Complication rate after cystectomy following pelvic radiotherapy: an international, multicenter, retrospective series of 682 cases.

PURPOSE: Conflicting evidence exists on the complication rates after cystectomy following previous radiation (pRTC) with only a few available series. We aim to assess the complication rate of pRTC for abdominal-pelvic malignancies. METHODS: Patients treated with radical cystectomy following any previous history of RT and with available information on complications for a minimum of 1 year were included. Univariable and multivariable logistic regression models were used to assess the relationship between the variable parameters and the risk of any complication. RESULTS: 682 patients underwent pRTC after a previous RT (80.5% EBRT) for prostate, bladder (BC), gynecological or other cancers in 49.1%, 27.4%, 9.8% and 12.9%, respectively. Overall, 512 (75.1%) had at least one post-surgical complication, classified as Clavien ≥ 3 in 29.6% and Clavien V in 2.9%. At least one surgical complication occurred in 350 (51.3%), including bowel leakage in 6.2% and ureteric stricture in 9.4%. A medical complication was observed in 359 (52.6%) patients, with UTI/pyelonephritis being the most common (19%), followed by renal failure (12%). The majority of patients (86%) received an incontinent urinary diversion. In multivariable analysis adjusted for age, gender and type of RT, patients treated with RT for bladder cancer had a 1.7 times increased relative risk of experiencing any complication after RC compared to those with RT for prostate cancer (p = 0.023). The type of diversion (continent vs non-continent) did not influence the risk of complications. CONCLUSION: pRTC carries a high rate of major complications that dramatically exceeds the rates reported in RT-naïve RCs.

Technical solutions to improve the management of non-muscle-invasive transitional cell carcinoma: summary of a European Association of Urology Section for Uro-Technology (ESUT) and Section for Uro-Oncology (ESOU) expert meeting and current and future perspectives.

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.

TriMatch comparison of the efficacy of FloSeal versus TachoSil versus no hemostatic agents for partial nephrectomy: results from a large multicenter dataset.

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.

Sutureless hemostatic control during laparoscopic NSS for the treatment of small renal masses.

BACKGROUND: This study aimed to evaluate the safety and efficacy of a sutureless hemostatic control during laparoscopic nephron sparing surgery (LNSS) for the treatment of small renal masses. METHODS: Between November 2007 and August 2010, 245 patients underwent nephron sparing surgery. Overall, 100 patients (41%) had LNSS. Hemostasis was controlled either by a knot-tying suture repair (standard-LNSS) or by a sutureless technique (s-LNSS). The s-LNSS was done using a bipolar cauterization of the resection bed, followed by Floseal apposition. Operative and warm ischemia time (WIT), intraoperative blood loss, hospital stay, blood tests, and perioperative complications were recorded. RESULTS: In 32 cases (32%) hemostasis was controlled by the sutureless technique. The s-LNSS was the treatment of choice for small tumors ≤1.5 cm, and it was also used for the treatment of tumors between 1.6 and 2.5 cm, aside from their spatial extension. Indeed, the mean (range; interquartile range) clinical dimension of the tumors in the s-LNSS group was 1.9 (1-3.5; 1.5-2.1) cm. On the contrary, the vast majority of tumors >2.5 cm were treated with standard-LNSS. Mean (range; interquartile range) WIT in the s-LNSS group was 16 (8-22; 12-16) minutes. The mean (range) intraoperative blood loss in the s-LNSS group was 107 cc (25-205). No postoperative early and late bleeding were reported in the s-LNSS group, and the mean (range) time to drainage removal and time to discharge were 3 (2-5) and 4 (3-7) days, respectively. CONCLUSIONS: The sutureless technique with bipolar cauterization of the surgical bed and Floseal apposition is safe and effective for the hemostatic control in the treatment of small cortical masses. It can be always used for tumors ≤1.5 cm and can be a valid option also for tumors between 1.6 and 2.5 cm, aside from their spatial extension.

Analysis of surgical complications of renal tumor enucleation with standardized instruments and external validation of PADUA classification.

PURPOSE: To assess surgical results and morbidity of tumor enucleation (TE), and to evaluate their correlation with PADUA nephrometric score. METHODS: We prospectively gathered data, including accurate analysis of tumor nephrometry, from 244 consecutive patients treated with TE for clinically localized renal cell carcinoma. All surgical results were collected, and perioperative complications were stratified for severity according to Clavien system. Correlation between preoperative variables and surgical results/complications was assessed with uni- and multivariate analysis. RESULTS: Mean (range) tumor size was 3.6 (0.8-10.0) cm, and mean (range) warm ischemia time was 16.8 (5-35) min. Overall, perioperative complications occurred in 45 patients (18.4 %), and of those 8 were medical and 37 were surgical (4 Clavien grade 1, 25 grade 2, and 8 grade 3) complications. Urine leakage rate was 2.0 %. No grade 4/5 complications occurred in this series. At univariate analysis PADUA score, endophytic tumor growth, tumor diameter, involvement of UCS and renal sinus resulted associated with warm ischemia time (p < 0.0001 each) and surgical complications (p = 0.0007, p = 0.049, p = 0.021, p = 0.036, and p = 0.029, respectively). At logistic regression, nephrometry score resulted independently associated with overall complications (related risk for each increased point 1.54; p = 0.017), surgical complications (related risk 1.58; p = 0.016), and Clavien grade 3 surgical complications (related risk 2.99; p = 0.008). CONCLUSIONS: The TE technique was associated with a 15.2 % surgical complication rate with a 3.3 % reintervention rate (including ureteral stenting and superselective renal artery embolization). Tumor nephrometry and surgical indication resulted independent predictors of Clavien grade 3 complications. The PADUA score is a reliable tool to predict surgical results and morbidity of TE.

Matching BRCA and prostate cancer in a public health system: Report of the Italian Society for Uro-Oncology (SIUrO) consensus project.

The recent approval of PARP inhibitors for the treatment of metastatic -castration-resistant prostate cancer (mCRPC) patients with BRCA mutations firstly introduced the possibility of proposing a targeted treatment in this disease. However, the availability of this therapeutic option raises a number of questions concerning the management of prostate cancer in everyday clinical practice: the timing and method of detecting BRCA mutations, the therapeutic implications of the detection, and the screening of the members of the family of a prostate cancer patient with a BRCA alteration. These challenging issues led the Italian Society for Uro-Oncology (SIUrO) to organise a Consensus Conference aimed to develop suggestions capable of supporting clinicians managing prostate cancer patients. The present paper described the development of the statements discussed during the consensus, which involved all of the most important Italian scientific societies engaged in the multi-disciplinary and multi-professional management of the disease.

Sunitinib-induced hyperparathyroidism: a possible mechanism to altered bone homeostasis.

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 D(3), and 1,25-dihydrovitamin D(3); 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 D(3) were stable over the course of treatment, whereas 1,25-OH vitamin D(3) 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.

Simple enucleation versus radical nephrectomy in the treatment of pT1a and pT1b renal cell carcinoma.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Morbidity of tumour enucleation for renal cell carcinoma (RCC): results of a single-centre prospective study.

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.

A randomized, placebo-controlled study to assess safety and efficacy of vardenafil 10 mg and tamsulosin 0.4 mg vs. tamsulosin 0.4 mg alone in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia.

INTRODUCTION: Safety and efficacy of tamsulosin and vardenafil are well established: however, there is no report regarding combined therapy with these drugs for lower urinary tract symptoms (LUTSs) secondary to benign prostatic hyperplasia (BPH). AIM: To compare the safety and efficacy of tamsulosin 0.4 mg/day vs. tamsulosin 0.4 mg/day plus vardenafil 10 mg/day in patients with LUTS/BPH in a randomized trial with 12-week follow-up. METHODS: We conducted a randomized, double-blind, placebo-controlled study on 60 men with persistent storage LUTS after 2-week run-in with tamsulosin. MAIN OUTCOME MEASURES: International Prostate Symptom Score (IPSS), IPSS-bother, International Index of Erectile Function, Version 5 (IIEF-5) and Over Active Bladder questionnaire (OAB-q) scores, uroflowmetry data (Qmax, Qave), and postvoiding residual urine were recorded after run-in (baseline), and 2 and 12 weeks after treatment. Differences between vardenafil and placebo at different times were calculated with unpaired samples t-test. Between-group differences in change from baseline to 2 and 12 weeks were evaluated with analysis of variance. RESULTS: We found a between-group significant difference from baseline to 12 weeks in the following: (i) Qmax (placebo: +0.07, vardenafil: +2.56, P = 0.034); (ii) Qave (placebo: -0.15, vardenafil: +1.02, P = 0.031); (iii) irritative-IPSS subscores (placebo: -1.67, vardenafil: -3.11, P = 0.039); and (iv) IIEF (placebo: +0.06, vardenafil: +2.61, P = 0.030). No patient reported any serious (grade ≥ 2) adverse event (AE). There were no differences in the incidence of common, treatment-related AEs between men undergoing combined therapy or tamsulosin alone. CONCLUSIONS: The combination of tamsulosin and vardenafil for 12 weeks was well tolerated and more effective to improve both LUTS and erectile function, as compared with tamsulosin alone. Further studies are needed to assess the role of combined therapy of phosphodiesterase type 5 inhibitors and alpha blockers in treating LUTS/BPH.

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

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

Nephron-sparing surgery for giant angiomyolipomas of kidney.

AIMS: To investigate the potential role of tumor enucleation (TE) for the treatment of giant angiomyolipomas (AML). METHODS: We retrospectively analyzed a prospectively derived database of 707 patients with kidney tumor, who were treated with conservative surgery, between January 1995 and September 2009. Overall, 31 patients had a histopathologic diagnosis of renal AML and of those, 3 patients had a diagnosis of unilateral or bilateral renal mass, with at least one clinically suggestive of giant AML (maximal tumor diameter > or = 9 cm), either central or perihilar. These patients were the subjects of the analysis. Nephron sparing surgery (NSS) was performed as tumor enucleation (TE), carried out by a blunt dissection, using the natural cleavage plane between the tumor and the normal parenchyma. RESULTS: Preoperative tumor size ranged between 9.0 and 15.0 centimetres. At surgery, after kidney capsule incision, TE was done in all cases. In critical surgical steps, in case of difficult visualization of the correct enucleation plane, a sharp dissection a few millimetres away from the tumor was adopted. Warm ischemia time (WIT) was always below 20 minutes. Intraoperative blood loss was negligible. Unsignificant postoperative creatinine variation was recorded in all cases. No intra- and post-operative complications occurred. At last follow up visit, no tumor recurrence at the enucleation site was reported. CONCLUSIONS: TE technique can be considered a viable and effective treatment option for this very rare pathologic condition, since it provides a maximal glomerular preservation and minimizes WIT and intra- and postoperative complications.

The prognostic role of preoperative chromogranin A expression in prostate cancer after radical prostatectomy.

PURPOSES: The aim was to analyze the prognostic role of preoperative chromogranin A CgA) as a marker of poor prognosis and recurrence after radical prostatectomy (RP) and to find a correlation with the other well known prognostic variables. MATERIALS AND METHODS: This study comprises 306 patients with prostate cancer prospectively recruited who underwent RP from between 2000 and 2005. A blood sample for the determination of serum preoperative CgA value was obtained in all cases. Spearman correlation test was used to compare CgA to other variables, Kruskal-Wallis test to analyze CgA differences among > or = 3 groups (PSA, GS, Stage), Mann-Whitney test for 2 grouping variables. Survival analysis was estimated by Kaplan-Meier method, log-rank test to estimate differences among the analyzed variables. RESULTS: Median CgA level was 68 ng/ml. Correlation between age and CgA levels was positive and statistically significant (p < 0.001). Patient were divided in 2 groups based on median age.The difference was statistically significant (p = 0.002). Comparison of CgA among patients grouped according to other variables and patient stratified on normal (123 ng/ml) and cut-off value (68 ng/ml) of CgA did not achieve significant risk stratification. CONCLUSION: Studies on a possible prognostic role of CgA have provided conflicting results. In our series we found a significant positive correlation between CgA and age, but no significant statistical correlation with other available variables analyzed.

Validation of a Novel Three-Dimensional (3D Fusion) Gross Sampling Protocol for Clear Cell Renal Cell Carcinoma to Overcome Intratumoral Heterogeneity: The Meet-Uro 18 Study.

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.

Local recurrence after tumour enucleation for renal cell carcinoma with no ablation of the tumour bed: results of a prospective single-centre study.

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.

Frequency of regulatory T cells in peripheral blood and in tumour-infiltrating lymphocytes correlates with poor prognosis in renal cell carcinoma.

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.

Prognostic role of perineural invasion in 239 consecutive patients with pathologically organ-confined prostate cancer.

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 χ(2) 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.

Oncological impact of inflammatory biomarkers in elderly patients treated with radical cystectomy for urothelial bladder cancer.

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 <75 years, with distant metastases, other-than-urothelial histological type, comorbidities that could affect the systemic inflammatory markers, and patients who received neoadjuvant chemotherapy were excluded. Multivariable regression models were built for the prediction of major postoperative surgical complications, disease recurrence, cancer-specific mortality (CSM), and overall mortality (OM). RESULTS: The median (interquartile range [IQR]) age at surgery was 79 (75-83) years. Major postoperative surgical complications were registered in 41.9% of the patients. The 5-year overall survival, cancer-specific survival and recurrence-free survival rates were 42.4% (95% confidence interval [CI] 34.7-49.9%), 70.3% (95% CI 62.3-76.9%), and 59.8% (95% CI 52.4-66.5), respectively. At multivariable analysis, higher levels of fibrinogen and a modified Glasgow Prognostic Score (mGPS) of 1 and 2 at baseline were independently associated with higher risk of major postoperative complications and of CSM. The inclusion of mGPS and fibrinogen to a standard multivariable model for recurrence and for CSM increased discrimination from 69.4% to 73.0% and from 71.3% to 73.9%, respectively. Preoperative neutrophil-to-lymphocyte ratio of >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.

CXCR3-B expression correlates with tumor necrosis extension in renal cell carcinoma.

PURPOSE: We investigated the expression of the 2 spliced variants of the CXCR3 receptor (CXCR3-A and CXCR3-B) and their ligands (MIG, IP-10 and I-TAC) in patients with renal cell carcinoma according to conventional prognostic factors and the necrosis pattern. MATERIALS AND METHODS: A total of 59 patients with renal cell carcinoma were selected for study. Histotype, stage, grade and tumor diameter were first analyzed. Subsequently tumor necrosis extension, stratified as low-less than 30%, intermediate-30% to 75% and high-greater than 75%, was determined while blinded to pathological data, and CXCR3-B, IP-10, MIG and I-TAC mRNA levels were assessed. The overall correlation between CXCR3-B expression with the specific ligands, and tumor histotype, stage, grade, volume, necrosis extension and ligand expression were assessed on univariate and multivariate analyses. CXCR3-B levels stratified according to necrosis pattern were analyzed with the unpaired t test. RESULTS: CXCR3-B correlated with tumor necrosis and I-TAC (p = 0.0005 and 0.032, respectively). We did not note any correlation between CXCR3-B and histotype, stage, grade, diameter and expression of the other ligands IP-10 and MIG. Moreover, I-TAC did not correlate with tumor necrosis (p = 0.1102). In the multiple regression model a correlation between tumor necrosis and CXCR3-B expression was noted (p = 0.0005). Significant differences in CXCR3-B expression according to the necrosis pattern were observed between low and high, and between intermediate and high patterns (p = 0.0007 and 0.0183, respectively). CONCLUSIONS: Results demonstrate that CXCR3-B is an independent determinant factor for the extensive tumor necrosis pattern. These data emphasize the immunoangiostatic activity of the CXCR3/CXCR3 ligand biological axis for nonmetastatic human renal cell carcinoma.

Antegrade stenting in laparoscopic pyeloplasty: feasibility of the technique and time required for stent insertion.

BACKGROUND: This study aimed to evaluate the authors' initial experience with antegrade stenting. It focused on the success rate, time required for stent insertion, possible complications, and relative solutions in the first 44 procedures. METHODS: Between March 2005 and April 2008, 44 patients (21 women and 23 men) with a mean age of 33 years (range, 17-59 years) underwent transperitoneal laparoscopic Anderson-Hynes pyeloplasty in the authors' department. Antegrade stenting was attempted for all the patients. The time required for stent insertion was recorded as the time from cannula insertion to the correct positioning of the stent in the pelvis. A 4.8-Fr, 26-cm stent was the stent of choice for the first four cases. Then the 6-Fr, 26-cm stent was adopted for all the remaining patients except for one, for whom a 6-Fr, 28-cm stent was adopted. RESULTS: The mean operative time was 197 min (median, 180 min; range, 150-390 min). No conversions to open surgery were required. The stent was positioned correctly in the bladder at the end of the antegrade procedure in 97.7% of the patients without the need for a postoperative X-ray in 95% of the cases. The mean time required for antegrade insertion of the stent was 7 min 30 s (median, 6 min 13 s; range, 3 min 40 s to 22 min 30 s). In the final 12 procedures, the time for stent insertion was constantly reduced to a mean of 4 min 10 s (median, 4 min; range, 3 min 40 s to 7 min). Neither intraoperative nor postoperative complications related to antegrade stent positioning were observed. CONCLUSION: Our data confirm the antegrade procedure to be an easy-to-learn, safe, and reliable stenting technique, with an overall mean time of 7 min 30 s required for insertion, and with a mean time of 4 min 10 s required for insertion in the final 12 procedures. It obviates the problem of having the stent in the renal pelvis during dissection and suturing and of repositioning the patient onto the flank for the laparoscopic procedure.