| Background and purposeNeuroendocrine neoplasms(NENs)is a kind of tumor which originates from stem cells and has neuroendocrine markers and can produce bioactive amines and / or polypeptide hormones,belonging to the category of diffuse neuroendocrine cell(APUD cell)tumors.It can occur in a variety of organs and tissues of the whole body,accounting for only 0.49% of all malignant tumors.NENs was once considered a rare disease,but over the past 30 years,the age-adjusted incidence has increased 6.4 times from 1.09 / 100,000 in 1973 to 6.98 / 100,000 in 2012.It was more common in the lung(1.49 / 100,000)and gastrointestinal pancreas(3.56 / 100,000).At the same time,with the gradual attention of doctors to the disease,the progress of endoscopy and other technologies,the diagnosis rate of NENs is increasing.Extrahepatic biliary system NENs including gallbladder NENs and extrahepatic bile duct NENs,tumor types are similar to digestive tract NENs,in which gallbladder NENs is the most common.Among the pathological types,neuroendocrine carcinomas(NECs)had a high incidence,accounting for 4% of the malignant tumors in this area.At the time of diagnosis of extrahepatic biliary system NECs,40% ~50% of the patients had tumor spread and the prognosis was poor.At present,the diagnosis and treatment of extrahepatic biliary system NECs is still under exploration,compared with gastrointestinal and pancreatic NENs,most of the published literature at home and abroad are case reports,and there are few reports on the survival and prognosis analysis of extrahepatic biliary system NECs.A standardized diagnosis and treatment scheme has not yet been formed.In this study,the Chinese and English literatures about NECs of extrahepatic biliary system reported since 1988 were searched,and the data of complete cases were selected.In order to explore the standardized diagnosis and treatment of extrahepatic biliary system NECs,the clinical features and prognostic factors of 20 patients with primary extrahepatic biliary system NECs diagnosed and treated by the first affiliated Hospital of Zhengzhou University from January 1,2010 to March 1,2018 were analyzed retrospectively.Datas and MethodsThe Chinese literature related to gallbladder and extrahepatic bile system NECs was searched by using Wanfang data service platform,Chinese academic journal network publishing database and VIP periodical resource integration service platform,and the related English literature was searched by PubMed and Web of Science.20 patients with primary extrahepatic biliary system NECs admitted and diagnosed in the first affiliated Hospital of Zhengzhou University from January 1,2010 to March 1,2018 were selected to report the complete data,and 20 patients with primary extrahepatic biliary system NECs were admitted and diagnosed in the first affiliated Hospital of Zhengzhou University from January 1,2010 to March 1,2018.Among them,there were 11 cases of gallbladder neuroendocrine carcinoma(GB-NECs)and 9 cases of extrahepatic bile duct NECs,a total of 129 cases of extrahepatic biliary system NECs.The cases with traceable pathology were reviewed,including pathological type,immunohistochemical staining,Ki-67 index and so on,and the patients were followed up.The effects of pathological type,stage and treatment on OS were analyzed retrospectively.The statistical software SPSS 25.0 was used to map and analyze the data,including univariate and multivariate survival analysis,survival analysis using Kaplan-Meier method,Log-rank test and COX proportional hazard model for difference analysis.There was significant difference between the two groups by Kruskal-Wallis rank sum test,Bonferrironi method and Wilcoxon rank sum test(P < 0.05).Results1.There were 68 cases of gallbladder and 61 cases of extrahepatic bile duct in 129 patients with extrahepatic biliary tract NECs,the ratio of male to female was 1.14:1,the age was 29~89 years old,the median age was 66 years old.In 68 patients with gallbladder NECs,the ratio of male to female was 1:1.18,the age was 38~89 years old,and the median age was 62 years old.In 61 patients with extrahepatic bile duct NECs,the ratio of male to female was 1.54:1,the age was 29~85 years old,the median age was 69 years old.The clinical manifestations of NECs patients with extrahepatic biliary system are not specific,most of them are jaundice,abdominal discomfort,anorexia and other symptoms.2.Immunohistochemistry showed that the positive rates of neuron-specific enolase(NSE),synaptophysin(Syn)and chromaffin A(CgA)were 78.3%(18/23),88.0%(81/92)and 85.2%(69/81),respectively.The positive rate of CD56 was 98.2%(55/56).3.In extrahepatic biliary tract NECs,the prognosis of small cell neuroendocrine carcinoma(SCNECs)was worse than that of large cell neuroendocrine carcinoma(LCNECs)(mOS was 7.7 vs 9.7 months,p = 0.647).The prognosis of stage Ⅰ-Ⅲ patients was better than that of stage Ⅳ patients(9.3 vs 4.8 months,p = 0.003),The multivariate survival analysis showed that stage(P = 0.011)was an independent prognostic risk factor.In extrahepatic bile duct NECs,the prognosis of SCNECs was better than that of LCNECs(mOS was 8.8 vs 6.4 months),but the difference was statistically significant(p = 0.623).In gallbladder NECs,the prognosis of SCNECs was worse than that of LCNECs(mOS was 6.8 vs 13 months),but the difference was not statistically significant(p = 0.299).4.The mOS of patients with extrahepatic biliary tract NECs was 8.9 months.according to the treatment method,the patients were divided into five groups: operation group,operation + radiotherapy and chemotherapy group,simple radiotherapy and chemotherapy group,radiotherapy and chemotherapy + operation group and symptomatic support treatment group.the mOS of the operation + radiotherapy and chemotherapy group was longer than that of the radiotherapy group(11.6 months).There was significant difference between the five groups in the comparison of symptomatic support group and operation + radiochemotherapy group,symptomatic support group and radiochemotherapy group + operation group,operation group and operation + radiotherapy group(p < 0.05).The prognosis of the radical operation group was better than that of the non-radical operation group(9.9 vs 6.6 months,p = 0.018).In the operation + radiotherapy group,19 patients were treated with etoposide / cisplatin(EP)regimen for 11.9 months,mOS was 11.9 months,and the 1-,2-and 3-year survival rates were 50.0%,12.5% and 0% respectively.Conclusion1.The clinical manifestations of NECs in extrahepatic biliary tract system were not specific.2.Surgery is the main treatment,postoperative adjuvant therapy,including radiotherapy,chemotherapy,SSA and so on,is helpful to prolong the survival time and improve the quality of life.3.Surgery did not show significant survival benefits for advanced patients.4.Stage is an independent risk factor for prognosis,and the prognosis of I-III patients is better than that of IV patients. |
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