Overexpression SPRY2 Suppresses Esophageal Squamous Cell Carcinoma Progression Via Inactivation of ERK/AKT Signaling / La Sobreexpresión SPRY2 Suprime la Evolución del Carcinoma de Células Escamosas de Esófago Mediante la Inactivación de la Señalización ERK/AKT

SUMMARY: Esophageal cancer is one of the most aggressive gastrointestinal cancers. Invasion and metastasis are the main causes of poor prognosis of esophageal cancer. SPRY2 has been reported to exert promoting effects in human cancers, which controls signal pathways including PI3K/AKT and MAPKs. However, the expression of SPRY2 in esophageal squamous cell carcinoma (ESCC) and its underlying mechanism remain unclear. In the present study, we aimed to investigate the detailed role of SPRY2 in the regulation of cell proliferation, invasion and ERK/AKT signaling pathway in ESCC. It was identified that the expression level of SPRY2 in ESCC was remarkably decreased compared with normal tissues, and it was related to clinicopathologic features and prognosis ESCC patients. The upregulation of SPRY2 expression notably inhibited the proliferation, migration and invasion of Eca-109 cells. In addition, the activity of ERK /AKT signaling was also suppressed by the SPRY2 upregulation in Eca-109 cells. Our study suggests that overexpression of SPRY2 suppress cancer cell proliferation and invasion of by through suppression of the ERK/AKT signaling pathways in ESCC. Therefore, SPRY2 may be a promising prognostic marker and therapeutic target for ESCC.

El cáncer de esófago es uno de los cánceres gastrointestinales más agresivos. La invasión y la metástasis son las principales causas de mal pronóstico del cáncer de esófago. Se ha informado que SPRY2 ejerce efectos promotores en los cánceres humanos, que controla las vías de señales, incluidas PI3K/AKT y MAPK. Sin embargo, la expresión de SPRY2 en el carcinoma de células escamosas de esófago (ESCC) y su mecanismo subyacente aún no están claros. En el presente estudio, nuestro objetivo fue investigar el papel detallado de SPRY2 en la regulación de la proliferación celular, la invasión y la vía de señalización ERK/AKT en ESCC. Se identificó que el nivel de expresión de SPRY2 en ESCC estaba notablemente disminuido en comparación con los tejidos normales, y estaba relacionado con las características clínico-patológicas y el pronóstico de los pacientes con ESCC. La regulación positiva de la expresión de SPRY2 inhibió notablemente la proliferación, migración e invasión de células Eca-109. Además, la actividad de la señalización de ERK/AKT también fue suprimida por la regulación positiva de SPRY2 en las células Eca-109. Nuestro estudio sugiere que la sobreexpresión de SPRY2 suprime la proliferación y la invasión de células cancerosas mediante la supresión de las vías de señalización ERK/AKT en ESCC. Por lo tanto, SPRY2 puede ser un marcador de pronóstico prometedor y un objetivo terapéutico para la ESCC.

Effect of Survivin Down-Regulation by Egr1-Survivin shRNA Combined with Radiotherapy on Radiosensitivity of Esophageal Squamous Carcinoma / Efecto de la Regulación Negativa de Survivina por shRNA de Egr1-Survivina Combinado con Radioterapia sobre la Radiosensibilidad del Carcinoma Escamoso de Esófago

SUMMARY: This study is to investigate the effect of survivin down-regulation by Egr1-survivin shRNA combined with radiotherapy on the apoptosis and radiosensitivity of esophageal squamous cell carcinoma ECA109 and KYSE150 cells. ECA109 and KYSE150 cells were transfected with Egr1-survivin shRNA, and then treated with radiotherapy. After 24 h, the mRNA and protein levels of Egr1-survivin were detected by qPCR and Western-Blot. Cell cycle and apoptosis were detected by flow cytometry. Western blot also detected levels of cleavaged Caspase 3 and Caspase 9. YM155 was used as a positive control to inhibit survivin expression. The levels of survivin mRNA and protein in ECA109 and KYSE150 cells treated with Egr1-survivin shRNA combined with radiotherapy were significantly lower than those of the blank control group, the empty vector control group, and, the YM155 + radiotherapy group (P<0.05). Meanwhile, after survivin down-regulation, the ratio of G2 to S phase of ECA109 and KYSE150 cells increased significantly, leading to significant G2 and S phase arrest. Additionally, apoptosis of ECA109 and KYSE150 cells increased significantly (P <0.01). Further, protein levels of cleavaged Caspase 3 and Caspase 9 significantly increased in Egr1-survivin shRNA combined with radiotherapy group. Egr1-survivin shRNA combined with radiotherapy can down-regulate survivin expression, which further increases the apoptosis, and enhances the radiosensitivity of ECA109 and KYSE150 cells.

Este estudio tuvo como objetivo investigar el efecto de la regulación negativa de survivina por el shRNA de Egr1-survivina combinado con radioterapia sobre la apoptosis y la radiosensibilidad del carcinoma de células escamosas de esófago Células ECA109 y KYSE150. Las células ECA109 y KYSE150 se transfectaron con shRNA de survivina Egr1 y luego se trataron con radioterapia. Después de 24 h, los niveles de ARNm y proteína de Egr1-survivina se detectaron mediante qPCR y Western-Blot. El ciclo celular y la apoptosis se detectaron mediante citometría de flujo. La transferencia Western también detectó niveles de Caspasa 3 y Caspasa 9 escindidas. Se usó YM155 como control positivo para inhibir la expresión de survivina. Los niveles de ARNm y proteína de survivina en células ECA109 y KYSE150 tratadas con shRNA de survivina Egr1 combinado con radioterapia fueron significativamente más bajos que los del grupo control en blanco, el grupo control de vector vacío y el grupo de radioterapia YM155 + (P <0,05). Mientras tanto, después de la regulación negativa de survivina, la proporción entre las fases G2 y S de las células ECA109 y KYSE150 aumentó significativamente, lo que llevó a una detención significativa de las fases G2 y S. Además, la apoptosis de las células ECA109 y KYSE150 aumentó significativamente (P <0,01). Además, los niveles de proteína de Caspasa 3 y Caspasa 9 escindidas aumentaron significativamente en el shRNA de Egr1- survivina combinado con el grupo de radioterapia. El shRNA de survivina de Egr1 combinado con radioterapia puede regular negativamente la expresión de survivina, lo que aumenta aún más la apoptosis y mejora la radiosensibilidad de las células ECA109 y KYSE150.

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 de pacientes operados de cáncer de esófago / Morbidity and Mortality of Patients Operated on for Esophageal Cancer

Introducción: El tratamiento principal del cáncer esofágico es la esofagectomía. Objetivo: Determinar la morbilidad y mortalidad de los pacientes operados de cáncer esofágico. Métodos: Se realizó un estudio observacional, descriptivo y transversal en 87 pacientes operados de cáncer esofágico en el Servicio de Cirugía General del Hospital Provincial Docente Saturnino Lora de Santiago de Cuba durante el período comprendido de 2014 a 2018. Resultados: Dos pacientes en estadio II (100,0 por ciento) recibieron tratamiento quirúrgico curativo y 12 en estadio III (17,9 por ciento). Recibieron tratamiento quirúrgico paliativo 55 (82,1 por ciento) enfermos en estadio III y 18 (100,0 por ciento) en estadio IV. Predominó la técnica transhiatal de Denk-Sloan-Orringer aplicada en 10 (71,4 por ciento) pacientes. La gastrostomía predominó como proceder paliativo para alimentación en 53 (76,2 por ciento) pacientes. Se reportaron 45 complicaciones; el 53,3 por ciento de tipo médica, en las que prevalecieron las respiratorias: bronconeumonía (13,3 por ciento) y distrés respiratorio (11,1 por ciento). En cambio, el 46,7 por ciento de las complicaciones fueron de tipo quirúrgicas: infección del sitio operatorio (20,0 por ciento), seguida de la fuga anastomótica (15,6 por ciento). Fallecieron 16 (18,4 por ciento) pacientes del total de la serie. Las causas de muerte predominantes fueron el distrés respiratorio (31,3 por ciento) y la disfunción múltiple de órganos (25,0 por ciento). Conclusiones: La esofagectomía abierta o mínimamente invasiva se erige como el tratamiento quirúrgico de elección para el tratamiento del cáncer esofágico con intención curativa, proceder con elevada morbilidad y mortalidad a escala mundial. Los resultados de esta investigación coinciden con los reportados en la literatura médica nacional y extranjera(AU)

Introduction: The main treatment for esophageal cancer is esophagectomy. Objective: To determine the morbidity and mortality of patients operated on for esophageal cancer. Methods: An observational, descriptive and cross-sectional study was carried out with 87 patients operated on for esophageal cancer in the general surgery service of Hospital Provincial Docente Saturnino Lora, of Santiago de Cuba, during the period from 2014 to 2018. Results: Curative surgical treatment was received by 2 patients (100.0 percent) in stage II and 12 patients (17.9 percent) in stage III. Palliative surgical treatment was received by 55 ill patients (82.1 percent) in stage III and 18 ill patients (100.0 percent) in stage IV. There was a predominance of the Denk-Sloan-Orringer transhiatal technique, applied in 10 (71.4 percent) patients. Gastrostomy predominated in 53 (76.2 percent) patients as a palliative procedure for feeding. Forty-five complications were reported, 53.3 percent of which were medical, with respiratory complications prevailing: bronchopneumonia (13.3 percent) and respiratory distress (11.1 percent). On the other hand, 46.7 percent of the complications were surgical: surgical site infection (20.0 percent), followed by anastomotic leak (15.6 percent). Out of the total series, 16 (18.4 percent) patients died. The predominant causes of death were respiratory distress (31.3 percent) and multiple organ dysfunction (25.0 percent). Conclusions: Open or minimally invasive esophagectomy stands out as the surgical treatment of choice for esophageal cancer with curative purposes, being a procedure with high morbidity and mortality worldwide. The results of this research coincide with those reported in the national and foreign medical literature(AU)

Clinicopathological features of esophageal carcinoma with ductal differentiation of esophageal gland / 中华病理学杂志

Objective: To investigate the clinicopathological characteristics of esophageal carcinoma with gland duct differentiation. Methods: The clinical, morphologic and immunohistochemical (IHC) features of eight cases of esophageal carcinoma with gland duct differentiation diagnosed from 2012 to 2022 at the First Affiliated Hospital of Soochow University were summarized. Results: There were four males and four females, with a mean age of 68.5 (range 59-82) years. Two tumors were located in middle esophagus, five in the lower esophagus, and one in the cardia. The mean diameter was 2.4 cm (range 0.6-4.5 cm). The tumor had a bilayer epithelial structure, including the inner luminal epithelium and the outer basal epithelium. Immunohistochemistry showed that CK7 (8/8) and CK18 (8/8) were positive in the inner epithelium. p40 (8/8), p63 (8/8) and CK5/6 (8/8) were positive in the outer epithelium. SMA, calponin and CD117 were all negative. p53 mutants were found in all eight cases (strong and diffuse positivity in 6/8; complete loss of expression in 2/8). No columnar metaplasia, intestinal metaplasia and ectopic gastric mucosa were observed in the surface squamous epithelium in the cases. The mean follow-up time was 21.5 months (range 5-51 months). Seven patients survived and one patient died 31 months after surgery due to recurrence and liver metastasis. Conclusion: Esophageal carcinoma with esophageal gland duct differentiation is a rare tumor with unique histologic and IHC characteristics.

Chinese expert consensus on celiac lymphadenectomy during open/minimally invasive esophagectomy (2023 edition) / 中华肿瘤杂志

Surgical resection remains the cornerstone of the multidisciplinary treatment for patient with localized esophageal cancer. Lymphadenectomy is a pivotal step of radical esophagectomy, which is advanced technique required. Although the consensus on mediastinal lymph node dissection in the radical esophagectomy had been published in China, no agreement or consensus are available on the abdominal lymph node dissection. Based on the latest guidelines or consensuses, available clinical evidence, and agreements from Chinese expert panel of abdominal lymph node dissection in the radical esophagectomy, Chinese Society of Esophageal Cancer, China Anti-cancer Association organized experts to discuss and write this consensus. The expert consensus focuses on the key points of and makes recommendations for surgical approach, extent of lymphadenectomy, quality control and complication management for abdominal lymph node dissection in the radical esophagectomy in China. Applying a standard and efficient abdominal lymph node dissection in the radical surgical resection for patient with esophageal cancer is important and indispensable.

Effect of Porphyromonas gingivalis infection on IFNGR1 palmitoylation in esophageal cancer cells / 南方医科大学学报

OBJECTIVE@#To investigate the effect of Porphyromonas gingivalis (Pg) infection on IFNGR1 palmitoylation and biological behaviors of esophageal squamous cell carcinoma (ESCC) cells and the clinical implications.@*METHODS@#The expression levels of IFNGR1 protein in ESCC cell lines KYSE30 and KYSE70 were detected using Western blotting at 24 and 48 h after Pg infection, and 2-BP was used to detect IFNGR1 palmitoylation in the cells. KYSE70 cells with wild-type IFNGR1 (IFNGR1-WT cells) and with IFNGR1-C122A palmitoylation site mutation induced by site-specific mutagenesis (IFNGR1-C122A cells) were both infected with Pg, and the changes in palmitoylation of IFNGR1-C122A were analyzed using immunofluorescence and Click-iT assays. The changes in proliferation, migration and invasion ability of the infected cells were evaluated using plate cloning assay, scratch assay and Transwell assay, and IFNGR1 co-localization with lysosomal marker LAMP2 was dected using immunofluorescence assay. Immunohistochemistry was used to detect Pg infection and IFNGR1 protein expression in 50 ESCC tissues, and their correlation with the clinicopathological characteristics and survival outcomes of the patients was analyzed.@*RESULTS@#Pg infection down-regulated the protein expression of IFNGR1 in ESCC and promoted IFNGR1 palmitoylation at site 122. In IFNGR1-WT cells, Pg infection significantly enhanced cell proliferation, migration and invasion (P < 0.05). Similarly, Pg also significantly promoted proliferation, migration and invasion of IFNGR1-C122A cells, but to a lesser extent as compared with the wild-type cells (P < 0.05). Immunofluorescence assay showed that Pg and ZDHHC3 promoted IFNGR1 degradation within the lysosome. Immunohistochemical studies of the ESCC tissue samples showed a negative correlation between IFNGR1 and Pg expression, and a reduced IFNGR1 expression was correlated with a poorer survival outcome of the patient.@*CONCLUSION@#Pg infection enhances IFNGR1 palmitoylation to promote progression of ESCC, and elimination of Pg and inhibiting IFNGR1 palmitoylation may effectively control ESCC progression.

Membrane anatomy-based radical resection for esophageal cancer / 中华胃肠外科杂志

Radical resection of gastrointestinal tumors based on the membrane anatomy theory has significantly reduced the postoperative recurrence rate and improved the surgical efficacy. However, the theory of membrane anatomy has not been widely adopted in radical surgery for esophageal cancer. Our study found that the esophagus also has a membranous anatomical structure. As a foregut organ, the esophagus also has a mesenteric structure, and there is also a fifth metastasis pathway within the esophageal mesentery for esophageal cancers. The leak and metastasis of cancer caused by destruction of the mesenteric integrity may be the fundamental reason for the high postoperative recurrence rate. Using the nano carbon and indocyanine green fluorescence tracing technique, we demonstrated the lymphatic drainage of the upper esophageal segment to the left gastric artery mesenteric lymph nodes. Therefore, in the radical resection of esophageal cancer, we used the membrane anatomy theory for guidance to completely remove the esophageal cancer, esophageal mesentery, left gastric artery and its mesentery, as well as all structures within the mesentery, preventing the spread of cancer cells through the blood vessels, lymphatic system, and mesentery, and improving the efficacy and prognosis. This article elaborates on the theoretical basis of the anatomical structure of the esophageal membrane, embryonic development, imaging, autopsy, and endoscopic observation of the structure, as well as the application effect of the esophageal membrane anatomical theory in esophageal cancer radical surgery. It elucidates the anatomical structure of the esophageal membrane and the lymphatic drainage characteristics of esophageal cancer, reveals the law of lymphatic metastasis in esophageal cancer, optimizes lymphatic dissection strategies, and improves the efficacy of esophageal cancer radical surgery.

Advances of immunotherapy-related biomarker in esophageal carcinoma / 中华胃肠外科杂志

Esophageal carcinoma is one of the most common malignant tumors in the world, with incidence and mortality rankings of 7th and 6th, respectively. In recent years, immunotherapy represented by immune checkpoint inhibitors of programmed death-1 and programmed death ligand 1 (PD-L1) has been introduced into clinical practice and has changed the treatment status of esophageal cancer. Although immunotherapy has provided long-term survival benefits for patients with advanced esophageal cancer and high pathological response rates in the neoadjuvant therapy, only a few of the patients have satisfactory therapeutic outcomes. Therefore, effective biomarkers for predicting immunotherapeutic effects are urgently needed to identify those patients who could benefit from immunotherapy. In this paper, we mainly discuss recent research advances of biomarkers related to the immunotherapy of esophageal cancer and the clinical application prospects of these biomarkers.

Feasibility of a single-port thoracoscopy-assisted five-step laparoscopic procedure via transabdominal diaphragmatic approach for No.111 lymphadenectomy in patients with Siewert type II esophageal gastric junction adenocarcinoma / 中华胃肠外科杂志

Objective: We aimed to explore the feasibility of a single-port thoracoscopy- assisted five-step laparoscopic procedure via transabdominal diaphragmatic(TD) approach(abbreviated as five-step maneuver) for No.111 lymphadenectomy in patients with Siewert type II esophageal gastric junction adenocarcinoma (AEG). Methods: This was a descriptive case series study. The inclusion criteria were as follows: (1) age 18-80 years; (2) diagnosis of Siewert type II AEG; (3) clinical tumor stage cT2-4aNanyM0; (4) meeting indications of the transthoracic single-port assisted laparoscopic five-step procedure incorporating lower mediastinal lymph node dissection via a TD approach; (5) Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1; and (6) American Society of Anesthesiologists classification I, II, or III. The exclusion criteria included previous esophageal or gastric surgery, other cancers within the previous 5 years, pregnancy or lactation, and serious medical conditions. We retrospectively collected and analyzed the clinical data of 17 patients (age [mean ± SD], [63.6±11.9] years; and 12 men) who met the inclusion criteria in the Guangdong Provincial Hospital of Chinese Medicine from January 2022 to September 2022. No.111 lymphadenectomy was performed using five-step maneuver as follows: superior to the diaphragm, starting caudad to the pericardium, along the direction of the cardio-phrenic angle and ending at the upper part of the cardio-phrenic angle, right to the right pleura and left to the fibrous pericardium , completely exposing the cardio-phrenic angle. The primary outcome includes the numbers of harvested and of positive No.111 lymph nodes. Results: Seventeen patients (3 proximal gastrectomy and 14 total gastrectomy) had undergone the five-step maneuver including lower mediastinal lymphadenectomy without conversion to laparotomy or thoracotomy and all had achieved R0 resection with no perioperative deaths. The total operative time was (268.2±32.9) minutes, and the lower mediastinal lymph node dissection time was (34.0±6.0) minutes. The median estimated blood loss was 50 (20-350) ml. A median of 7 (2-17) mediastinal lymph nodes and 2(0-6) No. 111 lymph nodes were harvested. No. 111 lymph node metastasis was identified in 1 patient. The time to first flatus occurred 3 (2-4) days postoperatively and thoracic drainage was used for 7 (4-15) days. The median postoperative hospital stay was 9 (6-16) days. One patient had a chylous fistula that resolved with conservative treatment. No serious complications occurred in any patient. Conclusion: The single-port thoracoscopy-assisted five-step laparoscopic procedure via a TD approach can facilitate No. 111 lymphadenectomy with few complications.

Optimization of perioperative treatment strategies for locally advanced esophageal squamous cell carcinoma from the perspective of tumor heterogeneity / 中华胃肠外科杂志

Recent advances in multimodality treatment offer excellent opportunities to rethink the paradigm of perioperative management for locally advanced esophageal squamous cell carcinoma. One treatment clearly doesn't fit all in terms of a broad disease spectrum. Individualized treatment of local control of bulky primary tumor burden (advanced T stage) or systemic control of nodal metastatic tumor burden (advanced N stage) is essential. Given that clinically applicable predictive biomarkers are still awaited, therapy selection guided by diverse phenotypes of tumor burden (T vs. N) is promising. Potential challenges regarding the use of immunotherapy may also boost this novel strategy in the future.

Prevention and treatment of postoperative complications of esophageal cancer / 中华胃肠外科杂志

Surgery is the primary treatment for esophageal cancer, but the postoperative complication rate remains high. Therefore, it is important to prevent and manage postoperative complications to improve prognosis. Common perioperative complications of esophageal cancer include anastomotic leakage, gastrointestinal tracheal fistula, chylothorax, and recurrent laryngeal nerve injury. Respiratory and circulatory system complications, such as pulmonary infection, are also quite common. These surgery-related complications are independent risk factors for cardiopulmonary complications. Complications, such as long-term anastomotic stenosis, gastroesophageal reflux, and malnutrition are also common after esophageal cancer surgery. By effectively reducing postoperative complications, the morbidity and mortality of patients can be reduced, and their quality of life can be improved.

Surgical approach for esophageal cancer / 中华胃肠外科杂志

Due to the anatomical specificity of esophagus, esophagectomy can be carried out using different approaches, such as left transthoracic, right transthoracic and transhiatal approaches. Each surgical approach is associated with a different prognosis due to the complex anatomy. The left transthoracic approach is no longer the primary choice due to its limitations in providing adequate exposure, lymph node dissection, and resection. The right transthoracic approach is capable of achieving a larger number of dissected lymph nodes and is currently considered the preferred procedure for radical resection. Although the transhiatal approach is less invasive, it could be challenging to perform in a limited operating space and has not been widely adopted in clinical practice. Minimally invasive esophagectomy offers a wider range of surgical options for treating esophageal cancer. This paper reviews different approaches to esophagectomy.

Extent of lymphadenectomy for esophageal cancer / 中华胃肠外科杂志

Esophageal cancer is a common malignant tumor in China. For resectable ones, surgery is still the primary treatment. At present, the extent of lymph node dissection remains controversial. Extended lymphadenectomy makes metastatic lymph nodes more likely to be resected, which contributed to pathological staging and postoperative treatment. However,it may also increase the risk of postoperative complications and affect prognosis. Therefore, it is controversial how to balance the optimal extent/number of dissected lymph nodes for radical resection with the lower risk of severe complications. In addition, whether the lymph node dissection strategy should be modified after neoadjuvant therapy needs to be investigated, especially for patients who have a complete response to neoadjuvant therapy. Herein, we summarize the clinical experience on the extent of lymph node dissection in China and worldwide, aiming to provide guidence for the extent of lymph node dissection in esophageal cancer.

Neoadjuvant therapy in locally advanced esophageal squamous cell carcinoma / 中华胃肠外科杂志

The efficacy of surgery alone for locally advanced esophageal squamous cell carcinoma (ESCC) is limited. In-depth studies concerning combined therapy for ESCC have been carried out worldwide, especially the neoadjuvant treatment model, including neoadjuvant chemotherapy (nCT), neoadjuvant chemoradiotherapy (nCRT), neoadjuvant chemotherapy combined with immunotherapy (nICT), neoadjuvant chemoradiotherapy combined with immunotherapy (nICRT), etc. With the advent of the immunity era, nICT and nICRT have attracted much attention from researchers. An attempt was thus made to take an overview of the evidence-based research advance regarding the neoadjuvant therapy of ESCC.

Hotspots and prospects of esophageal cancer research in China / 中华胃肠外科杂志

Esophageal cancer is a malignant tumor with a high incidence in China. At pesent, advanced esophageal cancer patients are still frequently encountered. The primary treatment for resectable advanced esophageal cancer is surgery-based multimodality therapy, including preoperative neoadjuvant therapy, such as chemotherapy, chemoradiotherapy or chemotherapy plus immunotherapy, followed by radical esophagectomy with thoraco-abdominal two-field or cervico-thoraco-abdominal three-field lymphadenectomy via minimally invasive approach or thoracotomy. In addition, adjuvant chemotherapy, radiotherapy, or chemoradiotherapy, or immunotherapy may also be administered if suggested by postoperative pathological results. Although the treatment outcome of esophageal cancer has improved significantly in China, many clinical issues remain controversial. In this article, we summarize the current hotspots and important issues of esophageal cancer in China, including prevention and early diagnosis, treatment selection for early esophageal cancer, surgical approach selection, lymphadenectomy method, preoperative neoadjuvant therapy, postoperative adjuvant therapy, and nutritional support treatment.

GDF15 negatively regulates chemosensitivity via TGFBR2-AKT pathway-dependent metabolism in esophageal squamous cell carcinoma / 医学前沿

Treating patients with esophageal squamous cell carcinoma (ESCC) is challenging due to the high chemoresistance. Growth differentiation factor 15 (GDF15) is crucial in the development of various types of tumors and negatively related to the prognosis of ESCC patients according to our previous research. In this study, the link between GDF15 and chemotherapy resistance in ESCC was further explored. The relationship between GDF15 and the chemotherapy response was investigated through in vitro and in vivo studies. ESCC patients with high levels of GDF15 expression showed an inferior chemotherapeutic response. GDF15 improved the tolerance of ESCC cell lines to low-dose cisplatin by regulating AKT phosphorylation via TGFBR2. Through an in vivo study, we further validated that the anti-GDF15 antibody improved the tumor inhibition effect of cisplatin. Metabolomics showed that GDF15 could alter cellular metabolism and enhance the expression of UGT1A. AKT and TGFBR2 inhibition resulted in the reversal of the GDF15-induced expression of UGT1A, indicating that TGFBR2-AKT pathway-dependent metabolic pathways were involved in the resistance of ESCC cells to cisplatin. The present investigation suggests that a high level of GDF15 expression leads to ESCC chemoresistance and that GDF15 can be targeted during chemotherapy, resulting in beneficial therapeutic outcomes.

Network Pharmacology and in vitro Experimental Verification on Intervention of Quercetin, Present in Chinese Medicine Yishen Qutong Granules, on Esophageal Cancer / 中国结合医学杂志

OBJECTIVE@#To explore the potential mechanism of Yishen Qutong Granules (YSQTG) for the treatment of esophageal cancer using network pharmacology and experimental research.@*METHODS@#The effective components and molecular mechanism of YSQTG in treating esophageal cancer were expounded based on network pharmacology and molecular docking. The key compound was identified by high-performance liquid chromatography and mass spectrometry (HPLC-MS) to verify the malignant phenotype of the key compounds in the treatment of esophageal cancer. Then, the interaction proteins of key compounds were screened by pull-down assay combined with mass spectrometry. RNA-seq was used to screen the differential genes in the treatment of esophageal cancer by key compounds, and the potential mechanism of key compounds on the main therapeutic targets was verified.@*RESULTS@#Totally 76 effective compounds of YSQTG were found, as well as 309 related targets, and 102 drug and disease interaction targets. The drug-compound-target network of YSQTG was constructed, suggesting that quercetin, luteolin, wogonin, kaempferol and baicalein may be the most important compounds, while quercetin had higher degree value and degree centrality, which might be the key compound in YSQTG. The HPLC-MS results also showed the stable presence of quercetin in YSQTG. By establishing a protein interaction network, the main therapeutic targets of YSQTG in treating esophageal cancer were Jun proto-oncogene, interleukin-6, tumor necrosis factor, and RELA proto-oncogene. The results of cell function experiments in vitro showed that quercetin could inhibit proliferation, invasion, and clonal formation of esophageal carcinoma cells. Quercetin mainly affected the biological processes of esophageal cancer cells, such as proliferation, cell cycle, and cell metastasis. A total of 357 quercetin interacting proteins were screened, and 531 genes were significantly changed. Further pathway enrichment analysis showed that quercetin mainly affects the metabolic pathway, MAPK signaling pathway, and nuclear factor kappa B (NF- κ B) signaling pathway, etc. Quercetin, the key compound of YSQTG, had stronger binding activity by molecular docking. Pull-down assay confirmed that NF- κ B was a quercetin-specific interaction protein, and quercetin could significantly reduce the protein level of NF- κ B, the main therapeutic target.@*CONCLUSION@#YSQTG can be multi-component, multi-target, multi-channel treatment of esophageal cancer, it is a potential drug for the treatment of esophageal cancer.