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Biomedical subjects

Ann G Zauber

Publications and source records attributed to Ann G Zauber.

15 recordsLinked to original sources
PubMed2006

How much can current interventions reduce colorectal cancer mortality in the U.S.? Mortality projections for scenarios of risk-factor modification, screening, and treatment.

BACKGROUND: Although colorectal cancer (CRC) is the second leading cause of cancer death in the U.S., available interventions to reduce CRC mortality are disseminated only partially throughout the population. This study assessed the potential reduction in CRC mortality that may be achieved through further dissemination of current interventions for risk-factor modification, screening, and treatment. METHODS: The MISCAN-COLON microsimulation model was used to simulate the 2000 U.S. population with respect to CRC risk-factor prevalence, screening use, and treatment use. The model was used to project age-standardized CRC mortality from 2000 to 2020 for 3 intervention scenarios. RESULTS: Without changes in risk-factor prevalence, screening use, and treatment use after 2000, CRC mortality would decrease by 17% by the Year 2020. If the 1995 to 2000 trends continue, then the projected reduction in mortality would be 36%. However, if trends in the prevalence of risk-factors could be improved above continued trends, if screening use increased to 70% of the target population, and if the use of chemotherapy increased among all age groups, then a 49% reduction would be possible. Screening drove most (23%) of the projected mortality reduction with these optimistic trends; however, decreasing risk-factors (16%) and increasing use of chemotherapy (10%) also contributed substantially. The contribution of risk-factors may have been overestimated, because effect estimates could not be obtained from randomized controlled trials. CONCLUSIONS: Currently available interventions for risk-factor modification, screening, and treatment have the potential to reduce CRC mortality by almost 50% by the Year 2020. However, without action now to further increase the uptake of current effective interventions, the reduction in CRC mortality may be only 17%.

Colorectal Neoplasms↗
PubMed2006

Effect of celecoxib on cardiovascular events and blood pressure in two trials for the prevention of colorectal adenomas.

BACKGROUND: Cyclooxygenase-2 (COX-2) inhibitors have been shown to reduce colorectal adenomas but have been associated with increased cardiovascular risk. METHODS AND RESULTS: The Adenoma Prevention With Celecoxib (APC) trial studied celecoxib 200 mg twice daily and 400 mg twice daily and the Prevention of Spontaneous Adenomatous Polyps (PreSAP) trial used 400 mg once daily totest the efficacy and safety of celecoxib against placebo in reducing colorectal adenoma recurrence after polypectomy. An independent safety committee for both studies adjudicated and categorized serious cardiovascular events and then combined individual patient data from these long-term trials to improve the estimate of the cardiovascular risk and blood pressure changes associated with celecoxib compared with placebo. For adjudicated cardiovascular events, 77% and 54% in APC and PreSAP, respectively, had 37 months of follow-up. For APC and PreSAP combined, 83 patients experienced cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or heart failure. The hazard ratio for this prespecified composite end point was 2.6 (95% confidence interval [CI], 1.1 to 6.1) in patients taking 200 mg twice daily, 3.4 (95% CI, 1.5 to 7.9) in patients taking 400 mg twice daily in APC, and 1.3 (95% CI, 0.6 to 2.6) in patients taking 400 mg once daily in PreSAP (P for heterogeneity = 0.13 comparing the combined doses in APC with the dose in PreSAP). The overall hazard ratio for this composite end point was 1.9 (95% CI, 1.1 to 3.1). Both dose groups in APC showed significant systolic blood pressure elevations at 1 and 3 years (200 mg twice daily: 1 year, 2.0 mm Hg; 3 years,2.6 mm Hg; 400 mg twice daily: 1 year, 2.9 mm Hg; 3 years, 5.2 mm Hg); however, the 400 mg once daily group inPreSAP did not (P0.0001 between studies). CONCLUSIONS: Celecoxib at 200 or 400 mg twice daily or 400 mg once daily showed a nearly 2-fold-increased cardiovascular risk. The trend for a dose-related increase in cardiovascular events and blood pressure raises the possibility that lower doses or other dose intervals may be associated with less cardiovascular risk.

Adenoma↗
PubMed2006

Celecoxib for the prevention of sporadic colorectal adenomas.

BACKGROUND: Studies showing that drugs that inhibit cyclooxygenase-2 (COX-2) reduce the number of colorectal adenomas in animals and patients with familial adenomatous polyposis suggest that COX-2 inhibitors may also prevent sporadic colorectal neoplasia. METHODS: We randomly assigned patients who had adenomas removed before study entry to receive placebo (679 patients) or 200 mg (685 patients) or 400 mg (671 patients) of celecoxib twice daily. Randomization was stratified for the use of low-dose aspirin. Follow-up colonoscopies were performed at one and three years after randomization. The occurrence of newly detected colorectal adenomas was compared among the groups with the life-table extension of the Mantel-Haenszel test. RESULTS: Follow-up colonoscopies were completed at year 1 in 89.5 percent of randomized patients, and at year 3 in 75.7 percent. The estimated cumulative incidence of the detection of one or more adenomas by year 3 was 60.7 percent for patients receiving placebo, as compared with 43.2 percent for those receiving 200 mg of celecoxib twice a day (risk ratio, 0.67; 95 percent confidence interval, 0.59 to 0.77; P<0.001) and 37.5 percent for those receiving 400 mg of celecoxib twice a day (risk ratio, 0.55; 95 percent confidence interval, 0.48 to 0.64; P<0.001). Serious adverse events occurred in 18.8 percent of patients in the placebo group, as compared with 20.4 percent of those in the low-dose celecoxib group (risk ratio, 1.1; 95 percent confidence interval, 0.9 to 1.3; P=0.5) and 23.0 percent of those in the high-dose group (risk ratio, 1.2; 95 percent confidence interval, 1.0 to 1.5; P=0.06). As compared with placebo, celecoxib was associated with an increased risk of cardiovascular events (risk ratio for the low dose, 2.6; 95 percent confidence interval, 1.1 to 6.1; and risk ratio for the high dose, 3.4; 95 percent confidence interval, 1.5 to 7.9). CONCLUSIONS: These findings indicate that celecoxib is an effective agent for the prevention of colorectal adenomas but, because of potential cardiovascular events, cannot be routinely recommended for this indication. (ClinicalTrials.gov number, NCT00005094 [ClinicalTrials.gov].).

Adenoma↗
PubMed2006

Celecoxib for the prevention of colorectal adenomatous polyps.

BACKGROUND: Overexpression of cyclooxygenase 2 (COX-2) has been associated with colorectal adenomatous polyps and cancer, prompting researchers to propose its inhibition as a chemopreventive intervention. METHODS: The Prevention of Colorectal Sporadic Adenomatous Polyps trial was a randomized, placebo-controlled, double-blind study of the COX-2 inhibitor celecoxib given daily in a single 400-mg dose. At 107 centers in 32 countries, we randomly assigned 1561 subjects who had had adenomas removed before enrollment to receive celecoxib (933 subjects) or placebo (628 subjects) daily, after stratification according to the use or nonuse of low-dose aspirin. The primary outcome was detection of adenomas at either year 1 or year 3 by colonoscopy and was compared among the groups with the use of the Mantel-Cox test. RESULTS: Colonoscopies were performed at year 1 on 88.7 percent of the subjects who had undergone randomization and at year 3 on 79.2 percent. Of the 557 subjects in the placebo group and the 840 subjects in the celecoxib group who were included in the efficacy analysis, 264 and 270, respectively, were found to have at least one adenoma at year 1, at year 3, or both. The cumulative rate of adenomas detected through year 3 was 33.6 percent in the celecoxib group and 49.3 percent in the placebo group (relative risk, 0.64; 95 percent confidence interval, 0.56 to 0.75; P<0.001). The cumulative rate of advanced adenomas detected through year 3 was 5.3 percent in the celecoxib group and 10.4 percent in the placebo group (relative risk, 0.49; 95 percent confidence interval, 0.33 to 0.73; P<0.001). Adjudicated serious cardiovascular events occurred in 2.5 percent of subjects in the celecoxib group and 1.9 percent of those in the placebo group (relative risk, 1.30; 95 percent confidence interval, 0.65 to 2.62). CONCLUSIONS: The use of 400 mg of celecoxib once daily significantly reduced the occurrence of colorectal adenomas within three years after polypectomy. (ClinicalTrials.gov number, NCT00141193 [ClinicalTrials.gov].).

Adenoma↗
PubMed2006

Guidelines for colonoscopy surveillance after polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society.

Adenomatous polyps are the most common neoplastic findings discovered in people who undergo colorectal screening or who have a diagnostic work-up for symptoms. It was common practice in the 1970s for these patients to have annual follow-up surveillance examinations to detect additional new adenomas and missed synchronous adenomas. As a result of the National Polyp Study report in 1993, which showed clearly in a randomized design that the first postpolypectomy examination could be deferred for 3 years, guidelines published by a gastrointestinal consortium in 1997 recommended that the first follow-up surveillance take place 3 years after polypectomy for most patients. In 2003 these guidelines were updated and colonoscopy was recommended as the only follow-up examination, stratification at baseline into low risk and higher risk for subsequent adenomas was suggested. The 1997 and 2003 guidelines dealt with both screening and surveillance. However, it has become increasingly clear that postpolypectomy surveillance is now a large part of endoscopic practice, draining resources from screening and diagnosis. In addition, surveys have shown that a large proportion of endoscopists are conducting surveillance examinations at shorter intervals than recommended in the guidelines. In the present report, a careful analytic approach was designed to address all evidence available in the literature to delineate predictors of advanced pathology, both cancer and advanced adenomas, so that patients can be stratified more definitely at their baseline colonoscopy into those at lower risk or increased risk for a subsequent advanced neoplasia. People at increased risk have either 3 or more adenomas, high-grade dysplasia, villous features, or an adenoma 1 cm or larger in size. It is recommended that they have a 3-year follow-up colonoscopy. People at lower risk who have 1 or 2 small (<1 cm) tubular adenomas with no high-grade dysplasia can have a follow-up evaluation in 5-10 years, whereas people with hyperplastic polyps only should have a 10-year follow-up evaluation, as for average-risk people. There have been recent studies that have reported a significant number of missed cancers by colonoscopy. However, high-quality baseline colonoscopy with excellent patient preparation and adequate withdrawal time should minimize this and reduce clinicians concerns. These guidelines were developed jointly by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society to provide a broader consensus and thereby increase the use of the recommendations by endoscopists. The adoption of these guidelines nationally can have a dramatic impact on shifting available resources from intensive surveillance to screening. It has been shown that the first screening colonoscopy and polypectomy produces the greatest effects on reducing the incidence of colorectal cancer in patients with adenomatous polyps.

Adenomatous Polyposis Coli↗
PubMed2005

Clinical and genetic findings in an Ashkenazi Jewish population with colorectal neoplasms.

BACKGROUND: The authors evaluated the frequency of the carrier status of three ancestral colorectal neoplasm-associated mutations (APC:I1307K, BLM(Ash), and MSH2*1906G>C) found in the Jewish population among a case series with documented colorectal neoplasms. They further compared family and personal histories plus environmental exposures of the carriers and noncarriers of the I1307K mutation and examined clinical differences with regard to the colorectal neoplasms and the specific molecular genetic changes in these lesions. METHODS: Analyses were performed on tissue from stored paraffin-embedded blocks for the three germline mutations plus the KRAS mutation and APC loss of heterozygosity (LOH) and APC gene sequencing. RESULTS: Fifty-four of the 429 individuals (12.6%) were found to carry the APC:I1307K mutation, whereas 4 (0.9%) were found to be heterozygous for the BLM(Ash) mutation and 3 (0.7%) were carriers of the MSH21906G>C* mutation. Carriers of the I1307K mutation did not appear to differ from noncarriers with regard to the number of neoplasms, patient age at detection, or tumor location within the colon. There was no significant difference noted between I1307K carriers and noncarriers with regard to the percentage of patients with first-degree relatives with colorectal carcinoma. A significant risk for APC LOH was found in lesions from carriers who smoked cigarettes compared with nonsmokers. The I1307K mutation was found to be clearly associated with a somatic additional adenine insertion in the region of codons 1306-1309, but other mutations in the region of codons 1277-1348 were found to be no more prevalent in carriers than in noncarriers. CONCLUSIONS: In Jewish individuals previously diagnosed with a colorectal neoplasm, MSH2*1906G>C is uncommon but has been associated with carcinoma occurring at a young age. The BLM(Ash) mutation is uncommon and appears to be of little effect. The I1307K mutation is common among Jews who have had colorectal neoplasms, but overall it was found to have little effect clinically in the current study group. There may be a gene-environment interaction between the I1307K mutation and cigarette use.

Adenosine Triphosphatases↗
PubMed2004

National Polyp Study data: evidence for regression of adenomas.

The data of the National Polyp Study, a large longitudinal study on surveillance of adenoma patients, is used for testing assumptions on the adenoma-carcinoma sequence. The observed adenoma and colorectal cancer incidence in the National Polyp Study were compared with the simulated outcomes of the MISCAN-COLON model of epidemiology and control of colorectal cancer for the U.S. population based on expert opinion. Variants of this model were explored in order to identify assumptions on the adenoma-carcinoma sequence that are consistent with the study observations. The high observed adenoma detection rates at surveillance and low observed colorectal cancer incidence in the National Polyp Study could only be explained by assuming a high incidence rate of adenomas accompanied by regression of adenomas. The National Polyp Study data suggest that adenoma prevalence results from a dynamic process of both formation as well as regression of adenomas. This lowers the expectations for the effects of colorectal cancer screening strategies that focus on adenoma detection.

Adenoma↗
PubMed2004

Flat adenomas in the National Polyp Study: is there increased risk for high-grade dysplasia initially or during surveillance?

BACKGROUND & AIMS: The flat adenoma may be a more aggressive pathway in colorectal carcinogenesis. Sessile adenomas from the National Polyp Study cohort were reclassified histopathologically as flat or polypoid and compared with initial and surveillance pathology. METHODS: A total of 933 sessile adenomas detected during 1980-1990 were reclassified as follows: (1) adenoma thickness (AT): < or =1.3 mm, and (2) adenoma ratio (AR): adenoma thickness <2x normal mucosa thickness. Logistic regression was used to assess whether flat adenomas had an effect on risk for high-grade dysplasia initially, and a Cox proportional hazards model assessed the risk for advanced adenomas at surveillance. RESULTS: The analysis encompassed 8401 person-years of follow-up evaluation. AT and AR measures of adenoma flatness were 95% concordant. By the AT measure, flat adenomas (n = 474) represented 27% of all baseline adenomas. Flat adenomas were found to be no more likely to exhibit high-grade dysplasia than sessile (polypoid) or pedunculated adenomas, the odds ratio for high-grade dysplasia was 1.91 (95% confidence interval [CI], 0.66-5.47; P = 0.23) for sessile (polypoid) vs. flat adenomas and 1.78 (95% CI, 0.63-5.02; P = 0.28) for pedunculated vs. flat adenomas adjusted for size, villous component, and location, and corrected for correlation of risk within an individual patient. Patients with flat adenomas at initial colonoscopy were not at greater risk for advanced adenomas at surveillance compared with those with polypoid adenomas only, the odds ratio was 0.76 (95% CI, 0.4-1.42; P = .39), adjusted for multiplicity, age, and family history of colorectal cancer. CONCLUSIONS: Flat adenomas identified in the National Polyp Study cohort at baseline were not associated with a higher risk for high-grade dysplasia initially, or for advanced adenomas at surveillance.

Adenoma↗
PubMed2002

The advanced adenoma as the primary target of screening.

The advanced adenoma bridges benign and malignant states and may be the most valid neoplastic surrogate marker for present and future colorectal cancer risk. We define the advanced adenoma as an adenoma with significant villous features (>25%), size of 1.0 cm or more, high-grade dysplasia, or early invasive cancer. Prevention studies should demonstrate a high efficacy in reducing the number of advanced adenomas. We should use the advanced adenoma in the evaluation of new screening technology, nutritional interventions, and chemoprevention agents because the advanced adenoma is a more desirable target for screening efficacy than is the more uncommon but life-threatening cancer stage or the more common but early, less significant small adenoma stage.

Adenoma↗
PubMed2002

Statin use and the risk of breast and prostate cancer.

BACKGROUND: Laboratory data suggest that the cholesterol-lowering "statin" drugs may have chemopreventive potential against cancer at various sites, including breast and prostate. However, in one trial of pravastatin there was a significant excess of breast cancer in the treatment group. In the present study, we assessed the relation of statin use to the risk of breast and prostate cancer in our hospital-based Case-Control Surveillance Study of Drugs and Serious Illnesses. METHODS: Cases were 1,132 women with breast cancer and 1,009 men with prostate cancer; controls were 1,331 women and 1,387 men admitted for conditions unrelated to statin use. We used multivariate unconditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for use of statins compared with no use. RESULTS: The OR for breast cancer among statin users was 1.5 (95% CI = 1.0-2.3), largely accounted for by an OR of 1.8 (95% CI = 0.9-3.6) among cases with carcinoma in situ. Among invasive cases, the OR was 1.2 (95% CI = 0.7-2.0). The odds ratio for prostate cancer overall was 1.2 (95% CI = 0.8-1.7), and it was 1.4 (95% CI = 0.7-2.5) for Stage A. CONCLUSIONS: The data from the present study do not support a protective effect of statins against breast or prostate cancer. Detection bias is a possible explanation for the higher ORs observed for carcinoma in situ or early-stage cancer as compared with more invasive cancer.

Aged↗
PubMedDate not supplied

Estrogen replacement therapy and risk of lung cancer.

PURPOSE: Some epidemiological data suggest that sex hormones may influence lung cancer risk, and estrogen receptors have been found in human non-small cell lung tumors. We assessed the relation of the use of estrogen replacement therapy (ERT) to the risk of lung cancer in our hospital-based Case-Control Surveillance Study, conducted in four US centers during 1976 to 2001. METHODS: Cases were 662 women aged 40 through 74 years with lung cancer and controls were 4671 women admitted for conditions unrelated to ERT use. We used multivariate unconditional logistic regression models to estimate odds ratios (OR) and 95% confidence intervals (CI) for ERT use for at least 3 months compared to no use or use for less than 3 months. RESULTS: The OR for lung cancer among ERT users was 1.0 (95%CI 0.8-1.4), and it was 1.0 (95%CI 0.7-1.4) among users of conjugated estrogens only. Risk did not increase as the duration of use increased. Odds ratios for specific lung cancer cell types were not significantly increased or decreased for use of ERT or conjugated estrogens. There were non-significant increases for non-small cell types other than squamous, but there was no consistent pattern across duration of use. CONCLUSION: Our data do not support an increased risk of lung cancer among women who use ERT.

Adult↗
PubMedDate not supplied

Guidelines for colonoscopy surveillance after polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society.

Adenomatous polyps are the most common neoplastic findings uncovered in people who undergo colorectal screening or have a diagnostic workup for symptoms. It was common practice in the 1970s for these patients to have annual follow-up surveillance examinations to detect additional new adenomas as well as missed synchronous adenomas. As a result of the National Polyp Study report in 1993, which demonstrated clearly in a randomized design that the first postpolypectomy examination could be deferred for 3 years, guidelines published by a gastrointestinal consortium in 1997 recommended that the first follow-up surveillance be 3 years after polypectomy for most patients. In 2003, these guidelines were updated, colonoscopy was recommended as the only follow-up examination, and stratification at baseline into lower and higher risk for subsequent adenomas was suggested. The 1997 and 2003 guidelines dealt with both screening and surveillance. However, it has become increasingly clear that postpolypectomy surveillance is now a large part of endoscopic practice, draining resources from screening and diagnosis. In addition, surveys have demonstrated that a large proportion of endoscopists are conducting surveillance examinations at shorter intervals than recommended in the guidelines. In the present paper, a careful analytic approach was designed addressing all evidence available in the literature to delineate predictors of advanced pathology, both cancer and advanced adenomas, so that patients can be more definitely stratified at their baseline colonoscopy into those at lower or increased risk for a subsequent advanced neoplasia. People at increased risk have either three or more adenomas, or high-grade dysplasia, or villous features, or an adenoma > or =1 cm in size. It is recommended that they have a 3-year follow-up colonoscopy. People at lower risk who have one or two small (< 1 cm) tubular adenomas with no high-grade dysplasia can have a follow-up in 5 to 10 years, whereas people with hyperplastic polyps only should have a 10-year follow-up as average-risk people. Recent papers have reported a significant number of missed cancers by colonoscopy. However, high-quality baseline colonoscopy with excellent patient preparation and adequate withdrawal time should minimize this and reduce clinicians' concerns. These guidelines were developed jointly by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society to provide a broader consensus and thereby increase utilization of the recommendations by endoscopists. Adoption of these guidelines nationally can have a dramatic impact on shifting available resources from intensive surveillance to screening. It has been shown that the first screening colonoscopy and polypectomy produces the greatest effects on reducing the incidence of colorectal cancer in patients with adenomatous polyps.

Adenomatous Polyps↗