Pruebas no invasivas para el tamizaje del cáncer colon: fundamentos básico-clínicos y recientes avances biotecnológicos / Non-invasive tests for colorectal cancer screening: basic-clinical fundamentals and recent biotechnological advances

Colorectal Cancer (CRC) is the third most frequent neoplasia worldwide. Despite the significant advances in surgical techniques and the development of new targeted antineoplastic therapies for this type of tumor, primary prevention and early diagnosis of malignant precursor lesions will continue to be the best strategies to reduce their incidence, morbidity, and mortality. Technologies for CRC screening can be classified into two groups, those of an invasive nature, such as colonoscopy and all its different modalities of use, and those of a non-invasive nature, such as laboratory tests and imaging. This review, will focus exclusively on non-invasive screening tests, excluding imaging. Specifically, it will address those that use depositions as a sample. This review will approach the latest international recommendations, regarding the age at which they should be used, their technical-biological bases, the two main types currently used (biochemical and immunological), and we will put into perspective their advantages and their possible disadvantages. Towards the end of this article, the most recent biotechnological developments in relation to molecular tests based on the study of blood samples, will be discussed. Although these tests are not yet in routine clinical use given their high costs, they are promising for the early detection of CRC.

El cáncer colorrectal (CCR) es la tercera neoplasia más común en todo el mundo. A pesar de los avances significativos en las técnicas quirúrgicas y en el desarrollo de nuevas terapias antineoplásicas para este tipo de tumor, la prevención primaria y el diagnóstico precoz de lesiones precursoras malignas siguen siendo las mejores estrategias para reducir la incidencia, morbilidad y mortalidad asociadas al CCR. Existen dos tipos de tecnologías para el tamizaje del CCR: las invasivas, como la colonoscopia, y las no invasivas, como los ensayos de laboratorio y la imagenología. Esta revisión, se centrará exclusivamente en las pruebas de tamizaje no invasivas que utilizan muestras de deposiciones, excluyendo las imágenes. Se abordarán las últimas recomendaciones internacionales sobre el momento etario en que se deben utilizar, sus bases técnico-biológicas, los dos principales tipos utilizados en la actualidad (bioquímico e inmunológico) y pondremos en perspectiva sus ventajas y posibles desventajas. Al final de esta revisión, se discutirá brevemente los últimos avances biotecnológicos relacionados con pruebas moleculares basadas en el estudio de muestras sanguíneas. Aunque estas pruebas aún no son de uso clínico habitual debido a sus altos costos, representan una prometedora innovación para la detección temprana del CCR.

Caracterización de la incidencia del cáncer de mama en un servicio público de salud chileno en el período 2006-2015 / Characterization of incidence rates of breast cancer in public health service, period 2006-2015

OBJETIVO: El cáncer de mama constituye la primera causa de muerte oncológica en mujeres chilenas. Las tasas de incidencia solo han sido estimadas según el registro 2003-2007. Nuestro objetivo fue estimar las tasas de incidencia en un período de 10 años en un servicio de salud y caracterizar dicha población. MÉTODO: Se calcularon las tasas de incidencia del período 2006-2015, por método directo, y se analizó la tendencia por Prais-Winsten. Se caracterizó la población según la edad y la etapa al diagnóstico. RESULTADOS: De 2862 casos, la tasa de incidencia estandarizada promedio fue de 66,6 por 100.000 mujeres. En el período hubo una tendencia al alza del diagnóstico de 0,63/100.000 anualmente (p = 0,5; intervalo de confianza del 95%: −1,73 a 2,99). La mayor tasa de incidencia bruta fue en el grupo de 70 y más años (154,8/100.000). El 49% correspondieron a casos diagnosticados de 50 a 69 años. El 56% se diagnosticó precozmente; la etapa I tuvo la más alta tasa (15,8/100.000). CONCLUSIONES: En este estudio, las tasas de incidencia son mayores que las reportadas en informes nacionales previos. El diagnóstico es mayoritariamente en etapas precoces, lo que difiere del resto de los países de la región. Nuestros datos pueden aportar a mejorar las políticas públicas.

OBJECTIVE: Breast cancer is the leading cause of cancer death in Chilean women. Incidence rates have only been estimated based on population records (2003-2007). Our objective was to estimate the incidence rates in a 10-year period in a health service and portray in words this cohort. METHOD: Incidence rates were calculated between 2006-2015 by direct method and trends were analyzed with the Prais-Winsten model. The population was defined according to age and stage at diagnosis. RESULTS: Of a total of 2862 cases, the average incidence rate was 66.6 out of 100,000 women. Between 2006-2015, the trend rose in breast cancer diagnosis of 0.63/100,000 annually (p = 0.5; 95% confidence interval: −1.73, 2.99). The highest crude rate of incidence was in the group aged 70 and over (154.8/100,000). 49% correspond to cases diagnosed between 50 and 69 years. 56% were in early stages, stage I, being the most frequent (15.8/100,000). CONCLUSIONS: On this research the incidence rates were higher than the ones reported on previous national reports. Diagnosis is mostly in early stages which differs from other countries in the region, our data can help improve public health policies.

Planificación sanitaria a partir de los datos ómicos: ¿es posible esta idea para Chile?

With or without a COVID19 pandemic, cancer is and will continue to be one of the greatest health challenges on the planet. In Chile, during 2016, this disease was the second cause of death in the country and during 2019, it was the first cause in seven Chilean regions, surpassing cardiovascular diseases. With the advent of precision medicine as a powerful tool for cancer control, it is necessary to have genomic, proteomic, and molecular data in general, ideally on a population scale. This is essential for decision-making, for example in public and private oncology, to be as cost-effective as possible. Chile has a mass of high-quality researchers in cancer. However, until today the investment in research and development is far below the peers in the OECD. In this work we put into perspective the role of precision medicine and omic sciences as essential tools for public health. We offer a brief national diagnosis of the knowledge collected to date by the local scientific community regarding onco-genomic data from our own population. We finally discuss the potential behind the strengthening of this scientific knowledge, aiming to optimize the comprehensive management of cancer.

Bases biológicas del cáncer: una propuesta de contenidos mínimos para las carreras de la salud / Biological bases of cancer: a proposal of minimum contents for health schools

El cáncer constituye la segunda de causa de muerte a nivel mundial y se estima será la primera, superando a las cardiovasculares. El estudio de sus bases moleculares ha permitido el desarrollo de la quimioterapia clásica, como de nuevas terapias biológicas. Si bien estos avances han redundado en un aumento en la sobrevida, no ha impactado en una menor incidencia de los casos. Esto último se debe, en parte, al desconocimiento de los múltiples factores carcinogénicos existentes y los efectos de sus interacciones para cada uno de los tumores. En este sentido, es interesante notar que, en los currículos de las escuelas de salud de las universidades chilenas, el cáncer u oncología como tal, no constituye una cátedra en sí misma, siendo sus contenidos tangencialmente abordados en distintos momentos de la formación; en biología celular, medicina interna y cirugía, entre otros. Con estos antecedentes, el propósito de este trabajo es ofrecer un propuesta sencilla y accesible para los estudiantes, respecto de los contenidos que, a nuestro juicio, son esenciales para comprender las bases biológicas de esta enfermedad y enfrentar con mejores conocimientos el ciclo clínico posterior. A continuación, el lector se encontrará con principios fundamentales de la biología humana normal (como el ciclo celular y el dogma central de la biología molecular), que permiten obtener una visión global de los mecanismos fisiológicos cuya desregulación conlleva a una neoplasia maligna. Luego se entregarán algunas definiciones amplias en relación con los conceptos de neoplasia, tumor benigno y maligno. Para, finalmente, abordar las principales etapas que permiten el desarrollo del cáncer; (i) iniciación, (ii) promoción y (iii) progresión. En esta última, se profundizará por separado, en angiogénesis, degradación de la matriz extracelular, migración y evasión de la respuesta inmune. Este trabajo no aborda materias relacionadas con la hipótesis metabólica del cáncer.

Cancer constitutes the second most common cause of death worldwide and is expected to become the leading one, even above cardiovascular diseases. The understanding of the cellular and molecular basis of cancer has led not only to the proper development of chemotherapy but also of target therapies. Although these advances are related with improved survival rates among cancer patients, it has poorly impacted its incidences. In this regard, the lack of knowledge regarding the impact that the several carcinogenic factors and their interactions have on different types of cancers may explain at least in part the difficulties to reduce incidence rates. However, is worth noticing that in several health schools of chilean universities, cancer does not constitute a formal course, being only partially approached during other courses, such as cell biology, internal medicine, and surgery. Thus, the aim of our work is to provide students a simple and resumed manuscript about essential topics necessary to understand the biological basis of cancer. First, the reader will find some fundamentals about human biology including the cell cycle and the central dogma of molecular biology, which offers an overview of the physiological mechanisms leading to malignant neoplasia. Then, we will provide current definitions of neoplasia, benign and malignant tumors are provided. Finally, the different stages of tumor progression will be approached to allow the understanding of cancer development. These stages include (i) initiation, (ii) promotion, and (iii) progression. For the last one, metastasis, angiogenesis, extracellular matrix degradation, migration, and immune evasion will also be addressed. This work will not consider the metabolic hypothesis of cancer.

Regional brain atrophy is related to social cognition impairment in multiple sclerosis / La atrofia cerebral regional se relaciona con el deterioro de la cognición social en sclerosis múltiple

ABSTRACT Background: Multiple sclerosis exhibits specific neuropathological phenomena driving to both global and regional brain atrophy. At the clinical level, the disease is related to functional decline in cognitive domains as the working memory, processing speed, and verbal fluency. However, the compromise of social-cognitive abilities has concentrated some interest in recent years despite the available evidence suggesting the risk of disorganization in social life. Recent studies have used the MiniSEA test to assess the compromise of social cognition and have found relevant relationships with memory and executive functions, as well as with the level of global and regional brain atrophy. Objective: The present article aimed to identify structural changes related to socio-cognitive performance in a sample of patients with relapsing-remitting multiple sclerosis. Methods: 68 relapsing-remitting multiple sclerosis Chilean patients and 50 healthy control subjects underwent MRI scans and neuropsychological evaluation including social-cognition tasks. Total brain, white matter, and gray matter volumes were estimated. Also, voxel-based morphometry was applied to evaluate regional structural changes. Results: Patients exhibited lower scores in all neuropsychological tests. Social cognition exhibited a significant decrease in this group mostly related to the declining social perception. Normalized brain volume and white matter volume were significantly decreased when compared to healthy subjects. The regional brain atrophy analysis showed that changes in the insular cortex and medial frontal cortices are significantly related to the variability of social-cognitive performance among patients. Conclusions: In the present study, social cognition was only correlated with the deterioration of verbal fluency, despite the fact that previous studies have reported its link with memory and executive functions. The identification of specific structural correlates supports the comprehension of this phenomenon as an independent source of cognitive disability in these patients.

RESUMEN Antecedentes: La esclerosis múltiple presenta fenómenos neuropatológicos específicos que conducen a la atrofia cerebral global y regional. A nivel clínico, la enfermedad está relacionada con el deterioro funcional de los dominios cognitivos como la memoria de trabajo, la velocidad de procesamiento y la fluidez verbal. Sin embargo, el compromiso de las habilidades socio-cognitivas ha concentrado cierto interés en los últimos años debido a la evidencia disponible que sugiere el riesgo de desorganización en la vida social. Estudios recientes han utilizado la prueba MiniSEA para evaluar el compromiso de la cognición social y han encontrado relaciones relevantes con la memoria y funciones ejecutiva, así como con el nivel de atrofia cerebral global y regional. Objetivo: El presente artículo tiene como objetivo identificar cambios estructurales relacionados con el rendimiento sociocognitivo en una muestra de pacientes con esclerosis múltiple recurrente-remitente. Métodos: 68 pacientes Chilenos con esclerosis múltiple recurrente-remitente y 50 sujetos de control sanos se sometieron a resonancias magnéticas y evaluación neuropsicológica, incluidas las tareas de cognición social. Se estimaron los volúmenes cerebrales totales, de materia blanca y materia gris. Además, se aplicó la morfometría basada en vóxel para evaluar los cambios estructurales regionales. Resultados: Los pacientes muestran puntuaciones más bajas en todas las pruebas neuropsicológicas. La cognición social exhibe una disminución significativa en este grupo principalmente relacionada con la disminución de la percepción social. El volumen normalizado del cerebro y el volumen de la materia blanca disminuyeron significativamente en comparación con los sujetos sanos. El análisis regional de atrofia cerebral mostró que los cambios en la corteza insular y la corteza frontal medial están significativamente relacionados con la variabilidad del rendimiento sociocognitivo entre los pacientes. Conclusiones: En el presente estudio, la cognición social sólo se correlacionó con el deterioro de la fluencia verbal, a pesar de que estudios previos han reportado su vinculación con la memoria y funciones ejecutivas. La identificación de correlatos estructurales específicos apoya la comprensión de este fenómeno como una fuente independiente de discapacidad cognitiva en estos pacientes.

Formación científica en el pregrado de medicina en Chile: ¿dónde estamos? y ¿hacia dónde vamos? / An analysis of scientific formation in medical schools

For more than a century the training of medical professionals has been organized according to the Flexnerian model, which comprises three cycles: basic, clinical and clerkship. On the other hand, the accelerated development of biomedical sciences modified the competences of the first cycle. Additionally, new skills required for medical practice, such as teamwork and innovation as a tool to solve health problems, challenged in recent years the classic paradigm of medical education. Therefore, the medical schools have developed multiple strategies to deal with it, such as curricular integration using competency-based education models, incorporating basic and clinical sciences in parallel during the curriculum, ensuring a relevant and applicable scientific knowledge throughout the training process. Although in Chile the Flexner prototype is still followed, the basic sciences are taught as single or integrated courses or using a systems approach. In this article we report a diagnosis about the local integration of fundamental sciences in medical training. We also compare our schools with those of Canada, Europe and Latin America. Recommendations aimed at modernizing medical school curricula are made.

Oportunidad en la salud digital: una respuesta al control de las demencias / Digital health services as a means to control dementia

The increase of the elderly population with a significant load of non-communicable diseases, accelerates pathological aging and increases the risk of dementia, generating a huge health, social and economic cost for any country. Dementia does not have an effective treatment yet, therefore, the focus must remain on prevention and early diagnosis. The early stages of dementia are known as mild cognitive impairment; at this stage is still possible to mitigate the progression of the disease, however, health systems worldwide face difficulties to provide universal access to health services, due to a lack of specialists and geographical distances, interfering with the access to healthcare centers. In this scenario, WHO urged countries to implement strategies to democratize and to expand the reach of health institutions. In this document, we briefly review the global and local situation of dementias and discuss some attempts to control their progression by using revolutionary digital tools. We believe the focus should be on the population that is just beginning to show cognitive impairment.

Situación actual del cáncer de colon en Chile: una mirada traslacional / The present situation of colorectal cancer in Chile

Colorectal (CRC) is one of the most common types of cancer worldwide. Most tumors develop from an adenoma in a period of 10 to 15 years, but some may appear without previous adenomatous lesions. Seventy-five percent of colorectal cancers are sporadic, 20% have a family component (first or second-degree relatives with CRC) and 5% have a hereditary predisposition with a Mendelian pattern. The epidemiological evolution in the recent years in Chile has a worrisome evolution and the treatment costs of advanced stages are a burden for the healthcare system. We herein highlight the main Chilean medical and scientific contributions on the pathogenesis, early diagnosis, and treatment of CRC, which lead to its better understanding, and therefore better management, based on local evidence.

Dieta cetogénica: mecanismos en el control de la epilepsia refractaria / Ketogenic diet: refractory epilepsy control mechanisms

Introducción: Existe un porcentaje relevante de pacientes con epilepsia que son refractarios al tratamiento con fármacos anticonvulsivan-tes. Este cuadro, se denomina epilepsia refractaria (ER), en el cual, la dieta cetogénica (DC), ha probado ser una alternativa efectiva. Existen diferentes versiones de la DC, y ciertos componentes de esta dieta han mostrado ser más efectivos que otros. Por otra parte, diferentes autores han propuesto hipótesis, de cómo, la DC podría actuar a nivel molecular y celular, para controlar estas crisis epilépticas. Los objetivos de esta revisión, son, explicar la DC, y analizar la evidencia existente, en relación con los mecanismos, a través de los cuales, la DC ejerce un control de las crisis convulsivas. Método y resultados: Se realizó una búsqueda avanzada en PubMed, considerando los términos «refrac-tory¼, «epilepsy¼, «ketogenic¼ y «diet¼, incluidos en el título y el resumen. La búsqueda, dio como resultado, 288 artículos publicados en los últimos 10 años. De estos artículos, se seleccionaron 134 potencialmente relevantes, posterior a la lectura de sus títulos. Se realizó la lectura del resumen para los 134 artículos, de los cuales, se seleccionaron 17, que fueron, a juicio de los autores, los que incluían la información pertinente para esta revisión. La búsqueda se centró en artículos originales y revisiones disponibles en inglés,con énfasis, en los artículos apropiados para comprender los conceptos generales de la DC y los mecanismos de acción, que podrían representar un rol relevante al momento de controlar la ER. Conclusiones: La DC ha probado ser efectiva en el tratamiento de la ER, sin embargo, hay pacientes que no la toleran adecuadamente. Existen ciertos compuestos asociados la DC que han probado ser más efectivos que otro como es el caso de los triglicéridos de cadena mediana (TCM). Finalmente, se han investigado numerosas hipótesis en relación con el mecanismo de acción de la DC, donde destacan las hipótesis de los cuerpos cetónicos, la adenosina y la del cortocircuito GABA.

Introduction: A percentage of epilepsy patients are refractory to treatment with anticonvulsant drugs. An effective alternative for treating this condition, known as refractory epilepsy (RE), is the ketogenic diet (KD). There are different variations of the KD, and certain components of this diet have been shown more effective than others. Various authors have proposed hypotheses for how the KD acts on the molecular and cellular levels in controlling seizures. The objectives of this review are to explain the KD and analyze existing evi-dence regarding the mechanisms through which the KD exercises control over seizures. Methods and results: PubMed was extensively searched using the terms «refractory¼, «epilepsy¼, «ketogenic¼, and«diet¼ included in the title and abstract. The search returned 288 published articles within the last ten years. Of these 288 manuscripts, 134 were selected as potentially relevant based on the title. After reading the abstract of each potentially relevant paper, 17 were finally included in the review. These manuscripts, per the judgement of the authors of this study, included information pertinent to the review. The search focused on original articles and reviews available in English, with an emphasis on texts appropriate for understanding the general concepts of the KD and the mechanisms of action that could play a relevant role in controlling RE. Conclusions: The KD has been proven effective in treating RE. However, some patients do not adequately tolerate this diet. There are certain compounds associated with the KD that are more effective than others, as is the case with medium-chain triglycerides. Finally, numerous hypotheses exist regarding the mechanisms of action for the KD. Notable among these hypotheses are ketone bodies, adenosine, and the GABA shunt.

Impacto cardiovascular secundario a la terapia para el control del cáncer / The cardiovascular impact of cancer control therapy

Cardiovascular diseases and cancer account for 27 and 25% of mortality in Chile, respectively. In the last decades, survival of people with cancer has improved due to preventive programs, early detection strategies, advances in technology and development of new antineoplastic therapies. Consequently, a progressive number of cancer-surviving patients have been generated, who may develop cardiovascular diseases, secondary to the same cancer therapy. Cardio-Oncology has emerged as the necessary link between both specialties to promote the prevention and early detection of cardiac complications, in patients undergoing oncological therapies. The aim is to curb cardiovascular complications. Also, to acquire knowledge about the mechanisms and effects of drugs that lead to heart damage aiming to develop efficient cardioprotective therapies. In this article we review and propose a didactic organization and classification of the main cardiovascular effects of cancer control therapy. We recognize that there is still a knowledge gap in basic sciences about the mechanisms that underlie these alterations.

Una red de biobancos para Chile: investigar hoy, para curar mañana / The implementation of a Biobank network for Chile

The concept "Biobank" is relatively new in the scientific literature, and is not yet consensually defined, even for the World Health Organization (WHO). However, the use of human samples in biomedical research is a very old activity. The organized development of Biobanks in different places has grown in the last decade. The experience in different countries and continents has been diverse. In this special article we intend to summarize, organize and communicate to the national medical and scientific community, (i) the concept of Biobank, (ii) the international experience and a map of the Research Biobanks working in Chile, (iii) the basic biomedical and essential operational aspects to manage a Biobank for Research and (iv) the impact of a National Network of Biobanks implementation in the Chilean Health System. Ethical and regulatory aspects will not be included, given their intrinsic complexity, which should be discussed elsewhere.

Obesidad: ¿Factor de riesgo o enfermedad? / Obesity: risk factor or primary disease?

Obesity is a global health problem. Its worldwide prevalence has tripled between 1975 and 2016, reaching a prevalence in Chile of 34.4%, according to the National Health Survey 2016-2017. If this condition corresponds to a risk factor or primary disease is a widely discussed issue. It is recognized as a disease by the American Medical Association and World Health Organization, based on its metabolic and hormonal features, such as dysregulation of appetite, abnormal energy balance and endocrine dysfunction, among others. Its main environmental risk factors are the consumption of ultra-processed foods and sedentariness. Preventive measures at the population level are fundamental, emphasizing promotion and prevention using a transdisciplinary approach. The individual approach in the management of obesity should improve the quality of life, avoid early mortality, reduce cardiovascular risk, and reduce the progression to type 2 diabetes and incidence of cancer. Thus, an adequate management and control of obesity would have a great impact in our society.

Realidad de la investigación en salud en Chile: participación de los médicos en el Fondo Nacional de Investigación (FONIS) en la última década / Reality of health research in Chile: participation of doctors in the National Research Fund (FONIS) in the last decade

Chile es uno de los países de la OCDE que menos invierte en ciencia y tecnología, y la investigación en salud no está exenta de este problema. Existe evidencia reportada en publicaciones nacionales de que la participación de médicos en la investigación ha experimentado un marcado retroceso en las últimas décadas. El objetivo de este artículo es analizar específicamente la participación de los médicos como investigadores responsables en proyectos financiados por el Fondo Nacional de Investigación en Salud (FONIS). Este programa fue diseñado para promover investigaciones que resuelvan problemas prioritarios de salud y de esa manera entregar enfoques diagnósticos y terapéuticos a la medida del fenotipo local. Nuestros análisis muestran un estancamiento real y una disminución porcentual, misma tendencia que estudios previos. La implementación de recomendaciones internacionales en el campo de la medicina rasnacional en las políticas de salud nacionales podría revertir el aparente proceso de retirada de los médicos de las actividades de I+D, lo que beneficiaría la salud de los pacientes y reduciría los costos para el sistema, de, por ejemplo, la importación de la terapéutica.(AU)

Chile is one of the OECD countries that invests less in science and technology, and health research is not exempt from this problem. Evidence reported in national publications shows that the participation of physicians in research has experienced a marked decline in recent decades. The objective of this article is to specifically analyze the participation of physicians as responsible researchers in projects funded by the National Fund for Health Research (FONIS). This program was designed to promote research that addresses priority health issues and thereby delivers diagnostic and therapeutic approaches tailored to the local phenotype. Our analyzes show a real stagnation and a percentage decrease, same trend as previous studies. The implementation of international recommendations in the field of translational medicine in national health policies could reverse the apparent process of withdrawal of physicians from R&D activities, which would benefit the health of patients and reduce the costs for the system, for instance, in the ones implied of importing therapeutics.(AU)