Teratoma quístico maduro con transformación maligna: serie de casos / Cystic teratoma with malignant transformation: Series of cases

Resumen OBJETIVO: Describir las características clínicas e histopatológicas de los casos de teratoma maduro con transformación maligna, su tratamiento y supervivencia. MATERIALES Y MÉTODOS: Estudio retrospectivo, transversal y observacional efectuado entre enero de 2014 y diciembre de 2018 en un servicio de oncología ginecológica. Parámetros de estudio: etapa patológica del tumor, concentraciones de Ca 125, supervivencia y tratamiento. El tamaño de la muestra no permitió aplicar pruebas estadísticas. RESULTADOS: Se estudiaron 147 pacientes con diagnóstico de teratoma maduro, de éstos 4 experimentaron transformación maligna a carcinoma epidermoide y se descartaron 18 por información incompleta. El estudio histopatológico transoperatorio identificó malignidad en 3 de los 4 tumores de ovario. No se practicaron cirugías conservadoras de la fertilidad porque en ninguno de los casos fue necesaria. En 3 de los 4 teratomas maduros con transformación maligna se indicó esquema de quimioterapia coadyuvante. Todas las pacientes permanecen vivas y sin recaída hasta el momento. CONCLUSIONES: El estudio histopatológico transoperatorio es indispensable en todas las lesiones de ovario, incluso las de aspecto quístico. El tratamiento quirúrgico cuidadoso de los tumores malignos de ovario evita su ruptura y cambio en el pronóstico y tratamiento de las pacientes. El tratamiento quirúrgico y médico de una neoplasia poco frecuente, como el teratoma maduro con transformación maligna, mejora la supervivencia y evita subtratamientos o sobretratamientos.

Abstract OBJECTIVE: Describe the clinical and histopathological characteristics of cases of mature teratoma with malignant transformation, its treatment and survival. MATERIALS AND METHODS: Retrospective, cross-sectional and observational study conducted between January 2014 and December 2018 in a gynecological oncology service. Study parameters: pathological stage of the tumor, concentrations of Ca 125, survival and treatment. The sample size did not allow statistical tests to be applied. RESULTS: 147 patients with a diagnosis of mature teratoma were studied of these 4 underwent malignant transformation to squamous cell carcinoma and 18 were ruled out due to incomplete information. The transoperative histopathological study identified 3 of the 4 ovarian tumors as malignant. Fertility conservative surgeries were not performed because in none of the cases was it necessary. In 3 of the 4 mature teratomas with malignant transformation, adjuvant chemotherapy scheme was indicated. All patients remain alive and have no relapse so far. CONCLUSIONS: The histopathological transoperatory study is absolutely necessary for an ovarian tumor, even in cystic ovarian tumors. Carefully management of ovarian tumors is very important, we should prevent a rupture of the malignant tumor because this changes the surgical stage and the prognosis. The surgical and medical treatment of infrequent tumor-like mature teratoma with malignant transformation improves survival and avoid sub treatments or overtreatment.

Micrometástasis ganglionares en pacientes con cáncer ginecológico. Serie de casos y revisión de la bibliografía / Nodal micrometastasis in gynecological cancer patients. Case series and literature review

Resumen OBJETIVO: Identificar micrometástasis ganglionares en neoplasias malignas ginecológicas, y las características histopatológicas y clínicas asociadas con los hallazgos. MATERIALES Y MÉTODOS: Estudio observacional, descriptivo y retrospectivo efectuado en pacientes con uno o más ganglios con micrometástasis identificados en cirugías primarias etapificadoras por cáncer de endometrio, ovario o cervicouterino, linfadenectomía sistemática o ganglio centinela, atendidas en el Hospital de Ginecoobstetricia Dr. Luis Castelazo Ayala, de enero de 2014 a diciembre de 2018. Criterios de exclusión: ausencia micrometástasis ganglionares. Criterios de eliminación: información incompleta en el expediente clínico, sin seguimiento y falta de evidencia patológica de micrometástasis ganglionar. Variables de estudio: identificación de ganglios con micrometástasis, diagnóstico de cáncer ginecológico por tratamiento quirúrgico y tasa de supervivencia. Para la revisión bibliográfica se consultó la base de datos de PubMed, con MeSH o palabras clave: "micrometástasis ganglionares" y "cáncer de ovario"; "cáncer de endometrio", "cáncer cervicouterino" y "cáncer ginecológico con micrometástasis". RESULTADOS: Se registraron 11 casos de micrometástasis ganglionares, de un total de 433 con cáncer de ovario, endometrio o cervicouterino. No se aplicaron pruebas estadísticas por lo limitado de la muestra. En todos los casos se identificó, mínimo, un ganglio con micrometástasis, con ganglio centinela o linfadenectomía sistemática. Todas las pacientes recibieron tratamiento coadyuvante. CONCLUSIONES: Es importante efectuar la identificación de micrometástasis en linfadenectomías sistemáticas mediante la tinción con hematoxilina-eosina (es la metodología más accesible y económica para el sistema público de salud de México) o búsqueda de ganglio centinela, con la finalidad de determinar la frecuencia en población mexicana y establecer la etapa patológica real de la enfermedad.

Abstract OBJECTIVE: To identify lymph node micrometastases in malignant gynecological neoplasms and their histopathological and clinical characteristics associated with the findings. MATERIALS AND METHODS: Observational, descriptive and retrospective study performed in patients with one or more lymph nodes with micrometastases in primary stage surgery for endometrial, ovarian or cervical cancer, systematic lymphadenectomy or sentinel node, attended at the Hospital de Ginecoobstetricia 4 Dr. Luis Castelazo Ayala, from January 2014 to December 2018. Exclusion criteria: no ganglion micrometastases. Elimination criteria: incomplete information in the clinical file, without follow-up and lack of pathological evidence of lymph node micrometastasis. The variables to be considered were: identification of lymph nodes with micrometastases, diagnosis of gynecological cancer by surgical treatment and survival rate. For the literature review, the PubMed database was consulted, with key words such as "ganglionic micrometastases" and "ovarian cancer", "endometrial cancer", "cervical cancer" and "gynecological cancer with micrometastasis". RESULTS: There were 11 cases of lymph node micrometastases, of a total of 433 with ovarian, endometrial or cervical cancer. No statistical tests were applied because of the limited sample. In all cases, a lymph node with micrometastasis, with a sentinel lymph node or systematic lymphadenectomy was identified. All patients received coadjuvant treatment. CONCLUSIONS: It is important to identify micrometastases in systematic lymphadenectomy by staining with haematoxylin-eosin (the most accessible and economical methodology for the public health system in Mexico) or sentinel lymph node search, in order to determine the frequency in the Mexican population and establish the actual pathological stage of the disease.

Resección ganglionar retroperitoneal en el cáncer ginecológico: utilidad como biomarcador predictivo / Retroperitoneal nodal dissection in gynecological cancer: utility as a predictive biomarker

Resumen Antecedentes: La linfadenectomía retroperitoneal y pélvica es parte del proceso quirúrgico de etapificación del cáncer de endometrio y ovario. La asignación de etapa y tratamiento de pacientes con cáncer cervicouterino es clínica; con radioterapia y quimioterapia concomitante, sin conocer factores pronósticos de la enfermedad local, ni el estado de la enfermedad ganglionar pélvica y retroperitoneal. En cáncer ginecológico la evaluación sistemática patológica de los ganglios retroperitoneales es decisiva para asignar la etapa (en ovario y endometrio), pero en el cáncer de cuello uterino tiene menos aprobación en las guías de tratamiento internacionales y existen menos estudios sólidos que estén a favor de la linfadenectomía etapificadora. Objetivo: Revisar el tema y demostrar la pertinencia y ventajas de la estadificación ganglionar retroperitoneal en las distintas neoplasias malignas ginecológicas. Método: Se revisó la bibliografía en la base de datos PubMed con búsqueda de palabras clave: linfadenectomía en cáncer ginecológico y metástasis ganglionares retroperitoneales en cáncer ginecológico. Resultados: Se localizaron 71 artículos con información de las variables de estudio. Al momento de su análisis sólo se incluyeron documentos con información de estudios con asignación al azar, y con información que incluyera al cáncer de endometrio, ovario o cuello uterino, abarcó 31 artículos para su análisis. Conclusiones: Además de la revisión de artículos se presenta una propuesta para evaluar las metástasis retroperitoneales y su utilidad futura como biomarcador. Con la bibliografía expuesta y nuestra propuesta de evaluación ganglionar retroperitoneal se favorece la estadificación del cáncer ginecológico (endometrio, ovario y cuello uterino).

Abstract Background: Retroperitoneal and pelvic lymphadenectomy is part of the surgical process staging of endometrial and ovarian cancer. The stage assignment and treatment of patients with cervical cancer is clinical; with radiotherapy and chemotherapy concomitant, without knowing prognostic factors of the local disease, neither status of pelvic and retroperitoneal lymph node disease. In gynecological cancer the systematic pathological evaluation of the retroperitoneal ganglia is decisive for stablished the stage (in ovarian and endometrial) but in cervical cancer has less approval in international treatment guidelines and there are fewer studies solids that are in favor of staging lymphadenectomy. Objective: To review the topic and demonstrate the relevance and advantages of staging retroperitoneal ganglionar in the different gynecological malignancies. Method: The bibliography was revised in the PubMed database with search of key words: lymphadenectomy in gynecological cancer and lymph node metastases retroperitoneal in gynecological cancer. Results: 71 articles were finded with information on the study variables. At the time of its analysis only documents with study information were included randomized, and with information that included endometrial cancer, ovary or cervix, covered 31 articles for analysis. Conclusions: In addition to the review of articles, a proposal is presented to evaluate retroperitoneal metastases and their future usefulness as a biomarker. With the exposed literature and our proposed retroperitoneal lymph node evaluation is it favors the staging of gynecological cancer (endometrium, ovary and cervix).

[Usefulness of the oncogenetic molecular counselling in adults whith familial cancer]. / Utilidad de la consulta oncogenética molecular en individuos adultos con cáncer familiar.

More than 200 cancer susceptibility syndromes (CSS) have been recognized through performing classic epidemiologic studies and genetic linkage analysis. In most CSSs clinical conditions of the patients have been identified as well as their hereditary patterns and the predisponent genes to cancer development. Cancer hereditary identification is a useful condition, since cancer family integrants may benefit of efficient strategies in early screening and in tumor prevention strategies; this consultation is performed by oncogenetic molecular medical consultants who must be scientifically competent for Human Genetics and Cancer molecular biology domains. The oncogenetic molecular consult of patients and family relatives of cancer predisposition families is a medical service in health programs of developed and developing countries; in our country this type of medical service needs to be organized and settled to be part of the integral oncology medical service. The oncogenetic molecular consultation is a structural process of assessment and communication of the associated integral problems of the cancer inherited susceptibility in familial cancer.

Se han descrito más de 200 síndromes de susceptibilidad hereditaria humana para desarrollar cáncer (SSHDC), los cuales han sido identificados a partir de estudios clásicos epidemiológicos y de análisis de ligamiento genético. En la mayoría de los SSHDC se han identificado las condiciones clínicas de los pacientes, sus patrones de herencia y los genes que predisponen al desarrollo del cáncer. La identificación de cánceres hereditarios es de gran utilidad, ya que los familiares de los pacientes podrán beneficiarse de medidas eficaces no solo en la detección precoz, sino también en la prevención de los tumores; esta identificación se realiza por medio de la consulta de especialistas en oncogenética molecular, quienes deben ser competentes en las áreas de genética humana y biología molecular del cáncer. La consulta oncogenética molecular de los pacientes y de los integrantes de familias con predisposición al cáncer es un servicio de atención médica en países desarrollados y en algunos en vías de desarrollo que se realiza desde hace más de una década; en nuestro país, este tipo de consulta requiere organizarse y establecerse para formar parte de la atención médica integral oncológica. La consulta oncogenética es un proceso estructurado de evaluación y comunicación de los problemas integrales asociados con la susceptibilidad hereditaria de padecer cáncer.

[Cell signaling pathways interaction in cellular proliferation: Potential target for therapeutic interventionism]. / Interacción de las vías de señalización intracelulares participantes en la proliferación celular: potencial blanco de intervencionismo terapéutico.

Nowadays, cellular physiology is best understood by analysing their interacting molecular components. Proteins are the major components of the cells. Different proteins are organised in the form of functional clusters, pathways or networks. These molecules are ordered in clusters of receptor molecules of extracellular signals, transducers, sensors and biological response effectors. The identification of these intracellular signaling pathways in different cellular types has required a long journey of experimental work. More than 300 intracellular signaling pathways have been identified in human cells. They participate in cell homeostasis processes for structural and functional maintenance. Some of them participate simultaneously or in a nearly-consecutive progression to generate a cellular phenotypic change. In this review, an analysis is performed on the main intracellular signaling pathways that take part in the cellular proliferation process, and the potential use of some components of these pathways as target for therapeutic interventionism are also underlined.

[Tissue regeneration strategies: cells, biochemical inductors, bionanomaterials and bioconstructions. Clinical and surgical achievements]. / Estrategias para la regeneración de tejidos: células, inductores bioquímicos, bionanomateriales y bioconstrucciones. Alcances clínico-quirúrgicos.

Regenerative medicine is a medical multidisciplinary area with the aim of morphologic and functional restoration of tissues or organs in order to re-establish normal function. The main bases of regenerative medicine are the use of autologous stem or progenitor cells and the ex vivo construction of physical-mechanical tissue structuring organization, which with stem cells may form bioartificial organs. Another eventual strategy is in vivo stem or progenitor cell stimulation for proliferation. Tissue engineering entirely combines the use of cells, biochemical and physicochemical factors, nanomaterials and bioengineering methods to improve or replace biological functions of tissues and organs. The progressive understanding of the proliferation and differentiation of the process of stem cells and their in vitro manipulation has been the launching platform for the field of regenerative medicine. In this review we describe the main strategies used for regenerative medicine in tissue regeneration along with the main obtained clinicalsurgical benefits.

La medicina regenerativa es una área multidisciplinaria destinada a la recuperación morfológica y funcional de tejidos y órganos severamente lesionados. Los principales recursos que emplea la medicina regenerativa son: células madre o troncales autólogas, y moldes estructurales de soporte físico-mecánico tisular construidos ex vivo, que pueden formar órganos bioartificiales; otra posibilidad es la estimulación de células madre in vivo para su proliferación. La ingeniería tisular combina, integralmente, el uso de células, factores bioquímicos y físicos, nanomateriales y métodos de bioingeniería para mejorar o remplazar las funciones biológicas de tejidos y órganos. El entendimiento progresivo de los procesos de proliferación y diferenciación celulares, y la manipulación in vitro de las células madre, ha sido la plataforma del desarrollo de la medicina regenerativa. En esta revisión se describen las diferentes estrategias que utiliza la medicina regenerativa en la regeneración de tejidos, y los principales beneficios clínico-quirúrgicos conseguidos con su aplicación.

[Targeted epigenetic therapy of cancer. Achievements and perspectives]. / Terapia epigenética en el cáncer. Logros y perspectivas.

In this review, we provide an overview of the physiological and pathophysiological epigenetic changes of normal cells and cancer cells, and emphasize the achievements and the perspectives of cancer epigenetic therapy. Cancer epigenetic alterations correspond foremost to hypermethylation of tumor suppressor genes promotors, global DNA hypomethylation, and overexpression and activity of histone deacetylases. The purpose of epigenetic therapy is to revert the epigenetic alterations in cancer cells and obtain the "normal epigenome" restoration. Epigenetic targets in cancer therapy have focused on HDACs and DNMTs inhibition. The azacitidine and the decitabine, the vorinostat and the romidepsin were approved by US-FDA for treatment of myelodysplastic syndrome, and cutaneous T-cell lymphoma, respectively. Epigenetic and epigenomic changes in single or multiple genes have showed potential impact in cancer as early detection, prognosis and predictive marks. The epigenetic revolution has arrived for biology. The significant progress in epigenetic studies have allowed us, to understand new looks in the physiology and pathophysiology of embryonic development, cancer and other chronic diseases. Specific molecular epigenetic alterations in different cancer types, give us new strategies to design improved cancer therapy. The challenge for epigenetic investigators is design more specific epidrugs with lesser side effects.

[Non-classical cellular and molecular deficits in cancer development]. / Alteraciones celulares y moleculares no clásicas en el desarrollo del cáncer.

A wide number of genetic and epigenetic changes are required to drive normal cells towards malignancy. These changes participate in oncogenic intracellular pathways that allow tumor cells proliferation and dissemination. Hanahan and Weinberg' in their seminal paper "The hallmarks of cancer" described the classic cell hallmarks acquired in cancer development and progression: self-sufficiency in growth signals, insensitivity to anti-growth signals, evading apoptosis, limitless replication potential, sustained angiogenesis, tissue invasion and metastasis. This review covers other recently described biological characteristics associated with the emergence of cancer. Some of the main non-classical hallmarks of cancer that are broadly accepted include: genetic instability, evasion of cell senescence, epigenetic alterations of cancer related-genes, RNA interference alterations in the expression of cancer related-genes, changes in glucose and glutamine metabolism, participation of cancer stem cells in cellular proliferation, stromal cell participation in the tumor's micro-environment, and changes in antigenic presentation and immunosuppression due to cytokines in the tumor's micro-environment. The identification of molecular biomarkers of classical and non classical tumor processes in a specific tumor will allow a better understanding of its pathophysiology. It will also permit the design of ad-hoc therapeutic strategies.

The translational research unit as support for the current practice of medicine.

In the first part of the present paper the basis and importance of translational medicine (TM) on the current status of quality of health care is discussed. This is exemplified by the application and benefit of translational oncology and personalized oncology in cancer patients as a model of TM. The second part of this article discusses the processes that have allowed the expansion of TM in developed countries and, likewise, the global conditions that have disabled the installation and expansion of TM in Mexico. The author suggests the establishment of translational research (TR) units in third-level hospitals, which will allow the formal initiation of TM in Mexico. The author concludes that the policy of TR in regard to national public health care is currently necessary. This policy requires the participation of government, national medical academies and societies, health sector medical centers, medical and research educators, centers of investigation, pharmaceutical and biotechnology industries, medical and biomedical physicians, and any other persons or entities who participate in the implicit improvement of the level of medical care. The installation of TR units located in hospitals represents a common benefit for the entire society and, specifically, for patients through the generation of a health care system with a higher scientific level, as well as higher quality of care.

La unidad de investigación traslacional como sustento de la medicina actual / The translational research unit as support for the current practice of medicine

Se discuten los principios, fundamentos e importancia de la medicina traslacional en la calidad de la atención de la salud en la actualidad. Se ejemplifica la medicina traslacional con la aplicación y el beneficio de la oncología traslacional y la oncología personalizada en pacientes con cáncer. Se describe el proceso que ha permitido la expansión de la medicina traslacional en los países desarrollados y las condiciones globales que han impedido en nuestra nación iniciar formalmente el proceso de expansión de la medicina traslacional. Se propone establecer unidades de investigación traslacional en hospitales de tercer nivel que permitan el inicio formal de la medicina traslacional en México. La implantación de una política de investigación traslacional en la atención es absolutamente obligada en el momento actual, y compromete la participación del Estado, academias y sociedades médicas nacionales, centros hospitalarios del sector salud, centros de educación e investigación biomédicos, industrias farmacéuticas biotecnológicas y profesionales médicos, así como de todos los agentes que intervienen en el mejoramiento tácito del nivel de atención médica. Con el funcionamiento de las unidades de investigación traslacional se generará un sistema de atención al enfermo de mayor calidad y mejor nivel científico.

In the first part of the present paper the basis and importance of translational medicine (TM) on the current status of quality of health care is discussed. This is exemplified by the application and benefit of translational oncology and personalized oncology in cancer patients as a model of TM. The second part of this article discusses the processes that have allowed the expansion of TM in developed countries and, likewise, the global conditions that have disabled the installation and expansion of TM in Mexico. The author suggests the establishment of translational research (TR) units in third-level hospitals, which will allow the formal initiation of TM in Mexico. The author concludes that the policy of TR in regard to national public health care is currently necessary. This policy requires the participation of government, national medical academies and societies, health sector medical centers, medical and research educators, centers of investigation, pharmaceutical and biotechnology industries, medical and biomedical physicians, and any other persons or entities who participate in the implicit improvement of the level of medical care. The installation of TR units located in hospitals represents a common benefit for the entire society and, specifically, for patients through the generation of a health care system with a higher scientific level, as well as higher quality of care.

[Alterations in cancer cell signaling pathways].

Transitions from normal cell to neoplastic malignant cell type require multiple alterations in cell signalling pathways. Transduction and transmission of these signalling pathways are dependent on integrated molecular circuits. A paramount aspect in cancer development is the concept that the cell loses its ability to detect and respond to extracellular signals and frequently develops autocrine signals for overcoming normal physiological controls. Therefore, we analyzed the current concepts of general principles in physiological and some oncogenic cell signalling pathway patterns. We carried out a documentary review of 29 scientific items in which we identified intracellular signalling pathway systems in each cell so complex due to the high number of participants and the multiple differences among specific cell types. The knowledge and identification of general principles regarding the whole physiological cell signaling pathway patterns help us to understand the oncogenic signaling pathways. Identification of these pathways in any tumor can be used as prognosis or predictor biomarkers in the patient's outcome or as target in clinical therapeutic trials.

Alteraciones en los señalamientos intracelulares en el cáncer / Alterations in cancer cell signaling pathways

La transición de una célula normal a una célula maligna implica diferentes alteraciones de sus vías de señalización intracelular. La transducción y transmisión de estos señalamientos intracelulares depende de circuitos moleculares. Un aspecto central del cáncer es el concepto de que las células pierden su capacidad para detectar y responder de forma adecuada a los señalamientos extracelulares y que frecuentemente desarrollan señalamientos autocrinos para superar los controles normales. El objetivo de esta investigación fue analizar los principios generales de las vías de señalamiento celulares fisiológicas y sus principales alteraciones en algunos modelos de células neoplásicas, para lo cual se realiza una revisión documental de 29 artículos recientes. Las redes de señalización intracelular en cada célula son muy complejas debido al gran número de vías participantes y a las múltiples diferencias de ellas en los tipos celulares específicos. El entendimiento e identificación de los principios generales comunes en la mayoría de las vías de señalamiento intracelulares normales, facilitará la comprensión de las vías de señalamiento oncogénicas. La identificación del patrón de las vías de señalamiento oncogénicas en cada tumor, podría servir como marcador pronóstico o predictivo en la evolución clínica del paciente o como blanco en protocolos de intervensionismo terapéutico molecular.

Transitions from normal cell to neoplastic malignant cell type require multiple alterations in cell signalling pathways. Transduction and transmission of these signalling pathways are dependent on integrated molecular circuits. A paramount aspect in cancer development is the concept that the cell loses its ability to detect and respond to extracellular signals and frequently develops autocrine signals for overcoming normal physiological controls. Therefore, we analyzed the current concepts of general principles in physiological and some oncogenic cell signalling pathway patterns. We carried out a documentary review of 29 scientific items in which we identified intracellular signalling pathway systems in each cell so complex due to the high number of participants and the multiple differences among specific cell types. The knowledge and identification of general principles regarding the whole physiological cell signaling pathway patterns help us to understand the oncogenic signaling pathways. Identification of these pathways in any tumor can be used as prognosis or predictor biomarkers in the patient's outcome or as target in clinical therapeutic trials.

[Molecular therapeutics in patients with cancer unresponsive to conventional treatments]. / Terapias moleculares dirigidas en los pacientes con cáncer: logros y perspectivas.

Recent advances and insights into the molecular pathogenesis of cancer provide unprecedented opportunities for discovery and development of molecularly target-therapeutic (MTT) strategies. Cancer is a complex process due to accumulation of multiple mutations and alterations in the genoma. Tumor cells seem to rely heavily on the continued deregulation of one or more signaling pathways. Complete identification on cell signaling deregulations have provided greater understanding on the biology that underlies most cancers. High-throughput technologies in genomics and proteomics can help to detect the response in vitro and in vivo of targeted MTT effects. Cancer MTT are drugs blocking specific oncogenes or oncogenic signaling pathways and can secondary block off the growth and spreading involved in carcinogenesis and tumor progression. In this paper we revised concepts of oncogene addiction, oncogenic pathways signature and commented the high-tech technologies related to their study. Also we revised the favorable clinical results using new MTT strategies for hard-to-treat cancers in the last year, and the limitations and perspectives to achieve more effective targeted cancer therapy results. Identification of a progressive number of molecularly targeted oncogenes and their corresponding blocking agents will give cancer MTT strategies great potential for development in the next years. Novel biologic endpoints and innovative clinical designs are also required to the successful application of the therapies.

Terapias moleculares dirigidas en los pacientes con cáncer: logros y perspectivas / Molecular therapeutics in patients with cancer unresponsive to conventional treatments

Los avances recientes en la patogénesis molecular del cáncer han permitido descubrir y desarrollar estrategias basadas en la utilización de moléculas con actividad biológica específicas o terapias moleculares dirigidas (TMD). El cáncer es un proceso complejo debido a la acumulación de mutaciones y alteraciones en el genoma. Las células tumorales parecen depender de una continua desregulación de una o varias vías de señalamiento intracelular. El conocimiento integral de estas vías logrará descifrar la biología de trasfondo de la mayoría de los cánceres. Las tecnologías de punta en genómica y proteómica pueden ayudar a identificar la respuesta in vitro e in vivo del intervensionismo de las TMD, las cuales comprenden agentes que bloqueando los oncogenes o las vías oncogénicas de señalamientos, pueden secundariamente detener la carcinogénesis y la progresión tumoral. Revisamos los conceptos de adicción oncogénica, de rúbrica de la vía oncogénica, algunas tecnologías, los resultados obtenidos con TMD en pacientes con cáncer que no responde a tratamiento convencional, y las limitaciones y perspectivas de esta nueva estrategia. Potencialmente, la TMD conseguirá mayor desarrollo a través de identificar un número progresivo de oncogenes blanco-moleculares y sus correspondientes agentes bloqueadores. Se requiere mejorar los criterios de diseño, ejecución y valoración clínicos en la aplicación de protocolos con terapias moleculares dirigidas.

Recent advances and insights into the molecular pathogenesis of cancer provide unprecedented opportunities for discovery and development of molecularly target-therapeutic (MTT) strategies. Cancer is a complex process due to accumulation of multiple mutations and alterations in the genoma. Tumor cells seem to rely heavily on the continued deregulation of one or more signaling pathways. Complete identification on cell signaling deregulations have provided greater understanding on the biology that underlies most cancers. High-throughput technologies in genomics and proteomics can help to detect the response in vitro and in vivo of targeted MTT effects. Cancer MTT are drugs blocking specific oncogenes or oncogenic signaling pathways and can secondary block off the growth and spreading involved in carcinogenesis and tumor progression. In this paper we revised concepts of oncogene addiction, oncogenic pathways signature and commented the high-tech technologies related to their study. Also we revised the favorable clinical results using new MTT strategies for hard-to-treat cancers in the last year, and the limitations and perspectives to achieve more effective targeted cancer therapy results. Identification of a progressive number of molecularly targeted oncogenes and their corresponding blocking agents will give cancer MTT strategies great potential for development in the next years. Novel biologic endpoints and innovative clinical designs are also required to the successful application of the therapies.

Atención de las emergencias y urgencias médico-quirúrgicas en un hospital oncológico / Emergencies and urgent medical-surgical conditions attended at a comprehensive cancer center

La incidencia global de las emergencias y urgencias médicoquirúrgicas en pacientes con cáncer ha sido descrita esporádicamente. El objetivo del estudio fue identificar los principales síntomas y diagnósticos de los pacientes que acudieron al Servicio de Urgencias del Hospital de Oncología, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social. El diseño fue observacional y retrospectivo. La información fue obtenida del registro de la consulta diaria del Servicio de Admisión Continua. En un periodo de seis meses fueron atendidos 4,937 pacientes. Los cuadros clínicos evaluados como emergencias correspondieron a 3.7 %, como condiciones médicas urgentes 52.5 % y como condiciones no urgentes, 43.7 %. Los síntomas más frecuentes motivo de las consultas de emergencia o urgencias en los pacientes con cáncer fueron dolor grave en 69.5 % y deshidratación con desequilibrio hidroelectrolítico en 11.4 %. Los principales síntomas fueron provocados por el tumor primario o su diseminación metastásica, en 89 %. Los tumores malignos sólidos más frecuentes fueron los carcinomas mamario, de colon/recto, cervicouterino, broncogénico y gástrico. Las principales emergencias registradas en los pacientes con cáncer en este estudio fueron choque séptico y neutropenia severa (20 %), choque hipovolémico por sangrado en diversos sitios (16.5 %) y disnea agudizada por neumonía o derrame pleural (12 %). En aproximadamente 80 % de quienes son tratados paso a paso de manera racional, el dolor por cáncer pudo ser controlado sólo con analgésicos. La analgesia no efectiva se asoció frecuentemente con prescripción inadecuada o ingesta insuficiente de analgésicos opioides. Los servicios de urgencias establecidos funcionalmente en los hospitales monográficos de cáncer ofrecen la mejor oportunidad de tratamiento a los pacientes con cáncer con condiciones emergentes o urgentes.

The global incidence of emergencies and urgent medical?surgical conditions in cancer patients has not been well described. The aim of the study was to identify the main symptoms and diagnoses in patients seen for consultation at the Urgent Care Service in a Mexican Comprehensive Cancer Center. This was a retrospective observational study. The information was obtained from the Continuous Admission Service daily consultation records at the Oncology Hospital, National Medical Center 21st Century, Institute of Social Security, Mexico City. During a 6-month period, 4937 patients were seen for consultation. True oncologic emergencies were 3.7%, urgencies 52.5% and non-urgent were 43.7%. Most common symptoms for emergency and urgency patient consultations were severe pain (69.5%) and dehydration with electrolyte imbalance (11.4%). Prevalent symptoms were associated with the primary tumor or metastatic dissemination (89% cases). The most frequent baseline diseases were breast, colorectal, cervical, lung and stomach carcinomas. Defined oncologic emergencies in this series were septic shock and severe neutropenia (20%), hypovolemic shock due to severe bleeding (16.5%), and severe dyspnea due to pneumonia or pleural efusion (12%). Data evaluating the use of analgesic drug therapy for cancer pain alone indicate that 80% of patients report adequate analgesia. Analgesia failures were associated with an insufficient prescription or with inadequate consumption of opioid analgesics. The Urgent Care Center at a Comprehensive Cancer Center offers the best opportunity for diagnosis and treatment of emergencies and urgent care conditions in cancer patients.

[Emergencies and urgent medical-surgical conditions attended at a comprehensive cancer center]. / Atencián de las emergencias y urgencias médico-quirúrgicas en un hospital oncológico.

The global incidence of emergencies and urgent medical?surgical conditions in cancer patients has not been well described. The aim of the study was to identify the main symptoms and diagnoses in patients seen for consultation at the Urgent Care Service in a Mexican Comprehensive Cancer Center. This was a retrospective observational study. The information was obtained from the Continuous Admission Service daily consultation records at the Oncology Hospital, National Medical Center "21st Century," Institute of Social Security, Mexico City. During a 6-month period, 4937 patients were seen for consultation. True oncologic emergencies were 3.7%, urgencies 52.5% and non-urgent were 43.7%. Most common symptoms for emergency and urgency patient consultations were severe pain (69.5%) and dehydration with electrolyte imbalance (11.4%). Prevalent symptoms were associated with the primary tumor or metastatic dissemination (89% cases). The most frequent baseline diseases were breast, colorectal, cervical, lung and stomach carcinomas. Defined oncologic emergencies in this series were septic shock and severe neutropenia (20%), hypovolemic shock due to severe bleeding (16.5%), and severe dyspnea due to pneumonia or pleural efusion (12%). Data evaluating the use of analgesic drug therapy for cancer pain alone indicate that 80% of patients report adequate analgesia. Analgesia failures were associated with an insufficient prescription or with inadequate consumption of opioid analgesics. The Urgent Care Center at a Comprehensive Cancer Center offers the best opportunity for diagnosis and treatment of emergencies and urgent care conditions in cancer patients.

Interdisciplinary clinical evaluation of 58 patients with lumbar-vertebral metastases from cervico-uterine cancer.

INTRODUCTION: Metastases in the vertebrae of patients with cervical cancer (CeCa) can be difficult to diagnose, and the treatment is palliative in many cases. OBJECTIVES: The aim of this study was to assess the ti-me required for diagnosis, the lesion's locoregional extent and the therapeutic schemes applied, in a retrospective series of 58 patients with CeCa and with lumbar spinal metastases. METHODS: The cases were studied using an updated interdisciplinary analysis to determine the clinical and radiological variables. This study evaluated the site and extent of bone lesions and correlated these variables with instability of the spine and cord compression. RESULTS: The diagnosis of vertebrae metastases of Ce-Ca required more than 3 months in most cases. Lumbar vertebrae L4 and L5 and specifically the vertebral body were the most-frequently affected si-tes. Systemic and/or extra-compartmental-extended metastases (MosV4) were observed in 44/58 patients. Radiotherapy was the only option in this group and the palliative effect achieved was minimal, or null. In 14/58 patients there was intra compartmental-extended (MosV2) and extra-compartmental limited (MosV3) single vertebral metastases and the 3 different treatment schemes were administered. In the cases treated with marginal resection of metastases, vertebroplasty plus adjuvant radiotherapy achieved significant palliative effect. CONCLUSIONS: In the present series of patients, the diagnosis of metastases of the lumbar vertebrae was late, and the disease was advanced. The results obtained with radiotherapy in advanced stage disease did not improve the quality of life of patients. Metastasectomy was the therapeutic scheme in cases with intermediate stage disease and was the basis of the integrated treatment We believe that it is necessary to shorten the diagnostic time and to apply a staging system for vertebral metastases so that appropriate individualised selection of interdisciplinary treatment would be facilitated.