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Rye consumption has shown beneficial effects on prostate cancer tumors, as indicated by slower initial tumor growth in animal models and lowering of prostate-specific antigen (PSA) in humans. This study evaluated the effects of whole grain/bran rye consumption on low-grade inflammation and endothelial function biomarkers in men with prostate cancer. Seventeen men with untreated, low-grade prostate cancer consumed 485 g rye whole grain and bran products (RP) per day or refined wheat products with added cellulose (WP) in a randomized crossover design. Fasting blood samples were taken before and after 2, 4, and 6 weeks of treatment. Concentrations of tumor nuclear factor-receptor 2 (TNF-R2), e-selectin, and endostatin were significantly lower after consumption of the RP diet compared with WP (p < 0.05). Cathepsin S concentration was positively correlated to TNF-R2 and endostatin concentrations across all occasions. Strong correlations were consistently found between intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and between interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1RA). No effect of intervention was found in 92 inflammation-related protein biomarkers measured in a proximity extension assay. RP diet lowered TNF-R2, e-selectin, and endostatin, compared with WP in men with prostate cancer. These effects were accompanied by a reduction in PSA. [ABSTRACT FROM AUTHOR]

Colonic acute graft-versus-host disease (aGVHD) affects approximately 10% of patients who have undergone allogeneic stem cell transplantation (allo-SCT). Diarrhea is a major clinical sign but also a common post-transplantation symptom in these patients. Comprehensive histopathologic examination of the colon is therefore regarded as crucial to establish a diagnosis, but the colonic segment that should be targeted for a diagnostic biopsy remains a topic of debate. The primary objective of this study was to compare prospectively colonoscopy with sigmoidoscopy regarding their capabilities to provide a histopathologically proven diagnosis of colonic aGVHD. Thirty-seven allo-SCT patients with diarrhea all underwent a colonoscopy. All biopsies collected from the descending colon were regarded as also attainable by sigmoidoscopy, whereas biopsies collected in regions further up the colon (from the transverse and ascending colon) were regarded as acquirable exclusively by colonoscopy. Biopsies attainable by colonoscopy and sigmoidoscopy were positive for GVHD in 25 (68%) and 24 (65%) patients, respectively (95% confidence interval for difference of proportions, −.185 to .245; P = .978; z = .0271 by the z-test). Sigmoidoscopy is as effective as colonoscopy in establishing a diagnosis of colonic aGVHD in patients who have diarrhea after allo-SCT. [ABSTRACT FROM AUTHOR]

Prostate cancer (PC) is the most common cancer in the Western world and the second most important cancer causing male deaths, after lung cancer, in the United States and Britain. Lifestyle and dietary changes are recommended for men diagnosed with early-stage PC. It has been shown that a diet rich in whole grain (WG) rye reduces the progression of early-stage PC, but the underlying mechanism is not clear. This study sought to identify changes in the metabolic signature of plasma in patients with early-stage PC following intervention with a diet rich in WG rye and rye bran product (RP) compared with refined white wheat product (WP) as a tool for mechanistic investigation of the beneficial health effects of RP on PC progression. Seventeen PC patients received 485 g RP or WP in a randomized, controlled, crossover design during a period of 6 wk with a 2-wk washout period. At the end of each intervention period, plasma was collected after fasting and used for ¹H NMR-based metabolomics. Multilevel partial least squares discriminant analysis was used for paired comparisons of multivariate data. A metabolomics analysis of plasma showed an increase in 5 metabolites, including 3-hydroxybutyric acid, acetone, betaine, N,N-dimethylglycine, and dimethyl sulfone, after RP. To understand these metabolic changes, fasting plasma homocysteine, leptin, adiponectin, and glucagon were measured separately. The plasma homocysteine concentration was lower (P = 0.017) and that of leptin tended to be lower (P = 0.07) after RP intake compared to WP intake. The increase in plasma 3-hydroxybutyric acid and acetone after RP suggests a shift in energy metabolism from anabolic to catabolic status, which could explain some of the beneficial health effects of WG rye, i.e., reduction in prostate-specific antigen and reduced 24-h insulin secretion. In addition, the increase in betaine and N,N-dimethylglycine and the decrease in homocysteine show a favorable shift in homocysteine metabolism after RP intake. [ABSTRACT FROM AUTHOR]

Rye whole grain and bran intake has shown beneficial effects on prostate cancer progression in animal models, including lower tumor take rates, smaller tumor volumes, and reduced prostate specific antigen (PSA) concentrations. A human pilot study showed increased apoptosis after consumption of rye bran bread. In this study, we investigated the effect of high intake of rye whole grain and bran on prostate cancer progression as assessed by PSA concentration in men diagnosed with prostate cancer. Seventeen participants were provided with 485 g rye whole grain and bran products (RP) or refined wheat products with added cellulose (WP), corresponding to --50% of daily energy intake, in a randomized controlled, crossover design. Blood samples were taken from fasting men before and after 2, 4, and 6 wk of treatment and 24-h urine samples were collected before the first intervention period and after treatment. Plasma total PSA concentrations were lower after treatment with RP compared with WP, with a mean treatment effect of -14% (P= 0.04). Additionally, fasting plasma insulin and 24-h urinary C- peptide excretion were lower after treatment with R P compared with WP (P< 0.01 and P= 0.01, respectively). Daily excretion of 5 lignans was higherafter the RPtreatmentthan after the WPtreatment (P< 0.001). We conclude thatwhole grain and bran from rye resulted in significantly lower plasma PSA compared with a cellulose-supplemented refined wheat diet in patients with prostate cancer. The effect may be related to inhibition of prostate cancer progression caused by decreased exposure to insulin, as indicated by plasma insulin and urinary C-peptide excretion. [ABSTRACT FROM AUTHOR]

Alkylresorcinols (AR), phenolic lipids exclusively present in the outer parts of wheat and rye grains, have been proposed as conceltration biomarkers of whole-grain wheat and rye intake. A key feature of a good biomarker is high reproducibility, which indicates how accurately a single sample reflects the true mean biomarker concentration caused by a certain intake. In this study, the short- to medium-term reproducibility of plasma AR was determined using samples from a crossover intervention study, where men with prostate cancer (n = 17) were fed rye whole-grain/bran or refined wheat products for 6-wk periods. AR homologs C17:0 and C21:0 differed between the treatments (P < 0.001). The reproducibility determined by the intraclass correlation coefficient (ICC) was high (intervention period 1: ICC = 0.90 [95% Cl = 0.82-0.98), intervention period 2: ICC = 0.88 [95% Cl = 0.78-0.981]. The results show that a single fasting plasma sample could be used to estimate the mean plasma AR concentration during a 6-wk intervention period with constant intake at a precision of ± 20% (80% Cl). This suggests that the plasma AR concentration can be used as a reliable short- to medium-term biomarker for whole-grain wheat and rye under intervention conditions where intake is kept constant. [ABSTRACT FROM AUTHOR]

There is a lack of an accepted standard of care for dental treatment before hematopoietic stem cell transplantation (HSCT). Therefore, in this international, prospective multicenter study (OraStem), we evaluated the differences in dental diseases, oral hygiene practices, and dental treatments before HSCT. Enrollment sites included Vancouver, BC (Canada); Gothenburg and Huddinge (Sweden); Nijmegen and Amsterdam (The Netherlands); and Charlotte, NC (USA). The frequency of dental diseases, oral hygiene practices, and dental treatments before HSCT are reported here. Data on the number, mean age, and gender (%) of the cohort included the following: Overall: n = 269, age 53.6 years, males 56%; Vancouver: n = 58, age 52.3 years, males 57%; Sweden: n = 29, age 57.2 years, males 56%; Nijmegen: n = 81, age 55.1 years, males 54%; Amsterdam: n = 43, age 55.2 years, males 59%; and Charlotte: n = 58, age 49.6 years, males 57%. Overall, the most frequent medical diagnoses necessitating HSCT were as follows: myeloma = 74 (27%), acute myelogenous leukemia = 67 (24%); lymphoma = 37 (13%), myelodysplastic syndrome = 19 (7%); and acute lymphoblastic leukemia = 17 (6%). Overall, most transplants were allogeneic (61%) versus autologous (36%). The numbers of patients reporting brushing 2 or more times per day were as follows: overall = 200 (73%); Vancouver = 40 (67%); Sweden = 27 (87%); Nijmegen = 63 (78%); Amsterdam = 34 (77%); and Charlotte = 36 (59%). The numbers of patients reporting seeing a dentist or dental therapist routinely were as follows: overall = 202 (73%); Vancouver = 41 (71%); Sweden = 24 (77%); Nijmegen = 70 (86%); Amsterdam = 37 (84%); and Charlotte = 30(49%). Conditions of teeth were recorded before and after dental treatment provided before HSCT. Upon enrollment, mean numbers of teeth with a natural root (with or without crown) were as follows: overall = 24.2; Vancouver = 23.2; Sweden = 26.3; Amsterdam = 23.5; Nijmegen = 23.8; and Charlotte = 25.5. The numbers of people who underwent tooth extraction and the numbers of dental extractions (% of existing teeth) before transplantation were as follows: overall: n = 44, 126 teeth (0.5%); Vancouver: n = 4, 5 teeth (0.1%); Sweden: n = 5, 28 teeth (0.32%); Nijmegen: n = 10, 41 teeth (0.5%); Amsterdam: n = 8, 14 teeth (0.3%); and Charlotte: n = 17, 59 teeth (1%). The numbers of teeth with periodontal pocketing greater than 5 mm left untreated were as follows: overall = 102 (0.4%); Vancouver = 23 (0.5%); Sweden = 25 (0.3%); Nijmegen = 25 (0.3%); Amsterdam = 12 (0.3%); and Charlotte = 35 (0.8%). The numbers of teeth with 1 or more carious lesions to dentin left untreated were as follows: overall = 246 (1.0%); Vancouver = 11 (0.2%); Sweden = 27 (0.3%); Nijmegen = 118 (1.5%); Amsterdam = 11 (0.3%); and Charlotte = 99 (1.7%). This baseline report reveals variations in dental diseases, oral hygiene practices, and dental treatments rendered before HSCT among different study centers. Establishment of an international standard of care for dental treatment before HSCT is needed. Prospective OraStem study data will increase the understanding of risk factors related to oral complications during HSCT. [ABSTRACT FROM AUTHOR]

Abstract: Epidemiologic studies on diabetes and body size in relation to risk of bladder cancer have yielded inconsistent results. We examined prospectively the associations between a history of diabetes, height, weight, body mass index and waist circumference, and the incidence of bladder cancer in the Cohort of Swedish Men, a prospective study of 45,906 men aged 45–79 years at baseline. During follow-up from 1998 through December 2007, 414 incident cases of bladder cancer were ascertained. A history of diabetes was not associated with risk of bladder cancer (multivariate rate ratio=1.16; 95% confidence interval=0.81–1.64). Similarly, no associations were observed for height, weight, body mass index or waist circumference. These findings in men do not support a role for diabetes, height or excess body mass in the aetiology of bladder cancer. [Copyright &y& Elsevier]

To evaluate the outcomes of salvage third autologous stem cell transplantation (ASCT) in patients with relapsed multiple myeloma. We analyzed 570 patients who had undergone a third ASCT between 1997 and 2010 (European Society for Blood and Marrow Transplantation data), of whom 482 patients underwent tandem ASCT and a third ASCT at first relapse (AARA group) and 88 patients underwent an upfront ASCT with second and third transplantations after subsequent relapses (ARARA group). With a median follow-up after salvage third ASCT of 61 months in the AARA group and 48 months in the ARARA group, the day +100 nonrelapse mortality in the 2 groups was 4% and 7%, the incidence of second primary malignancy was 6% and 7%, the median progression-free survival was 13 and 8 months, and median overall survival (OS) was 33 and 15 months. In the AARA group, according to the relapse-free interval (RFI) from the second ASCT, the median OS after the third ASCT was 17 months if the RFI was <18 months, 37 months if the RFI was between 18 and 36 months, and 64 months if the RFI was ≥36 months ( P  < .001). In the ARARA group, the median OS after the third ASCT was 7 months if the RFI was <6 months, 13 months if the RFI was between 6 and 18 months, and 27 months if the RFI was ≥18 months ( P  < .001). In a multivariate analysis of the AARA group, the favorable prognostic factor was an RFI after second ASCT of ≥18 months. Progressive disease and a Karnofsky Performance Status score of <70 at third ASCT were unfavorable factors. A salvage third ASCT is of value for patients with relapsed myeloma, particularly for those with a long duration of response and chemosensitive disease at the time of transplantation. [ABSTRACT FROM AUTHOR]

Background The optimal timing of endocrine therapy in non-metastatic prostate cancer (PCa) is still an issue of debate. Methods A randomised, double-blind, parallel-group trial comparing bicalutamide 150 mg once daily with placebo in addition to standard care in patients with hormone-naïve, non-metastatic PCa. Kaplan–Meier analysis was used to estimate overall survival (OS) and multivariate Cox proportional hazard model was performed to analyse time-to-event (death). Findings A total of 1218 patients were included into the Scandinavian Prostate Cancer Group (SPCG)-6 study of which 607 were randomised to receive bicalutamide in addition to their standard care and 611 to receive placebo. Median follow-up was 14.6 years. Overall, 866 (71.1%) patients died, 428 (70.5%) in the bicalutamide arm and 438 (71.7%) in the placebo arm, p = 0.87. Bicalutamide significantly improved OS in patient with locally advanced disease (hazard ratios (HR) = 0.77 (95% confidence interval (CI): 0.63–0.94, p = 0.01), regardless of baseline prostate-specific antigen (PSA), with a survival benefit which was apparent throughout the study period. In contrast, survival favoured randomisation to the placebo arm in patients with localised disease (HR = 1.19 (95% CI: 1.00–1.43), p = 0.056). However, a survival gain from bicalutamide therapy was present in patients with localised disease and a baseline PSA greater than 28 ng/mL at randomisation. In multivariate Cox proportional hazard model, only including patients managed on watchful waiting as their standard of care ( n = 991) OS depended on age, World Health Organisation (WHO) grade, baseline PSA, clinical stage and randomised treatment. Interpretation Throughout the 14.6 year follow-up period the addition of early bicalutamide to standard of care resulted in a significant OS benefit in patients with locally advanced PCa. In contrast, patients with localised PCa and low PSA derived no survival benefit from early bicalutamide. The optimal timing for initiating bicalutamide in non-metastatic PCa patients is dependent on disease stage and baseline PSA. [ABSTRACT FROM AUTHOR]

Eosinophilia has been associated with less severe graft-versus-host disease (GVHD), but the underlying mechanism is unknown. We hypothesized that eosinophils diminish allogeneic T cell activation in patients with chronic GVHD. The capacity of eosinophils derived from healthy subjects and hematopoietic stem cell (HSC) transplant recipients, with or without chronic GVHD, to reduce allogeneic T cell proliferation was evaluated using a mixed leukocyte reaction. Eosinophil-mediated inhibition of proliferation was observed for the eosinophils of both healthy subjects and patients who underwent HSC transplantation. Eosinophils from patients with and without chronic GVHD were equally suppressive. Healthy eosinophils required cell-to-cell contact for their suppressive capacity, which was directed against CD4 + T cells and CD8 + T cells. Neither eosinophilic cationic protein, eosinophil-derived neurotoxin, indoleamine 2,3-dioxygenase, or increased numbers of regulatory T cells could account for the suppressive effect of healthy eosinophils. Real-time quantitative PCR analysis revealed significantly increased mRNA levels of the immunoregulatory protein galectin-10 in the eosinophils of both chronic GVHD patients and patients without GVHD, as compared with those from healthy subjects. The upregulation of galectin-10 expression in eosinophils from patients suggests a stimulatory effect of HSC transplantation in itself on eosinophilic galectin-10 expression, regardless of chronic GVHD status. To conclude, eosinophils from HSC transplant recipients and healthy subjects have a T cell suppressive capacity. [ABSTRACT FROM AUTHOR]

Background: Hip surgery is associated with the risk of postoperative urinary retention. To avoid urinary retention hip surgery patients undergo urinary catheterisation. Urinary catheterisation, however, is associated with increased risk for urinary tract infection (UTI). At present, there is limited evidence for whether intermittent or indwelling urinary catheterisation is the preferred choice for short-term bladder drainage in patients undergoing hip surgery. Objectives: The aim of the study was to investigate differences between intermittent and indwelling urinary catheterisation in hip surgery patients in relation to nosocomial UTI and cost-effectiveness. Design: Randomised controlled trial with cost-effectiveness analysis. Setting: The study was carried out at an orthopaedic department at a Swedish University Hospital. Methods: One hundred and seventy hip surgery patients (patients with fractures or with osteoarthritis) were randomly allocated to either intermittent or indwelling urinary catheterisation. Data collection took place at four time points: during stay in hospital, at discharge and at 4 weeks and 4 months after discharge. Results: Eighteen patients contracted nosocomial UTIs, 8 in the intermittent catheterisation group and 10 in the indwelling catheterisation group (absolute difference 2.4%, 95% CI -6.9-11.6%) The patients in the intermittent catheterisation group were more often catheterised (p<0.001) and required more bladder scans (p<0.001) but regained normal bladder function sooner than the patients in the indwelling catheterisation group (p<0.001). Fourteen percent of the patients in the intermittent group did not need any catheterisation. Cost-effectiveness was similar between the indwelling and intermittent urinary catheterisation methods. Conclusions: Both indwelling and intermittent methods could be appropriate in clinical practice. Both methods have advantages and disadvantages but by not using routine indwelling catheterisation, unnecessary catheterisations might be avoided in this patient group. [ABSTRACT FROM AUTHOR]

Abstract: Background: Studies enumerating the dynamics of physical and emotional symptoms following prostate cancer (PCa) treatment are needed to guide therapeutic strategy. Yet, overcoming patient selection forces is a formidable challenge for observational studies comparing treatment groups. Objective: To compare patterns of symptom burden and distress in men with localized PCa randomized to radical prostatectomy (RP) or watchful waiting (WW) and followed up longitudinally. Design, setting, and participants: The three largest, Swedish, randomization centers for the Scandinavian Prostate Cancer Group-4 trial conducted a longitudinal study to assess symptoms and distress from several psychological and physical domains by mailed questionnaire every 6 mo for 2 yr and then yearly through 8 yr of follow-up. Intervention: RP compared with WW. Outcome measurements and statistical analysis: A questionnaire was mailed at baseline and then repeatedly during follow-up with questions concerning physical and mental symptoms. Each analysis of quality of life was based on a dichotomization of the outcome (yes vs no) studied in a binomial response, generalized linear mixed model. Results and limitations: Of 347 randomized men, 272 completed at least five questionnaires during an 8-yr follow-up period. Almost all men reported that PCa negatively influenced daily activities and relationships. Health-related distress, worry, feeling low, and insomnia were consistently reported by approximately 30–40% in both groups. Men in the RP group consistently reported more leakage, impaired erection and libido, and fewer obstructive voiding symptoms. For men in the WW group, distress related to erectile symptoms increased gradually over time. Symptom burden and distress at baseline was predictive of long-term outlook. Conclusions: Cancer negatively influenced daily activities among almost all men in both treatment groups; health-related distress was common. Trade-offs exist between physiologic symptoms, highlighting the importance of tailored treatment decision-making. Men who are likely to experience profound long-term distress can be identified early in disease management. [Copyright &y& Elsevier]

Abstract: Background: Most localized prostate cancers are believed to have an indolent course. Within 15 yr of diagnosis, most deaths among men with prostate cancer (PCa) can be attributed to other competing causes. However, data from studies with extended follow-up are insufficient to determine appropriate treatment for men with localized disease. Objective: To investigate the long-term natural history of untreated, early-stage PCa. Design, setting, and participants: We conducted a population-based, prospective-cohort study using a consecutive sample of 223 patients with untreated, localized PCa from a regionally well-defined catchment area in central Sweden. All subjects were initially managed with observation. Androgen deprivation therapy was administered when symptomatic tumor progression occurred. Outcome measurements and statistical analysis: Based on >30 yr of follow-up, the main outcome measures were: progression-free, cause-specific, and overall survival, and rates of progression and mortality per 1000 person-years. Results and limitations: After 32 yr of follow-up, all but 3 (1%) of the 223 men had died. We observed 90 (41.4%) local progression events and 41 (18.4%) cases of progression to distant metastasis. In total, 38 (17%) men died of PCa. Cause-specific survival decreased between 15 and 20 yr, but stabilized with further follow-up. All nine men with Gleason grade 8–10 disease died within the first 10 yr of follow-up, five (55%) from PCa. Survival for men with well-differentiated, nonpalpable tumors declined slowly through 20 yr, and more rapidly between 20 and 25 yr (from 75.2% [95% confidence interval, 48.4–89.3] to 25% [95% confidence interval, 22.0–72.5]). It is unclear whether these data are relevant for tumors detected by elevated prostate-specific antigen levels. Conclusions: Although localized PCa most often has an indolent course, local progression and distant metastasis can develop over the long term, even among patients considered low risk at diagnosis. [Copyright &y& Elsevier]

Abstract: Background: Although there is randomized evidence that radical prostatectomy improves survival, there are few data on how benefit varies by baseline risk. Objective: We aimed to create a statistical model to calculate the decrease in risk of death associated with surgery for an individual patient, using stage, grade, prostate-specific antigen, and age as predictors. Design, setting, and participants: A total of 695 men with T1 or T2 prostate cancer participated in the Scandinavian Prostate Cancer Group 4 trial (SPCG-4). Intervention: Patients in SPCG-4 were randomized to radical prostatectomy or conservative management. Outcome measurements and statistical analysis: Competing risk models were created separately for the radical prostatectomy and the watchful waiting group, with the difference between model predictions constituting the estimated benefit for an individual patient. Results and limitations: Individualized predictions of surgery benefit varied widely depending on age and tumor characteristics. At 65 yr of age, the absolute 10-yr risk reduction in prostate cancer mortality attributable to radical prostatectomy ranged from 4.5% to 17.2% for low- versus high-risk patients. Little expected benefit was associated with surgery much beyond age 70. Only about a quarter of men had an individualized benefit within even 50% of the mean. A limitation is that estimates from SPCG-4 have to be applied cautiously to contemporary patients. Conclusions: Our model suggests that it is hard to justify surgery in patients with Gleason 6, T1 disease or in those patients much above 70 yr of age. Conversely, surgery seems unequivocally of benefit for patients who have Gleason 8, or Gleason 7, stage T2. For patients with Gleason 6 T2 and Gleason 7 T1, treatment is more of a judgment call, depending on patient preference and other clinical findings, such as the number of positive biopsy cores and comorbidities. [Copyright &y& Elsevier]

Summary: Background: For men with localised prostate cancer, surgery provides a survival benefit compared with watchful waiting. Treatments are associated with morbidity. Results for functional outcome and quality of life are rarely reported beyond 10 years and are lacking from randomised settings. We report results for quality of life for men in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) after a median follow-up of more than 12 years. Methods: All living Swedish and Finnish men (400 of 695) randomly assigned to radical prostatectomy or watchful waiting in SPCG-4 from 1989 to 1999 were included in our analysis. An additional 281 men were included in a population-based control group matched for region and age. Physical symptoms, symptom-induced stress, and self-assessed quality of life were evaluated with a study-specific questionnaire. Longitudinal data were available for 166 Swedish men who had answered quality-of-life questionnaires at an earlier timepoint. Findings: 182 (88%) of 208 men in the radical prostatectomy group, 167 (87%) of 192 men in the watchful-waiting group, and 214 (76%) of 281 men in the population-based control group answered the questionnaire. Men in SPCG-4 had a median follow-up of 12·2 years (range 7–17) and a median age of 77·0 years (range 61–88). High self-assessed quality of life was reported by 62 (35%) of 179 men allocated radical prostatectomy, 55 (34%) of 160 men assigned to watchful waiting, and 93 (45%) of 208 men in the control group. Anxiety was higher in the SPCG-4 groups (77 [43%] of 178 and 69 [43%] of 161 men) than in the control group (68 [33%] of 208 men; relative risk 1·42, 95% CI 1·07–1·88). Prevalence of erectile dysfunction was 84% (146 of 173 men) in the radical prostatectomy group, 80% (122 of 153) in the watchful-waiting group, and 46% (95 of 208) in the control group and prevalence of urinary leakage was 41% (71 of 173), 11% (18 of 164), and 3% (six of 209), respectively. Distress caused by these symptoms was reported significantly more often by men allocated radical prostatectomy than by men assigned to watchful waiting. In a longitudinal analysis of men in SPCG-4 who provided information at two follow-up points 9 years apart, 38 (45%) of 85 men allocated radical prostatectomy and 48 (60%) of 80 men allocated watchful waiting reported an increase in number of physical symptoms; 50 (61%) of 82 and 47 (64%) of 74 men, respectively, reported a reduction in quality of life. Interpretation: For men in SPCG-4, negative side-effects were common and added more stress than was reported in the control population. In the radical prostatectomy group, erectile dysfunction and urinary leakage were often consequences of surgery. In the watchful-waiting group, side-effects can be caused by tumour progression. The number and severity of side-effects changes over time at a higher rate than is caused by normal ageing and a loss of sexual ability is a persistent psychological problem for both interventions. An understanding of the patterns of side-effects and time dimension of their occurrence for each treatment is important for full patient information. Funding: US National Institutes of Health; Swedish Cancer Society; Foundation in Memory of Johanna Hagstrand and Sigfrid Linnér. [Copyright &y& Elsevier]

Abstract: Background: Observational data indicate that retropubic radical prostatectomy (RRP) for prostate cancer (PCa) may induce inguinal hernia (IH) formation. Little is known about the influence of robot-assisted radical prostatectomy (RALP) on IH risk. Objective: To compare the incidence of IH after RRP and RALP to that of nonoperated patients with PCa and to a population control. Design, setting, and participants: We studied two groups. All 376 men included in the Scandinavian Prostate Cancer Group Study Number 4 constitute study group 1. Patients were randomly assigned RRP or watchful waiting (WW). The 1411 consecutive patients who underwent RRP or RALP at Karolinska University Hospital constitute study group 2. Men without PCa, matched for age and residence to each study group, constitute controls. Measurements: Postoperative IH incidence was detected through a validated questionnaire. The participation rates were 82.7% and 88.4% for study groups 1 and 2, respectively. Results and limitations: The Kaplan-Meier cumulative occurrence of IH development after 48 mo in study group 1 was 9.3%, 2.4%, and 0.9% for the RRP, the WW, and the control groups, respectively. There were statistically significant differences between the RRP group and the WW and control groups, but not between the last two. In study group 2 the cumulative risk of IH development at 48 mo was 12.2%, 5.8%, and 2.6% for the RRP, the RALP, and the control group, respectively. There were statistically significant differences between the RRP group and the RALP and control groups, but not between the last two. Conclusions: RRP for PCa leads to an increased risk of IH development. RALP may lower the risk as compared to open surgery. [ABSTRACT FROM AUTHOR]

Abstract: Background: Incidence of prostate cancer (PCa) has greatly increased in the Nordic region over the past two decades, following the advent of prostate-specific antigen (PSA) screening. Consequently, interpreting temporal trends in PCa has become difficult, and the impact of changes in exposure to causal factors is uncertain. Objective: To reveal geographic differences and temporal trends in PCa in the Nordic countries. Because the recorded incidence of PCa has been profoundly influenced by PSA screening, we focused our analyses primarily on PCa mortality. Design, setting, and participants: We analyzed national PCa incidence and mortality data from Denmark, Finland, Norway, and Sweden from 1965 to 2006 using the PC-NORDCAN software program and the online NORDCAN database. Measurements: Cumulative incidence and cumulative mortality from PCa were calculated for selected calendar years during four decades, along with age-standardized mortality rates. Incidence data in NORDCAN come from individual countries’ cancer registries, and mortality data come from national mortality registries. Results and limitations: From 1965 to 2006, 172 613 deaths from PCa were reported in the four Nordic countries. A substantial rise in incidence was observed across the region, with some geographic variation, since the late 1980s. In contrast, both disease-specific mortality rates and cumulative risk of PCa mortality lacked consistent temporal trends over the same period. Cumulative mortality from PCa ranged between 3.5% and 7.5% in the region over four decades, whereas cumulative incidence jumped from about 9% to >20%. Mortality has remained fairly constant among the countries, with a minimally lower risk in Finland. Conclusions: Unlike most malignancies, the occurrence of lethal PCa showed minimal geographic variation and lacked consistent temporal trends over four decades. These findings may guide our search for important causes of PCa, a malignancy with etiology that is still largely unknown. [Copyright &y& Elsevier]

Abstract: Background: Quality-of-life outcomes are important in the choice of treatment strategy for men with localized prostate cancer. Objective: To evaluate how follow-up time, number of physical symptoms, and presence of androgen deprivation affected quality of life among men randomized to radical prostatectomy or watchful waiting. Design, setting, and participants: The study group was composed of all 376 living men included in the Swedish part of the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) [1] between January 1, 1989, and February 29, 1996. Quality-of-life data were collected after a mean follow-up time of 4.1 yr. Intervention: All patients were randomly assigned to radical prostatectomy or watchful waiting. Forty-five men were androgen deprived. Measurements: Data of specific symptoms, symptom-induced stress, sense of well-being, and self-assessed quality of life were obtained by means of a questionnaire. Psychological symptoms were assessed using seven-point visual digital scales. Results and limitations: In analyses stratified on the basis of the numbers of physical symptoms, anxiety and depressed mood were less common, and sense of well-being and self-assessed quality of life were better throughout in the radical prostatectomy group than in the watchful waiting group. As the number of physical symptoms increased, all psychological variables became worse and more prominent in the watchful waiting group. After a follow-up time of 6–8 yr, a significant decrease in quality of life (p =0.03) was seen in the watchful waiting group. Twenty-four percent of androgen-deprived patients assigned to watchful waiting reported high self-assessed quality of life compared with 60% in the radical prostatectomy group. Eighty-eight percent of patients had clinically detected tumors. Conclusions: Androgen deprivation negatively affected self-assessed quality of life in men assigned to watchful waiting. The number of physical symptoms was associated with the level of quality of life. Quality of life was lower with longer follow-up time in both groups and was statistically significant in the watchful waiting group (p =0.03). [Copyright &y& Elsevier]

Objectives: To report an exploratory subgroup analysis assessing the extent to which the overall benefit found in the Early Prostate Cancer program is dependent on lymph node status at randomization. The program is ongoing, and the overall survival data are immature. The first combined analysis of the bicalutamide (Casodex) Early Prostate Cancer program at 3 years'' median follow-up showed that bicalutamide, 150 mg once daily, plus standard care (radical prostatectomy, radiotherapy, or watchful waiting), significantly reduced the risk of objective progression and prostate-specific antigen (PSA) doubling in patients with localized/locally advanced prostate cancer.Methods: Men (n = 8113) with localized/locally advanced disease received bicalutamide 150 mg or placebo once daily, plus standard care. The time to event data (objective progression, PSA doubling) was analyzed by lymph node status at randomization.Results: Compared with standard care alone, bicalutamide significantly reduced the risk of objective progression, irrespective of lymph node status, with the most pronounced reduction in patients with N+ (hazard ratio [HR] 0.29; 95% confidence interval [CI] 0.15 to 0.56) compared with those with N0 (HR 0.59; 95% CI 0.48 to 0.73) and Nx (HR 0.60; 95% CI 0.50 to 0.72) disease. The largest decrease in risk of PSA doubling with bicalutamide was observed in N+ disease (HR 0.16; 95% CI 0.09 to 0.29), with significantly reduced risks seen in N0 (HR 0.45; 95% CI 0.40 to 0.51) and Nx (HR 0.38; 95% CI 0.33 to 0.44) disease.Conclusions: The greatest reduction in the risk of objective progression and PSA doubling with bicalutamide was seen in patients with N+ disease. However, bicalutamide also provided a statistically significant benefit in those with N0 and Nx disease. [Copyright &y& Elsevier]