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R S Sandler

Publications and source records attributed to R S Sandler.

At least 37 records · Page 2Linked to original sources
PubMed2000

Nonsteroidal anti-inflammatory drugs and cancer prevention.

Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, appear to have clinically significant anticarcinogenic effects in the gastrointestinal tract. Epidemiological data indicate that use of these drugs is inversely associated with the risk of sporadic colorectal cancer, and clinical trials among patients with familial polyposis coli show that NSAIDs can lead to the regression of large bowel adenomas. Animal studies have reported a similar efficacy of NSAIDs against experimental carcinogenesis. A consistent pattern in this research is that continued long-term use of NSAIDs is required for an anticancer effect--up to 15 or 20 years before a reduced risk of colorectal cancer appears. Epidemiological data also suggest possible protective effects in the stomach and esophagus. The mechanisms underlying any chemopreventive effect of NSAIDs are not clear. Inhibition of cyclooxygenase is one possibility, but pathways independent of cyclooxygenase and prostaglandins are also possible.

Adenoma↗
PubMed2000

Country of birth and prevalence of gallbladder disease in Mexican Americans.

OBJECTIVES: This research sought to describe the association between country of birth and gallbladder disease (GBD) in Mexican Americans, identify subgroups at especially high risk, and identify risk factors that may mediate a birthplace-GBD association. DESIGN: Cross-sectional. METHODS: Our study population included 4157 Mexican Americans aged 20-74 who participated in the 1988-94 third National Health and Nutrition Examination Survey. GBD was diagnosed by ultrasound. Information on country of birth, education, income, and selected GBD risk factors was obtained from interviews. Prevalence odds ratios (POR) for GBD in Mexico- vs. US-born Mexican Americans were estimated by unconditional logistic regression, along with 95% confidence intervals (CI). To evaluate the extent to which GBD risk factors mediated the birthplace-GBD association, PORs for country of birth were compared in models with and without additional covariates. RESULTS: Age-adjusted GBD prevalence was lower in Mexico- than in US-born Mexican-American women (POR = 0.70, 95% CI 0.50, 0.98) and men (POR = 0.63, 95% CI 0.40, 0.97). The difference was especially pronounced among subjects of lower socioeconomic status. Despite substantial differences in GBD risk factor distributions by birthplace, none could completely explain the prevalence difference. CONCLUSIONS: The observation that GBD prevalence is higher among US-born Mexican Americans is consistent with research showing poorer health in this group. Further research is needed to identify strategies for reducing morbidity from GBD in Mexican Americans.

Adult↗
PubMed2000

Serum ferritin concentration and recurrence of colorectal adenoma.

Both body iron stores and dietary iron intake have been reported to increase risk of colorectal neoplasms. We assessed whether serum ferritin concentration was associated with recurrence of colorectal adenomas among 733 individuals with baseline determinations of ferritin as part of a multicenter clinical trial of antioxidant supplements for adenoma prevention. All study participants had at least one adenoma removed within 3 months before enrollment, and 269 of them developed one or more adenomas between follow-up colonoscopies conducted 1 and 4 years after enrollment. Baseline serum ferritin concentrations were analyzed both as a log-transformed continuous variable and as a categorical variable, defined as whether iron stores were nonreplete and low (ferritin < or =30 microg/liter), nonreplete and borderline (31-70 microg/liter), replete and adequate (71-160 microg/liter), or replete and high (>160 microg/liter). Analyses were based on multiple logistic regression models, including age, sex, study center, energy, alcohol, fiber, folate, and total fat intake, number of months between colonoscopic examinations, smoking status, and aspirin use. Overall, there was no statistically significant linear association between log ferritin concentration and adenoma recurrence (P = 0.33). Risk of adenoma recurrence was modestly increased among participants with ferritin concentrations >70 microg/liter relative to those with lower ferritin (odds ratio, 1.39; 95% confidence interval, 0.96-2.02). This result seemed more pronounced among women than men. Dietary intake of iron and red meat was inversely associated with adenoma recurrence among participants with replete iron stores but not consistently associated among those with nonreplete stores. Our findings suggest that any role of iron stores and dietary iron in influencing risk of colorectal adenoma recurrence is likely complex.

Adenoma↗
PubMed2000

Rectal mucosal proliferation and risk of colorectal adenomas: results from a randomized controlled trial.

Although rectal mucosal labeling index is thought to be a useful surrogate biomarker for colorectal cancer, the ability of the index to predict future neoplasia is unclear. We obtained rectal mucosal biopsies from 333 participants of a randomized controlled chemoprevention trial of calcium supplementation to determine whether labeling index was correlated with concurrent or future colorectal neoplasms. Labeling index was measured using proliferating cell nuclear antigen immunohistochemistry. Adenomas were enumerated at the time of the biopsies (cross-sectional) and 3 years later (prospective). We used logistic regression to test for an association of adenoma occurrence with overall labeling index, the mean proliferative height, and labeling index in the upper 40% of colon crypts. In the cross-sectional analysis, we found indications that higher proliferation was associated with an increase in the prevalence of adenomas. The overall adjusted odds ratios (OR) (95% confidence interval) were 1.14 (0.90-1.45) per % crypt labeling index, OR 1.08 (0.99-1.19) for upper crypt proliferation, and OR 1.07 (1.03-1.12) for proliferative height. In contrast, individuals with higher labeling index at baseline were actually less likely to have adenomas in the prospective analyses: OR 0.80 (0.62-1.02) per % crypt labeling index, OR 0.86 (0.73-1.00) for upper crypt index, and OR 0.97 (0.93-1.01) for proliferative height. Proliferative index does not predict future colorectal neoplasia, although it may be weakly associated with the presence of current adenomas. These results have important implications for the design of future intervention studies. Although it may be attractive to include the measurement of intermediate markers in large controlled trials, until we have more confidence in their performance, we should rely on better proven and more reliable intermediates, such as adenomas.

Adenoma↗
PubMed2000

Disposable versus reusable biopsy forceps for colorectal epithelial cell proliferation in humans.

The performance of various measures of rectal mucosal proliferation has been evaluated in the literature, but the performance of the forceps used to obtain the tissue has received little attention. We used data from two large studies of proliferation at a single institution to compare reusable and disposable endoscopic forceps. Endoscopic pinch biopsies were taken 10 cm from the anal verge using either reusable or disposable, oval-cupped, sheathed forceps. The specimens were fixed, embedded, and sectioned, taking care to orient the specimens longitudinally. Five sections were placed on each slide. We determined how many slides did not contain eight scorable crypts (inadequate) and how many sections were necessary to identify eight complete crypts. There were 395 subjects who had biopsies taken with reusable forceps and 185 subjects who had biopsies taken with disposable forceps. The specimens were inadequate in 27.6% of the reusable forceps specimens versus 2.7% of the disposable forceps (P < 0.0001). The mean number of tissue sections necessary to identify eight scorable crypts for the reusable forceps was 3.82 (SD, 0.87) compared with 3.17 (SD, 0.83) for disposable forceps (P = 0.0001). The specimens taken with the disposable forceps were better, probably because the forceps were sharper. We believe that the better quality of the specimens and the sterility justify the higher cost of disposable forceps. We would urge investigators in proliferation studies to evaluate the biopsy equipment as carefully as they evaluate other aspects of their methods.

Biopsy↗
PubMed1999

Gastrointestinal symptoms in 3181 volunteers ingesting snack foods containing olestra or triglycerides. A 6-week randomized, placebo-controlled trial.

BACKGROUND: Olestra is a nonabsorbable, energy-free fat substitute. Because it is not absorbed, it may cause digestive symptoms when consumed in large amounts. OBJECTIVE: To compare the frequency and impact of gastrointestinal symptoms in adults and children who freely consume snacks containing olestra or regular snacks in the home. DESIGN: 6-week, double-blind, randomized, parallel, placebo-controlled trial. SETTING: General community. PARTICIPANTS: 3181 volunteers 2 to 89 years of age. INTERVENTION: Households received identical packages labeled as containing olestra corn or potato chips. These packages contained either olestra or regular chips (control). MEASUREMENT: Gastrointestinal symptoms and their impact on daily activities were reported in a daily record. RESULTS: At least one gastrointestinal symptom was reported by 619 of 1620 (38.2%) persons in the olestra group and 576 of 1561 (36.9%) controls (difference, 1.3 percentage points [95% CI, -3.6 to 6.2 percentage points]; P = 0.60). In general, the groups did not differ significantly in the proportion of participants who reported individual gastrointestinal symptoms; however, more controls reported nausea (8.4% compared with 5.7%; difference, -2.7 percentage points [CI, -4.9 to -0.4 percentage points]; P = 0.02). The only difference between groups for the mean numbers of days on which symptoms were reported was that participants in the olestra group had 1 more symptom-day of more frequent bowel movements than did controls (3.7 symptom-days compared with 2.8 symptom days; difference, 0.9 symptom-days [CI, 0.1 to 1.8 symptom-days]; P = 0.04). The groups did not differ in the impact of symptoms on daily activities. CONCLUSIONS: Clinically meaningful or bothersome gastrointestinal effects are not associated with unregulated consumption of olestra corn and potato chips in the home.

Abdominal Pain↗
PubMed1999

Calcium supplements for the prevention of colorectal adenomas. Calcium Polyp Prevention Study Group.

BACKGROUND AND METHODS: Laboratory, clinical, and epidemiologic evidence suggests that calcium may help prevent colorectal adenomas. We conducted a randomized, double-blind trial of the effect of supplementation with calcium carbonate on the recurrence of colorectal adenomas. We randomly assigned 930 subjects (mean age, 61 years; 72 percent men) with a recent history of colorectal adenomas to receive either calcium carbonate (3 g [1200 mg of elemental calcium] daily) or placebo, with follow-up colonoscopies one and four years after the qualifying examination. The primary end point was the proportion of subjects in whom at least one adenoma was detected after the first follow-up endoscopy but up to (and including) the second follow-up examination. Risk ratios for the recurrence of adenomas were adjusted for age, sex, lifetime number of adenomas before the study, clinical center, and length of the surveillance period. RESULTS: The subjects in the calcium group had a lower risk of recurrent adenomas. Among the 913 subjects who underwent at least one study colonoscopy, the adjusted risk ratio for any recurrence of adenoma with calcium as compared with placebo was 0.85 (95 percent confidence interval, 0.74 to 0.98; P=0.03). The main analysis was based on the 832 subjects (409 in the calcium group and 423 in the placebo group) who completed both follow-up examinations. At least one adenoma was diagnosed between the first and second follow-up endoscopies in 127 subjects in the calcium group (31 percent) and 159 subjects in the placebo group (38 percent); the adjusted risk ratio was 0.81 (95 percent confidence interval, 0.67 to 0.99; P=0.04). The adjusted ratio of the average number of adenomas in the calcium group to that in the placebo group was 0.76 (95 percent confidence interval, 0.60 to 0.96; P=0.02). The effect of calcium was independent of initial dietary fat and calcium intake. CONCLUSIONS: Calcium supplementation is associated with a significant - though moderate - reduction in the risk of recurrent colorectal adenomas.

Adenoma↗
PubMed1999

Decision-analysis of transjugular intrahepatic portosystemic shunt versus distal splenorenal shunt for portal hypertension.

Transjugular intrahepatic portosystemic shunt (TIPS) and surgical distal splenorenal shunt (DSRS) are treatments for complications of portal hypertension. TIPS is widely used because it is relatively easy to place. Because TIPS may malfunction over time, it is unclear whether TIPS is superior to DSRS in patients with Child's class A cirrhosis who enjoy a longer survival. This study compared the cost-effectiveness of TIPS to DSRS for portal hypertension in Child's class A cirrhosis. A decision analysis model was used to evaluate the number of procedures, life expectancy, and costs over the first 2 years in patients with Child's class A cirrhosis who underwent a TIPS or DSRS. Patients who received TIPS survived 1.96 years, required 1.7 procedures, and incurred $41,685 in costs. Patients who underwent a DSRS survived 1.86 years, required 1.0 procedure, and incurred $26,951 in costs. The cost-effectiveness of TIPS compared with DSRS was $147,340 per life-year saved. Adjusting the rate of TIPS dysfunction, 1-year survival, or the number of ultrasounds to detect TIPS dysfunction did not change the results. In patients with Child's class A cirrhosis, DSRS is a more cost-effective treatment than TIPS. Until the results of a randomized controlled trial comparing TIPS with DSRS are available, TIPS should be regarded as experimental and prohibitively expensive in Child's class A cirrhosis.

Decision Support Techniques↗
PubMed1999

Colorectal cancer screening.

Colorectal cancer is an important problem in the United States, with over 130,000 new cases and 55,000 deaths each year. There is now strong evidence that screening for colorectal cancer with fecal occult blood testing can decrease mortality, and additional evidence that removing benign adenomas can decrease cancer incidence. Evidence-based screening guidelines depend on colorectal cancer risk. Individuals at higher risk because of a personal or family history deserve more intensive screening than asymptomatic individuals over age 50.

Adenomatous Polyposis Coli↗
PubMed1999

Dietary intake and gallbladder disease: a review.

OBJECTIVE: Dietary intake has long been looked upon as a potentially modifiable risk factor for gallbladder disease (GBD), here defined as either having gallstones or having had surgery for gallstones. This paper reviews the epidemiological evidence for an association between dietary intake and GBD, focusing on six dietary factors that have received the most attention in studies in this area: energy intake, fatty acids, cholesterol, carbohydrates and fibre, calcium and alcohol. The objectives of this review are to evaluate the potential usefulness of altering the diet to prevent GBD and to consider future research in this area. DESIGN: We reviewed all English-language epidemiological studies on diet and cholelithiasis that were cross-sectional, cohort or case-control in design and that were indexed in the Medline database from 1966 to October 1997. RESULTS: A positive association was suggested with simple sugars and inverse associations with dietary fibre and alcohol. No convincing evidence was found for a role for energy intake or intake of fat or cholesterol. Variable means of ascertaining cases and inaccurate measurement of dietary intake may contribute to variation in results across studies. CONCLUSIONS: Some specific components of the diet that may affect GBD include simple sugars, fibre and alcohol, but whether risk for GBD can be reduced by altering intake of a specific dietary factor has not been established. Although no specific dietary recommendations can be made to reduce risk of GBD per se, a 'healthy' diet aimed at reducing risk of other diseases might be expected to reduce risk for GBD as well.

Alcoholic Beverages↗
PubMed1999

Epidemiology of constipation (EPOC) study in the United States: relation of clinical subtypes to sociodemographic features.

OBJECTIVE: Constipation is a common heterogeneous condition, possibly encompassing different clinical subtypes. Little is known about the comparative epidemiology of constipation subtypes. This study was conducted to estimate the prevalence of constipation subtypes and determine whether subtypes differ by sociodemographic factors. METHODS: Between June and September 1997, a telephone interview was conducted with individuals about their bowel habits in the preceding 3 months. Survey data on 15 constipation-related symptoms were used to identify individuals who met prespecified symptom criteria for the following mutually exclusive subgroups: functional constipation, irritable bowel syndrome (IBS), outlet obstruction or delay (outlet), both IBS and outlet (IBS-outlet), and frequent laxative users (i.e., at least every other day). A total of 10,018 eligible individuals in the United States 18 yr of age or older completed the interview. Test-retest reliability of reporting symptoms was assessed in a separate national survey. The Spearman's correlation coefficient for reporting symptoms ranged from 0.54 to 0.83; all but three symptoms had correlations above 0.68. RESULTS: The overall prevalence of constipation was 14.7%. By subtype, prevalence was 4.6% for functional, 2.1% for IBS, 4.6% for outlet, and 3.4% for IBS-outlet. An additional 1.8% of respondents reported laxative use at least every other day. Outlet was the most common subtype among women, whereas functional constipation was the most common subtype among men. The gender ratio varied by subtype, with elevated ratios for outlet (F/M = 1.65) and IBS-outlet (F/M = 2.27) subtypes. The age pattern differed among each of the four subtypes. Prevalence of functional subtype decreased with increasing age. In contrast, outlet subtype did not seem to vary by age, and IBS (both men and women) and IBS-outlet (women only) subtypes increased to age 35 yr and declined thereafter. Prevalence of functional constipation increased with increasing education. Outlet type was more common in nonwhites compared to whites. Finally, 45% of individuals with constipation reported having the condition for 5 yr or more. CONCLUSIONS: Constipation is a heterogeneous condition. Differences in epidemiological profile by age, sex ratio, and relation to other sociodemographical factors support the distinction of two and possibly more symptom-based subtypes.

Adolescent↗
PubMed1999

Calcium supplements and colorectal adenomas. Polyp Prevention Study Group.

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.

Adenoma↗
PubMed1998

Folate intake, alcohol consumption, cigarette smoking, and risk of colorectal adenomas.

BACKGROUND: Recent evidence suggests that folic acid (and derivatives) could contribute to the protective effect of fruits and vegetables against the risk of large-bowel cancer. Other evidence indicates that alcohol drinking and cigarette smoking may impair the biologic actions of folate. We used data from an adenoma prevention trial to investigate the occurrence of colorectal adenomas (possible precursors of colorectal cancer) in association with folate intake, alcohol consumption, and cigarette smoking. METHODS: Patients with at least one recent large-bowel adenoma were followed with colonoscopy 1 year and 4 years after their qualifying colon examinations. Adenomas detected after the year 1 examination were used as end points. A food-frequency questionnaire was administered at study entry and at study completion; nutrient intake at study entry was used in this analysis. All statistical tests were two-sided. RESULTS: After adjustment for caloric intake, dietary folate had a significant protective association with the risk of recurrence of large-bowel adenoma (P for trend = .04). However, this inverse association was attenuated by further adjustment for intake of dietary fiber and fat. Use of folate supplements was not associated with a reduction in risk. Alcohol intake (seven or more drinks/week) was associated with increased risk (odds ratio = 2.04; 95% confidence interval = 1.28-3.26). Cigarette smoking, even smoking for long duration, was not related to adenoma recurrence. CONCLUSIONS: These data provide only modest support for previous findings suggesting beneficial effects of folate on colorectal adenoma risk. We find no evidence that cigarette smoking increases risk. These findings do suggest a substantial increase in risk with alcohol consumption.

Adenoma↗
PubMed1998

Payer status, but not race, affects the cost of liver transplantation.

Prior studies evaluating the impact of race and payer on cost of liver transplantation did not adjust for clinical factors known to increase cost. We analyzed the impact of race and payer on the cost of liver transplantation after controlling for clinical factors. We analyzed data obtained on patient and graft survival, cost, race, age, sex, payer, and United Network for Organ Sharing (UNOS) status from 153 consecutive liver transplants in 130 patients performed at University of North Carolina Hospitals from September 1991 through December 1996. Race was classified as white or nonwhite, and payer status was classified as commercial or Medicare/Medicaid. Multivariate linear regression was used to compare costs, adjusting for age, sex, race, payer, and UNOS status. For the 130 patients, 1-year patient and graft survival rates were 88% and 82%, respectively. There were no significant differences in patient and graft survival or in the unadjusted average cost of liver transplantation by race or payer. After adjusting for demographic and clinical factors, the cost of transplantation was $28,494 more for Medicare/Medicaid recipients compared with the commercial insurance recipients (P = .02). The Medicare/Medicaid group had higher intensive care unit costs compared with the commercial insurance group ($17,807 and $9,359, respectively; P = .03), and a longer length of stay (41 and 31 days, respectively; P = .04). There was no significant difference in cost between whites and nonwhites adjusting for these factors. Medicare or Medicaid patients had a higher cost of transplantation compared with those with commercial insurance. The cost of liver transplantation was similar for whites and nonwhites.

Adolescent↗
PubMed1998

Aspirin and nonsteroidal anti-inflammatory agents and risk for colorectal adenomas.

BACKGROUND & AIMS: Aspirin and nonsteroidal anti-inflammatory drugs have been reported to protect against the development of colorectal cancer. Because adenomas are precursors to most colorectal cancers, the aim of this study was to examine the relationship of these medications to the risk for colorectal adenomas in a colonoscopy-based case-control study. METHODS: Study participants were drawn from patients who underwent colonoscopy at the University of North Carolina Hospitals. Medication use was assessed by telephone using a comprehensive list of prescription and nonprescription drugs as well as questions about dietary and lifestyle factors that might be relevant for adenoma development. RESULTS: There were 210 patients with adenomas and 169 adenoma-free controls. After adjusting for potential confounders, regular users were half as likely to currently have adenomas compared with nonusers (adjusted odds ratio, 0.56; 95% confidence interval, 0.34-0.92). Regular users who stopped medication at least 1 year before colonoscopy were still protected (adjusted odds ratio, 0.59; 95% confidence interval, 0.21-1.67), although small numbers make this conclusion tentative. The protective effects of aspirin and the nonaspirin nonsteroidal anti-inflammatory drugs were similar. CONCLUSIONS: The results suggest that aspirin and nonsteroidal anti-inflammatory drugs cause early disruption of the adenoma-carcinoma sequence. The challenge for the future will be to learn more about dose, duration, and mechanism of action.

Adenoma↗