Cancer prevention and the American Society of Clinical Oncology.
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Biomedical subjects
Publications and source records attributed to Bernard Levin.
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BACKGROUND: Despite advances in early detection and effective treatment, cancer remains one of the most feared diseases. Among the most common side effects of cancer and treatments for cancer are pain, depression, and fatigue. Although research is producing increasingly hopeful insights into the causes and cures for cancer, efforts to manage the side effects of the disease and its treatments have not kept pace. The challenge that faces us is how to increase awareness of the importance of recognizing and actively addressing cancer-related distress. The National Institutes of Health (NIH) convened a State-of-the-Science Conference on Symptom Management in Cancer: Pain, Depression, and Fatigue to examine the current state of knowledge regarding the management of pain, depression, and fatigue in individuals with cancer and to identify directions for future research. Specifically, the conference examined how to identify individuals who are at risk for cancer-related pain, depression, and/or fatigue; what treatments work best to address these symptoms when they occur; and what is the best way to deliver interventions across the continuum of care. STATE-OF-THE-SCIENCE PROCESS: A non-advocate, non-Federal, 14-member panel of experts representing the fields of oncology, radiology, psychology, nursing, public health, social work, and epidemiology prepared the statement. In addition, 24 experts in medical oncology, geriatrics, pharmacology, psychology, and neurology presented data to the panel and to the conference audience during the first 1.5 days of the conference. The panel then prepared its statement, addressing the five predetermined questions and drawing on submitted literature, the speakers' presentations, and discussions held at the conference. The statement was presented to the conference audience, followed by a press conference to allow the panel to respond to questions from the media. After its release at the conference, the draft statement was made available on the Internet. The panel's final statement is available at http://consensus.nih.gov. CONCLUSIONS: The panel concluded that the available evidence supports a variety of interventions for treating cancer patients' pain, depression, and fatigue. Clinicians should routinely use brief assessment tools to ask patients about pain, depression, and fatigue and to initiate evidence-based treatments. Assessment should include discussion about common symptoms experienced by cancer patients, and these discussions should continue over the duration of the illness. Impediments to effective symptom management in cancer patients can arise from different sources and interactions among providers, patients and their families, and the health care system. Numerous factors could interfere with adequate symptom management. Among these factors are incomplete effectiveness of some treatments, a lack of sufficient knowledge regarding effective treatment strategies, patient reluctance to report symptoms to caregivers, a belief that such symptoms are simply a part of the cancer experience that must be tolerated, and inadequate coverage and reimbursement for some treatments. Additional research is needed on the definition, occurrence, the treatment of pain, depression, and fatigue, alone and in combination, in adequately funded prospective studies. The panel also concluded that the state of the science in cancer symptom management should be reassessed periodically.
The primary objective of this study was to determine the prevalence of colorectal cancer (CRC) screening among eligible patients in a large medical practice. A secondary objective was to compare CRC screening rates obtained from medical records with physician self-reported CRC screening recommendation. We conducted a retrospective record review of 214 patients ages > or = 50 years of a large multispecialty medical organization in Houston, Texas, for receipt of fecal occult blood test (FOBT), flexible sigmoidoscopy (SIG), and/or colonoscopy (COL). We estimated prevalence using two definitions: (a) FOBT in past year or SIG in past 5 years or COL in past 10 years; and (b) FOBT in past year and SIG in past 5 years or COL in past 10 years. Age, gender, race/ethnicity, family history, number of chronic conditions, and index visit were independent variables. Contingency table and logistic regression analysis were used to test for associations between outcomes and independent variables. Our study population was 48% male with a mean age of 63 years (range: 53-84 years). One-quarter of the records showed FOBT by 3-day kit (51 of 214) and 27% by digital rectal exam (57 of 214). SIG was recorded in 32% of records. Half (54%) of the records had documentation of CRC screening according to definition no. 1 and 19% according to definition no. 2. Screening rates from medical record review were lower than those derived from physician self-report. Our findings underscore the need for interventions to improve CRC screening in primary care settings.
BACKGROUND: Celecoxib was shown to regress colorectal adenomas in familial adenomatous polyposis (FAP) patients relative to placebo. To address the mechanism of polyp regression, we determined whether celecoxib can modulate cell proliferation, apoptosis, and prostaglandin E(2) (PGE(2)) levels in colorectal epithelia from FAP trial participants and whether such alterations correlate with observed reductions in polyp number. MATERIALS AND METHODS: Colorectal mucosal biopsies were obtained at baseline and on last day of celecoxib (100 or 400 mg twice daily) or placebo administration (6 months). Residual paraffin-embedded adenomas and normal mucosa from the same patients (n = 17) or normal tissue alone (n = 15) were analyzed. Immunoperoxidase staining for Ki-67 was performed and apoptotic cells were identified by their morphology. Ki-67 and apoptotic labeling indices and their ratios were calculated in superficials (s) and nonsuperficial (ns) regions of adenomas and normal mucosa, and baseline to 6-month differences were calculated. PGE(2) levels were analyzed by mass spectroscopy (normal, n = 64; adenoma, n = 56). Biomarkers were analyzed by treatment arm and correlated with previously determined mean percentage reductions in colorectal polyp number. RESULTS: In adenomas, a reduction in the superficial proliferative activity i.e., Ki-67(s) labeling index, accompanied polyp regression (r = -0.76, P = 0.006). An increase in the apoptotic ratio [i.e., superficial apoptotic index (AI(s))/nonsuperficial apoptotic index (AI(ns))] was found to correlate with reduced polyp counts in that higher apoptotic ratios correlated with better response to celecoxib (r = 0.71, P = 0.004). Furthermore, the AI(s)/Ki-67(s) ratio (r = 0.58, P = 0.026) accompanied polyp regression. In normal mucosa, a trend toward increased AI(s) (r = 0.33, P = 0.053) and polyp regression was found. PGE(2) levels did not significantly correlate with polyp regression. Changes in biomarker levels (baseline to 6 months) were correlated in adenomas and normal mucosa (AI(s), r = 0.29, P = 0.024; AI(ns), r = 0.34, P = 0.009; PGE(2), r = 0.50, P = 0.059) within individual patients. CONCLUSION: Suppression of cell proliferation and an increased apoptotic ratio, as well as the ratio of apoptosis to cell proliferation, accompany polyp regression in a chemoprevention trial in FAP patients. These findings suggest potential mechanisms for the efficacy of celecoxib and warrant further study of these biomarkers as intermediate endpoints in FAP patients.
In vitro translation is a widely used tool for both analytical and preparative purposes. For analytical purposes, small amounts of proteins are synthesized and visualized by detection of labeled amino acids incorporated during translation. The original strategy of incorporating radioactively labeled amino acids, such as [35S]methionine or [14C]leucine, has been superseded by the addition of antigenic tags or the incorporation of biotin-labeled or BODIPY-FL-labeled amino acids. Such nonradioactive tags are easier to visualize after translation and do not pose a radiation hazard. Among the nonradioactive tags, BODIPY-FL-lysine offers the advantage that proteins that have incorporated this amino acid can be directly visualized after gel electrophoresis. We show here that multiple fluorophores introduced into proteins can considerably extend their usefulness, particularly for the comparison of in vitro-translated proteins from related sources. This technology can be applied in various situations, including the simplified detection of rare truncating mutations in clinical samples from cancer patients.
BACKGROUND: Despite advances in early detection and effective treatment, cancer remains one of the most feared diseases. Among the most common side effects of cancer and treatments for cancer are pain, depression, and fatigue. Although research is producing increasingly hopeful insights into the causes and cures for cancer, efforts to manage the side effects of the disease and its treatments have not kept pace. The challenge that faces us is how to increase awareness of the importance of recognizing and actively addressing cancer-related distress. The National Institutes of Health (NIH) convened a State-of-the-Science Conference on Symptom Management in Cancer: Pain, Depression, and Fatigue to examine the current state of knowledge regarding the management of pain, depression, and fatigue in individuals with cancer and to identify directions for future research. Specifically, the conference examined how to identify individuals who are at risk for cancer-related pain, depression, and/or fatigue; what treatments work best to address these symptoms when they occur; and what is the best way to deliver interventions across the continuum of care. State-of-the-Science Process: A non-advocate, non-Federal, 14-member panel of experts representing the fields of oncology, radiology, psychology, nursing, public health, social work, and epidemiology prepared the statement. In addition, 24 experts in medical oncology, geriatrics, pharmacology, psychology, and neurology presented data to the panel and to the conference audience during the first 1.5 days of the conference. The panel then prepared its statement, addressing the five predetermined questions and drawing on submitted literature, the speakers' presentations, and discussions held at the conference. The statement was presented to the conference audience, followed by a press conference to allow the panel to respond to questions from the media. After its release at the conference, the draft statement was made available on the Internet. The panel's final statement is available at http://consensus.nih.gov. CONCLUSIONS: The panel concluded that the available evidence supports a variety of interventions for treating cancer patients' pain, depression, and fatigue. Clinicians should routinely use brief assessment tools to ask patients about pain, depression, and fatigue and to initiate evidence-based treatments. Assessment should include discussion about common symptoms experienced by cancer patients, and these discussions should continue over the duration of the illness. Impediments to effective symptom management in cancer patients can arise from different sources and interactions among providers, patients and their families, and the health care system. Numerous factors could interfere with adequate symptom management. Among these factors are incomplete effectiveness of some treatments, a lack of sufficient knowledge regarding effective treatment strategies, patient reluctance to report symptoms to caregivers, a belief that such symptoms are simply a part of the cancer experience that must be tolerated, and inadequate coverage and reimbursement for some treatments. Additional research is needed on the definition, occurrence, the treatment of pain, depression, and fatigue, alone and in combination, in adequately funded prospective studies. The panel also concluded that the state of the science in cancer symptom management should be reassessed periodically.
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BACKGROUND: The purpose of the current study was to provide health professionals, professional organizations, policy makers, and the general public with a practical blueprint for increasing the practice of screening for colorectal carcinoma (CRC) and adenomatous polyps over the next decade. The National Colorectal Cancer Roundtable (NCCRT) was founded in 1997 by the American Cancer Society and the Centers for Disease Control and Prevention to provide strategic leadership, advocacy, long-range planning, and coordination of interventions targeted at reducing the disease burden of CRC through education, early detection, and prevention. The NCCRT and its three workgroups include CRC survivors; recognized experts in primary care, gastroenterology, radiology, colorectal surgery, nursing, public policy, epidemiology, and behavioral science; patient advocates; and representatives of health plans and insurers, government, and other organizations. METHODS: The NCCRT performed a literature review of published and unpublished data related to CRC screening guidelines, compliance, and barriers to adherence, as well as test effectiveness and cost-effectiveness. Members of the three NCCRT workgroups developed summary reports regarding professional education, public education and awareness, and health policy. A drafting committee developed the final strategic plan from workgroup reports, which was reviewed by the entire NCCRT membership, amended, and subsequently approved in final form. RESULTS AND CONCLUSIONS: Although the rationale for population-wide CRC screening is well established, the majority of adults in the U.S. are not currently being screened for CRC. Thus, the nation foregoes an opportunity to reduce CRC-related mortality by an estimated >or= 50%. To increase CRC screening rates, the issues of patient and physician barriers to screening, lack of universal coverage, lack of incentives to motivate adherence, and expanded infrastructure must be addressed.
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Colorectal cancer is a significant contributor to morbidity and mortality in the United States. Studies published in the early 1990s, showing that screening for colorectal cancer can reduce colorectal cancer-related mortality, led many organizations to recommend screening in asymptomatic, average-risk adults older than 50 years. Since then, however, national screening rates remain low. Several important studies published over the past four years have refined our understanding of existing screening tools and explored novel means of screening and prevention. The most important new developments, which are reviewed in this article, include the following: Additional trial results support the effectiveness of fecal occult blood testing in reducing the incidence of, and mortality from, colorectal cancer. New studies document the sensitivity of fecal occult blood testing, sigmoidoscopy, and double-contrast barium enema compared with colonoscopy. Cost-effectiveness models show that screening by any of several methods is cost-effective compared to no screening. Randomized trials show that calcium is effective but fiber is not effective in preventing reoccurrence of adenomatous polyps. Preliminary data suggest that nonsteroidal anti-inflammatory drugs may prevent adenomatous polyps and that DNA stool tests and virtual colonoscopy may show promise as screening tools. This new information provides further support for efforts to increase the use of colorectal cancer screening and prevention services in adults older than 50 years.
Detection of mutations in faecal DNA represents a promising, non-invasive approach for detecting colorectal cancers in average-risk populations. One of the first practical applications of this technology involves the examination of microsatellite markers in sporadic cancers with mismatch-repair deficiencies. Since such cancers nearly always occur in the proximal colon, this test might be useful as an adjunct to sigmoidoscopy, which detects only distal colorectal lesions. We report here the first in-depth analysis of faecal DNA from patients with proximal cancers to determine the feasibility, sensitivity, and specificity of this approach. Using a sensitive method for microsatellite mutation detection, we found that 18 of 46 cancers had microsatellite alterations and that identical mutations could be identified in the faecal DNA of 17 of these 18 cases.
BACKGROUND: Noninvasive methods for detecting colorectal tumors have the potential to reduce morbidity and mortality from this disease. The mutations in the adenomatous polyposis coli (APC) gene that initiate colorectal tumors theoretically provide an optimal marker for detecting colorectal tumors. The purpose of our study was to determine the feasibility of detecting APC mutations in fecal DNA with the use of newly developed methods. METHODS: We purified DNA from routinely collected stool samples and screened for APC mutations with the use of a novel approach called digital protein truncation. Many different mutations could potentially be identified in a sensitive and specific manner with this technique. RESULTS: Stool samples from 28 patients with nonmetastatic colorectal cancers, 18 patients with adenomas that were at least 1 cm in diameter, and 28 control patients without neoplastic disease were studied. APC mutations were identified in 26 of the 46 patients with neoplasia (57 percent; 95 percent confidence interval, 41 to 71 percent) and in none of the 28 control patients (0 percent; 95 percent confidence interval, 0 to 12 percent; P<0.001). In the patients with positive tests, mutant APC genes made up 0.4 to 14.1 percent of all APC genes in the stool. CONCLUSIONS: APC mutations can be detected in fecal DNA from patients with relatively early colorectal tumors. This feasibility study suggests a new approach for the early detection of colorectal neoplasms.
Colorectal cancer is the second leading cause of cancer death among men and women in the United States, and its incidence is increasing in other developed countries throughout the world. Efficacious and cost-effectiveness screening measures exist for colorectal cancer, but successful implementation at a community level remains challenging. This article is a summary of recently published information on cost-effectiveness of colorectal screening, attempts to enhance acceptance and compliance by physicians and the public, and legislative efforts to ensure access to screening.
BACKGROUND: Pancreatic cancer is predominantly a disorder of the elderly population in the United States. In Egypt, the disease has traditionally been considered rare, and there has not been a previous publication on its population-based incidence or age distribution. METHODS: We reviewed the records of 728 pancreatic cancer patients seen at the Gastrointestinal Surgery Center of Mansoura University in the East Nile Delta region of Egypt between 1995 and 2000. We computed population-based, age-specific, and age-adjusted incidence rates in this population and compared them with US incidence rates from the Epidemiology Surveillance and End Results (SEER) Program. We also analyzed clinical characteristics of the patients, as well as their surgical and medical management. RESULTS: Approximately one-fourth of all patients were under age 50. The mean ages of patients who had undergone Whipple's resection, other surgical procedures, and no surgical procedure were 52.9 +/- 11.6, 54.11 +/- 10.5, and 55.1 +/- 14.1 yr, with no statistically significant differences. Age-adjusted incidence rates were higher in Egyptian patients than in US patients under age 65 (7.1/100,000 vs 3.3/100,000) but were much higher in US patients than in Egyptian patients over age 65 (6.6/100,000 vs 59.1/100,000). Clinical management did not differ between patients under and over age 50. CONCLUSION: The population in the East Nile Delta region of Egypt exhibits an unusually high rate of young-onset pancreatic cancer. Further studies to investigate the epidemiology of pancreatic cancer in this population may provide clues to its etiology.
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