Search

Objectives: To compare simple enucleation (SE) and standard partial nephrectomy (SPN) in terms of surgical results in a multicenter dataset (RECORd Project)., Materials and Methods: patients treated with nephron sparing surgery (NSS) for clinical T1 renal tumors between January 2009 and January 2011 were evaluated. Overall, 198 patients who underwent SE were retrospectively matched to 198 patients who underwent SPN. The SPN and SE groups were compared regarding intraoperative, early post-operative and pathologic outcome variables. Multivariable analysis was applied to analyze predictors of positive surgical margin (PSM) status., Results: SE was associated with similar WIT (18 vs 17.8 min), lower intraoperative blood loss (177 vs 221 cc, p = 0.02) and shorter operative time (121 vs 147 min; p < 0.0001). Surgical approach (laparoscopic vs. open), tumor size and type of indication (elective/relative vs absolute) were associated with WIT >20 min. The incidence of PSM was significantly lower in patients treated with SE (1.4% vs 6.9%; p = 0.02). At multivariable analysis, PSM was related to the surgical technique, with a 4.7-fold increased risk of PSM for SPN compared to SE. The incidence of overall, medical and surgical complications was similar between SE and SPN., Conclusions: Type of NSS technique (SE vs SPN) adopted has a negligible impact on WIT and postoperative morbidity but SE seems protective against PSM occurrence., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

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.

Unlabelled: What's known on the subject? and What does the study add? The interest in metastatic renal cell carcinoma has increased in the last few years, mainly due to the advent of targeted therapies, but metastasectomy remains the sole therapy that can lead to a complete and durable regression, even if only in a minority of patients. The literature reports quite large series of metastasectomies for the most common sites of metastasis, e.g. lung, liver, bone, adrenal and brain, whereas little is known about the management of metastasis in 'atypical' sites. The prognosis of patients submitted to metastasectomy for a metastasis in an atypical site is equivalent to patients with lung metastasis. The characteristics of the primary tumour in these patients are not indicative, but atypical metastasis (AM) are often located in superficial sites and frequently associated with other metastases. So, physical examination should be included in all follow-up regimens and a complete re-staging should be performed after the diagnosis of an AM., Objective: • To review the clinical characteristics and oncological results in patients submitted to surgical removal of metastasis from renal cell carcinoma (RCC) in atypical sites (atypical metastasis [AM], i.e. metastasis in sites other than the chest, liver, bone, adrenal, brain, kidney, and lymph nodes), compared with patients submitted to metastasectomy due to a lung metastasis (LM)., Patients and Methods: • From an institutional database of ≈1800 patients surgically treated for a RCC, we retrospectively identified 37 cases that had undergone metastasectomy for AM and 57 operated for LM. • Clinicopathological features of the primary RCC and metastasis, and cancer-specific survival (CSS) computed from the time of metastasectomy of patients with AM and LM, were compared. • A univariate and multivariable analysis applying a Cox regression model was used to evaluate CSS., Results: • The patients with AM and LM were followed for an average of 40.8 and 50.7 months from metastasectomy, respectively (P= 0.372). • There were no significant differences in the characteristics of the primary tumour between patients with AM and LM. • In the cases with AM and LM the diagnosis was simultaneous with that of the primary tumour in 32.4% and 24.6%, (P= 0.40) respectively, and, when metachronous, occurred at an average delay of 53.4 and 44.3 months (P= 0.370). • More frequently in the cases with AM other metastases had been diagnosed in the previous medical history (35.2 vs 8.8%, P= 0.001) or simultaneously (48.6 vs 8.8%, P= 0.001). • CSS from metastasectomy was affected by the synchronicity in diagnosis between metastasis and primary tumour, and by the simultaneous presence of other metastases, while the type of metastasis (AM vs LM) did not affect CSS. In fact, metastasectomy in AM was as effective as in LM., Conclusion: • AM are an exceptional presentation of metastatic RCC, but the role of surgery is similar to that of pulmonary metastasis. In these cases, metastasectomy is accepted as possible care, and in AM the CSS after metastasectomy is similar., (© 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL.)

Renal collecting duct (Bellini) carcinoma is a very rare variant of renal cell carcinoma. It is associated with a poor prognosis and is often metastatic at the time of diagnosis. We report a case of a 44-year-old man affected by Bellini carcinoma, who underwent postoperative staging with 18F-FDG PET/CT. It revealed high tracer uptake at multiple lymph nodal metastases.

Unlabelled: Study Type - Outcomes (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? About 80% of RCCs have clear cell histology, and consistent data are available about the clinical and histological characteristics of this histological subtype. Conversely, less attention has been dedicated to the study of non-clear cell renal tumours Specifically, published data show that chromophobe RCC (ChRCC) have often favourable pathological stages and better nuclear grades as well as a lower risk of metastasizing compared with clear cell RCC (ccRCC). Patients with ChRCC were shown to have significantly higher cancer-specific survival (CSS) probabilities compared with ccRCC. However, an independent prognostic role of RCC histotype was not confirmed in some large multicenter series and only a few studies have focused on the oncological outcomes of ChRCC. The present study is one of the few to evaluate cancer-related outcomes of ChRCC and represents to our knowledge the largest series of ChRCCs. Consequently, the present findings may assist in elucidating the natural history of surgically treated ChRCC. The present study confirms that ChRCCs have good prognosis and a low tendency to progress and metastasize. Only 1.3% of patients presented with distant metastases at diagnosis, and the 5- and 10-year CSS were 93% and 88.9%, respectively. However, although ChRCCs are generally characterised by an excellent prognosis, we observed that patients with locally advanced or metastatic cancers as well as those with sarcomatoid differentiation have a poor outcome. The study also investigated prognostic factors for recurrence-free survival (RFS) and CSS for this RCC histotype. The definition of outcome predictors can be useful for patient counselling, planning of follow-up strategies, and patient selection for clinical trials. In the present study, gender, clinical T stage, pathological T stage, and presence of sarcomatoid differentiation were significantly associated with RFS and CSS at multivariable analysis. We also identified N/M stage as an independent predictor of CSS. Notably, as Fuhrman grade was not an independent predictor of cancer-related outcomes, the present study confirms that this histological variable is not a reliable prognostic factor for ChRCC., Objectives: To investigate cancer-related outcomes of chromophobe renal cell carcinoma (ChRCC) in a large multicentre dataset. To determine prognostic factors for recurrence-free survival (RFS) and cancer-specific survival (CSS) for this RCC histological type., Patients and Methods: In all, 291 patients with ChRCC were identified from a multi-institutional retrospective database including 5463 patients who were surgically treated for RCC at 16 Italian academic centres between 1995 and 2007. Univariable and multivariable Cox regression models were used to identify prognostic factors predictive of RFS and CSS after surgery for ChRCC., Results: At a median follow-up of 44 months, 25 patients (8.6%) had disease recurrence and 18 patients (6.2%) died from disease. The 5-year RFS and CSS rates were 89.3% and 93%, respectively. Gender (P= 0.014), clinical T stage (P= 0.017), pathological T stage (P= 0.003), and sarcomatoid differentiation (P= 0.032) were independent predictors of RFS at multivariable analysis. For CSS, there was an independent prognostic role for gender (P= 0.032) and T stage (P= 0.019) among the clinical variables and for T stage (P= 0.016), N/M stage (P= 0.023), and sarcomatoid differentiation (P= 0.015) among the pathological variables., Conclusions: Patients with ChRCC have a low risk of tumour progression, metastasis, and cancer-specific death. Patient gender, clinical and pathological tumour stage, and sarcomatoid differentiation are significant predictors of RFS and CSS for ChRCC., (© 2011 BJU INTERNATIONAL.)

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., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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.

Objective: To compare the oncological outcomes of patients who underwent elective partial nephrectomy (PN) or radical nephrectomy (RN) for clinically organ-confined renal masses ≤7 cm in size (cT1)., Patients and Methods: The records of 3480 patients with cT1N0M0 disease were extracted from a multi-institutional database and analyzed retrospectively., Results: In patients who underwent PN, the risk of clinical understaging was 3.2% in cT1a cases and 10.6% in cT1b cases. With regard to the cT1a patients, the 5- and 10-year cancer-specific survival (CSS) estimates were 94.7% and 90.4%, respectively, after RN and 96.1% and 94.9%, respectively, after PN (log-rank test: P = 0.01). With regard to cT1b patients, the 5-year CSS probabilities were 92.6% after RN and 90% after PN, respectively (log-rank test: P = 0.89). Surgical treatment failed to be an independent predictor of CSS on multivariable analysis, both for cT1a and cT1b patients. Interestingly, PN was oncologically equivalent to RN also in patients with pT3a tumours (log-rank test: P = 0.91)., Conclusions: Elective PN is not associated with an increased risk of recurrence and cancer-specific mortality in both cT1a and cT1b tumours. Data from the present study strongly support the use of partial nephrectomy in patients with clinically T1 tumours, according to the current recommendations of the international guidelines., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

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., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The aim of the study is to evaluate the safety and efficacy of high-intensity focused ultrasound (HIFU) treatment in patients with local prostate cancer recurrence after radiotherapy. From February 2009 to June 2010, 14 patients with prostate cancer recurrence after radiotherapy were selected for HIFU treatment; all patients had a positive TRUS-guided biopsy and the absence of distant metastases was confirmed by computer tomography, PET choline or bone scintigraphy. We classified all patients in 3 groups using D'Amico's classification: 4 patients high risk (PSA >20 ng/ml - 8≤ Gleason Score≤ 10 - clinical stage≥T2c), 8 patients intermediate risk (10 PSAnadir+1.2ng/ml) or after adjuvant therapy introduction. All complications were recorded. Of the 14 patients selected, 12 patients underwent HIFU treatments; 2 patients were excluded because of rectal strictures induced by radiotherapy. At a mean 13 months' follow-up, biochemical success rate was obtained in 1 of the high risk patients and in 5 of the low and intermediate risk patients; 1 man died for a disease not correlated with prostate cancer recurrence. Complications included urinary tract infection, acute urinary retentions, urethral strictures and light stress incontinence. In our experience salvage HIFU is a safe treatment option for local relapse after radiotherapy; its efficacy depends on a careful patient selection.

Introduction: The widespread screening for PSA has contributed to the increased incidence of prostate cancer (PCa), mostly identifying disease at earlier stages. Many of these patients will probably not require treatment because of the indolent course of the disease. The European Randomized Study of Screening for Prostate Cancer (ERSPC) has showed that 1410 men needed to be screened and 48 prostatectomies performed to prevent death. The aim of this study was to evaluate predictive factors of insignificant PCa in our experience., Materials and Methods: We analyzed various preoperative clinical and biopsy findings of 225 consecutive patients who underwent prostatectomy from October 2007 to June 2010. The indication for biopsy was placed in presence of an abnormal rectal examination and/or suspected transrectal ultrasound and/or PSA >4 ng/ml. We consider insignificant a tumor with a volume ≤5% of the entire gland with a Gleason score ≤ 6, with no grades 4 or 5 and organ confined., Results: The prevalence of potentially insignificant PCa in our experience was 12%. The preoperative findings of patients with insignificant PCa were significantly more favorable than the remaining cases with PCa not insignificant. Multivariate analysis did not reveal any independent predictors., Conclusions: In our experience, in a population not screened for PCa, we have not identified any factors that can predict with certainty the insignificant nature of a tumor and, therefore, useful to start a patient on an active surveillance program.

Objectives: During the last 3 decades ultrasonographic and cross-sectional imaging techniques have been widely adopted in the pre-operative staging of renal masses with a progressive technological refinement. The aim of this study is to evaluate if, according to such a change, the accuracy of pre-operative staging is getting better., Materials and Methods: A retrospective analysis of 1935 patients, surgically treated at our Institute since 1983 for a renal neoplasm, has been carried out. Dividing the experience in 2 periods, before and after the year 2000, the diagnostic tools adopted during pre-operative staging and their accuracy have been evaluated by a comparison with the post-operative data (accuracy=true positive+true negative/total number of cases), also taking into account each single aspect of staging (dimension of tumor, local extension, venous invasion, lymphnodal and distant metastasis)., Results and Discussion: 994 patients have been treated before 2000, and 941 afterwards. During time, a progressive reduction in the use of urography and, on the other hand, a diffusion of chest CT have been observed, whereas NMR maintained a similar and limited field of application in both periods. During time, the overall accuracy of staging has not significantly improved (69.5% vs 72.3%, p=0.18), but a slightly better staging of distant (93.9% vs 96.7%, p=0.01) and lymphnodal metastasis (90.9% vs 94.8%, p=0.01) can be found., Conclusions: The pre-operative staging of renal cancer has not really improved during the last 3 decades, in spite of the availability of more precise radiological tools. Anyway, due to the diffusion of CT scan, a slightly better definition of lymphnodal and distant metastasis can be observed. This fact could play a role in indicating a targeted therapy for advanced disease, especially in the light of a neo-adjuvant setting.

The aim of this study was to analyse the factors that predict the diagnosis of prostate cancer (PCa) after high-grade prostatic intraepithelial neoplasia (HGPIN). Data from 546 patients with HGPIN submitted up to a 6-month series of three rebiopsies, according to an institutional protocol, were reviewed. PCa has been found in 174 cases (31.8%), in 116 cases at the first and in 58 cases at a further rebiopsy. The risk of finding PCa at the first rebiopsy was correlated with the PSA value and with an anomalous digital rectal examination (DRE) at the time of the initial biopsy; the risk at a subsequent rebiopsy was correlated to the number of cores with HGPIN, with a cutoff of four, and to the ratio with the total number of cores ('PIN density'), with a cutoff of 50%, at the time of initial biopsy. A tailored protocol of controls can be suggested: (a) higher PSA value and/or anomalous DRE: early extended or saturation rebiopsy; (b) number of cores with HGPIN ≥4 and/or PIN density ≥50%: delayed rebiopsy; and (c) no risk factors: PSA and DRE controls.

Background and Aims: Cytogenetic analysis has a role in diagnosis of conventional renal cell carcinoma, but its role in prognosis is still matter of debate. This study reviews the Authors' experience in cytogenetic analysis of clear cell renal carcinoma., Patients and Methods: Data from 131 patients with clear cell renal carcinoma who underwent cytogenetic analysis of the tumour karyotype at the host institute between 1997 and 2002 were prospectively collected. In all cases, the cytogenetic analysis was carried out by a single experienced geneticist and the morphological features of the neoplasia were evaluated by a single experienced uropathologist., Results: Patients were followed up for an average period of 67.3 months, median of 73 months, range 12-136 months. The statistical association among chromosome alterations, clinico-pathological features and disease-free survival were investigated. At univariate analysis, symptoms at diagnosis, tumour diameter, Fuhrman's grading, TNM stage and sarcomatoid differentiation were all significantly correlated with survival, whereas among chromosomal abnormalities, deletion of chromosomes 19, 20 and 22 showed a significant impact on survival. At multivariate analysis of these factors, TNM stage and deletion of chromosome 19 maintained an independent and statistically significant association with disease-free survival., Conclusion: Although these results may be considered as preliminary, it is possible to conclude that the alterations of the tumour karyotype may contribute to determining prognosis of patients with clear cell renal carcinoma.

Aim of the Study: To analyze which factors allow to assess the risk of finding a prostate cancer (PCa) at repeated biopsies in patients with diagnosis of prostatic intraepithelial neoplasia (PIN)., Patients and Methods: At our institute all patients with a diagnosis of PIN undergo a 6-monthly control biopsy until the achievement of a benign histology or up to a maximum of 4 consecutive biopsies. For this study a retrospective review of clinical and bioptic data of patients with a diagnosis of isolated PIN (i.e. without associated atypical small acinar proliferation or small cancer foci) was carried out. The correlation between these features and the probability to find PCa at the first re-biopsy or at a further re-biopsy was independently analyzed., Results: The data of 546 patients subjected to a median number of 3 biopsies, (mean: 10.8 and 12.9 cores at initial biopsy and at first re-biopsy, respectively), and with a mean “bioptic” follow-up time of 14.8 months, were analyzed. PCa was found in 174 cases (31.8%): for 116 of them it took place at the first re-biopsy, with a mean latency of 7.8 months from PIN diagnosis, whereas for 58 at a further re-biopsy, with a mean latency of 21.6 months. The risk of diagnosing PCa at the first re-biopsy was statistically correlated with the PSA value--for which a cut-off value of 7 ng/mL was identified--and with an anomalous rectal prostatic examination at the time of the initial biopsy. Differently, the risk of diagnosing PCa after the first re-biopsy correlated with the number of cores positive for PIN at the initial biopsy--for which a cut-off of 4 was identified--and to the ratio between these and the total number of cores, defined as PIN density--for which a cut-off of 50% was determined. DISCUSSION AND CONCLUSIONS. It is possible to suggest a tailored protocol of controls in patients with a diagnosis of PIN on the basis of the data available at the initial biopsy: a) high PSA value and/or an anomalous prostatic rectal examination: the diagnosis of PCa is probably just unacknowledged by the initial sampling and it is advisable to carry out an early re-biopsy; b) number of cores with PIN equal to or higher than 4 and/or PIN density equal to or higher than 50%: a true transition from PIN to PCa is likely to happen with time and it is advisable to carry out a delayed re-biopsy; c) no risk factors: just clinical and PSA monitoring to establish the indication to re-biopsy.

The inferior vena cava (IVC) filter placement represents an excellent protection from significant pulmonary embolism in at-risk patients. Perforation of the wall of the IVC by components of caval filters is a recognized complication. We report a case of asymptomatic hydronephrosis caused by transcaval penetration of a Mobin-Uddin filter.

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.

Objective: To evaluate Sorafenib's efficacy (60 mg/kg/d per os) in preventing the transformation of high grade prostate intraepithelial neoplasia (HGPIN) into adenocarcinoma (ADC) and in inhibiting the onset and progression of poorly differentiated carcinoma (PDC) in transgenic adenocarcinoma mouse prostate (TRAMP) mice., Study Design: Forty-four TRAMP mice were randomly divided into 2 groups of 22 and assigned to daily treatment by gavage with vehicle only or Sorafenib from the 10th to the 26th week of age. At 26 weeks of age the mice were killed, and their genitourinary apparatus was removed and examined by histology, immunohistochemistry and confocal microscopy., Results: Sorafenib reduced HGPIN growth and progression to ADC and was probably also effective in PDC inhibition. The major effect of Sorafenib was on tumor angiogenesis. Interestingly a dissociation between endothelial cells and pericytes was noted in treated PDC since inhibition of pericyte recruitment was less complete than that of endothelial cells., Conclusion: Sorafenib's potent antiangiogenic action may be supposed to be exerted primarily by inhibiting endothelial proliferation and sprouting, whereas its inhibition of pericyte recruitment and maturation is less complete. These observations suggest that Sorafenib's effects could be improved by the joint employment of substances capable of interfering with the recruitment and organization of pericytes.

The purpose of this paper is to evaluate the clinical, pathologic, and cytogenetic features, as well as the disease-free survival in patients with papillary renal cell carcinoma (PRCC) subdivided into types 1 and 2, according to the definition given by Delahunt and Eble. The clinical, surgical, and follow-up data for the PRCC cases treated since 1995 were taken from an institutional database. The samples were revised by an experienced pathologist, who subdivided them into types 1 and 2. The data from the cases in which the tumor karyotype was available were analyzed. Out of 1,150 patients surgically treated for renal cancer, 132 cases of PRCC were detected (prevalence 11.5%), 57 with type 1 and 75 with type 2, followed for a mean period of 50 months. Tumor diameter, peri-renal tissues, as well as venous invasion, lymphnodal, and distant metastasis were highlighted to be distributed with a significant difference between the two groups, which indicated higher aggressiveness in type 2 cases. Survival analysis has showed a significantly higher-progression risk and a shorter disease-free survival in type 2 cases. An evaluable tumoral karyotype was obtained in 26 cases. An overlapping distribution was detected in chromosomes 7, 17, 12, 16, and 20, while some alterations in chromosomes 10, 5, 6, 11, 15, 18, 22, and 8 appeared as typical of type 2 cases. In conclusion, types 1 and 2 PRCC have different pathologic and cytogenetic features and a radically different biologic behavior - indolent in type 1 and aggressive in type 2., (Copyright 2010 Elsevier Inc. All rights reserved.)

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.

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.

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., ((c) 2008 Wiley-Liss, Inc.)

Objective: To compare the oncologic outcomes of nephron-sparing surgery versus radical nephrectomy in intracapsular renal cell carcinoma (RCC) up to 7 cm by reviewing surgical experience retrospectively., Methods: Data from 1290 consecutive patients who had surgery for RCC have been stored in a dedicated database since 1983. We selected and reviewed those related to disease-free patients who had been treated for unilateral pT1a/pT1b pN0/Nx M0 carcinomas up to 7 cm and later followed for a minimum of 12 mo., Results: A total of 642 patients with mean follow-up of 72.9 mo were selected; 313 had been treated for tumours <4 cm in diameter (176 nephron-sparing surgery, 137 nephrectomy), whereas 329 had been treated for tumours measuring > or =4 cm (52 nephron-sparing surgery, 277 nephrectomy). The comparison between tumours <4 cm or > or =4 cm in diameter showed worse progression and disease-free survival rates for the latter, but the type of surgery (nephron-sparing or radical) seemed to have no significant impact., Conclusions: Conservative management can be cautiously suggested for RCC up to 7 cm because the worsening of prognosis as diameter increases shows no statistical differences for either nephron-sparing or radical surgery. The agreement of our results with those of similar studies available in the literature may suggest designing a prospective study to compare conservative and more radical surgery in the management of RCC up to 7 cm.

A dysregulation of the nerve growth factor (NGF)-mediated control of prostate cell growth is associated with the malignant progression of prostate epithelial cells. Exogenous NGF induced in prostate cancer (PCa) cell lines DU145 and PC3 the expression of p75(NGFR), accompanied by a reduction of the cell malignancy. The aim of this study was to analyze the profile of NGF-regulated genes the PCa cell line DU145 by using the cDNA microarray technique. NGF treatment of DU145 cells decreased the expression of 52 known genes, while the expression of 40 known genes was increased. NGF treatment of the DU145 cell line modified the expression profile of clusters of genes involved in invasion and metastasis, in cell proliferation and apoptosis, inflammation, cell metabolism and transcriptional activity. Interestingly, NGF induced the same pattern of gene modifications in both PCa cell lines. Data presented here may help to identify gene/proteins that dispose to PCa progression and to assess future markers that could allow the development of new clinic diagnostic and therapeutical approaches.

Objectives: To compare the prognostic accuracy of the Solsona and European Association of Urology (EAU) risk groups in the identification of lymph node involvement in a cohort of patients with squamous cell carcinoma of the penis., Methods: The clinical and pathologic data of 175 patients who had undergone surgery for squamous cell carcinoma of the penis from 1980 to 2002 at 11 urologic centers of northeastern Italy were retrospectively collected., Results: According to the EAU risk group, 25 patients were categorized as at low (15.1%), 23 (13.9%) as intermediate, and 118 (71.1%) as high risk of lymph node metastasis. Similarly, using the criteria of the Solsona risk group stratification, 25 (15.1%), 55 (33.1%), and 86 patients (51.8%) were categorized as at low, intermediate, and high risk. At the median follow-up of 26 months, lymph node involvement was observed in 71 (40.6%) of 175 patients. Receiver operating characteristic curve analysis showed that both the EAU risk group (area under the curve = 0.632) and Solsona risk group (area under the curve = 0.697) had a low accuracy for predicting lymph node involvement. Both risk groups were independent predictors of lymph node involvement, as well as the clinical stage of lymph node involvement and the presence of vascular and/or lymphatic embolization., Conclusions: The Solsona and EAU risk groups were both independent predictors of lymph node involvement, although the receiver operating characteristic curve analysis showed that both risk groups had low predictive accuracy.

Aims: Muscarinic receptor subtypes expressed in the human urinary bladder mucosa were characterized, investigating whether there were gender-dependent differences and if aging could induce changes in their expression., Methods: The study was carried out on 34 subjects, 22 men and 12 women, divided in four groups, based on gender and age. Gene expression was evaluated by quantitative RT-PCR. The Western blot was performed using the 4-12% NuPAGE Bis-Tris Gel System., Results: The molecular expression of each subtype of the M(1) receptor family was observed and it was not influenced either by gender or age. M(2) receptor family transcripts revealed that both M(2) and M(4) were detected and that the M(2) transcripts were modified by both gender and age. Indeed, M(2) mRNA was lower in old rather than adult men (P < 0.05), but higher in rather old than adult women (P < 0.05). Further, adult men expressed more M(2) mRNA than adult women (P < 0.05), while the opposite was detected in old age (P < 0.05). The Western blot followed by quantification confirmed that the mRNAs were translated into proteins, and that the M(2) subtype showed similar modifications found at molecular level., Discussion: The selective modification of M(2) receptors observed at the urinary bladder mucosa levels indicates that this anatomical structure could play an active role in the pathophysiology of micturition and supports evidence suggesting an effect of antimuscarinic drugs at this level. Whether these results may influence the age-dependent development of micturition disorders remains to be determined.

Objectives: An observational study was planned by the QuABIOS group, to survey the hormonal treatment administered to prostate cancer patients in Italy within a time window of 12 months. We report here a prospective quality of life (QOL) evaluation over time and by hormonal treatment modalities., Methods: Patients with diagnosis of prostate cancer and treated with hormonal therapy were eligible for this study. The EORTC QLQ-C30 v.3 questionnaire was administered at enrolment, after 6 months and after 12 months from enrolment., Results: 587 patients were enrolled by 33 urological centers. When 1518 visits were considered together independently of time, antiandrogen monotherapy was associated with a significantly better QOL than LHRH-analogue containing treatment modalities in almost all functional scales; cyproterone acetate demonstrated a better physical function and general health status than bicalutamide. When QOL was analyzed in a prospective 12-month window, a worsening of physical function and general health status was observed, notwithstanding, antiandrogens remained significantly associated to a better QOL than LHRH-analogue therapies also over time: a favourable physical function and general health status appeared again to be related to cyproterone acetate than bicalutamide., Conclusions: Androgen deprivation therapy is associated with decline in QOL, particularly in the domains of physical function, energy, and general health status. This survey demonstrated that antiandrogens had a better QOL profile than LHRH-analogue containing therapies;furthermore, a more favourable tolerability for cyproterone acetate as compared to bicalutamide is suggested.

Objective: To define a follow-up protocol based on the University of California Los Angeles Integrated Staging System (UISS) for patients undergoing surgery for N0M0 renal cell carcinoma (RCC)., Patients and Methods: The clinical records of patients treated with radical surgery for N0/NXM0 RCC and monitored through periodic follow-up studies (> or =24 months in disease-free patients) were reviewed retrospectively from 1399 patients surgically treated for renal neoplasms between 1983 and 2005. Each case was assigned a UISS risk category; recurrence features, time and site were recorded. In particular, recurrence sites were categorized into local, renal (ipsilateral or contralateral) and distant (single-site or disseminated)., Results: The records were reviewed of 814 patients with a mean follow-up of 75.6 months. UISS risk categories were distributed as follows: high-risk (HR) 17.2%, intermediate-risk (IR) 51.6% and low-risk (LR) 31.2%. Disease-free survival rates at 5 years were 63.9%, 88.3% and 96.5% (log-rank test P < 0.001), respectively. The disease recurred in 193 patients (23.7%), at distant sites (73.0% of recurrences), locally (11.9%), in the contralateral kidney (10.9%) and in the ipsilateral kidney (4.1%). There was a significant correlation between UISS category and risk of distant or local (both P < 0.001) recurrences, whereas there was no correlation of recurrences in the operated kidney (P = 0.372) or contralateral kidney (P = 0.898)., Conclusions: The prognostic accuracy and applicability of the UISS for distant and local recurrences is confirmed, whereas renal relapses have an independent course. A follow-up scheme tailored to the recurrence patterns observed in each UISS risk group is recommended.

Objectives: To present and discuss clinical and surgical management of urologic endometriosis., Methods: Retrospective review of a database on surgical patients with endometriosis., Results: Thirty-one patients (incidence, 2.6%; mean age, 33.1 yr) were affected by urologic endometriosis (bladder, 12; ureter, 15; both, 4). Bladder endometriosis was revealed by symptoms related to menses and showed a typical endoscopic picture, whereas ureteral involvement had a nonspecific or silent symptomatology. All patients affected by bladder endometriosis and undergoing transurethral resection (2 cases) developed a bladder recurrence; a ureteral recurrence was observed in two of six patients submitted to laparoscopic ureterolysis and in one of two patients submitted to ureterectomy with ureteroureterostomy. Conversely, no relapses were observed among the 14 patients who had partial cystectomy or the 9 who had ureterectomy and ureterocystoneostomy. Finally, two patients underwent nephrectomy due to end-stage renal atrophy., Conclusions: Cystoscopy is advisable in women with pelvic endometriosis with lower urinary tract symptoms; the upper urinary tract should be evaluated in all patients with pelvic endometriosis to exclude asymptomatic ureteral involvement. Partial cystectomy gives the best results when used to treat bladder endometriosis. Ureterolysis can be successful only in case of limited ureteral involvement with no urinary obstruction, whereas terminal ureterectomy and ureterocystoneostomy should be preferred in case of obstructive ureteral endometriosis.

The sarcomatoid carcinoma of the urinary bladder is a rare variant of transitional carcinomas with an extremely aggressive clinical course and dismal prognosis regardless therapies. The diagnosis of a bladder sarcomatoid carcinoma involving perivesical tissues with limphnodal, hepatic and lung metastasis was done in a 34-years old male. The disease underwent complete remission after neoadjuvant chemotherapy with adriblastine and ifosfamide, radical surgery and adjuvant chemotherapy with the same drugs, as confirmed by CT, vesical biopsies during chemotherapy and by the findings detected on the surgical specimen. Follow-up is negative for relapses at 72 months. The sarcomatoid bladder carcinoma is a rare variant of transitional carcinoma (0.31%), usually diagnosed in the late decades of life, with a survival time of a few months for metastatic patients regardless of any adopted therapies. The case presented is remarkable due to the young age of the patient but, overall, for the complete and durable regression of the disease achieved applying a chemotherapic scheme commonly adopted to treat pure sarcomatous mesenchimal neoplasms. Due to the rarity of the disease and the consequent unfeasibility of randomized studies, in our opinion these results, even if obtained in a single case, suggest a viable therapeutic option.

Background: The objective of the current study was to identify independent clinical and pathologic variables that were predictive of lymph node involvement in patients with squamous cell carcinoma of the penis in a multicenter series with the intent to select patients who were suitable to undergo immediate inguinal lymphadenectomy., Methods: Data were analyzed from 175 patients who underwent surgery for penile carcinoma in 11 urologic centers participating in the Gruppo Uro-Oncologico del Nord-Est (Northeast Uro-Oncological Group) Penile Cancer Data Base. Pathologically positive lymph nodes were defined as the presence of histologically confirmed lymph node metastasis in patients who underwent either immediate or delayed inguinal and/or pelvic lymphadenectomy. Patients who had clinically positive lymph nodes with cytologically positive fine-needle aspiration results and who had not undergone lymphadenectomy were censored., Results: Overall, lymph-node involvement was observed in 71 of 175 patients (40.6%) included in the analyses. After analyzing the whole group of patients, the following variables were identified as independent predictors of pathologic lymph node metastasis: clinical lymph node status, pathologic stage of the primary tumor, venous and lymphatic embolizations, and histologic grade. In the subgroup of patients with clinically negative lymph nodes, tumor thickness, histologic grade, lymphatic and venous embolizations, infiltration of both corpus spongiosum and urethra, and pathologic stage of the primary tumor (according to the 1997 TNM classification system) were predictive of lymph node involvement on univariate analysis. The generated logistic regression model showed that venous and/or lymphatic embolizations and infiltration of the corpus spongiosum and/or urethra were independent predictors of pathologic lymph node metastasis in patients with clinically negative lymph nodes., Conclusions: Venous and/or lymphatic embolizations played relevant roles as predictors of pathologic lymph node involvement in patients with penile neoplasia and should be considered important parameters in determining which patients with clinically negative lymph nodes should undergo immediate lymphadenectomy., (Copyright 2005 American Cancer Society.)

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.

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.