Estudios clínicos y genéticos en tres miembros de una familia afectados con adenomas hipofisarios aislados con prolactinomas homogéneos / Clinical and genetic studies of a three-member familial isolated pituitary adenoma with homogeneous prolactinomas

La mayoría de los adenomas hipofisarios son esporádicos, pero un 3-5% puede ocurrir en un contexto familiar y hereditario. Este es el caso de la neoplasia endocrina múltiple de tipo 1 (NEM1), complejo de Carney (CNC) y adenomas hipofisarios aislados familiares (FIPA). El FIPA es una condición infrecuente, que ocurre en un contexto familiar, no asociada a NEM t ipo1 ni CNC. Los FIPA pueden ser homogéneos (todos los adenomas tienen el mismo fenotipo) o heterogéneos (diferente fenotipo tumoral). Describimos una familia congolesa en la que dos hermanas y una prima fueron diagnosticadas a los 29, 32 y 40 años, respectivamente, con un prolactinoma (FIPA homogéneo). Las pacientes presentaron macroadenomas no invasivos al momento del diagnóstico, con buena respuesta biológica y tumoral al tratamiento con cabergolina hasta una dosis máxima de 1.5 mg/semanal. De las dos hermanas, una cursó un embarazo sin complicaciones. Durante el seguimiento de 12 años, ninguna de ellas presentó elementos clínicos o biológicos compatibles con NEM1 o CNC, por lo que dichos genes no se estudiaron. El análisis genético en dos de las pacientes permitió descartar la posibilidad de una mutación germinal del gen aryl hydrocarbon receptor interacting protein (AIP). Se considera que el 80% de los pacientes con FIPA no presentan mutación del gen AIP, por lo que se requieren futuros estudios en este tipo de familias, para poder determinar otros genes afectados involucrados en su fisiopatología.

Most pituitary adenomas are sporadic, but 3-5% can occur in a family and hereditary context. This is the case of multiple endocrine neoplasia type 1 (MEN1), Carney complex (CNC) and familial isolated pituitary adenomas (FIPA). FIPA is an infrequent condition that occurs in a family context, not associated with MEN type1 or CNC. FIPA kindred can be homogeneous (all adenomas affected in the family having the same tumor phenotype) or heterogeneous (different tumor phenotypes in the affected members). We describe a Congolese family in which two sisters and a cousin were diagnosed with a prolactinoma (homogenous FIPA) at the ages of 29, 32 and 40 years, respectively. The patients presented with macroadenomas at the time of diagnosis, non-invasive tumors and good biological response to cabergoline treatment (maximum dose of 1.5 mg/weekly). Of these two sisters, one went through a pregnancy without complications. Because no MEN1 and CNC clinical and biochemical features were detected during the 12-year follow-up, these genes were not investigated. The genetic analysis of the aryl hydrocarbon receptor interacting protein (AIP) was normal. As nearly 80% of patients with FIPA do not have a mutation in the AIP gene, future studies in these families are required to identify other affected genes involved in their physiopathology.

Rastreio de câncer na prática clínica: recomendações para a população de risco habitual / Cancer screening in clinical practice: recommendations for average risk population

Objetivo: Compilar as evidências da literatura e as recomendações das principais sociedades médicas mundiais para o rastreamento populacional de câncer, contextualizando com a relevância epidemiológica de cada subtipo da doença. Métodos: Trata-se de revisão narrativa da literatura, realizada por levantamento na base de dados PubMed® e consulta aos posicionamentos de instituições governamentais e sociedades médicas nas áreas específicas. Resultados: O rastreamento populacional sistemático foi recomendado apenas para as neoplasias de mama, colo do útero e colorretal, utilizando-se métodos, idade e periodicidade específicos. O rastreio do câncer de próstata mostrou-se controverso, e o pulmonar e o hepático recomendados apenas em tabagistas com alta carga tabágica e cirróticos, respectivamente. Não houve evidência para se recomendar atualmente o rastreamento sistemático da população geral para as neoplasias de pele, tireoide, esôfago, estômago, pâncreas, ovário, endométrio, bexiga, rins, dentre outras. Conclusão: O exame periódico de saúde do paciente saudável abrangeu a prevenção e o rastreamento do câncer para redução de morbidade e mortalidade pela doença, e a estratificação das evidências atuais teve o potencial de melhorar o direcionamento dos esforços, aumentando a cobertura, havendo maior benefício e reduzindo riscos e custos de exames desnecessários.

Objective: To gather evidence from the literature, and recommendations of the main medical societies worldwide for the population screening of cancer, contextualizing with the epidemiological relevance of each subtype of the disease. Methods: This is a narrative review of the literature, carried out through research on PubMed® database, and consultation to the governmental institutions and medical societies' opinions in specific areas. Results: Systematic population screening was recommended only for breast, cervix and colorectal cancers, using specific methods, age and periodicity. Prostate cancer screening showed to be controversial, and pulmonary and hepatic screening are recommended only in heavy smokers and cirrhotic patients, respectively. Currently, there is no evidence to recommend the screening of the general population for neoplasms of skin, thyroid, esophagus, stomach, pancreas, ovary, endometrium, bladder, and kidneys. Conclusion: The periodic health screening of the healthy patient covered the prevention and screening for cancer to reduce morbidity and mortality from the disease; the stratification of current evidence has the potential to improve the direction of efforts, broadening coverage, with more benefit, and reducing risks and costs of unnecessary tests.

Síndrome de Lynch: aspectos genéticos, clínicos y diagnósticos / Lynch syndrome: genetic, clinical and diagnostic aspects

Esta revisión tiene como objetivo dar a conocer los aspectos genéticos, clínicos y diagnósticos del síndrome de Lynch, además de brindar la información más relevante acerca de la asesoría genética en estos pacientes y las recomendaciones actuales para su seguimiento.

This review aims to present the genetic, clinical and diagnostic aspects of Lynch syndrome, as well as providing the most relevant information about genetic counseling in these patients and the current recommendations for their surveillance.

Hemangiomas infantiles / [Infantile hemangiomas].

Infantile hemangiomas are the most common benign tumors of infancy. While most of them have an uncomplicated course, between 10 and 15

are at risk for complications, especially during the proliferative phase, and can cause impairment of vital functions or produce permanent cosmetic disfigurement. In this update we delineate the natural history of infantile hemangiomas, with special emphasis on identifying those that require special diagnostic evaluations and multidisciplinary and closer follow-up, reviewing the study and treatment indications and current treatment modalities.

Genómica en el diagnóstico del cáncer colorrectal hereditario / Genetics in diagnosis of hereditary colorectal cancer

Introducción: El cáncer colorrectal (CCR) se presenta en el 3 - 5% como formas hereditarias. Existen 4 síndromes en donde se han descubierto mutaciones responsables, el síndrome de Lynch (SL), la Poliposis Adenotamosa Familiar (PAF), la Poliposis Juvenil (PJ) y el síndrome de Peutz-Jeghers (SPJ). Cada uno de ellos presenta una patente genética distinta, vías de carcinogénesis y comportamientos distintos. Los conocimientos actuales sobre las mismas son limitados y los abordajes diagnósticos controvertidos. Material y Métodos: Se ha realizado la búsqueda bibliográfica sobre las técnicas de biología molecular que permiten detectar las mutaciones en los síndromes de CCR hereditario, así como las guías y estrategias diagnósticas. Se presenta una breve reseña sobre conceptos básicos de genómica y técnicas de biología molecular y luego sus usos en la práctica clínica en estas 4 enfermedades. Resultados: Hemos encontrado que con el avance de las técnicas de biología molecular cada día es mayor el conocimiento con respecto a la base genética de estas enfermedades. Esto provoca un impacto tanto en el diagnóstico como en la terapéutica y seguimiento. Las guías actuales de manejo muestran consenso en gran cantidad de puntos aunque todavía queda campo por explorar. Conclusiones: Hacen falta futuros ensayos que nos permitan arribar a estrategias de manejo en cada subgrupo de pacientes seguramente basados en las distintas patentes genotípicas. Esto permitirá un manejo más personalizado en el futuro del cáncer colorrectal hereditario.

Introduction: 3 - 5% of colorectal cancer (CRC) occurs as hereditary forms. There are 4 syndromes in which mutations have been found responsible, the Lynch syndrome (LS), the Family Adenotamosa polyposis (FAP), Juvenile Polyposis (JP) and Peutz-Jeghers syndrome (PJS). Each one has a distinct genetic patent, different process of carcinogenesis and different behaviors. Current knowledge about them is limited and the diagnostic approaches are controversial. Material and methods: We performed literature searches on molecular biology techniques to detect mutations in hereditary CRC syndromes and diagnostic guidelines and strategies. A review of basic concepts of genomics and molecular biology techniques are presented and then their uses in clinical practice in these 4 diseases. Results: We have found that with the progress of molecular biology techniques is growing the knowledge about the genetic basis of these diseases. This causes an impact on both diagnosis and therapy and monitoring. Current guidelines show consensus in handling large amount of points but there is still room to explore. Conclusions: Future trials are needed to enable us to arrive at management strategies in each subgroup of patients likely based in different genotypic patents. This will allow a more personalized management in the future of hereditary colorectal cáncer.