The potential of miRNA-based approaches in glioblastoma: An update in current advances and future perspectives.

Glioblastoma (GBM) is the most common malignant central nervous system tumor. The emerging field of epigenetics stands out as particularly promising. Notably, the discovery of micro RNAs (miRNAs) has paved the way for advancements in diagnosing, treating, and prognosticating patients with brain tumors. We aim to provide an overview of the emergence of miRNAs in GBM and their potential role in the multifaceted management of this disease. We discuss the current state of the art regarding miRNAs and GBM. We performed a narrative review using the MEDLINE/PUBMED database to retrieve peer-reviewed articles related to the use of miRNA approaches for the treatment of GBMs. MiRNAs are intrinsic non-coding RNA molecules that regulate gene expression mainly through post-transcriptional mechanisms. The deregulation of some of these molecules is related to the pathogenesis of GBM. The inclusion of molecular characterization for the diagnosis of brain tumors and the advent of less-invasive diagnostic methods such as liquid biopsies, highlights the potential of these molecules as biomarkers for guiding the management of brain tumors such as GBM. Importantly, there is a need for more studies to better examine the application of these novel molecules. The constantly changing characterization and approach to the diagnosis and management of brain tumors broaden the possibilities for the molecular inclusion of novel epigenetic molecules, such as miRNAs, for a better understanding of this disease.

Colombian consensus for the molecular diagnosis of endometrial cancer / Consenso colombiano para el diagnóstico molecular del cáncer de endometrio.

Objective: The Cancer Genome Atlas research program (TCGA) developed the molecular classification for endometrial cancer with prognostic and therapeutic utility, which was replaced by the ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer) classification by consensus and international guidelines due to its high cost. This article aims to present national recommendations from an expert consensus that allows unification and implementation of the molecular classification for women with endometrial cancer nationwide, with a rational use of resources and technology. Methods: Consensus of 36 experts in clinical oncology, oncological gynecology, pathology, and genetics, with clinical practice in the national territory. The leader group performed a literature review and structuring of questions rated 1 to 9 points. A modified nominal group technique was used. There was a face-to-face meeting with master presentations, deliberative dialogue, and Google Forms (Google LLC, Mountain View, CA, USA) questionnaire voting with analysis and discussion of responses. The non-consensual responses led to a second round of voting. The final manuscript was finally prepared and revised. Results: Seven recommendations were formulated integrating the panelist responses based on evidence, but adjusted to the Colombian context and reality. Recommendation 1. The molecular classification is recommended in all the endometrial cancers using the immunohistochemistry markers as subrogated results from the molecular profile initially proposed in the TCGA classification. Recommendation 2. The sequential test strategy is recommended, starting with the immunohistochemistry markers (p53, MLH1, MSH 2, MSH6, PMS2) simultaneously in all the patients, defining to request POLE (DNA polymerase epsilon) (if available) according to the risk classification based on the surgical piece. Recommendation 3. It is recommended, that the gynecologist oncologist should be the one to request the POLE (if available) according to the final pathology report. This test must be requested for all endometrial cancers stage I-II, except in low risk (stage IA low grade endometrioid histology without linfovascular invasion normal p53) and, stages III-IV without residual disease, without affecting the request of subrogated immunohistochemistry molecular markers upon histology. The consensus proposes that the POLE is requested after the immunohistochemistry and according to the categories in the risk classification established by the 2020 ESGO/ESTRO/ESP guidelines. Recommendation 4. It is recommended to perform immunohistochemistry for hormonal receptors for all women with endometrial cancer and the HER2 in patients with p53abn, simultaneously with the others immunohistochemistry markers. Recommendation 5. It is recommended to perform the immunohistochemistry markers (p53, MLH1, MSH2, MSH6 y PMS2) in an initial endometrial biopsy or curettage when the specimen is adequate and available. In case the initial immunohistochemistry is inconclusive, or there are histological discrepancies between the initial and definitive pathology, it is recommended to repeat the molecular profile in the surgical pathology. The immunohistochemistry markers must be reported in the pathology report according to the CAP (College of American Pathologists) recommendations, independently of the type of sample. Recommendation 6. It is recommended to perform MLH1 promoter methylation testing in patients who exhibit loss of expression of MLH1 in immunohistochemistry whether it is accompanied or not with loss of expression of PMS2. All the patients with deficient MMR (mismatch repair), should be sent for genetic counseling to rule out Lynch syndrome. Recommendation 7. It is recommended to consider the molecular classification in addition to the classical histopathological criteria when making adjuvant judgments, as incorporated by the classification of prognostic groups of the 2020 ESGO/ESTRO/ESP guidelines. Conclusions: It is necessary to implement the molecular classification of endometrial cancer in clinical practice in accordance to the Colombian context, due to its prognostic and probably predictive value. This will enable the characterization of the Colombian population in order to offer individualized guided treatments. This is an academic and nonregulatory document.

Objetivos: el programa Cancer Genome Atlas Research (TCGA) desarrolló la clasificación molecular para cáncer endometrial con utilidad pronóstica y terapéutica, la cual ha sido reemplazada por consensos y guías internacionales por la clasificación ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer) debido a su alto costo. El objetivo de este artículo es presentar recomendaciones a nivel nacional derivadas de un consenso de expertos que permitan unificar e implementar la clasificación molecular para mujeres con cáncer endometrial, mediante un uso racional de recursos y tecnología. Materiales y métodos: consenso de 36 expertos en oncología clínica, ginecología oncológica, patología y genética con práctica clínica en el territorio nacional. El grupo líder realizó una revisión de la literatura y estructuración de preguntas calificadas de 1 a 9 puntos. Se utilizó la técnica de grupo nominal modificada. Se efectuaron reuniones presenciales con presentaciones magistrales, diálogo deliberativo y votación de cuestionario Google Forms (Google LLC, Mountain View, CA, USA) con análisis y discusión de respuestas. Las respuestas no consensuadas se llevaron a una segunda ronda de votación. Finalmente, se elaboró y revisó el manuscrito final. Resultados: se formularon siete recomendaciones integrando las respuestas de las panelistas basadas en evidencia, pero ajustadas al contexto y a la realidad colombiana. Recomendación 1. Se recomienda realizar la clasificación molecular en todos los carcinomas endometriales utilizando los marcadores de inmunohistoquímica como resultados subrogados del perfil molecular inicialmente propuesto en la clasificación del TCGA. Recomendación 2. Se recomienda la estrategia secuencial de testeo iniciando por los marcadores de inmunohistoquímica (p53, MLH1, MSH 2, MSH6, PMS2) simultáneamente en todas las pacientes, y definir la solicitud del POLE (polimerasa épsilon del DNA) (si se encuentra disponible) de forma diferida de acuerdo con la clasificación de riesgo basado en la pieza quirúrgica. Recomendación 3. Se recomienda que sea el ginecólogo oncólogo quien solicite el POLE (si se encuentra disponible) de acuerdo con el reporte de patología definitivo. Esta prueba se debe solicitar a todos los cánceres endometriales de estadio I-II, excepto los de bajo riesgo (estadio IA endometrioide de bajo grado sin invasión linfovascular p53 normal) y estadio III-IV sin enfermedad residual, sin afectar la solicitud de los marcadores moleculares subrogados por inmunohistoquímica de acuerdo con la histología. El consenso propone que la solicitud del POLE se realice posterior a la inmunohistoquímica y de acuerdo con la clasificación del riesgo según las categorías establecidas por la guía ESGO/ESTRO/ESP del 2020. Recomendación 4. Se recomienda realizar simultáneamente con los otros marcadores de inmunohistoquímica la prueba para receptores hormonales en todas las pacientes con cáncer endometrial y el HER2 en pacientes con p53abn. Recomendación 5. Se recomienda que los marcadores de inmunohistoquímica (p53, MLH1, MSH2, MSH6 y PMS2) se realicen en la biopsia/legrado endometrial inicial cuando la muestra es adecuada y está disponible. En caso de inmunohistoquímica inicial no concluyente, o discrepancias histológicas entre la patología inicial y definitiva, se recomienda repetir el perfil molecular en la patología quirúrgica. Los marcadores de inmunohistoquímica deben reportarse en el informe de patología de acuerdo con las recomendaciones del CAP (College of American Pathologists), independientemente del tipo de muestra. Recomendación 6. Se recomienda realizar estudio de metilación de promotor de MLH1 en pacientes con pérdida de expresión de MLH1 en la inmunohistoquímica, acompañado o no de pérdida de expresión de PMS2. Todas las pacientes con déficit de MMR (mismatch repair), deben ser enviadas a genética para descartar síndrome de Lynch. Recomendación 7. Se recomienda tener en cuenta la clasificación molecular, además de los criterios histopatológicos clásicos para la toma de decisiones de adyuvancia, tal como los incorpora la clasificación de los grupos pronósticos de la guía ESGO/ ESTRO/ESP del 2020. Conclusiones: es necesario implementar la clasificación molecular de cáncer de endometrio en la práctica clínica acorde al contexto colombiano, dado su valor pronóstico y posiblemente predictivo. Esto permitirá la caracterización de la población colombiana para ofrecer tratamientos guiados de manera individualizada. Se trata de un documento académico y no regulatorio.

Diagnostic performance of immunohistochemistry markers for malignant pleural mesothelioma diagnosis and subtypes. A systematic review and meta-analysis.

BACKGROUND: Malignant pleural mesothelioma (MPM) poses diagnostic challenges due to its resemblance to benign pleural pathologies and different histological subtypes. Several immunohistochemistry markers have been employed to aid in accurate diagnosis. METHODS: The present systematic review and meta-analysis aimed to assess the diagnostic performance of various immunohistochemistry markers in malignant pleural mesothelioma diagnosis and its histological subtypes. Following the PRISMA guidelines, we systematically searched the literature for articles on using different immunohistochemical markers in MPM and its histological subtypes. EMBASE, LILACS, MEDLINE, and Virtual Health Library were searched for studies published up to August 2023. We used the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) criteria to assess the quality of the included articles. Meta-analyses were performed to determine prevalence using a random-effects model. RESULTS: 103 studies met the inclusion criteria, comprising a diverse range of immunohistochemistry markers. EMA and desmin-loss exhibited high sensitivity (96% and 92%, respectively) in distinguishing malignant pleural mesothelioma from benign pleural pathologies. Specificity was notably high for both BAP1-loss and survivin expression at 100%. Subtype-specific analyses demonstrated that EMA and HEG1 were sensitive markers for epithelioid mesothelioma, while GLUT1 showed high sensitivity for sarcomatoid mesothelioma. In cases comparing epithelioid mesothelioma and lung adenocarcinoma, CAM5.2 and calretinin displayed high sensitivity, while WT1 and BAP1-loss demonstrated exceptional specificity for malignant epithelioid mesothelioma. In the case of sarcomatoid mesothelioma and sarcomatoid lung carcinoma, GATA3 exhibited the most heightened sensitivity, while GATA3 and D2-40 displayed the best specificity for sarcomatoid malignant mesothelioma diagnosis. CONCLUSION: Immunohistochemistry markers are essential in accurately diagnosing malignant pleural mesothelioma and its histological subtypes. This systematic review and meta-analysis provide a comprehensive insight into the diagnostic performance of these markers, facilitating their potential clinical utility in the discrimination of malignant pleural mesothelioma from other pleural pathologies and the differentiation of malignant pleural mesothelioma subtypes.

Crossing the Andes: Challenges and opportunities for digital pathology in Latin America.

The most widely accepted and used type of digital pathology (DP) is whole-slide imaging (WSI). The USFDA granted two WSI system approvals for primary diagnosis, the first in 2017. In Latin America, DP has the potential to reshape healthcare by enhancing diagnostic capabilities through artificial intelligence (AI) and standardizing pathology reports. Yet, we must tackle regulatory hurdles, training, resource availability, and unique challenges to the region. Collectively addressing these hurdles can enable the region to harness DP's advantages-enhancing disease diagnosis, medical research, and healthcare accessibility for its population. Americas Health Foundation assembled a panel of Latin American pathologists who are experts in DP to assess the hurdles to implementing it into pathologists' workflows in the region and provide recommendations for overcoming them. Some key steps recommended include creating a Latin American Society of Digital Pathology to provide continuing education, developing AI models trained on the Latin American population, establishing national regulatory frameworks for protecting the data, and standardizing formats for DP images to ensure that pathologists can collaborate and validate specimens across the various DP platforms.

Gliomas difusos en áreas elocuentes: avances diagnósticos y terapéuticos / Diffuse gliomas within eloquent areas: diagnostic and therapeutic advances

Objetivo: presentar los avances diagnósticos, moleculares y radiológicos, así como en las estrategias terapéuticas para gliomas difusos en los últimos 5 años (2018-2023) en la Fundación Universitaria de Ciencias de la Salud (FUCS), Bogotá D.C., Colombia. Materiales y métodos: se describen las técnicas diagnósticas y terapéuticas utilizadas para gliomas difusos con casos ilustrativos. Resultados: se muestran los avances de las herramientas diagnósticas y terapéuticas para el manejo de gliomas difusos. Discusión: en los últimos 5 años se ha avanzado en la clasificación, diagnóstico y tratamiento de los gliomas difusos, gracias a los avances tecnológicos como los marcadores moleculares, la tractografía y la fusión de imágenes para la neuronavegación y las técnicas de estimulación cortical. Esto ha permitido que el tratamiento de los pacientes con dichos tumores mejore la tasa de morbilidad, la calidad de vida libre de enfermedad y la supervivencia global. Conclusiones: las técnicas de diagnóstico como la tractografía, la fusión integral de imágenes intraoperatorias y el mapeo cerebral electrofisiológico con estimulación cortical y subcortical han mejorado el diagnóstico y tratamiento de los gliomas difusos.

Objective: to present the diagnostic, molecular, radiological, and therapeutic advances, to address diffuse gliomas, made at Fundación Universitaria de Ciencias de la Salud (FUCS), Bogotá D.C., Colombia, in the last 5 years (2018-2023). Materials and methods: diagnostic and therapeutic techniques to address diffuse gliomas are described through illustrative cases. Results: the advances in diagnostic and therapeutic tools for managing diffuse gliomas, are shown. Discussion: in the last 5 years progress in characterizing, diagnosing, and treating diffuse gliomas, thanks to technological breakthroughs, such as molecular markers, tractography, image fusion for neuronavigation, and cortical stimulation techniques, has been achieved. This has allowed improving morbidity rate, disease-free quality of life and overall survival through the treatment provided to patients afflicted with gliomas. Conclusions: Diagnostic techniques based on tractography, comprehensive intraoperative image fusion, and electrophysiological brain mapping with cortical and subcortical stimulation, have improved the diagnostic and therapeutic approaches for diffuse gliomas.

Clinical characteristics of early-onset gastric cancer. A study in a Colombian population.

Gastric cancer is a multifactorial disease with important genetic and environmental factors. It is the fifth most common cancer in incidence, and the fourth cause of death secondary to cancer. The incidence of early-onset gastric cancer is increasing worldwide, but clinical information on these patients has not been well established. We analyzed the association between age and clinical, endoscopic, and histopathological characteristics of gastric cancer at the time of diagnosis in a Latin American population. A retrospective and descriptive cross-sectional study was carried out using the database of the Gastroenterology Service of the Clínica Foscal and Clínica Foscal Internacional in Bucaramanga, Colombia. Between January 2016 and December 2019, 259 de novo gastric cancer cases were diagnosed, of which 36 patients (13.9%) were 40 years old or younger. In patients with early-onset gastric, the prevalence of gastric cancer diagnosis was lower in men. A family history of gastric cancer or any other neoplasm was not associated with a higher prevalence of gastric neoplasms. In young patients, vomiting and ascites were more common, the preferred anatomical location was the body of the stomach, and the Borrmann IV classification and the diffuse-type histology were more likely. Our study showed an approximation of the characteristics of early-onset gastric cancer in a Latin American population, where we observed that early-onset gastric cancer has different demographic, anatomical, and histological features than late-onset gastric cancer.

Fusariosis in cancer patients: 13 case series report and literature review / Fusariosis en pacientes con cáncer: serie de 13 casos y revisión de la literatura

The fusariosis is an opportunistic mycosis caused by Fusarium spp. Its clinical presentation depends on the immunological status of the host, especially in patients with hematooncological diseases, whose manifestations vary from localized to invasive fungal infections. Skin or blood culture helps to guide combined antifungal treatment with amphotericin B and voriconazole. Here, we present 13 cases in a period of eleven years of patients with cancer who developed disseminated fusariosis and their outcomes, together with a review of the related literature. In this series of cases, mortality was 61.5 % (8/13), despite the use of the antifungal. Out of the 13 cases, 11 had hematological neoplasia and 2 solid neoplasia. The most determinant risk factor was profound neutropenia. Skin involvement and positive blood cultures in most cases allowed combined treatment prescription. Persistent febrile neutropenia associated with skin lesions, onychomycosis, nodules, or lung masses lead to suspicion of Fusarium spp. fungal invasive infection. The aim of this series of cases is to remind healthcare professionals that oncological patients with deep and persistent febrile neutropenia can develop fusariosis.

La fusariosis es una micosis oportunista producida por Fusarium spp. Su presentación clínica depende del estado inmunológico del huésped, especialmente, el de aquellos con enfermedades hematooncológicas, cuyas manifestaciones varían desde formas localizadas hasta infección fúngica invasora. El cultivo de piel o de sangre permite orientar el tratamiento antifúngico combinado con anfotericina B y voriconazol. Se presentan 13 casos de pacientes con cáncer en un periodo de once años que desarrollaron fusariosis diseminada; asimismo, se hizo con una revisión extensa de la literatura. En esta serie de casos, la mortalidad fue del 61,5 % (8/13), a pesar del uso del antifúngico. De los 13 pacientes, 11 tenían neoplasia hematológica y 2 neoplasia sólida. El factor de riesgo más importante fue la neutropenia profunda. El compromiso de la piel y los hemocultivos positivos facilitaron la prescripción del tratamiento combinado en la mayoría de los casos. La neutropenia febril persistente asociada a lesiones cutáneas, la onicomicosis, los nódulos o las masas pulmonares permitieron sospechar una infección fúngica invasora por Fusarium spp. El objetivo de la presentación de esta serie de casos es recordar el diagnóstico de fusariosis a la comunidad médica en contacto con pacientes oncológicos, con neutropenia febril profunda y persistentes.

Prevalence of oncogenic driver mutations in Hispanics/Latin patients with lung cancer. A systematic review and meta-analysis.

INTRODUCTION: The frequency of actionable mutations varies between races, and Hispanic/Latino (H/L) people are a population with different proportions of ancestry. Our purpose was to establish prevalence of actionable mutations in the H/L population with NSCLC. METHODS: EMBASE, LILACS, MEDLINE, and Virtual Health Library were searched for studies published up to April 2023 that evaluated the prevalence of ALK, BRAF, EGFR, HER-2, KRAS, MET, NTRK, RET, ROS1 in H/L patients. Meta-analyses were done to determine prevalence using a random effects model. RESULTS: Fifty-five articles were included. EGFR and KRAS were the most prevalent genes with high heterogeneity across the countries. The overall mutation frequency for EGFR was 22%. The most frequent mutations in the EGFR gene were del19 (10%) and L858R (7%). The mean of KRAS mutation was a 14% prevalence. KRASG12C was the most frequent mutation with a 7% prevalence in an entire population. The overall frequency of ALK rearrangement was 5%. The mean frequency of ROS-1 rearrangement was 2%, and the frequencies of HER-2, MET, BRAF, RET, NTRK molecular alterations were 4%, 3%, 2%, 2%, and 1% respectively. Almost half of the cases were male, and 65.8% had a history of tobacco exposure. The most common clinical stage was IV. CONCLUSIONS: The prevalence of driver mutations such as EGFR and KRAS in LA populations differs from what is reported in Asians and Europeans. In the present article, countries with a high proportion of Amerindian ancestry show a greater prevalence of EGFR in contrast to countries with a high proportion of Caucasians. Lack of information on some countries or studies with a small sample size affects the real prevalence data for the region.

Bioinformatics analysis and single-cell RNA sequencing: elucidating the ubiquitination pathways and key enzymes in lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is a prevalent subtype of lung cancer associated with high mortality rates. We aimed to utilize single-cell multiomics analysis to identify the key molecules involved in ubiquitination modification, which plays a role in LUAD development and progression. Methods: We use a systematic approach to analyze LUAD-related single-cell and bulk transcriptome datasets from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Single-cell RNA sequencing (scRNA-seq) data were normalized, clustered, and annotated with the Seurat package in R. InferCNV was used to distinguish malignant from epithelial cells, and AUCell evaluated the area under the curve (AUC) score of ubiquitination-related enzymes. Survival and differential analyses identified significant molecular markers associated with ubiquitination. PSMD14 expression was confirmed using reverse-transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot assays, and its knockdown cell lines were assessed for effects on cellular processes and tumor formation in mice. PSMD14's interacting proteins were predicted, and its impact on AGR2 protein half-life and ubiquitination was evaluated. Rescue experiments involving PSMD14 overexpression and AGR2 silencing assessed their impact on malignant behaviors. Results: By means of single-cell sequencing analysis, we probed the ubiquitination modification landscape in the LUAD microenvironment. Malignant cells had elevated scores for enzymes and ubiquitin-binding domains compared to normal epithelial cells, with 53 ubiquitination-related molecules showing prognostic disparities. FGR, PSMD14, and ZBTB16 were identified as genes with prognostic significance, with PSMD14 showing higher expression in epithelial and malignant cells. Two missense mutation sites were identified in PSMD14, which had a high copy number amplification ratio and positive correlation with messenger RNA (mRNA) expression. PSMD14 expression and tumor stage were found to be independent prognostic factors, and interfering with PSMD14 expression reduced the malignant behavior of LUAD cells. PSMD14 was found to bind to AGR2 protein and reduce its ubiquitination, leading to increased AGR2 stability. Knockdown of AGR2 inhibited the enhancement of cell viability, invasion, and migration resulting from PSMD14 overexpression. Conclusions: This study examined ubiquitination modifications in LUAD using sequencing data, identifying PSMD14's critical role in malignancy regulation and its potential as a prognostic and therapeutic biomarker. These insights enhance understanding of LUAD mechanisms and treatment.

Understanding the molecular profiling of diffuse gliomas classification: A brief overview.

Background: Gliomas represent almost 30% of all primary brain tumors and account for 80% of malignant primary ones. In the last two decades, significant progress has been made in understanding gliomas' molecular origin and development. These advancements have demonstrated a remarkable improvement in classification systems based on mutational markers, which contribute paramount information in addition to traditional histology-based classification. Methods: We performed a narrative review of the literature including each molecular marker described for adult diffuse gliomas used in the World Health Organization (WHO) central nervous system 5. Results: The 2021 WHO classification of diffuse gliomas encompasses many molecular aspects considered in the latest proposed hallmarks of cancer. The outcome of patients with diffuse gliomas relies on their molecular behavior and consequently, to determine clinical outcomes for these patients, molecular profiling should be mandatory. At least, the following molecular markers are necessary for the current most accurate classification of these tumors: (1) isocitrate dehydrogenase (IDH) IDH-1 mutation, (2) 1p/19q codeletion, (3) cyclin-dependent kinase inhibitor 2A/B deletion, (4) telomerase reverse transcriptase promoter mutation, (5) α-thalassemia/ mental retardation syndrome X-linked loss, (6) epidermal growth factor receptor amplification, and (7) tumor protein P53 mutation. These molecular markers have allowed the differentiation of multiple variations of the same disease, including the differentiation of distinct molecular Grade 4 gliomas. This could imply different clinical outcomes and possibly impact targeted therapies in the years to come. Conclusion: Physicians face different challenging scenarios according to the clinical features of patients with gliomas. In addition to the current advances in clinical decision-making, including radiological and surgical techniques, understanding the disease's molecular pathogenesis is paramount to improving the benefits of its clinical treatments. This review aims to describe straightforwardly the most remarkable aspects of the molecular pathogenesis of diffuse gliomas.

Clinical characteristics of early-onset gastric cancer. A study in a Colombian population

Gastric cancer is a multifactorial disease with important genetic and environmental factors. It is the fifth most common cancer in incidence, and the fourth cause of death secondary to cancer. The incidence of early-onset gastric cancer is increasing worldwide, but clinical information on these patients has not been well established. We analyzed the association between age and clinical, endoscopic, and histopathological characteristics of gastric cancer at the time of diagnosis in a Latin American population. A retrospective and descriptive cross-sectional study was carried out using the database of the Gastroenterology Service of the Clínica Foscal and Clínica Foscal Internacional in Bucaramanga, Colombia. Between January 2016 and December 2019, 259 de novo gastric cancer cases were diagnosed, of which 36 patients (13.9%) were 40 years old or younger. In patients with early-onset gastric, the prevalence of gastric cancer diagnosis was lower in men. A family history of gastric cancer or any other neoplasm was not associated with a higher prevalence of gastric neoplasms. In young patients, vomiting and ascites were more common, the preferred anatomical location was the body of the stomach, and the Borrmann IV classification and the diffuse-type histology were more likely. Our study showed an approximation of the characteristics of early-onset gastric cancer in a Latin American population, where we observed that early-onset gastric cancer has different demographic, anatomical, and histological features than late-onset gastric cancer.

El cáncer gástrico es una enfermedad multifactorial con importantes factores genéticos y ambientales. Es el quinto cáncer más común en incidencia y la cuarta causa de muerte secundaria al cáncer. La incidencia del cáncer gástrico de inicio temprano está aumentando en todo el mundo, pero la información clínica sobre estos pacientes no está bien establecida. Analizamos la asociación entre la edad y las características clínicas, endoscópicas e histopatológicas del cáncer gástrico al momento del diagnóstico en una población latinoamericana. Se realizó un estudio retrospectivo y descriptivo de corte transversal utilizando la base de datos del Servicio de Gastroenterología de la Clínica Foscal y Clínica Foscal Internacional en Bucaramanga, Colombia. Entre enero de 2016 y diciembre de 2019 se diagnosticaron 259 casos de cáncer gástrico de novo, de los cuales 36 pacientes (13,9%) tenían 40 años o menos. En pacientes con enfermedad gástrica de inicio temprano, la prevalencia del diagnóstico de cáncer gástrico fue menor en los hombres. El antecedente familiar de cáncer gástrico o cualquier otra neoplasia no se asoció con una mayor prevalencia de neoplasias gástricas. En pacientes jóvenes fueron más frecuentes los vómitos y la ascitis, la localización anatómica preferida fue el cuerpo del estómago, siendo más probable la clasificación de Borrmann IV y la histología de tipo difuso. Nuestro estudio mostró una aproximación a las características del cáncer gástrico de inicio temprano en una población latinoamericana, donde observamos que el cáncer gástrico de inicio temprano tiene diferentes características demográficas, anatómicas e histológicas que el cáncer gástrico de inicio tardío.

Early Metastasis of Clear Cell Renal Cell Carcinoma to the Esophagus: A Case Report.

Metastatic involvement of clear cell renal cancer in the esophagus has been described in the literature as an uncommon condition. These usually present as late relapse causing clinical manifestations such as dysphagia and melena. We present the case of a 57-year-old man with a history of renal cell carcinoma who presented an early metastasis to the esophagus. In addition, we made a comparison of the reason for examination, time of relapse, and metastasis in other anatomical places of all the cases reported in the literature of esophageal involvement due to clear cell metastasis.

A postmortem study of patients vaccinated for SARS-CoV-2 in Colombia.

INTRODUCTION AND OBJECTIVE: A new coronavirus produces a disease designated as coronavirus disease 2019 (COVID-19). Vaccination against COVID-19 has resulted in decreased mortality. Postmortems of vaccinated patients play an important part in the forensic analysis of adverse effects after vaccination, which is essential for determining its efficacy and security. The main objective of this study was to describe the results of autopsies of patients vaccinated for SARS-CoV-2 carried out in two major centers in Colombia. MATERIALS AND METHODS: A descriptive cross-sectional study of 121 autopsies was performed following Colombian regulations in two main hospitals in Bogotá, Colombia, between March 1st and April 31st, 2021. RESULTS: 118 of the 121 patients (97.52%) had been vaccinated with CoronaVac (Sinovac); only 3 had received other vaccines. Sudden cardiac death was the leading cause of death, with pulmonary embolism another critical finding. No relation between the cause of death and vaccination against SARS-CoV-2 was found. CONCLUSIONS: A clinical autopsy is a vital for an accurate post-mortem diagnosis. Any relation between the SARS-CoV-2 vaccine and the cause of death should be carefully studied in order to provide the general public with evidence-based information about the safety of the vaccination.

Metástasis tumor a tumor en pulmón: reporte de tres casos y revisión de la literatura / Tumor-to-tumor metastasis in the lung: report of three cases and review of the literature

Las metástasis tumor a tumor (MTT) corresponden a un evento poco frecuente en el cual se presenta metástasis de un tumor primario a otro tumor primario, bien sea benigno o maligno. El carcinoma de pulmón es un receptor poco habitual, pero uno de los donantes más frecuentes. En el presente articulo presentamos tres casos de MTT como órgano receptor el pulmón: el primero, de una mujer con antecedente de carcinoma papilar de tiroides y carcinoma ductal in situ de la mama, con presencia de MTT y carcinoma papilar de tiroides a un adenocarcinoma primario pulmonar. El segundo caso, es una mujer con MTT de carcinoma ductal de mama a un adenocarcinoma primario pulmonar. Y el tercero, de un MTT de un carcinoma ductal de mama a un hamartoma pulmonar. En los tres casos, fue fundamental la correlación clínico-patológica y los estudios complementarios de inmunohistoquímica.

Tumor-to-tumor metastases (TTM) correspond to a rare event in which a primary tumor metastasizes to another primary tumor, whether benign or malignant. Lung carcinoma is an unusual recipient, but one of the most frequent donors. In this article, we present three cases of TTM to the lung: the first one is of a woman with a history of papillary thyroid carcinoma and ductal carcinoma in situ of the breast, with the presence of TTM and papillary thyroid carcinoma to a primary adenocarcinoma of the lung. The second case is of a woman with TTM from ductal carcinoma of the breast to a primary pulmonary adenocarcinoma, and the third is TTM from a breast ductal carcinoma to a pulmonary hamartoma. In all three cases, the clinical-pathological connection and complementary immunohistochemical studies were essential

Fusariosis en pacientes con cáncer: serie de 13 casos y revisión de la literatura / Fusariosis in cancer patients: 13 case series report and literature review

La fusariosis es una micosis oportunista producida por Fusarium spp. Su presentación clínica depende del estado inmunológico del huésped, especialmente, el de aquellos con enfermedades hematooncológicas, cuyas manifestaciones varían desde formas localizadas hasta infección fúngica invasora. El cultivo de piel o de sangre permite orientar el tratamiento antifúngico combinado con anfotericina B y voriconazol. Se presentan 13 casos de pacientes con cáncer en un periodo de once años que desarrollaron fusariosis diseminada; asimismo, se hizo con una revisión extensa de la literatura. En esta serie de casos, la mortalidad fue del 61,5 % (8/13), a pesar del uso del antifúngico. De los 13 pacientes, 11 tenían neoplasia hematológica y 2 neoplasia sólida. El factor de riesgo más importante fue la neutropenia profunda. El compromiso de la piel y los hemocultivos positivos facilitaron la prescripción del tratamiento combinado en la mayoría de los casos. La neutropenia febril persistente asociada a lesiones cutáneas, la onicomicosis, los nódulos o las masas pulmonares permitieron sospechar una infección fúngica invasora por Fusarium spp. El objetivo de la presentación de esta serie de casos es recordar el diagnóstico de fusariosis a la comunidad médica en contacto con pacientes oncológicos, con neutropenia febril profunda y persistentes.

The fusariosis is an opportunistic mycosis caused by Fusarium spp. Its clinical presentation depends on the immunological status of the host, especially in patients with hemato-oncological diseases, whose manifestations vary from localized to invasive fungal infections. Skin or blood culture helps to guide combined antifungal treatment with amphotericin B and voriconazole. Here, we present 13 cases in a period of eleven years of patients with cancer who developed disseminated fusariosis and their outcomes, together with a review of the related literature. In this series of cases, mortality was 61.5 % (8/13), despite the use of the antifungal. Out of the 13 cases, 11 had hematological neoplasia and 2 solid neoplasia. The most determinant risk factor was profound neutropenia. Skin involvement and positive blood cultures in most cases allowed combined treatment prescription. Persistent febrile neutropenia associated with skin lesions, onychomycosis, nodules, or lung masses lead to suspicion of Fusarium spp. fungal invasive infection. The aim of this series of cases is to remind healthcare professionals that oncological patients with deep and persistent febrile neutropenia can develop fusariosis.

Familial Adenomatous Polyposis: Case Report and Literature Review.

Familial adenomatous polyposis (FAP) is an autosomal inheritance disease characterized by 100 or more adenomatous polyps in the colon and rectum with a high risk of developing colorectal carcinoma (CRC). The management of this disease is based on early screening and timely follow up, with subsequent planning of risk-reducing or therapeutic surgeries. We present a case of a patient with a strong family history of FAP with a "de novo" diagnosis of CRC. Furthermore, a literature discussion of current and future perspectives of treatment is performed.

Multiple mutations in the EGFR gene in lung cancer: a systematic review.

Background: Lung cancer is a public health problem worldwide. Currently, identifying genetic mutations in the epidermal growth factor receptor (EGFR) has brought significant changes in diagnosing and managing patients with lung cancer. The presence of multiple mutations, defined as the presence of more than one EGFR mutation, has been reported in a few studies. Therefore, we carried out this systematic review to describe the most common multiple mutations in the EGFR gene. Methods: We conduct a systematic review of descriptive studies, cohorts, and clinical trials published in Scopus, PubMed, Scielo, and Virtual Health Library literature. The inclusion criteria for the systematic review were descriptive studies, cohorts, and clinical trials with the presence of multiple mutations in the EGFR gene. It was followed the Preferred Reporting Items for Systematic Meta-Analyses (PRISMA) guidelines. Results: In the systematic review, 41 articles were included. Four hundred and forty-six cases with multiple mutations in the EGFR gene were found (0.95% of the patients included in the studies). The most prevalent dual mutations observed were T790M + L858R and deletions in exon 19 + T790M. Triple mutations were found in 9 cases (2.017%). According to reports, the presence of T790M mutation in the multiple mutations has been associated with poor clinical outcomes. Discussion: The presence of multiple mutations in the EGFR gene is rare. It is of great importance to consider the T790M mutation since it generates resistance to pharmacological management and has worse outcomes. The most important limitation was that clinical information data and follow-up could not be collected in a large percentage of patients. Therefore, future work should be focused on clinical characteristics, follow-up and repercussions in the treatment of patients with multiple mutations.

Adenocarcinoma primario de pulmón con células en anillo de sello y reordenamiento de ALK. Reporte de dos casos / Primary adenocarcinoma of the lung with signet-ring cells and ALK rearrangement. Two case reports.

El adenocarcinoma primario de pulmón con células en anillo de sello representa una variante rara y muy agresiva de cáncer de pulmón. El carcinoma de células en anillo de sello es un tipo particular de adenocarcinoma secretor de mucina, que se deposita intracitoplasmáticamente y desplaza el núcleo hacia la periferia de la célula. El origen pulmonar de este subtipo tumoral es raro y el hallazgo de reordenamiento de ALK es una asociación común. Presentamos dos casos de adenocarcinomas mucinosos primarios de pulmón con células en anillo de sello y reordenamiento de ALK. Todos los pacientes con cáncer de pulmón deben contar con estudios histopatológicos, inmunohistoquímicos y de biología molecular con los que se puedan obtener las principales características del tumor, que permitan ofrecer la mejor opción terapéutica para el paciente.

Primary adenocarcinoma of the lung with signet-ring cells represents a rare and highly aggressive variant of lung cancer. Signet­ring cell carcinoma is a particular type of mucin­secreting adenocarcinoma, which is deposited intracytoplasmatically and displaces the nucleus towards the periphery of the cell. The pulmonary origin of this tumor subtype is rare, and the finding of ALK rearrangement is a common association. We present two cases of primary mucinous adenocarcinomas of the lung with signet-ring cells and ALK rearrangement. All patients with lung cancer must have histopathological, immunohistochemical, and molecular biology studies with which the main features of the tumor can be obtained, which allow the clinician to offer the best possible treatment for the patient.

Opportunistic infections as a cause of death in patients with autoimmune diseases: An autopsy-based study / Infecciones oportunistas como causa de muerte en pacientes con enfermedades autoinmunes: estudio basado en autopsias

Background: Infections are an important cause of mortality in patients with autoimmune diseases and opportunistic infections account for a large percentage of these cases. It is often a clinical challenge to find a balance between immunosuppressive therapy and the risk of developing an infectious process. Methods: A retrospective, descriptive study of autopsy reports. Results: 15 patients with a premortem diagnosis of autoimmune disease were included. All patients died due to an opportunistic infection. The most commonly reported infection was tuberculosis, followed by invasive fungal infections. Conclusions: The most prevalent pathogens were found in our autopsy-based study of patients with autoimmune diseases and opportunistic infections. Prevention and early detection strategies are vital in order to reach a correct diagnosis and begin the appropriate treatment as soon as possible.(AU)

Antecedentes: Las infecciones son una causa importante de mortalidad en pacientes con enfermedades autoinmunes. Las infecciones oportunistas engloban un gran porcentaje de estos casos. Encontrar un equilibrio entre la terapia inmunosupresora y el riesgo de desarrollar procesos infecciosos normalmente constituye un desafío clínico. Métodos: Estudio retrospectivo y descriptivo de informes de autopsias. Resultados: Se incluyó a 15 pacientes con diagnóstico pre mortem de enfermedad autoinmune. Todos los pacientes fallecieron debido a infecciones oportunistas. La infección más frecuentemente reportada fue la tuberculosis, seguida de infecciones fúngicas invasivas. Conclusiones: En este estudio basado en autopsias, realizado en pacientes con enfermedades autoinmunes e infecciones oportunistas, se recogieron los patógenos más prevalentes. Es clave establecer estrategias de prevención y detección temprana en estos grupos de pacientes para realizar un diagnóstico precoz e introducir con prontitud el tratamiento adecuado.(AU)