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.

18F-FDG PET/CT in a patient affected by renal collecting duct (Bellini) carcinoma.

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.

Surgical treatment of atypical metastasis from renal cell carcinoma (RCC).

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.

[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.

Prognostic role of tumour multifocality in renal cell carcinoma.

UNLABELLED: What's known on the subject? and What does the study add? In RCC about 5% of the patients presented multifocal disease. Prevalence of tumour multifocality was associated with a higher percentage of symptomatic RCC, higher pathological TNM stages, higher tumour grade and higher prevalence of tumour necrosis. Although in univariable analysis multifocal tumours had lower probability of CSS, tumour multifocality did not retain an independent predictive role in multivariable analysis. Patient age at surgery, gender, mode of presentation, pathological N stage and presence of metastases were independent predictors of CSS in multivariable analyses. OBJECTIVE: • To evaluate the prevalence and the prognostic role of multifocality in a large multi-institutional series of patients who underwent radical or partial nephrectomy for renal cell carcinoma (RCC). METHODS: • We retrospectively collected the data of 5378 patients who were surgically treated for RCC in 16 academic centres involved in the Surveillance and Treatment Update Renal Neoplasms (SATURN) project. • Univariable and multivariable Cox regression models addressed time to cancer-specific survival (CSS) after surgery. RESULTS: • Tumour multifocality was identified in 249 patients (5%). The median follow-up of the whole cohort was 42 months. At last follow-up, 786 (14.6%) were dead of cancer and 336 (6.2%) had experienced non-cancer-related death. • The 5- and 10-year CSS estimates were 84.1% and 77.3%, respectively, in patients with monofocal RCC, compared with 71.1% and 63.6%, respectively, in patients with multifocal disease (P < 0.001). • In univariable Cox regression analysis, tumour multifocality was significantly associated with CSS (hazard ratio [HR]= 1.83; P < 0.001). • On multivariate Cox regression analysis adjusted for the effects of other covariates, tumour multifocality did not retain an independent predictive value (HR = 1.24; P= 0.291). CONCLUSIONS: • In the present multi-institutional collaboration, about 5% of the patients presented multifocal RCC. • The presence of multifocal cancer was associated with some unfavourable clinical and pathological features. • Although in univariable analysis multifocal tumours had lower CSS probabilities, tumour multifocality did not retain an independent predictive role in multivariable analysis, once adjusted for the effect of the other clinical and pathological covariates.

Elective partial nephrectomy is equivalent to radical nephrectomy in patients with clinical T1 renal cell carcinoma: results of a retrospective, comparative, multi-institutional study.

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.

Chromophobe renal cell carcinoma (RCC): oncological outcomes and prognostic factors in a large multicentre series.

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.

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.

[Insignificant prostate cancer: charateristics and predictive factors]. / Carcinoma prostatico insignificante: caratteristiche e fattori predittivi.

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.

[Did the staging of renal neoplasm improve with time? Retrospective study on a cohort of 2000 patients]. / La stadiazione della neoplasia renale è migliorata nel tempo? Studio retrospettivo su una coorte contemporanea di 2000 pazienti.

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.

[High-intensity focused ultrasound (HIFU): our experience in the treatment of prostate cancer relapsing after radiotherapy]. / Ultrasuoni focalizzati ad alta intensità (HIFU): la nostra esperienza nel trattamento del carcinoma prostatico recidivo a radioterapia.

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.

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.

Prognostic value of cytogenetic analysis in clear cell renal carcinoma: a study on 131 patients with long-term follow-up.

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.

[Hydronephrosis caused by inferior vena cava penetration by a mobin-uddin filter]. / Idroureteronefrosi secondaria a perforazione della parete della vena cava inferiore da parte di filtro cavale.

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.

Sorafenib's inhibition of prostate cancer growth in transgenic adenocarcinoma mouse prostate mice and its differential effects on endothelial and pericyte growth during tumor angiogenesis.

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.

Cytogenetic features, clinical significance and prognostic impact of type 1 and type 2 papillary renal cell carcinoma.

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.

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.

[Which factors allow to anticipate the diagnosis of prostate cancer in pin patients? A study on 546 patients]. / Quali fattori permettono di prevedere la diagnosi di carcinoma prostatico nei pazienti con PIN? Studio su 546 pazienti.

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.

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.