Multidisciplinary, evidence-based guidelines for quality assurance in colorectal cancer screening and diagnosis have been developed by experts in a project coordinated by the International Agency for ...Research on Cancer. The full guideline document covers the entire process of population-based screening. It consists of 10 chapters and over 250 recommendations, graded according to the strength of the recommendation and the supporting evidence. The 450-page guidelines and the extensive evidence base have been published by the European Commission. The chapter on colonoscopic surveillance following adenoma removal includes 24 graded recommendations. The content of the chapter is presented here to promote international discussion and collaboration by making the principles and standards recommended in the new EU Guidelines known to a wider professional and scientific community. Following these recommendations has the potential to enhance the control of colorectal cancer through improvement in the quality and effectiveness of surveillance and other elements in the screening process, including multi-disciplinary diagnosis and management of the disease.
Background
A single flexible sigmoidoscopy at around the age of 60 years has been proposed as an effective strategy for colorectal cancer (CRC) screening.
Methods
We conducted a randomized controlled ...trial to evaluate the effect of flexible sigmoidoscopy screening on CRC incidence and mortality. A questionnaire to assess the eligibility and interest in screening was mailed to 236 568 men and women, aged 55-64 years, who were randomly selected from six trial centers in Italy. Of the 56 532 respondents, interested and eligible subjects were randomly assigned to the intervention group (invitation for flexible sigmoidoscopy; n = 17 148) or the control group (no further contact; n = 17 144), between June 14, 1995, and May 10, 1999. Flexible sigmoidoscopy was performed on 9911 subjects. Intention-to-treat and per-protocol analyses were performed to compare the CRC incidence and mortality rates in the intervention and control groups. Per-protocol analysis was adjusted for noncompliance.
Results
A total of 34 272 subjects (17 136 in each group) were included in the follow-up analysis. The median follow-up period was 10.5 years for incidence and 11.4 years for mortality; 251 subjects were diagnosed with CRC in the intervention group and 306 in the control group. Overall incidence rates in the intervention and control groups were 144.11 and 176.43, respectively, per 100 000 person-years. CRC-related death was noted in 65 subjects in the intervention group and 83 subjects in the control group. Mortality rates in the intervention and control groups were 34.66 and 44.45, respectively, per 100 000 person-years. In the intention-to-treat analysis, the rate of CRC incidence was statistically significantly reduced in the intervention group by 18% (rate ratio RR = 0.82, 95% confidence interval CI = 0.69 to 0.96), and the mortality rate was non-statistically significantly reduced by 22% (RR = 0.78; 95% CI = 0.56 to 1.08) compared with the control group. In the per-protocol analysis, both CRC incidence and mortality rates were statistically significantly reduced among the screened subjects; CRC incidence was reduced by 31% (RR = 0.69; 95% CI = 0.56 to 0.86) and mortality was reduced by 38% (RR = 0.62; 95% CI = 0.40 to 0.96) compared with the control group.
Conclusion
A single flexible sigmoidoscopy screening between ages 55 and 64 years was associated with a substantial reduction of CRC incidence and mortality.
Multidisciplinary, evidence-based guidelines for quality assurance in colorectal cancer screening and diagnosis have been developed by experts in a project coordinated by the International Agency for ...Research on Cancer. The full guideline document covers the entire process of population-based screening. It consists of 10 chapters and over 250 recommendations, graded according to the strength of the recommendation and the supporting evidence. The 450-page guidelines and the extensive evidence base have been published by the European Commission. The chapter on quality assurance in endoscopy includes 50 graded recommendations. The content of the chapter is presented here to promote international discussion and collaboration by making the principles and standards recommended in the new EU Guidelines known to a wider professional and scientific community. Following these recommendations has the potential to enhance the control of colorectal cancer through improvement in the quality and effectiveness of endoscopy and other elements in the screening process, including multidisciplinary diagnosis and management of the disease.
Independent studies undertaken on the US National Polyp Study dataset 21 showed that the observed reduction in incidence of colorectal cancer could be accounted for entirely by the initial ...colonoscopic polypectomy. ...this study does not provide evidence that colonoscopic surveillance reduces risk further than achieved by the initial clearing colonoscopy. ...data to the contrary are available, it must be assumed that patients with "high risk" adenomas remain at increased risk despite a single negative follow up examination.
This randomised controlled trial is examining the hypothesis that a single flexible sigmoidoscopy screening offered at around age 60 years can lower the incidence and mortality of colorectal cancer. ...We report here on acceptability, safety, feasibility, and yield.
Men and women aged 55–64 years, in 14 UK centres, who responded to a mailed questionnaire that they would attend for flexible sigmoidoscopy screening if invited, were randomly assigned screening or control (ratio one to two). The control group was not contacted. Small polyps were removed during screening, and colonoscopy was undertaken if high-risk polyps (three or more adenomas, size 1 cm or greater, villous, severely dysplastic, or malignant) were found.
Of 354 262 people asked about their interest in having flexible sigmoidoscopy screening, 194 726 (55%) responded positively, and 170 432 eligible individuals were randomised. Attendance among those assigned screening was 71% (40 674 of 57 254). 2131 (5%) were classified as highrisk and referred for colonoscopy; 38 525 with no polyps or only low-risk polyps detected were discharged. Distal adenomas were detected in 4931 (12·1%) and distal cancer in 131 (0·3%). Proximal adenomas were detected in 386 (18·8% of those undergoing colonoscopy) and proximal cancer in nine cases (0·4%). 62% of cancers were Dukes' stage A or locally excised. There was one perforation after flexible sigmoidoscopy and four after colonoscopy. An average of 48 people were screened, and two or three colonoscopy referrals generated, per centre each week.
Our flexible sigmoidoscopy screening regimen is acceptable, feasible, and safe. The prevalence of neoplasia is high, and colonoscopy referral rates of 5% are acceptable.
Angiogenesis is characterised by activation, migration and proliferation of endothelial cells and is central to the pathology of cancer, cardiovascular disease and chronic inflammation. Somatostatin ...is an inhibitory polypeptide that acts through five receptors (sst 1, 2, 3, 4, 5). Sst has previously been reported in endothelium, but their role remains obscure. Here, we report the expression of sst in human umbilical vein endothelial cells (HUVECs) in vitro, during proliferation and quiescence. A protocol for culturing proliferating and quiescent HUVECs was established, and verified by analysing cell cycle distribution in propidium-iodide-stained samples using flow cytometry. Sst mRNA was then quantified in nine proliferating and quiescent HUVEC lines using quantitative reverse transcriptase-polymerase chain reaction. Sst 2 and 5 were preferentially expressed in proliferating HUVECs. All samples were negative for sst 4. Sst 1 and 3 expression and cell cycle progression were unrelated. Immunostaining for sst 2 and 5 showed positivity in proliferating but not quiescent cells, confirming sst 2 and 5 protein expression. Inhibition of proliferating cells with somatostatin analogues Octreotide and SOM230, which have sst 5 activity, was found (Octreotide 10(-10)-10(-6) M: 48.5-70.2% inhibition; SOM230 10(-9)-10(-6) M: 44.9-65.4% inhibition) in a dose-dependent manner, suggesting that sst 5 may have functional activity in proliferation. Dynamic changes in sst 2 and 5 expression during the cell cycle and the inhibition of proliferation with specific analogues suggest that these receptors may have a role in angiogenesis.
The putative locus for hereditary mixed polyposis syndrome (HMPS) in a large family of Ashkenazi descent (SM96) was previously reported to map to chromosome sub-bands 6q16–q21. However, new clinical ...data, together with molecular data from additional family members, have shown 6q linkage to be incorrect. A high-density genomewide screen for the
HMPS gene was therefore performed on SM96, using stringent criteria for assignment of affection status to minimize phenocopy rates. Significant evidence of linkage was found only on a region on chromosome 15q13-q14. Since this region encompassed
CRAC1, a locus involved in inherited susceptibility to colorectal adenomas and carcinomas in another Ashkenazi family (SM1311), we determined whether
HMPS and
CRAC1 might be the same. We found that affected individuals from both families shared a haplotype between D15S1031 and D15S118; the haplotype was rare in the general Ashkenazi population. A third informative family, SM2952, showed linkage of disease to
HMPS/CRAC1 and shared the putative ancestral haplotype, as did a further two families, SMU and RF. Although there are probably multiple causes of the multiple colorectal adenoma and cancer phenotype in Ashkenazim, an important one is the
HMPS/CRAC1 locus on 15q13–q14.
There is no national screening programme for colorectal cancer in the UK despite the fact that the annual death toll from this disease exceeds that of breast and cervical cancer. Faecal occult blood ...testing (FOBT) is under evaluation for screening, but screening by sigmoidoscopy is not considered viable. This situation contrasts with the USA where both annual FOBT and screening by flexible sigmoidoscopy every 3 to 5 years are recommended from 50 years old.
We seek to demonstrate that most of the benefit from the US screening policy would accrue from a single flexible sigmoidoscopy examination at age 55 to 60 years with appropriate colonoscopic surveillance for the 3% to 5% found to have high-risk adenomas (≥1 cm or villous histology). If applied nationally, this screening regimen could prevent about 5500 colorectal cancer cases and 3500 deaths in the UK each year, thus saving 40 000 years of life. We estimate that there would be little net cost to the National Health Service because savings obtained from treating fewer patients would largely offset the cost of screening.
We recommend that a randomised trial to evaluate screening by single flexible sigmoidoscopy should start without delay. Such a trial would involve about 120 000 participants, and 15 years of follow-up would be required to obtain a clear answer on mortality, although information on incidence reduction would be available sooner.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBJE, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
In studies of adult humans and in animal models, dietary intakes of the macronutrients, particularly fat, are related to body composition; however, data on children are more scarce.
We sought to ...determine whether diet composition is related to percentage body fat in children aged 1.5-4.5 y.
In 77 preschool children, a 4-d weighed-food record was used to determine intakes of total energy and energy from each macronutrient. An oxygen-18 dilution method was used to calculate percentage body fat. Habitual physical activity level was determined by calculating the ratio of total energy expenditure (from stable isotope analyses) to predicted basal metabolic rate. Dietary intake and body-composition data were analyzed to evaluate whether diet composition was related to body fat. Further analyses incorporating physical activity level were performed.
Percentage body fat was not significantly correlated with dietary intake variables (total energy or percentage of energy from fat, carbohydrate, or protein) and did not differ significantly among 3 increasing levels of each dietary intake variable by analysis of variance. In multiple regression analysis, physical activity level was related to body fat whereas diet composition was not.
We found no relations between dietary intakes of total energy, fat, carbohydrate, or protein and percentage body fat in children. The relation between fat intake and body fat may develop over time and may not be evident in preschool children. Energy expenditure, in particular physical activity level, may have a greater influence on body composition in early childhood.
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