Predicting long-term survival, and the need for hormonal therapy: a meta-analysis of RTOG prostate cancer trials

PURPOSE: To assess the impact of short-term and long-term androgen suppression on the disease-specific and overall survival of 2200 men treated with radiotherapy on one of 5 prospective randomized trials when stratified by prognostic risk groups. METHODS AND MATERIALS: Between 1975 and 1992, 2742 men were treated for clinically localized prostate cancer on one of 5 consecutive prospective Phase III randomized trials. Patients were selected for this analysis if they were deemed evaluable and eligible for the trial, and if follow-up information was available. For this analysis patients were stratified into four previously described prognostic risk groups: Group 1 patients had a Gleason score (GS) = 2-6, and T1-2Nx; Group 2: GS = 2-6, T3Nx; or GS = 2-6, N+, or GS = 7, T1-2Nx; Group 3: T3Nx, GS = 7; or N+, GS = 7, or T1-2Nx, GS = 8-10; and Group 4 patients were T3Nx, GS = 8-10, or N+, GS = 8-10. The median pretreatment prostate-specific antigen (PSA) was 25 ng/ml for the 434 evaluable patients for whom this information was available. The median follow-up times for patients treated on early studies exceeded 11 years, and for more recent studies 6 years. RESULTS: Risk group 2 patients with "bulky" or T3 disease appeared to have a disease-specific survival benefit at 8 years with the addition of 4 months of goserelin and flutamide. Group 3 and 4 patients were noted to have an approximately 20% higher survival at 8 years with the addition of long-term hormonal therapy (p < or =0.0004). CONCLUSIONS: Based on this meta-analysis of RTOG trials, subsets of patients can be identified who either do not appear to benefit from the use of hormonal therapy, benefit from short-term hormonal therapy, or who benefit only from long-term hormonal therapy. These observations should be confirmed by prospective randomized trials before they can be considered conclusive. In the meantime, however, these observations provide rational guidelines for deciding who should receive hormonal therapy and for how long.     

Impact of body weight and weight loss on cardiovascular risk factors

Overwieght and obesity are classified as a major risk for cardiovascular disease (CVD). An increase in the body mass index is associated with adverse changes in the plasma lipid and lipoprotein profile resulting in elevated total cholesterol, low-density lipoprotein-cholesterol, and triglyceride levels and a decrease in high-density lipoprotein levels. An android pattern of obesity is associated with a more deleterious plasma lipoprotein profile as well as hypertension and insulin resistance, resulting in an even greater increase in CVD risk. Weight loss through caloric restriction improves the plasma lipoprotein profile. A Step-1 diet plus exercise confer even greater benefits.     

Does Laparoscopic Gastric Bypass Result in a Healthier Body Composition? An Affirmative Answer

Background: Bariatric surgery results in sustained weight loss. While weight loss is the goal of bariatric surgery, fat loss and muscle conservation are germaine goals. This study investigated the hypothesis that body composition would significantly change after laparoscopic Roux-en-Y gastric bypass (LRYGBP). Methods: Patients undergoing LRYGBP were studied. Percent fat and percent water were calculated via bioelectrical impedance analysis (BIA). Waist and hip circumference were measured in all patients as well. Measurements were taken preoperatively, and at 1 month, 3 months, 6 months, and 1 year. Non-parametric ANOVA was utilized for statistical analysis. Results: There were 151 patients included in this study. Fat percentage (48.6 ± 10.0 vs 34.6 ± 10.8; P<0.001), total fat mass (141 ± 37 vs 67 ± 30; P<0.0001) and total water mass (108 ± 27 vs 93 ± 23; P<0.0001) decreased postoperatively at 1 year. Water percentage increased postoperatively at 1 year (37.0 ± 6.6 vs 52.5 ± 3.3; P<0.001). Waist:hip ratio improved from preoperatively to 1 year postoperatively (0.895 ± 0.115 vs 0.811 ± 0.076; P<0.001). Conclusions: Bariatric surgery results not only in fat loss but also in a change in body composition. Improved waist:hip ratio, fat percentage decreases, and water percentage increases all indicate an overall healthy body composition. While weight loss is important, improvement in body composition should be another recognized benefit of bariatric surgery.     

HYAL1-v1, an alternatively spliced variant of HYAL1 hyaluronidase: a negative regulator of bladder cancer

Tumor cells express HYAL1 hyaluronidase, which degrades hyaluronic acid. HYAL1 expression in bladder cancer cells promotes tumor growth, invasion, and angiogenesis. We previously described five alternatively spliced variants of HYAL1 that encode enzymatically inactive proteins. The HYAL1-v1 variant lacks a 30-amino acid sequence that is present in HYAL1. In this study, we examined whether HYAL1-v1 expression affects bladder cancer growth and invasion by stably transfecting HT1376 bladder cancer cells with a HYAL1-v1 cDNA construct. Although HYAL1-v1 transfectants expressed equivalent levels of enzymatically active HYAL1 protein when compared with vector transfectants, their conditioned medium had 4-fold less hyaluronidase activity due to a noncovalent complex formed between HYAL1 and HYAL1-v1 proteins. HYAL1-v1 transfectants grew 3- to 4-fold slower due to cell cycle arrest in the G(2)-M phase and increased apoptosis. In HYAL1-v1 transfectants, cyclin B1, cdc2/p34, and cdc25c levels were > or =2-fold lower than those in vector transfectants. The increased apoptosis in HYAL1-v1 transfectants was due to the extrinsic pathway involving Fas and Fas-associated death domain up-regulation, caspase-8 activation, and BID cleavage, leading to caspase-9 and caspase-3 activation and poly(ADP-ribose) polymerase cleavage. When implanted in athymic mice, HYAL1-v1-expressing tumors grew 3- to 4-fold slower and tumor weights at day 35 were 3- to 6-fold less than the vector tumors (P < 0.001). Whereas vector tumors were infiltrating and had high mitoses and microvessel density, HYAL1-v1 tumors were necrotic, infiltrated with neutrophils, and showed low mitoses and microvessel density. Therefore, HYAL-v1 expression may negatively regulate bladder tumor growth, infiltration, and angiogenesis.     

Cyclooxygenase-2 (COX-2) expression is an independent predictor of prostate cancer recurrence

Lack of reliable prognostic markers hinders accurate prediction of disease progression in prostate cancer. The inducible proinflammatory enzyme cyclooxygenase-2 (COX-2) is implicated in prostate carcinogenesis, but its role in cancer progression is less clear. We examined whether COX-2 expression evaluated by immunohistochemistry (IHC) in radical prostatectomy (RP) specimens can predict biochemical recurrence. Archival prostate cancer specimens (n = 60) were obtained from patients who underwent RP, but had not received neoadjuvant hormonal therapy. Twenty-three patients had biochemical or clinical recurrence (mean time of recurrence: 38.2 months), and 37 patients were recurrence free (mean follow-up: 95 months). COX-2 expression was determined by IHC, using an anti-COX-2 antibody. Three individuals scored the staining independently, as high- or low-expression. COX-2 was expressed in prostate cancer cells, in adjacent normal glands and in specimens from patients who later progressed. At 62-months follow-up, COX-2 staining predicted progression with 82.4% sensitivity and 81.3% specificity. Sensitivity (86.4%) and specificity (86.7%) improved at > or = 100-months follow-up. In univariate analysis, Gleason score, preoperative PSA, extraprostatic extension, margin, seminal vesicle invasion, and high COX-2 expression were significant predictors of biochemical recurrence (p < 0.05). In multivariate analysis, preoperative PSA (hazard ratio/unit PSA change 1.080; p = 0.0036) and COX-2 expression (hazard ratio 16.442; p < 0.0001) were independent prognostic indicators. Patients with PSA > 7 ng/ml and high COX-2 expression had the highest probability of recurrence (Kaplan-Meier analysis). COX-2 expression is an independent predictor of prostate cancer progression following RP and underscores the significance of inflammatory factors in this process.     

Calcium requirements for the athlete

There is oftentimes a notion of "the more, the better" with regard to vitamin and mineral intake among individuals, and especially among athletes. Although adequate calcium intake is necessary to promote bone health and prevent osteoporosis, increased physical activity alone does not necessarily demand an increased intake of dietary calcium or other micronutrients. Athletes may lose calcium via sweat, in which case replenishment is advocated either via dietary intake of calcium-rich foods or a commercial calcium supplement. The important message to athletes is to consume a diet adequate in energy, protein, fat, vitamins, minerals, and fluids to support the physical demands and replenish the physiologic losses incurred with physical training.     

Upper tract tumour after radical cystectomy for transitional cell carcinoma of the bladder: incidence and risk factors

OBJECTIVE: To review the incidence, pattern and outcome of upper tract transitional cell carcinoma (TCC) after radical cystectomy for carcinoma of the bladder, and identify risk factors for its development. PATIENTS AND METHODS: The records of 235 consecutive patients who had a radical cystectomy and urinary diversion for TCC at the authors' institution by one surgeon between January 1992 and August 2003 were retrospectively reviewed. RESULTS: Five (2%) of 235 patients developed an upper tract urothelial tumour. The mean follow-up for all patients was 42 months, and was 52.2 months for those with an upper tract tumour. Four of the five patients presented with haematuria and one was diagnosed on routine follow-up intravenous urography. The mean time to the diagnosis of an upper tract tumour was 39.6 months. Of the potential risk factors, only the presence of TCC of the prostatic urethra had a statistically significant association with eventual upper tract tumour (P < 0.01). At the last follow-up, four patients died from urothelial cancer and one was disease-free. CONCLUSIONS: The incidence of upper tract tumour after cystectomy for TCC is low; most patients present with symptoms (haematuria) and have advanced disease at diagnosis. Patients with prostatic urethral involvement at cystectomy are at greater risk of developing upper tract tumour.     

Position of The American Dietetic Association: Total Diet Approach to Communicating Food And Nutrition Information

It is the position of the American Dietetic Association that all foods can fit into a healthful eating style. The ADA strives to communicate healthful eating messages to the public that emphasize the total diet, or overall pattern of food eaten, rather than any one food or meal. If consumed in moderation with appropriate portion size and combined with regular physical activity, all foods can fit into a healthful diet. Public policies that support the total diet approach include Reference Dietary Intakes, Food Guide Pyramid, Dietary Guidelines for Americans, Nutrition Labeling and Healthy People 2010. The value of a food should be determined within the context of the total diet because classifying foods as "good" or "bad" may foster unhealthy eating behaviors. Eating practices are influenced by taste and food preferences, concerns about nutrition and weight control, physiology, lifestyle, environment, and food product safety. To increase the effectiveness of nutrition education in promoting sensible food choices, dietetics professionals plan communications and educational programs that utilize theories and models related to human behavior. Communication campaigns/programs should implement an active, behaviorally focused approach within the larger context of food choices. Nutrition confusion can be reduced by emphasizing moderation, appropriate portion size, balance and adequacy of the total diet over time, the importance of obtaining nutrients from foods, and physical activity.