How do people interpret information about colorectal cancer screening: observations from a think-aloud study.

BACKGROUND: The English NHS Bowel Cancer Screening Programme biennially invites individuals aged 60-74 to participate in screening. The booklet, 'Bowel Cancer Screening: The Facts' accompanies this invitation. Its primary aim is to inform potential participants about the aims, advantages and disadvantages of colorectal cancer screening. OBJECTIVE: To provide detailed commentary on how individuals process the information contained within 'The Facts' booklet. DESIGN, SETTING AND PARTICIPANTS: This study comprised of 18 interviews with individuals aged 45-60 and used a 'think-aloud' paradigm in which participants read aloud the booklet. Participant utterances (verbal statements made in response to researcher-led prompts) were transcribed and analysed using a combination of content and thematic analysis. RESULTS: A total of 776 coded utterances were analysed (mean = 43.1 per person; range = 8-95). While overall comprehension was satisfactory, several problem areas were identified such as the use of complex unfamiliar terminology and the presentation of numerical information. Specific sections such as colonoscopy risk information evoked negative emotional responses. Participants made several suggestions for ways in which comprehension might be improved. CONCLUSION: Public perceptions of the NHS Bowel Cancer Screening Programme information materials indicated that specific aspects of the booklet were difficult to process. These materials may be an appropriate target to improve public understanding of the aims, benefits and disadvantages of colorectal cancer screening. These findings will contribute to a broader NIHR-funded project that aims to design a supplementary 'gist-based' information leaflet suitable for low literacy populations.

The effect of a supplementary ('Gist-based') information leaflet on colorectal cancer knowledge and screening intention: a randomized controlled trial.

Guided by Fuzzy Trace Theory, this study examined the impact of a 'Gist-based' leaflet on colorectal cancer screening knowledge and intentions; and tested the interaction with participants' numerical ability. Adults aged 45-59 years from four UK general practices were randomly assigned to receive standard information ('The Facts', n = 2,216) versus standard information plus 'The Gist' leaflet (Gist + Facts, n = 2,236). Questionnaires were returned by 964/4,452 individuals (22 %). 82 % of respondents reported having read the information, but those with poor numeracy were less likely (74 vs. 88 %, p < .001). The 'Gist + Facts' group were more likely to reach the criterion for adequate knowledge (95 vs. 91 %; p < .01), but this was not moderated by numeracy. Most respondents (98 %) intended to participate in screening, with no group differences and no interaction with numeracy. The improved levels of knowledge and self-reported reading suggest 'The Gist' leaflet may increase engagement with colorectal cancer screening, but ceiling effects reduced the likelihood that screening intentions would be affected.

Protein biomarkers in exfoliated cells collected from the human rectal mucosa: implications for colorectal disease detection and monitoring.

PURPOSE: Colorectal disease biomarkers in stool are actively explored, but instability of biomolecules in faeces constitutes a problem. Collection of exfoliated cells from the surface of the rectal mucosa provides an alternative to stool-based methods. We aimed to develop an original approach allowing preservation and quantification of protein biomarkers in exfoliated material and tested it in a pilot clinical study. METHODS: A novel method of cell and protein preservation in ammonium sulphate-rich buffers was developed using cultured human cells and applied to exfoliated cell samples collected from 139 faecal occult blood test (FOBT)-positive patients prior to colonoscopies. Protein biomarkers comprising calprotectin, eosinophil-derived neurotoxin (EDN), dimeric pyruvate kinase type M2 (M2PK), soluble cytokeratin-18, d-dimer and glyceraldehyde 3-phosphate dehydrogenase were quantified using enzyme-linked immunosorbent assays with parallel cytological and immunocytochemical analysis. RESULTS: Long-term preservation of cells and their protein constituents at ambient temperature was achieved using buffers containing saturated ammonium sulphate. Application of this approach to exfoliated cell samples allowed consistent protein quantification. Calprotectin, EDN, M2PK, soluble cytokeratin 18 and d-dimer showed dramatic increase in a few cases of inflammatory bowel disease (IBD) detected among trial participants. Cytological signs of inflammation were also present in these samples. CONCLUSIONS: Application of exfoliated cells collected from the surface of the rectal mucosa provides a reliable method for quantifying protein biomarkers of gastrointestinal diseases. Our preliminary results obtained in a limited number of cases indicate that the approach might be especially useful for IBD diagnosis and monitoring, but further studies are needed to assess its diagnostic value.

Mural inflammation in Crohn disease: location-matched histologic validation of MR imaging features.

PURPOSE: To validate proposed magnetic resonance (MR) imaging features of Crohn disease activity against a histopathologic reference. MATERIALS AND METHODS: Ethical permission was given by the University College London hospital ethics committee, and informed written consent was obtained from all participants. Preoperative MR imaging was performed in 18 consecutive patients with Crohn disease undergoing elective small-bowel resection. The Harvey-Bradshaw index, the C-reactive protein level, and disease chronicity were recorded. The resected bowel was retrospectively identified at preoperative MR imaging, and wall thickness, mural and lymph node/cerebrospinal fluid (CSF) signal intensity ratios on T2-weighted fat-saturated images, gadolinium-based contrast material uptake, enhancement pattern, and mesenteric signal intensity on T2-weighted fat-saturated images were recorded. Precise histologic matching was achieved by imaging the ex vivo surgical specimens. Histopathologic grading of acute inflammation with the acute inflammatory score (AIS) (on the basis of mucosal ulceration, edema, and quantity and depth of neutrophilic infiltration) and the degree of fibrostenosis was performed at each site, and results were compared with MR imaging features. Data were analyzed by using linear regression with robust standard errors of the estimate. RESULTS: AIS was positively correlated with mural thickness and mural/CSF signal intensity ratio on T2-weighted fat-saturated images (P < .001 and P = .003, respectively) but not with mural enhancement at 30 and 70 seconds (P = .50 and P = .73, respectively). AIS was higher with layered mural enhancement (P < .001), a pattern also commonly associated with coexisting fibrostenosis (75%). Mural/CSF signal intensity ratio on T2-weighted fat-saturated images was higher in histologically edematous bowel than in nonedematous bowel (P = .04). There was no correlation between any lymph node characteristic and AIS. CONCLUSION: Increasing mural thickness, high mural signal intensity on T2-weighted fat-saturated images, and a layered pattern of enhancement reflect histologic features of acute small-bowel inflammation in Crohn disease.

Mural Crohn disease: correlation of dynamic contrast-enhanced MR imaging findings with angiogenesis and inflammation at histologic examination--pilot study.

PURPOSE: To determine mural perfusion dynamics in Crohn disease by using dynamic contrast material-enhanced magnetic resonance (MR) imaging and to correlate these with histopathologic markers of inflammation and angiogenesis. MATERIALS AND METHODS: Ethical permission was given by the University College London Hospital ethics committee, and informed consent was obtained from all participants. Eleven consecutive patients with Crohn disease (eight female patients, three men; mean age, 39.5 years; range, 16.4-66.6 years) undergoing elective small-bowel resection were recruited between July 2006 and December 2007. Harvey-Bradshaw index, C-reactive protein (CRP) level, and disease chronicity were recorded. Preoperatively, dynamic contrast-enhanced MR imaging was performed through the section of bowel destined for resection, and slope of enhancement, time to maximum enhancement, enhancement ratio, the volume transfer coefficient K(trans), and the extracellular volume fraction v(e) were calculated for the affected segment. Ex vivo surgical specimens were imaged to facilitate imaging-pathologic correlation. Histopathologic sampling of the specimen was performed through the imaged tissue, and microvascular density (MVD) was determined, together with acute and chronic inflammation scores. Correlations between clinical, MR imaging, and histopathologic data were made by using the Kendall rank correlation and linear regression. RESULTS: Disease chronicity was positively correlated with enhancement ratio (correlation coefficient, 0.82; P = .002). Slope of enhancement demonstrated a significant negative correlation with MVD (correlation coefficient, -0.86; P < .001). There was a negative correlation between CRP level and slope of enhancement (correlation coefficient, -0.77; P = .006). Neither acute nor chronic inflammation score correlated with any other parameter. CONCLUSION: Certain MR imaging-derived mural hemodynamic parameters correlate with disease chronicity and angiogenesis in Crohn disease, but not with histologic and clinical markers of inflammation. Data support the working hypothesis that microvessel permeability increases with disease chronicity and that tissue MVD is actually inversely related to mural blood flow.

The Impact of Diet-Induced Weight Loss on Biomarkers for Colorectal Cancer: An Exploratory Study (INTERCEPT).

OBJECTIVE: The aim of this study was to explore the potential effects of diet-induced weight loss on molecular biomarkers of colorectal cancer risk in serum and colorectal tissue. METHODS: This single-arm exploratory study included 20 adults with BMI ≥ 30 kg/m2 completing an 8-week, complete, low-energy liquid diet. Pre- and postintervention anthropometric measurements, fasting blood draws, and endoscopic examinations to procure colorectal biopsies were performed. Fasting insulin, glucose, insulinlike growth factor 1 (IGF-1), C-reactive protein (CRP), and blood lipids were measured in serum, and tissue markers of apoptosis (M30), colonocyte proliferation (Ki-67), and insulin signaling (phospho-mTOR) were assessed using immunohistochemical staining. RESULTS: Participants achieved substantial weight loss (mean = 13.56%). Mean concentrations of insulin, glucose, and cholesterol were significantly reduced (P < 0.05), but IGF-1 and CRP were not. Colorectal tissue expression of Ki-67 was significantly reduced (preintervention mean score = 7, postintervention mean score = 3.9, mean % change -43.8; P = 0.027). There were no significant changes in M30 or phospho-mTOR. CONCLUSIONS: Weight loss in individuals with obesity was associated with improvements in insulin sensitivity and blood lipid profiles and a significant reduction in tissue Ki-67 expression. This is one of the first studies to demonstrate potential cancer-relevant changes in colorectal tissue following weight loss achieved through diet.

Contemporary perioperative management of adult familial dysautonomia (Riley-Day syndrome).

Familial dysautonomia (Riley-Day syndrome) is a rare multisystem disorder associated with an excess risk of perioperative morbidity and mortality. Because life expectancy is limited, few reports consider the perioperative management of familial dysautonomia in adults with advanced disease and end-organ dysfunction. Here, we report on the management of an adult patient with familial dysautonomia, highlighting recent developments in perioperative technology and pharmacology of special relevance to this challenging population.

The development and testing of a brief ('gist-based') supplementary colorectal cancer screening information leaflet.

OBJECTIVE: To design and user-test a 'gist-based' colorectal cancer screening information leaflet, which promotes comprehension of the screening offer. METHODS: Twenty-eight individuals approaching screening age were recruited from organisations in deprived areas of England. Using a between-subjects design, we tested iterations of a newly-designed gist-based information leaflet. Participants read the leaflet and answered 8 'true' or 'false' comprehension statements. For the leaflet to be considered fit-for-purpose, all statements had to be answered correctly by at least 80% of participants in each round. Alterations were made if this threshold was not met and additional rounds of testing were undertaken. RESULTS: At round 1, answers to 2/8 statements did not meet the threshold. After changes, answers in round 2 did not reach the threshold for 1/8 statements. In round 3, all answers were adequate and the leaflet was deemed fit-for-purpose. Qualitative data offered solutions such as language and layout changes which led to improved comprehension of the leaflet. CONCLUSION: User-testing substantially improved the design and subsequent comprehensibility of a theory-driven gist-based colorectal cancer screening information leaflet. PRACTICAL IMPLICATIONS: This leaflet will be evaluated as part of a large national randomised controlled trial designed to reduce socioeconomic inequalities in colorectal cancer screening participation.

Inequalities in participation in an organized national colorectal cancer screening programme: results from the first 2.6 million invitations in England.

BACKGROUND: An organized, population-based, colorectal cancer screening programme was initiated in England in 2006 offering biennial faecal occult blood testing (FOBT) to adults aged 60-69 years. Organized screening programmes with no associated financial costs to the individual should minimize barriers to access for lower socio-economic status (SES) groups. However, SES differences in uptake were observed in the pilot centres of the UK programme, so the aim of this analysis was to identify the extent of inequalities in uptake by SES, ethnic diversity, gender and age in the first 28 months of the programme. Design Cross-sectional analysis of colorectal cancer screening uptake data. METHODS: Between October 2006 and January 2009, over 2.6 million adults aged 60-69 years were mailed a first FOBT kit by the five regional screening hubs. Uptake was defined as return of a test kit within 13 weeks. We used multivariate generalized linear regression to examine variation by area-based socioeconomic deprivation, area-based ethnicity, gender and age. RESULTS: Uptake was 54%, but showed a gradient across quintiles of deprivation, ranging from 35% in the most deprived quintile to 61% in the least deprived. Multivariate analyses confirmed an independent effect of deprivation, with stronger effects in women and older people. The most ethnically diverse areas also had lower uptake (38%) than other areas (52-58%) independent of SES, age, gender and regional screening hub. Ethnic disparities were more pronounced in men but equivalent across age groups. More women than men returned a kit (56 vs 51%), but there was also an interaction with age, with uptake increasing with age in men (49% at 60-64 years; 53% at 65-69 years) but not women (57 vs 56%). CONCLUSIONS: Overall uptake rates in this organized screening programme were encouraging, but nonetheless there was low uptake in the most ethnically diverse areas and a striking gradient by SES. Action to promote equality of uptake is needed to avoid widening inequalities in cancer mortality.

Social variations in access to hospital care for patients with colorectal, breast, and lung cancer between 1999 and 2006: retrospective analysis of hospital episode statistics.

OBJECTIVES: To determine the extent to which type of hospital admission (emergency compared with elective) and surgical procedure varied by socioeconomic circumstances, age, sex, and year of admission for colorectal, breast, and lung cancer. DESIGN: Repeated cross sectional study with data from individual patients, 1 April 1999 to 31 March 2006. SETTING: Hospital episode statistics (HES) dataset. PARTICIPANTS: 564 821 patients aged 50 and over admitted with a diagnosis of colorectal, breast, or lung cancer. MAIN OUTCOME MEASURES: Proportion of patients admitted as emergencies, and the proportion receiving the recommended surgical treatment. RESULTS: Patients from deprived areas, older people, and women were more likely to be admitted as emergencies. For example, the adjusted odds ratio for patients with breast cancer in the least compared with most deprived fifth of deprivation was 0.63 (95% confidence interval 0.60 to 0.66) and the adjusted odds ratio for patients with lung cancer aged 80-89 compared with those aged 50-59 was 3.13 (2.93 to 3.34). There were some improvements in disparities between age groups but not for patients living in deprived areas over time. Patients from deprived areas were less likely to receive preferred procedures for rectal, breast, and lung cancer. These findings did not improve with time. For example, 67.4% (3529/5237) of patients in the most deprived fifth of deprivation had anterior resection for rectal cancer compared with 75.5% (4497/5959) of patients in the least deprived fifth (1.34, 1.22 to 1.47). Over half (54.0%, 11 256/20 849) of patients in the most deprived fifth of deprivation had breast conserving surgery compared with 63.7% (18 445/28 960) of patients in the least deprived fifth (1.21, 1.16 to 1.26). Men were less likely than women to undergo anterior resection and lung cancer resection and older people were less likely to receive breast conserving surgery and lung cancer resection. For example, the adjusted odds ratio for lung cancer patients aged 80-89 compared with those aged 50-59 was 0.52 (0.46 to 0.59). Conclusions Despite the implementation of the NHS Cancer Plan, social factors still strongly influence access to and the provision of care.