European Neuroendocrine Tumor Society Staging Research Articles

Appendiceal Neuroendocrine Neoplasms: A Comprehensive Review.

Appendiceal neuroendocrine neoplasm (NEN) is the most common adult appendiceal malignant tumor, constituting 16% of gastrointestinal NENs. They are versatile tumors with varying morphology, immunohistochemistry, secretory properties, and cancer genomics. They are slow growing and clinically silent, to begin with, or present with features of nonspecific vague abdominal pain. Most acute presentations are attributed clinically to appendicitis, with most cases detected incidentally on pathology after an appendectomy. Approximately 40% of them present clinically with features of hormonal excess, which is likened to the functional secretory nature of their parent cell of origin. The symptoms of carcinoid syndrome render their presence clinically evident. However, slow growing and symptomatically silent in its initial stages, high-grade neuroendocrine tumors and neuroendocrine carcinomas of the appendix are aggressive and usually have hepatic and lymph node metastasis at presentation. This review article focuses on imaging characteristics, World Health Organization histopathological classification and grading, American Joint Committee on Cancer/Union or International Cancer Control, European Neuroendocrine Tumor Society staging, European Neuroendocrine Tumor Society standardized guidelines for reporting, data interpretation, early-stage management protocols, and advanced-stage appendiceal NENs. Guidelines are also set for the follow-up and reassessment. The role of targeted radiotherapy, chemotherapy, and high-dose somatostatin analogs in treating advanced disease are discussed, along with types of ablative therapies and liver transplantation for tumor recurrence. The search for newer location-specific biomarkers in NEN is also summarized. Regarding the varying aggressiveness of the tumor, there is a scope for research in the field, with plenty of data yet to be discovered.

Comment on: Are Parenchyma-Sparing Resections Really Appropriate for Small (

Comment on: Are Parenchyma-Sparing Resections Really Appropriate for Small (<3 cm) Nonfunctional Pancreatic Neuroendocrine Tumors?

Prognostic validity of the American joint committee on cancer eighth edition staging system for well-differentiated pancreatic neuroendocrine tumors

The American Joint Committee on Cancer (AJCC) made improvements for staging pancreatic neuroendocrine tumors (pNETs) in its 8th Edition; however, multicenter studies were not included. We collected multicenter datasets (n=1,086, between 2004 and 2018) to validate the value of AJCC 8 and other coexisting staging systems through univariate and multivariate analysis for well-differentiated (G1/G2) pNETs. Compared to other coexisting staging systems, AJCC 7 only included 12 (1.1%) patients with stage III tumors. Patients with European Neuroendocrine Tumor Society (ENETS) stage IIB disease had a higher risk of death than patients with stage IIIA (hazard ratio [HR]: 4.376 vs. 4.322). For the modified ENETS staging system, patients with stage IIB disease had a higher risk of death than patients with stage III (HR: 6.078 vs. 5.341). According to AJCC 8, the proportions of patients with stage I, II, III, and IV were 25.7%, 40.3%, 23.6%, and 10.4%, respectively. As the stage advanced, the median survival time decreased (NA, 144.7, 100.8, 72.0 months, respectively), and the risk of death increased (HR: II=3.145, III=5.925, and IV=8.762). These findings suggest that AJCC 8 had a more reasonable proportional distribution and the risk of death was better correlated with disease stage.

Modified staging system for gastric neuroendocrine carcinoma based on American Joint Committee on Cancer and European Neuroendocrine Tumor Society systems.

The prognostic values of the AJCC staging system for gastric cancer (GC-AJCC), the AJCC staging system for gastric neuroendocrine tumours (NET-AJCC) and the European Neuroendocrine Tumor Society (ENETS) system for gastric neuroendocrine carcinoma and mixed adenoneuroendocrine carcinoma (MA)NEC remain controversial. Data on patients with (MA)NEC from 21 centres in China were analysed. Different staging systems were evaluated by performing Kaplan-Meier survival analysis and calculating the concordance index (C-index) and Akaike information criterion (AIC). Based on three existing systems, a modified staging system (mTNM) was developed. A total of 871 patients were included. In the GC-AJCC system, an overlap was noticed for pT2 and pT3 categories. Patients with stage IIIC disease had a similar prognosis to those with stage IV disease. The pT categories of the NET-AJCC system had a lower C-index and higher AIC than those of the other systems. In the ENETS system, there was a low proportion (0·2 per cent) of patients with stage IIIA and a high proportion (67·6 per cent) of stage IIIB disease. The mTNM system adopted the NET-AJCC pT and GC-AJCC pN and pM definitions, and was developed based on the ENETS stage definitions. The proportion of patients in each stage was better distributed and the mTNM system showed improved prognostic performance in predicting overall and disease-free survival. The mTNM system offers more accurate prognostic value for gastric (MA)NEC than the AJCC or ENETS staging systems.

Clinicopathological features and prognostic validity of the European Neuroendocrine Tumor Society (ENETS) and American Joint Committee on Cancer (AJCC) 8th staging systems in colonic neuroendocrine neoplasms.

PurposeThis study aimed to investigate the characteristics of colonic neuroendocrine neoplasms (NENs) and to validate the prognostic value of the European Neuroendocrine Tumor Society (ENETS) and American Joint Committee on Cancer (AJCC) 8th staging systems.MethodsA total of 167 and 1248 patients with colonic NENs from 12 medical centers across China and from the Surveillance, Epidemiology, and End Results (SEER) cancer registry in the United States, respectively, were reviewed. Patients were staged according to the ENETS and AJCC 8th staging systems.ResultsClinicopathological features of colonic NENs in the Chinese cohort and SEER cohort were significantly distinct. In both the Chinese cohort and the SEER cohort, colonic neuroendocrine carcinoma (NEC) and mixed adeno‐neuroendocrine carcinoma (MANEC) were more frequent in the midgut than in the hindgut. Tumors originating from the midgut tended to be larger and at a more advanced stage than those from the hindgut. The AJCC 8th staging system and the ENETS system appeared to have similar prognostic ability for colonic NEC/MANEC.ConclusionsOur study revealed that tumors originating from the midgut and the hindgut shared different clinicopathological features. The AJCC 8th staging system and the ENETS system appeared to have similar prognostic ability for colonic NEC/MANEC.

The latest exploration of staging and prognostic classification for pancreatic neuroendocrine tumors: a large population-based study.

Background: A modified European Neuroendocrine Tumor Society (mENETS) staging system has been confirmed to be more suitable for pancreatic neuroendocrine tumors (pNETs) when compared to the American Joint Committee on Cancer (AJCC) or the European Neuroendocrine Tumor Society (ENETS) systems in the last few years. However, the importance of N stage has been recently published with several significant updates.Methods: SEER registry (n = 2,209) was used to evaluate the application of the AJCC 7th staging system, ENETS staging system, mENETS staging system and reformed ENETS (rENETS) staging system in this study.Results: For the ENETS staging system, patients with stage I disease had a similar prognosis to patients with stage II disease (P=0.154), and patients with stage IIIA and stage IIIB diseases showed adverse prognostic potential. The proportion of patients with stage III diseases using AJCC 7th staging system was extremely lower than those with mENETS staging system or rENETS staging system (3.6%, 23.0% and 23.7%, respectively). Furthermore, the hazard ratio of death for patients with stage II or III disease using rENETS staging system was slightly higher than that of mENETS staging system. Besides, survival curves were better separated by rENETS staging system. A prognostic nomogram for overall survival (OS) was formulated to obtain superior discriminatory abilities.Conclusions: The rENETS staging system has superior distribution in proportion than the AJCC 7th, ENETS or mENETS staging system, and one more accurate and advanced predictive model will be achieved via the incorporation to be adopted in clinical practice.

Association between ABO blood types and sporadic pancreatic neuroendocrine tumors in the Chinese Han population.

BackgroundAlthough the relationship between non-O blood types and the risk of exocrine pancreatic cancer has been demonstrated, the association between ABO blood types and sporadic pancreatic neuroendocrine tumor (PNET) has not been reported thus far.MethodsThis hospital-based, case-control study included 387 patients with PNET and 542 age- and sex-matched controls. Unconditional multivariable logistic regression analysis was performed to estimate the adjusted odds ratios (AORs) and 95% confidence intervals (CIs). The relationship between ABO blood types and clinicopathologic features was also analyzed.ResultsAfter adjusting for age, sex, smoking status, alcohol drinking, and first-degree family history of any cancer, the AORs (95% CI) of functional PNET were 0.87 (0.59–1.28) for blood type A, 0.86 (0.58–1.28) for blood type B, and 0.71 (0.39–1.26) for blood type AB compared with subjects with blood type O. A similar ABO blood-type distribution was observed among cases with non-functional PNETs compared with controls. On comparing blood type B with non-B blood type, cases with non-functional PNETs had marginally higher rates of lymph node invasion (P = 0.047), distant metastasis (P = 0.044), and advanced European Neuroendocrine Tumor Society Stage (P = 0.040).ConclusionsThere is no association between the ABO blood group and the development of functional and non-functional PNETs. The ABO blood types are not associated with the clinicopathologic features in patients with functional and non-functional PNETs.

Cystic pancreatic neuroendocrine tumors (cPNETs): a systematic review and meta-analysis of case series.

Cystic pancreatic neuroendocrine tumors represent 13% of all neuroendocrine tumors. The aim of this study is to analyze the phenotype and biologic behavior of resected cystic neuroendocrine tumors. A systematic review and meta-analysis were conducted until September 2016 using a search in Medline, Scopus, and EMBASE with the terms "cystic pancreatic endocrine neoplasm", "cystic islets tumors" and "cystic islets neoplasms". From the 795 citations recovered 80 studies reporting on 431 patients were selected. 87.1% (n = 387) were sporadic tumors and 10.3% (n = 40) corresponded to multiple endocrine neoplasia endocrine type 1. Were diagnosed incidentally 44.6% (n = 135). Cytology was found to have a sensitivity of 78.5%. Were non-functional tumors 85% (n = 338), and among the functional tumors, insulinoma was the most frequent. According to the European Neuroendocrine Tumor Society staging, 87.8% were limited to the pancreas (I-IIb), and 12.2% were advanced (III-IV). Disease-free survival at 5 years in stages (I-IIIa) and (IIIb-IV) was 91.5% and 54.2%, respectively; and was significantly lower (p = 0.0001) in functional tumors. In patients with multiple endocrine neoplasia there was a higher incidence of functional (62.5%) and multifocal (28.1%) tumors. Disease-free survival at 5 and 10 years was 60%. Cystic pancreatic neuroendocrine tumors exhibit phenotypical characteristics which are different to those of solid neuroendocrine tumors.

432P - Prognostic validity of AJCC staging system in neuroendocrine tumors of the appendix

Neuroendocrine tumors (NETs) are the most common appendiceal tumors and can be categorized as well-differentiated NETs (WDNETs) and mixed adenoneuroendocrine tumors (MANECs). Currently, WDNETs are classified based on the American Joint Committee on Cancer (AJCC) staging (seventh edition), first proposed in 2010 or according to the European Neuroendocrine Tumor Society staging systems (ENETS). Both systems differ slightly in the T stage. MANECs, which are more aggressive, are staged according to AJCC staging for appendiceal adenocarcinomas. However, the prognostic value of AJCC staging system in WDNETs and MANECs has not been validated. Patients (pts) diagnosed with appendiceal WDNET and MANEC (between 1988-2012) in the Surveillance, Epidemiology and End Results (SEER) program were assigned stages I-IV according ENETS (WDNETs only) or AJCC 7th edition (WDNETs and MANECs). Kaplan-Meier method and univariate Cox model were used to evaluate overall survival (OS) and differences in OS across stages, respectively. We identified 860 and 1173 pts with WDNET and MANEC, respectively. The 10-year survival rates for WDNETs according to ENETS stages I-IV were 96%, 95%, 92%, and 55%, respectively (P < 0.001, log rank). The corresponding rates for AJCC stages I-IV were 96%, 95%, 93%, and 55%, respectively (P < 0.001, log rank). Using univariate cox regression for WDNETs, only stage IV was associated with poor OS in both ENETS and AJCC (per ENET: HR = 8.27, 95%CI = 3.72-18.35, p < 0.001 and per AJCC: HR = 9.37, 95%CI = 5.11-17.19, p < 0.001). The agreement between AJCC and ENETS per weighted Cohen's kappa coefficient was estimated to be 0.73 (95% CI = 0.70-0.76), indicating substantial agreement and moderate discrepancy. For MANEC, the number of pts with stage I-IV was 230 (19.61%), 625 (53.28%), 176 (15.26%), and 139 (11.85%) respectively. By AJCC staging, median OS was 52 months, 43 months, 28 months and 17 months for stage I-IV, respectively (p < 0.001, log rank). For WDNET, stage IV is associated with worse survival in both the AJCC and ENETS classifications. In MANEC, both stages III and IV are associated with worse survival.

Prognostic Validity of the American Joint Committee on Cancer and the European Neuroendocrine Tumors Staging Classifications for Pancreatic Neuroendocrine Tumors: A Retrospective Nationwide Multicenter Study in South Korea.

Pancreatic neuroendocrine tumors (pNETs) are diverse diseases with different prognosis. The American Joint Committee on Cancer (AJCC) and the European Neuroendocrine Tumor Society (ENETS) introduced 2 different tumor node metastasis (TNM) stages, and the World Health Organization (WHO) proposed WHO 2010 grading system for pNETs. Therefore, we aimed to validate the prognostic relevance of these 3 systems for pNETs in South Korea. The Korean Society of Gastrointestinal Cancer created a retrospective registry of pNETs in 153 patients from 15 hospitals between 2002 and 2012. On the basis of the WHO 2010 grade, 2-year progression-free-survival (PFS) rates for G1, G2, and G3 were 92%, 62%, and 25% (P < 0.01). According to ENETS and AJCC staging, 2-year PFS rates for stages I through IV were 94%, 87%, 49%, 20%, and 92%, 61%, 60%, 20%, respectively (P < 0.01). A Cox multivariate regression analysis revealed that the only statistically significant prognostic factor was the TNM classification of either the AJCC or the ENETS stage (P < 0.01). In addition, the κ value between the AJCC and the ENETS stages was 0.46 indicating a "moderate" agreement (P < 0.01). The AJCC and ENETS TNM classifications for pNETs are prognostic for PFS and can be adopted in clinical practice in South Korea.

A Review on Management Discussions of Small Intestinal Neuroendocrine Tumors ‘Midgut Carcinoids’

European Neuroendocrine Tumor Society staging, together with the Ki67 grading system, has appeared as superior for classification of neuroendocrine tumors (NET). The management of small intestinal NET (SI-NET) has been overall controversial. Mesenteric metastases occur also with the smallest SI-NET, and the majority of patients risk to ultimately progress with liver metastases. 68Gallium (somatostatin receptor)/PET/CT has appeared as most sensitive for imaging, and fluorodeoxyglucose-PET is recommended to identify lesions with high proliferation. Our treatment policy for SI-NET is to initiate somatostatin analog treatment, and in order to prevent abdominal complications we recommend early intestinal resection for removal of primary tumors and clearance of lymph node metastases. Liver metastases are liberally treated by resection (or ablation), as this can efficiently palliate carcinoid syndrome-associated symptoms.

Discrepancies between two staging systems (European-ENETS versus. American-AJCC) of neuroendocrine neoplasms of the pancreas: A study of 77 cases.

318 Background: Pancreatic neuroendocrine tumors (pNETs) comprise a spectrum of neoplasm with variable biological behaviour and heterogeneous prognosis. The European Neuroendocrine Tumor Society (ENETS) and the American Joint Cancer Committee/Union for International Cancer Control (AJCC/UICC) TNM staging systems have been recently published. The aim of this study was to evaluate the consistency of both staging systems on outcomes for patients with pNETs. Methods: A retrospective clinico-pathological study of 77 consecutive patients with pNETs who were surgically treated from 1993 to 2014 was carried out. Results: The male to female ratio was 1.0 (38 men, 39 women); 56 tumors were non-functionating and 21 functionating. Most of the tumors were G1 (57) and 20 were classified as G2-G3. The AJCC/UICC stage was IA in 29 patients, IB in 14, IIA in 10, IIB in 7 and IV in 17. Meanwhile, according with the ENETS staging system was: stage I in 30, IIa in 14, IIb in 3, IIIa in 6, IIIb in 7 and IV in 17. We found 18 (23.3%) cases of ENETS - AJCC/UICC discrepancies regarding the primary tumor. They included 6 cases (33%) disagreement between IIA (T3 N0 M0) and IIIa (T4 N0 M0); and 7 cases (38.8%) between IIB (T1-T3 N1 M0) and IIIb (anyT N1 M0). Conclusions: The AJCC and ENETS TNM classification staging for pNETs provide meaninful prognostic value of long-term survival por patients with pNETs. The T staging discrepancies between AJCC/UICC and ENETS are relative frequent and should be strictly recognized.

Surgical management of advanced pancreatic neuroendocrine tumors: short-term and long-term results from an international multi-institutional study.

The role of extended resections in the management of advanced pancreatic neuroendocrine tumors (PNETs) is not well defined. Between 1995 and 2012, 134 patients with PNET underwent isolated (isoPNET group: 91 patients) or extended pancreatic resection (synchronous liver metastases and/or adjacent organs) (advPNET group: 43 patients). The associated resections included 27 hepatectomies, 9 vascular resections, 12 colectomies, 10 gastrectomies, 4 nephrectomies, 4 adrenalectomies, and 3 duodenojejunal resections. R0 was achieved in 41 patients (95%) in the advPNET. The rates of T3-T4 (73 vs 16%; p < .0001) and N+ (35 vs 13%; p = .007) were higher in the advPNET group. Mortality (5 vs 2%) and major morbidity (21 vs 19%) rates were similar between the 2 groups. The 5-year overall survival (OS) of the series was 87% in the isoPNET group and 66% in the advPNET group (p = .006). Only patients with both locally advanced disease and liver metastases showed worse survival (p = .0003). The advPNET group developed recurrence earlier [disease-free survival (DFS) at 5 years: 26 vs 81%; p < .001]. In univariate analysis, negative prognostic factors of survival were: poor degree of differentiation (p < .001), liver metastasis (p = .011), NE carcinoma (p < .001), and resection of adjacent organs (p = .013). The multivariate analysis did not highlight any factor that influenced OS. In multivariate analysis independent DFS factors were a poor degree of differentiation (p = .03) and the European Neuroendocrine Tumor Society stage (p = .01). An aggressive surgical approach for locally advanced or metastatic tumors is safe and offers long-term survival.

A Single Institution's 26-Year Experience With Nonfunctional Pancreatic Neuroendocrine Tumors

To validate the 2010 American Joint Committee on Cancer (AJCC) and 2006 European Neuroendocrine Tumor Society (ENETS) tumor staging systems for pancreatic neuroendocrine tumors (PanNETs) using the largest, single-institution series of surgically resected patients in the literature. The natural history and prognosis of PanNETs have been poorly defined because of the rarity and heterogeneity of these neoplasms. Currently, there are 2 main staging systems for PanNETs, which can complicate comparisons of reports in the literature and thereby hinder progress against this disease. Univariate and multivariate analyses were conducted on the prognostic factors of survival using 326 sporadic, nonfunctional, surgically resected PanNET patients who were cared for at our institution between 1984 and 2011. Current and proposed models were tested for survival prognostication validity as measured by discrimination (Harrel's c-index, HCI) and calibration. Five-year overall-survival rates for AJCC stages I, II, and IV are 93% (88%-99%), 74% (65%-83%), and 56% (42%-73%), respectively, whereas ENETS stages I, II, III, and IV are 97% (92%-100%), 87% (80%-95%), 73% (63%-84%), and 56% (42%-73%), respectively. Each model has an HCI of 0.68, and they are no different in their ability to predict survival. We developed a simple prognostic tool just using grade, as measured by continuous Ki-67 labeling, sex, and binary age that has an HCI of 0.74. Both the AJCC and ENETS staging systems are valid and indistinguishable in their survival prognostication. A new, simpler prognostic tool can be used to predict survival and decrease interinstitutional mistakes and uncertainties regarding these neoplasms.

Comparison of WHO Classifications (2004, 2010), the Hochwald Grading System, and AJCC and ENETS Staging Systems in Predicting Prognosis in Locoregional Well-differentiated Pancreatic Neuroendocrine Tumors

It is difficult to predict prognosis in patients with locoregional well-differentiated (WD) pancreatic neuroendocrine tumors (PanNET). We aimed to examine commonly used stratification systems [World Health organization (WHO) 2004 and 2010 classifications, American Joint Committee on Cancer (AJCC) and European Neuroendocrine Tumor Society (ENETS) staging, and the Hochwald grading system] for their power in predicting recurrence-free survival (RFS) in these patients. Seventy-five such patients (mean age 56 y, mean follow-up 79 mo) who underwent resection with sufficient tissue material and follow-up data were studied. RFS was correlated with variable clinicopathologic features and stratified with above-mentioned systems. Concordance index (CI) was then calculated. With the WHO 2004 classification, 16, 35, and 24 PanNETs were classified as benign behavior, uncertain behavior, and WD endocrine carcinoma, respectively. By the WHO 2010 classification, 26, 41, and 8 tumors were grade 1, 2, and 3, respectively. Using the Hochwald system, 47 were low grade, and 28 were intermediate grade. The AJCC staging information was complete for 62 patients (13 had the lymph node status Nx) and included: stages IA (19/62), IB (10/62), IIA (10/62), and IIB (23/62). The ENETS staging information was stages I (16/62), IIa (8/62), IIb (14/62), IIIa (0/62), and IIIb (24/62). The average Ki-67 proliferation index (PI) was 8.1%. Factors that predicted RFS included tumor size, nodal metastasis, vascular invasion, perineural invasion, necrosis, mitosis, and Ki-67 PI (all P<0.01). The CI for each system was: 0.6361 for WHO 2004, 0.6735 for WHO 2010, 0.6495 for AJCC staging, 0.6642 for ENETS staging, and 0.6851 for the Hochwald grading system. When these systems were analyzed in conjunction with various additional important pathologic features, combination of the Hochwald grading system and Ki-67 PI achieved the highest CI (0.7946). Therefore, although all these systems predict RFS well in locoregional WD PanNETs, the Hochwald grading system achieves the highest predictive ability. Further predictive power can be achieved by combining the Hochwald grading system and Ki-67 PI.

Are Neuroendocrine Tumors Going Mainstream?

Are Neuroendocrine Tumors Going Mainstream?

Cystic Pancreatic Neuroendocrine Tumors

Pancreatic neuroendocrine tumors (PanNETs) are typically solid neoplasms but in rare instances may present as cystic lesions. This unusual presentation can make clinical diagnosis challenging. In addition, the clinical and histopathologic characteristics of cystic PanNETs are poorly defined. We identified 53 cystic PanNETs in our single-institution experience of 491 surgically resected PanNETs. Similar to solid PanNETs, cystic PanNETs developed with an equal sex distribution and over a wide age range (23 to 91 y; mean, 52 y). The unusual cystic appearance made radiologic differentiation from other cystic pancreatic neoplasms difficult with a misdiagnosis in 23 of 53 (43%) cases. An association between cystic PanNETs and multiple endocrine neoplasia type 1 or multifocal disease [5 of 53 (9%) and 7 of 53 (13%), respectively] was not observed as compared with solid PanNETs (P=0.34 and P=0.31, respectively). Grossly, cystic PanNETs were predominantly located in the tail of the pancreas (n=28, 53%) and were similar in size (mean, 3.3 cm) to solid PanNETs (mean, 4.1 cm; P=0.12). All cysts were unilocular (n=53, 100%) and filled with clear to straw-colored fluid. Larger cysts were sometimes noted to be hemorrhagic. Histologically, the cysts were lined by a thin fibrous band that separated the cyst from the neoplastic cells. In comparison with their solid counterparts, cystic PanNETs were less likely to demonstrate tumor necrosis (6%; P=0.04), perineural invasion (8%; P<0.001), vascular invasion (4%; P<0.001), regional lymph node metastasis (13%; P<0.001), and synchronous distant metastasis (4%; P=0.015). The neoplastic cells of the cystic PanNETs were well differentiated (n=53, 100%) with a low mitotic rate and low Ki-67 proliferation index (range, 0.2% to 11%; mean, 1.8%). On the basis of both the American Joint Cancer Committee and European Neuroendocrine Tumor Society staging systems, the majority of cystic PanNETs presented at a lower pathologic stage as compared with solid PanNETs. In summary, cystic PanNETs are a distinctive subgroup of PanNETs with unique clinical, radiographic, and pathologic features.

Gastroenteropancreatic neuroendocrine tumours: the current incidence and staging based on the WHO and European Neuroendocrine Tumour Society classification: an analysis based on prospectively collected parameters

As incidence data on gastroenteropancreatic neuroendocrine tumours (GEP-NETs) have so far only been retrospectively obtained and based on inhomogeneous material, we conducted a prospective study in Austria collecting all newly diagnosed GEP-NETs during 1 year. Using the current WHO classification, the tumor, nodes, metastases (TNM) staging and Ki67 grading and the standard diagnostic procedure proposed by the European Neuroendocrine Tumor Society (ENETS), GEP-NETs from 285 patients (male: 148; female: 137) were recorded. The annual incidence rates were 2.51 per 100,000 inhabitants for men, 2.36 per 100,000 for women. The stomach (23%) was the main site, followed by appendix (21%), small intestine (15%) and rectum (14%). Patients with appendiceal tumours were significantly younger than patients with tumours in any other site. About 46.0% were classified as benign, 15.4% as uncertain, 31.9% as well differentiated malignant and 6.7% as poorly differentiated malignant. Patients with benign or uncertain tumours were significantly younger than patients with malignant tumours. Among the malignant tumours of the digestive tract, 1.49% arose from neuroendocrine cells. For malignant gastrointestinal NETs, the incidence was 0.80 per 100,000: 40.9% were ENETS stage I, 23.8% stage II, 11.6% stage III and 23.8% stage IV. The majority (59.7%) were grade 1, 31.2% grade 2 and 9.1% grade 3. NETs of the digestive tract are more common than previously reported; the majority show benign behaviour, are located in the stomach and are well differentiated. G3 tumours are very rare.