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Biomedical subjects

B A Lashner

Publications and source records attributed to B A Lashner.

At least 19 recordsLinked to original sources
PubMed1997

The effect of folic acid supplementation on the risk for cancer or dysplasia in ulcerative colitis.

BACKGROUND & AIMS: Two case-control studies have shown that folate may protect against neoplasia in ulcerative colitis. This historical cohort study was performed to better define this association. METHODS: The records of 98 patients with ulcerative colitis who had disease proximal to the splenic flexure for at least 8 years were reviewed. Documented folate use of at least 6 months was deemed a positive exposure. RESULTS: Of the patients, 29.6% developed neoplasia and 40.2% took folate supplements. The adjusted relative risk (RR) of neoplasia for patients taking folate was 0.72 (95% confidence interval [CI], 0.28-1.83). The dose of folate varied with the risk of neoplasia (RR, 0.54 for 1.0 mg folate; RR, 0.76 for 0.4 mg folate in a multivitamin compared with patients taking no folate). Folate use also varied with the degree of dysplasia (RR for cancer, 0.45; RR for high-grade dysplasia, 0.52; RR for low-grade dysplasia, 0.75 compared with patients with no dysplasia) (P = 0.08). CONCLUSIONS: Although not statistically significant, the RR for folate supplementation on the risk of neoplasia is < 1 and shows a dose-response effect, consistent with previous studies. Daily folate supplementation may protect against the development of neoplasia in ulcerative colitis.

Adult↗
PubMed1997

Short chain fatty acid rectal irrigation for left-sided ulcerative colitis: a randomised, placebo controlled trial.

BACKGROUND: Short chain fatty acid (SCFA) deficiency is associated with colitis in animals and humans, and the mucosal metabolism of these compounds is decreased in ulcerative colitis. AIMS: To assess the efficacy of topical SCFA treatment in ulcerative colitis. PATIENTS AND METHODS: 103 patients with distal ulcerative colitis were entered into a six week, double-blind, placebo controlled trial of rectal SCFA twice daily; patients who were unchanged on placebo were offered SCFA in an open-label extension trial. RESULTS: Of the 91 patients completing the trial, more patients in the SCFA treated than in the placebo treated group improved (33% v 20%, p = 0.14, NS). Those on SCFA also had larger, but statistically non-significant, reductions in every component of their clinical and histological activity scores. In patients with a relatively short current episode of colitis (< 6 months, n = 42), more responded to SCFA than to placebo (48% v 18%, p = 0.03). These patients also had larger, but statistically non-significant, decreases in their clinical activity index (p = 0.08 v placebo). Every patient who improved used at least five of six of the prescribed rectal SCFA irrigations, whereas only 37% who did not improve were as compliant. In the open-label extension trial, 65% improved on SCFA; these patients also had significant reductions (p < 0.02) in their clinical and histological activity scores. CONCLUSIONS: Although SCFA enemas were not of therapeutic value in this controlled trial, the results suggest efficacy in subsets of patients with distal ulcerative colitis including those with short active episodes. Prolonged contact with rectal mucosa seems to be necessary for therapeutic benefit.

Acute Disease↗
PubMed1997

Cancer biology in ulcerative colitis and potential use in endoscopic surveillance.

Because patients with longstanding ulcerative colitis are at an increased risk for developing colorectal cancer, surveillance colonoscopy and colectomy for dysplasia or asymptomatic cancer is advised as a method of reducing cancer-related mortality. Generally, the use of dysplasia as a criterion for a positive test in cancer surveillance has performed poorly. The emerging field of colon cancer genetics has identified several important tumor markers that have the potential to improve sensitivity for the detection of early neoplasia. Specifically, p53 tumor suppressor gene mutations, aneuploidy, and mucin-associated sialosyl-Tn expression appear most promising for future use in surveillance programs.

Aneuploidy↗
PubMed1997

The risk of cancer and dysplasia among ulcerative colitis patients with primary sclerosing cholangitis.

BACKGROUND: Ulcerative colitis (UC) patients with primary sclerosing cholangitis (PSC) may have an increased risk for colonic dysplasia or cancer. They also may have higher levels of carcinogenic secondary bile acids and, thus, be more likely to develop cancer in the right side of the colon, where secondary bile acid concentrations are highest. METHODS: Since 1983, 1212 UC patients have undergone total proctocolectomy with ileal pouch-anal anastomosis at the Cleveland Clinic. All 27 patients with PSC were compared with the remaining 1185 patients in a historical cohort study. RESULTS: Dysplasia detected during cancer surveillance was the indication for surgery in 16 (59.5%) PSC patients and 136 (11.5%) controls [adjusted relative risk (RR), 6.9; 95% confidence interval (CI), 3.0-16.0]. Dysplasia or cancer was found in the resected specimen in 18 (66.7%) PSC patients and 145 (12.2%) controls (RR 10.4, CI 4.1-26.1). Right-sided cancers (proximal to the splenic flexure) were found in all four PSC patients with cancer and in 20 of 49 controls with cancer (RR 2.5, CI 1.3-5.4). CONCLUSIONS: UC patients with PSC are at a significantly increased risk for dysplasia or cancer. The high proportion of right-sided cancers supports the contention that secondary bile acids are carcinogenic and increase the likelihood of cancer in the proximal colon.

Adolescent↗
PubMed1995

Worsening risk for the development of dysplasia or cancer in patients with chronic ulcerative colitis.

OBJECTIVES: Patients with ulcerative colitis (UC) are at increased risk for developing dysplasia or cancer (neoplasia) and are usually offered colonoscopic surveillance to reduce their risk of cancer-related mortality. The causes of neoplasia may be related to features of UC (the extent, severity, activity, and age at onset of the disease) and to environmental factors (medications, vitamin and mineral supplementation, diet, or industrial pollutants). To determine whether and how the risk (and hence the risk factor profile) for the development of neoplasia changes over time, we conducted an historical cohort study. METHODS: From 445 adult patients with UC proximal to the splenic flexure seen in the Department of Gastroenterology between 1986 and 1992, a random sample of 209 patients was selected. Patients with UC for less than 8 yr or colectomy or neoplasia detected within 2 yr of referral were excluded, leaving 98 patients in the cohort, half of whom had disease onset during or before 1972. RESULTS: After controlling for age at disease onset and duration of disease at first colonoscopy, we found that patients with an earlier year of disease onset were 85% less likely to develop neoplasia than patients with a later year of disease onset (hazard rate ratio 0.15, 95% confidence interval 0.03-0.66). CONCLUSION: These data suggest that the risk for developing neoplasia in UC patients increases with increasing calendar year, implying a worsening risk factor profile.

Adult↗
PubMed1995

Epidemiology of inflammatory bowel disease.

The search for the cause of inflammatory bowel disease through epidemiologic investigation is centered on documenting disease variability and determining the reason for such variability. An examination of the person, place, and time variability of inflammatory bowel disease can provide important clues to disease pathogenesis. Although there is a great deal of variability in the epidemiology of inflammatory bowel disease among populations, there is little difference in these populations between Crohn's disease and ulcerative colitis with regard to person, place, or time variability. With notable exceptions, such as cigarette smoking, the epidemiologic variability of ulcerative colitis and Crohn's disease is remarkably similar. Such similarities are unlikely to be coincidences. The possible implications from this observation are that ulcerative colitis and Crohn's disease are actually different expressions of the same disease, expressions determined by such factors as cigarette smoking, or that two separate diseases share a near complete set of risk factors. Whichever theory is correct, environmental risk factors, which are preventable, are certain to be involved in causative mechanisms.

Age Factors↗
PubMed1994

Cigarette smoking and ulcerative colitis: a case-control study.

OBJECTIVE: To determine whether the previously reported decreased risk of ulcerative colitis in current smokers and increased risk in former smokers are explained by age, sex, race, ethnicity, or socioeconomic status. DESIGN: We conducted a case-control study at a university hospital gastroenterology clinic. MATERIAL AND METHODS: One hundred patients with ulcerative colitis and 100 age- and sex-matched community control subjects were randomly selected for a telephone interview to collect information on smoking habits, race, religion, income, education, and occupation. Smoking habits at the onset of symptoms were analyzed with use of conditional logistic regression for matched data to obtain adjusted odds ratios and 95% confidence intervals for current or former smokers. RESULTS: In comparison with those who had never smoked, current smokers were less likely to have ulcerative colitis: odds ratio = 0.13; 95% confidence interval = 0.05 to 0.38. Former smokers had no increased risk for ulcerative colitis: odds ratio = 1.24; 95% confidence interval = 0.52 to 2.95. No dose-response effect was noted on the basis of pack-years of cigarette smoking, and among former smokers, the interval since quitting smoking was not significantly associated with the relative risk of ulcerative colitis. No confounding effect was detected from race, religion, income, education, or occupation. CONCLUSION: An association seems to exist between ulcerative colitis and nonsmoking; perhaps patients with ulcerative colitis who smoke are less likely to experience symptoms than are nonsmokers because of the effects of nicotine.

Adult↗
PubMed1993

Red blood cell folate is associated with the development of dysplasia and cancer in ulcerative colitis.

Patients with extensive ulcerative colitis have a high risk of developing colon cancer. The etiology of mucosal dysplasia, a premalignant lesion that is used as a screening test in surveillance programs, is unknown. Previously, a case-control study [Lashner et al. (1989) Gastroenterology 97:255-259] suggested that folate supplementation was associated with a 62% reduction in the risk of developing dysplasia or cancer. The current case-control study was performed to obtain a better definition of this risk. All 67 patients with chronic ulcerative pancolitis having surveillance colonoscopy during a 1-year period were entered. There were 6 cases (4 with dysplasia and 2 with cancer) and 61 controls (no cancer or dysplasia). Red blood cell folate, reflecting intermediate-term stores, was a mean of 66.2 ng/ml lower in cases compared to controls. Serum folate, reflecting short-term stores, was not different between groups. Adjusting for confounding effects of age, sex, race, disease duration, and folate supplementation, the risk of dysplasia or cancer was significantly decreased by 18% for each 10 ng/ml increase in red blood cell folate (odds ratio 0.82, 95% confidence interval 0.68-0.99). Vitamins A, D, and E and carotene were lower in cases than in controls, but no water-soluble vitamin other than red blood cell folate was associated with an increased cancer risk. Depressed red blood cell folate is associated with an increased risk of dysplasia and cancer in patients with ulcerative colitis and may be a risk factor for neoplastic transformation.

Adult↗
PubMed1993

Adenocarcinoma complicating Crohn's disease.

We report on 14 cases of intestinal adenocarcinoma complicating Crohn's disease, seven occurring in the small bowel and seven in the large bowel. In both locations, two-thirds of patients were male. The average ages at the time of diagnosis of Crohn's disease and of cancer were similar between the two groups of patients: 28 and 48 years, respectively. The diagnosis of cancer was suspected or obtained preoperatively in only four cases of large bowel cancer; in two patients with large bowel cancer and five with small bowel cancer, the diagnosis was made at laparotomy. In the remaining cases, only careful histologic examination revealed the carcinoma. Six small bowel cancers were located in the ileum, and five colonic cancers were distal to the splenic flexure. Two small bowel and one large bowel cancer were multifocal and had surrounding mucosal dysplasia. All tumors, except one small bowel cancer, underwent resection. Survival correlated with stage of tumor at resection; no patient with regional or distant metastasis survived five years, in comparison with an 83 percent five-year actuarial survival rate of patients with tumor confined to the intestinal wall. Mean survival was six months for patients with small bowel cancer in comparison with 65 months for patients with large bowel cancer, reflecting a tendency toward more advanced lesions in the small bowel cancer group.

Adenocarcinoma↗
PubMed1993

Prior esophageal variceal bleeding does not adversely affect survival after orthotopic liver transplantation.

Prior variceal bleeding may adversely affect the prognosis of orthotopic liver transplantation. We studied this question by evaluating all 175 adult patients undergoing orthotopic liver transplantation at our institution to determine risk factors associated with mortality after transplantation. Seventy patients demonstrated prior variceal bleeding, and of those, 32 had a course of sclerotherapy. Thirteen also had portal systemic shunts. Compared with the 105 transplant patients who had no prior bleeding, patients who bled were more likely to have parenchymal liver disease (74% vs. 50%), equally likely to have cholestatic liver disease (19%), and less likely to have malignancy (6% vs. 19%) or fulminant liver failure (1% vs. 12%). Bleeding patients also were more likely to be Child-Pugh class C (46% vs. 35%). By the common closing date of December 31, 1990, 26 patients (37%) with prior bleeding and 48 patients (46%) without bleeding died after transplantation. From survival curves, patients with prior bleeding had improved survival rates at 1 yr (65% vs. 54%), at 3 yr (60% vs. 47%) and at 5 yr (55% vs. 43%), although the differences were not statistically significant. With a proportional hazards model to adjust for confounding effects, the relative risk of mortality among patients with prior bleeding was 0.60 (95% confidence interval, 0.27 to 1.30). Sclerotherapy or portal systemic shunts did not alter survival. Important adverse risk factors for mortality included older age at transplantation, black race, malignant disease and more advanced Child-Pugh class. This study suggests that prior esophageal variceal bleeding did not adversely affect the mortality of patients undergoing orthotopic liver transplantation.

Adult↗
PubMed1993

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.

Adult↗
PubMed1993

Passive smoking is associated with an increased risk of developing inflammatory bowel disease in children.

Adult cigarette smoking is associated with the development of Crohn's disease and protection from the development of ulcerative colitis. Children usually are nonsmokers whose risk of developing inflammatory bowel disease (IBD) may be related to passive smoking. The purpose of this matched case-control study was to evaluate passive smoking exposure in 72 nonsmoking children with recently diagnosed IBD (39 with ulcerative colitis and 33 with Crohn's disease), and in an equal number of peer-nominated controls. Passive smoking exposure at birth was significantly associated with the development of IBD (odds ratio 3.02, 95% confidence interval 1.28-7.06). The effect was greater in Crohn's disease (odds ratio 5.32) than in ulcerative colitis (odds ratio 2.19). Maternal smoking at birth also was significantly associated with the development of IBD (odds ratio 2.09, 95% confidence interval 1.02-4.29), an effect that also was greater in Crohn's disease than in ulcerative colitis. There was a dose-response relationship between packs smoked per day and IBD, and packs smoked at home per day and IBD. At symptom onset, the risk of developing IBD from passive smoking exposure was increased but was not significant (odds ratio 1.88, 95% confidence interval 0.84-4.18). The magnitude of the effect was greater in Crohn's disease than in ulcerative colitis, and the association demonstrated dose-response. In conclusion, passive smoking exposure and maternal smoking at birth and, to a lesser extent, passive smoking exposure at symptom onset are associated with an increased risk of developing IBD in children. The association is stronger in Crohn's disease than in ulcerative colitis, and there is a dose-response effect. The specific toxic exposure is more likely to be inhaled rather than passed through the placenta or in breast milk.

Case-Control Studies↗