Definition and taxonomy of interval colorectal cancers: a proposal for standardising nomenclature.

OBJECTIVE: Interval colorectal cancers (interval CRCs), that is, cancers occurring after a negative screening test or examination, are an important indicator of the quality and effectiveness of CRC screening and surveillance. In order to compare incidence rates of interval CRCs across screening programmes, a standardised definition is required. Our goal was to develop an internationally applicable definition and taxonomy for reporting on interval CRCs. DESIGN: Using a modified Delphi process to achieve consensus, the Expert Working Group on interval CRC of the Colorectal Cancer Screening Committee of the World Endoscopy Organization developed a nomenclature for defining and characterising interval CRCs. RESULTS: We define an interval CRC as a "colorectal cancer diagnosed after a screening or surveillance exam in which no cancer is detected, and before the date of the next recommended exam". Guidelines and principles for describing and reporting on interval CRCs are provided, and clinical scenarios to demonstrate the practical application of the nomenclature are presented. CONCLUSIONS: The Working Group on interval CRC of the World Endoscopy Organization endorses adoption of this standardised nomenclature. A standardised nomenclature will facilitate benchmarking and comparison of interval CRC rates across programmes and regions.

Meat consumption and the risk of incident distal colon and rectal adenoma.

BACKGROUND: Most studies of meat and colorectal adenoma have investigated prevalent events from a single screening, thus limiting our understanding of the role of meat and meat-related exposures in early colorectal carcinogenesis. METHODS: Among participants in the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who underwent baseline and follow-up sigmoidoscopy (n=17,072), we identified 1008 individuals with incident distal colorectal adenoma. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations between meat and meat-related components and incident distal colorectal adenoma using multivariate logistic regression. RESULTS: We observed suggestive positive associations for red meat, processed meat, haeme iron, and nitrate/nitrite with distal colorectal adenoma. Grilled meat (OR=1.56, 95% CI=1.04-2.36), well or very well-done meat (OR=1.59, 95% CI=1.05-2.43), 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) (OR=1.75, 95% CI=1.17-2.64), benzo[a]pyrene (OR=1.53, 95% CI=1.06-2.20), and total mutagenic activity (OR=1.57, 95% CI=1.03-2.40) were positively associated with rectal adenoma. Total iron (diet and supplements) (OR=0.69, 95% CI=0.56-0.86) and iron from supplements (OR=0.65, 95% CI=0.44-0.97) were inversely associated with any distal colorectal adenoma. CONCLUSION: Our findings indicate that several meat-related components may be most relevant to early neoplasia in the rectum. In contrast, total iron and iron from supplements were inversely associated with any distal colorectal adenoma.

Obesity, weight change, and risk of adenoma recurrence: a prospective trial.

BACKGROUND AND STUDY AIMS: Obesity is a risk factor for colorectal neoplasia. Lifestyle modifications, including weight loss, have been advocated to reduce the risk. However, no prospective study has evaluated whether weight loss actually affects adenoma recurrence. The aim of this study was to examine whether weight change (loss or gain) over 4 years is associated with adenoma recurrence. PATIENTS AND METHODS: A total of 1826 patients with colorectal adenoma in the Polyp Prevention Trial had their height and weight measured at baseline. Adenoma recurrence was determined by end of trial colonoscopy 4 years after study entry when patients' weights were re-measured. Poisson regression models were used to evaluate body mass index (BMI), weight change over 4 years, and the risk of any adenoma and advanced adenoma recurrence. RESULTS: Adenoma recurrence was observed in 723 patients (39.6%), 118 (6.5%) of whom had advanced adenoma recurrence. Among those with baseline BMI < 25 kg/m² (n = 466), BMI 25-29 kg/m² (n = 868), and BMI ≥ 30 kg/m² (n = 492), the recurrence rate was 34.5%, 41.0%, and 41.9%, respectively. Obesity was associated with an increased risk of adenoma recurrence (RR = 1.19; 95%CI 1.01-1.39) and advanced adenoma recurrence (RR = 1.62; 95%CI 1.01-2.57). However, when compared with those with relatively stable weight (weight change < 5 lb) over the 4-year trial, weight gain or loss was not associated with adenoma recurrence. This was consistent, regardless of the baseline BMI. CONCLUSIONS: Weight loss or gain over 4 years does not affect adenoma recurrence. This study does not support weight loss alone as an effective intervention for reducing adenoma recurrence.

Increased blood glucose and insulin, body size, and incident colorectal cancer.

BACKGROUND: Abdominal obesity--an elevated level of visceral adipose tissue--has been linked to colorectal cancer. Furthermore, elevated levels of visceral adipose tissue have been associated with hyperinsulinemia, and insulin is a growth factor in the colon. We assessed whether waist circumference, a surrogate measure of visceral adipose tissue, and metabolic parameters associated with visceral adipose tissue were related to colorectal cancer. METHODS: In the Cardiovascular Health Study cohort, we examined the relationship of baseline measurements of body size, glucose, insulin, and lipoproteins to incident colorectal cancer. All P values are two-sided. RESULTS: Among 5849 participants, 102 incident cases of colorectal cancer were identified. Individuals in the highest quartile of fasting glucose had a nearly twofold increased risk of colorectal cancer (relative risk [RR] = 1.8; 95% confidence interval [CI] = 1.0-3.1), and the linear trend RR (LT RR = 1.2; 95% CI = 1.0-1.5) for fasting glucose level was statistically significant (P =. 02). Glucose and insulin levels 2 hours after oral glucose challenge also exhibited statistically significant associations with colorectal cancer (2-hour glucose levels: RR = 2.4 [95% CI = 1.2-4. 7]/LT RR = 1.3 [95% CI = 1.0-1.6; P =.02]; 2-hour insulin levels: RR = 2.0 [95% CI = 1.0-3.8]/LT RR = 1.2 [95% CI = 1.0-1.5; P =.04]). Analysis of fasting insulin levels suggested a threshold effect, with values above the median associated with colorectal cancer (RR = 1.6; 95% CI = 1.1-2.4; P =.02). Higher levels of waist circumference were also statistically significantly associated with colorectal cancer (RR = 1.9; 95% CI = 1.1-3.3; P =.02). CONCLUSIONS: These data provide, to our knowledge, the first direct evidence of an association between elevated visceral adipose tissue level, its associated metabolic effects, and colorectal cancer.

Patient satisfaction with screening flexible sigmoidoscopy.

BACKGROUND: Screening flexible sigmoidoscopy is an underused cancer prevention procedure. Physicians often cite patient discomfort as a reason for not requesting sigmoidoscopy, but patient experiences and attitudes toward sigmoidoscopy have not been well studied. OBJECTIVE: To measure patient satisfaction and the determinants of satisfaction with screening sigmoidoscopy. METHODS: An instrument to assess satisfaction with screening sigmoidoscopy was developed. Responses were evaluated with a factor analysis, tested for reproducibility and internal consistency, and validated against an external standard. RESULTS: A total of 1221 patients (666 men and 555 women; mean age, 61.8 years) were surveyed after sigmoidoscopy. Examinations were performed by a nurse practitioner (n = 668), internist (n = 344), or gastrointestinal specialist (n= 184). More than 93% of the participants strongly agreed or agreed they would be willing to undergo another examination, and 74.9% would strongly recommend the procedure to their friends. Regarding pain and discomfort, 76.2% strongly agreed or agreed that the examination did not cause a lot of pain, 78.1% stated that it did not cause a lot of discomfort, and 68.5% thought that it was more comfortable than they expected. Fifteen percent to 25% of the patients indicated they had a lot of pain, great discomfort, or more discomfort than expected. Women were more likely to have significant pain or discomfort than men (adjusted odds ratio, 2.9; 95% confidence interval, 1.9-4.3; P<.001). CONCLUSIONS: Approximately 70% of individuals who undergo screening sigmoidoscopy are satisfied and find the procedure more comfortable than expected, whereas only 15% to 25% find the procedure unpleasant. Physicians should not project discomfort onto patients as a reason for not requesting screening sigmoidoscopy.

Hormonal and metabolic effects of calcium channel antagonists in man.

Calcium is a component of many metabolic reactions. By blocking calcium transport across cell membranes, calcium channel antagonists can therefore theoretically affect numerous metabolic and hormonal processes. In vitro studies have often documented just such an effect. Because of the expanding use and prevalence of calcium antagonists in clinical practice, a review of their in vivo effects on hormones and metabolism is warranted. The effect on glucoregulatory hormones, calcium regulatory hormones, anterior and posterior pituitary secretion, the renin-angiotensin axis, plasma catecholamines, and plasma lipids and lipoproteins is herein reviewed. The various calcium antagonists, by virtue of their distinct chemical structures, influence metabolism in their own unique manner. Despite the widespread involvement of calcium in hormone action, however, calcium channel antagonists have little dramatic impact on hormone regulation. This is, in part, due to the drug dosage used in clinical practice and to the inherent compensatory mechanisms built into normal endocrine function. The development of agents with greater and more potent metabolic specificity, however, coupled with the ability to target drug action, holds promise for expanded therapeutic application in the future.

Quality of life of patients after intestinal transplantation.

BACKGROUND: Quality of life is an important consideration in evaluating new medical or surgical treatments. Intestinal transplantation is now available for patients with irreversible intestinal failure. We compared quality of life among patients with intestinal failure receiving home parenteral nutrition (HPN) to that among patients who underwent intestinal transplantation (ITx) at the University of Pittsburgh Medical Center. METHODS: The results of the Quality of Life Inventory, a self-administered questionnaire, were compared among 10 ITx recipients and 10 HPN patients. Change in quality of life was examined longitudinally over a 2-year period with repeat testing in four patients in each group. RESULTS: ITx recipients were evaluated at mean time of 2.7 years after transplantation and after a mean period of 5.3 years of intestinal failure. HPN patients were evaluated after a mean period of 5.1 years of intestinal failure and were similar to the transplant recipients in age, gender, race, social status, education, etiology, and duration of disease. Assessed quality of life was markedly similar between HPN-dependent patients and ITx recipients, with significant differences in only 2 of 25 domains, despite the difficult early postoperative course and complex management that accompany intestinal transplantation. In longitudinal follow-up (n=4), ITx recipients reported significant improvement in anxiety (P=0.02), sleep (P=0.03), and impulsiveness/control (P<0.001), reflecting a progressive adjustment to their posttransplant status. CONCLUSION: The quality of life in ITx recipients is similar to that in HPN-dependent patients. Quality of life among ITx recipients improves over time with decreased anxiety over physical functioning. Further research and efforts to improve quality of life in transplant recipients are needed.

Risk factors for hospitalized gastrointestinal bleeding among older persons. Cardiovascular Health Study Investigators.

OBJECTIVES: We sought to estimate the incidence of hospitalization for upper and lower gastrointestinal bleeding among older persons and to identify independent risk factors. DESIGN: Prospective cohort study. SETTING: The Cardiovascular Health Study (CHS). PARTICIPANTS: 5,888 noninstitutionalized men and women age 65 years or older in four U.S. communities enrolled in the CHS. MEASUREMENTS: Gastrointestinal bleeding events during the period 1989 through 1998 were identified using hospital discharge diagnosis codes and confirmed by medical records review. Risk-factor information was collected in a standardized fashion at study baseline and annually during follow-up. RESULTS: Among CHS participants (mean baseline age 73.3 years, 42% male), the incidence of hospitalized gastrointestinal bleeding was 6.8/1,000 person-years. In multivariate analyses, advanced age, male sex, unmarried status, cardiovascular disease, difficulty with daily activities, use of multiple medications, and use of oral anticoagulants were independent risk factors. Compared with nonsmokers, subjects who smoked more than half a pack per day had a multivariate-adjusted hazard ratio (HR) of 2.14 (95% confidence interval [CI] = 1.22-3.75) for upper gastrointestinal bleeding and a multivariate-adjusted HR of 0.21 (95% CI = 0.03-1.54) for lower gastrointestinal bleeding. Aspirin users did not have an elevated risk of upper gastrointestinal bleeding (HR = 0.76, 95% CI = 0.52-1.11), and users of other nonsteroidal anti-inflammatory drugs had a HR of 1.54 (95 % CI = 0.99-2.36). Low ankle-arm systolic blood pressure index was associated with higher risk of gastrointestinal bleeding among subjects with clinical cardiovascular disease but not among those without clinical cardiovascular disease. CONCLUSION: This study identifies risk factors for gastrointestinal bleeding, such as disability, that may be amenable to modification. The findings will help clinicians to identify older persons who are at high risk for gastrointestinal bleeding.

Is electroconvulsive therapy safe?

Electroconvulsive therapy is controversial and readily arouses the passions of both its supporters and detractors. In this article, Dr Schoen, an internist, discusses various aspects of this 50-year-old technique, including risks, contraindications, and physiologic effects.

Evidence of a healthy volunteer effect in the prostate, lung, colorectal, and ovarian cancer screening trial.

Volunteers for prevention or screening trials are generally healthier and have lower mortality than the general population. The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) is an ongoing, multicenter, randomized trial that randomized 155,000 men and women aged 55-74 years to a screening or control arm between 1993 and 2001. The authors compared demographics, mortality rates, and cancer incidence and survival rates of PLCO subjects during the early phase of the trial with those of the US population. Incidence and mortality from PLCO cancers (prostate, lung, colorectal, and ovarian) were excluded because they are the subject of the ongoing trial. Standardized mortality ratios for all-cause mortality were 46 for men, 38 for women, and 43 overall (100 = standard). Cause-specific standardized mortality ratios were 56 for cancer, 37 for cardiovascular disease, and 34 for both respiratory and digestive diseases. Standardized mortality ratios for all-cause mortality increased with time on study from 31 at year 1 to 48 at year 7. Adjusting the PLCO population to a standardized demographic distribution would increase the standardized mortality ratio only modestly to 54 for women and 55 for men. Standardized incidence ratios for all cancer were 84 in women and 73 in men, with a large range of standardized incidence ratios observed for specific cancers.

Quality in the technical performance of screening flexible sigmoidoscopy: recommendations of an international multi-society task group.

BACKGROUND: Flexible sigmoidoscopy (FS) is a complex technical procedure performed in a variety of settings, by examiners with diverse professional backgrounds, training, and experience. Potential variation in technical quality may have a profound impact on the effectiveness of FS on the early detection and prevention of colorectal cancer. AIM: We propose a set of consensus and evidence based recommendations to assist the development of continuous quality improvement programmes around the delivery of FS for colorectal cancer screening. RECOMMENDATIONS: These recommendations address the intervals between FS examinations, documentation of results, training of endoscopists, decision making around referral for colonoscopy, policies for antibiotic prophylaxis and management of anticoagulation, insertion of the FS endoscope, bowel preparation, complications, the use of non-physicians as FS endoscopists, and FS endoscope reprocessing. For each of these areas, continuous quality improvement targets are recommended, and research questions are proposed.

Families at risk for colorectal cancer: risk assessment and genetic testing.

As befits a common cancer, a family history of colorectal cancer (CRC) is reported by about 10% of individuals. The discovery of the genetic basis of hereditary nonpolyposis CRC and familial adenomatous polyposis has opened up the possibility for determining genetic predisposition to CRC in asymptomatic family members of affected cases. This article reviews the information needed for accurate risk assessment for those with a family history of CRC. Screening recommendations and the current status of genetic testing, including review of available tests such as microsatellite instability, immunohistochemistry for hMSH2 and hMLH1, testing for I1307K, and gene testing for germline mutations in hMSH2 and hMLH1 are discussed. At the current time, reliable, informative genetic testing, capable of application to broad segments of the population, is an unrealized goal. But as the methodology for testing improves and as better appreciation of the significance and meaning of a positive or negative test result ensues conditions for increased use of genetic testing could emerge.

Interrupting the adenoma-carcinoma sequence: screening for adenomas and cancer, now and in the future.

Screening for colorectal cancer is only beginning to receive the attention it deserves. As screening emerges into the mainstream and utilization increases, competing technologies will battle to assume a greater percentage of the market share of testing. In this review, the standards and principles with which screening tests are evaluated are outlined. Current modalities for screening, including fecal occult blood testing (FOBT), flexible sigmoidoscopy, colonoscopy, barium enema, and the combination of FOBT with sigmoidoscopy, are discussed and critically reviewed. New techniques and technologies for screening, including virtual colonoscopy and molecular methods of screening stool, are previewed. Increased attention on screening and the competition for supremacy among the modalities undergoing evaluation make the prospects for a continued diminution in colorectal cancer mortality promising.

Pseudo-obstruction associated with colonic ischemia: successful management with colonoscopic decompression.

Colonic pseudo-obstruction has been associated with colonic ischemia in only 7-10% of cases. When both conditions are present, most authors recommend immediate laparotomy because of the additional weakening of the bowel wall induced by the presence of ischemia and the resultant increased risk of perforation. We report on three patients with pseudo-obstruction and right-sided colonic ischemia who were successfully managed with colonoscopic decompression with tube placement. Surgery may not be required in patients with pseudo-obstruction and associated colonic ischemia.

Sigmoidoscopy use among primary care physicians.

BACKGROUND: Despite endorsement by a variety of professional societies, screening sigmoidoscopy is performed on a small minority of patients. We performed a survey of primary care physicians in Allegheny County to examine in detail their current practice and attitude toward screening sigmoidoscopy. METHODS: Physicians were surveyed by mail or telephone. Eligible respondents were required to practice in the county and perform direct patients care. RESULTS: Of 732 adult primary care physicians in Allegheny County, 400 were randomly selected for sampling and 279, or 70%, responded. Over 88% of physicians agreed completely or partly with current American Cancer Society recommendations for screening sigmoidoscopy, but only 34% (95% CI 29-39%) reported they regularly refer or schedule patients for screening. Physicians who screen were more likely to be from internal medicine or family practice (P < 0.001) and to be trained in (P < 0.001) or to personally perform (P < 0.001) sigmoidoscopy. The greater the number of barriers to screening cited by physicians, including cost, patient discomfort, equipment availability, low probability of finding a lesion, time it takes to do sigmoidoscopy, and the risk of the procedure, the lower the screening rate (P = 0.002). CONCLUSION: (a) Although primary care physicians in Allegheny County report that they support screening sigmoidoscopy, only one-third regularly refer or schedule patients, (b) physicians who are trained in or who perform sigmoidoscopy are more likely to screen patients, and (c) further education and training of primary care physicians in sigmoidoscopy will be required to increase screening rates.

Factors associated with the use of screening mammography in a primary care setting.

Despite consensus recommendations the use of screening mammography remains low. We examined physician and patient related variables associated with requests to undergo screening mammography in a primary care setting, in order to assess current barriers to screening mammography at the level of the physician-patient interaction. A sample of 261 women over the age of 50, whose primary care was provided by resident physicians in a large, urban, academic medical center were examined. Data concerning patients and physicians demographic and clinical characteristics were abstracted. The data were analyzed by Chi-square and stepwise logistic regression. Forty-five percent of the patients were offered screening mammography within the study year and 53% were offered mammography over the preceding two years. Variables significantly associated with a request for screening included a previous history of breast disease (p < .001) and the severity of the patient's overall medical condition. Patients with an overall medical condition rated as mild were more likely to be requested to undergo screening than patients rated as moderately or severely ill (p < .01). Patients with higher educational levels were also more likely to be offered screening (P = .06). First year postgraduate (PGY 1) physicians requested more mammograms than PGY 2 or PGY 3 physicians (P < .05). A multivariable model utilizing logistic regression confirmed the association of the significant variables above with screening requests. Physicians were more likely to request mammography in patients at higher risk for developing breast cancer and less likely to request it in patients who had co-morbid illness. Increasing physician understanding of the importance and benefits of mammography and further investigation of strategies to ensure physician compliance with mammography recommendations are necessary to increase utilization.

The impact of health care reform on gastroenterology fellows: are training programs preparing them for the future? American College of Gastroenterology Educational Affairs Subcommittee on Training.

OBJECTIVE: Health care reform is dramatically changing the practice and delivery of medical care. The goal of this investigation was to examine gastroenterology trainees' outlook on the impact of health care reform on training programs. METHODS: A 24-question survey was mailed in February 1996 to 780 GI fellows obtained from the comprehensive American College of Gastroenterology (ACG) database. RESULTS: A total of 362 fellows responded (46%): 85% were male, 57% Caucasian, 75% married, and 86% were university-based. Ninety-six percent of fellows believed that health care reform is adversely affecting the quality of health care and 94.1% felt that it was adversely affecting fellowship training. Eighty-eight percent expressed concern over the impact of health care reform on practice opportunities. Only 9% of fellows reported that their training program had established a specific educational program addressing health care reform, whereas 83% of fellows felt that their program should do so. CONCLUSION: Gastroenterology fellows are concerned about the impact of health care reform on the quality of care and the quality of their fellowship training. Trainees believe that programs are not providing sufficient education to help them respond to the changes in health care.

Are women with breast, endometrial, or ovarian cancer at increased risk for colorectal cancer?

OBJECTIVES: Evidence is accumulating supporting the use of screening for colorectal cancer. Patients at higher risk for colorectal cancer are more likely to benefit from screening. Women with breast, endometrial, or ovarian cancer are often classified as at high risk for subsequent colorectal cancer, and are urged to undergo screening, but the basis for this is uncertain. METHODS: We performed a meta-analysis of published data to assess the risk of colorectal cancer after these cancers. RESULTS: Based on 154,270 women and 779,251 person-yr of observation (PYO) after breast cancer, 37,266 women and 229,498 PYO after endometrial cancer, and 41,366 women and 126,688 PYO after ovarian cancer, the age-adjusted relative risk (95% CI) for colorectal cancer after breast cancer was 1.1 (1.07, 1.19), after endometrial cancer 1.4 (1.32, 1.55), and after ovarian cancer 1.6 (1.40, 1.80). CONCLUSIONS: 1) Women with a history of breast, endometrial, or ovarian cancer are at a statistically significant increased risk for subsequent colorectal cancer. 2) Women with a history of endometrial or ovarian cancer are at higher risk than are women with breast cancer, but ascertainment bias from heightened medical surveillance after the diagnosis of a gynecologic malignancy may contribute to this observed increase in risk. 3) The association between these cancers and colorectal cancer suggests common etiologic factors, either environmental or genetic, but the degree of increased risk is small.