Comparación de desenlaces a corto plazo de gastrectomía laparoscópica mínimamente invasiva en adultos mayores con cáncer gástrico localmente avanzado / Comparison of short-term outcomes of minimally invasive laparoscopic gastrectomy in older adults with locally advanced gastric cancer

Introducción. El objetivo de este estudio fue comparar los desenlaces a corto plazo de la gastrectomía laparoscópica en adultos vs. adultos mayores con cáncer gástrico localmente avanzado en una cohorte de un país occidental. Métodos. Estudio de cohorte prospectivo en pacientes sometidos a gastrectomía laparoscópica por cáncer gástrico localmente avanzado, en el Hospital Universitario Erasmo Meoz, de Cúcuta, Colombia, entre noviembre de 2014 y diciembre de 2018. Se realizó análisis descriptivo, de comparación de grupos y bivariado. Resultados. De un total de 116 pacientes, 51 pacientes (44 %) tenían 65 años o más y 63 pacientes (54 %) eran hombres. No se encontró diferencia estadísticamente significativa al comparar los pacientes menores de 65 años con los de 65 años o más. La mediana del tiempo operatorio fue de 240 minutos en ambos grupos (p>0,05), la mediana de los márgenes de resección macroscópica fue 6 cm vs. 5 cm (p>0,05), la mediana de los ganglios linfáticos disecados fue 25 vs. 19 (p>0,05), la mediana de ganglios linfáticos positivos fue 4 vs. 3 (p>0,05), la mediana de estancia fue de 7 días en ambos grupos (p>0,05). La tasa general de complicaciones posoperatorias no difirió significativamente entre adultos (7%) y adultos mayores (11 %) (p>0,05) y no se observaron diferencias significativas en las tasas de complicaciones menores (Clavien-Dindo grado II; 3-5 % vs. 6-12 %; p>0,05) y graves (Clavien-Dindo ≥ IIIa; 3-5 % vs. 4-8 %; p>0,05). Conclusiones. No se encontraron diferencias estadísticamente significativas en los resultados a corto plazo entre los pacientes adultos y adultos mayores con cáncer gástrico localmente avanzado tratados con gastrectomía laparoscópica. Esta técnica es segura en ancianos.

Introduction. The objective of this study was to compare the short-term outcomes of laparoscopic gastrectomy in adults vs. older patients with locally advanced gastric cancer from a Western country cohort. Methods. Prospective cohort study in patients undergoing laparoscopic gastrectomy for locally advanced gastric cancer at the Hospital Universitario Erasmo Meoz, de Cúcuta, Colombia, between November 2014 and December 2018. Descriptive, group comparison and bivariate analysis was performed. Results. Of a total of 116 patients, 51 patients (44%) were 65 years or older and 63 patients (54%) were men. No statistically significant difference was found when comparing patients under 65 years of age with those 65 years of age or older. The median operating time was 240 minutes in both groups (p>0.05), the median macroscopic resection margins were 6 cm vs. 5 cm (p>0.05), the median number of lymph nodes dissected was 25 vs. 19 (p>0.05), the median number of positive lymph nodes was 4 vs. 3 (p>0.05), the median stay was 7 days in both groups (p>0.05). The overall rate of postoperative complications did not differ significantly between adults (7%) and older adults (11%) (p>0.05) and no significant differences were observed in the rates of minor (Clavien-Dindo grade II; 3-5% vs. 6-12%; p>0.05) and severe complications (Clavien-Dindo ≥ IIIa; 3-5% vs. 4-8%; p>0.05). Conclusions. No statistically differences were found in short-term outcomes between adult and older patients with locally advanced gastric cancer treated with laparoscopic gastrectomy. This technique is safe in the elderly.

Caracterización de los desenlaces quirúrgicos a corto plazo en gastrectomía por laparoscopia en un centro de alto volumen: 10 años de experiencia / Short-term surgical outcomes of laparoscopic gastrectomy in a high-volume center: 10-year experience

Introducción. El cáncer gástrico en Colombia es la segunda neoplasia más común en hombres y la cuarta en mujeres. En los últimos años se han descrito ampliamente los beneficios del abordaje laparoscópico en el cáncer gástrico frente a sangrado, recuperación postoperatoria y complicaciones, sin afectar los resultados oncológicos. Métodos. Estudio observacional retrospectivo de pacientes llevados a gastrectomía laparoscópica en la Clínica Universitaria Colombia durante un período de diez años, entre 2013 y 2023. Se describieron los resultados perioperatorios en cuanto a estancia hospitalaria, sangrado operatorio, duración del procedimiento, complicaciones, causas de reintervención y mortalidad en los primeros 30 días. Resultados. Se incluyeron 418 pacientes, 58,9 % hombres, con una edad promedio de 60,8 años. Se documentó un tiempo quirúrgico promedio de 228,7 minutos, con un sangrado de 150 ml. La media de ganglios linfáticos resecados fue de 26,1 ± 11,4. La estancia hospitalaria en promedio fue de 4 ± 4 días, y se registraron complicaciones en 104 sujetos, con una tasa promedio de 24 %, de las cuales 29 (27,4 %) obtuvieron una clasificación Clavien-Dindo IIIB. Conclusiones. La gastrectomía por laparoscopia en un centro de alto volumen y con cirujanos experimentados en Colombia, tiene resultados perioperatorios similares a lo reportado en la literatura mundial. Aún se requiere de estudios de mayor fuerza de asociación para establecer recomendaciones sobre el uso rutinario de este abordaje en patología maligna avanzada.

Introduction. Gastric cancer in Colombia is the second most common neoplasm in men and the fourth in women. In recent years, the benefits of the laparoscopic approach in gastric cancer against bleeding, postoperative recovery com and complications have been widely described, without affecting oncological results. Methods. Retrospective observational study of patients undergoing laparoscopic gastrectomy at the Clínica Universitaria Colombia over a period of ten years, between 2013 and 2023. Perioperative results were described in terms of hospital stay, operative bleeding, duration of the procedure, complications, causes of reintervention, and mortality in the first 30 days. Results. 418 patients were included, 58.9% men, with an average age of 60.88 years. An average surgical time of 228.7 minutes was documented, with a blood loss of 150 ml. The mean number of lymph nodes resected was 26.1 ± 11.4. The average hospital stay was 4 ± 4 days, and complications were recorded in 104 subjects, with an average rate of 24%, of which 29 (27.4%) obtained a Clavien-Dindo IIIB classification. Conclusions. Laparoscopic gastrectomy in a high-volume center and with experienced surgeons in Colombia has perioperative results similar to those reported in the world literature. Studies with greater strength of association are still required to establish recommendations on the routine use of this approach in advanced malignant pathology.

Cáncer Gástrico Bifocal con Linfonodos Negativos en un Paciente con Cirrosis Hepática / Bifocal Gastric Cancer with Negative Lymph Nodes in a Hepatic Cirrhosis Patient

El cáncer gástrico (CG), es la primera causa de muerte por cáncer, en hombres, y la tercera en mujeres, en Chile. No obstante ello, el CG bifocal (CGB) es una situación poco frecuente. El objetivo de este manuscrito fue reportar un caso de CGB, con linfonodos negativos en un paciente con cirrosis hepática, que fue intervenido quirúrgicamente; y revisar la evidencia existente respecto de sus características morfológicas, terapéuticas y pronósticas. Caso clínico: Hombre de 74 años diabético, hipertenso, insuficiente cardíaco y cirrótico; portador de CGB (subcardial y antro-pilórico), diagnosticado por endoscopia y con confirmación histológica de ambas lesiones; operado en Clínica RedSalud Mayor Temuco en septiembre de 2023. En el intraoperatorio se verificó además la coexistencia de una lesión de aspecto metastásico en el segmento III del hígado, y adhesión de la región antro-pilórica a la vesícula biliar. Se realizó gastrectomía total, linfadenectomía D2, esófago-yeyuno anastomosis término-lateral, resección segmentaria hepática (segmento III) y colecistectomía. El paciente permaneció 6 días en la UCI debido a que desarrolló insuficiencia hepática (encefalopatía leve y ascitis). Se alimentó vía enteral por sonda naso-yeyunal. Posteriormente inició alimentación oral progresiva, la que fue bien tolerada. Completó 11 días de hospitalización en servicio médico-quirúrgico, donde mejoró actividad neurológica, hasta su alta domiciliaria. Actualmente, lleva dos meses desde su operación, se encuentra en buenas condiciones generales, y el Comité Oncológico decidió no dar quimioterapia adyuvante. Se presenta un caso inusual de CG de tipo bifocal, respecto de lo cual hay escasa información disponible. Se logró realizar cirugía con intención curativa en un paciente de alto riesgo, con un resultado exitoso.

SUMMARY: Gastric cancer (GC) is the first cause of death from cancer in men, and the third one in women, in Chile. However, a bifocal GC (BGC) is uncommon. The aim of this study was to report a case of CGB, with negative-lymph nodes in a patient with liver cirrhosis, who underwent surgery; and review the existing evidence regarding its morphological, therapeutic and prognostic characteristics. Clinical case: A 74-year-old male patient with a medical history of diabetes, hypertension, congestive heart failure, and cirrhosis underwent surgical intervention for GC located in subcardial and antro- pyloric regions. The diagnosis was established via endoscopy and confirmed histologically. Surgery was performed at the RedSalud Mayor Temuco Clinic in September 2023. During intraoperative assessment, the coexistence of a lesion with metastatic-like characteristics in segment III of the liver was also verified, along with adhesions between the antro-pyloric region and the gallbladder. Surgical approach encompassed total gastrectomy, D2 lymphadenectomy, esophago-jejunostomy, segmental hepatic resection, and cholecystectomy. Subsequently, the patient required a six-day stay in ICU due to the development of hepatic insufficiency, characterized by mild encephalopathy and ascites. Enteral nutrition was administered via a naso-jejunal tube, followed by a gradual transition to oral feeding, which was well-tolerated. The patient completed an 11-day hospitalization period in the medical-surgical ward, during which his neurological function improved significantly, resulting in his discharge. At present, 2 months post-surgery, the patient remains in satisfactory general health, and the Oncology Committee decided not to proceed with adjuvant chemotherapy. This case represents a rare instance of bifocal GC, for which there is limited available literature. Surgical intervention with curative intent was successfully carried out in a high-risk patient, yielding a positive outcome.

CLCA1 is Poorly Expressed in Stomach Adenocarcinoma and Correlates with Immune Infiltration / CLCA1 se Expresa Deficientemente en el Adenocarcinoma de Estómago y se Correlaciona con la Infiltración Inmune

SUMMARY: Calcium-activated chloride channel regulator 1 (CLCA1) is associated with cancer progression. The expression and immunologic function of CLCA1 in stomach adenocarcinoma (STAD) remain unclear. In this investigation, the expression of CLCA1 in STAD tissues and its involvement in the progression and immune response of STAD were examined using databases such as cBioPortal, TISIDB, and UALCAN. In order to validate the expression level of CLCA1 protein in gastric adenocarcinoma, thirty clinical tissue specimens were gathered for immunohistochemical staining. The findings indicated a downregulation of CLCA1 in STAD patients, which was correlated with race, age, cancer grade, Helicobacter pylori infection, and molecular subtype. Through the examination of survival analysis, it was identified that diminished levels of CLCA1 within gastric cancer cases were linked to decreased periods of post-progression survival (PPS), overall survival (OS), and first progression (FP) (P<0.05). The CLCA1 mutation rate was lower in STAD, but the survival rate was higher in the variant group. The correlation between the expression level of CLCA1 and the levels of immune infiltrating cells in STAD, as well as the immune activating molecules, immunosuppressive molecules, MHC molecules, chemokines, and their receptor molecules, was observed. Gene enrichment analysis revealed that CLCA1 may be involved in STAD progression through systemic lupus erythematosus (SLE), proteasome, cell cycle, pancreatic secretion, and PPAR signaling pathways. In summary, CLCA1 is anticipated to function as a prognostic marker for patients with STAD and is linked to the immunization of STAD.

El regulador 1 del canal de cloruro activado por calcio (CLCA1) está asociado con la progresión del cáncer. La expresión y la función inmunológica de CLCA1 en el adenocarcinoma de estómago (STAD) aún no están claras. En esta investigación, se examinó la expresión de CLCA1 en tejidos STAD y su participación en la progresión y respuesta inmune de STAD utilizando bases de datos como cBioPortal, TISIDB y UALCAN. Para validar el nivel de expresión de la proteína CLCA1 en el adenocarcinoma gástrico, se recolectaron treinta muestras de tejido clínico para tinción inmunohistoquímica. Los hallazgos indicaron una regulación negativa de CLCA1 en pacientes con STAD, que se correlacionó con la raza, la edad, el grado del cáncer, la infección por Helicobacter pylori y el subtipo molecular. Mediante el examen del análisis de supervivencia, se identificó que los niveles reducidos de CLCA1 en los casos de cáncer gástrico estaban relacionados con períodos reducidos de supervivencia posterior a la progresión (PPS), supervivencia general (OS) y primera progresión (FP) (P <0,05). La tasa de mutación CLCA1 fue menor en STAD, pero la tasa de supervivencia fue mayor en el grupo variante. Se observó la correlación entre el nivel de expresión de CLCA1 y los niveles de células inmunes infiltrantes en STAD, así como las moléculas activadoras inmunes, moléculas inmunosupresoras, moléculas MHC, quimiocinas y sus moléculas receptoras. El análisis de enriquecimiento genético reveló que CLCA1 puede estar involucrado en la progresión de STAD a través del lupus eritematoso sistémico (LES), el proteasoma, el ciclo celular, la secreción pancreática y las vías de señalización de PPAR. En resumen, se prevé que CLCA1 funcione como un marcador de pronóstico para pacientes con STAD y está vinculado a la inmunización de STAD.

División ganglionar posquirúrgica y su efecto en el recuento ganglionar y la estadificación en pacientes con cáncer gástrico / Postoperative lymph node division and its effect on lymph node count and staging in patients with gastric cancer

Introducción. La gastrectomía y disección ganglionar es el estándar de manejo para los pacientes con cáncer gástrico. Factores como la identificación de ganglios por el patólogo, pueden tener un impacto negativo en la estadificación y el tratamiento. El objetivo de este estudio fue comparar el recuento ganglionar de un espécimen quirúrgico después de una gastrectomía completa (grupo A) y de un espécimen con un fraccionamiento por grupos ganglionares (grupo B). Métodos. Estudio de una base de datos retrospectiva de pacientes sometidos a gastrectomía D2 en el Servicio de Cirugía gastrointestinal de la Liga Contra el Cáncer seccional Risaralda, Pereira, Colombia. Se comparó el recuento ganglionar en especímenes quirúrgicos con y sin división ganglionar por regiones anatómicas previo a su envío a patología. Resultados. De los 94 pacientes intervenidos, 65 pertenecían al grupo A y 29 pacientes al grupo B. El promedio de ganglios fue de 24,4±8,6 y 32,4±14,4 respectivamente (p=0,004). El porcentaje de pacientes con más de 15 y de 25 ganglios fue menor en el grupo A que en el grupo B (27 vs 57, p=0,432 y 19 vs 24, p=0,014). El promedio de pacientes con una relación ganglionar menor 0,2 fue mayor en el grupo B (72,4 % vs 55,4 %, p=0,119). Conclusiones. Los resultados de nuestro estudio mostraron que una división por grupos ganglionares previo a la valoración del espécimen por el servicio de patología incrementa el recuento ganglionar y permite establecer de manera certera el pronóstico de los pacientes, teniendo un impacto positivo en su estadificación, para evitar el sobretratamiento

Introduction. A gastrectomy and lymph node dissection is the standard of management for patients with gastric cancer. Factors such as the identification of nodes by the pathologist can have a negative impact on staging and treatment. The objective of this study was to compare the lymph node count of a surgical specimen after a complete gastrectomy (group A) and of a specimen with lymph node by groups (group B). Methods. Study of a retrospective database of patients undergoing D2 gastrectomy in the Risaralda section of the Liga Contra el Cancer Gastrointestinal surgical service, Pereira, Colombia. The lymph node count was compared in surgical specimens with and without lymph node division by anatomical regions, prior to sending them to pathology. Results. Of the 94 patients who underwent surgery, 65 were from group A and 29 patients were from group B. The average number of nodes was 24.4±8.6 and 32.4±14.4, respectively (p=0.004). The percentage of patients with more than 15 and 25 nodes was lower in group A than in group B (27 vs 57, p=0.432 and 19 vs 24, p=0.014). The average number of patients with a nodal ratio less than 0.2 was higher in group B (72.4% vs 55.4%, p=0.119). Conclusions. The results of our study showed that a division by lymph node groups prior to the evaluation of the specimen by the pathology service increases the lymph node count and allows the prognosis of patients to be accurately established, having a positive impact on their staging, to avoid overtreatment.

Clinicopathological features of gastric alpha-fetoprotein-producing adenocarcinoma with SWI/SNF complex deletion / 中华病理学杂志

Objective: To investigate the clinicopathological features and treatment of gastric alpha-fetoprotein (AFP)-producing adenocarcinoma with SWI/SNF complex deletion. Methods: Four cases of gastric AFP-producing adenocarcinoma with SWI/SNF complex deletion diagnosed in Zhongshan Hospital of Fudan University from January 2021 to December 2022 were collected, and their histomorphological characteristics, immunohistochemical (IHC), in situ hybridization of Epstein-Barr virus-encoded RNA (EBER), next-generation sequencing results, clinicopathological features and treatment were summarized, and literature review was conducted. Results: Among the 4 patients, there were three males and one female. They presented with abdominal pain, belching and melena. Serum AFP was significantly elevated in three patients, and endoscopy showed ulcerative lesions. Microscopically, the tumor cells showed mainly diffuse flaky or nest-like growth and typical characteristics of hepatoid adenocarcinoma. In two cases there were adenoid growth, and the tumor cells in these areas possessed clear cytoplasm, suggesting enteroblastic differentiation. The tumor cell nuclei were pleomorphic with large nucleoli and brisk mitoses. The IHC results showed that the tumor cells expressed AFP, GPC3 and SALL4, and there was retained expression of broad-spectrum keratin (CKpan) and E-cadherin. IHC detection of SWI/SNF complex subunits, namely INI1 (SMARCB1), BRG1 (SMARCA4), BRM (SMARCA2), ARID1A protein was performed. In all four cases the hepatoid adenocarcinoma region and enteroblastic differentiation region showed SMARCA2 deletion, and one case with enteroblastic differentiation also showed ARID1A deletion. SMARCB1 and SMARCA4 deletions were not seen. All the four cases were diffusely positive for p53 protein, and the Ki-67 proliferation index was 80%-90%. There were no mismatch repair deletion detected; one cases showed HER2 was strongly positive (3+), and EBER was negative. None of the four cases had mutations in the SWI/SNF complex-related subunits detected by next-generation sequencing. Among the four patients, two underwent palliative surgery due to distant metastasis at the time of surgery, two underwent radical resection. Postoperative adjuvant chemotherapy was given to three patients. Conclusions: AFP-producing adenocarcinoma is a rare subtype of gastric cancer, which can be combined with SWI/SNF complex deletion, and the pathomorphological manifestations are different from the classical SWI/SNF complex deletion of undifferentiated carcinoma with rhabdoid phenotype.

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.

Diagnóstico y tratamiento de los tumores de la unión esofagogástrica. Experiencia en el Instituto Nacional de Cancerología / Diagnosis and treatment of esophagogastric junction tumors. Experience at the National Cancer Institute

Introducción. El diagnóstico adecuado de los tumores de la unión esofagogástrica es esencial para el tratamiento de estos pacientes. La clasificación propuesta por Siewert-Stein define las características propias, factores de riesgo y estrategias quirúrgicas según la localización. El objetivo de este estudio fue describir las características de los pacientes con adenocarcinoma de la unión esofagogástrica tratados en nuestra institución. Métodos. Estudio retrospectivo, descriptivo, de corte longitudinal, que incluyó los pacientes con diagnóstico de adenocarcinoma de la unión esofagogástrica intervenidos quirúrgicamente en el Instituto Nacional de Cancerología, Bogotá, D.C., Colombia, entre enero de 2012 y mayo de 2017. Resultados. Se operaron 59 pacientes (84,7 % hombres), con una edad media de 62,5 años. En su orden de frecuencia los tumores fueron tipo II (57,6 %), tipo III (30,7 %) y tipo I (11,9 %). El 74,6 % recibieron neoadyuvancia y se realizó gastrectomía total en el 73 % de los pacientes. La concordancia diagnóstica moderada con índice Kappa fue de 0,56, difiriendo con la endoscópica en 33,9 %. El 10,2 % de los pacientes presentó algún tipo de complicación intraoperatoria. La supervivencia a tres años en los tumores tipo II fue del 89,6 % y del 100 % en aquellos con respuesta patológica completa. Conclusión. Es necesario el uso de diferentes estrategias para un proceso diagnóstico adecuado en los tumores de la unión esofagogástrica. En esta serie, los pacientes Siewert II, aquellos que recibieron neoadyuvancia y los que obtuvieron una respuesta patológica completa, tuvieron una mejor supervivencia a tres años

Introduction: Proper diagnosis of gastroesophageal junction tumors is essential for the treatment of these patients. The classification proposed by Siewert-Stein defines its own characteristics, risk factors and surgical strategies according to the location. This study describes the characteristics of patients with adenocarcinoma of the esophagogastric junction treated at our institution. Methods. Retrospective, descriptive, longitudinal study, which includes patients diagnosed with adenocarcinoma of the esophagogastric junction who underwent surgery at the National Cancer Institute in Bogotá, Colombia, between January 2012 and May 2017. Results. Fifty-nine patients (84.7% men) were operated on, with a mean age of 62.5 years. In their order of frequency, the tumors were type II (57.6%), type III (30.7%) and type I (11.9%). 74.6% received neoadjuvant therapy and total gastrectomy was performed in 73% of the cases. The moderate diagnostic concordance with the Kappa index was 0.56, differing from the endoscopic one in 33.9%. 10.2% of the patients presented some type of intraoperative complication. Three-year survival in type II tumors was 89.6% and 100% in those with complete pathologic response. Conclusion. The use of different strategies is necessary for an adequate diagnostic process in tumors of the esophagogastric junction. In this series, Siewert II patients, those who received neoadjuvant therapy, and those who obtained a complete pathological response had a better three-year survival

Morbilidad y mortalidad en pacientes llevados a gastrectomía por cáncer gástrico / Morbidity and mortality in patients undergoing gastrectomy for gastric cancer

Introducción. El cáncer gástrico es la cuarta causa de muerte por cáncer a nivel mundial, con más de un millón de casos diagnosticados cada año. La cirugía con intención curativa sigue siendo el pilar del manejo para los pacientes resecables. La identificación de pacientes con mayor riesgo de morbimortalidad es importante para el proceso de toma de decisiones, sin existir hasta el momento una herramienta ideal. La revisión y el análisis de la experiencia de un centro oncológico de referencia pueden generar información útil. Métodos. Estudio observacional de cohorte histórica, en el que se incluyeron los pacientes llevados a gastrectomía por adenocarcinoma gástrico en el Instituto Nacional de Cancerología, Bogotá, D.C., Colombia, entre el 1° de enero del 2010 y el 31 de diciembre del 2017. Resultados. Se evaluaron 332 pacientes, de los cuales el 57,2 % eran hombres con edad promedio de 61 años. La mortalidad en esta serie fue del 4,5 % y la morbilidad de 34,9 %. El factor asociado con mayor riesgo de muerte fue la edad, con un HR de 1,05 (p=0,021). Se encontró un mayor riesgo en el grupo de pacientes con ASA mayor a II (p=0,009).El 17,4 % presentaron complicaciones mayores a IIIA de la clasificación de Clavien-Dindo. Conclusiones. En el presente trabajo las cifras de morbilidad y mortalidad son similares a las reportadas en la literatura. Solo la edad y la clasificación de ASA mostraron asociación con valor estadístico significativo para complicaciones postoperatorias

Introduction. Gastric cancer is the fourth leading cause of cancer death worldwide with more than one million cases diagnosed each year. Surgery with curative intent remains the mainstay of management for resectable patients. Identify patients at increased risk of morbidity and mortality is important for the decision making process, with no ideal tool available yet. Review and analysis of the experience of a referral cancer center may generate useful information. Methods. Historical cohort observational study. Patients undergoing gastrectomy for gastric adenocarcinoma at the National Cancer Institute in Bogotá, Colombia, between January 1, 2010 and December 31, 2017 were included. Results. We included 332 patients of which 57.2% were men with mean age of 61 years. Mortality in this series was 4.5% and morbidity was 34.9%. The factor associated with higher risk of death was age with a HR of 1.05 statistically significant value (p=0.021). A higher risk was found in the group of patients with ASA greater than II (p=0.009). The 17.4% presented complications greater than IIIA of the Clavien Dindo classification. Conclusions. In this study morbidity and mortality seem similar to those reported in the literature. Only age and ASA score showed an association with significant statistical value for postoperative complications

Supervivencia a dos años en pacientes con cáncer gástrico localmente avanzado en una institución de Popayán entre 2018 y 2020 / Two-year survival in patients with locally advanced gastric cancer at an institution in Popayán between 2018 and 2020

Introducción. El tratamiento oncológico perioperatorio en pacientes con cáncer gástrico localmente avanzado está indicado; aun así, no siempre es posible. El objetivo de este estudio fue evaluar la supervivencia de los pacientes según la administración de quimioterapia perioperatoria. Métodos. Estudio observacional, tipo cohorte ambispectivo, incluyendo pacientes con cáncer gástrico localmente avanzado quienes recibieron o no quimioterapia perioperatoria. Resultados. Se incluyeron 33 pacientes, 90,9 % pertenecían al régimen subsidiado de salud y el 78,8 % en estadio T4. El grupo que recibió quimioterapia perioperatoria, que solo tuvo 5 pacientes (15,1 %), presentó mayor supervivencia global a 2 años (100 %), seguido del grupo de quimioterapia postoperatoria (58,8 %) y del grupo sin quimioterapia, que alcanzó una supervivencia global a 2 años de 54,5 %. Discusión. La supervivencia global fue mayor en el grupo de quimioterapia perioperatoria, consonante a lo descrito a nivel internacional, aunque los pacientes se encontraban en un estadío localmente más avanzado, la mayoría con T4 y N+ según AJCC VIII edición. Conclusiones. El estadío clínico es un factor pronóstico importante y, en nuestro medio, la mayoría de los pacientes consultan en estadíos localmente más avanzados. A eso se suman las dificultades en el acceso a la atención en salud. Aun así, la quimioterapia perioperatoria mostró una supervivencia mayor en pacientes con cáncer gástrico localmente avanzado

Introduction. Perioperative cancer treatment in patients with locally advanced gastric cancer is indicated; even so, it is not always possible. The objective was to evaluate survival according to time and receipt of perioperative chemotherapy. Methods. Observational study, ambispective cohort type, including patients with locally advanced gastric cancer who received or did not receive perioperative chemotherapy. Results. Thirty-three patients were included, 90.9% belonged to the subsidized regimen and 78.8% with TNM T4. The perioperative chemotherapy group, which only had five patients (15.1%), had a higher overall survival at 2 years (100%), followed by the postoperative chemotherapy group and by the group without chemotherapy, with an overall survival at 2 years of 58.8% and 54.5%, respectively. Discussion. Overall survival was higher in the perioperative chemotherapy group, consistent with what has been described internationally, although the patients were in a more advanced stage, most being with T4 and N+ according to the AJCC VIII edition. Conclusions. The clinical stage is an important prognostic factor and in our environment, most patients consult in more advanced stages, coupled with difficulties in accessing health care. Even so, perioperative chemotherapy showed a longer survival in patients with locally advanced gastric cancer, the data should not be extrapolated since the number of patients in each group is significantly different

Helicobacter pylori: Microorganismo patógeno o mutualista en poblaciones colombianas / Helicobacter pylori: Pathogenic or mutualistic microorganism in Colombian populations / Helicobacter pylori: microrganismo patógeno ou mutualista em populações Colombianas

Introducción: El riesgo de desarrollar cáncer gástrico varía entre continentes, países y regiones. A pesar de que existe una alta prevalencia de Helicobacter pylori su rol como patógeno o mutualista define el riesgo de cáncer gástrico en las regiones de Colombia. Objetivo: Discutir el rol de Helicobacter pylori en el riesgo de cáncer gástrico en Colombia. Materiales y métodos: Revisión de literatura mediante la búsqueda, en las bases de datos LILACS, SciELO, PubMed. Resultados: La coevolución del humano y de Helicobacter pylori; la virulencia de genes cagA, vacA; el tipo de respuesta inmune inflamatoria a Helicobacter pylori (Th1) o antinflamatoria (Th2) y la susceptibilidad humana a cáncer gástrico (IL1β, IL10), junto a la dieta y factores ambientales explican el papel de Helicobacter pylori como patógeno o mutualista asociado al riesgo de cáncer gástrico en Colombia. Conclusiones: Helicobacter pylori tiene un rol mutualista principalmente en poblaciones de bajo riesgo de cáncer gástrico (costas), no obstante, en poblaciones con alto riesgo de cáncer gástrico (andes), su papel como patógeno amerita la erradicación; única estrategia para mitigar la alta incidencia de este cáncer en Colombia.

Introduction: The risk to develop gastric cancer varies between continents, countries and regions. Although there is a high prevalence of Helicobater pylori, its role as either pathogen or mutualistic bacteria defines the risk of gastric cancer in Colombian regions. Objective: To discuss the role of Helicobacter pylori in the risk of gastric cancer in Colombia. Materials and methods: A literature review based on searching LILACS, SciELO, and PubMed databases. Results: Helicobacter pylori role as either a pathogen or mutualistic microorganism associated with gastric cancer risk in Colombia can be explained by analyzing elements such as: human and Helicobacter pylori coevolution; cagA and vacA gene virulence; inflammatory (Th1) or anti-inflammatory (Th2) responses induced by Helicobacter pylori; human susceptibility to gastric cancer (IL1β, IL10); diet; and environmental factors. Conclusions: Even though Helicobacter pylori has a mutualistic role in populations at low gastric cancer risk (coastal regions), its role as a pathogen in populations at higher risk (Andean regions) justifies its eradication as a key strategy to mitigate the incidence of this cancer in Colombia.

Introdução: O risco de desenvolver câncer gástrico varia entre continentes, países e regiões. Embora haja uma alta prevalência de Helicobacter pylori, seu papel como patógeno ou mutualista define o risco de câncer gástrico nas regiões da Colômbia. Objetivo: Discutir o papel do Helicobacter pylori no risco de câncer gástrico na Colômbia. Materiais e métodos: Revisão da literatura por meio da busca, nas bases de dados LILACS, SciELO e PubMed. Resultados: A coevolução de humanos e Helicobacter pylori; a virulência dos genes cagA, vacA; o tipo de resposta imune inflamatória ao Helicobacter pylori (Th1) ou anti-inflamatório (Th2) e a suscetibilidade humana ao câncer gástrico (IL1β, IL10), juntamente com a dieta e fatores ambientais explicam o papel do Helicobacter pylori como patógeno ou mutualista associado ao risco de câncer gástrico na Colômbia. Conclusões: Helicobacter pylori tem um papel mutualista principalmente em populações de baixo risco de câncer gástrico (litoral), porém, em populações com alto risco de câncer gástrico (andes), seu papel como patógeno justifica a erradicação; única estratégia para mitigar a alta incidência deste câncer na Colômbia.

Aspectos histológicos, genéticos y moleculares de las lesiones preneoplásicas de la mucosa gástrica / Histological, genetic and molecular aspects of preneoplastic lesions of the gastric mucosa

Siendo el cáncer gástrico la 3ª causa de muerte por cáncer en Chile, y existiendo estrategias de tamizaje consistentes en pesquisa de lesiones preneoplásicas de la mucosa gástrica, es relevante conocer los aspectos genéticos y moleculares que puedan ser aplicados, en la optimización de dichas estrategias a grupos de mayor riesgo. El objetivo de este manuscrito fue revisar la evidencia actual en los aspectos señalados, y de la inmunohistoquímica de 4 marcadores (p53, CDX2, MUC2 y S100A9) en la mucosa gástrica normal y en las lesiones preneoplásicas de la misma.

SUMMARY: Since gastric cancer is the 3rd leading cause of death from cancer in Chile, and there are screening strategies consisting of screening for preneoplastic lesions of the gastric mucosa, it is important to know certain genetic and molecular aspects that can be applied in optimizing these strategies for higher risk groups. The aim of this manuscript was to review the current evidence on the aforementioned aspects, and on the immunohistochemistry of 4 markers (p53, CDX2, MUC2 and S100A9) in normal gastric mucosa and in its preneoplastic lesions.

Relación de edad y sobrevida tras cirugía con intención curativa por cáncer gástrico en adultos: Un estudio observacional de centro único / Relationship of age and survival after surgery with curative intent for gastric cancer in adults: A single center observational study

Introducción: El cáncer gástrico constituye como una de las enfermedades de mayor morbimortalidad a nivel mundial; no obstante, la mortalidad se puede reducir con intervenciones tempranas. El objetivo del presente estudio fue determinar la relación entre la edad y la sobrevida tras cirugía con intención curativa por cáncer gástrico en pacientes atendidos en el Instituto del cáncer SOLCA, Cuenca, en el periodo 2012-2017. Métodos: El presente estudio analítico, retrospectivo fue realizado con la base de datos del Instituto del Cáncer SOLCA-Cuenca. Los datos fueron presentados en tablas de frecuencia y porcentajes. Se aplicó Chi-cuadrado (X2), análisis de Kaplan Meier y regresión de Cox, para relacionar las variables edad y años de sobrevida, considerándose estadísticamente significativo cuando P<0.05. Resultados: De los 603 pacientes con cáncer gástrico registrado durante el periodo de evaluación, el 35.3% fueron intervenidos quirúrgicamente, lográndose el seguimiento del 45.1%. Un total de 96 pacientes fueron incluidos, el 70.8% fueron intervenidos quirúrgicamente con intención curativa. En la muestra predominaba los hombres (52.9%) y el grupo etario de 70 a 79 años (30.2%). La tasa de sobrevida a los 5 años fue de 69.1% con un tiempo promedio de supervivencia de 7.24±0.49 años. La edad no se relacionó significativamente con la sobrevida de los pacientes (X2=3.15; P=0.667). Conclusión: existe una elevada tasa de sobrevida a los 5 años en los pacientes con cáncer gástrico intervenidos quirúrgicamente con intención curativa, la cual no asoció con la edad.

Introduction: Gastric cancer is one of the diseases with the highest morbidity and mortality worldwide; however, early interventions can reduce mortality. This study aimed to determine the relationship between age and survival after surgery with curative intent for gastric cancer in patients treated at the SOLCA Cancer Institute, Cuenca, in 2012-2017. Methods: The present analytical, retrospective study was carried out with the database of the SOLCA-Cuenca Cancer Institute. Data were presented in frequency and percentage tables. Chi-square (X2), Kaplan Meier analysis, and Cox regression were applied to relate the variables age and years of survival, being considered statistically significant when P<0.05. Results: Of the 603 patients with gastric cancer registered during the evaluation period, 35.3% underwent surgery, achieving a follow-up of 45.1%. A total of 96 patients were included, 70.8% underwent surgery with curative intent. The sample was dominated by men (52.9%) and the age group of 70 to 79 (30.2%). The 5-year survival rate was 69.1%, with a median survival time of 7.24±0.49 years. Age was not significantly related to patient survival (X2=3.15; P=0.667). Conclusion: there is a high 5-year survival rate in patients with gastric cancer who underwent surgery with curative intent, which was not associated with age. Keywords:

Over-expression of gastrin inhibits apoptosis of gastric cancer cells via reactive oxygen species and annexin A2-mediated mitochondrial dysfunction / La sobreexpresión de gastrina inhibe la apoptosis de las células de cáncer gástrico a través de especies reactivas de oxígeno y disfunción mitocondrial mediada por anexina A2

SUMMARY: Gastrin plays a vital role in the development and progression of gastric cancer (GC). Its expression is up-regulated in GC tissues and several GC cell lines. Yet, the underlying mechanism remains to be investigated. Here, we aim to investigate the role and mechanism of gastrin in GC proliferation. Gastrin-overexpressing GC cell model was constructed using SGC7901 cells. Then the differentially expressed proteins were identified by iTRAQ analysis. Next, we use flow cytometry and immunofluorescence to study the effect of gastrin on the mitochondrial potential and mitochondria-derived ROS production. Finally, we studied the underlying mechanism of gastrin regulating mitochondrial function using Co-IP, mass spectrometry and immunofluorescence. Overexpression of gastrin promoted GC cell proliferation in vitro and in vivo. A total of 173 proteins were expressed differently between the controls and gastrin- overexpression cells and most of these proteins were involved in tumorigenesis and cell proliferation. Among them, Cox17, Cox5B and ATP5J that were all localized to the mitochondrial respiratory chain were down-regulated in gastrin-overexpression cells. Furthermore, gastrin overexpression led to mitochondrial potential decrease and mitochondria-derived ROS increase. Additionally, gastrin-induced ROS generation resulted in the inhibition of cell apoptosis via activating NF-kB, inhibiting Bax expression and promoting Bcl-2 expression. Finally, we found gastrin interacted with mitochondrial membrane protein Annexin A2 using Co-IP and mass spectrometry. Overexpr ession of gastrin inhibits GC cell apoptosis by inducing mitochondrial dysfunction through interacting with mitochondrial protein Annexin A2, then up-regulating ROS production to activate NF-kB and further leading to Bax/Bcl-2 ratio decrease.

La gastrina juega un papel vital en el desarrollo y progresión del cáncer gástrico (CG). Su expresión está regulada al alza en tejidos de CG y en varias líneas celulares de CG. Sin embargo, el mecanismo subyacente aun no se ha investigado. El objetivo de este estudio fue investigar el papel y el mecanismo de la gastrina en la proliferación de CG. El modelo de células CG que sobre expresan gastrina se construyó usando células SGC7901. Luego, las proteínas expresadas diferencialmente se identificaron mediante análisis iTRAQ. A continuación, utilizamos la citometría de flujo y la inmunofluorescencia para estudiar el efecto de la gastrina en el potencial mitocondrial y la producción de ROS derivada de las mitocondrias. Finalmente, estudiamos el mecanismo subyacente de la gastrina que regula la función mitocondrial utilizando Co-IP, espectrometría de masas e inmunofluorescencia. La sobreexpresión de gastrina promovió la proliferación de células CG in vitro e in vivo. Un total de 173 proteínas se expresaron de manera diferente entre los controles y las células con sobreexpresión de gastrina y la mayoría de estas proteínas estaban implicadas en la tumorigenesis y la proliferación celular. Entre estas, Cox17, Cox5B y ATP5J, todas localizadas en la cadena respiratoria mitocondrial, estaban reguladas a la baja en las células con sobreexpresión de gastrina. Además, la sobreexpresión de gastrina provocó una disminución del potencial mitocondrial y un aumento de las ROS derivadas de las mitocondrias. Por otra parte, la generación de ROS inducida por gastrina resultó en la inhibición de la apoptosis celular mediante la activación de NF-kB, inhibiendo la expresión de Bax y promoviendo la expresión de Bcl-2. Finalmente, encontramos que la gastrina interactuaba con la proteína de membrana mitocondrial Anexina A2 usando Co-IP y espectrometría de masas. La sobreexpresión de gastrina inhibe la apoptosis de las células CG al inducir la disfunción mitocondrial a través de la interacción con la proteína mitocondrial Anexina A2, luego regula el aumento de la producción de ROS para activar NF-kB y conduce aún más a la disminución de la relación Bax/Bcl-2.

Identification of novel biomarkers with potential for diagnosis and prognosis of gastric cancer: a bioinformatics approach

INTRODUCTION: Gastric cancer (GC) is the fifth most diagnosed neoplasia and the third leading cause of cancer-related deaths. A substantial number of patients exhibit an advanced GC stage once diagnosed. Therefore, the search for biomarkers contributes to the improvement and development of therapies. OBJECTIVE: This study aimed to identify potential GC biomarkers making use of in silico tools. METHODS: Gastric tissue microarray data available in Gene Expression Omnibus and The Cancer Genome Atlas Program was extracted. We applied statistical tests in the search for differentially expressed genes between tumoral and non-tumoral adjacent tissue samples. The selected genes were submitted to an in-house tool for analyses of functional enrichment, survival rate, histological and molecular classifications, and clinical follow-up data. A decision tree analysis was performed to evaluate the predictive power of the potential biomarkers. RESULTS: In total, 39 differentially expressed genes were found, mostly involved in extracellular structure organization, extracellular matrix organization, and angiogenesis. The genes SLC7A8, LY6E, and SIDT2 showed potential as diagnostic biomarkers considering the differential expression results coupled with the high predictive power of the decision tree models. Moreover, GC samples showed lower SLC7A8 and SIDT2 expression, whereas LY6E was higher. SIDT2 demonstrated a potential prognostic role for the diffuse type of GC, given the higher patient survival rate for lower gene expression. CONCLUSION: Our study outlines novel biomarkers for GC that may have a key role in tumor progression. Nevertheless, complementary in vitro analyses are still needed to further support their potential.

Effect of acupuncture on functional delayed gastric emptying after gastric cancer surgery based on enhance recovery after surgery / 中国针灸

OBJECTIVE@#To observe the clinical effect of acupuncture for functional delayed gastric emptying after gastric cancer surgery on the basis of routine treatment.@*METHODS@#A total of 80 patients with functional delayed gastric emptying after gastric cancer surgery were randomly divided into an observation group (40 cases, 3 cases dropped off) and a control group (40 cases, 1 case dropped off). The control group was treated with routine treatment, e.g. continuous gastrointestinal decompression. On the basis of the treatment in the control group, the observation group was treated with acupuncture at Zusanli (ST 36), Shangjuxu (ST 37), Xiajuxu (ST 39), Gongsun (SP 4), Sanyinjiao (SP 6), 30 min each time, once a day, 5 days as a course, 1-3 courses were required. The first exhaust time, remove gastric tube time, liquid food intake time and hospital stay were compared in the two groups, and the clinical effect was evaluated.@*RESULTS@#The first exhaust time, remove gastric tube time, liquid food intake time and hospital stay in the observation group were shorter than the control group (P<0.001).@*CONCLUSION@#On the basis of routine treatment, acupuncture could accelerate the recovery of patients with functional delayed gastric emptying after gastric cancer surgery.

Hsa_circ_0000670 promoted the progression of gastric cancer through the miR-515-5p/SIX1 molecular axis / 中华肿瘤杂志

Objective: To explore whether hsa_circ_0000670 promotes the progression of gastric cancer by regulating the miR-515-5p/SIX1 molecular axis. Methods: The gastric cancer and adjacent normal tissues of 35 gastric cancer patients admitted to Rugao Hospital Affiliated to Nantong University from 2014 to 2015 were collected. The expression levels of circ_0000670, miR-515-5p and Sine oculis homeobox 1 (SIX1) in gastric cancer tissues and cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. The correlations between circ_0000670 and miR-515-5p, miR-515-5p and SIX1, circ_0000670 and SIX1 were analyzed by the Pearson method. Patients were divided into low circ_0000670 expression group (17 cases) and high circ_0000670 expression group (18 cases) based on the median of circ_0000670 expression level, and Kaplan-Meier was used to analyze the 5-year survival of patients. Cell proliferation was assessed via clone formation assay. Cell cycle and apoptosis were detected by flow cytometry. Wound healing and Transwell assays were used to detect cell migration and invasion ability. The targeting relationship between miR-515-5p and circ_0000670 or SIX1 was confirmed by the dual luciferase reporter assay. Nude mice were injected into HGC-27 cells transfected with sh-NC or sh-circ_0000670, and the volume and weight of the transplanted tumor were measured, also, the levels of circ_0000670, miR-515-5p and SIX1 in the transplanted tumor tissue were detected. Results: The expression levels of circ_0000670 and SIX1 in gastric cancer tissues and cell lines were significantly increased (P<0.05), while the expression levels of miR-515-5p were significantly decreased (P<0.05). The survival rate of patients in the low circ_0000670 expression group (82.4%) was significantly higher than that in the high circ_0000670 expression group (28.7%, P=0.034). Circ_0000670 was negatively correlated with miR-515-5p (r=-0.846, P<0.001), and miR-515-5p was negatively correlated with SIX1 (r=-0.615, P<0.001), but circ_0000670 was positively correlated with SIX1 (r=0.814, P<0.001). Transfection of si-circ_0000670 or miR-515-5p mimic could significantly reduce the number of clone-forming cells, migration distance, migration and invasion cells (P<0.05), and increase the ratio of G(0)/G(1) phase cells, apoptosis rate and the protein level of E-cadherin (P<0.05), decreased the proportion of S-phase cells and the protein level of Vimentin (P<0.05). The dual luciferase report assay confirmed that circ_0000670 could target miR-515-5p, and miR-515-5p could bind to SIX1. Co-transfection of si-circ_0000670 and miR-515-5p inhibitor could significantly attenuate the effects of si-circ_0000670 on cell proliferation, migration, invasion, cell cycle and apoptosis (P<0.05). Co-transfection of miR-515-5p mimic and pcDNA-SIX1 could significantly reduce the effects of miR-515-5p mimic on cell proliferation, migration, invasion, cell cycle and apoptosis (P<0.05). Compared with the sh-NC group [volume=(596.20±125.46) mm(3) and weight=(538.00±114.39) g], the volume and weight of transplanted tumors in the sh-circ_0000670 group [volume=(299.20±47.58) mm 3 and weight=(289.80±48.73 g)] were significantly reduced (P<0.05), the expression levels of circ_0000670 and SIX1 were significantly reduced (P<0.05), and the expression level of miR-515-5p was significantly increased (P<0.05). Conclusion: Knockdown of circ_0000670 could inhibit cell proliferation, migration, invasion of gastric cancer cells, induce cell cycle arrest in G(0)/G(1) phase and promote cell apoptosis by regulating the miR-515-5p/SIX1 axis.

Mechanism of Astragali Radix-Curcumae Rhizoma in treating gastric cancer based on network pharmacology and experimental verification / 中国中药杂志

This study aims to investigate the mechanism of Astragali Radix-Curcumae Rhizoma(HQEZ) in the treatment of gastric cancer based on network pharmacology. Further, the SGC7901 cell model of gastric cancer was employed to validate the efficacy and key targets of the herb pair. Firstly, the CCK-8 assay was employed to evaluate the direct effect of HQEZ on the proliferation of gastric cancer SGC7901 cells. Then, network pharmacology methods were employed to investigate the active ingredients, key targets, and key signaling pathways involved in the treatment of gastric cancer with HQEZ. The results showed that HQEZ contained 18 potential active ingredients, such as quercetin, naringenin, and curcumin. The results of gene ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment suggested that the main targets of HQEZ in treating gastric cancer were involved in the regulation of protein serine/threonine kinase activity, activation of mitogen-activated protein kinase(MAPK) activity, cysteine-type endopeptidase activity, and negative regulation of protein serine/threonine kinase activity. The hypoxia-inducible factor-1(HIF-1) signaling pathway, ATP-binding cassette(ABC) transporters, cytochrome P450-mediated metabolism of xenobiotics, p53 signaling pathway, and cell apoptosis were key signaling pathways of HQEZ in treating gastric cancer. The cell experiments demonstrated that HQEZ significantly downregulated the expression of ATP-binding cassette subfamily B member 1(ABCB1), epidermal growth factor receptor(EGFR), phosphorylated serine/threonine kinase(p-AKT), hypoxia inducible factor 1 subunit alpha(HIF1A), B-cell lymphoma 2(BCL2), breast cancer susceptibility protein 1(BRCA1), DNA polymerase theta(POLH), ribonucleotide reductase M1(RRM1), and excision repair cross-complementation group 1(ERCC1), and upregulated the expression of tumor protein P53(TP53) and cysteinyl aspartate-specific proteinase(CAPS3). Finally, a multivariate COX regression model was adopted to study the relationship between gene expression and clinical information data of gastric cancer patients in the TCGA database, which demonstrated that the key targets of HQEZ were associated with the poor prognosis in gastric cancer patients. Further feature selection using the LASSO algorithm showed that EGFR, HIF1A, TP53, POLH, RRM1, and ERCC1 were closely associated with the survival of gastric can-cer patients. In conclusion, HQEZ regulates the expression of genes involved in DNA repair, survival, and apoptosis in gastric cancer cells via multiple targets and pathways, assisting the treatment of gastric cancer.

High expression of death-associated protein 5 promotes glucose metabolism in gastric cancer cells and correlates with poor survival outcomes / 南方医科大学学报

OBJECTIVE@#To investigate the prognostic value of death-associated protein 5 (DAP5) in gastric cancer (GC) and its regulatory effect on aerobic glycolysis in GC cells.@*METHODS@#We analyzed DAP5 expression levels in GC and adjacent tissues and its association with survival outcomes of GC patients using public databases. We collected paired samples of GC and adjacent tissues from 102 patients undergoing radical resection of GC in our hospital from June, 2012 to July, 2017, and analyzed the correlation of DAP5 expression level detected immunohistochemically with the clinicopathological parameters of the patients. Cox regression analysis, Kaplan-Meier analysis, and ROC curves were used to explore the independent risk factors and the predictive value of DAP5 expression for 5-year survival of the patients. In the cell experiments, we observed the changes in aerobic glycolysis in MGC-803 cells following lentivirus-mediated DAP5 knockdown or overexpression by measuring glucose uptake and cellular lactate level and using qRT-PCR and Western blotting.@*RESULTS@#Analysis using the public databases showed that DAP5 was highly expressed in GC and correlated with tumor progression and poor survival outcomes of the patients (P < 0.05). In the clinical samples, DAP5 expression was significantly higher in GC than in the adjacent tissues (3.19±0.60 vs 1.00±0.12; t=36.863, P < 0.01), and a high expression of DAP5 was associated with a reduced 5-year survival rate of the patients (17.6% vs 72.5%; χ2=29.921, P < 0.05). A high DAP5 expression, T3-4, N2-3, and CEA≥5 ng/mL were identified as independent risk factors affecting 5-year survival outcomes of GC (P < 0.05), for which DAP5 expression showed a prediction sensitivity, specificity and accuracy of 73.2%, 80.4% and 79.0%, respectively. In MGC-803 cells, DAP5 knockdown significantly reduced glucose uptake, lactate level and the expressions of GLUT1, HK2 and LDHA, and DAP5 overexpression produced the opposite effects (P < 0.05).@*CONCLUSION@#A high expression of DAP5 in GC, which enhances cellular aerobic glycolysis to promote cancer progression, is correlated with a poor survival outcome and may serve as a biomarker for evaluating long-term prognosis of GC patients.

FJX1 overexpression is associated with poor prognosis and promotes gastric cancer proliferation via the PI3K/AKT signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the expression of four-jointed box kinase 1 (FJX1) in gastric cancer (GC), its correlation with survival outcomes of the patients, and its role in GC progression.@*METHODS@#The expression level of FJX1 in GC tissues and normal gastric mucosal tissues and its correlation with the survival outcomes of GC patients were analyzed using TCGA and GEO database GC cohort. Immunohistochemistry was used to detect FJX1 expression level in clinical specimens of GC tissue, and its correlations with the patients' clinicopathological parameters and prognosis were analyzed. Bioinformatic analysis was performed to identify the potential pathways of FJX1 in GC. The effects of FJX1 overexpression or FJX1 silencing on GC cell proliferation and expressions of proliferation-related proteins, PI3K, AKT, p-PI3K, and p-AKT were evaluated using CCK-8 assay and Western blotting. The effect of FJX1 overexpression on GC cell tumorigenicity was evaluated in nude mice.@*RESULTS@#GC tissues showed significantly higher expressions of FJX1 mRNA and protein compared with normal gastric mucosa tissues (P < 0.05). The high expression of FJX1 was associated with poor prognosis of GC patients (P < 0.05) and served as an independent risk factor for poor survival outcomes in GC (P < 0.05). FJX1 was expressed mainly in the cytoplasm of GC cells in positive correlation with Ki67 expression (R=0.34, P < 0.05), and was correlated with CA199 levels, depth of tumor infiltration and lymph node metastasis of GC (P < 0.05). In the cell experiment, FJX1 level was shown to regulate the expressions of Ki67 and PCNA and GC cell proliferation (P < 0.05). Gene set enrichment analysis indicated that the PI3K/AKT pathway potentially mediated the effect of FJX1, which regulated the expressions of PI3K and AKT and their phosphorylated proteins. In nude mice, FJX1 overexpression in GC cells significantly promoted the growth of the transplanted tumors (P < 0.05).@*CONCLUSION@#FJX1 is highly expressed in GC tissues and is correlated with poor prognosis of GC patients. FJX1 overexpression promotes GC cell proliferation through the PI3K/AKT signaling pathway, and may serve as a potential prognostic biomarker and therapeutic target for GC.