Algoritmo para el diagnóstico integrado de los gliomas 2021. Nuestra experiencia / Algorithm for the integrated diagnosis of gliomas 2021. Our experience

Resumen La aplicación de las diferentes técnicas moleculares para el diagnóstico de los gliomas según la clasificación de la OMS, sigue sin estar al alcance de todos en nuestro país. Nuestro objetivo fue describir el protocolo diagnóstico desarrollado en función de los recursos disponibles, conforme con la clasificación vigente (2021). También, describir el perfil epidemiológico de los gliomas diagnosticados entre 2018-2021 en el Instituto Roffo y contrastarlo con la literatura. Se evaluó la mutación en IDH1-R132H, ATRX, el estado del 1p19q, CDKN2A, EGFR y del p53. Se incluyeron 94 pacientes, 53.2% fueron masculinos, con una edad promedio de 50.9 años. El diagnóstico más frecuente fue el de GB IDH1-no mutado (63.8%). Considerando únicamente a los gliomas grado 2 y 3, el astrocitoma difuso IDH1-Mutado/ATRX-Mutado/p53-sobreexpresado, grado 2 (11.7%) fue el más frecuente. En cuanto a su localización, el 67% de los tumores se ubicaron en el telencéfalo neocortical: 24.5% del total en el lóbulo frontal. En el 95.7% de los casos se arribó a un diagnóstico integrado concluyente siguiendo el algoritmo propuesto. Las características epidemiológicas coinciden con lo publicado en la literatura. La biología molecular nos permitió diferenciar nítidamente enfermedades que suponíamos emparentadas desde un punto de vista histológico, pero que observando su historia natural, su genética y su respuesta a tratamientos instaurados eran tumores distintos, aunque todos fueran llamados "gliomas". Los estándares internacionales no conciben su diagnóstico sin la biología molecular. No es aceptable que se siga diagnosticando únicamente con estándares histológicos. El algoritmo propuesto podría ser una alternativa viable y confiable.

Abstract The utilization of the different molecular techniques for the diagnosis of gliomas according to the WHO classification is still not available to everyone in our country. Our objective was to describe the diagnostic algorithm devel oped based on available resources, in accordance with the current classification (2021). Also, to describe the epidemiological profile of gliomas diagnosed between 2018-2021 at the Roffo Institute and compare it with the international literature. IDH1-R132H and ATRX mutation, as well as 1p19q status, CDKN2A, EGFR, and p53 were evaluated. 94 patients were included, 53.2% were male, with a mean age of 50.9 years. The most frequent diagnosis was GB IDH1-wild type (63.8%). Considering only grade 2 and 3 gliomas, diffuse astrocytoma IDH1- Mutated / ATRX-Mutated / p53-overexpressed, grade 2 (11.7%) was the most frequent diagnosis. Regarding their location, 67% of the tumors were located in the neocortical telencephalon: 24.5% of the total in the frontal lobe. In 95.7% of cases, a conclusive integrated diagnosis was reached following the proposed algorithm. The epidemiological characteristics coincide with what has been published in the literature. Molecular biology allowed us to clearly differentiate pathologies that we assumed were related from a histological point of view, but which, observing their natural history, their genetics and their response to established treatments were different tumors, although they were all called "gliomas". International standards do not conceive CNS tumor diagnosis without molecular biology. It is not acceptable to continue to diagnose only with histological standards. The proposed algorithm could be a viable and reliable alternative.

[Algorithm for the integrated diagnosis of gliomas 2021. Our experience]. / Algoritmo para el diagnóstico integrado de los gliomas 2021. Nuestra experiencia.

The utilization of the different molecular techniques for the diagnosis of gliomas according to the WHO classification is still not available to everyone in our country. Our objective was to describe the diagnostic algorithm developed based on available resources, in accordance with the current classification (2021). Also, to describe the epidemiological profile of gliomas diagnosed between 2018-2021 at the Roffo Institute and compare it with the international literature. IDH1-R132H and ATRX mutation, as well as 1p19q status, CDKN2A, EGFR, and p53 were evaluated. 94 patients were included, 53.2% were male, with a mean age of 50.9 years. The most frequent diagnosis was GB IDH1-wild type (63.8%). Considering only grade 2 and 3 gliomas, diffuse astrocytoma IDH1-Mutated / ATRX-Mutated / p53-overexpressed, grade 2 (11.7%) was the most frequent diagnosis. Regarding their location, 67% of the tumors were located in the neocortical telencephalon: 24.5% of the total in the frontal lobe. In 95.7% of cases, a conclusive integrated diagnosis was reached following the proposed algorithm. The epidemiological characteristics coincide with what has been published in the literature. Molecular biology allowed us to clearly differentiate pathologies that we assumed were related from a histological point of view, but which, observing their natural history, their genetics and their response to established treatments were different tumors, although they were all called "gliomas". International standards do not conceive CNS tumor diagnosis without molecular biology. It is not acceptable to continue to diagnose only with histological standards. The proposed algorithm could be a viable and reliable alternative.

La aplicación de las diferentes técnicas moleculares para el diagnóstico de los gliomas según la clasificación de la OMS, sigue sin estar al alcance de todos en nuestro país. Nuestro objetivo fue describir el protocolo diagnóstico desarrollado en función de los recursos disponibles, conforme con la clasificación vigente (2021). También, describir el perfil epidemiológico de los gliomas diagnosticados entre 2018-2021 en el Instituto Roffo y contrastarlo con la literatura. Se evaluó la mutación en IDH1-R132H, ATRX, el estado del 1p19q, CDKN2A, EGFR y del p53. Se incluyeron 94 pacientes, 53.2% fueron masculinos, con una edad promedio de 50.9 años. El diagnóstico más frecuente fue el de GB IDH1-no mutado (63.8%). Considerando únicamente a los gliomas grado 2 y 3, el astrocitoma difuso IDH1-Mutado/ATRX-Mutado/p53-sobreexpresado, grado 2 (11.7%) fue el más frecuente. En cuanto a su localización, el 67% de los tumores se ubicaron en el telencéfalo neocortical: 24.5% del total en el lóbulo frontal. En el 95.7% de los casos se arribó a un diagnóstico integrado concluyente siguiendo el algoritmo propuesto. Las características epidemiológicas coinciden con lo publicado en la literatura. La biología molecular nos permitió diferenciar nítidamente enfermedades que suponíamos emparentadas desde un punto de vista histológico, pero que observando su historia natural, su genética y su respuesta a tratamientos instaurados eran tumores distintos, aunque todos fueran llamados "gliomas". Los estándares internacionales no conciben su diagnóstico sin la biología molecular. No es aceptable que se siga diagnosticando únicamente con estándares histológicos. El algoritmo propuesto podría ser una alternativa viable y confiable.

Effects of time to chemoradiation on high-grade gliomas from the Buenos Aires Metropolitan Area.

High-Grade Gliomas (HGG) are the most frequent brain tumor in adults. The gold standard of clinical care recommends beginning chemoradiation within 6 weeks of surgery. Disparities in access to healthcare in Argentina are notorious, often leading to treatment delays. We conducted this retrospective study to evaluate if time to chemoradiation after surgery is correlated with progression-free survival (PFS). Our study included clinical cases with a histological diagnosis of Glioblastoma (GBM), Anaplastic Astrocytoma (AA) or High-Grade Glioma (HGG) in patients over 18 years of age from 2014 to 2020. We collected data on clinical presentation, type of resection, time to surgery, time to chemoradiation, location within the Buenos Aires Metropolitan Area (BAMA) and type of health insurance. We found 63 patients that fit our inclusion criteria, including 26 (41.3%) females and 37 (58.7%) males. Their median age was 54 years old (19-86). Maximal safe resection was achieved in 49.2% (n = 31) of the patients, incomplete resection in 34.9% (n = 22) and the other 15.9% (n = 10) received a biopsy, but no resection. The type of health care insurance was almost evenly divided, with 55.6% (n = 35) of the patients having public vs. 44.4% (n = 28) having private health insurance. Median time to chemoradiation after surgery was 8 (CI 6.68-9.9) weeks for the global population. When we ordered the patients PFS by time to chemoradiation we found that there was a statistically significant effect of time to chemoradiation on patient PFS. Patients had a PFS of 10 months (p = 0.014) (CI 6.89-13.10) when they received chemoradiation <5 weeks vs a PFS of 7 months (CI 4.93-9.06) when they received chemoradiation between 5 to 8 weeks and a PFS of 4 months (CI 3.76-4.26 HR 2.18 p = 0.006) when they received chemoradiation >8 weeks after surgery. Also, our univariate and multivariate analysis found that temporal lobe location (p = 0.03), GMB histology (p = 0.02) and biopsy as surgical intervention (p = 0.02) all had a statistically significant effect on patient PFS. Thus, time to chemoradiation is an important factor in patient PFS. Our data show that although an increase in HGG severity contributes to a decrease in patient PFS, there is also a large effect of time to chemoradiation. Our results suggest that we can improve patient PFS by making access to healthcare in Buenos Aires more equitable by reducing the average time to chemoradiation following tumor resection.

Navegando por la fisura silviana: anatomía microquirúrgica, neuroimágenes y técnica quirúrgica / Navigating the sylvian fissure: microsurgical anatomy, neuroimaging, and surgical technique

Objetivo: Describir la anatomía quirúrgica de la fisura silviana (FS) a través de disecciones cadavéricas y neuroimágenes; desarrollar su aplicación microquirúrgica. Materiales y métodos: Se estudiaron 10 hemisferios cadavéricos humanos fijados y un cráneo humano en seco, a través de la disección de fibras blancas y de la anatomía arterial y neural, utilizando un microscopio quirúrgico. Las arterias cerebrales fueron inyectadas con silicona coloreada. La anatomía quirúrgica fue correlacionada con la anatomía neuroimagenológica. Finalmente, se recolectó la experiencia microquirúrgica adquirida y, a su vez, la anatomía del Complejo Silviano, fue revisada. Resultados: La FS se extiende desde la cara basal a la lateral del cerebro. Cada superficie tiene una parte superficial (tronco silviano y sus ramos), intermedia (compartimientos anterior y opercular lateral) y profunda (compartimiento esfenoidal, hendidura insular anterior y lateral y la región retroinsular). En 7 de los 10 hemisferios, el surco central no se intersectó con la FS en la superficie lateral del cerebro. En el 80% de los hemisferios, la principal bifurcación de la arteria cerebral media se localizó en o proximal al limen insular. Debajo de la pars triangularis se localiza el punto más ancho de la superficie lateral de la FS. Los autores comienzan la disección de la misma en o proximalmente a este punto. Conclusiones: El conocimiento anatómico profundo y su aplicación a las neuroimágenes, son herramientas esenciales para el planeamiento prequirúrgico y son requisitos mandatorios para operar con seguridad a través y alrededor de la FS

Objective: The aim of this study is to describe the microsurgical anatomy of the sylvian fissure, through cadaveric dissections and neuroimaging and to elucidate its clinical application for microsurgery. Methods: One human skull and ten cadaveric human hemispheres were studied through white matter fiber dissections and arterial and neural anatomy of the sylvian fissure and insular dissections under the microscope. The cerebral arteries were perfused with colored latex. The surgical anatomy was correlated with neuroimaging anatomy. Finally, the microsurgical experienced gained applying this anatomical knowledge was gathered, and the literature about the anatomy of the sylvian complex was revised, as well. Results: The Sylvian fissure extends from the basal to the lateral surface of the brain. Each surface has a superficial (sylvian stem and its rami), intermediate (anterior and lateral opercular compartments) and deep parts (sphenoidal compartment, anterior and lateral insular clefts and retroinsular region). In 7 out of 10 hemispheres, the central sulcus did not intersect with the sylvian fissure on the lateral surface of the brain. In 80% of the hemispheres, the middle cerebral artery main bifurcation was localized at or proximal to the limen insulae. Beneath the pars triangularis, the widest point of the lateral surface of the sylvian fissure is located. The authors start dissecting the sylvian fissure at this point. Conclusion: The thorough anatomical knowledge with its clinical application in modern neuroimaging are essential tools for preoperative planning and are mandatory requisites to safely operate through and around the sylvian fissure anatomical complex.