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BACKGROUND In the National Polyp Study (NPS), colorectal cancer was prevented by colonoscopic removal of adenomatous polyps. We evaluated the long-term effect of colonoscopic polypectomy in a study on mortality from colorectal cancer. METHODS We included in this analysis all patients prospectively referred for initial colonoscopy (between 1980 and 1990) at NPS clinical centers who had polyps (adenomas and nonadenomas). The National Death Index was used to identify deaths and to determine the cause of death; follow-up time was as long as 23 years. Mortality from colorectal cancer among patients with adenomas removed was compared with the expected incidence-based mortality from colorectal cancer in the general population, as estimated from the Surveillance Epidemiology and End Results (SEER) Program, and with the observed mortality from colorectal cancer among patients with nonadenomatous polyps (internal control group). RESULTS Among 2602 patients who had adenomas removed during participation in the study, after a median of 15.8 years, 1246 patients had died from any cause and 12 had died from colorectal cancer. Given an estimated 25.4 expected deaths from colorectal cancer in the general population, the standardized incidence-based mortality ratio was 0.47 (95% confidence interval [CI], 0.26 to 0.80) with colonoscopic polypectomy, suggesting a 53% reduction in mortality. Mortality from colorectal cancer was similar among patients with adenomas and those with nonadenomatous polyps during the first 10 years after polypectomy (relative risk, 1.2; 95% CI, 0.1 to 10.6). CONCLUSIONS These findings support the hypothesis that colonoscopic removal of adenomatous polyps prevents death from colorectal cancer. (Funded by the National Cancer Institute and others.)

A range of new therapeutic agents are now available for the management of Alzheimer's disease. With limited resources available however, policy-makers and other health care professionals have to prioritise and judge competing treatments on criteria such as the magnitude of clinical effectiveness and cost-effectiveness. Policy guidance that restricts treatments to defined patient sub-groups can improve the cost-effectiveness of treatments, and can help limit rises in health care expenditures. Budget impact models that estimate the amount of additional costs and potential savings are being increasingly used by policy-makers. However, the amount of savings estimated in such models depends on the effectiveness of treatment in changing morbidity, and the association between morbidity and costs.To examine the magnitude of cost savings arising from provision of treatment to different patient sub-groups, using policy guidance decisions made by the National Institute for Health and Clinical Excellence (NICE) for cholinesterase inhibitor therapies in Alzheimer's Disease (AD) in the United Kingdom National Health Service (NHS).Cohort simulation modelling.Policy guidance decisions that restricted treatment to smaller patient sub-groups were associated with lower overall care costs, but did not reduce drug costs.Given increasing recognition by health policy-makers of the importance of affordability of new treatments, greater attention should be paid to measurement of cost impacts by sub-groups within health economic modelling.

Colon cancers diagnosed in the interval after a complete colonoscopy may occur due to limitations of colonoscopy or due to rapid tumor growth. The aim of this study was to compare the association of BRAF V600E mutation in interval versus non-interval colorectal cancers and to determine the relationship between BRAF mutation and 5-year survival.We searched our institution's cancer registry for interval cancers, defined as colon cancers that developed within 5 years of a complete colonoscopy. These were frequency matched to patients with non-interval cancers. Archived cancer specimens were tested for BRAF V600E mutation and MSI.There were 63 interval and 131 non-interval cancers. BRAF mutation was present in 28% of interval cancers compared to 19% of non-interval cancers (P = 0.18). In a multivariable logistic regression model, proximal location (OR 1.85; 95% CI 1.01-3.8) and MSI (OR 2.7; 95% 1.1-6.8) were independently associated with interval cancers while BRAF mutation was not (OR 0.93; 95% CI 0.36-2.38). BRAF mutation portended a poor 5-year survival, particularly among microsatellite stable cancers.BRAF mutation is not associated with interval cancers but is a marker of poor prognosis, particularly in microsatellite stable cancers.

To determine the effect of anticoagulants and antiplatelet medications on the positive-predictive-value of fecal occult blood test (FOBT).All patients who underwent a colonoscopy at our institution from 1995 to 2006 for a positive FOBT were identified. Medical records were searched, and patients were stratified into five groups selected a priori: low-dose aspirin, NSAIDs, warfarin, clopidogrel, or controls. The positive-predictive-value of FOBT for advanced colonic neoplasia was computed for each group.During the study period, 1,126 patients underwent colonoscopy for a positive FOBT and met entry criteria. The average age of study participants was 69 years and most were men. The positive-predictive-value of FOBT for advanced colon neoplasia was significantly higher in the control group (30.5%) when compared to those on low-dose aspirin (20.5%; p = 0.003), NSAIDs (19.7%; p = 0.003), clopidogrel (7.3%; p = 0.002), or warfarin (20%; p = 0.05). The positive-predictive-value of FOBT was significantly lower for those on clopidogrel than those on low-dose aspirin (p = 0.04) and NSAIDs (p = 0.05), but not warfarin (p = 0.08). The positive-predictive-value for FOBT was similar for those on aspirin, NSAIDs, and warfarin. There was a linear trend between the number of number of positive FOBT cards and prevalence of advanced colon neoplasia (p = 0.01).Anticoagulants and antiplatelet medications lower the positive-predictive-value of FOBT for advance colonic neoplasia and should be stopped if clinically feasible prior to stool collection.

BACKGROUND & AIMS: There has been no prospective, community-based study to track changes in adenoma detection by individual physicians over time and to determine the effectiveness of targeted educational interventions. METHODS: We prospectively collected information on 47,253 screening colonoscopies in average-risk individuals 50 years and older performed by a community-based practice in the Twin Cities of Minnesota. During a period of 3 years, 5 specific interventions were implemented; each was designed to improve adenoma detection rates. Controlling for patient-related and procedure-related factors, rates of adenoma detection and 3-year trends for individual physicians were plotted, and intraclass correlation coefficients were calculated. Generalized estimating equations were used to identify factors associated with detection of adenomas and polyps. RESULTS: At least 1 polyp and 1 adenoma were found in 36% and 22% of examinations, respectively. Adenoma detection rates by endoscopists ranged from 10%-39%. There was no significant improvement during the study period despite planned, systematic interventions. Factors associated with adenoma detection included age of the patient (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.02-1.02), male sex (OR, 1.53; 95% CI, 1.34-1.74), and adequate preparation quality (OR, 2.26; 95% CI, 1.64-3.12). CONCLUSIONS: The detection of adenomas by individual physicians during a 3-year period varied and did not appear to change between individual endoscopists, despite planned, systematic interventions. This indicates that other targeted interventions might be required to improve adenoma detection rates among experienced, community gastroenterologists.

A dramatic rise in incidence, an aging population, and expensive palliative treatments have led to an escalating burden on clinicians managing inoperable esophageal cancer with only limited evidence of effectiveness. This study compares the clinical effectiveness and cost-effectiveness of self-expanding metal stents (SEMSs) with other palliative therapies to aid clinicians in making an evidence-based treatment choice.We conducted a prospective, multicenter, randomized, controlled, clinical trial with 215 patients followed until death or study closure. The primary outcome measures were dysphagia, quality of life (QL) 6 weeks following treatment, and total cost of treatment. Secondary outcome measures included treatment-associated morbidity, mortality, survival, and cost-effectiveness. An intention-to-treat analysis was carried out.There was a significant difference in mean dysphagia grade between treatment arms 6 weeks following treatment (P=0.046), with worse swallowing reported by rigid stent-treated patients (mean dysphagia score difference=-0.49; 95% confidence interval (CI) -0.10 to -0.89, P=0.014). Global QL scores were lower at both 1 and 6 weeks following treatment for patients treated by SEMSs (mean difference QL index week 1=-0.66; 95% CI: -0.02 to -1.30, P=0.04; mean difference QL index week 6=-1.01; 95% CI -0.30 to -1.72, P=0.006). These findings were associated with higher post-procedure pain scores in the SEMS patient group (mean difference of the European Organisation for Research and Treatment of Cancer QLQ C-30 pain symptom score at week 1=11.13; 95% CI: 2.89-19.4; P=0.01). Although mean EQ-5D QL values differed between the treatments (P0.001), this difference dissipated following generation of quality-adjusted life year values. Total costs varied between treatment arms but these findings canceled out when SEMSs were compared with non-SEMS therapies (95% CI -845.15-1,332.62). These results were robust to sensitivity analysis. There were no differences in the in-hospital mortality or early complication rates, but late complications were more frequent after rigid stenting (risk ratio=2.47; 95% CI 1.88-3.04). There was a survival advantage for non-stent-treated patients (log-rank statistic=4.21, P=0.04).The treatment choice for patients with inoperable esophageal cancer should be between a SEMS or a non-stent treatment after consideration has been given to both patient and tumor characteristics and clinician and patient preferences.

BACKGROUND AND STUDY AIMS: Postpolypectomy bleeding is a rare but serious adverse event. The aim of this study was to identify factors associated with the risk of severe delayed postpolypectomy bleeding. PATIENTS AND METHODS: This was a case-control study, comparing cases who developed hematochezia and required medical evaluation 6 hours to 14 days after colonoscopic polypectomy, and control patients who underwent polypectomy without delayed bleeding, and who were selected in approximately a 3 : 1 ratio. The following risk factors were specified a priori: resuming anticoagulation (within 1 week following polypectomy), aspirin use, hypertension, and polyp diameter. RESULTS: Of the 4592 patients who underwent colonoscopy with polypectomy, 41 patients (0.9 %) developed delayed postpolypectomy bleeding (cases), and 132 patients were selected as controls. The mean age was 64.3 years for cases and 65.4 years for controls. Cases presented on average 6 days after polypectomy (range 1-14 days), and 48 % required blood transfusion (average 4.2 units, range 0-17). Two patients required surgery. Anticoagulation was resumed following polypectomy in 34 % of cases compared with 9 % of controls (OR 5.2; 95 % CI 2.2-12.5; p < 0.001). For every 1 mm increase in polyp diameter, the risk of hemorrhage increased by 9 % (OR 1.09; 95 % CI 1.0-1.2; p = 0.008). Hypertension (OR 1.1) and aspirin use (OR 1.1) did not increase the risk of postpolypectomy bleeding. In exploratory analysis, diabetes (OR 2.5) and coronary artery disease (OR 3.0) were associated with postpolypectomy hemorrhage, but the association was no longer statistically significant once adjusted for the use of anticoagulation. CONCLUSIONS: Resuming anticoagulation following polypectomy and polyp diameter were strongly associated with increased risk of severe delayed postpolypectomy bleeding.

Background & Aims: Colon cancers that develop after a complete colonoscopy may be the result of "failure of colonoscopy" or rapid tumor growth. Tumors that develop via the mismatch repair gene pathway demonstrate rapid tumor growth. The aim of this study was to determine if interval colon cancers were more likely than noninterval cancers to result from the loss of function of mismatch repair genes and hence demonstrate microsatellite instability (MSI). Methods: We searched our institution's cancer registry for interval cancers, defined as colon cancers that developed within 5 years of a complete colonoscopy. These were frequency matched in a 1:2 ratio by age and sex to patients with noninterval cancers (defined as colon cancers diagnosed on a patient's first recorded colonoscopy). Archived cancer specimens for all subjects were retrieved and tested for MSI. Results: Of the 993 colon cancers diagnosed during the study period, 51 (5.1%) were identified as an interval cancer, and 112 subjects with noninterval cancer served as a comparison group. Study subjects were almost all men. MSI was found in 30.4% of interval cancers compared with 10.3% of noninterval cancers ( P = .003). After adjusting for age, interval cancers were 3.7 times more likely to show MSI than noninterval cancers (95% confidence interval, 1.5–9.1). This association was strongest for tumors located in the distal colon (odds ratio, 17.5; P = .008). No difference in TNM stage at diagnosis, histologic type or grade, or 5-year survival was found between groups. Conclusions: Interval colon cancers were almost 4 times as likely as noninterval colon cancers to be associated with mismatch repair gene dysfunction.

Patients with resected colorectal cancer are at risk for recurrent cancer and metachronous neoplasms in the colon. This joint update of guidelines by the American Cancer Society and the US Multi-Society Task Force on Colorectal Cancer addresses only the use of endoscopy in the surveillance of these patients. Patients with endoscopically resected Stage I colorectal cancer, surgically resected Stages II and III cancers, and Stage IV cancer resected for cure (isolated hepatic or pulmonary metastasis) are candidates for endoscopic surveillance. The colorectum should be carefully cleared of synchronous neoplasia in the perioperative period. In nonobstructed colons, colonoscopy should be performed preoperatively. In obstructed colons, double-contrast barium enema or computed tomography colonography should be performed preoperatively, and colonoscopy should be performed 3 to 6 months after surgery. These steps complete the process of clearing synchronous disease. After clearing for synchronous disease, another colonoscopy should be performed in 1 year to look for metachronous lesions. This recommendation is based on reports of a high incidence of apparently metachronous second cancers in the first 2 years after resection. If the examination at 1 year is normal, then the interval before the next subsequent examination should be 3 years. If that examination is normal, then the interval before the next subsequent examination should be 5 years. Shorter intervals may be indicated by associated adenoma findings (see "Guidelines for Colonoscopy Surveillance After Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society"). Shorter intervals also are indicated if the patient's age, family history, or tumor testing indicate definite or probable hereditary nonpolyposis colorectal cancer. Patients undergoing low anterior resection of rectal cancer generally have higher rates of local cancer recurrence compared with those with colon cancer. Although effectiveness is not proven, performance of endoscopic ultrasound or flexible sigmoidoscopy at 3- to 6-month intervals for the first 2 years after resection can be considered for the purpose of detecting a surgically curable recurrence of the original rectal cancer.

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.

Patients with resected colorectal cancer are at risk for recurrent cancer and metachronous neoplasms in the colon. This joint update of guidelines by the American Cancer Society (ACS) and US Multi-Society Task Force on Colorectal Cancer addresses only the use of endoscopy in the surveillance of these patients. Patients with endoscopically resected Stage I colorectal cancer, surgically resected Stage II and III cancers, and Stage IV cancer resected for cure (isolated hepatic or pulmonary metastasis) are candidates for endoscopic surveillance. The colorectum should be carefully cleared of synchronous neoplasia in the perioperative period. In nonobstructed colons, colonoscopy should be performed preoperatively. In obstructed colons, double contrast barium enema or computed tomography colonography should be done preoperatively, and colonoscopy should be performed 3 to 6 months after surgery. These steps complete the process of clearing synchronous disease. After clearing for synchronous disease, another colonoscopy should be performed in 1 year to look for metachronous lesions. This recommendation is based on reports of a high incidence of apparently metachronous second cancers in the first 2 years after resection. If the examination at 1 year is normal, then the interval before the next subsequent examination should be 3 years. If that colonoscopy is normal, then the interval before the next subsequent examination should be 5 years. Shorter intervals may be indicated by associated adenoma findings (see Postpolypectomy Surveillance Guideline). Shorter intervals are also indicated if the patient's age, family history, or tumor testing indicate definite or probable hereditary nonpolyposis colorectal cancer. Patients undergoing low anterior resection of rectal cancer generally have higher rates of local cancer recurrence, compared with those with colon cancer. Although effectiveness is not proven, performance of endoscopic ultrasound or flexible sigmoidoscopy at 3- to 6-month intervals for the first 2 years after resection can be considered for the purpose of detecting a surgically curable recurrence of the original rectal cancer.

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.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 thickness2x 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.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.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.

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

In summary, high-quality scientific studies indicate that the use of the FOBT for colorectal cancer screening has a number of important advantages. The test is capable of detecting most early colorectal cancers and many advanced adenomas. It has been shown in randomized, controlled trials to reduce substantially colorectal cancer mortality and incidence. The FOBT is feasible, widely available, and acceptable to most individuals. It has a low up-front cost and is highly cost-effective. Combining annual FOBT with periodic flexible sigmoidoscopy seems to be an especially effective screening option. Limitations of FOBT screening include its low sensitivity for polyps, especially smaller ones. Some of the trials report a relatively low sensitivity for detecting cancers located in the distal colon. The test has a relatively low specificity, so there are many false-positive screens; and for it to be most effective, repetitive screening is necessary. Balancing these advantages and disadvantages, the evidence-based screening guidelines have concluded that FOBT screening has a major role to play in colorectal cancer control and a program of annual FOBT plus flexible sigmoidoscopy every 5 years is a preferred option for screening the asymptomatic, average-risk population for colorectal cancer. Short of doing direct colonoscopy screening for the entire at-risk population, the FOBT currently is the best available method of identifying asymptomatic, average-risk people most likely to benefit from colonoscopy.

Virtual colonoscopy is a promising new technique that combines rapid spiral CT scanning of the abdomen with advanced computer programs capable of re-creating two- and three-dimensional views of the colon and rectum. Recent studies comparing this method with conventional colonoscopy show that virtual colonoscopy already is more accurate than barium enema X-ray studies for the detection of colorectal polyps, and that it approaches the accuracy of colonoscopy for diagnosing advanced lesions. Before virtual colonoscopy can be promoted for population-based screening for colorectal cancer, a number of issues discussed in this review need to be addressed. These include questions of accuracy, availability, acceptability, and cost-effectiveness.

BackgroundAn important factor determining future health care expenditure is the relationship between ageing, health status and development of age-related disorders such as dementia.AimsTo estimate the formal care costs associated with dementia in England and Wales between 1994 and 2031.MethodEpidemiological cost model, applied to individuals aged 65 years or over with dementia, using estimates of life expectancy with dementia and dementia-free life expectancy.ResultsTotal costs per year were £0.95 billion (men) and £5.35 billion (women) using 1994 population estimates. For 2031, costs were £2.34 billion and £11.20 billion, respectively. Reduced dementia prevalence rates and improvements in mental and physical functioning resulted in lower estimates: £1.01 billon (men) and £5.77 billion (women), and £1.65 billion (men) and £7.87 billion (women), respectively.ConclusionsFuture increases in the population aged 65 years or over lead to rising formal care costs. However, the magnitude of cost changes depends on assumptions over dementia prevalence and levels of mental and physical functioning.

Fecal occult-blood testing and sigmoidoscopy have been recommended for screening for colorectal cancer, but the sensitivity of such combined testing for detecting neoplasia is uncertain. At 13 Veterans Affairs medical centers, we performed colonoscopy to determine the prevalence of neoplasia and the sensitivity of one-time screening with a fecal occult-blood test plus sigmoidoscopy.Asymptomatic subjects (age range, 50 to 75 years) provided stool specimens on cards from three consecutive days for fecal occult-blood testing, which were rehydrated for interpretation. They then underwent colonoscopy. Sigmoidoscopy was defined in this study as examination of the rectum and sigmoid colon during colonoscopy, and sensitivity was estimated by determining how many patients with advanced neoplasia had an adenoma in the rectum or sigmoid colon. Advanced colonic neoplasia was defined as an adenoma 10 mm or more in diameter, a villous adenoma, an adenoma with high-grade dysplasia, or invasive cancer. Classification of subjects according to the findings was based on the most advanced lesion.A total of 2885 subjects returned the three specimen cards for fecal occult-blood testing and underwent a complete colonoscopic examination. A total of 23.9 percent of subjects with advanced neoplasia had a positive test for fecal occult blood. As compared with subjects who had a negative test for fecal occult blood, the relative risk of advanced neoplasia in subjects who had a positive test was 3.47 (95 percent confidence interval, 2.76 to 4.35). Sigmoidoscopy identified 70.3 percent of all subjects with advanced neoplasia. Combined one-time screening with a fecal occult-blood test and sigmoidoscopy identified 75.8 percent of subjects with advanced neoplasia.One-time screening with both a fecal occult-blood test with rehydration and sigmoidoscopy fails to detect advanced colonic neoplasia in 24 percent of subjects with the condition.

Colonoscopy and polypectomy effectively reduce the incidence and mortality of colorectal cancer, but some patients present with fully developed cancers within 1-4 yr of a colonoscopy that apparently cleared the colon of neoplasia. These events may result in medical-legal action against colonoscopists, generally based on an assumption of negligent technical performance of the procedure. Alternative explanations for the development of interval cancers include variable growth rates of colorectal cancers, the inherent miss rate of the procedure even when optimal examination techniques are used, and the possibility of flat lesions that are not readily detected by standard colonoscopic techniques. This paper discusses issues relevant to reduction of medical-legal risks associated with interval cancers after clearing colonoscopy. These issues include informed consent, documentation of cecal intubation, appropriate description of preparation, documentation of examination time and technique, and attention to potential atypical neoplasms.

Background Both annual testing for fecal occult blood and biennial testing significantly reduce mortality from colorectal cancer. However, the effect of screening on the incidence of colorectal cancer remains uncertain, despite the diagnosis and removal of precancerous lesions in many persons who undergo screening. Methods We have followed the participants in the Minnesota Colon Cancer Control Study for 18 years. A total of 46,551 people, most of whom were 50 to 80 years old, were enrolled between 1975 and 1978 and randomly assigned to annual screening, biennial screening, or usual care (the control group). Those assigned to the screening groups were asked to prepare and submit two samples from each of three consecutive stools for guaiac-based testing. Those with at least one positive slide in the set of six were offered a diagnostic examination that included colonoscopy. Screening was conducted between 1976 and 1982 and again between 1986 and 1992. Study participants have been followed with respect to ne...

Background: there is a causal association between carotid sinus hypersensitivity, falls and syncope in elderly subjects. Neurological complications during carotid sinus massage have been reported in case studies and two retrospective series. Our aim was prospectively to ascertain the incidence of complications occurring after carotid sinus massage performed for diagnostic purposes in a consecutive series of patients. Methods: 1000 consecutive subjects aged 50 years or over who attended the accident and emergency department with syncope or ‘unexplained’ falls had carotid sinus massage. Carotid sinus massage was performed for 5 s on the right and then left sides both supine and upright (708 head-up tilt) with continuous heart rate and phasic blood pressure recording. Contraindications to carotid sinus massage were the presence of a carotid bruit, recent history of stroke or myocardial infarction or previous ventricular tachyarrhythmia. Results: complications occurred in nine patients immediately after cessation of carotid sinus massage. Eight had transient neurological complications possibly attributable to carotid sinus massage: visual disturbance, ‘pins and needles’ and sensation of finger numbness in two cases each, leg weakness in one and sensation of ‘being drunk’ in one. All transient complications resolved within 24 h. In one patient mild weakness of the right hand persisted. Conclusions: no subjects had cardiac complications and 1% had possible neurological symptoms, which resolved in most cases. Persistent neurological complications are uncommon, occurring in 1 : 1000 patients (0.1%) or 1 : 3805 episodes of carotid sinus massage (0.03%).

Colorectal cancer is the fourth most prevalent carcinoma in the United States and the second most common cancer killer. 48 In 1999, more than 140,000 new cases were diagnosed in the United States, and more than 56,000 people died from the disease. The average lifetime risk of developing colorectal cancer in the United States is greater than 6%. Contrary to a common belief that the disease affects mainly men, it is the only major malignancy that afflicts men and women almost equally. In 1999, the 5-year survival from this cancer was about 55%. Although the incidence is about the same in all racial groups, survival is lower in African-Americans. The incidence and mortality from colorectal cancer have been decreasing slightly since 1988; however, in 2000, it still causes great suffering, death, and expenditure of health care resources. Colorectal cancer actually is highly curable or even largely avoidable if current preventive, screening, and surveillance recommendations discussed in this article are followed.

Background and Methods The role of colonoscopy in screening for colorectal cancer is uncertain. At 13 Veterans Affairs medical centers, we performed colonoscopy to determine the prevalence and location of advanced colonic neoplasms and the risk of advanced proximal neoplasia in asymptomatic patients (age range, 50 to 75 years) with or without distal neoplasia. Advanced colonic neoplasia was defined as an adenoma that was 10 mm or more in diameter, a villous adenoma, an adenoma with high-grade dysplasia, or invasive cancer. In patients with more than one neoplastic lesion, classification was based on the most advanced lesion. Results Of 17,732 patients screened for enrollment, 3196 were enrolled; 3121 of the enrolled patients (97.7 percent) underwent complete examination of the colon. The mean age of the patients was 62.9 years, and 96.8 percent were men. Colonoscopic examination showed one or more neoplastic lesions in 37.5 percent of the patients, an adenoma with a diameter of at least 10 mm or a villous...

Background After patients have undergone colonoscopic polypectomy, it is uncertain whether colonoscopic examination or a barium enema is the better method of surveillance. Methods As part of the National Polyp Study, we offered colonoscopic examination and double-contrast barium enema for surveillance to patients with newly diagnosed adenomatous polyps. Although barium enema was performed first, the endoscopist did not know the results. Results A total of 973 patients underwent one or more colonoscopic examinations for surveillance. In the case of 580 of these patients, we performed 862 paired colonoscopic examinations and barium-enema examinations that met the requirements of the protocol. The findings on barium enema were positive in 222 (26 percent) of the paired examinations, including 94 of the 242 colonoscopic examinations in which one or more adenomas were detected (rate of detection of adenomas, 39 percent; 95 percent confidence interval, 33 to 45 percent). The proportion of examinations in which ...

Experimental and observational findings suggest that calcium intake may protect against colorectal neoplasia. To investigate this hypothesis, we conducted a randomized, double-blind trial of colorectal adenoma recurrence. Nine hundred thirty patients with a recent history of colorectal adenomas were randomly given calcium carbonate (3 gm daily; 1200 mg elemental calcium) or placebo, with follow-up colonoscopies one and four years after the qualifying examination. The main analysis focused on new adenomas found after the first follow-up endoscopy, up to (and including) the second follow-up examination. Risk ratios of at least one recurrent adenoma and ratios of the average numbers of adenomas were calculated as measures of calcium effect. There was a lower risk of recurrent adenomas in subjects assigned calcium. Eight hundred thirty-two patients had two follow-up examinations and were included in the main analysis; the adjusted risk ratio of one or more adenomas was 0.81 (95% CI 0.67 to 0.99); the adjusted ratio of the average numbers of adenomas was 0.76 (95% CI 0.60 to 0.96). Among subjects who had at least one follow-up colonoscopy, the adjusted risk ratio of one or more recurrent adenomas was 0.85 (95% CI 0.74 to 0.98). The effect of calcium seemed independent of initial dietary fat and calcium intake. No toxicity was associated with supplementation. These findings indicate that calcium supplementation has a modest protective effect against colorectal adenomas, precursors of most colorectal cancers.

Background In 1993, a randomized controlled trial in Minnesota showed, after 13 years of follow-up, that annual fecal occult blood testing was effective in reducing colorectal cancer mortality by at least 33%. Biennial screening (i.e., every 2 years) resulted in only a 6% mortality reduction. Two European trials (in England and in Denmark) subsequently showed statistically significant 15% and 18% mortality reductions with biennial screening. Herein, we provide updated results-through 18 years of follow-up--from the Minnesota trial that address the apparent inconsistent findings among the trials regarding biennial screening. Methods From 1976 through 1977, a total of 46551 study subjects, aged 50-80 years, were recruited and randomly assigned to an annual screen, a biennial screen, or a control group. A screen consisted of six guaiac-impregnated fecal occult blood tests (Hemoccult) prepared in pairs from each of three consecutive fecal samples. Participants with at least one of the six tests that were positive were invited for a diagnostic examination that included colonoscopy. All participants were followed annually to ascertain incident colorectal cancers and deaths. Results The numbers of deaths from all causes were similar among the three study groups. Cumulative 18-year colorectal cancer mortality was 33% lower in the annual group than in the control group (rate ratio, 0.67; 95% confidence interval [CI] = 0.51-0.83). The biennial group had a 21% lower colorectal cancer mortality rate than the control group (rate ratio, 0.79; 95% CI = 0.62-0.97). A marked reduction was also noted in the incidence of Dukes' stage D cancers in both screened groups in comparison with the control group. Conclusion The results from this study, together with the other two published randomized trials of fecal occult blood screening, are consistent in demonstrating a substantial, statistically significant reduction in colorectal cancer mortality from biennial screening.

The drive towards clinical effectiveness and cost‐effective care within the NHS is becoming increasingly apparent. Consequently, there is a need to change clinical practice, and a set of activities with which to implement the necessary and desirable changes is required. Resistance to accepting change at an individual and organisational level is common and it is postulated that the solution lies in adopting an eclectic approach where the range of factors affecting the implementation of change is considered. A possible framework for identifying suitable behaviour change strategies is proposed. Factors included are the context of change, the relevant theoretical and empirical literature and the implementation and maintenance of change. With practical application in mind, the framework is intended as a tool to assist health care professionals analyse the change process in a structured manner and develop potential strategies for achieving desirable behaviour changes within their own and others’ practice.

Evidence-based guidelines recommend that all asymptomatic, average-risk U.S. citizens >50 years of age be encouraged to undergo screening for colorectal cancer. Those at higher risk should be offered more intensive screening and follow-up surveillance. It is estimated that widespread adoption of these recommendations could reduce mortality from colorectal cancer by >50%. The only screening methods that have been evaluated directly are the fecal occult blood test and flexible sigmoidoscopy. Current guidelines now recommend annual screening for fecal occult blood plus flexible sigmoidoscopy every 5 years for asymptomatic, average-risk men and women >50 years of age. Indirect evidence supports the options of colonoscopy or barium enema x-ray screening for highly motivated individuals, but these methods have not yet been tested in prospective trials. In the future, gene-based screening tests may be developed, and computed tomography of the colon ("virtual colonoscopy") may prove effective and feasible.

Colorectal cancer is the second most common cancer killer of Americans. Recently developed and tested methods of screening and surveillance can effectively diagnose and treat the disease in most patients before symptoms develop when the chance of cure is high. It is also possible to prevent colorectal cancer by detecting and resecting premalignant adenomatous polyps. Evidence-based guidelines recommend that the average-risk population greater than age 50 be screened with annual faecal occult blood tests plus periodic flexible sigmoidoscopy. This approach is feasible, efficacious, affordable and cost-effective in a high-risk country such as the US. Widespread compliance with these recommendations could reduce the mortality from this malignancy by more than 50%.

Comprehensive evidence-based guidelines for screening and surveillance for colorectal cancer were published in 1997. Backed by compelling scientific data from recently completed controlled trials and case-control studies, these guidelines recommend annual fecal occult blood test screening plus periodic flexible sigmoidoscopy about every 5 years for asymptomatic, average-risk individuals over 50 years of age. Other screening studies published during the past year refine knowledge about how these screening tests detect early cancer and polyps and assess factors that influence compliance with screening recommendations. Preliminary reports suggest revolutionary new methods of screening that may become clinically feasible in the next millennium.

Clinical guidelines have been identified as key components of improving clinical effectiveness. Local development of national guidelines is advocated to ensure that recommendations are relevant to local needs and context. This paper discusses the methods used in adapting national guidelines for geriatric day hospitals for use in the Northern and Yorkshire Region, and highlights differences between guidelines developed at national and regional levels.

The Place of Fecal Occult Blood Test in Colorectal Cancer Screening in 2006: The U.S. Perspective

Recent large series of direct colonoscopy screening for colorectal cancer increase our understanding of the advantages of this approach, and have indirectly confirmed efficacy. When performed by well-trained, experienced endoscopists, colonoscopy screening is successful and safe. The prevalence of advanced neoplasia is low under the age of 50 yr but increases substantially with each decade of life thereafter at least until the age of 80 yr. Most detected cancers are at an early, curable stage. A substantial number of proximal advanced neoplasia are detected that would be missed by screening flexible sigmoidoscopy. Widespread population-based colonoscopy screening would markedly decrease the incidence and mortality of this major malignancy. Issues of compliance and capacity related to direct colonoscopy have not yet been adequately addressed.

Current practice guidelines recommend annual fecal occult blood test screening for colorectal cancer in the average-risk population over the age of 50. Efficacy of fecal occult blood test screening is supported by several controlled prospective trials and case-control studies. Implementation of this recommendation, in combination with periodic flexible sigmoidoscopy every 5 years, is feasible, affordable, highly effective, and has the potential for reducing colorectal cancer mortality by at least 50%. With over 50,000 Americans dying of this malignancy each year, we cannot afford not to do this.

Second only to lung cancer in mortality, colon cancer is amenable to cure if detected early. Because fecal occult blood testing and flexible sigmoidoscopy are effective individually but have limitations, both are now recommended for screening. However, after successful polyp removal, surveillance colonoscopy does not need to be performed as often as previously thought.

In randomized trials, fecal occult-blood testing reduces mortality from colorectal cancer. However, the duration of the benefit is unknown, as are the effects specific to age and sex.In the Minnesota Colon Cancer Control Study, 46,551 participants, 50 to 80 years of age, were randomly assigned to usual care (control) or to annual or biennial screening with fecal occult-blood testing. Screening was performed from 1976 through 1982 and from 1986 through 1992. We used the National Death Index to obtain updated information on the vital status of participants and to determine causes of death through 2008.Through 30 years of follow-up, 33,020 participants (70.9%) died. A total of 732 deaths were attributed to colorectal cancer: 200 of the 11,072 deaths (1.8%) in the annual-screening group, 237 of the 11,004 deaths (2.2%) in the biennial-screening group, and 295 of the 10,944 deaths (2.7%) in the control group. Screening reduced colorectal-cancer mortality (relative risk with annual screening, 0.68; 95% confidence interval [CI], 0.56 to 0.82; relative risk with biennial screening, 0.78; 95% CI, 0.65 to 0.93) through 30 years of follow-up. No reduction was observed in all-cause mortality (relative risk with annual screening, 1.00; 95% CI, 0.99 to 1.01; relative risk with biennial screening, 0.99; 95% CI, 0.98 to 1.01). The reduction in colorectal-cancer mortality was larger for men than for women in the biennial-screening group (P=0.04 for interaction).The effect of screening with fecal occult-blood testing on colorectal-cancer mortality persists after 30 years but does not influence all-cause mortality. The sustained reduction in colorectal-cancer mortality supports the effect of polypectomy. (Funded by the Veterans Affairs Merit Review Award Program and others.).

In December 1995, the U.S. Preventive Services Task Force (USPSTF) for the first time urged primary care clinicians to screen for colorectal cancer.1 The USPSTF is an independent expert panel charged by the U.S. Department of Health and Human Services (HSS) with developing preventive health guidelines based on an objective, in-depth review of available scientific data. During the release of the 1995 edition of their Guide to Clinical Preventive Services, Dr. Harold C. Sox, chairman of the USPSTF, emphasized that there is now strong new evidence of efficacy for both fecal occult blood test (FOBT) screening and for screening flexible sigmoidoscopy in the form of prospective controlled trials and high quality case-control studies. He further noted that although the panel's recommendations technically call for FOBT and/or flexible sigmoidoscopy, most clinicians will choose to recommend both screening tests for their average-risk, asymptomatic patients older than 50 years of age. Table 1 contains the summary recommendation of the USPSTF for screening for colorectal cancer. GASTROENTEROLOGY 1996;111:1381-1384

Background The adenoma–adenocarcinoma sequence in colorectal cancer suggests an increased risk of colorectal cancer in the families of patients with adenomatous polyps. Methods A random sample of participants in the National Polyp Study who had newly diagnosed adenomatous polyps were interviewed for information on the history of colorectal cancer in their parents and siblings. The risk of colorectal cancer in family members was analyzed according to the characteristics of the patients with adenomas and in comparison with a sample of patients' spouses, who served as controls. Results Among the patients with adenomas, 1199 provided information on whether they had a family history of colorectal cancer. After the exclusion of families for which information was incomplete and of 48 patients who had been referred for colonoscopy solely because they had a family history of colorectal cancer, there were 1031 patients with adenomas, 1865 parents, 2381 siblings, and 1411 spouse controls. The relative risk of colore...

BACKGROUND Data from studies using rodents suggest that dietary calcium inhibits bile acid-induced mucosal damage and experimental carcinogenesis in the large bowel. However, in humans, the effect of dietary calcium and calcium supplementation on proliferation and carcinogenesis in the large bowel has been unclear. PURPOSE To assess the effect of calcium supplementation on rectal mucosal proliferation in humans, we conducted a multicenter, randomized, placebo-controlled, double-blinded trial. METHODS Participants were part of a larger multicenter chemoprevention trial; all were at high risk for large-bowel neoplasia, with at least one large-bowel adenoma removed endoscopically within the 3 months before study entry but with no known polyps remaining. Subjects were randomly assigned to receive daily either 3000 mg of calcium carbonate (providing 1200 mg elemental calcium) or an identical-appearing placebo tablet. During a scheduled endoscopy 6-9 months after random assignment (approximately 1 year after the qualifying endoscopy), rectal mucosal samples were obtained from 333 patients (173 assigned to calcium and 160 assigned to placebo). Proliferating cell nuclear antigen (PCNA) labeling indices (LIs) were computed as the measure of proliferation in specimens from 146 patients receiving calcium and 129 patients receiving placebo. Bromodeoxyuridine (BrdU) labeling was used to measure proliferation in a smaller number of specimens (27 calcium-receiving and 31 placebo-receiving participants). For each scorable crypt having at least one labeled cell (or surrounded by crypts with at least one labeled cell), a crypt LI was calculated as the number of labeled cells divided by the total number of crypt cells. Crypt LIs were averaged to produce a participant's average LI. RESULTS The overall unadjusted mean PCNA LIs (+/- SE) were similar in the calcium and placebo groups (3.85% +/- 0.08% versus 3.92% +/- 0.08%, respectively, P = .30). The overall unadjusted mean BrdU LIs (+/- SE) were 3.88% +/- 0.30% in the calcium group and 3.54% +/- 0.21% in the placebo group (P = .54). PCNA labeling indices in the most luminal 40% of the crypt were small but, if anything, were higher in the calcium group. There was no patient subgroup within which calcium had an antiproliferative effect; the overall findings persisted among patients with high and low calcium intake, high and low fat intake, and high and low fiber intake. CONCLUSIONS Calcium supplementation does not decrease rectal mucosal proliferation, as measured by PCNA (and BrdU) immunohistochemistry, in patients with previous large-bowel adenomas. This study, therefore, does not provide evidence for an anticarcinogenic effect of calcium.

The ongoing evaluation of endoscopic competence is an essential element of every medical and surgical endoscopic training program. The primary goal of this evaluation is to assure the greatest benefit for patients with digestive diseases. Observational methods to assess competence plus current guideline recommendations for certification and proctoring are discussed in this article.

Background People who consume a diet high in vegetables and fruits have a lower risk of cancer of the large bowel. Antioxidant vitamins, which are present in vegetables and fruits, have been associated with a diminished risk of cancers at various anatomical sites. We conducted a randomized, controlled clinical trial to test the efficacy of beta carotene and vitamins C and E in preventing colorectal adenoma, a precursor of invasive cancer. Methods We randomly assigned 864 patients, using a two-by-two factorial design, to four treatment groups, which received placebo, beta carotene (25 mg daily), vitamin C (1 g daily) and vitamin E (400 mg daily), or beta carotene plus vitamins C and E. In order to identify new adenomas, we performed complete colonoscopic examinations in the patients one year and four years after they entered the study. The primary end points for analyses were new adenomas identified after the first of these two follow-up examinations. Results Patients adhered well to the prescribed regimen...