Browsing by Author "Calais da Silva, F"
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- Diagnóstico do Cancro da BexigaPublication . Calais da Silva, FExame físico (incluindo toque rectal). Ultrasonografia renal e da bexiga e/ou UIV Cistoscopia com descrição de tamanho, e localização do tumor (o diagrama da bexiga deve ser incluído). Urina Tipo II; Citologia urinária, RTU com biópsia da base tumoral. Biópsias de todas as áreas suspeitas; biópsias randomizadas na presença da citologia positiva, tumor >3cm, ou tumor não papilar; biópsia da uretra prostática em casos de Cis ou suspeita de carcionoma in situ. Quando o tumor da bexiga é invasivo e está indicado um tratamento radical, é mandatório RX do tórax, UIV e/ou tomografia axial computorizada abdominal e pélvica, Ultasonografia hepática, cintigrafia óssea se houver sintomas ou se fosfatase alcalina for elevada.
- EORTC Nomograms and Risk Groups for Predicting Recurrence, Progression, and Disease-Specific and Overall Survival in Non-Muscle-Invasive Stage Ta-T1 Urothelial Bladder Cancer Patients Treated with 1-3 Years of Maintenance Bacillus Calmette-GuérinPublication . Cambier, S; Sylvester, RJ; Collette, L; Gontero, P; Brausi, MA; van Andel, G; Kirkels, WJ; Calais da Silva, F; Oosterlinck, W; Prescott, S; Kirkali, Z; Powell, PH; de Reijke, TM; Turkeri, L; Collette, S; Oddens, JBACKGROUND: There are no prognostic factor publications on stage Ta-T1 non-muscle-invasive bladder cancer (NMIBC) treated with 1-3 yr of maintenance bacillus Calmette-Guérin (BCG). OBJECTIVE: To determine prognostic factors in NMIBC patients treated with 1-3 yr of BCG after transurethral resection of the bladder (TURB), to derive nomograms and risk groups, and to identify high-risk patients who should be considered for early cystectomy. DESIGN, SETTING, AND PARTICIPANTS: Data for 1812 patients were merged from two European Organization for Research and Treatment of Cancer randomized phase 3 trials in intermediate- and high-risk NMIBC. INTERVENTION: Patients received 1-3 yr of maintenance BCG after TURB and induction BCG. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Prognostic factors for risk of early recurrence and times to late recurrence, progression, and death were identified in a training data set using multivariable models and applied to a validation data set. RESULTS AND LIMITATIONS: With a median follow-up of 7.4 yr, 762 patients recurred; 173 progressed; and 520 died, 83 due to bladder cancer (BCa). Statistically significant prognostic factors identified by multivariable analyses were prior recurrence rate and number of tumors for recurrence, and tumor stage and grade for progression and death due to BCa. T1G3 patients do poorly, with 1- and 5-yr disease-progression rates of 11.4% and 19.8%, respectively, and 1- and 5-yr disease-specific death rates of 4.8% and 11.3%. Limitations include lack of repeat transurethral resection in high-risk patients and exclusion of patients with carcinoma in situ. CONCLUSIONS: NMIBC patients treated with 1-3 yr of maintenance BCG have a heterogeneous prognosis. Patients at high risk of recurrence and/or progression do poorly on currently recommended maintenance schedules. Alternative treatments are urgently required. PATIENT SUMMARY: Non-muscle-invasive bladder cancer patients at high risk of recurrence and/or progression do poorly on currently recommended bacillus Calmette-Guérin maintenance schedules, and alternative treatments are urgently required.
- A Gencitabina como Alternativa Terapêutica na Ausência de BCG: A Experiência do CHLC (Hospital S. José)Publication . Andrade, V; Medeiros, M; Guimarães, T; Bernardino, R; Falcão, G; Fernandes, F; Farinha, R; Calais da Silva, F; Campos Pinheiro, LIntrodução: Os tumores não músculo invasivos da bexiga devem ser estratificados em grupos de risco de forma a adequar o tratamento após cirurgia a cada doente. Nos tumores de alto risco deve ser realizada terapêutica adjuvante com bacilo de Calmette-Guérin (BCG) intravesical durante 1 a 3 anos. Têm sido reportadas roturas de stock de BCG intravesical, tendo sido o Centro Hospitalar de Lisboa Central (CHLC) afectado nos anos 2014 e 2015, o que obrigou a uma reformulação no tratamento dos doentes que tinham indicação para realização desta terapêutica. A gencitabina poderá ser uma alternativa válida, dado que alguns estudos mostram que poderá ter um papel nos doentes de risco intermédio, como alternativa à mitomicina C, e nos de alto risco, refractários à BCG, com um perfil de toxicidade mais favorável. Material e Métodos: Trata-se de um estudo retrospectivo descritivo que incluiu doentes com tumores da bexiga não musculo-invasivos de alto risco, com início da doença em 2013/2014, afectados pelo período de escassez de BCG no Centro Hospitalar. Resultados: No CHLC, 11 doentes com tumores de alto risco foram submetidos a terapêutica com gencitabina, apenas dois exclusivamente, os restantes sequencialmente com BCG. Apenas dois doentes, tratados com BCG e gencitabina, apresentaram recidiva tumoral. No entanto, um número significativo (6 em 11) sofreram efeitos adversos, dois dos quais que levaram à interrupção da terapêutica. Conclusão: Aparentemente, a gencitabina foi uma boa alternativa de terapêutica adjuvante na ausência do tratamento gold standard (BCG), dada a existência de baixo número de recidivais tumorais, apesar do elevado número de efeitos adversos reportados.
- Locally Advanced and Metastatic Prostate Cancer Treated with Intermittent Androgen Monotherapy or Maximal Androgen Blockade: Results from a Randomised Phase 3 Study by the South European Uroncological GroupPublication . Calais da Silva, F; Calais da Silva, FM; Gonçalves, F; Santos, A; Kliment, J; Whelan, P; Oliver, T; Antoniou, N; Pastidis, S; Queimadelos, AM; Robertson, CBACKGROUND: Few randomised studies have compared antiandrogen intermittent hormonal therapy (IHT) with continuous maximal androgen blockade (MAB) therapy for advanced prostate cancer (PCa). OBJECTIVE: To determine whether overall survival (OS) on IHT (cyproterone acetate; CPA) is noninferior to OS on continuous MAB. DESIGN, SETTING, AND PARTICIPANTS: This phase 3 randomised trial compared IHT and continuous MAB in patients with locally advanced or metastatic PCa. INTERVENTION: During induction, patients received CPA 200 mg/d for 2 wk and then monthly depot injections of a luteinising hormone-releasing hormone (LHRH; triptoreline 11.25 mg) analogue plus CPA 200 mg/d. Patients whose prostate-specific antigen (PSA) was <4 ng/ml after 3 mo of induction treatment were randomised to the IHT arm (stopped treatment and restarted on CPA 300 mg/d monotherapy if PSA rose to ≥20 ng/ml or they were symptomatic) or the continuous arm (CPA 200 mg/d plus monthly LHRH analogue). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome measurement was OS. Secondary outcomes included cause-specific survival, time to subjective or objective progression, and quality of life. Time off therapy in the intermittent arm was recorded. RESULTS AND LIMITATIONS: We recruited 1045 patients, of which 918 responded to induction therapy and were randomised (462 to IHT and 456 to continuous MAB). OS was similar between groups (p=0.25), and noninferiority of IHT was demonstrated (hazard ratio [HR]: 0.90; 95% confidence interval [CI], 0.76-1.07). There was a trend for an interaction between PSA and treatment (p=0.05), favouring IHT over continuous therapy in patients with PSA ≤1 ng/ml (HR: 0.79; 95% CI, 0.61-1.02). Men treated with IHT reported better sexual function. Among the 462 patients on IHT, 50% and 28% of patients were off therapy for ≥2.5 yr or >5 yr, respectively, after randomisation. The main limitation is that the length of time for the trial to mature means that other therapies are now available. A second limitation is that T3 patients may now profit from watchful waiting instead of androgen-deprivation therapy. CONCLUSIONS: Noninferiority of IHT in terms of survival and its association with better sexual activity than continuous therapy suggest that IHT should be considered for use in routine clinical practice.
- Rastreio do Cancro da PróstataPublication . Calais da Silva, F
- Sialyl Tn-Expressing Bladder Cancer Cells Induce a Tolerogenic Phenotype in Innate and Adaptive Immune CellsPublication . Carrascal, M; Severino, P; Cabral, MG; Silva, M; Ferreira, JA; Calais da Silva, F; Quinto, H; Pen, C; Ligeiro, D; Lara Santos, L; Dall'Olio, F; Videira, PDespite the wide acceptance that glycans are centrally implicated in immunity, exactly how they contribute to the tilt immune response remains poorly defined. In this study, we sought to evaluate the impact of the malignant phenotype-associated glycan, sialyl-Tn (STn) in the function of the key orchestrators of the immune response, the dendritic cells (DCs). In high grade bladder cancer tissue, the STn antigen is significantly overexpressed and correlated with the increased expression of ST6GALNAC1 sialyltransferase. Bladder cancer tissue presenting elevated expression of ST6GALNAC1 showed a correlation with increased expression of CD1a, a marker for bladder immature DCs and showed concomitant low levels of Th1-inducing cytokines IL-12 and TNF-α. In vitro, human DCs co-incubated with STn+ bladder cancer cells, had an immature phenotype (MHC-IIlow, CD80low and CD86low) and were unresponsive to further maturation stimuli. When contacting with STn+ cancer cells, DCs expressed significantly less IL-12 and TNF-α. Consistent with a tolerogenic DC profile, T cells that were primed by DCs pulsed with antigens derived from STn+ cancer cells were not activated and showed a FoxP3high IFN-γlow phenotype. Blockade of STn antigens and of STn+ glycoprotein, CD44 and MUC1, in STn+ cancer cells was able to lower the induction of tolerance and DCs become more mature. Overall, our data suggest that STn-expressing cancer cells impair DC maturation and endow DCs with a tolerogenic function, limiting their capacity to trigger protective anti-tumour T cell responses. STn antigens and, in particular, STn+ glycoproteins are potential targets for circumventing tumour-induced tolerogenic mechanisms.
- The HIF1A Functional Genetic Polymorphism at Locus +1772 Associates with Progression to Metastatic Prostate Cancer and Refractoriness to Hormonal CastrationPublication . Fraga, A; Ribeiro, R; Príncipe, P; Lobato, C; Pina, F; Maurício, J; Monteiro, C; Sousa, H; Calais da Silva, F; Lopes, C; Medeiros, RThe hypoxia inducible factor 1 alpha (HIF1a) is a key regulator of tumour cell response to hypoxia, orchestrating mechanisms known to be involved in cancer aggressiveness and metastatic behaviour. In this study we sought to evaluate the association of a functional genetic polymorphism in HIF1A with overall and metastatic prostate cancer (PCa) risk and with response to androgen deprivation therapy (ADT). The HIF1A +1772 C>T (rs11549465) polymorphism was genotyped, using DNA isolated from peripheral blood, in 1490 male subjects (754 with prostate cancer and 736 controls cancer-free) through Real-Time PCR. A nested group of cancer patients who were eligible for androgen deprivation therapy was followed up. Univariate and multivariate models were used to analyse the response to hormonal treatment and the risk for developing distant metastasis. Age-adjusted odds ratios were calculated to evaluate prostate cancer risk. Our results showed that patients under ADT carrying the HIF1A +1772 T-allele have increased risk for developing distant metastasis (OR, 2.0; 95%CI, 1.1-3.9) and an independent 6-fold increased risk for resistance to ADT after multivariate analysis (OR, 6.0; 95%CI, 2.2-16.8). This polymorphism was not associated with increased risk for being diagnosed with prostate cancer (OR, 0.9; 95%CI, 0.7-1.2). The HIF1A +1772 genetic polymorphism predicts a more aggressive prostate cancer behaviour, supporting the involvement of HIF1a in prostate cancer biological progression and ADT resistance. Molecular profiles using hypoxia markers may help predict clinically relevant prostate cancer and response to ADT.
- The Impact of Multidisciplinary Team Conferences in Urologic Cancer in a Tertiary HospitalPublication . Gil, M; Guerra, J; Andrade, V; Medeiros, M; Guimarães, T; Bernardino, R; Falcão, G; Calais da Silva, F; Campos Pinheiro, LPurpose: Multidisciplinary team (MDT) conferences are currently the standard of care in cancer patients' management. Despite evidence supporting benefits to the majority of malignancies, a paucity of data exists examining the impact in urinary and male genital cancers. This study aims to evaluate the impact of MDT conferences in urologic cancer practice. Methods: Clinical plans discussed in urologic MDT conferences in Centro Hospitalar Universitário de Lisboa Central between January 2019 and December 2019 were retrospectively analysed. Clinical plans were categorized as accepted, changed, rejected (cases that had to be re-presented to the MDT because of insufficient staging or administrative issues) or no plan. MDT conferences' impact was assessed according to type of consultation, referral medical specialty and primary tumour type. Results: 710 clinical plans were discussed at the MDT conferences. 61.8% were accepted, 10.6% were changed, 16.5% were rejected and 11.1% of cases referred to MDT discussion had no defined clinical plan. First consultations had a higher rate of accepted clinical plans (63.4%) versus subsequent consultations (56.4%). Referrals by the urology specialty had the highest rate of acceptances (64.3%). On the stratification by primary tumour site, testicular cancer had the highest acceptance rate (70.3%), whereas bladder cancer had the lowest (47.8%). Conclusions: MDT conferences had an important impact in the management of 38.2% of cases. Therefore, all patients with urologic malignancies should be referred to MDT review to ensure optimal clinical care.