| Background Neuroendocrine neoplasms(NENs)are a diverse group of tumors that derive from epithelial cells with neuroendocrine differentiation.According to an analysis of the National Cancer Institute's Surveillance,Epidemiology and End Results(SEER)database,which is currently the largest epidemiological series,the incidence of NENs has risen substantially in the past 30 years.Gastroenteropancreatic(GEP)-NENs are a subset of NENs that arise from tissues throughout the gastrointestinal tract,which is the most commonly affected site.To date,many studies on GEP-NENs refer to western countries.However,for Asian populations,especially China,there is a paucity of large epidemiological studies of patients with this condition.For this reason,detailed data are needed for comprehensive knowledge of GEP-NENs in China.Based on the 13-year data of the Affiliated Hospital of Qingdao University,a retrospective study was carried out to explore the clinicopathological features and survival of GEP-NENs.Methods A review of all the cases with histologically confirmed GEP-NENs was carried out in the medical record library of the Affiliated Hospital of Qingdao University over a period of 13 years(2001-2013).Clinical features,including age,gender,location,clinical symptoms,histopathological characteristics and outcomes,were collected.The cases were reclassified according to the WHO 2010 criteria.Follow-up data were obtained both via query system of social health insurance and by phone call,if available.Overall survival(OS)was defined as the time from diagnosis to death or last follow-up in living patients.Data were exported to SPSS 17.0(SPSS Inc.,Chicago,IL,USA).Descriptive analyses were applied to determine the patients' baseline of clinicopathological characteristics.Kaplan-Meier survival curve was used to estimate the mean survival time or median survival time(if available).In univariate analysis,survival time was compared by Log-rank test.Multivariate Cox-proportional hazard model was employed to identify predictors of survival outcomes.Hazard ratio(HR)with 95% confidence interval(95% CI)was computed,and P<0.05(two-side)was considered statistically significant.The study was approved by the Ethics Committee of the Affiliated Hospital of Qingdao University(with a reference number:QYFYECKY 2014-012-01)andcomplied with the Declaration of Helsinki(6th revision,2008).Patient records were anonymized and de-identified prior to analysis.Results The median follow-up time was 22 months(range 1-157 months).Complete data accounted for 18.2% of the total.During the observation period,28 deaths occurred.The median survival time was not reached during the observation period.The mean survival time was 121±8 months(95% CI 106-136).The estimated 3-and 5-year survival rates were 84.0% and 81.9%,respectively Gender and age at diagnosis Of 154 patients with GEP-NENs,88(57.1%)were men and 66(42.9%)were women.The male to female ratio was 1.33.Univariate analysis showed no significant difference in survival according to gender(?2=2.692,P=0.101).The Median age at diagnosis was 56 years(range 9-86 years).For 54 patients aged <50 years,the survival was significantly higher compared with that of 100 patients aged ?50 years(?2=9.647,P=0.002)Primary tumor sites The pancreas was the primary tumor site in 63 patients(40.9%),the large intestine(rectum plus colon)in 43(27.9%),and the stomach in 34(22.1%).Among the nonpancreatic tumors,the rectum(35/91,38.5%)and stomach(34/91,37.4%)were the most frequent sites of origin.A trend toward longer survival for pancreatic NENs as compared to nonpancreatic NENs was found(?2=16.309,P<0.001)Clinical presentation Nonfunctional tumors comprised the majority of GEP-NENs(102/154,66.2%),whereas functional tumors accounted for the remainder(52/154,33.8%).Of the 102 nonfunctional cases,abdominal pain was the most frequent symptom(49/102,48.0%),which was not specific for the diagnosis.Other nonspecific symptoms were abdominal distension(16/102,15.7%),gastrointestinal bleeding(12/102,11.8%),jaundice(5/102,4.9%),nausea or vomiting(4/102,3.9%),and diarrhea(3/102,2.9%).Incidental diagnosis occurred in 9/102 cases(8.8%),which were usually asymptomatic.Of the 52 functional cases,the most frequent functionality was fasting hyperinsulinemic-hypoglycemia-neuroglycopenia syndrome(46/52,88.5%)induced by insulinoma primarily located in the pancreas.Carcinoid syndrome was the second most frequent functionality found in four cases,including three gastric NENs with liver metastases and one colonic NEN with pulmonary metastasis.Mean survival time was significantly different between functional and nonfunctional patients(?2=14.159,P<0.001).Tumor-node-metastasis characteristics The median tumor diameter was 1.2 cm(range 0.3-16.0 cm): 57(42.9%)were <2 cm in diameter,41(30.8%)were 2-4 cm,and 35(26.3%)were >4 cm.Difference in mean survival time was significant between subgroups when divided by diameter(?2=22.135,P<0.001).The absence of lymphnode metastases improved survival compared to those patients with lymph node metastasis with a mean survival time of 131 months vs.39 months(?2=17.633,P<0.001).Metastases were found in 16/154(10.4%)patients at initial diagnosis.The absence of metastases improved survival compared to those patients with metastases with a mean survival time of 130 months vs.19 months(?2=30.826,P<0.001)Immunohistochemistry and histopathology grading Immunohistochemical staining showed an 83.0% positive rate for chromogranin A and an 89.0% positive rate for synaptophysin.According to the current WHO 2010 criteria,145/154(94.2%)cases were available for analysis of grading.Among these,51.0% were reclassified as NEN grade 1(G1),while 20.0% were NEN grade 2(G2),and 29.0% were NEC grade 3(G3).The difference in survival among G1,G2 and G3 was significant(?2=36.266,P<0.001)Surgical intervention After initial diagnosis,tumor removal was performed in 151/154(98.1%)patients,of which 142(94.0%)were with curative intent and 9(6.0%)were for palliative purpose.The mean survival time for these 142 patients with curative resection was higher compared with those with palliative treatment(?2=14,441,P<0.001).Multivariate analysis Univariate analysis mentioned above showed significance for age at diagnosis,primary tumor site,status of functionality,tumor size,regional lymphatic metastasis,distant organ metastasis,histopathological grading,and treatment modality.Multivariate analysis of the above factors showed that tumor size,status of lymphatic metastasis,and distant organ metastasis were the most significant predictors of survival.Disscusion and Conclusions The pancreas was the most common site of involvement.Tumor size varied from 0.3 cm to 16.0 cm(median 1.2 cm).The estimated 3-and 5-year overall survival rates for all patients were 84.0% and 81.9%,respectively.Additionally,we identified tumor size,lymphatic metastases and distant metastases as independent prognostic factors for long-term survival.Our data provide further information on the clinicopathological features of GEP-NENs in China.This lays the groundwork for further characterization of GEP-NENs in the Asian population and worldwide.Additionally,this analysis raised discussion of modification to the G grading system. |
PDF Full Text Request