Intravescical prostatic protrusion is a predictor of alpha blockers response: results from an observational study.

BACKGROUND: To investigate the efficacy of tamsulosin in patients with lower urinary tract symptoms (LUTS) and benign prostatic enlargement (BPE) with intravesical prostatic protrusion (IPP). Ultrasound measurement of the IPP has been previously described as an effective instrument for the evaluation of benign prostatic obstruction (BPO) and could help in clarifying the role of alpha-blockers in patients with (BPE). METHODS: Patients with BPE and LUTS were enrolled in this observational study. Intravesical prostatic protrusion was graded as grade 1 (< 5 ml), 2 (5 < IPP < 10 ml) and 3 (> 10 ml). Patients were treated with tamsulosin for twelve weeks. Evaluation was performed before and at the end of treatment by means of International Prostate Symptom Score (IPSS) and uroflowmetry. Patients were considered responders if a reduction of IPSS > 3 points was reported. RESULTS: One hundred forty-two patients were enrolled. Twelve patients were excluded because of incomplete data. Fifty patients showed an IPP grade 1 (group A), 52 a grade 2 (group B) and 28 a grade 3 (group C). Treatment success was obtained in 82%, 38,5% and 7,1% of patients respectively; these differences (group A vs B-C and group B vs C) were highly significant. The odd ratio to obtain a treatment success was of 59 and 8.1 in group A and group B respectively, in comparison to group C. After a multivariate regression, the relationship between IPP grade and treatment success remained significant. Improvement of uroflowmetry parameters has been reported in all the groups especially in patients with a low grade IPP (p value = 0,016 group A vs group B; p value = 0,005 group A vs group C). Prostate volume seems not to influence this relationship. CONCLUSIONS: Intravesical prostatic protrusion has found to be significantly and inversely correlated with treatment success in patients with LUTS and BPE under alpha-blockers therapy. Alpha blockers odd ratio of success is 59 times higher in patients with a low grade IPP in comparison to patients with a high grade.

Increased aquaporin 1 expression in the tunica albuginea of Peyronie's disease patients: an in vivo pilot study.

Peyronie's disease (PD) is a localized disorder of the connective tissue of the tunica albuginea (TA) whose etiology has not been elucidated. Although several studies have implicated genetic susceptibility and/or mechanical trauma as triggering events for PD, the underlying molecular mechanisms remain largely unknown. Aquaporin 1 (AQP1) is a water channel protein potentially implicated in connective tissue resistance to mechanical stress, acting primarily by increasing tension within the collagen network. Although it represents a potentially attractive molecular target in PD, to date no studies had ever addressed whether AQP1 is detectable and/or differentially expressed in the TA of these patients. Herein the present study, through immunohistochemical and biochemical approaches, we were able to detect AQP1 expression in the TA of control and PD affected patients. We demonstrated that AQP1-like immunoreactivity and expression are significantly increased in plaques of PD patients Vs controls, implying that AQP1 overexpression might be the consequence of a localized maladaptive response of the connective tissue to repeated mechanical trauma. In summary, these data support the idea that AQP1 might represent a potentially useful biomarker of mechanical injury in the TA and a promising target for the treatment of PD.

Care manager to control cardiovascular risk factors in primary care: the Raffaello cluster randomized trial.

BACKGROUND AND AIM: This cluster randomized trial evaluated the efficacy of a disease and care management (D&CM) model in cardiovascular (CVD) prevention in primary care. METHODS AND RESULTS: Eligible subjects had ≥ 1 among: blood pressure ≥ 140/90 mmHg; glycated hemoglobin ≥ 7%; LDL-cholesterol ≥ 160 or ≥ 100 mg/dL (primary or secondary prevention, respectively); BMI ≥ 30; current smoking. The D&CM intervention included a teamwork including nurses as care managers for the implementation of tailored care plans. Control group was allocated to usual-care. The main outcome was the proportion of subjects achieving recommended clinical targets for ≥ 1 of uncontrolled CVD risk factors at 12-month. During 2008-2009 we enrolled 920 subjects in the Abruzzo/Marche regions, Italy. Following the exclusion of L'Aquila due to 2009 earthquake, final analyses included 762 subjects. The primary outcome was achieved by 39.1% (95%CI: 34.2-44.2) and 25.2% (95%CI: 20.9-29.9) of subjects in the intervention and usual-care group, respectively (p < 0.001). The D&CM intervention significantly increased the proportion of subjects who achieved clinical targets for both diabetes and hypertension, with no differences in hypercholesterolemia, smoking status and obesity. CONCLUSIONS: The D&CM intervention was effective in controlling cardiovascular risk factors, in particular hypertension and diabetes. Numbers needed to treat were small. Such intervention may deserve further consideration in clinical practice. REGISTRATION NUMBER: ACTRN12611000813987.

Improving quality of care in people with Type 2 diabetes through the Associazione Medici Diabetologi-annals initiative: a long-term cost-effectiveness analysis.

AIMS: The Associazione Medici Diabetologi-annals initiative is a physician-led quality-of-care improvement scheme that has been shown to improve HbA1c concentration, blood pressure, lipid profiles and BMI in enrolled people with Type 2 diabetes. The present analysis investigated the long-term cost-effectiveness of enrolling people with Type 2 diabetes in the Associazione Medici Diabetologi-annals initiative compared with conventional management. METHODS: Long-term projections of clinical outcomes and direct costs (in 2010 Euros) were made using a published and validated model of Type 2 diabetes in people with Type 2 diabetes who were either enrolled in the Associazione Medici Diabetologi-annals initiative or who were receiving conventional management. Treatment effects were based on mean changes from baseline seen at 5 years after enrolment in the scheme. Costs and clinical outcomes were discounted at 3% per annum. RESULTS: The Associazione Medici Diabetologi-annals initiative was associated with improvements in mean discounted life expectancy and quality-adjusted life expectancy of 0.55 years (95% CI 0.54-0.57) years and 0.48 quality-adjusted life years (95% CI 0.46-0.49), respectively, compared with conventional management. Whilst treatment costs were higher in the Associazione Medici Diabetologi-annals arm, this was offset by savings as a result of the reduced incidence and treatment of diabetes-related complications. The Associazione Medici Diabetologi-annals initiative was found to be cost-saving over patient lifetimes compared with conventional management [€ 37,289 (95% CI 37,205-37,372) vs € 41,075 (95% CI 40,956-41,155)]. CONCLUSIONS: Long-term projections indicate that the physician-led Associazione Medici Diabetologi-annals initiative represents a cost-saving method of improving long-term clinical outcomes compared with conventional management of people with Type 2 diabetes in Italy.

Intravesical glycosaminoglycans in the management of chronic cystitis.

In this article we review the current status of evidence on the clinic applications of glycosaminoglycans (GAGs) in urology, with particular emphasis on the therapeutic use in all the chronic forms of cystitis. The so called "bladder layer" is mainly composed by chondroitin sulphate, dermatan sulphate and heparan sulphate. Demages of this mucus film seem to be involved in the pathogenesis of several bladder diseases. Hence, GAG replenishment therapy is widely accepted as a therapy for interstitial cystitis/ bladder pain syndrome (IC/BPS), recurrent urinary tract infections (UTIs), radiation and chemo-immunotherapy cystis and overactive bladder (OAB). A MEDLINE search from the first clinical application in 1996 allowed us to find a total of 33 works regarding the use of intravesical GAGs. Although the evidences regarding GAG replenishment therapy are very encouraging in all the forms of chronic cystitis, well-powered randomized clinical trials are needed to better comprehend the exact role of this treatment.

Factors influencing initial choice of insulin therapy in a large international non-interventional study of people with type 2 diabetes.

AIM: To use baseline characteristics of the Cardiovascular Risk Evaluation in people with type 2 Diabetes on Insulin Therapy study population to identify factors that could explain the choice of insulin therapy when beginning insulin. METHODS: The source, non-interventional, longitudinal, long-term study involves 314 centres in 12 countries in five regions. People were enrolled having started any insulin regimen in the previous 12 months. To identify factors associated with the choice of insulin regimen, multivariable backward logistic regression was performed on eligible physician and participant explanatory variables. RESULTS: Participants (N = 3031) had mean age 62 years, diabetes duration 11 years, body mass index 29.3 kg/m² and an HbA1c of 9.5%. Participants in Japan had less hypertension, smoked more and used fewer concomitant medications than those of other regions. Only physician location (rural or urban) influenced the choice of insulin in Japan. In the other four-regions-combined, physician location, specialty, sex and practice type influenced choice of insulin as did participant location, baseline HbA1c, use of glucose-lowering therapies and prior insulin secretagogue use. CONCLUSION: Choice of initial insulin regimen was influenced by several physician and participant characteristics in Canada and Europe, but only by physician location in Japan.

Four-year impact of a continuous quality improvement effort implemented by a network of diabetes outpatient clinics: the AMD-Annals initiative.

AIMS: We evaluated the impact of a continuous quality improvement effort implemented by a network of Italian diabetes clinics operating in the national healthcare system. METHODS: This was a controlled before-and-after study involving 95 centres, of which 67 joined the initiative since 2004 (group A) and 18 were first involved in 2007 (group B, control). All centres used electronic medical record systems. Information on quality indicators was extracted for the period 2004-2007. Data were centrally analysed anonymously and results were published annually. Each centre's performance was ranked against the 'best performers'. We compared quality indicators between the two groups of centres over 4 years. RESULTS: Over 100 000 Type 2 diabetes mellitus patients were evaluated annually. The proportion of patients with glycated haemoglobin levels < 7% increased by 6% in group A (2007-2004 difference) and by 1.3% in group B. The proportion of patients with low-density lipoprotein-cholesterol < 100 mg/dl improved by over 10% in both groups. The rate of patients with blood pressure values < or = 130/85 mmHg increased in group A (+6.4%), but not in group B (-1.4%). The use of insulin increased in group A only (+5.2%), while the use of statins increased by over 20% in both groups. CONCLUSIONS: A physician-led quality improvement effort, based on the systematic evaluation of routine data, is effective in improving the performance of a large number of diabetes clinics. The small percentage increase in the number of patients at target, if applied to large numbers of patients, would translate into a significant impact on public health.

Obesity and changes in urine albumin/creatinine ratio in patients with type 2 diabetes: the DEMAND study.

BACKGROUND AND AIMS: Obesity is a potential risk factor for renal disease in non-diabetic subjects. It remains unclear whether this also applies to diabetic patients. We investigated whether obesity predicted changes in albumin excretion rate in individuals with type 2 diabetes. METHODS AND RESULTS: Fifty Italian diabetes outpatient clinics enrolled a random sample of 1289 patients. A morning spot urine sample was collected to determine urinary albumin/creatinine ratio (ACR) at baseline and after 1 year from the study initiation. Progression of albumin excretion was defined as a doubling in ACR, while regression was defined as a 50% reduction. Multivariate logistic regression analyses were used to evaluate correlates of these outcomes. Data are expressed as odds ratios (OR) with 95% confidence intervals (CI). The risk of progression increased by 7% (OR=1.07; 95%CI 1.00-1.15) for every 5-cm increase in waist circumference measured at baseline, and by 17% (OR=1.17; 95%CI 1.03-1.33) for every one-unit increase in BMI during follow-up. The likelihood of regression was not independently associated with any of the variables investigated. The effect of obesity on progression of ACR was independent of metabolic control, blood pressure, treatment, and baseline level of albumin excretion. CONCLUSIONS: We found a tight link between obesity and changes in albumin excretion in diabetic subjects, suggesting potential benefits of interventions on body weight on end-organ renal damage.

A possible role of BDNF in prostate cancer detection.

Many studies have demonstrated that both normal and malignant prostate cells respond to a variety of growth factors, while several significant differences were found between normal and tumoural cells. The aim of this study was to focus on the localization and distribution of the immuno-reactivity for neurotrophins (NTs) and neurotrophin receptors (NTRs) in normal, hyperplastic and prostate cancer cells, obtained from 40 subjects. We studied samples obtained from 16 prostate cancer (PC, retropubic radical prostatectomy), 20 benign prostatic hyperplasia (BPH, supra-pubic prostatectomy) and normal peripheral prostate tissue from four fresh male cadavers. Samples were examined via immunohistochemical techniques in order to detect the expression of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT3) and their own receptors TrkA, p75, TrkB and TrkC. We observed a high expression of BDNF and TrkB in PC and BPH, though no immuno-reactivity was found for p75. Low expression was reported by other NTs and NTRs in the normal peripheral prostate zone, BPH and PC. These data suggest a possible predictive role for NTs and NTRs, especially for BDNF and TrkB, in the diagnosis and/or management of prostate cancer. The absence of p75 expression confirms its supposed role in apoptotic phenomenon.

[High-intensity focused ultrasound and prostate cancer: technology, state of the art and future].

BACKGROUND. The potential applications of the high-intensity focused ultrasound (HIFU) as a minimally invasive therapy of the localized prostate cancer explain the growing interest of the urologic community towards this technique. HIFU has been assessed for its role in the treatment of localized prostate cancer in patients who otherwise would not have benefited from surgery, and in local recurrences after radiation failure. Methods. Relevant information on HIFU treatment was identified through a literature search of published studies. RESULTS. High biochemical efficacy, excellent tumor local control and favorable mid- and long-term oncological data with a low morbidity rate have been shown in many series of patients. CONCLUSIONS. Although HIFU is a recent and emerging technology, it has been well studied and developed to a point that HIFU will undoubtedly be an effective alternative to radiation therapy.

The RNA-binding protein Sam68 contributes to proliferation and survival of human prostate cancer cells.

The tyrosine kinase Src is frequently activated in advanced human prostate carcinomas and its activation correlates with tyrosine phosphorylation of the RNA-binding protein Sam68. Herein, we have investigated the expression and function of Sam68 in human prostate cancer cells. Analysis of specimens obtained from 20 patients revealed that Sam68 is upregulated at the protein level in 35% of the samples. Real-time polymerase chain reaction confirmed the results at the mRNA level in most patients. Downregulation of Sam68 by RNAi in LNCaP prostate cancer cells delayed cell cycle progression and reduced the proliferation rate. Moreover, depletion of Sam68 sensitized cells to apoptosis induced by DNA-damaging agents. Similarly, stable cell lines expressing a truncated GFP-Sam68(GSG) protein displayed reduced growth rates and higher sensitivity to cisplatin-induced apoptosis. Microarray analyses revealed that a subset of genes involved in proliferation and apoptosis were altered when Sam68 was knocked down in LNCaP cells. Our results indicate that Sam68 expression supports prostate cancer cells proliferation and survival to cytotoxic agents.

Evaluating body composition of Italian prostate cancer patients without metastases.

Prostate cancer (PCa) is becoming an increasingly important public health problem worldwide, and anthropometric studies have revealed that body composition is a potential risk factor for this type of cancer. The objective of the present study was to compare Italians with PCa and no history of androgen deprivation therapy or bone metastases with healthy controls in terms of body composition. We recruited 11 PCa patients [mean age (+/-SD), 68.67+/-4.93 years; body mass index (BMI), 28.42+/-2.96 kg/m(2)] and 11 healthy controls matched for age and BMI. Anthropometric and body composition parameters were measured for all participants using dual X-ray absorptiometry and bioelectric impedance analysis techniques. We found that lean body mass, but not fat mass, was significantly lower for PCa patients in comparison with healthy controls (50.24+/-5.03 vs. 53.63+/-5.61 kg, p<0.05). Thus, PCa patients with no history of androgen deprivation therapy and no bone metastasis suffer muscle mass depletion.

Transdermal electromotive administration of verapamil and dexamethasone for Peyronie's disease.

OBJECTIVE: To evaluate the effects of the transdermal electromotive administration of verapamil and dexamethasone on plaque size, penile deviation, pain, erectile function and capacity for vaginal penetration in patients with Peyronie's disease. PATIENTS AND METHODS: Forty-nine patients were treated four times weekly for six consecutive weeks. During each session the drug mixture was administered from a receptacle fixed to the skin overlying the plaques, using 2.4 mA pulsed current for 20 min. Plaque size and penile deviation were evaluated by dynamic penile duplex ultrasonography, X-ray and photographs; pain, erectile function and capacity for vaginal penetration were assessed using a questionnaire. Vital signs and side-effects were recorded. Differences before and after treatment were assessed. RESULTS: The plaque disappeared in 8% of patients, with a measurable reduction in volume in 74% and no change in 18% (P < 0.001). Penile deviation resolved in 10% of the men, decreased in 74% and remained unchanged in 16% (P < 0.001). The plaque volume was halved in two-thirds of the men, to a mean (sd) of 515 (301) mm3, and the penile deviation halved in 45% of patients, to 24 (5) degrees; pain was completely eliminated in 88% (P < 0.001). Erectile function was completely restored in 42% of patients with initial erectile dysfunction and improved in 17% (P < 0.001); vaginal penetration improved in 73%. No toxicity was noted, except for a transient skin erythema at the site of the penile and dispersive electrodes. CONCLUSION: The transdermal electromotive administration of verapamil and dexamethasone is clinically safe and appears to be an effective treatment in patients with Peyronie's disease.

Clinical implications of left ovarian vein incomplete duplicity with embryonic intersubcardinal anastomosis-derived branches.

During the dissection of a female human cadaver a case of a duplex ovarian vein was observed. It was unique in its upper course where it anastomosed with an inferior polar renal vein, which in turn was linked to an upper polar renal vein by means of a joining branch. It is hypothesised that this represent a persistent link between the left subcardinal vein and the left sacrocardinal vein, together with some branches of a venous net, which represent the embryological intersubcardinal anastomosis. The gonadal vein arises from the distal (or postrenal) left subcardinal vein portion; the left renal vein develops from the intersubcardinal anastomosis. The venous net derived from the intersubcardinal anastomosis may represent a bypass system in cases of left renal vein occlusion. Left gonadal vein duplicity may also play an important role in the anatomical basis of idiopathic left ovarian vein syndrome or left varicocele, and can lead to mistakes being made during venous sclerotherapy.

Retroperitoneal lipoma. Unusual presentation with detrusor instability.

Retroperitoneal lipomas are a heterogeneous group of mesenchymal tumors. They are usually large and occur most frequently in the retroperitoneal, perineal and pelvic regions. Lipomas grow slowly surrounding the retroperitoneal and pelvic organs, with a displacement of bowel and vascular axis. A case of a 61-year-old male patient which referred urinary frequency, urgency and nocturia is presented. Urodynamics evidenced a detrusor instability in a low capacity bladder. CT scan demonstrated a bladder dome compression due to a huge retroperitoneal mass extending from the right hepatic lobe to the hypogastric region and the right thigh. Surgical complete resection was performed: histology demonstrated a lipoma with areas of well differentiated myxoid degeneration. After surgery the irritative urinary symptoms disappeared. This is the first case described in literature of detrusor instability due to bladder compression by retroperitoneal lipoma.

Urinary N-acetyl-beta-D-glucosaminidase concentration in patients with spinal cord injury: relationship with urodynamic parameters.

OBJECTIVES: To investigate the relationships between urinary N-acetyl-beta-D-glucosaminidase (NAG) concentrations and urodynamic parameters in patients with spinal cord injury (SCI). NAG has been proposed as a marker of renal damage. METHODS: Twenty-three patients with SCI were evaluated with urodynamic studies. Urine samples were collected from the 23 patients and 10 healthy volunteers, the NAG levels were evaluated, and the urodynamic parameters were compared with the urinary NAG levels. The patients were divided into two groups according to the amplitude of the hyperreflexic detrusor contractions (HDCs): group A, patients with an HDC amplitude of 40 cm H(2)O or greater, and group B, patients with an HDC amplitude of less than 40 cm H(2)O; group C was composed of healthy volunteers. The urinary NAG concentrations in the three groups were compared. RESULTS: A positive correlation was found between the urinary NAG levels and the HDC amplitude and detrusor leak point pressure (P = 0.015 and 0.007, respectively). The urinary NAG concentration was 3.38 U/g in group A, 2.14 U/g in group B, and 2.12 U/g in group C. The differences in the urinary NAG concentrations between groups A and B and between groups A and C were statistically significant (P = 0.03 and P <0.001, respectively). The concentrations between groups B and C were comparable. CONCLUSIONS: In our experience, the only urodynamic parameters that clearly and positively correlated with the urinary NAG levels were those expressing the amplitude of intravesical pressure. This result stresses the importance of reducing the intravesical pressure in patients with SCI using alternative treatments or surgical procedures if the usual conservative therapies are not effective.

Prostatic small cell carcinoma diagnosed by tru-cut needle biopsy: discussion of clinico-pathological findings.

The small cell carcinoma is a neuroendocrine tumour characterised by an aggressive clinical course and a high mortality rate. It occurs most commonly in the lung. Small cell carcinomas originating in the genitourinary system have been diagnosed with increasing frequency in recent years, because of the use of immunohistochemistry. Prostatic small cell carcinomas present the same biological behavior and similar histological, immunohistochemical and ultrastructural features to small cell carcinomas of the lungs. We describe the clinico-pathological findings in a 65-year-old male patient with a diagnosis of prostatic small cell carcinoma, obtained by means of a tru-cut needle biopsy. We performed the immunohistochemical tests using neuron-specific enolase and chromogranin A antibodies, according to the literature. On the basis of our experience we stress the malignant features of small cell carcinoma and the difficulty in obtaining an early diagnosis and treatment because of the aggressive course of the lesion and the late symptomatology.

[Inflammatory pseudotumor of the bladder: etiopathologic and clinical features]. / Pseudotumore infiammatorio vescicale: aspetti etiopatologici e clinici.

The Authors present a case of inflammatory pseudotumour (IPT) of the urinary bladder occurring in a 57-year-old female patient, who was referred to our department with haematuria, stranguria and hypogastric pain. Ultrasonographic, radiological and endoscopic examinations showed a sessile, ulcerated, easily bleeding bladder formation; urinary cytology revealed no atypical transitional cells. Abdomino-pelvic computed tomography analysis showed thickening of the bladder walls and infiltration of the perivesical fat. Histopathologically, the formation was indicated as an inflammatory pseudotumour (IPT) of the bladder. The patient underwent TURB (transurethral resection of the bladder) and was discharged clinically healed on postoperative day 4. A one-year follow up revealed no evidence of recurrence. On the basis of their experience and a thorough review of the literature review, the Authors discuss the clinico-pathological features of IPT of the bladder and the possible factors involved in the malignant transformation of IPT. In conclusion, the benign nature of the lesion is stressed.

The relationship between physicians' self-reported target fasting blood glucose levels and metabolic control in type 2 diabetes. The QuED Study Group--quality of care and outcomes in type 2 diabetes.

OBJECTIVE: To investigate the relationship between beliefs of physicians relative to intensive metabolic control in type 2 diabetes and levels of HbA1c obtained in a sample of their patients. RESEARCH DESIGN AND METHODS: Physicians' beliefs were investigated through a questionnaire sent to a sample of self-selected clinicians participating in a nationwide initiative aimed at assessing the relationship between the quality of care delivered to patients with type 2 diabetes and their outcomes. At the same time, physicians were asked to collect clinical data on a random sample of their patients, stratified by age (<65 vs. > or = 65 years). Mean HbA1c levels in the study population were thus evaluated according to target fasting blood glucose (FBG) used by their physicians. RESULTS: Of 456 physicians, 342 (75%) returned the questionnaire. Among the responders, 200 diabetologists and 99 general practitioners (GPs) recruited 3,297 patients; 2,003 of whom were always followed by the same physician and 1,294 of whom were seen by different physicians in the same structure on different occasions. Only 14% of the respondents used target FBG levels < or = 6.1 mmol/l, whereas 38% pursued values >7.8 mmol/l, with no statistically significant difference between diabetologists and GPs. The analysis of the relationship between FBG targets and metabolic control, restricted to those patients always seen by the same physician, showed a strong linear association, with mean HbA1c values of 7.0 +/- 1.6 for patients in the charge of physicians pursuing FBG levels < or = 6.1 mmol/l and 7.8 +/- 1.8 for those followed by physicians who used target values >7.8 mmol/l. After adjusting for patients' and physicians' characteristics, the risk of having HbA1c values > 7.0% was highly correlated with physicians' beliefs. Patients followed by different physicians in the same unit showed a risk of inadequate metabolic control similar to that of patients followed by physicians adopting a nonaggressive policy. CONCLUSIONS: Doctors adopt extremely heterogeneous target FBG levels in patients with type 2 diabetes, which in turn represent an important independent predictor of metabolic control. To improve patient outcomes, physicians-centered educational activities aimed at increasing the awareness of the potential benefits of a tight metabolic control in patients with type 2 diabetes are urgently needed.