Predictive potential of preoperative Naples prognostic score-based nomogram model for the prognosis in surgical resected thoracic esophageal squamous cell carcinoma patients: A retrospective cohort study.

The present study aimed to establish an effective prognostic nomogram model based on the Naples prognostic score (NPS) for resectable thoracic esophageal squamous cell carcinoma (ESCC). A total of 277 patients with ESCC, who underwent standard curative esophagectomy and designated as study cohort, were retrospectively analyzed. The patients were divided into different groups, including NPS 0, NPS 1, NPS 2, and NPS 3 or 4 groups, for further analysis, and the results were validated in an external cohort of 122 ESCC patients, who underwent surgery at another cancer center. In our multivariate analysis of the study cohort showed that the tumor-node-metastasis (TNM) stage, systemic inflammation score, and NPS were the independent prognostic factors for the overall survival (OS) and progression-free survival (PFS) durations. In addition, the differential grade was also an independent prognostic factor for the OS in the patients with ESCC after surgery (all P < .05). The area under the curve of receiver operator characteristics for the PFS and OS prediction with systemic inflammation score and NPS were 0.735 (95% confidence interval [CI] 0.676-0.795, P < .001) and 0.835 (95% CI 0.786-0.884, P < .001), and 0.734 (95% CI 0.675-0.793, P < .001) and 0.851 (95% CI 0.805-0.896, P < .001), respectively. The above independent predictors for OS or PFS were all selected in the nomogram model. The concordance indices (C-indices) of the nomogram models for predicting OS and PFS were 0.718 (95% CI 0.681-0.755) and 0.669 (95% CI 0.633-0.705), respectively, which were higher than that of the 7th edition of American Joint Committee on Cancer TNM staging system [C-index 0.598 (95% CI 0.558-0.638) for OS and 0.586 (95% CI 0.546-0.626) for PFS]. The calibration curves for predicting the 5-year OS or PFS showed a good agreement between the prediction by nomogram and actual observation. In the external validation cohort, the nomogram discrimination for OS was better than that of the 7th edition of TNM staging systems [C-index: 0.697 (95% CI 0.639-0.755) vs 0.644 (95% CI 0.589-0.699)]. The calibration curves showed good consistency in predicting the 5-year survival between the actual observation and nomogram predictions. The decision curve also showed a higher potential of the clinical application of predicting the 5-years OS of the proposed nomogram model as compared to that of the 7th edition of TNM staging systems. The preoperative NPS-based nomogram model had a certain potential role for predicting the prognosis of ESCC patients.

EphA5 knockdown enhances the invasion and migration ability of esophageal squamous cell carcinoma via epithelial-mesenchymal transition through activating Wnt/ß-catenin pathway.

BACKGROUND: The erythropoietin-producing hepatocellular (Eph) receptor A5 (EphA5) has been found to be overexpressed in some malignant tumors and is associated with disease prognosis. However, the role of EphA5 in esophageal squamous cell carcinoma (ESCC) is not clear. METHODS: In the present study, we measured the expression of EphA5 in ESCC tissues and cell lines including KYSE150 and KYSE450 cells. siRNA transfection was used to interfere with EphA5 expression in ESCC cell lines. Cell viability, colony formation, scratch and invasion assays were performed to explore the roles of EphA5 in ESCC cell lines. Flow cytometry analysis was performed to investigate whether EphA5 could affect the cell apoptosis and cycle. The biomarkers related to epithelial-mesenchymal transition (EMT) and molecules associated with Wnt/ß­catenin signaling were also measured by western blot and immunofluorescence. RESULTS: The protein and mRNA expression of EphA5 were significantly higher in fresh ESCC tissues and cell lines compared with normal control groups and human normal esophageal epithelial cells (HEEC). The cell viability assay and colony formation assay revealed that EphA5 knockdown enhanced the proliferation of KYSE150 and KYSE450 cells in vitro. The invasion and migration of ESCC cells were accelerated after EphA5 knockdown. The expression of EMT biomarkers was altered in ESCC cells transfected with siRNA targeting EphA5. Moreover, EphA5 downregulation enhanced the protein levels of ß­catenin and p-GSK-3ßSer9, which play a key role in the Wnt/ß­catenin pathway. CONCLUSIONS: EphA5 knockdown promotes the proliferation of esophageal squamous cell carcinoma,enhances invasion and migration ability via epithelial-mesenchymal transition through activating Wnt/ß­catenin pathway.

Pretreatment NRS-2002 scores combined with hematologic inflammation markers are independent prognostic factors in patients with resectable thoracic esophageal squamous cell carcinoma.

BACKGROUND: The purpose of this study was to investigate the prognostic values of Nutritional Risk Screening 2002 (NRS-2002) and hematologic inflammation markers in patients with esophageal squamous cell carcinoma (ESCC) receiving curative esophagectomy. MATERIALS AND METHODS: A total of 277 patients with ESCC treated with standard curative esophagectomy were retrospectively analyzed. These patients were grouped for further analysis according to the systemic inflammation score (SIS), the combination of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio (CNP) score and NRS-2002 score. The Kaplan-Meier method and log-rank test were adopted to calculate and compare the progression-free survival (PFS) and overall survival (OS) rates with these parameters. The Cox proportional hazards model was used to carry out univariate and multivariate analyses. Receiver operating characteristic (ROC) curves were applied to verify the accuracy of SIS, CNP and NRS-2002 for survival prediction. RESULTS: In univariate analysis, the following factors were significantly associated with poor PFS and OS: sex, T stage, N stage, TNM stage, SIS, CNP and NRS-2002 (all P<0.05). Furthermore, multivariate Cox regression analysis showed that CNP (hazard ratio [HR]=1.602; 95% confidence interval [CI] 1.341-1.913; P=0.000), NRS-2002 (HR=2.062; 95% CI 1.523-2.792; P=0.000) and TNM stage (HR=1.194; 95% CI 1.058-1.565; P=0.048) were independent prognostic factors for PFS. Correspondingly, CNP (HR=1.707; 95% CI 1.405-2.074; P=0.000), NRS-2002 (HR=2.716; 95% CI 1.972-3.740; P=0.000) and TNM stage (HR=1.363; 95% CI 1.086-1.691; P=0.036) were also independent prognostic factors for OS. Finally, the results of ROC curves indicated that CNP and NRS-2002 were superior to SIS as a predictive factor for PFS or OS in patients with ESCC receiving surgery. CONCLUSION: This study demonstrated that CNP combined with NRS-2002 is promising as a predictive marker for predicting clinical outcomes in patients with ESCC receiving surgery.

Influential factors on radiotherapy efficacy and prognosis in patients with secondary lymph node metastasis after esophagectomy of thoracic esophageal squamous cell carcinoma.

BACKGROUND: The purpose of this study was to clarify whether pretreatment tumor burden-related index, including the gross tumor volume (GTV) of metastatic lymph nodes (VLN) and maximum diameter of metastatic lymph nodes (DLN), and inflammatory markers, consisting of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), are useful for assessing the therapeutic effects and prognosis with secondary lymph node metastasis (LNM) receiving chemoradiotherapy (CRT) or radiotherapy (RT) alone after resection of esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: A total of 119 patients with secondary LNM after resection of ESCC were recruited and received curative RT only or CRT. The enrolled patients were grouped according to the median values of NLR, PLR, VLN, and DLN. The relationship between the responsiveness to treatment and these markers was analyzed by logistic analysis. The Kaplan-Meier method and log-rank test were adopted to calculate and compare the overall survival (OS) rates with these markers. The Cox models were used to carry out multivariate analyses. RESULTS: Univariate logistic regression analysis showed that the responses to treatment were highly associated with treatment method (P=0.011), NLR (P=0.000), PLR (P=0.003), VLN (P=0.000), and DLN (P=0.000). Next, multivariate logistic regression analysis showed that therapeutic method (hazard ratio [HR]=1.225, P=0.032), NLR (HR=2.697, P=0.019), and VLN (HR=4.607, P=0.034) were independent risk factors for tumor response. Additionally, Kaplan-Meier survival analysis of this cohort revealed that NLR (χ2 =27.298, P=0.000), PLR (χ2=16.719, P=0.000), VLN (χ2=48.823, P=0.000), DLN (χ2=40.724, P=0.000), and treatment methods (χ2=18.454, P=0.018) were significantly associated with OS. Furthermore, multivariate analysis was performed, and the results showed that therapeutic method (HR=1.223, P=0.048), NLR (HR=2.000, P=0.018), VLN (HR=2.379, P=0.020), and DLN (HR=2.901, P=0.002) were considered independent prognostic factors for OS. CONCLUSION: This study found that NLR and VLN were promising as predictive markers for therapeutic effects, and NLR combined with VLN and with DLN might be useful biomarkers in predicting outcomes in patients with secondary LNM receiving CRT or single RT after esophagectomy.

Clinical observation of three dimensional conformal radiotherapy with tamoxifen in treatment of postoperative malignant glioma.

OBJECTIVE: To evaluate the efficacy and adverse effects of three dimensional conformal radiotherapy (3D-CRT) with tamoxifen in treating patients with postoperative malignant glioma. PATIENTS AND METHODS: 60 patients of postoperative malignant glioma were randomly assigned into two groups, 30 patients were treated with 3D-CRT plus tamoxifen (treatment group), and the other 30 patients with 3D-CRT plus temozolomide (control group). All patients were radiated by 6MV X-ray, 2.0 Gy per fraction, once daily, with a total dose (DT) of 56~60 Gy. Tamoxifen was delivered at 60 mg /m2/d, temozolomide was given at 75 mg/m2/d. All patients were treated with concurrent radiotherapy. RESULTS: One, 2, 3 year survival rates of treatment and control group were 63.3%, 30.0%, 23.0% and 70.0%, 33.3%, 26.7%, respectively (χ2=0.01, 0.23, 0.09, P>0.05). The rate of thromboembolism in treatment group was 6.7%. CONCLUSION: Therapeutic efficacy of two groups was similar, but it was more cost- effective in treatment group, and toxicity did not increase.

Phase II study on breast conservative surgery plus chemo- and radiotherapy in treating Chinese patients with early staged breast cancer.

PURPOSE: To evaluate the efficacy of conservative surgery plus chemo-, radio-therapy in treating patients with early stage breast cancer. PATIENTS AND METHODS: Eligible patients were treated by postoperative chemotherapy as well as whole-breast irradiation with tumor bed boost. Postoperative radiotherapy consisted of 6 MV whole breast linear accelerator irradiation with two tangential half fields to a total dose of 45~50 Gy, followed by 10~15 MeVß boost irradiation to tumor bed for 10~20 Gy, total dose 56~66 Gy. RESULTS: Fifty-two patients were enrolled. Overall 1-, 2- and 3 year survival rates were 98.1%, 92.3%, and 90.4%, respectively, with a local recurrence rate of 5.77%. Cosmetic results were evaluated as good by doctors in 90.4% of patients. CONCLUSIONS: Breast conservative surgery combined with chemo- radio-therapy could be a treatment option for Chinese patients with early stage breast cancer.

Chemotherapy and late course three dimensional conformal radiotherapy for treatment of patients with stage III non- small cell lung cancer.

OBJECTIVE: To compare the efficacy and complications of chemotherapy and late course three-dimensional conformal radiotherapy (3DCRT) in treating patients with stage III non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: All patients were divided into two groups: to receive chemotherapy and late course 3DCRT (3DCRT group), or chemotherapy and conventional fraction radiation (control group). In the 3DCRT-group, patients were given 6~15 MV X-rays with a total dose of 40 Gy, followed by 3DCRT, 2.5 Gy~3.0 Gy per fraction, 1 fraction/ every day, total 68 Gy~70 Gy; in the control group, with conventional fraction radiation the total dose was 64~66 Gy. The chemotherapy regimen in both cases was EP (VP-16 and DDP). RESULTS: Sixty four patients with stage III NSCLC were divided into two groups: 32 patients into 3DCRT, 32 into the control group. One and 2-year survival rates in 3DCRT and control group were 87.5%, 56.3%mad 65.6%, 34.4%, respectively (P<0.05); local control rates were 90.6%, 81.3% and 65.6%, 53.1%, respectively (P<0.05). CONCLUSION: Chemotherapy and late course 3DCRT is associated with improved survival rate in patients with stage III NSCLC with good tolerability.

[Drug release properties of sodium alginate hydrophobically modified by star polylactic acid].

Inorganic/polymer hybrid star polylactic acid (POSS-PLA) was obtained through ring-opening polymerization of lactide by using polyhydroxyl cage silsesquioxane (POSS-OH) as the core and tin (II) octoate as the catalyst. The star polylactic acid (POSS-PLA) was used to modify sodium alginate hydrophobically and a drug carrier was obtained. The drug release behavior was investigated by using ibuprofen as the model drug. The results showed that the drug loading rate could be improved and the release rate was postponed with an increase of POSS-PLA content in the carries. The release mechanism gradually changed from the first-order to the zero-order pattern after the modification.