Importance Colorectal cancer is the second leading cause of cancer death in the United States. In 2016, an estimated 134 000 persons will be diagnosed with the disease, and about 49 000 will die from it. Colorectal cancer is most frequently diagnosed among adults aged 65 to 74 years; the median age at death from colorectal cancer is 73 years. Objective To update the 2008 US Preventive Services Task Force (USPSTF) recommendation on screening for colorectal cancer. Evidence Review The USPSTF reviewed the evidence on the effectiveness of screening with colonoscopy, flexible sigmoidoscopy, computed tomography colonography, the guaiac-based fecal occult blood test, the fecal immunochemical test, the multitargeted stool DNA test, and the methylated SEPT9 DNA test in reducing the incidence of and mortality from colorectal cancer or all-cause mortality; the harms of these screening tests; and the test performance characteristics of these tests for detecting adenomatous polyps, advanced adenomas based on size, or both, as well as colorectal cancer. The USPSTF also commissioned a comparative modeling study to provide information on optimal starting and stopping ages and screening intervals across the different available screening methods. Findings The USPSTF concludes with high certainty that screening for colorectal cancer in average-risk, asymptomatic adults aged 50 to 75 years is of substantial net benefit. Multiple screening strategies are available to choose from, with different levels of evidence to support their effectiveness, as well as unique advantages and limitations, although there are no empirical data to demonstrate that any of the reviewed strategies provide a greater net benefit. Screening for colorectal cancer is a substantially underused preventive health strategy in the United States. Conclusions and Recommendations The USPSTF recommends screening for colorectal cancer starting at age 50 years and continuing until age 75 years (A recommendation). The decision to screen for colorectal cancer in adults aged 76 to 85 years should be an individual one, taking into account the patient’s overall health and prior screening history (C recommendation).

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Screening for Colorectal Cancer: US Preventive Services Task Force Recommendation Statement

In the United States, colorectal cancer (CRC) is the fourth most common cancer diagnosed among adults and the second leading cause of death from cancer. For this guideline update, the American Cancer Society (ACS) used an existing systematic evidence review of the CRC screening literature and microsimulation modeling analyses, including a new evaluation of the age to begin screening by race and sex and additional modeling that incorporates changes in US CRC incidence. Screening with any one of multiple options is associated with a significant reduction in CRC incidence through the detection and removal of adenomatous polyps and other precancerous lesions and with a reduction in mortality through incidence reduction and early detection of CRC. Results from modeling analyses identified efficient and model-recommendable strategies that started screening at age 45 years. The ACS Guideline Development Group applied the Grades of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria in developing and rating the recommendations. The ACS recommends that adults aged 45 years and older with an average risk of CRC undergo regular screening with either a high-sensitivity stool-based test or a structural (visual) examination, depending on patient preference and test availability. As a part of the screening process, all positive results on noncolonoscopy screening tests should be followed up with timely colonoscopy. The recommendation to begin screening at age 45 years is a qualified recommendation. The recommendation for regular screening in adults aged 50 years and older is a strong recommendation. The ACS recommends (qualified recommendations) that: 1) average-risk adults in good health with a life expectancy of more than 10 years continue CRC screening through the age of 75 years; 2) clinicians individualize CRC screening decisions for individuals aged 76 through 85 years based on patient preferences, life expectancy, health status, and prior screening history; and 3) clinicians discourage individuals older than 85 years from continuing CRC screening. The options for CRC screening are: fecal immunochemical test annually; high-sensitivity, guaiac-based fecal occult blood test annually; multitarget stool DNA test every 3 years; colonoscopy every 10 years; computed tomography colonography every 5 years; and flexible sigmoidoscopy every 5 years. CA Cancer J Clin 2018;68:250-281. © 2018 American Cancer Society.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.3322/caac.21457

Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society

Colorectal cancer (CRC) ranks third among the most commonly diagnosed cancers worldwide, with wide geographical variation in incidence and mortality across the world. Despite proof that screening can decrease CRC incidence and mortality, CRC screening is only offered to a small proportion of the target population worldwide. Throughout the world there are widespread differences in CRC screening implementation status and strategy. Differences can be attributed to geographical variation in CRC incidence, economic resources, healthcare structure and infrastructure to support screening such as the ability to identify the target population at risk and cancer registry availability. This review highlights issues to consider when implementing a CRC screening programme and gives a worldwide overview of CRC burden and the current status of screening programmes, with focus on international differences.

https://gut.bmj.com/content/gutjnl/64/10/1637.full.pdf

Colorectal cancer screening: a global overview of existing programmes

Importance Colorectal cancer (CRC) remains a significant cause of morbidity and mortality in the United States. Objective To systematically review the effectiveness, diagnostic accuracy, and harms of screening for CRC. Data Sources Searches of MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials for relevant studies published from January 1, 2008, through December 31, 2014, with surveillance through February 23, 2016. Study Selection English-language studies conducted in asymptomatic populations at general risk of CRC. Data Extraction and Synthesis Two reviewers independently appraised the articles and extracted relevant study data from fair- or good-quality studies. Random-effects meta-analyses were conducted. Main Outcomes and Measures Colorectal cancer incidence and mortality, test accuracy in detecting CRC or adenomas, and serious adverse events. Results Four pragmatic randomized clinical trials (RCTs) evaluating 1-time or 2-time flexible sigmoidoscopy (n = 458 002) were associated with decreased CRC-specific mortality compared with no screening (incidence rate ratio, 0.73; 95% CI, 0.66-0.82). Five RCTs with multiple rounds of biennial screening with guaiac-based fecal occult blood testing (n = 419 966) showed reduced CRC-specific mortality (relative risk [RR], 0.91; 95% CI, 0.84-0.98, at 19.5 years to RR, 0.78; 95% CI, 0.65-0.93, at 30 years). Seven studies of computed tomographic colonography (CTC) with bowel preparation demonstrated per-person sensitivity and specificity to detect adenomas 6 mm and larger comparable with colonoscopy (sensitivity from 73% [95% CI, 58%-84%] to 98% [95% CI, 91%-100%]; specificity from 89% [95% CI, 84%-93%] to 91% [95% CI, 88%-93%]); variability and imprecision may be due to differences in study designs or CTC protocols. Sensitivity of colonoscopy to detect adenomas 6 mm or larger ranged from 75% (95% CI, 63%-84%) to 93% (95% CI, 88%-96%). On the basis of a single stool specimen, the most commonly evaluated families of fecal immunochemical tests (FITs) demonstrated good sensitivity (range, 73%-88%) and specificity (range, 90%-96%). One study (n = 9989) found that FIT plus stool DNA test had better sensitivity in detecting CRC than FIT alone (92%) but lower specificity (84%). Serious adverse events from colonoscopy in asymptomatic persons included perforations (4/10 000 procedures, 95% CI, 2-5 in 10 000) and major bleeds (8/10 000 procedures, 95% CI, 5-14 in 10 000). Computed tomographic colonography may have harms resulting from low-dose ionizing radiation exposure or identification of extracolonic findings. Conclusions and Relevance Colonoscopy, flexible sigmoidoscopy, CTC, and stool tests have differing levels of evidence to support their use, ability to detect cancer and precursor lesions, and risk of serious adverse events in average-risk adults. Although CRC screening has a large body of supporting evidence, additional research is still needed.

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Screening for Colorectal Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force

长期以来,对于肿瘤的发病机制,就存在两种意见,一种意见认为,肿瘤的发生是由于基因突变导致的遗传特性改变引起的,另一种意见认为,肿瘤的发生是由于基因表达的失调,即通过表遗传学机制引起的.只是近几十年来,由于癌基因与抑癌基因的发现及对之研究的巨大进步,使得肿瘤表遗传学的研究一直处于遗传学研究的阴影之下而已[1]。

Cancer epigenetics

Background As screening methods for colorectal cancer (CRC) are limited by uptake and adherence, further options are sought. A blood test might increase both, but none has yet been tested in a screening setting. Objective We prospectively assessed the accuracy of circulating methylated SEPT9 DNA (mSEPT9) for detecting CRC in a screening population. Design Asymptomatic individuals ≥50 years old scheduled for screening colonoscopy at 32 US and German clinics voluntarily gave blood plasma samples before colon preparation. Using a commercially available assay, three independent blinded laboratories assayed plasma DNA of all CRC cases and a stratified random sample of other subjects in duplicate real time PCRs. The primary outcomes measures were standardised for overall sensitivity and specificity estimates. Results 7941 men (45%) and women (55%), mean age 60 years, enrolled. Results from 53 CRC cases and from 1457 subjects without CRC yielded a standardised sensitivity of 48.2% (95% CI 32.4% to 63.6%; crude rate 50.9%); for CRC stages I–IV, values were 35.0%, 63.0%, 46.0% and 77.4%, respectively. Specificity was 91.5% (95% CI 89.7% to 93.1%; crude rate 91.4%). Sensitivity for advanced adenomas was low (11.2%). Conclusions Our study using the blood based mSEPT9 test showed that CRC signal in blood can be detected in asymptomatic average risk individuals undergoing screening. However, the utility of the test for population screening for CRC will require improved sensitivity for detection of early cancers and advanced adenomas. Clinical Trial Registration Number: NCT00855348

https://gut.bmj.com/content/gutjnl/63/2/317.full.pdf

Prospective evaluation of methylated SEPT9 in plasma for detection of asymptomatic colorectal cancer

https://www.cghjournal.org/article/S1542-3565(13)01841-7/pdf

Endoscopic Detection of Proximal Serrated Lesions and Pathologic Identification of Sessile Serrated Adenomas/Polyps Vary on the Basis of Center

Objectives To identify a biomarker panel with sufficient sensitivity and negative predictive value to identify children with abdominal pain at low risk for acute appendicitis in order to avoid unnecessary imaging. Methods We prospectively enrolled 503 subjects aged two to 20 years with Results The prevalence of acute appendicitis was 28.6%. A mathematical combination of three inflammation-related markers in a panel comprised of white blood cell count (WBC), C-reactive protein (CRP), and myeloid-related protein 8/14 complex (MRP 8/14) provided the best discrimination. This panel exhibited a sensitivity of 96.5% (95% CI, 92-99%), a negative predictive value of 96.9% (95% CI, 93-99%), a negative likelihood ratio of 0.08 (95% CI, 0.03- 0.19), and a specificity of 43.2% (95% CI, 38-48%) for acute appendicitis. Sixty of 185 CT scans (32.4%) were done for patients with negative biomarker panel results which, if deferred, would have reduced CT utilization at initial presentation by one third at the cost of missing five of 144 (3.5%) patients with appendicitis. Conclusion This panel may be useful in identifying pediatric patients with signs and symptoms suggestive of acute appendicitis who are at low risk and can be followed clinically, potentially sparing them exposure to the ionizing radiation of CT.

Michael Wandell

Papers

Prospective evaluation of methylated SEPT9 in plasma for detection of asymptomatic colorectal cancer

Endoscopic Detection of Proximal Serrated Lesions and Pathologic Identification of Sessile Serrated Adenomas/Polyps Vary on the Basis of Center

A novel biomarker panel to rule out acute appendicitis in pediatric patients with abdominal pain.