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The American Cancer Society has recommended initiating colorectal cancer (CRC) screening at age 45 years instead of 50 years. We estimated the cost effectiveness and national effects of adopting this recommendation. We compared screening strategies and alternative resource allocations in a validated Markov model. We based national projections on screening participation rates by age and census data. Screening colonoscopy initiation at age 45 years instead of 50 years in 1000 persons averted 4 CRCs and 2 CRC deaths, gained 14 quality-adjusted life-years (QALYs), cost $33,900/QALY gained, and required 758 additional colonoscopies. These 758 colonoscopies could instead be used to screen 231 currently unscreened 55-year-old persons or 342 currently unscreened 65-year-old persons, through age 75 years. These alternatives averted 13–14 CRC cases and 6–7 CRC deaths and gained 27–28 discounted QALYs while saving $163,700–$445,800. Improving colonoscopy completion rates after abnormal results from a fecal immunochemical test yielded greater benefits and savings. Initiation of fecal immunochemical testing at age 45 years instead of 50 years cost $7700/QALY gained. Shifting current age-specific screening rates to 5 years earlier could avert 29,400 CRC cases and 11,100 CRC deaths over the next 5 years but would require 10.7 million additional colonoscopies and cost an incremental $10.4 billion. Improving screening rates to 80% in persons who are 50–75 years old would avert nearly 3-fold more CRC deaths at one third the incremental cost. In a Markov model analysis, we found that starting CRC screening at age 45 years is likely to be cost effective. However, greater benefit, at lower cost, could be achieved by increasing participation rates for unscreened older and higher-risk persons. [ABSTRACT FROM AUTHOR]

Myeloid derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells that accumulate in circulation of cancer patients and at tumor sites where they suppress anti-tumor immunity. We previously reported that in a colon cancer prevention trial of a MUC1 vaccine tested in individuals at increased risk for colon cancer, those who did not mount immune response to the vaccine had higher pre-vaccination levels of circulating MDSC compared to those who did. We also reported that individuals with pancreatic premalignancy, Intraductal Papillary Mucinous Neoplasm (IPMN), had increased circulating levels of MDSC that inversely correlated with spontaneous antibody responses against the pancreatic tumor associated antigen MUC1, abnormally expressed on IPMN. Accumulation of MDSC in cancer and their immunosuppressive role had been well established but their presence in premalignancy was unexpected. In this study we compared MDSC in premalignancy with those in cancer with the hypothesis that there might be differences in the composition of various MDSC subpopulations and their immunosuppressive functions due to different lengths of exposure to disease and/or different tissue microenvironments. In cohorts of patients with premalignant polyps, colon cancer, premalignant IPMN, and pancreatic cancer, we confirmed higher levels of MDSC in premalignancy compared to healthy controls, higher levels of MDSC in cancer compared to premalignancy, but no difference in their subpopulation composition or immunosuppressive capacity. We show that levels of MDSC in premalignancy correlate negatively in vivo with spontaneous MUC1-specific antibody responses and in vitro with polyclonal T cell proliferation and IFN-γ secretion. [ABSTRACT FROM AUTHOR]

Background and Aims: Different post‐polypectomy guidelines underscore the need for high‐quality baseline colonoscopy before appropriate surveillance recommendations can be made. Standards for colonoscopy practice have been advocated by gastrointestinal societies. Our aims were to define standards for the procedural practice of colonoscopy in this particular setting of surveillance and to generate a colonoscopy procedural quality checklist that could be implemented in clinical practice. Methods: This study was based on the Delphi process methodology. The baseline questionnaire included 12 domains and 56 individual statements. A total of three rounds were carried out between September 2015 and March 2016 until consensus or lack of consensus was reached. Results: In total, consensus was reached on 27 statements in nine domains. High levels of agreement and consensus were reached that: (i) colonoscopy should be considered complete only if the whole cecum has been inspected, including the ileocecal valve and the appendiceal orifice (agreement score 4.63; degree of consensus 82%); (ii) quality of the bowel preparation should always be reported (agreement score 4.9, degree of consensus 94%); and (iii) it is preferable to use a segmental validated scale (agreement score 4.36, degree of consensus 86%). Consensus was also reached regarding multiple statements related to documentation of polyps and their resection. Finally, a colonoscopy quality checklist was drafted. Conclusion: Consensus on different statements regarding quality of colonoscopy has been reached. Based on this consensus, we propose a colonoscopy quality checklist that would be helpful for post‐polypectomy surveillance recommendations. [ABSTRACT FROM AUTHOR]

Background: Serrated polyps are important colorectal cancer precursors that are variably detected during colonoscopy. We measured serrated polyp detection rate (SPDR) in a large, multicenter, cross-sectional study of colonoscopy quality to identify drivers of SPDR variation.Methods: Colonoscopy and pathology reports were collected for a 2-year period (10/2013-9/2015) from four sites across the United States. Data from reports, including size, location, and histology of polyps, were abstracted using a validated natural language processing algorithm. SPDR was defined as the proportion of colonoscopies with ≥ 1 serrated polyp (not including hyperplastic polyps). Multivariable logistic regression was performed to determine endoscopist characteristics associated with serrated polyp detection.Results: A total of 104 618 colonoscopies were performed by 201 endoscopists who varied with respect to specialty (86 % were gastroenterologists), sex (18 % female), years in practice (range 1 - 51), and number of colonoscopies performed during the study period (range 30 - 2654). The overall mean SPDR was 5.1 % (SD 3.8 %, range 0 - 18.8 %). In multivariable analysis, gastroenterology specialty training (odds ratio [OR] 1.89, 95 % confidence interval [CI] 1.33 - 2.70), fewer years in practice (≤ 9 years vs. ≥ 27 years: OR 1.52, 95 %CI 1.14 - 2.04)], and higher procedure volumes (highest vs. lowest quartile: OR 1.77, 95 %CI 1.27 - 2.46)] were independently associated with serrated polyp detection.Conclusions: Gastroenterology specialization, more recent completion of training, and greater procedure volume are associated with serrated polyp detection. These findings imply that both repetition and training are likely to be important contributors to adequate detection of these important cancer precursors. Additional efforts to improve SPDR are needed. [ABSTRACT FROM AUTHOR]

Importance: Individuals with adenomatous polyps are advised to undergo repeated colonoscopy surveillance to prevent subsequent colorectal cancer (CRC), but the relationship between adenomas at colonoscopy and long-term CRC incidence is unclear.Objective: To compare long-term CRC incidence by colonoscopy adenoma findings.Design, Setting, and Participants: Multicenter, prospective cohort study of participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer randomized clinical trial of flexible sigmoidoscopy (FSG) beginning in 1993 with follow-up for CRC incidence to 2013 across the United States. Participants included 154 900 men and women aged 55 to 74 years enrolled in PLCO of whom 15 935 underwent colonoscopy following their first positive FSG screening result. The final day of follow-up was December 31, 2013.Exposures: Enrolled participants had been randomized to FSG or usual care. Participants who underwent FSG and had abnormal findings were referred for follow-up. Subsequent colonoscopy findings were categorized as advanced adenoma (≥1 cm, high-grade dysplasia, or tubulovillous or villous histology), nonadvanced adenoma (<1 cm without advanced histology), or no adenoma.Main Outcomes and Measures: The primary outcome was CRC incidence within 15 years of the baseline colonoscopy. The secondary outcome was CRC mortality.Results: There were 15 935 participants who underwent colonoscopy (men, 59.7%; white, 90.7%; median age, 64 y [IQR, 61-68]). On initial colonoscopy, 2882 participants (18.1%) had an advanced adenoma, 5068 participants (31.8%) had a nonadvanced adenoma, and 7985 participants (50.1%) had no adenoma; median follow-up for CRC incidence was 12.9 years. CRC incidence rates per 10 000 person-years of observation were 20.0 (95% CI, 15.3-24.7; n = 70) for advanced adenoma, 9.1 (95% CI, 6.7-11.5; n = 55) for nonadvanced adenoma, and 7.5 (95% CI, 5.8-9.7; n = 71) for no adenoma. Participants with advanced adenoma were significantly more likely to develop CRC compared with participants with no adenoma (rate ratio [RR], 2.7 [95% CI, 1.9-3.7]; P < .001). There was no significant difference in CRC risk between participants with nonadvanced adenoma compared with no adenoma (RR, 1.2 [95% CI, 0.8-1.7]; P = .30). Compared with participants with no adenoma, those with advanced adenoma were at significantly increased risk of CRC death (RR, 2.6 [95% CI, 1.2-5.7], P = .01), but mortality risk in participants with nonadvanced adenoma was not significantly different (RR, 1.2 [95% CI, 0.5-2.7], P = .68).Conclusions and Relevance: Over a median of 13 years of follow-up, participants with an advanced adenoma at diagnostic colonoscopy prompted by a positive flexible sigmoidoscopy result were at significantly increased risk of developing colorectal cancer compared with those with no adenoma. Identification of nonadvanced adenoma may not be associated with increased colorectal cancer risk.Trial Registration: clinicaltrials.gov Identifier: NCT00002540. [ABSTRACT FROM AUTHOR]

Colorectal tumorigenesis is driven by genetic alterations in the adenomatous polyposis coli (APQ tumor suppressor pathway and effectively inhibited by nonsteroidal antiinflammatory drugs (NSAIDs). However, how NSAIDs prevent colorectal tumorigenesis has remained obscure. We found that the extrinsic apoptotic pathway and the BH3 interacting-domain death agonist (BID) are activated in adenomas from NSAID-treated patients. Loss of BID abolishes NSAID-mediated tumor suppression, survival benefit, and apoptosis in tumor-initiating stem cells in APCMin/+ mice. BID-mediated cross-talk between the extrinsic and intrinsic apoptotic pathways is responsible for selective killing of neoplastic cells by NSAIDs. We further demonstrate that NSAIDs induce death receptor signaling in both cancer and normal cells, but only activate BID in cells with APC deficiency and ensuing c-Myc activation. Our results suggest that NSAIDs suppress intestinal tumorigenesis through BID-mediated synthetic lethality triggered by death receptor signaling and gatekeeper mutations, and provide a rationale for developing more effective cancer prevention strategies and agents. [ABSTRACT FROM AUTHOR]

Background: The benefits of endoscopic testing for colorectal-cancer screening are uncertain. We evaluated the effect of screening with flexible sigmoidoscopy on colorectal-cancer incidence and mortality. Methods: From 1993 through 2001, we randomly assigned 154,900 men and women 55 to 74 years of age either to screening with flexible sigmoidoscopy, with a repeat screening at 3 or 5 years, or to usual care. Cases of colorectal cancer and deaths from the disease were ascertained. Results: Of the 77,445 participants randomly assigned to screening (intervention group), 83.5% underwent baseline flexible sigmoidoscopy and 54.0% were screened at 3 or 5 years. The incidence of colorectal cancer after a median follow-up of 11.9 years was 11.9 cases per 10,000 person-years in the intervention group (1012 cases), as compared with 15.2 cases per 10,000 person-years in the usual-care group (1287 cases), which represents a 21% reduction (relative risk, 0.79; 95% confidence interval [CI], 0.72 to 0.85; P<0.001). Significant reductions were observed in the incidence of both distal colorectal cancer (479 cases in the intervention group vs. 669 cases in the usual-care group; relative risk, 0.71; 95% CI, 0.64 to 0.80; P<0.001) and proximal colorectal cancer (512 cases vs. 595 cases; relative risk, 0.86; 95% CI, 0.76 to 0.97; P=0.01). There were 2.9 deaths from colorectal cancer per 10,000 person-years in the intervention group (252 deaths), as compared with 3.9 per 10,000 person-years in the usual-care group (341 deaths), which represents a 26% reduction (relative risk, 0.74; 95% CI, 0.63 to 0.87; P<0.001). Mortality from distal colorectal cancer was reduced by 50% (87 deaths in the intervention group vs. 175 in the usual-care group; relative risk, 0.50; 95% CI, 0.38 to 0.64; P<0.001); mortality from proximal colorectal cancer was unaffected (143 and 147 deaths, respectively; relative risk, 0.97; 95% CI, 0.77 to 1.22; P=0.81). Conclusions: Screening with flexible sigmoidoscopy was associated with a significant decrease in colorectal-cancer incidence (in both the distal and proximal colon) and mortality (distal colon only). (Funded by the National Cancer Institute; PLCO ClinicalTrials.gov number, NCT00002540.) [ABSTRACT FROM PUBLISHER]

Background Among randomized trials evaluating flexible sigmoidoscopy (FSG) for its effect on colorectal cancer mortality, only the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial screened its participants more than one time. We report outcomes from the PLCO screening FSG program and evaluate the increased yield produced by a second FSG. Methods Participants were screened by 60-cm FSG in 10 regional screening centers at study entry and 3 or 5 years later, depending on the time of random assignment. Results from subsequent diagnostic intervention were tracked and recorded in a standardized fashion, and outcomes were compared according to sex and age. The protocol discouraged repeat FSG in persons with colorectal cancer or adenoma diagnosed after the initial FSG. Results Of 77 447 enrollees, 67 073 (86.6%) had at least one FSG and 39 443 (50.9%) had two FSGs. Diagnostic intervention occurred in 74.9% after a positive first FSG and in 78.7% after a positive repeat FSG. The second FSG increased the screening yield by 32%: Colorectal cancer or advanced adenoma was detected in 37.8 per 1000 persons after first screening and in 49.8 per 1000 persons after all screenings. The second FSG increased the yield of cancer or advanced adenoma by 26% in women and by 34% in men. Of 223 subjects who received a diagnosis of colorectal carcinoma within 1 year of a positive FSG, 64.6% had stage I and 17.5% had stage II disease. Conclusions Repeat FSG increased the detection of colorectal cancer or advanced adenoma in women by one-fourth and in men by one-third. Screen-detected carcinomas were early stage (stage I or II) in greater than 80% of screened persons. Colorectal cancer mortality data from the PLCO, as the definitive endpoint, will follow in later publications. [ABSTRACT FROM PUBLISHER]

Background: It is unclear whether the disproportionately higher incidence and mortality from colorectal cancer among blacks compared with whites reflect differences in health-care utilization or colorectal cancer susceptibility. [ABSTRACT FROM PUBLISHER]

Background & Aims: The recommended timing of surveillance colonoscopy for individuals with adenomatous polyps is based on adenoma histology, size, and number. The burden and cost of surveillance colonoscopy are significant. The aim of this study was to examine the use of surveillance colonoscopy on a community-wide basis. Methods: We retrospectively queried participants in the Prostate, Lung, Colorectal, and Ovarian Cancer screening trial in 9 US communities about use of surveillance colonoscopy. Subjects whose initial colonoscopy showed advanced adenoma (AA), nonadvanced adenoma (NAA), or no adenoma (NA) findings were included. Colonoscopy examinations were confirmed by reviewing colonoscopy reports. Results: Of 3876 subjects selected for inquiry, 3627 (93.6%) responded. The cumulative probability of a surveillance colonoscopy within 5 years was 58.4% (n = 1342) in the AA group, 57.5% in those with ≥3 NAAs (n = 117), 46.7% in those with 1–2 NAAs (n = 905), and 26.5% (n = 1263) in subjects with NAs. Within 7 years, 33.2% of subjects with AAs received ≥2 surveillance examinations versus 26.9% for those with ≥3 NAAs, 18.2% for those with 1 or 2 NAAs, and 10.4% for those with NAs. Incomplete colonoscopy, family history of colorectal cancer, or interval adenomatous findings could explain only a minority of surveillance colonoscopy in low-risk subjects. Conclusions: In community practice, there is substantial overuse of surveillance colonoscopy among low-risk subjects and underuse among subjects with AAs. Interventions to better align use of surveillance colonoscopy with risk for advanced lesions are needed. [Copyright &y& Elsevier]

Abstract: Colorectal cancer (CRC) expresses a hypoglycosylated (abnormal) form of MUC1 different than MUC1 expressed in normal colon, which elicits antibodies in patients with CRC. This form of MUC1 is expressed in other abnormal but non-malignant lesions in the colon, such as adenomatous polyps, precursors to CRC. Estimates of the prevalence of anti-MUC1 antibodies in subjects with these lesions are lacking. We evaluated IgM and IgG anti-MUC1 antibodies in 148 subjects with non-advanced adenomas (NAA), advanced adenomas (AA), colorectal cancer, hyperplastic polyps (HPP), and normal controls. We hypothesized that the prevalence of anti-MUC1 antibodies would increase along the adenoma-carcinoma sequence as more dysplastic tissues express more abnormal MUC1. Anti-MUC1 IgM was found in 5/47 (10.6%) of normals, 5/45 (11.1%) of NAA, 7/47 (14.9%) of AA, and 4/20 (20.0%) of CRC (p =0.70). The prevalence of anti-MUC1 IgG was 8/47 (17.0%) of normals, 14/45 (31.1%) of NAA, 14/47 (29.8%) of AA, and 6/20 (30.0%) of CRC (p =0.36). We found no significant differences in the prevalence of anti-MUC1 antibodies between subjects along the adenoma-carcinoma sequence. However, in an exploratory analysis, the median normalized anti-MUC1 IgG OD level of the combined abnormal groups (NAA, AA, CRC) was significantly higher than the normals (0.045 OD vs. 0.030 OD; p =0.017). Our data support further studies into the potential role of anti-MUC1 immunity in preventing progression of premalignant colon lesions to colon cancer. [Copyright &y& Elsevier]

Background and Aims: Prospective information on the use and yield of surveillance colonoscopy is limited. We examined the use and yield of surveillance colonoscopy among participants in the Polyp Prevention Trial (PPT) after the 4-year dietary intervention trial ended. Methods: We followed a cohort of 1297 participants. We calculated the cumulative probability of posttrial colonoscopy and investigated the yield and predictive factors for adenoma and advanced adenoma recurrence over a mean time of 5.9 years. Results: Seven-hundred seventy-four subjects (59.7%) had a repeat colonoscopy. Among 431 subjects with low-risk adenomas (1–2 nonadvanced adenomas) at baseline and no adenoma recurrence at the end of the PPT (lowest-risk category), 30.3% underwent a repeat colonoscopy within 4 years. Among 55 subjects who had high-risk adenomas (advanced adenoma and/or ≥3 nonadvanced adenomas) at baseline and again at the final PPT colonoscopy (highest-risk category), 41.3% had a colonoscopy within 3 years and 63.5% had an examination within 5 years. The cumulative yield of advanced adenoma through 6 years was 3.6% for the lowest-risk category, 38.9% for the highest-risk category, and ranged from 6.6% to 13.8% for intermediate-risk categories. An advanced adenoma at the final PPT colonoscopy was associated significantly with an advanced adenoma recurrence during surveillance (hazard ratio, 6.2; 95% confidence interval, 2.5–15.4). Conclusions: Surveillance colonoscopy was overused for low-risk subjects and underused for high-risk subjects. Advanced adenoma yield corresponded with the adenoma risk category. Resource consumption can be better managed by aligning use with the risk of adenoma recurrence. [Copyright &y& Elsevier]

Background and Aims: Recent studies have suggested that some hyperplastic polyps may be associated with an increased risk of colorectal cancer. Prospective information on the risk of adenoma recurrence associated with hyperplastic polyps is limited. We sought to investigate whether the coexistence of hyperplastic polyps with adenomas increases the risk of adenoma recurrence. Methods: We used unconditional logistic regression models to examine the association between baseline hyperplastic polyps and subsequent adenoma recurrence during a 3-year follow-up evaluation, among 1637 participants in the Polyp Prevention Trial. Results: A total of 437 participants (26.7%) had hyperplastic polyps coexisting with adenomas at baseline. Of these, 132 (30.2%) had at least one hyperplastic polyp in the proximal colon, whereas 305 (69.8%) had only distal hyperplastic polyps. When compared with subjects without any hyperplastic polyps at baseline, there was no statistically significant association between the presence of baseline hyperplastic polyps and recurrence of any adenoma (odds ratio [OR], 1.19; 95% confidence interval [CI], 0.94–1.51) or advanced adenoma (OR, 1.25; 95% CI, 0.78–2.03). Also, there was no association between hyperplastic polyp location and adenoma recurrence (OR, 1.01; 95% CI, 0.69–1.48) for any proximal hyperplastic polyp (OR, 1.26; 95% CI, 0.96–1.65) and for distal hyperplastic polyps. Conclusions: The coexistence of hyperplastic polyps with adenomas, irrespective of location, does not confer an increased risk of adenoma recurrence beyond that of adenomas alone within 3 years of follow-up evaluation. Prospective long-term studies on adenoma recurrence risk associated with hyperplastic polyps in screening populations are needed. [Copyright &y& Elsevier]

The article provides information on a study on the enhanced office and patient management on a compliance with colorectal cancer screening. The study aims to analyze the methods for promoting colorectal cancer screening in primary care practice. The impact of a tailored versus nontailored physician recommendation letter and an enhanced versus nonenhanced physician office and patient management intervention on colorectal cancer screening adherence were evaluated through 2x2 factorial randomnized clinical trial. Results showed that the enhanced office and patient management system significantly improved colorectal cancer screening.

Background: The Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial is a randomized clinical trial to test the effectiveness of cancer screening, including the effect of flexible sigmoidoscopy screening on colorectal cancer mortality. Here we report findings from the baseline screening flexible sigmoidoscopy examination. Methods: Analyses included 77465 men and women aged 55-74 years who were enrolled at 10 screening centers. The trial administered baseline risk factor questionnaires, offered 60-cm flexible sigmoidoscopy examinations, referred patients with screen-detected colorectal polyps or masses to personal physicians, and tracked subjects with polyps or masses to determine results from diagnostic follow-up. Cochran-Mantel-Haenszel statistics and logistic regression were used to test for differences in proportions according to sex and age. Results: A total of 64 658 subjects (83.5%) underwent screening flexible sigmoidoscopy, and at least one polyp or mass was identified in 15150 subjects (23.4%). Of these, 74.2% received follow-up lower endoscopic procedures. Follow-up lower endoscopy was more frequent in subjects with at least one larger (⩾0.5 cm) polyp or mass (86.0% 195% confidence interval (CI) = 84.6% to 87.4%] and 81.0% [95% CI = 79.8% to 82.2%] in women and men, respectively) than in those with a smaller (<0.5 cm) polyp or mass (69.1% [95% CI = 67.5% to 70.6%] and 65.4% 195% CI = 64.1% to 66.7%] in women and men, respectively). The yields per 1000 screened, depending on 5-year age group, were as follows: for colorectal cancer, 1.1-2.5 in women and 2.4-5.6 in men; for advanced adenoma, 18.0-30.4 in women and 36.1-49.1 in men; and for colorectal cancer or any adenoma, 50.6-79.6 in women and 101.9-128.6 in men. Approximately 77% (130/169) of the colorectal adenocarcinoma patients were stage I or II at diagnosis. Conclusions: Acceptance of screening flexible sigmoidoscopy was high. Diagnostic follow-up varied according to polyp size, yet cancer or adenoma detection rates met expectations. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States. Endoscopic screening is now in favor and its use is increasing, but overall participation rates are poor. A substantial percentage of the population will likely continue to resist endoscopic screening. As such, a noninvasive biomarker for the early detection of CRC remains a priority. Herein, we (i) review the currently available noninvasive screening markers for the early detection of CRC, (ii) discuss newer markers that have undergone preliminary testing, and (iii) introduce and explain potentially promising markers of the future.METHODS: The published literature on markers for early detection of CRC was identified using a MEDLINE/PubMed search with secondary review of cited publications.RESULTS: Noninvasive testing for CRC is most advanced in testing for stool fecal occult blood, globin, or DNA mutations. Study of abnormal mucins has also been explored. Research for serum-based markers is just beginning and includes serum proteomics, nuclear matrix proteins, and serum DNA testing.CONCLUSIONS: Serial guaiac-based fecal occult blood testing (FOBT) is simple, inexpensive, and proven effective at reducing mortality from CRC. Immunochemical fecal occult blood tests facilitate compliance and offer improved specificity, but at increased cost in comparison to FOBT. Fecal DNA testing may provide enhanced sensitivity for detection of CRC in comparison with FOBT, but its high cost limits its use for generalized screening. Rectal mucin testing requires additional evaluation to determine its sensitivity and specificity in comparison with guaiac-based FOBT. Serum tests, such as proteomics, nuclear matrix proteins, and serum DNA, are still in their infancy, but remain a hope for the future.(Am J Gastroenterol 2005;100:1–11) [ABSTRACT FROM AUTHOR]

OBJECTIVES: Insulin is a growth factor for colorectal cancer. Visceral adipose tissue (VAT) is strongly associated with insulin levels, and insulin and visceral obesity have been associated in cohort studies with colorectal cancer. The aim of this investigation was to determine whether VAT is associated with recurrence of adenomatous polyps, the precursor to colorectal cancer.METHODS: As an ancillary study to the Polyp Prevention Trial, a randomized clinical trial that evaluated the effect of a low-fat, high-fiber, high vegetable and fruit diet on adenomatous polyp recurrence, subjects at one clinical center underwent measurement of VAT with a single-slice CT scan through the L4–L5 interspace. The scan was performed around the time of the subject's year 4 colonoscopy that determined adenoma recurrence.RESULTS: Of 119 subjects, 44 of 84 men (52%) and 16 of 35 women (46%) had a recurrent adenoma (p= 0.51). Body mass index (BMI) and weight at baseline and at year 4 colonoscopy were unrelated to adenoma recurrence. In a multivariate model including visceral fat quartile, remote history of polyps, gender, age, and randomization group, only remote history of polyps was statistically significantly associated with recurrent adenoma with a relative risk of 4.6 (95% CI 1.7, 12.4,p= 0.001). There was no consistent monotonic trend of increased or decreased risk of recurrence as one ascended quartiles of adipose tissue for visceral, subcutaneous, or total abdominal fat.CONCLUSION: In this study, no association between visceral adipose tissue and adenomatous polyp recurrence was observed. Further study and exploration of the role of VAT in adenoma progression is required. [ABSTRACT FROM AUTHOR]

Context: The necessary frequency of endoscopic colorectal cancer screening after a negative examination is uncertain. Objective: To examine the yield of adenomas and cancer in the distal colon found by repeat flexible sigmoidoscopy (FSG) 3 years after a negative examination. Design, Setting, and Participants: Participants were drawn from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), a randomized, controlled community-based study of cancer screening. The mean (SD) age was 65.7 (4.0) years at study entry (1993-1995) and 61.6% were men. Individuals underwent screening FSG at baseline and at 3 years as part of the protocol and were referred to their personal physicians for further evaluation of screen-detected abnormalities. Results from subsequent diagnostic evaluations were tracked in a standardized fashion. Of 11 583 eligible for repeat screening FSG 3 years after an initial negative examination, 9317 (80.4%) returned. Main Outcome Measures: Polyp or mass detection in distal colon at year 3 repeat FSG; incidence of adenoma or cancer in distal colon at year 3 examination; determination of reason for detection (increased depth of insertion or improved preparation at the year 3 examination or detection in a previously examined area). Results: A total of 1292 returning participants (13.9%) had a polyp or mass detected by FSG 3 years after the initial examination. In the distal colon, 3.1% (292/9317) were found to have an adenoma or cancer. The incidence of advanced adenoma (n = 72) or cancer (n = 6) in the distal colon was 78 (0.8%) of 9317. Of individuals with advanced distal adenomas detected at the year 3 examination, 80.6% (58/72) had lesions found in a portion of the colon that had been adequately examined at the initial sigmoidoscopy. Conclusions: Repeat FSG 3 years after a negative examination will detect advanced adenomas and distal colon cancer. Although the overall percentage with detected abnormalities is modest, these data... [ABSTRACT FROM AUTHOR]

OBJECTIVE:Colorectal cancer screening is underutilized. Total colon examination (TCE), such as with colonoscopy, can have a significant effect on the measured compliance with screening, as colonoscopy may be able to be performed as infrequently as once every 10 yr. In a population-based survey we determined the prevalence and validated the self-reporting of TCE and assessed its impact on compliance with screening.METHODS:We interviewed an age- and sex-stratified random sample of 50- to 79-yr-old residents in two communities in southwestern Pennsylvania. Subjects reported ever having had and duration since last use of fecal occult blood testing (FOBT), flexible sigmoidoscopy (FS), rigid proctoscopy, barium enema, and colonoscopy. Self-reports of colorectal testing were validated via retrieval of procedure reports.RESULTS:Out of 1223 individuals sampled, 496 completed a telephone interview (40.6% overall and 58.3% of eligible contacts). In those without personal or family histories of colorectal cancer or personal histories of polyps (n = 377), 50%, 19.6%, 39.8%, and 17.5% reported ever having had FOBT, FS, barium enema, and colonoscopy, respectively. Thirty-one percent reported having FOBT within the previous year or FS within the previous 5 yr. Including TCE within the previous 5 yr increased the measured compliance to 39.7%. Compliance was significantly greater among subjects with family histories of colorectal cancer (62.9% vs 39.7%, odds ratio = 2.6, 95% CI = 1.3–5.2). Self-reports of recent colonoscopy were verified in 29 of 35 instances (83%).CONCLUSION:The prevalence of TCE in this population was significant, and including TCE substantially increased measured compliance with colorectal cancer screening. Self-reported use of colonoscopy was validated as accurate. [Copyright &y& Elsevier]

Screening for colorectal cancer is commanding increasing attention. Other cancer screening programmes have been a part of public consciousness for some time, but, until recently, colorectal cancer screening has remained in the background. Fuelled by new research, market opportunities and increased recognition of individual risk, screening for colorectal cancer is becoming a recommended procedure, but controversy about how best to implement widespread screening remains. [ABSTRACT FROM AUTHOR]

Objectives: Evidence is accumulating supporting the use of screening for colorectal cancer. Patients at higher risk for colorectal career are more likely to benefit from screening. Women with breast, endometrial, or ovarian cancer are often classified as at high risk for subsequent colorectal cancer, and are urged to undergo screening, but the basis for this is uncertain. Methods: We performed a meta-analysis of published data to assess the risk of colorectal cancer after these cancers. Results: Based on 154,270 women and 779,251 person-yr of observation (PYO) after breast cancer, 37,266 women and 229,498 PYO after endometrial cancer, and 41,366 women and 126,688 PYO after ovarian cancer, the age-adjusted relative risk (95%CI) for colorectal cancer after breast cancer was 1.1 (1.07, 1.19), after endometrial cancer 1.4 (1.32, 1.55), and after ovarian cancer 1.6 (1.40, 1.80). Conclusions: 1) Women with a history of breast, endometrial, or ovarian cancer are at a statistically significant increased risk for subsequent colorectal cancer. 2) Women with a history of endometrial or ovarian cancer are at higher risk than are women with breast cancer, but ascertainment bias from heightened medical surveillance after the diagnosis of a gynecologic malignancy may contribute to this observed increase in risk. 3) The association between these cancers and colorectal cancer suggests common etiologic factors, either environmental or genetic, but the degree of increased risk is small. [ABSTRACT FROM AUTHOR]

The contribution of surveillance colonoscopy, as opposed to that of initial colonoscopy examination, to prevention of colorectal cancer (CRC) is uncertain. We estimated the preventive effect of surveillance colonoscopy by applying the recently developed metric of adenoma dwell time avoided needed to prevent 1 CRC case (DTA). We followed subjects in the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial who underwent colonoscopies following positive findings from sigmoidoscopies (colonoscopy cohort, n = 15,935) for CRC incidence for 10 years. The number and timing of adenomas removed during surveillance were measured in a subset (n = 3492) of patients and extrapolated to the entire cohort to estimate the total avoided adenoma dwell time. A previously determined DTA value of 612 dwell years was applied to estimate the number of CRC cases prevented by surveillance. Proportional reduction in CRC was computed as C P /(C O +C P), where C O and C P are observed and estimated prevented cases, respectively. In the colonoscopy cohort of the PLCO, 2882 subjects had advanced adenomas (AAs), 572 had 3 or more non-advanced adenomas (NAA 3+), 4496 had 1–2 non-advanced adenomas (NAA 1-2), and 7985 had no adenoma (NA). The mean number of subsequent colonoscopy examinations over 10 years were 1.80 for subjects with AAs, 1.63 for subjects with NAA 3+ , and 1.46 for subjects with NAA 1–2. Average years of avoided adenoma dwell time per subject were 4.0 for subjects with AAs, 5.5 for subjects with NAA 3+ , and 2.4 for subjects with NAA 1–2. There were 56 cases of CRC in subjects with AAs, 4 cases of CRC in subjects with NAA 3+ , and 33 cases of CRC in subjects with NAA 1–2. Estimated proportional reductions in CRC incidence were 25.0% in subjects with AAs (95% CI, 16%–34%), 34.4% in subjects with NAA 1–2 (95% CI, 25%–40%), and 30.4% overall (in subjects with AAs, NAA 3+ , or NAA 1–2 ; 95% CI, 25%–40%). Absolute CRC incidence reductions were 7.1 per 10,000 PY in subjects with AAs and 4.1 per 10,000 PY in subjects with NAA 1-2. Using the recently developed metric of DTA, we estimated that surveillance colonoscopy in the PLCO colonoscopy cohort during 10 years of follow up prevented 30% of CRC cases. Because the methodology for estimation is indirect, the true effect is uncertain. [ABSTRACT FROM AUTHOR]

The article argues that screening colonoscopy is reasonable on an 88-year-old patient with colorectal cancer (CRC). Given the patient's average life expectancy and risk of death from CRC, the author argues that the patient can still benefit from the procedure because colonoscopy can reduce the mortality to colorectal cancer due to early diagnosis. The author further states that CRC screening can decrease the incidence of cancer.

The article informs that ten years between screening colonoscopies have been confirmed as a safe and reasonable interval after a negative procedure for colorectal cancer treatment.

Background & Aims Screening for colorectal cancer (CRC) with sigmoidoscopy reduces CRC incidence by detecting and removing adenomas. The number needed to screen is a measure of screening efficiency, but is not directly associated with adenoma removal. We propose the following 2 new metrics for quantifying the relationship between adenoma removal and CRC prevented: number of adenomas needed to remove (NNR) and adenoma dwell time avoided (DTA). Methods We collected data from 4 randomized trials of sigmoidoscopy screening (1 in the United States and 3 in Europe) to assess NNR and DTA. For each trial, NNR was computed as the number of adenomas removed from subjects in the intervention group, divided by the number of CRCs prevented. DTA was computed similarly but taking into account the timing of adenoma removal. Combined results across trials were assessed using standard meta-analytic techniques. Results The estimated NNR for the PLCO (Prostate, Lung, Colorectal and Ovarian) trial was 74 (95% confidence interval [CI], 56–110), for the NORCCAP (Norwegian Colorectal Cancer Prevention) trial was 71 (95% CI, 44–174), for the SCORE (Screening for Colon Rectum) trial was 27 (95% CI, 14–135), and for the UKFSST (UK Flexible Sigmoidoscopy Screening Trial) was 36 (95% CI, 28–52). The combined estimate (meta-analysis) of NNR was 52 (95% CI, 36–93) assuming heterogeneity (P for heterogeneity =.014). DTA estimates among trials ranged from 278 to 730 years, with a combined estimate of 500 (95% CI, 344–833) years assuming heterogeneity (P for heterogeneity =.035), or 2 CRC cases prevented per 1000 adenoma dwell years avoided. The combined estimates of NNR and DTA restricted to advanced adenomas were 13 (95% CI, 9–22) and 122 (95% CI, 90–190) years, respectively. Conclusions We collected data from 4 randomized trials of sigmoidoscopy screening for CRC to develop metrics of endoscopic efficiency, NNR and DTA, which are directly linked to adenoma detection and removal. They can be used to compare screening among endoscopic modalities and to more precisely measure adenoma to carcinoma transition rates. Graphical abstract [ABSTRACT FROM AUTHOR]

Background & Aims Guidelines for initiating colorectal cancer (CRC) screening are based on family history but do not consider lifestyle, environmental, or genetic risk factors. We developed models to determine risk of CRC, based on lifestyle and environmental factors and genetic variants, and to identify an optimal age to begin screening. Methods We collected data from 9748 CRC cases and 10,590 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colorectal Transdisciplinary study, from 1992 through 2005. Half of the participants were used to develop the risk determination model and the other half were used to evaluate the discriminatory accuracy (validation set). Models of CRC risk were created based on family history, 19 lifestyle and environmental factors (E-score), and 63 CRC-associated single-nucleotide polymorphisms identified in genome-wide association studies (G-score). We evaluated the discriminatory accuracy of the models by calculating area under the receiver operating characteristic curve values, adjusting for study, age, and endoscopy history for the validation set. We used the models to project the 10-year absolute risk of CRC for a given risk profile and recommend ages to begin screening in comparison to CRC risk for an average individual at 50 years of age, using external population incidence rates for non-Hispanic whites from the Surveillance, Epidemiology, and End Results program registry. Results In our models, E-score and G-score each determined risk of CRC with greater accuracy than family history. A model that combined both scores and family history estimated CRC risk with an area under the receiver operating characteristic curve value of 0.63 (95% confidence interval, 0.62–0.64) for men and 0.62 (95% confidence interval, 0.61–0.63) for women; area under the receiver operating characteristic curve values based on only family history ranged from 0.53 to 0.54 and those based only E-score or G-score ranged from 0.59 to 0.60. Although screening is recommended to begin at age 50 years for individuals with no family history of CRC, starting ages calculated based on combined E-score and G-score differed by 12 years for men and 14 for women, for individuals with the highest vs the lowest 10% of risk. Conclusions We used data from 2 large international consortia to develop CRC risk calculation models that included genetic and environmental factors along with family history. These determine risk of CRC and starting ages for screening with greater accuracy than the family history only model, which is based on the current screening guideline. These scoring systems might serve as a first step toward developing individualized CRC prevention strategies. [ABSTRACT FROM AUTHOR]

Background & Aims Little is known about the change in risk conferred by family history of colorectal cancer (CRC) as a person ages. We evaluated the effect of family history on CRC incidence and mortality after 55 years of age, when the risk of early onset cancer had passed. Methods We collected data from participants in the randomized, controlled Prostate, Lung, Colorectal and Ovarian cancer screening trial of flexible sigmoidoscopy versus usual care (55–74 years old, no history of CRC), performed at 10 US centers from 1993 to 2001. A detailed family history of colorectal cancer was obtained at enrollment, and subjects were followed for CRC incidence and mortality for up to 13 years. Results Among 144,768 participants, 14,961 subjects (10.3%) reported a family of CRC. Of 2090 incident cases, 273 cases (13.1%) had a family history of CRC; among 538 deaths from CRC, 71 (13.2%) had a family history of CRC. Overall, family history of CRC was associated with an increased risk of CRC incidence (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.10–1.50; P <.0001) and increased mortality (HR, 1.31; 95% CI, 1.02–1.69; P = .03). Subjects with 1 first degree relative (FDR) with CRC ( n = 238; HR, 1.23; 95% CI, 1.07–1.42) or ≥2 FDRs with CRC ( n = 35; HR, 2.04; 95% CI, 1.44–2.86) were at increased risk for incident CRC. However, among individuals with 1 FDR with CRC, there were no differences in risk based on age at diagnosis in the FDR (for FDR <60 years of age: HR, 1.27; 95% CI, 0.97–1.63; for FDR 60–70 years of age: HR, 1.33; 95% CI, 1.06–1.62; for FDR >70 years of age: HR, 1.14; 95% CI, 0.93–1.45; P trend = .59). Conclusions After 55 years of age, subjects with 1 FDR with CRC had only a modest increase in risk for CRC incidence and death; age of onset in the FDR was not significantly associated with risk. Individuals with ≥2 FDRs with CRC had continued increased risk in older age. Guidelines and clinical practice for subjects with a family history of CRC should be modified to align CRC testing to risk. ClinicalTrials.gov number, NCT00002540 . [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Five-year Risk of Colorectal Neoplasia After Negative Screening Colonoscopy," by T.F. Imperiale, E.A. Glowinski, C. Lin-Cooper, G.N. Larkin, J.D. Rogge, and D.F. Ransohoff in the September 18, 2008 issue.

Prevention or early detection is one of the most promising strategies against colorectal cancer (CRC), the second leading cause of cancer death in the US. Recent studies indicate that antitumor immunity plays a key role in CRC prevention. Accumulating evidence suggests that immunosurveillance represents a critical barrier that emerging tumor cells have to overcome in order to sustain the course of tumor development. Virtually all of the agents with cancer preventive activity have been shown to have an immune modulating effect. A number of immunoprevention studies aimed at triggering antitumor immune response against early lesions have been performed, some of which have shown promising results. Furthermore, the recent success of immune checkpoint blockade therapy reinforces the notion that cancers including CRC can be effectively intervened via immune modulation including immune normalization, and has stimulated various immune-based combination prevention studies. This review summarizes recent advances to help better harness the immune system in CRC prevention. [ABSTRACT FROM AUTHOR]

Background & Aims: The efficacy of flexible sigmoidoscopy (FSG) in reducing colorectal cancer mortality is being evaluated in randomized trials. In 2 European trials, wide variability across examiners in FSG performance was noted. We report on the performance of examiners in the US randomized trial: the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Methods: Screening was performed at 10 geographically dispersed clinical centers. Patients with screens positive for a lesion or mass were referred to their private health care providers for endoscopic follow-up evaluation; lesions were not removed and a biopsy examination was not performed at screening. FSG performance among 64 examiners at these centers, each performing 100 or more baseline FSG examinations, with an aggregate of almost 50,000 examinations, was analyzed. Results: Screen-positivity results among examiners ranged from 9%–58%, with a coefficient of variation (CV) of 36%. CVs were 29% for distal polyp detection and 21% for distal adenoma detection. Inadequate rates ranged from 1%–27% (CV, 52%). Examiners with higher screen-positivity rates had higher false-positive rates, defined as a positive screen with no distal lesion found on endoscopic follow-up evaluation. Conclusions: Considerable variability exists in the rates of positive screens and in polyp and adenoma detection rates among FSG examiners performing the procedures using a common protocol. [Copyright &y& Elsevier]

Familial adenomatous polyposis represents approximately 1% of all colorectal cancers and is caused by germline mutations in the adenomatous polyposis coli ( APC) gene. Most mutations are located within the first 2000 codons, and several mutational hot spots have been identified. The relative location of the mutation may be associated with the number of polyps and partially predicts specific phenotypic expression. Mutations associated with the attenuated phenotype are found predominantly in the 59 region of the gene or in the last third. We describe a patient with a mutation in codon 161 of the APCgene, which displays a phenotype most closely resembling the attenuated form of familial adenomatous polyposis, and review the literature, the implications of this mutation, and the importance of the molecular testing in the proper and more complete characterization of these patients. Differences in the APC mutation sites alone cannot completely account for intrafamilial and interfamilial variation in the polyposis phenotypes. [ABSTRACT FROM AUTHOR]