Telomere-based risk models for the early diagnosis of clinically significant prostate cancer.

BACKGROUND: The objective of this study was to explore telomere-associated variables (TAV) as complementary biomarkers in the early diagnosis of prostate cancer (PCa), analyzing their application in risk models for significant PCa (Gleason score > 6). METHODS: As part of a larger prospective longitudinal study of patients with suspicion of PCa undergoing prostate biopsy according to clinical practice, a subgroup of patients (n = 401) with PSA 3-10 ng/ml and no prior biopsies was used to evaluate the contribution of TAV to discern non-significant PCa from significant PCa. The cohort was randomly split for training (2/3) and validation (1/3) of the models. High-throughput quantitative fluorescence in-situ hybridization was used to evaluate TAV in peripheral blood mononucleated cells. Models were generated following principal component analysis and random forest and their utility as risk predictors was evaluated by analyzing their predictive capacity and accuracy, summarized by ROC curves, and their clinical benefit with decision curves analysis. RESULTS: The median age of the patients was 63 years, with a median PSA of 5 ng/ml and a percentage of PCa diagnosis of 40.6% and significant PCa of 19.2%. Two TAV-based risk models were selected (TAV models 1 and 2) with an AUC ≥ 0.83 in the full study cohort, and AUC > 0.76 in the internal validation cohort. Both models showed an improvement in decision capacity when compared to the application of the PCPT-RC in the low-risk probabilities range. In the validation cohort, with TAV models 1 and 2, 33% /48% of biopsies would have been avoided losing 0/10.3% of significant PCa, respectively. The models were also tested and validated on an independent, retrospective, non contemporary cohort. CONCLUSIONS: Telomere analysis through TAV should be considered as a new risk-score biomarker with potential to increase the prediction capacity of significant PCa in patients with PSA between 3-10 ng/ml.

Analytical Validation of Telomere Analysis Technology® for the High-Throughput Analysis of Multiple Telomere-Associated Variables.

BACKGROUND: A large number of studies have suggested a correlation between the status of telomeres and disease risk. High-throughput quantitative fluorescence in situ hybridization (HT Q-FISH) is a highly accurate telomere measurement technique that can be applied to the study of large cell populations. Here we describe the analytical performance testing and validation of Telomere Analysis Technology (TAT®), a laboratory-developed HT Q-FISH-based methodology that includes HT imaging and software workflows that provide a highly detailed view of telomere populations. METHODS: TAT was developed for the analysis of telomeres in peripheral blood mononuclear cells (PBMCs). TAT was compared with Terminal Restriction Fragment (TRF) length analysis, and tested for accuracy, precision, limits of detection (LOD) and specificity, reportable range and reference range. RESULTS: Using 6 different lymphocyte cell lines, we found a high correlation between TAT and TRF for telomere length (R2 ≥ 0.99). The standard variation (assay error) of TAT was 454 base pairs, and the limit of detection of 800 base pairs. A standard curve was constructed to cover human median reportable range values and defined its lower limit at 4700 bp and upper limits at 14,400 bp. Using TAT, up to 223 telomere associated variables (TAVs) can be obtained from a single sample. A pilot, population study, of telomere analysis using TAT revealed high accuracy and reliability of the methodology. CONCLUSIONS: Analytical validation of TAT shows that is a robust and reliable technique for the characterization of a detailed telomere profile in large cell populations. The combination of high-throughput imaging and software workflows allows for the collection of a large number of telomere-associated variables from each sample, which can then be used in epidemiological and clinical studies.

Enprostil versus cimetidina en el tratamiento de la úlcera gástrica benigna / Enprostil versus cimetidine in the treatment of bening gastric ulcer

En el presente estudio se comparó el beneficio terapéutico del Enprostil (dehidropostaglandina E2 sintética). En 10 pacientes consecutivos con úlcera gástrica benigna, contra el efecto de la Cimetidina en otros 10 pacientes consecutivos con el mismo padecimiento. El porciento de cicatrización de la úlcera, confirmado por endoscopía, fue similar para ambos productos en la 6a. semana de tratamiento, sin embargo, en la 4a. semana se obtuvo un mayor porciento de cicatrización con el Enprostil. En el grupo de Enprostil, 2 casos con úlcera muy grande y que ya había recibido otras medicaciones antiulcerosas previas, el tratamiento se prolongó hasta la semana 14, confirmándose la desparición de la úlcera por endoscopia. Asimismo, en otro caso de este grupo cicatrizó la úlcera a pesar de continuar con medicación agresiva para la mucosa gastrica. Con la aparición de nuevos medicamentos y esquemas más prolongados de tratamiento se reducirá el número de las llamadas úlceras gástricas benignas resistentes al tratamiento médico

Hemangioma hepático: tratar u observar? / Hepatic hemangioma: to treat or to observe?

El hemangioma hepático habitualmente es un hallazgo de autopsia o laparotomía. Ocurre en cualquier edad y por lo general mide menos de 4 cm. de diámetro mayor. En una revisión de 10,523 autopsias se encontraron 63 hemangiomas hepáticos. Ninguna muerte fue atribuible a esta tumoración. De 1975 a 1983 se sometieron a estudio histológico postquirúrgico 10 hemangiomas hepáticos. Cuatro estudios fueron hechos en pacientes intervenidos por la tumoración: a dos se les efectuó hepatectomía derecha, a otra ligadura de arterias hepáticas y a otro solo biopsia. En esta revisión no encontramos ningún paciente en quien la ruptura del tumor haya motivado una intervención de urgencia. Una paciente de 60 años tenía insuficiencia cardiaca y un gran hemangioma. La centelleografía, el ultrasonido, la tomografía axial computarizada y la arteriografía son los métodos que permiten establecer el diagnóstico. Si el paciente no es candidato a cirugía mayor o la lesión causa molestias mínimas, debe ser observado periódicamente con métodos no invasores. Si la lesión mide más de 4 cm. y está en un sitio accesible la resección es curativa