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Carol A Burke

Publications and source records attributed to Carol A Burke.

15 recordsLinked to original sources

ACG Clinical Guideline: Diagnosis and Management of Adenomatous Colorectal Polyposis Syndromes.

The hereditary adenomatous colorectal polyposis syndromes are incurable, systemic, cancer risk predisposition syndromes with substantial morbidity and mortality. They differ in their mode of inheritance, age at disease onset, phenotypic expression, and cancer risk. The most common cancer risks involve the gastrointestinal tract including the colon, rectum, duodenum, ampulla, and stomach. Identifying these syndromes through personal and family history risk assessment and germline genetic testing, along with timely surgical and endoscopic management, can reduce cancer incidence and mortality. These guidelines use the Grading of Recommendations, Assessment, Development, and Evaluation methodology to provide clinical guidance on the selection of individuals who should undergo a risk assessment for a hereditary adenomatous colorectal polyposis syndrome, modality and timing of germline genetic testing, cancer risk mitigation through endoscopic and surgical interventions, and the role of chemoprevention. This document reviews the approach to genetic testing in patients with phenotypic colorectal polyposis and the impact of presymptomatic diagnosis in families with a known familial germline pathogenic variant or clinical features suggestive of a hereditary adenomatous polyposis syndrome. Management strategies for patients based on genetic test results or without genetic testing are provided. We also review colorectal and extracolonic phenotypic benign and malignant manifestations of the known hereditary syndromes with a focus on the 2 most common hereditary colorectal polyposis syndromes: familial adenomatous polyposis and MUTYH-associated polyposis. The document concludes with recommendations on polyposis and cancer risk mitigation strategies and highlights updates to management since the previous guideline was published.

Humans↗

Ornithine decarboxylase polymorphism modification of response to aspirin treatment for colorectal adenoma prevention.

BACKGROUND: Previous research suggests that the G315A single-nucleotide polymorphism in the ornithine decarboxylase (ODC) gene may be a genetic marker for risk of colorectal neoplasia and may also modify the association of aspirin use with risk. METHODS: We tested these hypotheses among participants in the Aspirin/Folate Polyp Prevention Study who were randomly assigned to placebo or to aspirin treatment (81 or 325 mg daily) and followed for 3 years for the occurrence of new adenomas. Genomic DNA from 973 subjects was analyzed for ODC genotype. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated to test the association between ODC genotype and adenoma occurrence and interactions with aspirin treatment. All statistical tests were two-sided. RESULTS: Of the 973 subjects, 54% were homozygous wild-type (GG), 7% were homozygous variant (AA), and 39% were heterozygous individuals; the allele frequencies varied statistically significantly by race and ethnicity. Among these subjects, the absolute risk of any adenoma was 45% and the risk of an advanced lesion was 10%. Overall, no association was found between ODC genotype and the occurrence of new adenomas, but genotype did modify the effect of aspirin on adenoma risk. Although aspirin treatment had no protective effect among subjects with a GG genotype, among subjects with at least one A allele, it was associated with statistically significant reduced risks of any adenoma (RR = 0.77, 95% CI = 0.63 to 0.95; P = .02, P(interaction) = .04) and of advanced lesions (RR = 0.51, 95% CI = 0.29 to 0.90; P = .02, P(interaction) = .02). Among subjects with at least one A allele, 40.8% who took aspirin versus 52.9% who took placebo developed adenomas; 7.1% versus 14.0% developed advanced lesions. CONCLUSION: ODC genotype may modify the response to aspirin treatment for colorectal adenoma prevention.

Adenoma↗

Aspirin may be more effective in preventing colorectal adenomas in patients with higher BMI (United States).

Obesity is a risk factor for colon cancer, possibly due to elevated levels of circulating cytokines derived from adipose tissue. Aspirin, which may affect the levels of these cytokines, has been shown in randomized controlled trials to decrease the risk of colorectal adenomas. We hypothesized that the chemopreventive effect of aspirin might be greater in individuals with higher body mass index (BMI). Data were available from the Aspirin/Folate Polyp Prevention Study, a randomized controlled trial of aspirin and folic acid to prevent recurrent colorectal adenomas. Obesity was defined as BMI > or = 30 (kg/m2), overweight as BMI of 25-29 (kg/m2) and normal weight as BMI <25 (kg/m2). For the analysis of the effect of aspirin on the recurrence of colorectal adenoma by BMI, we computed risk ratios for aspirin versus placebo within the three BMI strata using a modified Poisson model. Overall the risk reduction of adenomas with a daily dose of 325 mg aspirin was greater among subjects with higher BMI. Among obese subjects the risk ratio (RR) for advanced adenomas compared with placebo was 0.44 (95% CI 0.17-1.10), versus RR = 1.23 (95% CI 0.55-2.77) among those with normal weight. However, 81 mg aspirin daily did not interact with BMI to modify the risk of adenomas in such a fashion. The more pronounced effect of 325 mg aspirin in individuals with higher BMI suggests a possible protective role of anti-inflammatory aspirin against increased adipose-driven cytokines among obese subjects.

Adenomatous Polyps↗

Screening for colorectal cancer with flexible sigmoidoscopy: is a 5-yr interval appropriate? A comparison of the detection of neoplasia 3 yr versus 5 yr after a normal examination.

CONTEXT: The recommended interval for colorectal cancer screening with flexible sigmoidoscopy (FS) was recently lengthened from 3 to 5 yr. Direct evidence supporting the longer interval is lacking. The appropriateness of the longer interval has been questioned. OBJECTIVE: To compare the incidence of neoplasia detected on FS in individuals who had undergone an FS either 3 yr or 5 yr after a normal examination. DESIGN, SETTINGS, AND PATIENTS: Subjects were drawn from 5,359 individuals who underwent two FS examinations performed for colorectal cancer screening. Examinations were performed by gastroenterologists at a single academic medical center between 1987 and 2002. A total of 2,146 subjects with a normal baseline examination and a follow-up examination 3 and 5 yr later was included. MAIN OUTCOME MEASURE: To compare the incidence of neoplasia, including advanced neoplasia, detected 3 yr versus 5 yr after a normal FS. RESULTS: 915 subjects underwent FS at 3 yr and 1,231 subjects at 5 yr after a normal examination. Neoplasia was detected in 3.2% of the 3-yr and 4.3% of the 5-yr subjects (p=0.17). No significant differences were detected in the pathology, multiplicity, or size of neoplasms between the 3- and 5-yr groups. Advanced neoplasms occurred in 0.9% (including one adenocarcinoma) of subjects at 3 yr and 1.1% of subjects at 5 yr (p=0.67). CONCLUSIONS: Few individuals will develop rectosigmoid neoplasms 3 or 5 yr after a normal FS. The majority of neoplasms detected are low-risk lesions. A screening interval of 5 yr after a normal FS does not portend an increased risk of advanced neoplasms including cancer. This direct evidence supports the current recommendations of a 5-yr interval for colorectal cancer screening with FS.

Adult↗

Colorectal cancer in patients under close colonoscopic surveillance.

BACKGROUND & AIMS: Colonoscopic polypectomy is considered effective for preventing colorectal cancer (CRC), but the incidence of cancer in patients under colonoscopic surveillance has rarely been investigated. We determined the incidence of CRC in patients under colonoscopic surveillance and examined the circumstances and risk factors for CRC and adenoma with high-grade dysplasia. METHODS: Patients were drawn from 3 adenoma chemoprevention trials. All underwent baseline colonoscopy with removal of at least one adenoma and were deemed free of remaining lesions. We identified patients subsequently diagnosed with invasive cancer or adenoma with high-grade dysplasia. The timing, location, and outcome of all cases of cancer and high-grade dysplasia identified are described and risks associated with their development explored. RESULTS: CRC was diagnosed in 19 of the 2915 patients over a mean follow-up of 3.7 years (incidence, 1.74 cancers/1000 person-years). The cancers were located in all regions of the colon; 10 were at or proximal to the hepatic flexure. Although most of the cancers (84%) were of early stage, 2 participants died of CRC. Seven patients were diagnosed with adenoma with high-grade dysplasia during follow-up. Older patients and those with a history of more adenomas were at higher risk of being diagnosed with invasive cancer or adenoma with high-grade dysplasia. CONCLUSIONS: CRC is diagnosed in a clinically important proportion of patients following complete colonoscopy and polypectomy. More precise and representative estimates of CRC incidence and death among patients undergoing surveillance examinations are needed.

Adenoma↗

Gender disparity in the practice of gastroenterology: the first 5 years of a career.

BACKGROUND: Despite an unprecedented demand for gastroenterology services, the number of gastroenterology trainees has decreased over 50% since 1993. Women comprise nearly 50% of the U.S. medical school student population; yet only occupy 16% of gastroenterology fellowship positions. In order to recruit the best candidates to gastroenterology we must be able to demonstrate the attractiveness of a career in the field. A prospective study was performed to identify the career choices of graduates from gastroenterology fellowship programs using a prospective study model and to identify whether gender differences exist in the practice of gastroenterologists up to 5 yr after completion of training. METHODS: A survey gathering information on demographics, practice pattern, and income was mailed to two cohorts of gastroenterology fellows 3 and 5 yr after graduation. RESULTS: A total of 247 subjects completed the 3 yr and 220 subjects responded to the 5-yr survey. At 3 yr, men reported higher income (p < 0.001), worked longer hours per week (p < 0.002), and were more likely to be part owner of the practice (p= 0.027). Females reported fewer children (p < 0.007), lower board certification rates (p < 0. 002), worked for larger, multispecialty practices (p < 0.001), and practiced more internal medicine. These differences were still present at 5 yr into gastroenterology practice. CONCLUSIONS: Significant differences in practice type, earnings, board certification, professional standing, and alterations in family planning are noted between male and female gastroenterologists in the initial 5 yr of their practice.

Career Choice↗

The utility of capsule endoscopy small bowel surveillance in patients with polyposis.

BACKGROUND: Small intestinal (SI) surveillance is recommended for polyposis patients. The utility and safety of capsule endoscopy (CE) for surveillance of SI neoplasia in patients with familial adenomatous polyposis (FAP) and Peutz-Jeghers syndrome (PJS) is unknown. METHODS: CE was offered to consecutive FAP and PJS patients due for routine upper endoscopic surveillance. The prevalence, location (jejunum, ileum), size (1-5 mm, 6-10 mm, >10 mm) and number (1-5, 6-12, >20) of polyps detected by CE was assessed. RESULTS: 19 subjects (15 FAP/4 PJS) with a mean age of 43 were included. All subjects had previous intestinal surgery. No complications occurred with CE. CE in FAP: 9/15 (60%) of subjects with FAP had SI polyps. The prevalence of SI polyps was related to the duodenal polyposis stage and subject age. The location, size and number of polyps progressed as duodenal polyposis stage advanced. CE in PJS: 3/4 (75%) of subjects with PJS had SI polyps. The polyps were diffuse in 2/4 and only in the ileum in one subject. CE findings led to laparotomy with intra-operative endoscopic polypectomy in two PJS patients. CONCLUSION: SI polyps are common in FAP but their importance is unknown. CE should be performed in FAP patients with stage III and IV duodenal disease. Clinically significant polyps are commonly detected by CE in PJS and lead to change in management in 50% of PJS subjects. CE should replace radiographic SI surveillance for PJS patients. CE is safe in polyposis patients who have undergone major intestinal surgery.

Adenomatous Polyposis Coli↗

The association of physical activity and body mass index with the risk of large bowel polyps.

PURPOSE AND METHOD: Several studies have suggested that physical inactivity and obesity increase the risk for colorectal neoplasia. In this study, we investigated the association of physical activity and body mass index (BMI) with the risk of different types of large bowel polyps. We did an observational analysis nested within a randomized double-blind placebo-controlled chemoprevention trial among patients with one or more recently resected histologically confirmed colorectal adenoma. Nine hundred thirty patients were randomized to calcium (1,200 mg/d, as carbonate) or placebo. Follow-up colonoscopies were conducted approximately 1 and 4 years after the qualifying examination. At study entry, we obtained each subject's current body weight and height, which we used to calculate BMI. After the second study colonoscopy, we asked subjects questions about their leisure time physical activity. Seven hundred eighty-seven subjects completed at least part of the physical activity questionnaire. RESULTS: We found no association between measures of physical activity or BMI and tubular adenomas or hyperplastic polyps. However, among men, there were strong inverse associations observed between physical activity and advanced neoplastic polyps. Compared with men whose total daily energy expenditure was in the lowest tertile, those in the highest tertile had a risk ratio of 0.35 (95% confidence interval, 17-0.72); there was no similar reduction observed among women (risk ratio, 1.21; 95% confidence interval, 0.36-4.03; P for interaction = 0.04). DATA INTERPRETATIONS: We found a significant inverse relationship between several measures of physical activity and risk of advanced colorectal neoplasms, particularly among men. No associations were found between BMI and hyperplastic polyps, tubular adenomas, or advanced neoplastic polyps.

Aged↗

Effect of calcium supplementation on the risk of large bowel polyps.

BACKGROUND: Clinical trials have shown that calcium supplementation modestly decreases the risk of colorectal adenomas. However, few studies have examined the effect of calcium on the risk of different types of colorectal lesions or dietary determinants of this effect. METHODS: Our analysis used patients from the Calcium Polyp Prevention Study, a randomized, double-blind, placebo-controlled chemoprevention trial among patients with a recent colorectal adenoma. Nine hundred thirty patients were randomly assigned to calcium carbonate (1200 mg/day) or placebo. Follow-up colonoscopies were conducted approximately 1 and 4 years after the qualifying examination. We used general estimating equation (GEE) and generalized linear regression analyses to compute risk ratios and 95% confidence intervals (CIs) to assess the effect of calcium treatment versus placebo on the risk of hyperplastic polyps, tubular adenomas, and more advanced lesions. Additionally, we used GEE analyses to compare the calcium treatment effects for various types of polyps with that for tubular adenomas. We also examined the interaction between calcium treatment and baseline intake of dietary calcium, fat, and fiber. All P values were obtained using Wald tests based on the corresponding models. All tests of statistical significance were two-sided. RESULTS: The calcium risk ratio for hyperplastic polyps was 0.82 (95% CI = 0.67 to 1.00), that for tubular adenomas was 0.89 (95% CI = 0.77 to 1.03), and that for histologically advanced neoplasms was 0.65 (95% CI = 0.46 to 0.93) compared with patients assigned to placebo. There were no statistically significant differences between the risk ratio for tubular adenomas and that for other types of polyps. The effect of calcium supplementation on adenoma risk was most pronounced among individuals with high dietary intakes of calcium and fiber and with low intake of fat, but the interactions were not statistically significant. CONCLUSION: Our results suggest that calcium supplementation may have a more pronounced antineoplastic effect on advanced colorectal lesions than on other types of polyps.

Adenomatous Polyposis Coli↗

A randomized trial of aspirin to prevent colorectal adenomas.

BACKGROUND: Laboratory and epidemiologic data suggest that aspirin has an antineoplastic effect in the large bowel. METHODS: We performed a randomized, double-blind trial of aspirin as a chemopreventive agent against colorectal adenomas. We randomly assigned 1121 patients with a recent history of histologically documented adenomas to receive placebo (372 patients), 81 mg of aspirin (377 patients), or 325 mg of aspirin (372 patients) daily. According to the protocol, follow-up colonoscopy was to be performed approximately three years after the qualifying endoscopy. We compared the groups with respect to the risk of one or more neoplasms (adenomas or colorectal cancer) at least one year after randomization using generalized linear models to compute risk ratios and 95 percent confidence intervals. RESULTS: Reported adherence to study medications and avoidance of nonsteroidal antiinflammatory drugs were excellent. Follow-up colonoscopy was performed at least one year after randomization in 1084 patients (97 percent). The incidence of one or more adenomas was 47 percent in the placebo group, 38 percent in the group given 81 mg of aspirin per day, and 45 percent in the group given 325 mg of aspirin per day (global P=0.04). Unadjusted relative risks of any adenoma (as compared with the placebo group) were 0.81 in the 81-mg group (95 percent confidence interval, 0.69 to 0.96) and 0.96 in the 325-mg group (95 percent confidence interval, 0.81 to 1.13). For advanced neoplasms (adenomas measuring at least 1 cm in diameter or with tubulovillous or villous features, severe dysplasia, or invasive cancer), the respective relative risks were 0.59 (95 percent confidence interval, 0.38 to 0.92) and 0.83 (95 percent confidence interval, 0.55 to 1.23). CONCLUSIONS: Low-dose aspirin has a moderate chemopreventive effect on adenomas in the large bowel.

Adenoma↗

Colonoscopy screening in the elderly: when to stop?

OBJECTIVES: The age to begin colorectal cancer (CRC) screening is based on the risk of neoplasia and is published in screening guidelines. The age to stop screening is unknown but should be based, in part, on the same principle. The purpose of this study was to establish whether the prevalence of neoplasia detected by colonoscopy diminished with advancing age, to warrant ceasing colonoscopic screening. METHODS: The endoscopic and pathology reports of all asymptomatic subjects undergoing colonoscopy for the purpose of CRC screening or an evaluation of abdominal pain or change in bowel habits between 1997 and 2000 were reviewed. A multivariate logistic regression analysis was used to assess the effect of age, gender, and indication for examination on the prevalence of neoplasia, as well as on having more than two adenomas, advanced adenomas (tubulovillous, villous, severe dysplasia, or size > or = 1 cm), and invasive cancers. RESULTS: A total of 915 patients were included. Of these, 50% were male, with a mean age of 65 yr (range 50-100). Neoplasia peaked in the seventh decade, with a fall thereafter (p = 0.009). Numerous adenomas, advanced adenomas, and invasive cancers increased with age. The yield for overall neoplasia, advanced adenomas, and more than two adenomas was higher in the screening group than in the symptomatic group. More invasive cancers were found in the symptomatic group compared with the asymptomatic group, but this did not achieve statistical significance (4 vs 1, p = 0.44). CONCLUSIONS: The prevalence of advanced neoplasia continues to increase with age. Subjects undergoing colonoscopy for screening had a greater risk for neoplasia than did subjects with symptoms. There is no decline in yield of advanced neoplasia to justify stopping screening colonoscopy in the elderly.

Age Factors↗

The accuracy of an endoscopy nurse in interpreting capsule endoscopy.

OBJECTIVE: The average physician time required to view a wireless capsule endoscopy study at our institution is 50 min. It is unknown whether a nurse could preview the capsule endoscopy video and accurately detect all significant lesions. If so, it may allow the physician to review only the predetected abnormalities and thereby greatly reduce physician reading time. Our aim was to evaluate whether a nurse can accurately detect lesions on capsule endoscopy. METHODS: An endoscopy nurse who was trained to read capsule endoscopy reviewed 20 consecutive capsule endoscopy studies and recorded all findings. The same studies were viewed independently by a gastroenterologist. The two sets of recorded findings were reviewed, and a comparison of the accuracy in detecting landmarks and clinically significant lesions was made. RESULTS: The nurse missed two of 27 significant lesions seen by the gastroenterologist (93% sensitivity, 95% CI = 74-99%), and the gastroenterologist missed three seen by the nurse. The nurse accurately recorded gastric emptying time and time of passage through the ileocecal valve to within 1 min of the times recorded by the gastroenterologist in 18 of 20 patients (90% agreement, 95% CI = 67-98%). CONCLUSIONS: In this study, the endoscopy nurse detected 93% of the clinically significant lesions seen by the gastroenterologist. The clinical implication of this is that a physician extender could preread capsule endoscopies, allowing the gastroenterologist to view only the demarcated abnormalities. This could improve the cost effectiveness of capsule endoscopy and lead to wider physician acceptance of the test.

Clinical Competence↗

Chemoprevention of colorectal cancer: slow, steady progress.

In population-based observational studies, people had lower rates of colorectal cancer if they were taking various agents, including nonsteroidal anti-inflammatory drugs, calcium, and folate. In placebo-controlled trials in patients with familial adenomatous polyposis and in patients with sporadic colon adenomas, nonsteroidal anti-inflammatory drugs reduced the rates of adenomas, and there is a biologic rationale that they would be effective in reducing colorectal cancer as well. Randomized trials of chemopreventive agents are underway in the general population.

Adenomatous Polyposis Coli↗