Gregory N. Larkin

Risk of advanced proximal neoplasms in asymptomatic adults according to the distal colorectal findings

BACKGROUND AND METHODS The clinical significance of a distal colorectal polyp is uncertain. We determined the risk of advanced proximal neoplasia, defined as a polyp with villous features, a polyp with high-grade dysplasia, or cancer, among persons with distal hyperplastic or neoplastic polyps as compared with the risk among persons with no distal polyps. We analyzed data from 1994 consecutive asymptomatic adults (age, 50 years or older) who underwent colonoscopic screening for the first time between September 1995 and December 1998 as part of a program sponsored by an employer. The location and histologic features of all polyps were recorded. Colonoscopy to the level of the cecum was completed in 97.0 percent of the patients. RESULTS Sixty-one patients (3.1 percent) had advanced lesions in the distal colon, including 5 with cancer, and 50 (2.5 percent) had advanced proximal lesions, including 7 with cancer. Twenty-three patients with advanced proximal neoplasms (46 percent) had no distal polyps. The prevalence of advanced proximal neoplasia among patients with no distal polyps was 1.5 percent (23 cases among 1564 persons; 95 percent confidence interval, 0.9 to 2.1 percent). Among patients with distal hyperplastic polyps, those with distal tubular adenomas, and those with advanced distal polyps, the prevalence of advanced proximal neoplasia was 4.0 percent (8 cases among 201 patients), 7.1 percent (12 cases among 168 patients), and 11.5 percent (7 cases among 61 patients), respectively. The relative risk of advanced proximal neoplasia, adjusted for age and sex, was 2.6 for patients with distal hyperplastic polyps, 4.0 for those with distal tubular adenomas, and 6.7 for those with advanced distal polyps, as compared with patients who had no distal polyps. Older age and male sex were associated with an increased risk of advanced proximal neoplasia (relative risk, 1.3 for every five years of age and 3.3 for male sex). CONCLUSIONS Asymptomatic persons 50 years of age or older who have polyps in the distal colon are more likely to have advanced proximal neoplasia than are persons without distal polyps. However, if colonoscopic screening is performed only in persons with distal polyps, about half the cases of advanced proximal neoplasia will not be detected.

RESULTS OF SCREENING COLONOSCOPY AMONG PERSONS 40 TO 49 YEARS OF AGE

BACKGROUND The prevalence of colorectal lesions in persons 40 to 49 years of age, as identified on colonoscopy, has not been determined. METHODS We reviewed the procedure and pathology reports for 906 consecutive persons 40 to 49 years of age who voluntarily participated in an employer-based screening-colonoscopy program. The histologic features of lesions that were identified and removed on endoscopy were categorized according to those of the most advanced lesion removed proximally (up to the junction of the splenic flexure and the descending colon) and the most advanced lesion removed distally. An advanced lesion was defined as an adenoma at least 1 cm in diameter, a polyp with villous histologic features or severe dysplasia, or a cancer. RESULTS Among those who underwent colonoscopic screening, 78.9 percent had no detected lesions, 10.0 percent had hyperplastic polyps, 8.7 percent had tubular adenomas, and 3.5 percent had advanced neoplasms, none of which were cancerous (95 percent confidence interval for cancer, 0 to 0.4 percent). Eighteen of 33 advanced neoplasms (55 percent) were located distally and were potentially within reach of a sigmoidoscope. If these results are applicable to the general population, at least 250 persons, and perhaps 1000 or more, would need to be screened to detect one cancer in this age group. CONCLUSIONS Colonoscopic detection of colorectal cancer is uncommon in asymptomatic persons 40 to 49 years of age. The noncancerous lesions are equally distributed proximally and distally. The low yield of screening colonoscopy in this age group is consistent with current recommendations about the age at which to begin screening in persons at average risk.

Five-year risk of colorectal neoplasia after negative screening colonoscopy

BACKGROUND The appropriate interval for endoscopic rescreening after a negative colonoscopic examination is uncertain. METHODS We identified persons with no adenomas on baseline screening colonoscopy who returned at 5 years for follow-up colonoscopy. Findings were categorized according to the most advanced lesion present: no polyp, a hyperplastic polyp, a tubular adenoma less than 1 cm in diameter, an advanced adenoma (a tubular adenoma > or = 1 cm in diameter or a polyp with villous histologic features or high-grade dysplasia), or a cancer. RESULTS Baseline screening colonoscopy had identified 2436 persons with no adenomas; 1256 of them (51.6%) were rescreened a mean (+/-SD) of 5.34+/-1.34 years later. The mean age of this group at baseline was 56.7 years; 56.7% of its members were men. No cancers were found on rescreening (95% confidence interval [CI] for the detection rate, 0 to 0.24%). One or more adenomas were found in 201 persons (16.0%). A total of 19 advanced adenomas, of which 10 (52.6%) were distal to the splenic flexure, were found in 16 persons (1.3%). The risk of an advanced adenoma did not differ significantly between persons with no polyps at baseline and those with hyperplastic polyps at baseline (1.1% [12 of 1057] and 2.0% [4 of 199], respectively; P=0.30). Men were more likely than women to have any adenoma (tubular less than 1 cm in diameter or advanced) (relative risk, 1.88; 95% CI, 1.42 to 2.51) and to have an advanced adenoma (relative risk, 3.31; 95% CI, 1.02 to 10.8). CONCLUSIONS Among persons with no colorectal neoplasia on initial screening colonoscopy, the 5-year risk of colorectal cancer is extremely low. The risk of advanced adenoma is also low, although it is higher among men than among women. Our findings support a rescreening interval of 5 years or longer after a normal colonoscopic examination.

Using Risk for Advanced Proximal Colonic Neoplasia To Tailor Endoscopic Screening for Colorectal Cancer

Context Screening for colorectal cancer with sigmoidoscopy alone often misses proximal neoplasia. Contribution Using data from a company-based program of screening colonoscopy, these authors developed a risk index for advanced proximal neoplasia that stratified patients on the basis of age, sex, and distal colon findings. The prevalence of proximal neoplasia was 0.4%, 1.9%, and 3.8% among low-, intermediate-, and high-risk patients, respectively, in the validation sample. Implications A risk index that includes distal findings identifies low-risk patients whose probability of advanced proximal neoplasia is 1 in 250. The index may help identify patients who do not need colonoscopy after sigmoidoscopy. Cautions The index needs validation in additional populations. The Editors Use of colonoscopy as a primary screening test has been suggested (1, 2) because recent studies of screening colonoscopy in asymptomatic persons have reported the risk for advanced proximal neoplasia to be 2.5% to 4% in persons with no distal polyps (3, 4). These studies indicate that about half of advanced proximal neoplasms would remain undetected if the decision to perform colonoscopy after sigmoidoscopy were based only on distal findings (3, 4). On the basis of how distal findings are used in decision making, colonoscopy will be performed in 5% of the population if high-risk adenoma is used as the criterion, 12% if any adenoma is used, and 25% if any polyp is used (5). Issues of cost, safety, and availability may limit feasibility of this strategy (6), however, and some experts have noted the importance and necessity of shifting use of colonoscopy from lower-risk to higher-risk groups (7). Although sigmoidoscopy is recommended as a primary screening technique in all current recommendations (8-12), some health care providers are uncomfortable recommending an incomplete endoscopic examination. However, the marginal benefit of screening colonoscopy compared with sigmoidoscopy remains unclear. The decision about who requires colonoscopy, whether after sigmoidoscopy or in place of it, could be guided by knowledge about a persons risk for advanced proximal neoplasia. Several studies have evaluated the predictive utility of distal anatomy (13-17), but it might be possible to refine prediction by also considering clinical features, such as age, sex, and family history. Desirable properties of a predictive index include the ability to discriminate well between persons with and without advanced proximal neoplasia; the use of reliable, objective, and readily available information; ease of use in clinical practice; and generalizability to different groups (18). We sought to create an index to stratify risk for advanced proximal neoplasia in asymptomatic adults. The main goal was to identify a subgroup with very low risk for advanced proximal neoplasia, in which sigmoidoscopy alone might suffice even if a general strategy of widespread screening colonoscopy were to be implemented. A second goal was to determine whether a subgroup could be identified in which risk for advanced proximal neoplasia is sufficiently high a priori to warrant consideration for initial colonoscopic screening. Methods Design We performed a cross-sectional analysis of consecutive asymptomatic adults 50 years of age or older who underwent first-time screening colonoscopy between September 1995 and June 2001. The study was approved by the institutional review board of Indiana University at Indianapolis. Because the study is a retrospective analysis of an existing data set, written informed consent from participants was not required. Screening Program In September 1995, self-insured Eli Lilly and Co., Inc., began providing screening colonoscopy as a health benefit. Employees and retirees and their dependents 40 years of age or older receive written information about the screening program and may call a toll-free number to obtain more information or to schedule an appointment for screening. A brief telephone interview is used to determine eligibility for the screening program. To qualify, persons must be asymptomatic (that is, report no visible rectal bleeding, no change in bowel habits, and no recent or current lower abdominal pain) and must have no personal history of colorectal cancer, polyps, or inflammatory bowel disease. Persons with such symptoms or conditions are urged to seek medical care from their usual provider. Eligible persons may undergo colonoscopy at 1 of 8 sites in central Indiana, where 36 board-certified gastroenterologists and colorectal surgeons participate in the program. Study Procedures and Definitions Polyethylene glycol lavage solution was used for bowel preparation. Fecal occult blood testing and sigmoidoscopy were not performed before colonoscopy. Information about previous screening or diagnostic tests involving the colon and about family history of colorectal cancer was unavailable for analysis because it is not routinely obtained or recorded. During colonoscopy, the location and size of all polyps were determined before their removal. The methods for assessing location and size were chosen by the endoscopist. Pathologic specimens were examined by 1 of 3 board-certified pathologists, who classified polyps according to World Health Organization criteria (19). The pathologists who interpreted proximal polyps would have interpreted distal polyps as well, but they were unaware of the study hypothesis. Histologic characteristics of polyps were reported as normal mucosa, hyperplastic, tubular, tubulovillous, or villous. An advanced neoplasm was defined as a tubular adenoma 1 cm or larger or any polyp with villous histologic characteristics, high-grade dysplasia, or cancer. Such findings as lipomas, lymphoid aggregates, and nonspecific inflammation were considered to indicate normal mucosa. No specimens were considered to be nondiagnostic. For the purpose of categorizing location, distal was defined as descending colon, sigmoid colon, or rectum, as determined by the endoscopist. All other locations were considered proximal. If either or both the proximal or distal segments of the colon had more than 1 polyp, the colonic segment was categorized according to its most advanced polyp. Statistical Analysis The subgroup from which the index was derived consisted of 1994 asymptomatic adults 50 years of age or older who underwent first-time screening colonoscopy between September 1995 and December 1998. In a previous analysis of this subgroup, age, sex, and distal findings were independent risk factors for advanced proximal neoplasia (4). On the basis of these results, we derived a risk index and then validated it on a subsequent subgroup of 1031 consecutively screened persons. The scoring system for the risk index was generated by assigning points a priori to each category of age, sex, and distal findings (Table 1). For these 3 factors (or variables) taken together, the range for the index score was 0 to 7. For example, a 50-year-old woman with no distal polyps would have a score of 0, whereas a 70-year-old man with an advanced distal polyp would have a score of 7. The points for each variable were based on their coefficients from logistic regression, modified for ease of clinical use on the basis of the linear and ordinal relationships between the categories for each variable and risk for advanced proximal neoplasia. Our goal was to create a simple and logical scoring system. Among the derivation subgroup, the risk for advanced proximal neoplasia was measured for each score level (that is, from 0 to 7). In developing an ordinal set of categories of risk, we combined score levels with similar magnitudes of risk, so that scores of 0 and 1 were combined into a low-risk category, scores of 2 and 3 into an intermediate-risk category, and scores 4 through 7 into a high-risk category. The risk for advanced proximal neoplasia was then measured for each risk category, and 95% CIs for each proportion were derived by using exact methods for the binomial distribution. The proportions of persons with advanced proximal neoplasms in each risk category were compared by using the chi-square method, and the P value represents the probability of no difference in risk across categories. Table 1. Scoring System for the Risk Index* The concordance (or c) statistic was used to measure discrimination among persons with and without advanced proximal neoplasia (18). The c-statistic considers all pairs of study patients, of whom one has an advanced proximal neoplasm and one does not. The statistic itself is the percentage of pairs for which the model correctly predicts a higher probability of advanced proximal neoplasia for the patient with this lesion. The c-statistic can range from 0.0 (all incorrect predictions) to 0.5 (chance prediction equivalent to a coin toss) to 1.0 (all correct predictions) (20). A c-statistic of 0.7 to 0.8 indicates good discrimination, and a value higher than 0.8 indicates excellent discrimination. For binary logistic regression models, the c-statistic is the same as the area under the receiver-operating characteristic curve (21, 22). The scoring system and risk index were validated on the next 1031 consecutive adults 50 years of age or older who underwent screening colonoscopy between January 1999 and June 2001. These examinations were done in the same setting by the same endoscopists and pathologists, who remained unaware of the study hypothesis. With the same risk categories defined in the derivation subgroup, we measured the absolute risk for advanced proximal neoplasia for each category, along with exact confidence limits. To compare risk across categories, P values and the c-statistic were measured. A P value less than 0.05 was considered significant. Analyses were done by using SPSS for Windows software, version 10.0 (SPSS, Inc., Chicago, Illinois). Role of the Funding Source The funding source had no direct role in the design, data collection, analysis

Beliefs Associated With Fecal Occult Blood Test and Colonoscopy Use at a Worksite Colon Cancer Screening Program

Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. Although regular screening can decrease morbidity and mortality from CRC, screening rates nationwide are very low. This descriptive study assessed beliefs associated with fecal occult blood test and colonoscopy use among participants of a worksite colon cancer screening program. Randomly selected employees, aged 40 and older, were mailed a survey on CRC screening-related beliefs. Instruments were tested for reliability and validity. Results indicated that fecal occult blood test use was significantly associated with being female, Caucasian, having low perceived barriers, and provider recommendation. Colonoscopy use was significantly associated with higher knowledge, lower barriers, higher benefits, higher self-efficacy, and provider recommendation. Findings may be used to develop interventions designed to improve CRC screening rates.

A new clinical index to stratify risk for advanced proximal neoplasia in asymptomatic adults

A New Clinical Index to Stratify Risk for Advanced Proximal Neoplasia in AcymptomaUc Adults Thomas F. Imperiale, Indiana Univ Sch of Medicine, Indianapolis, IN; David R. Wagner, Indianapolis Gastroenterology Research Fdn, Indianapolis, IN; Ching Y. Lin, Indiana Univ Medical Ctr, Indianapolis, IN; Gregory N. Larkin, Eli Lilly & Co, Inc, Indianapolis, IN; James 0. Rogue, Indianapolis Gastroenterology Research Fdn, Indianapolis, IN; David F. Ransohoff, Univ of North Carolina, Chapel Hill, NC