You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology III (MP65)1 May 2024MP65-20 BLADDER CANCER PATIENT-DERIVED ORGANOIDS: A NEW FRONTIER FOR PERSONALIZED THERAPY Riccardo Mastroianni, Carlotta Frascolla, Sara Donzelli, Claudio Pulito, Andrea Russo, Sabrina Strano, Manuela Costantini, Giovanni Blandino, and Giuseppe Simone Riccardo MastroianniRiccardo Mastroianni , Carlotta FrascollaCarlotta Frascolla , Sara DonzelliSara Donzelli , Claudio PulitoClaudio Pulito , Andrea RussoAndrea Russo , Sabrina StranoSabrina Strano , Manuela CostantiniManuela Costantini , Giovanni BlandinoGiovanni Blandino , and Giuseppe SimoneGiuseppe Simone View All Author Informationhttps://doi.org/10.1097/01.JU.0001008756.24343.22.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Patient-Derived Organoids (PDOs) are proving to be reliable preclinical models for characterization of bladder cancer (BCa). PDOs can be used for molecular assessment of BCa heterogeneity, prediction of chemotherapy response and for generation of patients' biobank. This study aimed to investigate the optimal culturing conditions for BCa PDOs generation and to preliminarily evaluate PDOs response to chemotherapy treatments. METHODS: BCa tissue samples (≥3 cm3) were collected from either TURB or Radical Cystectomy (RC). For RC specimens, tissues from both peripheric tumor (PT) and central tumor (CT) were collected in order to replicate BCa heterogeneity. BCa specimens were mechanically and enzymatically digested to obtain single cells suspension and then freshly or frozen processed. Subsequently, cells were included in drops of extracellular matrix (EM) or without extracellular matrix in Ultra Low Attachment (ULA) cell culture plates and then cultured with 3 different groups of growth factors. BCa PDOs were treated with different concentrations and combinations of cisplatin (CDDP), gemcitabine (GEM) or CDDP and GEM. PDOs drugs' response was assessed by ATPlite assays upon 96 hrs of treatment. Chi-Square test was used to compare categorical variables. RESULTS: Out of 47 BCa tissues analyzed, 39 (83%) were collected from RC (Figure 1). Overall, 20 (43%) BCa PDOs were successfully generated. PDOs seeded in EM had a significantly lower success rate compared to PDOs cultured in ULA plates (EM: 19% vs ULA: 71%; p<0.001). No differences were reported in PDOs generation from fresh or frozen cells suspension (Fresh: 37% vs Freezing: 46%; p=0.51) and from peripheric or central tumor tissues (PT: 33% vs CT: 47%; p=0.38). Growth factors group 3 significantly increased PDOs generation (67%; p=0.02) (Figure 2-3). ATPlite assays reported a PDOs viability rate of 50% and 25%, with 5 µM and 10 µM CDDP, respectively, and a viability rate of 4% and 10% with 5 µM and 10 µM GEM. The combination of CDDP and GEM did not have a synergic effect, mainly due to the strong cytotoxic effect of GEM. CONCLUSIONS: We successfully developed successful culture conditions for BCa PDOs generation. By closely replicating the complexity of BCa tissue, PDOs seem to provide a promising tool to preclinically evaluate response to chemotherapy treatments, paving the way for the modern precision medicine. Download PPTDownload PPTDownload PPTDownload PPT Source of Funding: No © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1084 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Riccardo Mastroianni More articles by this author Carlotta Frascolla More articles by this author Sara Donzelli More articles by this author Claudio Pulito More articles by this author Andrea Russo More articles by this author Sabrina Strano More articles by this author Manuela Costantini More articles by this author Giovanni Blandino More articles by this author Giuseppe Simone More articles by this author Expand All Advertisement PDF downloadLoading ...
You have accessJournal of UrologyBladder Cancer: Invasive III (PD34)1 May 2024PD34-01 IMPACT OF TRANSVAGINAL SPECIMEN EXTRACTION ON URINARY CONTINENCE AFTER ROBOT-ASSISTED RADICAL CYSTECTOMY AND INTRACORPOREAL ORTHOTOPIC NEOBLADDER Riccardo Mastroianni, Gabriele Tuderti, Umberto Anceschi, Alfredo Maria Bove, Aldo Brassetti, Simone D'Annunzio, Mariaconsiglia C. Ferriero, Rocco Simone Flammia, Leonardo Misuraca, Flavia Proietti, Marianna Anselmi, Salvatore Guaglianone, Costantino Leonardo, and Giuseppe Simone Riccardo MastroianniRiccardo Mastroianni , Gabriele TudertiGabriele Tuderti , Umberto AnceschiUmberto Anceschi , Alfredo Maria BoveAlfredo Maria Bove , Aldo BrassettiAldo Brassetti , Simone D'AnnunzioSimone D'Annunzio , Mariaconsiglia C. FerrieroMariaconsiglia C. Ferriero , Rocco Simone FlammiaRocco Simone Flammia , Leonardo MisuracaLeonardo Misuraca , Flavia ProiettiFlavia Proietti , Marianna AnselmiMarianna Anselmi , Salvatore GuaglianoneSalvatore Guaglianone , Costantino LeonardoCostantino Leonardo , and Giuseppe SimoneGiuseppe Simone View All Author Informationhttps://doi.org/10.1097/01.JU.0001008768.36634.79.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Robot-assisted Radical Cystectomy (RARC) with totally intracorporeal (i) orthotopic neobladder (ON) is progressively increasing. However, functional outcomes and their predictors are under-investigated, particularly in female patients. In the robotic era, transvaginal specimen extraction has become routinely performed. The aim of this study was to predict day- and night-time continence recovery in patients receiving RARC and i-ON. METHODS: Our single center IRB approved BCa database was queried for "RARC", "female" and "iON". Baseline demographic, clinical, perioperative and functional outcomes of all consecutive patients treated between Jan 2016 and Jul 2022 were collected. Patients receiving a sex-sparing approach were excluded, due to its established impact on functional outcomes. Continence status was evaluated trough 3-day voiding diaries; day-time continence was defined as "totally dryness" (0gr), night-time continence as pad wetness ≤50gr. Continence recovery probabilities were compared with Kaplan-Meier (KM) method and Cox regression analysis were performed to identify predictors of day-time and night-time continence recovery. RESULTS: Overall, 35 female patients were included. Baseline and perioperative outcomes were reported. Median age was 62 (IQR 55-66) and BMI was 24.5 (IQR 21.5-28.0). High-grade complications (Clavien ≥3) occurred in 11% of patients (Table 1). At KM analysis patients receiving a suprapubic incision for specimen extraction displayed significantly higher day-time continence recovery probabilities (log-rank p=0.013), while no differences were observed for nigh-time continence recovery between transvaginal and suprapubic cohorts (Figure 1-2). At cox-regression analysis, transvaginal specimen extraction predicted a 65% reduced probability of day-time continence recovery (HR 0,35 95% CI 0.14-0.89; p=0.03), while no impact was observed on night-time continence recovery probabilities (p=0.86) (Table 2). CONCLUSIONS: In this single center series, transvaginal specimen extraction seems to negatively affect day-time continence recovery, while night-time continence recovery remained unaltered by specimens extraction site. Larger multi-institutional cohorts and longer follow-up are needed to confirm these findings. Download PPTDownload PPT Source of Funding: No © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e717 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Riccardo Mastroianni More articles by this author Gabriele Tuderti More articles by this author Umberto Anceschi More articles by this author Alfredo Maria Bove More articles by this author Aldo Brassetti More articles by this author Simone D'Annunzio More articles by this author Mariaconsiglia C. Ferriero More articles by this author Rocco Simone Flammia More articles by this author Leonardo Misuraca More articles by this author Flavia Proietti More articles by this author Marianna Anselmi More articles by this author Salvatore Guaglianone More articles by this author Costantino Leonardo More articles by this author Giuseppe Simone More articles by this author Expand All Advertisement PDF downloadLoading ...
Our study explored frozen section reliability in prostate cancer (PCa) diagnoses and described surgical steps of a 3D magnetic resonance imaging (MRI)-ultrasound (US)-guided prostate biopsy (PB) and focal cryoablation of the index lesion (IL) in a single-setting procedure. Patients with a suspicious prostatic specific antigen (PSA) value, with a PIRADS 4 or 5 single lesion, were enrolled for trans perineal 3D MRI-US-guided PB and TRUS-guided focal cryoablation. Three cores were taken from the IL, three cores from the surrounding area, while systematic sampling was performed for the rest of the gland. After confirmation of PCa in frozen sections, focal cryoablation was performed. The 1st-year follow-up schedule included a PSA test at a 3-month interval, MRI 3 months and 1 year postoperatively and PB of the treated area at 1 year. Following the follow-up schedule, an involved PSA test at a 3-month interval and yearly MRI were performed. The PCa diagnosis was histologically confirmed in all three patients with frozen sections. At final histology, a single Gleason score upgrade from 6 (3 + 3) to 7 (3 + 4) was observed. All patients were discharged on postoperative day 1. At the 3-month evaluation, mean PSA values decreased from 12.54 (baseline) to 1.73 ng/mL and MRI images showed complete ablation of the IL in all patients. Urinary continence and potency were preserved in all patients. At the 1-year follow-up, one patient had suspicious ipsilateral recurrence on MRI and underwent a new analogous procedure. Post follow-up was uneventful and PSA remained stable in all patients. Three-dimensional MRI-US-guided frozen sectioning and focal cryoablation of the IL is a step forward towards a "patient-tailored" minimally invasive approach to the diagnosis and cure of PCa.
You have accessJournal of UrologyBladder Cancer: Upper Tract Transitional Cell Carcinoma II (MP38)1 May 2024MP38-17 REAL-WORLD MANAGEMENT OF HIGH-RISK UPPER TRACT UROTHELIAL CARCINOMA: LEVEL OF ADHERENCE TO EAU-AUA GUIDELINES—ANALYSIS OF THE ROBUUST REGISTRY Gabriele Tuderti, Flavia Proietti, Zhenjie Wu, Antonio Franco, Linhui Wang, Vitaly Margulis, Raj Bhanvadia, Firas Abdollah, Marco Finati, Alessandro Antonelli, Francesco Ditonno, Nirmish Singla, Stephan Broenimann, Ithaar H. Derweesh, Dhruv Puri, Soroush Rais-Bahrami, Sol C. Moon, Matteo Ferro, Marco Tozzi, Francesco Porpiglia, Enrico Checcucci, Andreas Correa, Emma Helstrom, Mark L. Gonzalgo, Dinno F. Mendiola, Sisto Perdonà, Antonio Tufano, Benjamine M. Eilender, Reza Mehrazin, Courtney Yong, Chandru P. Sundaram, Alireza Ghoreifi, Hooman Djaladat, Riccardo Autorino, and Giuseppe Simone Gabriele TudertiGabriele Tuderti , Flavia ProiettiFlavia Proietti , Zhenjie WuZhenjie Wu , Antonio FrancoAntonio Franco , Linhui WangLinhui Wang , Vitaly MargulisVitaly Margulis , Raj BhanvadiaRaj Bhanvadia , Firas AbdollahFiras Abdollah , Marco FinatiMarco Finati , Alessandro AntonelliAlessandro Antonelli , Francesco DitonnoFrancesco Ditonno , Nirmish SinglaNirmish Singla , Stephan BroenimannStephan Broenimann , Ithaar H. DerweeshIthaar H. Derweesh , Dhruv PuriDhruv Puri , Soroush Rais-BahramiSoroush Rais-Bahrami , Sol C. MoonSol C. Moon , Matteo FerroMatteo Ferro , Marco TozziMarco Tozzi , Francesco PorpigliaFrancesco Porpiglia , Enrico CheccucciEnrico Checcucci , Andreas CorreaAndreas Correa , Emma HelstromEmma Helstrom , Mark L. GonzalgoMark L. Gonzalgo , Dinno F. MendiolaDinno F. Mendiola , Sisto PerdonàSisto Perdonà , Antonio TufanoAntonio Tufano , Benjamine M. EilenderBenjamine M. Eilender , Reza MehrazinReza Mehrazin , Courtney YongCourtney Yong , Chandru P. SundaramChandru P. Sundaram , Alireza GhoreifiAlireza Ghoreifi , Hooman DjaladatHooman Djaladat , Riccardo AutorinoRiccardo Autorino , and Giuseppe SimoneGiuseppe Simone View All Author Informationhttps://doi.org/10.1097/01.JU.0001008700.92603.b1.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The European Association of Urology (EAU) and American Urological Association (AUA) guidelines (GL) are reference cornerstones in the international urological scenario. We aimed to assess the adherence to EAU-AUA GL in a large multicenter cohort of patients with Upper Tract Urothelial Carcinoma (UTUC), treated with nephroureterectomy (NU). METHODS: A multicenter retrospective analysis utilizing the ROBUUST (ROBotic surgery for Upper tract Urothelial cancer STudy) registry was performed. We assessed the region-specific GL adherence rates for bladder cuff management, post-operative bladder instillation, performance of lymphadenectomy (LND) and adoption of adjuvant chemotherapy (AdCHT). We subsequently assessed the impact of these variables on oncologic outcomes. RESULTS: Overall, data of 2,307 patients were evaluated. Concerning bladder cuff management, strongly recommended from both GL, excision was the most adopted approach world-wide (US 88.6%, Europe (EU) 90.5%, Asia (A) 89.8%). Regarding post-operative bladder instillation, although strongly recommended in both GL, its adoption rate was only 28.4%; notably, at KM analysis patients receiving instillation did not display improved bladder recurrence-free survival (BRFS) (p=0.45). Concerning LND in high-risk disease, weakly recommended for EAU and a strongly recommended for AUA, it appears underused in both locally advanced (cT3-4: US 35.8%, EU 46.8%, A 25%) and cN positive stages (US 41.9%, EU 47.9%, A 43%); however, patients receiving LND had not any benefit in terms of cancer-specific survival (CSS); this data was homogenous across all stages (all p≥0.53). Concerning the use of AdCHT, strongly recommended in both GL for pT2-T4 and/or pN+ disease, overall administration rate was only 27.8% for pT2-T4; moreover, in pN+ disease, its overall use was 30.2%, homogeneously low across all regions. At KM analysis, patients receiving AdCHT hadn't significant CSS benefit. CONCLUSIONS: Real world data highlights poor adherence to UTUC EAU-AUA GL for most of main topics. Despite its retrospective nature, real world data seem to support the need for further research supporting clinical benefits of these intra and postoperative procedures. Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e648 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Gabriele Tuderti More articles by this author Flavia Proietti More articles by this author Zhenjie Wu More articles by this author Antonio Franco More articles by this author Linhui Wang More articles by this author Vitaly Margulis More articles by this author Raj Bhanvadia More articles by this author Firas Abdollah More articles by this author Marco Finati More articles by this author Alessandro Antonelli More articles by this author Francesco Ditonno More articles by this author Nirmish Singla More articles by this author Stephan Broenimann More articles by this author Ithaar H. Derweesh More articles by this author Dhruv Puri More articles by this author Soroush Rais-Bahrami More articles by this author Sol C. Moon More articles by this author Matteo Ferro More articles by this author Marco Tozzi More articles by this author Francesco Porpiglia More articles by this author Enrico Checcucci More articles by this author Andreas Correa More articles by this author Emma Helstrom More articles by this author Mark L. Gonzalgo More articles by this author Dinno F. Mendiola More articles by this author Sisto Perdonà More articles by this author Antonio Tufano More articles by this author Benjamine M. Eilender More articles by this author Reza Mehrazin More articles by this author Courtney Yong More articles by this author Chandru P. Sundaram More articles by this author Alireza Ghoreifi More articles by this author Hooman Djaladat More articles by this author Riccardo Autorino More articles by this author Giuseppe Simone More articles by this author Expand All Advertisement PDF downloadLoading ...