GPNMB/OA protein increases the invasiveness of human metastatic prostate cancer cell lines DU145 and PC3 through MMP-2 and MMP-9 activity.

Non-metastatic glycoprotein melanoma protein B (GPNMB), also known as osteoactivin (OA) is expressed in a wide array of tumors and represents an emerging target for drug development. In this study, we investigated the role of GPNMB/OA in the progression of human metastatic DU145 and PC3 prostate cancer cells. GPNMB/OA contribution in PCa malignant phenotype has been analyzed by small interfering RNA-induced GPNMB/OA silencing. We found that following GPNMB/OA silencing the migration capability of both DU145 and PC3 cells, evaluated by using in vitro invasivity assay, as well as the metalloproteinases MMP-2 and MMP-9 activity were equally strongly inhibited. By contrast knocking down GPNMB/OA weakly attenuated cell proliferation rate of DU145, an effect that paralleled with an increase number of apoptotic cells. However, PC3 cell growth seems to be not affected by GPNMB/OA. Together, these data reveal that GPNMB/OA acts as a critical molecular mediator promoting the acquisition of the more aggressive, pro-metastatic phenotype distinctive of human DU145 and PC3 cell lines.

Different muscarinic receptor subtypes modulate proliferation of primary human detrusor smooth muscle cells via Akt/PI3K and map kinases.

While acetylcholine (ACh) and muscarinic receptors in the bladder are mainly known for their role in the regulation of smooth muscle contractility, in other tissues they are involved in tissue remodelling and promote cell growth and proliferation. In the present study we have used primary cultures of human detrusor smooth muscle cells (HDSMCs), in order to investigate the role of muscarinic receptors in HDSMC proliferation. Samples were obtained as discarded tissue from men >65 years undergoing radical cystectomy for bladder cancer and cut in pieces that were either immediately frozen or placed in culture medium for the cell culture establishment. HDSMCs were isolated from samples, propagated and maintained in culture. [(3)H]-QNB radioligand binding on biopsies revealed the presence of muscarinic receptors, with a Kd of 0.10±0.02nM and a Bmax of 72.8±0.1fmol/mg protein. The relative expression of muscarinic receptor subtypes, based on Q-RT-PCR, was similar in biopsies and HDSMC with a rank order of M2≥M3>M1>M4>M5. The cholinergic agonist carbachol (CCh, 1-100µM) concentration-dependently increased [(3)H]-thymidine incorporation (up to 46±4%). This was concentration-dependently inhibited by the general muscarinic receptor antagonist atropine and by subtype-preferring antagonists with an order of potency of darifenacin >4-DAMP>AF-DX 116. The CCh-induced cell proliferation was blocked by selective PI-3 kinase and ERK activation inhibitors, strongly suggesting that these intracellular pathways mediate, at least in part, the muscarinic receptor-mediated cell proliferation. This work shows that M2 and M3 receptors can mediate not only HDSM contraction but also proliferation; they may also contribute bladder remodelling including detrusor hypertrophy.

Efficacy of a Short-Term Lifestyle Change Intervention in Healthy Young Men: The FASt Randomized Controlled Trial.

The aim of this study was to investigate the impact of dietary habits and physical activity intervention on lifestyle behavior as a prevention tool supported also by personalized motivational counseling. A two-arm randomized controlled trial was carried out. A sample of 18-22-year-old students was randomly assigned to a four-month intervention based on the Mediterranean diet and moderate physical activity program (N = 66) or to a control group (N = 63). The outcomes were adherence to the Mediterranean diet, physical activity level, and nutrients intake, assessed at enrollment (t0), end of intervention (t4, 4 months after the start), and end of follow-up (t8, 8 months after the start). Adherence to the Mediterranean diet increased from t0 to t4 and t8, more in the intervention (6.83, 9.85, and 9.12, respectively) than in the control group (6.73, 7.00, 7.69, respectively) (p < 0.001). Physical activity showed a moderate increase from t0 to t4 and t8 in both groups, without significant differences between them. Significant differences were seen between the two groups in food intake changes, from t0 to t4 and t8. This randomized controlled trial showed that a moderate short-term intervention based on the Mediterranean diet and regular physical activity determined a positive change in the lifestyle of healthy, normal-weight, young men.

Polychlorinated Biphenyls and Semen Quality in Healthy Young Men Living in a Contaminated Area.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants and endocrine disruptors that have been implicated in potential damage to human semen. However, the studies conducted so far provide contrasting results. Our study aimed to investigate the associations between PCB serum and semen levels and semen quality in high school and university students living in a highly PCB-polluted area of Italy. Subjects with a normal body mass index who did not make daily use of tobacco, alcohol, drugs, or medication were selected. All participants provided a fasting blood and a semen sample. Gas chromatography-mass spectrometry was used to determine the concentrations of 26 PCB congeners. The concentrations of PCB functional groups and total PCBs were also computed. A total of 143 subjects (median age 20, range 18-22 years) were enrolled. The median total PCB concentrations were 3.85 ng/mL (range 3.43-4.56 ng/mL) and 0.29 ng/mL (range 0.26-0.32 ng/mL) in serum and semen, respectively. The analysis of the associations between sperm PCB concentration and semen parameters showed (a) negative associations between some PCB congeners, functional groups and total PCBs and sperm total motility; (b) negative associations of total PCBs with sperm normal morphology; and (c) no association of PCBs with sperm concentration. Subjects at the highest quartile of semen total PCB concentration had 19% and 23% mean reductions in total motility and normal morphology, respectively, compared to those at the lowest quartile. The analysis of the associations of serum PCB levels with sperm parameters yielded null or mixed (some positive, other negative) results. In conclusion, the present study provides evidence of a negative effect of some PCB congeners and total PCBs in semen on sperm motility and normal morphology. However, the associations between the concentration of serum and semen PCB congeners and functional groups and sperm quality parameters were inconsistent.

A comparison of hexaminolevulinate (Hexvix(®)) fluorescence cystoscopy and white-light cystoscopy for detection of bladder cancer: results of the HeRo observational study.

BACKGROUND: To date, no study has presented results of photodynamic diagnosis (PDD) cystoscopy compared with white-light cystoscopy (WLC) in daily practice. The aim of the present study is to evaluate the diagnostic accuracy of hexylaminolevulinate hydrochloride (Hexvix(®)) PDD cystoscopy compared with standard WLC used in daily practice. METHODS: An observational, open-label, comparative, controlled (within patient), multicenter study was carried out on 96 consecutive patients with suspected or confirmed bladder cancer. All patients had standard WLC followed by blue-light cystoscopy (BLC). Positive lesions detected using WLC and BLC were recorded. Biopsies/resection of each positive lesion were taken after the bladder was inspected. Sensitivity, specificity, positive predictive value, and negative predictive value with each method were calculated. RESULTS: Overall, 234 suspicious lesions were detected; 108 (46.2%) were histologically confirmed to be bladder tumors/carcinoma in situ (CIS). The sensitivity of BLC biopsies was significantly higher than for WLC technique (99.1 vs 76.8%; p < 0.00001). The relative sensitivity of BLC versus WLC was 1.289, showing superiority of BLC of 28.9%. The specificity of BLC biopsies was not significantly different compared with WLC (36.5 vs 30.2%). Positive predictive value for BLC- and WLC-guided biopsies was 54.9 and 50.9%, respectively. Negative predictive value per biopsy for BLC- and WLC-guided biopsies was 97.4 and 64.8%, respectively. BLC and WLC reached the correct diagnosis in 97.9 and 88.5% of patients, respectively. This difference was statistically significant (p = 0.0265). The lack of a random biopsy protocol was the major limitation of the study. CONCLUSIONS: Hexvix(®) PDD cystoscopy used in daily practice enhances the diagnostic accuracy of standard cystoscopy with higher negative predictive value, potentially permitting an improvement in patient prognosis.

Effects of a Lifestyle Change Intervention on Semen Quality in Healthy Young Men Living in Highly Polluted Areas in Italy: The FASt Randomized Controlled Trial.

BACKGROUND: Human semen quality is affected by lifestyle and environmental factors. OBJECTIVE: To evaluate the short-term effects of a diet and physical activity intervention on semen quality of healthy young men living in highly polluted areas of Italy. DESIGN, SETTING, AND PARTICIPANTS: A randomized controlled trial was conducted. Healthy young men were assigned to an intervention or a control group. INTERVENTION: A 4-mo Mediterranean diet and moderate physical activity program. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcomes were sperm concentration, motility and morphology, concentration of round cells, and semen total antioxidant capacity. Secondary outcomes were adherence to Mediterranean diet and physical activity. All outcomes were measured twice, at the enrollment (t0) and at the end of the intervention (t4). RESULTS AND LIMITATIONS: A total of 263 individuals attended all visits, and underwent examinations and laboratory analyses: 137 in the intervention group and 126 in the control group. The adherence to Mediterranean diet and physical activity level increased more in the intervention group than in the control group from t0 to t4. Sperm concentration, total and progressive motility, and proportion of normal morphology cells increased in the intervention group but decreased in the control group, with statistically significant differences between the two groups at t4. The total antioxidant capacity increased in the intervention group but decreased in the control group, from t0 to t4. CONCLUSIONS: Study results showed that an intervention based on Mediterranean diet and regular physical activity can determine an improvement of semen quality in healthy young men. PATIENT SUMMARY: Our study aimed to evaluate the effect of a lifestyle intervention on semen quality of healthy young men. We assigned the 263 enrolled individuals to an intervention or a control group. The intervention group followed a 4-mo Mediterranean diet and moderate physical activity program, at the end of which the participants showed an improvement of semen quality parameters.

Muscarinic receptors stimulate cell proliferation in the human urothelium-derived cell line UROtsa.

The widespread non-neuronal synthesis of acetylcholine (ACh) has changed the paradigm of ACh acting solely as a neurotransmitter. Indeed, the presence of ACh in many types of proliferating cells suggests a role for this neurotransmitter in the control of cell division. The parasympathetic system is a major pathway regulating micturition, but ACh-mediated control plays a more complex role than previously described, acting not only in the detrusor muscle, but also influencing detrusor function through the activity of urothelial muscarinic receptors. Here we investigated the role of muscarinic receptors in mediating cell proliferation in the human UROtsa cell line, which is a widely used experimental model to study urothelium physiology and pathophysiology. Our results demonstrate that UROtsa cells express the machinery for ACh synthesis and that muscarinic receptors, with the rank order of M3>M2>M5>M1=M4, are present and functionally linked to their known second messengers. Indeed, the cholinergic receptor agonist carbachol (CCh) (1-100 µM) concentration-dependently raised IP(3) levels, reaching 66±5% over basal. The forskolin-mediated adenylyl cyclase activation was reduced by CCh exposure (forskolin: 1.4±0.14 pmol/ml; forskolin+100 µM CCh: 0.84±0.12 pmol/ml). CCh (1-100 µM) concentration-dependently increased UROtsa cell proliferation and this effect was inhibited by the non-selective antagonist atropine and the M(3)-selective antagonists darifenacin and J104129. Finally, CCh-induced cell proliferation was blocked by selective PI-3 kinase and ERK activation inhibitors, strongly suggesting that these intracellular pathways mediate, at least in part, the muscarinic receptor-mediated cell proliferation.

Nerve growth factor signaling in prostate health and disease.

The prostate is one of the most abundant sources of nerve growth factor (NGF) in different species, including humans. NGF and its receptors are implicated in the control of prostate cell proliferation and apoptosis and it can either support or suppress cell growth. The co-expression of both NGF receptors, p75(NGFR) and tropomyosin-related kinase A (trkA), represents a crucial condition for the antiproliferative effect of NGF; indeed, p75(NGFR) is progressively lost during prostate tumorigenesis and its disappearance represents a malignancy marker of prostate adenocarcinoma (PCa). Interestingly, a dysregulation of NGF signal transduction was found in a number of human tumors. This review summarizes the current knowledge on the role of NGF and its receptors in prostate and in PCa. Conclusions bring to the hypothesis that the NGF network could be a candidate for future pharmacological manipulation in the PCa therapy: in particular the re-expression of p75(NTR) and/or the negative modulation of trkA could represent a target to induce apoptosis and to reduce proliferation and invasiveness of PCa.

Molecular and pharmacological detection of dopaminergic receptors in the human male urinary tract.

AIMS: Evidence indicates that dopamine (DA) and DA receptors play a role in the central nervous system (CNS) control of micturition; however, while the central DAergic role in the micturition physiology has been extensively investigated, the expression and the function of DA receptors in the urinary tract are still under investigation. Here, we studied the distribution of DA receptor subtypes in different parts of the human male urinary tract. METHODS: Fragments were collected from 34 men. The mRNAs encoding DA receptors were assessed by RT-PCR, followed by densitometric analysis. Adenylyl cyclase (AC) activity was evaluated using a commercially available RIA kit. Statistical analysis was carried out using one-way ANOVA, with the Bonferroni's post hoc test. RESULTS: Results obtained indicated that RT-PCR products of D(1), D(4), and D(5) subtypes were obtained in each part studied, while no signal was observed for the D(2) and D(3) receptor subtypes. The pharmacological characterization demonstrated that the expressed DA receptors were linked to AC. CONCLUSIONS: DA receptors were expressed throughout the human male urinary tract, from the ureter to the prostatic urethra. In particular, we observed a distinctive DA receptor subtype distribution, with evidence of the presence of mRNA encoding both subtypes of the D(1)-like DA receptor family (D(1) and D(5)), while the D(4) receptors were the only expressed subtype of the D(2)-like family. These results suggested that DAergic drugs used for the treatment of a number of diseases may influence the micturition physiology not only in the CNS, but at the peripheral level as well.

Tissue engineering in urinary bladder: morphological and functional characterization.

INTRODUCTION: In the last years, tissue engineering has attracted lots of researchers, in urology too. This is due to the possibility to use this technique in several pathologies' therapies, which generally require reconstructive surgical solutions. Our work's aim is to evaluate morphological and functional aspects of cultivated urothelial and detrusorial tissues, both in "monolayer growth" and on scaffolds, in order to understand the chance of using them in reconstructive surgery. MATERIALS AND METHODS: Tissue cultures of detrusorial and urothelial cells have been obtained from animals (pigs, rabbits) and men. The urothelial nature of obtained cells has been demonstrated by traditional histological observation (Hematoxylin - Eosin), by immuno-fluorescence assay (specific for cyto-keratins antibodies), by immuno-histo-chemistry techniques (using specific cyto-keratins 7, 17, and 20 antibodies). Detrusorial tissue has been studied by using antibodies specific for alpha-actin. RESULTS: Urothelial and smooth muscle cells, when isolated and expanded in vitro, keep the typical characteristics of original tissue, as showed by classical histological observation (H-E), immuno-histo-chemistry and immuno-fluorescence assays. These results were positive both in monolayer colonies and on scaffolds. In vitro results are encouraging and they demonstrate that it is possible to obtain in vitro vesical tissue that could have analogous characteristics to the original organ; even though clinical utilisation of this technique must be more investigated, both in vitro and in vivo.

Second surgery for renal relapse after nephron sparing surgery: review of seven cases.

OBJECTIVE: Anatomo-pathologic review of the cases which underwent a second surgery operation for a renal neoplasm relapsed after conservative surgery, in order to find possible relations with the surgical technique. PATIENTS AND METHODS: At our institution nephron sparing surgery (NSS) is currently indicated for neoplasms smaller than 4 centimetres in diameter. The technique involves the removal of the neoplasm with a margin of healthy parenchyma and with the perilesional fat. Patients are firstly monitored by a CT check after 4 months and then with ultrasound/CT checks every 6 months in the first 2 years and then once a year In this study we analyze in the 1994-2005 period the records of cases undergoing a second operation for a renal tumour relapsed in the operated kidney after NSS. All specimens were reviewed by an individual experienced uro-pathologist who determined the size of surgical margins and relations between the site of the recidivism and the site of the preceding NSS procedure. RESULTS: Seven cases with renal relapse have been found out of 267 undergoing conservative surgery in the same period (incidence 2.6%). The diagnosis has always been made in the lack of other localizations of disease at a complete re-staging and the average latency of the relapse was 19.4 months (8-46 months). In 5 cases the second tumour has been found in the site of the previous NSS: for these cases the minimum margin of the enucleo-resection was lower then 3 millimetres (median minimum margin 1.6 mm). Differently, in the remaining 2 cases, both with a wider surgical margin (median minimum margin 12.0 mm), the site of thefirst and that of the second neoplasm were distant. In particular, in one case a multifocal recidivism with a spread microvascular embolisation has been found, while in the other the primary neoplasms and the relapse presented a different histotype. CONCLUSIONS: In the 5 cases with a narrow resection margin and relapsing tumour in the site of the enucleo-resection one can hypothise the persistence of a peritumoral microscopic neoplastic disease. In the other 2 cases with a wider surgical margin the relapse can be attributed to the widespread microscopic multifocality in one case and to the development of a second de novo neoplasm in the other one. The extension of the surgical margin seems then to have played a role in determining a relapse in the site of enucleo-resection.

Fistulas between lower urinary tract and bowel: our experience in 15 years.

OBJECT: Fistulas between bowel and low urinary tract are not frequent and could be due to different causes. Diagnosis and treatment need a particular care to assure to patient a good result. Authors report their last 15-years experience. MATERIALS AND METHODS: From 1990 and 2005 22 patients have been quite carefully investigated and surgically treated; 17 men and 5 women of age between 39 and 81 years old. In particular 2 vesico-ileal fistulas, 12 colo-vesical have been treated: in all these situations we proceed by intestinal resection and fistulas repairing at the same time. Three rectovesical and 3 recto-urethral fistulas have been treated by fistula's way removal (with different approaches) and in a case by preparing a definitive urinary derivation. Finally, 2 complex fistulas have been treated by preparing a definitive urinary derivation. RESULTS: The typical symptoms presence must be carefully researched because it could be useful in diagnosis; radiological and endoscopic procedures could be useful for treatment planning, also if they have a quite low sensibility. In 20 cases, the treatment has achieved a good and lasting result. In 1 case we had a relapse, in another one patient died for sepsis. CONCLUSION: Diagnosis of fistulas has to be quite careful and it is necessary to plan the treatment, that is always surgical, also considering that sometimes it's leading to serious complications.

Surgical approach to urinary endometriosis: experience on 28 cases.

OBJECTIVES: Endometriosis (e.) involving the urinary tract must be regarded as a rare condition with specific surgical implications. Our experience on the treatment of 28 patients is presented. PATIENTS AND METHODS: Twenty-eight patients with a urological e. (bladder 11 patients, ureter 14, both bladder and ureter 3) were observed and treated between 1995 and 2005. Thirteen patients (46%) had been previously surgically treated for pelvic e. at a mean distance of 22 months before. All the patients with bladder e. presented with typical symptoms related to menses and the urinary location was isolated in 42.8%. Differently, the patients having ureteral involvement complained often a vague or silent symptomatology, but they always showed some extra-urinary pelvic locations. Among the cases with bladder e., 2 patients underwent TUR and hormonal therapy and 12 partial cystectomy. The patients with ureteral e. were submitted to ureterolysis in 5 cases, segmentary ureterectomy and uretero-ureteroanastomosis in 2 and terminal ureterectomy and ureterocystoneostomy in 8. Two more cases with ureteral e. were nephrectomized due to end-stage renal atrophy. RESULTS: At a mean distance of 58 months (9-110 months) from surgery, 22 patients have a unremarkable follow-up. On the other hand, an urological relapse was evidenced in 5 cases previously submitted to TUR (2 cases), ureterolysis (2 cases) or segmentary ureterectomy and termino-terminal ureteral anastomosis (1 case). The relapsing e. was treated by partial cystectomy or terminal ureterectomy with ureterocystoneostomy, with good results over time. CONCLUSION: Urinary tract is rarely involved by e., but this condition has peculiar clinical and surgical implications. Being TUR ineffective, the therapy of choice of bladder e. is partial cystectomy, possibly via a laparoscopic approach. Differently from bladder e., the preoperative diagnosis of ureteral e. is surely hard. So, a high index of suspect should be regarded in each young female patient with a ureteral stricture and a study of the upper urinary tract (US and/or urography) should be performed in all the patients with pelvic e. Ureterolysis can be successful only in a minority of the cases showing a very limited disease not determining any urinary flow obstructions. In all the other cases the procedure of choice is terminal ureterectomy and ureterocystoneostomy without employing the distal ureter.

Inhibition of Survivin Is Associated with Zoledronic Acid-induced Apoptosis of Prostate Cancer Cells.

BACKGROUND/AIM: Evidence suggests that zoledronic acid (ZA) exerts direct antitumor effects on cancer cells but the underlying mechanisms of these actions are unknown. This study investigated the possible involvement of survivin in the antiproliferative effects of ZA in prostate cancer. MATERIALS AND METHODS: 3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H-tetrazolium bromide (MTT) dye reduction assay was used to assess cell viability and acridine orange/ethidium bromide double staining to analyze cell death. Human Apoptosis Array evaluated the expression of apoptosis-related proteins. Survivin protein was measured by western blot technique and miR-203 levels were quantified by quantitative real-time polymerase chain reaction. RESULTS: ZA induced inhibition of cell proliferation and apoptosis activation, with down-regulation of survivin protein. A negative regulation at gene expression level may be hypothesized because we observed a significant decrease of survivin mRNA level and an increase of miR-203 expression after ZA exposure. CONCLUSION: This study provides evidence that ZA may directly inhibit cancer cell proliferation, identifying survivin as one of its downstream targets.

Use of the appendix as ureteral substitute in a patient with a single kidney affected by relapsing upper urinary tract carcinoma.

The treatment of upper urinary tract transitional cell carcinoma (UT-TCC) in single-kidney patients requires the radical removal of cancer, but also, when feasible, the preservation of the continuity of the urinary tract by various surgical techniques. In case of wide resections during ureteral surgery, a ureteral replacement could be advocated. In the literature, the cecal appendix has rarely been used as a ureteral substitute, moreover in benign pathological conditions, showing encouraging early results. The positive functional and oncological outcomes obtained after a lengthy follow-up in a single-kidney patient with UT-TCC treated by ureteral resection and appendix interposition confirm the viability of this surgical option.

Surgical treatment of metastases from renal cell carcinoma.

INTRODUCTION: Even if the number of curable renal cancers increased during the last decades, there is still a considerable amount of patients with distant metastases, evidenced at diagnosis or during the follow-up, without real curative therapeutic options. MATERIALS AND METHODS: In the period between January 1983 and December 2003 we observed 252 metastatic patients among the 1187 surgically treated for renal cancer (21.2%). The metastatic disease was evidenced at the diagnosis of renal tumour in 118 patients (9.9%), during the follow up at a mean distance of 18.6 months in 134 (11.3%) and was in a single organ in 200 patients, in multiple sites in 52. A surgical treatment of metastases was performed in 113 cases, associated with chemo-immunotherapy in 16. Conversely, 44 patients received chemo-immunotherapy alone, 18 radiotherapy, and in the remaining 77 cases no curative therapies were applied. RESULTS: The patients with a single-site metastasis who underwent of metastases removal, especially when pulmonary or adrenal, showed a better prognosis than the ones otherwise treated, while in the patients with bony metastases, multiple-site metastases and the ones who did not receive any curative therapies an extremely dismal prognosis was evidenced. However, a large amount of the patients with a single-site metastasis (79% on 159 treated patients) had a relapse of the disease, even when surgically treated (69%). CONCLUSIONS: At present, in the lack of any effective systemic therapies for metastatic renal cancer, surgery offers better survival rates than other choices (chemo-immunotherapy or radiotherapy). Thus, even if the initial bias in the selection of patients is surely significant, in our opinion, each patient with good performance status and a resectable metastatic lesion, better if pulmonary or adrenal, should undergo surgical treatment of metastases, that could provide long-term survival in a small part of the patients. The high rate of relapses remarks the actual need of an effective systemic therapy both for the patients who can and cannot undergo surgery for their metastatic disease.

Renal mass with caval thrombus as atypical presentation of xantogranulomatous pyelonephritis. A case report and literature review.

INTRODUCTION: Xantogranulomatous pyelonephritis is a rare, severe, chronic renal infection typically resulting in diffuse renal destruction. Enlarged kidney is typical radiological finding. In this work we describe an extremely rare case in which a clinically classified cT3b Tumor (level II IVC thrombus) was detected; at specimen analysis to be xantogranulomatous pyelonephritis with IVC extension. MATERIAL AND METHOD: U.V., female, 86 years old, we diagnosed with right renal mass, with extension to IVC. By pathological analysis, it was found that renal mass and the thrombus was not due to RCC, but by xantogranulomatous pyelonephritis. DISCUSSION: Xantogranulomatous pyelonephritis with IVC thrombus is exceptional and has been described in 4 cases. Such a diagnosis could have anesthesiologic importance, in particular related to antimicrobial treatment. Xantogranulomatous pyelonephritis has its own classification, based on extension and organ involvement, but this case fall out of current classification. CONCLUSION: This possibility could be suspected and updating of disease's classification could be suggested.

Clinical features and prognosis of patients with renal cancer and a second malignancy.

OBJECTIVE: To evaluate the epidemiologic aspects, the clinical features, and the prognosis of patients with renal cancer affected by a second malignancy. MATERIALS AND METHODS: Since 1983, at our institution, a database concerning all the patients who underwent surgery for renal neoplasia has been prospectively compiled. In the present study, we compared patients with renal cancer and a second primary malignancy, diagnosed before, at the same time, or after the renal cancer, to those affected only by a renal malignancy. RESULTS: Out of 1,673 patients with renal cancer, 285 (17%) were diagnosed with a second malignancy. The follow-up lasted on average 71 months after the treatment of renal neoplasia. The second neoplasia was antecedent in 115 patients (average latency period 8.5 years), synchronous in 97 patients, and subsequent in 103 patients (average latency period 4.4 years). The sites of associated neoplasia were, in descending order of frequency, prostate, bladder, and bowel for men and breast, gynecologic organs, thyroid, and bladder for women. Compared with the patients not affected by a second neoplasm, those with multiple malignancies generally were older and had a smaller, low-grade, low-stage, and asymptomatic renal tumor. Comparing patients with associated neoplasia with a group without associated neoplasia matched for gender, mode of diagnosis, dimension, grade, stage, and histologic subtype of renal cancer, at survival analysis, no significant differences were noticed in renal cancer-related survival. However, among patients with multiple malignancies, the contemporaneous diagnosis of renal and associated cancer had an independent negative impact on survival. CONCLUSIONS: The association between renal cancer and other malignancies is a frequent event with an unremarkable impact on prognosis, and it shall not limit surgical indication to treat renal cancer, even if the negative prognostic impact of synchronous occurrence of multiple neoplasias should be regarded, especially in older or unhealthy patients, since ablative therapies or active surveillance could be considered as viable alternative options.

[ProACT (Adjustable Continence Therapy) implants in case of failure of other techniques for urinary incontinence]. / Reimpianto del sistema ProACT in caso di fallimento precoce nella cura dell'incontinenza urinaria dopo prostatectomia radicale.

BACKGROUND: Urinary incontinence after radical prostatectomy is one of the most feared problems. It can affect almost 40% of patients, with different degrees of severity according to each specific case. The aim of this work is to analyze our experience in ProACT (Adjustable Continence Therapy) implants, especially in case of failure of other techniques. METHODS: Between November 2007 and December 2010, 31 patients with post-radical prostatectomy incontinence underwent a ProACT implant. Eight patients had their device explanted (in local anesthesia): in two cases the device spontaneously broke, three of them migrated in the urethra (one patient received radiation therapy), another one was infected in the device site (one in BCG treatment for non-muscle invasive bladder cancer), two devices were wrongly placed. Seven of these patients had had their device replaced with success. Using pad score, incontinence was classified as mild, moderate and severe. Overall, the total amount of procedures, most of them fluoroscopic-guided in spinal anesthesia, were 38; the average duration of the surgery was 37.6 minutes. In one patient with impaired balloon volume due to monolateral device malfunction, we noticed good results in controlling incontinence; therefore, we successfully applied the same technique in other four cases with previous partial results. RESULTS: With a total amount of 28 implants, we had 17 (60.7%) complete responses, 6 (25%) partial and 4 (14.3%) failures. We had 4 post-radiotherapy implants: one was completely dry, two were in balloon adjustment, and one of them had a replacement due to urethral erosion of the first implant.
All patients with impaired balloon inflation were satisfied: one was completely dry and three had sensible improvement. CONCLUSIONS: The ProACT is a minimally invasive surgical therapy for post-radical prostatectomy urinary incontinence. Early failure is frequent and is mainly due to rupture and migration of the device. In these cases the solution can be the replacement, even with impaired balloon inflation.

[Acetylcholine induces human detrusor muscle cell proliferation: molecular and pharmacological characterization]. / L'acetilcolina induce la proliferazione delle cellule da muscolo detrusore umano: caratterizzazione molecolare e farmacologica.

INTRODUCTION: The purpose of the study is to understand whether the cholinergic stimulation is important, not only in inducing contraction of the detrusor muscle, but also in modulating the proliferation of smooth muscle cells. These results could help to better understand the role of antimuscarinic drugs, which are currently used for the treatment of many urological diseases. PATIENTS AND METHODS: Primary cultures were prepared from biopsies of human detrusor muscle of subjects >65 years. From the cell culture set-up for each patient, mRNA was extracted and both the gene expression and the influence of increasing passages on the expression of muscarinic receptor subtypes were evaluated by semi-quantitative and quantitative PCR (RT-PCR and Q-RT-PCR). The rate of cell proliferation induced by cholinergic drugs was assessed by the evaluation of the [3H]-thymidine incorporation. RESULTS: The gene expression analysis demonstrated that the range of expression of muscarinic subtypes in human detrusor smooth muscle cells (HDSMCs) is M2 > M3 > M1 > M4 >> M5. The exposure to the cholinergic agonist carbachol induced a concentration-dependent increase in cell proliferation rate. The pharmacological characterization indicated that this effect was mainly mediated by the receptor subtypes M3 and M2. DISCUSSION: The cholinergic stimulation led to an increase in HDSMC proliferation, suggesting that this phenomenon might be involved in the pathogenic mechanism through which the cervico-urethral obstruction causes a detrusor hypertrophy, followed by a loss of function. These results could then provide an indication of the use of antimuscarinic drugs in the treatment of lower urinary tract disorders.