The economic burden of esophageal cancer in Iran

Background: Studies on economic burden demonstrate the impacts of some diseases and provide invaluable information for specifying priorities and resource needs when designing cancer control strategies. The current study aimed to estimate the cost of esophageal carcinoma (EC) in Iran in 2018. Methods: This study was conducted on the prevalence approach to estimate the economic burden of EC in Iran from a social perspective. The direct cost was estimated by summing the diagnosis, treatment, follow-up, terminal care, and transport costs. Additionally, a human capital approach was adopted to estimate productivity losses. Various resources were used for data collection, including the GLOBOCAN 2018 report, and the medical record in the Cancer Institute of Iran. Also, data such as exchange rates, employment, and housekeeping rates were extracted from the Central Bank of Iran Statistics. Results: The economic burden of EC in Iran was $69.2 million in 2018, of which $38.7 million is caused by indirect costs and $30.5 million by direct costs. The mortality cost accounted for 49% of the economic burden, followed by 34% direct medical cost, 10% direct non-medical cost, and 7% morbidity cost. Conclusions: Mortality and medical cost appeared to be the main contributor to the economic burden. Therefore, policy-makers are recommended to adopt early detection and effective treatment as a highly cost-effective strategy for controlling costs

Research status of patient-reported outcome in esophageal carcinoma surgery / 中国胸心血管外科临床杂志

@#Esophageal carcinoma is a malignant tumor with high morbidity and mortality worldwide, and surgery is the main treatment currently. With the development of patient-centered care, the effect of surgery should not be limited to the improvement of the incidence of postoperative complications, mortality and other indicators. It is also important to provide experience related to disease and surgery from the perspective of patients. Therefore, more and more attention is paid to patient-reported outcomes by scholars. This paper will provide an overview of the international widely used, reliable and effective scales and researches about patient-reported outcomes in esophageal carcinoma.

The IL-6/STAT3 signaling pathway mediated by radiotherapy regulates the expression of PD-L1 in esophageal cancer cells / 中华肿瘤杂志

Objective: To explore the possible mechanism of radiotherapy regulating the expression of PD-L1 in esophageal carcinoma. Methods: Three esophageal cancer cell lines (Eca109, Kyse150, TE1) were irradiated with different doses of X-rays, and 6 Gy+ AG490 group was set. The mRNA expression of PD-L1 was detected by real-time quantitative polymerase chain reaction (RT-qPCR). The protein expressions of PD-L1, STAT3, p-STAT3 were detected by western blotting and the protein level of IL-6 was detected by ELISA. Results: The mRNA expressions of PD-L1 in Eca109, Kyse150 and TE1 were 2.86±0.30, 960.01±21.27 and 106.78±6.67, higher than 1.07±0.15 in normal esophageal cell line HET-1A (P<0.01). The protein expressions of PD-L1 in Eca109, Kyse150 and TE1 were 0.091±0.036, 1.533±0.079 and 0.914±0.035, higher than 0.063±0.01 in normal esophageal cell line HET-1A (P<0.01). After 48 hours of 6 Gy irradiation, the protein expression levels of PD-L1 in Eca109, Kyse150 and TE1 were 0.135±0.007, 1.66±0.06 and 1.32±0.06, higher than 0.09±0.01, 1.21±0.05 and 0.93±0.03 of the 0 Gy group (P<0.01), while the protein expression levels of p-STAT3 in Eca109, Kyse150 and TE1 were 1.44±0.26, 0.75±0.04 and 1.92±0.17, higher than 0.18±0.05, 0.48±0.02 and 0.36±0.06 of the 0 Gy group (P<0.01). IL-6 protein expression increased significantly after different doses of irradiation (P<0.01). After the IL-6/STAT3 signaling pathway was blocked by the specific inhibitor AG490, the expressions of PD-L1 of Eca109, Kyse150 and TE1 in the 6 Gy+ AG490 groups were 0.11±0.03, 1.07±0.08 and 0.96±0.11, without significant differences of 0.09±0.01, 0.96±0.05 and 0.85±0.09 of the 0 Gy group (P>0.05), while the protein expressions of p-STAT3 were 0.76±0.11, 0.59±0.06 and 0.96±0.12, without significant differences of 0.67±0.08, 0.54±0.06 and 0.84±0.11 of the 0 Gy group (P>0.05). Conclusion: Radiotherapy may regulate the expression of PD-L1 in esophageal cancer cells through IL-6 / STAT3 signaling pathway.

Effect of antidepressant therapy on cellular immunity and quality of life of patients with depression after thoracoscopic radical resection of esophageal cancer / 中华胸心血管外科杂志

Objective:To investigate the effect of antidepressant therapy on cellular immunity and quality of life of patients with depression after thoracoscopic radical resection of esophageal cancer.Methods:Between June 2015 to March 2019, our hospital during the period of line thoracoscope comorbid depressive patients, 186 cases of esophageal cancer radical, according to the indicator method were randomly divided into treatment group and the control group (n=93), the treatment group after surgery for antidepressant treatment, the control group did not give any postoperatively in patients with depressive drugs treatment, routine for psychological counseling. Self-rating Depression Scale SDS and Generic Quality of Life Inventory-74 (GQoli-74) were used to evaluate the changes of depression status and Quality of Life in 2 groups before and after treatment. Flow cytometry was used to detect the levels of CD 4+ and CD 8+ subsets in peripheral blood to evaluate the changes of immune system function in 2 groups before and after treatment. Results:After treatment, the SDS score of the treatment group was significantly lower than that before treatment, the difference was statistically significant( P<0.05), while the SDS score of the control group was not significantly changed before and after treatment, the difference was not statistically significant( P>0.05). After antidepressant treatment, CD 4+ and CD 4+ /CD 8+ levels in the immune system in the treatment group were significantly increased, and CD 8+ levels were significantly decreased, with statistical significance ( P<0.05), while CD 4+ , CD 8+ and CD 4+ /CD 8+ levels in the control group were not significantly changed before and after treatment. There was no significant difference ( P>0.05). After treatment, the body function, psychological function, social function, material state and total score of quality of life of patients in the treatment group were significantly improved compared with before treatment, the difference was statistically significant ( P<0.05), while the score of quality of life of patients in the control group was not significantly changed before and after treatment, the difference was not statistically significant ( P>0.05). Conclusion:Antidepressant therapy can significantly improve the depression status of postoperative esophageal cancer patients, and improve the immune system function and quality of life.

Analysis of the predictive effect of early postoperative blood lipid metabolism and ratio of C-reactive protein to albumin on postoperative anastomotic fistula of esophageal cancer / 中国综合临床

Objective:To investigate the predictive effect of postoperative blood lipid metabolism and C-reactive protein/albumin ratio (CAR) on anastomotic fistula after radical resection of esophageal cancer.Methods:A retrospective case-control study was conducted on 256 patients with esophageal squamous cell carcinoma (all aged >50 years) who underwent radical esophagectomy in the thoracic surgery of the Second Affiliated Hospital of Zhengzhou University from January 2017 to December 2020. Total cholesterol, triglyceride, high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C), ratio of C-reactive protein to albumin (CAR) and hemoglobin test index were collected. According to whether there was anastomotic fistula after operation, the patients were divided into anastomotic fistula group and non-anastomotic fistula group. The measurement data of normal distribution were compared by t-test, the measurement data of non-normal distribution were expressed by M( Q 1, Q 3), the comparison between groups was expressed by Mann-Whitney U test, and the counting data were expressed by (case(%)).The comparison between groups was performed by χ 2 test. Logistic regression model was used for multivariate analysis. ROC curve and Kappa value were used to evaluate the predictive value of total cholesterol and CAR in postoperative anastomotic fistula. Results:The preoperative body mass index (BMI) ((18.71±1.90) kg/m 2) in anastomotic fistula group was higher than that in non-anastomotic fistula group ((20.59±2.88) kg/m 2), and the difference was statistically significant ( t=3.48, P=0.001). The postoperative total cholesterol ((5.44±1.09) mmol/L), LDL-C ((3.82±1.15) mmol/L) and CAR(0.64(0.41, 0.95)) in anastomotic fistula group were higher than those in non-anastomotic fistula group ((4.54±0.94) mmol/L, (2.92±0.76) mmol/L, 0.27(0.13,0.45)). There were significant differences between the two groups (the statistical values were t=4.84, t=5.69, Z=5.16, all P<0.001)). The hemoglobin concentration of 103.20 (84.94,110.48) g/L was lower than that of non anastomotic fistula group (107.68 (99.20,125.20) g/L), the difference was statistically significant ( Z=2.82, P=0.005). Lower BMI( OR=0.652,95% CI 0.482-0.882), higher total cholesterol( OR=3.240,95% CI 1.430-7.340), lower hemoglobin ( OR=0.837,95% CI 0.777-0.902) and higher CAR( OR=2.161,95% CI 1.597-2.925) were the risk factors of anastomotic fistula in esophageal squamous cell carcinoma( P values were 0.006, 0.005, <0.001 and <0.001,respectively). ROC curve analysis showed that the areas under the curve of total cholesterol and CAR were 0.742 (95% CI:0.643-0.841, P<0.001) and 0.790 (95% CI:0.690-0.890, P<0.001) respectively. The cutoff values were 4.915 mmol/L and 0.605, the sensitivity were 80.0% and 80.0%, the specificity were 82.3% and 92.5%, respectively, and the Kappa values were 0.418 and 0.625 respectively (all P<0.001). Conclusion:Total cholesterol and CAR after radical resection of esophageal cancer have a certain predictive value for postoperative anastomotic fistula in patients with esophageal squamous cell carcinoma. The predictive result of CAR is better than that of total cholesterol.

Development and validation of a prognostic model based on SEER data for patients with esophageal carcinoma after esophagectomy / 南方医科大学学报

OBJECTIVE@#To develop a nomogram to predict the long-term survival of patients with esophageal cancer following esophagectomy.@*METHODS@#We collected the data of 7215 patients with esophageal carcinoma from the Surveillance, Epidemiology, and End Results (SEER) database during the period from 2004 and 2016. Of these patients, 5052 were allocated to the training cohort and the remaining 2163 patients to the internal validation cohort using bootstrap resampling, with another 435 patients treated in the Department of Cardiothoracic Surgery of Jinling Hospital between 2014 and 2016 serving as the external validation cohort.@*RESULTS@#In the overall cohort, the 1-, 3-, and 5-year cancer-specific mortality rates were 14.6%, 35.7% and 41.6%, respectively. Age (≥80 years vs < 50 years, P < 0.001), gender (male vs female, P < 0.001), tumor site (lower vs middle segment, P=0.013), histology (EAC vs ESCC, P=0.012), tumor grade (poorly vs well differentiated, P < 0.001), TNM stage (Ⅳ vs Ⅰ, P < 0.001), tumor size (> 50 mm vs 0-20 mm, P < 0.001), chemotherapy (yes vs no, P < 0.001), and LNR (> 0.25 vs 0, P < 0.001) were identified as independent risk factors affecting long-term survival of the patients. The nomograms established based on the model for predicting the survival probability of the patients at 1, 3 and 5 years after operation showed a C-index of 0.726 (95% CI: 0.714-0.738) for predicting the overall survival (OS) and of 0.735 (95% CI: 0.727-0.743) for cancer-specific survival (CSS) in the training cohort. In the internal validation cohort, the C-index of the nomograms was 0.752 (95% CI: 0.738-0.76) for OS and 0.804 (95% CI: 0.790-0.817) for CSS, as compared with 0.749 (95% CI: 0.736-0.767) and 0.788 (95%CI: 0.751-0.808), respectively, in the external validation cohort. The nomograms also showed a higher sensitivity than the TNM staging system for predicting long-term prognosis.@*CONCLUSION@#This prognostic model has a high prediction efficiency and can help to identify the high-risk patients with esophageal carcinoma after surgery and serve as a supplement for the current TNM staging system.

Cancer Associated Cells in Tumor Microenvironment of Esophageal Carcinoma： A Review / 中国实验方剂学杂志

Esophageal carcinoma is one of the malignant tumors with a high mortality rate， accounting for nearly 570，000 cancer deaths worldwide annually， and this number is increasing year by year. In recent years， despite the continuous improvement of treatment programs for esophageal carcinoma， the overall five-year survival rate of esophageal carcinoma is still less than 20% due to the development of drug resistance and the tolerance of patients during the treatment process. Tumor microenvironment （TME） is composed of various cells and related components with tumor cells as the core and featured by hypoxia， acidosis， chronic inflammation and immunosuppression， which plays an important role in the progression of tumors. Studies have found that tumor-associated fibroblasts， tumor-associated macrophages， myeloid-derived suppressor cells and regulatory T cells in TME can promote the proliferation， migration， invasion， and lymph node metastasis of cancer cells by secreting cytokines and activating pro-inflammatory pathways， and promote cancer progression by inducing the drug resistance of cancer cells and evading immunosuppression. Because cancer-associated cells in TME are genetically more stable than cancer cells， have fewer mutations and have lower chance of drug resistance， targeting cancer-associated cells in TME by regulating TME is a new research direction of cancer therapy. Traditional Chinese medicine has the advantages of multi-component and multi-target. It can participate in the regulation of TME through multiple ways， reduce the number of cancer-associated cells in TME， inhibit crosstalk between TME and cancer cells， and restore immune cell function. It is an important source for the regulation of TME and the research and development of drugs targeting cancer-associated cells in TME. In this paper， the role of cancer-associated cells in the TME of esophageal cancer and the current application of traditional Chinese medicine targeting cancer-associated cells in TME are reviewed， so as to provide reference for the research and development of TME targeted drugs for esophageal carcinoma.

Radiosensitization Effect and Mechanism of Xuefu Zhuyutang on Transplanted Esophageal Carcinoma in Nude Mice / 中国实验方剂学杂志

ObjectiveTo explore the radiosensitization and underlying mechanism of Xuefu Zhuyutang on subcutaneous transplanted esophageal carcinoma. MethodThe subcutaneous xenograft model of human esophageal carcinoma ECA-109 in nude mice was induced and the model mice were divided into a model group， an irradiation group， a Xuefu Zhuyutang group， and a combination group， with six nude mice in each group. After the intervention， the transplanted tumors were removed and weighed， and the tumor inhibition rate of each group was calculated according to the formula. The protein expression of hypoxia-inducible factor-1α （HIF-1α） and vascular endothelial growth factor A （VEGFA） was detected by immunohistochemistry （IHC）. The protein expression of mammalian target of rapamycin （mTOR）， HIF-1α， VEGFA， and vascular endothelial growth factor receptor 2 （VEGFR2） in transplanted tumors was detected by Western blot. The mRNA expression of mTOR， HIF-1α， and VEGFA in transplanted tumors was detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the conditions in the model group， the tumor weight decreased in the irradiation group and the Xuefu Zhuyutang group （P<0.05）， as well as the combination group （P<0.01）. Compared with the irradiation group， the combination group showed decreased tumor weight （P<0.05）， with tumor inhibition rate of 57.37%. Compared with the model group， the irradiation group， the Xuefu Zhuyutang group， and the combination group showed decreased protein expression of VEGFR2， p-mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01） and reduced mRNA expression of mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01）. Compared with the irradiation group， the combination group showed down-regulated protein expression of VEGFR2， p-mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01） and reduced mRNA expression of mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01）. ConclusionXuefu Zhuyutang can inhibit the growth of transplanted esophageal carcinoma ECA-109 in nude mice and shows an obvious radiosensitization effect in combination with radiotherapy. The mechanism may be related to the inhibition of the mTOR/HIF-1α/VEGFA signaling pathway to improve the hypoxic state of tumors.

Polysaccharide of Atractylodis Macrocephalae Rhizoma inhibits expression of immune checkpoint PD-L1 by targeting miR-34a in esophageal carcinoma cells / 中国中药杂志

The immune checkpoint programmed cell death-ligand 1(PD-L1)-mediated immunosuppression is among the important features of tumor. PD-L1, an immunosuppressant, can induce T cell failure by binding to programmed cell death-1(PD-1). Thus, the key to restoring the function of T cells is inhibiting the expression of PD-L1. The Chinese medicinal Atractylodis Macrocephalae Rhizoma(AMR) has the anti-tumor, anti-inflammatory, antioxidant, and hypoglycemic activities, and the polysaccharide in AMR(PAMR) plays a crucial role in immunoregulation, but the influence on the immune checkpoints which are closely related to immunosuppression has not been reported. MicroRNA-34 a(miR-34 a) expression in esophageal carcinoma tissue is significantly lower than that in normal tissue. This study aims to investigate the inhibitory effect of PAMR on esophageal carcinoma cells, and the relationship between its inhibitory effect on PD-L1 expression and miR-34 a, which is expected to clarify the anti-tumor mechanism of PAMR. Firstly, different human esophageal carcinoma cell lines(EC9706, EC-1, TE-1, EC109 cells) were screend out, and expression of PD-L1 was determined. Then, EC109 cells, with high expression of PD-L1, were selected for further experiment. The result showed that PAMR suppressed EC109 cell growth. According to the real-time quantitative PCR(qPCR) and Western blot, it significantly suppressed the mRNA and protein expression of PD-L1, while promoting the expression of tumor suppressor miR-34 a. The confocal microscopy and luci-ferase assay proved that PAMR alleviated the inhibitory effect of PD-L1 while blocked miR-34 a. Additionally, the expression of PD-L1 was controlled by miR-34 a, and the combination of miR-34 a inhibitor with high-dose PAMR reversed the inhibitory effect of PAMR on PD-L1 protein expression. Thus, the PAMR may inhibit PD-L1 by increasing the expression of miR-34 a and regulating its downstream target genes. In conclusion, PAMR inhibits the expression of PD-L1 mainly by inducing miR-34 a.

Cost-utility analysis of pembrolizumab combined with chemotherapy in the first-line treatment of advanced or metastatic esophageal carcinoma / 中国药房

OBJECTIVE To evaluate the cost-utility of pembrolizumab combined with chemotherapy versus chemotherapy alone in the first-line treatment of advanced or metastatic esophageal carcinoma. METHODS Cost-utility analysis of pembrolizumab combined with chemotherapy versus chemotherapy alone for advanced or metastatic esophageal carcinoma was conducted by using a three-state partitioned survival model from the perspective of health system in China. The model use d a lifetime simulation time frame with 3 weeks as a cycle. The survival data were extrapolated using KEYNOTE- 590 data；cost data were obtained from the median of 2022 public winning bid on Yaozhi network ，among which the price of pembrolizumab was obtained after discounting by a patient assistance program ；utility data were obtained from the literatures ，and a 5％ discount rate was used for both cost and utility. One-way sensitivity analysis and probabilistic sensitivity analysis were also conducted to examine model robustness. RESULTS Analysis of the base case results showed that compared to chemotherapy alone ，the incremental cost-effectiveness ratio （ICER）of pembrolizumab combined with chemotherapy regimens were 950 528.42 yuan/QALY，107 845.39 yuan/QALY and 315 754.56 yuan/QALY for esophageal squamous cell carcinoma （ESCC），programmed deathligand- 1 combined positive score （PD-L1 CPS）≥10 and intention-to-treat population （ITT），respectively. The results of sensitivity analysis verified the robustness of the basic analysis results. CONCLUSIONS Under our healthcare system ，using a threshold of willingness-to-pay of 1-3 times our GDP per capita in 2021，pembrolizumab combined with chemotherapy regimen isn ’t cost-utility compared with chemotherapy alone in the ESCC and ITT subgroups of patients ，while it is cost-utility in the PD-L 1 CPS≥10 subgroup of patients.

Human esophageal fibroblast-derived exosomal miR-21 reduced the cisplatin sensitivity to esophageal carcinoma EC9706 cells

The objective of this study was to investigate the effect of human esophageal fibroblast-derived exosomal miR-21 on cisplatin sensitivity against esophageal squamous EC9706 cells. EC9706 cells were co-cultured indirectly with human esophageal fibroblasts (HEF) or miR-21 mimics transfected-HEF in the transwell system. The exosomes in HEF-culture conditioned medium were extracted by differential ultracentrifugation. EC9706 cells were co-cultured with HEF-derived exosomes directly. The cisplatin sensitivity against EC9706 cells was revealed via half maximal inhibitory concentration (IC50) values using MTT assay. The expressions of miR-21, programmed cell death 4 (PDCD4) mRNA, and gene of phosphate and tension homology deleted on chromosome ten (PTEN) mRNA were determined by qRT-PCR. The changes of the protein level were detected using western blot assay. IC50 values of cisplatin against EC9706 cells were increased after EC9706 cells were co-cultured with either HEF or exosomes derived from miR-21 mimics-transfected HEF. Following the increased level of miR-21, the mRNA expression and protein levels of PTEN and PDCD4 were decreased in EC9706 cells. The cisplatin sensitivity to EC9706 cells was reduced by HEF-derived exosomal miR-21 through targeting PTEN and PDCD4. This study suggested that non-tumor cells in the tumor micro-environment increased the tumor anti-chemotherapy effects through their exosomes.

Analysis of Effective Terpenoids in Xinjiang Pleurotus ferulae Against Esophageal Carcinoma by UPLC-Q/TOF-MS Technique / 中国实验方剂学杂志

Objective:To discover the effective terpenoids in Xinjiang <italic>Pleurotus ferulae</italic> with the activity of anti-esophageal carcinoma. Method:By screening the activity of human esophageal cancer Eca109 cells， the ethyl acetate extract phase of <italic>P. ferulae </italic>ethanol extract （PFEP-E） was separated and purified by silica gel chromatography and preparative thin layer chromatography. Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q/TOF-MS） combined with online network databases such as Metlin， MassBank， PubChem and related literature were used to identify the effective elution sites and analyze their contents. Result:The elution fraction （Fr_2-3∶1） of petroleum ether-ethyl acetate （3∶1） on the silica gel column had the strongest inhibitory activity on the proliferation of human esophageal cancer Eca109 cells. The component analysis showed that 24 effective terpenoids were identified under positive ion mode， and 28 effective terpenoids were identified under negative ion mode， a total of 52 terpenoids were identified， which were isolated from this edible fungus for the first time. Content of total terpenoids in Fr_2-3∶1 were 62.88 mg·g^-1， including 2 monoterpenoids， 5 sesquiterpenoids， 15 diterpenoids and 30 triterpenoids， accounting for 1.32%， 12.04%， 47.55%， 39.09% of the total terpenoids， respectively. Diterpenoids and triterpenoids were the main components of the effective terpenoids in <italic>P. ferulae</italic>， accounting for 86.64% of the total terpenoids. Gibberellins were the main diterpenoids， accounting for 79.70% of the total diterpenoids， triterpenoids were mainly ganoderic acids， accounting for 29.25% of the total triterpenoids. The results of methyl thiazolyl tetrazolium （MTT） test showed that gibberellin A₃ and gibberellin A₅ had weak anti-esophageal cancer activity， while gypsogenin and oleanolic acid had strong anti-esophageal cancer activity. Conclusion:The effective terpenoids of <italic>P. ferulae</italic> against esophageal cancer are triterpenoids mainly composed of ganoderic acids， which can provide theoretical basis for the development of terpenoids of <italic>P. ferulae</italic> as anti-tumor drugs and the development of functional foods， and help to effectively improve the additional output value of <italic>P. ferulae</italic>.

Effect of phantoms with different cavity thickness on dose verificationupper esophageal cancer / 中国辐射卫生

Objective To investigate the dose calculation accuracy of two algorithms in Monaco TPS for self-made phantoms with different cavity thickness, and analyze the influence of phantoms with different cavity thickness on dose verification of upper esophageal cancer. Methods The phantoms with different cavity thickness were placed on the simulated CT positioning machine to scan and acquire images. In Monaco TPS, the irradiation fields with energy of 6 MV, 100 MU and different square field sizes were added to the acquired images. The dose of the cavity of the ionization chamber was calculated by two algorithms, and measured on the accelerator by dosimeter under the same conditions. At the same time, 20 patients with upper esophageal cancer who received dynamic intensity modulation in fixed field were randomly selected and included in the study, and two algorithms were used for dose verification on phantoms with different cavity thickness. The results were statistically analyzed by SPSS 22.0 software. Results The maximum deviations between the calculated values and the measured values were 0.66% and −1.8%, in the calculation of phantoms with different cavity thickness by algorithms of Monte Carlo and Pencil Beam. In Monte Carlo algorithm, the result of RD pair t test is P > 0.05. Paired t test of AD (0 mm, 10 mm), (5 mm, 10 mm) and (10 mm, 20 mm) groups showed no significant difference (P < 0.05). The maximum deviation was 1.1%, and the rest groups were not statisticely significant (P > 0.05); In Pencil Beam algorithm the t test results of RD (0 mm, 20 mm) and (5 mm, 20 mm) pairs were (P < 0.05), the maximum deviation was 0.58%, and the rest groups were (P > 0.05). In AD group, (P < 0.05), the maximum deviation was 2.78%; The paired t test between the two algorithms was (P < 0.05), and the maximum deviations in RD and AD groups were 2.49% and 4.14%, respectively. Conclusion Monte Carlo algorithm has accurate calculation and high gamma pass rate of dose verification, and there is no clinical difference in gamma pass rate of dose verification among phantoms with different cavity thickness, pencil Beam algorithm is not recommended in cavity phantom calculation.

The modified minimally invasive esophagectomy using the concept of "single-direction" thoracoscopic technique / 中国胸心血管外科临床杂志

@#Objective    To explore the safety and feasibility of the modified and improved thoracoscopic surgery for esophageal cancer using the concept of "single-direction" thoracoscopic technique. Methods    The clinical data of 65 patients undergoing this modified minimally invasive esophagectomy based on "single-direction" thoracoscopic system between June 2018 and April 2019 were retrospectively analyzed, including 54 males and 11 females aged 62.5±7.8 years. Results    The thoracoscopic operation time was 133.4±28.6 min, and intraoperative blood loss was 61.9±29.2 mL. No intraoperative blood transfusion was needed. One patient was transferred to open thoracotomy (due to severe pleural adhesion atresia). Major complications included anastomotic leak, pneumonia, chylothorax, incisional infection, recurrent laryngeal nerve paralysis and gastric emptying disorders, which were recovered by conservative treatment. No postoperative death occurred. The median number of lymph nodes and lymph node station harvested was 19 and 10, respectively. The median postoperative hospital stay was 10 days. The volume of chest drainage was 1 117.3±543.4 mL. Conclusion    The minimally invasive operation mode of esophageal cancer based on "single-direction" thoracoscopic system is safe and feasible, and has good field vision and smooth and simplified procedure.

Effect of thoraco-laparoscopic esophagectomy on postoperative immune function of patients with esophageal carcinoma / 南方医科大学学报

OBJECTIVE@#To investigate the effect of thoraco-laparoscopic esophagectomy on postoperative immune function of patients with esophageal carcinoma.@*METHODS@#Eighty-one patients undergoing radical esophagectomy in our hospital between January, 2017 and December, 2019 were enrolled in this study.According to the surgical approach, the patients were divided into endoscopic group (41 cases) and open surgery (3 incisions) group (40 cases).The immunological indicators (CD3@*RESULTS@#No death occurred in either of the group after the operation.On days 4 and 7 after the operation, CD3@*CONCLUSIONS@#Thoraco-laparoscopic resection of esophageal cancer can reduce postoperative secretion of proinflammatory factors, alleviate inflammatory responses, and promote the recovery of immune functions to accelerate postoperative recovery of the patients.

Prediction of radiotherapy effect by diffusion-weighted imaging in esophageal carcinoma xenograft model

Aim: This study was to evaluate the value of diffusion-weighted imaging (DWI) in predicting the efficacy of radiotherapy for esophageal cancer from xenograft model level. Subjects and Methods: Thirty-two tumor-bearing mice from the Eca-109 cell line nude mice models were established. The experimental group (n = 16) received a single dose of 15 Gy (6MV X-ray), whereas the control group (n = 16) did not receive any treatment. The tumor volume and apparent diffusion coefficient (ADC) were obtained. The cell density, tissue necrosis ratio, and CD31 expression were determined at matched time points. Results: The tumor volume was smaller in the experimental group than in the control group (P < 0.05) on the 7th day after radiotherapy (1.580 ± 0.965 cm3 vs. 2.671 ± 0.915 cm3). The ADC values were higher in the experimental group than in the control group on the 3rd day (P < 0.05) (998.15 ± 163.76 ×10− 6 mm2/s vs. 833.32 ± 142.15 ×10− 6 mm2/s). On the 3rd day after radiotherapy, the differences in cell density and necrosis ratio between the two groups were statistically significant; the tumor cell density was lower in the experimental group (25.56 ± 1.40%) than in the control group (33.48 ± 4.18%) (P < 0.05), and the proportion of tissue necrosis was higher in the experimental group (32.19 ± 1.21%) than in the control group (29.16 ± 2.16%) (P < 0.05). The negative and weak positive rate of CD31 expression in the experimental group was higher than the control group, whereas the generally positive and strong positive rate of CD31 expression was significantly lower than the control group in the early stage (P < 0.05). Conclusion: ADC values may change at the early stage before the morphological changes of tumors. Changes in cell density and necrosis ratio of transplanted tumors correspond to the changes in ADC values. DWI can be used for the early prediction of esophageal cancer radiotherapy efficacy

The relationship between the dose-volume indexes and acute toxicity of intrathoracic stomach in esophageal cancer patients receiving radiotherapy after esophagectomy / 中华放射医学与防护杂志

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.

Dosimetric comparison among volumetric modulate arc therapy plans with different fluence smoothing in the treatment of patients with middle and upper thoracic esophageal carcinoma / 中华放射医学与防护杂志

Objective To compare the dosimetric differences of volumetric modulated arc therapy (VMAT) plans optimized with 3 different fluence smoothing parameters using Monaco treatment planning system.Methods A total of 15 patients with middle and upper esophageal carcinoma were planned with Low fluence smoothing (Low),Medium fluence smoothing (Medium) and High fluence smoothing (High) during VMAT optimization.The dosimetric differences in D95,D conformity index (CI),homogeneity index (HI) of targets,dose volume histogram (DVH) of organs at risk (OARs),and monitor unit (MU) were compared.Results There were no significant differences in D95,D CI and HI of targets,as well as in V40 and D of the heart,V10,V20 and D of the lung,and segment number among plans optimized with different fluence smoothing techniques (P＞0.05).Plans with high fluence smoothing achieved less V30 of heart,Dmax of cord PRV (t=-2.167,-0.999,P＜0.05),lower MU (t=-3.148,-6.692,P＜O.05),but increased V5 of both lungs (t=1.306,-2.027,P＜O.05)compared with plans with Medium and Low fluence smoothing.Plans with low fluence smoothing irradiated higher dose to the V30 and D to heart (t=O.411,0.589,0.013,P＜0.05),but less V5 of the lungs (t=O.423,P＜0.05) compared with plans with medium fluence smoothing.Conclusions All VMAT plans with 3 different fluence smoothing can meet the clinical requirements.VMAT plans optimized with high fluence smoothing are recommended in the treatment of patients middle and upper thoracic esophageal carcinoma.

Effects of Bufalin on Human Esophageal Cancer Cells Proliferation and Mechanism Study / 中国药学杂志

OBJECTIVE: To investigate the effect of bufalin on the proliferation of esophageal cancer and its possible molecular mechanism. METHODS: The effects of bufalin on the activity of esophageal cancer cell line KYSE-70 were determined by MTT assay and LDH assay kit. Colony-forming and EdU (5-ethynyl-2-deoxyuridine) assay were performed to detect the inhibitory effect of bufalin on the proliferation of KYSE-70 cells. DAPI staining, TUNEL and flow cytometry were used to assess the effects of bufalin on the apoptosis of KYSE-70 cells. Quantitative real-time PCR (qPCR) and Western blotting were used to determine the relevant expression changes in mRNA and protein of apoptosis-related factors Bcl-2, Bax, NF-κBp65, NF-κBpp65. The mitochondrial function changes of KYSE-70 cells were studied by using JC-1 fluorescent probe kit and ATP detection kit after bufalin treatment. Finally, the effect of bufalin on esophageal cancer proliferation in vivo was studied by xenograft model in nude mice. RESULTS: The results of MTT and LDH assay shown that bufalin inhibited the activity of KYSE-70 cells. Colony-forming and EdU assay showed that bufalin significantly suppressed KYSE-70 cells proliferation. DAPI staining showed that chromatin heterogeneity, nuclear concentration and fragmentation were observed after bufalin treatment. It was found that bufalin treatment significantly promoted KYSE-70 cells apoptosis by TUNEL staining and flow cytometry assay of qPCR and Western blot showed that Bcl-2 expression was down-regulated, Bax expression was up-regulated and Bax/ Bcl-2 expression ratio was increased after bufalin treatment. The mitochondrial membrane potential and the ATP production of KYSE-70 cells were significant reduced after bufalin treatment. In vivo, the growth of xenograft tumors was significantly inhibited in bufalin group. CONCLUSION: Bufalin markedly inhibits KYSE-70 cells proliferation by promoting apoptosis, and the possible mechanism of apoptosis may be related to mitochondrial pathway. Our results indicate that bufalin may be a potential therapeutic agent for esophageal cancer.

Treatment for resectable cervical esophageal carcinoma: A surgical perspective / 中国胸心血管外科临床杂志

@#Definitive chemoradiotherapy (dCRT) is the general recommendation for the treatment of cervical esophageal cancer for organ preservation. However, the long-term survival of dCRT is not satisfactory. Surgical resection alone is not superior to dCRT in the treatment of cervical esophageal cancer. Surgical resection is often combined with laryngectomy, which will affect the quality of life. Recent evidence suggests that neoadjuvant therapy combined with surgery improves the long-term survival of cervical esophageal cancer. On the other hand, the development of technologies such as laryngeal preservation surgery and minimally invasive esophagectomy has reduced the risk of operation and improved the quality of life. This article will review the new progress in the comprehensive treatment of cervical esophageal cancer from the perspective of surgery.