Luiz Carlos D. de Miranda

Prostate cancer and acromegaly

Acromegalic patients have an increased prevalence of prostatic disorders compared to age-matched healthy subjects. Increased size of the whole prostate or the transitional zone, together with an elevated incidence of other structural changes, such as nodules, cysts, and calcifications, have been reported. Prostate enlargement in young acromegalic patients with low testosterone levels due to central hypogonadism supports the hypothesis that chronic GH and IGF-I excess cause prostate hyperplasia. The relationship between prostatic carcinoma and acromegaly is, until now, only circumstantial. Long-term follow-up of these patients is necessary since epidemiologic studies showed association between serum IGF-I levels in the upper normal limit and prostate cancer in the general population. This review approaches prostate diseases in patients with acromegaly.

IGF-I, insulin and prostate cancer

Prostate cancer is the second most frequent malignancy diagnosed in adult men. Androgens are considered the primary growth factors for prostate normal and cancer cells. However, other non-androgenic growth factors are involved in the growth regulation of prostate cancer cells. The association between IGF-I and prostate cancer risk is well established. However, there is no evidence that the measurement of IGF-I enhances the specificity of prostate cancer detection beyond that achievable by serum prostate-specific antigen (PSA) levels. Until now, there is no consensus on the possible association between IGFBP-3 and prostate cancer risk. Although not well established, it seems that high insulin levels are particularly associated with risk of aggressive prostatic tumours. This review describes the physiopathological basis, epidemiological evidence, and animal models that support the association of the IGFs family and insulin with prostate cancer. It also describes the potential therapies targeting these growth factors that, in the future, can be used to treat patients with prostate cancer.

Transgenitalização masculino / feminino: experiência do Hospital Universitário da UFRJ

OBJETIVO: Mostrar a experiencia do tratamento cirurgico do transgenitalismo (masculino/feminino) realizado no Programa de Transgenitalizacao do Hospital Universitario Clementino Fraga Filho, - UFRJ. METODOS: A selecao dos pacientes para operacao de transgenitalismo obedeceu a avaliacao de equipe multidisciplinar, atendendo aos criterios definidos, apos dois anos de acompanhamento conjunto: diagnostico medico de transexualismo; paciente maior de 21 anos; ausencia de caracteristicas fisicas inapropriadas para a mudanca; apoio de pelo menos um familiar proximo. RESULTADOS: De 1997 a 2004 foram atendidas dezessete, pessoas quinze confirmaram a condicao transexual, uma foi afastada por ter trazido exames falsos. Do total de dezesseis transexuais, foram realizadas seis operacoes. As pacientes operadas situavam-se na faixa de 25 a 40 anos com media de 31 anos. O procedimento cirurgico foi concluido sem dificuldades tecnicas em todas as pacientes . Uma paciente apresentou estenose do neo meato e em outra foi necessario encurtar um pouco mais a uretra. CONCLUSAO: A tecnica operatoria nao oferece maiores dificuldades em sua execucao, mas pode depender das condicoes locais e da criatividade do cirurgiao. A dificuldade maior esta em preparar estes pacientes para que nao haja frustracoes ou expectativas demasiadas.

Insulin-like growth factor (IgF)-I, IgF binding protein-3, and prostate cancer: correlation with gleason score

Introduction Non-androgenic growth factors are involved in the growth regulation of prostate cancer (PCa). Objective This is the first Brazilian study to correlate, in a population of patients operated for PCa, PSA, total testosterone, insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-3 (IGFBP-3) with Gleason score and to compare with a control group with benign prostate hyperplasia (BPH). Materials and Methods This retrospective single-center study included 49 men with previously diagnosed PCa and 45 with previously diagnosed BPH. PSA, testosterone, IGF-I, IGFBP-3 were determined in both groups. Results PSA and IGFBP-3 levels were significantly higher in the PCa group as compared to the BPH group (p<0.001 and p=0.004, respectively). There was a significant difference when we compared the PSA before surgery (p<0.001) and at the inclusion in the study (p<0.001) and IGFBP3 (0.016) among patients with Gleason <7, ≥7 and BPH. In the PCa group, PSA, testosterone, IGF-I and IGFBP-3 levels were comparable between Gleason <7 and ≥7. Conclusions Our data suggest that in localized PCa, the quantification of PSA and, not of IGF-1, may provide independent significant information in the aggressiveness. IGFBP-3 could be a biochemical marker of disease control in PCa patients.

Prostatic disorders in acromegalic patients experience of a Brazilian center

INTRODUCTION Published data suggest that patients with acromegaly have an increased prevalence of prostate disorders. OBJECTIVE To evaluate prostatic disorders in acromegalic patients comparing these results after one year of treatment of acromegaly and with a group of healthy men. MATERIALS AND METHODS This study was composed of two parts: sectional study comparing patients with healthy controls (baseline) and prospective, longitudinal study (at baseline and after one year of treatment). Forty acromegalic patients were enrolled and evaluated at baseline and after one year with the application of international prostatic symptoms score (IPSS), digital rectal examination, measurements of growth hormone (GH), insulin-like growth factor-I (IGF-I), insulin-like growth factor-binding protein-3 (IGFBP-3), sex hormone-binding globulin (SHBG), prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone, total and free prostate-specific antigen (PSA) levels and prostate ultrasonography (US). Thirty healthy men were selected as control group. RESULTS We stratified patients and controls according to age, considering 40 years-old as cut off. Healthy controls under 40 had IPSS values lower than acromegalic patients. When considering only older patients and controls prostate hyperplasia and structural abnormalities were more frequent in acromegalics. After one year of treatment there was significant decrease in GH, IGF-I and prostate volume in acromegalics over 40 years-old. CONCLUSIONS Acromegalics under 40 have more urinary symptoms according to IPSS and above 40 years-old higher frequency of structural changes and increased prostate volume than healthy men. Significant reduction of GH and IGF-I levels during treatment of acromegaly leads to decrease in the prostate volume.

A produção científica e a ética em pesquisa

As pesquisas cientificas que envolvem a participa-cao de individuos em seus protocolos, nao raro se defrontamcom dilemas de ordem etica, cuja solucao requer uma reflexaocuidadosa, apoiada por preceitos ja estabelecidos por resolu-coes e bom senso por parte dos pesquisadores.O conhecimento minimo em relacao aos preceitosdas Resolucoes em vigor, nao so dinamiza o processo de apro-vacao junto aos comites de etica, bem como fortalece o con-teudo humano do protocolo que se pretende desenvolver.As resolucoes vem sendo aprimoradas ao longo dostempos, recebendo novos conceitos em funcao das necessi-dades de cada epoca, fazendo-nos perceber que se trata deum processo dinâmico, passivel de reformulacoes e aquisi-coes. Conhecendo um pouco de sua evolucao, entendemosmelhor o âmago de sua estrutura, que, na verdade, e a essen-cia da preservacao do bem estar e da dignidade da nossaespecie.O primeiro conjunto de diretrizes para pesquisa emhumanos, aceito pela comunidade cientifica, data de 1833,publicado por William Beaumont, onde se destacaram: umtexto onde o sujeito da pesquisa manifestaria o seu consenti-mento voluntario, ainda, uma adequacao metodologica doprojeto de pesquisa e a condicao imutavel de liberdade parasair da pesquisa ¹.A primeira condenacao judicial por realizar pesquisa“sem autorizacao antecipada”, data de 1880, quando a corteda cidade de Bergen, na Noruega, condenou o doutor GerhardtA. Hansen. Naquela ocasiao o Dr. Hansen inoculou um liqui-do de uma ferida nos olhos de uma ancia, querendo compro-var a facil transmissao daquela molestia (lepra), mas nao co-lheu o seu consentimento previo, e foi condenado a prisao ².Em 1947, em consequencia das atrocidades cometi-das na Segunda Grande Guerra, foi elaborada a Declaracao deNuremberg, cujos dez principios passaram a determinar asorientacoes eticas para experimentos com humanos. Nela,alem de considerar o consentimento voluntario do sujeito dapesquisa como absolutamente essencial, condicionou o es-tudo a um desenho cientificamente solido (com experimentosprevios em animais), e a necessidade de que fosse conduzidopor individuos “qualificados”, com a expressa preocupacaode “nao fazer mal”, e declarar os riscos e beneficios espera-dos para aquela experiencia ².Em 1964, surge a Declaracao de Helsinque estabele-cendo duas novas exigencias: 1) Formular um Protocolo dapesquisa e 2) Submete-lo a um Comite de Etica. De 1964 ate oano 2000 (Edimburgo) esta Declaracao ja foi modificada por5 vezes.A Regulamentacao Brasileira de Etica em Pesquisaem Seres Humanos data de 1996, quando em 10 de outubro oentao ministro de Saude, Prof. Dr. Adib Jatene, assinou a Re-solucao 196/96, que veio para atualizar as Resolucoes 1246/88do Conselho Federal de Medicina e a 01/88 do Conselho Na-cional de Saude. A partir daquela data, novas resolucoesforam incluidas, destacando-se a 240/97 estabelecendo aobrigatoriedade de um representante dos USUARIOS nosComites de Etica em Pesquisa (CEP); ainda: 251/97 estabele-cendo regras para experiencias com novos farmacos; a 292/99organizando as pesquisas que tem coordenacao multicentricae internacional; a 303/00 estipulando os conceitos validospara estudos que envolvem a reproducao humana; a 304/00para com as pesquisas que utilizam povos indigenas e a 340/04 para os estudos incluindo genetica humana ¹

Importance of bone assessment and prevention of osteoporotic fracture in patients with prostate cancer in the gonadotropic hormone analogues use

The antiandrogenic therapy (ADT) for prostate cancer represents an additional risk factor for the development of osteoporosis and fragility fractures. Still, bone health of patients on ADT is often not evaluated. After literature research we found that simple preventive measures can prevent bone loss in these patients, resulting in more cost-effective solutions to the public health system and family when compared to the treatment of fractures.

A ressonância magnética no estadiamento locorregional do câncer de próstata: resultados comparados com a análise histopatológica pós-cirúrgica

Conventional staging for locoregional prostate adenocarcinoma has been demonstrated as potentially underdiagnosing. Therefore, prostate MRI is emerging as an important tool for staging before surgery. Advanced techniques such as diffusion and dynamic contrast enhancement also contribute to increasing its accuracy. In this preliminary study, MRI was compared with prostate histopathology samples, reaching 78% sensitivity and 100% specificity for tumor localization; 33% sensitivity and 100% specificity for extracapsular extension; 100% sensitivity and 100% specificity for involvement of the seminal vesicles. It is possible to believe that these preliminary results are promising, and more cases will tend to confirm these data.

Embolização pré operatória de tumores renais com microparticulas esféricas de tecnologia nacional. (Spherus®-First line Brasil)

The authors report a brand new component for embolization composed by a polivinil acetate core and a polivinil-alcohol coat in a microspherical form ( Spherus®-First Line Brasil) used as preoperative management in three patients with renal tumors in an attempt to reduce the size of the tumors and to avoid hemorrhagic complications during the operations. This new component was developed in COPPE/UFRJ laboratories. The preoperative arterial embolization with this new component caused strong ischemia in the tumor tissue , facilitating the operative procedure.

Interference of enalaprilat on glomerular permeability to macromolecules (IGG) in acute unilateral ureteral obstruction in rats

INTRODUCTION Unilateral ureteral obstruction breaks out events that cause the transitory increase of glomerular permeability to macromolecules, both in the obstructed kidney and in the contralateral kidney, suggesting the presence of some factor, with a systemic action, liberated as a response to the obstruction. We know that the rennin-angiotensin system is activated by acute ureteral obstruction. We have developed an experiment to assess the role of angiotensin II on the glomerular permeability to IgG due to acute ureteral obstruction, using enalaprilat, an angiotensin enzyme conversion inhibitor, to block the effects of the activation of the rennin-angiotensin system. MATERIALS AND METHODS We have used 45 adult Wistar female rats, distributed into 3 main groups: a control group with 5 animals and 2 experiment groups each one with 10 animals submitted to unilateral ureteral obstruction and nephrectomy at 60 and 120 minutes. Each experiment group had its simulation correspondent (sham). We have studied both kidneys through the direct immunofluorescence method. RESULTS We have found positive permeation in animals without enalaprilat in both kidneys and negative permeation in those in which the drug was used. CONCLUSION We have concluded that enalaprilat interferes in this alteration of permeability, suggesting that angiotensin II is involved in the loss of selectivity of the glomerular membrane.