| Background:Neuroendocrine neoplasms(NEN)are a type of tumor in which the originating cells are distributed throughout the nervous system and the endocrine system.They are heterogeneous and can occur in various tissues and organs of the human body.The digestive system is the most common site of NEN,such as high-incidence sites in the stomach,intestines,and pancreas,or rare sites in the liver,bile ducts,and gallbladder.Although the incidence and treatment rate of NEN has increased significantly in the past three decades,it is still rare compared to other types of tumors.Diagnosis and treatment of such diseases are still under-recognized.Moreover,such diseases are insufficient in terms of naming,diagnosis,treatment,grading,prognosis,radiotherapy and chemotherapy,and have been continuously improved.In order to investigate the characteristics of the disease population,clinicopathological features,and prognostic factors in China,it is expected to improve the understanding of clinicians.This study conducted a comprehensive retrospective analysis of patients with pathological diagnosis of NEN at Qilu Hospital of Shandong University.Objective:To analyze the clinical and pathological data of patients with digestive system NEN,to explore the characteristics of the population,clinical manifestations and treatment methods of NEN,and to explore the risk factors related to tumor prognosis.Methods:The clinical and follow-up data of 125 patients with NEN who were treated at Qilu Hospital of Shandong University from January 2012 to December 2018 was retrospectively analyzed.The data of all patients was extracted from Qilu Hospital’s United Public system or Dean’s case query system,including the patient’s name,age,gender,treatment date,treatment method,and pathological results(including immunohistochemistry results).All patients were treated by surgery or endoscopic digestion,and all the patients were indicated whether they had lymph node metastasis or not.Follow-up mode was performed by telephone or outpatient visit.The age groups were divided into two groups according to the average age:<51 years of age and≥51 years of age.The sex groups were divided into male and female groups.The primary sites were divided into pancreas,stomach,rectum,duodenum,colon,small intestine,liver,bile duct,gallbladder,appendix group.The treatment methods were divided into surgery and endoscopy group.Pathological grading could be divided into G1 phase,G2 phase and G3 phase.Statistical methods(SPSS 22.0 software)were used to analyze differences in age,gender,primary site,clinical symptoms,pathological type,depth of invasion,tumor grade,immunohistochemical Syn,CgA,Ki-67 positive rate,and the relationship between the prognosis.The count data was compared with the χ2 test.The data that did not meet the χ2 test conditions was tested by Fisher’s exact probability test.The survival curve was calculated by Kaplan-Meier method and the survival rate of the patients was calculated.The survival rate between the groups was compared.The curve was calculated using the Log-rank test and P<0.05 was used to indicate that the difference was statistically significant.Result:(1)A total of 125 patients with NEN were collected,including 7 cases(accounting for 5.6%)in 2012,12 cases(9.6%)in 2013,19 cases(15.2%)in 2014,and 21 cases(16.8%)in 2015,22 cases(17.6%)in 2016,15 cases(12.0%)in 2017,29 cases(23.2%)in 2018.70 cases(accounting for 56%)of male patients and 55 cases of female patients(44%),and the ratio of male to female was 1.27:1.The onset age ranged from 14 to 79 year-old,with an average age of 50.94±14.60 years and a median age of 51 years.(2)The primary site of 125 cases of NEN was more common in the pancreas,for 68 cases(accounting for 54.4%),and 21 cases(16.8%)in the stomach,16 cases(12.8%)in the rectum,9 cases in the duodenum(7.2%),3 cases(2.4%)in the colon,2 cases(1.6%)in small intestine,2 cases(1.6%)in liver,2 cases(1.6%)in bile duct,1 case(0.8%)in appendix,and 1 case(0.8%)in gallbladder.(3)The clinical manifestations of 125 patients with NEN were mainly non-functional tumors,95 cases(76%),whose clinical manifestations were non-specific and mainly local symptoms.The remainder were 30 cases of functional NEN(24%),whose clinical manifestations were typical hormone-related symptoms and all of them were located in the pancreas,showing symptoms of hypoglycemia.(4)For the 125 patients with NEN,104(83.2%)had NET,and 21(16.8%)had NEC;63 patients(50.4%)in G1 phase and 39 patients in G2 phase(31.2%),23 patients(18.4%)in G3 phase(including mixed glandular neuroendocrine carcinoma).The immunohistoche-mistry showed Syn(124 cases,positive 122 cases,positive rate of 98.4%),CgA(122 cases,positive 106 cases,the positive rate was 86.9%),Ki-67(113 cases,the positive rate was 100%).(5)For the 125 patients,32(25.6%)were in T1,35(28.0%)in T2,38(30.4%)in T3,and 20(16.0%)in T4.(6)111 cases of 125 patients with NEN had been undergone surgical treatment,and the other 14 patients had been undergone endoscopic resection(11.2%);surgical patients had lymph node metastasis in 29 cases(lymph node metastasis rate 26.13%).There were 3 cases of lymph node metastasis(transfer positive rate 5.88%)in 51 cases of G1 stage,7 cases of lymph node metastasis in 39 cases of G2 stage(transfer positive rate 17.79%),and 19 cases of lymph node metastasis in 21 cases of G3 stage(transfer positive rate was 90.48%).(7)For patients with G1,the average survival time of patients treated by surgery was 74.89±1.10 months,and the average survival time of patients under endoscopic resection was 72.00±4.08 months.There was no significant difference in the prognosis between the two(P=0.38)..The survival period of G1+G2 group in neuroendocrine tumor(NET)was 72.95±1.60 months,and the survival period of neuroendocrine carcinoma(NEC+MANEC)G3 group was 20.6812.90 months.Statistical analysis showed that the neuroendocrine tumor group had a longer life cycle than the neuroendocrine carcinoma group.The difference was of statistically significant(P<0.05).(8)125 patients with neuroendocrine tumors were successfully followed up for 118 cases,and the follow-up rate was 94.4%.The survival period was from 1 to 77 months,and the average survival period was 34.69 months.The result of univariate analysis to age,gender,location,depth of invasion,tumor grade,lymph node metastasis,immunohistochemical analysis of prognosis was as follows:age(P = 0.26),gender(P = 0.06),the location of the disease(P = 0.04),depth of invasion(P=0.00),tumor grade(P=0.00),lymph node metastasis(P=0.00),in which age and gender were not statistically significant and the location of the disease,tumor grade,depth of invasion,lymph node metastasis had a greater relationship with prognosis.Conclusion:1.The number of confirmed patients with NEN was increasing year by year,and occurred in all ages.40-69 years old was a high-risk group,accounting for 68.8%.The male-female ratio was 1.27:1,the difference between which was not obvious.The most prevalent part of the digestive system NEN was the pancreas,and the following were stomach,rectum,colon,small intestine,liver,bile duct,appendix,and gallbladder.The clinical manifestations of NEN were mainly related to the location of the disease and the presence or absence of functional secretion.In immunohistochemistry,Syn and CgA were the main markers,and Syn sensitivity was superior to CgA.The treatment of NEN was mainly surgery,and supplemented by chemotherapy,as well as somatostatin analogues and molecular targeted drugs.Early patients could choose surgery or endoscopic treatment.The study showed that the difference was not statistically significant,but it was the only possible cure for patients with advanced disease.Statistical analysis showed that patients with early(G1,G2)survival cycle are significantly longer than patients with advanced(G3).The prognosis of NEN is related to the location of the disease,tumor grade,depth of invasion,lymph node metastasis,etc.,regardless of age and gender. |
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