Multiethnic genome-wide association study of differentiated thyroid cancer in the EPITHYR consortium.

Incidence of differentiated thyroid carcinoma (DTC) varies considerably between ethnic groups, with particularly high incidence rates in Pacific Islanders. DTC is one of the cancers with the highest familial risk suggesting a major role of genetic risk factors, but only few susceptibility loci were identified so far. In order to assess the contribution of known DTC susceptibility loci and to identify new ones, we conducted a multiethnic genome-wide association study (GWAS) in individuals of European ancestry and of Oceanian ancestry from Pacific Islands. Our study included 1554 cases/1973 controls of European ancestry and 301 cases/348 controls of Oceanian ancestry from seven population-based case-control studies participating to the EPITHYR consortium. All participants were genotyped using the OncoArray-500K Beadchip (Illumina). We confirmed the association with the known DTC susceptibility loci at 2q35, 8p12, 9q22.33 and 14q13.3 in the European ancestry population and suggested two novel signals at 1p31.3 and 16q23.2, which were associated with thyroid-stimulating hormone levels in previous GWAS. We additionally replicated an association with 5p15.33 reported previously in Chinese and European populations. Except at 1p31.3, all associations were in the same direction in the population of Oceanian ancestry. We also observed that the frequencies of risk alleles at 2q35, 5p15.33 and 16q23.2 were significantly higher in Oceanians than in Europeans. However, additional GWAS and epidemiological studies in Oceanian populations are needed to fully understand the highest incidence observed in these populations.

Objective Endoscopic Measurements of Central Airway Stenosis: A Pilot Study.

BACKGROUND: Endoscopic estimation of the degree of stenosis in central airway obstruction is subjective and highly variable. OBJECTIVE: To determine the benefits of using SENSA (System for Endoscopic Stenosis Assessment), an image-based computational software, for obtaining objective stenosis index (SI) measurements among a group of expert bronchoscopists and general pulmonologists. METHODS: A total of 7 expert bronchoscopists and 7 general pulmonologists were enrolled to validate SENSA usage. The SI obtained by the physicians and by SENSA were compared with a reference SI to set their precision in SI computation. We used SENSA to efficiently obtain this reference SI in 11 selected cases of benign stenosis. A Web platform with three user-friendly microtasks was designed to gather the data. The users had to visually estimate the SI from videos with and without contours of the normal and the obstructed area provided by SENSA. The users were able to modify the SENSA contours to define the reference SI using morphometric bronchoscopy. RESULTS: Visual SI estimation accuracy was associated with neither bronchoscopic experience (p = 0.71) nor the contours of the normal and the obstructed area provided by the system (p = 0.13). The precision of the SI by SENSA was 97.7% (95% CI: 92.4-103.7), which is significantly better than the precision of the SI by visual estimation (p < 0.001), with an improvement by at least 15%. CONCLUSION: SENSA provides objective SI measurements with a precision of up to 99.5%, which can be calculated from any bronchoscope using an affordable scalable interface. Providing normal and obstructed contours on bronchoscopic videos does not improve physicians' visual estimation of the SI.

Fine-mapping of two differentiated thyroid carcinoma susceptibility loci at 2q35 and 8p12 in Europeans, Melanesians and Polynesians.

Differentiated thyroid carcinoma (DTC) incidence is characterized by wide ethnic and geographic variations, with high incidence rates observed in Oceanian populations. Genome-wide association studies (GWAS) identified mainly four DTC susceptibility loci at 9q22.33, 14q13.3, 2q35 and 8p12. Here we performed fine-mapping of the 2q35 and 8p12 loci in the population of the EPITHYR consortium that includes Europeans, Melanesians and Polynesians to identify likely causal variants for DTC risk. We conducted a colocalization analysis using eQTLs data to determine the SNPs with the highest probability of causality. At 2q35, we highlighted rs16857609 located in DIRC3. This SNP has a high probability of causality in the three populations, and a significant association in Europeans (OR = 1.4, p = 1.9 x 10-10). It is also associated with expression of DIRC3 and of the nearby gene IGFBP5 in thyroid tumour cells. At 8p12, we identified rs7844425 which was significantly associated with DTC in Europeans (OR = 1.32, p = 7.6 x 10-8) and rs2439304, which was highlighted by the colocalization analysis but only moderately associated with DTC in our dataset (OR = 1.2, p = 0.001). These SNPs are linked to the expression of NRG1 in thyroid tissue. Hence, our study identified novel variants at 2q35 and 8p12 to be prioritized for further functional studies.

Gene network and biological pathways associated with susceptibility to differentiated thyroid carcinoma.

Variants identified in earlier genome-wide association studies (GWAS) on differentiated thyroid carcinoma (DTC) explain about 10% of the overall estimated genetic contribution and could not provide complete insights into biological mechanisms involved in DTC susceptibility. Integrating systems biology information from model organisms, genome-wide expression data from tumor and matched normal tissue and GWAS data could help identifying DTC-associated genes, and pathways or functional networks in which they are involved. We performed data mining of GWAS data of the EPITHYR consortium (1551 cases and 1957 controls) using various pathways and protein-protein interaction (PPI) annotation databases and gene expression data from The Cancer Genome Atlas. We identified eight DTC-associated genes at known loci 2q35 (DIRC3), 8p12 (NRG1), 9q22 (FOXE1, TRMO, HEMGN, ANP32B, NANS) and 14q13 (MBIP). Using the EW_dmGWAS approach we found that gene networks related to glycogenolysis, glycogen metabolism, insulin metabolism and signal transduction pathways associated with muscle contraction were overrepresented with association signals (false discovery rate adjusted p-value < 0.05). Additionally, suggestive association of 21 KEGG and 75 REACTOME pathways with DTC indicate a link between DTC susceptibility and functions related to metabolism of cholesterol, amino sugar and nucleotide sugar metabolism, steroid biosynthesis, and downregulation of ERBB2 signaling pathways. Together, our results provide novel insights into biological mechanisms contributing to DTC risk.

Neuroendocrine tumors: a population-based study of incidence and survival in Girona Province, 1994-2004.

BACKGROUND: Neuroendocrine tumors (NETs) belong to a rare and heterogeneous group of neoplasms with a wide range of aggressiveness. Little information is available about incidence and mortality of NETs in the World population. The objective of this study was to report the incidence and survival of these tumors in Girona Province. METHODS: We include all ICD-O3 codes that codified a NET, period 1994-2004. Data from malignant NETs came directly from the Girona Cancer Registry, and data from benign or with uncertain behavior NETs directly from the Anatomic-Pathological Laboratories. RESULTS: We identified 698 NETs, the most frequent were those aroused in the bronco-pulmonary system (65.75%), followed by the gastro-entero-pancreatics (GEP) (12.75%). Small cell lung carcinomas were the most frequent NETs of the bronco-pulmonary system (92.59%), with an age-standardized incidence rate (ASRw, world population standard) of 4.29/100,000 person-years. Carcinoid lung tumors had an ASRw of 0.32/100,000 person-years and a 5-year relative survival (RS) of 77%. The ASRw of GEP NETs was 1.07/100,000 person-years, and the 5-year RS was 95%. The 5-year RS of pancreas was 43%. Thyroid NETs had an ASRw of 0.17/100,000 person-years, and a 5-year RS of 75%. Pheocromocytomas had an ASRw of 0.47/100,000 person-years and a 5-year RS of 85%. Merkel cell carcinomas had an ASRw of 0.11/100,000 person-years, with a 5-year RS of 50%. CONCLUSION: To our knowledge, this is the first population-based study reporting incidence of NETs in Spain. Our data was consistent with other European reports. By providing the incidence and survival of NETs in Girona Province, this study contributes to a better understanding of these rare tumors.

Recomendaciones para el estudio patológico de las metástasis hepáticas de cáncer colorrectal tras neoadyuvancia. Consenso Nacional de la Sociedad Española de Anatomía Patológica / Recommendations for the study of liver metastases of colorectal cancer after neoadjuvant therapy. National Consensus of the Spanish Society of Pathology (SEAP)

Las resecciones hepáticas por metástasis de cáncer colorrectal (CCR) son una pieza quirúrgica frecuente en muchos servicios de anatomía patológica. Si al aumento de la incidencia de CCR añadimos otros factores como la frecuencia de metástasis hepáticas sincrónicas o metacrónicas, la ampliación en los criterios quirúrgicos de resecabilidad y el tratamiento neoadyuvante que facilita la resecabilidad, nos encontramos con una patología en aumento. El estudio anatomopatológico de estas piezas quirúrgicas se ha modificado y ha aumentado su complejidad debido a que se deben valorar nuevos datos histológicos como son los cambios potenciales producidos por el tratamiento neoadyuvante quimioterápico en el hígado no tumoral, y en el tumor el grado de regresión tumoral patológico, por su valor pronóstico. Teniendo en cuenta estos antecedentes, un grupo de patólogos se propuso revisar su papel en el diagnóstico y pronóstico de los pacientes con metástasis hepáticas de CCR con el objetivo de elaborar unas recomendaciones prácticas de procedimiento. De esta revisión se han obtenido unas directrices que podrían ser adaptadas por los distintos departamentos de patología con el fin de unificar procedimientos y obtener diagnósticos comparables. En este trabajo se exponen los resultados de este consenso (AU)

Liver resections for colorectal cancer (CRC) metastasis are common in most pathology departments. In addition, the frequency of liver resections for CRC specimens has increased due to an increased incidence of CRC the frequency of synchronous or metachronous liver metastases, the use of neoadjuvant therapy, and the increased surgical criteria of resectability. The pathological study of the specimens should include new histological data, i.e.: changes caused by therapy, both in the tumour and in the liver parenchyma, such as the pathological tumour regression grade, and the histologic degree of liver damage by the therapy, because of its prognostic value. On this setting, a group of pathologists has elaborated a guideline proposal, in order to obtain a more uniform procedure and diagnosis of CRC liver metastasis specimens. The aim was to give useful recommendations in order to obtain homogeneous and comparable pathologic reports among different pathology departments. The results of this consensus are presented in this paper (AU)

La participación de las mujeres en la odontología (primer parte) / The participation of women in dentistry (first part)

La incursión de las mujeres en el mundo de la odontología es presentada, así como los antecedentes que lo permitieron

El análisis de algunos de los planes de estudio que ha tenido la enseñanza de la odontología en la UNAM / The analysis of some plans of study for education in odontology at UNAM

Identifica los planes de estudio que ha tenido la enseñanza de la Odontología en la UNAM para realizar un ejercício de análisis. La investigación abarca 24 planes de estudio.(AU)

Estudio de heridos por armas de fuego y explosivos ingresados al Hospital Militar de Santiago por el Servicio de Urgencia adultos durante un año calendario / Gunshot wounded patients study at Hospital Militar de Santiago during 1 year

a) Se analizan los resultados obtenidos en 38 pacientes que llegaron al Servicio de Urgencia del Hospital Militar de Santiago por lesiones por armas de fuego y explosivos en el período de 1 año. b) Se efectúa un análisis básico de aspectos generales de balística y heridas por armas de fuego. c) Se analizan causas de las lesiones, el tipo de lesión, tipo de proyectil y los procedimientos de Enfermería utilizados. d) Se destaca la importancia de la atención precoz y de la participación de la Enfermera en la primera atención de urgencia en estos pacientes

En la calle: menores trabajadores de la calle en Asunción

Relata sobre los menores que trabajan en la calle, características del sector informal, historia, condiciones del trabajo; algunos datos sobre escolaridad, educación, aprendisaje entre la casa y la calle. Cuanto viven con su padres, historia familiar, economía familiar