Leerdam, M.E. van

Informed decision-making in colorectal cancer screening using colonoscopy or CT-colonography (Article)

2013-06-01T00:00:00Z

Objective: To evaluate the level of informed decision making in a randomized controlled trial comparing colonoscopy and CT-colonography for colorectal cancer screening. Methods: 8844 citizens aged 50-75 were randomly invited to colonoscopy (. n=. 5924) or CT-colonography (. n=. 2920) screening. All invitees received an information leaflet. Screenees received a questionnaire within 4 weeks before the planned examination, non-screenees 4 weeks after the invitation. A decision was categorized as informed when characterized by sufficient decision-relevant knowledge and consistent with personal attitudes toward participation in screening. Results: Knowledge and attitude items were completed by 1032/1276 colonoscopy screenees (81%), by 698/4648 colonoscopy non-screenees (15%), by 824/982 CT-colonography screenees (84%) and by 192/1938 CT-colonography non-screenees (10%). 1027 colonoscopy screenees (>99%) and 815 CT-colonography screenees (99%) had adequate knowledge; 915 (89%) and 742 (90%) had a positive attitude. 675 non-screenees invited to colonoscopy (97%) and 182 invited to CT-colonography (95%) had adequate knowledge; 344 (49%) and 94 (49%) expressed a negative attitude. Conclusion: A large majority of screenees made an informed decision on participation. Almost half of responding non-screenees, made an uninformed decision, suggesting additional barriers to participation. Practice implications: Efforts to understand the additional barriers will create opportunities to facilitate informed participation to colorectal cancer screening.

Cost-effectiveness of one versus two sample faecal immunochemical testing for colorectal cancer screening (Article)

2013-05-01T00:00:00Z

Objective The sensitivity and specificity of a single faecal immunochemical test (FIT) are limited. The performance of FIT screening can be improved by increasing the screening frequency or by providing more than one sample in each screening round. This study aimed to evaluate if two-sample FIT screening is cost-effective compared with one-sample FIT. Design The MISCANecolon microsimulation model was used to estimate costs and benefits of strategies with either one or two-sample FIT screening. The FIT cut-off level varied between 50 and 200 ng haemoglobin/ml, and the screening schedule was varied with respect to age range and interval. In addition, different definitions for positivity of the two-sample FIT were considered: at least one positive sample, two positive samples, or the mean of both samples being positive. Results Within an exemplary screening strategy, biennial FIT from the age of 55-75 years, one-sample FIT provided 76.0-97.0 life-years gained (LYG) per 1000 individuals, at a cost of $259000-264000 (range reflects different FIT cut-off levels). Two-sample FIT screening with at least one sample being positive provided 7.3-12.4 additional LYG compared with one-sample FIT at an extra cost of $50000-59 000. However, when all screening intervals and age ranges were considered, intensifying screening with one-sample FIT provided equal or more LYG at lower costs compared with two-sample FIT. Conclusion If attendance to screening does not differ between strategies it is recommended to increase the number of screening rounds with one-sample FIT screening, before considering increasing the number of FIT samples provided per screening round.

Extracolonic cancer risk in patients with serrated polyposis syndrome and their first-degree relatives (Article)

2013-04-17T00:00:00Z

Serrated polyposis syndrome is associated with an increased colorectal cancer risk. Although the underlying genetic cause of the condition is unknown, first-degree relatives of patients with serrated polyposis have an increased risk for colorectal cancer compared with the general population. This suggests an inheritable component. Since other hereditary polyposis syndromes are often associated with an expanded extracolonic tumour spectrum, our aim was to determine the extra colonic cancer risks for patients with serrated polyposis and their first-degree relatives and compare these risks with the general population. Serrated polyposis index patients from 5 medical centres were included. Demographic data concerning age, sex and reported malignancies were ascertained by reviewing medical charts and histopathology reports. Family history was obtained by examining pedigree records from the department of Clinical Genetics. Incidence rates of extracolonic malignancies were compared with the general population through a person-year analysis, adjusted for age and sex. Population-based incidence data were derived from the Eindhoven Cancer Registry. A total of 105 patients with serrated polyposis and 341 first-degree relatives were included. Among the patients with serrated polyposis, 9 extracolonic cancers were observed, compared to 13 expected malignancies in the general population (RR 0.69 95 % CI 0.36-1.33; p = 0.27). Among the first-degree relatives, 44 extracolonic malignancies were observed, compared to 48 expected malignancies (RR 0.92 95 % CI 0.69-1.24; p = 0.60). In this study, the overall incidence of extracolonic malignancies in patients with serrated polyposis and their first-degree relatives was not increased. Large international studies are required to confirm these results.

Optimal resource allocation in colonoscopy: Timing of follow-up colonoscopies in relation to adenoma detection rates (Article)

2013-04-12T00:00:00Z

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.

What influences the decision to participate in colorectal cancer screening with faecal occult blood testing and sigmoidoscopy? (Article)

2013-04-08T00:00:00Z

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.

Differences in proximal serrated polyp detection among endoscopists are associated with variability in withdrawal time (Article)

2013-04-01T00:00:00Z

Background: Insufficient detection of proximal serrated polyps (PSP) might explain the occurrence of a proportion of interval carcinomas in colonoscopy surveillance programs. Objective: To compare PSP detection among endoscopists and to identify patient-related and endoscopist-related factors associated with PSP detection. Design: Prospective study in unselected patients. Setting: Colonoscopy screening program for colorectal cancer at two academic medical centers. Patients: Asymptomatic consecutive screening participants (aged 50-75 years). Intervention: Colonoscopies were performed by 5 experienced endoscopists. All detected polyps were removed. Multiple colonoscopy quality indicators were prospectively recorded. Main Outcome Measurements: We compared PSP detection among endoscopists by calculating odds ratios (OR) with logistic regression analysis. Logistic regression also was used to identify patient features and colonoscopy factors associated with PSP detection. Results: A total of 1354 patients underwent a complete screening colonoscopy: 1635 polyps were detected, of which 707 (43%) were adenomas and 685 (42%) were serrated polyps, including 215 PSPs. In 167 patients (12%) 1 or more PSPs were detected. The PSP detection rate differed significantly among endoscopists, ranging from 6% to 22% (P <.001). Longer withdrawal time (OR 1.12; 95% confidence interval, 1.10-1.16) was significantly associated with better PSP detection, whereas patient age, sex, and quality of bowel preparation were not. Limitations: Limited number of highly experienced endoscopists. Conclusion: The PSP detection rate differs among endoscopists. Longer withdrawal times are associated with better PSP detection, but patient features are not. (Clinical trial registration number: NTR1888.) © 2013 American Society for Gastrointestinal Endoscopy.

[Peutz-Jeghers syndrome]. (Article)

2013-01-01T00:00:00Z

Peutz-Jeghers syndrome is a rare, autosomal dominant inherited disorder, which is characterized by mucocutaneous pigmentations, gastrointestinal polyposis and an increased risk of cancer. It is caused by germline mutations in the LKB1 tumour suppressor gene, as a result of which hamartomatous polyps can develop already at an early age, which may cause various complications, including abdominal pain, anaemia, and acute intestinal obstruction. Patients have an increased risk of developing cancer, in the gastroinstestinal tract and in other organs. As a result of the risk of complications related to the hamartomatous polyps and the increased risk of cancer, the medical management mainly consists of surveillance. Upper and lower endoscopies are recommended for surveillance, the small bowel should be investigated with magnetic resonance imaging and regular inspection of the pancreas with imaging techniques is recommended. Women are advised to seek regular breast- and gynaecological screening from an early age. The pathogenesis of hamartomas and carcinomas is unclear. More insight into the molecular background might lead to targeted medicinal therapies for patients with this syndrome.

Burden of colonoscopy compared to non-cathartic CT-colonography in a colorectal cancer screening programme: Randomised controlled trial (Article)

2012-11-01T00:00:00Z

Objective: CT-colonography has been suggested to be less burdensome for primary colorectal cancer (CRC) screening than colonoscopy. To compare the expected and perceived burden of both in a randomised trial. Design: 8844 Dutch citizens aged 50-74 years were randomly invited for CRC screening with colonoscopy (n=5924) or CT-colonography (n=2920). Colonoscopy was performed after full colon lavage, or CT-colonography after limited bowel preparation (non-cathartic). All invitees were asked to complete the expected burden questionnaire before the procedure. All participants were invited to complete the perceived burden questionnaire 14 days later. Mean scores were calculated on 5-point scales. Results: Expected burden: 2111 (36%) colonoscopy and 1199 (41%) CT-colonography invitees completed the expected burden questionnaire. Colonoscopy invitees expected the bowel preparation and screening procedure to be more burdensome than CT-colonography invitees: mean scores 3.0±1.1 vs 2.3±0.9 (p<0.001) and 3.1±1.1 vs 2.2±0.9 (p<0.001). Perceived burden: 1009/1276 (79%) colonoscopy and 801/982 (82%) CT-colonography participants completed the perceived burden questionnaire. The full screening procedure was reported as more burdensome in CT-colonography than in colonoscopy: 1.8±0.9 vs 2.0±0.9 (p<0.001). Drinking the bowel preparation resulted in a higher burden score in colonoscopy (3.0±1.3 vs 1.7±1.0, p<0.001) while related bowel movements were scored more burdensome in CT-colonography (2.0±1.0 vs 2.2±1.1, p<0.001). Most participants would probably or definitely take part in a next screening round: 96% for colonoscopy and 93% for CT-colonography (p=0.99). Conclusion: In a CRC screening programme, colonoscopy invitees expected the screening procedure and bowel preparation to be more burdensome than CT-colonography invitees. In participants, CT-colonography was scored as more burdensome than colonoscopy. Intended participation in a next screening round was comparable.

The Global Rating Scale in clinical practice: A comprehensive quality assurance programme for endoscopy departments (Article)

2012-11-01T00:00:00Z

Background: The Global Rating Scale is an endoscopy quality assurance programme, successfully implemented in England. It remains uncertain whether it is applicable in another health care setting. Aim: To assess the applicability of the Global Rating Scale as benchmark tool in an international context. Methods: Eleven Dutch endoscopy departments were included for a Global Rating Scale-census, performed as a cross-sectional evaluation, July 2010. Two Global Rating Scale-dimensions - 'clinical quality' and 'patient experience' - were assessed across six items using a range of levels: from level-D (basic) to level-A (excellent). Construct validity was assessed by comparing department-specific colonoscopy audit data to GRS-levels. Results: For 'clinical quality', variable scores were achieved in items '. safety' (9%=B, 27%=C, 64%=D) and '. communication' (46% = A, 18% = C, 36% = D). All departments achieved a basic score in '. quality' (100% = D). For 'patient experience', variable scores were achieved in '. timeliness' (18% = A, 9% = B, 73% = D) and '. booking-choice' (36% = B, 46% = C, 18% = D). All departments achieved basic scores in '. equality' (100% = D). Departments obtaining level-C or above in '. information', '. comfort', '. communication', '. timeliness' and '. aftercare', achieved significantly better audit outcomes compared to those obtaining level-D (p<0.05). Conclusion: The Global Rating Scale is appropriate to use outside England. There was significant variance across departments in dimensions. Most Global Rating Scale-levels were in line with departments' audit outcomes, indicating construct validity.

Authors' response (Article)

2012-10-01T00:00:00Z

PTEN in colorectal cancer: A report on two Cowden syndrome patients (Article)

2012-06-01T00:00:00Z

Heterozygous germline PTEN mutations cause Cowden syndrome. The risk of colorectal cancer in Cowden patients, however, remains a matter of debate. We describe two patients presenting with colorectal cancer at a young age (28 and 39 years) and dysmorphisms fitting the Cowden spectrum. Heterozygous germline mutations in PTEN were found in both patients. Moreover, analysis of the resected colorectal cancer specimens revealed loss of heterozygosity at the PTEN locus with retention of the mutated alleles, and greatly reduced or absent PTEN expression. Histologically and molecularly, the tumours showed resemblance with sporadic colorectal cancers, although they had prominent fibrotic stroma. Our data indicate that PTEN loss was involved in carcinogenesis in the two patients, supporting that colorectal cancer is part of the Cowden syndrome-spectrum. This is in line with data on sporadic colorectal cancer, mice studies and emerging epidemiological data on Cowden syndrome. Although the exact role of germline PTEN mutations in the carcinogenesis of colorectal cancer remains unclear, we think that Cowden syndrome should be in the differential diagnosis of colorectal cancer certainly in view of the possible prognostic and therapeutic consequences. Prospective follow-up and surveillance of PTEN mutation carriers from the age of 25 to 30 years in a study setting should clarify this issue.

Are fecal immunochemical test characteristics influenced by sample return time a population-based colorectal cancer screening trial (Article)

2012-01-01T00:00:00Z

Objectives: Fecal immunochemical tests (FIT) are preferred over guaiac-based fecal occult blood testing as colorectal cancer (CRC) screening tool. However, hemoglobin (Hb) degradation over time may influence FIT outcome. We therefore evaluated the effect of sample return time on FIT performance characteristics in a population-based CRC screening trial. Methods: A representative random sample of the Dutch population (n=17,677), aged 50-74 years, was invited for FIT screening (OC-Sensor Micro; cutoff 50 ng Hb/ml). Sample return time was defined as the interval in days between fecal sampling and FIT laboratory delivery. Moreover, a random sample of positive FITs were selected to be stored at room temperature and re-tested every 3-4 days. Results: In total, 8,958 screenees fulfilled our inclusion criteria. The mean sample return time was 3 days (±3). Overall, 792 screenees (8.8%) had a positive test. Between the sample return time groups, the positivity rate (PR) varied between 7.7 and 9.0%. No statistically significant associations were found between PR or detection rate (DR) and the different sample return time groups (P value=0.84 and 0.76, respectively). For the laboratory experiment, 71 positive FITs were stored at room temperature and re-tested with standard intervals. The mean daily fecal Hb decrease was 5.88% per day (95% confidence interval 4.78-6.96%). None of the positive FITs became negative before 10 days after fecal sampling. Conclusions: This population-based CRC screening trial demonstrates that both the PR and DR of FITs do not decrease with prolonged sample return times up to 10 days. This means that a delay in sending the FIT back to the laboratory, of up to at least 1 week, does not necessitate repeat sampling in case of a negative test result. These data support the use of FIT-based screening as a reliable tool for nationwide CRC screening programs.

Participation and yield of colonoscopy versus non-cathartic CT colonography in population-based screening for colorectal cancer: A randomised controlled trial (Article)

2012-01-01T00:00:00Z

Background: Screening for colorectal cancer is widely recommended, but the preferred strategy remains unidentified. We aimed to compare participation and diagnostic yield between screening with colonoscopy and with non-cathartic CT colonography. Methods: Members of the general population, aged 50-75 years, and living in the regions of Amsterdam or Rotterdam, identified via the registries of the regional municipal administration, were randomly allocated (2:1) to be invited for primary screening for colorectal cancer by colonoscopy or by CT colonography. Randomisation was done per household with a minimisation algorithm based on age, sex, and socioeconomic status. Invitations were sent between June 8, 2009, and Aug 16, 2010. Participants assigned to CT colonography who were found to have one or more large lesions (≥10 mm) were offered colonoscopy; those with 6-9 mm lesions were offered surveillance CT colonography. The primary outcome was the participation rate, defined as number of invitees undergoing the examination relative to the total number of invitees. Diagnostic yield was calculated as number of participants with advanced neoplasia relative to the total number of invitees. Invitees and screening centre employees were not masked to allocation. This trial is registered in the Dutch trial register, number NTR1829. Findings: 1276 (22%) of 5924 colonoscopy invitees participated, compared with 982 (34%) of 2920 CT colonography invitees (relative risk [RR] 1·56, 95% CI 1·46-1·68; p<0·0001). Of the participants in the colonoscopy group, 111 (9%) had advanced neoplasia of whom seven (<1%) had a carcinoma. Of CT colonography participants, 84 (9%) were offered colonoscopy, of whom 60 (6%) had advanced neoplasia of whom five (<1%) had a carcinoma; 82 (8%) were offered surveillance. The diagnostic yield for all advanced neoplasia was 8·7 per 100 participants for colonoscopy versus 6·1 per 100 for CT colonography (RR 1·46, 95% CI 1·06-2·03; p=0·02) and 1·9 per 100 invitees for colonoscopy and 2·1 per 100 invitees for CT colonography (RR 0·91, 0·66-2·03; p=0·56). The diagnostic yield for advanced neoplasia of 10 mm or more was 1·5 per 100 invitees for colonoscopy and 2·0 per 100 invitees for CT colonography, respectively (RR 0·74, 95% CI 0·53-1·03; p=0·07). Serious adverse events related to the screening procedure were post-polypectomy bleedings: two in the colonoscopy group and three in the CT colonography group. Interpretation: Participation in colorectal cancer screening with CT colonography was significantly better than with colonoscopy, but colonoscopy identified significantly more advanced neoplasia per 100 participants than did CT colonography. The diagnostic yield for advanced neoplasia per 100 invitees was similar for both strategies, indicating that both techniques can be used for population-based screening for colorectal cancer. Other factors such as cost-effectiveness and perceived burden should be taken into account when deciding which technique is preferable. Funding: Netherlands Organisation for Health Research and Development, Centre for Translational Molecular Medicine, and the Nuts Ohra Foundation.

Fecal occult blood testing when colonoscopy capacity is limited (Article)

2011-12-07T00:00:00Z

Background Fecal occult blood testing (FOBT) can be adapted to a limited colonoscopy capacity by narrowing the age range or extending the screening interval, by using a more specific test or hemoglobin cutoff level for referral to colonoscopy, and by restricting surveillance colonoscopy. Which of these options is most clinically effective and cost-effective has yet to be established. Methods We used the validated MISCAN-Colon microsimulation model to estimate the number of colonoscopies, costs, and health effects of different screening strategies using guaiac FOBT or fecal immunochemical test (FIT) at various hemoglobin cutoff levels between 50 and 200 ng hemoglobin per mL, different surveillance strategies, and various age ranges. We optimized the allocation of a limited number of colonoscopies on the basis of incremental cost-effectiveness. Results When colonoscopy capacity was unlimited, the optimal screening strategy was to administer an annual FIT with a 50 ng/mL hemoglobin cutoff level in individuals aged 45-80 years and to offer colonoscopy surveillance to all individuals with adenomas. When colonoscopy capacity was decreasing, the optimal screening adaptation was to first increase the FIT hemoglobin cutoff value to 200 ng hemoglobin per mL and narrow the age range to 50-75 years, to restrict colonoscopy surveillance, and finally to further decrease the number of screening rounds. FIT screening was always more cost-effective compared with guaiac FOBT. Doubling colonoscopy capacity increased the benefits of FIT screening up to 100%. Conclusions FIT should be used at higher hemoglobin cutoff levels when colonoscopy capacity is limited compared with unlimited and is more effective in terms of health outcomes and cost compared with guaiac FOBT at all colonoscopy capacity levels. Increasing the colonoscopy capacity substantially increases the health benefits of FIT screening.

Pitfalls in molecular analysis for mismatch repair deficiency in a family with biallelic pms2 germline mutations (Article)

2011-12-01T00:00:00Z

Heterozygous germline mutations in the mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2 cause Lynch syndrome. Biallelic mutations in the MMR genes are associated with a childhood cancer syndrome [constitutional mismatch repair deficiency (CMMR-D)]. This is predominantly characterized by hematological malignancies and tumors of the bowel and brain, often associated with signs of neurofibromatosis type 1 (NF1). Diagnostic strategies for selection of patients for MMR gene analysis include analysis of microsatellite instability (MSI) and immunohistochemical (IHC) analysis of MMR proteins in tumor tissue. We report the clinical characterization and molecular analyses of tumor specimens from a family with biallelic PMS2 germline mutations. This illustrates the pitfalls of present molecular screening strategies. Tumor tissues of five family members were analyzed for MSI and IHC. MSI was observed in only one of the analyzed tissues. However, IHC analysis of brain tumor tissue of the index patient and his sister showed absence of PMS2 expression, and germline mutation analyses showed biallelic mutations in PMS2: p.Ser46IIe and p.Pro246fs. The same heterozygous mutations were confirmed in the father and mother, respectively. These data support the conclusion that in case of a clinical phenotype of CMMR-D, it is advisable to routinely combine MSI analysis with IHC analysis for the expression of MMR proteins. With inconclusive or conflicting results, germline mutation analysis of the MMR genes should be considered after thorough counselling of the patients and/or their relatives.

Cost-effectiveness analysis of a quantitative immunochemical test for colorectal cancer screening (Article)

2011-11-01T00:00:00Z

Background & Aims: Two European randomized trials (N = 30,000) compared guaiac fecal occult blood testing with quantitative fecal immunochemical testing (FIT) and showed better attendance rates and test characteristics for FIT. We aimed to identify the most cost-effective FIT cutoff level for referral to colonoscopy based on data from these trials and allowing for differences in screening ages. Methods: We used the validated MIcrosimulation SCreening ANalysis (MISCAN)-Colon microsimulation model to estimate costs and effects of different screening strategies for FIT cutoff levels of 50, 75, 100, 150, and 200 ng/mL hemoglobin. For each cutoff level, screening strategies were assessed with various age ranges and screening intervals. We assumed sufficient colonoscopy capacity for all strategies. Results: At all cost levels, FIT screening was most effective with the 50 ng/mL cutoff level. The incremental cost-effectiveness ratio of biennial screening between ages 55 and 75 years using FIT at 50 ng/mL, for example, was 3900 euro per life year gained. Annual screening had an incremental cost-effectiveness ratio of 14,900 euro per life year gained, in combination with a wider age range (between ages 45 and 80 years). In the sensitivity analysis, 50 ng/mL remained the preferred cutoff level. Conclusions: FIT screening is more cost-effective at a cutoff level of 50 ng/mL than at higher cutoff levels. This supports the recommendation to use FIT at a cutoff level of 50 ng/mL, which is considerably lower than the values used in current practice.

How much colonoscopy screening should be recommended to individuals with various degrees of family history of colorectal cancer? (Article)

2011-09-15T00:00:00Z

BACKGROUND: Individuals with a family history of colorectal cancer (CRC) are at increased risk for CRC. Current screening recommendations for these individuals are based on expert opinion. The authors investigated optimal screening strategies for individuals with various degrees of family history of CRC based on a cost-effectiveness analysis. METHODS: The MISCAN-Colon microsimulation model was used to estimate costs and effects of CRC screening strategies, varying by the age at which screening was started and stopped and by screening interval. The authors defined 4 risk groups, characterized by the number of affected first-degree relatives and their age at CRC diagnosis. For all risk groups, the optimal screening strategy had an incremental cost-effectiveness ratio of approximately $50,000 per life-year gained. RESULTS: The optimal screening strategy for individuals with 1 first-degree relative diagnosed after age 50 years was 6 colonoscopies every 5 years starting at age 50 years, compared with 4 colonoscopies every 7 years starting at age 50 years for average risk individuals. The optimal strategy had 10 colonoscopies every 4 years for individuals with 1 first-degree relative diagnosed before age 50 years, 13 colonoscopies every 3 years for individuals with 2 or more first-degree relatives diagnosed after age 50 years, and 15 colonoscopies every 3 years for individuals with 2 or more first-degree relatives of whom at least 1 was diagnosed before age 50 years. CONCLUSIONS: The optimal screening strategy varies considerably with the number of affected first-degree relatives and their age of diagnosis. Shorter screening intervals than the currently recommended 5 years may be appropriate for the highest risk individuals.

Quality evaluation of colonoscopy reporting and colonoscopy performance in daily clinical practice (Article)

2011-09-12T00:00:00Z

Background: Comprehensive monitoring of colonoscopy quality requires complete and accurate colonoscopy reporting. Objective: This study aimed to assess the compliance with colonoscopy reporting and to assess the quality of colonoscopy performance. Design: Consecutive colonoscopy reports were reviewed by hand. Four hundred reports were included from each department. Setting: Daily clinical practice in 12 Dutch endoscopy departments. Patients: Consecutive patients undergoing scheduled colonoscopy procedures. Main Outcome Measurements: Quality of reporting was assessed by using the American Society for Gastrointestinal Endoscopy criteria for colonoscopy reporting. Quality of colonoscopy performance was evaluated by using the cecal intubation rate and adenoma detection rate (ADR). Results: A total of 4800 colonoscopies were performed by 116 endoscopists: 70% by gastroenterologists, 16% by gastroenterology fellows, 10% by internists, 3% by nurse-endoscopists, and 1% by surgeons. The mean age of the patients was 59 years (standard deviation 16), and 47% were male. Reports contained information on indication, sedation practice, and extent of the procedure in more than 90%. Only 62% of the reports mentioned the quality of bowel preparation (range between departments 7%-100%); photographic documentation of the cecal landmarks was present in 71% (range 22%-97%). The adjusted cecal intubation rate was 92% (range 84%-97%). The ADR was 24% (range 13%-32%). Limitations: Dependent on reports, no intervention in endoscopic practice. No analysis for performance per endoscopist. Conclusion: Colonoscopy reporting varied significantly in clinical practice. Colonoscopy performance met the suggested standards; however, considerable variability between endoscopy departments was found. The results of this study underline the importance of the implementation of quality indicators and guidelines. Moreover, by continuous monitoring of quality parameters, the quality of both colonoscopy reporting and colonoscopy performance can easily be improved.

Peutz-Jeghers syndrome and family planning: the attitude towards prenatal diagnosis and pre-implantation genetic diagnosis (Article)

2011-08-10T00:00:00Z

Peutz-Jeghers syndrome (PJS) is a hereditary disorder caused by LKB1 gene mutations, and is associated with considerable morbidity and decreased life expectancy. This study was conducted to assess the attitude of PJS patients towards family planning, prenatal diagnosis (PND) and pregnancy termination, and pre-implantation genetic diagnosis (PGD). In a cross-sectional study, 61 adult PJS patients were asked to complete a questionnaire concerning genetic testing, family planning, PND and PGD. The questionnaire was completed by 52 patients (85% response rate, 44% males) with a median age of 44 (range 18-74) years. A total of 37 (71%) respondents had undergone genetic testing. In all, 24 respondents (46%, 75% males) had children. A total of 15 (29%) respondents reported that their diagnosis of PJS had influenced their decisions regarding family planning, including 10 patients (19%, 9/10 females) who did not want to have children because of their disease. Termination of pregnancy after PND in case of a foetus with PJS was considered 'acceptable' for 15% of the respondents, whereas 52% considered PGD acceptable. In conclusion, the diagnosis of PJS influences the decisions regarding family planning in one third of PJS patients, especially in women. Most patients have a negative attitude towards pregnancy termination after PND, while PGD in case of PJS is judged more acceptable. These results emphasise the importance of discussing aspects regarding family planning with PJS patients, including PND and PGD.European Journal of Human Genetics advance online publication, 10 August 2011; doi:10.1038/ejhg.2011.152.

Influence of Antiflatulent Dietary Advice on Intrafraction Motion for Prostate Cancer Radiotherapy (Article)

2011-06-09T00:00:00Z

Purpose: To evaluate the effect of an antiflatulent dietary advice on the intrafraction prostate motion in patients treated with intensity-modulated radiotherapy (IMRT) for prostate cancer. Methods and Materials: Between February 2002 and December 2009, 977 patients received five-beam IMRT for prostate cancer to a dose of 76 Gy in 35 fractions combined with fiducial markers for position verification. In July 2008, the diet, consisting of dietary guidelines to obtain regular bowel movements and to reduce intestinal gas by avoiding certain foods and air swallowing, was introduced to reduce the prostate motion. The intrafraction prostate movement was determined from the portal images of the first segment of all five beams. Clinically relevant intrafraction motion was defined as ≥50% of the fractions with an intrafraction motion outside a range of 3 mm. Results: A total of 739 patients were treated without the diet and 105 patients were treated with radiotherapy after introduction of the diet. The median and interquartile range of the average intrafraction motion per patient was 2.53 mm (interquartile range, 2.2-3.0) without the diet and 3.00 mm (interquartile range, 2.4-3.5) with the diet (p < .0001). The percentage of patients with clinically relevant intrafraction motion increased statistically significant from 19.1% without diet to 42.9% with a diet (odds ratio, 3.18; 95% confidence interval, 2.07-4.88; p < .0001). Conclusions: The results of the present study suggest that antiflatulent dietary advice for patients undergoing IMRT for prostate cancer does not reduce the intrafraction movement of the prostate. Therefore, antiflatulent dietary advice is not recommended in clinical practice for this purpose.

Authors' response (Article)

2011-06-02T00:00:00Z

Overview of the quality assurance movement in health care (Article)

2011-06-01T00:00:00Z

This chapter aims to describe the origin and current status of quality assurance (QA) in health care and to provide a background of similar developments in other industries, which have provided a major impetus for QA initiatives in health care. The interest in quality and safety in the health care sector has rapidly risen over the past decade. Without important lessons learnt from other industries, the interest and obtained improvements would have been far less fast. Knowledge on basic principles and challenges faced by other industries like the airline, car, and nuclear energy industry, that drove quality improvement projects, is of major relevance to understand the evolutions taking place in health care. To fully appreciate the QA movement, and design or implement quality improvement projects, its basic principles need to be understood. This chapter aims to give insights in basic principles underlying QA, and to discuss historical lessons that have been learnt from other industries. Furthermore, it discusses how to implement and assure a sustainable QA program.

Advance notification letters increase adherence in colorectal cancer screening: A population-based randomized trial (Article)

2011-06-01T00:00:00Z

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.

High cumulative risk of intussusception in patients with peutz-jeghers syndrome: Time to update surveillance guidelines (Article)

2011-05-01T00:00:00Z

Objectives: Peutz-Jeghers syndrome (PJS) is characterized by gastrointestinal hamartomas. The hamartomas are located predominantly in the small intestine and may cause intussusceptions. We aimed to assess the characteristics, risk, and onset of intussusception in a large cohort of PJS patients to determine whether enteroscopy with polypectomy should be incorporated into surveillance recommendations. Methods: All PJS patients from two academic hospitals were included in this cohort study (prospective follow-up between 1995 and July 2009). We obtained clinical data by interview and chart review. Deceased family members with PJS were included retrospectively. Cumulative intussusception risks were calculated by Kaplan-Meier analysis. Results: We included 110 PJS patients (46% males) from 50 families. In all, 76 patients (69%) experienced at least one intussusception (range 1-6), at a median age of 16 (3-50) years at first occurrence. The intussusception risk was 50% at the age of 20 years (95% confidence interval 17-23 years) and the risk was independent of sex, family history, and mutation status. The intussusceptions occurred in the small intestine in 95% of events, and 80% of all intussusceptions (n128) presented as an acute abdomen. Therapy was surgical in 92.5% of events. Based on 37 histology reports, the intussusceptions were caused by polyps with a median size of 35 mm (range 15-60 mm). Conclusions: PJS patients carry a high cumulative intussusception risk at young age. Intussusceptions are generally caused by polyps 15 mm and treatment is mostly surgical. These results support the approach of enteroscopic surveillance, with removal of small-intestinal polyps 10-15 mm to prevent intussusceptions. The effect of such an approach on the incidence of intussusception remains to be established in prospective trials.

Inter-observer variation in the histological diagnosis of polyps in colorectal cancer screening (Article)

2011-05-01T00:00:00Z

Aim: To determine the inter-observer variation in the histological diagnosis of colorectal polyps. Methods and results: Four hundred and forty polyps were randomly selected from a colorectal cancer screening programme. Polyps were first evaluated by a general (324 polyps) or expert (116 polyps) pathologist, and subsequently re-evaluated by an expert pathologist. Conditional agreement was reported, and inter-observer agreement was determined using kappa statistics. In 421/440 polyps (96%), agreement for their non-adenomatous or adenomatous nature was obtained, corresponding to a very good kappa value of 0.88. For differentiation of adenomas as non-advanced and advanced, consensus was obtained in 266/322 adenomas (83%), with a moderate kappa value of 0.58. For the non-adenomatous or adenomatous nature, both general and expert pathologists, and expert pathologists between each other, showed very good agreement {kappa values of 0.89 [95% confidence interval (CI) 0.83-0.95] and 0.86 (95% CI 0.73-0.98), respectively}. For categorization of adenomas as non-advanced and advanced, moderate agreement was found between general and expert pathologists, and between expert pathologists [kappa values of 0.56 (95% CI 0.44-0.67) and 0.64 (95% CI 0.43-0.85), respectively]. Conclusions: General and expert pathologists demonstrate very good inter-observer agreement for differentiating non-adenomas from adenomas, but only moderate agreement for non-advanced and advanced adenomas. The considerable variation in differentiating non-advanced and advanced adenomas suggests that more objective criteria are required for risk stratification in screening and surveillance guidelines.

Inter-observer variation in the histological diagnosis of polyps in colorectal cancer screening (Article)

2011-05-01T00:00:00Z

Prevalence and prognosis of synchronous colorectal cancer: A Dutch population-based study (Article)

2011-04-05T00:00:00Z

Background: A noticeable proportion of colorectal cancer (CRC) patients are diagnosed with synchronous CRC. Large population-based studies on the incidence, risk factors and prognosis of synchronous CRC are, however, scarce, and are needed for better determination of risks of synchronous CRC in patients diagnosed with colonic neoplasia. Methods: All newly diagnosed CRC between 1995 and 2006 were obtained from the Rotterdam Cancer Registry in The Netherlands, and studied for synchronous CRC. Results: Of the 13,683 patients diagnosed with CRC, 534 patients (3.9%) were diagnosed with synchronous CRC. The risk of having synchronous CRC was significantly higher in men (OR 1.54, 95% CI 1.29-1.84) and in patients aged >70 years (OR 1.83, 95% CI 1.39-2.40). Synchronous CRC patients had a significantly higher risk of distant metastases (OR 1.69, 95% CI 1.27-2.26). In 34% (184/534) the two tumours were located in different surgical segments. Five-year relative survival of synchronous CRC was similar to patients with solitary CRC after multivariate adjustment for the presence of distant metastases. Conclusion: One out of 25 patients diagnosed with CRC presents with synchronous CRC. In the multivariate analysis, survival of patients with synchronous CRC was similar to patients with solitary CRC, when corrected for the presence of distant metastases at first presentation. One third of the synchronous CRC were located in different surgical segments, which stresses the importance of performing total colon examination preferably prior to surgery.

Diagnostic Yield Improves With Collection of 2 Samples in Fecal Immunochemical Test Screening Without Affecting Attendance (Article)

2011-04-01T00:00:00Z

Background & Aims: The fecal immunochemical test (FIT) is superior to the guaiac-based fecal occult blood test in detecting neoplasia. There are not much data on the optimal number of FITs to perform. We conducted a population-based trial to determine attendance and diagnostic yield of 1- and 2-sample FIT screening. Methods: The study included 2 randomly selected groups of subjects aged 50-74 years (1-sample FIT, n = 5007; 2-sample FIT, n = 3197). The 2-sample group was instructed to collect fecal samples on 2 consecutive days. Subjects were referred for colonoscopy when at least 1 sample tested positive (≥50 ng hemoglobin/mL). Results: Attendance was 61.5% in the 1-sample group (2979 of 4845; 95% confidence interval, 60.1%-62.9%) and 61.3% in the 2-sample group (1875 of 3061; 95% confidence interval, 59.6%-63.0%; P = .84). In the 1-sample group 8.1% tested positive, and in the 2-sample group 12.8% had at least 1 positive test outcome and 5.0% had 2 positive test outcomes (P < .05). When the mean from both test results in the 2-sample group was used, 10.1% had a positive test outcome (P < .05). The detection rates for advanced neoplasia were 3.1% in the 1-sample group, 4.1% in the 2-sample group with at least 1 positive test outcome, 2.5% when both test results were positive, and 3.7% among subjects with the mean from both test results being positive. Conclusions: There is no difference in attendance for subjects offered 1- or 2-sample FIT screening. The results allow for the development of efficient FIT screening strategies that can be adapted for local colonoscopy capacities, rather than varying the cut-off value in a 1-sample strategy.

Systematic literature review and pooled analyses of risk factors for finding adenomas at surveillance colonoscopy (Article)

2011-03-25T00:00:00Z

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 10mm (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 10mm, 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.

Opinion of gastroenterologists towards quality assurance in endoscopy (Article)

2011-03-01T00:00:00Z

Background: Quality assurance has become an important issue. Many societies are adopting quality assurance programs in order to monitor and improve quality of care. Aim: To assess the opinion of gastroenterologists towards quality assurance on the endoscopy department. Methods: A survey was sent to all gastroenterologists (n=319) in the Netherlands. It assessed their opinion on a quality assurance program for endoscopy units, including its design, logistics, and content. Results: 200 gastroenterologists (63%) completed the questionnaire. 95% had a positive opinion towards quality assurance and 67% supposed an increase in quality. 28% assumed a negative impact on the time available for patient contact by introducing a quality assurance program and 35% that the capacity would decrease. A negative attitude towards disclosure of results to insurance companies (23%) and media (53%) was reported. Female gastroenterologists were less positive to share the results with other stakeholders (p<0.05).Most important quality measurements were assessment of complications (97%), standardised reporting (96%), and adequate patient information (95%). Conclusion: Gastroenterologists have a positive attitude towards quality assurance. However, concerns do exist about time investment and disclosure of results to others. Information provision and procedure characteristics were considered the most important aspects of quality assurance.

High cancer risk and increased mortality in patients with Peutz - Jeghers syndrome (Article)

2011-02-01T00:00:00Z

Background: Peutz-Jeghers syndrome (PJS) is associated with an increased cancer risk. As the determination of optimal surveillance strategies is hampered by wide ranges in cancer risk estimates and lack of data on cancer-related mortality, we assessed cancer risks and mortality in a large cohort of patients with PJS. Methods: Dutch PJS patients were included in this cohort study. Patients were followed prospectively between January 1995 and July 2009, and clinical data from the period before 1995 were collected retrospectively. Data were obtained by interview and chart review. Cumulative cancer risks were calculated by Kaplan-Meier analysis and relative cancer and mortality risks by Poisson regression analysis. Results: We included 133 PJS patients (48% males) from 54 families, contributing 5004 person-years of follow-up. 49 cancers were diagnosed in 42 patients (32%), including 25 gastrointestinal (GI) cancers. The median age at first cancer diagnosis was 45 years. The cumulative cancer risk was 20% at age 40 (GI cancer 12%), increasing to 76% at age 70 (GI cancer 51%). Cumulative cancer risks were higher for females than for males (p=0.005). The relative cancer risk was higher in PJS patients than in the general population (HR 8.96; 95% CI 6.46 to 12.42), and higher among female (HR 20.40; 95% CI 13.43 to 30.99) than among male patients (HR 4.76; 95% CI 2.82 to 8.04). 42 patients had died at a median age of 45 years, including 28 cancer-related deaths (67%). Mortality was increased in our cohort compared to the general population (HR 3.50; 95% CI 2.57 to 4.75). Conclusions: PJS patients carry high cancer risks, leading to increased mortality. The malignancies occur particularly in the GI tract and develop at young age. These results justify surveillance in order to detect malignancies in an early phase to improve outcome.

Uptake of faecal immunochemical test screening among non-participants in a flexible sigmoidoscopy screening programme (Article)

2011-01-01T00:00:00Z

CT colonography with limited bowel preparation for the detection of colorectal neoplasia in an FOBT positive screening population (Article)

2010-12-01T00:00:00Z

Purpose: Aim was to evaluate the accuracy of computed tomography colonography (CTC) for detection of colorectal neoplasia in a Fecal Occult Blood Test (FOBT) positive screening population. Methods: In three different institutions, consecutive FOBT positives underwent CTC after laxative free iodine tagging bowel preparation followed by colonoscopy with segmental unblinding. Each CTC was read by two experienced observers. For CTC and for colonoscopy the per-polyp sensitivity and per-patient sensitivity and specificity were calculated for detection of carcinomas, advanced adenomas, and adenomas. Results: In total 22 of 302 included FOBT positive participants had a carcinoma (7%) and 137 had an adenoma or carcinoma ≥ 10 mm (45%). CTC sensitivity for carcinoma was 95% with one rectal carcinoma as false negative finding. CTC sensitivity for advanced adenomas was 92% (95% CI: 88-96) vs. 96% (95% CI: 93-99) for colonoscopy (P = 0.26). For adenomas and carcinomas ≥ 10 mm the CTC per-polyp sensitivity was 93% (95% CI: 89-97) vs. 97% (95% CI: 94-99) for colonoscopy (P = 0.17). The per-patient sensitivity for the detection of adenomas and carcinomas ≥ 10 mm was 95% (95% CI: 91-99) for CTC vs. 99% (95% CI: 98-100) for colonoscopy (P = 0.07), while the per-patient specificity was 90% (95% CI: 86-95) and 96% (95% CI: 94-99), respectively (P < 0.001). Conclusion: CTC with limited bowel preparation performed in an FOBT positive screening population has high diagnostic accuracy for the detection of adenomas and carcinomas and a sensitivity similar to that of colonoscopy for relevant lesions.

Quality of life and psychological distress in patients with Peutz-Jeghers syndrome (Article)

2010-09-01T00:00:00Z

Little is known about psychological distress and quality of life (QoL) in patients with Peutz-Jeghers syndrome (PJS), a rare hereditary disorder. We aimed to assess QoL and psychological distress in PJS patients compared to the general population, and to evaluate determinants of QoL and psychological distress in a cross-sectional study. PJS patients completed a questionnaire on QoL, psychological distress, and illness perceptions. The questionnaire was returned by 52 patients (85% response rate, 56% females, median age 44.5 years). PJS patients reported similar anxiety (p = 0.57) and depression (p = 0.61) scores as the general population. They reported a lower general health perception (p = 0.003), more limitations due to emotional problems (p = 0.045) and a lower mental well-being (p = 0.036). Strong beliefs in negative consequences of PJS on daily life, a relapsing course of the disease, strong emotional reactions to PJS, and female gender were major determinants for a lower QoL. PJS patients experience a similar level of psychological distress as the general population, but a poorer general health perception, more limitations due to emotional problems, and a poorer mental QoL. Illness perceptions and female gender were major predictors for this lower QoL. These results may help to recognize PJS patients who might benefit from psychological support.

Increased colorectal cancer risk during follow-up in patients with hyperplastic polyposis syndrome: A multicentre cohort study (Article)

2010-08-01T00:00:00Z

Background and aims: Patients with hyperplastic polyposis syndrome (HPS) receive endoscopic surveillance to prevent malignant progression of polyps. However, the optimal treatment and surveillance protocol for these patients is unknown. The aim of this study was to describe the clinical and pathological features of a large HPS cohort during multiple years of endoscopic surveillance. Methods: Databases were searched for patients with HPS, who were analysed retrospectively. Endoscopy reports and histopathology reports were collected to evaluate frequency of endoscopic surveillance and to obtain information regarding polyp and the presence of colorectal cancer (CRC). Results: In 77 patients with HPS, 1984 polyps were identified during a mean follow-up period of 5.6 years (range: 0.5-26.6). In 27 (35%) patients CRC was detected of which 22 (28.5%) at initial endoscopy. CRC was detected during surveillance in five patients (cumulative incidence: 6.5%) after a median follow-up time of 1.3 years and a median interval of 11 months. Of these interval CRCs, 4/5 were detected in diminutive serrated polyps (range: 4-16 mm). The cumulative risk of CRC under surveillance was 7% at 5 years. At multivariate logistic regression, an increasing number of hyperplastic polyps (OR 1.05, p=0.013) and serrated adenomas (OR 1.09, p=0.048) was significantly associated with CRC presence. Conclusions: HPS patients undergoing endoscopic surveillance have an increased CRC risk. The number of serrated polyps is positively correlated with the presence of CRC in HPS, thus supporting a 'serrated pathway' to CRC. To prevent malignant progression, adequate detection and removal of all polyps seems advisable. If this is not feasible, surgical resection should be considered

Performance improvements of stool-based screening tests (Article)

2010-08-01T00:00:00Z

Stool testing is a widely accepted, non-invasive, technique for colorectal cancer (CRC) screening. Guaiac-based faecal occult blood test (gFOBT) screening has been proven to decrease CRC-related mortality; however gFOBT is hampered by a low sensitivity. Faecal immunochemical tests (FITs) have several advantages over gFOBT. First of all, FIT has a better sensitivity and higher uptake. Furthermore, the quantitative variant of the FIT allows choices on cut-off level for test-positivity according to colonoscopy resources available, personal risk profile, and/or intended detection rate in the screened population. Stool-based DNA (sDNA) tests aiming at the detection of specific DNA alterations may improve detection of CRC and adenomas compared to gFOBT screening, but large-scale population based studies are lacking. This review focuses on factors influencing test performance of those three stool based screening tests.

Screening for colorectal cancer: Comparison of perceived test burden of guaiac-based faecal occult blood test, faecal immunochemical test and flexible sigmoidoscopy (Article)

2010-07-01T00:00:00Z

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.

A back-to-back comparison of white light video endoscopy with autofluorescence endoscopy for adenoma detection in high-risk subjects (Article)

2010-06-01T00:00:00Z

Objective: To compare the sensitivity of autofluorescence endoscopy (AFE) and white light video endoscopy (WLE) for the detection of colorectal adenomas in high-risk patients belonging to Lynch syndrome (LS) or familial colorectal cancer (CRC) families. Methods: This was a prospective single-centre study carried out in a tertiary referral centre. The subjects were 75 asymptomatic patients originating from LS or familial CRC families. Patients were examined with either WLE followed by AFE or AFE followed by WLE. Back-to-back colonoscopy was performed by two blinded endoscopists. All lesions were removed during the second endoscopic procedure. Lesions missed during the second procedure were identified and removed on third pass. The sensitivity calculations for colorectal adenomas were based on histology results. The main outcome measures were the difference in sensitivity between WLE and AFE for the detection of adenomas in patients with LS or familial CRC. Results: At least one adenoma was detected in 41 (55%) patients. WLE identified adenomas in 28/41 patients and AFE in 37/41 patients, corresponding to a 32% increase. In total 95 adenomas were detected, 65 by WLE and 87 by AFE, resulting in a significantly higher sensitivity of AFE compared with WLE (92% vs 68%; p=0.001). The additionally detected adenomas with AFE were significantly smaller than the adenomas detected by WLE (mean 3.0 mm vs 4.9 mm, p<0.01). Conclusions: AFE improves the detection of colorectal adenomas in patients with LS or familial CRC. The results of this study suggest that AFE may be preferable for surveillance of these high-risk patients.

High cancer risk in peutz-jeghers syndrome: A systematic review and surveillance recommendations (Article)

2010-06-01T00:00:00Z

Objectives: Peutz-Jeghers syndrome (PJS) is an autosomal dominant inherited disorder associated with increased cancer risk. Surveillance and patient management are, however, hampered by a wide range in cancer risk estimates. We therefore performed a systematic review to assess cancer risks in PJS patients and used these data to develop a surveillance recommendation.Methods: A systematic PubMed search was performed up to February 2009, and all original articles dealing with PJS patients with confirmed cancer diagnoses were included. Data involving cancer frequencies, mean ages at cancer diagnosis, relative risks (RRs), and cumulative risks were collected.Results: Twenty-one original articles, 20 cohort studies, and one meta-analysis fulfilled the inclusion criteria. The cohort studies showed some overlap in the patient population and included a total of 1,644 patients; 349 of them developed 384 malignancies at an average age of 42 years. The most common malignancy was colorectal cancer, followed by breast, small bowel, gastric, and pancreatic cancers. The reported lifetime risk for any cancer varied between 37 and 93%, with RRs ranging from 9.9 to 18 in comparison with the general population. Age-related cumulative risks were given for any cancer and gastrointestinal, gynecological, colorectal, pancreatic, and lung cancers.Conclusions: PJS patients are markedly at risk for several malignancies, in particular gastrointestinal cancers and breast cancer. On the basis of these elevated risks, a surveillance recommendation is developed to detect malignancies in an early phase and to remove polyps that may be premalignant and may cause complications, so as to improve the outcome.

Study protocol: Population screening for colorectal cancer by colonoscopy or CT colonography: A randomized controlled trial (Article)

2010-05-19T00:00:00Z

Background: Colorectal cancer (CRC) is the second most prevalent type of cancer in Europe. Early detection and removal of CRC or its precursor lesions by population screening can reduce mortality. Colonoscopy and computed tomography colonography (CT colonography) are highly accurate exams and screening options that examine the entire colon. The success of screening depends on the participation rate. We designed a randomized trial to compare the uptake, yield and costs of direct colonoscopy population screening, using either a telephone consultation or a consultation at the outpatient clinic, versus CT colonography first, with colonoscopy in CT colonography positives.Methods and design: 7,500 persons between 50 and 75 years will be randomly selected from the electronic database of the municipal administration registration and will receive an invitation to participate in either CT colonography (2,500 persons) or colonoscopy (5,000 persons) screening. Those invited for colonoscopy screening will be randomized to a prior consultation either by telephone or a visit at the outpatient clinic. All CT colonography invitees will have a prior consultation by telephone. Invitees are instructed to consult their general practitioner and not to participate in screening if they have symptoms suggestive for CRC. After providing informed consent, participants will be scheduled for the screening procedure. The primary outcome measure of this study is the participation rate. Secondary outcomes are the diagnostic yield, the expected and perceived burden of the screening test, level of informed choice and cost-effectiveness of both screening methods.Discussion: This study will provide further evidence to enable decision making in population screening for colorectal cancer.Trial registration: Dutch trial register: NTR1829.

Colorectal cancer in post-liver transplant recipients (Article)

2010-05-01T00:00:00Z

PURPOSE: Several malignancies have been reported to occur more often after liver transplantation. Whether this is also true for colorectal carcinoma is controversial. Our aims were 1) to compare the observed rate of colorectal carcinoma in a post-liver transplantation cohort with incidence data from the general Dutch population, and 2) to stratify for patients with and without primary sclerosing cholangitis, because primary sclerosing cholangitis is well established as a risk factor for colorectal carcinoma. METHODS: We searched the medical records of liver transplantation patients who had a liver transplantation in our center between 1986 and 2007 with a follow-up of at least 3 months. Incidence data from the general population were retrieved from the Dutch Comprehensive Cancer Registry. Outcome measures were defined as standardized incidence ratio and incidence rate per 100,000 person-years. RESULTS: Three hundred ninety-four patients (58% men; mean age at liver transplantation, 46.6 y) were included in the 1986 to 2007 period. Bowel investigation before liver transplantation had been performed in 73% of patients. Median follow-up was 5.1 years (range, 0.25-20 y). The mean age at the end of follow-up was 52 years (SD, 13 y). Colorectal carcinoma was diagnosed in four patients (1%) during follow-up. The overall standardized incidence ratio for colorectal carcinoma in post-liver transplant recipients was 2.16 (95% CI: 0.81-5.76) compared with the general population and 1.26 (95% CI: 0.31-5.03) for nonprimary sclerosing cholangitis post-liver transplant recipients. CONCLUSION: This study suggests that the incidence of colorectal carcinoma is not increased in non-primary sclerosing cholangitis post-liver transplantation compared with the general population. A more intense colorectal carcinoma surveillance program based on this result remains controversial in nonprimary sclerosing cholangitis post-liver transplant recipients.

On the advent of MSI testing of all colorectal cancers and a substantial part of other Lynch syndrome-related neoplasms (Article)

2010-05-01T00:00:00Z

Risk of colorectal carcinoma in post-liver transplant patients: A systematic review and meta-analysis (Article)

2010-04-01T00:00:00Z

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.

Endoscopic therapy of small-bowel polyps by double-balloon enteroscopy in patients with Peutz-Jeghers syndrome (Article)

2010-04-01T00:00:00Z

Background: Peutz-Jeghers syndrome (PJS) is a hereditary disorder characterized by mucocutaneous pigmentations and hamartomatous polyps mainly in the small bowel. These polyps may cause complications such as intussusception. Objective: To assess therapeutic efficacy and safety of double-balloon enteroscopy (DBE) for detection and treatment of small-bowel polyps in patients with PJS. Design: Prospective cohort study. Setting: Tertiary-care referral center. Patients: This study involved 13 patients with PJS, defined as a proven STK11 gene mutation or according to international diagnostic criteria. Intervention: DBE with enteroscopic removal of pedunculated polyps of ≥10 mm. Main Outcome Measurements: Location, number and size of small-bowel polyps, polypectomy data, and complications and long-term complications associated with development of small-intestine polyps. Results: Thirteen patients with PJS (8 male, mean age 31 years) underwent 29 DBE procedures. Ten patients (77%) had a history of partial small-bowel resection because of small-bowel polyps. Small-bowel polyps were found in all 13 patients. The majority of polyps (94%) were located in the proximal jejunum. A total of 82 polyps of ≥10 mm were detected, and 79 (96%) were endoscopically removed without complications. After the introduction of DBE, no small-intestine-polyp-related complications occurred during a follow-up period of 356 person-months. Limitations: Small number of patients. Conclusion: DBE is clinically useful and safe for diagnosis and therapy of small-bowel polyps in patients with PJS, even in patients with a history of extensive abdominal surgery. DBE may decrease the need for laparotomy in patients with PJS.

Exposure to colorectal examinations before a colorectal cancer diagnosis: A case-control study (Article)

2010-04-01T00:00:00Z

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=7790) 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 457024 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.

Preferences for colorectal cancer screening strategies: a discrete choice experiment (Article)

2010-03-01T00:00:00Z

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.British Journal of Cancer advance online publication, 2 March 2010; doi:10.1038/sj.bjc.6605566 www.bjcancer.com.

Labeled versus unlabeled discrete choice experiments in health economics: An application to colorectal cancer screening (Article)

2010-03-01T00:00:00Z

Objectives: Discrete choice experiments (DCEs) in health economics commonly present choice sets in an unlabeled form. Labeled choice sets are less abstract and may increase the validity of the results. We empirically compared the feasibility, respondents' trading behavior, and convergent validity between a labeled and an unlabeled DCE for colorectal cancer (CRC) screening programs in The Netherlands. Methods: A labeled DCE version presented CRC screening test alternatives as "fecal occult blood test," "sigmoidoscopy," and "colonoscopy," whereas the unlabeled DCE version presented them as "screening test A" and "screening test B." Questionnaires were sent to participants and nonparticipants in CRC screening. Results: Total response rate was 276 (39%) out of 712 and 1033 (46%) out of 2267 for unlabeled and labeled DCEs, respectively (P < 0.001). The labels played a significant role in individual choices; approximately 22% of subjects had dominant preferences for screening test labels. The convergent validity was modest to low (participants in CRC screening: r = 0.54; P = 0.01; nonparticipants: r = 0.17; P = 0.45) largely because of different preferences for screening frequency. Conclusion: This study provides important insights in the feasibility and difference in results from labeled and unlabeled DCEs. The inclusion of labels appeared to play a significant role in individual choices but reduced the attention respondents give to the attributes. As a result, unlabeled DCEs may be more suitable to investigate trade-offs between attributes and for respondents who do not have familiarity with the alternative labels, whereas labeled DCEs may be more suitable to explain real-life choices such as uptake of cancer screening.

A review on the molecular diagnostics of Lynch syndrome: A central role for the pathology laboratory (Article)

2010-01-01T00:00:00Z

Lynch syndrome (LS) is caused by mutations in mismatch repair genes and is characterized by a high cumulative risk for the development of mainly colorectal carcinoma and endometrial carcinoma. Early detection of LS is important since surveillance can reduce morbidity and mortality. However, the diagnosis of LS is complicated by the absence of a pre-morbid phenotype and germline mutation analysis is expensive and time consuming. Therefore it is standard practice to precede germline mutation analysis by a molecular diagnostic work-up of tumours, guided by clinical and pathological criteria, to select patients for germline mutation analysis. In this review we address these molecular analyses, the central role for the pathologist in the selection of patients for germline diagnostics of LS, as well as the molecular basis of LS.

What determines individuals' preferences for colorectal cancer screening programmes? A discrete choice experiment. (Article)

2010-01-01T00:00:00Z

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-naive 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-naive 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.

What determines individuals' preferences for colorectal cancer screening programmes? A discrete choice experiment. (Article)

2010-01-01T00:00:00Z

Screening for colorectal cancer: Randomised trial comparing guaiac-based and immunochemical faecal occult blood testing and flexible sigmoidoscopy (Article)

2010-01-01T00:00:00Z

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 >10 mm; adenoma with >25% villous component or high grade dysplasia; serrated adenoma; >3 adenomas; >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 CRCscreening 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.

Cancer risk in MLH1, MSH2 and MSH6 mutation carriers; different risk profiles may influence clinical management (Article)

2009-12-23T00:00:00Z

Background: Lynch syndrome (LS) is associated with a high risk for colorectal cancer (CRC) and extracolonic malignancies, such as endometrial carcinoma (EC). The risk is dependent of the affected mismatch repair gene. The aim of the present study was to calculate the cumulative risk of LS related cancers in proven MLH1, MSH2 and MSH6 mutation carriers.Methods: The studypopulation consisted out of 67 proven LS families. Clinical information including mutation status and tumour diagnosis was collected. Cumulative risks were calculated and compared using Kaplan Meier survival analysis.Results: MSH6 mutation carriers, both males and females had the lowest risk for developing CRC at age 70 years, 54% and 30% respectively and the age of onset was delayed by 3-5 years in males. With respect to endometrial carcinoma, female MSH6 mutation carriers had the highest risk at age 70 years (61%) compared to MLH1 (25%) and MSH2 (49%). Also, the age of EC onset was delayed by 5-10 years in comparison with MLH1 and MSH2.Conclusions: Although the cumulative lifetime risk of LS related cancer is similar, MLH1, MSH2 and MSH6 mutations seem to cause distinguishable cancer risk profiles. Female MSH6 mutation carriers have a lower CRC risk and a higher risk for developing endometrial carcinoma. As a consequence, surveillance colonoscopy starting at age 30 years instead of 20-25 years is more suitable. Also, prophylactic hysterectomy may be more indicated in female MSH6 mutation carriers compared to MLH1 and MSH2 mutation carriers.

Mutation prediction models in Lynch syndrome: evaluation in a clinical genetic setting (Article)

2009-07-31T00:00:00Z

Background/aims: The identification of Lynch syndrome is hampered by the absence of specific diagnostic features and underutilization of genetic testing. Prediction models have therefore been developed, but they have not been validated for a clinical genetic setting. The aim of the present study was to evaluate the usefulness of currently available prediction models. METHODS: We collected data of 321 index probands who were referred to the department of Clinical Genetics of the Erasmus Medical Center because of a family history of colorectal cancer. These data were used as input for five previously published models. External validity was assessed by discriminative ability (AUC: area under the receiver operating characteristic curve) and calibration. For further insight, predicted probabilities were categorized with cut-offs of 5%, 10%, 20% and 40%. Furthermore, costs of different testing strategies were related to the number of extra detected mutation carriers. RESULTS: Of the 321 index probands, 66 harboured a germline mutation. All models discriminated well between high risk and low risk index probands (AUC: 0.82-0.84). Calibration was well for the Premm1,2 and Edinburgh model, but poor for the other models. Cut-offs could be found for the prediction models where costs could be saved while missing only few mutations. CONCLUSIONS: The Edinburgh and Premm1,2 model were the models with the best performance for an intermediate to high-risk setting. These models may well be of use in clinical practice to select patients for further testing of mismatch repair gene mutations.

Underutilization of microsatellite instability analysis in colorectal cancer patients at high risk for lynch syndrome (Article)

2009-05-01T00:00:00Z

Objective. The revised Bethesda Guidelines were published to improve the efficiency of recognizing Lynch syndrome (LS) by identifying LS-related malignancies that should be analyzed for microsatellite instability (MSI). The aim of this study was to evaluate whether MSI analysis was performed in colorectal cancer patients at risk for LS according to the revised Bethesda Guidelines. Material and methods. Patients diagnosed with colorectal cancer in 11 Dutch hospitals in 2005 and 2006 were selected from a regional database. The patients were included in the study if they met any of the following criteria; 1) diagnosed with colorectal cancer 50 years, 2) a second LS-associated tumor prior to the diagnosis of colorectal cancer in 2005/2006, and 3) colorectal cancer 60 years with a tumor displaying mucinous or signet-ring differentiation or medullary growth pattern. Results. Of 1905 colorectal cancer patients, 169 met at least one of the inclusion criteria. MSI analysis had been performed in 23 (14%) of the 169 tumors. MSI status had been determined in 18 of 80 included patients aged 50 years, in 4 of 70 patients with a second LS-related tumor, and in 3 of 41 patients aged 60 years with high-risk pathology features. Conclusions. There is marked underutilization of MSI analysis in patients at risk for LS. As a result LS might be underdiagnosed both in patients with colorectal cancer and in their relatives.

Screening for colorectal cancer: Random comparison of guaiac and immunochemical faecal occult blood testing at different cut-off levels (Article)

2009-04-07T00:00:00Z

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 (n10 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%; P0.001), whereas the number needed to scope (NNscope) to find one screenee with advanced neoplasia was similar (2.2 vs 1.9; P0.69). 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.

The views of gastroenterologists about the role of nurse endoscopists, especially in colorectal cancer screening (Article)

2009-04-01T00:00:00Z

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.

Risk analyses for screening sigmoidoscopy based on a colorectal cancer (CRC) population (Article)

2009-02-01T00:00:00Z

Objective. Although colonoscopy can be effective in the prevention of colorectal cancer (CRC), it requires many endoscopic facilities, has a high patient burden and risk of complications, and it is expensive. The aim of this study was to determine the risk for proximal CRC and to identify subgroups in which screening sigmoidoscopy can be effective. Material and methods. A database search was carried out on all patients who underwent endoscopy of the lower gastrointestinal (GI) tract between 1997 and 2005. All patients diagnosed with CRC were included. Variables including age, gender and the presence of distal colonic neoplasia were used for risk analyses. Results. In total, 783 patients were diagnosed with CRC. Tumour was located in the proximal colon in 68/255 (27%) of the patients<65 years. Of the patients<65 years, 22% (57/255) had proximal CRC without synchronous distal lesions and would thus have been missed by sigmoidoscopy screening. Among patients >65 years, 41% (216/528) were diagnosed with proximal CRC, significantly more often in women than in men (p<0.001). In 35% of patients (185/528) proximal CRC without distal colonic neoplasia was found, significantly more than in those under 65 years of age (p<0.001). Conclusions. Significantly more proximal localized CRC would have been missed by sigmoidoscopy screening in elderly patients, especially in women. In subjects<65 years of age, sigmoidoscopy screening allows detection of almost 80% of CRC cases and might suffice as a screening method.

A high incidence of MSH6 mutations in Amsterdam criteria II-negative families tested in a diagnostic setting (Article)

2008-11-01T00:00:00Z

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.

Colon tumors and colonoscopy (Article)

2008-10-01T00:00:00Z

Sporadic duodenal adenoma and the association with colorectal neoplasia: A case-control study (Article)

2008-06-01T00:00:00Z

OBJECTIVES: Sporadic duodenal adenomas are an uncommon finding. It is not clear whether patients with sporadic duodenal adenoma have a greater risk for colorectal neoplasia and should undergo colonoscopy. The aims of the present study were to estimate the prevalence of colorectal neoplasia in patients with sporadic duodenal adenoma, and to compare colorectal neoplasia rates in patients with sporadic duodenal adenomas versus those without them. METHODS: A retrospective case-control study was conducted to identify sporadic duodenal adenoma patients using the databases of two academic and one regional hospital in the Netherlands. Colonoscopic findings in the sporadic duodenal adenoma patients were compared with those of a control group of patients who underwent both gastroduodenoscopy and colonoscopy. Furthermore, the frequency of colorectal cancer in the sporadic duodenal adenoma patients was compared with the population incidence of colorectal cancer. RESULTS: During the period 1991-2006, 102 patients in total with sporadic duodenal adenomas were identified. Colonoscopy was performed in 49 patients (48%), and colorectal neoplasia was present in 21 of these patients (43%). There was a significantly higher rate of both colorectal neoplasia (43% vs 17%, odds ratio [OR] 3.6, 95% confidence interval [CI] 1.7-7.4) and advanced colorectal adenoma (18% vs 3%, OR 7.8, 95% CI 2.1-29.4) in the patients with sporadic duodenal adenoma compared to that in the control group. Also, the incidence of colorectal cancer was higher in sporadic duodenal adenoma patients compared to that in the population (P = 0.02). CONCLUSIONS: Individuals with sporadic duodenal adenomas appear to be at a significantly higher risk of colorectal neoplasia, and therefore should undergo colonoscopy.

A nationwide survey evaluating adherence to guidelines for follow-up after polypectomy or treatment for colorectal cancer (Article)

2008-05-01T00:00:00Z

BACKGROUND: Endoscopic follow-up (FU) in patients treated for colorectal adenomas or cancer (CRC) is intended to reduce the incidence of CRC. In the Dutch postpolypectomy guidelines, the FU interval is solely determined by the number of previous adenomas, whereas in other countries size and histology are also taken into account. Whether this difference in policy is also reflected in clinical practice is unknown. Furthermore, FU guidelines after CRC are not standardized in The Netherlands, even though national recommendations are available. GOAL: To assess the adherence to the current Dutch postpolypectomy guidelines and to evaluate the FU policy after CRC resection. STUDY: A survey was sent to all Gastrointestinal Departments in The Netherlands. The survey consisted of questions on logistic organization of FU, postpolypectomy FU intervals, and FU after CRC. RESULTS: The response rate was 85%. In contrast to the national guidelines, size and histology of the adenomas were often taken into account, leading to shortening of the FU interval. With respect to the CRC cases, 52% of the respondents advised shorter FU intervals than advised by the national recommendations. CONCLUSIONS: Despite recent Dutch postpolypectomy guidelines, clinicians incorporate histology and size into their clinical strategy. Either further education on the guidelines is needed, or the guidelines need to be reconsidered. Furthermore, evidence-based guidelines for FU after CRC should be formulated.

Epidemiology of acute upper gastrointestinal bleeding (Article)

2008-04-01T00:00:00Z

Acute upper gastrointestinal bleeding is an important emergency situation. Population-based epidemiology data are important to get insight in the actual healthcare problem. There are only few recent epidemiological surveys regarding acute upper gastrointestinal bleeding. Several surveys focusing on peptic ulcer disease showed a significant decrease in admission and mortality of peptic ulcer disease. Several more recent epidemiological surveys show a decrease in incidence of all cause upper gastrointestinal bleeding. The incidence of peptic ulcer bleeding remained stable. Peptic ulcer bleeding is the most common cause of upper gastrointestinal bleeding, responsible for about 50% of all cases, followed by oesophagitis and erosive disease. Variceal bleeding is the cause of bleeding in cirrhotic patients in 50-60%. Rebleeding in upper gastrointestinal bleeding occurs in 7-16%, despite endoscopic therapy. Rebleeding is especially high in variceal bleeding and peptic ulcer bleeding. Mortality ranges between 3 and 14% and did not change in the past 10 years. Mortality is increasing with increasing age and is significantly higher in patients who are already admitted in hospital for co-morbidity. Risk factors for peptic ulcer bleeding are NSAIDs use and H. pylori infection. In patients at risk for gastrointestinal bleeding and using NSAIDs, a protective drug was only used in 10%. COX-2 selective inhibitors do cause less gastroduodenal ulcers compared to non-selective NSAIDs, however, more cardiovascular adverse events are reported. H. pylori infection is found in about 50% of peptic ulcer bleeding patients. H. pylori should be tested for in all ulcer patients and eradication should be given.

Preface (Article)

2008-04-01T00:00:00Z

The use of genetic testing in hereditary colorectal cancer syndromes: Genetic testing in HNPCC, (A)FAP and MAP (Article)

2007-12-01T00:00:00Z

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. © 2007 The Authors Journal compilation

Review article: Detection and management of hereditary non-polyposis colorectal cancer (Lynch syndrome) (Article)

2007-12-01T00:00:00Z

Background: The most common hereditary colorectal cancer syndrome is hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome. Diagnosis of this syndrome is difficult, because of lack of specific diagnostic fatures. Aim: To discuss the diagnostic criteria and laboratory work up for HNPCC. Furthermore, survelillance programs for HNPCC and treatment of HNPCC associated colorectal cancer are discussed. Results: Current diagnostic criteria, including the Amsterdam II and Bethesda criteria, are suboptimal for the detection of HNPCC. Molecular screening by microsatellite instability (MSI) and immunohistochemistry (IHC) is useful in the diagnosis of HNPCC. Both techniques have a higher sensitivity compared to the Amsterdam II and Bethesda criteria. A combination of both MSI and IHC provides the most optimal selection for mutation analysis. After identification of a mutation in an affected individual, genetic counselling and presymptomatic mutation analysis should be offered to relatives. Furthermore, colonoscopic surveillance should be performed in proven mutation carriers. Conclusions: Identification of HNPCC is a clinical challenge involving many clinicians. Identification of persons at risk can be achieved by a combination of a detailed family history, testing with molecular and mutation analysis.

Tumor pyruvate kinase isoenzyme type M2 and immunochemical fecal occult blood test: Performance in screening for colorectal cancer (Article)

2007-10-01T00:00:00Z

OBJECTIVES: Immunochemical fecal occult blood test (FOBT) and determination of tumor pyruvate kinase isoenzyme type M2 (TuM2-PK) in stool samples may be valuable new screening tools for colorectal cancer (CRC). The aim of this study was to compare the accuracy of fecal TuM2-PK testing with immunochemical FOBT in patients with CRC or adenomas. METHODS: A total of 52 patients with CRC were analyzed, 47 with colorectal adenomas, and 63 matched controls with a normal colonoscopy. Nineteen additional patients with inflammatory bowel disease were tested to determine influence of inflammation. Stool samples were analyzed with two immunochemical FOBTs, Immo-care and OC-Light, and with a commercial enzyme-linked immunosorbent assay for TuM2-PK. RESULTS: In patients with CRC, the sensitivity of TuM2-PK, Immo-care and OC-Light was respectively 85, 92 and 94%. In patients with adenomas, the sensitivity was respectively 28, 40 and 34%. Specificity for these tests was 90% for TuM2-PK and 97% for both immunochemical FOBTs. All tests showed a high positivity rate in patients with inflammatory bowel disease (79% for TuM2-PK and Immo-care, and 89% for OC-Light). CONCLUSION: Both immunochemical FOBTs appear valuable and are sensitive tests for CRC screening. TuM2-PK does not have supplemental value for screening for CRC because of a lower sensitivity and specificity. None of these tests is sensitive enough for detection of advanced adenomas. Patients with inflammatory bowel disease should be excluded from CRC screening when using immunochemical FOBT or TuM2-PK.

Attendance at surveillance endoscopy of patients with adenoma or colorectal cancer (Article)

2007-01-01T00:00:00Z

Objective. Surveillance of patients treated for adenoma or colorectal cancer (CRC) is intended to reduce the incidence of CRC. Responsibility for the adherence to surveillance advice is often left to the patients and family physician. It is not known whether this type of passive policy affects the efficacy of surveillance. The aim of this study was to determine the yield of surveillance without active invitation to follow-up endoscopy. Material andmethods. The study comprised a cohort follow-up of patients under 75 years of age with adenomas or CRC at index endoscopy in the period 1997-99. Adherence and intervals of follow-up endoscopy were determined up to December 2004. Results. During the inclusion period 2946 patients underwent lower endoscopy. In total, 393 patients were newly diagnosed with colorectal polyps (n=280) or CRC (n=113). Polyps were classified as adenomas in 167/280 (61%) patients. Forty-five (27%) of the adenoma patients underwent surveillance endoscopy within the guideline interval, 63 (38%) underwent delayed endoscopy, and 59 (35%) did not have any follow-up at all. CRC was diagnosed in 113 patients. Thirty-six patients who died during the first year or were diagnosed with metastases were excluded from the analysis. Twenty-three (30%) of the remaining 77 patients underwent endoscopic surveillance according to the guidelines, 40 (52%) had delayed surveillance endoscopy, and 14/77 (18%) did not undergo surveillance endoscopy at all. Conclusions. In surveillance for colorectal neoplasia, active follow-up invitation is important. Given the low follow-up rate in our series, passive follow-up policies may lead to underperformance of surveillance programs. An active and controlled follow-up is advisable.