The Effectiveness of Glutathione Redox Status as a Possible Tumor Marker in Colorectal Cancer.

The role of oxidative stress (OS) in cancer is a matter of great interest due to the implication of reactive oxygen species (ROS) and their oxidation products in the initiation of tumorigenesis, its progression, and metastatic dissemination. Great efforts have been made to identify the mechanisms of ROS-induced carcinogenesis; however, the validation of OS byproducts as potential tumor markers (TMs) remains to be established. This interventional study included a total of 80 colorectal cancer (CRC) patients and 60 controls. By measuring reduced glutathione (GSH), its oxidized form (GSSG), and the glutathione redox state in terms of the GSSG/GSH ratio in the serum of CRC patients, we identified significant changes as compared to healthy subjects. These findings are compatible with the effectiveness of glutathione as a TM. The thiol redox state showed a significant increase towards oxidation in the CRC group and correlated significantly with both the tumor state and the clinical evolution. The sensitivity and specificity of serum glutathione levels are far above those of the classical TMs CEA and CA19.9. We conclude that the GSSG/GSH ratio is a simple assay which could be validated as a novel clinical TM for the diagnosis and monitoring of CRC.

Comprehensive NGS Panel Validation for the Identification of Actionable Alterations in Adult Solid Tumors.

The increasing identification of driver oncogenic alterations and progress of targeted therapies addresses the need of comprehensive alternatives to standard molecular methods. The translation into clinical practice of next-generation sequencing (NGS) panels is actually challenged by the compliance of high quality standards for clinical accreditation. Herein, we present the analytical and clinical feasibility study of a hybridization capture-based NGS panel (Action OncoKitDx) for the analysis of somatic mutations, copy number variants (CNVs), fusions, pharmacogenetic SNPs and Microsatellite Instability (MSI) determination in formalin-fixed paraffin-embedded (FFPE) tumor samples. A total of 64 samples were submitted to extensive analytical validation for the identification of previously known variants. An additional set of 166 tumor and patient-matched normal samples were sequenced to assess the clinical utility of the assay across different tumor types. The panel demonstrated good specificity, sensitivity, reproducibility, and repeatability for the identification of all biomarkers analyzed and the 5% limit of detection set was validated. Among the clinical cohorts, the assay revealed pathogenic genomic alterations in 97% of patient cases, and in 82.7%, at least one clinically relevant variant was detected. The validation of accuracy and robustness of this assay supports the Action OncoKitDx's utility in adult solid tumors.

MR Imaging Findings in Molecular Subtypes of Breast Cancer According to BIRADS System.

To evaluate magnetic resonance imaging (MRI) findings, according to Breast Imaging-Reporting and Data System (BI-RADS), and to relate them with molecular subtypes of breast cancer. The MRI findings were reviewed retrospectively in 201 women diagnosed of invasive breast cancer confirmed by surgery and were compared with the molecular subtypes. Following the BI-RADS, MRI findings included disease type, size, enhancement, morphology and contrast kinetics. In mass-like lesion types were studied shape, margin and enhancement, and in nonmass-like lesion types, distribution modifiers and internal enhancement. Chi-squared analysis showed significant association (p < 0.01) between molecular subtypes and lesion type on MRI and histologic grade. Shape, margin and mass enhancement (p < 0.05) also showed significant association among molecular subtypes. Triple negative were more frequently unifocal and mass-like lesion, high histologic grade, round shape, smooth margin, and rim enhancement. Luminal-A were more frequently low grade, mass-like lesion, irregular shape and spiculated or irregular margin. Luminal-B were more frequently moderate-low grade, mass-like lesion, nonirregular shape and spiculated margin. HER-2-enriched were more frequently moderate grade, nonmass-like lesion and multicentric lesions were more present than in other subtypes. There are significantly different MRI features, according to BI-RADS, between the molecular subtypes breast cancer.

Linfoma MALT de vesícula biliar / MALT lymphoma of the gallbladder

No disponible

Defectos congénitos en recién nacidos y fetos procedentes de interrupción del embarazo tras diagnóstico prenatal en el período 1982-2009 / Evolution of the frequency of congenital defects in newborn infants and fetuses from terminations of pregnancy after prenatal diagnosis in the period 1982-2009

Fundamento y objetivo: El estudio de la frecuencia de los defectos congénitos (DC) requiere incluir interrupciones voluntarias del embarazo (IVE) por DC y evaluar los factores que influyen en aquella. Pacientes y método: Serie consecutiva de 517 recién nacidos (RN) y 202 IVE con DC en 38.191 nacimientos entre 1982-2009. Resultados: La frecuencia media de RN con DC es 13,54‰ y la de RN + IVE por DC de 18,73‰. Los DC aislados suponen el 61,12% en RN y el 52,17% en IVE. El 18,37% de los DC en RN y el 40,58% en IVE son sindrómicos. La media de edad gestacional en IVE es 17,92 semanas. La frecuencia global de anencefalia es 2,62 y 6,77 por 10.000, respectivamente, en RN y en RN + IVE. La de la espina bífida es 3,14 y 5,99 por 10.000, respectivamente. La frecuencia global de síndrome de Down es 10,74 por 10.000 RN y 22,14 por 10.000 RN + IVE. El porcentaje de madres extranjeras en nuestra maternidad alcanza el 35,9% en 2009. La media de edad materna asciende significativamente a lo largo del tiempo. Conclusiones: Observamos una disminución estadísticamente significativa de DC en RN, pero no en su concepción. No detectamos prevención primaria de anencefalia ni espina bífida. El descenso de síndrome de Down en RN no alcanza significación estadística. La diversidad étnica y la mayor edad materna pueden estar modificando la frecuencia. El 53% de los casos (RN + IVE) con DC del trienio 2007-2009 fueron IVE. Se precisa el estudio completo de IVE por DC para ofrecer consejo reproductivo (AU)

Background and objective: The study of congenital defects (CD) must include termination of pregnancy (TOP) for CD and evaluate risk factors that modify their frequency. Patients and methods: Consecutive series of 517 newborn and 202 TOP with CD among 38,191 childbirths, between 1982-2009 years. Results: The mean frequency for newborns with CD is 13.54‰ and for newborn and TOP with CD is 18.73‰. Single CD are 61.12% in newborns and 52.17% in TOP. The 18.37% of CD in newborn and 40.58% of TOP are syndromic. Mean gestational age for TOP is 17.92 weeks. Overall frequency of anencephaly is 2.62‰ for newborns and 6.77 for 10,000 for newborns and TOP. Spina bifida is 3.14 for 10,000 newborns and 5.99 for 10,000 newborns and TOP. Overall frequency of Down syndrome (DS) is 10.74 for 10,000 newborns and 22.14 for 10,000 newborns and TOP. The percentage of foreign mothers was 35.9% in 2009 and the mean maternal age significantly increased in this period. Conclusion: We observe a significant decrease of CD in newborns but not in their conception. We have not detected primary prevention for neural tube defects. The decrease in DS in newborns is not statistically relevant but ethnic diversity and maternal aging may be modifying the frequency. The 53% of CD were TOP in the period 2007-2009. It is mandatory a complete study for CD in TOP in order to offer serious reproductive counseling (AU)

[Evolution of the frequency of congenital defects in newborn infants and fetuses from terminations of pregnancy after prenatal diagnosis in the period 1982-2009]. / Defectos congénitos en recién nacidos y fetos procedentes de interrupción del embarazo tras diagnóstico prenatal en el período 1982-2009.

BACKGROUND AND OBJECTIVE: The study of congenital defects (CD) must include termination of pregnancy (TOP) for CD and evaluate risk factors that modify their frequency. PATIENTS AND METHODS: Consecutive series of 517 newborn and 202 TOP with CD among 38,191 childbirths, between 1982-2009 years. RESULTS: The mean frequency for newborns with CD is 13.54‰ and for newborn and TOP with CD is 18.73‰. Single CD are 61.12% in newborns and 52.17% in TOP. The 18.37% of CD in newborn and 40.58% of TOP are syndromic. Mean gestational age for TOP is 17.92 weeks. Overall frequency of anencephaly is 2.62‰ for newborns and 6.77 for 10,000 for newborns and TOP. Spina bifida is 3.14 for 10,000 newborns and 5.99 for 10,000 newborns and TOP. Overall frequency of Down syndrome (DS) is 10.74 for 10,000 newborns and 22.14 for 10,000 newborns and TOP. The percentage of foreign mothers was 35.9% in 2009 and the mean maternal age significantly increased in this period. CONCLUSION: We observe a significant decrease of CD in newborns but not in their conception. We have not detected primary prevention for neural tube defects. The decrease in DS in newborns is not statistically relevant but ethnic diversity and maternal aging may be modifying the frequency. The 53% of CD were TOP in the period 2007-2009. It is mandatory a complete study for CD in TOP in order to offer serious reproductive counselling.

Reflexiones sobre la patología ocular / No disponble

No disponible

No disponible

Prognostic value of the detection of lymph node micrometastases in colon cancer.

INTRODUCTION AND OBJECTIVES: A study is made of the clinical repercussions of occult metastases-micrometastases (MMs+)-or isolated tumour cells (ITCs+) in the lymph nodes of patients with stage IIA and IIB colon adenocarcinoma initially considered as corresponding to N0. MATERIAL AND METHODS: A retrospective study of 39 patients with stage IIA and IIB (T3-T4 N0 M0) colon adenocarcinoma, subjected to similar surgical and adjuvant chemotherapy treatment, with long and careful follow-up (minimum: 5 years, mean: 81.7 months) was performed on their previously resected lymph nodes, with the aid of new histological and immunohistochemical (cytokeratin) sections, in order to detect MMs or ITCs. Disease-free survival (DFS) and global survival (GS) in the two groups (patients with MMs+ or ITCs+ vs. patients without MMs or ITCs) were compared at 5 years based on the corresponding Kaplan-Meier survival curves, with the Breslow test. RESULTS: A total of 382 lymph nodes from the 39 patients (mean: 9.8; standard deviation: 6.09) were revised. MMs+ were detected in 2 cases and ITCs+ in 2 more cases on the Cytokeratin study. GS of the whole series at 5 years was 89.74% (35 patients alive) with a DFS at 5 years of 79.49% (31 patients free of disease), but the 2 cases with MMs+ were dead at 5 years, with high statistical differences between both groups (MMs+/MMs-) (p<0.0001). When comparing the group of MMs+/ITCs+ patients and the group of MM-/ITCs- patients, the DFS and GS times at 5 years were higher in the MMs-/ITCs- group (p=0.0692 and p=0.006 respectively). CONCLUSIONS: Although the incidence of MMs+ or ITCs+ in the examined lymph nodes was low, the presence of MMs is related to a dramatic reduction in GS and DFS at 5 years. We encourage a detailed histological study of lymph nodes resected in patients with deep penetrating colon tumours in order to assure a pN0 status.

Sarcoma histiocítico con rasgos inmunohistoquímicos yultraestructurales de células dendríticas interdigitantes / Histiocytic sarcoma with immunohistochemical and ultraestructural interdigitating dendritic cell features

Introducción: El Sarcoma histiocítico (SH) es una neoplasiamuy poco frecuente, con mucha controversia respectoa los criterios diagnósticos de esta entidad. Desde que lastécnicas inmunohistoquímicas y citogenéticas presentan unamayor disponibilidad universal, muchos casos que inicialmentese diagnosticaron como sarcoma histiocítico, hansido reclasificados como otras enfermedades. Presentacióndel caso: Describimos el caso de un sarcoma histiocíticoque se presentó como una masa abdominal. En la autopsiatambién se observó afectación tumoral de pulmones, hígado,bazo y múltiples adenopatías. El examen histológicomostró proliferación difusa de células grandes con áreas denecrosis. Las células malignas eran de aspecto histiocitarioy pleomórficas. Inmunohistoquímicamente, las célulastumorales fueron positivas para tinciones contra marcadoreshistiocíticos y negativas para marcadores mieloides, dendríticos,CD30, ALK1, y otros marcadores linfoides. En elestudio ultraestructural las células mostraron extensionescitoplásmicas interdigitantes, pero no gránulos de Birbeck.Conclusiones: El sarcoma histiocítico plantea diagnósticodiferencial con otras neoplasias. El diagnóstico en este caso,se basa en la morfología, técnicas inmunohistoquícas yultraestructurales (AU)

Introduction: Histiocytic sarcoma (HS) is a rare disease.There has been much confusion concerning the diagnosticcriteria for this entity. Since immunohistochemicaland cytogenetic techniques have become more universallyavailable, many cases that were initially diagnosed as histiocyticsarcoma are now being classified as other diseases.Case presentation:We describe a case of HS that began asabdominal mass. At autopsy the tumour also involved lungs,liver, spleen and multiple lymph nodes. Histological examinationshowed proliferation of numerous large histiocyticpleomorphic and malignant cells with areas of necrosis.Immunohistochemically, tumour cells expressed histiocyticmarkers but did not stain with antibodies directed againstmyeloid markers, dendritic markers, CD30, ALK1, or otherlymphoid markers. Ultrastructural examination demostratedinterdigitating cytoplasmic extensions, but not Birbeckgranules. Conclusions: Histiocytic sarcoma raises differentialdiagnosis with other neoplasms. In this case, morphological,immunohistochemical and ultraestructural findingsare necessary for diagnosis (AU)

Análisis de clonalidad en el linfoma cerebral primario mediante PCR / No disponible

Introducción: Establecer la diferencia entre poblaciones linfocitarias monoclonales y reactivas puede ser de gran ayuda en el diagnóstico del linfoma cerebral primario (LCP), especialmente en pequeñas muestras obtenidas por biopsia estereotáxica. El objetivo de este estudio ha sido evaluar la frecuencia de reordenamientos clonales del gen de la cadena pesada de las inmunoglobulinas (IgH) en el LCP. Métodos: Se han estudiado 24 LCP, 16 en pacientes inmunocompetentes y 8 asociados a SIDA. Mediante el método de reacción en cadena de la polimerasa (PCR) se analizó el gen IgH utilizando ADN extraído de tejido fijado en formol e incluido en parafina. Para ello se amplificaron las regiones CDR II y CDR III de dicho gen mediante cebadores consenso para las regiones VH (Fr2 y Fr3, respectivamente) y JH (LJH y VLJH). Resultados: El análisis molecular confirmó la existencia de clones de células B en un importante numero de casos de LCP. Al usar ambas combinaciones de cebadores (Fr2 y Fr3) se detectaron reordenamientos clonales del gen IgH en 19 de los 24 casos (79%), observándose en 5 de éstos un patrón biclonal debido a la presencia de dos bandas discretas con Fr3. La frecuencia de detección de clonalidad fue similar en los dos grupos de pacientes. Conclusiones: Nuestras observaciones apoyan que el estudio de la clonalidad del gen IgH mediante PCR en biopsias incluidas en parafina es de utilidad en el diagnóstico del LCP (AU)

Introduction: To determine differences between monoclonal and reactive lymphoid populations may be a great help in the diagnosis of primary brain lymphoma (PBL). The aim of this study was to evaluate the frequency of clonal immunoglobulin heavy chain (IgH) gene rearrangements in PBL. Methods: Twenty-four PBL were studied, 16 of them from immunocompetent patients and another 8 from AIDS patients. DNA was extracted from formalin-fixed, paraffin- embedded tissue. IgH gene rearrangements were analyzed using the polymerase chain reaction method (PCR) by amplifying CDRII and CDRIII regions using consensus primers directed to framework regions VH (Fr2 and Fr3 respectively) and JH (LJH and VLJH). Results: Molecular analysis confirmed the existence of B-cell clones in an important number of cases of PBL. Using both primer combinations (Fr2 and Fr3) we detected clonal IgH gene rearrangements in 19 of the 24 cases (79%), and 5 of these cases showed a biclonal pattern due to the presence of two discrete bands with Fr3. The frequency of detection of clonality was similar in both groups of patients. Conclusions: Our data confirm that PCR analysis of IgH rearrangements in paraffin-embedded biopsies is useful in the diagnosis of PBL (AU)