AbstractObjectiveTo review and summarise the evidence on the prevalence of colorectal adenomas and cancers at a follow-up screening colonoscopy after negative index colonoscopy, stratified by ...interval between examinations and by sex.DesignSystematic review and meta-analysis of all available studies.Data sourcesPubMed, Web of Science, and Embase. Two investigators independently extracted characteristics and results of identified studies and performed standardised quality ratings.Eligibility criteriaStudies assessing the outcome of a follow-up colonoscopy among participants at average risk for colorectal cancer with a negative previous colonoscopy (no adenomas).Results28 studies were identified, including 22 cohort studies, five cross sectional studies, and one case-control study. Findings for an interval between colonoscopies of one to five, five to 10, and more than 10 years were reported by 17, 16, and three studies, respectively. Summary estimates of prevalences of any neoplasm were 20.7% (95% confidence interval 15.8% to 25.5%), 23.0% (18.0% to 28.0%), and 21.9% (14.9% to 29.0%) for one to five, five to 10, and more than 10 years between colonoscopies. Corresponding summary estimates of prevalences of any advanced neoplasm were 2.8% (2.0% to 3.7%), 3.2% (2.2% to 4.1%), and 7.0% (5.3% to 8.7%). Seven studies also reported findings stratified by sex. Summary estimates stratified by interval and sex were consistently higher for men than for women.ConclusionsAlthough detection of any neoplasms was observed in more than 20% of participants within five years of a negative screening colonoscopy, detection of advanced neoplasms within 10 years was rare. Our findings suggest that 10 year intervals for colonoscopy screening after a negative colonoscopy, as currently recommended, may be adequate, but more studies are needed to strengthen the empirical basis for pertinent recommendations and to investigate even longer intervals.Study registrationProspero CRD42019127842.
Lymphoid and myeloid cells are abundant in the tumor microenvironment, can be quantified by immunohistochemistry and shape the disease course of human solid tumors. Yet, there is no comprehensive ...understanding of spatial immune infiltration patterns ('topography') across cancer entities and across various immune cell types. In this study, we systematically measure the topography of multiple immune cell types in 965 histological tissue slides from N = 177 patients in a pan-cancer cohort. We provide a definition of inflamed ('hot'), non-inflamed ('cold') and immune excluded patterns and investigate how these patterns differ between immune cell types and between cancer types. In an independent cohort of N = 287 colorectal cancer patients, we show that hot, cold and excluded topographies for effector lymphocytes (CD8) and tumor-associated macrophages (CD163) alone are not prognostic, but that a bivariate classification system can stratify patients. Our study adds evidence to consider immune topographies as biomarkers for patients with solid tumors.
Contradictory results were reported for the prognostic role of CpG island methylator phenotype (CIMP) among colorectal cancer (CRC) patients. Differences in the definitions of CIMP were the most ...common explanation for these discrepancies. The aim of this systematic review was to give an overview of the published studies on CRC prognosis according to the different definitions of CIMP. A systematic literature search was performed in MEDLINE and ISI Web of Science for articles published until 3 April 2015. Data extraction included information about the study population, the definition of CIMP, and investigated outcomes. Thirty-six studies were included in this systematic review. Among them, 30 studies reported the association of CIMP and CRC prognosis and 11 studies reported the association of CIMP with survival after CRC therapy. Overall, 16 different definitions of CIMP were identified. The majority of studies reported a poorer prognosis for patients with CIMP-positive (CIMP+)/CIMP-high (CIMP-H) CRC than with CIMP-negative (CIMP-)/CIMP-low (CIMP-L) CRC. Inconsistent results or varying effect strengths could not be explained by different CIMP definitions used. No consistent variation in response to specific therapies according to CIMP status was found. Comparative analyses of different CIMP panels in the same large study populations are needed to further clarify the role of CIMP definitions and to find out how methylation information can best be used to predict CRC prognosis and response to specific CRC therapies.
Colonoscopy is thought to be a powerful and cost-effective tool to reduce colorectal cancer (CRC) incidence and mortality. Empirical evidence for overall and risk group-specific definition of ...screening intervals is sparse. We aimed to assess the risk of CRC according to time since negative colonoscopy, overall, and by sex, smoking, and family history of CRC, in a large population-based case-control study.
In all, 1,945 patients with CRC and 2,399 population controls were recruited in 22 hospitals and through population registers in the Rhine-Neckar region of Germany from 2003 to 2007. Data on history of colonoscopy and important covariates were obtained by personal interviews and from medical records.
Compared with people who had never undergone colonoscopy, people with a previous negative colonoscopy had a strongly reduced risk of CRC. Adjusted odds ratios for time windows of 1 to 2, 3 to 4, 5 to 9, 10 to 19, and 20+ years after negative colonoscopy were 0.14 (95% CI, 0.10 to 0.20), 0.12 (95% CI, 0.08 to 0.19), 0.26 (95% CI, 0.18 to 0.39), 0.28 (95% CI, 0.17 to 0.45), and 0.40 (95% CI, 0.24 to 0.66), respectively. Low risks even beyond 10 years after negative colonoscopy were observed for both left- and right-sided CRC and in all risk groups assessed except current smokers, who had a risk similar to that of never smokers with no previous colonoscopy 10 or more years after a negative colonoscopy.
These results support suggestions that screening intervals for CRC screening by colonoscopy could be longer than the commonly recommended 10 years in most cases, perhaps even among men and people with a family history of CRC, but probably not among current smokers.
Colorectal tumors with mutations in BRAF and microsatellite stability (MSS) have been associated with adverse outcomes of patients. Combined tests for microsatellite instability-high (MSI-H) and BRAF ...mutations might therefore be used in risk assessment, particularly for patients with stage II tumors. We investigate the stage-specific prognostic value of combined testing for MSI-H and BRAF for patients with colorectal cancer.
We performed a retrospective analysis of colorectal tumor samples collected from 1995 patients at 22 hospitals in Germany, between 2003 and 2010. Samples were analyzed for MSI-H using an established mononucleotide marker panel; BRAF mutations (BRAFV600E) were detected by Sanger sequencing or in tissue microarray blocks using immunohistochemistry. Cancers were assigned to categories of having MSS without mutations in BRAF, MSS with mutant BRAF, MSI-H without mutations in BRAF, and MSI-H with mutant BRAF. We investigated the association between tumor categories with clinical and pathologic features and patient's overall, disease-specific, and recurrence-free survival (median follow-up time, 5.1 y).
Tumors were stage I in 364 (18%), stage II in 678 (34%), stage III in 673 (34%), and stage IV (14%) in 280 patients. Sixty-three percent of tumors were located in the colon and 37% in the rectum. Most tumors (85%) had MSS without mutations in BRAF, 3% had MSS with mutant BRAF, 7% had MSI-H without mutations in BRAF, and 5% had MSI-H with mutant BRAF. In patients whose tumors were MSI-H, mutation of BRAF did not significantly affect survival time. Patients whose tumors had MSS with mutant BRAF had significantly reduced overall survival (hazard ratio HR, 2.16; 95% CI, 1.54-3.04; P < .001), disease-specific survival (HR, 2.59; 95% CI, 1.77-3.79; P < .001), and recurrence-free survival (HR, 2.45; 95% CI, 1.70-3.52; P < .001) than patients whose tumors had MSS without BRAF mutation. Although BRAF mutations in tumors with MSS were associated with disease-specific survival of patients with stage III or IV tumors (P < .001), these features did not affect survival of patients with stage II tumors (P = .639).
In an analysis of almost 2000 patients with colorectal cancer, we found BRAF mutations to reduce survival of patients in stage III or IV (but not stage II) tumors with MSS. These findings do not support testing stage I or II colorectal tumors for BRAF mutations, although additional large studies are needed.
Empirical evidence for recommendations of surveillance intervals after detection and removal of adenomas at colonoscopy is still sparse and mostly based on observations of adenoma recurrence. We ...aimed to assess risk of colorectal cancer (CRC) according to time since polypectomy and factors that might be relevant for risk stratification.
In a population-based case-control study conducted in Germany, detailed history and results of previous large-bowel endoscopies were obtained by interview and from medical records. Risk of CRC among participants with detection of at least one adenoma at a preceding colonoscopy compared with participants without previous large-bowel endoscopy was assessed according to time since polypectomy among 2,582 cases with CRC and 1,798 matched controls.
Adjusted odds ratios (95% CIs) of CRC for participants with polypectomy less than 3, 3 to 5, and 6 to 10 years ago (using participants without previous endoscopy as reference group) were 0.2 (0.2 to 0.3), 0.4 (0.3 to 0.6), and 0.9 (0.5 to 1.5), respectively. Strong, significant risk reduction within 5 years was consistently seen for women and men, younger and older participants, patients with and without high-risk polyps (three or more polyps, at least one polyp ≥ 1 cm, at least one polyp with villous components), and those with and without polypectomy in the right colon. With adjusted odds ratios of 0.1 (0.1 to 0.2), 0.3 (0.2 to 0.5) and 0.4 (0.2 to 0.8) for patients with polypectomy less than 3, 3 to 5, and 6 to 10 years ago, risk reduction was particularly strong for left-sided CRC.
Extension of surveillance intervals to 5 years should be considered, even after detection and removal of high-risk polyps.
According to the International Agency for Research on Cancer (IARC), there is sufficient evidence for the carcinogenicity of processed meat consumption in humans, specifically regarding colorectal ...cancer (CRC) risk. Evidence for the carcinogenicity of red meat consumption is more limited but points in the same direction.
A macro-simulation approach was used to calculate age- and sex-specific potential impact fractions in a 30-year period (2020-2050).
We estimated numbers and proportions of future CRC cases preventable under different scenarios of reducing the intake of processed and red meat in the German population.
Eliminating processed meat intake could reduce the burden of CRC by approximately 205,000 cases in Germany (9.6%) in 2020-2050, 2/3 among males (145,000) and 1/3 among females (60,000). Without red meat intake, approximately 63,000 CRC cases could be avoided (2.9%), 39,000 among males and 24,000 among females. Reductions in the mean consumption of both processed and red meat by one or two servings (each 11 or 22 g) per day would be expected to reduce CRC case numbers by 68,000 (3.1%) and 140,000 (6.5%), respectively.
A reduction in red and processed meat intake might substantially reduce the incidence of CRC in Germany. The means of achieving such a reduction might include price and taxation policies, food labeling, and clearer risk communication aiming to reduce individual intake.
Abstract Background and Aims Colonoscopy has been demonstrated to be effective in reducing colorectal cancer (CRC) incidence and mortality, and has been widely used for primary CRC screening in ...Germany and the United States. We performed a population-based analysis to evaluate and compare the public health impact of recent colonoscopy use on CRC deaths among adults aged 55 to 79 years in Germany and the United States from 2008 to 2011. Methods The epidemiologic metrics of attributable fraction and prevented fraction as well as the impact numbers were calculated using colonoscopy utilization data from nationally representative health surveys, relative risk estimates from medical literature, and CRC death registry data. Results Overall, 36.6% (95% credible interval CrI, 27.3%-45.5%) of CRC deaths in Germany were estimated to be attributable to nonuse of colonoscopy, compared with the U.S. estimates of 38.2% (95% CrI, 28.6%-47.1%) and 33.6% (95% CrI, 24.8%-42.2%) for years 2008 to 2009 and 2010 to 2011, respectively. The proportion of CRC deaths theoretically prevented by colonoscopy use within 10 years was 30.7% (95% CrI, 24.8%-35.7%) in Germany, whereas in the United States this proportion ranged from 29.0% (95% CrI, 23.4%-33.6%) for 2008 to 2009 to 33.9% (95% CrI, 27.4%-39.2%) for 2010 to 2011. Conclusions Recent colonoscopy use is likely to have prevented a considerable fraction of CRC mortality in both countries, and more deaths could be avoided by increasing colonoscopy utilization in the target population. Attributable and prevented fraction can provide valuable information on the public health impact of colonoscopy use and guide the policy making.
Individuals with Lynch syndrome (LS), one of the most common inherited cancer syndromes, are at increased risk of developing malignancies, in particular colorectal cancer (CRC). Regular colonoscopy ...with polypectomy is recommended to reduce CRC risk in LS individuals. However, recent independent studies demonstrated that a substantial proportion of LS individuals develop CRC despite regular colonoscopy. The reasons for this surprising observation confirmed by large prospective studies are a matter of debate. In this review, we collect existing evidence from clinical, epidemiological and molecular studies and interpret them with regard to the origins and progression of LS‐associated CRC. Alongside with hypotheses addressing colonoscopy quality and pace of progression from adenoma to cancer, we discuss the role of alternative precursors and immune system in LS‐associated CRC. We also identify gaps in current knowledge and make suggestions for future studies aiming at improved CRC prevention for LS individuals.
Previous meta-analyses have shown an improved survival with higher blood 25-hydroxyvitamin D (25(OH)D) concentrations in patients with colorectal cancer (CRC). However, a number of much larger ...studies have been published since then. We provide an updated meta-analysis to synthesize current evidence. PubMed and Web of Science databases were systematically searched for eligible studies. The dose-response relationships and pooled hazard ratios for overall and CRC-specific survival comparing the highest versus the lowest categories of blood 25(OH)D concentrations were assessed. Subgroup analyses based on study geographic location, year of publication, sample size, length of follow-up time and stage were conducted to explore potential sources of heterogeneity. Overall, 11 original studies with a total of 7718 CRC patients were included. The dose-response meta-analysis showed an improvement in survival outcomes with increasing blood 25(OH)D concentrations. Pooled hazard ratios (95% confidence intervals) comparing highest versus lowest categories were 0.68 (0.55⁻0.85) and 0.67 (0.57⁻0.78) for overall and CRC-specific survival, respectively. Associations were more prominent among studies conducted in Europe, with larger sample sizes, and including stage I⁻IV patients. This updated meta-analysis reveals robust evidence of an association between higher blood 25(OH)D concentrations and better survival in CRC patients. The potential for enhancing prognosis of CRC patients by vitamin D supplementation should be explored by randomized trials.
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