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08 March 2019, Volume 46 Issue 3 Previous Issue    Next Issue

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Curative effect analysis of different clinical characteristics and treatment modalities for primary esophageal small cell carcinoma Li Zhe，Xing Yanke，Li Baosheng 2019, 46 (3):  129-134.  doi: 10.3760/cma.j.issn.1673-422X.2019.03.001 Abstract ( 550 )   PDF (1377KB) ( 572 )   Save ObjectiveTo analyze the efficacy of different clinical characteristics and treatment modalities for patients with primary esophageal small cell carcinoma (PESC), and to find out the prognostic factors, and provide reference for clinical treatment decision. MethodsPatients with PESC who were treated at Shandong Cancer Hospital Affiliated to Shandong University from January 2008 to May 2017 were retrospectively enrolled. The clinical features were collected. Their disease progression time and survival status were determined by followup, and the followup ended  in October 2017. Data analysis was performed using SPSS 25.0 software, and GraphPad Prism 7.0 was used for mapping. Survival analysis was performed by KaplanMeier method, and logrank test was used to compare the differences in survival curves of each group. Factors with significant differences in univariate analysis were included in the Cox multivariate survival analysis. ROC curve was used to verify the sensitivity and specificity of the model. ResultsA total of 83 PESC patients with a complete followup were included in the study, including 68 males and 15 females. The average age was 61.93 years old (4182 years old). The median progressionfree survival (PFS) was 9.1 months (1.060.0 months) and the median overall survival (OS) was 26.1 months (1.860.0 months). Cox multivariate survival analysis showed radiotherapy or not (HR=0.321, 95%CI: 0.1840.559, P＜0.001) and chemotherapy cycles (HR=0.841, 95%CI: 0.7370.960，P=0.010) were independent prognostic factors for PFS. The Veterans Administration Lung Study Group (VALSG) staging (HR=3.050, 95%CI: 1.6065.794, P=0.001), radiotherapy or not (HR=0.312, 95%CI: 0.1740.560, P＜0.001), and chemotherapy cycle (HR=0.711, 95%CI: 0.6010.842, P＜0.001) were independent predictors of OS. The ROC curve showed that the sensitivity and specificity of the PFS prediction model were 78.26% and 73.33%, and the sensitivity and the specificity of the OS prediction model were 80.00% and 58.49%. ConclusionVALSG staging is an independent predictor of PESC survival. Comprehensive therapy based on radiotherapy and chemotherapy can improve disease control, reduce metastasis, and improve survival. References | Related Articles | Metrics

Treatment and prognosis of limitedstage small cell cancer of the esophagus Chen Junsheng, Jiao Yan, Han Dali, Yang Wenfeng 2019, 46 (3):  135-140.  doi: 10.3760/cma.j.issn.1673-422X.2019.03.002 Abstract ( 826 )   PDF (829KB) ( 710 )   Save ObjectiveTo investigate the treatment options  and prognostic factors of limitedstage small cell cancer of the esophagus. MethodsA retrospective analysis of 58 limitedstage cases admitted to Shandong Cancer Hospital Affiliated to Shandong University from June 2009 to July 2017 was performed. KaplanMeier and logrank methods were used for survival analysis. Cox regression model was used for prognostic factors analysis. ResultsThe median overall survival (OS) of the whole group was 21.3 months (5.397.2 months). The 6month, 1year, 2year, 3year and 5year survival rates were 93%, 84%, 44%, 28% and 11% respectively. Univariate analysis suggested that treatment and stage affected patient survival. The median OS of the chemotherapy, chemotherapy + radiotherapy, surgery + chemotherapy and surgery + chemotherapy + radiotherapy groups were 14.5, 18.0, 23.8 and 46.5 months respectively, with a significant difference(χ2=11.148, P=0.011). The combination therapy was better than chemotherapy alone (all P<0.05), but there was no significant difference between the different combinations of treatments (all P＞0.05). The median OS of the stage Ⅱ, Ⅲ, Ⅳ patients were 27.0, 17.8 and 9.9 months respectively, with a significant difference (χ2=48.114, P<0.001). The prognosis of patients with stage Ⅱ and Ⅲ was better than that of patients with stage Ⅳ (both P<0.001), but there was no significant difference in OS between stage Ⅱ and stage Ⅲ patients (P＞0.05). Multivariate analysis found that treatment (HR=0.567, 95%CI: 0.3870.830, P=0.004) and stage (HR=3.009, 95%CI: 1.8114.999, P<0.001) were independent prognostic factors for OS. The stratified analysis found no significant difference in the prognosis between the surgical and nonsurgical patients (median OS: 28.6 and 16.9 months; χ2=3.938, P=0.052). Preoperative neoadjuvant therapy did not improve the prognosis of the patients (17.8 months vs. 43.4 months; χ2=0.571, P=0.450). The analysis showed that there was no statistical difference in OS between patients with Ki67 index ≤ 80% and > 80% (median OS: 16.9 and 24.5 months; χ2=3.341, P=0.068). ConclusionThe treatment and stage are independent prognostic factors for patients with limitedstage small cell cancer of the esophagus. The effect of chemotherapy alone is poor for patients with limitedstage small cell cancer of the esophagus. Multimodality therapy can benefit patients. References | Related Articles | Metrics

Study of texture analysis based on CT images to predict radiochemotherapy sensitivity in patients with esophageal squamous cell carcinoma Yi Minghui, Li Zhenjiang, Cao Qiang, Li Baosheng 2019, 46 (3):  141-146.  doi: 10.3760/cma.j.issn.1673-422X.2019.03.003 Abstract ( 757 )   PDF (892KB) ( 504 )   Save ObjectiveTo investigate the relationship between texture features based on CT and radiochemotherapy sensitivity in patients with esophageal squamous cell carcinoma (ESCC). MethodsA total of 92 ESCC patients treated at Shandong Cancer Hospital Affiliated to Shandong University between January 2014 and December 2017 were retrospectively collected. All patients were divided into responders (complete response + partial response) and nonresponders (stable disease + progression disease) according to therapeutic sensitivity. The texture features were extracted from CT images for positioning. And the patients were divided into training set (46 patients) and test set (46 patients) using traintestsplit, training set for establishing predictive model and test set for model validation. ResultsThere were 31 responders and 15 nonresponders in the training set, and the portion of responders was 67.4%. Univariate analyses showed that the histogram matrix (HISTO)sknewess was significantly different between the two groups (Z=2.097, P=0.036) and the area under the curve (AUC) was 0.692 with 95%CI of 0.5390.820. Sknewess ≤-2.58 intended to be responders. Binary logistic regression of sknewess (Z=2.097, P=0.036) in HISTO, high gray level zone emphasis (HGZE) (Z=1.722, P=0.085) and small zone high gray level emphasis (SZHGE) (Z=1.640, P=0.101) in gray level zonelength matrix (GLZLM) showed that sknewess was the independent influence factor of sensitivity (OR=0.558, 95%CI: 0.3380.923, P=0.023), and the AUC of logistic regression model was 0.718 with 95%CI of 0.5500.886, which indicted that the model had the ability to predict treatment response of ESCC patients. The model was validated by using test set and the AUC was 0.706, and the sensitivity of the model was 70.6% while the specificity was 69.0%. It showed that the model had certain ability in predicting treatment response. ConclusionCT texture analysis can predict the radiochemotherapy sensitivity in patients with ESCC to some extent. References | Related Articles | Metrics

Shortterm clinical efficacy and analysis of quality of life of anlotinib in thirdline and above treatment for advanced nonsmall cell lung cancer Liu Nan, Wu Xiuwei, Li Fanfan, Wang Nianfei, Zhang Mingjun, Sun Tong, Chen Zhendong 2019, 46 (3):  147-152.  doi: 10.3760/cma.j.issn.1673-422X.2019.03.004 Abstract ( 682 )   PDF (645KB) ( 1243 )   Save ObjectiveTo evaluate the shortterm efficacy, safety and impact on the quality of life of anlotinib in thirdline and above treatment for advanced nonsmall cell lung cancer (NSCLC) patients. MethodsAll the patients received alotinib 12 mg/d. One cycle was defined as 2 weeks ontreatment followed by 1 week offtreatment until disease progression or treatment intolerance. Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was used to assess tumor responses. Common Terminology Criteria for Adverse Events (CTCAE) 4.02 was used to assess the adverse events. The European Organization for Research on Treatment of Cancer (EORTC) QLQC30 and QLQLC13 were used to assess quality of life. ResultsAmong 27 patients in study, no complete response (CR) was found, 2 patients (7.4%) achieved partial response (PR), 16 patients (59.3%) achieved stable disease (SD), 9 patients (33.3%) achieved progressive disease (PD), objective response rate (ORR) was 7.4%, and disease control rate (DCR) was 66.7%. The scores of physical functioning (76.00±10.55 vs. 64.44±11.59), emotional functioning (81.67±8.71 vs. 76.11±6.71) and global health status (48.87±7.97 vs. 40.56±12.49) of the QLQC30 scale after treatment were higher than those before treatment, with statistically significant differences (t=-4.516, P<0.001; t=-2.646, P=0.019; t=-3.872, P=0.002). Fatigue (50.37±8.95 vs. 40.74±13.86), nausea and vomiting (26.54±16.18 vs. 14.20±11.97), loss of appetite ［M(QR): 33.33(33.33) vs. 33(33.33)］  were better than before (t=-2.476, P=0.027; t=-5.036, P＜0.001; Z=-2.923, P=0.003); pain (28.88±14.23 vs. 33.33±13.60) and dyspnea ［33.33(33.33) vs. 33.33(66.67)］ scores were lower than before (t=3.674, P=0.003; Z=-3.266, P=0.001). The scores of cough (24.44±19.12 vs. 45.24±20.34), shortness of breath ［11.11(22.22) vs. 33.33(22.22)］ and chest pain ［0.00(33.33) vs. 33.33(33.33)］ in the QLQLC13 scale after treatment were lower than those before treatment, with statistically significant differences (t=4.000, P=0.001; Z=-4.125, P＜0.001; Z=-1.890, P=0.034); the scores of sore mouth or tongue ［0.00(33.33) vs. 0.00(0.00)］ and hands and feet tingling ［33.33(33.33) vs. 0.00(0.00)］ were higher than before (Z=-2.000, P=0.046; Z=-2.264, P=0.024). Common adverse reactions included hypertension, fatigue, elevated thyroid stimulating hormone, proteinuria, handfoot syndrome, oral mucositis, hemoptysis, etc, mainly grade 12, and they were all improved after the treatments. ConclusionAnlotinib as a thirdline and further therapy is positive effected and well tolerated. It can alleviate the clinical symptoms and significantly improve the quality of life of NSCLC  patients. References | Related Articles | Metrics

Expression and clinical significance of cullin 4A in cholangiocarcinoma Xue Dong, Xia Xiuliang, Song Dekun, Xiang Tinghai, Wang Jianqiang, Gong Bengang 2019, 46 (3):  153-156.  doi: 10.3760/cma.j.issn.1673-422X.2019.03.005 Abstract ( 515 )   PDF (943KB) ( 516 )   Save ObjectiveTo explore the expression of cullin 4A (CUL4A) in cholangiocarcinoma tissues and its clinical significance. MethodsPrimary fresh cholangiocarcinoma tissues (n=35) and normal bile duct tissues (n=15) from patients who underwent curative surgery in Binzhou People′s Hospital of Shandong Province from February 2011 to December 2013 were collected. The expressions of CUL4A mRNA were detected by quantitative realtime PCR (qRTPCR). Then, cholangiocarcinoma tissues (n=72) and normal bile duct tissues (n=36) from patients who underwent curative surgery in Binzhou People′s Hospital of Shandong Province from January 2008 to January 2014 were collected. The expressions of CUL4A protein were tested by immunohistochemistry. The relationships between the expression of CUL4A and the patients′ clinicopathologic features and prognosis were analyzed. ResultsThe expression of CUL4A mRNA in cholangiocarcinoma tissues was obviously higher than that in normal bile duct tissues (3.876±0.975 vs. 1.216±0.265), and the difference was statistically significant (t=12.23, P＜0.001). The positive rates  of CUL4A protein in cholangiocarcinoma and  normal bile duct tissues were 70.8% (51/72) and 2.8% (1/36) respectively, and the difference was statistically significant (χ2=44.524, P＜0.001). The expression of CUL4A protein in cholangiocarcinoma was related to the differentiated degree (χ2=4.341, P=0.037), neural invasion (χ2=8.326, P=0.004), TNM stage (χ2=7.745, P=0.005), lymph node metastasis (χ2=3.869, P=0.049) and vascular invasion (χ2=5.555, P=0.018). Survival analysis results showed that the median survival time of CUL4A positive patients was significantly shorter than that of CUL4A negative patients (32.40 months vs. 51.30 months), and the difference was statistically significant (χ2=6.561, P=0.011). ConclusionThe expression of CUL4A in cholangiocarcinoma tissues is higher than that in normal bile tissues. CUL4A plays an important role in the process of tumor invasion and metastasis and indicates poor prognosis, which may become a potential target for the diagnosis and therapy of the cholangiocarcinoma. Related Articles | Metrics

Overexpression of miR-613 enhanced radiosensitivity of colorectal cancer cells via targeting downregulation of Wee1 Zhao Weishan, Zhu Yankun, Wang Ruotian, Guan Aoran, Li Ruhong 2019, 46 (3):  157-165.  doi: 10.3760/cma.j.issn.1673-422X.2019.03.006 Abstract ( 506 )   PDF (4864KB) ( 547 )   Save ObjectiveTo explore the effect of  microRNA613 (miR613)/Wee1 axis on the radiosensitivity  of colorectal cancer cells. MethodsA total of  20 patients with radiosensitive colorectal cancer and 20 patients with radioresistance were selected from Yan′an Hospital Affiliated to Kunming Medical University from November 2016 to May 2017. Human colorectal cancer cell lines LoVo and HCT116 were selected and the radioresistant cell lines LoVo/R and HCT116/R were established  for subsequent experiments. Realtime fluorescence quantitative PCR (qRTPCR) was used to detect the expression of miR613 and Wee1 in colorectal cancer tissues and cell lines. The radioresistant cells were transfected by miR613 mimic, and nontransfected cells were used as control group. The effects of miR613 overexpression on the proliferation, invasion and cell cycle of radiation resistance of colorectal cancer cells  at different radiation doses were evaluated by CCK8 assay, Transwell assay and Western blotting, respectively. Furthermore, dualluciferase reporter gene assay was used to verify whether Wee1 was a target gene of miR613. siWee1 was transfected into radioresistant cells of colorectal cancer, or cotransfected with siWee1 and miR613 inhibitor, and nontransfected cells were used as control group. The effects of miR613/Wee1 axis on cell proliferation, invasion and cell cycle were detected by CCK8, Transwell and Western blotting at different radiation doses. ResultsThe expression of miR613 was downregulated in the radiation resistance group of patients (1.54±0.25 vs. 2.64±0.45; t=3.140，P=0.009) and radiation  resistance cell lines (LoVo/R vs. LoVo: 1.03±0.12 vs. 3.05±0.15; t=8.944, P=0.006; HCT116/R vs. HCT116: 1.01±0.11 vs. 2.85±0.16; t=8.050, P=0.008). Overexpression of miR613 was significantly inhibited the proliferation (LoVo/R: t6 Gy=6.018, P=0.013; HCT116/R: t6 Gy=5.634, P=0.015) and invasion (LoVo/R: 45.00±8.95 vs. 180.15±6.95, t6 Gy=11.93, P=0.003; HCT116/R: 49.97±6.21 vs. 170.20±7.03, t6 Gy=12.82, P=0.006) of LoVo/R and HCT116/R cells and decreased the expression levels of G2M phase cell cycle correlated proteins (CDK1 and cyclin B). Moreover, dualluciferase reporter gene assay confirmed that Wee1 was a target of miR613. Mechanistically, overexpression of miR613 promoted the radiosensitivity  of LoVo/R and HCT116/R cells through inhibiting cell proliferation (compared with siWee1 group, cotransfected with siWee1 and miR613 inhibitor, and control group, LoVo/R: F8 Gy=40.742, P=0.007; HCT116/R: F8 Gy=28.958, P=0.011),  invasion (LoVo/R: F8 Gy=55.413, P=0.004; HCT116/R: F8 Gy=65.634, P=0.003) and arresting cell at G2M phase via downregulating Wee1. ConclusionmiR613/Wee1 axis plays a certain role in regulating the radiation resistance of colorectal cancer cells, overexpression of miR613 may reverse the radiation resistance of colorectal cancer cells. References | Related Articles | Metrics

Roles of AGGF1 in tumor and its regulatory mechanisms Shen Xiabo, Li Yan, Wang Wei 2019, 46 (3):  166-169.  doi: 10.3760/cma.j.issn.1673-422X.2019.03.007 Abstract ( 961 )   PDF (630KB) ( 644 )   Save Angiogenic factor with G and FHA domain 1 (AGGF1) is an identified angiogenic factor in recent years, which is highly expressed in vascular endothelial cells and exhibits the same function as vascular endothelial growth factor, and can promote angiogenesis. Recently, it has been found that AGGF1 is highly expressed in various tumors such as liver cancer, leukemia, glioma and gastric cancer. Based on its participation in the regulation of tumor angiogenesis, DNA repair and autophagy, tumors with high expression of AGGF1 are prone to drug resistance and metastasis, and the survival and prognosis of patients are worse. Deep understanding of the roles of AGGF1 in tumor angiogenesis and its specific molecular mechanisms will provide new strategies for antitumor angiogenesis therapy in the future. References | Related Articles | Metrics

Regulating effect of lncRNA on aerobic glycolysis in tumor cells Zhong Chenyi, Mao Yundong 2019, 46 (3):  170-173.  doi: 10.3760/cma.j.issn.1673-422X.2019.03.008 Abstract ( 425 )   PDF (631KB) ( 625 )   Save Long noncoding RNA (lncRNA) is a kind of RNA with a length greater than 200 nucleotides and lacks proteincoding function. Varieties of lncRNAs have been found to play major roles in the aerobic glycolysis of tumor cells, such as lncRNAp21, H19, prostate specific transcript 1 (PGCEM1) and so on. In tumor cells, lncRNA can directly regulate the ratelimiting enzyme in the glycolytic pathway, also can indirectly regulate the glycolysis by hypoxia inducible factor1α (HIF1α) or protooncogene cmyc. Further study on the mechanism of lncRNA regulating tumor cell glycolysis is expected to open up new ideas for the diagnosis and treatment of tumor diseases. References | Related Articles | Metrics

M2 macrophage marker CD206 and tumor Li Yue, Gao Lei, Li Hongchang, Yu Hongjie, Zhang Yong 2019, 46 (3):  174-177.  doi: 10.3760/cma.j.issn.1673-422X.2019.03.009 Abstract ( 13929 )   PDF (631KB) ( 4746 )   Save Tumorassociated macrophages exist in all stages of tumor progression, and stimulate angiogenesis and invasion of tissues. M2 macrophages are predominant. CD206 is a M2 macrophage marker with high specificity and plays an important role in tumor cell proliferation and metastasis. Studies have shown that CD206 is closely related to malignant tumors such as breast cancer, ovarian cancer, pancreatic cancer and prostate cancer. Deepening the research on CD206 has certain clinical guiding significance for expounding the formation mechanism of tumor immune microenvironment and finding more targeted drugs. References | Related Articles | Metrics

Functional mechanism of malate dehydrogenase 2 in tumors Wu Ying1, Fu Baixue, Dai Lu, Huang Jun, Teng Yibin, Li Linlin, Zhang Jingwen, Huang Yuhong 2019, 46 (3):  178-180.  doi: 10.3760/cma.j.issn.1673-422X.2019.03.010 Abstract ( 507 )   PDF (624KB) ( 469 )   Save The role of malate dehydrogenase 2 (MDH2) in tumors is doublesided, it has a cancerpromoting effect in some tumors and an inhibitory effect in other tumors. The function of MDH2 is related to energy metabolism, tumor resistance and its pseudo hypoxia. MDH2 plays an important role in the occurrence, development, invasion and metastasis of tumors. An indepth understanding of the functional mechanism of MDH2 in tumors can provide new molecular targets for tumor intervention in the clinic. References | Related Articles | Metrics

Roles of HOXC gene in tumors Li Jingzhang, Ni Bingqiang 2019, 46 (3):  181-185.  doi: 10.3760/cma.j.issn.1673-422X.2019.03.011 Abstract ( 584 )   PDF (638KB) ( 581 )   Save The protein encoded by the HOXC gene regulates multiple processes during embryonic development, including cell growth, differentiation, apoptosis, migration  and angiogenesis. The HOXC gene is also involved in the occurrence and development of various human solid tumors, such as colorectal cancer, gastric cancer, liver cancer, breast cancer, endometrial cancer, etc. In addition, the HOXC gene is closely related to the clinical stage and distant metastasis of the tumor. Thus, the HOXC gene can be used as a biological predictor of tumor metastasis and prognosis. References | Related Articles | Metrics

Research progress of benign anastomotic stricture after esophagectomy Wang Xinyu, Li Chunguang, Chen Hezhong 2019, 46 (3):  186-190.  doi: 10.3760/cma.j.issn.1673-422X.2019.03.012 Abstract ( 585 )   PDF (635KB) ( 1019 )   Save Benign anastomotic stricture is one of the most common complications after esophagectomy, which can result in the dysphagia and weight loss of patients. It can severely impair the patient′s quality of life with the progress of the stricture. What is more, refractory benign stricture is a major challenge for physicians and needs repeated treatments, which aggravates the patient′s pain and increases extra costs. Benign anastomotic stricture is associated closely with various risk factors, which can be prevented by adopting some measures. Dilation remains the firstline treatment to manage benign anastomotic stricture and it may be effective to combine with drug therapy. Endoscopic incisional therapy is a promising method as a new treatment therapy. The use of various stents fails to improve overall longterm dysphagiafree rate. In addition, stent has a possible risk of migration and hyperplastic tissue growth, which should be used by weighing the pros and cons. References | Related Articles | Metrics