0.6; CI, 0.4 to 0.8) or FIT (1.5; CI, 1.2 to 1.9) screening., Conclusion: This randomised population-based CRC-screening trial demonstrated superior participation and detection rates for FIT compared to gFOBT screening. FIT screening should therefore be strongly preferred over gFOBT screening. FS screening demonstrated a higher diagnostic yield per 100 invitees than both FOBTs.

Introduction: In many countries uptake of colorectal cancer (CRC) screening remains low., Aim: To assess how procedural characteristics of CRC screening programmes determine preferences for participation and how individuals weigh these against the perceived benefits from participation in CRC screening., Methods: A discrete choice experiment was conducted among subjects in the age group of 50-75 years, including both screening-naïve subjects and participants of a CRC screening programme. Subjects were asked on their preferences for aspects of CRC screening programmes using scenarios based on pain, risk of complications, screening location, preparation, duration of procedure, screening interval and risk reduction of CRC-related death., Results: The response was 31% (156/500) for screening-naïve and 57% (124/210) for CRC screening participants. All aspects proved to significantly influence the respondents' preferences. For both groups combined, respondents required an additional relative risk reduction of CRC-related death by a screening programme of 1% for every additional 10 min of duration, 5% in order to expose themselves to a small risk of complications, 10% to accept mild pain, 10% to undergo preparation with an enema, 12% to use 0.75l of oral preparation combined with 12h fasting and 32% to use an extensive bowel preparation. Screening intervals shorter than 10 years were significantly preferred to a 10-year screening interval., Conclusion: This study shows that especially type of bowel preparation, risk reduction of CRC related death and length of screening interval influence CRC screening preferences. Furthermore, improving awareness on CRC mortality reduction by CRC screening may increase uptake.

Background: Nurse endoscopists may provide a solution for the insufficient endoscopic capacity in colorectal cancer (CRC) screening., Aim: To determine the views of gastroenterologists about the potential role of nurse endoscopists in gastrointestinal endoscopy., Methods: A postal questionnaire was sent to all registered gastroenterologists (n = 301) and gastroenterology residents (n = 79) in the Netherlands., Results: Two hundred and thirty five of 380 (62%) gastroenterologists and residents completed the questionnaire. Overall, 48% were positive towards introduction of nurse endoscopists, whereas 18% were neutral and 34% negative. Respondents expected no major differences in endoscopic quality between physicians and nurse endoscopists. Nevertheless, 69% expected that patient experiences would be better met by physicians. Multivariate analysis showed that actual experience with nurse endoscopists and beliefs that nurse endoscopists are able to provide adequate endoscopic quality and good patient experiences, were independent predictors for a positive attitude towards introduction of nurse endoscopists [OR 6.6 (2.3-18.4), OR 1.9 (1.2-3.5) and OR 2.1 (1.2-2.9), respectively]. Respectively 89% and 66% of the respondents considered sigmoidoscopy and colonoscopy for CRC screening as appropriate procedures to be performed by nurse endoscopists. Diagnostic and therapeutic endoscopies were considered less appropriate., Conclusion: A majority of gastroenterologists have a positive attitude towards introduction of nurse endoscopists, especially for CRC screening endoscopies.

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 Aims: In Lynch syndrome, the clinical phenotype in MSH6 mutation families differs from that in MLH1 and MSH2 families. Therefore, MSH6 mutation families are less likely to fulfil diagnostic criteria such as the Amsterdam II criteria (AC II) and the revised Bethesda guidelines (rBG), and will be underdiagnosed. The aim of the present study was to evaluate the contribution of MSH6 gene mutations in families that were analysed for Lynch syndrome in a diagnostic setting., Methods: Families that had molecular analysis for Lynch syndrome were included in this study. Complete molecular screening of the MLH1, MSH2 and MSH6 genes was performed in all families. Microsatellite instability (MSI) and immunohistochemical (IHC) analysis was performed in almost all families. Clinical data were collected from medical records and family pedigrees., Results: A total of 108 families were included. MSI and IHC analysis was performed in 97 families, and in 40 an MSI-high phenotype with absent protein expression was found. Germline mutation analysis detected mutations in 23 families (7 MLH1, 4 MSH2 and 12 MSH6). The majority of MSH6 families were AC II negative, but fulfilled the rBG., Conclusions: There is a high incidence of MSH6 mutations in families tested for Lynch syndrome in a diagnostic setting. Many of these families remain underdiagnosed using the AC II. The rBG are more useful to select these families for further analysis. However, to optimise the detection of MSH6 families, MSI and IHC analysis should also be performed in families with clustering of late-onset endometrial carcinoma.

This study evaluated the use of genetic testing and time trends in hereditary non-polyposis colorectal cancer (HNPCC), (attenuated) familial adenomatous polyposis [(A)FAP] and human MutY homolog (MUTYH) associated polyposis (MAP) families. Eighty-seven families, who were diagnosed with disease-causing mutations between 1995 and 2006, were included in this study. The families consisted of 1547 individuals at risk. Data of these individuals were collected from medical records and family pedigrees. There was considerable interest in genetic testing with test rates of 41% in HNPCC families, 42% in (A)FAP families and 53% in MAP families. The use of genetic testing was associated with age and parenthood. Despite the interest in genetic testing, many risk carriers do not apply for testing. Moreover, time trend analysis showed a decline in test rate in HNPCC families. Studies evaluating the reasons for not testing are needed. Furthermore, a better implementation of genetic testing in clinical practice is desirable.

Colorectal carcinoma (CRC) is a common cancer and the second most common cause of death. The therapeutic costs for this disease will continue to rise due to an increasing incidence and the introduction of new chemotherapeutic modalities. Colorectal carcinoma is preceded by precursor lesions, which can be used as a target for early detection and therapy. Biennial population screening with faecal occult blood tests (FOBT) lowers CRC mortality with 14-18%. Five year screening with flexible sigmoidoscopy is a cost-effective alternative, which yields a higher preventive effect when similar participation rates are achieved. Screening colonoscopy has the advantage of examination of the complete colon but disadvantages are the high participant burden and the higher demand for endoscopic personnel and endoscopy units. Future screening modalities like faecal DNA markers and CT colonography are promising but need further improvement. In Europe, faecal occult blood testing and flexible sigmoidoscopy are currently the most suitable screening modalities for colorectal cancer screening.

Colorectal cancer incidence after adenoma removal has been studied in selected populations of adenoma patients. Our study estimates the trend in colorectal cancer incidence after adenoma removal in actual clinical practice. From PALGA, a nationwide network and registry of histo- and cytopathology in the Netherlands, we extracted data of all patients diagnosed with colorectal adenomas between 1 January 1988 and 1 October 1998. The data were used to calculate population-based colorectal cancer incidence rates after adenoma removal. A total of 78,473 adenoma patients were followed for a mean of 4.5 years after the first adenoma removal. The colorectal cancer incidence ratio compared with the general population matched by age and gender was 38.4 (37.3-39.5) in the first year after adenoma removal and 1.5 (95% confidence interval (CI): 1.4-1.6) after Year 1. The incidence ratio decreased from 2.8 (2.5-3.1) in Year 2 to 0.9 (0.6-1.2) in Years 9-11. This time trend is the opposite of the upward time trend that was expected after adenoma removal. Adenoma patients in the Netherlands are at increased risk for colorectal cancer compared to the general population. The high cancer incidence in Years 1-5 after polypectomy can be explained by a colonoscopic sensitivity for cancer of approximately 90%., (Copyright 2004 Wiley-Liss, Inc.)

Patients with chronic inflammatory bowel disease (IBD) have a higher risk of colorectal carcinoma, and present with this malignancy at a younger age than non-IBD individuals. In three patients, two men aged 20 and 36 years and one woman aged 34 years, colorectal cancer developed at a young age, following a long history of ulcerative colitis. Surveillance for colorectal cancer in IBD patients needs to be performed by regular colonoscopy with extensive biopsy sampling for the detection of dysplasia, regarded by many as predictive for colon carcinoma. Whenever a dysplasia-associated lesion or mass or a highgrade dysplasia is identified, there is a strong indication for colectomy. When low-grade dysplasia is found, the findings should be discussed with the patient and it should be decided whether the patient should resume surveillance or opt for colectomy.