Pericholangitis and sclerosing cholangitis are risk factors for dysplasia and cancer in ulcerative colitis

Known risk factors for the development of dysplasia and cancer in ulcerative colitis (UC) patients are: 1) increased extent and duration of disease and 2) increased age at symptom onset. This case-control study was performed to determine whether cholestatic liver disease is associated with neoplastic transformation. Twenty-nine UC patients with extensive disease of long duration and dysplasia or cancer detected in a cancer surveillance program were pair-matched to UC patients without neoplasia from a large inflammatory bowel disease registry matched on extent of disease, sex, and calendar year of disease onset. Of the 29 cases, 10 were found to have cholestatic liver disease; nine with pericholangitis and one with primary sclerosing cholangitis (PSC). Two controls had PSC. Cholestatic liver disease was a significant risk factor for the development of dysplasia or cancer (odds ratio 9.00, 95% confidence interval 1.14-71.0). Increased age at symptom onset also was found to be a significant risk factor for neoplasia (odds ratio 1.04 for each additional year, 95% confidence interval 1.00-1.08) that did not exhibit confounding or interacting effects with cholestatic liver disease. The degree of neoplasia (low-grade dysplasia, high-grade dysplasia, or cancer) did not appeared to affect the results. Therefore, cholestatic liver disease, either pericholangitis or PSC, was significantly associated with the development of dysplasia or cancer in UC patients and should be considered an important risk factor for neoplastic transformation.     

Differential effects of insulin-like growth factor-I and follicle-stimulating hormone on proliferation and differentiation of bovine cumulus cells and granulosa cells

BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) has been suggested as a risk factor for the development of colorectal cancer in ulcerative colitis (UC); however, previous studies of this association have been limited by small numbers of patients with PSC or have been performed retrospectively. This study prospectively evaluates the risk and natural history of colonic tumorigenesis in patients with PSC and UC and compares it with patients with UC without PSC. METHODS: Twenty patients with PSC and UC and 25 control patients with UC were followed prospectively by colonoscopic surveillance using extensive mucosal biopsy sampling. All control patients with UC had disease extending beyond the sigmoid colon of > or = 8 years' duration; patients with PSC and UC were studied regardless of disease duration. RESULTS: Forty-five percent (9 of 20) of the patients with PSC and UC had dysplasia compared with 16% (4 of 25) of the control patients with UC (P < or = 0.002). Prior liver transplantation did not affect the risk of colonic dysplasia. The time course for progression to dysplasia was similar between the patients with PSC and UC and the patients with UC; however, the patients with PSC and UC were five times more likely to develop dysplasia. CONCLUSIONS: Patients with PSC and UC represent a subset of patients with UC who are at markedly increased risk for colonic neoplasia and who need close colonoscopic surveillance with extensive biopsy sampling.     

Hormone replacement therapy and endometrial cancer risk: a meta-analysis

OBJECTIVE: To assess the association of unopposed estrogen or estrogen plus progestin and the risk of developing endometrial cancer or dying of that disease. DATA SOURCES: A literature search of English-language studies was performed using MEDLINE, a review of bibliographies, and consultations with experts. METHODS OF STUDY SELECTION: We identified 30 studies with adequate controls and risk estimates. DATA EXTRACTION AND SYNTHESIS: Risk estimates were extracted by two authors and summarized using meta-analytic methods. The summary relative risk (RR) was 2.3 for estrogen users compared to nonusers (95% confidence interval [CI] 2.1-2.5), with a much higher RR associated with prolonged duration of use (RR 9.5 for 10 or more years). The summary RR of endometrial cancer remained elevated 5 or more years after discontinuation of unopposed estrogen therapy (RR 2.3). Interrupting estrogen for 5-7 days per month was not associated with lower risk than daily use. Users of unopposed conjugated estrogen had a greater increase in RR of developing endometrial cancer than users of synthetic estrogens. The risk for endometrial cancer death was elevated among unopposed estrogen users (RR 2.7, 95% CI 0.9-8.0). Among estrogen plus progestin users, cohort studies showed a decreased risk of endometrial cancer (RR 0.4), whereas case-control studies showed a small increase (RR 1.8). CONCLUSIONS: Endometrial cancer risk increases substantially with long duration of unopposed estrogen use, and this increased risk persists for several years after discontinuation of estrogen. Although not statistically significant, the risk of death from endometrial cancer among unopposed estrogen users is increased, similar to the increased risk of developing the disease. Data regarding risk for endometrial cancer among estrogen plus progestin users are limited and conflicting.     

Endoscopic screening for dysplasia and mucosal aneuploidy in adolescents and young adults with childhood onset colitis

OBJECTIVES: In adults, the premalignant nature of ulcerative colitis (UC) has long been accepted. Currently there is increasing concern that Crohn's disease (CD) may be equally premalignant. As a consequence, most adults with long-standing UC and many with chronic CD are enrolled in ongoing endoscopic cancer surveillance programs. In contrast, the risk of colonic cancer in adolescents and young adults with either form of colitis is less well recognized, and the need for dysplasia and cancer screening in this population has not been systematically evaluated. We therefore report the prospective results of colonoscopic cancer screening in such a young population. METHODS: Thirty-five adolescents and young adults with long-standing colitis (18 UC, 17 CD; 21 +/- 3 yr old, 11 +/- 3 yr colitis duration) underwent colonoscopic cancer screening. All had multiple biopsies for flow cytometry and light microscopy. RESULTS: Seven subjects had aneuploidy (3/18 UC, 4/17 CD). Of these seven, only two had dysplasia [one high grade (UC), one low grade (CD)]. One additional subject had indefinite dysplasia with normal flow cytometry. The remaining 27 subjects had both normal flow cytometry and light microscopy. Five of the seven aneuploid subjects underwent surgery within 1 yr of screening. Four, including both subjects with dysplasia, had no evidence of colon cancer at surgery. However, a 24-yr-old female with a 14-yr history of UC and no evidence of dysplasia or cancer at screening had a Dukes C adenocarcinoma. CONCLUSIONS: Adolescents and young adults with childhood onset UC or CD are at risk for aneuploidy, dysplasia, and colon cancer. Aneuploidy can be evident 10 yr after the onset of colitis and in patients as young as 16 yr of age. Therefore, the risk for colon cancer in patients with childhood onset colitis must be based on the duration of the illness, not on their chronological age. Incorporation of flow cytometry into an endoscopic screening protocol appears to enhance the ability to identify individuals at highest risk for colon cancer.     

Association of malignant brain tumors and cancers of other sites

PURPOSE: We conducted an exploratory study of brain tumors that occurred as a second primary malignancy to identify potential risk factors for brain tumors. METHODS: Using data from the Surveillance, Epidemiology, and End Results (SEER) Program, we calculated the sex-specific standardized incidence ratio (SIR), adjusted to age and time period, as an estimate of the relative risk (RR) of developing a second primary brain tumor following other cancers. RESULTS: We found an elevated RR of brain tumors after bladder cancer in both men (RR, 1.7; 95% confidence interval [CI], 1.2 to 2.3) and women (RR, 1.7; 95% CI, 0.8 to 3.2); this effect was present for both astrocytoma and glioblastoma multiforme. Elevated RRs of brain tumors were also found after sarcoma (RR, 4.4; 95% CI, 1.8 to 9.0) and leukemia (RR, 2.9; 95% CI, 1.6 to 4.8) in men, and after colorectal cancer (RR, 1.8; 95% CI, 1.3 to 2.4) and endometrial cancer (RR, 1.4; 95% CI, 1.0 to 1.9) in women. The highest RR observed in this study was for CNS lymphoma following any first primary malignancy in men (RR, 7.9; 95% CI, 5.5 to 11.0). CONCLUSION: The associations of brain tumors with bladder, colorectal, and endometrial cancers in women, and an increased occurrence of CNS lymphoma as a second malignancy in men, are new findings that have not been described previously.     

Relation between the incidence of invasive cervical cancer and the screening interval: is a five year interval too long?

OBJECTIVE: To examine the incidence of invasive cervical cancer per 100,000 women years at risk and relative risk according to screening history among eligible women aged 25-69 in Southampton and South West Hampshire during the three years after completion of the first round of comprehensive screening. RESULTS: There was a significantly higher incidence of invasive cervical cancer in women who had not been screened during the preceding 0.5-5.5 years than in those who had been screened (relative risk (RR) 2.6; 95% confidence interval (CI) 1.6 to 4.3). Among the latter group of women (with interval cancers) there was a significantly higher incidence in those with a long interval of 3.5-5.5 years since their most recent smear than in those with a short interval of 0.5-3.5 years (RR 2.2; 95% CI 1.3 to 3.8). Among women with non-interval cancers, there was a significantly higher incidence among those who had no cytology record than among those who had been screened but were overdue for a smear (RR 3.0; 95% CI 1.2 to 7.3). When screen detected cancers were excluded from the figures the relative risks for all the comparative groups described above were greater, though the 95% confidence limits were wider because the numbers were smaller. The most pronounced difference in incidence was between symptomatic cancers in women with a short screening interval (5.8 per 100,000 women years at risk) and in women with no cytology record (71.3 per 100,000 years at risk). Most cancers were interval cancers (76%) because of the high screening coverage: 89.2% of eligible women aged 25-69 had been screened during the preceding 0.5-5.5 years. The overall incidence per 100000 women years at risk approached that of interval cancers, and was nearer to that observed in the short than the long interval because 74.7% of women had been screened within 3.5 years. CONCLUSION: The results confirm the effectiveness of screening but suggest that a five year screening interval may be too long, at least during the early rounds of screening.     

Benefits of colonoscopic surveillance and prophylactic colectomy in patients with hereditary nonpolyposis colorectal cancer mutations

BACKGROUND: Predisposition genetic testing is now possible for many hereditary cancer syndromes, including hereditary nonpolyposis colorectal cancer. The optimal management of the elevated risk for cancer in carriers of mutations for hereditary nonpolyposis colorectal cancer is unclear. OBJECTIVE: To assess the life expectancy and quality-adjusted life expectancy benefits derived from endoscopic surveillance and prophylactic colectomy for persons who carry a mutation associated with hereditary nonpolyposis colorectal cancer. DESIGN: Decision analysis model. Lifetime risk for colorectal cancer, efficacy of surveillance and colectomy, stage-specific colorectal cancer mortality, and quality of life were included in the model. SETTING: Decision about a cancer prevention strategy at the time of a positive result on genetic testing. PATIENTS: Carriers of a mutation for hereditary nonpolyposis colorectal cancer who were 25 years of age. INTERVENTIONS: Immediate prophylactic colectomy; delayed colectomy on the basis of age, adenoma, or diagnosis of colorectal cancer; and endoscopic surveillance. Prophylactic surgical options were proctocolectomy with ileoanal anastomosis and subtotal colectomy with ileorectal anastomosis. MEASUREMENTS: Life expectancy and quality-adjusted life expectancy. RESULTS: All risk-reduction strategies led to large gains in life expectancy for carriers of a mutation for hereditary nonpolyposis colorectal cancer, with benefits ranging from 13.5 years for surveillance to 15.6 years for prophylactic proctocolectomy at 25 years of age compared with no intervention. The benefits of colectomy compared with surveillance decreased with increasing age and were minimal if colectomy was performed at the time of colorectal cancer diagnosis. When health-related quality of life was considered, surveillance led to the greatest quality-adjusted life expectancy benefit (3.1 years compared with proctocolectomy and 0.3 years compared with subtotal colectomy). CONCLUSIONS: Colonoscopic surveillance is an effective method of reducing risk for cancer in carriers of a mutation for hereditary nonpolyposis colorectal cancer. The individual patient's choice between prophylactic surgery and surveillance is a complex decision in which personal preferences weigh heavily.     

A prospective study of methylenetetrahydrofolate reductase and methionine synthase gene polymorphisms, and risk of colorectal adenoma

We examined the relationship between a functional polymorphism (667C-->T, ala-->val) of the methylenetetrahydrofolate reductase gene (MTHFR) and the risk of colorectal adenomas in the prospective Nurses' Health Study. Among 257 incident polyp cases and 713 controls, the MTHFR val/val polymorphism [relative risk (RR) = 1.35, 95% confidence interval (CI) 0.84-2.17] was not significantly associated with risk of adenomas. This lack of association was observed for both small (RR = 1.36, 95% CI 0.76-2.45) and large (RR = 1.32, 95% CI 0.66-2.66) adenomas. Furthermore, there was no significant interaction between this polymorphism and consumption of either folate, methionine or alcohol. We also examined the relationship of a newly identified polymorphism (asp919gly) of the methionine synthase gene (MS) with the risk of colorectal adenomas in the same population. The MS gly/gly polymorphism was also not significantly associated with risk of colorectal adenomas (RR = 0.66, 95% CI 0.26-1.70). These results, which need to be confirmed in other studies, suggest that the MTHFR val/val polymorphism, which has been previously inversely associated with risk of colorectal cancer, plays a role only in a late stage (adenoma-->carcinoma) of colorectal tumorigenesis, and/or may protect against malignant transformation in the subset of benign adenomas, which may progress to malignancy.     

Increased cutaneous toxicity to ionizing radiation in HIV-positive patients. Military Medical Consortium for the Advancement of Retroviral Research (MMCARR)

Little is known about the etiology of esophageal and gastric cardia adenocarcinoma (EGA), a cancer with one of the fastest-rising incidences in the developed world. To explore the etiology of this cancer, we conducted a retrospective cohort analysis using data from the Surveillance, Epidemiology and End Results Program of the United States National Cancer Institute to study EGA and esophageal squamous cell carcinoma (ESC), in association with cancers of other sites. Standardized incidence ratios, adjusted for age, sex, and time period, were calculated as a measure of the relative risk (RR) of developing a second primary cancer (EGA or ESC) following a given first primary site. We found a moderately elevated risk of EGA following cancers of the lung (RR = 1.9 in men and RR = 2.0 in women) and of the head and neck (RR = 2.1 in men and RR = 6.3 in women) and a strongly elevated risk of ESC following cancers of the lung (RR = 2.8 in men and RR = 5.1 in women) and of the head and neck (RR = 9.6 in men and RR = 38.8 in women). A significantly elevated risk following breast cancer in women was observed for both EGA (RR = 2.6; 95% confidence interval, 1.8-3.7) and ESC (RR = 1.4; 95% confidence interval, 1.1-1.9). We also found a significantly elevated risk of EGA following bladder (RR = 2.0), colorectal (RR = 1.7), and prostate (RR = 1.4) cancer in men and of ESC following colorectal cancer (RR = 1.7) in women in this study. The strong association with tobacco-related malignancies in this study reinforces the role of tobacco in the etiology of esophageal cancers, which appears stronger for squamous cell carcinoma than for adenocarcinoma and stronger in women than in men. The study also suggests a possible shared etiology between esophageal adenocarcinoma and colorectal cancer in men and provides new evidence about the association of both adenocarcinoma and squamous cell carcinoma of the esophagus with breast cancer in women. Findings of this study provide clues to the etiology of EGA and ESC.     

A prospective study of family history and the risk of colorectal cancer

BACKGROUND: A family history of colorectal cancer is recognized as a risk factor for the disease. However, as a result of the retrospective design of prior studies, the strength of this association is uncertain, particularly as it is influenced by characteristics of the person at risk and the affected family members. METHODS: We conducted a prospective study of 32,085 men and 87,031 women who had not previously been examined by colonoscopy or sigmoidoscopy and who provided data on first-degree relatives with colorectal cancer, diet, and other risk factors for the disease. During the follow-up period, colorectal cancer was diagnosed in 148 men and 315 women. RESULTS: The age-adjusted relative risk of colorectal cancer for men and women with affected first-degree relatives, as compared with those without a family history of the disease, was 1.72 (95 percent confidence interval, 1.34 to 2.19). The relative risk among study participants with two or more affected first-degree relatives was 2.75 (95 percent confidence interval, 1.34 to 5.63). For participants under the age of 45 years who had one or more affected first-degree relatives, the relative risk was 5.37 (95 percent confidence interval, 1.98 to 14.6), and the risk decreased with increasing age (P for trend, < 0.001). CONCLUSIONS: A family history of colorectal cancer is associated with an increased risk of the disease, especially among younger people.     

A case-control study of HIV seroconversion in health care workers after percutaneous exposure. Centers for Disease Control and Prevention Needlestick Surveillance Group

BACKGROUND: The average risk of human immunodeficiency virus (HIV) infection after percutaneous exposure to HIV-infected blood is 0.3 percent, but the factors that influence this risk are not well understood. METHODS: We conducted a case-control study of health care workers with occupational, percutaneous exposure to HIV-infected blood. The case patients were those who became seropositive after exposure to HIV, as reported by national surveillance systems in France, Italy, the United Kingdom, and the United States. The controls were health care workers in a prospective surveillance project who were exposed to HIV but did not seroconvert. RESULTS: Logistic-regression analysis based on 33 case patients and 665 controls showed that significant risk factors for seroconversion were deep injury (odds ratio= 15; 95 percent confidence interval, 6.0 to 41), injury with a device that was visibly contaminated with the source patient's blood (odds ratio= 6.2; 95 percent confidence interval, 2.2 to 21), a procedure involving a needle placed in the source patient's artery or vein (odds ratio=4.3; 95 percent confidence interval, 1.7 to 12), and exposure to a source patient who died of the acquired immunodeficiency syndrome within two months afterward (odds ratio=5.6; 95 percent confidence interval, 2.0 to 16). The case patients were significantly less likely than the controls to have taken zidovudine after the exposure (odds ratio=0.19; 95 percent confidence interval, 0.06 to 0.52). CONCLUSIONS: The risk of HIV infection after percutaneous exposure increases with a larger volume of blood and, probably, a higher titer of HIV in the source patient's blood. Postexposure prophylaxis with zidovudine appears to be protective.     

In a resource-poor country, mutation identification has the potential to reduce the cost of family management for hereditary nonpolyposis colorectal cancer

PURPOSE: Colonoscopic surveillance of family members at risk of hereditary nonpolyposis colorectal cancer is difficult in a resource-poor country because of its expense. For family members who live in remote areas, poor communication and limited access to sophisticated medical care make surveillance even more difficult. The identification of the mutation causing the disease will simplify surveillance. Our aim was to assess the impact of mutation analysis on the management of a South African family with more than 150 members at risk for hereditary nonpolyposis colorectal cancer. METHODS: We studied a family that met the Amsterdam criteria for hereditary nonpolyposis colorectal cancer. Colorectal cancer affected 27 members in three generations (evidence from histology in 12, barium enema in 1, and family statements in 14 family members). Leukocyte DNA from family members was tested for linkage to candidate loci for colorectal cancer, and DNA from formalin-fixed cancers from six family members was studied for microsatellite instability. DNA from all available family members was then screened for mutations in the hMLH1 gene. The number of individuals at 50 percent risk was calculated by family pedigree and compared with the number who have the mutation. RESULTS: A disease-causing mutation in exon 13 of hMLH1 segregated with the disorder in members of this kindred. Test results of 100 chromosomes from population-matched controls were negative. Sixty family members between the ages of 16 and 50 years are at 50 percent risk for colon cancer by pedigree analysis, but of these, only 26 (43 percent) have the mutation. CONCLUSION: A mutation in the DNA repair gene hMLH1 was found in family members with hereditary nonpolyposis colorectal cancer and in some unaffected relatives previously at 50 percent risk, but not in unrelated subjects. The blood test for the mutation will simplify management, counseling, and surveillance and help to establish prophylactic colectomy.     

QT interval as a cardiac risk factor in a middle aged population

OBJECTIVE: To evaluate the value of QT interval as a cardiac risk factor in middle aged people. METHODS: The association between QT interval and cardiac risk factors and mortality in a middle aged Finnish population of 5598 men and 5119 women was evaluated over a 23 year follow up. To adjust the QT interval confidently for heart rate, a nomogram was constructed from the baseline electrocardiograms separately for men and women. RESULTS: Nomogram-corrected QT interval (QTNc) prolongation was associated with elevated blood pressure and signs of cardiovascular disease; QTNc shortening was associated with smoking. Over 10% prolongation of QTNc predicted death in men with heart disease: adjusted relative risk (RR) was 2.17 (95% confidence interval 0.67-7.45) for sudden death; 2.12 (1.25-3.59) for total cardiovascular mortality; and 1.92 (1.23-3.00) for all cause mortality. In healthy men the increase in RR was not significant: sudden death, 1.48 (0.67-3.25); total cardiovascular mortality, 1.25 (0.92-1.70); all cause mortality, 1.21 (0.96-1.53). However, healthy men with long QTNc in the lowest heart rate quartile exhibited an RR of 2.75 (1.00-7.40) for sudden death. Over 10% shortened QTNc predicted cardiovascular death in men with heart disease who smoked; RR 3.72 (1.45-9.54). Non-smoking men with short QTNc had low mortality risks irrespective of possible signs of cardiovascular disease. The trends in mortality risks were similar but weaker for women. CONCLUSIONS: In a middle aged population, prolonged QT interval predicts cardiac mortality in men with signs of cardiovascular disease. In women and healthy men this risk is weak and may reflect subclinical heart disease. A shortened QT interval predicts death in men with heart disease who smoke.     

Association between coronary heart disease and cancers of the breast, prostate, and colon

Coronary heart disease (CHD) and cancers of the breast, prostate, and colon are more common in industrialized countries than in the developing world, and to some degree, these conditions appear to share risk factors. To investigate whether there is an association between these cancers and a prior history of CHD, a hospital-based case-control study was conducted at Columbia-Presbyterian Medical Center in New York. The study was based on 252 breast cancer cases, 256 colorectal cancer cases, and 322 benign surgical controls, all of whom underwent biopsy or surgery between January 1989 and December 1992, and on 319 prostate cancer cases and 189 benign prostatic hypertrophy controls diagnosed between January 1984 and December 1986 (prior to widespread use of prostate-specific antigen screening). Medical records were reviewed on each, focusing on the preoperative anesthesia and surgical clearances. No association was found between a history of CHD and breast or colorectal cancer, but an elevated risk was found for prostate cancer (odds ratio, 2.00; 95% confidence interval, 1.18-3.39), using unconditional logistic regression with adjustment for appropriate confounders. No association was found between cigarette smoking and any of the three cancers. Aspirin use was protective for colorectal cancer (odds ratio, 0.35; 95% confidence interval, 0.17-0.73) but had no association with breast or prostate cancer. The study suggests that individuals with CHD are at elevated risk for prostate cancer but not breast or colorectal cancer. Etiological risk factors associated with CHD should be investigated with regard to prostate cancer. Patients with CHD may represent a high-risk group for prostate cancer and potential future targets for prostate cancer screening interventions.     

Nonsustained ventricular tachycardia in severe heart failure. Independent marker of increased mortality due to sudden death. GESICA-GEMA Investigators

BACKGROUND: The goal of the study was to determine the prognostic value of nonsustained ventricular tachycardia (NSVT) in total mortality in severe congestive heart failure (CHF) and in death modes. NSVT is associated with an increased mortality in CHF. However, the predictive value of NSVT as a marker for sudden death or death due to progressive heart failure has not been determined. METHODS AND RESULTS: Five hundred sixteen patients from the GESICA trial (33.4% with NSVT) were initially studied with the results of 24-hour Holter and 2 years of follow-up. Within 2 years, 87 of 173 patients (50.3%) with NSVT and 106 of 343 patients (30.9%) without NSVT died. Relative risk (RR) was 1.69 (95% confidence interval [CI], 1.27 to 2.24; P < .0002), and Cox proportional hazard analysis was 1.62 (95% CI, 1.22 to 2.16; P < .001). Sudden death increased from 8.7% (30 of 343) to 23.7% (41 of 173) in patients with NSVT (RR, 2.77; 95% CI, 1.78 to 4.44; P < .001). Progressive heart failure death was also increased from 17.5% (60 of 343) to 20.8% (36 of 173) (P = .22). Quantitative analysis of 24-hour Holter (first 295 patients) demonstrated that couplets had a similar RR to that of NSVT for both total mortality (RR, 1.81; 95% CI, 1.22 to 2.66; P < .002) and sudden death (RR, 3.37; 95% CI, 1.57 to 7.25; P < .0005). Couplets and/or NSVT (ventricular repetitive beats) were even more predictive for sudden death (RR, 10.1; 95% CI, 1.91 to 52.7; P < .01). CONCLUSIONS: In patients with CHF, NSVT is an independent marker for increased overall mortality rate and sudden death. The absence of NSVT and ventricular repetitive beats in a 24-hour Holter indicates a low probability of sudden death.     

A clinical trial of antioxidant vitamins to prevent colorectal adenoma. Polyp Prevention Study Group

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 the 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, and 751 completed the four-year clinical trial. There was no evidence that either beta carotene or vitamins C and E reduced the incidence of adenomas; the relative risk for beta carotene was 1.01 (95 percent confidence interval, 0.85 to 1.20); for vitamins C and E, it was 1.08 (95 percent confidence interval, 0.91 to 1.29). Neither treatment appeared to be effective in any subgroup of patients or in the prevention of any subtype of polyp defined by size or location. CONCLUSIONS: The lack of efficacy of these vitamins argues against the use of supplemental beta carotene and vitamins C and E to prevent colorectal cancer. Although our data do not prove definitively that these antioxidants have no anticancer effect, other dietary factors may make more important contributions to the reduction in the risk of cancer associated with a diet high in vegetables and fruits.     

Race, treatment, and survival among colorectal carcinoma patients in an equal-access medical system

BACKGROUND: The aim of this study was to assess the influence of race on the treatment and survival of patients with colorectal carcinoma. METHODS: This retrospective cohort study included all white or black male veterans given a new diagnosis of colorectal carcinoma in 1989 at Veterans Affairs Medical Centers nationwide. After adjusting for patient demographics, comorbidity, distant metastases, and tumor location, the authors determined the likelihood of surgical resection, chemotherapy, radiation therapy, and death in each case. RESULTS: Of the 3176 veterans identified, 569 (17.9%) were black. Bivariate analyses and logistic regression revealed no significant differences in the proportions of patients undergoing surgical resection (70% vs. 73%, odds ratio 0.92, 95% confidence interval 0.74-1.15), chemotherapy (23% vs. 23%, odds ratio 0.99, 95% confidence interval 0.78-1.24), or radiation therapy (17% vs. 16%, odds ratio 1.10, 95% confidence interval 0.85-1.43) for black versus white patients. Five-year relative survival rates were similar for black and white patients (42% vs. 39%, respectively; P=0.16), though the adjusted mortality risk ratio was modestly increased (risk ratio 1.13, 95% confidence interval 1.01-1.28). CONCLUSIONS: Overall, race was not associated with the use of surgery, chemotherapy, or radiation therapy in the treatment of colorectal carcinoma among veterans seeking health care at Veterans Affairs Medical Centers. Although mortality from all causes was higher among black veterans with colorectal carcinoma, this finding may be attributed to underlying racial differences associated with survival. This study suggests that when there is equal access to care, there are no differences with regard to race.     

Radial scars in benign breast-biopsy specimens and the risk of breast cancer

BACKGROUND: Radial scars are benign breast lesions of uncertain clinical significance. In particular, it is not known whether these lesions alter the risk of breast cancer in women with benign breast disease. We conducted a case-control study of women who had benign breast lesions with or without radial scars. METHODS: We reviewed benign breast-biopsy specimens from 1396 women enrolled in the Nurses' Health Study, including 255 women in whom breast cancer subsequently developed and 1141 women without subsequent breast cancer (controls). The controls were matched to the women with subsequent breast cancer according to age and the year when the benign lesion was identified. The median follow-up after biopsy of the benign lesions was 12 years. RESULTS: Radial scars were identified in biopsy specimens from 99 women (7.1 percent). Most biopsy specimens with radial scars had only one radial scar (60.6 percent), and they tended to be incidental microscopical findings (median size, 4.0 mm). The women with radial scars had a risk of breast cancer that was almost twice the risk of the women without scars, regardless of the histologic type of benign breast disease (relative risk, 1.8; 95 percent confidence interval, 1.1 to 2.9). Among women who had proliferative disease without atypia as compared with women who had nonproliferative disease, the relative risk of breast cancer was 3.0 (95 percent confidence interval, 1.7 to 5.5) for those with radial scars and 1.5 (95 percent confidence interval, 1.1 to 2.1) for those without radial scars. Among women with atypical hyperplasia as compared with women with nonproliferative disease, the relative risk of breast cancer was 5.8 (95 percent confidence interval, 2.7 to 12.7) for those with radial scars and 3.8 (95 percent confidence interval, 2.4 to 5.9) for those without radial scars. CONCLUSIONS: Radial scars are an independent histologic risk factor for breast cancer.     

Thrombophilia and inflammatory bowel disease: does factor V mutation have a role?

BACKGROUND: An increased tendency for thromboembolism is a well known problem of inflammatory bowel disease (IBD). Microvascular thrombosis has also been claimed as a pathogenic factor in IBD. Recently a point mutation in the gene coding factor V (FV Leiden) has been identified in various thromboembolic diseases, but the role in IBD is unknown. OBJECTIVE: To determine the frequency of FV Leiden in IBD patients and compare with a group of controls. METHODS: Sixty-three IBD patients [43 ulcerative colitis (UC) patients and 20 Crohn's disease (CD) patients] and 36 healthy controls were included in the study. Only one of the UC patients had a history of cerebral thromboembolism. The extracted DNA from frozen blood was subjected to polymerase chain reaction for the amplification of FV gene. The amplicons were hybridized both with the mutant and wild-type probes to detect FV mutation. Readings of optical density above 0.3 were considered as positive results. According to the patterns of ELISA, heterozygosity and homozygosity for normal and mutant alleles were determined. RESULTS: Eight (18%) of UC patients were heterozygous normal and one (2%) patient had homozygous mutation. Eight (45%) of the 20 CD patients had a heterozygous pattern and one (5%) had a homozygous pattern. In the control group four (11%) subjects showed a heterozygous genotype. FV Leiden was found to be statistically more frequent in CD patients (P < 0.005) (odds ratio 6.5, 95% confidence interval 1.3-18.), but not in the UC patients as compared with controls (P> 0.05). There was no significant correlation between FV Leiden presence and disease activity, gender or disease duration for both UC and CD. CONCLUSION: The results suggest that FV Leiden is more frequent in CD patients, but not in the UC patients as compared with controls. The high rate of factor V mutation in our CD patients suggests the need for further studies to confirm a relationship between this mutation and aetiology of the disease.     

Results of the double stapling procedure in colorectal surgery

In this report we review our results with the double stapling technique (DST) in 162 patients with colorectal diseases in an attempt to identify some of the potential pitfalls of this new technique. Among these 162 patients, there were 125 patients with colorectal cancer, 25 with chronic ulcerative colitis (UC), 9 with familial adenomatous polyposis (FAP), 2 with adult Hirschsprung's disease, and 1 with sigmoid colon fistula. A total of 46 anastomoses (28 for rectal cancer, 13 for UC, 3 for FAP, and 2 for adult Hirschsprung's disease) were performed at or near the dentate line. Of these, 10 had protective diverting colostomy or ileostomy. The results showed that 6 patients with rectal cancer had anastomotic leakage (3.7%); however, 4 of the 6 patients had also received preoperative irradiation. All the leaks healed after the patients had undergone diverting colostomy, but 7 patients with rectal cancer suffered from neurogenic bladder postoperatively (4.3%). Wound infection occurred in 4 patients (2.5%), anastomotic bleeding in 3 (1.9%), and anal pain in 1 (0.6%), respectively. One patient with rectal cancer and multiple liver metastases died of disseminated intravascular coagulation (DIC). These results thus suggest that the double stapling technique provides a safe anastomosis at or near the dentate line not only for rectal cancer but also for UC, FAP, and adult Hirschsprung's disease.