Coffee consumption and risk of localized, advanced and fatal prostate cancer: a population-based prospective study.

BACKGROUND: The epidemiological evidence on possible relationships between coffee consumption and prostate cancer (PCa) risk by subtype of the disease (localized, advanced) and fatal PCa risk is limited. MATERIALS AND METHODS: A population-based cohort of 44 613 Swedish men aged 45-79 years was followed up from January 1998 through December 2010 for incidence of localized (n = 2368), advanced (n = 918) and fatal (n = 515) PCa. We assessed the associations between coffee consumption and localized, advanced and fatal PCa risk using competing-risk regressions. We examined possible effect modification by body mass index (BMI). RESULTS: For localized PCa, each one cup increase in daily coffee consumption was associated with a 3% reduced risk [sub-hazard ratio (SHR) = 0.97, 95% confidence interval (CI) = 0.95-0.99]. For advanced and fatal PCa, we found a non-significant inverse association; each one cup increase was associated with a 2% reduced risk of advanced [SHR (95% CI) = 0.98 (0.95-1.02)] and fatal PCa [SHR (95% CI) = 0.98 (0.93-1.03)]. We observed evidence of effect modification by BMI for localized PCa (Pinteraction = 0.03); the inverse association was stronger among overweight and obese men (BMI ≥ 25 kg/m(2)) compared with normal-weight men (BMI < 25 kg/m(2)). CONCLUSIONS: We observed a clear inverse association between coffee consumption and risk of localized PCa, especially among overweight and obese men.

Thoracic epidural analgesia inhibits the neuro-hormonal but not the acute inflammatory stress response after radical retropubic prostatectomy.

BACKGROUND: Epidural anaesthesia and analgesia has been shown to suppress the neuro-hormonal stress response, but its role in the inflammatory response is unclear. The primary aim was to assess whether the choice of analgesic technique influences these processes in patients undergoing radical retropubic prostatectomy. METHODS: Twenty-six patients were randomized to Group P (systemic opioid-based analgesia) or Group E (thoracic epidural-based analgesia) perioperatively. Induction and maintenance of anaesthesia followed a standardized protocol. The following measurements were made perioperatively: plasma cortisol, glucose, insulin, C-reactive proteins, leucocyte count, plasma cytokines [interleukin (IL)-6, tumour necrosis factor (TNF)-α], and pokeweed mitogen-stimulated cytokines [interferon (IFN)-γ, IL-2, IL-12p70, IL-10, IL-4, and IL-17]. Other parameters recorded were pain, morphine consumption, and perioperative complications. RESULTS: Plasma concentration of cortisol and glucose were significantly higher in Group P compared with Group E at the end of surgery, the mean difference was 232 nmol litre(-1) [95% confidence interval (CI) 84-381] (P=0.004) and 1.6 mmol litre(-1) (95% CI 0.6-2.5) (P=0.003), respectively. No significant differences were seen in IL-6 and TNF-α at 24 h (P=0.953 and 0.368, respectively) and at 72 h (P=0.931 and 0.691, respectively). IL-17 was higher in Group P compared with Group E, both at 24 h (P=0.001) and 72 h (P=0.018) after operation. Pain intensity was significantly greater in Group P compared with Group E (P<0.05) up to 24 h. CONCLUSIONS: In this small prospective randomized study, thoracic epidural analgesia reduced the early postoperative stress response but not the acute inflammatory response after radical retrobupic prostatectomy, suggesting that other pathways are involved during the acute phase reaction.

Dietary cadmium exposure and prostate cancer incidence: a population-based prospective cohort study.

BACKGROUND: Experimental data convincingly propose the toxic metal cadmium as a prostate carcinogen. Cadmium is widely dispersed into the environment and, consequently, food is contaminated. METHODS: A population-based cohort of 41 089 Swedish men aged 45-79 years was followed prospectively from 1998 through 2009 to assess the association between food frequency questionnaire-based estimates of dietary cadmium exposure (at baseline, 1998) and incidence of prostate cancer (3085 cases, of which 894 were localised and 794 advanced) and through 2008 for prostate cancer mortality (326 fatal cases). RESULTS: Mean dietary cadmium exposure was 19 µg per day±s.d. 3.7. Multivariable-adjusted dietary cadmium exposure was positively associated with overall prostate cancer, comparing extreme tertiles; rate ratio (RR) 1.13 (95% confidence interval (CI): 1.03-1.24). For subtypes of prostate cancer, the RR was 1.29 (95% CI: 1.08-1.53) for localised, 1.05 (95% CI: 0.87-1.25) for advanced, and 1.14 (95% CI: 0.86-1.51) for fatal cases. No statistically significant difference was observed in the multivariable-adjusted risk estimates between tumour subtypes (P(heterogeneity)=0.27). For localised prostate cancer, RR was 1.55 (1.16-2.08) among men with a small waist circumference and RR 1.45 (1.15, 1.83) among ever smokers. CONCLUSION: Our findings provide support that dietary cadmium exposure may have a role in prostate cancer development.

Thoracic epidural analgesia or patient-controlled local analgesia for radical retropubic prostatectomy: a randomized, double-blind study.

BACKGROUND: Postoperative pain after radical retropubic prostatectomy is moderate to severe. The primary aim of this study was to assess whether intra-abdominal local anaesthetics provide similar analgesia compared with thoracic epidural analgesia (TEA). METHODS: Fifty patients, ASA I-II, participated in this prospective, double-blinded study. All patients had TEA. After operation, they were randomized into two groups of 25 patients: Group PCLA (patient-controlled local analgesia): self-administration of 10 ml of ropivacaine 2 mg ml⁻¹ via the intra-abdominal catheter for 48 h. Group TEA: infusion of 10 ml h⁻¹ of ropivacaine 1 mg ml⁻¹, fentanyl 2 µg ml⁻¹, and epinephrine 2 µg ml⁻¹ epidurally for 48 h. The primary endpoint was pain on coughing at 4 h after operation. Rescue medication was morphine i.v. as required. RESULTS: Pain on coughing at 4, 24, and 48 h was significantly lower in Group TEA [0 (0-10)] compared with Group PCLA [4 (0-10)] (P<0.05). Significantly lower pain intensity was also found in Group TEA compared with Group PCLA at the incision site, deep pain, and pain on coughing at 4 and 24 h (P<0.05). Morphine consumption was significantly greater in Group PCLA [12 (0-46)] compared with Group TEA [0 (0-20)] at 0-48 h after operation [median (range)] (P=0.015). Maximum expiratory pressure was higher in Group TEA compared with Group PCLA at 24 h (P<0.01). CONCLUSIONS: TEA provides superior postoperative pain relief with better preservation of expiratory muscle strength compared with PCLA.

Body mass index in early and middle-late adulthood and risk of localised, advanced and fatal prostate cancer: a population-based prospective study.

BACKGROUND: The relationships between body mass index (BMI) during early and middle-late adulthood and incidence of prostate cancer (PCa) by subtype of the disease (localised, advanced) and fatal PCa is unclear. METHODS: A population-based cohort of 36,959 Swedish men aged 45-79 years was followed up from January 1998 through December 2008 for incidence of PCa (1530 localised and 554 advanced cases were diagnosed) and through December 2007 for PCa mortality (225 fatal cases). RESULTS: From a competing-risks analysis, incidence of localised PCa was observed to be inversely associated with BMI at baseline (middle-late adulthood; rate ratio (RR) for 35 kg m(-2) when compared with 22 kg m(-2) was 0.69 (95% CI 0.52-0.92)), but not at age 30. For fatal PCa, BMI at baseline was associated with a nonstatistically significant increased risk (RR for every five-unit increase: 1.12 (0.88-1.43)) and BMI at age 30 with a decreased risk (RR for every five-unit increase: 0.72 (0.51-1.01)). CONCLUSION: Our results indicate an inverse association between obesity during middle-late, but not early adulthood, and localised PCa. They also suggest a dual association between BMI and fatal PCa--a decreased risk among men who were obese during early adulthood and an increased risk among those who were obese during middle-late adulthood.

A prospective study of lifetime physical activity and prostate cancer incidence and mortality.

BACKGROUND: The possible benefit of lifetime physical activity (PA) in reducing prostate cancer incidence and mortality is unclear. METHODS: A prospective cohort of 45,887 men aged 45-79 years was followed up from January 1998 to December 2007 for prostate cancer incidence (n=2735) and to December 2006 for its subtypes and for fatal (n=190) prostate cancer. RESULTS: We observed an inverse association between lifetime (average of age 30 and 50 years, and baseline age) total PA levels and prostate cancer risk. Multivariate-adjusted incidence in the top quartile of lifetime total PA decreased by 16% (95% confidence interval (CI)=2-27%) compared with that in the bottom quartile. We also observed an inverse association between average lifetime work or occupational activity and walking or bicycling duration and prostate cancer risk. Compared with men who mostly sit during their main work or occupation, men who sit half of the time experienced a 20% lower risk (95% CI=7-31%). The rate ratio linearly decreased by 7% (95% CI=1-12%) for total, 8% (95% CI=0-16%) for localised and 12% (95% CI=2-20%) for advanced prostate cancer for every 30 min per day increment of lifetime walking or bicycling in the range of 30 to 120 min per day. CONCLUSIONS: Our results suggest that not sitting for most of the time during work or occupational activity and walking or bicycling more than 30 min per day during adult life is associated with reduced incidence of prostate cancer.

Incidence and mortality of incidental prostate cancer: a Swedish register-based study.

In a national register-based study of incidence trends and mortality of incidental prostate cancer in Sweden, we found that a significant proportion (26.6%) of affected men diagnosed died of their disease, which challenges earlier descriptions of incidental prostate cancer as a non-lethal disease.

Deletion polymorphism of the UGT2B17 gene is associated with increased risk for prostate cancer and correlated to gene expression in the prostate.

Metabolism of androgens includes glucuronidation, the major pathway of steroid elimination in several steroid target tissues. Glucuronidation is catalysed by UDP-glucuronosyltransferases (UGTs). UGT2B17 has been shown to be particularly active against androgens and is highly abundant in the prostate. Recently, we discovered that deletion of the UGT2B17 gene is associated with low or undetectable urinary testosterone levels. Here, we determined the phenotypic outcome of the deletion by quantifying the UGT2B17 mRNA expression in normal prostate tissues in individuals with different genotypes. Additionally, the frequency of UGT2B17 deletion polymorphism was studied in a Swedish population-based case-control study including 176 patients diagnosed with prostate cancer and 161 controls. We found that the individuals homozygous for the insertion allele expressed 30 times more UGT2B17 mRNA in prostate tissue than the heterozygotes. Carriers of the deletion allele had a significantly increased risk of prostate cancer (OR=2.07; 95% CI=1.32-3.25). In conclusion, these results show the UGT2B17 deletion polymorphism is associated with prostate cancer risk.

MUC-1 gene is associated with prostate cancer death: a 20-year follow-up of a population-based study in Sweden.

Anti-adhesion mucins have proven to play an important part in the biology of several types of cancer. Therefore, we test the hypothesis that altered expression of MUC-1 is associated with prostate cancer progression. We retrieved archival tumour tissue from a population-based cohort of 195 men with localised prostate cancer (T1a-b, Nx, M0) that has been followed for up to 20 years with watchful waiting. Semi-automated, quantitative immunohistochemistry was undertaken to evaluate MUC-1 expression. We modelled prostate cancer-specific death as a function of MUC-1 levels accounting for age, Gleason grade and tumour extent, and calculated age-adjusted and multivariate adjusted hazard ratios (HR). Men that had tumours with an MUC-intensity lower or higher than normal tissue had a higher risk of dying in prostate cancer, independent of tumour extent and Gleason score (HR 5.1 and 4.5, respectively). Adjustment for Gleason grade and tumour stage did not alter the results. Men with a Gleason score > or =7 and MUC-1 deviating from the normal had a 17 (RR=17.1 95% confidence interval=2.3-128) times higher risk to die in prostate cancer compared with men with Gleason score <7 and normal MUC-1 intensity. In summary, our data show that MUC-1 is an independent prognostic marker for prostate cancer death.

TMPRSS2:ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort.

The identification of the TMPRSS2:ERG fusion in prostate cancer suggests that distinct molecular subtypes may define risk for disease progression. In surgical series, TMPRSS2:ERG fusion was identified in 50% of the tumors. Here, we report on a population-based cohort of men with localized prostate cancers followed by expectant (watchful waiting) therapy with 15% (17/111) TMPRSS2:ERG fusion. We identified a statistically significant association between TMPRSS2:ERG fusion and prostate cancer specific death (cumulative incidence ratio=2.7, P<0.01, 95% confidence interval=1.3-5.8). Quantitative reverse-transcription-polymerase chain reaction demonstrated high ets-related [corrected] gene (ERG) expression to be associated with TMPRSS2:ERG fusion (P<0.005). These data suggest that TMPRSS2:ERG fusion prostate cancers may have a more aggressive phenotype, possibly mediated through increased ERG expression.

'If only I manage to get home I'll get better'--interviews with stroke patients after emergency stay in hospital on their experiences and needs.

OBJECTIVE: To find out about the experiences of stroke patients concerning their falling ill, their stay in hospital, discharge and homecoming. DESIGN: Qualitative methods using in-depth interviews. SUBJECTS AND SETTING: Nine strategically chosen patients and in five cases near family members were interviewed in their homes four months post stroke and following care at the Stroke Centre, University Hospital of Northern Sweden, Umeå. RESULTS: Three main categories with subcategories were brought to the fore from the interviews: 'Responsible and implicated', 'Depersonalized object for caring measures' and 'The striving for repersonalization and autonomy'. The patients got the most important insights and understanding about their state and the consequences when they came home. CONCLUSION: The three main categories that were found mirror the crisis which becoming ill entails and the process gone through when the individual takes control again of his or her life. The patients saw coming home as an important factor for their recovery and rehabilitation. The health care system needs to develop strategies to make use of the power of this attitude with the patients and to use the patients' own milieu in rehabilitation after stroke.

Sexual function and satisfaction in men after laser treatment for penile carcinoma.

PURPOSE: We evaluate sexual function, sexual satisfaction and cosmetic results after laser treatment of penile carcinoma. MATERIALS AND METHODS: A total of 67 patients were treated at our clinic for penile cancer using combined carbon dioxide and neodymium:YAG lasers from 1986 to 2000. At the time of this study 58 men, with a mean age of 64 years were alive, of whom 46 (79%) agreed to participate in a structured face-to-face interview addressing sexual function, sexual satisfaction and cosmetic results. The length of time that had elapsed since treatment ranged from 6 months to 15 years (median 3 years). RESULTS: Of 40 patients (87%) who had been sexually active before treatment 30 (75%) had resumed activities at the time of the interview. Unaltered erectile function after treatment was reported by 33 patients (72%), 10 patients (22%) reported decreased function and 3 (6%) reported improved function. Of the 46 patients 23 (50%) were satisfied/very satisfied with their sexual life. After treatment only 3 of 30 (10%) of the evaluable men had dyspareunia. The cosmetic results were considered satisfying/very satisfying by 36 (78%) men. CONCLUSIONS: Laser treatment of localized penile carcinoma preserves the penis and generally provides satisfactory sexual function and cosmetic results.

Efficacy of epoetin beta on hemoglobin, quality of life, and transfusion needs in patients with anemia due to hormone-refractory prostate cancer--a randomized study.

OBJECTIVE: Erythropoietin is shown to be an effective treatment for anemia in various types of cancers, however only limited studies have evaluated its benefits in advanced hormone-refractory prostate cancer (HRPC). This multi-center study investigated the influence of 2 different doses of epoetin beta on quality of life, hemoglobin level, need for blood transfusion, and safety, in the treatment of anemia in patients with metastatic HRPC. MATERIALS AND METHODS: This study randomized 180 patients to receive either epoetin beta 1000 IU or 5000 IU subcutaneously 3 times per week for 12 weeks. Hemoglobin was evaluated at study start and 6 time-points during the study. Quality of life (QoL) was assessed by the European Organization for Research and Treatment of Cancer questionnaire, QLC-C30, before treatment start and after 6 and 12 weeks of treatment. Best supportive care and blood transfusions were given, if clinically indicated. Additional laboratory values and adverse events were followed for safety. RESULTS: Hemoglobin increased significantly (>20 g/l) in 43% in the high dose (HD) group and 25% in the low dose (LD) group in response to treatment. Levels were significantly higher in the HD group than the LD group (p < 0.001) after 8 and 12 weeks. QoL improved significantly if the increase in hemoglobin was >20 g/l. Significantly more patients in the LD group received blood transfusions than the HD group (p < 0.005). There were no differences between the groups regarding overall quality of life and fatigue. The treatment was well tolerated in both groups. CONCLUSIONS: Epoetin beta is shown to be safe and effective for the treatment of anemia in many patients with HRPC. It is found to improve QoL and physical functioning, and relieve fatigue symptoms, in many of these critically ill patients.

Can measurements of IGF-1 and IGFBP-3 improve the sensitivity of prostate-cancer screening?

Further well designed studies are urgently needed to clarify if use of prostate-specific antigen (PSA) as a diagnostic test for prostate cancer can be improved by incorporating measurements of serum insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding-protein 3 (IGFBP-3), and if these measurements might also identify men at higher risk.

Follow-up of prostate cancer patients by on-demand contacts with a specialist nurse: a randomized study.

OBJECTIVE: The effectiveness of traditional follow-up programs and the intensive search for disease progression in men with prostate cancer have been questioned. The aims of this randomized multi-centre study were to evaluate medical safety, patient satisfaction and resource utilization in an on-demand follow-up by a specialist nurse compared with traditional follow-up by a urologist. MATERIAL AND METHODS: Four hundred consecutively approached men with newly diagnosed or previously known prostate cancer in any stage at three hospitals in Sweden were randomized to follow-up in the nurse group (NG, 200 patients) or the urologist group (UG, 200 patients). In the NG, the nurse contacted the patient by phone every 6 months unless the patient himself initiated the contact. Patient satisfaction was evaluated twice a year via questionnaire. The questionnaire included the validated Hospital Anxiety and Depression Scale (HADS). The costs of all medical interventions and adverse events related to prostate cancer were calculated for all patients. RESULTS: Medical safety, measured as complication frequency and lag time from symptoms to intervention, during the first 3 years of the observation period, was similar in the NG and the UG. The total number of interventions due to symptoms from prostate cancer was also similar in both groups. The analysis of accessibility and the HAD scale showed no significant differences between the groups. The mean outpatient cost (excluding pharmaceutical costs) per patient was lower in the NG compared to the UG, especially among patients without metastases at inclusion (37% lower cost). CONCLUSIONS: Our study indicates that men with prostate cancer can be safely followed up by a specialist nurse. The study results show that this alternative follow-up is cost-effective, especially in men without metastases.

Effects of consulting psychiatrist in primary care. 1-year follow-up of diagnosing and treating anxiety and depression.

OBJECTIVE: Epidemiological screening of anxiety and depressive disorders in primary care and evaluation of how these patients are identified and treated. Follow-up after 1 year of psychiatric consultation/liaison (C/L) and educational activities. SUBJECTS AND DESIGN: In the baseline study 374 unselected and consecutive patients, and in the follow-up study 254 patients (response rate 94.5% and 90.3%, respectively) answered the screening instrument HAD scale (Hospital Anxiety and Depression scale). The HAD results were compared to clinical diagnosis and treatment according to the medical records. Differences after 1 year were analysed. RESULTS: At follow-up the prevalence of anxiety had increased from 11.8% to 16.5% (p < 0.05), and of depression from 3.7% to 4.7% (NS) according to HAD. Also, at the follow-up more cases of anxiety disorders were clinically diagnosed--13% vs 8%--as well as an increased number of cases of depressive disorders--7.9% vs 4.0%. The agreement between HAD diagnosis and clinical judgement had increased significantly (p < 0.001) for anxiety disorders from 37% to 70%, and for depression from 20% to 45%. Treatment prevalence had also improved (p < 0.001) at the follow-up for anxiety disorders from 33% to 55% and for depression from 47% to 80%. In total, 4.0% of the baseline and 11.4% of the follow-up population were treated for anxiety and/or depression. CONCLUSIONS: Anxiety and depressive disorders are prevalent in primary care. However, only a minority of these patients are identified and treated. Psychiatric consultant support seems to be effective in improving GP's diagnostic and therapeutic skills thus enabling these widespread disorders to be identified at an early stage and properly treated.

Polymorphisms in NAT2, CYP2D6, CYP2C19 and GSTP1 and their association with prostate cancer.

The development of prostate cancer is dependent on heredity, androgenic influences, and exposure to environmental agents. A high intake of dietary fat is associated with an increased risk of prostate cancer, either through influence on steroid hormone profiles or through production of carcinogenic compounds that require biotransformation by enzymes. The polymorphic glutathione S-transferase (GST), N-acetyltransferase (NAT), and cytochrome P450 (CYP) enzymes are of particular interest in prostate cancer susceptibility because of their ability to metabolize both endogenous and exogenous compounds, including dietary constituents. Association between different NAT2, CYP2D6, CYP2C19 and GSTP1 genotypes and prostate cancer was studied in a Swedish and Danish case-control study comprising 850 individuals. The combined Swedish and Danish study population was analysed by polymerase chain reaction for the NAT2 alleles *4, *5A, *5B, *5C, *6 and *7, and for the CYP2D6 alleles *l, *3 and *4. The Swedish subjects were also analysed for the CYP2C19 alleles *1 and *2, and the GSTP1 alleles *A, *B and *C. No association was found between prostate cancer and polymorphisms in NAT2, CYP2D6, CYP2C19 or GSTP1. An association between CYP2D6 poor metabolism and prostate cancer was seen among smoking Danes; odds ratio 3.10 (95% confidence interval 1.07; 8.93), P = 0.03, but not among smoking Swedes; odds ratio 1.19 (95% confidence interval 0.41; 3.42), P = 0.75. Smoking is not a known risk factor for prostate cancer, and the association between CYP2D6 poor metabolism and prostate cancer in Danish smokers may have arisen by chance.

Insulin-like growth factor 1 and prostate cancer risk: a population-based, case-control study.

BACKGROUND: Recent epidemiologic investigations have suggested an association between increased blood levels of insulin-like growth factor 1 (IGF-1) and increased risk of prostate cancer. Our goal was to determine whether an association exists between serum levels of IGF-1 and one of its binding proteins, insulin-like growth factor-binding protein 3 (IGFBP-3), and prostate cancer risk. METHODS: An immunoradiometric assay was used to quantify IGF-1 levels and IGFBP-3 levels in serum samples as part of a population-based, case-control study in Sweden. The study population comprised 210 patients with newly diagnosed, untreated prostate cancer and 224 frequency-matched control subjects. Data were analyzed by use of unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Reported P values are two-sided. RESULTS: The mean serum IGF-1 level for case patients (158.4 ng/mL) was significantly higher than that for control subjects (147.4 ng/mL) (P = .02); corresponding mean serum IGFBP-3 levels were not significantly different between case patients (2668 ng/mL) and control subjects (2518 ng/mL) (P =.09). We found a moderately strong and statistically significant (P = .04) positive association between serum levels of IGF-1 levels and risk of prostate cancer (OR = 1.51; 95% CI = 1.0-2.26 per 100 ng/mL increment); the association was particularly strong for men younger than 70 years of age (OR = 2.93; 95% CI = 1.43-5.97). No association was found between serum IGF-1 levels and disease stage. Serum IGFBP-3 levels were not significantly associated with increased risk of disease, and adjustment for IGFBP-3 had little effect on the association between IGF-1 levels and risk of prostate cancer. CONCLUSION: Elevated serum IGF-1 levels may be an important predictor of risk for prostate cancer. However, our results do not support an important role for serum IGFBP-3 as a predictor of risk for this disease.