ABSTRACT: Iron deficiency anemia (IDA) in humans is defined as the decrease of total hemoglobin concentration and the non-production of the adult hemoglobin subtype 2 - HbA2 (α2δ2 chains), which is considered a marker of IDA severity in humans, dosed together with the iron serum. This study aimed to determine the standard of hemoglobin types in piglets induced to experimentally IDA in the first 21 days of life (delivery to weaning). In the present study, 40 piglets born from four naïve gilts, were randomly and equally assigned among the gilts. On the third day after delivery, the groups were randomly distributed in different environments (cement and clay floors) and according to the iron supplementation (iron dextran and placebo). Erythrocyte parameters, serum iron, and hemoglobin trait were analyzed at four moments between birth and weaning days. The group of piglets that did not receive iron dextran supplementation on the third-day post-birth and were placed in the pen without soil did not present HbA2 from the seventh day onwards on the agarose electrophoretogram (pH 8.6) and this observation was correlated to decrease of serum iron (ρ: 0.156, p=0.003) when compared to the other groups’ piglets that did not present iron deficiency. In the present study was possible to determine the swine hemoglobin pattern in IDA, since HbA2 was absent in piglets with IDA in comparison to the non-ferropenic groups and the correlation between the reduction of iron levels and the absence of HbA2.

RESUMO: A anemia por deficiência de ferro (ADF) em humanos é definida como a diminuição da concentração de hemoglobina total e a não produção da hemoglobina adulta subtipo 2 - HbA2 (cadeias α2δ2), que é considerada um marcador de gravidade de IDA em humanos, dosado em conjunto com o soro de ferro. Este estudo teve como objetivo determinar o padrão dos tipos de hemoglobina em leitões induzidos experimentalmente à IDA nos primeiros 21 dias de vida (parto ao desmame). Quarenta leitões, nascidos de quatro marrãs nulíparas, foram distribuídos aleatoriamente e igualmente entre as leitoas. No terceiro dia após o parto, os grupos foram distribuídos aleatoriamente em diferentes ambientes (piso de cimento e barro) e de acordo com a suplementação de ferro (ferro dextrano e placebo). Parâmetros eritrocitários, ferro sérico e traço de hemoglobina foram analisados em quatro momentos, entre o nascimento e o desmame. O grupo de leitões que não recebeu suplementação de ferro dextrano no terceiro dia pós-parto e foi colocado em baia sem solo não apresentou HbA2 a partir do sétimo dia no eletroforetograma de agarose (pH 8,6) e esta observação foi correlacionada com diminuição da concentração sérica ferro (ρ: 0,156, p=0,003) quando comparados aos demais grupos leitões que não apresentavam deficiência de ferro. No presente estudo foi possível determinar o padrão hemoglobinêmico suíno na IDA, uma vez que, a HbA2 estava ausente nos leitões com ADF em comparação aos grupos não ferropênicos e há correlação entre a redução dos níveis de ferro e a ausência de HbA2.

Abstract In this study, it is investigated the anti-adhesive effectiveness of ZrN/Ti and TiN/Ti, deposited by magnetron sputtering, as coating materials of electrosurgical electrodes of steel in protein adhesion tests. Stoichiometry and the thickness of the systems were assessed with Rutherford backscattering spectrometry measurements. Vertical surface deviations were evaluated with the five-point mean height and the arithmetic average height and correlations between the amount of adhered protein in the electrosurgical electrodes and measurements of wettability and electrical resistivity were investigated. The quality of both coatings was put to the test through protein adhesion tests at high temperatures. Cuts with electrosurgical electrodes were performed in an abdominal flap for different electric power and cutting times. The results indicate less adhesion of protein on both proposed coatings, compared to the traditional electrodes of stainless steel, proving to be cheaper alternatives for the surgical industry than other massive anti-adherent electrodes as Au and Ti.

O S. adstringens, árvore típica do Cerrado, tem sido explorada visando suas propriedades medicinais e tanantes. Em razão do ainda incipiente conhecimento genético da espécie, este trabalho teve como objetivo caracterizar a diversidade e a estrutura genética de S. adstringens por meio de marcadores aloenzimáticos. Foram coletadas sementes em cinco mesorregiões brasileiras, sendo amostrados 627 indivíduos divididos em 16 populações localizadas nos Estados de Minas Gerais e Goiás. Foram testados 14 sistemas isoenzimáticos; destes, sete foram polimórficos com o total de 10 locos e 28 alelos. O valor de diversidade genética média (H) foi 0,226, a proporção média de locos polimórficos (P) foi 68,75, o número médio de alelos por loco polimórfico (AP) foi 2,65 e o número efetivo de alelos (Ae) foi igual a 1,29. Resultados do índice de fixação total (F= 0,003), do índice de fixação dentro de populações (f = -0,114) e, da medida de diferenciação genética (θ =0,105) foram não significativos, indicando a inexistência de estruturação genética. Na análise de agrupamento (UPGMA) foram observados dois grupos principais, o primeiro formado pela população do Parque Estadual (PE) do Rio Preto (MG), e outro, formado pelas demais populações. Se excluída a população do PE do Rio Preto das análises, G ST é drasticamente reduzido de 0,077 para 0,026. Assim, aproximadamente 2/3 do valor total de G ST verificado em S. adstringens foi devido à variação entre a população do PE do Rio Preto e as demais populações. De modo geral, os valores H e P observados em S. adstringens são compatíveis aos constatados em árvores tropicais comumente distribuídas. Por outro lado, excluindo a população do PE do Rio Preto, o valor da medida de diferenciação genética G ST foi menor que o verificado em árvores tropicais nativas e pinheiros de zonas temperadas. A semelhança entre populações avaliadas indica que o fluxo gênico ainda é alto o suficiente para prevenir a diferenciação genética, pelo menos em nível local.

The S. adstringens, a typical Cerrado (Brazilian savannah) tree, is used because of its medicinal and tanning properties. Because of the still incipient genetic knowledge of the species, the objective of this work was to characterize the diversity and genetic structure of S. adstringens by using allozyme markers. Seeds were collected in five Brazilian mesoregions, in which 627 individuals in 16 populations in the states of Minas Gerais and Goiás were sampled. Fourteen isoenzyme systems were assessed, out of which seven were polymorphic with a total of 10 loci and 28 alleles. Average genetic diversity (H) was 0.226, average proportion of polymorphic loci (P) was 68.75, average number of alleles per polymorphic locus (AP) was 2.65 and effective number of alleles (Ae) was equal to 1.29. The results of total fixation index (F= 0.003), within population fixation index (f =-0.114) and genetic differentiation measure (θ =0.105) were not significant, which shows the inexistence of genetic structure. Two principal groups were found in the cluster analysis (UPGMA), where the first one was formed by the population of State Park (PE) of Rio Preto (MG) and the other, by the other populations. If the population of PE of Rio Preto is excluded from the analysis, G ST is drastically reduced from 0.077 to 0.026. Thus, approximately 2/3 of the total value of G ST found in S. adstringens was due to the variation among the population of PE of Rio Preto and the other populations. Overall, the values of H and P found in S. adstringens are compatible with the ones found in typically distributed tropical trees. On the other hand, by excluding the population of PE of Rio Preto, the value of the G ST genetic differentiation measure was smaller than the one found in native tropical trees from temperate zones. The similarity between the assessed populations shows that the gene flow is still high enough to avoid genetic differentiation, at the local level, at least.

Foram simuladas diferentes estratégias de seleção para estimar o desempenho fenotípico e a endogamia média na seleção assistida por marcadores, em características quantitativas com valores de herdabilidade de 0,10; 0,40 e 0,70. O sistema de simulação genética (Genesys) foi utilizado para a simulação de três genomas (cada qual constituído de uma única característica cuja distinção estava no valor da herdabilidade), e das populações base e inicial. Cada população inicial foi submetida à seleção assistida por marcadores por 20 gerações consecutivas. Avaliaram-se estratégias de acasalamento entre os genitores selecionados, em diferentes intensidades de seleção (tamanhos populacionais), por meio do acasalamento seletivo entre os melhores e os piores, acasalamento apenas entre os melhores e/ou entre os piores e acasalamento aleatório. Em todos os cenários combinando herdabilidade e intensidade, o acasalamento estratégico utilizando a metodologia da genotipagem seletiva foi superior aos demais, tornando-se mais eficaz na detecção de QTL e, consequentemente, no incremento do valor fenotípico e na minimização das médias endogâmicas ao longo das gerações. Ao utilizar a estratégia seletiva de amostragem, menor tamanho populacional é requerido para otimizar a detecção de QTL à medida que o valor da herdabilidade da característica aumenta.

Different strategies of selection were simulated to estimate the phenotypic performance and average inbreeding in selection assisted by markers, for quantitative traits with heritability values of 0.10, 0.40, and 0.70. The genetic simulation system (Genesys) was used for the simulation of three genomes (each one consisting of a single characteristic which distinction was the value of heritability) and base and original populations. Each initial population was subjected to selection assisted by markers for 20 consecutive generations. Strategies of mating between the parents selected in different intensities of selection (population size) were evaluated by selective mating between the best and worst, mating only among the best and/or among the worst and random mating. In all scenarios combining heritability and intensity, the strategic mating using the methodology of selective genotyping was superior to the others, becoming more effective in detecting QTL and, consequently, in the increase of phenotypic value and in the minimization of the inbred average over the generations. By using the selective sampling strategy, smaller population size to optimize the detection of QTL is required, since the value of the heritability of the characteristic increases.

No presente estudo, objetivou-se avaliar a divergência genética de indivíduos de quatro populações de fáfia [Pfaffia glomerata (Spreng.) Pedersen] coletadas na região do rio Paraná por meio de estudos de caracteres morfológicos associados à produção de β-ecdisona. A divergência foi avaliada entre 64 indivíduos utilizando 14 caracteres morfológicos quantitativos, incluindo o teor de β-ecdisona. Os dados foram interpretados pelas médias dos caracteres, índice de dissimilaridade de Mahalanobis, agrupamento pelo método UPGMA e correlação simples de Pearson. Os resultados demonstraram maiores valores de divergência entre indivíduos pertencentes a diferentes populações e menores, entre indivíduos da mesma população. Os indivíduos pertencentes à população 1, coletados à margem do rio Ivaí, destacaram-se pelos altos valores de β-ecdisona, predominando o seguinte perfil: matéria seca da raiz abaixo da média geral (135,1 g planta-1); antese precoce em relação a média geral (135,8 dias); dias para ocorrer a senescência de 90% das folhas abaixo da média geral (201,4 dias); e intervalo entre antese e senescência acima da média (65,6 dias). Os caracteres avaliados demonstraram significativa variação entre os indivíduos, no entanto, não foi possível observar dados que evidenciam a correlação entre a produção de β-ecdisona e caracteres morfológicos avaliados no presente estudo.

The present study aimed to evaluate the genetic divergence among individuals from four Pfaffia glomerata populations collected in the region of Paraná River, Brazil, based on the study of morphological characters associated with β-ecdysone production. The divergence among 64 individuals was estimated using 14 quantitative morphological characters, including -ecdysone content. Data were evaluated considering general mean of the characters, Mahalanobis dissimilarity index, UPGMA grouping method, and Pearson correlation. Results indicated higher divergence among individuals from different populations and lower divergence among those from the same population. Individuals from population 1, collected at the shore of Ivaí River, had high β-ecdysone content, with predominance of the following profile, compared to the general mean: lower root dry matter (135.1 g plant-1); earlier anthesis (135.8 days); smaller number of days to senescence of 90% of the leaves (201.4 days); and longer interval between anthesis and senescence (65.6 days). The evaluated characters significantly varied among individuals; nevertheless, the correlation between β-ecdysone production and the evaluated morphological characters could not be evidenced.

Listeria monocytogenes é um patógenode grande preocupação para as indústrias alimentícias, principalmente aquelas produtoras de alimentos prontos para consumo (RTE). Este microrganismo pode sobreviver às etapas de cura e defumação a frio, além de tolerar temperaturas de refrigeração. A presença de L. monocytogenes em pescados RTE com vida de prateleira longa representa um risco para a população susceptível, sendo o salmão gravlax deste tipo de produto. No presente estudo avaliou-se a incidência e disseminação de L. monocytogenes em 415 amostras de salmão gravlax obtidas de diferentes etapas de processamento de uma indústria localizada no Estado de São Paulo. A presença de L. monocytogenes foi confirmada em amostras de salmão (41%), superfícies de contato (32%) e não contato (43%) e manipuladores (34%), porém não se isolou o microrganismo em nenhum ingrediente. Do total de cepas isoladas, 179 destas foram escolhidas aleatoriamente e submetidas a sorologia e tipagem por PFGE. A maioria dos isolados pertenceu ao sorogrupo 1 (73%), sendo identificados 61 pulsotipos quando se combinou os resultados de sorologia e PFGE e 6 clusters foram distribuídos em um dendrograma. O cluster A agrupou a maioria das cepas (120). Pode-se sugerir que as cepas foram introduzidas na linha de processamento por meio da matéria prima e contaminando o produto final. Estes resultados indicam que a eliminação de L. monocytogenes deste estabelecimento requer um grande esforço, ainda que o microrganismo não se multiplicou no produto final estocado a 4ºC por 90 dias.

Listeria monocytogenes is a cause of concern to food industries, mainly for those producing ready-to-eat (RTE) products. This microorganism can survive processing steps such as curing and cold smoking and is capable of growing under refrigeration temperatures. Its presence in RTE fish products with extended shelf life may be a risk to the susceptible population. One example of such a product is gravlax salmon; a refrigerated fish product not exposed to listericidal processes and was the subject of this study. In order to evaluate the incidence and dissemination of L. monocytogenes 415 samples were collected at different steps of a gravlax salmon processing line in São Paulo state, Brazil. L. monocytogenes was confirmed in salmon samples (41%), food contact surfaces (32%), non-food contact surfaces (43%) and of food handlers' samples (34%), but could not be detected in any ingredient. 179 L. monocytogenes isolates randomly selected were serogrouped and typed by PFGE. Most of L. monocytogenes strains belonged to serogroup 1 (73%). 61 combined pulsotypes were found and a dendrogram identified six clusters: most of the strains (120) belonged to cluster A. It was suggested that strains arriving into the plant via raw material could establish themselves in the processing environment contaminating the final product. The wide dissemination of L. monocytogenes in this plant indicates that a great effort has to be taken to eliminate the microorganism from these premises, even though it was not observed multiplication of the microorganism in the final product stored at 4ºC up to 90 days.

Introduction and objectives: It is usual to identify patients with a negative prostate biopsy who are still at risk of prostate cancer. We try to analyse if the classical variables used in the prostate cancer screening are useful for those patients with a previous negative prostate biopsy, and if there is a possibility for making a nomogram witch would help us in the decision to repeat the biopsy. Material and methods: We studied 179 patients with at least 1 initial negative biopsy. At each biopsy session we recorded: Patient age, serum prostate specific antigen (PSA), free PSA/total PSA, PSA slope, digital rectal examination, prostate volume, PSA density, cancer suspicion in previous transrectal ultrasounds findings, number of negative cores previously obtained, history of precarcinomatous lesions and time between biopsies. Through Logistic regression analysis we determined the association of each variable a positive biopsy. A nomogram was constructed using all variables and discrimination was calculated as the concordance index. Results: Overall 46% of patients had cancer at the repeated biopsy session. In the univariate analysis: Age, digital rectal examination, prostate volume, PSA density, cancer suspicion in ultrasounds findings, and precarcinomatous lesions were associated with repeat positive biopsy for cancer (all p < 0.05). In the multivariate study, age, digital rectal examination, prostate volume and history of precarcinomatous lesions were associated with repeat positive biopsy. A nomogram was constructed that had a concordance index of 0.80.

Objetivo: Analizamos las variables clínicas e histopatológicas de los pacientes hombres a biopsiar por sospecha de cáncer de próstata y cuáles de ellos tienen carácter pronóstico para los pacientes con biopsia previa sin hallazgos de neoplasia. Pretendemos desarrollar un nomograma que nos ayude en la decisión de indicar la repetición de la prueba. Material y método: Incluimos 179 pacientes con, al menos una biopsia previa sin hallazgos neoplásicos. Registramos, antes de cada biopsia, edad del paciente, antígeno próstatico específico (PSA) total, PSA libre/total, densidad del PSA, velocidad del PSA, tacto rectal, volumen ecográfico, aparición de área sospechosa en la escala de grises durante la ecografía transrectal, número de cilindros biopsiados, lesiones histológicas premalignas en alguna de las biopsias previas, así como el tiempo transcurrido entre las biopsias. Mediante un modelo de regresión logística determinamos la asociación de cada variable con la presencia de cáncer (biopsia positiva). Construimos un nomograma con las variables estadísticamente más relevantes y averiguamos la capacidad de discriminación del modelo mediante el índice de concordancia. Resultados: Nuestras biopsias de repetición consiguen una tasa de detección de cáncer del 46%. En el estudio univariante la edad, el tacto rectal, el volumen prostático, la densidad del PSA, las zonas sospechosas en la escala de grises, y las lesiones histológicas premalignas se asocian a biopsia de repetición positiva para cáncer (p < 0,05). En el análisis multivariante, la edad, el tacto rectal, el volumen prostático y los antecedentes histológicos de una lesión preneoplásica se asociaron a biopsia positiva. Construimos un nomograma con un índice de concordancia de 0,80. Conclusión: A expensas de una validación prospectiva externa de nuestro modelo, el nomograma desarrollado podría ser de ayuda en la difícil de tarea de indicar una biopsia de repetición.

Background: New approaches for prostate cancer are needed due to limitations of current therapies for the treatment in advanced stages of the disease. In fact, there is no effective treatment for these patients. Development in molecular biology research on prostate cancer has improved the knowledge of common alterations encoded in DNA sequence, which may be useful as targets for prostate cancer approach. In this review we give an overview of current gene therapy concepts, the most common gene alterations in prostate cancer and the gene therapy treatment strategies.

Introducción: Debido a las limitaciones existentes en el tratamiento del cáncer de próstata en estadios avanzados, se precisan nuevas estrategias de tratamiento para estos pacientes. El desarrollo de la biología molecular en el campo del cáncer de próstata, ha proporcionado un mayor conocimiento de las alteraciones más comunes a nivel del ADN de las células cancerígenas, que podrían ser utilizadas como dianas terapéuticas. En este artículo se han revisado los conceptos actuales en el campo de la terapia génica, las alteraciones génicas más frecuentes en el cáncer de próstata y posibles estrategias de tratamiento.

Photodynamic therapy is based on the administration of an energy source in form of light of a specific wavelength, on a previously photosensitized tissue by a chemical compound, in the presence of oxygen, so that the great deal of free radicals and oxygen derivatives generated (hydroxyl compounds) produces necrosis of the treated tissue. Technique improvement during the last years has allowed its recent development as a therapeutic method for localised prostate cancer. At present, several clinical trials are ongoing in patients with organ-confined prostate cancer both as a first line and salvage treatment. There is no risk either of cancer dissemination in surrounding tissues or accumulative pharmaco-toxicity. Therefore, the technique can be repeated as often as needed and can be administered on a previously irradiated tissue. The literature review shows that photodynamic treatment will become a therapeutic option for patients with prostate cancer in the very near future.

La terapia fotodinámica se basa en la aplicación de una fuente de energía en forma de luz con una determinada longitud de onda, sobre un tejido previamente fotosensibilizado mediante un compuesto químico, en presencia de oxígeno; de modo que se generan gran cantidad de radicales libres y derivados del oxígeno (compuestos hidroxilo) que producen necrosis del tejido tratado. El perfeccionamiento de esta técnica en los últimos años ha permitido su reciente desarrollo como modalidad terapéutica del cáncer de próstata localizado. En este momento, se están llevando a cabo varios ensayos clínicos en pacientes con cáncer de próstata órgano-confinados tanto como tratamiento de primera línea como de rescate. No hay riesgo de diseminar el cáncer en los tejidos adyacentes, o de fármaco-toxicidad acumulativa. Por lo tanto, se puede repetir la terapia las veces que se crea necesaria y se puede aplicar sobre un tejido previamente irradiado. De la literatura se desprende que la terapia fotodinámica, en un futuro muy próximo, será una opción terapéutica para los pacientes con cáncer de próstata.

Introduction and Objective: Prostate brachytherapy is a first-line therapeutic approach for localized prostate cancer in selected patients. We present our experience in brachytherapy and a thorough review of the literature. Materials and Methods: A review of the literature and evaluation of patient's selection was done. Furthermore the implantation technique, oncological results according to the different risk groups and acute and chronic complications were also analyzed. Results: The biochemical relapse-free 10 year survival rate was 87-96% in low risk tumours and 63-86% in intermediate risk tumours. A total of 3-24% underwent urinary retention that required TURP in 0-8,7%. Other complications were urinary incontinence in 0-6,7%, proctitis in 0-15,5%, erectile dysfunction in 6,3-30%, rectal ulcer/fistula in 0-5,4%. Conclusions: Prostate brachytherapy is a safe and effective treatment in low and intermediate risk patients with prostate cancer.

Introducción y Objetivo: La braquiterapia prostática se ha consolidado en los últimos años como tratamiento de primera línea en pacientes seleccionados con cáncer de próstata localizado. Pretendemos realizar una actualización del tema. Material y Métodos: Revisión bibliográfica de las principales series publicadas analizando, indicaciones (selección de pacientes), las diferentes técnicas de implantación, los resultados oncológicos en función de grupos de riesgo y las complicaciones agudas y crónicas. Resultados: La supervivencia libre de recaída bioquímica fue del 87-96% a 10 años en tumores de bajo riesgo y del 63-86% a 10 años en tumores de riesgo intermedio. Las principales complicaciones fueron la retención urinaria en el 3-24%, necesitando RTU de próstata en 0-8,7%, la incontinencia urinaria en el 0-6,7%, proctitis en 0-15,5%, disfunción eréctil en 6,3-30%, úlceras/fístulas rectales en 0-5,4%. Conclusiones: La braquiterapia prostática constituye una alternativa terapéutica en el cáncer de próstata localizado de bajo riesgo y en pacientes seleccionados de riesgo intermedio, con escasas complicaciones y una aceptable tasa de control bioquímico.

This article reviews the current status of the prostatic cryosurgery in the management of patients with prostate cancer. Recent advances in cryoablative technology have allowed to treat these patients successfully with decreased morbidity. Using transrectal high-resolution ultrasound imaging, prostate cryotherapy is delivered with multiple ultrathin (17-gauge) cryo-needles, via percutaneous transperineal approach. The extent of freezing can be precisely controlled and monitored with thermic devices, tissue destruction is monitored with real-time visualization of the prostate and surrounding structures, and urethral warming is used to avoid urethral sloughing. However, the results with the second and third-generation cryosurgical equipment will have to be confirmed by means of prospective and randomized trials, because up to now we only have data based on retrospective analyses, which are very heterogeneous. The ability of prostate-specific antigen (PSA) to predict long-term outcome after cryotherapy for localized prostate cancer is not well known because experience with this treatment modality is still limited; however, it seems that a PSA value of 0.5 ng/ml or less after 6 months or longer after cryotherapy would be associated with a high probability (greater than 95%) of negative post-treatment biopsy. Cryosurgery could also be an option of treatment for men with recurrent local disease who have undergone radiotherapy or radical prostatectomy. We have to keep in mind possible complications (incontinence, impotency, urethrorectal fistula or bladder outlet obstruction. The favorable side effect profile and preliminary oncologic and funtional results could suggest that cryosurgery will have a role in the minimally invasive management of selected patients with prostate cancer.

En este trabajo se realiza una revisión sobre le estado actual de la criocirugía prostática en el tratamiento de los pacientes con cáncer de próstata. Los avances recientes acontecidos en la tecnología crioablativa permiten tratar eficazmente estos pacientes con una menor morbilidad. La utilización de ultrasonografía transrectal de alta resolución permite realizar la crioterapia prostática mediante la colocación percutánea transperineal de múltiples "crioagujas" de pequeño calibre (17-gauge). La extensión de la congelación puede ser controlada con precisión mediante dispositivos térmicos, la destrucción tisular prostática y en vecindad puede ser visualizada en tiempo real y el uso de calentadores uretrales evita el esfacelamiento uretral. Sin embargo, los resultados con los equipos de criocirugía de segunda y tercera generación tienen que ser validados mediante estudios aleatorizados y prospectivos, ya que hasta la actualidad sólo disponemos de datos basados en estudios retrospectivos, que son muy heterogéneos. La capacidad del antígeno prostático específico para predecir la evolución a largo plazo tras la criocirugía en los pacientes con cáncer prostático localizado no es bien conocida puesto que la experiencia con esta modalidad terapéuticas es todavía limitada; aunque parece que un valor de PSA <0,5 ng/ml a los 6 meses del tratamiento indicaría una alta probabilidad (95%) de biopsia negativa post-tratamiento. La criocirugía podría ser útil también en el tratamiento de la recurrencia local en pacientes tratados mediante prostatectomía radical o radioterapia. Debemos tener presente la posibilidad de complicaciones (incontinencia, impotencia, fístula uretrorectal, u obstrucción infravesical). El perfil favorable de efectos adversos y los resultados preliminares oncológicos y funcionales sugieren que la criocirugía tendrá indicación en el tratamiento mínimamente invasivo de pacientes seleccionados con cáncer de próstata.

It is well documented the effectiveness of intravesical chemotherapy following transurethral resection to prevent recurrences of superficial bladder cancer. But it is also known that efficacy may be limited by tumour cell resistance to one or several of the drugs available for instillation. In addition to the genetically determined unicellular mechanisms classically described in the literature such as glycoprotein P-170 expression (mdr-1), overexpression of Bcl-2 or glutation S-transferase activity, it has been recently shown that multicellular mechanisms may also be involved in drug resistance. Multicellular resistance can only be demonstrated in three-dimensional cultures and fails to be shown in monolayers or cell suspensions. This is explained by the fact that cell-to-cell and cell-to-stroma adhesion limits drug penetration and by the variable susceptibility to cytotoxicity determined by oxygen and tissue proliferation gradients. A better understanding of the molecular mechanisms involved in drug resistance is necessary to increase intravesical chemotherapy effectiveness. Current research includes improving drug penetration, searching resistance reversing agents and developing in vitro chemosensitivity tests to identify drug resistance.

Numerosos estudios han demostrado la utilidad de la quimioterapia intravesical en la profilaxis de las recidivas del tumor vesical superficial después de la resección transuretral. Pero la eficacia de esta práctica puede verse limitada por la existencia de resistencias a agentes individuales o de multirresistencias a varios fármacos. Además de los mecanismos de resistencia clásicos o "unicelulares" determinados genéticamente, como la expresión de la glicoproteína P-170 (gen mdr-1), la sobreexpresión del gen Bcl-2 o la actividad de la glutation S-transferasa, existen otros mecanismos de resistencia "multicelular" que han podido ser demostrados en cultivos de agregados celulares tridimensionales, y no en las mismas células cultivadas en monocapa o en suspensión de células individuales. La adhesión célula-célula y célula-estroma condiciona por un lado una limitada penetración de las drogas y, por otro, unos gradientes de oxígeno y proliferación en los tejidos que crean distintas susceptibilidades al efecto citotóxico. El conocimiento de las resistencias y sus mecanismos es de gran importancia, puesto que se trata de uno de los puntos donde se puede actuar para optimizar la eficacia de la quimioterapia intravesical. Muchos investigadores han dedicado sus esfuerzos a la búsqueda de medios contra las resistencias mediante la aplicación de métodos para mejorar la penetración de los fármacos, la búsqueda de agentes reversores o la identificación de las resistencias con tests in vitro de quimiosensibilidad.

INTRODUCTION AND OBJECTIVES: Angiogenic activity has been considered like prognostic factor in several solid tumors. This activity can be analysed by two ways: immunohistochemical determination of molecules that activate/inhibit angiogenesis or quantitive measure of microvascular density (MD). Our objective is to determine the prognostic value of Vascular Endothelial Growth Factor (VEGF) and Microvascular Density (MD) in pT1G3 bladder tumours. MATERIAL AND METHODS: We have studied retrospectively 83 patients with pT1G3 tumors treated by TUR + endovesical instillations with a follow up of 3 years at least. We analysed VEGF expression monoclonal antibody Nº 360P. To determine MD we have marked vessels with FVIII antibody and detected "hot spots" areas. The number of microvessels is quantited by a digital image analyser excluding those that have more than 50 micras of diameter. We established the correlation of these findings with recurrence, progression and survival by using Chi-square test and Kaplan-Meier curves (log-rank). RESULTS: Average follow up was 58 ± months. We have established like cut-off 50% of tumor cells (VEGF) and 30 microvessels/fields (MD). Chi-square test did not show correlation with survival neither recurrence but it was positive for progression p(VEGF) 0.048 and p(DM) 0.021. Kaplan Meier curves determined significative differences only for free of progression time respect to MD (p 0.038). CONCLUSIONS: We did not find statistically significant value for recurrence nor survival. Just MD reached prognostic value for progression. More studies and multivariant analysis are required to determine the clinical utility of MD, specially in order to make more aggressive therapeutic options in this kind of patients.

INTRODUCCIÓN Y OBJETIVOS: La actividad angiogénica ha sido considerada como factor pronóstico en diversos tumores sólidos. Podemos analizarla de dos formas: determinación inmunohistoquímica de moléculas activadoras/ inhibidoras de la angiogénesis y cuantificación de la densidad microvascular (DM). Nuestro objetivo es determinar en tumores vesicales pT1G3, el valor de la inmunohistoquímica del Vascular Endotelial Growth Factor (VEGF) y de la DM como factores pronóstico. MATERIAL Y MÉTODOS: Estudio retrospectivo de 83 tumores vesicales pT1G3 con un seguimiento mínimo de 3 años. Analizamos la expresión del VEGF utilizando el Ac. monoclonal AbNo.360P. Para determinar la DM, marcamos los vasos (Ac.-FVIII) y cuantificamos el número de microvasos mediante un analizador digital de imagen, excluyendo aquellos que sobrepasan las 50 micras de diámetro. Correlacionamos los hallazgos con la recidiva, progresión y supervivencia, mediante tablas de contingencia (Chi-cuadrado) y curvas de Kaplan-Meier (Log-rank). RESULTADOS: El tiempo medio de seguimiento ha sido de 58 ± 28 meses. El análisis Chi-cuadrado no muestra correlación ni con la recidiva ni con la supervivencia, pero si con la progresión: p(VEGF): 0,048, p(DM): 0,021. Las curvas de Kaplan-Meier determinan diferencias significativas únicamente en el tiempo libre de progresión respecto de la DM (p:0,038). CONCLUSIONES: La DM podría considerarse como factor pronóstico de progresión en base a estos resultados. No obstante son necesarios más estudios y un análisis multivariante que determine su aplicación clínica en este grupo de tumores de alto riesgo.