Valor diagnóstico y predictivo del estudio en orina del gen PCA3 para el manejo clínico de pacientes con antígeno prostático específico alterado / Diagnostic and Predictive Value of Urine PCA3 Gene Expression for the Clinical Management of Patients with Altered Prostatic Specific Antigen

Objetivo: Analizar el impacto de la introducción del estudio del gen PCA3 en orina posmasaje prostático, en el manejo clínico de pacientes con PSA alterado, valorando su capacidad diagnóstica y predictiva de agresividad tumoral. Métodos: Estudio observacional, prospectivo y multicéntrico de pacientes con sospecha de adenocarcinoma de próstata (AP) candidatos a biopsia. Presentamos una serie de 670 muestras consecutivas de orina posmasaje prostático recogidas durante 3 años en las que se determinó el «score de PCA3» (s-PCA3). Se indicó biopsia únicamente en los casos con s-PCA3 positivo. Resultados: El s-PCA3 fue positivo en el 43,7% de las muestras. En las 124 biopsias realizadas, la incidencia de AP o proliferación microacinar atípica fue del 54%, llegando al 68,6% en s-PCA3 ≥ 100. Demostramos relación estadísticamente significativa entre el s-PCA3 y el grado tumoral. En los casos con s-PCA3 positivo pero inferior a 50, solo el 23% de AP fueron de alto grado (Gleason ≥ 7); en cambio, en los casos con s-PCA3 superior a 50 lo fueron el 76,7%. La relación entre el s-PCA3 y el porcentaje de cilindros afectados en la biopsia fue significativa. Ambas relaciones se confirmaron al aplicar el modelo log-lineal. Conclusiones: La incorporación del PCA3 permite prescindir de la biopsia en un 54% de los pacientes. La positividad del s-PCA3 aumenta la probabilidad de biopsia positiva, especialmente en s-PCA3 superior a 100 (68,6%). El s-PCA3 es también un indicador de agresividad tumoral y aporta información esencial en la toma de decisiones terapéuticas

Objective: Analyze the impact of the introduction of the study of PCA3 gene in post-prostatic massage urine in the clinical management of patients with PSA altered, evaluating its diagnosticability and predictive value of tumor aggressiveness. Methods: Observational, prospective, multicenter study of patients with suspected prostate cancer (PC) candidates for biopsy. We present a series of 670 consecutive samples of urine collected post-prostatic massage for three years in which we determined the «PCA3 score»(s-PCA3). Biopsy was only indicated in cases with s-positive PCA3. Results: The s-PCA3 was positive in 43.7% of samples. In the 124 biopsies performed, the incidence of PC or atypical small acinar proliferation was 54%, reaching 68,6% in s-PCA3≥100. Statistically significant relationship between the s-PCA3 and tumor grade was demonstrated. In cases with s-PCA3 between 35 and 50 only 23% of PC were high grade (Gleason≥7), compared to 76.7% in cases with s-PCA3 over 50. There was a statistically significant correlation betweens-PCA3 and cylinders affected. Both relationships were confirmed by applying a log-linear model. Conclusions: The incorporation of PCA3 can avoid the need for biopsies in 54% of patients.s-PCA3 positivity increases the likelihood of a positive biopsy, especially in higher s-PCA3 100(68.6%). s-PCA3 is also an indicator of tumor aggressiveness and provides essential information nin making treatment decisions

Circulating tumour cells in locally advanced breast cancer

MATERIAL AND METHODS: A prospective study was conducted to determine the value of changes in circulating tumour cell (CTC) levels prior to and after the first cycle of neoadjuvant treatment in early prediction of pathologic response in locally advanced breast cancer (LABC). Two blood samples were obtained from 72 eligible LABC patients to isolate and enumerate CTCs before neoadjuvant chemotherapy started on day 1, and on day 21, immediately before second cycle administration. RESULTS: Sixty patients (83.3%) had <1 CTC in the first sample and response rates in this cohort were pathologic complete response (PCR) in 2 patients (5%), partial response (PR) in 35 (87.5%), stable disease (SD) in 2 (5%) and progressive disease (PD) in 1 (2.5%). Twelve patients (16.7%) had >2 CTCs in the first sample; these patients were more likely to have triple negative tumours. All 12 had fewer CTCs in the second sample. Response rates in this second cohort of 12 patients were PCR in 4 (34%), PR in 6 (50%), SD in 1 (8%) and PD in 1 (8%). PCR rate was markedly better in this second cohort (p<0.0042; OR 14.5, 95% CI 2.3-92). DISCUSSION: This study suggests that the presence of CTCs prior to neoadjuvant therapy might be a predictor of response to this therapy (AU)

Telomerase activity in colorectal cancer, prognostic factor and implications in the microsatellite instability pathway.

AIM: To determine whether the telomerase activity is related to the Microsatellite instability (MSI) genetic pathway and whether it means a difference in the survival. METHODS: The population consisted of 97 colorectal cancer patients. MSI determination was performed in accordance with the NCI criteria using PCR and Genescan. Telomerase activity was determined by the TRAP-assay, an ELISA procedure based on the amplification of telomeric repeat sequences. RESULTS: 6.2% showed high MSI (MSI-H), 10.3% showed low MSI (MSI-L) and 83.5% did not show this alteration (MSS). Positive telomerase activity was detected in 92.8% of the patients. 83.3% of MSI-H tumors showed positive telomerase against 93.8% of MSS tumors. In the overall survival analysis the absence of telomerase activity conferred a better prognosis. CONCLUSION: Previous works have shown that tumors which develop via the MSI pathway present a better prognosis. No link between telomerase activity and MSI status is observed, although sample sizes are small. Patients with telomerase negative tumors had better overall survival than patients with telomerase positive tumors.

Effects of pork vs veal consumption on serum lipids in healthy subjects / Efecto del consumo de cerdo y de ternera sobre el perfil lipídico de sujetos sanos

AIMS: To analyse the influence of lean pork (P) and veal (V) consumption on the lipid profile of healthy subjects within the framework of a healthy diet comprising low levels of total fat (TF), saturated fatty acids (SFA) and cholesterol. DESIGN: Double-crossover, randomized and controlled trial SUBJECTS: 44 healthy individuals (22 male and 22 female), recruited voluntarily from the University Complutense of Madrid. The weight and lipid profiles of these volunteers were normal and their dietary patterns were typical for people in our area. INTERVENTIONS: The study comprised 4 phases: stabilisation phase (5 weeks), the participants followed their normal diet; second phase (6 weeks), half of the subjects, were randomised to lean pork or veal consumption, 150 g per day, for their main meal of the day; washout period (5 weeks) and final phase, which was the second phase of intervention (6 weeks). During the intervention stages, only the main meal of the day was taken in the Hospital. The rest of the subjects' diets consisted of different fortnightly menus designed in accordance with the recommendations of the Spanish Society of Arteriosclerosis (SEA). RESULTS: After both stages of intervention had been completed, there was a mean reduction of 5.5% in lowdensity lipoprotein cholesterol. However, after each intervention there were no significant differences between those who had consumed P, 2.62 (0.55) mmol/L and those who had consumed V, 2.71 (0.47) mmol/L. No differences were observed in any of the other parameters between those who had consumed P and those who had consumed V. CONCLUSIONS: Lean pork and veal produces similar effects on the lipid profiles of healthy subjects. Its consumption, as part of the saturated fat and cholesterolcontrolled diet, could therefore be included in food guidelines, both for normal and therapeutic diets (AU)

OBJETIVO: Analizar la influencia del consumo de carne magra de cerdo (P) y de ternera (V) en el perfil lipídico de sujetos sanos, cuando se realiza dentro de un patrón de dieta saludable con bajo contenido en grasa total (TF), ácidos grasos saturados (SFA) y en colesterol. DISEÑO: Ensayo cruzado doble, aleatorizado y controlado. SUJETOS: 44 sujetos sanos (22 varones y 22 mujeres), reclutados de forma voluntaria de la Universidad Complutense de Madrid. Los pesos y los perfiles lipídicos de estos voluntarios y su patrón de alimentación eran típicos de las personas de nuestra área. INTERVENCIONES: El estudio consta de 4 fases: fase de estabilización (5 semanas), los participantes seguían su dieta normal; segunda fase (6 semanas), la mitad de los sujetos se randomizaron para que consumieran carne magra de cerdo o de ternera, 150 g al día, durante la principal comida del día; periodo de lavado (5 semanas) y fase final, que era la segunda fase de intervención (6 semanas). Durante las fases de intervención, sólo la principal comida se realizaba en el hospital. El resto de las dietas de los sujetos estaba constituida por menús diferentes para 2 semanas que seguían las recomendaciones de la Sociedad Española de Arteriosclerosis (SEA). RESULTADOS: Tras ambas intervenciones, hubo una reducción media de un 5,5% en el LDL colesterol. Sin embargo, después de cada intervención no encontramos diferencias significativas entre los que consumieron P, 2.62 (0.55) mmol/L y estos que consumieron V, 2.71 (0.47) mmol/L. No se observó diferencias en el resto de los parámetros analizados entre los que consumieron P y los que consumieron V. CONCLUSIONES: El consumo de P y B produce efectos similares sobre el perfil lipídico de sujetos sanos. Su consumo, formando parte de dietas controladas en grasa saturada y colesterol, podrían incluirse en pautas alimentarias, tanto de dietas normales como terapéuticas (AU)