Access to information and expectations of treatment decisions for prostate cancer patients--results of a European survey.

We surveyed patients in France, Germany, Italy, Spain and Poland to examine information requirements and expectations of patients with prostate cancer. Patients were identified via their healthcare teams or via existing databases and interviewed by telephone, or in face-to-face interviews (Italy). Survey questions were either multiple choice or rank-based, and additional information was available to assist patient comprehension. Overall, 80% of patients received information about prostate cancer at diagnosis and 76% rated their physician as the most useful information source. However, around a third of French and German patients did not receive any information about their condition at diagnosis, compared with 8%, 12% and 10% of Spanish, Italian and Polish patients, respectively. Most patients rated the information they received as 'very informative', but there were regional variations, with German patients being the least satisfied with the quality of information received. Despite receiving the least amount of information at diagnosis, more patients from France and Germany preferred to be involved in treatment decisions than patients from Spain, Italy and Poland. Results from this survey highlight important gaps in information provision for patients with prostate cancer in terms of information supplied and patient expectations regarding treatment decisions.

Improving the management of patients with prostate cancer receiving long-term androgen deprivation therapy.

In many patients with prostate cancer, androgen deprivation therapy (ADT) is administered over prolonged periods of time. The benefits of long-term ADT in patients with advanced disease are well established and, more recently, studies have shown that long-term adjuvant ADT used in combination with radiotherapy improves survival in patients with earlier stages of disease. Nevertheless, clinicians should remain aware of the potential long-term side effects of ADT and the strategies that can be used to manage or prevent long-term complications. One such strategy is intermittent androgen deprivation (IAD), in which patients receive cycles of ADT, the duration of which is usually determined by PSA levels. Accumulating data indicate that this approach improves the tolerability of ADT (particularly sexual dysfunction) and patients' quality of life, without compromising clinical outcomes (progression and survival). Indeed, the latest European Association of Urology guidelines state that IAD should no longer be considered investigational. Nevertheless, some questions remain unanswered, including: who are the most suitable patients for IAD and what are the optimal PSA levels for stopping and restarting treatment? Osteoporosis (and the resultant increased risk of fractures) is a well-recognized complication of long-term ADT. Bone mineral density should be measured before and during long-term ADT and patients advised to make appropriate lifestyle changes to help preserve bone health. Pharmacological intervention is also an option. Denosumab (an NF-κB ligand inhibitor) significantly reduces ADT-induced bone loss and the risk of fractures in patients with non-metastatic disease. In those whose disease has metastasized, zoledronate and denosumab are licensed to prevent skeletal-related events and a large randomized study has shown that denosumab is more effective than zoledronate in this setting.

Erectile dysfunction and cardiovascular diseases.

Erection is a vascular phenomenon under a psychologic control in a hormonal environment. Erectile dysfunction is defined as the inability to obtain and to maintain sufficient erection for satisfactory intercourse. Organic erectile dysfunction results mainly from vascular problems due to atherosclerosis, a process that begins during childhood, and becomes clinically evident from middle age. Endothelial dysfunction is the first step of atherosclerosis. As the endothelial cells recover the sinusoid spaces in the cavernous tissue and because common risk factors for atherosclerosis have been frequently found in patients with erectile dysfunction, it is logical that vascular impotence presents the same pathophysiology of the other vascular diseases. They share a similar pathogenic involvement of nitric oxide pathway leading to impairment of endothelium dependent vasodilatation and structural vascular abnormalities. Circulating markers of endothelial cell damage have been reported in patients with erectile dysfunction while they have not yet presented any other vascular pathology. Endothelial progenitor cells of bone marrow origin that play a role in promoting endothelial repair are also reduced in vascular abnormalities.As penile arteries have the smallest diameter in the vascular network and because atherosclerosis is a systemic disease, erectile dysfunction could be a sentinel symptom of a more generalized vascular pathology. Modifications of reversible causes or risk factors at the base of the pathogenesis of atherosclerosis remain the first approach toward improving endothelial function and associated with chronic exposure to PDE5-I, they could improve or even cure ED and could avoid fatal cardiovascular attacks in the future.

Testosterone and prostate safety.

For several decades it has been assumed that higher testosterone (T) leads to greater growth of benign and malignant prostate tissue, but this view has come under greater scrutiny over the last several years. Although there are as yet no large-scale, long-term controlled studies of T therapy to provide a definitive assessment of risk, numerous smaller clinical trials as well as population-based longitudinal studies consistently fail to support the historical idea that T therapy poses an increased risk of prostate cancer or exacerbation of symptoms due to benign prostatic hyperplasia. This lack of prostate risk despite increased serum T appears to be explained by data showing that exogenous T does not raise intraprostatic concentrations of T or dihydrotestosterone, suggesting a saturation model. In contrast, there is mounting evidence that low serum T is associated with greater prostate cancer risk, and more worrisome features of prostate cancer. In conclusion, the available evidence strongly suggests that T therapy is safe for the prostate. Given that the population at risk for T deficiency overlaps with the population at risk for prostate cancer, it is strongly recommended that men undergoing T therapy undergo regular monitoring for prostate cancer.

[Decrease ApoB/ApoA-1 ratio and cardiovascular risk improvement: a tadalafil pleiotropic effect? Preliminary study on healthy volunteers]. / Diminution du rapport ApoB/ApoA-1 et amélioration du risque cardiovasculaire : effet pleïotropique du tadalafil ? Etude préliminaire sur volontaires sains.

OBJECTIVES: Recognition of erectile dysfunction (ED) as an early sign of systemic cardiovascular disease offers an opportunity for prevention. Cardiac risk assessment may deserve measurement of Apolipoprotein B/Apolipoprotein A-1 ratio. An elevated ApoB/ApoA-1 ratio is a risk factor for future coronary artery disease. ApoA-1 production, which is recognized as a cardioprotective lipid fraction, is down regulated by NFkappaB activation in vitro. Because inhibition of phosphodiesterases (PDEs) 5, 6 and 9 negatively attenuates NFkappaB translocation/activation, tadalafil, a selective PDE 5 inhibitor used for treatment of ED could present some interesting pleiotropic effects. The objective of this open study is to test the hypothesis that tadalafil treatment could decrease serum ApoB/ApoA-1 ratio. MATERIAL AND METHODS: Ten healthy men without any complain of ED or known cardiovascular risk factors were administered tadalafil 10mg intake on alternate days for 4 weeks. Lipid profile with total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, ApoA-1 and ApoB, was assessed at baseline (T0), after 2weeks (T1), at the end of the treatment period (T2) and after 2weeks of wash-out follow-up (T3). RESULTS: ApoB/ApoA-1 ratio was significantly decreased during treatment (mean+/-SEM, T0: 0.80+/-0.11, T1: 0.64+/-0.06, T2: 0.65+/-0.06; p<0.05) and remained lower after wash-out (T3: 0.67+/-0.05; p=0.08). Serum ApoA-1 (mg/dl) increased but not significantly during the treatment period (15.2+/-8.8, 16.5+/-7.9, 16.9+/-6, 15.3+/-7, p=0.26) and ApoB (mg/dl) significantly decreased (11.7+/-10.8, 10.3+/-8.4, 10.6+/-9.9, 10.2+/-8.6, p=0.03). HDL and LDL cholesterol were unchanged. CONCLUSION: This preliminary study showed the interest of PDE 5 inhibitors to decrease the cardiac risk factor ApoB/ApoA-1 ratio. Randomised controlled studies with longer follow-up are needed to confirm those results.

Is there an optimal time for laparoscopic cholecystectomy in acute cholecystitis?

BACKGROUND: Laparoscopic cholecystectomy (LC) is safe in acute cholecystitis, but the exact timing remains ill-defined. This study evaluated the effect of timing of LC in patients with acute cholecystitis. METHODS: Prospective data from the hospital registry were reviewed. All patients admitted with acute cholecystitis from June 1994 to January 2004 were included in the cohort. RESULTS: Laparoscopic cholecystectomy was attempted in 1,967 patients during the study period; 80% were women, mean patient age was 44 years (range, 20-73 years). Of the 1,967 LC procedures, 1,675 were successful, and 292 were converted to an open procedure (14%). Mean operating time for LC was 1 h 44 min (SD +/- 50 min), versus 3 h 5 min (SD +/- 79 min) when converted to an open procedure. Average postoperative length of stay was 1.89 days (+/- 2.47 days) for the laparoscopic group and 4.3 days (+/- 2.2 days) for the conversion group. No clinically relevant differences regarding conversion rates, operative times, or postoperative length of stay were found between patients who were operated on within 48 h compared to those patients who were operated on post-admission days 3-7. CONCLUSIONS: The timing of laparoscopic cholecystectomy in patients with acute cholecystitis has no clinically relevant effect on conversion rates, operative times, or length of stay.

The SceneScore for improved pre-hospital triage of motor-vehicle crash victims.

The SceneScore is a simple mechanism of injury scoring system designed to facilitate the appropriate triage of crash victims. It comprises 7 variables including age, collision type, impact location, airbag deployment, steering wheel deformity, intrusion, and restraint use. A cutoff value of 7 or 8 provides the maximum balance between sensitivity and specificity, with sensitivities of 75% to 83% and specificities of 29% to 46%. For cases triaged to the trauma center based only on high suspicion of injury, the SceneScore reduces the overtriage rate by almost half. Proper application of the SceneScore may lead to improved triage and enhanced communication of mechanism of injury criteria.

Pyogenic liver abscess after gunshot injury: 10 years' experience at a single level 1 trauma center.

OBJECTIVES: Liver abscesses are approximately 50 % of all visceral abscesses, and trauma presents as a rare cause of the liver abscess. Otherwise, hepatic abscess is an uncommon complication of gunshot wound (GSW) to the liver among all trauma cases. Here we reviewed their experience in detail. METHOD: From January 1, 2004 to September 30, 2013, there were 2143 patients admitted to Ryder Trauma Center at Jackson Memorial Hospital/University of Miami with severe abdominal trauma: 1227 penetrating and 866 blunt. Among the patients who had penetrating trauma, 637 had GSWs and 551 had stab wounds. Thirty-nine patients had other kinds of penetrating traumas. Eleven patients were identified as having liver abscess, with 8 of them belonging to the GSW group, and 3 to the blunt injury group. The diagnosis and management of the 8 patients with a hepatic abscess after GSW to the liver were demonstrated. RESULT: There were seven males and one female with a mean age of 29 ± 10 years. There were one grade 2, four grade 3, two grade 4 and one grade 5 injuries. The mean abscess size was 10 ± 2 cm. The abscesses were usually caused by infection from mixed organisms. These abscesses were treated with antibiotics and drainage. No mortality and long-term morbidity were seen. CONCLUSION: Hepatic abscess after GSW to the liver is a rare condition, with an incidence of 1.2 %. It is usually seen in severe liver injury (grade 3 and above), but our patients were all treated successfully, with no mortality.

The quiz electrocardiogram: a new diagnostic and research technique for evaluating the relation between emotional stress and ischemic heart disease.

To evaluate possible cardiovascular effects of emotional stress, a specially designed 12 minute tape-recorded stress quiz was administered to 43 subjects while blood pressure and the electrocardiogram were monitored. For the entire group, the heart rate and blood pressure rose from respective control levels of 76 beats/min and 136/87 mm Hg to a mean during the quiz of 87 beats/min and 158/94 mm Hg. This difference was highly significant. Of the 43 subjects, 33 were classified as executives and 10 as nonexecutives. There were three groups of executives: control and angina with and without a history of hypertension. Both groups of executives with angina responded with a significantly higher heart rate than that of the executive control group. Blood pressure response was significantly greater in executives with angina and hypertension than in the other groups. Heart rate and systolic blood pressure responses to the quiz were lower in nonexecutives with angina than in executives with angina. During the quiz, 10 of 14 executives with angina had S-T segment depression greater than 0.5 mm; of these, 7 evidenced greater than 1.0 mm depression, andin 3 of these the depression was greater than 1.5 mm and in 2 greater than or equal to 2.0 mm. None of the executive control subjects had S-T depression greater than 0.5 mm Among nonexecutives, 2 had S-T depression greater than 0.5 mm but none greater than 1.0 mm S-T depression. Seventeen of the patients also were given a bicycle exercise tolerance test. There was a significant correlation between S-T depression in response to exercise and to the quiz (r = 0.63; P less than 0.01). The quiz electrocardiogram is presented as a new research technique and diagnostic test for evaluating the relation of emotional stress to ischemic heart disease.

Mxt mammary-tumor treatment with a high-temperature radiofrequency ablation device.

A special catheter with a deploying needle was used to treat MXT mouse mammary tumors transplanted onto the flanks of B6D2F1 mice. The catheter was connected to a radiofrequency generator. Treatment was applied for five minutes, with central tumor temperatures reaching over 100 degrees C. Histopathological examination revealed extensive localized, reproducible and controlled necrosis of the tumors in animals sacrificed at days 5 and 15 after treatment. The effectiveness of this device against MXT tumor growth was enhanced when a combination of radiofrequency and intraperitoneal chemotherapy (9 injections of adriamycin, etoposide and cyclophosphamide) was administered. This study demonstrates the effectiveness and reproducibility of tumor destruction and the increase in effectiveness of chemotherapy effects by radiofrequency heating.

In-vitro characterization of dihydrotestosterone-induced, epidermal growth factor-induced and basic fibroblastic growth factor-induced modifications in the growth dynamics of the human prostate-cancer cell-line lncap, du145 and pc3.

The influence of dihydrotestosterone (DHT), the epithelial growth factor (EGF) and the basic fibroblast growth factor (bFGF) was investigated on LNCaP, DU145 and PC3 cell growth, which represents the ratio between cell gain (cell proliferation) and cell loss (cell death). In the present study, cell growth was assessed by means of the computer-assisted microscope analysis of Feulgen-stained nuclei combined with the mathematical Delaunay triangulation and Voronoi paving techniques, which enabled the cell colony patterns, i.e. their density and level of organisation, to be determined. The results from a previous study (Janssen et al, Prostate, in press) combined with those of the present one show that DHT was found to activate proliferation of the LNCaP model, as evidenced by increase in size of colonies, increase in number of cells within colonies, increase in cell colony density and, accordingly, decrease in mean segment length value (which is the distance between adjacent cell nuclei). Using the same criteria, DHT was found inhibitory on growth of DU145 cell line, and devoid of significant effect on PC3 cell line. Basic FGF was found to be a powerful stimulator of growth of PC3 cell Line and to induce a weaker stimulation of DU145 cell line. On LNCaP cell line, it increased the size of colonies without increase of the number of cells per colony. This feature can be explained by a decrease in cell colony density. With respect to the same colonies, the proliferation index (percentage of cells in the S+G2 phases of the cell cycle) was found similar to that of the controls. This suggests that the increase in the size of the colonies is due to a difference of spreading of the cells on their supports. EGF had no significant effect on LNCaP and PC3 models, and was decreasing cell density of DU145 colonies.

Differential histochemical peanut agglutinin stain in benign and malignant human prostate tumors: relationship with prostatic specific antigen immunostain and nuclear DNA content.

The histochemical binding pattern of the peanut (Arachis hypogaea) lectin (PNA) was quantitatively described by means of computer-assisted microscope analysis in 28 benign prostatic hyperplasias (BPH), 15 prostatic intraepithelial neoplasias (PIN), and 119 prostatic adenocarcinomas. PNA exhibits nonimmune but selective binding to glycoproteins with beta-D-galactosyl(1,3)-N-acetyl-D-galactosamine residues. We also investigated whether a relationship existed between the number of histochemical-related PNA acceptors and the histochemical prostate-specific antigen (PSA) stain intensity, and between the number of PNA receptors and DNA ploidy level. The results show that neoplastic prostate tissues and high-grade intraepithelial prostatic neoplasias (PIN2_3) exhibit a significantly higher number of PNA acceptors than benign prostatic hyperplasias and low (PIN1) grade prostatic intraepithelial neoplasias. A statistically significant correlation was observed between the number of histochemically related PNA acceptors and PSA immunostain intensity. Lastly, diploid prostatic tumors, whether benign or malignant, exhibited a significantly higher number of PNA acceptors than aneuploid ones. These results suggest that PNA acceptors play an important role in the biology of prostate tumors.

Image cytometry determination of ploidy level, proliferative activity, and nuclear size in a series of 314 transitional bladder cell carcinomas.

Image cytometry was carried out on 281 superficial (Ta and T1) and 33 invasive (T2 to T4) bladder cancers. The parameters used to characterize these bladder tumors were: (1) histopathological grading, (2) clinical staging, (3) tumor size, (4) deoxyribonucleic acid (DNA) index (DI), (5) DNA histogram type (DHT), (6) percentage of euploid (diploid plus tetraploid) cells, (7) percentage of polyploid cells (> 5C DNA content), (8) proliferative activity (S phase fraction value), and (9) nuclear area (NA). The proliferative activity of the tumors was not related to either histopathological grade or to clinical stage, but it was related to the DHT parameter, which made it possible to identify diploid, hyperdiploid, triploid, hypertriploid, tetraploid, and polymorphic tumors. The hypertriploid tumors exhibited a significantly lower proliferative activity than the nonhypertriploid ones. Although both the DI and the NA values correlated significantly with histopathological grading, only the NA values correlated significantly with clinical staging. We further observed that some grade III bladder tumors were definitely diploid, whereas some grade I tumors were highly aneuploid. We thus hypothesize that the ploidy level of a given tumor reflects its age directly and its aggressiveness only very indirectly. In our opinion aneuploidy is only an indirect marker of aggressiveness because it reflects the fact that a malignant tumor is old, ie, has been present in a patient over a long period of time and has had ample time to express its malignancy at the clinical level. A significant relationship was accordingly obtained between tumor size and ploidy level with the highest proportion of aneuploid tumors and the highest percentage of polyploid cell nuclei being observed among the largest bladder tumors.

Osteopetrosis: a single centre experience of stem cell tranisplantation and prenatal diagnosis.

Malignant osteopetrosis (MOP) is an autosomal recessive disease in which osteoclast dysfunction results in excessive bone deposition and early infant death. Thirteen children suffering from MOP from four related families all belonging to one Bedouin tribe, were studied. The disease was diagnosed as early as at a few days postnatal to 5 months. Nine children underwent BMT, four of whom are still alive; one is blind and two have markedly reduced vision. Four children who did not undergo BMT died between 4 and 6 months of age. Recently, the gene for MOP has been mapped for this Bedouin tribe allowing prenatal diagnosis. Seven pregnancies were subsequently prenatally diagnosed and two fetuses were found to be affected. Pregnancy was electively terminated in one case. In the other case the parents refused and after establishing the diagnosis, the newborn was transplanted at the age of 7 days.

Pathological changes in prostate lesions after androgen manipulation.

The number of newly diagnosed cases of prostate cancer has doubled in the past four years because of the aging of the population coupled with growing awareness of the importance of early detection. The issues of clinical understaging and resection limit positivity have led to the development of novel management practices, including neoadjuvant hormonal treatment, which aims to downstage the primary tumour and decrease the positive margin rate before definitive localised treatment (radical prostatectomy or definitive radiation treatment (neoadjuvant)). There is conflicting evidence regarding pathological downstaging, with some studies suggesting benefit and others no benefit of androgen manipulation before radical prostatectomy. The problem might be related to incomplete sampling of the prostates and difficulties associated with the pathological interpretation of morphological changes. The least controversial aspect of neoadjuvant treatment is its impact on surgical margins. Most series have shown that neoadjuvant treatment in clinical T2 tumours is associated with a 20-25% decrease in positive margins in radical prostatectomy specimens. In patients with clinical T3 tumours, the effects of neoadjuvant treatment on positive margins are less clear. Even if some early significant advantages can be observed following hormonal treatment this may not alter the metastatic spread and overall survival rate. Only long term follow up studies evaluating biological and clinical failures, time to progression, and survival will allow definitive conclusions from this approach.

Burn-activated neutrophils and tumor necrosis factor-alpha alter endothelial cell actin cytoskeleton and enhance monolayer permeability.

BACKGROUND: This study examined the hypothesis that exposure of an endothelial cell (EC) monolayer to tumor necrosis factor-alpha (TNF-alpha) and that burn-activated neutrophils alter EC actin cytoskeleton and enhance the permeability of the monolayer. METHODS: Neutrophils were harvested from rats that had undergone a 45% surface area burn (BURN-neutrophil) or uninjured control rats. ECs were grown on polyester filters or fibronectin-coated glass slides and exposed for 4 hours to media, TNF-alpha (100 ng/mL), or TNF-alpha plus BURN-neutrophil or uninjured control rats (10(7) cells). Monolayer permeability was assessed by measuring the flux of albumin across the cells. EC surface area and microfilament number and length were determined by the staining of actin microfilaments with rhodamine phalloidin followed by fluorescent microscopy. RESULTS: The amount of albumin that moved across the monolayer in response to TNF-alpha plus BURN-neutrophil was twice that of media alone (P <.05) or TNF-alpha alone (P <.05). The number and length of actin microfilaments in ECs exposed to TNF-alpha plus BURN-neutrophil were significantly less than that of cells exposed to media alone or TNF-alpha alone. CONCLUSIONS: These data are consistent with a hypothesis that TNF-alpha plus BURN-neutrophil affect endothelial monolayer permeability by altering EC actin cytoskeletal organization.

Systemic complication of intracavernous papaverine injection in patients with venous leakage.

Intracavernous papaverine injection is often used in the diagnosis and treatment of male impotence. Prolonged erection and/or priapism are well known local complications. Systemic side-effects characterized by discomfort and dizziness due to rapid escape of the drug into the vascular circulation also can occur in patients with venous leakage. Thus, venous leakage should be ruled out prior to intracavernous injection of papaverine in the treatment of impotence. Ligation of the deep dorsal vein and the small veins around the tunica albuginea will lessen the problem.

Transurethral needle ablation of the prostate for treatment of benign prostatic hyperplasia: early clinical experience.

OBJECTIVES: Many attempts have been made to develop a method for treatment of benign prostatic hyperplasia (BPH) that is minimally invasive, efficacious, and low-cost. Transurethral needle ablation (TUNA) is a new, fast outpatient anesthesia-free procedure, using interstitial low-level radio frequency energy to produce a temperature above 100 degrees C. We describe our early clinical experience with TUNA as an outpatient procedure. METHODS: This technique was used in 20 patients with symptomatic BPH. All men were evaluated prior to treatment with flow rates, residual urine, International Prostate Symptom Score (IPSS), and quality of life. Follow-up occurred at 3 and 6 months after treatment, analyzing the same parameters. RESULTS: Tolerance using topical anesthetic and intravenous diazepam was excellent. Peak flow rate increased from a mean 9.5 +/- 3.3 mL/s to 14.7 +/- 6.3 mL/s (P < 0.05) at 3 months (19 patients) and to 15.0 +/- 4.9 mL/s (P < 0.05) at 6-month follow-up (12 patients). IPSS and quality of life improved from an average of 21.9 +/- 5.0 and 4.4 +/- 0.7 (P < 0.005) to 10.2 +/- 4.8 and 2.4 +/- 1.2 (P < 0.005), respectively, at 3-month follow-up. No significant complications were encountered. Retention was observed in 25% of the cases after the TUNA treatment. CONCLUSIONS: This initial study demonstrates the safety and effectiveness of TUNA. TUNA is a promising, anesthesia-free alternative treatment for men with symptomatic BPH. Long-term follow-up and randomized comparative studies with transurethral resection of the prostate (TURP) are planned to establish the place of this new alternative treatment of BPH in the urologist's armamentarium.

Study of human penile venous system and hypothesis on its behavior during erection.

To determine the role of the venous outflow restriction during human erection, we compared intracavernous pressure with deep dorsal vein pressure in 6 normal subjects during papaverine-induced erection and penile saline infusion. In addition, flows necessary to produce and maintain erection were measured in 10 cadavers before and after resection of the deep dorsal vein alone or together with ligation of the cavernous veins. Elongation of tunica albuginea was measured at the crural and mid portions of the penis. At rigidity there was complete blockage of the venous return through the emissary veins. The venous outflow through the cavernous veins was reduced but still persisted. The distention of the tunica albuginea was less important at the crural portion than at the distal portion and could explain why the cavernous veins were not blocked completely.