| Background and purposeNeuroendocrine neoplasms(NENs)are a heterogeneous group of tumors originating from peptidergic neurons and neuroendocrine cells;these tumors can be divided into neuroendocrine tumors(NETs),neuroendocrine carcinomas(NECs)and mixed neuroendocrine/nonneuroendocrine neoplasms(MiNENs).NETs are rare with a low incidence.However,the surveillance,epidemiology,and end results(SEER)program showed an increase from 1.09 new cases per 100,000 in 1973 to 6.98 per 100,000 in 2012,an increase of 540%.The United States,Norway,Japan,and South Korea have established similar databases.However,only single-center reports have been published,the number of cases is small,and survival analyses are scarce in China.Therefore,this study retrospectively analyzed the clinical data of 547 patients with a pathological diagnosis of NETs at the First Affiliated Hospital of Zhengzhou University between January 2011 and April 2018,to explore its epidemiological characteristics,clinical features and to analyze its treatments and prognosis.MethodsThe clinicopathologic characteristics of 547 patients who were pathologically diagnosed with NETs were retrospectively analyzed,including age,sex,primary and metastatic sites,symptoms,pathology,treatment and prognosis.Patients with medullary thyroid carcinoma,pheochromocytoma and paraganglioma were excluded.Relevant case dataswere obtained from the database of the Department of Pathology of the First Affiliated Hospital of Zhengzhou University.This study was approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University.SPSS statistical software version 22.0(SPSS Inc.Chicago,IL,USA)was used to analyze data.Normally distributed continuous variables are expressed as the mean and standard deviation,and significant differences between groups were assessed with independent samples t-tests.Categorical variables were analyzed using the Chi-square test.The Kaplan-Meier method was employed for survival analysis,and log-rank tests were applied for comparisons among groups.When calculating the survival rate,the specified end point event was NET-related death.Survival at the end of the follow-up period was recorded as censored data.Statistical significance was assessed by two-tailed tests with an α level of 0.05.Results1.Clinical information:Among the 547 patients with a pathological diagnosis of NETs at the First Affiliated Hospital of Zhengzhou University between January 2011 and April 2018,the age range was 9-87 years,the average age was 50.2±13.8 years,the peak incidence age group at diagnosis was 50-59 years,and the sex ratio(male/female)was 1:1.1(265/282).There were 161 patients who were 50-59 years old,accounting for 29.3%of all patients;143 patients and 100 patients who were 40-49 years and 60-69 years,respectively,accounting for 24.9%and 19.3%.The average ages of males and females were 51.1 ± 14.1 years and 49.3±13.5 years,respectively,and the difference was not statistically significant(t=1.5,P=0.1).The average diameter of the primary tumor was 2.7±3.0 cm(range,0.1-20.4 cm),as based on postopera-tive resection specimens or imaging examinations performed before surgery.2.Primary tumor sites:Of the NETs,413 were in the digestive system(75.5%),74 were pulmonary(13.5%),15 were mediastinal(2.7%),8 were of unknown primary origin(1.5%),and 37 were in other sites(6.8%).Of the 413 digestive system NETs,the pancreas(25.8%),rectum(24.9%)and stomach(14.8%)were the common sites,and the patients with NETs in the duodenum(3.5%),liver(2.7%),appendix(1.3%),gallbladder and common bile duct(0.9%),jejunum/ileum(0.7%),colon(0.7%),and esophagus(0.2%)composed a relatively small proportion of all patients.Sixty-one patients(11.2%)had insulinoma,and 2 patients had VIPoma.3.Common metastatic sites:Blood metastases were found in 84(15.4%)patients at initial diagnosis.The most frequent site of distant metastasis was the liver(75.0%),followed by bone(21.4%)and the lungs(16.7%).Among the 84 NETs with blood metastases,45 were GEP-NETs with liver metastases,3 were lung NETs with liver metastases,2 were lung NETs with lung metastases,2 were adrenal NETs with lung metastases,6 were lung NETs with bone metastases,4 were rectal NETs with bone metastases,and 4 were mediastinal NETs with bone metastases.Lymph node metastases were found in 82(15.0%)patients at initial diagnosis.Nineteen were lung NETs and 50 were GEP-NETs,and of these,8 were rectal NETs,20 were gastric NETs,and 17 were pancreatic NETs.4.Initial symptoms:Patients with different primary tumor sites have different initial symptoms.Common symptoms in patients with lung NETs were cough and hemoptysis(31.1%,23/74)and blood in the sputum(28.4%,21/74).Common symptoms of rectal NETs were abdominal pain,abdominal distension(27.2%,37/136),blood in the stool(13.2%,18/136)and changes in stool habits(12.5%,17/136).Most patients with stomach NETs had abdominal pain and abdominal distension(50.6%,41/81).Among the pancreatic NETs,61 were insulinomas,which were characterized by hypoglycemia(100%,61/61).Patients with nonfunctional pancreatic NETs had abdominal pain and abdominal distension(36.3%,29/80).5.Pathologic features:Among the 392 patients with GEP-NETs,which accounted for 94.9%of all patients with digestive system NETs,the most common tumor grade was G1,followed by G2 and NET-G3.Among the 74 patients with pulmonary NETs,39 had typical carcinoid tumors,and 35 had atypical carcinoid tumors.Of the 547 cases of NETs,355(64.9%)were stage Ⅰ/Ⅱ,50(9.1%)were stageⅢ,and 84(15.4%)were stage Ⅳ.Fifty-eight cases(10.6%)could not be staged.The positive rates of immunohistochemical staining for synaptophysin(Syn),CD56 and chromogranin A(CgA)were 97.8%,84.7%and 41.9%,respectively.Of the 547 NETs stained for Ki-67,a Ki-67 index ≤2%accounted for 45.2%,an index>2%and ≤20%accounted for 47.2%,and an index>20%and ≤60%accounted for 7.7%.6.Treatment methods:Of the 547 patients,approximately two-thirds(64.4%)underwent surgery,of whom 20.7%underwent endoscopic surgery.Fifty-three(7.5%)of the 547 patients were treated with chemotherapy and other medical treatments,of whom 34(6.2%)received an etoposide plus platinum regimen,8(1.5%)received a temozolomide and capecitabine regimen,4(0.7%)received a temozolomide and tegafur regimen,2(0.4%)received a temozolomide regimen,and 5(0.9%)received octreotide treatment.Thirty-eight patients(6.9%)received postoperative adjuvant chemotherapy,and 95 patients(17.4%)received only supportive treatment;Of the 63 patients with NETs that metastasized to the liver,6 patients underwent hepatic chemoembolization,8 underwent liver radiofrequency ablation,and 5 underwent hepatectomy;the remaining underwent resection of the primary lesions or chemotherapy.7.Follow-up and survival:All patients were followed-up by telephone.The duration was from the date of pathological diagnosis to the date of death or the last follow-up,which was on September 5,2018.The follow-up rate was 72.4%,and 151 patients were lost to follow-up.The overall median survival time of the patients with NETs was not observed during the observation period due to the relatively short follow-up period and low mortality of patients with NETs.The relationships between age,sex,stage,grade,treatment,primary sites and prognosis of patients with NETs were analyzed.The statistical analysis showed that an age less than 50 years,female sex,lower grade,lack of distant metastasis,intestinal NETs and surgery were associated with a favorable prognosis.Conclusion1.In China,NETs are rare with a low incidence.However,according to epidemiological surveys in this study,domestic different centers and abroad,it has been found that the incidence of NETs has been increasing significantly in the past few decades.2.NETs have a good prognosis.Gastroenteropancreatic neuroendocrine tumors are the most common primary sites of NETs.The most frequent site of distant metastasis was the lymph node,liver,bone and lung.3.The statistical analysis showed that age,sex,stage,grade,treatment and primary sites were associated with prognosis.4.No uniform solution exists for the treatment of NETs.However,it has become a consensus to combine surgery with somatostatin analogs,targeted therapy,chemotherapy and immunotherapy. |
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