| Neuroendocrine neoplasms(NENs),which originate from neuroendocrine cells,comprise a heterogeneous family with a broad spectrum of clinical behavior [1].The neoplasms occur in diverse sites throughout the body,and more than half are gastroenteropancreatic NENs(GEP-NENs)[2].According to the Surveillance,Epidemiology,End Results database(SEER),which has the largest epidemiologic series,the incidence of NENs has risen substantially over the past 30 years [2].Although the prevalence of GEP-NENs seems to be increasing in China,there is no accurate database of the characteristics of GEP-NENs in Chinese patients.In 2010,the World Health Organization [3] proposed a new classification of NENs,with comparisons of clinical,pathological,therapeutic,and prognostic factors.In western countries,the epidemiology,treatment,and survival rates of NENs have been well-studied [1,2],but comparable information in Asian populations is limited [4,5].In order to investigate the clinical pathological characteristics,risk factors of metastasis,and prognosis of NENs in a Chinese population,we performed a comprehensive retrospective review of the recent 5-year experience with this disease in our center.ObjectiveGastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)are the most common type of neuroendocrine tumors,accounting for more than half of neuroendocrine neoplasms(NENs).We performed a retrospective study in our center to investigate the clinicopathological features,risk factors of metastasis,and prognosis of GEP-NENs in a Chinese population.In addition,the NENs G3 were classified as NET G3(well-differentiated NET with a G3 grading)or NEC,and the prognoses of these were compared.MethodsFour hundred forty patients with GEP-NENs treated at the First Affiliated Hospital of Zhengzhou University between January 2011 and March 2016 were analyzed retrospectively.Multivariate logistic regression was performed to identify independent risk factors for metastasis of the tumors.The Kaplan-Meier method was used for survival analysis,and log-rank tests for comparisons among groups.The pathological diagnosis of the NENs depended on typical morphological findings and immunohistochemical staining of chromogranin(CgA)and/or synaptophysin(Syn)[7].Grading was based on morphological criteria and tumor proliferative activity.According to the Ki-67 index,the grading was G1,G2 and G3 ?2%,3~20%,>20%,respectively.Similarly,tumors with mitotic rates of less than two in 10 high-power fields(HPF)were classified as G1,2~20/HPF as G2,and >20/HPF as G3.If the grading of the Ki-67 index differed from that of the mitotic rate,the higher of the two was given priority.Therefore,GEP-NENs were classified as neuroendocrine tumor(NET)(G1 and G2),neuroendocrine carcinoma(NEC)(G3),and mixed adenoendocrine carcinoma(MANEC)(G3)[3,4].The well-differentiated G3 NENs(Ki-67 positive index > 20%;generally less than 60%)were classified as well-differentiated NET(NET G3)[8,9].Results1.Clinical featuresAmong the 440 patients with GEP-NENs,259(58.9%)were men and 181(41.1%)were women;the male to female ratio was 1.43.Ages ranged from 9 to 86 years,and the mean age was(54.3±13.5)years.The most common tumor site was the stomach(24.3%,107/440),followed by the rectum(24.1%,106/440),pancreas(20.5%,90/440),esophagus(12.3%,54/440).Non-functional tumors comprised the majority of GEP-NENs(389/440,88.4%);the other 51(11.6%)were functional.The most frequent initial presentation was abdominal pain(101/440,23%),which was not specific for the diagnosis of tumor,followed by dysphagia(45/440,10.2%).The main detection methods are digestive endoscopy,endoscopic ultrasonography,ultrasound,CT,MRI and PET-CT.The detection rates were: endoscopy(99.1%),endoscopic ultrasonography(92.7%),ultrasound(86.7%),CT(85.4%),MRI(79.5%),PET-CT(93.1%).2.Histopathologic characteristicsThe average diameter of GEP-NENs tumors was 2.27 cm(0.2 to 16 cm).The most common tumor type was NET(250,56.8%),followed by NEC(146,33.2%)and MANEC(14,3.2%);the other 30 cases of G3 were classified as NET G3.The positive rates of immunohistochemistry of Syn and CgA were 97.7%(416/426)and 48.7%(135/277),respectively.Local infiltration and lymphatic metastasis occurred in 63%(277/440)and 12.3%(54/440)of patients,respectively.Distant metastases were found in 90(20.5%)patients at initial diagnosis;during follow-up,the number increased to 109(24.8%).Distant metastases were present at initial diagnosis in 38.4%(73/190)of patients with G3 tumors.The most frequent site of distant metastasis was liver(67/109,61.5%),followed by peritoneum(18.3%,20/109),lung(10.1%,11/109)and bone(6.4%,7/109).3.Analysis of risk factors for metastasisUnivariate analysis showed that the risk factors of NEN metastasis were related to the sex,age,tumor diameter,location,tumor function status,grade and type of the patients.The risk factors of GEP-NENs metastases were then analyzed by the logistic regression method.Multivariate logistic regression analysis revealed that the diameter and pathological classification of tumors were the most important predictors for metastasis.4.Therapeutic interventions,Survival and prognostic factorsAbout two-thirds of the patients(62.5%;275/440)underwent an operation with curative intent or palliation;50 patients were treated with endoscopic radical surgery,mainly for rectal lesions.Seventy-three patients received chemotherapy,34 of whom received postoperative adjuvant chemotherapy.The 1-,3-and 5-year survival rates of all patients were 78.7%,60.8% and 54.5,respectively.The 1-,3-and 5-year survival rates of patients with G3 lesions were 54.3%,19.4% and 7.8%,respectively.Univariate analysis confirmed that patients with NET G3 and patients without regional or distant metastasis survived longer than did other patients with NENs G3.Median overall survival among all the patients with G3 NENs was 13.0 months,and survival was significantly longer for these patients(median 34 months)than for those with NEC(median 11 months).Median overall survival of patients with localized G3 NENs was 36 months,15 months for patients with regional disease,and 6 months for patients with distant disease.Conclusion1.Among the patients with GEP-NENs,the most common tumor site was the stomach,followed by the rectum,pancreas.Non-functional tumors comprised the majority of GEP-NENs.The most frequent initial presentation was abdominal pain,which was not specific for the diagnosis of tumor,followed by dysphagia.2.The diameter and pathological classification of tumors were the most important predictors for metastasis.3.Patients with NET G3 and patients without regional or distant metastasis survived longer than did other patients with NENs G3.Median survival was significantly longer for NET G3 patients(median 34 months)than for those with NEC(median 11 months).Median overall survival of patients with localized G3 NENs was 36 months,15 months for patients with regional disease,and 6 months for patients with distant disease. |
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