Estandarización de requerimientos mínimos para la formación de centro de detección temprana de cáncer de pulmón en América Latina / Standardization of Minimum Requirements for the Formation of an Early Detection Center for Lung Cancer in Latin America

Introducción: El cáncer de pulmón (CP) es una enfermedad con gran impacto a nivel mundial en el número de muertes y en costos en salud. La alta incidencia y mortalidad de esta enfermedad asociada al diagnóstico tardío, y la mejoría del pronóstico ante una detección temprana, determinan que sea una patología pasible de beneficiarse mediante detección temprana. La tomografía de baja dosis de radiación (TCBD) demostró ser un método que se pue- de realizar periódicamente a un grupo de personas con alto riesgo de desarrollar CP y así reducir la mortalidad por esta enfermedad. Sin embargo, este beneficio es tal cuan- do se encuentra desarrollado bajo un programa organizado y con participación multi- disciplinaria especializada en cáncer de pulmón. Métodos: Se plantea determinar lineamientos básicos para el desarrollo de la detección temprana de cáncer de pulmón en América Latina para que pueda ser realizada en forma uniforme, con el menor riesgo y el máximo beneficio esperado. Se analizaron las principales publicaciones referidas a este tema, contemplando la diversidad de atención y acceso de América Latina. Resultado: Se desarrollan requerimientos mínimos para la implementación de un pro- grama. Discusión: El número de programas en la región es escaso y depende más de esfuerzos individuales que de políticas generales de salud. Consideramos que estos lineamien- tos pueden servir de apoyo para el desarrollo de más programas en la región y de for- ma más homogénea.

Introduction: Lung cancer (LC) is a disease with a great impact worldwide in the number of deaths and health costs. The high incidence and mortality of this disease associated with late diagnosis and the improved prognosis with early detection determine that it is a pathology that can benefit from early detection. Low radiation dose tomography (LDCT) demonstrated a method that can be performed periodically to a group of people at high risk of developing CP and thus reduce mortality from this disease. However, this benefit is such when it is developed under an organized program with multidisciplinary participation specialized in lung cancer. Methods: It is proposed to determine basic guidelines for the development of early de- tection of lung cancer in Latin America so that it can be carried out uniformly, with the lowest risk and the maximum expected benefit. The main publications referring to this topic were analyzed, considering the diversity of care and access in Latin America. Result: Minimum requirements are developed for the implementation of a program. Discussion: The number of programs in the region is small and depends more on individual efforts than on general health policies. We consider that these guidelines can serve as support for the development of more programs in the region and in a more ho- mogeneous way.

Identificación de las características de los ganglios evaluados en el procedimiento EBUS y su relación con el diagnóstico de malignidad en instituto de alta complejidad en cáncer / Identification of the Characteristics of the Lymph Nodes Evaluated in the EBUS Procedure and their Relationship with the Diagnosis of Malignancy in a Highly Complex Cancer Institute

Introducción: La EBUS ha sido el foco de numerosos estudios destinados a evaluar su utilidad y rendimiento diagnóstico en diversas patologías. Objetivo principal: Identificación de las características ganglionares evaluadas en el procedimiento de Ultrasonido Endobronquial (EBUS) y su relación con el diagnóstico de malignidad en pacientes del Instituto Nacional del Cáncer de Colombia del 1 de enero de 2017 al 31 de marzo de 2021.Métodos: Estudio analítico observacional transversal. La recopilación de datos implicó un muestreo de casos consecutivos no probabilísticos entre individuos que cumplían los criterios de inclusión.Resultados: Un total de 75 pacientes fueron sometidos a EBUS. Se identificaron 6 características ecográficas de los ganglios de la biopsia asociadas a malignidad destacándose los ganglios mayores de 1 cm, márgenes mal definidos, ecogenicidad heterogénea, ausencia de una estructura hiliar central, presencia de signos de necrosis o coagulación y presencia de conglomerado ganglionar. Conclusión: Este estudio caracterizó la frecuencia de los hallazgos en la ultrasonografía endobronquial destacando algunas características ecográficas de los ganglios mediastínicos que podrían predecir patología maligna.

Introduction: The EBUS has been the focus of numerous studies aiming to evaluate its utility and diagnostic performance across various pathologies. Objective: Identification of the node characteristics evaluated in the Endobronchial Ultrasound (EBUS) procedure and their relationship with malignancy diagnosis in patients at the National Cancer Institute of Colombia from January 1st, 2017, to March 31st, 2021. Methods: Observational cross-sectional analytical study. Data collection involved non-probabilistic consecutive case sampling among individuals meeting the inclusion criteria.Results: A total of 75 patients underwent the EBUS procedure. Our findings revealed six predictors of malignancy based on sonographic features of biopsy nodes, including nodes larger than 1 cm, poorly defined margins, heterogeneous echogenicity, absence of a central hilar structure, presence of signs indicating necrosis or coagulation, and the presence of a ganglion conglomerate. Conclusions: This study showed that endobronchial ultrasonography has several sonographic characteristics at the time of evaluating mediastinal nodes that could predict malignant and benign pathology.

Factores pronósticos y la influencia en la supervivencia de operados de cáncer de pulmón en el Hospital Universitario General Calixto García / Prognostic Factors and their Influence of Patients Operated on for Lung Cancer at Hospital Universitario General Calixto García

Introducción: El cáncer de pulmón ocupa el primer lugar entre las causas de mortalidad por cáncer a nivel mundial y solamente el 15,6 por ciento de los que padecen esta enfermedad sobreviven los 5 años. Objetivo: Evaluar la influencia de los factores pronósticos en la supervivencia de operados por cáncer de pulmón. Métodos: Estudio observacional descriptivo, tipo serie de casos de 107 enfermos operados en el Hospital Universitario General Calixto García en el período 2015-2020. Se utilizaron las variables tipo histológico, estadio clínico, estado físico e intervención quirúrgica. Resultados: Predominó el sexo masculino en edades entre 60-69 años, con antecedentes de hipertensión arterial y tabaquismo. Los síntomas que predominaron fueron la disnea, la tos y el dolor torácico. Las etapas clínicas más frecuentes fueron en orden: IIIA, IIB, IIA y las variantes histopatológicas adenocarcinoma y epidermoide. La técnica quirúrgica más empleada fue la lobectomía. Conclusiones: Los factores pronósticos de mayor significación estadística son la comorbilidad, la presencia de síntomas y el diagnóstico tardío. Los factores pronósticos relacionados con el tumor y el tratamiento quirúrgico con adyuvancia tienen una alta repercusión en la supervivencia(AU)

Introduction: Lung cancer ranks first among the causes of cancer mortality worldwide and only 15.6 percent of those with this disease survive the 5 years. Objective: To assess the influence of prognostic factors on the survival of patients operated on for lung cancer. Methods: A descriptive observational study of case series was carried out with 107 patients operated on at Hospital Universitario General Calixto García in the period 2015-2020. The variables histological type, clinical stage, physical condition and surgical intervention were used. Results: There was a predominance of the male sex, aged 60-69 years, with a history of arterial hypertension and smoking. The predominant symptoms were dyspnea, cough and chest pain. The most frequent clinical stages were IIIA, IIB, IIA, in that order; and the predominant histopathological variants were adenocarcinoma and epidermoid. The most commonly used surgical technique was lobectomy. Conclusions: The prognostic factors of greatest statistical significance are comorbidity, presence of symptoms and late diagnosis. Prognostic factors related to the tumor or the adjuvant surgical treatment have a high impact on survival(AU)

Impacto de la COVID-19 en los enfermos con diagnóstico de cáncer de pulmón en el Hospital Universitario General Calixto García / Impact of COVID-19 on Ill Patients Diagnosed with Lung Cancer at Hospital Universitario General Calixto García

Introducción: En enero de 2020 la Organización Mundial de la Salud declara el estado de pandemia por COVID-19. Los enfermos con cáncer de pulmón tienen gran vulnerabilidad ante esta enfermedad. Objetivo: Evaluar el impacto de la COVID-19 en los enfermos con diagnóstico de cáncer de pulmón. Método: Se realizó un estudio descriptivo, retrospectivo y longitudinal en 273 enfermos con cáncer de pulmón, discutidos en el Grupo Multidisciplinario de Tórax del Hospital Universitario General Calixto García desde el 2019 hasta el 2021. Se analizaron diferentes variables y se aplicaron análisis estadísticos, tales como porcentaje, desviación estándar y media. Resultados: El mayor número de enfermos operados discutidos en el grupo multidisciplinario fue durante el 2019 (21 para un 19,45 porciento). La etapa clínica II predominó en el año 2019, en 10 pacientes. La lobectomía fue la técnica más empleada y predominó en el 2019 en 16 enfermos (76,2 porciento), mientras que durante el 2020-2021 fueron 7. En estos años se diagnosticaron con COVID-19 un total de 17 individuos no operados y fallecieron 11. Conclusiones: Durante el período 2020-2021 disminuyó el número de casos discutidos por cáncer de pulmón en el Grupo Multidisciplinario de Tórax del Hospital Universitario General Calixto García. La mayoría no tuvo criterio de cirugía. La lobectomía fue la técnica quirúrgica más empleada, aunque se redujo su realización durante el 2020-2021. La mayoría de los enfermos que contrajeron COVID-19 no fueron operados y más de la mitad de ellos fallecieron(AU)

Introduction: In January 2020, the World Health Organization declares a pandemic status due to the COVID-19. Lung cancer patients are highly vulnerable to this disease. Objective: To evaluate the impact of COVID-19 in patients diagnosed with lung cancer. Methods: A descriptive, retrospective and longitudinal study was carried out in 273 patients with lung cancer, discussed in the multidisciplinary thorax group at Hospital Universitario General Calixto García from 2019 to 2021. Different variables were analyzed and statistical analyses were applied, such as percentage, standard deviation and mean. Results: The highest number of operated patients discussed in the multidisciplinary group was reported during 2019 (21, accounting for 19.45 percent). The clinical stage II predominated in 2019, with 10 patients. Lobectomy was the most used technique and the predominant in 2019, with 16 patients (76.2 percent), while 7 were reported during 2020-2021. A total of 17 nonoperated individuals were diagnosed with COVID-19 in these years and 11 died. Conclusions: During 2020-2021, there was a decrease in the number of lung cancer cases discussed in the multidisciplinary thorax group at Hospital Universitario General Calixto García decreased. Most of them did not have surgery criteria. Lobectomy was the most used surgical technique, although its realization was reduced during 2020-2021. Most of the patients who contracted COVID-19 were not operated and over half of them died(AU)

Biliotórax: una entidad rara para un diagnóstico frecuente. Un reporte de caso / Bilothorax: a Rare Entity for a Frequent Diagnosis. A Case Report

Introducción: El biliotórax es una condición infrecuente definida por la presencia de bilis en el espacio pleural. Actualmente, hay alrededor de 70 casos descritos en la litera-tura. Sigue siendo relativamente desconocido, por lo tanto, poco sospechado. Esta entidad suele ser el resultado de una lesión iatrogénica, a menudo secundaria a cirugías o traumatismos del tracto biliar, que conduce a la formación de una fístula pleurobiliar.

Introduction: Bilothorax is a rare condition defined by the presence of bile in the pleural space. Currently, there are around 70 cases described in the literature. It remains relatively unknown and, therefore, little suspected. This entity is usually the result of an iatrogenic injury, often secondary to surgery or trauma to the biliary tract, leading to the formation of a pleurobiliary fistula

Carcinomatosis peritoneal en cáncer de pulmón: revisión de la literatura con reporte de caso / Peritoneal Carcinomatosis in Lung Cancer: Literature Review with a Case Report

En Colombia, para 2020, el cáncer de pulmón se reportó como la segunda neoplasia con mayor incidencia y la primera con mayor tasa de mortalidad según las cifras del minis-terio de salud de Colombia. El compromiso peritoneal en el cáncer de pulmón es algo extremadamente raro, se considera <1%. A continuación, exponemos un caso de car-cinomatosis peritoneal en cáncer de pulmón en un hospital en la ciudad de Bogotá. Se incorpora una posterior revisión descriptiva de la literatura de los casos clínicos de car-cinomatosis peritoneal en cáncer de pulmón reportados en la literatura mundial en los últimos 20 años, con el objetivo de resumir las principales características de estos pa-cientes que permiten plantear hipótesis de su enfoque terapéutico y pronóstico

In Colombia for 2020, lung cancer was reported as the fifth neoplasm with the highest incidence and the second with the highest mortality rate. Peritoneal involvement in lung cancer is extremely rare, it is considered <1%. Next, we present a case of peritoneal car-cinomatosis in lung cancer in Bogotá, with a subsequent literature review of the litera-ture of clinical cases of peritoneal carcinomatosis in lung cancer reported in the world li-terature in the last 20 years. The aim is to summarize the main characteristics of these patients that allow to hypothesize their prognostic and therapeutic approach

Evolução da mortalidade por neoplasias entre os anos de 2010 a 2020 no Brasil segundo sexo e localização primária do tumor / Evolution of mortality from neoplasms between the years 2010 to 2020 in Brazil according to gender and primary location of the tumour

Introdução: o câncer é um grave problema de saúde pública, considerado a segunda causa de óbitos no Brasil. Devido à sua relevância, é indispensável um controle eficiente dos casos através do acompanhamento da taxa de mortalidade. Dessa forma, o trabalho analisou a evolução da mortalidade por câncer para as localizações primárias mais frequentes, segundo sexo, durante o período de 2010 a 2020. Metodologia: trata-se de um estudo observacional descritivo, no qual os dados foram obtidos através do Atlas On-line de Mortalidade por Câncer. Os dados colhidos correspondem ao número de óbitos estratificados por tipo de câncer mais frequente, por ano estudado e por sexo, além das taxas de mortalidade específica bruta e a taxa de mortalidade ajustada por idade para o sexo masculino e feminino, para cada tipo de câncer em estudo, considerando a população padrão mundial, sendo avaliado por regressão linear a significância da tendência temporal. Resultados: no Brasil, no período de 2010 a 2020, as neoplasias mais frequentes em mulheres foram câncer de mama, câncer nos brônquios e pulmões, câncer no colo do útero, câncer no cólon e no pâncreas e em homens foram brônquios e pulmões, câncer de próstata, câncer de estômago, de esôfago e no fígado e vias biliares, sendo observado uma tendência crescente na taxa de mortalidade em mulheres e decrescente na taxa de mortalidade em homens. Conclusão: os resultados demonstram um possível comprometimento com a notificação durante o período de pandemia por Covid-19 e um possível rastreamento ainda deficiente de câncer na população masculina.

Introduction: cancer is a severe public health problem, considered the second cause of death in Brazil. Due to its relevance, efficient control of cases by monitoring the mortality rate is essential. Thus, the work analysed the evolution of cancer mortality for the most frequent primary locations, according to sex, from 2010 to 2020. Methodology: this is a descriptive observational study in which data were obtained through the Atlas Online Cancer Mortality Report. The data collected correspond to the number of deaths stratified by the most frequent type of cancer, by year studied and by sex, in addition to the crude specific mortality rates and the age-adjusted mortality rate for males and females, for each type of cancer. Understudy, considering the standard world population, the significance of the temporal trend is evaluated by linear regression. Results: in Brazil, from 2010 to 2020, the most frequent neoplasms in women were breast cancer, bronchial and lung cancer, cervical cancer, colon and pancreas cancer and in men, they were bronchial and lung cancer, cancer prostate, stomach, oesophagal and liver and biliary tract cancer, with an increasing trend in the mortality rate in women and a decreasing trend in the mortality rate in men. Conclusion: the results demonstrate a possible compromise with notification during the Covid-19 pandemic and a possible still poor screening of cancer in the male population.

Papel de la persona navegadora del paciente en el cáncer de pulmón / The Role of the Navigator Person for a Patient with Lung Cancer

Introducción: la medicina basada en el valor ha logrado mejorar la calidad de atención del paciente y/o la satisfacción de las personas, reduciendo costos y obteniendo mejores resultados. Se apoya sobre tres pilares básicos: la medicina basada en la evidencia, la atención centralizada en el paciente, y la sustentabilidad. Sin embargo, existen pocas publicaciones sobre la estrategia de personas navegadoras para pacientes con cáncer de pulmón, que podrían ser una herramienta clave para brindar apoyo, asegurando que tengan acceso al conocimiento y los recursos necesarios a fin de completar la vía de atención clínica recomendada. Estado del arte: se trata de una intervención en salud cuyo objetivo principal es lograr vencer las barreras relacionadas con la atención (p. ej., logísticas, burocrático-administrativas, de comunicación y financieras) para poder mejorar la calidad y el acceso a la salud en el marco de la atención del cáncer. Estas personas cumplen un papel de guía para pacientes durante el proceso de diagnóstico y tratamiento activo. Su labor consiste en vincular al paciente con los proveedores clínicos, brindar un sistema de apoyo, asegurar un acompañamiento individualizado, garantizar que tengan acceso al conocimiento y a los recursos necesarios para completar el seguimiento y/o tratamiento adecuado. Discusión/Conclusión: indudablemente, es un elemento cada vez más reconocido en los programas de cáncer, centrado en el paciente y de alta calidad. Su implementación será de especial interés en la Unidad de Práctica Integrada para personas con cáncer de pulmón. (AU)

Introduction: Value-based medicine has succeeded in improving the quality of patient care and or patient satisfaction, reducing costs, and obtaining better outcomes. It rests on three fundamental pillars: evidence-based medicine, patient-centered care, and sustainability. However, there are few publications on the people navigator strategy for lung cancer patients, which could be a crucial tool for providing support, ensuring that they have access to the knowledge and resources needed to complete the recommended clinical care pathway. State of the art: It is a health intervention whose main objective is to overcome care-related barriers (e.g., logistical, bureaucratic-administrative, communication, and financial) to improve quality and access to health in the context of cancer care. These individuals play a guiding role for patients during the diagnostic and active treatment process. Their job is to link the patient with clinical providers, provide a support system, ensure individualized accompaniment, and guarantee that they get access to the knowledge and resources necessary to complete the appropriate follow-up and, or treatment. Discussion/Conclusion: Undoubtedly, patient navigators represent an increasingly recognized element of high-quality, patient-centered cancer programs. Its implementation will be of specific interest in the Integrated Practice Unit for people with lung cancer. (AU)

Neumotórax espontáneo persistente como manifestación primaria de sarcoma sinovial pleuropulmonar primario: a propósito de un caso / Persistent spontaneous pneumothorax as a primary manifestation of primary synovial sarcoma of the lung: a case report

El sarcoma sinovial pleuropulmonar (SSPP) es un tumor primario de pulmón, maligno, infrecuente en pediatría (prevalencia 0,1-0,5 %) que afecta predominantemente a adolescentes y adultos jóvenes. Se ha descrito una sobrevida global cercana al 30 % a los 5 años. Se reporta el caso de un paciente de 12 años de edad, previamente sano, que presentó tos, dolor torácico y disnea de comienzo súbito, como manifestación inicial de neumotórax izquierdo, el que persistió a los 4 días y requirió resección quirúrgica de lesión bullosa pulmonar. Se realizó diagnóstico histológico de sarcoma sinovial pleuropulmonar confirmado por estudio molecular, que evidenció la translocación cromosómica entre el cromosoma X y el 18: t(X;18) (p11.2;q11.2) de la pieza quirúrgica extirpada. Ante pacientes con neumotórax persistente o recidivante, es importante descartar causas secundarias, entre ellas, sarcoma sinovial pleuropulmonar. Su ominoso pronóstico determina la necesidad de arribar a un diagnóstico temprano e implementar un tratamiento agresivo

Pleuropulmonary synovial sarcoma (PPSS) is a primary malignancy of the lung, uncommon in pediatrics (prevalence: 0.1­0.5%) that predominantly affects adolescents and young adults. Overall survival has been reported to be close to 30% at 5 years. Here we report the case of a previously healthy 12-year-old male patient who presented with cough, chest pain, and dyspnea of sudden onset as initial manifestation of left pneumothorax, which persisted after 4 days and required surgical resection of pulmonary bullous lesion. A histological diagnosis of pleuropulmonary synovial sarcoma was made and confirmed by molecular study, which showed chromosomal translocation between chromosomes X and 18: t(X;18) (p11.2;q11.2) in the surgical specimen removed. In patients with persistent or recurrent pneumothorax, it is important to rule out secondary causes, including pleuropulmonary synovial sarcoma. Such poor prognosis determines the need for early diagnosis and aggressive treatment.

COVID-19 en pacientes oncológicos / COVID-19 in cancer patients

Introducción: La Organización Mundial de la Salud declaró el COVID-19 como una pandemia el 11 de marzo de 2020. El antecedente de cáncer es considerado un factor de riesgo de mortalidad para múltiples padecimientos; la evolución de los pacientes con enfermedades neoplásicas puede verse influida por afecciones sobreañadidas como fue el caso del COVID-19. Objetivo: Caracterizar, desde el punto de vista clínico, a los pacientes oncológicos que ingresaron con COVID-19. Métodos: Se realizó una investigación descriptiva y transversal en pacientes con diagnóstico de enfermedad oncológica ingresados por COVID-19, en el Hospital Universitario Dr. Celestino Hernández Robau, Villa Clara, en el período de enero-diciembre 2021. Se incluyeron en el estudio 78 pacientes con diagnóstico de neoplasia de 5 años o menos de evolución. Resultados: Predominó el sexo masculino y los mayores de 60 años de edad. El 39,7 % de los pacientes presentó cáncer de pulmón o de laringe seguido por cáncer de mama, hemolinfopoyético y colorrectal. El 46,2 % se encontraba en estadio estable y el 29,5 % en paliativo. El 34,6 % de los pacientes recibía tratamiento con quimioterapia en el momento del ingreso. Los fármacos más utilizados fueron: esteroides (85,9 %), interferón alfa (73,1 %) y heparina sódica (55,1 %). Conclusiones: En los pacientes oncológicos hospitalizados con COVID-19, los tumores de pulmón y laringe fueron los más frecuentes, aunque el de mama, próstata y colorrectal, en ese orden, se relacionaron con mayor mortalidad. Los pacientes que se encontraban en progresión de la enfermedad y los que recibían tratamiento con quimioterapia presentaron mayor probabilidad de morir.

Introduction: the World Health Organization declared COVID-19 as a pandemic on March 11, 2020. A history of cancer is considered a mortality risk factor for multiple diseases; the evolution in patients with neoplastic diseases can be influenced due to superadded conditions such as the case of COVID-19. Objective: to characterize, from a clinical point of view, cancer patients admitted with COVID-19. Methods: a descriptive and cross-sectional research was carried out in cancer patients admitted with COVID-19 at "Dr. Celestino Hernández Robau" University Hospital in Villa Clara from January to December 2021. A number of 78 cancer patients with 5 years or less of evolution was included in the study. Results: male gender and those over 60 years of age predominated. The 39.7% of the patients had lung or laryngeal cancer followed by breast, hemolymphopoietic and colorectal cancers. The 46.2% were in a stable state and 29.5% in palliative care. The 34.6% of them were receiving chemotherapy treatment at the time of admission. Steroids (85.9%), alpha interferon (73.1%) and sodium heparin (55.1%) were the most used drugs. Conclusions: lung and laryngeal tumours were the most common malignancy in cancer patients hospitalized with COVID-19, although breast, prostate, and colorectal tumours, in that order, were associated with higher mortality. Patients with disease progression and those receiving chemotherapy were more likely to die.

TTYH3 is a prognostic biomarker and associates with immune cell infiltrations of lung adenocarcinoma / TTYH3 es un biomarcador pronóstico y se asocia con infiltraciones de células inmunitarias del adenocarcinoma de pulmón

SUMMARY: We investigated Tweety Family Member 3 (TTYH3) level in lung adenocarcinoma (LUAD) and its relationship with immune infiltration in tumors by bioinformatics. Differential expressions of TTYH3 in lung cancer were analyzed with Oncomine, TIMER, GEO, UALCAN and HPA. Relationship of TTYH3 mRNA/protein levels with clinical parameters was analyzed by UALCAN. Co-expressed genes of TTYH3 in LUAD were analyzed using Cbioportal. Its relationship with LUAD prognosis was analyzed by Kaplan-Meier plotter. GO and KEGG analysis were performed. Correlation between TTYH3 and tumor immune infiltration were tested by TIMER, TISIDB and GEPIA. We found that TTYH3 was significantly increased in LUAD tissues. TTYH3 high expression was closely related to poor overall survival, post progression survival and first progression in LUAD patients. TTYH3 mRNA/protein levels were significantly associated with multiple pathways. Specifically, TTYH3 up-regulation was mostly related to biological regulation, metabolic process, protein blinding, extracellular matrix organization and pathways in cancer. Moreover, TTYH3 was positively associated with immune cell infiltration in LUAD. Finally, TTYH3 was highly expressed in LUAD as revealed by meta-analysis. TTYH3 is closely related to the prognosis of LUAD and immune cell infiltration, and it can be used as a prognostic biomarker for LUAD and immune infiltration.

Investigamos por bioinformática el nivel de Tweety Family Member 3 (TTYH3) con adenocarcinoma de pulmón (LUAD) y su relación con la infiltración inmune en tumores. Las expresiones diferenciales de TTYH3 en cáncer de pulmón se analizaron con Oncomine, TIMER, GEO, UALCAN y HPA. Con UALCAN se analizó la relación de los niveles de ARNm/proteína de TTYH3 con los parámetros clínicos. Los genes coexpresados de TTYH3 en LUAD se analizaron utilizando Cbioportal. Su relación con el pronóstico LUAD se analizó mediante plotter de Kaplan- Meier. Se realizaron análisis GO y KEGG. TIMER, TISIDB y GEPIA probaron la correlación entre TTYH3 y la infiltración inmune tumoral. Encontramos que TTYH3 aumentó significativamente en los tejidos LUAD. La alta expresión de TTYH3 estuvo estrechamente relacionada con una supervivencia general deficiente, supervivencia posterior a la progresión y primera progresión en pacientes con LUAD. Los niveles de ARNm/ proteína de TTYH3 se asociaron significativamente con múltiples vías. Específicamente, la regulación positiva de TTYH3 se relacionó principalmente con la regulación biológica, el proceso metabólico, el cegamiento de proteínas, la organización de la matriz extracelular y las vías en el cáncer. Además, TTYH3 se asoció positivamente con la infiltración de células inmunitarias en LUAD. Finalmente, TTYH3 se expresó altamente en LUAD como lo reveló el metanálisis. TTYH3 está estrechamente relacionado con el pronóstico de LUAD y la infiltración de células inmunitarias, y se puede utilizar como biomarcador pronóstico para LUAD y la infiltración de células inmunitarias.

Tumor cell lysate with low content of HMGB1 enhances immune response of dendritic cells against lung cancer in mice / 南方医科大学学报

OBJECTIVE@#To assess the effect of tumor cell lysate (TCL) with low high-mobility group B1 (HMGB1) content for enhancing immune responses of dendritic cells (DCs) against lung cancer.@*METHODS@#TCLs with low HMGB1 content (LH-TCL) and normal HMGB1 content (NH-TCL) were prepared using Lewis lung cancer (LLC) cells in which HMGB1 was inhibited with 30 nmol/L glycyrrhizic acid (GA) and using LLC cells without GA treatment, respectively. Cultured mouse DCs were exposed to different doses of NH-TCL and LH-TCL, using PBS as the control. Flow cytometry was used to detect the expressions of CD11b, CD11c and CD86 and apoptosis of the stimulated DCs, and IL-12 levels in the cell cultures were detected by ELISA. Mouse spleen cells were co-cultured with the stimulated DCs, and the activation of the spleen cells was assessed by detecting CD69 expression using flow cytometry; TNF-β production in the spleen cells was detected with ELISA. The spleen cells were then co-cultured with LLC cells at the effector: target ratios of 5:1, 10:1 and 20:1 to observe the tumor cell killing. In the animal experiment, C57/BL6 mouse models bearing subcutaneous LLC xenograft received multiple injections with the stimulated DCs, and the tumor growth was observed.@*RESULTS@#The content of HMGB1 in the TCL prepared using GA-treated LLC cells was significantly reduced (P < 0.01). Compared with NH-TCL, LH-TCL showed a stronger ability to reduce apoptosis (P < 0.001) and promote activation and IL- 12 production in the DCs. Compared with those with NH-TCL stimulation, the DCs stimulated with LH-TCL more effectively induced activation of splenic lymphocytes and enhanced their anti-tumor immunity (P < 0.05). In the cell co-cultures, the spleen lymphocytes activated by LH-TCL-stimulated DCs showed significantly enhanced LLC cell killing activity (P < 0.01). In the tumor-bearing mice, injections of LH-TCL-stimulated DCs effectively activated host anti-tumor immunity and inhibited the growth of the tumor xenografts (P < 0.05).@*CONCLUSION@#Stimulation of the DCs with LH-TCL enhances the anti-tumor immune activity of the DCs and improve the efficacy of DCbased immunotherapy for LLC in mice.

S100A10 promotes proliferation and invasion of lung adenocarcinoma cells by activating the Akt-mTOR signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effects of expression levels of S100 calcium-binding protein A10 (S100A10) in lung adenocarcinoma (LUAD) on patient prognosis and the regulatory role of S100A10 in lung cancer cell proliferation and metastasis.@*METHODS@#Immunohistochemistry was used to detect the expression levels of S100A10 in LUAD and adjacent tissues, and the relationship between S100A10 expression and clinicopathological parameters and prognosis of the patients was statistically analyzed. The lung adenocarcinoma expression dataset in TCGA database was analyzed using gene enrichment analysis (GSEA) to predict the possible regulatory pathways of S100A10 in the development of lung adenocarcinoma. Lactate production and glucose consumption of lung cancer cells with S100A10 knockdown or overexpression were analyzed to assess the level of glycolysis. Western blotting, CCK-8 assay, EdU-594 assay, and Transwell assays were performed to determine the expression level of S100A10 protein, proliferation and invasion ability of lung cancer cells. A549 cells with S100A10 knockdown and H1299 cells with S100A10 overexpression were injected subcutaneously in nude mice, and tumor growth was observed.@*RESULTS@#The expression level of S100A10 was significantly upregulated in LUAD tissues as compared with the adjacent tissues, and an elevated S100A10 expression level was associated with lymph node metastasis, advanced tumor stage and distant organ metastasis (P < 0.05), but not with tumor differentiation or the patients' age or gender (P > 0.05). Survival analysis showed that elevated S100A10 expressions in the tumor tissue was associated with a poor outcome of the patients (P < 0.001). In the lung cancer cells, S100A10 overexpression significantly promoted cell proliferation and invasion in vitro (P < 0.001). GSEA showed that the gene sets of glucose metabolism, glycolysis and mTOR signaling pathway were significantly enriched in high expressions of S100A10. In the tumor-bearing nude mice, S100A10 overexpression significantly promoted tumor growth, while S100A10 knockdown obviously suppressed tumor cell proliferation (P < 0.001).@*CONCLUSION@#S100A10 overexpression promotes glycolysis by activating the Akt-mTOR signaling pathway to promote proliferation and invasion of lung adenocarcinoma cells.

High expression of MYH9 inhibits apoptosis of non-small cell lung cancer cells through activating the AKT/c-Myc pathway / 南方医科大学学报

OBJECTIVE@#To investigate the role of myosin heavy chain 9 (MYH9) in regulation of cell proliferation, apoptosis, and cisplatin sensitivity of non-small cell lung cancer (NSCLC).@*METHODS@#Six NSCLC cell lines (A549, H1299, H1975, SPCA1, H322, and H460) and a normal bronchial epithelial cell line (16HBE) were examined for MYH9 expression using Western blotting. Immunohistochemical staining was used to detect MYH9 expression in a tissue microarray containing 49 NSCLC and 43 adjacent tissue specimens. MYH9 knockout cell models were established in H1299 and H1975 cells using CRISPR/Cas9 technology, and the changes in cell proliferation cell were assessed using cell counting kit-8 (CCK8) and clone formation assays; Western blotting and flow cytometry were used to detect apoptosis of the cell models, and cisplatin sensitivity of the cells was evaluated using IC50 assay. The growth of tumor xenografts derived from NSCLC with or without MYH9 knockout was observed in nude mice.@*RESULTS@#MYH9 expression was significantly upregulated in NSCLC (P < 0.001), and the patients with high MYH9 expression had a significantly shorter survival time (P=0.023). In cultured NSCLC cells, MYH9 knockout obviously inhibited cell proliferation (P < 0.001), promoted cell apoptosis (P < 0.05), and increased their chemosensitivity of cisplatin. In the tumor-bearing mouse models, the NSCLC cells with MYH9 knockout showed a significantly lower growth rate (P < 0.05). Western blotting showed that MYH9 knockout inactivated the AKT/c- Myc axis (P < 0.05) to inhibit the expression of BCL2- like protein 1 (P < 0.05), promoted the expression of BH3- interacting domain death agonist and the apoptosis regulator BAX (P < 0.05), and activated apoptosis-related proteins caspase-3 and caspase-9 (P < 0.05).@*CONCLUSION@#High expression of MYH9 contributes to NSCLC progression by inhibiting cell apoptosis via activating the AKT/c-Myc axis.

Thoracic SMARCA4-deficient undifferentiated tumor-pathological diagnosis and combined immune checkpoint inhibitor treatment / 北京大学学报(医学版)

We explored clinicopathological features and treatment strategies for thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT). Thoracic SMARCA4-UT is a new entity recently acknowledged in the 2021 edition of World Health Organization Classification of Thoracic Tumors, and doctors are relatively unfamiliar with its diagnosis, treatment, and prognosis. Taking a case of SMARCA4-UT treated in Peking University First Hospital as an example, this multi-disciplinary discussion covered several hot issues on diagnosing and treating thoracic SMARCA4-UT, including histological features, immu- nohistochemical and molecular phenotype, immune checkpoint inhibitor (ICI) therapy, and pathological assessment of neoadjuvant therapy response. The patient was an older man with a long history of smoking and was admitted due to a rapidly progressing solid tumor in the lower lobe of the right lung. Histologically, tumor cells were epithelioid, undifferentiated, diffusely positive for CD34, and partially positive for SALL4.The expression of BRG1 protein encoded by SMARCA4 gene was lost in all of tumor cells, and next-generation sequencing(NGS)confirmed SMARCA4 gene mutation (c.2196T>G, p.Y732Ter). The pathological diagnosis reached as thoracic SMARCA4-UT, and the preoperative TNM stage was T1N2M0 (ⅢA). Tumor proportion score (TPS) detected by immunohistochemistry of programmed cell death 1-ligand 1 (PD-L1, clone SP263) was 2%. Tumor mutation burden (TMB) detected by NGS of 1 021 genes was 16. 3/Mb. Microsatellite detection showed the tumor was microsatellite stable (MSS). Neo-adjuvant therapy was implemented with the combined regimen of chemotherapy and ICI. Right lower lobectomy was performed through thoracoscopy after the two weeks' neoadjuvant. The pathologic assessment of lung tumor specimens after neoadjuvant therapy revealed a complete pathological response (CPR). The post-neoadjuvant tumor TNM stage was ypT0N0M0. Then, five cycles of adjuvant therapy were completed. Until October 2022, neither tumor recurrence nor metastasis was detected, and minimal residual disease (MRD) detection was negative. At present, it is believed that if BRG1 immunohistochemical staining is negative, regardless of whether SMARCA4 gene mutation is detected, it should be classified as SMARCA4-deficient tumors. SMARCA4-deficient tumors include a variety of carcinomas and sarcomas. The essential criteria for diagnosing SMARCA4-UT includes loss of BRG1 expression, speci-fic histological morphology, and exclude other common thoracic malignant tumors with SMARCA4-deficiency, such as squamous cell carcinoma, adenocarcinoma and large cell carcinoma. SMARCA4-UT is a very aggressive malignant tumor with a poor prognosis. It has almost no targeted therapy mutations, and little response to chemotherapy, but ICI is currently the only effective drug. The successful diagnosis and treatment for this case of SMARCA4-UT should enlighten significance for various kinds of SMARCA4-deficient tumors.

Consistency comparison of programmed cell death 1-ligand 1 in different immuno-histochemical staining methods / 北京大学学报(医学版)

OBJECTIVE@#To compare the consistency of programmed cell death 1-ligand 1 (PD-L1, clone E1L3N, 22C3, SP263) in different immunohistochemical staining methods.@*METHODS@#The first step was to select the optimal process: The PD-L1(clone E1L3N) antibody recommended process, self-built process ①, self-built process ② and self-built process ③ were used to perform immunohistochemical staining in 5 cases of tonsil tissue. The quality of all slides was scored by expert pathologists (0-6 points). The process with the highest score was selected. The second step was to compare the consistency between the optimal procedure and the two standard procedures. Thirty-two cases of lung non-small cell carcinoma diagnosed by pathology in Peking University First Hospital in the past two years were randomly selected. The 32 cases were stained in parallel with the SP263 and 22C3 standard procedures, and all stained slides were scored by specialized pathologists for tumor proportion score (TPS). The scoring results were grouped according to < 1%, ≥1% to < 10%, ≥10% to < 50%, and ≥50%. The consistency of PD-L1 detection antibody clone E1L3N and 22C3, E1L3N and SP263 staining results was analyzed.@*RESULTS@#Tonsil stained slides scores (0-6 points) were as follows: The recommended protocol was 5, 5, 5, 5 and 5. The self-built process ① was 5, 6, 6, 5 and 6. The self-built process ② was 4, 4, 4, 4 and 4.The self-built process ③ was 3, 3, 3, 3 and 3. The self-built process ① was the best with the highest score. The TPSs of 32 non small cell lung carcinoma (NSCLC) cases were as follows: Of self-built process ①, 6 cases were lower than 1%, 5 cases were from 1% to 10%, 10 cases were from 10% to 50%, and 11 cases were higher than 50%; of 22C3 standard procedure, 5 cases were lower than 1%, 3 cases were from 1% to 10%, 13 cases were from 10% to 50%, 11 cases were higher than 50%; of SP263 standard procedure, 7 cases were lower than 1%, 4 cases were from 1% to 10%, 11 cases were from 10% to 50%, 10 cases were higher than 50%. The results of the consistency test were as follows: The κ value for self-built process ① and 22C3 standard procedure was 0.736 (P < 0.001), the agreement was good; the κ value for self-built process ① and SP263 standard procedure was 0.914 (P < 0.001), the agreement was very good.@*CONCLUSION@#The immunostaining using PD-L1(E1L3N) with validated self-built staining protocol ① by Ventana Benchmark GX platform can obtain high quality of slides, and the TPSs based on these slides are in good agreement with 22C3 and SP263 standard procedures.

A case of stage Ⅲ pneumoconiosis with large shadow by burr-like changes misdiagnosed as lung cancer / 中华劳动卫生职业病杂志

Pneumoconiosis is characterized by chronic lung inflammation and fibrosis, and inflammation can promote pulmonary fibrosis, which in turn leads to pneumoconiosis. When a large shadow with a long diameter of not less than 2 cm and a short diameter of not less than 1 cm appears in the lung, it can be classified as stage Ⅲ pneumoconiosis. This paper reports a case of stage Ⅲ pneumoconiosis with a large shadow in the upper right lung accompanied by burr-like changes misdiagnosed as lung cancer by CT examination.When the large shadow lesions in patients with pneumoconiosis and lung cancer are difficult to distinguish on CT, an additional MRI examination, particularly T(2)W imaging sequence is useful sequence for identifying the two.

A case of malignant peritoneal mesothelioma / 中华劳动卫生职业病杂志

Malignant mesothelioma is a highly malignant disease that most often occurs in the pleural cavity, followed by the peritoneum and pericardium. Malignant peritoneal mesothelioma (MPM) accounts for 10%-15% of all mesothelioma. The most important risk factor for MPM is exposure to asbestos. MPM has no specific clinical symptoms, imaging and histopathology are critical for the diagnosis. There are currently no generally accepted guidelines for curative treatment of MPM. The patient mainly presented with abdominal pain, abdominal distension and discomfort. Due to extensive omentum metastasis, no further surgical treatment was performed. Pemetrexed combined with cisplatin chemotherapy was given for 2 cycles, and the patient is still alive.

CT perfusion combined with energy spectrum imaging to evaluate the short-term efficacy of bronchial arterial chemoembolization for lung cancer / 中华内科杂志

Objective: To evaluate the clinical value of dynamic volumetric CT perfusion combined with energy spectrum imaging in bronchial arterial chemoembolization (BACE) in patients with lung cancer. Methods: The data of 31 patients with lung cancer confirmed by pathology and treated with BACE in Lishui Central Hospital from January 2018 to February 2022 were retrospectively collected, including 23 men and 8 women, aged 31-84 (67) years. All patients received perfusion scans of lesion sites within 1 week before surgery and 1 month after surgery. We collected and compared the changes in preoperative and postoperative perfusion parameters such as blood flow (BF), blood volume (BV), mean through time (MTT), permeability surface (PS) and energy spectrum parameters including arterial phase CT value (CTA), venous phase CT value (CTV), arterial phase iodine concentration (ICA), venous phase of iodine concentration (ICV), arterial standardization iodine concentration (NICA), and intravenous standardized iodine concentration (NICV) to confirm the significance of these parameters in evaluating the short-term efficacy of BACE in the treatment of advanced lung cancer. Data normality was tested using the Kolmogorov-Smirnov test and normally distributed measurement data are expressed here as mean ± standard deviation; the independent-samples t-test was used for comparisons between two groups. The measurement data that were not normally distributed are expressed as median (interquartile interval) [M (Q1, Q3)], and the comparison between the two groups used the Kruskal-Wallis test. Count data are expressed as cases (%), and comparisons between groups used the χ2 test. Results: The objective response rate (ORR) and disease control rate (DCR) at 1 month after BACE were 54.8% (17/31) and 96.8% (30/31), respectively. CT perfusion parameters and energy spectrum parameters of patients before and after BACE treatment were compared. The results showed that BF, BV, MTT, ICA, ICV and NICV were significantly decreased after BACE treatment compared with before treatment, and the differences were statistically significant[58.06 (40.47,87.22) vs.23.57(10.92, 36.24) ml·min-1·100g-1,3.33(2.86,6.09) vs.2.12(1.96,3.61)ml/100g,2.70(2.19,3.88) vs.1.53 (1.12,2.25)s, 3.51 (3.11,4.14)vs.1.74 (1.26,2.50)mg/ml,2.00 (1.30,2.45) vs.1.32(0.92,1.76)mg/ml,0.51(0.42,0.57) vs.0.33(0.23,0.39)](all P<0.05). At the same time, compared with the non-remission group, the study results showed that the difference of parameters in remission group before and after BACE was more obvious, including ΔBF, ΔBV, ΔMTT, ΔPS, ΔCTA, ΔCTV, ΔICA, ΔICV, ΔNICA, ΔNICV were significantly increased, and the difference was statistically significant [36.82(32.38, 45.34) vs.9.50(-1.43, 12.34) ml·min-1·100g-1,4.46(2.52, 5.79) vs.0.22(-0.76, 4.09) ml/100g,4.22(2.25, 6.77) vs.0.43(-2.53, 1.88) s,10.07 (2.89, 13.13) vs.-2.01(-6.77, 4.28) ml·min-1·100g-1,14.22(11.88, 20.57) vs.4.18(-5.25, 6.37) HU, 34.6(14.88, 43.15) vs.11.60(0.26, 25.05) HU,0.95(0.54, 1.47) vs.0.11(0.20, 0.59) mg/ml,1.57(1.10, 2.38) vs. 0.26(-0.21, 0.63) mg/ml,0.05(0.03, 0.08) vs.-0.02(-0.04, 0.01),0.18(0.13, 0.21)vs. 0.11(-0.06, 0.16)](all P<0.05). Conclusions: CT perfusion combined with spectral imaging could effectively evaluate the changes in tumor vascular perfusion in patients with advanced lung cancer before and after BACE treatment, which has important value in judging the short-term efficacy after treatment.

Clinicopathological features and prognosis of SMARCA4-deficient non-small cell lung carcinoma: an analysis of 127 cases / 中华病理学杂志

Objective: To investigate and elucidate the clinicopathological and prognostic characteristics of SMARCA4-deficient non-small cell lung cancer. Methods: The clinicopathological and prognostic data were collected in 127 patients with SMARCA4-deficient non-small cell lung cancer diagnosed in Shanghai Pulmonary Hospital, Shanghai, China from January 2020 to March 2022. The variation and expression of biomarkers related to treatment were retrospectively reviewed. Results: One hundred and twenty-seven patients were eligible for enrollment. Among them 120 patients (94.5%) were male and 7 cases (5.5%) were female, while the average age was 63 years (range 42-80 years). There were 41 cases (32.3%) of stage Ⅰ cancer, 23 cases (18.1%) of stage Ⅱ, 31 cases (24.4%) of stage Ⅲ and 32 cases (25.2%) of stage Ⅳ. SMARCA4 expression detected by immunohistochemistry was completely absent in 117 cases (92.1%) and partially absent in 10 cases (7.9%). PD-L1 immunohistochemical analyses were performed on 107 cases. PD-L1 was negative, weakly positive and strongly positive in 49.5% (53/107), 26.2% (28/107) and 24.3% (26/107) of the cases, respectively. Twenty-one cases showed gene alterations (21/104, 20.2%). The KRAS gene alternation (n=10) was most common. Mutant-type SMARCA4-deficient non-small cell lung cancer was more commonly detected in females, and was associated with positive lymph nodes and advanced clinical stage (P<0.01). Univariate survival analysis showed that advanced clinical stage was a poor prognosis factor, and vascular invasion was a poor predictor of progression-free survival in patients with surgical resection. Conclusions: SMARCA4-deficient non-small cell lung cancer is a rare tumor with poor prognosis, and often occurs in elderly male patients. However, SMARCA4-deficient non-small cell lung cancers with gene mutations are often seen in female patients. Vascular invasion is a prognostic factor for disease progression or recurrence in patients with resectable tumor. Early detection and access to treatment are important for improving patient survivals.