Italian prostate biopsies group: 2016 updated guidelines insights

AIM: To present a summary of the updated guidelines of the Italian Prostate Biopsies Group following the best recent evidence of the literature. MATERIALS AND METHODS: A systematic review of the new data emerging from 2012-2015 was performed by a panel of 14 selected Italian experts in urology, pathology and radiology. The experts collected articles published in the English-language literature by performing a search using Medline, EMBASE and the Cochrane Library database. The articles were evaluated using a systematic weighting and grading of the level of the evidence according to the Grading of Recommendations Assessment, Development and Evaluation framework system. RESULTS: An initial prostate biopsy is strongly recommended when i) prostate specific antigen (PSA) >10 ng/ml, ii) digital rectal examination is abnormal, iii) multiparametric magnetic resonance imaging (mpMRI) has a Prostate Imaging Reporting and Data System (PIRADS) ≥4, even if it is not recommended. The use of mpMRI is strongly recommended only in patients with previous negative biopsy. At least 12 cores should be taken in each patient plus targeted (fusion or cognitive) biopsies of suspicious area (at mpMRI or transrectal ultrasound). Saturation biopsies are optional in all settings. The optimal strategy for reducing infection complications is still a controversial topic and the instruments to reduce them are actually weak. The adoption of Gleason grade groups in adjunction to the Gleason score when reporting prostate biopsy results is advisable. CONCLUSION: These updated guidelines and recommendations are intended to assist physicians and patients in the decision-making regarding when and how to perform a prostatic biopsy.

Production of epidermal growth factor in human prostatic cells cultured in vitro.

The Epidermal Growth Factor (EGF) plays an important role in the regulation of in vitro growth of prostate cells inducing a strong mitogenic effect. Nevertheless in our previous study we observed that the treatment of human hypertrophic prostate cell line U285 with exogenous EGF produces a restricted effect on the cellular growth rate. This phenomenon could be due to the capacity of the cells to produce EGF. In this study we aimed to verify this hypothesis by evaluating the presence of mRNA of EGF and EGF receptor (EGF-R) and of their translation products in U285 cells, before and after the treatment with suramin and exogenous EGF. Moreover we studied the effects exerted by these substances on the proliferative rate of the cells U285 after different treatment protocols. The presence in the cells of mRNA for EGF and EGF-R and of their translation products was demonstrated by means of reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemical methods respectively. The modification of growth rate induced by these drugs was studied by FRAME Cytotoxicity Test. The operative modalities adopted to carry out these growth assays tended to 1) focus the effects of suramin in relation to in vitro cellular growth phase; 2) verify the reversibility of its effects; 3) ascertain if it was possible to antagonize the action of suramin by adding exogenous EGF. The results obtained from the RT-PCR showed the presence, in the control cells and in the treated ones, of mRNA coding for EGF and EGF-R. The immunocytochemical analysis indicated that 20% of the control cells are EGF positive, and 83% are EGF-R positive, confirming the results obtained with RT-PCR. Moreover, these stainings showed that the treatment with EGF does not significantly modify the percentage of cells marked by the anti-EGF antibody, while treatments with suramin and suramin plus EGF double this percentage. None of the treatments modifies the percentage of EGF-R positive cells. The growth assays showed that the exposition to highest doses of suramin in the first 24 h of cultures causes a decrease (p < 0.05) of the cellular proliferation during the following 48 h and 72 h and that these effects are irreversible. Moreover, a contemporaneous exposition of the cells to EGF and suramin at seeding strengthens the cytotoxic action of the last drug. To sum up, the demonstration of the presence in the U285 cells of mRNA coding for EGF and EGF-R and of the corresponding proteins, confirms the hypothesis that these cells can produce EGF. Moreover, the cytotoxicity experiments allowed a focusing of the role of the endogenous EGF in the regulation of the U285 cells proliferation and confirmed the importance of biological events that take place in U285 cells during the first 24 h of culture.

Clinical evaluation of percent free prostate-specific antigen using the AxSYM system in the best analytical scenario.

OBJECTIVE: Percent free prostate-specific antigen (PSA) is a promising tool for prostate cancer (CaP) diagnosis. However, its diagnostic performances have not yet been established. The present study was carried out with the aim of evaluating percent free PSA in the most favourable analytical conditions. MATERIALS AND METHODS: Eighty-eight patients affected by newly diagnosed, untreated, primary CaP, and 169 cases with biopsy-confirmed, untreated, benign prostatic hypertrophy (BPH) were prospectively enrolled. Abbott AxSYM total and free PSA were measured by the same technician using the same instrument and the same reagent batch. RESULTS: Percent free PSA was more effective than total PSA in differential diagnosis between CaP and BPH in every evaluated dose range of total PSA. In cases with total PSA >4 microg/l, percent free PSA could have reduced by about 50% the rate of unnecessary biopsies with a probably still acceptable 93% cancer detection rate. The likelihood of CaP after the determination of percent free PSA was in fact higher than 50% using cut-off points which provide low sensitivity values (i.e. 58% in men aged 50-59 years). CONCLUSIONS: Percent free PSA is superior to total PSA in distinguishing primary CaP from BPH in patients with total PSA between 2 and 30 microg/l and in reducing the rate of unnecessary biopsies in men with total PSA higher than 4 microg/l. However, percent free PSA should be cautiously interpreted in decision making in individual patients since post-test probability is relatively low in men aged 50-70 years.

Percent free prostate-specific antigen in assessing the probability of prostate cancer under optimal analytical conditions.

Although general consensus exists that percent free prostate-specific antigen (PSA) is superior to total immunoreactive PSA for prostate cancer (CaP) detection, its diagnostic performance is not yet well established. Analytical problems may account for difficulties in evaluating percent free PSA because the free PSA concentration is substantially lower than that of total PSA. The aim of the present study was to establish the diagnostic performances of the IMMULITE percent free PSA assay from Diagnostics Products Corp. under experimental conditions optimized to minimize analytical variability. Eighty-five patients with untreated primary CaP and 261 with untreated benign prostate hypertrophy (BPH) were prospectively enrolled. The Diagnostics Products IMMULITE total (Third Generation) and free PSA were measured by the same technician, using the same instrument and the same reagent batch. We calculated the post-test probability to express how the likelihood of the diagnosis of CaP changed after the percent free PSA was determined. Areas under the ROC curves of percent free PSA were better than those of total PSA in every evaluated range of total PSA. The percent free PSA could have reduced the rate of unnecessary biopsies by 47% in patients with total PSA >/=4 microg/L with only 3.8% false-negative results. The post-test probability of percent free PSA was, however, <50% in men 50-70 years of age, using cutoff points providing sensitivity from 99% to 80%. Percent free PSA is superior to total PSA in distinguishing primary CaP from BPH in patients with total PSA between 2 and 30 microg/L. In men with low total PSA, the diagnostic performance of the percent free PSA assay may be optimized by controlling methodological variability. The percent free PSA assay is effective in reducing the rate of unnecessary biopsies in men with total PSA >4 microg/L. However, the post-test probability provided by percent free PSA is relatively low in asymptomatic patients 50-70 years of age.

Prostate cancer probability after total PSA and percent free PSA determination.

UNLABELLED: The percent free PSA value is a promising diagnostic tool for prostate cancer. However, its actual role has not yet been established because of the widely diverging sensitivity and specificity values. This could depend at least in part on analytical difficulties, since the free PSA concentration is much lower than that of total PSA. The present investigation was designed to evaluate the diagnostic performance of the percent free PSA in the most favorable analytical conditions. MATERIALS AND METHODS: 81 patients affected by newly diagnosed, untreated primary prostate cancer (CaP) and 239 patients with untreated benign prostatic hyperplasia (BPH) were prospectively enrolled. Hybritech total and free PSA were measured by the same technician using the same reagent batch. RESULTS: The percent free PSA was not significantly associated with age, tumor stage, gland volume, Gleason score, and total PSA, nor was it significantly affected by concomitant prostatic complications either in CaP or BPH. Percent free PSA was more effective than total PSA in the differential diagnosis between CaP and BPH in every evaluated dose range of total PSA. Percent free PSA determination could have reduced the rate of unnecessary biopsies in cases with total PSA > or = 4 ng/mL and > or = 10 ng/mL (avoided biopsies 61% and 63%, respectively). The post-test probability of the disease, which represents the proportion of patients with a positive percent free PSA value who have the disease, was, however, relatively low in younger patients with total PSA within the normal range. CONCLUSIONS: The diagnostic performance of the percent free PSA value is enhanced when the methodological variability is reduced, particularly in men with low total PSA. Percent free PSA is superior to total PSA in distinguishing primary CaP from BPH in patients with total PSA between 2 and 30 ng/mL. The percent free PSA value is effective in reducing the rate of unnecessary biopsies in men with total PSA higher than 4 or 10 ng/mL. However, due to its relatively low post-test probability, the percent free PSA value should be interpreted with caution in the decision-making related to individual patients and should be used in association with clinical and instrumental evaluation of the patient.

[Cost analysis of ultrasound-guided transrectal needle biopsy in prostatic carcinoma]. / Analisi dei costi dell'agobiopsia transrettale eco-guidata nel carcinoma prostatico.

INTRODUCTION: The literature mortality and morbidity rates from prostatic carcinoma prompt to the better use of some routine diagnostic tools such as transrectal ultrasound-guided biopsy. We evaluated the overall cost of transrectal ultrasound biopsy (TRUSB) of the prostate and investigated the economic impact of the procedures currently used to diagnose prostatic carcinoma. MATERIAL AND METHODS: The total cost of TRUSB was calculated with reference to 247 procedures performed in 1996. The following cost factors were evaluated: personnel, materials, maintenance-equipment depreciation, energy consumption and hospital overheads. A literature review was also carried out to check if our extrapolated costs corresponded to those of other authors worldwide and to consider them in the wider framework of the cost effectiveness of the strategies for the early diagnosis of prostatic cancer. RESULTS: The overall cost of TRUSB was Itl. 249,000, obtained by adding together the costs of: personnel (Itl. 160,000); materials (Itl. 59,000); equipment maintenance and depreciation (Itl. 12,400); energy consumption (Itl. 100); hospital overheads (Itl. 17,500). The literature review points out TRUSB as a clinically invasive tool for diagnosing prostatic carcinoma whose cost-effectiveness is debated. Cadaver studies report the presence of cancer cells in the prostate of 50% of 70-year-old men, while extrapolations calculate a morbidity from prostatic carcinoma in 9.5% of 50-year-old men. It is therefore obvious that randomized prostatic biopsies, methods apart, are very likely to be positive. This probability varies with the patient's age, the level of prostate specific antigen (PSA), the density of PSA/cm3 of prostate volume (PSAD), and the positivity of exploration and/or transrectal ultrasound findings. CONCLUSIONS: Despite the strict application of all these criteria and the critical assessment of the patient's general conditions, TRUSB is indicated for 16% of the male population over 50, with obvious implications. It has been recently suggested that the ratio between free PSA (antigen fraction of the total serum PSA) and total PSA could be clinically useful as an effective predict of TRUSB positivity or negativity. Free PSA evaluation might thus help reduce the number of TRUSB.

Effects of DHT and EGF on human hyperplastic prostate cells cultured in vitro: growth, morphology and phenotype characterisation.

This work studies the effects of dihydrotestosterone (DHT) and epidermal growth factor (EGF) on the growth, morphology and phenotype characterisation of the U285 line obtained from human prostate hyperplastic tissue. Modifications of growth rate induced by these two substances have been evaluated by means of the neutral red assay formulated by Borenfreund and Puerner (1985) as well as by means of Kenacid blue assay described by Knox et al. (1986), culturing cells for 24, 48 and 72 hr with scalar doses of DHT (0.5, 1, 2, 5, 10 microM) and EGF (5, 10, 20, 100 ng/ml). An optical microscope connected to a computer aided system and a scanning electron microscope were used to monitor morphological changes induced by DHT and EGF. The immunophenotype characterisation of the treated and control cells was carried out by using a monoclonal antibody panel. Our results show that the expression of anti-cytokeratin 5+6+18, anti-cytokeratin 8+18+19 and anti-proline-4-hydroxylase antibodies varied in relation to the type of treatment undergone by the cells. Moreover, exogenous DHT does provoke a flattening of the U285 cells without modifying their rate of growth, while EGF both shortens the lag phase reactivating the quiescent cells and regulates the subsequent log growth phase, thus causing no cellular overgrowth.

Vesicoureteral reflux after kidney transplantation: clinical significance in the medium to long-term.

103 patients who received a cyclosporine-treated primary cadaver kidney transplant (TX) at our center between 1985 and 1989, whose graft survived for more than 1 year and who accepted to undergo voiding cystography after TX were analyzed and grouped according to the highest grade (regardless to whether active or passive) of vesicourteral reflux (VUR): group 0, absent (n = 14); group 1-2, grade I or II (n = 62); group 3, grade III (n = 27). Patient follow-up ranged from 5 to 10 (median 7) years. Patient and graft survivals and prevalence of hypertension (defined as the persistent need of antihypertensive therapy), did not differ significantly between groups (Mantel-Cox test p: n.s. in all cases). GFR (Cockroft and Gault) and proteinuria were evaluated with ANOVA for repeated measures at 1, 2, 3, 4 and 5 years in the 96 patients (group 0: 13, group 1-2: 56, group 3: 27) whose grafts lasted for 5 years or more. Neither GFR values (p: n.s.) nor GFR behaviour over time (p: n.s.) differed between groups, although a progressive decline of GFR was noted in all groups (p < 0.002). Proteinuria neither showed any significant differences between groups in values (p: n.s.) or behaviour over time (p: n.s.), nor any trend in behaviour over time in all groups as a whole (p: n.s.). Finally, in the first 5 years after TX the 3 groups did not differ for number of urinary tract infections (UTIs) (mean value for all patients: 2.5, range 0-22, episodes/pt/5 years) (p: n.s.), or for number of UTIs with leukocyturia (mean 0.6, range 0-6, episodes/pt/5 years) (p: n.s.), or for number of febrile UTIs (mean 0.3, range 0-5, episodes/pt/5 years) (p: n.s.), or for number of UTIs with sepsis (mean 0.1, range 0-2, episodes/pt/5 years) (p: n.s.). The same results were obtained when, instead of episodes/ pt/5 years, percentages of patients without or with 1 or more of such episodes in the same period were considered. In conclusion, VUR does not seem to be hazardous for the transplanted kidney in the medium to long-term.

Uptake and intracellular distribution of idarubicin in secondary cultures of normal and neoplastic urothelium.

This study analyzes the uptake and endocellular distribution of idarubicin (IDA) in normal and neoplastic urothelial secondary cultures in relation to the changes in concentration and time of exposure. The urothelial lines were isolated by Freshney's method from biopsy fragments taken from five patients with superficial bladder cancer. Pharmacological experiments were carried out on subcultures previously immunophenotypically characterized and did not exceed ten passages. The uptake and endocellular distribution of IDA was analyzed by densitometric image analysis on cells treated for 10, 20, 30 and 60 min and 2 h with scalar dosages from 10 ng/ml to 2430 ng/ml. Microscopic observations and densitometric analyzes revealed that in the cells treated with IDA, fluorescence was higher in the cytoplasm compared to the nucleus and increased with the change in dosage. Moreover, densitometric data showed that IDA uptake in the first 20 min was higher in the neoplastic cells, but after that period its behavior became heterogeneous at 30 and 60 min, while at 2 h there was an inversion of the trend. These results suggest that the in vitro cytotoxicity should be evaluated in order to verify whether the elevated uptake of IDA in the first 20 min of treatment is really correlated to a more elevated toxicity in the neoplastic cells with respect to the normal cells. This is presently under investigation.

Growth, morphology, and morphometry of human hypertrophic prostate cells treated with suramin in vitro.

This work studies the effects of suramin on the growth and morphology of cell strain U285, obtained from human prostate hypertrophic tissue and cultured in vitro. The FRAME cytotoxicity test was performed to evaluate the inhibition of growth induced by suramin. Cells were exposed to suramin at the time of seeding and 24 hours later; neutral red was added with and without suramin. An optical microscope connected to a computer-aided system and a scanning electron microscope were used to study morphological changes induced by suramin. Growth inhibition depends on drug concentration and exposure period. Moreover, the effect of suramin on neutral red uptake is reversible. Suramin 1,000 microM causes the cells to become spheroid, and they fail to form a monolayer. Our data indicate that the addition of suramin during the lag phase decreases the rate of cell proliferation.

Effect of alkaline citrate therapy on clearance of residual renal stone fragments after extracorporeal shock wave lithotripsy in sterile calcium and infection nephrolithiasis patients.

The natural history of post-extracorporeal shock wave lithotripsy residual stone fragments (clearance, growth and aggregation) is incompletely known, even though they are believed to constitute a risk in terms of new stone formation and persistent infection of the urinary tract. We addressed this issue and the hypothesis that alkaline citrate therapy improves residual stone fragment clearance in a 12-month followup study. There were 40 sterile calcium and 30 struvite stone patients with residual fragments after extracorporeal shock wave lithotripsy (diameter less than 5 mm.) consecutively enrolled and randomly assigned to a citrate therapy (6 to 8 gm. per day) or control (hygienic measures only) group. Infection stone patients also received adequate antibiotic therapy throughout the study. Among the patients in the untreated sterile group 21% and 32% were stone-free at 6 and 12 months, respectively. In the infection group these figures were 27% and 40%, respectively. Among the untreated sterile calcium stone patients in whom clearance was not achieved a high percentage experienced residual fragment growth or reaggregation. Citrate therapy significantly improved the stone clearance rate in the sterile (at 6 and 12 months 65% and 74% were stone-free, respectively) and infection (71% and 86%, respectively) stone patients, and prevented residual fragment growth or reaggregation in subjects in whom clearance was not achieved. The data show that growth and persistence are common in the natural history of residual stone fragments. Citrate ameliorated the outcome of these residual fragments by reducing the growth or agglomeration, and by increasing the clearance rate in calcium oxalate and in infection stone patients.

Clinical significance of vesicoureteral reflux after kidney transplantation.

In this study 103 out of our 125 CsA-treated patients who received between January 1985 and December 1989 a first cadaver kidney transplant that functioned for at least one year were studied with voiding cystography (VC) for vesicoureteral reflux (VUR). All patients had an external uretero-neo-cystostomy. VUR occurred in 89 (86.4%) patients. Patients were grouped according to VUR: absence of VUR (group 0), VUR grade I-II (group 1-2), and VUR grade III (group 3). The 3 groups were comparable for male/female ratio, cause of renal failure, cause of donor death, recipient and dialytic age, immunosuppressive therapy, follow-up, time of VC performance after transplantation. At 6 months and 1, 2, 3, 4, and 5 years after transplantation graft function, number of rejection episodes, and number of urinary tract infections (UTIs) were similar in the 3 groups. In groups 1-2 and 3 hypertension was more frequent than in group 0 and occurred even after the 6th month (whereas this did not happen in group 0), but the differences between the 3 groups were not significant. However, when only the 13 patients who were followed for 5 years were considered, the prevalence of hypertension after 5 years was significantly higher in groups 1-2 and 3 (both 100.0%) than in group 0 (33.3%) (chi-square = 7.88; p < 0.02). Finally, 4.5% of patients with VUR and no patients without VUR had septic episodes linked to UTIs, but the difference was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Epistaxis in renal carcinoma.

A 62-year-old man presented with recurrent epistaxis and a mass in the left nostril. Histological examination of the excised tissue showed clear cell carcinoma and he was found to have an asymptomatic carcinoma of the right kidney. A year after right nephrectomy, excision of the left maxilla, and radiotherapy he was well with no sign of recurrence. Early recognition of this rare condition and excision of both primary and metastatic tumours are recommended.

[Effects of mepartricin on the growth of hypertrophic prostatic tissue in primary culture. Creation of the experimental model and preliminary results]. / Gli effetti della mepartricina sulla crescita del tessuto prostatico ipertrofico in coltura primaria. Creazione del modello sperimentale e risultati preliminari.

The aim of this study was to standardise a method for the in vitro culture of hypertrophic prostatic tissue, to assay the morphological type of isolated cells, to evaluate the degree of proliferation and to identify their differentiated iter. In addition, the effects of mepartricina on growth was also studied obtaining preliminary results. Of a total of 40 biopsies used in this experiment, 30 were placed directly in culture using Freshney's method, whereas the remaining 10 were used in a method involving the primary culture of the dispersed cells obtained from enzymatically disaggregated tissue. In vitro proliferation was analysed using optic microscopy, histological and histochemical techniques, and a scanning electron microscope. Cellular kinetics were also studied by bromodeoxyuridine marking. Using these tests it was found that it is possible to obtain the development and growth in this form of culture of fibroblastic-type colonies of epithelial origin characterised by different morphologies and growth curves. In addition, cells from the epithelioid colonies are characterised by a high level of proliferative activity and a low degree of differentiation. Mepartricina appears, on the other hand, to inhibit the in vitro growth of hypertrophic prostatic tissue.

Fractures of the penis: therapeutic approach and long-term results.

Injury to the external male genitalia is considered, with attention focused on accidental fracture of the corpora cavernosa (by coitus or masturbation). Such injuries are often complicated by urethral lesions. We present 13 patients with either simple or complicated fracture of the penis, all of whom were operated on between 2 h and 8 days following injury, with excellent functional results. The need for immediate surgery is emphasised, in order to avoid erectile failure and curvature, which are typical complications of conservative treatment. Surgery consists of complete evacuation of haematoma, curettage and repair of the albuginea. If the fracture is associated with urethral disruption, the latter is also repaired.

Antegrade ureterolitholapaxy in the treatment of obstructing or incarcerated proximal ureteric stones.

Extracorporeal shockwave lithotripsy (ESWL) and retrograde ureterorenoscopy (RU) have transformed the management of ureteric calculi. Nevertheless, patients with obstructing proximal ureteric calculi are not suitable for ESWL or RU. From January 1986 to September 1988, 17 patients with fixed upper ureteric stones underwent antegrade renoureteroscopy and percutaneous surgery. The technique was effective in removing incarcerated proximal ureteric calculi: all patients were stone-free at follow-up 3 months later.

[Cancer of the prostate. Clinical estimation and results of radical prostatectomy]. / Cancer de la prostate. Appréciation clinique et résultats de la prostatectomie radicale.

The authors present their experience about the accuracy of staging and the results of radical prostatectomy in prostatic cancer. From january 1978 to september 1988, 47 patients with clinically localized prostatic carcinoma underwent staging pelvic lymphadenectomy, of whom 36 had proven negative pelvic lymph nodes and 1 had only a micrometastasis in the obturatory nodes. We reviewed the surgical results and survival of these 37 patients who underwent radical prostatectomy. The postoperative complications were compared to those reported in Literature: partial incontinence occurred in 3 patients and there were no symptomatic urethral strictrues. 1 patient died in the early postoperative period by DIC. 35 patients are alive, 27 free of disease, with average follow-up of 36 months. The over-all accuracy of staging was 87%. Our experience suggests that radical prostatectomy with staging bilateral pelvic lymphadenectomy can be performed in a safe manner with minimal postoperative morbidity.

Congenital polyp of the prostatic urethra: report on 2 cases.

Congenital polyps of the prostatic urethra are an uncommon cause of obstructive uropathy, infection and/or hematuria in male children. A filling defect localized in the posterior urethra on the voiding cystourethrogram represents the peculiar diagnostic finding. Transurethral resection is the treatment of choice, according to the size of the polyp. Two cases of congenital posterior urethral polyps are reported and the main clinical and radiological features are discussed. This lesion has to be considered in the differential diagnosis of the voiding dysfunction in young boys.

[Preventive bilateral pulmonary irradiation in renal neoplasms]. / Irradiation pulmonaire bilatérale "prophylactique" en cours de néoplasie rénale.

The aim of the study was to evaluate the role of bilateral lung radiotherapy in the prevention of lung metastases from renal cell carcinoma. The preliminary results are presented. Between 1981-1984, 38 patients with renal cell carcinoma with no evident lung metastases and with normal respiratory function (confirmed by gas analysis, spirometry, diffusion test) were submitted to radical nephrectomy with regional lymphadenectomy. The patients were randomly assigned to two groups. 19 patients were treated with lung radiotherapy (1,500 rad in 5 times with overlap on the mediastinum--3,000 rad) two weeks after surgery, 19 patients did not undergo further treatment after surgery. Chest X-rays and functional lung evaluation were performed at 3.6 and 12 months, and then every six months. Results in the first group (lung radiotherapy) showed no cases of lung fibrosis; 15 patients are disease-free (follow-up: 3-36 months); 4 patients died from cancer, only 1 of whom with lung metastases. In the second group (no lung Radiotherapy) 14 patients are disease-free whilst 5 patients died with lung metastases.