Can benign prostatic hyperplasia be identified in the primary care setting using only simple tests? Results of the Diagnosis IMprovement in PrimAry Care Trial.

AIMS: Diagnosis IMprovement in PrimAry Care Trial (D-IMPACT) was a prospective, multicentre epidemiological study in three European countries to identify the optimal subset of simple tests applied in primary care to diagnose benign prostatic hyperplasia (BPH) in men who spontaneously present with lower urinary tract symptoms (LUTS). METHODS: Consecutive male patients aged ≥ 50 years who spontaneously attended their regular general practitioner (GP) office with LUTS were eligible for inclusion if they had not previously undergone BPH diagnostic tests or received treatment for BPH. Patients were assessed on three occasions, twice by their regular GP (visits 1 and 2) and once by a urologist (visit 3). The diagnostic accuracy of each variable was determined using the urologists' final BPH diagnosis (at visit 3) as gold-standard. Independent variables analysed were as follows: age; BPH diagnosis performed by GP in visit 1 (yes/no); probability of BPH diagnosis assessed by GP in visit 1; urinalysis (normal/abnormal); prostate-specific antigen (PSA); International Prostate Symptom Score (IPSS); diagnosis of BPH performed by GP in visit 2 (yes/no); and probability of BPH diagnosis assessed by GP in visit 2. Statistically significant variables (p < 0.1) were included in a logistic regression model to identify the best algorithm and describe each test contribution. RESULTS: The most frequent spontaneously reported LUTS were nocturia and weak urinary stream. BPH study prevalence was 66.0% (95%CI: 62.3-69.5) and 32% of patients were at risk of BPH progression (PSA > 1.5 ng/ml and prostate volume ≥ 30 cm(3)). Among the independent variables analysed, only age, IPSS and PSA showed a statistically significant relationship with BPH diagnosis. In a logistic regression model including age, IPSS, PSA and probability of BPH (based on physical examination and symptoms), positive predictive value (PPV) was 77.1%. Exclusion of BPH probability resulted in a PPV of 75.7%. CONCLUSIONS: A diagnostic algorithm including only objective variables (age, IPSS and PSA), easily implemented in any GP office, allows GPs to accurately diagnose BPH in approximately three-quarters of patients spontaneously reporting LUTS.

Can simple tests performed in the primary care setting provide accurate and efficient diagnosis of benign prostatic hyperplasia? Rationale and design of the Diagnosis Improvement in Primary Care Trial.

Effective treatment of benign prostatic hyperplasia (BPH) improves lower urinary tract symptoms (LUTS) and patient quality of life, and reduces the risk of complications arising from disease progression. However, treatment can only be initiated when men with BPH are identified by accurate diagnostic tests. Current evidence suggests that diagnostic procedures employed by primary care physicians vary widely across Europe. The expected increases in BPH prevalence accompanying the gradual aging of the population, coupled with greater use of medical therapy, mean that general practitioners (GPs) are likely to have an increasingly important role in managing the condition. The GP/primary care clinic is therefore an attractive target location for strategies designed to improve the accuracy of BPH diagnosis. The Diagnosis Improvement in Primary Care Trial (D-IMPACT) is a prospective, multicentre, epidemiological study that aims to identify the optimal subset of simple tests applied by GPs in the primary care setting to diagnose BPH in men who spontaneously report obstructive (voiding) and/or irritative (storage) LUTS. These tests comprise medical history, symptom assessment with the International Prostate Symptom Score questionnaire, urinalysis, measurement of serum levels of prostate-specific antigen and subjective GP diagnosis after completing all tests including digital rectal examination. GP diagnoses and all other tests will be compared with gold-standard diagnoses provided by specialist urologists following completion of additional diagnostic tests. D-IMPACT will establish the diagnostic performance using a non-subjective and reproducible algorithm. An adjusted and multivariate analysis of the results of D-IMPACT will allow identification of the most efficient combination of tests that facilitate accurate BPH diagnosis in the primary care setting. In addition, D-IMPACT will estimate the prevalence of BPH in patients who present spontaneously to GPs with LUTS.

Erectile dysfunction and alcohol intake.

The objective of this work is to evaluate in a selection of patients with erectile dysfunction the influence of alcohol consumption and the response to alcohol abstinence with and without sildenafil association. Materials and Methods. In a population of 150 consecutive patients with erectile dysfunction we studied 50 patients aged between 22 and 77 years (mean 56±14 SD). These 50 patients were divided into three different treatment groups and were screened for three different levels of alcohol risk with two questionnaires. All patients were evaluated with an International Index Erectile Dysfunction (IIEF) questionnaire before and after one month of treatment. RESULTS. The 50 patients included 14 patients with high alcohol risk, 34 patients with low alcohol risk and only 2 patients with no alcohol risk. After one month, 29 patients responded to the therapy, and 21 did not respond. The IIEF questionnaire presented a statistically significant difference between the different risk groups before and after treatment (p≤0.05). All the patients were examined with a penile Doppler Ultrasound. Only 10 of them had an abnormal diastolic peak velocity (PDV) and only 1 presented both pathologic systolic peak velocity (PSV) and PDV. These 11 patients did not respond to therapies and 10 of them were at high alcohol risk. The alcohol consumption risk was directly correlated with PDV (p=0.00001; R2=0.4). CONCLUSIONS. The results of this study demonstrated a significant relationship between alcohol consumption and erectile dysfunction. This underlines the important therapeutic issue of alcohol abstinence in treating patients with erectile dysfunction.

Sexual dysfunction in patients under dialytic treatment.

AIM: Erectile dysfunction (ED) is very common in patients with renal failure, probably as a side effect of long-term treatments and dialysis, among other etiologic factors. Over the last few years, new highly effective oral treatments for ED have been introduced in the market. We designed a prospective trial in 42 dialytic patients with ED, focusing on the therapeutic effect of syldenafil and apomorphine. METHODS: Forty-two patients aged 57 years (range 34-71), [40 on hemodialysis (HD) and 2 on peritoneal dialysis (PD)] were enrolled in a prospective study comparing sildenafil with apomorphine. After a careful nephrologic anamnesis and uroandrological examination, all patients underwent, before and after each treatment, the International Index Erectile Function (IIEF) test, and the Life Satisfaction test. Expert opinion was based on grading of evidence based medical literature, widespread internal committee discussion, public presentations and debates. RESULTS: The 2 patients on PD were the only responders to 25 mg sildenafil; 25 patients on HD had a clear improvement of the IIEF score after 50 mg sildenafil administration; finally, 11 patients on HD would benefit only from 100 mg sildenafil; the nonresponders to sildenafil were only 4 patients, having to switch to PgE1. When apomorphine was tested on the same patients, a mild response was seen only in 6 patients at the 3 mg dose. No response was seen in the 2 patients on PD. CONCLUSIONS: There was a statistically significant difference in the therapeutic role of sildenafil versus apomorphine, the first producing an overall improvement of the IIEF in 90.5% of patients, compared to 14% of the same patients receiving apomorphine (P<0.001).

Chromosomal numerical aberrations detected by fluorescence in situ hybridization on bladder washings from patients with bladder cancer.

OBJECTIVE: Previous studies on touch biopsy specimens have determined numerical or structural changes involving many different chromosomes in bladder cancer. The aim of this study was to evaluate the use of fluorescence in situ hybridization (FISH) assay in bladder washings as an objective technique to detect chromosomal numerical aberrations in bladder cancer. The main advantages of bladder washings are that they can be easily collected during the clinical follow-up of patients with superficial bladder cancer and they do not contain so many degenerate cells as urine samples. METHODS: We collected specimens from 25 patients who underwent transurethral resection of bladder tumors. Double target FISH assays with centromeric labeled probes for chromosomes 7, 8, 9 and 11 were used on the bladder washings and on the touch biopsy slides. The results were compared to flow cytometry and tumor grade and stage. RESULTS: We found monosomy 9 and trisomy 7, 8, 9 and 11 in 28, 32, 36, 28 and 25% respectively of the patients. FISH analysis of bladder washing versus touch biopsy specimens were concordant in approximately 90% of the slides. Total DNA aneuploidy correlated well with numerical aberrations of chromosomes 7, 8 and 11, but not with chromosome 9. CONCLUSION: Although better hybridization efficiency was obtained on touch biopsy slides, the results in bladder washings were in high concordance. FISH analysis on bladder washing samples may become a simple tool to improve the accuracy of cytology.

Prevalence and risk factors for urinary incontinence in Italy.

OBJECTIVES: To analyze the frequency and risk factors for urinary incontinence (UI) in Italy. METHODS: Eligible for this cross-sectional study were men aged >/=50 years and women aged >/=40, randomly identified among registered subjects of a network of general practitioners during the period March-October 1997. All subjects were invited by telephonic interview to determine the presence of UI, reported by the subjects as loss of urine in the last year. The subjects with UI were further questioned at home for evaluation of the type, degree and frequency of UI episodes. RESULTS: Of the 5,488 subjects interviewed (2,767 women and 2,721 men), 92 (3%) men and 316 (11%) women reported at least one episode of UI during the year before the interview. The frequence of UI increased with age both in men and women, being 2 and 11% in men and women, respectively, aged 50-60 years and 7 and 16% in those aged >/=70. Of the subjects with UI identified, 229 women and 64 men and a group of 289 subjects without UI were questionned at home using a detailed questionnaire. Six and 55% of men and women, respectively, reported stress incontinence, 20 and 12% urge incontinence and 20 and 24% mixed incontinence. The risk of UI increased with body mass index in women. A history of recurrent urinary infection was associated with UI in men and less markedly in women. No association emerged between education, smoking and alcohol or coffee consumption and risk of UI. Parity was directly associated with the risk of UI in women. CONCLUSIONS: The study offers a quantitative estimate of the prevalence of UI and its main risk factors in this Italian population.

Comparison of nuclear matrix protein 22 and bladder tumor antigen in urine of patients with bladder cancer.

Recently, two new tumor markers for bladder cancer have been introduced: NMP22 test and BTA TRAK assay. This study was designed to evaluate the urinary values of these two proteins using quantitative enzyme immunoassays in well microplates. Urine samples from 47 healthy subjects, 26 with benign genitourinary disorders and 109 patients with a histological diagnosis of bladder cancer were collected. The specificity, the positive predictive value, the negative predictive value and the efficiency were established for NMP 22 and BTA, and the cut off values were fixed at a specificity of 95% in the benign disease group (12 U/ml and 23 U/ml respectively). We observed a very high concordance between the two urinary tumor markers (73%), although the overall sensitivity of BTA in bladder cancer patients seems to be better than that of NMP22 (62% vs 54% respectively), especially in the superficial disease group (36% for BTA and 14% for NMP22).

[Systematic biopsy with multiple samples per lobe in the diagnosis of prostatic carcinoma]. / Biopsia sistematica a prelievi multipli per lobo nella diagnosi di carcinoma della prostata.

A new fashion of prostate transperineal biopsy (seven cores from each lobe) is described, in order to evaluate a potential increase of prostate cancer detection rate. From June 1996 to PSA. April 1997, 247 patients underwent transperineal biopsy for an abnormal DRE and/or elevated In addition to apex, base and lateral peripheral samples, two more were obtained from middle-lateral peripheral zone and tow more from transition zone of each lobe of the prostate. In 14 patients (13.1%) carcinoma was detected in the additional samples only. This new biopsy fashion seems to be safe and more accurate than sextant biopsy for a significant percentage of cancer that otherwise would have been missed.

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.

[La Peyronie's disease: anatomical and functional evaluation using color Doppler echography]. / Malattia di La Peyronie: valutazione anatomica e funzionale con ecocolor Doppler.

We performed color duplex ultrasound in patients with Peyronie's disease in order to define the anatomy of corpora cavernosa and penile vascular abnormalities. We evaluated 20 patients, affected by Peyronie's disease, using echo-color-doppler after pharmaco-injection of PGE1 and autostimulation. We find that impotent patients had decreased EDV after 30 Minutes and after autostimulation; all patients had a normal PSV. The echo-colo-doppler is a useful tool in the evaluation of the penile vasculature, in patients with Peyronie disease, for its high sensitivity, low invasiveness, and good acceptance from patients. The results of this test could safely guide the therapeutic choice.

[Role of expectant therapy in prostatic carcinoma of low grade and staging]. / Ruolo della expectant therapy nel carcinoma della prostata di basso grado e stadio.

Low stage and grade prostate cancer can be treated by radical prostatectomy, radiotherapy and expectant therapy. Preoperative evaluation with biopsy is in many cases unreliable to pathological stage and grade. In this study we considered 31 patients with prostate cancer, evaluated with directed ultrasound guided biopsy (15) or with sextant biopsy (16). Sextant biopsy showed better results. Grading was confirmed by radical prostatectomy specimen in 62.5%. The role of expectant therapy is then discussed.

[Echo-guided biopsy of the transitional zone in the diagnosis of prostatic carcinoma]. / La biopsia ecoguidata della zona di transizione nella diagnosi di carcinoma prostatico.

Approximately 24% of prostate cancer originate in transition zone. To define the indications for transition zone biopsies from April 1994 to February 1996 we evaluated 112 men ranging in age from 56 to 84 years (mean 67.4). 94 patients presented elevated PSA levels and normal rectal examination (24 with negative prior systematic sextant biopsies). A group included 6 patients with palpable nodularity and normal PSA levels. A third group consisted of 12 men with sonographic abnormalities. Of the 112 patients evaluated 38 (34%) were found to have cancer on the prostate biopsies and 7 (18%) were positive only in sample of transition zone biopsies. We conclude that transition zone biopsies don't substantially improve the cancer detection rates in patients with palpable nodularity or sonographic abnormalities but are useful in patients with elevated PSA levels and/or negative prior systematic sextant biopsies.

[Preoperative staging of prostatic carcinoma: evaluation of the role of transrectal echography]. / Stadiazione preoperatoria del carcinoma prostatico: valutazione del ruolo dell'ecografia transrettale.

Radical Retropubic Prostatectomy (RRP) is the choice treatment for localized prostate cancer. Transrectal ultrasonography (TRUS) was used to predict local tumor extension in ninety-one patients prior RRP. In these patients 41% showed histologic evidence of extracapsular spread. These data suggest that ultrasonography is associated with considerable staging errors when used to evaluate men with clinically localized prostate cancer.

Preliminary results of clinical evaluation of the free/total prostate-specific antigen ratio in a multicentric study.

AIMS AND BACKGROUND: The free/total (F/T) prostate-specific antigen (PSA) ratio is probably the most promising tool proposed to increase the specificity of PSA in the diagnosis of prostate cancer. The aim of the present study was to evaluate the clinical value of the F/T ratio in 138 patients with benign hyperplasia, 101 with untreated prostate cancer, and 176 apparently healthy men. METHODS: We used a new immunometric assay of free PSA (FPSA-RIACT, CIS Diagnostici, Italy) which has shown good analytical performance; sample handling and storage under routine conditions did not affect the antigen stability. RESULTS: The diagnostic efficiency of the F/T ratio was significantly better than that of total PSA. In patients with total PSA ranging from 4 to 10 ng/ml, at a specificity level of 95% total PSA showed a sensitivity of 7%, whereas the sensitivity of F/T increased to 70%. Using the F/T ratio as a decision tool in association with total PSA and considering all cases candidate to biopsy (total PSA greater than 3.79 ng/ml corresponding to the 95% level), we demonstrated a 35% reduction of total biopsies that would have been required on the basis of total PSA alone. CONCLUSIONS: The determination of the percentage of F/T serum PSA significantly improves the specificity of the marker, particularly in the 4-10 ng/ml dose range where unnecessary prostate biopsies can be reduced.

Compliance to longterm vasoactive intracavernous therapy.

From December 1986 to December 1991, 107 patients with organic impotence were advised to intracavernous pharmacological therapy with papaverine. Sixteen patients refused such treatment: 91 patients, after the determination of the therapeutical dose, underwent self injection. The follow up was 30-90 months. Thirty-seven patients (40.7%) withdraw the treatment within 3 months: 3 patients (3.3%) after losing the partner; 9 (9.9%) for intercurrent disease; 23 (25.3%) were unsatisfied for the therapy; 2 (2.2%) regained spontaneous erections. Complications were: local haematomas in 23 (42.6%); prolonged erections in 6 (11.1%); fibrotic changes of the corpora cavernosa in 9 patients (16.7%); liver enzymes changes in 2 (3.7%). The reasons for the low compliance to the intracavernous pharmacological therapy with papaverine were analysed.

Paroxetine in the treatment of premature ejaculation.

OBJECTIVE: To test the efficacy and the adverse effects of a new anti-depressant drug (paroxetine) in the treatment of premature ejaculation. PATIENTS AND METHODS: The study comprised 32 men (mean age 28 years) with premature ejaculation (14 of whom ejaculated before penetration) who were treated with paroxetine (20 mg orally each evening for 2 months). The study group excluded those with neurological and psychiatric disorders, urinary tract infections and drug or alcohol abuse. RESULTS: After about 14 days, the patients' symptoms improved and all patients reported a longer interval before ejaculation. The adverse effects were sleepiness in 19 patients (61%) and mild sensory confusion in 21 (68%), but only one had to withdraw from therapy. Three weeks after the end of therapy, the premature ejaculation recurred in 28 (90%) of the patients. CONCLUSIONS: These results indicate that paroxetine is an effective therapy for premature ejaculation. Further studies with different dosages are necessary to decrease the adverse effects and to prolong the efficacy.

Treatment of advanced urothelial carcinoma with M-VECA (methotrexate, vinblastine, epirubicin and carboplatin).

Transitional cell carcinoma of the urinary tract is actually considered very sensitive to cisplatin-containing regimens. Nevertheless, the generally impaired renal function and poor performance status of these patients are responsible for the severe toxicity usually occurring when cisplatin, either alone or in combination with other agents, is administered to these patients. The aim of this study was to verify the possibility of substituting carboplatin for cisplatin, and epirubicin for doxorubicin in the M-VAC regimen in order to reduce toxicity and improve patient tolerance. Thirty-five patients with advanced urothelial tract carcinoma were treated with a chemotherapeutic regimen composed of methotrexate (30 mg/m2 iv on days 1, 15, 22), vinblastine (3 mg/m2 iv on days 2, 15, 22), epirubicin (35 mg/m2 iv on day 2) and carboplatin (250 mg/m2 iv on day 2) every 4 weeks (M-VECA). All patients had bidimensionally measurable disease. Of the 32 evaluable patients, 5 (16%) obtained a complete response and 10 (31%) a partial response (response rate: 47% C.I. = 30%-64%). Grade III-IV leuko-thrombocytopenia was observed in 25%, and mucositis in 19% of cases. Nevertheless, recovery was prompt and opportune dosage reductions avoided severe toxicity in subsequent cycles in most patients. In conclusion, M-VECA is a safe and effective regimen for the treatment of patients with metastatic urothelial tumors.

Preliminary clinical evaluation of free/total PSA ratio by the IMMULITE system.

The role of free (F) and complexed serum PSA is now under investigation. In the present study, we evaluated the clinical significance of F-PSA and F/Total (T) PSA ratio in a preliminary series of samples from 88 patients with prostate cancer (PC), 113 with benign prostatic disease (BPD), and 98 with non-prostatic disease (NP). We used the F-PSA and third generation T-PSA (DPC, Los Angeles, USA) chemiluminescent enzyme immunometric assays with the IMMULITE automated system. At the 10 ng/ml cutoff for T-PSA levels, we obtained a sensitivity of 83% with a specificity of 100% in NP and 80% in BPD. The addition of the F/T ratio--rather than F-PSA levels--was useful to better discriminate PC and BPD in the cases erroneously classified by T-PSA alone: 44/68 samples (65%) were correctly diagnosed. Moreover, the F/T ratio was particularly effective in the critical T-PSA range between 4.1-9.9 ng/ml; 26/40 cases (65%) were correctly evaluated. In conclusion, the F/T ratio seems to be an interesting auxiliary test to T-PSA, to be reserved for selected cases where additional diagnostic information is necessary.

Advanced prostate cancer follow-up with prostate-specific antigen, prostatic acid phosphatase, osteocalcin and bone isoenzyme of alkaline phosphatase.

We report our experience in the follow-up of 63 patients with advanced prostate adenocarcinoma. We used prostate-specific antigen and prostatic acid phosphatase in 27 patients; in 36 patients we evaluated osteocalcin and bone isoenzyme of alkaline phosphatase, two markers of bone metabolism which seem to be good markers in the follow-up of patients with bone metastases.