Theodore R. Levin

Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology.

In the United States, colorectal cancer (CRC) is the third most common cancer diagnosed among men and women and the second leading cause of death from cancer. CRC largely can be prevented by the detection and removal of adenomatous polyps, and survival is significantly better when CRC is diagnosed while still localized. In 2006 to 2007, the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology came together to develop consensus guidelines for the detection of adenomatous polyps and CRC in asymptomatic average-risk adults. In this update of each organizations guidelines, screening tests are grouped into those that primarily detect cancer early and those that can detect cancer early and also can detect adenomatous polyps, thus providing a greater potential for prevention through polypectomy. When possible, clinicians should make patients aware of the full range of screening options, but at a minimum they should be prepared to offer patients a choice between a screening test that primarily is effective at early cancer detection and a screening test that is effective at both early cancer detection and cancer prevention through the detection and removal of polyps. It is the strong opinion of these 3 organizations that colon cancer prevention should be the primary goal of screening.

Screening and Surveillance for the Early Detection of Colorectal Cancer and Adenomatous Polyps, 2008: A Joint Guideline from the American Cancer Society, the US Multi‐Society Task Force on Colorectal Cancer, and the American College of Radiology*†

In the United States, colorectal cancer (CRC) is the third most common cancer diagnosed among men and women and the second leading cause of death from cancer. CRC largely can be prevented by the detection and removal of adenomatous polyps, and survival is significantly better when CRC is diagnosed while still localized. In 2006 to 2007, the American Cancer Society, the US Multi Society Task Force on Colorectal Cancer, and the American College of Radiology came together to develop consensus guidelines for the detection of adenomatous polyps and CRC in asymptomatic average‐risk adults. In this update of each organizations guidelines, screening tests are grouped into those that primarily detect cancer early and those that can detect cancer early and also can detect adenomatous polyps, thus providing a greater potential for prevention through polypectomy. When possible, clinicians should make patients aware of the full range of screening options, but at a minimum they should be prepared to offer patients a choice between a screening test that is effective at both early cancer detection and cancer prevention through the detection and removal of polyps and a screening test that primarily is effective at early cancer detection. It is the strong opinion of these 3 organizations that colon cancer prevention should be the primary goal of screening.

Guidelines for Colonoscopy Surveillance After Screening and Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colorectal Cancer

Screening for colorectal cancer (CRC) in asymptomatic patients can reduce the incidence and mortality of CRC. In the United States, colonoscopy has become the most commonly used screening test. Adenomatous polyps are the most common neoplasm found during CRC screening. There is evidence that detection and removal of these cancer precursor lesions may prevent many cancers and reduce mortality.1 Howver, patients who have adenomas are at increased risk for eveloping metachronous adenomas or cancer compared with atients without adenomas. There is new evidence that some atients may develop cancer within 3–5 years of colonoscopy nd polypectomy—so-called interval cancers. Ideally, screening and surveillance intervals should be ased on evidence showing that interval examinations preent interval cancers and cancer-related mortality. We have ocused on the interval diagnosis of advanced adenomas as surrogate marker for the more serious end point of cancer ncidence or mortality. In 2006, the United States Multiociety Task Force (MSTF) on CRC issued a guideline on ostpolypectomy surveillance,2 which updated a prior 1997 guideline. A key principle of the 2006 guideline was risk stratification of patients based on the findings at the baseline colonoscopy. The surveillance schema identified 2 major risk groups based on the likelihood of developing advanced neoplasia during surveillance: (1) low-risk adenomas (LRAs), defined as 1–2 tubular adenomas 10 mm, and (2) high-risk adenomas (HRAs), defined as adenoma with villous histology, high-grade dysplasia (HGD), 10 mm, or 3 or more denomas. The task force also published recommendations or follow-up after resection of CRC.3 More recently, the British Society of Gastroenterology updated their 2002 surveillance guideline in 2010.4 Their risk stratification differs from the US guideline, dividing patients into 3 groups: low risk (1–2 adenomas 10 mm), intermediate risk (3–4 small adenomas or one 10 mm), nd high risk ( 5 small adenomas or 3 with at least one 10 mm). They recommend that the high-risk group unergo surveillance at 1 year because of concerns about issed lesions at baseline. US guidelines place emphasis on erforming a high-quality baseline examination. In 2008, the STF published screening guidelines for CRC, which inluded recommendations for the interval for repeat colonocopy after negative findings on baseline examination.5 New issues have emerged since the 2006 guideline, including risk of interval CRC, proximal CRC, and the role of serrated polyps in colon carcinogenesis. New evidence suggests that adherence to prior guidelines is poor. The task force now issues an updated set of surveillance recommendations. During the past 6 years, new evidence has emerged that endorses and strengthens the 2006 recommendations. We believe that a stronger evidence base will improve adherence to the guidelines. The 2012 guidelines are summarized in Table 1 and are based on risk stratification principles used in the 2006 guideline. The ensuing discussion reviews the new evidence that supports these guidelines. This guideline does not address surveillance after colonoscopic or surgical resection of a malignant polyp.

Quality in the technical performance of colonoscopy and the continuous quality improvement process for colonoscopy: Recommendations of the U.S. Multi-Society Task Force on Colorectal Cancer

Quality in the technical performance of colonoscopy and the continuous quality improvement process for colonoscopy: recommendations of the U.S. Multi-Society Task Force on Colorectal Cancer

Multitarget Stool DNA Testing for Colorectal-Cancer Screening

BACKGROUND An accurate, noninvasive test could improve the effectiveness of colorectal-cancer screening. METHODS We compared a noninvasive, multitarget stool DNA test with a fecal immunochemical test (FIT) in persons at average risk for colorectal cancer. The DNA test includes quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, and β-actin, plus a hemoglobin immunoassay. Results were generated with the use of a logistic-regression algorithm, with values of 183 or more considered to be positive. FIT values of more than 100 ng of hemoglobin per milliliter of buffer were considered to be positive. Tests were processed independently of colonoscopic findings. RESULTS Of the 9989 participants who could be evaluated, 65 (0.7%) had colorectal cancer and 757 (7.6%) had advanced precancerous lesions (advanced adenomas or sessile serrated polyps measuring ≥1 cm in the greatest dimension) on colonoscopy. The sensitivity for detecting colorectal cancer was 92.3% with DNA testing and 73.8% with FIT (P=0.002). The sensitivity for detecting advanced precancerous lesions was 42.4% with DNA testing and 23.8% with FIT (P<0.001). The rate of detection of polyps with high-grade dysplasia was 69.2% with DNA testing and 46.2% with FIT (P=0.004); the rates of detection of serrated sessile polyps measuring 1 cm or more were 42.4% and 5.1%, respectively (P<0.001). Specificities with DNA testing and FIT were 86.6% and 94.9%, respectively, among participants with nonadvanced or negative findings (P<0.001) and 89.8% and 96.4%, respectively, among those with negative results on colonoscopy (P<0.001). The numbers of persons who would need to be screened to detect one cancer were 154 with colonoscopy, 166 with DNA testing, and 208 with FIT. CONCLUSIONS In asymptomatic persons at average risk for colorectal cancer, multitarget stool DNA testing detected significantly more cancers than did FIT but had more false positive results. (Funded by Exact Sciences; ClinicalTrials.gov number, NCT01397747.).

Complications of Colonoscopy in an Integrated Health Care Delivery System

Context Data on the frequency of colonoscopy complications from population-based samples are lacking. Contribution The authors searched electronic health records at Kaiser-Permanente of Northern California for patients who died or who had complications due to colonoscopy within 30 days of the procedure. Almost all procedures were diagnostic or for surveillance of previous abnormal findings. Of16318 eligible procedures, 82 involved serious complications (5 in 1000 procedures). Of the 82 complications, 95% followed biopsy or removal of polyps, and 62% of the polyps removed were smaller than 10 mm. The perforation rate was 1 in 1000 procedures. One death was related to colonoscopy. Cautions Less than 1% of procedures studied were screening colonoscopies, so these complication rates might not apply to screening examinations. The Editors Colonoscopy is the final step in colorectal cancer screening, regardless of the initial test chosen, and is recommended for primary colorectal cancer screening in average- risk persons (14). Colorectal cancer screening targets apparently healthy people; therefore, the magnitude of the risk and severity of the harms from screening are important issues to consider when selecting a screening strategy (5). Described complications of colonoscopy include colonic perforation, postbiopsy and postpolypectomy bleeding, and postpolypectomy syndrome (a transmural colonic burn, marked by localized abdominal pain without evidence of frank perforation) (6). Diverticulitis, which is caused by a microscopic perforation of the colon, can also theoretically be caused by colonoscopy in persons with preexisting diverticulosis. Most estimates of colonoscopy complications come from referral centers (712) or closely monitored clinical trials (13), limiting the generalizability of the results to community practice. In a large series by a group of ambulatory endoscopy centers (14), endoscopists self-reported complications, possibly underestimating them (15). In this study, researchers were unable to evaluate postpolypectomy bleeding. Postpolypectomy bleeding is particularly difficult to assess in studies because its occurrence is often delayed. The U.S. Preventive Services Task Force (16), in a recent evidence review of colonoscopy complications, concluded that postpolypectomy bleeding was reported in relatively few studies and delayed bleeding was not reported at all. Studies using administrative databases typically lack access to detailed records, including indications, depth of insertion, and whether or how polyps are removed (17). For the present study, we relied on the automated data of Kaiser Permanente, Northern California (KPNC), an integrated health care delivery system. Colonoscopy was most often used to follow-up other tests, such as fecal occult blood tests, flexible sigmoidoscopy, or barium enema, or to conduct surveillance in persons with a personal or family history of colorectal cancer or colorectal adenoma. Few colonoscopies were performed for primary screening. We identified patients undergoing colonoscopy and followed them for 30 days after the procedure for hospitalization for procedure-related complications. For this analysis, we defined any procedure-related complication that led to hospitalization as a serious complication. Methods We used KPNC electronic medical records to select patients who had undergone colonoscopies between 1 January 1994 and 16 July 2002. This was an observational study, conducted in medical centers throughout the KP health care system, evaluating practice patterns as they existed at the time the included colonoscopies were performed by the endoscopists in the study. Electronic records were reviewed to identify immediate complications, outpatient visits, or hospital admission within 30 days of colonoscopy. Colonoscopies were included in the analysis if they were performed for patients 40 years of age or older who were undergoing coloscopy because of a family history of colorectal cancer or adenomatous polyp, as a follow-up to a positive screening test (that is, polyp or cancer at sigmoidoscopy, positive results on a fecal occult blood test, or abnormal barium enema radiography), for surveillance because of a previously detected adenomatous polyp or colorectal cancer, or for primary screening. Colonoscopies were not included if the procedure was being performed to diagnose symptoms (for example, diarrhea, abdominal pain, gastrointestinal bleeding, history of rectal bleeding, or anemia) or if patients had outpatient visits 6 months before the procedure for abdominal pain, anemia, diarrhea, or constipation. A total of 35945 procedures performed at KPNC between 1 January 1994 and 16 July 2002 were identified by using 2 electronic KPNC endoscopy databases. The first database, the Colorectal Cancer Prevention (CoCaP) program database, contains detailed information from 1994 to 1996 on sigmoidoscopies, follow-up colonoscopies, and the results of pathologic testing. Information available in the CoCaP database includes depth of insertion; size, number, and treatment of polyps; limitations of the procedure; and identity of the examiner. The second database, the EndoLog Pro database, includes colonoscopy reports from 1995 to 2002 from 5 KP facilities. The database contains information on number of polyps found and their treatment, depth of insertion, quality of bowel preparation, identity of the examiner, and any immediate complications. Some patients underwent more than 1 colonoscopy during the study period. If a colonoscopy was incomplete because of poor bowel preparation, and a second colonoscopy was performed within 3 months, only the second colonoscopy was included in the cohort. If a patient required a second colonoscopy to complete removal of a polyp, only the first colonoscopy was included in the cohort. Patients requiring frequent surveillance may have been screened more than once during the 7-year study period; colonoscopies were included for these patients if the interval between the colonoscopies was greater than 6 months. Identification of Eligible Cases Of the 35945 procedures, 4646 were excluded because patients were younger than 40 years of age; 9499 were excluded because the procedures were performed for excluded indications or for symptoms; and 2411 were excluded because of poor preparation (with a second examination rescheduled in 90 days), interval since previous procedure was less than 6 months, previous colon surgery, or because the procedure was for follow-up removal of residual polyps or for marking polyp site for surgery. Inpatient procedures (n= 125) and procedures for KPNC nonmembers (n= 57) were excluded. Procedures were also excluded if patients had inpatient or outpatient visits for lower gastrointestinal bleeding, abdominal pain, anemia, diarrhea, or constipation 6 months before the procedures (n= 2689). A total of 16318 procedures were included in the analysis. Identification of Possible Complications A 2-step procedure was used to identify serious complications. First, we analyzed KP electronic databases for evidence of patients being admitted to the hospital (a KPNC or nonprogram hospital) within 30 days of colonoscopy. We focused on admissions that could be associated with colonoscopy complications or complications of procedural sedation, including colonic perforation (International Classifications of Diseases, 9th revision, [ICD-9] codes 569.83 and 998.2]; lower gastrointestinal bleeding (ICD-9 558.9, 578.1, 995.2, 995.89, and 998.1 to 998.13); anemia, not explained by preexisting conditions (ICD-9 280.0 and 285.0 to 285.9); diverticulitis (ICD-9 562.11); colitis, not present during initial endoscopy (ICD-9 556 to 556.9); aspiration pneumonia (ICD-9 507); pneumonia, organism unspecified (ICD-9 486); infection (ICD-9 780.6, 790.7, and 424.9 to 424.99); abdominal pain (ICD-9 789.0 to 789.09); complications of procedure (E872, E872.8, E872.9, E879, E879.8, and E879.9); complications secondary to anesthesia (ICD-9 995.4, 997.1, and 997.3); myocardial infarction (ICD-9 410 to 410.92 and 414); and stroke (ICD-9 436). Deaths within 30 days of colonoscopy were identified through linkage with the National Death Index. After possible cases were identified from electronic records, medical records analysts at KPNC reviewed the hardcopy medical records, computerized medical records, and laboratory records of 183 patients by using chart review forms. Analysts made photocopies of histories and physicals, discharge summaries, colonoscopy reports, operative notes, and pathology reports, and these were used to make decisions. Two physicians reviewed the photocopied records to determine whether the hospitalization or death was related to colonoscopy. Clinical judgment was used in making these decisions through a collaborative process, and decisions were made by mutual agreement. A third physician adjudicated the 1 case in which there were ongoing questions. A subsample of 44 records was reviewed by both physicians independently. The -statistic for this statistical analysis was 0.71 (CI, 0.52 to 0.89). Statistical Analysis Individual complication measures were created to reflect the incidence of serious complications in the first 30 days after colonoscopy for the following: 1) colonic perforation; 2) the postpolypectomy syndrome; 3) bleeding requiring overnight hospitalization, overall and separately for patients with or without surgery or transfusion; 4) diverticulitis requiring overnight hospitalization, overall and separately for patients with or without surgery; and 5) any other hospitalization within 30 days that was likely to have been caused or exacerbated by the procedure. Two aggregate measures were used. The first was for all of the above categories combined and the second for the most serious complications, including perforation, bleeding with transfusion, and diverticulitis requiring surgery. For each complication measure, we calculated the inc

The American Society for Gastrointestinal Endoscopy PIVI (Preservation and Incorporation of Valuable Endoscopic Innovations) on real-time endoscopic assessment of the histology of diminutive colorectal polyps

The PIVI (Preservation and Incorporation of Valuable endoscopic Innovations) initiative is an ASGE program whose objectives are to identify important clinical questions related to endoscopy and to establish a priori diagnostic and/or therapeutic thresholds for endoscopic technologies designed to resolve these clinical questions. Additionally, PIVIs may also outline the data and or the research study design required for proving an established threshold is met. Once endoscopic technologies meet an established PIVI threshold, those technologies are appropriate to incorporate into clinical practice presuming the appropriate training in that endoscopic technology has been achieved. The ASGE encourages and supports the appropriate use of technologies that meet its established PIVI thresholds. The PIVI initiative was developed primarily to direct endoscopic technology development toward resolving important clinical issues in endoscopy. The PIVI initiative is also designed to minimize the possibility that potentially valuable innovations are prematurely abandoned due to lack of utilization and to avoid widespread use of an endoscopic technology before clinical studies documenting their effectiveness have been performed. The following document, or PIVI, is one of a series of statements defining the diagnostic or therapeutic threshold that must be met for a technique or device to become considered appropriate for incorporation into clinical practice. It is also meant to serve as a guide for researchers or those seeking to develop technologies that are designed to improve digestive health outcomes. An ad hoc committee under the auspices of the existing ASGE Technology and Standards of Practice Committees Chairs develops PIVIs. An expert in the subject area chairs the PIVI, with additional committee members chosen for their individual expertise. In preparing this document, evidence-based methodology was employed, using a MEDLINE and PubMed literature search to identify pertinent clinical studies on the topic. PIVIs are ultimately submitted to the ASGE Governing Board for approval, as is done for all Technology and Standards of Practice documents. This document is provided solely for educational and informational purposes and to support incorporating these endoscopic technologies into clinical practice. It should not be construed as establishing a legal standard of care.

Accuracy of Fecal Immunochemical Tests for Colorectal Cancer: Systematic Review and Meta-analysis

Colorectal cancer (CRC) is the second-leading cause of cancer-related deaths in the United States (1). Randomized, controlled trials have shown that annual or biennial fecal occult blood tests (FOBTs) are associated with a 15% to 33% decrease in CRC mortality rates (24). However, FOBTs only detect approximately 13% to 50% of cancer with 1 round of screening in asymptomatic patients (5, 6). In addition, adherence to repeated rounds of FOBTs in real-world screening programs is low, raising concern about their effectiveness as screening tests (7, 8). Fecal immunochemical tests (FITs) are more sensitive at detecting both CRC and adenomas than FOBTs (9, 10). Many FITs require only 1 or 2 stool samples, and none require dietary or medication restrictions, increasing ease of use. In 2008, several U.S. professional societies endorsed the use of FITs to replace FOBTs because of the formers improved performance characteristics and potential for higher participation rates (10, 11). Countries in Europe and Asia have also adopted widespread CRC screening programs using FITs (12, 13). However, the diagnostic characteristics of these tests have been difficult to estimate, with reported sensitivities ranging from 25% to 100% for CRC and specificities usually exceeding 90% (9, 14, 15). The lack of a precise estimate of sensitivity has resulted in confusion among health care providers about the sources of this variation, how best to apply FITs for CRC screening, the optimal number of stool samples for testing, optimal cutoff value for a positive test result, and whether any brand of FIT is superior to others. Our analysis provides a quantitative meta-analysis of the diagnostic accuracy (sensitivity and specificity) of FITs for CRC. In addition, we explored potential sources of heterogeneity by analyzing subgroups classified by FIT sample number, cutoff value for a positive test result, FIT brand, and the reference standard. Methods We developed a protocol on the basis of standard guidelines for the systematic review of diagnostic studies (16, 17) and the strategy used for the U.S. Preventive Services Task Force review in 2008 (9). We followed the STARD (Standards for the Reporting of Diagnostic Accuracy Studies) (18) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) (19) statements for reporting our systematic review. This study was conducted as part of the National Cancer Institutefunded consortium, Population-Based Research Optimizing Screening through Personalized Regimens. The overall aim of this consortium is to conduct multisite, coordinated, transdisciplinary research to evaluate and improve cancer screening processes. Data Sources and Searches We included all studies identified in the previous USPSTF report (9) plus other studies identified by a search of FIT for CRC between 1 January 2008 and 31 August 2013 using MEDLINE (via Ovid), EMBASE, Database of Abstracts of Reviews of Effects, Health Technology Assessment Database, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials. We also searched bibliographies and reference lists of eligible papers and related reviews, consulted experts in the field, and contacted several authors from the included studies to locate additional studies. The Appendix Table 1 provides further details of our search strategy. Appendix Table 1. Search Strategy Study Selection Two persons independently reviewed the pertinent studies to determine eligibility. We included studies if they met all of the following criteria: evaluated the diagnostic accuracy of FITs for CRC; reported absolute numbers of true-positive, false-negative, true-negative, and false-positive observations, or if these same variables could be obtained from personal communication; used a randomized trial or cohort study design; evaluated adult participants who were asymptomatic and older than 18 years with a mean age greater than 40 years; and reported an appropriate reference standard (colonoscopy or 2-year longitudinal follow-up of controls with medical records or cancer registry). Given that only a subset of studies reported data on adenomatous polyps and that there is variability in definitions of polyps, we limited the scope of this analysis to test performance characteristics for detecting CRC; we excluded studies reporting test performance estimates for detection of adenomas only. We did not include conference abstracts and casecontrol studies, which, by creating spectrum bias, can overestimate the accuracy of a test (20). To avoid duplicate reporting of the same population for studies reporting several cutoff values or numbers of samples, we used the cutoff value or sample number most commonly used in current practice in the United States, used in national recommendations, or recommended by expert opinion in the main analyses. In addition, we selected the sample number or cutoff value a priori that was most similar to those in other studies for our subgroup analyses. Data Extraction and Quality Assessment Two reviewers independently evaluated and extracted relevant information from each included study and assessed study quality via the Quality Assessment of Diagnostic Accuracy Studies 2 instrument (21). For studies with incomplete or unavailable information, we contacted the corresponding authors or coauthors to complete missing information. Of the 15 contacted authors, 12 provided additional data. We converted units for cutoff thresholds for a positive test result in each study to micrograms of hemoglobin per gram of stool, as recommended by leading experts (22). Data Synthesis and Analysis We calculated the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio (LR), and negative LR with 95% CI of each study. A positive LR greater than 5 and a negative LR less than 0.2 provide strong diagnostic evidence to rule in or rule out diagnoses, respectively (23). The overall pooled sensitivity and specificity of FIT for CRC were estimated using a bivariate random-effects model (24). We calculated the pooled positive LR and negative LR along with the respective CI using the bivariate model (24) according to the method used by Zwinderman and colleagues (25). We also generated a hierarchical summary receiver-operating characteristic curve that plots the individual and summary estimates of sensitivities and specificities along with a 95% confidence and prediction region (26). Last, we calculated the area under the hierarchical summary receiver-operating characteristic curve. An area under the curve between 0.9 and 1.0 indicates that the test in question is highly accurate (27). The Q value and the inconsistency index (I 2) test were used to estimate the heterogeneity between each study (28). We regarded values of 25%, 50%, and 75% for the I 2 as indicative of low, moderate, and high statistical heterogeneity, respectively (28). In addition, we calculated the between-study variance of logit sensitivity and logit specificity (24, 29). In diagnostic accuracy studies, 1 of the primary causes of heterogeneity is the threshold effect, which occurs when different cutoff values are used between studies to define a positive (or negative) test result. We searched for evidence of a threshold effect by calculating the squared correlation coefficient estimated from the between-study covariance variable in the bivariate model (30). We stratified studies into 4 subgroups on the basis of the number of FIT samples (1, 2, or 3 samples), prespecified cutoff values of fecal hemoglobin concentration for a positive test result (<20 g/g, 20 to 50 g/g, and >50 g/g), brand, and reference standard used to follow up on patients with negative FIT results. Cutoff values were grouped to ensure an adequate number of data sets for each analysis. To determine whether studies using older (discontinued) FITs were causing heterogeneity in our summary estimates, we did sensitivity analyses by removing these studies and recalculating the I 2 test for the remaining group. In addition to threshold effect and subgroup analyses, we did a bivariate random-effects meta-regression analysis to identify additional sources of heterogeneity that may have influenced our overall summary estimates (30). We used the following prespecified variables for our meta-regression: type of FIT (qualitative, point-of-care tests or quantitative, automated tests), geographic region (Asian or non-Asian countries), and enrollment of patients younger than 40 years. We used Stata, version 12.0 (StataCorp, College Station, Texas), for all statistical analyses. All tests were 2-sided, and we considered P values less than 0.05 to be statistically significant. Role of the Funding Source The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Cancer Institute. The funding source had no role in the conception, design, analysis, or conduct of the review. Results Study Selection The 2008 USPSTF report (9) included 9 studies in its systematic review (3139); our literature search identified 1771 additional new potential sources (Figure 1). After abstract review, we identified 53 articles for full-text review; of these, 18 unique articles satisfied all inclusion criteria and were included in our analysis (14, 15, 3146). Because 1 article (46) evaluated more than 1 FIT brand in a head-to-head comparison, the final analysis included 19 studies or data sets. Figure 1. Summary of evidence search and selection. USPSTF = U.S. Preventive Services Task Force. Characteristics of Included Studies Table 1 and the Supplement show the main characteristics of the included studies. Eighteen articles described 19 cohort studies of FIT sensitivity and specificity for CRC in average-risk asymptomatic patients; sample sizes ranged from 80 to 27860. Twelve studies (14, 3336, 4042, 4446) used colonoscopy in all patients, regardless of FIT results, as the re

Guidelines on Genetic Evaluation and Management of Lynch Syndrome: A Consensus Statement by the US Multi-Society Task Force on Colorectal Cancer

The Multi-Society Task Force, in collaboration with invited experts, developed guidelines to assist health care providers with the appropriate provision of genetic testing and management of patients at risk for and affected with Lynch syndrome as follows: Figure 1 provides a colorectal cancer risk assessment tool to screen individuals in the office or endoscopy setting; Figure 2 illustrates a strategy for universal screening for Lynch syndrome by tumor testing of patients diagnosed with colorectal cancer; Figures 3,4,5,6 provide algorithms for genetic evaluation of affected and at-risk family members of pedigrees with Lynch syndrome; Table 10 provides guidelines for screening at-risk and affected persons with Lynch syndrome; and Table 12 lists the guidelines for the management of patients with Lynch syndrome. A detailed explanation of Lynch syndrome and the methodology utilized to derive these guidelines, as well as an explanation of, and supporting literature for, these guidelines are provided.

Diet and lifestyle factor associations with CpG island methylator phenotype and BRAF mutations in colon cancer

It has been proposed that dietary factors such as folate, alcohol and methionine may be associated with colon cancer because of their involvement in DNA methylation processes. Data from a large population‐based case‐control study of incident colon cancer were used to evaluate whether intake of dietary, obesity, physical activity and nonsteroidal antiinflammatory drugs are associated with a CpG island methylator phenotype (CIMP). The BRAF V600E mutation and 5 CpG island markers (MINT1, MINT2, MINT31, p16 and hMLH1) were assessed in 1154 cases of colon cancer. We hypothesized that dietary factors involved in DNA methylation, cruciferous vegetables and use of aspirin/NSAIDs would be associated with CIMP‐high tumors. Dietary folate, vitamins B6 and B12, methionine and alcohol were not associated with increased likelihood of colon tumors with the CIMP‐high (2 or more markers methylated) phenotype. Dietary fiber, physical activity and aspirin and other nonsteroidal antiinflammatory drugs were inversely associated with both CIMP‐low and CIMP‐high tumors. Our results also suggested non‐CIMP pathways as well. Obese individuals were at 2‐fold increased risk of having a CIMP‐low tumor. Alcohol was associated with an increased risk of tumors that were MSI+ and CIMP‐low. In the presence of smoking 20 or more cigarettes per day, use of NSAIDs did not protect against a BRAF mutation. Our data suggest multiple pathways to colon cancer. They do not support a unique role for dietary folate, alcohol, vitamins B6 and B12 and methionine in a CpG island methylator phenotype.