ABSTRACTS <strong>XIV</strong> <strong>Congresso</strong> <strong>Nazionale</strong> <strong>Società</strong> <strong>Italiana</strong> <strong>di</strong> Urologia OncologicaIntroduzione: Descriviamo l’approccio chirurgico conservativo,organ sparing, in un caso <strong>di</strong> neoplasia testicolare bilateralemetacrona.Materiali e Meto<strong>di</strong>: In un paziente <strong>di</strong> anni 27, già sottoposto adorchiectomia destra <strong>per</strong> carcinoma embrionario (sta<strong>di</strong>o clinicoII B), chemioterapia a<strong>di</strong>uvante e linfadenectomia retro<strong>per</strong>itonealebilaterale, veniva riscontrata, a <strong>di</strong>stanza <strong>di</strong> 2 anni, unaneoformazione del polo su<strong>per</strong>iore del <strong>di</strong><strong>di</strong>mo su<strong>per</strong>siste <strong>di</strong>circa 2 cm con contestuale incremento dell’AFP (alfa feto proteina).Su richiesta del paziente, dopo averne comprovato ilnormale assetto ormonale, veniva eseguita una orchiectomiaparziale sinistra. La tecnica prevede la enucleo-resezione deltumore, previo clampaggio del funicolo, e multiple biopsie del“letto <strong>di</strong> resezione” <strong>per</strong> esame istologico estemporaneo.Biopsie random del parenchima <strong>di</strong>stale devono essere eseguite<strong>per</strong> escludere la contestuale presenza <strong>di</strong> T.I.N. L’esame istologicodefinitivo riba<strong>di</strong>va la <strong>di</strong>agnosi <strong>di</strong> neoplasia maligna acellule germinali a componente mista teratomatosa e del tipocarcinoma embrionario.Risultati: A <strong>di</strong>stanza <strong>di</strong> 12 mesi dall’intervento non è statariscontrata reci<strong>di</strong>va neoplastica, con normalizzazione dell’AFP;il paziente non riferisce <strong>di</strong>sturbi della libido e della potenza epresenta un normale assetto ormonale.Discussione: La chirurgia organ-sparing dei tumori del testicoloè in<strong>di</strong>cata <strong>per</strong> tumori bilaterali, sincroni o metacroni, e <strong>per</strong>quelli insorti in testicolo singolo, purché organo-confinati e <strong>di</strong><strong>di</strong>ametro inferiore a 2,5 cm (1). Tale approccio si propone <strong>di</strong>preservare la fertilità e la qualità <strong>di</strong> vita dei pazienti, altrimentiinficiata dalla deplezione androgenica e dallo stress psicologicodella castrazione. I rischi <strong>di</strong> malattia multifocale e <strong>di</strong> reci<strong>di</strong>valocale impongono una attenta valutazione intrao<strong>per</strong>atoriadel parenchima residuo ed uno stretto follow-up.Bibliografia:1. Heidenreich et al. J Urol 20012. Kirkalli et al. Int J Urol 2001Comunicazioni selezionate N. 60C-REACTIVE PROTEIN: A BIOMARKER OF SURVIVAL INMETASTATIC RENAL CELL CARCINOMA TREATED WITHSUBCUTANEOUS INTERLEUKIN-2-BASED IMMUNOTHE-RAPYCasamassima A. 1 , Picciariello M. 1 , Berar<strong>di</strong>no R. 1 , QuarantaM. 1 , Lorusso V. 2 , Guida M. 21Department of Ex<strong>per</strong>imental Oncology, Laboratory ofImmunology; 2Department of Me<strong>di</strong>cal Oncology, OncologyInstitute, Bari, ItalyIntroduction and Purpose: Renal cell carcinoma (RCC) is the mostprevalent malignancy within the kidney. Metastatic RCC(MRCC) has a poor prognosis with a me<strong>di</strong>an overall survival ofabout one year (1). There is no standard treatment for MRCC.Chemotherapy is generally ineffective and immunotherapybasedregimens are considered of a modest efficacy.Nevertheless, cytokines are the only drugs that have beenshown to induce tumour regression in some patients. á-IFN andIL-2 have been found to induce objective response rates from15% to 20% as monotherapy and are now being investigated ascomponents of combined regimens (2, 3). In our Institution weanalysed a panel of pre-treatment bio-humoral and clinical factorsto verify their pre<strong>di</strong>ctive impact on survival and clinicalresponse of patients affected by MRCC treated with three <strong>di</strong>fferentregimens inclu<strong>di</strong>ng low dose subcutaneous IL-2.Methods: A total of 110 patients treated at the OncologyInstitute of Bari, Italy from 1992 until 2002, were analysed.Three <strong>di</strong>fferent therapeutic regimens IL-2-based were used.Pre-treatment total lymphocytes, lactate dehydrogenase(LDH), erytrose<strong>di</strong>mentation rate (ESR), albumin, C-reactiveprotein (CRP), and fibrinogen were analysed. Moreover, clinicalparameters (<strong>per</strong>formance status, age, sex, prior nephrectomy,number of metastatic sites, <strong>di</strong>sease site, and <strong>di</strong>sease freeinterval from nephrectomy to metastatic <strong>di</strong>sease (DFI)) wereconsidered.Results: The me<strong>di</strong>an survival of all patients was 12 months (33months for PR+CR, 14 months for SD, 7 months for PRO).Overall response was 24% PR+CR, 37% SD and 39% PRO. Inunivariate analysis, a good ECOG PS (P=0.0000), prior nephrectomy(P=0.0001), DFI longer than 12 months (P=0.0003),bone <strong>di</strong>sease site (P=0.0013), low number of metastatic site(P=0.0449), normal albumin levels (P=0.0001), low/normalfibrinogen levels (P=0.0140) and low/normal LDH levels(P=0.0430) were related to a better survival. In a final multivariateanalysis only CRP (P=0.002; Hazard Ratio=4.12; IC 95%1.68 – 10.15) and DFI (P=0.0497; Hazard Ratio=0.44; IC 95%0.20 – 0.99) were found to have an independent role on survival.When we correlated clinical and bio-humoral factorsonly CRP was found correlated with DFI (P=0.021) and priornephrectomy (P=0.041). When we carried out a multivariateanalysis considering CRP as continuous variable, we confirme<strong>di</strong>ts strong impact on survival (P=0.0003; HR = 1.1 and IC 95%HR 1.04-1.15).Conclusions: Our data confirm that some clinical and biohumoralfactors may be strongly related to survival in MRCCpatients. The interesting new aspect emerging from this studyis the prognostic value of the basal levels of CRP and fibrinogen,which seem to be <strong>di</strong>scriminating factors between a goodor bad prognosis. Particularly, in the multivariate analysis CRPresulted the most important independent prognostic factorableof survival.References:1. Bleumer I, et al. Immonotherapy for renal cell carcinoma. Eur Urol 2003;44:652. Negrier S, et al. Recombinant human inteleukin-2, recombinant humaninterferon alfa-2a or both in metastatic renal cell carcinoma. N Engl J Med1998; 333:12723. Atzpo<strong>di</strong>en J, et al. Thirteen-year, long-term efficacy of Interferon 2a andInterleukin-2-based home therapy in pazients with advanced renal cell carcinoma.Cancer 2002; 95:1045Poster n. 61TRATTAMENTO DEL CARCINOMA PROSTATICO LOCA-LIZZATO CON HIFU: 3 ANNI DI ESPERIENZATasso M., Volpe A., Varvello F., Ferrando U.S.C. Urologia 3, A.S.O. S. Giovanni Battista (Molinette), TorinoIntroduzione: La termoablazione con ultrasuoni focalizzati adalta frequenza è una opzione terapeutica <strong>di</strong> crescente interessenel trattamento del carcinoma prostatico localizzato in pazientiche rifiutano o <strong>per</strong> i quali non è in<strong>di</strong>cata la terapia chirurgicatra<strong>di</strong>zionale.Materiali e Meto<strong>di</strong>: Le in<strong>di</strong>cazioni al trattamento sono state: sta<strong>di</strong>oclinico cT1-2 N0 M0, PSA 70 anni, volumeghiandolare
ABSTRACTS <strong>XIV</strong> <strong>Congresso</strong> <strong>Nazionale</strong> <strong>Società</strong> <strong>Italiana</strong> <strong>di</strong> Urologia OncologicaConclusioni: Il trattamento HIFU nel carcinoma prostaticolocalizzato è una valida alternativa alla chirurgia e alla ra<strong>di</strong>oterapiain pazienti che rifiutano o che non sono eleggibili <strong>per</strong>l’intervento tra<strong>di</strong>zionale. E’ un intervento ben tollerato daipazienti, con accettabili effetti collaterali, comporta un brevericovero e non pregiu<strong>di</strong>ca la possibilità <strong>di</strong> eseguire successiveterapie in caso <strong>di</strong> insuccesso.Comunicazioni n. 62IL SINERGISMO FAS-CELECOXIB POTENZIA L’EFFETTOAPOPTOTICO DELL’INIBIZIONE DELLA CICLOOSSIGE-NASI-2 NELLE LINEE CELLULARI ORMONO-SENSIBILIED ORMONO-REFRATTARIE DI CARCINOMA PROSTATI-CORinal<strong>di</strong> L. 1 , Catalano A. 2 , Milanese G. 1 , Faronato M. 1 ,Procopio A. 2 , Muzzonigro G. 11Clinica Urologica e Dottorato <strong>di</strong> Oncologia Urologia;2Dipartimento Patologia Molecolare e Terapie Innovative,Università Politecnica delle Marche, AnconaIntroduzione: L’inibitore della cicloossigenasi <strong>di</strong> tipo 2 (COX-2)celecoxib, viene attualmente proposto nella chemioprevenzione<strong>di</strong> varie forme <strong>di</strong> cancro, grazie alla sua capacità <strong>di</strong> sensibilizzarele cellule tumorali agli stimoli apoptotici. Tuttavia nonsono stati ancora ben in<strong>di</strong>viduati i meccanismi che a seguitodell’inibizione del COX-2 inducono all’apoptosi. Abbiamovalutato l’azione antitumorale del celecoxib su due linee cellulari,PC-3 e LNCaP (ormono-resistente ed ormono-sensibile),che costitutivamente esprimono COX-2, e abbiamo valutatocontemporaneamente l’espressione <strong>di</strong> Fas, proteina dellasu<strong>per</strong>ficie cellulare espressa dalle cellule in apoptosi.Materiali e Meto<strong>di</strong>: La vitalità cellulare delle due linee cellulariPC3 e LNCaP è stata valutata a dosi crescenti <strong>di</strong> farmaco (6,7,10, 12,5 e 20 g) e a <strong>di</strong>versi tempi <strong>di</strong> coltura (3, 6, 19 e 24 ore;26g <strong>di</strong> celecoxib) attraverso conta con trypan-blue. L’effettoapoptotico è stato valutato attraverso colorazione con Hoechst33342. Saggi <strong>di</strong> sinergismo celecoxib-FasL sono stati eseguitiaggiungendo alle colture con celecoxib il ligando <strong>per</strong> il Fas(FasL, clone CH-11). L’analisi con RT-PCR è stata utilizzata <strong>per</strong>valutare gli effetti dell’apoptosi indotta dall’inibizione <strong>di</strong> COX-2 (Akt e Blc-2). Attraverso RT-PCR e Western blotting è statavalutata l’espressione genica e proteica del Fas.Risultati: Il trattamento con celecoxib determinava una riduzionesignificativa della crescita cellulare sia <strong>di</strong> PC3, sia <strong>di</strong>LNCaP in maniera tempo e dose <strong>di</strong>pendente. Contemporaneamentesi osservava un significativo aumento dell’apoptosi.La correlazione tra riduzione della crescita cellulare e incrementodell’apoptosi risultava alta. Il celecoxib determinava unsignificativo aumento dei livelli <strong>di</strong> espressione <strong>di</strong> Fas nellelinee cellulari trattate rispetto ai controlli, ma non <strong>di</strong> akt e bcl-2. Il celecoxib da solo induceva un aumento dell’apoptosisignificativamente maggiore rispetto al FasL da solo. L’aggiunta<strong>di</strong> FasL al celecoxib induceva un incremento significativo dell’apoptosi,sia rispetto al FasL solo, sia rispetto al celecoxibsolo, sia rispetto al controllo in entrambe le linee cellulari. Ilsinergismo FasL-celecoxib determinava una riduzionedell’IC50 del celecoxib.Conclusioni: Questo stu<strong>di</strong>o <strong>di</strong>mostra <strong>per</strong> la prima volta che ilcelecoxib è coinvolto nell’induzione dell’apoptosi cellulareattraverso il sistema Fas, sistema appartenente alla famiglia delTNF. Questo risultato implica una possibile interazione tra lavia degli enzimi COX-2 ed il sistema immunitario sia nellelinee cellulari <strong>di</strong> carcinoma prostatico ormono-sensibile, sia inquelle ormono-insensibili. La simile risposta apoptotica al trattamentocon celecoxib riscontrata nelle linee cellulari PC-3 eLNCaP suggerisce il razionale <strong>per</strong> l’impiego in vivo <strong>di</strong> questofarmaco non solo a scopo preventivo, ma anche nella terapiadelle forme ormono-insensibili. Il <strong>di</strong>mostrato sinergismo Fascelecoxibed il conseguente potenziato effetto apoptotico chene risulta aprono la strada a futuri stu<strong>di</strong> sul possibile effettoimmunostimolante del celecoxib nella terapia del carcinomaprostatico.Bibliografia:1. Song X et al. Cyclooxygenase-2, player or spectator in cyclooxygenase-2inhibitor-induced apoptosis in prostate cancer cells. J Natl Cancer Inst 2002;94:585Comunicazioni selezionate N. 63ANGIOGENESIS AS PROGNOSTIC FACTOR IN SMALLRENAL TUMORSMinar<strong>di</strong> D. 1 , Lucarini G. 2 , Mazzucchelli R. 3 , Natali D. 2 ,Milanese G. 1 , Galosi A.B. 1 , Montironi R. 3 , Biagini G. 2 ,Muzzonigro G. 11Institute of Urology; 2 Institute of Morphology-Histology; 3 Instituteof Pathology, Polytechnic University of the Marche Region Me<strong>di</strong>calSchool, Ancona, ItalyIntroduction: Angiogenesis is a critical step in the growth, invasiveprogression and metastatic spread of solid tumors and ithas been correlated with prognosis in patients with carcinomas,and significant <strong>di</strong>fferences in vascular pattern have beenobserved between benign and malignant lesions. VEGF is themost potent growth factor of tumor vasculature, has beenshown to be up-regulated in every tumor stu<strong>di</strong>ed thus far, an<strong>di</strong>s correlated with tumor stage and progression. Microvesseldensity (MVD) is correlated with advanced pathological fin<strong>di</strong>ngsand poor clinical outcome in various cancer. VEGF triggersendothelial cell proliferation by bin<strong>di</strong>ng to tyrosine kinasereceptors, termed VEGFR-1 (Flt-1) and VEGFR-2 (Flk-1), ina paracrine fashion. Nephron-sparing surgery has been establishedas the method of necessity for solid and localizedtumors in a solitary kidney, for bilateral tumors, or if chronicrenal failure is present or might happen. The objective of ourstudy was to investigate VE-GF, MVD and FLK-1 immunohistochemicalexpression in a large series of small conventionalclear cell renal carcinomas treated by enucleation and to assessthe prognostic value of their expression in terms of patientssurvival in a long follow-up.Methods: Study endpoints were overall survival and <strong>di</strong>seasefree<strong>per</strong>iod, which were measured from the date of surgery.Forty-eight conventional renal cell carcinoma were retrospectivelyselected among those o<strong>per</strong>ated on at our Institute between1987 and 2000. We selected only cases of RCC in which enucleationwas <strong>per</strong>formed. The following parameters were consideredwhen evaluating the cases: patient sex and age, side(right or left kidney), <strong>di</strong>ameter and gra<strong>di</strong>ng of the tumor, <strong>di</strong>seasefree interval, patient survival; tumor gra<strong>di</strong>ng has beenclassified in accor<strong>di</strong>ng to Fuhrman gra<strong>di</strong>ng. All the consideredparameters have been correlated with VEGF, MVD and FLK-1expression. Disease free interval was defined as no evidence ofrecurrence and/or metastasis at the time of the last follow-up.Results. No statistically significant <strong>di</strong>fferences were observed forage and tumour size between the 4 gra<strong>di</strong>ng groups. The <strong>di</strong>stributionof the intensity of staining for VEGF was significantly<strong>di</strong>fferent when considering the Fuhrman gra<strong>di</strong>ng groups; inparticular, grouping together the patients with a Fuhrmangrade III and IV, it was possible to observe that they showed anhigher intensity of staining than patients belonging to grade Iand II. The <strong>di</strong>fference of VEGF staining between patientsbelonging to grade I and II was non significant. The me<strong>di</strong>anMVD count wasn’t <strong>di</strong>fferent between the 4 gra<strong>di</strong>ng groups, aswell as <strong>di</strong>stribution of VEGF staining and FLK1 <strong>per</strong>centage ofthe staining. Analysing the <strong>di</strong>stribution of FLK1 intensity of24Archivio Italiano <strong>di</strong> Urologia e Andrologia 2004; 76, 3, Supplemento 1