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.
ObjectiveTo evaluate the expression level of histone deacetylase 9 (HDAC9) in lung squamous cell carcinoma (LUSC) tissues, to analyze its correlations with clinicopathological characteristics and prognosis of LUSC patients, and to explore the effect it exerts on the proliferation of LUSC cells.MethodsThe expression level of HDAC9 was detected by immunohistochemistry staining (IHC), and its correlations with clinicopathological characteristics were analyzed by χ2 test. Survival analysis was performed using Kaplan-Meier method. Univariate and multivariate Cox proportional hazards model were employed to analyze independent predictors for overall survival (OS) of LUSC patients. CRISPR/dCas9 activation system was used to activate the transcription of HDAC9 gene in LUSC cell line EBC-1. CCK8 cell proliferation assay and colony formation test were performed to investigate the effect that transcriptional activation of HDAC9 exerts on the proliferation of LUSC cells.ResultsOf the 129 LUSC patients, 39 (30.2%) were in the HDAC9 low expression group and 90 (69.8%) were in the HDAC9 high expression group. The OS of the patients with HDAC9 high expression was shorter than that of patients with HDAC9 low expression (P=0.032). The expression level of HDAC9 was associated with tumor grade (P=0.035), primary tumor size (P=0.041), and lymph node metastasis (P=0.013). The expression level of HDAC9 (P=0.023), tumor grade (P=0.003), primary tumor size (P=0.003), and lymph node metastasis (P=0.002) were independent predictors for OS of LUSC patients. Transcriptional activation of HDAC9 promoted colony formation of LUSC cells and cell proliferating curves showed that LUSC cells with HDAC9 transcriptional activation proliferated faster than non-targeting cells (F=52.7, P=0.002).ConclusionLUSC patients with HDAC9 high expression have poorer prognosis than HDAC9 low expression ones. The expression level of HDAC9 is associated with tumor grade, primary tumor size, and lymph node metastasis, and is identified as an independent predictor for prognosis of LUSC. Transcriptional activation of HDAC9 promotes cell proliferation in LUSC. These results suggest that HDAC9 may serve as a promising biomarker for prognosis in LUSC.
ObjectiveTo explore the mechanism of DDX46 regulation of esophageal squamous cell carcinoma.MethodsPicture signals of fluorescence in gene array were scanned and differential expression of gene in two groups (a DDX46-shRNA-LV group and a control-LV group) were compared by GCOSvL.4 software. These differential expressed genes were analyzed by bioinformatics methods finally, and validated by quantitative real time polymerase chain reaction (qRT-PCR) analysis.ResultsAccording to the screening criteria of fold change ≥2 and P<0.05, 1 006 genes were differentially expressed after DDX46 knockdown, including 362 up-regulated and 644 down-regulated genes. Bioinformatics analysis and gene co-expression network building identified that these differentially expressed genes were mainly involved in cell cycle, proliferation, apoptosis, adhesion, energy metabolism, immune response, etc. Phosphatidylinositol 3-kinase (PI3K) was the key molecule in the network. The results of RT-qPCR were completely consistent with the results of gene microarra.ConclusionBioinformatics can effectively exploit the microarray data of esophageal squamous cell carcinoma after DDX46 knockdown, which provides a valuable clue for further exploration of DDX46 tumorigenesis mechanism and helps to find potential drug therapy.
ObjectiveTo explore whether surgery combined with adjuvant chemotherapy can bring survival benefits to patients with cervical and upper thoracic esophageal squamous cell carcinoma (ESCC).MethodsThe clinical data of patients with cervical and upper thoracic ESCC who underwent R0 resection and neck anastomosis in our department from 2006 to 2010 were retrospectively analyzed. Patients received neoadjuvant therapy or adjuvant radiotherapy were excluded. The adjuvant chemotherapy group was given a combination of taxanes and platinum based chemotherapy after surgery; the surgery alone group did not receive adjuvant chemotherapy. The Kaplan-Meier method was used to analyze the survival difference between the adjuvant chemotherapy group and the surgery alone group. ResultsA total of 181 patients were enrolled, including 141 (77.9%) males and 40 (22.1%) females, with an average age of 61.0±8.2 years (80 patients aged≤61 years, 101 patients aged>61 years). There were 70 (38.7%) patients of cervical ESCC, and 111 (61.3%) patients of upper thoracic ESCC. Eighty-seven (48.1%) patients underwent postoperative adjuvant chemotherapy, and 94 (51.9%) patients underwent surgery alone, and the basic clinical characteristics were well balanced between the two groups (P>0.05). The median survival time of patients in the adjuvant chemotherapy group and the surgery alone group was 31.93 months and 26.07 months, and the 5-year survival rate was 35.0% and 32.0%, respectively (P=0.227). There was no statistical difference in median survival time between the cervical ESCC and upper thoracic ESCC group (31.83 months vs. 29.76 months, P=0.763). For cervical ESCC patients, the median survival time was 45.07 months in the adjuvant chemotherapy group and 14.70 months in the surgery alone group (P=0.074). Further analysis showed that the median survival time of lymph node negative group was 32.53 months, and the lymph node positive group was 24.57 months (P=0.356). The median survival time was 30.43 months in the lymph-node positive group with adjuvant chemotherapy and 17.77 months in the lymph-node positive group with surgery alone. The survival curve showed a trend of difference, but the difference was not statistically significant (P=0.557).ConclusionThere is no statistical difference in the long-term survival of cervical and upper thoracic ESCC patients after R0 resection. Postoperative adjuvant chemotherapy may have survival benefits for patients with cervical ESCC and upper ESCC with postoperative positive lymph nodes, but the differences are not statistically significant in this setting.
ObjectiveTo establish the gene-based esophageal cancer (ESCA) risk score prediction models via whole transcriptome analysis to provide ideas and basis for improving ESCA treatment strategies and patient prognosis.MethodsRNA sequencing data of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC) and adjacent tissues were obtained from The Cancer Genome Atlas database. The edgeR method was used to screen out the differential genes between ESCA tissue and normal tissue, and the key genes affecting the survival status of ESCC and EAC patients were initially identified through univariate Cox regression analysis. The least absolute shrinkage and selection operator regression analysis and multivariate Cox regression analysis were used to further screen genes and establish ESCC and EAC risk score prediction models.ResultsThe risk score prediction models were the independent prognostic factors for ESCA, and the risk score was significantly related to the survival status of patients. In ESCC, the risk score was related to T stage. In EAC, the risk score was related to lymph node metastasis, distant metastasis and clinical stage. The constructed nomogram based on risk score showed good predictive ability. In ESCC, the risk score was related to tumor immune cell infiltration and the expression of immune checkpoint genes. However, this feature was not obvious in EAC.ConclusionThe ESCC and EAC risk score prediction models have shown good predictive capabilities, which provide certain inspiration and basis for optimizing the management of ESCA and improving the prognosis of patients.
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.