Antonino Battaglia

Proteomic identification of Reticulocalbin 1 as potential tumor marker in renal cell carcinoma.

UNLABELLED Renal cell carcinoma (RCC) biomarkers are necessary for diagnosis and prognosis. They serve to monitor therapy response and follow-up, as drug targets, and therapy predictors in personalized treatments. Proteomics is a suitable method for biomarker discovery. Here we investigate differential protein expression in RCC, and we evaluate Reticulocalbin 1 (RCN1) use as a new potential marker. Neoplastic and healthy tissue samples were collected from 24 RCC patients during radical nephrectomy. Seven specimens were firstly processed by proteomic analysis (2-DE and MALDI-TOF) and 18 differentially expressed proteins from neoplastic and healthy renal tissues were identified. Among them, RCN1 was over-expressed in all cancer specimens analyzed by proteomics. Consequently RCN1 use as a potential marker was further evaluated in all 24 donors. RCN1 expression was verified by Western blotting (WB) and immunohistochemistry (IHC). WB analysis confirmed RCN1 over-expression in 21 out of 24 tumor specimens, whereas IHC displayed focal or diffuse expression of RCN1 in all 24 RCC tissues. Thus RCN1 appears as a potential marker for clinical approaches. A larger histopathological trial will clarify the prognostic value of RCN1 in RCC. BIOLOGICAL SIGNIFICANCE The present work aimed at finding new biomarkers for RCC - a life-threatening disease characterized by high incidence in Western countries - by performing differential proteomic analysis of neoplastic and normal renal tissues obtained from a small cohort of RCC patients. Some of the identified proteins have been previously associated to renal cancer however data confirming the possible use of these proteins in clinical practice are not available to date. By IHC we demonstrated that RCN1 could be easily employed in clinical practice, confirming RCN1 over-expression in RCC tissues of all examined patients, and weak protein expression in healthy renal tissues only in correspondence to the renal tubule section. These data indicate a promising role of RCN1 as a possible marker in RCC and indicate the proximal convoluted renal tubule as a putative origin point for RCC. Since IHC staining displayed different grades of intensity in tested tissues, we hypothesized that RCN1 could also be employed as a prognostic marker or as a response predictor for RCC-targeted therapy. To test such a hypothesis, a larger retrospective trial on paraffin-embedded tissues obtained from radical or partial nephrectomy of RCC patients is planned to be performed by our group.

Role of HLA-G and extracellular vesicles in renal cancer stem cell-induced inhibition of dendritic cell differentiation

BackgroundTumor immune-escape has been related to the ability of cancer cells to inhibit T cell activation and dendritic cell (DC) differentiation. We previously identified a tumor initiating population, expressing the mesenchymal marker CD105, which fulfills the criteria for definition as cancer stem cells (CD105+ CSCs) able to release extracellular vesicles (EVs) that favor tumor progression and metastases. The aim of the present study was to compare the ability of renal CSCs and derived EVs to modulate the behavior of monocyte-derived DCs with a non-tumor initiating renal cancer cell population (CD105- TCs) and their EVs.MethodsMaturation of monocyte-derived DCs was studied in presence of CD105+ CSCs and CD105- TCs and their derived EVs. DC differentiation experiments were evaluated by cytofluorimetric analysis. T cell proliferation and ELISA assays were performed. Monocytes and T cells were purified from peripheral blood mononuclear cells obtained from healthy donors.ResultsThe results obtained demonstrate that both CD105+ CSCs and CD105- TCs impaired the differentiation process of DCs from monocytes. However, the immune-modulatory effect of CD105+ CSCs was significantly greater than that of CD105- TCs. EVs derived from CD105+ CSCs and in less extent, those derived from CD105- TCs retained the ability to impair monocyte maturation and T cell activation. The mechanism has been mainly related to the expression of HLA-G by tumor cells and to its release in a form associated to EVs. HLA-G blockade significantly reduced the inhibitory effect of EVs on DC differentiation.ConclusionsIn conclusion, the results of the present study indicate that renal cancer cells and in particular CSCs and derived EVs impair maturation of DCs and T cell immune response by a mechanism involving HLA-G.

Urology Residency Training in Italy: Results of the First National Survey

BACKGROUND Numerous surveys have been performed to determine the competence and the confidence of residents. However, there is no data available on the condition of Italian residents in urology. OBJECTIVE To investigate the status of training among Italian residents in urology regarding scientific activity and surgical exposure. DESIGN, SETTING, AND PARTICIPANTS A web-based survey that included 445 residents from all of the 25 Italian Residency Programmes was conducted between September 2015 and November 2015. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The main outcomes were represented by scientific activity, involvement in surgical procedures, and overall satisfaction. RESULTS AND LIMITATIONS In total, 324 out of 445 (72.8%) residents completed the survey. Overall, 104 (32%) residents had not published any scientific manuscripts, 148 (46%) published ≤5, 38 (12%) ≤10, 26 (8%) ≤15, four (1%) ≤20, and four (1%) >20 manuscripts, respectively. We did not observe any differences when residents were stratified by sex (p=0.5). Stent positioning (45.7%), extracorporeal shock wave lithotripsy (30.9%), transurethral resection of bladder tumor (33.0%), hydrocelectomy (24.7%), varicocelectomy (17%), ureterolithotripsy (14.5%), and orchiectomy (12.3%) were the surgical procedures more frequently performed by residents. Overall, 272 residents (84%) expressed a good satisfaction for urology specialty, while 178 (54.9%) expressed a good satisfaction for their own residency programme. We observed a statistically decreased trend for good satisfaction for urology specialty according to the postgraduate year (p=0.02). CONCLUSIONS Italian Urology Residency Programmes feature some heavy limitations regarding scientific activity and surgical exposure. Nonetheless, satisfaction rate for urology specialty remains high. Further improvements in Residency Programmes should be made in order to align our schools to others that are actually more challenging. PATIENT SUMMARY In this web-based survey, Italian residents in urology showed limited scientific productivity and low involvement in surgical procedures. Satisfaction for urology specialty remains high, demonstrating continuous interest in this field of study from residents.

Radiofrequency Ablation for Renal Cancer in Von Hippel–Lindau Syndrome Patients: A Prospective Cohort Analysis

Introduction Management of renal‐cell carcinoma (RCC) in patients with Von Hippel–Lindau syndrome (VHL) represents a clinical dilemma: the oncologic outcomes must be weighed against preservation of renal function. Radiofrequency ablation (RFA) is currently used in selected cases for treatment of small‐size RCC. The aim of this study was to evaluate the safety, complications, and functional and oncologic outcomes of RFA in the treatment of RCC in VHL patients. Patients and Methods RCCs were treated with ultrasound‐guided RFA or with laparoscopic RFA. Clinical and radiologic response, disease recurrence, and survival outcomes were evaluated during follow‐up. Early and late complications were recorded and graded. Results Nine RCC patients underwent RFA. The median number of RCCs per patient was 3 (interquartile range, 2‐4). Among these 9 patients, a total of 20 RCCs were treated by RFA (19 ultrasound‐guided RFA and 1 laparoscopic procedure). Median RCC size was 2.5 cm (interquartile range, 2.0‐3.0). RFA did not impair renal function (P = .35). In 2 cases disease persisted, and in 1 case disease recurred after 18 months. These patients were retreated with ultrasound‐guided RFA with complete response and no renal function impairment. RFA treatment was overall well tolerated and safe. No complications were recorded. Postoperative stay was no longer than 1 day. Conclusion RCC occurred in about two‐thirds of VHL patients, who had young age at presentation; it was frequently multifocal and recurrent. The use of RFA, with extended indications, could represent a tailored treatment for VHL patients, reducing the risk of renal failure and resulting in satisfying oncologic results. Micro‐Abstract Management of renal‐cell carcinoma (RCC) in Von Hippel–Lindau syndrome (VHL) patients represents a clinical challenge. Radiofrequency ablation (RFA) is currently used in selected cases for treatment of small‐size RCC. The aim of this study was to evaluate the safety and complication rate of RFA in treating RCC in VHL patients. The treatment did not impair renal function and resulted in complete oncologic control.

Treatment of multiple synchronous misdiagnosed renal cell cancers in a young patient affected by a “de novo” Von Hippel-Lindau syndrome

Introduction Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited syndrome occurring in one out of 36,000 live births. Diagnosis could be a challenge in patients with no familial VHL history. Renal cancer (RCC) represents one of the most important manifestations. RCC is usually recurrent and multifocal. Actually treating RCC in VHL patients represent a clinical dilemma: the oncological outcomes must be balanced against renal function preservation. Case Presentation A young man with a negative familial history was referred to our department with seven misdiagnosed renal masses. VHL disease was determined through genetic test. The multiple RCCs were treated by surgery and percutaneous thermal ablation by radiofrequency ablation (RFA) with complete control of RCC and no impairment of renal function. Conclusions This case history confirms that VHL disease has to be suspected in young patients with evidence of synchronous multiple renal masses and in presence of specific clinical criteria. RFA appears to be safe in terms of oncological radicalism and in renal function preservation. In hereditary RCC, we should purpose, whenever it is possible, minimally invasive treatment in terms of low hospital stay and a minimal loss of renal tissue.

Targeting Taxanes to Castration-Resistant Prostate Cancer Cells by Nanobubbles and Extracorporeal Shock Waves

To target taxanes to castration-resistant prostate cancer cells, glycol-chitosan nanobubbles loaded with paclitaxel and docetaxel were constructed. The loaded nanobubbles were then combined with Extracorporeal Shock Waves, acoustic waves widely used in urology and orthopedics, with no side effects. Nanobubbles, with an average diameter of 353.3 ± 15.5 nm, entered two different castration-resistant prostate cancer cells (PC3 and DU145) as demonstrated by flow cytometry and immunofluorescence. The shock waves applied increased the amount of intracellular nanobubbles. Loading nanobubbles with paclitaxel and docetaxel and combining them with shock waves generated the highest cytotoxic effects, resulting in a paclitaxel GI50 reduction of about 55% and in a docetaxel GI50 reduction of about 45% respectively. Combined treatment also affected cell migration. Paclitaxel-loaded nanobubbles and shock waves reduced cell migration by more than 85% with respect to paclitaxel alone; whereas docetaxel-loaded nanobubbles and shock waves reduced cell migration by more than 82% with respect to docetaxel alone. The present data suggest that nanobubbles can act as a stable taxane reservoir in castration-resistant prostate cancer cells and shock waves can further increase drug release from nanobubbles leading to higher cytotoxic and anti-migration effect.

MP77-01 11C-CHOLINE VERSUS 68GA-PSMA PET/CT SCAN FOR THE DETECTION OF NODAL RECURRENCE FROM PROSTATE CANCER: RESULTS FROM A LARGE, MULTI-INSTITUTIONAL SALVAGE LYMPH NODE DISSECTION SERIES

with uncomplicated UTIs (OBGYNs: OR 21.01, p< 0.001; urologists: OR 2.37, p1⁄4 0.044) compared to internists. Of those who correctly selected a first-line agent, 29.8% prescribed a longer than recommended duration of therapy. IDSA guideline awareness was not associated with physicians’ practices in managing women with bacteriuria. CONCLUSIONS: Most physicians surveyed were unfamiliar with guidelines related to managing ASB and uncomplicated UTIs in women, likely contributing to overscreening and overtreatment of ASB and the use of inappropriate antibiotic regimens in treating uncomplicated UTIs. However, superior antibiotic stewardship was not associated with knowledge of IDSA guidelines, suggesting that guideline dissemination alone may not alter practice patterns among physicians managing women with bacteriuria.

PD72-10 ASSESSING THE RISK OF EARLY AND LATE TOXICITY OF POST-PROSTATECTOMY RADIATION THERAPY: A LONG-TERM MULTI-INSTITUTIONAL ANALYSIS

function, respectively, at 6, 12 and 24 months. All patients in the FBT group had a control prostate biopsy; PCa recurrence was defined as positive biopsy at the same treatment site. In the WBT group, PCa recurrence was defined by PSA increase > nadir + 2. RESULTS: Forty patients were included in the FBT group with complete oncological follow-up. Twenty-seven patients had completed questionnaires with 24 months of follow-up (included in the functional assessment). Initial presentation and treatment characteristics are exhibited on table 1. Median follow-up for FBT and WBT groups were 34 months (range: 10-68 months) and 24 months (range: 24-36 months), respectively. There was no difference in recurrence rates between-groups (FBT 7.5% vs. WBT 3%, p 1⁄4 0.35) (fig. 1). WBT group had significant worsening of urinary symptoms when compared to FBT group at 6 months (p 1⁄4 0.003), but not with 12 and 24 months. Urinary continence and sexual function was similar between-groups. CONCLUSIONS: FBT has satisfactory oncological outcomes and less urinary symptoms at early follow-up when compared to WBT. Urinary continence and sexual functional is the same as WBT.

PD15-09 IDENTIFYING THE OPTIMAL CANDIDATE FOR SALVAGE LYMPH NODE DISSECTION FOR NODAL RECURRENCE OF PROSTATE CANCER: RESULTS FROM A LARGE, MULTI-INSTITUTIONAL ANALYSIS

Nicola Fossati*, Nazareno Suardi, Giorgio Gandaglia, Armando Stabile, Milan, Italy; Michele Colicchia, R. Jeffrey Karnes, Rochester, NY; Friederike Haidl, David Pfister, Daniel Porres, Axel Heidenreich, Cologne, Germany; Christian Gratzke, Annika Herlemann, Christian Stief, Munich, Germany; Antonino Battaglia, Wouter Everaerts, Steven Joniau, Hein Van Poppel, Leuven, Belgium; Alexey V. Aksenov, Daniar K. Osmonov, Klaus-Peter Juenemann, Kiel, Germany; ADL Abreu, Fabio Almeida, Phoenix, AZ; C. Fay, Inderbir Gill, Los Angeles, CA; Alexandre Mottrie, Aalst, Belgium; Francesco Montorsi, Alberto Briganti, Milan, Italy

PD72-06 ADJUVANT VERSUS EARLY SALVAGE RADIATION THERAPY IN NODE POSITIVE PROSTATE CANCER PATIENTS: A LONG-TERM SURVIVAL ANALYSIS

Nicola Fossati*, Milan, Italy; R. Jeffrey Karnes, Stephen Boorjian, Michele Colicchia, Rochester, NY; Alberto Bossi, Thomas Seisen, Villejuif, France; Cesare Cozzarini, Claudio Fiorino, Barbara Noris Chiorda, Giorgio Gandaglia, Milan, Italy; Thomas Wiegel, Ulm, Germany; Shahrokh F. Shariat, Gregor Goldner, Vienna, Austria; Steven Joniau, Antonino Battaglia, Karin Haustermans, Gert De Meerleer, Leuven, Belgium; Val erie Fonteyne, Piet Ost, Ghent, Belgium; Hein Van Poppel, Leuven, Belgium; Francesco Montorsi, Alberto Briganti, Milan, Italy