A phase I/II study of intraoperative radiotherapy in advanced unresectable or recurrent carcinoma of the rectum: A radiation therapy oncology group (RTOG) study

The Radiation Therapy Oncology Group (RTOG) initiated a phase I/II study of intraoperative radiotherapy (IORT) in advanced or recurrent rectal cancer to assess therapeutic efficacy, toxicity, and establish quality control guidelines prior to beginning a phase III trial. From October 1985 through December 1989, 87 patients with histologically proven adenocarcinoma of the rectum or rectosigmoid with recurrent/persistent disease after surgery or those primarily inoperable were entered by 14 institutions. Of 86 evaluable patients, 42 patients received IORT either alone (n = 15) or in combination with external beam (n = 27). Local control was dependent on the amount of residual disease prior to IORT, with 2-year actuarial local control of 77% if no gross residual disease remained vs. 10% with gross residual disease (P = 0.0001). For the recurrent/residual group (n = 33), this observation was also significant with a 2-year actuarial local control rate of 64% if no gross residual remained vs. 10% with gross residual disease (P = 0.004). Local control translated into an improved survival for all patients and the recurrent/residual group with 2-year actuarial survival of 88% and 89% if no gross residual disease remained vs. 48% and 45% with gross residual disease, respectively (P = .0005, 0.006). Six patients (14.6%) experienced four grade 3 and three grade 4 complications as a possible result of IORT during follow-up with a 2-year actuarial risk of major complications of 16%. We conclude that IORT is feasible within a cooperative group and can be performed with acceptable complication rates. A phase III trial to demonstrate a therapeutic advantage for IORT over external beam alone is currently in progress. © 1993 Wiley-Liss, Inc.     

Weight change and risk of postmenopausal breast cancer (United States)

Objective: Although many studies have shown that higher weight increases the risk of postmenopausal breast cancer, some aspects of this association are unclear. In order to examine the risk associated with different patterns of weight change, we analyzed data from a large case–control study of postmenopausal breast cancer. Methods: Participants included women aged 50–79 years (n = 5031) who are newly diagnosed with invasive breast cancer in Massachusetts, New Hampshire, and Wisconsin. Similarly-aged population controls (n = 5255) were selected at random from driver's license files and Medicare beneficiary lists. Height, weight, and information on other breast cancer risk factors were ascertained by structured telephone interviews from 1992 to 1995, and logistic regression was used to estimate multivariable-adjusted odds ratios (OR) and 95% confidence intervals (CI). Results: Women in the top quintile groups for height at age 20, recent weight, and recent body mass index had significantly increased risks of breast cancer. Among women who reached their highest adult weight at younger ages (45 years), increasing weight loss since that age was associated with a reduced risk of postmenopausal breast cancer (OR 0.90, CI 0.84–0.98, per 5 kg). However, weight loss among women whose highest weight occurred after age 45 was not associated with risk (OR 1.00, CI 0.95–1.05, per 5 kg). Weight gain since the lowest adult weight increased risk by 8% for each 5 kg of gain (OR 1.08, CI 1.06–1.11). Temporary weight cycling (weight loss followed by weight gain) was not associated with increased risk. Conclusions: Weight gain clearly increased risk of postmenopausal breast cancer. These data lend further support to efforts aimed at helping women avoid weight gain as they age.     

Bowel movement, use of laxatives and risk of colorectal adenomatous polyps among women (United States)

Background: Infrequent bowel movements and use of laxatives have been hypothesized to increase risk of colorectal neoplasia. However, the few existing epidemiologic studies in humans have been inconclusive. Purpose: To investigate prospectively the associations of bowel movement frequency and laxative use with the occurrence of adenomatous colorectal polyps in women. Methods: A total of 17,400 women 36–61 years of age, without previous diagnosis of cancer or polyps, responded to a mailed questionnaire in 1982 that assessed bowel movement frequency and use of laxatives and had an endoscopy between 1984 and 1996. Between 1984 and 1996, 906 cases of adenomatous polyps (496 classified as small (<1 cm), 358 classified as large (1 cm) and 52 unclassified) were documented. Relative risks (RRs) of adenomas and 95% confidence intervals (CIs) were calculated using logistic regression. Results: After controlling for adenoma risk factors, the multivariate RRs associated with having bowel movements every third day or less compared to once daily were 0.9 (95% CI: 0.7–1.2) for total colorectal adenomas, 1.0 (95% CI: 0.7–1.5) for large adenomas and 1.0 (95% CI: 0.7–1.3) for adenomas of the colon only. The multivariate RRs associated with weekly to daily laxative use compared to never use were 0.9 (95% CI: 0.7–1.1) for total colorectal adenomatous polyps, 1.0 (95% CI: 0.7–1.5) for large adenomas and 0.8 (95% CI: 0.6–1.2) for colon adenomatous polyps only. Conclusion: These findings do not support an association between infrequent bowel movement or laxative use and risk of colorectal adenomas.     

Diet and cancer

The large differences in cancer rates among countries, striking changes in these rates among migrating populations, and rapid changes over time within countries indicate that some aspect of lifestyle or environment is largely responsible for the common cancers in Western countries. Dietary fat has been hypothesized to be the key factor because national consumption is correlated with the international differences. However, detailed analyses in large prospective studies have not supported an important role of dietary fat. Instead, positive energy balance, reflected in early age at menarche and weight gain as an adult, is an important determinant of breast and colon cancers, consistent with numerous studies in animals. As a contributor to positive energy balance, and possibly by other mechanisms, physical inactivity has also been shown to be a risk factor for these diseases and in part accounts for the international differences. Although the percentage of calories from fat in the diet does not appear related to risk of colon cancer, greater risks have been seen with higher consumption of red meat, suggesting that factors other than fat per se are important. In many case-control studies, a high consumption of fruits and vegetables has been associated with reduced risks of numerous cancers, but recent prospective studies suggest these associations may have been overstated. Among the factors in fruits and vegetables that have been examined in relation to cancer risk, present data most strongly support a benefit of higher folic acid consumption in reducing risks of colon and breast cancers. These findings have been bolstered by an association between incidence of colon cancer and a polymorphism in the gene for methylenetetrahydrofolate reductase, an enzyme involved in folic acid metabolism. The benefits of folic acid appear strongest among persons who regularly consume alcohol, which itself is associated with risk of these cancers. Numerous other aspects of diet are hypothesized to influence the risks of cancers in Western countries, but for the moment the evidence is unclear.     

Plasma noradrenaline kinetics in humans

Recently developed radiotracer methods for measuring the overall rate of release of noradrenaline to plasma, for the body as a whole, can be used to estimate 'total sympathetic nervous system activity' in humans. These techniques find application in clinical studies of sympathetic nervous physiology and pharmacology. The inherent weakness of any biochemical test of global sympathetic tone such as this lies in the fact that sympathetic nervous system responses typically show regional differentiation. Biochemical indices of overall sympathetic activity are insufficiently discriminating to delineate patterns of sympathetic nervous response, representing instead an algebraic sum of all regional increases or decreases in sympathetic tone. Modification of the whole-body radiotracer methodology enables organ-specific sympathetic nervous system activity to be estimated, from measurements of regional release of noradrenaline to plasma. This should facilitate investigation of possible sympathetic pathophysiology in disease states. Illustrative of potential application of the method are preliminary findings of increased renal sympathetic nervous tone in young patients with essential hypertension, and of selective activation of sympathetic nerves to the kidney by diuretics.     

Prospective study of dietary fat and risk of cataract extraction among US women

The authors examined prospectively the association between dietary fat intake and cataract extraction in adult women from the Nurses' Health Study. A total of 71,083 women were followed prospectively for up to 16 years between 1984 and 2000. Dietary fat was assessed by repeated food frequency questionnaires. Incident cases of cataract extraction were determined by a biennial questionnaire. The multivariate-adjusted relative risk for the highest compared with the lowest quintile of total fat intake was 1.10 (95% confidence interval (CI): 0.99, 1.22; p(trend) = 0.01). Women in the highest quintile of long-chain omega-3 fatty acid had a 12% lower risk of cataract extraction compared with those in the lowest quintile (relative risk = 0.88, 95% CI: 0.79, 0.98; p(trend) = 0.02). Total fish intake was inversely associated with cataract (for intake of > or = 3/week vs. <1/month: relative risk = 0.89, 95% CI: 0.81, 0.98; p(trend) = 0.01). The authors' findings suggest that higher intake of long-chain omega-3 fatty acid (eicosapentaenoic acid and docosahexaenoic acid) and consumption of fish may modestly reduce the risk of cataract.     

Sexually transmitted infections, prostatitis, ejaculation frequency, and the odds of lower urinary tract symptoms

Early life sexual factors, including histories of sexually transmitted infections, young-onset prostatitis, and frequency of ejaculation, were investigated in relation to lower urinary tract symptoms (LUTS) in a large case-control study nested within the Health Professionals Follow-up Study. In 1992, study participants were asked to provide information on their histories of sexually transmitted infections, prostatitis, ejaculation frequency, surgery for an enlarged prostate, and LUTS. Information on prostate surgery and LUTS was updated every 2 years. LUTS cases were defined as men who reported surgery for an enlarged prostate or high-moderate to severe LUTS (> or = 15 points on the American Urological Association symptom index) on any study questionnaires (n = 4,608). Controls were men who did not report surgery for an enlarged prostate and who scored 0-7 points on the American Urological Association symptom index on all questionnaires (n = 17,967). History of gonorrhea (adjusted odds ratio = 1.76, 95% confidence interval: 1.43, 2.15) or young-onset prostatitis (adjusted OR = 1.55, 95% confidence interval: 1.22, 1.96) was positively associated with LUTS. No association was observed between ejaculation frequency in early adulthood and LUTS. These results suggest that early genitourinary infections may contribute to later development of LUTS, although confirmation in additional population settings is warranted.