Familial Focal Segmental Glomerulosclerosis With Late-Onset Presentation and R229Q/R291W Podocin Mutations.

INTRODUCTION: Pathogenic variants in different genes have been described as involved in the development of familial focal segmental glomerulosclerosis (FSGS). A more precise genotype-phenotype correlation would be helpful to better characterize the clinical and laboratorial manifestations of this disease, as well as response to treatment. We analyzed podocin (NPHS2) gene variants in 50 members of four generations of a family with late-onset presentation of glomerular disease. RESULTS AND DISCUSSION: The NPHS2 gene variants R229Q and/or R291W were detected in several individuals, and the phenotype of FSGS with progressive loss of renal function was observed in all the family members carrying both mutations simultaneously. Patients manifested ongoing proteinuria over the years and progressive loss of renal function, which in three women culminated in renal replacement therapy by the 4th decade of life. In two affected patients with nephrotic syndrome, remission was not reached by the use of corticosteroids and other immunosuppressive drugs. The R229Q variant was pathogenic only when trans-associated with specific mutations, as the R291W variant in this family. CONCLUSION: Coexistence of the two NPHS2 variants R229Q and R291W in compound heterozygosis was a determinant of the FSGS phenotype. The presence of these variants alone in heterozygosis did not cause significant proteinuria.

Micrornas and Cardiovascular Diseases: From Bench to Bedside.

MicroRNAs (microRNAs or miRs) are small, non-coding RNAs that control gene expression by binding to and repressing specific mRNA target and have emered as powerful regulators of many biological processes. Understanding miRNAs-biology and functions may be pivotal to get a better insight into pathophysiological mechanisms responsible for a large number of morbid conditions and may lay the foundations for the development of novel therapeutic interventions. Moreover, besides their intracellular functions, miRs are present in the human circulation in a remarkably stable cell-free form, and their plasmatic levels have been proposed as biomarkers for several pathological conditions. The present review aims to summarize the current evidences with regard to biological role of miRNAs in cardiovascular system and their involvement in the pathogenesis of cardiovascular diseases including atherosclerosis, heart failure and pathological heart and vascular remodelling and to highlight their potential use as novel biomarkers and as therapeutic targets in cardiac and vascular diseases.

Insulin/glucose induces natriuretic peptide clearance receptor in human adipocytes: a metabolic link with the cardiac natriuretic pathway.

Cardiac natriuretic peptides (NP) are involved in cardiorenal regulation and in lipolysis. The NP activity is largely dependent on the ratio between the signaling receptor NPRA and the clearance receptor NPRC. Lipolysis increases when NPRC is reduced by starving or very-low-calorie diet. On the contrary, insulin is an antilipolytic hormone that increases sodium retention, suggesting a possible functional link with NP. We examined the insulin-mediated regulation of NP receptors in differentiated human adipocytes and tested the association of NP receptor expression in visceral adipose tissue (VAT) with metabolic profiles of patients undergoing renal surgery. Differentiated human adipocytes from VAT and Simpson-Golabi-Behmel Syndrome (SGBS) adipocyte cell line were treated with insulin in the presence of high-glucose or low-glucose media to study NP receptors and insulin/glucose-regulated pathways. Fasting blood samples and VAT samples were taken from patients on the day of renal surgery. We observed a potent insulin-mediated and glucose-dependent upregulation of NPRC, through the phosphatidylinositol 3-kinase pathway, associated with lower lipolysis in differentiated adipocytes. No effect was observed on NPRA. Low-glucose medium, used to simulate in vivo starving conditions, hampered the insulin effect on NPRC through modulation of insulin/glucose-regulated pathways, allowing atrial natriuretic peptide to induce lipolysis and thermogenic genes. An expression ratio in favor of NPRC in adipose tissue was associated with higher fasting insulinemia, HOMA-IR, and atherogenic lipid levels. Insulin/glucose-dependent NPRC induction in adipocytes might be a key factor linking hyperinsulinemia, metabolic syndrome, and higher blood pressure by reducing NP effects on adipocytes.

Percentage change of FSH value: new variable to predict the seminal outcome after varicocelectomy.

In the literature, there is no good agreement with variables to predict seminal outcome after varicocelectomy. The purpose of this study was to evaluate the FSH percentage change (Δ% FSH) as a predictor of the seminal outcome after varicocelectomy together with other known predictors. We evaluated 118 patients who underwent varicocelectomy. We assessed factors that could be predictors of the improvement of semen characteristics: LH, FSH, total and free testosterone before operation, testis volume, age, testicular pain, body mass index (BMI), Δ% FSH, varicocele Doppler ultrasound grade using regression analysis. Mean sperm concentration increased from 27 ± 12 to 52 ± 15 million per ml post-operatively (P < 0.003), mean sperm motility increased from 31 ± 12 to 40 ± 13 million per ml following the operation (P < 0.02), also mean FSH value changed from 10.2 ± 8.3 to 6.7 ± 7.2 UI/L (P < 0.01). In unvaried regression analysis, Δ% FSH, BMI and age were predictors of the improvement of semen characteristics. In multiple regression analysis, only Δ% FSH and age were predictors. Negative correlation with age and positive correlation with Δ% FSH were observed. Our findings suggest that Δ% FSH (before and after varicocelectomy) and age are significant factors predicting the improvement of semen characteristics.

Hemodynamic responses during lower-limb resistance exercise with blood flow restriction in healthy subjects.

AIM: The purpose of this study was to compare hemodynamic responses during low-intensity resistance exercise, with (LI-BFR) and without (LI) blood flow restriction, with high-intensity resistance exercise (HI). METHODS: In a randomized crossover design, 17 healthy subjects performed 3 sets (15 repetitions, 20% 1RM, 45-second rest interval between sets) of 45° bilateral leg press exercises for the LI-BFR and LI protocols; and 3 sets (8 repetitions; 80% 1RM; 1-minute rest interval between sets) for the HI protocol. The BFR was established using two sphygmomanometers (18x90 cm) inflated to partially occlude blood flow to the femoral artery. Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), stroke volume (SV), cardiac output (CO) and total peripheral resistance (TPR) were evaluated continuously and noninvasively by beat-to-beat measurements during each protocol. RESULTS: Significantly smaller values were demonstrated during the LI-BFR session versus the HI session between the first and second sets for SBP; during the first, second and third sets for DBP; during the first set for HR; during the first, second and third sets for SV; during the first set for CO, and during the second set for TPR. Conversely, perceived exertion was significantly higher in the LI-BFR session versus the HI session. CONCLUSION: The LI-BFR session was associated with significantly reduced cardiovascular responses versus the HI session, but showed higher values of subjective perceived exertion.

Penile plication for Peyronie's disease: our results with mean follow-up of 103 months on 89 patients.

To evaluate the outcome of the long-term follow-up in patients who underwent corporoplasty-straightening treatment for Peyronie's disease. Between 1990 and 2012, a total of 89 patients underwent corporoplasty-straightening surgery using penile plication for Peyronie's disease. We followed up on all the patients for the following: (a) the correction of the curvature; (b) any penile shortening; (c) sexual function; and (d) complications. The mean follow-up period was 103 months. Complete correction of the curvature was obtained in 81 patients (91%). Shortening of the penis (1.5 to <3 cm) occurred in 20 patients (22.5%) and 79 patients (88.7%) had good erectile function (International Index of Erectile Function (IIEF) 5> 21). The most frequent complication was the sensitivity reduction of the glans in eight patients (8.9%), which was resolved within about a year after surgery (mean 11 months) and the shortening of the penis in 20 patients (22.5%), which, however, did not result in problems during sexual intercourse. Corporoplasty using penile straightening plication is a safe procedure whose results are maintained for even many years after surgery. It is a procedure that can be applied to any type of curvature. Any reduction in the length of the penis, as a result of the surgery procedure, does not lead to difficulties in sexual intercourse.

Cardiovascular adaptations to resistance training in elderly postmenopausal women.

The purpose of this study was to investigate the effect of resistance training on resting blood pressure and heart rate variability in elderly postmenopausal women. 29 untrained, non-hypertensive elderly women were randomly assigned to 2 groups: an intervention group (n=15, 65.5±5.0 years, 57.3±6.5 kg, 156.7±5.1 cm) that underwent a supervised resistance training program (8 exercises, 2 sets, 10-15 repetitions, 3 times/week) or a control group (n=14, 66.2±4.1 years, 61.1±11.7 kg, 157.5±7.1 cm) that participated in a supervised stretching program (25-30 min/session, 2 times/week). Resting auscultatory blood pressure, heart rate variability, evaluated from short recordings in a seated position, and maximal dynamic strength (1-RM test) were measured at baseline and after 12 weeks. A group x time ANOVA revealed that muscular strength increased significantly in the resistance training group (+ 10.2% for bench press and +12.7% for leg extension, P<0.05). Systolic blood pressure was reduced significantly in the resistance training group from pre- to post-intervention period (- 5 mmHg; P<0.05), while no significant effect was noted for diastolic blood pressure and heart rate variability indexes (P>0.05). None of these variables changed in the control group throughout the study. In conclusion, a supervised resistance training program improved muscular strength and reduced systolic blood pressure without affecting diastolic blood pressure and heart rate variability in elderly postmenopausal women.

Do DNA-methylation and histone acetylation play a role in clear cell renal carcinoma? Analysis of radical nephrectomy specimens in a long-term follow-up.

We investigated global methylation and histone acetylation in 50 conventional clear cell renal carcinomas (RCC), treated with radical nephrectomy, to assess their possible role as diagnostic biomarkers. The features considered in this study were patient age, tumor size and grade, percentage and intensity of 5-methylcytosine (5mc) and Acetyl-Histone (Lys 9) expression in tumor tissue. All considered parameters were correlated with patient specific survival. The mean percentage of global cellular methylation in tumoral tissue was significantly higher compared to normal peritumoral tissue (p<0.0001), while the intensity of cellular methylation was significantly higher in normal tissue than in tumoral tissue (p=0.001). The mean percentage of histone cellular acetylation in tumoral tissue was significantly lower compared to normal peritumoral tissue (p=0.0005), while the intensity of mean acetylation in neoplastic tissue was similar to the normal tissue. The percentage of global DNA methylation was significantly higher in grades 3 and 4 tumors (p=0.033). Global DNA methylation and histone acetylation in tumoral tissue did not correlate with survival. Fuhrman grade was statistically significant for prognosis (p=0.031). In conclusion, global hypermethylation and histone hypoacetylation play an important role in RCC carcinogenesis; Fuhrman grade is still considered the most important factor for patient survival; 5mc can have a role as markers of aggressiveness.

Cardiac autonomic responses to repeated shuttle sprints.

Team sport match play requires athletes to perform a number of repeated shuttle sprints. However, the acute effects of these repeated sprint sequences on lactic acidosis and resulting autonomic state perturbation are not known. The aim of this study was to observe and compare the blood lactate and post-exercise cardiac autonomic responses of a repeated shuttle-sprint ability test with the 30-15 Intermittent Fitness Test (30-15 (IFT)); the latter test representing a standard for exhaustive supramaximal effort. Thirteen adult team sport players performed the repeated shuttle-sprint ability test and the 30-15 (IFT) on separate days in a counter-balanced order. The repeated shuttle-sprint ability test consisted of six repetitions of maximal 2x15 m shuttle sprints ( approximately 5 s) departing every 20 s, while the 30-15 (IFT) involved progressive 30 s shuttle runs interspersed with 15 s of passive recovery until exhaustion. Blood lactate was measured before and after the tests, while autonomic responses were assessed using immediate heart rate recovery and heart rate variability indices. Peak blood lactate (10.6+/-2.1 vs. 10.2+/-2.8 mM) and heart beats recovered in one minute after exercise cessation (36.4+/-7.8 vs. 39.3+/-7.9 bpm) were similar after both the repeated shuttle-sprint ability test and the 30-15 (IFT). With the exception of the vagal-related time-varying root mean square of successive R-R interval differences at each 30 s, which recovered earlier after the repeated shuttle-sprint ability test compared with 30-15 (IFT), all heart rate variability indices decreased similarly after both tests in comparison to baseline values. In conclusion, the repeated shuttle-sprint ability test was shown to induce comparable levels of lactic acidosis and post-exercise autonomic state as the 30-15 (IFT). These levels of metabolic and autonomic states are likely to occur during team sport match play.

[Testicular cancer. Open questions: prevention, early diagnosis and infertility]. / Le neoplasie del testicolo. Problemi aperti: prevenzione, diagnosi precoce e infertilità

Testicular cancer is the most common malignancy in men aged 15-35 years. Histologically, testicular germ-cell tumors have two main subtypes: pure seminoma and nonseminoma. Knowing the histopathological tumor type and detecting the relevant prognostic factors helps to guide the subsequent therapeutic course. At present there are no recommendations for testicular cancer screening in healthy young men, even among men showing high risk; however, a testicular cancer should be diagnosed as soon as a young man presents with suggestive signs and symptoms. Furthermore, thanks to highly effective treatments including surgery, chemotherapy, and radiation therapy, it is very important to effectively manage secondary prevention and improve these patients' quality of life. Secondary prevention of relapses or secondary malignancy onsets should be carried out through a regular follow-up of the patient; in selected cases of positive family history, it is possible to perform genome-wide analyses aiming at searching the genes possibly causing testicular germ-cell tumor in affected first-degree male relatives. Long-term therapies can yield infertility and sexual dysfunction, issues gaining more and more importance from a clinical point of view. Sperm cryopreservation should be systematically offered to all requiring patients; moreover, screening for gonadal dysfunction should be considered in the follow-up of testicular cancer survivors, with the aim of hormone supplementation in symptomatic patients.

Magnetic resonance imaging of posterior cruciate ligament injuries: a new classification of traumatic tears.

PURPOSE: The aim of our study was to propose a new classification of acute posterior ligament (PCL) injuries based on magnetic resonance imaging (MRI). MATERIALS AND METHODS: Using MRI, we reviewed 220 patients presenting an acute posterior ligament injury. The MRI exam was performed on a 0.2-Tesla (T) magnet and a 1.5-T magnet using T1-weighted spin echo (SE), T2-weighted SE and fat-suppression scans [short-tau inversion recovery (STIR)] in axial, sagittal and coronal planes. In no case was paramagnetic contrast agent injected. RESULTS: Twenty-five per cent of patients were identified as having type I lesions and another 30% as having type II lesions according to the Gross classification. Out of 77 patients, 35% of the whole sample, 37 had a tear of the posteromedial fascicle (type II lesion), and the remaining 40 had anterolateral fascicle tears (type III). In 10% of cases, the ligaments appeared completely interrupted, and these were classified as type IV lesions. CONCLUSIONS: T1-weighted SE sequences need to be integrated with T2-weighted and STIR sequences to detect the real extent of the remaining fascicle. The MRI exam could thus be able to provide a qualitative evaluation of PCL injuries and establish how the injury compromises joint stability.

Cardiovascular effects of sildenafil in hypertensive men with erectile dysfunction and different alleles of the type 5 cGMP-specific phosphodiesterase (PDE5).

Erectile dysfunction (ED) is frequent in patients with essential hypertension (EH); a likely common pathogenetic pathway could be a reduced ability of arteriolar vascular smooth muscle (VSM) to relax. Increasing intracellular levels of cGMP reduce the contractile status of VSM; on the contrary, type 5 cGMP-specific phosphodiesterase (PDE5, codified by PDE5A gene) regulates cGMP levels through its clearance. The PDE5A gene represents a good candidate for the intermediate phenotype EH/ED: genetic variants of the PDE5A may predispose to EH and ED and could affect the local and systemic response to sildenafil administration. Thus, a functionally relevant portion of PDE5 5'-flanking promoter region was analyzed by PCR and direct sequencing in patients with EH and idiopathic ED. The sequences obtained showed a T/G polymorphism at position -1142, near an AP1 regulatory element, that was not apparently associated with the intermediate phenotype. We also studied the relationship between this polymorphism and the effects of oral sildenafil on blood pressure (BP) and heart rate (HR) in men with ED. Sildenafil caused a significant decrease of BP, but had no effects on HR; statistical analysis showed no differences in BP and HR variations among PDE5A genotypes. In conclusion, our data showed no correlations of a novel polymorphism of the PDE5A promoter gene with the intermediate phenotype EH/ED and the BP and HR response to sildenafil administration. Further studies are necessary to define the role of this polymorphism and to study the genetic predisposition for EH with ED.

Percutaneous therapy of varicocele: effects on semen parameters in young adults.

BACKGROUND: In spite of many years of debate, the impact of varicocele on male infertility is still controversial since its pathogenetic role on the impairment of semen quality has never been fully demonstrated. METHODS: In the present work, a series of 426 young adult males undergoing percutaneous treatment of varicocele were studied and semen parameters were evaluated at baseline and 12 months of follow-up. RESULTS: A significant increase in sperm cell concentration and a decrease in immotile spermatozoa were found after varicocele repair, but we failed to detect any significant positive change in progressive motility as well in sperm morphology after treatment. Similar results were also obtained when semen parameters were correlated with the degree of varicocele. CONCLUSION: Since a spontaneous improvement in semen quality has been mathematically established as a model of regression toward the mean, we conclude that the correction of varicocele in young adults is not a major indication when semen alteration is the only clinical problem.

Diagnostic accuracy of percent free prostate-specific antigen in prostatic pathology and its usefulness in monitoring prostatic cancer patients.

INTRODUCTION: The aim of our study was to evaluate the clinical usefulness of percent free prostate-specific antigen (PSA) [ratio of free PSA (fPSA) to total PSA (tPSA); f/tPSA] in prostatic pathology and its usefulness in monitoring prostatic cancer patients. PATIENTS AND METHODS: Our prospective study was carried out on 470 consecutive male patients referred to our outpatient urological clinic for observation. We looked for relationships between tPSA, fPSA and percent free PSA and the patient's age, prostatic volume and histologic diagnosis as assessed by prostatic biopsies or surgical specimens (benign prostatic hypertrophy, carcinoma, hypertrophy with inflammation). In all cases, we calculated the specificity, sensitivity and diagnostic accuracy of percent free PSA in the diagnosis of prostatic diseases, using cutoff values ranging from 14 to 20%. In prostatic cancer patients, we considered the relationships between the various PSA molecular forms and staging, grading and follow-up values. We also evaluated the effects of hormonosuppressive therapy on the serum markers and noted for which tPSA value percent free PSA possessed the greatest diagnostic accuracy. RESULTS: While tPSA and fPSA values appeared to be correlated with patient age and prostatic volume, percent free PSA did not show a relationship with these parameters. The specificity, sensitivity and overall diagnostic accuracy were better assuming a 16% cutoff value for percent free PSA than with other cutoff values. Prostatic inflammation associated with benign hypertrophy can cause false positives in both tPSA and f/tPSA measurements, since 60% of these patients have an f/tPSA ratio below 16%. In diagnosing carcinoma, the diagnostic accuracy of percent free PSA is 100% when tPSA is between 2.5 and 4.0 ng/ml. Percent free PSA is not linked with staging in prostatic cancer, but it does appear to be related to the Gleason score. In patients receiving hormonosuppressive treatment, f/tPSA decreased significantly, and more so in patients with a higher Gleason score. In patients with disease in rapid progression, percent free PSA was lower than in patients in a stable condition. CONCLUSIONS: Based on our experience, 16% as the f/tPSA cutoff value for discriminating between benign and malignant pathologies is the best possible choice, as it provides the highest overall values of sensitivity, specificity and diagnostic accuracy (80, 61.5 and 84.5%, respectively) in the diagnosis of prostatic cancer. We believe that f/tPSA is not a definitive test for diagnosing prostatic cancer. Our observations on the behavior of percent free PSA in relation to prostatic carcinoma grading and staging and in the follow-up of carcinoma patients are interesting; however, further studies are needed to define the appropriate role of f/tPSA in patients with an established diagnosis of prostatic carcinoma and in the follow-up of patients with prostatic cancer.

Sexual function in patients with LUTS suggestive of BPH.

BACKGROUND: Sexual function has been detected in a large sample of Italian patients affected by LUTS suggestive of BPH, by means of the ICS-Sex questionnaire. RESULTS: A number of 877 questionnaires were returned completely filled and were analyzed. Fifty percent of patients declared that their sexual life was significantly affected by their urinary symptoms. Difficulty in getting erections (58.2% of patients) and ejaculation problems (55.6%) were reported by the majority of patients, but the relevant bother was significantly different (48.3 and 33.4%, respectively). The ICS-Sex score was significantly associated with all the measures of symptoms and QoL employed in the study (IPSS and ICS-BPH). The urinary symptoms most frequently associated with sexual dysfunction were those related to incontinence. CONCLUSIONS: The QUIBUS study shows that sexual dysfunctions are commonly complained of by Italian men with LUTS and are significantly associated with urinary symptoms, in particular with urine loss. These findings support the recommendation by the 5th International Consultation on BPH to better evaluate both sexual function and incontinence symptoms in patients affected by LUTS suggestive of BPH.

Surgical pathology examination of radical prostatectomy specimens. Updated protocol based on the Italian TAP study.

Between January 1996 and June 2000, 192 men with prostate cancer underwent radical retropubic prostatectomy (RP) and bilateral pelvic node dissection in 26 centers participating in the Italian randomized prospective TAP study. The reviewing pathologist evaluated 145 RP specimens. Seventy-five cases had not been treated with total androgen ablation before RP was performed, whereas 70 had been treated for three months. Whole-mount sectioning of the complete radical prostatectomy specimens was adopted in each center for accurately evaluating the pathological stage of prostate cancer and resection limit status. The results of this study suggest that total androgen ablation before RP is beneficial in men with clinical stage T2 because of the significant pathological down-staging and decrease in the number of positive margins in the RP specimens. On the basis of the experience acquired through the Italian TAP study and recent publications on prognostic factors in prostate cancer, the original practice protocol for examination of RP specimens removed from patients with carcinoma of the prostate glands was updated.

Tunable supramolecular synthons and versatile, water-soluble building blocks for crystal engineering:.

It is shown that the water-soluble dicarboxylic cationic acid [(eta5-C5H4COOH)2Co(III)]+ (1) is an extremely versatile building block for the construction of organometallic crystalline edifices. Removal of one proton from 1 leads to formation of the neutral zwitterion [(eta5-C5H4COOH)(eta5-C5H4COO)Co(III)] (2), while further deprotonation leads to formation of the dicarboxylate monoanion [(eta5-C5H4COO)2Co(III)]- (3). Compounds 1. 2 and 3 possess different hydrogen-bonding capacity and participate in a variety of hydrogen-bonding networks. The cationic form 1 has been characterised as its [PF6]- and Cl- salts 1-[PF6] and 1-Cl.H2O, as well as in its co-crystal with urea, 1-Cl.3(NH2)2CO, and with the zwitterionic form 2, [(eta5-CH4COOH)(eta5-C5H4COO)Co(III)][(eta5-C5H4COOH)2Co(III)]+[PF6]-, 2.1-[PF6]. The neutral zwitterion 2 behaves as a supramolecular crown ether: it encapsulates the alkali cations K+, Rb+ and Cs+ as well as the ammonium cation NH4+ in cages sustained by O-H...O and C-H...O hydrogen bonds to form co-crystalline salts of the type 2(2)-M[PF6] (M = K, Rb, Cs) and 2(2)-[NH4][PF6]. The deprotonated acid 3 has been characterised as its Cs+ salt, Cs+-3.3H2O.

[Ultrasound-guided cryosurgery of the prostate: short- and long-term experience]. / Criochirurgia ecoguidata della prostata: esperienza a breve e medio termine.

We have assessed 24 patients consecutively treated with cryosurgery and chosen according to the guidelines of the European Study Group of Urologic Cryosurgeons. Of the 24 patients (average age about 70, range 61-79), all were not considered candidates for radical prostatectomy, 9 (37%) were clinical stage cT2 N0M0, 15 (63%) cT3 N0M0 who had not received any prior treatment, except 1 patient (61 years old) who was treated with TCT and successive recurrence of the disease (cT2). Of the 24 chosen patients, 13 (55%) were over the age of 71, 11 (45%) had important factors of co-morbidity and an elevated risk of surgery (ASA 3). The average PSA was of 19.3 ng/ml (range 2.2-61). Gleason score was 2-5 in 9 cases, 6-7 in 14 and 8-10 in 1 case. In the follow-up, we evaluated serum PSA every 3 months and transrectal ultrasound and the echoguided prostatic biopsies at 6, 12 and 24 months. Post-operative complications included: ecchymosis and edema of external genitals (16/24), fever > 38 degrees C (1/24), sloughing syndrome (6/24), urinary tract infections (10/24) acute urine retention (1/24). In 2 cases, 6 months after treatment, a transrectal resection was carried out. After a follow-up at 6 months, the PSA was 0.4 ng/ml (range 0.1-0.9), in 1 case. In positive core biopsy out of 6 showed neoplastic cells with fibrous tissue; the patient had a PSA of 0.58 ng/ml. At 12 months there were 11 assessable patients. The average PSA was 0.3 ng/ml (range 0.1-0.9). At 24 months there were 4 assessable patients, 1 of 4 showed serum PSA level of 4 ng/ml and cancer in apical biopsy. Erectile dysfunction was assessed on 8 patients affective before surgery: 1 referred to sufficient erections at penetration (1/8, 12.5%). After removal of the catheter, 4 of the 20 patients suffered stress and urge incontinence with the use of 1 pad a day. In 1 case, 18 months from surgery, slight stress incontinence was found (1 pad/day). Cryoablation is an efficient method and is given to slight post-operative morbidity and no intra-operative mortality, also in patients with high risk for open surgery. Indications may be found in patients with the following conditions: older than 72 years, severe co-morbidity and high risk for surgery, neoplasia at high risk of progression, and disease recurrence after radiotherapy. Our case history is at the moment encouraging and a larger number of cases as well as longer follow-up are needed.

[Role of transrectal ultrasonography in the follow-up of patients treated with prostatic cryosurgery]. / Ruolo dell'ecografia transrettale nel follow-up dei pazienti sottoposti a criochirurgia prostatica.

Cryosurgery of prostate is a minimally invasive treatment for localized cancer. Imaging techniques (transrectal ultrasound (TRUS) or magnetic resonance) have been proposed to evaluate tumor persistence/recurrence after cryosurgical treatment other than serum PSA and prostate biopsies. Actually, criteria to identify cancer after cryosurgical ablation are not well assessed. Aim of this study is to evaluate the clinical significance and role of TRUS in detecting tumor within the former prostate gland after cryoablation. We evaluated ultrasound (US) features and imaging, serum PSA and biopsies in 20 patients treated by cryosurgery at our Hospital with a mean follow-up of 18 months. Twenty patients (mean age 70 years, PSA 25.9 ng/ml, clinical stage: 10 T2 N0M0 and 10 T3 N0M0) were followed up for a mean of 16 months. Ultrasound findings (gland volume, capsule, hypoechoic area, post-voided urine volume, seminal vesicles) were correlated to PSA levels (every 3 months) and prostate biopsies (6, 12 and 24 months). All cases were evaluated by the same ultrasound scanner (Eidos, Hitachi-5-6.5 MHz) and by two operators. Prostate capsule was interrupted by hypo-hyperechoic areas in all cases. Transition zone was no more recognizable. Ultrasound findings showed in all cases hypoechoic areas, but US did not identified tumor recurrence in 2 patients. During follow-up, PSA below 0.5 ng/ml was recorded in 75% of cases. We detected tumor in 2 cases, respectively 12 and 18 months after cryosurgery: in the first case few residual cancer cells within fibrous tissue were found in 1 out of 6 biopsies at 6 months (PSA 0.58 ng/ml), in the second one, tumor with viable normal prostatic glands was found in one biopsy of the apex at 18 months (PSA 4.0 ng/ml). TRUS showed several anaechoic foci with necrotic tissue and coalescence of liquid areas in 2 patients (one developed acute urinary retention). Actually, serum PSA is the best marker in order to detect clinically significant tumor after cryosurgery. Hypoechoic areas and capsule interruptions observed by ultrasound imaging of prostate gland after cryosurgery are not correlated with tumor recurrence or tumor persistence. TRUS is only indicated for ultrasound-guided biopsies during follow-up and to confirm urologic complications.

[Urinary NMP22 as a new marker in patients with transitional cell carcinoma]. / NMP22 urinario come nuovo marcatore tumorale in pazienti con carcinoma uroteliale.

To evaluate urinary NMP22 dosage as a marker of urothelial tumours, we have selected a group of 90 patients (85 males and 5 females, mean age 66 years) with clinical suspicion of transitional cell carcinoma (TCC), with microscopic or macroscopic hematuria, flank pain, urographic abnormalities and dysuria. All the patients have been evaluated by urinary cytology, renal and bladder ultrasound, cystoscopy. When a bladder tumour has been detected, bladder biopsies and, when required, I.V.P., CT or retrograde pyelography have been performed. A urine sample has been collected between midnight and noon; all samples from patients who were undergoing invasive procedures such as cystoscopy, were collected before or at least 5 days after the procedure. The test has been performed according to ELISA NMP22 (Matritech) technique; the test is specific for the nuclear matrix protein/nuclear mitotic apparatus protein expressed by cancer cells. When performing the test, 30 patients presented macroscopic hematuria. 22 patients resulted to have benign urinary tract conditions, 65 patients had TCC and 3 patients had a final evaluation suspicious for TCC. The NMP22 values were respectively 7.1 +/- 4.7 U/ml, 21.9 +/- 21.0 U/ml and 16 +/- 8.0 U/ml. From our study the sensitivity of the test is 67% (with a threshold value of 10 U/ml) and 55% (with a threshold value of 20 U/ml), while the urinary cytology resulted to have a sensitivity of 26% (p < 0.05). The sensitivity of the test in relation to staging was as follow: Tis 66% with a mean NMP22 value of 23.3 U/ml, Ta 26% with a mean NMP22 value of 13.2 U/ml, T1 100% with a mean NMP22 value of 40 U/ml, T2 73% with a mean NMP22 value of 36.4 U/ml. The specificity of the test was 100% with a threshold value of 20 U/ml. When considering a threshold value of 10 U/ml, the NMP22 test has a sensitivity higher than cytology, especially in low stage TCC. Macroscopic hematuria does not affect its sensitivity; the diagnostic efficacy of the test is not increased by the association of urinary cytology. It has an important role in the diagnosis of residual disease after TURB and in the follow-up evaluation of bladder cancer patients, since its dosage is not influenced by inflammatory conditions of the mucosa. We believe therefore that NMP22 is useful in clinical practice.