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      TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system

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          Abstract

          The need for standards in the management of patients with endocrine tumors of the digestive system prompted the European Neuroendocrine Tumor Society (ENETS) to organize a first Consensus Conference, which was held in Frascati (Rome) and was based on the recently published ENETS guidelines on the diagnosis and treatment of digestive neuroendocrine tumors (NET). Here, we report the tumor–node–metastasis proposal for foregut NETs of the stomach, duodenum, and pancreas that was designed, discussed, and consensually approved at this conference. In addition, we report the proposal for a working formulation for the grading of digestive NETs based on mitotic count and Ki-67 index. This proposal, which needs to be validated, is meant to help clinicians in the stratification, treatment, and follow-up of patients.

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          Most cited references 32

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          Updated population-based review of carcinoid tumors.

          To determine the population-based incidence, anatomic distribution, and survival rates of gastrointestinal carcinoid tumors. Carcinoid tumors arise from neuroendocrine cells and may develop in almost any organ. Many textbooks and articles represent single institution studies and report varying incidence rates, anatomic distribution of tumors, and patient survival rates. Population-based statistics remain largely unknown. Data was obtained from the National Cancer Institute Surveillance, Epidemiology, and End Results program (1973 to 1997). Incidence rates, distribution, and 5-year survival rates were analyzed. Multivariate Cox regression was used to identify predictors of survival using age, race/ethnicity, gender, and tumor characteristics (size, lymph node status, and stage). Of the 11,427 cases analyzed, the average age was 60.9 years, and 54.2% were female. The overall incidence rates for carcinoid tumors have increased significantly over the past 25 years, although rates for some sites have decreased (eg, appendix). The gastrointestinal tract accounted for 54.5% of the tumors. Within the gastrointestinal tract, the small intestine was the most common site (44.7%), followed by the rectum (19.6%), appendix (16.7%), colon (10.6%), and stomach (7.2%). The 5-year survival rates for the most common gastrointestinal sites were stomach (75.1%), small intestine (76.1%), appendix (76.3%), and rectum (87.5%). Using national, population-based cancer registry data, this study demonstrates that (1) incidence rates for carcinoid tumors have changed, (2) the most common gastrointestinal site is not the appendix (as is often quoted), but the small intestine, followed in frequency by the rectum, and (3) survival rates differ between individual anatomic sites.
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            Guidelines for the Diagnosis and Treatment of Neuroendocrine Gastrointestinal Tumours

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              Prognostic factors and survival in endocrine tumor patients: comparison between gastrointestinal and pancreatic localization.

              Since gastro-entero-pancreatic endocrine tumors are rare and heterogeneous diseases, their prognosis and long-term survival are not well known. This study aimed at identifying prognostic factors and assessing long-term survival in gastro-entero-pancreatic endocrine tumors. A total of 156 patients enrolled. Prognostic factors were determined by univariate/multivariate analysis; survival rates were assessed by the Kaplan-Meier method. The tumors were non-functioning in 59.6% of patients, and originated from the pancreas in 42.9%. At diagnosis, 64.3% of patients had metastases. The tumors were well differentiated in 89.6% of patients. Ki67 was >2% in 39.6% of patients. Primary tumor size was >3 cm in 49.6% of cases studied. For the univariate analysis, the negative prognostic factors were: pancreatic origin (rate ratio 4.64, P = 0.0002), poorly differentiated tumor (rate ratio 7.70, P = 0.0001), primary tumor size >3 cm (rate ratio 4.26, P = 0.0009), presence of distant metastases (liver: rate ratio 5.88, P = 0.01; distant extra-hepatic: rate ratio 13.41, P = 0.0008). The pancreatic site, the poor degree of differentiation and the distant metastases were confirmed as negative prognostic factors at multivariate analysis. Overall 5-year survival rate was 77.5%. Survival rates differed according to: primary tumor site (62% for pancreatic vs 89.9% for gastrointestinal tract, P = 0.0001) and size (65.7% for >3 cm vs 88.8% for 2% vs 90.1% for 50 years, P = 0.03). Although 64.3% of gastro-entero-pancreatic endocrine tumors present metastases at diagnosis, the 5-year survival rate is 77.5%. Pancreatic site, a poor degree of tumor cell differentiation and distant extra-hepatic metastases are the major negative prognostic factors.
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                Author and article information

                Contributors
                +39-0521-702636 , +39-0521-292710 , guido.rindi@unipr.it
                Journal
                Virchows Arch
                Virchows Archiv
                Springer-Verlag (Berlin/Heidelberg )
                0945-6317
                1432-2307
                12 September 2006
                October 2006
                : 449
                : 4
                : 395-401
                Affiliations
                [1 ]Dipartimento di Patologia e, Medicina di Laboratorio, Sezione di Anatomia Patologica, Università di Parma, Via Gramsci, 14, 43100 Parma, Italy
                [2 ]Department of Pathology, University of Kiel, Kiel, Germany
                [3 ]Department of Surgery, Gothenburg University, Gothenburg, Sweden
                [4 ]Department of Internal Medicine, Royal Free Hospital, London, UK
                [5 ]Department of Pathology, Hôpital Beaujon, Clichy, France
                [6 ]Department of Internal Medicine, Erasmus, Rotterdam The Netherlands
                [7 ]Department of Endocrinology, University Hospital, Uppsala, Sweden
                [8 ]Department of Internal Medicine, University of Florence, Florence, Italy
                [9 ]Department of Surgery, University of Verona, Verona, Italy
                [10 ]Department of Pathology, Kantosspital Baden, Baden, Switzerland
                [11 ]Department of Pathology, University of Bern, Bern, Switzerland
                [12 ]Department of Pathology, Porto Medical School and IPATIMUP, University of Porto, Porto, Portugal
                [13 ]Department of Pathology, Glasgow Royal Infirmary, Glasgow, Scotland UK
                [14 ]Department of Pathology, Gothenborg University, Gothenburg, Sweden
                [15 ]Department of Pathology, Universitätsspital Zürich, Zürich, Switzerland
                [16 ]Department of Pathology, University of Verona, Verona, Italy
                [17 ]Department of Pathology, University of Lyon, Lyon, France
                [18 ]Department of Internal Medicine, Campus Virchow Klinikum, Berlin, Germany
                Article
                250
                10.1007/s00428-006-0250-1
                1888719
                16967267
                © Springer-Verlag 2006
                Categories
                Original Article
                Custom metadata
                © Springer-Verlag 2006

                Pathology

                grading, neuroendocrine tumors, mitotic index, staging, pancreas, ki-67 index, gut, tnm

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