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ABSTRACT Background: Esophageal endoscopic submucosal dissection (EESD) is a complex and time-consuming procedure at which training are mainly available in Japan. There is a paucity of data concerning the learning curve to master EESD by Western endoscopists. Objective: This study aimed to assess the learning curve effect on patient's clinical outcome for EESD. Methods: This is a retrospective observational study. Enrolling patients that underwent EESD from 2009 to 2021. The analysis was divided into two periods; T1: case 1 to 49 and T2: case 50 to 98. The following features were analyzed for each group: patients and tumors characteristics, en-bloc, complete and curative resection rates, procedure duration and adverse events rate. Results: Ninety-eight EESD procedures were performed. Mean procedure time was 111.8 min and 103.6 min for T1 and T2, respectively (P=0.004). En bloc resection rate was 93.8% and 97.9% for T1 and T2, respectively (P=0.307). Complete resection rate was 79.5% and 85.7% for T1 and T2, respectively (P=0.424). Curative resection rate was 65.3% and 71.4% for T1 and T2, respectively (P=0.258). Four patients had complications; three during T1 period and one during T2 period. Overall mortality rate: 0%. Conclusion: The esophageal endoscopic submucosal dissection could be performed effectively and safely by an adequately trained Western endoscopist.
RESUMO Contexto: A dissecção endoscópica da submucosa do esôfago (DSEE) é um procedimento complexo, cujo treinamento está disponível principalmente no Japão. Há uma escassez de dados sobre a curva de aprendizado para se capacitar na realização da DSEE por endoscopistas ocidentais. Objetivo: Este estudo teve como objetivo avaliar o efeito da curva de aprendizado no resultado clínico dos pacientes submetidos a DSEE. Métodos: Trata-se de um estudo observacional retrospectivo. Foram incluídos pacientes submetidos a DSEE no período de 2009 a 2021. A análise foi dividida em dois períodos; T1: caso 1 a 49 e T2: caso 50 a 98. Os seguintes parâmetros foram analisados para cada grupo: características clínicas dos pacientes e dos tumores de esôfago, taxas de ressecção em bloco, completa e curativa, duração do procedimento e taxa de eventos adversos. Resultados: Noventa e oito procedimentos de DSEE foram realizados. O tempo médio do procedimento foi de 111,8 min e 103,6 min nos períodos T1 e T2, respectivamente (P=0,004). A taxa de ressecção em bloco foi de 93,8% e 97,9% nos períodos T1 e T2, respectivamente (P=0,307). A taxa de ressecção completa foi de 79,5% e 85,7% nos períodos T1 e T2, respectivamente (P=0,424). A taxa de ressecção curativa foi de 65,3% e 71,4% para T1 e T2, respectivamente (P=0,258). Quatro pacientes tiveram complicações; três durante o período T1 e um durante o período T2. Taxa de mortalidade geral: 0%. Conclusão: A DSEE pode ser realizada de forma eficaz e segura por um endoscopista ocidental adequadamente treinado.
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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
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Humans , Esophageal Neoplasms , Esophagogastric Junction , Stomach Neoplasms , Survival , ClassificationABSTRACT
@#With the widespread application of minimally invasive esophagectomy, inflatable video-assisted mediastinoscopic transhiatal esophagectomy (IVMTE) has gradually become one of the alternative surgical methods for transthoracic esophagectomy due to less trama, fewer perioperative complications and better short-term efficacy. However, there is no uniform standard for surgical methods and lymph node dissection in medical centers that perform IVMTE, which affects the standardization and further promotion of IVMTE. Therefore, on the basis of fully consulting domestic and foreign literature, our team proposed an expert consensus focusing on IVMTE, in order to standardize the clinical practice, guarantee the quality of treatment and promote the development of IMVTE.
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Objective:To explore the quality of life (QOL) and the related influencing factors of patients with early esophageal cancer after endoscopic submucosal dissection (ESD).Methods:A questionnaire survey was conducted in 167 early esophageal cancer patients who underwent ESD in Shanxi Province Cancer Hospital from January 2022 to July 2022. European Organization for Research and Treatment of Cancer Quality of Life Assessment Core Scale (EORTC QLQ-C30) and the Esophageal Cancer Supplementary Scale (EORTC QLQ-OES18) were used to compare QOL of patients with different clinical characteristics before surgery, 1 month after surgery and 6 months after surgery, And multiple logistic regression analysis was used to analyze the influencing factors of patients' QOL at 6 months after surgery.Results:EORTC QLQ-C30 showed that the scores of the patients' physical function, role function, and social function at 1 month and 6 months after surgery were lower than those before surgery, and the differences were statistically significant (all P < 0.05). The scores of dyspnea, constipation, nausea and vomiting, fatigue, and economic status in the symptom area were higher than those before surgery, and the differences were statistically significant (all P < 0.05). According to EORTC QLQ-OES18, the scores of difficulty in swallowing oral fluid, obstruction, poor eating initiative, dry mouth, and cough at 1 month and 6 months after surgery were higher than those before surgery, and the differences were statistically significant (all P < 0.05). The score of dysphagia at 1 month after surgery was higher than that before surgery, while the score at 6 months after surgery was lower than that before surgery, and the differences were statistically significant (all P < 0.05). The score of dyspepsia at 1 month and 6 months after surgery was lower than that before surgery, and the difference was statistically significant (all P < 0.05). Multivariate analysis showed that the lesion perimeter >1/2 perimeter (lesion perimeter >1/2 perimeter vs. lesion perimeter ≤ 1/2 perimeter: OR = 2.072, 95% CI 1.536-2.796, P < 0.05) and postoperative esophageal stricture dilatation (undergoing esophageal stricture dilatation or not: OR = 2.193, 95% CI 1.429-2.789, P < 0.05) were independent risk factors affecting the QOL of patients at 6 months after surgery. Conclusions:The QOL of early esophageal cancer patients after ESD is decreased compared with that before surgery, and the main manifestations include physical function, role function, social function, and symptom. The area of lesion and undergoing esophageal stricture dilatation or not are factors affecting the QOL of patients after surgery.
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Objective:To investigate the aspiration risk of preventive placement of nasal jejunum nutrition tube in advanced esophageal cancer patients receiving radiotherapy and the influencing factors.Methods:The clinical data of 220 patients with advanced esophageal cancer who received radiotherapy and preventive placement of nasal jejunum nutrition tube feeding from November 2020 to November 2021 in Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively analyzed. The level of aspiration risk was measured according to the standard swallowing function assessment scale (SSA). The questionnaire collected the following data: (1) the general data including gender, age, educational level, history of smoking, history of alcoholism, knowledge of aspiration; (2) the disease factors including tumor staging, tumor site, swallowing function, abdominal distention; (3) the nosocomial factors including history of esophageal cancer surgery, sedation and analgesia treatment, combination of chemotherapy or not, cumulative radiotherapy dose, grade of radiation esophagitis, the position, time and tube feeding method of enteral nutrition. The standard swallowing function of patients was measured and repeated saliva swallowing test (RSST) was used to screen the patients with the difficulty in the esophageal function swallowing. Multiple linear regression was used to analyze the factors affecting aspiration risk.Results:A total of 220 patients with advanced esophageal cancer were enrolled in the investigation. Finally, 70 patients (31.8%) had grade 0 aspiration risk, and SSA score was 19; 23 patients (10.5%) had grade I aspiration risk, and SSA score was (23.4±1.3); 103 patients (46.8%) had grade Ⅱ aspiration risk, and SSA score was (27.5±1.1); 24 patients (10.9%) had grade Ⅲ aspiration risk, and SSA score was (33.2±1.5); 136 patients (61.8%) in total had aspiration risk. There were 32.7% (72/220) patients knowing the knowledge of aspiration. Multifactor analysis showed that esophageal tumor site ( t = -2.869, P = 0.005), cumulative radiotherapy dose ( t = 5.558, P < 0.001), grade of radiation esophagitis ( t = 11.405, P < 0.001), the duration time of enteral nutrition ( t = 4.050, P < 0.001) were independent factors affecting the aspiration risk. Conclusions:The aspiration risk of preventive placement of nasal jejunum nutrition tube in advanced esophageal cancer patients receiving radiotherapy is high, which is related to esophageal tumor site, grade of radiation esophagitis, cumulative radiotherapy dose and the duration time of enteral nutrition.
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Objective:To investigate the correlation between the expression levels of STMN1, BubR1, bcl-2 and Bad and the chemotherapy effect of paclitaxel-containing regimen in patients with esophageal squamous cell carcinoma (ESCC).Methods:The clinical data of ESCC patients who received paclitaxel-containing chemotherapy at Fenyang Hospital Affiliated to Shanxi Medical University from September 2016 to June 2021 were retrospectively analyzed. Among them, 59 cases received maintenance chemotherapy and 27 cases received surgery after 3 courses of neoadjuvant chemotherapy. The expression levels of STMN1, BubR1, bcl-2 and Bad in tumor tissues before chemotherapy were detected by immunohistochemistry. The imaging efficacy after 3 courses of chemotherapy and pathological efficacy after neoadjuvant chemotherapy were evaluated. The imaging efficacy, pathological efficacy and progression-free survival (PFS) were compared between the high expression group and the low expression group of each protein.Results:The proportion of patients with stage Ⅳ (46.3%, 19/41), the proportion of patients with low differentiation (22%, 9/41) and the incidence of lymph node metastasis (95.1%, 39/41) in STMN1 high expression group were higher than those in STMN1 low expression group (17.8%, 8/45; 4.4%, 2/45; 64.4%, 29/45), and the differences were statistically significant (all P < 0.05). The proportion of patients with stage Ⅳ in Bad high expression group was lower than that in Bad low expression group, and the difference was statistically significant ( P < 0.05). In the evaluation of imaging efficacy, the chemotherapy sensitivity rates in STMN1 and BubR1 high expression groups (29.3%, 12/41; 37.9%, 22/58) were lower than those in STMN1 and BubR1 low expression groups (75.6%, 34/45; 85.7%, 24/28), and the chemotherapy sensitivity rate of patients in Bad high expression group (65.9%, 27/41) was higher than that in Bad low expression group (42.2%, 19/45), and the difference was statistically significant (all P < 0.05). There was no statistical correlation between bcl-2 expression and chemotherapy sensitivity rate ( P > 0.05). In the evaluation of pathological efficacy, the proportion of patients with tumor regression grade (TRG) score 0-1 after neoadjuvant therapy in STMN1 high expression group (27.3%, 3/11) was lower than that in STMN1 low expression group (75.0%, 12/16), and the difference was statistically significant ( P = 0.022). There were no statistical differences in the proportions of patients with TRG score 0-1 after neoadjuvant therapy between high and low expression groups of BubR1, bcl-2 and Bad (all P > 0.05). The PFS rate was 15.2% (9/59) for patients received maintenance chemotherapy, and the median PFS time was 6 months. Kaplan-Meier analysis showed that PFS in STMN1 low expression group was better than that in STMN1 low expression group ( χ2 = 12.90, P < 0.001). PFS in BubR1 low expression group was better than that in BubR1 high expression ( χ2 =12.04, P < 0.001). PFS in Bad high expression group was better than that in Bad low expression group ( χ2 =9.69, P = 0.004). There was no statistical difference in PFS between high and low bcl-2 expression groups ( χ2 =1.43, P = 0.320). Conclusions:ESCC patients with low expression of STMN1, low expression of BubR1 and high expression of Bad have better chemotherapy effect after receiving paclitaxel-containing regimen, but there is no correlation between bcl-2 expression and chemotherapy efficacy.
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Esophageal cancer is the most common malignant tumor in the digestive system in China. Because of the hidden clinical symptoms, the disease has reached the local advanced stage once discovered. For patients who have lost the opportunity of surgery, synchronous chemoradiotherapy is recommended, however, the recurrence rate after chemoradiotherapy is still high. Chemotherapy, radiotherapy and surgery are commonly used for recurrent patients, but the survival rate of recurrent patients after treatment is not satisfying. In recent years, immunotherapy has been successfully applied in various solid tumors, and its efficacy and safety in the treatment of advanced and recurrent metastatic esophageal cancer have also been recognized in the field of esophageal cancer. This article aims to provide high efficacy and low toxicity treatment methods for patients with recurrent esophageal cancer after chemoradiotherapy through summarizing the relevant literatures of various treatments including immunotherapy.
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Objective:To analyze the correlation of epidermal growth factor receptor (EGFR) expression in esophageal cancer tissues with sensitivity of radical radiotherapy and prognosis of patients.Methods:A total of 98 esophageal cancer patients admitted to the Affiliated Hospital of Jiangnan University from January 2017 to July 2019 were selected, and all patients received radical radiotherapy. The efficacy was assessed after 4 weeks of radiotherapy, partial remission (PR) + complete remission (CR) was treated as the sensitive group and disease progression (PD) + stable disease (SD) was treated as the tolerated group. The expression of EGFR in cancer tissues and paraneoplastic tissues (more than 5cm from the margin of cancer tissues) was measured by using immunohistochemistry. The expression of EGFR in cancer tissues and paraneoplastic tissues and the clinicopathological characteristics of the sensitive and tolerant groups were compared. Cox proportional risk model was used to analyze the factors influencing the prognosis of esophageal cancer patients; the Kaplan-Meier method was used to analyze the relationship between EGFR expression in cancer tissues and prognosis of patients.Results:The positive expression rate of EGFR in esophageal cancer tissues (66.3%, 65/98) was higher than that in paraneoplastic tissues (29.6%, 29/98), and the difference between the two groups was statistically significant (χ 2=26.49, P < 0.001). All 98 patients successfully completed radical radiotherapy, including 4 cases of CR, 60 cases of PR, 26 cases of SD and 8 cases of PD. The proportion of patients with highly differentiated and tumor length ≤1.5 cm in the sensitive group was higher than that in the tolerant group, and the differences were statistically significant (all P < 0.05). The positive expression rate of EGFR in cancer tissues in the sensitive group (56.3%, 36/64) was lower than that in the tolerant group (85.3%, 29/34), and the difference between the two groups was statistically significant ( χ2=8.39, P < 0.001). Multifactorial Cox regression analysis showed that poor differentiation, tumor long diameter >1.5 cm, and positive EGFR expression were independent risk factors for overall survival in patients with esophageal cancer (all P < 0.05). The difference in overall survival between patients with positive and negative EGFR expression was statistically significant ( χ2=9.70, P = 0.002). Conclusions:Highly-expressed EGFR in esophageal cancer tissues may suggest low sensitivity of radical radiotherapy and poor prognosis of patients.
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Objective:To investigate the efficacy and adverse reactions of simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) combined with chemotherapy in the treatment of superior mediastinal lymph node metastasis after esophageal cancer surgery.Methods:The clinical data of 72 patients with concurrent chemoradiotherapy for superior mediastinal lymph node metastasis after esophageal cancer surgery in Tai'an Cancer Prevention and Treatment Hospital from January 2019 to May 2021 were retrospectively analyzed, and they were divided into intensity-modulated radiotherapy (IMRT) group (36 cases) and SIB-IMRT group (36 cases) according to different radiotherapy methods. The short-term efficacy, long-term survival rate and adverse reactions of the two groups were compared.Results:The response rate in the IMRT group was 66.7% (24/36), the response rate in the SIB-IMRT group was 86.1% (31/36), and the difference between the two groups was statistically significant ( χ2 = 3.77, P = 0.047). The 1-, 2- and 3-year overall survival rates in the IMRT group were 75.0%, 44.4% and 27.8%, and the 1-, 2- and 3-year overall survival rates in the SIB-IMRT group were 83.3%, 52.8% and 33.3%; the difference in the overall survival between the two groups was not statistically significant ( χ2 = 0.70, P = 0.401). There were statistical differences in the incidence of leukopenia, radiation esophagitis and radiation pleural gastritis between the two groups (all P < 0.05). There were no statistical differences in the incidence of radiation pneumonia and gastrointestinal reactions between the two groups (both P > 0.05). Conclusions:SIB-IMRT combined with chemotherapy in patients with superior mediastinal lymph node metastasis after esophageal cancer surgery has good local control rate and mild adverse reactions.
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Objective:To investigate the effects of long non-coding RNA (lncRNA) RP11-1212A22.4 on the cell viability and invasive ability of esophageal cancer cell lines by targeting miRNA-483-5p (miR-483-5p).Methods:The expression of RP11-1212A22.4 in esophageal cancer tissues was analyzed by using GEPIA online database. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of RP11-1212A22.4 in human esophageal cancer cell lines EC9706, KYSE30, TE-13, Eca109 and normal esophageal epithelial cell line HET-1A. The lowest expression level of EC9706 cell line in RP11-1212A22.4 was divided into RP11-1212A22.4 group (transfected with pcDNA-RP11-1212A22.4 plasmid) and the control group (transfected with pcDNA-NC plasmid). The cell viability of EC9706 cell was analyzed by using methyl thiazolyl tetrazolium (MTT) method, and the invasion ability of EC9706 cell was detected by using Transwell assay. The targeting relationship between RP11-1212A22.4 and miR-483-5p was verified by using StarBase database prediction and dual luciferase reporter assay. The relative expression level of miR-483-5p of EC9706 cell in two groups was detected by using qRT-PCR. Western blot was used to detect the expressions of cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase 2 (MMP-2), cyclin-dependent kinase 4 (CDK4), and matrix metalloproteinase 9 (MMP-9) proteins in two groups.Results:In GEPIA online database, compared with adjacent tissues, the relative expression level of RP11-1212A22.4 in esophageal cancer tissues was decreased, and the difference was statistically significant ( P < 0.001). The relative expression levels of RP11-1212A22.4 in esophageal cancer cell lines EC9706, KYSE30, TE-13, Eca109 and normal esophageal mucosal epithelial cell line HET-1A were 0.11±0.08, 0.32±0.09, 0.72±0.09, 0.59±0.13 and 0.97±0.12, and the difference was statistically significant ( F = 40.42, P < 0.001). The relative expression levels of RP11-1212A22.4 in EC9706 cells of RP11-1212A22.4 group and the control group were 11.9±2.4 and 1.0±0.3, respectively, and the difference was statistically significant ( t = 8.89, P < 0.001). Compared with the control group, the cell viability of EC9706 cell in RP11-1212A22.4 group was decreased (all P < 0.05). The number of invasive cells in RP11-1212A22.4 group was lower than that in the control group (48±12 vs. 106±22, t = 4.63, P < 0.001). StarBase database prediction and dual luciferase reporter assay both showed that RP11-1212A22.4 targeted miR-483-5p. The relative expression level of miR-483-5p in RP11-1212A22.4 group was lower than that in the control group (0.24±0.11 vs. 1.02±0.23, t = 5.98, P = 0.001). Compared with the control group, the expressions of CDK6, MMP-2, CDK4 and MMP-9 proteins in the RP11-1212A22.4 group were decreased. Conclusions:RP11-1212A22.4 is lowly expressed in esophageal cancer tissues and cell lines, and it inhibits the cell viability and invasive ability of esophageal cancer cells by targeting miR-483-5p.
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Objective:To explore the distribution features of resident CD8 + T cells infiltration in human esophageal cancer tissues and its clinical significance. Methods:Data from the Cancer Genome Atlas database were retrieved, the correlation between CD103 + CD8 + T cells and infiltration degree of conventional type 1 dendritic cell (cDC1), conventional type 2 dendritic cell (cDC2), type 3 dendritic cell(DC3) was investigated. From January 2006 to December 2008, 78 esophageal cancer tissues and 75 adjacent normal tissues from 78 esophageal cancer patients were collected by Shanghai Outdo Biotechnology Co., Ltd, the clinical data of patients was followed up by telephone until July 2015. The distribution of CD8 + T cells and CD103 + CD8 + T cells in cancer tissues and adjacent normal tissues was detected by multi-color labeling techniques and multispectral tissue imaging. The differences of the number and the ratio of CD8 + T cells and CD103 + CD8 + T cells in cancer tissues and adjacent normal tissues were compared. The Kaplan-Meier survival curves of patients with tissue infiltration of CD8 + T cells and CD103 + CD8 + T cells at different levels were drawn through the R language " survminer" package, and the best cut-off value was obtained. TNM stage, pathological stage and other clinical parameters of patients with high and low infiltration of CD8 + T cells, CD103 + CD8 + T cells were compared. Wilcoxon rank sum test, chi-square test, log-rank test and Cox proportional risk regression model statistical analysis were used to evaluate the prognostic value of the above indicators. Spearman correlation analysis was used for correlation analysis. Results:In the cancer tissues of patients with esophageal cancer, the infiltration degree of CD103 + CD8 + T cells was positively correlated with the infiltration degree of cDC1 cells, cDC2 cells and DC3 cells ( r=0.67, 0.53 and 0.47, all P<0.001). The percentage of CD8 + T cells in all cells in the whole tissue core of tumor tissues (63.09% (42.14%, 76.21%)) was higher than that of adjacent normal tissues (2.56% (1.68%, 5.38%)), and the difference was statistically significant ( U=41.00, P<0.001). The proportion of CD103 + CD8 + T cells in all cells in the whole tissue core of tumor tissues (7.92% (1.60%, 20.61%)) was higher than that of adjacent normal tissues (0.04% (0.01%, 0.10%)), and the difference was statistically significant ( U=857.50, P<0.001). The percentage of high CD8 + T cells infiltration in esophageal cancer tissues of patients with pathological stage Ⅰ+ Ⅱ was lower than that of patients with stage Ⅲ+ Ⅳ (57.9%, 33/57 vs. 85.7%, 18/21); the percentage of high CD103 + CD8 + T cells in CD8 + T cells in esophageal cancer tissues of patients with TNM stage Ⅰ+ Ⅱ was lower than that of patients with stage Ⅲ+ Ⅳ (21.6%, 8/37 vs. 48.8%, 20/41), and the differences were both statistically significant ( χ2=5.25 and 6.23, P=0.022 and 0.013). The results of Kaplan-Meier survival analysis and univariate Cox proportional risk regression model showed that the overall survival (OS) of patients with high CD8 + T cell infiltration was longer than that of patients with low CD8 + T cell infiltration ( HR=0.57, 95% confidence interval (95% CI) 0.34 to 0.96, P=0.034). There was no significant difference in OS between patients with high CD103 + CD8 + T cell infiltration and patients with low CD103 + CD8 + T cell infiltration ( HR=0.66, 95% CI 0.40 to 1.08, P>0.05). Conclusion:The high infiltration of CD103 + CD8 + T cells in esophageal cancer tissues are expected to be used as a prognostic predictor for patients with esophageal cancer, which is an important component of anti-tumor immune response in tumor microenvironment of esophageal cancer.
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Objective:To investigate the expression of circ_0063865 in esophageal squamous cell carcinoma(ESCC)tissues and cells and its effect on the biological properties of the cells.Methods:The loop structure and stability of circ_0063865 were identified by Sanger sequencing, back-to-back primer validation and the ribonuclease R(Rnase R)tolerance assay.The expression of circ_0063865 was detected by RNA fluorescence in situ hybridization in an ESCC tissue microarray and its clinical relevance was analyzed.The expression levels of circ_0063865 in a normal esophageal epithelial cell line and ESCC cell lines were measured by real-time quantitative polymerase chain reaction(RT-qPCR). Cell counting Kit-8, the colony formation assay, the scratch assay, the transwell invasion assay and flow cytometry were used to detect the effects of circ_0063865 on cell proliferation, migration, invasion abilities and apoptosis, respectively.Results:The loop formation of circ_0063865 was verified by Sanger sequencing, back-to-back primer and Rnase R tolerance assays.The results of RNA fluorescence in situ hybridization showed that the mean fluorescence intensity of circ_0063865 expressed in ESCC tissues was significantly higher than in its paired paracancerous normal tissues( t=2.267, P<0.05). The expression of circ_0063865 was significantly associated with lymph node metastasis( χ2=4.356, P<0.05). The average overall survival time of patients with high circ_0063865 expression ESCC was lower than that of patients with low circ_0063865 expression ESCC.RT-qPCR results demonstrated that, compared with HEEC, circ_0063865 expression was elevated in ESCC cell lines( F=18.413, P<0.05). In addition, after circ_0063865 knockdown, the proliferation, migration and invasion abilities of KYSE-30 and KYSE-150 cells were significantly decreased, and the level of apoptosis was significantly increased(both P<0.05). Conclusions:The expression of circ_0063865 in ESCC is high, and changes in its expression are significantly correlated with lymph node metastasis.Additionally, circ_0063865 can promote the proliferation, migration and invasion of ESCC cells.
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Objective:To evaluate the effect of niraparib, the poly (ADP-ribose) polymerase (PARP) inhibitor, on the radiosensitivity of esophageal squamous cell carcinoma (ESCC) and to preliminarily investigate its mechanism.Methods:Human esophageal squamous cell carcinoma cells ECA-109 and KYSE-150 were divided into the control, niraparib, single irradiation, combined (niraparib+irradiation) groups. Cell proliferation was measured by CCK-8 assay. The changes of cell survival rate were detected by colony formation assay. The changes of cell cycle and apoptosis were analyzed by flow cytometry. The number of γH2AX foci was detected by immunofluorescence, and the expression levels of PARP-1, cleaved-PARP, RAD51, mitogen-activated protein kinase (MAPK) [extracellular signal-regulated kinase 1 and 2 (ERK1/2) ] and p-MAPK (ERK1/2) proteins were determined by Western blot. All data were expressed as Mean±SD. Data between two groups conforming to normal distribution through the normality test were subject to independent sample t-test and multiple groups were analyzed using one-way ANOVA. Results:In human ESCC cells ECA-109 and KYSE-150, the proliferation of ESCC cells was significantly inhibited by niraparib combined with irradiation, and the values of average lethal dose (D 0), quasi-threshould dose(D q), survival fraction after 2 Gy irradiation (SF 2) in the combined group were decreased compared with those in the single irradiation group. The effect of irradiation alone on apoptosis of ECA-109 and KYSE-150 cells was limited. Compared to single irradiation group, irradiation combined with niraparib further increased the apoptosis rate in ESCC cells ( P=0.015, P=0.006). In ECA-109 cells, G 2/M phase arrest was significantly increased in combined group compared with irradiation alone group ( P<0.001). In ECA-109 cells, the number of γH2AX foci in combined group was higher than that in the single irradiation group after 2 h, and showed a significantly slower decay of γH2AX foci ( P<0.001). Moreover, niraparib combined with irradiation enhanced the radiation-induced cleavage of PARP-1 and down-regulated the expression of Rad51 and p-MAPK(ERK1/2). Conclusion:Niraparib can increase the radiosensitivity of esophageal cancer cells by inhibiting cell proliferation, promoting cell apoptosis, inhibiting the repair of DNA damage and regulating the MARK-ERK signaling pathway.
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Objective:To investigate the prognostic value of Onodera's prognostic nutrition index (PNI) before treatment in patients with cervical and upper thoracic esophageal squamous cell carcinoma (CUTESCC) undergoing definitive chemoradiotherapy (dCRT) and its predictive value in the occurrence of ≥ grade 2 radiation esophagitis (RE).Methods:The data of 163 CUTESCC patients eligible for inclusion criteria admitted to the Fourth Hospital of Hebei Medical University from January 2012 to December 2017 were retrospectively analyzed. The receiver operating characteristic (ROC) curve was used to calculate the best cut-off value of PNI for predicting the prognosis of patients. The prognosis of patients was analyzed by univariate and Cox multivariate analyses. Logistics binary regression model was adopted to analyze the risk factors of ≥ grade 2 RE in univariate and multivariate analyses. The significant factors in logistic multivariate analysis were used to construct nomogram for predicting ≥ grade 2 RE.Results:The optimal cut-off value of PNI was 48.57 [area under the curve (AUC): 0.653, P<0.001]. The median overall survival (OS) and progression-free survival (PFS) were 26.1 and 19.4 months, respectively. The OS ( χ2=6.900, P=0.009) and PFS ( χ2=9.902, P=0.003) of patients in the PNI ≥ 48.57 group ( n=47) were significantly better than those in the PNI < 48.57 group ( n=116). Cox multivariate analysis showed that cTNM stage and PNI were the independent predictors of OS ( HR=1.513, 95% CI: 1.193-1.920, P=0.001; HR=1.807, 95% CI: 1.164-2.807, P=0.008) and PFS ( HR=1.595, 95% CI: 1.247-2.039, P<0.001; HR=2.260, 95% CI: 1.439-3.550, P<0.001). Short-term efficacy was another independent index affecting PFS ( HR=2.072, 95% CI: 1.072-4.003, P=0.030). Logistic multivariate analysis showed that the maximum transverse diameter of the lesion ( OR=3.026, 95% CI: 1.266-7.229, P=0.013), gross tumor volume (GTV) ( OR=3.456, 95% CI: 1.373-8.699, P=0.008), prescription dose ( OR=3.124, 95% CI: 1.346-7.246, P=0.009) and PNI ( OR=2.072, 95% CI: 1.072-4.003, P=0.030) were the independent factors affecting the occurrence of ≥ grade 2 RE. These four indicators were included in the nomogram model, and ROC curve analysis showed that the model could properly predict the occurrence of ≥ grade 2 RE (AUC=0.686, 95% CI: 0.585-0.787). The calibration curve indicated that the actually observed values were in good agreement with the predicted RE. Decision curve analysis (DCA) demonstrated satisfactory nomogram positive net returns in most threshold probabilities. Conclusions:PNI before treatment is an independent prognostic factor for patients with CUTESCC who received definitive chemoradiotherapy. The maximum transverse diameter of the lesion, GTV, prescription dose and PNI are the risk factors for ≥ grade 2 RE in this cohort. Establishing a prediction model including these factors has greater predictive value.
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Advanced esophageal cancer accounts for a large proportion of all esophageal cancer cases, and the treatment modality recommended by the current guidelines is systemic treatment. Radiotherapy is an important treatment option for malignant tumors, which is widely applied in clinical practice. Retrospective analysis and small-sample prospective studies have shown that combination of radiotherapy with chemotherapy, targeted therapy, and immunotherapy has the advantages of improving disease control rate, symptom remission rate and prolonging survival of advanced esophageal cancer patients. Therefore, it is an important clinical topic issue to make better use of the advantages of radiotherapy for esophageal cancer, such as rapid relief of symptoms, durable efficacy, and stimulation of immune neoantigens, etc. To optimize the treatment strategy of advanced esophageal cancer, the radiotherapy strategy for esophageal cancer with oligometastases or multiple metastases, and the screening method for the eligible population for radiotherapy were reviewed, aiming to provide reference for improving the status of radiotherapy in comprehensive treatment of advanced esophageal cancer.
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Neoadjuvant therapy, especially neoadjuvant chemoradiotherapy, has become the standard preoperative treatment for locally advanced resectable esophageal cancer, whereas the recurrence and distant metastasis rates after surgery remain high. In recent years, programmed cell death protein 1 (PD-1) / programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors have been widely adopted in immunotherapy for cancer. Whether PD-1/PD-L1 immune checkpoint inhibitors combined with neoadjuvant chemotherapy / neoadjuvant chemoradiotherapy could further improve clinical efficacy, increase the complete surgical resection rate and safety are current research hotspots. In this article, neoadjuvant immunotherapy combined with chemotherapy / radiochemotherapy for esophageal cancer was reviewed.
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Objective:To study the risk factors and prediction model of radiation pneumonitis (RP) after radical chemoradiotherapy for locally advanced esophageal cancer based on dosiomics.Methods:Clinical data of 105 patients with esophageal cancer undergoing radical chemoradiotherapy at Zhejiang Cancer Hospital between January 2020 and August 2021 were retrospectively analyzed. RP was scored using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0 (CTCAE 5.0). Clinical factors, traditional dosimetric features and dosiomics features were collected, respectively. The features for predicting PR were analyzed by limma package. Support vector machine, k-nearest neighbor, decision tree, random forest and extreme gradient boosting were used to establish the prediction model, and the ten-fold cross-validation method was employed to evaluate the performance of the model. The differences of this model when different features were chosen were analyzed by delong test.Results:The incidence of RP in the whole group was 21.9%. One clinical factor, 6 traditional dosimetric features and 42 dosiomics features were significantly correlated with the occurrence of RP (all P<0.05). Support vector machine using linear kernel function yielded the optimal prediction performance, and the area under the receiver operating characteristic (ROC) without and with dosiomics features was 0.72 and 0.75, respectively. The models established by support vector machine, random forest and extreme gradient boosting were significantly different with and without dosiomics features (all P<0.05). Conclusion:The addition of dosiomics features can effectively improve the performance of the prediction model of RP after radiotherapy for esophageal cancer.
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Objective:To compare dosimetric and radiobiological parameters between automatic and manual uARC plans in the treatment of esophageal cancer patients, aiming to provide reference for clinical application.Methods:High-quality uARC plans of 100 patients with esophageal cancer were selected, and the mean values of the dosimetric parameters in the target area and organs at risk (OAR) were counted, and the goal table of uRT-TPOIS intelligent plan was established. Automatic and manual uARC plans were generated with UIH (United Imaging) treatment planning system (TPS) for 21 esophageal cancer patients. The differences in mean dose (D mean), approximate minimum (D 98%) and maximum (D 2%) dose of planning target volume (PTV), homogeneity index (HI) and conformity index (CI), dose of OAR, mean planning time, monitor unit (MU), tumor control probability (TCP) and normal tissue complication probability (NTCP) were compared between automatic and manual uARC plans. Normally distributed data between two groups were compared by paired t-test, and non-normally distributed data were assessed by nonparametric Wilcoxon test. Results:The D 98% (PTV 60 Gy: P<0.001, PTV 54 Gy: P=0.001) , CI (PTV 60 Gy: P<0.001, PTV 54 Gy: P=0.002) and target volume of area covered by prescription dose (V 54 Gy: P<0.001) of the automatic uARC plans were better than those of manual uARC plans (all P<0.05). There was no significant difference in D mean or HI between the two plans [PTV 54 Gy (59.32±1.87) Gy vs. (59.13±1.64) Gy, (0.19±0.02) vs. (0.18±0.02), all P>0.05]. The D mean and D max of spinal cord of the automatic plan were better than those of the manual plan [(13.22±4.27) Gy vs. (13.75±4.44) Gy, P=0.020 and (36.99±1.67) Gy vs. (38.14±1.31) Gy, P=0.011]. There was no significant difference in the mean dose of V 20 Gy of the lung between two plans ( P>0.05), whereas the mean doses of V 5 Gy and V 10 Gy of the lung of the manual plan were less than those of the automatic plan ( both P<0. 001). Automatic uARC plan had a significantly shorter mean planning time than manual uARC plan [(11.79±1.71) min vs. (53.36±8.23) min, P<0.001]. MU did not significantly differ between two plans [(762.84±74.83) MU vs. (767.41±80.63) MU, P>0.05]. The TCP of the automatic plan was higher than that of the manual plan (PTV 60 Gy 89.15%±0.49% vs. 86.75%±6.46%, P=0.004 and PTV 54 Gy 79.79%±3.48% vs. 77.51%±5.04%, P=0.006). However, manual plan had a lower NTCP of the lung than automatic uARC plan (0.46%±0.40% vs. 0.35%±0.32%, P<0.001). There was no significant difference in NTCP of heart and spinal cord between two plans (all P>0.05). Conclusion:It is feasible to generate automatic uARC plan with uRT-TPOIS TPS for esophageal cancer patients, which can increase the target CI and shorten the plan design time.
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Objective:To investigate the efficacy of camrelizumab combined with second-line therapy in patients with recurrent or metastatic esophageal squamous cell carcinoma (ESCC) in the real-world settings.Methods:Clinical data of 48 patients with esophageal cancer who met the inclusion criteria were retrospectively analyzed. The types of failure after first-line treatment, clinical efficacy, side effects and prognostic factors of second-line treatment were analyzed. SPSS 25.0 software was used for statistical analysis. Count data were expressed by composition ratio and analyzed by Chi-square test or Fisher's exact test. Survival analysis was conducted by Kaplan-Meier curve and log-rank test. Non-normally distributed data were recorded with the median, range and quartile. Results:There were 26, 14, and 4 cases of combined chemoradiotherapy, chemotherapy and radiotherapy in the treatment of second-line camrelizumab, and 4 cases received immunotherapy alone. The median duration of immunotherapy was 6 cycles (range, 2-39 cycles). After second-line treatment, the short-term efficacy of 17, 27 and 4 cases was partial remission (PR), stable disease (SD) and progressive disease (PD), respectively. The overall response rate (ORR) was 35.4% and disease control rate (DCR) was 91.7%. The 1- and 2-year OS rates were 42.9% and 22.5%, and 1- and 2-year PFS rates were 29.0% and 5.8%. The median OS and PFS were 9.0 months (95% CI=6.4-11.7) and 8.5 months (95% CI=1.5-5.6), respectively. Multivariate analysis showed that combined immunotherapy mode, number of cycles of immunotherapy and short-term efficacy were the independent prognostic indicators affecting OS in this group of patients ( HR=2.598, 0.222, 8.330, P=0.044, <0.001, <0.001). Lymphocyte count, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), combined immunotherapy mode and short-term efficacy were the independent prognostic indicators affecting PFS in this group ( HR=3.704, 3.598, 6.855, 2.159, 2.747, P=0.009, 0.008, <0.001, 0.049, 0.012). Conclusions:Camrelizumab combined with second-line therapy can bring survival benefit to patients with recurrent or metastatic ESCC after first-line therapy, especially immunotherapy combined with chemoradiotherapy can significantly provide survival benefit. Peripheral blood inflammatory biomarkers are independent indicators affecting clinical prognosis of patients. Patients with better short-term efficacy also achieve better prognosis. The final conclusion remains to be validated by a large number of randomized controlled studies.
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Radiotherapy plays an important role in the treatment of advanced esophageal cancer. Under the premise of effective systemic treatment, selecting patients who may benefit from local radiotherapy can effectively relieve symptoms and improve quality of life, and it is expected to prolong the survival time of patients. Moreover, immunotherapy plays an increasingly significant role in advanced esophageal cancer, and the efficacy of radiotherapy combined with immunotherapy is promising.