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We aimed to overcome intratumoral heterogeneity in clear cell renal cell carcinoma (clearRCC). One hundred cases of clearRCC were sampled. First, usual standard sampling was applied (1 block/cm of tumor); second, the whole tumor was sampled, and 0.6 mm cores were taken from each block to construct a tissue microarray; third, the residual tissue, mapped by taking pieces 0.5 × 0.5 cm, reconstructed the entire tumor mass. Precisely, six randomly derived pieces of tissues were placed in each cassette, with the number of cassettes being based on the diameter of the tumor (called multisite 3D fusion). Angiogenic and immune markers were tested. Routine 5231 tissue blocks were obtained. Multisite 3D fusion sections showed pattern A, homogeneous high vascular density (10%), pattern B, homogeneous low vascular density (8%) and pattern C, heterogeneous angiogenic signatures (82%). PD-L1 expression was seen as diffuse (7%), low (33%) and absent (60%). Tumor-infiltrating CD8 scored high in 25% (pattern hot), low in 65% (pattern weak) and zero in 10% of cases (pattern desert). Grading was upgraded in 26% of cases (G3–G4), necrosis and sarcomatoid/rhabdoid characters were observed in, respectively, 11 and 7% of cases after 3D fusion (p = 0.03). CD8 and PD-L1 immune expressions were higher in the undifferentiated G4/rhabdoid/sarcomatoid clearRCC subtypes (p = 0.03). Again, 22% of cases were set to intermediate to high risk of clinical recurrence due to new morphological findings of all aggressive G4, sarcomatoid/rhabdoid features by using 3D fusion compared to standard methods (p = 0.04). In conclusion, we propose an easy-to-apply multisite 3D fusion sampling that negates bias due to tumor heterogeneity.

Objective To evaluate the impact of preoperative markers of systemic inflammation on complications and oncological outcomes in patients aged ≥75 years treated with radical cystectomy (RC) for urothelial bladder cancer (UBC). Patients and methods The clinical data of 694 patients treated with open RC for UBC at our institution between January 2008 and December 2015 were retrospectively reviewed. Patients aged 3 was independently associated with OM (hazard ratio 1.38, 95% CI 1.01–1.77; P = 0.01). Conclusions In a cohort of elderly patients with UBC treated with RC, fibrinogen and mGPS appeared to be the most relevant prognostic measurements and increased the accuracy of clinicopathological preoperative models to predict major postoperative complications, disease recurrence and mortality. Abbreviations ASA: American Society of Anesthesiologists; CCI: Charlson Comorbidity Index; CIS: carcinoma in situ; CRP: C-reactive protein; CSM: cancer-specific mortality; CSS: cancer-specific survival; ECOG PS: Eastern Cooperative Oncology Group Performance Status; HDL: high-density lipoprotein; (S)HR: (subdistribution) hazard ratio; LND: lymphadenectomy; LVI: lymphovascular invasion; mGPS: modified Glasgow Prognostic Score; NLR: neutrophil-to-lymphocyte ratio; NOC: non-organ-confined; OM: overall mortality; OR: odds ratio; OS: overall survival; RC: radical cystectomy; RNU: radical nephroureterectomy; UBC: urothelial bladder cancer; UTUC: upper urinary tract urothelial carcinoma

In the past two decades, the treatment landscape for patients with metastatic renal cell carcinoma has significantly changed thanks to the approval of several targeted molecular therapies (VEGF and mTOR inhibitors) and recently immune-checkpoint inhibitors. The Italian Association of Medical Oncology (AIOM) Renal Cell Cancer (RCC) Guidelines Panel has developed clinical guidelines to provide evidence-based information and recommendations to oncologists, urologists and all professionals involved in the management of patients with renal cell cancer.

We describe a rare multicentric neoplastic disease arising bilteraly in the kidney. The patient was a 70-year-old man, who, during a period of 3 years, was treated for five independent tumors of three histotypes (three multilocular cystic clear cell renal cell neoplasms of low malignant potential, one clear cell renal cell carcinoma, and one clear cell papillary renal cell carcinoma, respectively). Pathologic diagnosis of the reported tumors was confirmed by immunohistochemical analyses, including CD10, CA IX, CK7, AMACR/RACEMASE, and 34 beta E12. Molecular detection of KRAS, BRAF, NRAS, PIK3CA, ALK, ERBB2, DDR2, MAP2K1, RET, and EGFR gene mutational analysis was also performed in all tumors.

Introduction Open Simple Enucleation (OSE) has been demonstrated to be an oncologically safe alternative to standard partial nephrectomy. We assessed the mid-term oncologic outcomes and predictors of disease recurrence in patients treated with Endoscopic Robot-Assisted Simple Enucleation (ERASE) verified through a standardized reporting system at a single institution. Material and methods The clinical data of patients treated with ERASE for renal cell carcinoma at our Institution from January 2012 to September 2018 were retrospectively reviewed. Surface-Intermediate-Base (SIB) score was evaluated immediately after surgery. Patients with a ≥2 SIB score were excluded. The local and distant recurrence rates, the recurrence-free (RFS), cancer-specific (CSS) and overall (OS) survival were assessed. Kaplan-Meier and log-rank test were used to estimate survivals and to compare recurrence-free survival. Results Overall, 259 patients were considered eligible for the present study. The median PADUA score was 7 (interquartile range [IQR] 6–9). Positive surgical margins (PSM) were registered in 7 (2.7%) cases. Median (IQR) follow-up time was 36 (27–51) months. Overall, 4 (1.5%) patients experienced systemic recurrence (SR) and 5 (1.9%) patients experienced local recurrence alone (LR) of whom 3 (1.1%) were on tumor resection bed, and 2 (0.8%) experienced recurrence elsewhere in the ipsilateral kidney. The 5-year RFS, CSS and OS were 94.2%, 98.9% and 93.6%, respectively. Higher nucleolar grade and PSM were the two factors significantly associated with worse RFS. Conclusions ERASE is a safe procedure, achieving negative surgical margins in the vast majority of patients and providing excellent mid-term local control and oncologic outcomes.

Background: The availability of a number of agents that are efficacious in patients with metastatic prostate cancer (mPC) has led to them being used sequentially, and this has prolonged patient survival. However, in order to maximize their efficacy, clinicians need to be able to obtain a reliable picture of disease evolution by means of monitoring procedures. Methods: As the intensive monitoring protocols used in pivotal trials cannot be adopted in everyday clinical practice and there is no agreement among the available guidelines, a multidisciplinary panel of Italian experts met to develop recommendations for monitoring mPC patients using a modified Delphi method. Results: The consensus project considered methods of clinically, radiographically, and biochemically monitoring patients with metastatic hormone-sensitive and metastatic castration-resistant prostate cancer undergoing chemotherapy and/or hormonal treatment. The panelists also considered the methods and timing of monitoring castration levels, bone health, and the metabolic syndrome during androgen deprivation therapy. Conclusions: The recommendations, which were drawn up by experts following a formal and validated consensus procedure, will help clinicians face the everyday challenges of monitoring metastatic prostate cancer patients.

Background In recent years, new-onset hypothyroidism was extensively reported in patients receiving sunitinib for malignancy. Effects of sunitinib on serum lipids are not described, however a hyperlipidemic state is commonly observed in hypothyroid patients. Here we report about the incidence and severity of hypercholesterolemia and hypertriglyceridemia in a cohort of patients receiving sunitinib for metastatic renal cell carcinoma. Patients and Methods Thyroid function tests, serum triglycerides, and cholesterol were prospectively evaluated in 39 consecutive metastatic renal cell carcinoma patients, who were receiving sunitinib as a first-line treatment. Incidence of hyperlipidemia, thyroid function impairment, and their possible relationship were investigated. Results Thyroid function tests, serum cholesterol, and triglycerides were assessed at baseline and before the beginning of each sunitinib cycle. During treatment, median triglyceride levels increased up to 271.3 mg/dL, and median cholesterol increased up to 234.7 mg/dL (+113% and +22%, respectively). A hyperlipidemic state developed in 27 patients (69.2%) within a mean time of 1.8 six-week cycles (range, 1-5 cycles) and persisted during treatment. Hypothyroidism was observed in 20 patients (51.2%) and usually developed within 2.3 cycles. Because hypothyroidism and hyperlipidemia developed at different time points of treatment and among different patients, our results failed to demonstrate a correlation between these adverse events. Conclusion New-onset hyperlipidemia was observed in an increased percentage of patients taking sunitinib. The mechanism of this side effect is still unclear. We recommend careful monitoring of serum lipid levels during sunitinib administration to recognize possible consequences, especially on cardiovascular health.

Primary penile cancer is a rare malignant disease. In most cases, it presents as a clinically obvious lesion leading to early diagnosis in most patients. However, even in developed Countries, it carries a significant social stigma leading to diagnosis at locally advanced stages in a non-negligible proportion of patients. Yet, bulky penile lesions are becoming extremely rare in current clinical practice. We present a case of a patient with a giant primary penile cancer managed with radical penectomy, bilateral inguinal lymphadenectomy and perineal urethrostomy, who experienced disease recurrence six months after surgery and died with metastatic disease after denial of further treatment. The management of our case was challenging due to the extremely late diagnosis, the huge dimensions and the infiltrative nature of the tumor; however, from a histopathological perspective, the cancer itself did not display any microscopic peculiarity. Our case highlights that such bulky penile tumors can still occur in current urologic practice and require complex salvage surgical interventions in the context of a multidisciplinary setting.

Objectives To evaluate the efficacy of hemostatic agents, TachoSil and FloSeal, during partial nephrectomy using a large multicenter dataset. Methods Data of 1055 patients who underwent partial nephrectomy between January 2009 and December 2012 in 19 Italian centers were collected within an observational multicentric study (RECORd Project). The decision whether or not to use hemostatic agents after renorrhaphy and the type of hemostatic agents applied was adopted according to the centers' and surgeons' preference. A TriMatch propensity score analysis was applied to balance three study groups (no hemostatic agents, TachoSil, FloSeal) for sex, age, surgical indication (elective/relative vs imperative), clinical stage (cT1a vs cT1b), tumor exophyticity, approach (open vs minimally invasive), technique (standard partial nephrectomy vs simple enucleation), preoperative hemoglobin and creatinine. Postoperative complications and variation of hemoglobin and creatinine values between preoperative versus third postoperative day were compared. Results TriMatch analysis allowed us to obtain 66 well-balanced triplets. No differences were found in terms of outcomes between the study groups. Conclusions The present findings suggest that adding hemostatic agents to renorraphy during partial nephrectomy does not provide better surgical outcomes.

To compare surgical, pathological, short-term functional data, and complications of endoscopic robotic-assisted simple enucleation (ERASE) and open simple enucleation (OSE).We undertook matched-pair analysis (age, tumor size, and preoperative aspects and dimensions used for an anatomical [PADUA] score) of 392 patients treated with simple enucleation (SE) for T1a-T1b renal tumors in our department, including 160 patients in the OSE group and 80 in the ERASE group. Perioperative outcomes were compared with univariate analysis. Variables associated with warm ischemia time (WIT)25 minutes, complications, and postoperative acute kidney dysfunction (AKD) were assessed with multivariate analysis.The groups were comparable in body mass index (BMI), comorbidity, and preoperative renal function. In the ERASE vs the OSE group, no significant differences resulted regarding WIT (18.5 vs 16.4 minutes, P = .5), complications, transfusion rate, reoperation rate for Clavien grade ≥ 3 complications, and positive surgical margin rate (2.9% vs 2.1%, P = .63). In elective patients, no significant difference resulted in variation of estimated glomerular filtration rate from baseline (8.5 vs 13.9 mL/min, P = .17) and AKD. In the ERASE group, the clamping of renal pedicle was used with a lower frequency (P.0001), with lower estimated blood loss (EBL), longer operative time, and a 1-day shorter hospitalization (P = .001). On the multivariate analysis, the surgical approach was not independently associated with WIT25 minutes, postoperative complications, and AKD.The ERASE is a feasible technique with a positive surgical margin rate comparable to OSE; it showed WIT and complication rates similar to the open approach, along with the advantages of mini-invasivity.

We report a case of a 30 years old male affected by synchronous bilateral germ cell tumor with a history of unilateral cryptorchidism; the patient underwent surgical treatment followed by adjuvant radiotherapy on paraaortic and iliac lymphnodes. Patients with synchronous tumors usually present with a higher stage disease in contrast to those with unilateral testicular carcinoma, yet the prognosis remains equally favorable.

Androgen deprivation therapy is commonly employed for the treatment of non-metastatic prostate cancer as primary or adjuvant treatment. The skeleton is greatly compromised in men with prostate cancer during androgen deprivation therapy because of the lack of androgens and estrogens, which are trophic factors for bone. Men receiving androgen deprivation therapy sustain variable degrees of bone loss with an increased risk of fragility fractures. Several bone antiresorptive agents have been tested in randomized controlled trials in these patients. Oral bisphosphonates, such as alendronate and risedronate, and intravenous bisphosphonates, such as pamidronate and zoledronic acid, have been shown to increase bone density and decrease the risk of fractures in men receiving androgen deprivation therapy. Denosumab, a fully monoclonal antibody that inhibits osteoclastic-mediated bone resorption, is also effective in increasing bone mineral density and reducing fracture rates in these patients. The assessment of fracture risk, T-score and/or the evaluation of prevalent fragility fractures are mandatory for the selection of patients who will benefit from antiresorptive therapy. In the future, new agents modulating bone turnover and skeletal muscle metabolism will be available for testing in these subjects.

The new WHO 2016 classification of renal neoplasia encounters the new entity called “clear cell papillary renal cell carcinoma” (ccpRCC). The ccpRCC has been long included as a subtype of clear cell RCC histotype and it actually ranges from 2 to 9% in different routinely available cohort of renal carcinomas. Of important note, ccpRCC does not show any recurrences or metastases or lymph-node invasion and the outcome is always good. We reviewed twenty-four publications with available follow-up for patients (no. 362) affected by clear cell papillary RCCs/renal adenomatoid tumours and notably ccpRCC harbors an indolent clinical behavior after a mean of 38 months (3,5 years) of follow-up. This paper reviews the histological, molecular and clinical features characterizing ccpRCC, with the goal of focusing the knowledge of the benign fashion of this new tumour entity, supporting the idea of a new renal cell adenoma recruited morphologically from ex conventional clear cell RCC tumours.

In men with adverse pathology after radical prostatectomy, the most appropriate timing to administer radiotherapy (RT) remains a topic of debate. We analyzed in terms of efficacy, prognostic factors and toxicity the two therapeutic strategies: immediate postoperative radiotherapy (PORT) and salvage radiotherapy (SART). Between January 1995 and November 2010, 307 patients underwent adjuvant or salvage radiotherapy, after prostatectomy. In the PORT group, 42 patients (20.7 %) had biochemical failure, with a median time to biochemical failure of 1.8 years; two parameters (age at diagnosis and PSA pre-RT) resulted to be significant at the survival analysis for overall survival (p = 0.003 and p = 0.046, respectively). In the SART group, 33 patients (31.7 %) had biochemical relapse; sixteen patients died of prostate cancer; postoperative hormones therapy, conformal radiotherapy and level of PSA pre-RT >1.0 ng/ml resulted to be significant at the survival analysis, p = 0.009, p = 0.039 and p = 0.002, respectively. Our study is limited by its retrospective and nonrandomized design. As such, decisions to treat with adjuvant or salvage radiotherapy and the time to initiate therapy were based on patient preference and physician counseling. Our recommendation is to suggest adjuvant radiotherapy for all patients with adverse prognostic factors and to reserve salvage radiotherapy for low-risk patients, when the biochemical recurrence occurs.

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. 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. 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

BACKGROUND: Sunitinib malate is an orally bioavailable tyrosine kinase inhibitor that is active against many tyrosine kinase receptors involving crucial pathways in both healthy tissues and malignant tissues. Because its use in clinical practice is quite recent, many of its possible side effects remain unknown. In this report, the authors describe the incidence of new-onset hyperparathyroidism in a cohort of patients with metastatic renal cell carcinoma who received treatment with sunitinib. METHODS: Twenty-six patients who received first-line sunitinib for metastatic renal cell carcinoma were enrolled in this study for a mineral and parathyroid function assessment. Plasma levels of intact parathyroid hormone; serum levels of calcium, phosphorus, 25-hydroxyvitamin D3, and 1,25-dihydrovitamin D3; and urinary 24-hour calcium and phosphorus excretion all were measured in each patient. Biochemical evaluations were performed before the beginning of treatment and at the end of each sunitinib treatment period. RESULTS: Eighteen of 26 patients (69.2%) developed hyperparathyroidism with normal serum calcium levels, and 6 of them developed hypophosphatemia. Patients presented with a mean elevation of parathyroid hormone after 2.2 cycles of sunitinib. The levels of 25-OH vitamin D3 were stable over the course of treatment, whereas 1,25-OH vitamin D3 levels were increased in 5 hyperparathyroid patients. Those who presenting with elevated parathyroid hormone levels had low or undetectable urinary calcium levels. Parathyroid hormone elevation usually persisted but did not progress during long-term therapy with sunitinib. Permanent treatment interruption resulted in a resolution of hyperparathyroidism. CONCLUSIONS: Hyperparathyroidism developed in an high percentage of patients on sunitinib. Therefore, the authors concluded that sunitinib may affect parathyroid function and bone mineral homeostasis, possibly resulting in abnormal bone remodeling. Cancer 2012;118: 3165–72. © 2011 American Cancer Society.

Simple tumor enucleation (TE) showed excellent oncologic results in large retrospective series. No study has compared oncologic outcomes after TE and radical nephrectomy (RN) for the treatment of pT1 renal cell carcinoma (RCC). The aim of the present study is to compare the oncologic outcomes after TE and RN in pT1 RCCs. We retrospectively analyzed 475 patients who underwent TE or RN for pT1 RCC, N0, M0, between 1995 and 2007. TE was performed in 332 patients and RN in 143. Local recurrence, progression-free survival (PFS), and cancer-specific survival (CSS) were the main outcomes of this study. The Kaplan-Meier method was used to calculate survival functions, and differences were assessed with the log rank statistic. Univariate and multivariate Cox regression models were also used. The 5- and 10-year PFS estimates were 91.3 and 88.7% after RN and 95.3 and 92.8% after TE (P = NS), respectively. The 5- and 10-year CSS estimates were 92.1 and 89.4% after RN and 94.4% (5- and 10-year CSS) after TE (P = NS), respectively. No statistically significant differences between RN and TE were found after adjusting CSS probabilities according to age at surgery, grade, stage, or clear cell subtype. Surgical treatment was not a predictor of PFS or CSS by both univariate and multivariate analyses. The potential limitation of this study is that the data originate from a retrospective review. TE can achieve oncologic results similar to those of RN for the treatment of pT1 RCCs, provided tumors are carefully selected on the basis of their safe and complete removal.

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Nephron sparing surgery is the standard treatment for RCC up to a diameter of 7 cm, but it’s intra and postoperative morbidity is not negligable. Tumour enucleation is a nephron sparing technique with a demonstrated oncological efficacy while no prospective study evaluated its surgical results and postoperative morbidity to date. Our study adds a prospective evaluation of tumour enucleation morbidity. Our results showed that this technique has a low incidence of postoperative complications, especially of urinary fistula. Major tumour dimension and endorenal tumour growth resulted predictors of postoperative complications. OBJECTIVE • To evaluate the incidence and risk factors of adverse events (AEs) after tumour enucleation (TE). PATIENTS AND METHODS • Between 2006 and 2009, clinical, surgical and functional data were prospectively gathered from 200 consecutive patients who had open TE. • TE was done by blunt dissection using the natural cleavage plane between the tumour capsule and normal parenchyma. • All the AEs were stratified for severity according to the National Cancer Institute Common Toxicity Criteria version 2.0 grading system. • Risk factors for AEs were determined by univariate analysis. RESULTS • The mean (range) tumour size was 3.2 (0.8–10.0) cm, and mean (range) warm ischaemia time (WIT) was 16.5 (5–31) min. • Overall, 32 AEs (six grade I, 20 grade II, and six grade III) occurred after TE in 30 patients and of those 27 were surgical (13.5%) and five were medical AEs (2.5%). • On univariate analysis, imperative/relative surgical indication was the only predictive factor for the development of medical AEs. Statistically significant predictors of overall surgical AEs and urinary fistula were clinical tumour dimension, completely endorenal tumour growth and a positive tumour relationship with the urinary collecting system (UCS). • A completely endorenal tumour growth and a positive tumour relationship with the UCS also correlated with bleeding requiring transfusions. Completely endorenal tumour growth was significantly associated with major (grade III) AEs. CONCLUSIONS • The TE technique was associated with a 16% AE rate and of those only 3% required re-intervention (grade III). • Urinary fistula occurred in six patients (3%) and ureteric stenting was required in 0.5% of cases.

Objective Tumor enucleation has been shown to be oncologically safe for elective treatment of renal cell carcinoma (RCC); yet, evidence on long-term oncologic outcomes after robotic tumor enucleation is lacking. In this study we provide a detailed histopathological analysis of tumor–parenchyma interface and the long-term oncologic outcomes after robotic tumor enucleation for sporadic RCC in a high-volume referral center. Materials and Methods We selected consecutive patients undergoing robotic tumor enucleation for sporadic RCC by experienced surgeons with at least 4 years of follow-up. Pattern of pseudocapsule (PC) invasion, thickness of healthy renal margin removed with the tumor, margin status and recurrence rate were the main study endpoints. Multivariable models evaluated independent predictors of PC invasion. Results Overall, 140 patients were eligible for the study. Of these, 127 (91%) had complete data available for analysis. Median thickness of healthy renal margin was 0.57 mm (interquartile range [IQR] 0.24–103). A distinct peritumoral PC was present in 121/127 (95%) tumors with a median thickness of 0.28 mm (IQR 0.14–0.45). In 24/121 (19.8%) cases, RCC showed complete PC invasion. At multivariable analysis, increasing tumor diameter, endophytic rate > 50% and papillary histology were significantly associated with complete PC invasion. Positive surgical margins were reported in 3/127 (2.4%) cases. At a median follow-up of 61 months (range 48–76), one patient died due to metastatic RCC. Among patients alive at follow-up, no cases of recurrence at the enucleation site were recorded, while three cases (2.4%) of renal recurrence (elsewhere in the ipsilateral kidney) and three cases (2.4%) of systemic recurrence were found. Conclusions Distinct RCC-related features were associated with complete PC invasion. By providing a microscopic layer of healthy renal margin in almost all cases, robotic tumor enucleation achieved negative surgical margins in the vast majority of patients, even in case of complete PC invasion. At long-term follow-up, no recurrences were found at the enucleation site. Although our findings need to be confirmed by larger studies with longer follow-up, robotic tumor enucleation appears oncologically safe in experienced hands for the treatment of sporadic RCC.

OBJECTIVE • To prospectively evaluate the risk of positive surgical margins and local recurrence after blunt tumour enucleation (TE) with no ablation of the tumour bed. PATIENTS AND METHODS • Between 2005 and 2007, data were gathered prospectively from 201 consecutive patients who had open TE with no ablation of the tumour bed. • Overall, 164 consecutive patients had TE for single sporadic renal cell carcinoma (RCC). • All patients had an abdominal computed tomography (CT) at the last follow-up visit. RESULTS • The pathological review showed that 70.2% of tumours were pT1a, 18.9% were pT1b, 1.8% were pT2 and 9.1% were pT3a. • The mean (range, interquartile range) tumour greatest dimension was 3.5 (0.5-12.5, 2.4-4.1) cm. • Although no deliberate attempt to resect normal parenchyma was performed, the pathological analysis showed the presence of a thin layer of parenchyma with a mean (range) thickness of 0.97 (0.31-1.60) mm, around the tumour. None of the patients had positive surgical margins. • At a mean (median, range) follow up of 40 (38, 25-62) months, three (1.8%) patients had local recurrence, of whom one (0.6%) had a true local recurrence at the enucleation site detected 35 months after surgery, while two had kidney recurrence elsewhere associated with concurrent systemic metastases diagnosed 16 and 13 months after surgery. CONCLUSIONS • TE with no ablation of the tumour bed is a safe technique with a local recurrence rate of 0.6%. • The histopathological analysis showed the presence of a minimal tumour-free surgical margin, although no deliberate attempt to resect normal parenchyma is performed.

What’s known on the subject? and What does the study add? Treg overexpression has been demonstrated in several neoplasms, including liver, breast, pancreas and melanoma, while it has not been well evaluated in renal cancer. In renal cancer patients versus controls we found an increased expression of these cells, especially in tumour-infiltrating lymphocytes. Moreover, Treg frequency significantly correlated with pathological stage, nuclear grade and prognostic models. OBJECTIVE • To compare the frequency of T regulatory cells (Tregs) in peripheral blood of patients (pPB) affected by renal cell carcinoma (RCC) both with the frequency of Tregs found in PB of healthy donors (hPB) and that of Tregs present in tumour infiltrating lymphocytes (TILs). To verify in vitro the inhibitory activity of tumour isolated Tregs on the effector T cells and, finally, to assess the prognostic role of Treg frequency determination. PATIENTS AND METHODS • Treg frequency in hPB, pPB and TILs was evaluated in 30 patients and 20 healthy controls by measuring both membrane-CD25 and intracytoplasmic-Foxp3 expression by flow cytometry. • Treg inhibitory activity was evaluated by an in vitro proliferation assay performed on total, CD25-depleted mononuclear cells (MNC) and CD25-depleted MNC cultured in the presence of purified CD25+ Tregs. • Finally, Treg frequency in pPB and TIL were correlated with conventional prognostic factors and scores of University of California Los Angeles and Kattan predictive models. RESULTS • Treg frequency was higher in TILs than in pPB (P= 0.002), whereas there were no important differences between hPB and pPB. CD25+ cells isolated either from PB and tumours showed the ability to significantly suppress in vitro both proliferation and interferon-γ production by CD25-depleted MNC, thus demonstrating that they are active Tregs. • Treg frequency was found to significantly correlate both with pathological stage (pPB, P= 0.03; TIL, P= 0.04) and nuclear grade (TIL, P= 0.005), both for UCLA and Kattan models (all: P < 0.05 for both pPB and TIL). CONCLUSION • Treg frequency is significantly higher in TIL than in pPB of patients with RCC. Tregs showed in vitro an inhibitory activity on effector T cells isolated from kidney tumours. The increase in both peripheral and intratumoral Tregs in subjects affected with RCC were associated with worse prognosis.

Objective: The aim of our study was to analyze the role of perineural invasion (PNI) as a predictive parameter of outcome after radical prostatectomy (RRP) in pathologically organ-confined prostate cancer (PCa) and to assess its possible correlation with other well-known prognostic features. Patients and Methods: At our institution between January 2000 and December 2007, we prospectively collected data from 251 consecutive patients with pathologically localized PCa after antegrade RRP. In our analysis 239 patients were included. PNI was defined as adenocarcinoma within the perineural space adjacent to a nerve. We evaluated the biochemical progression-free survival rate using the Kaplan-Meier method to establish the correlation between PNI and prognosis, the log-rank test to verify the statistical significance, and χ2 test to investigate the correlation between PNI and other clinicopathological parameters. Results: We found intraprostatic PNI in 157 patients (65.7%). The PNI rate was 73% (149/204) in pT2b–c vs. 26% (8/35) in pT2a surgical specimens (p < 0.001), and it was 78.5% (73/93) in patients with a Gleason score of 7–10 vs. 57% (84/146) in a Gleason score of 2–6 (p < 0.01). The mean follow-up was 65.4 (median 62, range 24–118) months. Overall, 11/239 (4.6%) patients presented biochemical recurrence after surgery and 7 (63.6%) of these patients showed PNI, but this was not statistically higher than in patients free from progression (150/228, 65.7%). The actuarial biochemical progression-free survival rate for all patients was 96.9 and 93.5% at 60 and 84 months, respectively, and the stratification based on the presence or absence of PNI did not allow us to identify different prognostic groups. Conclusions: Perineural infiltration frequently takes part in the pathway of extraprostatic extension. In our series, patients with pathological T2 stages and PNI were found to present a higher pT2 stage and Gleason score, even though our early biochemical-free outcome was not significantly higher than in patients without PNI.

Objectives To review the treatment, toxicity, and outcomes in patients with Stage II seminoma after orchidectomy. Materials and methods A retrospective chart review of all patients with Stage II seminoma referred for initial treatment, from 1965 to 2005, was performed. Treatment approaches, toxicity, and outcomes were analyzed. Results A total of 106 patients (83 with Stage IIA, 19 with Stage IIB, and 4 with Stage IIC) were seen between 1965 and 2005. Median age at diagnosis was 36 years (range: 19–71). Median follow-up was 21 years (range: 1.2–42). Eighty-nine patients were treated with adjuvant radiotherapy alone; 13 patients received a combined treatment modality with chemotherapy and radiotherapy after orchidectomy, 4 patients were treated with chemotherapy alone. Generally the treatment was well tolerated, with the main toxicity occurring in patients treated with extended-field radiotherapy. The 5-year disease-specific survival was 96% for the entire group. The 5-year relapse-free survivals for Stages IIA, IIB, and IIC disease were 94%, 72.5%, and 75%, respectively. Fifteen patients developed a relapse and were managed by chemotherapy; 5 of them achieved complete remission and remain free from further recurrence at last follow-up, while 10 died of the disease. Second malignancies were diagnosed in 4 (3.7%) patients during the follow-up. Conclusions In Stage IIA seminoma, radiotherapy continues to provide excellent results, as the majority of patients will be cured with this treatment alone. Radiotherapy or chemotherapy should be offered as an alternative to Stage IIB patients. Chemotherapy remains the treatment of choice for Stage IIC seminoma.

Background: The oncologic safety of blunt tumor enucleation (TE) of renal cell carcinoma (RCC) depends on the presence of a continuous pseudocapsule (PS) around the tumor and on the possibility of obtaining negative surgical margins (SMs). Objective: To investigate the PS and SMs after TE to define the real need to take a rim of healthy parenchyma around the tumor to avoid the risk of positive SMs. The risk of PS invasion related to other clinical and pathologic variables was also evaluated. Design, setting, and participants: Between September 2006 and December 2007, data were gathered prospectively from 187 consecutive patients who had kidney surgery. Overall, 90 consecutive patients who had TE for RCC were eligible for the study. All specimens were evaluated using an image analyzer by a dedicated uropathologist. Intervention: TE was done by blunt dissection using the natural cleavage plane between the tumor and the normal parenchyma. Measurements: PS,SM, and routinely availableclinical andpathologic variableswere recorded.

To evaluate the variation of interpretation of the same bladder urothelium image in different Storz Professional Image Enhancement System (SPIES) modalities. SPIES contains a White light (WL), Spectra A (SA), Spectra B (SB), and Clara and Chroma combined (CC) modality. An App for the iPAD retina was developed to study evaluation of images. A total of 80 images from 20 bladder areas acquired in four modalities were included. Seventy-three participants completed the study. Images were analyzed on differences in delineated tumor margin variation, perceived quality of the image, and delineation time. A separation between high agreement (n = 14) and low agreement (n = 6) images was found. In high agreement images, no difference in root mean square (RMS) was found between modalities. In low agreement images, WL (26.5 pixels) and SA (33.4 pixels) had a higher RMS than CC (18 pixels) and SB (21.4 pixels). The quality of SPIES modalities images was rated significantly higher. Delineation time was similar. In low agreement cases, images in CC and SB have less variation in interpretation than WL and SA. The image quality in SPIES modalities is graded significantly higher than WL. There is no difference in delineation time between modalities

We assessed urodynamic changes after vardenafil administration in spinal cord injured male patients on oxybutynin treatment.We performed a single center, randomized, double-blind, placebo controlled trial in 25 patients with spinal cord injury who had erectile dysfunction and micturition disorders. A baseline urodynamic test was performed as well as a second urodynamic test 1 to 3 hours after the administration of 20 mg vardenafil and placebo in 15 and 10 cases, respectively. In all patients standard oral oxybutynin administration was not discontinued. Statistical assessment included the 3 urodynamic parameters maximum detrusor pressure during voiding, maximum cystometric capacity and detrusor overactivity volume.Placebo administration did not affect urodynamic parameters. After vardenafil administration maximum detrusor pressure was significantly decreased (59.3 vs 52.1 cm H(2)O, p0.001) and maximum cystometric capacity considerably improved (233.5 vs 272 ml, p0.001). The most dramatic variations were observed for detrusor overactivity volume (174 vs 218 ml, p0.0001). In 7 patients with American Spinal Injury Association classification A and spinal cord injury above T6 we observed the most significant improvement in the evaluated urodynamic items, including maximum detrusor pressure 57 vs 52 cm H(2)O (p = 0.039), maximum cystometric capacity 253 vs 296 ml (p = 0.004) and detrusor overactivity volume 177 vs 229 ml (p = 0.003).This trial demonstrates that in spinal cord injured patients a single 20 mg vardenafil administration achieved a significant decrease in maximum detrusor pressure, an improvement in maximum cystometric capacity and a remarkable increase in detrusor overactivity volume value.

Aims and Background Analysis of patients with late relapse of testicular germ cell tumors (GCTs) with reports on clinicopathological features and outcomes. Methods We identified all patients diagnosed with testicular GCTs at our Institute between 1988 and 2004 who developed relapse ≥24 months after completion of primary therapy. A retrospective case-note review was performed to extract clinical, pathological, treatment and outcome data. Results Six patients (1.25%) developed late relapse. All patients presented with stage I disease and were classified as “good risk” according to the International Germ Cell Consensus Classification. Mean time to late relapse was 48 months. Markers at late relapse were normal in all patients. Relapse was confined to retroperitoneal sites in five patients and located in the mediastinum in one patient. Five patients were managed by chemotherapy alone while one underwent combined treatment with surgery followed by chemotherapy. All patients obtained a complete response and all remained free from recurrence with a mean follow-up of 115 months. Conclusions The incidence of late relapse in this small series is low. Chemonaive patients with late relapse were successfully salvaged with chemotherapy alone or surgical excision followed by cisplatin-based chemotherapy. The optimal duration of follow-up in patients with testicular GCTs is not known and practice varies widely. At our Institute we advise lifelong follow-up of all patients with malignant GCTs of the testis.

Chronic prostatitis/chronic pelvic pain syndrome is a major healthcare burden. Affected patient quality of life is poor and currently no investigated treatments have significant long-term benefit. We performed a preliminary investigation of the role of physical activity and its effects on select patients with chronic prostatitis/chronic pelvic pain syndrome.Between 2002 and 2004 we recruited a volunteer sample of 231 eligible males 20 to 50 years old with chronic prostatitis/chronic pelvic pain syndrome who were unresponsive to conventional treatments and free of any contraindication for moderate intensity physical exercise. This group was screened and, if in accordance with study inclusion/exclusion criteria, patients were randomized into 2 groups. Participants were randomly assigned to the aerobic exercise group (52) and the placebo/stretching and motion exercises group (51). Main outcome measures were the Italian version of the National Institutes of Health Chronic Prostatitis Symptom Index, Beck Depression Inventory, State Anxiety Inventory-Y and a pain intensity visual analog scale administered at baseline, and 6 and 18 weeks.At 18 weeks 36 subjects (75%) in the aerobic exercise group vs 40 (81.63%) in the placebo/stretching and motion exercises group completed the 18-week program and evaluation. Differences between the 2 groups were found in total National Institutes of Health Chronic Prostatitis Symptom Index, pain and quality life impact subscales, and pain visual analog score (ANCOVA p = 0.006, 0.0009, 0.02 and 0.003, respectively).Improvements in the aerobic exercise group were significantly superior compared to those in the placebo/stretching and motion exercises group. Aerobic exercise represents a valid treatment option and it should be further investigated in a larger study with longer followup.

The aim of the present review was to compare state-of-the-art care and future perspectives for the detection and treatment of non-muscle-invasive transitional cell carcinoma (TCC) of the bladder. We provide a summary of the third expert meeting on 'Optimising the management of non-muscle-invasive bladder cancer, organized by the European Association of Urology Section for Uro-Technology (ESUT) in collaboration with the Section for Uro-Oncology (ESOU), including a systematic literature review. The article includes a detailed discussion on the current and future perspectives for TCC, including photodynamic diagnosis, optical coherence tomography, narrow band imaging, the Storz Professional Image Enhancement system, magnification and high definition techniques. We also provide a detailed discussion of future surgical treatment options, including en bloc resection and tumour enucleation. Intensive research has been conducted to improve tumour detection and there are promising future perspectives, that require proven clinical efficacy. En bloc resection of bladder tumours may be advantageous, but is currently considered to be experimental.

Objectives To evaluate the safety and efficacy of simple enucleation as a conservative treatment for pT1a RCC, and to report on the incidence of major complications, local recurrence, and progression-free and disease-specific survival rates. Methods We retrospectively reviewed the data of 232 patients who had nephron-sparing surgery (NSS) by simple enucleation between 1986 and 2004 for sporadic, unilateral, pathologically confirmed pT1a RCC. The patients' status was evaluated last in September 2005. The mean (median, range) follow-up was 76 (61, 12–225) months. Results The mean (SD, median, range) tumor greatest dimension was 2.8 (0.78, 2.85, 0.6–4) cm. The histopathologic review according to the International Union Against Cancer and American Joint Commission for Cancer (1997) classification revealed 198 clear cell (85.3%), 18 papillary (7.8%), 15 chromophobe (6.5%) and one (0.4%) collecting duct RCCs. There were no major complications, such as prolonged acute tubular necrosis/chronic renal insufficiency and bleeding requiring open reoperation. One patient developed postoperative late retroperitoneal fluid collection consistent with urinoma, which required aspiration, drainage position and JJ stenting for 3 weeks. The 5- and 10-year cancer-specific survival were 96.7% and 94.7%, respectively. The 5- and 10-year progression-free survival were 96% and 94%, respectively. Overall, 13 (6.4%) patients had disease progression, three of whom had local recurrences alone (1.5%) elsewhere in the kidney; none had local recurrence at the level of the enucleation bed. Conclusions Simple tumor enucleation is a safe and acceptable nephron-sparing treatment that provides excellent long-term local control and cancer-specific survival rates.