ObjectiveTo compare the clinical efficacy of modified Ivor-Lewis esophagectomy, which preserves azygos vein, thoracic duct and peripheral tissues, and classic Ivor-Lewis esophagectomy, which resects these tissues, in the treatment of esophageal cancer, so as to evaluate whether it is necessary to resect azygos vein, thoracic duct and peripheral tissues in esophagectomy for esophageal cancer.MethodsPatients scheduled for surgical treatment of thoracic esophageal cancer in Department of Thoracic Surgery of Sichuan Cancer Hospital from June 2011 to June 2013 were randomly assigned to the retention group and the resection group, each including 100 patients. The retention group included 87 males and 13 females with an average age of 60.53±7.72 years. In the resection group, there were 80 males and 20 females with an average age of 60.69±7.69 years. Patients in the two groups were compared for the duration of surgery, intraoperative blood loss, postoperative thoracic drainage volume, postoperative complications, and number of dissected lymph nodes, etc. Postoperative relapse and survival rates at 1, 3 and 5 years postoperatively were also followed up and compared for patients in the two groups.ResultsThere was no statistical difference between the two groups in general patient characteristics, number of dissected lymph nodes, or postoperative pathological stage, etc. (P>0.05). Compared to the resection group, there were shorter duration of surgery, less intraoperative blood loss, and less thoracic drainage volume in the first 3 days following surgery in the retention group, with statistical differences (P<0.05). There was no statistical difference between the two groups in type or site of relapse or metastasis (P>0.05). The survival rates at 1, 3, and 5 years postoperatively was 78.7% vs. 81.3%, 39.4% vs. 37.5%, and 23.4% vs. 17.7%, respectively, in the retention group and the resection group, with no statistical difference (P>0.05).ConclusionModified Ivor-Lewis esophagectomy preserving azygos vein, thoracic duct and peripheral tissues could reduce surgical trauma, would not increase postoperative relapse or metastasis, and could produce long-term efficacy comparable to that of extended resection.
ObjectiveTo evaluate the safety and necessity of recurrent laryngeal lymph node resection by comparing the complications and prognosis of patients with recurrent laryngeal nerve injury receiving different recurrent laryngeal lymph node resections.MethodsWe reviewed the clinical data of 153 patients with stage T1N0M0 esophageal squamous cell carcinoma who underwent radical esophageal cancer surgery at the Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from June 2014 to May 2016. Among them, 125 were male and 28 were female, at an average age of 62 years. All patients underwent bilateral recurrent laryngeal nodes sampling. They were divided into 3 groups according to the dissection situation: patients with only one recurrent laryngeal lymph node resection on both sides during the operation were treated as a sampling group (n=49); patients with only one recurrent laryngeal lymph node resection on one side and more than one recurrent laryngeal lymph nodes resection on the other side were treated as a unilateral dissection group (n=49); patients with more than one recurrent laryngeal lymph nodes resection on both sides were treated as a bilateral dissection group (n=55). Follow-up was performed to compare the prognostic differences among the three groups. Seven days after the operation, the vocal cords of the patients were examined with an electronic laryngoscope and classified using the Clavien-Dindo system. The differences in complications related to recurrent laryngeal nerve injury among the three groups were compared.ResultsThe 5-year overall survival (OS) rate of the patients in the sampling group, unilateral dissection group and bilateral dissection group was 66.8%, 88.5%, 93.8%, respectively. There was statistical difference between the sampling group and the unilateral dissection group or the bilateral dissection group (P<0.05), and no statistical difference between the unilateral dissection group and the bilateral dissection group (P>0.05). The incidence of complications among the three groups was not statistically different (P>0.05).ConclusionFor patients with esophageal squamous cell carcinoma of stage T1N0M0, the lymph nodes of the bilateral recurrent laryngeal nerves should be removed during the operation as many as possible, which will help improve the 5-year survival rate of the patients.
Objective To compare short-term quality of life and postoperative complications in esophageal squamous cell carcinoma patients with different routes reconstruction after McKeown esophagectomy. Methods The clinical data of 144 patients with esophageal squamous cell carcinoma who received McKeown esophagectomy in Shanghai Chest Hospital from January 2016 to October 2016 were retrospectively reviewed. Among them 93 patients accepted retrosternal approach (a RR group, 71 males and 22 females at an average age of 63.5±7.7 years) and 51 patients accepted posterior mediastinal approach (a PR group, 39 males and 12 females at an average age of 62.3±8.0 years). Short-term surgical outcomes were compared and a Quality of Life Questionnaire of Patients Underwent Esophagectomy 1.0 was performed at postoperative 1st and 3rd month. Results There was no difference in two groups in sex, age, Body Mass Index (BMI), and location and clinical stage of tumors (P>0.05). The neoadjuvant therapy was more performed in the RR group (16.1%vs. 5.9%, P=0.075). There were more robot-assisted esophagecctomy operations performed in the PR group (52.9% vs. 45.2%, P=0.020). No significant difference was noted in operation duration, intraoperative blood loss or length of ICU stay between the RR and PR groups (251.3±59.1 min vs. 253.1±27.7 min, P=0.862; 223.7±75.1 ml vs. 240.0±75.1 ml, P=0.276; 3.7±6.6 d vs. 2.3±2.1 d, P=0.139). The patients in the PR group had more lymph nodes dissected and shorter hospital stay (P<0.001). Rate of R1/2 resection was higher in the RR group (12.9%vs. 5.9%, P=0.187). No surgery-related mortality was observed in both groups. The anastomotic leak and the anastomotic stricture was higher in the RR group than that in the PR group (25.8% vs. 5.9%, P=0.003). No significant difference was found between the two groups in the quality of life at postoperative 1st and 3rd month. However, the quality of life at postoperative 3rd month significantly improved in both groups (P<0.001). Compared with the PR group, the dysphagia was more severe in the RR group at postoperative 1st month (3.3±1.5 vs. 2.6±1.1, P=0.007), while the reflux symptom was lighter at postoperative 3rd month (3.0±1.8 vs. 3.6±1.6, P=0.045). Conclusion The two different routes reconstruction after McKeown esophagectomy are both safe and feasible. The anterior mediastinal approach increases the risk of anastomotic leak, but with low incidence of reflux symptom.
Objective To explore the role of versican (VCAN) in ESCC prognosis based on bioinformatics data. MethodsFirst, three RNA microarray datasets of ESCC were downloaded from GEO database, which were then integrated and used to explore differentially expressed genes (DEGs). The subsequent analysis was conducted based on the results of these DEGs: (1) The STRING database was used to construct a protein-protein interaction (PPI) network; (2) molecular complex detection software was used to analyze the modules of the PPI network, of which the most significant modules were chosen, and hub genes were the genes included in the chosen modules; (3) high-throughput RNA sequencing data from TCGA and GTEx databases were used to verify the expression of these hub genes to confirm whether they were differentially expressed; (4) the survival curve analysis of confirmed DEGs was conducted to select genes that had significant influence on the survival of ESCC; (5) TIMER database was used to analyze the relationship between the gene expression of VCAN and the abundance of tumor-infiltrating immune cells (TIICs) and gene markers in these cells; (6) Targetscan and miRDB software were used to predict the miRNAs that could regulate VCAN, and Cytoscape software was used to construct the regulatory network. ResultsA total of 630 DEGs and 32 hub genes were found, of which VCAN was an up-regulated DEG, and high expression of VCAN was significantly associated with poor prognosis of ESCC. Moreover, VCAN could also play a role in the immune microenvironment of ESCC, which was mainly manifested by a significant positive correlation between the abundance of VCAN and the abundance of M2 macrophages gene markers, some of which had been reported to be associated with poor prognosis of ESCC. Finally, we also found that VCAN could be regulated by 15 miRNAs in ESCC, some of which had been reported to be associated with ESCC prognosis. ConclusionThis study provides direct and indirect comprehensive evidence for the role of VCAN in ESCC prognosis. The direct evidence is that the survival curve shows that highly expressed VCAN is significantly associated with the poor prognosis of ESCC, and the indirect evidence is that VCAN is positively related to some markers which indicate poor prognosis in the ESCC immune microenvironment, and VCAN can be regulated by some prognostic miRNAs in ESCC.
ObjectiveTo construct a prognostic model of esophageal squamous cell carcinoma (ESCC) based on immune checkpoint-related genes and explore the potential relationship between these genes and the tumor microenvironment (TME). Methods The transcriptome sequencing data and clinical information of immune checkpoint genes of samples from GSE53625 in GEO database were collected. The difference of gene expression between ESCC and normal paracancerous tissues was evaluated, and the drug sensitivity of differentially expressed genes in ESCC was analyzed. We then constructed a risk model based on survival-related genes and explored the prognostic characteristics, enriched pathway, immune checkpoints, immune score, immune cell infiltration, and potentially sensitive drugs of different risk groups. ResultsA total of 358 samples from 179 patients were enrolled, including 179 ESCC samples and 179 corresponding paracancerous tissues. There were 33 males and 146 females, including 80 patients≤60 years and 99 patients>60 years. 39 immune checkpoint genes were differentially expressed in ESCC, including 14 low expression genes and 25 high expression genes. Drug sensitivity analysis of 8 highly expressed genes (TNFRSF8, CTLA4, TNFRSF4, CD276, TNFSF4, IDO1, CD80, TNFRSF18) showed that many compounds were sensitive to these immunotherapy targets. A risk model based on three prognostic genes (NRP1, ICOSLG, HHLA2) was constructed by the least absolute shrinkage and selection operator analysis. It was found that the overall survival time of the high-risk group was significantly lower than that of the low-risk group (P<0.001). Similar results were obtained in different ESCC subtypes. The risk score based on the immune checkpoint gene was identified as an independent prognostic factor for ESCC. Different risk groups had unique enriched pathways, immune cell infiltration, TME, and sensitive drugs. Conclusion A prognostic model based on immune checkpoint gene is established, which can accurately stratify ESCC and provide potential sensitive drugs for ESCC with different risks, thus providing a possibility for personalized treatment of ESCC.
Objective To analyze the efficacy of and recurrence mode after adjuvant radiotherapy for lower thoracic esophageal squamous cell carcinoma (TESCC) patients after radical operation with anastomosis above aortic arch. Methods Sixty-three patients with lower TESCC who received adjuvant radiotherapy after R0 radical operation with anastomosis above aortic arch between February 2011 and February 2019 were retrospectively enrolled. The clinical tumor volume (CTV) included anastomotic stoma, and lymph node drainage area in mediastinum and upper abdomen. The survival status, recurrence and metastasis of tumors, and the influencing factors were analyzed. Results The 1-, 2-, and 3-year overall survival rates were 98.3%, 83.3%, and 63.7%, respectively. The median disease-free survival (DFS) was 33 months [95% confidence interval (23.2, 42.8) months], and the 1-, 2-, and 3-year DFS rates were 76.3%, 58.5%, and 41.7%, respectively. Patients with N0-1 had longer DFS than those with N2-3 (median: not reached vs. 15 months, P=0.045). The recurrence rate of anastomotic site was 7.9%. The recurrence rates of lymph nodes in supraclavicular region, upper middle mediastinum, and upper abdomen were 4.8%, 15.9%, and 1.6%, respectively. The distant metastasis rate was 17.5%. The incidence of grade 2-3 radiation pneumonitis, grade 3 anastomotic stenosis, and grade 3 tracheal fistula were 4.8%, 3.2%, and 1.6%, respectively. Conclusions N2-3 is a poor prognostic factor for such patients. Regional lymph node recurrence is mainly revealed in the middle and upper mediastinum. Whether the CTV should include anastomotic stoma and lymph node drainage area in lower mediastinum and upper abdomen is questionable.
ObjectiveTo explore the effects and molecular mechanisms of histone methylase G9a inhibitor BIX-01294 on apoptosis in esophageal squamous cell carcinoma (ESCC).MethodsMTT assay and Colony-forming Units were adopted to determine the effects of BIX-01294 on the growth and proliferation of ESCC cell lines EC109 and KYSE150. Flow cytometry was used to analyze the apoptosis status of ESCC cells after the treatment of BIX-01294. The effects of BIX-01294 treatment on the expressions of G9a catalytic product H3K9me2, DNA double-strand break (DSB) markers, and apoptosis-related proteins were detected by Western blotting.ResultsBIX-01294 inhibited the growth of EC109 and KYSE150 cells in a dose-dependent manner (P<0.05), and BIX-01294 with the inhibitory concentration 50% (IC50) significantly inhibited the formation of colony (P<0.05). After 24 hours treatment of BIX-01294 (IC50), the apoptosis rate of EC109 cells increased from 11.5%±2.1% to 42.5%±5.4%, and KYSE150 cells from 7.5%±0.9% to 49.2%±5.2% (P<0.05). The expression level of the G9a catalytic product, H3K9me2, significantly decreased (P<0.05); while the expression of the DSB marker γH2AX was dramatically enhanced (P<0.05). We also found that the mitochondrial apoptosis pathway was activated and the expression levels of cleaved caspase3 and cleaved PARP were significantly elevated (P<0.05).ConclusionBIX-01294, the inhibitor of methyltransferase G9a, prompted apoptosis in ESCC cells by inducing DSB damage and activating mitochondrial apoptosis pathway.
ObjectiveTo compare the long-term survival of elderly patients with esophageal squamous cell carcinoma (ESCC) treated with surgical versus non-surgical treatment. MethodsA retrospective analysis was conducted on the clinical data of elderly patients aged ≥70 years with ESCC who underwent esophagectomy or radiotherapy/chemotherapy at Sichuan Cancer Hospital from January 2009 to September 2017. Patients were divided into a surgical group (S group) and a non-surgical group (NS group) according to the treatment method. The propensity score matching method was used to match the two groups of patients at a ratio of 1∶1, and the survival of the two groups before and after matching was analyzed. ResultsA total of 726 elderly patients with ESCC were included, including 552 males and 174 females, with 651 patients aged ≥70-80 years and 75 patients aged ≥80-90 years. There were 515 patients in the S group and 211 patients in the NS group. The median follow-up time was 60.8 months, and the median overall survival of the S group was 41.9 months [95%CI (35.2, 48.5)], while that of the NS group was only 24.0 months [95%CI (19.8, 28.3)]. The 1-, 3-, and 5-year overall survival rates of the S group were 84%, 54%, and 40%, respectively, while those of the NS group were 72%, 40%, and 30%, respectively [HR=0.689, 95%CI (0.559, 0.849), P<0.001]. After matching, 138 patients were included in each group, and there was no statistical difference in the overall survival between the two groups [HR=0.871, 95%CI (0.649, 1.167), P=0.352]. ConclusionCompared with conservative treatment, there is no significant difference in the long-term survival of elderly patients aged ≥70 years who undergo esophagectomy for ESCC. Neoadjuvant therapy combined with surgery is still an important choice to potentially improve the survival of elderly patients with ESCC.
ObjectiveTo explore the expression of vascular endothelial growth factor receptor-2(VEGFR-2) protein in esophageal squamous cell carcinoma (ESCC) and to analyze the relationship between VEGFR-2 and prognostic of esophageal cancer in Uygur of Xinjiang. MethodsThe expression of VEGFR-2 protein including 72 patients with ESCC[with 56 males and 16 females at age of 57 (43-79) years] and paracarcinomatous tissues of 28 patients were detected by immunohistochemistry staining (SP) between January 2007 and september 2009 in this hospital. The Kaplan-Meier and Cox proportional hazards analysis were used to analyze the prognosis of ESCC. ResultsThe positive expression rate of VEGFR-2 protein in 72 patients with ESCC was 80.56% (58/72) and 0 in paracarcinomatous tissues. The expression of VEGFR-2 protein in the ESCC was much higher than that in paracarcinomatous tissues with a statistical difference (P<0.05). The expression of VEGFR-2 protein was significantly correlated with depth of invasion, lymph node metastasis, distant metastasis and TNM staging (P<0.05). Tumor size was no correlation with expression of VEGFR-2 protein (P>0.05). Kaplan-Meier survival analysis indicated that five-year survival rate in positive expression of VEGFR-2 was higher than that in the negative group. Lymph node metastasis, TNM staging, and the positive expression of VEGFR-2 protein were independent prognostic factors. ConclusionVEGFR-2 protein is expressed more in ESCC and might be used as the index to predict prognosis and metastasis of esophagedal carcinoma in Uygur.
ObjectiveTo investigate the expression of Cyclin D1 in stage T2-3N0M0 esophageal squamous cell carcinoma (ESCC) and its relationship with patient prognosis. MethodsExpression of Cyclin D1 in 227 ESCC specimens at stage T2-3N0M0 was detected by immunohistochemistry (IHC). Receiver operating characteristic (ROC) curve analysis was performed to select the cut-off score for high or low IHC reactivity. Correlations between Cyclin D1 expression and clinicopathological features as well as prognosis of ESCC patients were determined. ResultsAmong the 227 patients, 90 (39.6%) patients had low expression of Cyclin D1, and 137 (60.4%) patients had high expression of Cyclin D1.No significant correlation was observed between Cyclin D1 expression and patient gender (P=0.298), age(P=0.525), tumor location (P=0.570), tumor length (P=0.056), tumor grade (P=0.713), and depth of invasion (P=0.557). There was significant difference in prognosis between low-expression Cyclin D1 group and high-expression Cyclin D1 group (3-year survival rate:51.1% vs. 43.8%, 5-year survival rate:43.3% vs. 30.7%, P=0.047). Cox proportional-hazards regression model analysis showed that Cyclin D1 was not an independent prognostic factor for ESCC patients at stage T2-3N0M0 (relative risk=1.378, 95% CI:0.990-1.919, P=0.057). ConclusionOver expression of Cyclin D1 may be an adverse prognostic factor of ESCC patients at stage T2-3N0M0.