Leila A. Mott

Neuropsychologic Impact of Standard-Dose Systemic Chemotherapy in Long-Term Survivors of Breast Cancer and Lymphoma

PURPOSE The primary purpose of this study was to compare the neuropsychologic functioning of long-term survivors of breast cancer and lymphoma who had been treated with standard-dose systemic chemotherapy or local therapy only. PATIENTS AND METHODS Long-term survivors (5 years postdiagnosis, not presently receiving cancer treatment, and disease-free) of breast cancer or lymphoma who had been treated with systemic chemotherapy (breast cancer: n = 35, age, 59.1 +/- 10.7 years; lymphoma: n = 36, age, 55.9 +/- 12.1 years) or local therapy only (breast cancer: n = 35, age, 60.6 +/- 10.5 years; lymphoma: n = 22, age, 48.7 +/- 11.7 years) completed a battery of neuropsychologic and psychologic tests (Center for Epidemiological Study-Depression, Spielberger State-Trait Anxiety Inventory, and Fatigue Symptom Inventory). RESULTS Multivariate analysis of variance, controlling for age and education, revealed that survivors who had been treated with systemic chemotherapy scored significantly lower on the battery of neuropsychologic tests compared with those treated with local therapy only (P <.04), particularly in the domains of verbal memory (P <.01) and psychomotor functioning (P <.03). Survivors treated with systemic chemotherapy were also more likely to score in the lower quartile on the Neuropsychological Performance Index (39% v 14%, P <.01) and to self-report greater problems with working memory on the Squire Memory Self-Rating Questionnaire (P <.02). CONCLUSION Data from this study support the hypothesis that systemic chemotherapy can have a negative impact on cognitive functioning as measured by standardized neuropsychologic tests and self-report of memory changes. However, analysis of the Neuropsychological Performance Index suggests that only a subgroup of survivors may experience long-term cognitive deficits associated with systemic chemotherapy.

Increase in incidence rates of basal cell and squamous cell skin cancer in New Hampshire, USA

We conducted a study to estimate the current incidence rates of basal‐cell carcinoma (BCC) and squamous‐cell carcinoma (SCC) of the skin in the population of New Hampshire (NH), USA, and to quantify recent changes in the incidence rates of these malignancies. BCCs and SCCs diagnosed among NH residents were identified through physician practices and central pathology laboratories in NH and bordering regions from June 1979 through May 1980 and from July 1993 through June 1994. For each diagnosis period, we estimated the age‐adjusted incidence rates for both BCC and SCC among both men and women and for separate anatomic sites. Between 1979–1980 and 1993–1994, incidence rates of SCC increased by 235% in men and by 350% in women. Incidence rates of BCC increased by more than 80% in both men and women. While the absolute increase was greatest for tumors of the head and neck, the relative change was most pronounced for tumors on the trunk in men and on the lower limb in women. Thus, there has been a marked rise in the incidence rates of BCC and SCC skin cancers in NH in recent years. The anatomic pattern of increase in BCC and SCC incidence is consistent with an effect of greater sunlight exposure. Studies of BCC and SCC occurrence are needed to identify possible behavioral and environmental factors and to assess possible changes in diagnostic practices that might account for the rise in incidence of these common malignancies. Int. J. Cancer 81:555–559, 1999.

Viewing tobacco use in movies: does it shape attitudes that mediate adolescent smoking?

BACKGROUND Social cognitive theory posits that children develop intentions and positive expectations (utilities) about smoking prior to initiation. These attitudes and values result, in part, from observing others modeling the behavior. This study examines, for the first time, the association between viewing tobacco use in movies and attitudes toward smoking among children who have never smoked a cigarette. DESIGN/SETTING Cross-sectional school-based survey was used among randomly selected Vermont and New Hampshire middle schools. The sample consisted of 3766 middle school students (grades 5-8). The sample was primarily white and equally distributed by gender. The primary exposure was number of movie tobacco-use occurrences viewed. We first counted occurrences of tobacco use in each of 601 recent popular motion pictures. Each student was asked to select movies they had seen from a random subset of 50 movies. Based on movies the adolescent had seen, movie tobacco-use occurrences were summed to determine exposure . The outcome was susceptibility to smoking, positive expectations, and perceptions of smoking as normative behavior for adolescents or adults. RESULTS The movies in this sample contained a median of five occurrences of tobacco use (interquartile range=1, 12). The typical adolescent never-smoker had viewed 15 of the 50 movies on his/her list. From movies adolescents reported seeing, exposure to movie tobacco-use occurrences varied widely: median=80, and interquartile range 44 to 136. The prevalence of susceptibility to smoking increased with higher categories of exposure: 16% among students who viewed 0 to 50 movie tobacco occurrences; 21% (51 to 100); 28% (101 to 150); and 36% (>150). The association remained statistically significant after controlling for gender, grade in school, school performance, school, friend, sibling and parent smoking, sensation-seeking, rebelliousness, and self-esteem. Compared with adolescents exposed to < or =50 occurrences of tobacco use, the adjusted odds ratio of susceptibility to smoking for each higher category was 1.2 (95% confidence interval 0.9, 1.5), 1.4 (1.1, 1.9), and 1.6 (1.3, 2.1), respectively. Similarly, higher exposure to tobacco use in movies significantly increased the number of positive expectations endorsed by the adolescent and the perception that most adults smoke, but not the perception that most peers smoke. CONCLUSIONS This study provides empirical evidence that viewing movie depictions of tobacco use is associated with higher receptivity to smoking prior to trying the behavior.

Incidence of transitional cell carcinoma of the bladder and arsenic exposure in New Hampshire

AbstractObjective: Arsenic is a known bladder carcinogen and populations exposed to high arsenic levels in their water supply have reported elevated bladder cancer mortality and incidence rates. To examine the effects of lower levels of arsenic exposure on bladder cancer incidence, we conducted a case–control study in New Hampshire, USA where levels above 10 μ/l are commonly found in private wells. Methods: We studied 383 cases of transitional cell carcinoma of the bladder cancer, newly diagnosed between July 1, 1994 and June 30, 1998 and 641 general population controls. Individual exposure to arsenic was determined in toenail clippings using instrumental neutron activation analysis. Results: Among smokers, an elevated odds ratio (OR) for bladder cancer was observed for the uppermost category of arsenic (OR: 2.17, 95% CI: 0.92–5.11 for greater than 0.330 mcg/g compared to less than 0.06 μ/g). Among never smokers, there was no association between arsenic and bladder cancer risk. Conclusions: These, and other data, suggest that ingestion of low to moderate arsenic levels may affect bladder cancer incidence, and that cigarette smoking may act as a co-carcinogen.

Quality of Life of Long-Term Survivors of Breast Cancer and Lymphoma Treated With Standard-Dose Chemotherapy or Local Therapy

PURPOSE This study compared the quality of life (QOL) of long-term survivors of breast cancer and lymphoma who had been treated with standard-dose systemic chemotherapy or local therapy only. PATIENTS AND METHODS Long-term survivors (mean, 10.0 +/- 5.3 years after treatment) of breast cancer or lymphoma who had been treated with systemic chemotherapy (breast, n = 141, age = 57.0 +/- 10.1 years; lymphoma, n = 66, age = 55.8 +/- 13.5 years) or local therapy only (breast, n = 294, age = 65.8 +/- 9.1 years; lymphoma, n = 37, age = 50.4 +/- 12.8 years) were interviewed by phone using the Quality of Life-Cancer Survivors Tool. RESULTS Multivariate analysis of covariance, controlling for sex, age, education, stage of disease, and time since last treatment, revealed that survivors who had been treated with systemic chemotherapy scored significantly lower on overall QOL compared with survivors treated with local therapy only (P = .04). Analysis of covariance on the subscale scores revealed that, compared with survivors who received local therapy, survivors treated with chemotherapy scored significantly lower on the Social subscale (P < .0001), but no differences emerged on the Psychological or Spiritual subscales. There was a statistically significant interaction between treatment and diagnosis (P = .01), as measured by the Physical subscale, indicating that lymphoma survivors treated with chemotherapy scored worse than all other groups. CONCLUSION Important QOL differences emerged between the chemotherapy and local therapy groups, suggesting that long-term QOL may vary depending on the type of treatment and diagnosis.

The colonoscopic miss rate and true one-year recurrence of colorectal neoplastic polyps

Objective: Studies of tandem colonoscopies have reported that 15–25% of neoplastic polyps <1 cm in size and 0–6% of larger polyps are overlooked at the time of colonoscopy. We determined the miss rate and “true” 1-yr recurrence of neoplastic polyps in a population of patients reflecting a broad spectrum of different gastroenterology practice settings. Methods: Patient data from several sources were examined for repeat colonoscopies performed on the same patient within 120 days of each other. Examination pairs were included for analysis if both colonoscopies had good preps and reached the cecum. The miss rate was calculated by two methods: 1) a pooled rate, the total number of polyps on all second examinations divided by the total number on both examinations, and 2) a within-person rate, the average of the individual miss-rates. We estimated a “true” 1-yr recurrence rate by subtracting the proportion of patients with a missed neoplastic polyp from the proportion of patients with a neoplastic polyp found at 1 yr. Results: A total of 76 colonoscopy pairs a mean 47 days apart (range, 1–119 days) were identified from a total of approximately 15,000 examinations and used to calculate the overall miss rates. For the category “all polyps” (neoplastic and nonneoplastic polyps), 17% by the pooled method and 11% by the within-person method were missed. The corresponding rates for neoplastic polyps were 12% by the pooled method and 8% by the within-person method. A total of 17% of patients had one or more neoplastic polyps missed on the initial examination. The observed 1-yr recurrence rate was determined from 1,314 colonoscopy pairs performed a mean of 379 days apart and found to be 28% for neoplastic polyps. By comparing this to the proportion of patients with one or more missed neoplastic polyps, we found the true 1-yr recurrence of neoplastic polyps to be 11%. Conclusion: There is a significant colonoscopic miss rate for neoplastic polyps and “all polyps” in clinical practice that is comparable to that previously stated in special research settings. The within-person rate more accurately reflects the true colorectal polyp miss rate for any given colonoscopic exam than does the pooled rate. The difference between the observed 1-yr recurrence rate and the proportion of patients with a missed polyp represents the true 1-yr recurrence of neoplastic polyps.

A trial of calcium and Vitamin D for the prevention of colorectal adenomas

BACKGROUND Epidemiologic and preclinical data suggest that higher intake and serum levels of vitamin D and higher intake of calcium reduce the risk of colorectal neoplasia. To further study the chemopreventive potential of these nutrients, we conducted a randomized, double-blind, placebo-controlled trial of supplementation with vitamin D, calcium, or both for the prevention of colorectal adenomas. METHODS We recruited patients with recently diagnosed adenomas and no known colorectal polyps remaining after complete colonoscopy. We randomly assigned 2259 participants to receive daily vitamin D3 (1000 IU), calcium as carbonate (1200 mg), both, or neither in a partial 2×2 factorial design. Women could elect to receive calcium plus random assignment to vitamin D or placebo. Follow-up colonoscopy was anticipated to be performed 3 or 5 years after the baseline examinations, according to the endoscopists recommendation. The primary end point was adenomas diagnosed in the interval from randomization through the anticipated surveillance colonoscopy. RESULTS Participants who were randomly assigned to receive vitamin D had a mean net increase in serum 25-hydroxyvitamin D levels of 7.83 ng per milliliter, relative to participants given placebo. Overall, 43% of participants had one or more adenomas diagnosed during follow-up. The adjusted risk ratios for recurrent adenomas were 0.99 (95% confidence interval [CI], 0.89 to 1.09) with vitamin D versus no vitamin D, 0.95 (95% CI, 0.85 to 1.06) with calcium versus no calcium, and 0.93 (95% CI, 0.80 to 1.08) with both agents versus neither agent. The findings for advanced adenomas were similar. There were few serious adverse events. CONCLUSIONS Daily supplementation with vitamin D3 (1000 IU), calcium (1200 mg), or both after removal of colorectal adenomas did not significantly reduce the risk of recurrent colorectal adenomas over a period of 3 to 5 years. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00153816.).

Surface area of human cerebral cortex and its gross morphological subdivisions: In vivo measurements in monozygotic twins suggest differential hemisphere effects of genetic factors

We measured the surEdce area of the cerebral cortex and its gross morphological subdivisions in 10 pairs of monozygotic twins. Cortical surface area was estimated in vivo using magnetic resonance imaging and threedimensional computer models of the intra- and extrasulcal pial surface. The means and standard deviations of regional (e.g., gyral), lobar, hemisphere, and total cortical surface area were tabulated for the entire population of 20 young, right-handed adults (10 females, 10 males). To determine whether genotypic differences were associated with morphometric differences, analyses of variance were carried out on each measure across unrelated twin pairs (genotype factor) and within co-twins (birth order factor). Across unrelated pairs, there was wide variation in regional cortical surface area for the left hemisphere (normalized by total cortical surface area, p 0.0001) but not for the right hemisphere (normalized, p = 0.12). More variation in lobar surface area was also observed for the left hemisphere (normalized, p = 0.05) than for the right (normalized, p = 0.48). Within co-twins, no signifcant variation in regional surface area or lobar surface area was found for the left or right hemisphere. Although normalized regional and lobar surface area in the left hemisphere differed across unrelated pairs, overall left hemisphere surface area normalized by total cortical surface area did not (p = 0.73). Total cortical surface area normallzed by body weight varied across unrelated pairs (p = 0.001) but not within co-twins (p = 0.39). The effects observed across unrelated pairs were not attributable to sex differences. These results suggest: 1) both the total area and folding of the cortical surface are heavily influenced by genetic factors in humans; and 2) the cerebral hemispheres may be differentially affected by genetic influences on cortical morphogenesis, with the languagedominant left cerebral cortex under stronger genetic control than the right.

Folic acid and prevention of colorectal adenomas: A combined analysis of randomized clinical trials

Observational data suggest that lower folate status is associated with an increased risk of colorectal neoplasia, implying that folate may be useful as a chemopreventive agent. We conducted a combined analysis of three large randomized trials of folic acid supplementation for the prevention of metachronous adenomas in patients with an adenoma history. Participants included 2,632 men and women who had a history of adenomas randomized to either 0.5 or 1.0 mg/day of folic acid or placebo and who had a follow‐up endoscopy 6 to 42 months after randomization [mean = 30.6 (standard deviation = 8.1) months]. We used random‐effects meta‐analysis to estimate risk ratios (RRs) and 95% confidence intervals (CIs). The RR comparing folic acid versus placebo was 0.98 (95% CI = 0.82–1.17) for all adenomas and 1.06 (95% CI = 0.81–1.39) for advanced lesions. Folic acid was associated with a nonsignificant decreased risk of any adenoma among subjects in the lowest quartile of baseline plasma folate (≤11 nmol/L) and no effect among individuals in the highest quartile (>29 nmol/L, p for trend = 0.17). There was a nonsignificant trend of decreasing risk of any adenoma associated with folic acid supplements with increasing alcohol intake. During the early follow‐up reported here, more deaths occurred in the placebo group than in the folic acid group (1.7% vs. 0.5%, p = 0.002). In conclusion, after up to 3.5 years of folic acid use, there is no clear decrease or increase in the occurrence of new adenomas in patients with a history of adenoma.

Constipation and a Low-Fiber Diet Are Not Associated With Diverticulosis

BACKGROUND & AIMS Asymptomatic diverticulosis is commonly attributed to constipation caused by a low-fiber diet, although evidence for this mechanism is limited. We examined the associations between constipation and low dietary fiber intake with risk of asymptomatic diverticulosis. METHODS We performed a cross-sectional study that analyzed data from 539 individuals with diverticulosis and 1569 without (controls). Participants underwent colonoscopy and assessment of diet, physical activity, and bowel habits. Our analysis was limited to participants with no knowledge of their diverticular disease to reduce the risk of biased responses. RESULTS Constipation was not associated with an increased risk of diverticulosis. Participants with less frequent bowel movements (<7/wk) had reduced odds of diverticulosis compared with those with regular bowel movements (7/wk) (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.40-0.80). Those reporting hard stools also had reduced odds (OR, 0.75; 95% CI, 0.55-1.02). There was no association between diverticulosis and straining (OR, 0.85; 95% CI, 0.59-1.22) or incomplete bowel movement (OR, 0.85; 95% CI, 0.61-1.20). We found no association between dietary fiber intake and diverticulosis (OR, 0.96; 95% CI, 0.71-1.30) in comparing the highest quartile with the lowest (mean intake, 25 vs 8 g/day). CONCLUSIONS In our cross-sectional, colonoscopy-based study, neither constipation nor a low-fiber diet was associated with an increased risk of diverticulosis.