| 1 Background and objective Esophageal cancer is a high mortality rate of the digestive tract tumor,which seriously threatens the physical health of human beings.According to a cancer survey released by the World Health Organization,there were 572,034 new cases of esophageal cancer and 508,585 deaths in 2018,ranking seventh and sixth in the number of new cancers and deaths in the world that year,respectively.The main pathological types of esophageal cancer are esophageal squamous cell carcinoma(ESCC)and esophageal adenocarcinoma(EAC),while small cell carcinoma is relatively rare,accounting for about esophageal tumor 0.4~2.8%.According to the fourth edition of World Health Organization(WHO)classification of tumours of the digestive system,primary esophageal small cell carcinoma(PESC)belongs to a lowdifferentiated esophageal neuroendocrine carcinoma.In recent years,the incidence rate of PESC has been increasing year by year,its malignant degree is extremely high,most of the findings have been accompanied by metastasis,the prognosis is very poor.At present,there is no large-scale prospective randomized controlled study of PESC,the prognostic factors are not clear,and its optimal treatment model has not yet been established.Because PESC and small cell carcinoma of lung are similar in histological and immunohistochemical,and the study of small cell carcinoma of lung is more than mature,clinical PESC treatment is more reference to the treatment mode of small cell carcinoma of lung,emphasizing the role of chemotherapy,the value of surgery,radiotherapy and its combined treatment model is still quite unclear.Compared with ESCC and EAC,PESC lacks specificity in clinical symptoms and imaging examination.The diagnosis depends on histopathology,and immunohistochemical antigen detection is necessary for differential diagnosis.Before treatment,gastroscopy was used to diagnose tumor tissue,but due to the small amount of tissue and the existence of mixed PESC,the misdiagnosis rate of simple pathological biopsy was high.Postoperative pathology is still the gold standard for the diagnosis of PESC.Therefore,the diagnosis of PESC patients before treatment and without surgery is not sufficient to rely on biopsy pathology alone,and other diagnostic and differential diagnosis methods still need to be explored to supplement it.At present,the detection of serum tumor markers is considered simpler and more operational than gastroscopy,which requires special equipment and specialized operation physicians.Compared with the clinical symptoms and imaging changes in tumor patients,abnormal changes of serum tumor markers occurred earlier.It is very important for the prognosis of cancer patients to detect,diagonose and treat early.Limited-stage patients surgical resection of the swelling can even achieve the effect of clinical cure,and when the patient appears clinical symptoms to visit,most of the tumor has spread,the prognosis survival period is greatly reduced.Specific tumor markers can play a role in screening,assisting in the diagnosis and differential diagnosis,reflecting treatment effect,and predicting prognosis.There are currently serum tumor markers,including neuron-specific alcohols(NSE),Alpha fetoprotein(AFP),carcinoembryonic antigen(CEA),cancerous antigen 125(CA125),carbohydrate antigen 19-9(CA19-9),carbohydrate antigen 72-4(CA72-4),Cytokeratin fragment Antigen 21-1(CYFRA21-1)is considered to be of great value in the early detection rate of malignant tumors such as small cell lung cancer,hepatocellular carcinoma and ovarian cancer.However,the study of serum tumor markers in PESC is rare.This study group collected and collated the clinical diagnosis and treatment information of 98 patients with PESC,61 patients with ESCC and 61 patients with EAC trented in the first affiliated Hospital of Zhengzhou University,aiming to analyze PESC’s prognostic factors and explore the optimal treatment mode,and explore the significance of serum tumor markers NSE,AFP,CEA,CA125,CA19-9,CA72-4 and CYFRA21-1 in the differential diagnosis of PESC2 Materials and methods In this study,the clinical data of 98 patients with PESC admitted to the first affiliated Hospital of Zhengzhou University from January 2003 to September 2017 were collected and followed up,and 61 cases were detected by serum tumor markers before treatment,according to the distribution of the clinical characteristics of the 61 PESC patients(sex,age,tumor site,AJCC staging),matching 61 cases of ESCC and EAC were detected before the treatment of serum tumor markers.The test results and basic clinical information of serum tumor markers were supplemented.All the data were analyzed with SPSS 21.0 software.The normal distribution data are described using the mean ± standard deviation,and the bias distribution data is described by the median(P25,P75).The median survival period,survival rate and survival curve of each group were calculated by using Kaplan-Meier method,and the difference between the survival curves was tested by Log-rank.Cox’s hazard regression model was used to identify prognostic factors.Chi-square test was used to compare differences between groups.Shapiro-Wilk method was used to test the normality,kruskal-wallis method was used to test the difference between groups of bias distribution quantitative data,Wilcoxon rank-sum test was used to test the difference between two groups of bias distribution quantitative data,multivariate logistic regression was used to analyze the differential diagnosis factors of PESC.ROC curve was used to determine the value of tumor markers in the differential diagnosis of PESC.The cutoff value was calculated according to the Youden index.Test Standard α=0.05(two-sided inspection).3 Results3.1 PESC Survival analysis 98 patients were included in survival analysis.The median survival time was 20.0 months.The survival rates of 1,3 and 5 years were 62.4%,21.2% and 8.8%,respectively.According to single factor analysis,the prognosis was significantly correlated with N stage,M stage,AJCC stage,VALSG stage,operation and chemotherapy(P=0.036,0.047,0.001,0.047,0.026,0.003).However,there was no statistically significant effect of sex,diagnosis age,tumor location,T staging,or radiotherapy on the survival of patients in this study(p>0.05).Multivariate analysis showed that AJCC stage(P=0.001)and chemotherapy(P=0.000)were independent prognostic factors.The later the AJCC staging,the higher the risk of death for PESC patients,HR=1.169(95%CI1.169-1.904).PESC patients treated with chemotherapy had a low risk of death and HR=0.306(95%CI0.165-0.567)compared to PESC patients who did not use chemotherapy.3.2 Therapeutic model analysis of PESCFor patients in LD(limited disease)stage,those treated with multimodality therapy(30 months)had a longer MST than those treated with a monotherapy(12 months)(P=0.002).For patients in ED(extensive disease)stage,those treated with multimodality therapy(23 months)had a longer MST than those treated with monotherapy(11 months)(P=0.029).3.3 Significance of tumor markers in differential diagnosis of PESC The NSE level was higher in the PESC group than in the EAC group and ESCC group,p=0.000,0.000.The carcinoembryonic antigen(CEA)of PESC Group and EAC group was higher than that of ESCC group,P=0.000,0.000.The carbohydrate antigen 19-9(CA 19-9)in PESC Group and EAC group was higher than that of ESCC group,P=0.001,0.004.The carbohydrate antigen 72-4(CA72-4)of EAC Group was higher than that of ESCC group,P=0.018.The cytokeratin 19 fragment antigen 21-1(CYFRA21-1)in PESC Group and EAC group was higher than that of ESCC group,p=0.008,0.004.There was no statistically significant difference between AFP and CA125 levels in three groups(both p>0.05).Multi-factor logistic regression showed that NSE and CYFRA21-1 could be used as indexes for independent identification of PESC(OR=0.694,95%CI:0.587~0.822,P=0.000)(OR=0.025,95%CI:1.055~2.193,P=0.025).Logistic regression equation is that Y=-4.836+0.365XNSE-0.419XCYFRA21-1.We define it as a differential diagnostic model.The area under the ROC curve of NSE is 0.770(95% CI:0.684-0.855).The truncation value is 12.470ng/ml,the point is 71.70% sensitive and 71.00% specific.The area under the ROC curve of the differential diagnostic model is 0.835(95% CI:0.756-0.914).The truncation value is-0.513,the point is 63.60% sensitive and 86.70% specific.4 Conclusions The prognosis of PESC patients was correlated with N stage,M stage,AJCC stage,VALSG stage,operation and chemotherapy.AJCC stage and chemotherapy were independent prognostic factors of the prognosis of PESC patients.Multimodality therapy based on chemotherapy is recommended for patients with PESC no matter in LD stage or ED stage.There were differences in the expression of NSE、CEA、CA19-9、CA72-4、CYFRA21-1 in PESC Group,EAC Group and ESCC Group(P<0.05).NSE and CYFRA21-1 are independent predictors in differential diagnosis of PESC.NSE played an important role in the differential diagnosis of PESC.And the differential diagnosis model Y=-4.836+0.365XNSE-0.419XCYFRA21-1 may provide some reference for the diagnosis of PESC. |
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