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Objective:To investigate the prognostic value of Onodera's prognostic nutrition index (PNI) before treatment in patients with cervical and upper thoracic esophageal squamous cell carcinoma (CUTESCC) undergoing definitive chemoradiotherapy (dCRT) and its predictive value in the occurrence of ≥ grade 2 radiation esophagitis (RE).Methods:The data of 163 CUTESCC patients eligible for inclusion criteria admitted to the Fourth Hospital of Hebei Medical University from January 2012 to December 2017 were retrospectively analyzed. The receiver operating characteristic (ROC) curve was used to calculate the best cut-off value of PNI for predicting the prognosis of patients. The prognosis of patients was analyzed by univariate and Cox multivariate analyses. Logistics binary regression model was adopted to analyze the risk factors of ≥ grade 2 RE in univariate and multivariate analyses. The significant factors in logistic multivariate analysis were used to construct nomogram for predicting ≥ grade 2 RE.Results:The optimal cut-off value of PNI was 48.57 [area under the curve (AUC): 0.653, P<0.001]. The median overall survival (OS) and progression-free survival (PFS) were 26.1 and 19.4 months, respectively. The OS ( χ2=6.900, P=0.009) and PFS ( χ2=9.902, P=0.003) of patients in the PNI ≥ 48.57 group ( n=47) were significantly better than those in the PNI < 48.57 group ( n=116). Cox multivariate analysis showed that cTNM stage and PNI were the independent predictors of OS ( HR=1.513, 95% CI: 1.193-1.920, P=0.001; HR=1.807, 95% CI: 1.164-2.807, P=0.008) and PFS ( HR=1.595, 95% CI: 1.247-2.039, P<0.001; HR=2.260, 95% CI: 1.439-3.550, P<0.001). Short-term efficacy was another independent index affecting PFS ( HR=2.072, 95% CI: 1.072-4.003, P=0.030). Logistic multivariate analysis showed that the maximum transverse diameter of the lesion ( OR=3.026, 95% CI: 1.266-7.229, P=0.013), gross tumor volume (GTV) ( OR=3.456, 95% CI: 1.373-8.699, P=0.008), prescription dose ( OR=3.124, 95% CI: 1.346-7.246, P=0.009) and PNI ( OR=2.072, 95% CI: 1.072-4.003, P=0.030) were the independent factors affecting the occurrence of ≥ grade 2 RE. These four indicators were included in the nomogram model, and ROC curve analysis showed that the model could properly predict the occurrence of ≥ grade 2 RE (AUC=0.686, 95% CI: 0.585-0.787). The calibration curve indicated that the actually observed values were in good agreement with the predicted RE. Decision curve analysis (DCA) demonstrated satisfactory nomogram positive net returns in most threshold probabilities. Conclusions:PNI before treatment is an independent prognostic factor for patients with CUTESCC who received definitive chemoradiotherapy. The maximum transverse diameter of the lesion, GTV, prescription dose and PNI are the risk factors for ≥ grade 2 RE in this cohort. Establishing a prediction model including these factors has greater predictive value.
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Objective:To establish Wistar rat models of acute radiation esophagitis, and observe the histopathological changes at different time points after modeling.Methods:Wistar rats were locally irradiated with different doses of 6 MV X-rays, and the rats were sacrificed on the 3 rd, 5 th, 7 th, and 14 th days after irradiation. The full-length esophagus tissue was taken for paraffin embedding, sectioning, and hematoxylin and eosin (HE) staining for pathological assessment. The pathological changes of the esophagus of the rats were observed at the 3 rd, 5 th, 7 th, and 14 th days after 25 Gy and 30 Gy irradiation. The changes of daily dietary intake of rats in different irradiation groups within 1-2 weeks after radiation exposure were observed. Results:No rat died in two groups after being irradiated with 25 Gy and 30 Gy rays. All the rats in the 30 Gy group had esophagus injury. On the 7 th day, the degree of injury was the most serious, with a pathological score of 5.00±0.75 and a food intake of 0 g. On the 14 th day, the degree of injury was relieved, and the food intake was restored to the level before irradiation. Conclusions:The Wistar rat model of acute radiation esophagitis can be established by a single dose of 6 MV X-ray 30 Gy irradiation to the esophagus. The 7 th day after irradiation is an ideal observation time for the acute injury phase, which is gradually alleviated after the 7 th day. The time can be chosen from 7-14 days after irradiation as the observation point for the healing repair phase.
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Objective:To validate the effect of TUT4 on the radiosensitivity of esophageal epithelial cells (HEEC) by regulating the uridylation of miR132/212 clusters.Methods:The expression of TUT4 in HEEC at 0, 6, 18, 24 and 48 h after 0, 2, 4, 6 and 8 Gy X-ray irradiation was detected by PCR. The HEEC cells were divided into four groups: NC group, shTUT4 group, 6 Gy group, and 6 Gy+ shTUT4 group. The effects of TUT4 on cell radiosensitivity, cell proliferation, cell cycle, mitochondrial damage, and oxygen free radical production were detected respectively. The effect of down-regulated TUT4 expression on miR132/212 uridylation was detected by RT-PCR, and the radiosensitivity of HEEC with overexpression of miR132/212 or miR132/212+ UUU was detected by clone formation and proliferation assay, respectively. Proliferation assay was performed to detect the proliferation of HEEC when TUT4 expression was down-regulated and miR132/212 or miR132/212+ UUU was overexpressed.Results:TUT4 expression increased after different doses of X-ray irradiation ( t=12.84, 62.06, 27.86, 32.43, P<0.05). Downregulation of TUT4 expression increased the radiosensitivity of HEEC ( t=13.2, 5.85, 7.31, P<0.05) with a SER D0of 1.41 and D0=0.79, Dq=1.61, SF2=0.47. Compared with 6 Gy group, cell proliferation in 6 Gy+ shTUT4 group was decreased ( t=7.12, 13.63, P<0.05), cells in S phase were increased ( t=11.98, P<0.05), mitochondrial damage was increased ( t=11.98, P<0.05), and ROS level was increased ( t=15.65, P<0.05). Down-regulation of TUT4 expression increased miR132/212 expression and decreased miR132/212+ UUU expression ( t=27.90, 60.99, P<0.05). Overexpression of miR132/212 increased the radiosensitivity of HEEC, and overexpression of miR132/212+ UUU decreased the radiosensitivity of HEEC, with SER D0 of 1.20 and 0.71, respectively. Cell proliferation of shTUT4 + miR132/212 group waslower than that of shTUT4 group( t=4.76, 7.65, P<0.05), and cell proliferation of shTUT4 + miR132/212+ UUU group was higher than that of shTUT4 ( t=7.22, P<0.05). Conclusions:X-ray irradiation increased the expression of TUT4 in HEEC, and the down-regulation of TUT4 reduced HEEC radiosensitivity and radiation damage, where the uridylation of miR132/212 was involved in.
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Objective To investigate the risk factors for acute radiation esophagitis andpneumonitis after radiation therapy in esophageal cancer (EC) patients with diabetes or hypertension.Methods A total of 373 EC patients receiving three dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) were included in this study.Among these patients,42 showed concurrent with diabetes and 99 with hypertension.Radiation esophagitis or pneumonitis in patients with or without diabetes,and with or without hypertension were monitored in the 1-year follow up,respectively.Results The prevalence of grade 1,2,3 and 4 radiation esophagitis in diabetes and non-diabetes patients was 40.5％,38.1％,14.3％,4.8％ and 66.2％,27.8％,2.7％,1.8％,respectively,while that of the grade 1,2 and 3 radiation pneumonitis in diabetes and non-diabetes patients was 31.0％,16.7％,9.5％ and 30.8％,15.7％,1.2％,respectively.The prevalence of grade 3 or above radiation esophagitis and pneumonitis in patients with diabetes and was significantly higher than those with non-diabetes (x2 =13.573,12.279,P ＜ 0.05).The prevalence of grade 1,2,3 and 4 radiation esophagitis in hypertension and non-hypertension patients was 49.5％,38.4％,8.1％,3.0％ and 68.2％,25.5％,2.6％,1.8％,respectively,while that of the grade 1,2 and 3 radiation pneumonitis in hypertension and non-hypertension patients were 30.3％,18.2％,5.1％ and 31.0％,15.0％,1.1％,respectively.The prevalence of grade 3 or above radiation esophagitis and pneumonitis in patients with hypertension was significantly higher than those with non-hypertension (x2 =5.695、5.422,P ＜ 0.05).Diabetes is an independent risk factor for grade 3 or above acute radiation esophagitis and pneumonitis.Conclusions Diabetes or hypertension might be risk factors for severe radiation esophagitis and pneumonitis in EC patients receiving radiation therapy.
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Objective:To explore the curative effect and toxic and side effects of Xihuang Capsule in the patients with advanced esophageal cancer treated with chemoradiotherapy, and to clarify its mechanism.Methods:The patients with advanced esophagealcancer without treatment were selected.The patients treated with Xihuang Capsule combined with concurrent chemoradiotherapy were defined as combination treatment group(n=27), and then other 27 patients were randomly selected from 87 patients treated with concurrent chemoradiotherapy alone as chemoradiotherapy group.The observation time was 90 d from the begining of chemotherapy.The differences in KPS, degree of dysphagia, incidence, occurrence time and degrees of acute radiation esophagitis of the patients in two groups were compared, and local control of tumor was analyzed.Results: After treatment, the KPS scores of the pateints in two groups were decreased, and the KPS score in combined treatment group was significantly higher than that in chemoradiotherapy group (P0.05).Conclusion:Xihuang Capsule can improve the quality of life, reduce dysphagia degree and the incidence of acute radiation esophagitis,and delay the occurrence time;it can be used as an effective auxiliary treatment of advanced esophageal cancer.
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Objective To study the correlation between microRNA (miRNA) polymorphism and the risk and clinical prognosis of acute radiation esophagitis in patients with esophageal neoplasms. Methods 256 patients with acute radiation esophagitis during radiotherapy were chosen as the experimental group, and 256 patients matched by age and sex without acute radiation esophagitis during radiotherapy were chosen as the control group. The polymorphism types of miRNA-146a (rs2910164) were determined by Taqman gene typing technology of ABI7900HT. The genotype distribution of miRNA-146a rs2910164 polymorphism in the experimental and control groups was analyzed. Logistic regression was performed to estimate the odds ratio (OR) and 95%confidence interval (95%CI ). Results The genotype frequencies of CC, GG and CG at miRNA-146a polymorphic site rs2910164 in the experiment and control group were 20.70 % (53/256) and 33.20 % (85/256), 45.32 % (116/256) and 40.63 % (104/256), 33.98 % (87/256) and 26.17 % (67/256), respectively. There was a statistically significant difference between two groups (all P< 0.05). Compared with gene type CC, the OR values of acute radiation esophagitis in patients with gene type GC and GG were 0.654 and 0.627, respectively (P< 0.05), indicating that they had a low risk. The negative effect rates in patients with gene type GG, CG and CC were 7.69 % (8/104), 19.40 % (13/67) and 41.18 % (35/85), respectively. There was a statistically significant difference in the clinical prognosis among these genotypes (P< 0.05). Conclusion Gene type CC at miRNA-146a polymorphic site rs2910164 can increase the risk of acute radiation esophagitis and decrease the clinical prognosis in patients with esophageal neoplasms.
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Objective To evaluate the feasibility and effect of taking Actovegin orally in cureing acute radiation esophagitis ,and to compare the curative effect of oral drugs and abdominal cavity medicine .Methods Thirty male mouses were randomly divided in-to three groups after upper moiety esophageal radiation :the control group(irradiation only) ,the oral group(take Actovegin orally) , and the celiac injection group .The weight chang was tracked record weekly ,and the mouses were killed in batches at the seventh day ,the fourteenth day ,and the twenty eighth day .The grade about esophageal breakage ,inflammation and immunochemical colour-ation by TGF-βwere analysed .Results Esophageal breakage in the oral group and the celiac injection group had not significantly deffrence (P=0 .318) ,but they had better than the control group(P<0 .05);The celiac injection group had less weight decrease than the control group(P=0 .030) .Conclusion The mouses′cacotrophia with acute radiation esophagitis can be improved by Acto-vegin mainline .Taking Actovegin orally can reduce esophageal damnification .
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Objective To investigate the prevention and treatment effects of Compound Kushen Injection on acute radiation esophagitis. Methods Eighty-two eligible patients with esophageal cancer were randomly divided into the treatment group (41 cases) and the control group (41 cases). All the patients received radiotherapy. Throughout the course of radiotherapy, patients in the treatment group received Compound Kushen Injection, and patients in the control group received Kangfuxin Liquid. Occurrence time and level of radiation esophagitis, and dosage of painkillers were observed. Results Different degrees of acute esophageal toxicity were observed in the two groups. The occurrence rate of high level (degree III and degree IV) acute radiation esophagitis was 7.3%(3/41) in the treatment group, and 31.7%(13/41) in the control group. There was significant difference between the two groups (P<0.05). The dosage of the analgesic drug (Fentanyl Transdermal System) in the treatment group was far less than the controlled group (P<0.001). Conclusion Compound Kushen Injection could decrease the incidence rate of acute radiation esophagitis, and reduce the high-level esophagitis and the dosage of the analgesic drug, which can help the completion of radiation.
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Objective To analyze the clinical and dosimetric risk factors for acute radiation esophagitis (ARE) in non-small cell lung cancer (NSCLC) patients treated with three-dimensional conformal radiotherapy (3D-CRT),and to find significant risk factors for clinical therapy.Methods A total of 102 NSCLC patients treated with 3D-CRT were retrospectively analyzed.ARE was scored according to the Radiation Therapy Oncology Group (RTOG) criteria with grade 2 or worse.Patients were divided into non-concurrent chemoradiotherapy group and concurrent chemoradiotherapy group.The clinical and dosimetric factors associated with grade 2 or worse ARE were analyzed using univariate logistic regression,multivariate logistic analysis and receiver operating characteristic ( ROC ) curve.Results There were no grade 4 or5 ARE observed in the 102 patients.Nineteen developed grade 2,15 developed grade 3.In nonconcurrent chemoradiotherapy group,multivariate analysis showed that V55 was the only risk factor of grade 2/3 ARE.For ROC curve analysis,the cut-off point of V55 was 16.0 while the area under ROC curve was 0.870 ( 95 ％ CI:0.782 - 0.957,P ＜ 0.05 ).In concurrent chemoradiotherapy group,multivariate analysis showed that V35 and chemotherapy regimens during radiotherapy were risk factors of grade 2/3 ARE.The cut-off point of V35 was 23.75 while the area under ROC curve was 0.782 (95％ CI:0.636 -0.927,P ＜0.05).Vinorelbine and cisplatin regimen showed low incidence of ARE contrast with gemcitabine/docetaxel and cisplatin regimens (33.3％ and 66.7％ ).Conclusions V55 is the only statistically significant risk factor associated with grade 2 or worse ARE for patients who don't accepted concurrent chemotherapy.V35 and chemotherapy regimens during radiotherapy are statistically significant risk factors associated with grade 2 or worse ARE for patients who accept concurrent chemotherapy.Vinorelbine and cisplatin regimen during radiotherapy shows low incidence of ARE.