The uncertain relationship between obesity and prostate cancer: an Italian biopsy cohort analysis.

BACKGROUND: The study aims to investigate the relationship between obesity and prostate cancer diagnosis at biopsy. METHODS: From 2005 onwards, a consecutive series of patients undergoing 12-core prostate biopsy for PSA value ≥ 4 ng/ml and/or positive digital rectal examination (DRE) were enrolled. Before the biopsy, patients underwent a physical examination, including height and weight measurement. Obesity was defined as body mass index (BMI) ≥30 kg/m(2). Blood samples were drawn from all patients and analyzed for total PSA and testosterone. RESULTS: 885 patients were enrolled with a median age and PSA of 67 years (range 37-95) and 6.4 ng/ml (range 1-30) respectively. Median BMI was 27.1 kg/m(2) (range 18-46.6) with 185 patients classified as obese. 363 patients had cancer at biopsy; 76 were obese. PSA was independently associated with a higher risk of cancer (OR 1.09 per 1 unit PSA, p = 0.01). On multivariate analysis, the BMI was not significantly associated with an increased prostate cancer risk (p = 0.19). Out of 363 patients with prostate cancer, 154 had a Gleason score 6 (23 were obese) and 209 a Gleason score ≥7 (53 were obese). Among men with cancer, a higher BMI on univariate (p = 0.001) and multivariate analysis (p = 0.005) was associated with high-grade disease (Gleason ≥ 7). CONCLUSIONS: In our single center study and less aggressively screened cohort, obesity is associated with an increased risk of a high-grade Gleason score when prostate cancer is diagnosed at biopsy.

[Overactive bladder: modulating the effects of antimuscarinic therapy]. / Valutazione clinica e modulazione degli effetti della terapia antimuscarinica.

Overactive bladder (OAB) is a prevalent pathologic condition affecting millions of young, adult and aging people in the world. Although it is a underestimated disease, it causes a significant negative socio-economic impact and determines a severe deterioration of quality of life (QoL) of sufferers. The epidemiologic data today available regarding OAB incidence, prevalence and burden, have prompted a great interest about it. The effect of this research resulted in the availability of new clinical tools useful to investigate and easier diagnose OAB, such as voiding diary and specific symptomatic questionnaires. The most used drugs in the OAB treatment are the antimuscarinics, whose use is still limited due to their some side effects, mostly dry mouth and constipation. For this reason the pharmacologic research is involved in the development of drugs with a better receptorial selectivity, organ specificity, new extended release formulations or new ways of administration. The new extended release formulation of tolterodine, one of the most used drugs in OAB treatment, present a better tolerability maintaining its efficacy, with a consequent better therapeutic efficacy. Furthermore, the recent proposed night-time administration of the drug resulted in a even more lowering of side-effects due to their occurrence during the nocturnal resting.

A prospective study of the safety and efficacy of suprapubic transvesical prostatectomy in patients with benign prostatic hyperplasia.

PURPOSE: We investigate the safety and efficacy of suprapubic transvesical prostatectomy, and the change in bladder wall thickness after surgery. MATERIALS AND METHODS: We conducted a prospective 1 center study of 32 consecutive patients who underwent transvesical prostatectomy from December 1996 to March 1997 for benign prostatic hyperplasia with large prostate volume, who were followed for 1 year. Pressure flow study and transrectal sonography were performed at baseline and repeated at 6 months. Bladder wall thickness was measured at baseline and regular intervals postoperatively. A morbidity questionnaire was completed during the first 6 weeks after surgery. RESULTS: An average of 63 gm. prostate adenoma were enucleated at surgery. An indwelling catheter was required for an average plus or minus standard deviation of 5.4 +/- 2.6 days after treatment. The International Prostate Symptom Score decreased from 19.9 +/- 4.4 to 1.5 +/- 2.7 and the quality of life score decreased from 4.9 +/- 1.0 to 0.2 +/- 0.4 at year 1, respectively. Maximum flow rate improved from 9.1 +/- 5.3 to 29.0 +/- 8.9 ml. per second. Residual urine decreased from 128 +/- 113 to 8 +/- 18 ml. Before surgery 30 patients had obstruction and 2 were in the equivocal zone of the International Continence Society nomogram. At 6 months after prostatectomy 30 patients did not have obstruction, and 2 who were subsequently operated on for bladder neck sclerosis were equivocal and had obstruction, respectively. No patient had significant postoperative bleeding and no heterologous blood transfusions were required. There were 4 men who had urinary tract infection and 1 who had wound infection. A slight decrease in erectile function was observed 6 weeks postoperatively, and no change in patient libido and quality of sex life was reported. The total complication rate was 31.3%. The bladder was unstable in 7 men before and 3 after surgery. A significant decrease in bladder wall thickness was observed from 5.2 +/- 0.7 at baseline to 2.9 +/- 0.9 mm. at year 1 postoperatively. CONCLUSIONS: Our study confirms the excellent clinical outcome of transvesical prostatectomy, and rapid improvement of most subjective and objective parameters during the 4 weeks after surgery. Bladder hypertrophy appears to be significantly reduced after prostate surgery. The urodynamic results in patients who underwent open surgery probably represent the maximum obtainable relief of obstruction and should be considered the reference standard to which all other treatments, including transurethral resection, should aspire.

Invasive and minimally invasive treatment modalities for lower urinary tract symptoms: what are the relevant differences in randomised controlled trials?

OBJECTIVES: This manuscript reviews the outcomes of invasive and minimally-invasive treatments of lower urinary tract symptoms due to prostatic enlargement. METHODS: The MEDLINE database was searched for Medical Subject headings and text words including prostatic hyperplasia, treatment, surgery, thermal treatments, thermotherapy, laser, TUNA and vaportrode. Data from both randomised and non-randomised controlled trials were considered. RESULTS: All invasive treatments produce significant changes of all subjective and objective outcome parameters. The best clinical outcome has been reported for open prostatectomy followed by transurethral resection of the prostate. Complications of the different invasive techniques were difficult to analyse because of the heterogeneity of categories among different papers and lack of standard criteria. The major attraction of all minimally invasive treatment options is the low risk of bleeding requiring blood transfusions. Retrograde ejaculation was one of the most frequently reported complications for all invasive techniques. Some of the so-called less invasive treatment options appeared to be associated with a rather high incidence of minor complications somehow contradicting their minimally invasiveness. Re-treatment rate observed in patients receiving various minimally invasive treatments was always higher than following standard treatment options such as transurethral resection. CONCLUSIONS: Open prostatectomy and transurethral resection of the prostate outperform all minimally invasive treatment modalities as regards efficacy and durability of outcome. The lack of standard criteria to evaluate complications and side effects makes treatment comparisons difficult. Endorsement of the clinical research criteria proposed by the last WHO-sponsored International Consultation on BPH is strongly recommended to improve the clinical value of randomised and non-randomised controlled trials. More information is needed on long-term complications and cost-effectiveness of minimally invasive treatment modalities.

[International prostate symptom score: comparison of doctor and patient]. / International prostate symptom score: medico e paziente a confronto.

The AUA 7 score was originally designed and validated to be self administrated to patients with LUTS, its subsequent endorsement by the WHO - BPH committee made it the most widely used. Translation into different was provided and sometime validated. Aim of the study was to investigate the possibility to self administer the IPSS questionnaire to patients referred to our Institution for lower urinary tract symptoms. Two hundred and thirty-tree consecutive patients were given the IPSS questionnaire as a part of the routine diagnostic schedule; a senior resident was available to answer any possible question from the patient. After the form was returned, a second IPSS questionnaire was filled in by investigator following patient interview. Data were entered into an Excel database and the following parameters were investigate: number of forms completely filled in by patient, number of question answered in incomplete forms, degree of concordance between patient and investigator. One hundred and fifteen patients were able to fill the AUA 7 form completely; the quality of life question was answered by ninety-six patients only. Comparison of individual scores provided by the patient or assigned by the investigator showed a trend for the physician to underscore the patient problem for question 1-4 and to overestimate it in questions 5 to 7. At the lower range of the IPS score (0-7) no significant different between physician and patient was found. In the intermediate range (8-19) the physician tended to overestimate the patient symptoms. The reverse situations was found in the high score range (20-35). Globally, there was a trend for the patient score to be higher than the one assigned by the investigator, Doctor IPSS and quality of life scores appeared to be significantly related. No relation was found between doctor IPSS and the degree of bladder outlet obstruction as measured by parameter of pressure-flow study and diagnostic nomograms. The IPSS form appeared to be a difficult questionnaire for our patients and less than half of them were able to fill it in properly. Overall, the investigators tended to underestimate the patient voiding disturbances. Careful linguistic review of the Italian version of the IPSS questionnaire is required to make self evaluation of patient symptom possible. Symptom grading by a trained investigator did not seem to introduce any significant bias which might be of importance for the sake of clinical trials.

[The Studer orthotopic ileal neobladder: patient compliance]. / Neovesciche ileali ortotopiche sec. Studer: "compliance" del paziente.

Radical cystectomy represents the gold standard for locally advanced bladder cancer. Orthotopic neobladder is considered the surgical option which may offer the least modification of body image and the best life condition to the unfortunate patient requiring radical cystectomy. Objective of this study was to investigate long term clinical outcome of orthotopic ileal bladder substitute with special reference to late complications and patient compliance. Twenty male patients 48 to 71 years old (mean age 59.8 + 7.4 years) underwent radical cystectomy and Studer orthotopic ileal neobladder for invasive carcinoma of the bladder. Before surgery all patients filled in a phycometric test for evaluating their knowledge capacity; after surgery they underwent a course of biofeedback and instructed to avoid overfilling of the neobladder with timed micturitions and a regular regimen of fluid intake. Pressure flow study was included in the routine follow-up carried out at six months and then yearly. Seventeen patients (85%), with a good knowledge capacity, reported a good compliance to the modified life style imposed by the bladder substitute, they all were dry during the day with 3 to 5.5 hour interval between micturitions; fourteen of these patients were continent at night with timed micturitions every 3-4 hours (mean: 3.2); an average cystometric capacity of 450 ml was found in these patients with no residual urine; three patients (18%) had incontinence episodes once or twice a week during the night; no decompensation of the neobladder, significant ureteral reflux or dilatation were reported; elongation of the afferent loop was found in one patient following small bowel resection for ileal volvulus. Three patients (15%), with a reduced knowledge capacity, who did not follow the suggested life style: fluid intake was irregular, micturitions were not timed during both day and night time, had residual urine larger than 400 ml. and incontinence episodes requiring pads; nevertheless no dilation of the upper urinary tract was found. Our experience suggests that careful compliance of patients to the new life style imposed by the orthotopic neobladder is of importance to avoid its decompensation. The possible causative role of gastrointestinal hormones such as enteroglucagon (EG) and peptide tyrosine-tyrosine (PYY) in the elongation of the afferent limb of the Studer neobladder is proposed. In conclusion, we believe that orthotopic ileal neobladder is an ideal surgical option on in the young, educated and cooperative patients.

Nocturnal enuresis and daytime wetting: a multicentric trial with oxybutynin and desmopressin.

OBJECTIVE: Different etiopathological mechanisms of enuresis are today under study, and different therapies and drugs have been proposed. The Italian Multicentric Trial was undertaken in twelve pediatric and urological centers in order to assess the efficacy of two of the most popular drugs, desmopressin (DDAVP) and oxybutynin. METHODS: 114 enuretic patients were enrolled in the study. After a 2-week observation period, 66 patients with primary monosymptomatic enuresis were treated with DDAVP, 30 micrograms/day intranasally, for 6 weeks, 48 patients with enuresis and voiding dysfunction were randomly assigned to a protocol with oxybutynin alone or oxybutynin plus DDAVP. The efficacy of the two drugs was measured in terms of reduction of wet nights per week during the 6-week treatment period and a 2-week follow-up period. Children with 0-3 dry nights/week were considered as nonresponders. RESULTS: Patients with monosymptomatic enuresis treated with DDAVP reported a significantly lower number of wet night during treatment than during the baseline period, with 79% showing a 'good' (6-7 dry nights/week) or 'intermediate' response (4-5 dry nights/week). Of the patients with diurnal voiding disturbances and enuresis, those treated with oxybutynin alone had a 54% success rate. The patients treated with both oxybutynin and DDAVP showed a better response, with a 71% rate of success. CONCLUSIONS: The efficacy of the two drugs is confirmed in patients carefully selected on the clinical basis of voiding disturbances. In patients with enuresis and voiding dysfunction, the reduced urinary output and the lower bladder filling rate due to DDAVP can reduce uninhibited bladder contractions, thus enhancing the oxybutynin action.

"Platicas y merienda": reaching Spanish-speaking patients in an oncology setting.

PURPOSE: The United States Hispanic population has tripled since the mid-1950s and is projected to be the largest growing segment of the population through the year 2000. The traditional support group model has not been effective in reaching this population. Healthcare professionals must become innovative to better understand and provide programs for Spanish-speaking cancer patients. DESCRIPTION OF PROJECT: At the M.D. Anderson Cancer Center, a group program titled "Platicas y Merienda" was developed that derived from several group modalities: education, social, and peer support. The program is coordinated and facilitated by Spanish-speaking social workers and uses other professionals within the institution as speakers to promote a multidisciplinary approach to providing support services. FINDINGS: Participants experienced an increased sense of social and emotional well-being, expanded their knowledge of health-related information, and became aware of other services and benefits available to them. CLINICAL IMPLICATIONS: During this time of change in the healthcare environment, innovation in clinical practice and program development is necessary to address the needs of the growing Hispanic population.

Vesicostomy in childhood: indications and results.

The authors report their experience with 27 patients who underwent cutaneous vesicostomy (CV) diversion for either lower tract disorders or obstruction. The indications for CV included 18 cases of neurogenic bladder, 3 pseudo-prune belly syndrome, 3 bladder exstrophy, 2 vesicoureteral reflux, and 1 posterior urethral valves. A Lapides-type technique with minor changes was performed in all cases. Improvement of renal function occurred after CV in all but 3 patients (11.1%). No early surgical complications were observed. Late complications occurred in 8 patients (29.6%): 4 (14.8%) had a stomal stenosis and 4 (14.8%) urinary tract infections. The overall revision rate was 7.4%. We believe this technique is simple to perform, tubeless, easy to manage, and readly reversible. Our experience tends to confirm CV to be an easy, effective, and reversible means to treat children and infants with selected pathology of the lower urinary tract. Results and complications are discussed.

The prediction of clinical outcome from transurethral microwave thermotherapy by pressure-flow analysis: a European multicenter study.

A total of 100 patients treated with a single session of microwave thermotherapy at 4 European centers was stratified according to 2 different types of obstruction (constrictive and compressive) and compared to clinical outcome at 6 months. Patients had a Madsen-Iversen score of 8 or more, maximum flow rate of 15 ml. per second or less and residual urine volume of 300 ml. or less at entry. The change in Madsen-Iversen score was the same in the 2 groups. Maximum flow rate increased from 8.71 +/- 2.62 to 14.73 +/- 4.04 ml. per second in the constrictive group, and from 8.54 +/- 2.26 to 10.41 +/- 4.52 in the compressive group (p < or = 0.0001). Residual urine decreased from 96.00 +/- 72.85 to 40.34 +/- 56.33 ml. in the constrictive group and from 109.86 +/- 67.09 to 84.65 +/- 81.45 ml. in the compressive group (p < or = 0.0001). Success, as defined by an increase of 50% or more in maximum flow rate and Madsen-Iversen score, was noted in 68% of the constrictive but only 15% of the compressive groups (p < or = 0.0001 chi-square test for trend). Selection by pressure-flow criteria for patients being considered for thermotherapy should improve the overall clinical results.

Plasminogen activator activities in short-term tissue cultures of benign prostatic hyperplasia and prostatic carcinoma.

The high prevalence of prostatic carcinoma (PRCA) and the limited therapeutic possibilities provide a strong stimulus for exploring new approaches in experimental research that ultimately may lead to improved therapy. Indeed, methods for assessing carcinoma prognosis, such as clinical staging (clinical examination, ultrasound, and plasmatic levels of prostatic acid phosphatase and prostate specific antigen) and histopathological grading according to the Gleason score, usually fail to provide consistent predictive information regarding the clinical outcome of single tumors. Increased plasminogen activator (PA) activities have been associated with high-grade malignancies and with the potential for invasion/metastasis in many tumors. Urokinase-type plasminogen activator (uPA) is present in prostatic secretion, and an increased uPA activity has been noted in human prostatic cell lines with metastatic behavior. Unfortunately, any study of uPA production or gene regulation in primary tumors is complicated by the inherent mixture of host stromal cells, infiltrating macrophages, and subpopulations of tumor cells that may have variable metastatic capacity and ability to synthesize uPA. In short-term tissue culture of prostatic samples, it is possible to grow in vitro cancer prostatic epithelial cells and thus exclude the presence of contaminant cells. We have shown elsewhere that the levels of a type IV collagenase, 92-kDa matrix metalloproteinase, a protease involved in tumor progression and invasion, are increased in PRCA primary cell cultures if compared with benign prostatic hyperplasia (BPH) cell cultures (C. Festuccia et al., manuscript in preparation). Activation of matrix metalloproteinases also can be correlated with uPA expression; therefore we studied the expression of uPA in serum-free culture media of primary cultures of PRCA or BPH tissue samples.(ABSTRACT TRUNCATED AT 250 WORDS)

[New prospective therapy for benign prostatic hyperplasia with finasteride]. / Nuove prospettive terapeutiche nella iperplasia prostatica benigna con la Finasteride.

A randomized, double blind, placebo-controlled study (placebo and Finasteride 1 or 5 mg/die) was carried out in 34 patients with benign prostatic hyperplasia (BPH). After 12 months of treatment all patients received Finasteride 5 mg/die. Follow-up ranges from 18 to 36 months. One year after treatment, patients receiving Finasteride 1 or 5 mg/die, showed significant decrease (one-way ANOVA) of serum dihydrotestosterone (-70.1% and -69.6%, respectively), serum prostate specific antigen (-50% and -50.8%, respectively) and prostate volume (-36.3% and -31.8%, respectively). Comparable modifications of such parameters were observed in the placebo group only during the second year of the study when they were shifted to Finasteride treatment (5 mg/die). No increase of serum testosterone was observed in any group. Maximum urinary flow rate increased on the average, after one year, by 2.6 and 3.6 ml/s in patients receiving Finasteride 1 and 5 mg/die, respectively; a 1.3 ml/s increase occurred in the placebo group. The total urinary symptom score (Boyarsky) decreased in all three patient groups. Results of this study show that a few months are necessary to exert a significant therapeutic effect. The drug is well tolerated and does not decrease the patient's sexual activity. Finasteride certainly opens new perspectives in the treatment of BPH.

Early diagnosis of prostatic carcinoma may be achieved through in vitro culture of tumor cells harvested by prostatic massage.

As a new method for early diagnosis of prostatic carcinoma we succeeded in growing in vitro the epithelial cells which can be collected from prostatic fluid after rectal prostatic massage. We report here the updated and statistically analyzed series of data (174 patients) on this new approach, which allows all the harvested cells to express their biological features. The method reaches a sensitivity of 72-86% and a specificity of 88-100%. This noninvasive test, which is also suitable for mass screening, may be very useful for an early diagnosis of the neoplasm.

[Transurethral thermotherapy by microwaves in patients with benign obstructive prostatic hypertrophy]. / La thermothérapie transurétrale par micro-ondes chez les patients ayant une hypertrophie prostatique bénigne obstructive.

The effect of transurethral microwave thermotherapy (TUMT) with Prostatron in patients with benign prostatic hypertrophy was investigated. Two hundred and one patients were treated between January 1991 and June 1992 after informed consent was signed. The following examinations were carried out at screening: interview (including symptoms score evaluation), physical examination (including digital rectal examination), haematology and blood chemistry (including prostate specific antigen), ECG, chest Xray, kidney, bladder and prostate (transrectal) ultrasound sonography (USS) and uroflowmetry; pressure-flow study was performed in a selected group of patients. All enrolled patients had Madsen symptom score > or = 8; peak flow rate < or = 15 ml/s and post void residual urine < or = 200 ml. Patients with obstructive middle lobe of the prostate, any BPH complication or any suspicion of prostatic carcinoma were excluded from the study. Microwave thermotherapy with Prostatron was carried out according to software generation 2.0 (Prostasoft 2.0), the c10 (black) catheter was used in all patients. Follow-up visits were scheduled at 1 week, 1, 3, 6, 12, 18 months after microwave thermotherapy. Overall short- and long-term morbidity rates were 6.09 and 2.73 per cent, respectively. At 12 months, Madsen score was found to be reduced from 11.7 +/- 4.78 to 4.43 +/- 3.30; maximum flow rate (Qmax) was increased from 8.91 +/- 4.20 to 13.20 +/- 4.86; post void residual urine (PVRU) was reduced from 131 +/- 17.6 to 67.40 +/- 34.50.(ABSTRACT TRUNCATED AT 250 WORDS)

[The alpha blockers]. / Les alphabloquants.

Because the bladder neck contains a large number of alpha-adrenergic receptors, use of alpha-blockers to facilitate micturition in early benign prostatic hypertrophy has been advocated. Effects on micturition and urinary flow were fairly favorable. No adverse effects were recorded. The effect of therapy was transient and slightly greater than the effect of the placebo.

Coffee and cholesterol, an Italian study.

In the present study, conducted in northern Italy between 1986 and 1989, the authors investigated the possible association between coffee consumption and serum cholesterol levels in 8,983 subjects, 7,432 men and 1,551 women, managers and employees aged 18-65 years, who were examined during a program of preventive medicine upon an agreement between various companies and the Centro Diagnostico Italiano. Analysis of covariance was used to compare the serum cholesterol levels of the subjects subdivided according to coffee consumption, along with age, body mass index, alcohol consumption, cigarette smoking, and physical activity. An important relation was demonstrated between coffee intake and cholesterol, particularly in the men, the differences in serum cholesterol in the coffee users compared with the nonusers being 6.1 +/- 1.4 (standard error) mg/dl for consumers of 1-3 cups/day (3.4 +/- 1.4 mg/dl after adjustment for age, body mass index, alcohol and cigarette consumption, and physical activity), 9.9 +/- 1.6 mg/dl for those drinking 4-5 cups/day (5.8 +/- 1.6 mg/dl after adjustment), and 14.8 +/- 2.0 mg/dl for those drinking over 5 cups/day (9.6 +/- 2.0 mg/dl after adjustment). This relation remained substantially unvaried when nonsmokers and smokers were analyzed separately. It has been suggested that it is coffee prepared by boiling rather than other methods that has a hypercholesterolemic effect. Our observations demonstrate an interesting relation between coffee and cholesterol, even though the coffee drunk in Italy is mainly filtered and nonboiled. However, our finding is not necessarily in disagreement with the above hypothesis since, when coffee is prepared in the Italian way (with the mocha method), ground coffee is preheated by steam and more importantly, the water passes through the ground coffee at a higher temperature than with the other brewing methods.

Defects in diagnostic kits for determination of urate in serum.

Certain diagnostic kits that measure serum urate by the Barham and Trinder principle of enzymic liberation of oxygen and its combination with chromogens can give results for urate in fresh serum that are approximately 20% lower than results from serum stored at ambient temperature for 72 h. In fresh serum, antioxidants compete with chromogen for liberated peroxyl-oxygen. We postulate that during storage the interfering antioxidant substances are destroyed. In some diagnostic kits, L-ascorbate oxidase is added to the reaction, eliminating some but not all of this effect. We discuss defects of several commercially available kits for determination of serum urate and recommend comparing results of these kits with results from the phosphotungstic acid method as a precaution against falsely low results.

Body mass index and liver enzyme activity in serum.

The association between body mass index (BMI) and serum liver enzyme activity [gamma-glutamyltransferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST)] was studied in 3167 subjects, 2373 men and 794 women. The subjects were managers and employees, ages 18-64 years, who were examined during a program of preventive medicine. Analysis of covariance was used to compare the serum liver enzyme activities (expressed as natural logarithms) of the subjects, who were subdivided according to BMI, while also considering age, alcohol and cigarette consumption, and physical activity. In men, the percentage increase in the geometric mean of liver enzyme activity of the obese subjects (BMI greater than 30 kg/m2) compared with that of the normal subjects (BMI less than or equal to 25 kg/m2) was 47.7% (P less than 0.001) for GGT, 55.3% (P less than 0.001) for ALT, and 19.7% (P less than 0.001) for AST; in women, the increase was 63.2% (P less than 0.01) for GGT, 58.4% (P less than 0.001) for ALT, and 7.3% (P greater than 0.05) for AST. Thus, our observations demonstrate a relation between BMI and serum liver enzyme activity.