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Objective:To analyze the local recurrence patterns after concurrent chemoradiotherapy (CCRT) for thoracic esophageal squamous cell carcinoma (ESCC) through image fusion, and to explore the risk factors of local recurrence and its relationships with dosimetric indices.Methods:A retrospective analysis was conducted for 209 thoracic ESCC patients who received radical CCRT in Fourth Hospital of Hebei Medical University during 2016-2019. For the patients diagnosed as the local recurrence of esophageal lesions, their CT images were fused with the original planning CT images using image registration software to identify the recurrence sites. Through 1∶1 propensity score matching (PSM) of the clinal data of patients with local recurrence (the recurrence group, nbefore = 81, nafter = 62) and those without local recurrence (the recurrence-free group, nbefore = 128, nafter=62), the dose and volume parameters of the treatment plans for the two groups were compared. Univariate and multivariate analyses were conducted using the Kaplan-Meier method and the Cox regression model to analyze the factors affecting the overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS). Results:All patients had 1-, 3-, and 5-year OS rates of 80.9%, 42.6%, and 33.0%, respectively, 1-, 3-, and 5-year PFS rates of 67.9%, 34.0%, and 27.9%, respectively, and 1-, 3-, and 5-year RFS rates of 71.3%, 39.2%, and 30.5%, respectively. T stage, N stage, and radiation dose were independent prognostic factors for the OS, PFS, and RFS ( HR = 1.42-1.87, P < 0.05) of the patients, respectively. Among 68 patients with local recurrence, 62 cases (91.2%) suffered recurrence within the gross tumor volume (GTV). The dose and volume parameters of patients with local recurrence, such as GTV- D95%, clinical target volume (CTV)- D95%, GTV- D50%, CTV- D50%, and planning target volume (PTV)- D50%, GTV- V60, CTV- V60, and PTV- V60, were significantly lower than those of patients free from the local recurrence ( t=1.90-2.15, P < 0.05). Conclusions:Local recurrence of patients with thoracic ESCC after radical CCRT occurs mainly within the GTV. Increasing radiation doses may contribute to their survival benefits. The D50% for each target volume in the radiotherapy plan may be related to local recurrence, and it is necessary to conduct further research.
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Objective:To evaluate the recurrence patterns of esophageal squamous cell carcinoma (ESCC) after radical surgery and analyze the predictors of post-recurrence survival (PRS).Methods:A total of 382 ESCC patients who developed recurrence after radical surgery were retrospectively reviewed from January 2007 to December 2011. All of them received salvage treatment after recurrence. The Univariate analysis was determined using the Kaplan-Meier method and log-rank test. Multivariate prognostic analysis was determined using the Cox proportional hazard model.Results:The 1-, 3-, 5-year overall survival (OS) rates were 80.9%, 35.6% and 20.4%, respectively. The median survival time and recurrence time were 29.2 months and 15.0 months. The 1-, 3-, 5-year PRS rates were 37.7%, 14.6% and 11.9%, respectively. The median PRS time was 10.2 months. Locoregional recurrence was noted at 462 sites among 382 patients including 20.5% (95/462) of sites in supraclavicular LN (lymph node), 10.0% (46/462) in anastomosis, 56.1% (259/462) in mediastinal regional LN and 13.4% (62/462) in upper abdominal LN. There were 156, 43, 82 and 101 patients treated with salvage radiotherapy, chemotherapy, chemoradiotherapy and palliative care after recurrence, respectively. The univariate analysis showed that T stage, N stage, TNM stage, recurrence site, number of recurrent regions and treatment regimen after recurrence were significantly correlated with PRS ( χ2=5.336, 4.292, 8.067, 7.482, 4.093, 76.426, P<0.05). Patients receiving salvage radiotherapy with the median dose of 60 Gy, were divided into <60 Gy group and ≥ 60 Gy group. The ≥60 Gy group had a better PRS than <60 Gy group ( χ2=8.320, P<0.05). Multivariate analysis showed that number of recurrent regions and treatment regimen were independent prognostic factors of PRS. Conclusions:Mediastinal and supraclavicular regions were the most common sites of recurrence in ESCC patients after radical surgery. Salvage radiotherapy and chemoradiotherapy could significantly improve PRS in recurrent ESCC patients.
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Objective To study the relationship between the dose-volume indexes and acute toxicity of intrathoracic stomach in esophageal cancer patients receiving radiotherapy after esophagectomy.Methods A total of 104 patients treated with postoperative radiotherapy followed by radical esophagectomy were enrolled.The dose-volume indexes of intrathoracic stomach were collected from treatment planning system.The ROC curve and logistic regression were performed to analyze the relationship between acute toxicity of intrathoracic stomach and clinical parameters,dose-volume indexes.Results A total of 29 patients (27.88 ％) suffered from grade 2 or above acute toxicity.The ROC curve analysis showed that the dose-volume indexes including D D L5-L45 and V5-V50were associated with occurrence of grade 2 or above acute toxicity,The univariate analysis showed that location,D D L5-L45 and V5-V50 were significantly correlated with the incidence of grade 2 or above acute toxicity (P＜0.05).The multivariate analysis showed that location,L5 and V35 were independent factors for incidence of grade 2 or above acute toxicity.The ROC curve analysis showed that cut-off values of L5 and V35 were 14.00 cm and 44.00％,respectively.And the rates of Grade 2 or above acute toxicity were 20.00％ for L5＞ 14.00 cm and 38.64％ for L5 ≥ 14.00 cm (x2 =4.473,P＜0.05),14.08％ for V35＜44.00％ and 57.58％ for V35 ≥44.00％ (x2 =7.263,P＜0.05),respectively.The incidence of grade 2 or above acute toxicity was significantly higher in post-mediastinum stomach group than the other two groups (x2 =12.881,P＜0.05).Conclusions Dosevolume index may be indicator to predict acute toxicity of intrathoracic stomach.It is recommended that post-mediastinum stomach should be chosen carefully if esophageal cancer patients require postoperative radiotherapy.
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Objective@#To study the relationship between the dose-volume indexes and acute toxicity of intrathoracic stomach in esophageal cancer patients receiving radiotherapy after esophagectomy.@*Methods@#A total of 104 patients treated with postoperative radiotherapy followed by radical esophagectomy were enrolled. The dose-volume indexes of intrathoracic stomach were collected from treatment planning system. The ROC curve and logistic regression were performed to analyze the relationship between acute toxicity of intrathoracic stomach and clinical parameters, dose-volume indexes.@*Results@#A total of 29 patients (27.88 %) suffered from grade 2 or above acute toxicity. The ROC curve analysis showed that the dose-volume indexes including Dmax, Dmean, L5-L45 and V5-V50were associated with occurrence of grade 2 or above acute toxicity. The univariate analysis showed that location, Dmax, Dmean, L5-L45 and V5-V50 were significantly correlated with the incidence of grade 2 or above acute toxicity (P<0.05). The multivariate analysis showed that location, L5 and V35 were independent factors for incidence of grade 2 or above acute toxicity. The ROC curve analysis showed that cut-off values of L5 and V35 were 14.00 cm and 44.00%, respectively. And the rates of Grade 2 or above acute toxicity were 20.00% for L5>14.00 cm and 38.64% for L5≥14.00 cm (χ2=4.473, P<0.05), 14.08% for V35<44.00% and 57.58% for V35≥44.00% (χ2=7.263, P<0.05), respectively. The incidence of grade 2 or above acute toxicity was significantly higher in post-mediastinum stomach group than the other two groups (χ2=12.881, P<0.05).@*Conclusions@#Dose-volume index may be indicator to predict acute toxicity of intrathoracic stomach. It is recommended that post-mediastinum stomach should be chosen carefully if esophageal cancer patients require postoperative radiotherapy.
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Objective To compare the efficacy between different modalities in the treatment of positive lymph nodes after radical resection for squamous cell carcinoma of thoracic esophagus(TESCC),and to explore the best treatment mode. The Kaplan?Meier method was used to calculate survival rates. The log-rank test and Cox model were used for univariate and multivariate prognostic analyses,respectively. Methods A retrospective analysis was performed among 548 patients with TESCC who were admitted to our hospital and had positive lymph nodes after radical resection. The efficacy of different treatment methods was evaluated. Propensity scores(PSM)were used to make 1-to-1 patient matching between different treatment groups to further analyze and figure out the best treatment model for patients. The Kaplan?Meier method was used to calculate the overall survival(OS)and disease-free survival(DFS)rates. The log-rank test was used for survival analysis and univariate prognostic analysis. The Cox regression model was used for multivariate prognostic analysis. Results In all patients,the 1-,3-,and 5-year OS rates were 79.9%, 38.1% and 28.5%,respectively,while the 1-,3-,and 5-year DFS rates were 68.5%,39.8% and 32.5%, respectively. After 1-to-1 matching based on PSM,there were no differences in general clinical pathological data between the four groups. After PSM,there were significant differences in 1-,3-,and 5-year OS and DFS rates between the surgery alone group,the postoperative radiotherapy group,the postoperative chemotherapy group,and the postoperative chemoradiotherapy(POCRT)group(P=0.000,0.000).There were significant differences in OS and DFS rates between patients with stage N1,N2,and N3disease(P=0.000,0.000).The result of the Cox multivariate analysis showed that treatment method and N staging were two independent prognostic factors for OS and DFS(P=0.001,0.000,0.025,0.016). Conclusions Patients with positive lymph nodes after radical resection for TESCC have a poor prognosis. Moreover,the prognosis becomes worse with the increase in metastatic lymph nodes. POCRT may improve the survival in those patients. Prospective studies are needed to further confirm those conclusions.
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Objective To analyze the risk factors for abdominal lymph node recurrence after radical surgery in patients with middle thoracic esophageal squamous cell carcinoma (TE-SCC),and to design the target volume for postoperative radiotherapy based on the results.Methods A retrospective study was performed among 913 patients with middle TE-SCC undergoing radical surgery who were admitted to our hospital from 2007 to 2012.Influencing factors were analyzed for abdominal lymph node recurrence after treatment.The efficacy was compared between different treatment methods in the high-risk population.Comparison of categorical data was made by chi-square test.The overall survival rates (OS) were calculated by the Kaplan-Meier method and analyzed by the univariate log-rank analysis.The influencing factors for abdominal lymph node recurrence were analyzed by the multivariate logistic regression equation.Results After treatment,37 patients had abdominal lymph node recurrence,yielding a recurrence rate of 4.1％.A total of 53 recurrent sites were found.The univariate analysis showed that no/low differentiation,pT3+4 stage,no less than 3 positive postoperative lymph nodes,and positive postoperative abdominal lymph nodes were influencing factors for abdominal lymph node recurrence (P =0.032,0.001,0.009,0.000).The multivariate regression analysis showed that pathological T staging and positive postoperative abdominal lymph nodes were influencing factors for abdominal lymph node recurrence (P=0.011,0.000).For patients with pT3+4 stage disease and positive postoperative abdominal lymph nodes,postoperative radiotherapy improved OS and local control rates but failed to reduce the distant metastasis-free rate.Conclusions T staging and positive postoperative abdominal lymph nodes are important risk factors for abdominal lymph node recurrence after radical surgery in patients with middle TE-SCC.Postoperative adjuvant therapy is recommended for patients with pT3+4 stage disease and positive postoperative abdominal lymph nodes.
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Objective To compare the prognosis of patients with squamous cell carcinona of the upper thoracic esophagus after radical resection with and without postoperative chemoradiotherapy (POCRT).Methods From January 2007 to December 2011,168 patients with upper thoracic esophageal carcinoma who were treated in the Fourth Hospital of Hebei Medical University were retrospectively included in this study.According to the different treatment method,they were divided into simple surgery group (86 cases) and POCRT group (82 cases) respectively.Based on SPSS statistical software,the group data composition,prognostic analysis and multivariate prognostic analysis were performed by x2 test,Log-rank method and Cox regression model,respectively.Results The 1,3,5 year-survival rate,recurrence rate and distant metastasis rate were 83.9％,52.4％,43.5％,26.5％,40.8％,43.4％ and 5.3％,11.4％,16.9％,respectively.The result of multivariate analysis showed that gender,T stage,N stage and treatment method were independent prognostic factors of overall survival (P =0.020,0.008,0.005,0.000);N staging and treatment method were the independent prognostic factors of local/regional recurrence (P =0.001,0.003);differentiation and T staging were the independent prognostic factors of distant metastasis (P =0.045,0.020).The intrathoracic regional recurrence rate of operation only group and POCRT group patients were 44.2％ (38/86) and 29.3％ (24/82) respectively,where the difference was statistically significant (x2 =7.110,P ＜ 0.05).The rate of metastasis were 19.8％ (17/86) and 13.4％ (11/82) respectively without significant difference (P ＞0.05).Conclusions The recurrence rate of patients with upper thoracic esophageal squamous cell carcinoma after radical resection was still high.Postoperative chemoradiotherapy can improve the overall survival rate and reduce the recurrence rate,but whether it can reduce the patient's distant metastasis rate needs further study.
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Objective To analyze the failure patterns and prognostic factors of radical surgery in patients with T1-4N0-1M0 thoracic esophageal squamous cell carcinoma (TESCC),and the implications for the target area design of postoperative therapy.Methods We retrospectively analyzed 1 191 patients with TESCC who underwent radical surgery at our institution.The failure patterns,the prognostic factors,as well as the effects of lesion locations and N stage on the failure patterns were analyzed.Results The thoracic-region recurrence rate and the distant metastasis rate was 31.7％ and 16.4％ in all patients.The multivariate analysis showed that the lesion locations,the degree of inflammatory adhesion,T staging,N staging and the rate of lymph nodes metastasis were independent factors affecting the regional recurrence (P ＜ 0.05).Gender,tumor differentiation and the rate of lymph nodes metastasis were independent factors affecting distant metastasis (P ＜ 0.05).The intrathoracic lymph nodes recurrence rate of upper/middle TESCC was significantly higher than that of the lower TESCC (x2 =6.179,P =0.046),while the abdomen lymph nodes recurrence rate of the lower was significantly higher than that of upper/middle TESCC (x2 =15.853,P ＜ 0.05).The recurrence rate and distant metastasis rate of stage N1 patients were significantly higher than that of N0 patients (x2 =7.764-56.495,P ＜ 0.05).The abdomen lymph nodes recurrence rate of stage N1 patients was significantly higher than that of N0 in upper TESCC (x2 =7.905,P ＜0.05).The supraclavicular and intrathoracic lymph nodes recurrence rates of stage N1 patients were significantly higher than that of N0 patients in middle TESCC (x2 =12.506,18.436,P ＜ 0.05).The supraclavicular lymph nodes,anastomosis and abdomen lymph node recurrence rates of stage N1 were significantly higher than that of N0 patients in lower TESCC (x5 =5.272,4.878,18.006,P ＜ 0.05).The anastomotic recurrence rate of stage T3+4 was higher than that of T1+2 in middle/lower TESCC (x2 =4.341,7.154,P ＜ 0.05),and the abdominal lymph nodes recurrence rate of stage T3 +4 was higher than that of T1 +2 in lower TESCC (x2 =5.366,P ＜ 0.05).Conclusions The lymphatic drainage regions for postoperative radiotherapy (PORT) are selective.We suggest that abdominal lymph nodes drainage area should be noted for the stage N1 patients with upper TESCC,and the supraclavicular lymph nodes drainage area should be noted for the N1 patients with lower TESCC.In addition,the anastomosis is suggested to be included in PORT target area for stage T3/T4 middle/lower TESCC patients.
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Objective To evaluation and comparison the curative effect of different adjuvant therapy and prognostic factors with thoracic esophageal squamous cell carcinoma (ESCC) after surgery,and to find the best treatment for them.Methods A total of 863 patients with thoracic ESCC underwent surgery in the fourth hospital of Hebei Medical University,From January 2007 to December 2010,To analyze the influence factors of the patient′s independent prognosis and the effect of postoperative adjuvant therapy on the prognosis of patients.The 1:1, after the tendency of a total of 261 cases were used PSM method (87 cases/group).The Kaplan-Meier method was used to calculate OS,DFS and log-rank test and monovariable analysis,Cox model was used to multivariable analysis.Results The sample size in 1,3,5 was 123,589,863 cases.The 1-,3-,and 5-year overall survival (OS) and disease-free survival (DFS) of all patients were 89.7%,62.1%,51.7% and 76.8%,52.1%,44.2%,respectively.The 1,3,5-years of OS and DFS were 956%,73.3%,61.1% and 85.6%,61.1%,54.4%,78.9%,38.9%,31.3% and 67.8%,27.8%,20.0%,92.2%,55.6%,44.4% and 67.8%,44.4%,36.7%(all P=0.000) among postoperation chemoradiotherapy (POCRT),postoperation chemotherapy (POCT) and postoperation radiotherapy (PORT) after pairing with PSM.The result of COX analysis showed that the degree of inflammatory adhesion,pTNM stage and the number of positive lymph nodes were the independent prognostic factors in patients with OS (P=0.002,0.000,0.007).The history of drinking,pTNM stage and treatment model were the independent prognostic factors of DFS (P=0.009,0.000,0.012).Conclusions Patients with thoracic esophageal squamous cell carcinoma after surgery to receive adjuvant therapy has a good effect,compared with PORT and POCT,POCRT can significantly improve the OS and DFS,and POCRT was the independent prognostic factors of DFS.
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Objective To examine the effect of X-ray radiotherapy on cell proliferation, migration, apoptosis, and cell cycle of human esophageal carcinoma ECA-109 cells following RNA interference (RNAi)-mediated downregulation of RNF2 gene expression.Methods The level of RNF2 mRNA expression in the human esophageal carcinoma cell line ECA-109 was determined using RT-PCR.Cell proliferation of ECA-109 was measured by MTT assay, and the changes in RNF2 protein expression in ECA-109-R cells were determined using Western blot.The changes in cell cycle and cell apoptosis at different time points following radiation were analyzed by flow cytometry, and the effect of transduction on cell migration was examined using Transwell migration assay.Data were subjected to an analysis of variance with repeated measurement design.Results The mean mRNA and protein levels of RNF2 in ECA-109 cells were significantly increased in a dose-dependent manner in the radiation group than in the control group (P0.05).The Transwell migration assay showed that the number of migrating cells following 3.5 h of radiation was significantly lower in the ECA-109-R group than in the ECA-109 and ECA-109-N groups (P<0.01).The percentage of G2/M phase cells in each group was significantly lower following 6 Gy radiation compared to that in the corresponding untreated group (P<0.01), and the percentage of G2/M phase cells was significantly lower in the ECA-109-R group than in the ECA-109 and ECA-109-N groups (P<0.05).Furthermore,cell apoptosis following radiation was also significantly higher in the ECA-109-R group than in the ECA-109 and ECA-109-N groups (P<0.01).Conclusions RNAi-mediated downregulation of RNF2 expression in esophageal carcinoma cells can reduce cell proliferation and cell migration, rescue post-radiation G2/M cell cycle arrest, promote cell apoptosis,and increase radiosensitivity.
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Objective To determine the prognostic factors in patients with stage pT3N0M0 thoracic esophageal squamous cell carcinoma (TSCC) after esophagectomy, and to compare the effects of different treatment modalities on the prognosis of patients.Methods A retrospective analysis was conducted on 480 patients with stage pT3N0M0 TSCC from 2007 to 2010 to determine the prognostic factors in the patients, and to compare the effects of different treatment modalities on their prognosis.Survival rate was calculated using the Kaplan-Meier estimator, and multivariate analysis of prognostic factors was performed using the Cox model.Results Of the 439, 333, and 278 patients who completed the 1-, 3-, and 5-year follow-up, respectively, the 1-, 3-, and 5-year overall survival (OS) rates were 90.0%, 68.7%, and 57.9%(median 87 months, 95% confidence interval (CI=74.7-99.4), respectively, and the 1-, 3-, and 5-year disease-free survival (DFS) rates were 82.3%, 60.4%, and 52.3%(median 71.3 months, 95%CI=55.1-87.5), respectively.In order to account for the different constituent ratios of some clinical and pathological data between the three groups of patients, 55 patients in each group were matched using propensity score matching (PSM)(all P>0.05).It was found that the post-PSM 1-,3-, and 5-year OS and DFS were significantly different between patients who received surgery only, postoperative chemotherapy (POCT), and postoperative chemoradiotherapy/radiotherapy (POCRT/RT)(P=0.000 and 0.006,respectively).Multivariate Cox analysis showed that age, lesion location, and treatment modality were independent prognostic factors for OS and DFS (P=0.029,0.004,0.000 and P=0.009,0.003,0.002), and the length of lesion was also an independent prognostic factor for DFS (P=0.003).Conclusions Although the rate of post-operative treatment failure is still high among patients with stage pT3N0M0 TSCC, POCRT/PORT can improve the prognosis and the 5-year OS and DFS of these patients.However, further large-sample prospective studies will be required to confirm these findings.
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Objective To investigate the failure mode in patients with stage pT3N0M0 thoracic esophageal squamous cell carcinoma (TESCC) after surgery,and to discuss the significance and feasibility of postoperative radiotherapy according to the failure mode.Methods A retrospective analysis was performed on 227 patients with stage pT3N0M0 TESCC who met the inclusion criteria from January 2007 to December 2010.Their postoperative failure mode was analyzed,and,with reference to relevant research,the significance of postoperative radiotherapy and its target patients were explored.The Kaplan-Meier method was used to calculate overall survival (OS),local recurrence (LR),and distant metastasis (DM) rates,and the log-rank test was used for survival difference analysis and univariate prognostic analysis.The Cox model was used for multivariate prognostic analysis.Results After surgery,there were 58 patients (25.6％) with LR in the thoracic cavity and 27 patients (11.9％) with DM,and 10 patients had both LR and DM.Twentynine (50％) of the 58 patients had recurrence in the thoracic mediastinal lymph nodes.The results of univariate analysis showed that the 3-and 5-year OS rates of patients with upper thoracic esophageal cancer were significantly lower than those of patients with middle and lower esophageal cancer (P =0.000),and the chest-regional recurrence rate was significantly higher in the former group than in the latter two groups (P=0.047);the 3-and 5-year OS rates of patients with poorly differentiated squamous cell carcinoma were significantly lower than those of patients with moderately and well differentiated squamous cell carcinoma (P =0.005),and the DM rate was significantly higher than in the former group than in the latter two groups (P=0.000).The results of multivariate analysis showed that lesion site and the degree of pathological differentiation were independent prognostic factors for OS (P=0.014 and 0.010);lesion site was the independent prognostic factor for chest-regional recurrence (P=0.046);the degree of pathological differentiation was the independent prognostic factor for DM (P=0.000).Conclusions For patients with stage pT3N0M0 TESCC after two-field esophagectomy,the most common failure mode is chest-regional recurrence,especially in patients with upper thoracic esophageal cancer.Therefore,postoperative radiotherapy is suggested for upper-thoracic TESCC.
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Objective To investigate the failure model of patients with stage pN0 thoracic esophageal squamous cell carcinoma (TESCC) after surgery alone and to discuss the feasibility of postoperative radiotherapy.Methods A retrospective analysis was performed on 473 patients with TESCC who received surgery alone from January 2007 to December 2010.The feasibility of adjuvant radiotherapy for pN0 TESCC patients was investigated through the failure model of postoperative patients.Results Of all patients,there were 57 cases with chest-regional recurrence (12.1％),most of which occurred in the mediastinal lymph nodes(52 case).There were 42 (8.9％) patients were identified as distant metastasis (DM),of which 13 cases were found to have both local recurrence and DM,and the total failure rate was 20.9％.The chest-regional recurrence rate of upper TESCC was statistically significantly higher than middle and lower (x2 =7.469,P ＜ 0.05),but DM rate had no statistically significant difference (P ＞ 0.05).The chest-regional recurrence rate and DM rate of the advanced T stage were significantly higher than those of the early T stage(x2 =10.247,7.886,P ＜ 0.05).The result of univariate analysis showed that disease site,the degree of adhesion,postoperative stump were significant factors of chestregional recurrence rate (x2 =14.232,9.486,7.546,P ＜ 0.05).Gender,smoking and preoperative weight loss ≥5 kg significantly influenced DM (x2 =10.823,10.275,6.065,P ＜ 0.05).In addition,the T stage was the significant influence factor of chest-regional recurrence and DM(x2 =15.994,12.885,P ＜0.05).The result of multivariate analysis showed that T stage and postoperative stump were independent factors of chest-regional recurrence (P ＜ 0.05).Smoking was an independent factor of DM (P ＜ 0.05).Conclusions There was a high rate of chest-regional recurrence in patients with stage pN0 TESCC who received surgery alone.Postoperative radiotherapy was recommended for patients with upper TESCC,advanced T stage,severe local adhesion,positive margin in and postoperative stump.Male,smoking and preoperative weight loss≥5 kg were associated with higher DM rate.
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Objective The aim of this study was to evaluate the prognosis of resection followed by chemotherapy compared with chemoradiotherapy for limited-stage small cell lung cancer .Methods The clinical data of 230 limited-stage small cell lung cancer patients with curative treatment between January 2006 and December 2011 were retrospectively analyzed .All patients divided to two group: the resection plus chemotherapy ( S +C ) and chemoradiotherapy ( R +C ) .And the prognostic factors were further analyzed with limited stage small cell lung cancer .The Kaplan-Meier method was used for the survival analysis.Results The overall survival rates of 1-year, 3-year and 5-year were 87.0%, 38.9%, 25.4%, respectively and the media survival time ( MST) 26.0 months.When patients were stratified by clinical stageⅠ+Ⅱ, the 1-year , 3-year and 5-year overall survival rates of S +C group and R +C group were 92.6%, 63.2%, 47.3%and 76.2%, 42.9%, 30.6%, respectively (χ2 =7.851, P0.05).In univariate analysis, tumor location, tumor stage, lymph node metastasis, TNM stage, the cycle of chemotherapy , treatment modalities were significantly associated with survival ( RR=1.735, P<0.05).The multivariate analysis only showed TNM stage were independent factors of prognosis .Conclusions The results suggested that resection plus chemotherapy could improve the prognosis of early-stage(stageⅠ+Ⅱ) small cell lung cancer, but patients in ⅢA stage should received the definitive chemoradiotherapy .The TNM stage was still the independent factor of prognosis .
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Objective: To identify the relationship between the expression of protein tyrosine phosphatase non-receptor type 12 (PTPN12) and radiotherapy effect in non-small cell lung cancer (NSCLC) tissues and to determine whether PTPN12 deficiency can sensi-tize lung cancer cells to irradiation. Methods: From September 2013 to October 2014, 92 NSCLC patients undergoing radiotherapy with or without platinum-based combination chemotherapy were analyzed retrospectively. Before the treatment, PTPN12 expression was detected through immunohistochemistry. After the completion of radiotherapy, the patients' responses were assessed and radio-therapeutic efficacy analyzed. The human NSCLC cell line H1299 was infected with shPTPN12 knockdown, and colony survival assay was analyzed after irradiation. Chi-square test was used to examine the correlation between PTPN12 expression and clinicopathologi-cal characteristics. Univariate analyses and Logistic regression test were used to analyze the relationship between clinicopathological characteristics and radiotherapeutic response. Results: Patients with low PTPN12 expression were more sensitive to radiotherapy than those with high PTPN12 expression (80.0%vs. 57.1%, P=0.018). Multivariate analysis showed that PTPN12 expression was the on-ly independent predictor of radiotherapeutic response in NSCLC. The H1299-shPTPN12-knockdown cells were sensitive to irradiation. Conclusions:The results of the study indicated that downregulation of PTPN12 improved the radiosensitivity of NSCLC cells.
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Background and purpose:p53 binding protein (53BP1) expresses in many normal and tumor cells. In vitroexperiments have conifrmed that inhibition of the protein expression of 53BP1 can effectively eliminate cycle arrest of tumor cells, and increase the radiosensitivity after irradiation. However, thein vivo experiment has not been re-ported. This study aimed to explore the effect of silencing 53BP1 gene on the growth and radiosensitivity to esophageal cancer cell ECA109 xenograft in nude mice.Methods:Forty-eight male BALB/c/nu nude mice were randomly divided into 6 groups: ECA109, ECA109/R, ECA109/N, ECA109/NR, ECA109/B and ECA109/BR. Three kinds of prepared cells (ECA109, ECA109/N and ECA109/B) were subcutaneously injected into the paw pads of mice (2×106/100 μL per mouse). The nude mice in ECA109/R, ECA109/NR, and ECA109/BR groups were irradiated with 15 Gy. Tumor growth was monitored every other day on the 6th day after injection. Tumor volume was measured with calipers. Theexpression levels of CHK1, CHK2 and phosphorylated CHK2-T68 protein were examined in different groups by West-ern blot. Apoptotic cell and cell cycle distribution were detected by lfow cytometry assay.Results:Visible tumors were detectable by day 7 after implantation, and the tumor volumes showed no signiifcant differences among all the groups (F=0.67, P=0.69). After irradiation with 15 Gy, tumor volumes in ECA109/BR group were smaller than those in other groups (P=0.03); the growth inhibition rate increased, but the relative growth rate decreased signiifcantly (P=0.01). The q value which relfected the radiosensitizing effect in ECA109/BR group was 1.45. The expressions of CHK1 and CHK2 at protein level in ECA109/BR group were not inlfuenced (P=0.71). However, the level of phosphorylated CHK2-T68 expression decreased signiifcantly after irradiation with 15 Gy (P=0.03). Cell cycle distribution and apoptosis were not signiifcantly different among all the groups (P=0.45).Conclusion:Silencing 53BP1 gene expression could inhibit the growth of esophageal cancer cell xenograft and increase the radiosensitivity to tumors in the nude mice.
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Objective To investigate the association of local factors with local recurrence (LR) and distant metastasis ( DM) in patients with esophageal squamous cell carcinoma ( ESCC) who do not experience clinical metastasis.Methods A total of 236 eligible ESCC patients were analyzed retrospectively, and the association of lesion length on esophagography, maximum tumor diameter, and tumor volume with survival and treatment failure pattern was analyzed.Kaplan-Meier test and Cox regression were used for survival analysis and to identify prognostic factors.Results The 1-, 3-, and 5-year overall survival rates, LR rates, and DM rates were 88.6%,52.4%,30.2%, 15.5%,35.6%,45.8%, and 9.0%,22.2%, 30.6%, respectively.The multivariate analysis showed that short-term treatment outcome and maximum tumor diameter were independent prognostic factors for overall survival rate ( P=0.000, 0.019); sex, maximum tumor diameter, irradiation method, and short-term treatment outcome were independent prognostic factors for LR (P=0.039,0.003,0.045,0.000);maximum tumor diameter was the independence factor for DM (P=0.035).In the patients receiving elective nodal irradiation and involved-field irradiation, the maximum tumor diameter was the prognostic factor for LR (P=0.008,0.001), and the lesion length on esophagography, maximum tumor diameter, and tumor volume were prognostic factors for DM (P=0.009, 0.023,0.014).Conclusions In ESCC patients without clinical metastasis, local factors are significantly associated with LR and DM, among which maximum tumor diameter is the most important factor.
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Objective To analyze the efficacy of chemoradiotherapy in the treatment of esophageal carcinoma and its influencing factors,and to provide an optimal combination mode of chemoradiotherapy for treating esophageal carcinoma. Methods A retrospective analysis was performed on clinical data from 232 patients with esophageal carcinoma who were admitted to our hospital from January 2006 to December 2012 and received radical chemoradiotherapy. All patients received three?dimensional conformal radiotherapy or intensity?modulated radiotherapy as well as platinum?based chemotherapy. The overall survival ( OS ) and local control ( LC) rates were calculated using the Kaplan?Meier method and analyzed using the Logrank test. Univariate and multivariate prognostic analyses were made by the log?rank test and the Cox proportional hazard model,respectively. Results In all patients,the 1?,3?,and 5?year LC rates were 66?1%,42?2%, and 38?5%,respectively;the median LC time was 24?4 months;the 1?,3?,and 5?year OS rates were 73?3%, 37?2%,and 19?5%,respectively;the median OS time was 21 months. The univariate analysis revealed that T stage,N stage,clinical stage,irradiation range,and no less than 3 cycles of chemotherapy were influencing factors for OS ( P=0?000,0?000,0?000,0?030,0?001) and LC ( P=0?112,0?031,0?009,0?074,0?218) . The multivariate analysis revealed that N stage,clinical stage,and no less than 3 cycles of chemotherapy were independent prognostic factors for OS ( P=0?006,0?000,0?001) . Conclusions The LC and long?term OS rates in patients with early?stage esophageal carcinoma can be substantially improved by radical chemoradiotherapy. The irradiation range and no less than 3 cycles of chemotherapy improve the long?term survival in patients.
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Objective To investigate the effects of inhibition of MDC1 protein expression on xenografted tumors in nude mice,and to observe the histopathological and cellular changes in nude mice.Methods Three pairs of effective and control short hairpin RNA targeting MDC1 mRNA were designed and cloned into the pSIH1-H1-copGFP vector.Real-time PCR and Western blot were used to determine the mRNA and protein expression of MDC1.After selection by copGFP reporter gene,cells were divided into negative transfection group (ECA109-N) and MDC1 transfection group (ECA109-M).The transfected cells were injected into nude mice.The mice were divided into ECA109 group,ECA109-N group,and ECA109-M group.Each group was divided into irradiation subgroup and non-irradiation subgroup.The changes in tumor size after irradiation were evaluated in each group.Western blot was used to measure the expression of CHK1,CHK2,and CHK2T68 in xenografted tumors.Flow cytometry was used to analyze the cell cycle distribution and apoptosis of tumor cells in nude mice.The variance analysis was used to compare the mean of multiple groups,and the SNK-q test was used in the two two groups.Results The pMDC1-shRNA plasmid was successfully constructed and used to transfect ECA109 cells.ECA109-M cells were obtained by stable transfection with the recombinant plasmid.All inoculated nude mice survived with visible xenografted tumors at the underside of the paw in about one week.There was no swelling and wound in inoculation sites.There was no significant difference in tumor size between different groups (P＞0.05).The tumor growth in the ECA109 group and the ECA109-N group significantly slowed down after irradiation with a dose of 15 Gy (P＜0.05).Compared with the other two groups,the ECA109-M group had a significant smaller tumor size,significantly slower relative tumor growth,and significantly higher growth inhibition (all P＜0.05).The q value of the ECA109-M group was 1.36.In the ECA109-M group,there were no significant changes in the protein expression of CHK1 and CHK2 after irradiation (P＞ 0.05);however,the phosphorylation of CHK2T68 protein was significantly reduced after irradiation (P＜0.05).There were no significant differences in cell cycle distribution or the proportion of apoptotic cells in tumor tissue between the three groups (P＞0.05).Conclusions Inhibition of MDC1 protein expression by RNA interference can effectively inhibit the growth of xenografted tumors after irradiation in the nude mice by increasing their radiosensitivity.
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Objective To apply RNA interference technique for reducing the expression of MDC1 gene in esophageal carcinoma cell line ECA109, observe the changes in cell cycle and radiosensitivity after radiation, and discuss related mechanisms. Methods Three pairs of effective interference sequences and negative control sequences were synthesized for MDC1 mRNA sequence, and a recombinant plasmid was constructed with the vector pSIH1?H1?copGFP. RT?PCR and Western blot were used to determine the expression levels of MDC1 mRNA and protein. Colony?forming assay was applied to measure radiosensitivity, flow cytometry to determine cell cycle, Western blot to determine the expression of CHK1 and CHK2 proteins, and laser scanning confocal microscope to observe the number of MDC1 blotches inside the nucleus. One?way analysis of variance was used to analyze the differences between groups. Results The pSIH1?H1?copGFP plasmid was constructed successfully and ECA109 cells were infected to obtain ECA109M cells with stable transfection. The expression levels of MDC1 mRNA and protein in ECA109M cells were lower than those in ECA109N and ECA109 cells ( P= 0. 032 and 0. 041, respectively ) . After 5?Gy radiation, ECA109M cells had a lower proportion of G2+M cells than ECA109N and ECA109 cells ( P=0. 026) . After 5?Gy radiation, ECA109, ECA109N, and ECA109M cells had similar expression levels of CHK1 and CHK2 proteins ( P= 0. 345 and 0. 451, respectively ) , and ECA109M cells had a lower expression level of CHK2 T68 protein than ECA109 and ECA109N cells ( P=0. 012) . ECA109 cells had a D0 value of 3. 06 Gy and an SF2 value of 0. 91;the D0 values for ECA109N and ECA109M cells were 2. 90 Gy and 1. 88 Gy, respectively, and the SF2 values for them were 0. 89 and 0. 84, respectively ( P=0. 021 and 0. 037, respectively ) . Conclusions RNA interference can reduce the expression levels of MDC1 protein and cell cycle?related proteins, release cell cycle arrest, and enhance radiosensitivity in esophageal carcinoma ECA109 cells.