Objective To evaluate the security and outcomes of thoracolaparoscopic esophagectomy (TLE) versus open approach (OA) for thoracic esophageal squamous cell carcinoma. Methods From June 2014 to June 2015, 125 patients with thoracic esophageal squamous cell carcinoma underwent esophagectomy through McKeown approach, including TLE (a TLE group, 107 patients, 77 males and 30 females) and OA (an OA group, 18 patients, 13 males and 5 females). The data of operation and postoperative complications of the two groups were analyzed retrospectively. Results There was no statistical difference in the duration of operation and ICU stay and resected lymph nodes around laryngeal recurrent nerve between the TLE group and the OA group (333.58±72.84 min vs. 369.17±91.24 min, P=0.067; 2.84±1.44 d vs. 6.44±13.46 d, P=0.272; 4.71±3.87 vs. 3.89±3.97, P=0.408) . There was a statistical difference in blood loss, total resected lymph nodes and resected lymph nodes groups between TLE group and OA group (222.62±139.77 ml vs. 427.78±276.65, P=0.006; 19.62±9.61 vs. 14.61±8.07, P=0.038; 3.70±0.99 vs. 3.11±1.13, P=0.024). The rate of postoperative complications was 32.7% in the TLE group and 38.9% in the OA group (P=0.608). There was a statistical difference (P=0.011) in incidence of pulmonary infection (2.8% in the TLE group and 16.7% in the OA group). Incidences of complications, such as anastomotic leakage, cardiac complications, left-side hydrothorax, right-side pneumothorax, voice hoarse and incision infection, showed no statistical difference between two groups. Conclusion For patients with thoracic esophageal squamous cell carcinoma, TLE possesses advantages of more harvested lymph nodes, less blood loss and less pulmonary infection comparing with open approach, and is complied with the principles of security and oncological radicality of surgery.
Objective To summarize the progress and trend on clinical drug trials of esophageal squamous cell carcinoma in China. Methods Based on the clinical drug trial registration and information disclosure platform and the drug data query system of the National Medical Products Administration, the characteristics of clinical trials, investigational drugs and listed drugs of esophageal squamous cell carcinoma in China from 2012 to 2021 were analyzed. Results From 2012 to 2021, a total of 49 clinical drug trials of esophageal squamous cell carcinoma were registered in China, accounting for 1.6% of all clinical trials of anticancer drugs. Among them, there were 39 (79.6%) trials initiated by domestic pharmaceutical enterprises, 6 (12.2%) for adjuvant and neoadjuvant treatment, and 9 (18.4%) for local treatment. There were differences in the treatment line distribution between global and domestic enterprise-initiated trials (P=0.032). The above trials covered 29 investigational drugs, including 23 (79.3%) targeted drugs, most of which targeted programmed death-1, programmed death-ligand 1 and epidermal growth factor receptor. From 2012 to 2021, there were 2 drugs for esophageal squamous cell carcinoma listed in China, both of which were approved for the first-line and second- line treatment. Conclusion Great achievements have been made in the clinical development of esophageal squamous cell carcinoma drugs in China. It is suggested that domestic enterprises increase the investment of esophageal squamous cell carcinoma, pay attention to adjuvant and local treatment, explore novel targets and drug categories, and focus on the details of pivotal trials.
ObjectiveTo systematically review the effectiveness and safety of taxanes combined with cisplatin and fluorouracil (TFP) versus cisplatin and fluorouracil (FP) for locally advanced head and neck squamous cell carcinoma. MethodsDatabases such as The Cochrane Library (Issue 1, 2013), PubMed, EMbase, Web of Science, CBM, CNKI, VIP and WanFang Data were electronically searched to collect randomized controlled trials (RCTs) about taxanes combined with cisplatin and fluorouracil in the treatment of locally advanced head and neck squamous cell carcinoma from the date of their establishment to April 1st, 2013. Two reviewers independently screened studies according to the inclusion and exclusion criteria, extracted data and evaluated the methodological quality of included studies. Then meta-analysis was performed using RevMan 5.2 software. ResultsA total of 7 RCTs involving 2 088 patients were included. The TFP group included 1 051 cases, while the FP group included 1 037 cases. The results of meta-analyses showed that, there were significant differences between the two groups in the 1-year, 2-year, and 3-year overall survival rates (RR=1.12, 95%CI 1.02 to 1.23, P=0.02; RR=1.20, 95%CI 1.11 to 1.29, P < 0.000 01; RR=1.18, 95%CI 1.07 to 1.31, P=0.000 7), the 1-year, 2-year, and 3 year of progressions free survival (RR=1.18, 95%CI 1.08 to 1.28, P=0.000 2; RR=1.20, 95%CI 1.06 to 1.36, P=0.003; RR=1.48, 95%CI 1.25 to 1.74, P < 0.000 01), the complete remission rate (RR=1.67, 95%CI 1.26 to 2.23, P=0.000 4), and the overall response to chemotherapy (RR=1.18, 95%CI 1.11 to 1.27, P < 0.000 01). As for the side effect, the FP group was superior to the TFP group in the neutropenia (RR=1.42, 95%CI 1.24 to 1.63, P < 0.000 01), alopecia (RR=16.09, 95%CI 4.59 to 56.38, P < 0.000 1), and febrile neutropenia (RR=2.21, 95%CI 1.29 to 3.80, P < 0.004). ConclusionThe fluorouracil with cisplatin and fluorouracil for advanced head and neck squamous cell carcinoma might have better effects, but with higher side effects.
ObjectiveTo systematically review the correlation between the expression of cytokeratin 19 (CK19) and oral squamous cell carcinoma (OSCC). MethodsPubMed, EMbase, CJFD, CBM, CNKI, VIP, WanFang Data and The Cochrane Library (Issue 1, 2015) were electronically searched from inception to January 1st 2015 to collect case-control studies about the correlation between CK19 expression and clinical pathogenic features in OSCC. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.3 software. ResultsA total of 11 studies were included, involving 612 OSCC cases and 564 normal controls. The results of meta-analysis showed that:The expression levels of CK19 were significantly different between the OSCC group and the control group, between OSCC groups with and without lymph node metastasis, between the high differentiation group and the middle/poor differentiation group, and between the clinical stage I group and the clinical stages Ⅱ to Ⅲ group (all P values≤0.05). However, there were no significant differences in expression levels of CK19 between the male OSCC group and the female OSCC group, and between the carcinoma size T1/T2 group and the T3/T4 group (all P values >0.05). ConclusionCurrent evidence shows that, CK19 expression may be associated with the occurrence, development and transfer of OSCC, and may be positively corrected with tumor malignance. It may be an indicator of poor prognosis and can be considered as a molecular marker of OSCC.
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.
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.
Objective To evaluate the prognostic value of surgical treatment in gallbladder squamous cell carcinoma (GSCC) by using real-world data with a large sample in the Surveillance, Epidemiology and End Results (SEER) database. Methods The clinical data of patients with pathologically diagnosed GSCC from 2000 to 2019 were extracted from the SEER database. According to the inclusion and exclusion criteria, a total of 257 patients were included after strict screening. The patients were divided into operation group and non-operation group according to whether they underwent surgery. The cancer-specific survival (CSS) and the overall survival (OS) between the two groups were compared, and the influencing factors for the CSS and the OS were analyzed by using Cox proportional hazard model. Results Of 257 patients, 127 (49.4%) were in the operation group, and 130 (50.6%) in the non-operation group. The average follow-up ranged from 0 to 220 months, with the median follow-up time of 3 months. Of the 127 patients in the operation group, 105 died (82.7%), including 88 tumor-related deaths (69.3%). Of the 130 patients in the non-operation group, 124 died (95.4%), including 115 tumor-related deaths (88.5%). The median survival time for OS in the operation group and the non-operation group were 6 months and 3 months, respectively, and that for CSS were 7 months and 3 months, respectively. The estimated 1-year OS of the operation group and the non-operation group were 30.1% and 4.6% respectively; the estimated 1-year CSS were 35.1% and 5.8%, respectively. There were significant differences between the two groups on OS and CSS (χ2=41.400, P<0.001; χ2=42.750, P<0.001). That the OS [HR=0.44, 95%CI (0.25, 0.77), P=0.004] and the CSS [HR=0.46, 95%CI (0.25, 0.84), P=0.011] in GSCC patients were significantly improved by surgical treatment, showed by the results of multivariate prognostic analysis via Cox proportional hazard mode. Conclusions Surgical treatment was an independent factor affecting the prognosis of GSCC, and it could improve the OS and the CSS. As for the modus operandi, R0 resection should be recommended.
ObjectiveTo evaluate the prognostic value of preoperative inflammatory indexes in patients with local-advanced esophageal squamous cell carcinoma.MethodsWe retrospectively analyzed the clinical and prognostic data of 150 local-advanced esophageal squamous cell carcinoma patients who were treated by esophagectomy in Guangyuan Central Hospital from July 2014 to July 2015. There were 128 males and 22 females with average age of 62.23±8.48 years. The optimal cutoff value was determined by receiver operation characteristics (ROC) curve analysis. Patients were grouped according to the optimal cutoff values (NLR=3.49, PLR=152.28, MLR=0.36). Log-rank test, and multivariate Cox logistic regression modelling were used to assess the simultaneous influences of prognostic factors for survival outcomes after esophagectomy.ResultsThe patients with higher ratio (NLR>3.49, PLR>152.28, MLR>0.36) had significantly shorter median progression free survival (PFS) and lower postoperative recurrent rate than those of the patients with lower ratio. The stratified analyses found that thelymph node staging and postoperative recurrent rate were positively correlated with the higher ratio. However, the tumor differentiation was negatively correlated with it. In univariate analyses, patients with preoperative NLR>3.49, PLR>152.28 and MLR>0.36 had a poorer prognosis. Furthermore, in multivariate analyses we found MLR>0.36 was also significantly associated with a decreased postoperative recurrent rate (HR=12.945, 95%CI 2.31 to 72.548, P=0.00).ConclusionsThe preoperative NLR, PLR and MLR are useful prognostic markers in patients with stage ⅢA-ⅣA esophageal squamous cell carcinoma who conducted esophagectomy.
Increasing evidence suggests that many types of cancers contain a population of cells that display stem cell properties. These cells are called cancer stem cells （CSCs），which are closely related to tumor initiation，growth，metastasis and chemoresistance. CSCs are also found in esophageal squamous cell carcinoma （ESCC）. These cells are characterized by potential of self-renewal and differentiation，tumor formation in nude mice and chemotherapy resistance，and thus may play an important role in targeted cancer therapies. Current methods for culturing and sorting CSCs in ESCC mainly include fluorescence activated cell sorting （FACS），magnetic activated cell sorting （MACS），suspension culture，and side population （SP） cell sorting. In this review，we focus on current research methods for CSCs in ESCC，their biological characteristics and areas for improvement. We believe that a combination of multiple cell-surface makers is needed for research of CSCs in ESCC.
ObjectiveTo investigate the short-term therapeutic effect of neoadjuvant immunotherapy combined with chemotherapy in the locally advanced esophageal squamous cell carcinoma. MethodsThe clinical data of patients with esophageal squamous cell carcinoma treated with neoadjuvant treatment in Gaozhou People's Hospital from August 2019 to October 2020 were retrospectively analyzed. According to the different treatments, the patients were divided into two groups: a neoadjuvant immunotherapy combined with chemotherapy group (NIC group) and a neoadjuvant chemoradiotherapy group (NC group). The baseline data, incidence of adverse events during treatment, perioperative indicators, postoperative pathological remission rate and incidence of postoperative complications were compared between the two groups. ResultsTotally 33 patients were enrolled, including 15 males and 18 females, with an average age of 62.37±7.99 years. There were 17 patients in the NIC group and 16 patients in the NC group. In the NIC group, the carcinoma was mainly located in the middle and lower esophagus, with 5 paitents in stage Ⅱ, 9 patients in stage Ⅲ, and 3 patients in stage Ⅳa. In the NC group, the carcinoma was mainly located in the upper-middle esophagus, with 1 patient in stage Ⅱ and 15 patients in stage Ⅲ. During the neoadjuvant treatment, there was no significant difference in the occurrence of bone marrow suppression or gastrointestinal reactions between the two groups (P>0.05). There were 4 immune-related rashes in the NIC group and 1 esophageal perforation in the NC group. Fourteen (82.35%) patients in the NIC group and 12 (75.00%) patients in the NC group completed the operation on schedule. The postoperative ICU stay time and chest tube indwelling time in the NIC group were shorter than those in the NC group (P<0.05). There were 5 patients of complete remission in the NIC group, and 6 patients in the NC group. There was no significant difference in the pathological regression grade or residual tumor cells between the two groups (P>0.05). There was no significant difference in the incidence of anastomotic fistula, thoracic gastric fistula, bronchial mediastinal fistula, abdominal distension, pulmonary infection, stroke, or hoarseness during the perioperative period between the two groups of patients who completed the operation (P>0.05). In the NC group, 2 patients died during the perioperative period because of thoracic gastric fistula complicated by severe infection. ConclusionNeoadjuvant immunotherapy combined with chemotherapy dose not significantly increase the occurrence of adverse events and shows a good rate of pathological remission, which indicates that the neoadjuvant immunotherapy combined with chemotherapy is a safe, feasible and potential new treatment model.